2022 Update on contraception

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Tue, 10/25/2022 - 19:42

 

On June 24, 2022, the US Supreme Court ruled in Dobbs v Jackson to overturn the landmark Roe v Wade decision, deeming that abortion is not protected by statutes that provide the right to privacy, liberty, or autonomy. With this historic ruling, other rights founded on the same principles, including the freedom to use contraception, may be called into question in the future. Clinics that provide abortion care typically play a vital role in providing contraception services. Due to abortion restriction across the country, many of these clinics are predicted to close and many have already closed. Within one month of the Dobbs decision, 43 clinics in 11 states had shut their doors to patients, reducing access to basic contraception services.1 It is more important now than ever that clinicians address barriers and lead the effort to improve and ensure that patients have access to contraceptive services.

In this Update, we review recent evidence that may help aid patients in obtaining contraception more easily and for longer periods of time. We review strategies demonstrated to improve contraceptive access, including how to increase prescribing rates of 1-year contraceptive supplies and pharmacist-prescribed contraception. We also review new data on extended use of the levonorgestrel 52 mg intrauterine device (LNG 52 mg IUD).

 

One-year prescribing of  hormonal contraception  decreases an access barrier

Uhm S, Chen MJ, Cutler ED, et al. Twelve-month prescribing of contraceptive pill, patch, and ring before and after a standardized electronic medical record order change. Contraception. 2021;103:60-63.

Providing a 1-year supply of self-administered contraception can lead to higher likelihood of continued use and is associated with reduced cost, unintended pregnancy, and abortion rates.2-4 Although some patients may not use a full year’s supply of pills, rings, or patches under such programs, the lower rates of unintended pregnancy result in significant cost savings as compared with the unused contraceptives.2,3 Accordingly, the Centers for Disease Control and Prevention (CDC) advises dispensing a 1-year supply of self-administered hormonal contraception.5 Insurance coverage and providers’ prescribing practices can be barriers to patients obtaining a year’s supply of hormonal contraception. Currently, 18 states and the District of Columbia legally require insurers to cover a 12-month supply of prescription contraceptives (FIGURE 1). Despite these laws and the CDC recommendation, studies show that most people continue to receive only a 1- to 3-month supply.6-8 One strategy to increase the number of 1-year supplies of self-administered contraception is institutional changes to default prescription orders.

Study design

In California, legislation enacted in January 2017 required commercial and medical assistance health plans to cover up to  12 months of US Food and Drug Administration (FDA)-approved self-administered hormonal contraceptives dispensed at 1 time as prescribed or requested. To better serve patients, a multidisciplinary team from the University of California Davis Health worked with the institution’s pharmacy to institute an electronic medical record (EMR) default order change from dispensing 1-month with refills to dispensing 12-month quantities for all combined and progestin-only pills, patches, and rings on formulary.

After this EMR order change in December 2019, Uhm and colleagues conducted a retrospective pre-post study using outpatient prescription data that included nearly  5,000 contraceptive pill, patch, and ring prescriptions over an 8-month period. They compared the frequency of 12-month prescriptions for each of these methods 4 months before and 4 months after the default order change. They compared the proportion of 12-month prescriptions by prescriber department affiliation and by clinic location. Department affiliation was categorized as obstetrics-gynecology or non–obstetrics-gynecology. Clinic location was categorized as medical center campus or community clinics.

Increase in 12-month prescriptions

The authors found an overall increase in 12-month prescriptions, from 11% to 27%, after the EMR order change. Prescribers at the medical center campus clinics more frequently ordered a 12-month supply compared with prescribers at community clinics both before (33% vs 4%, respectively) and after (53% vs 19%, respectively) the EMR change. The only group of providers without a significant increase in 12-month prescriptions was among obstetrics-gynecology providers at community clinics (4% before  vs 6% after).

The system EMR change modified only the standard facility order settings and did not affect individual favorite orders, which may help explain the differences in prescribing practices. While this study found an increase in 12-month prescriptions, there were no data on the actual number of supplies a patient received or  on reimbursement.

 

WHAT THIS EVIDENCE MEANS FOR PRACTICE
The study by Uhm and colleagues showed that making a relatively simple change to default EMR orders can increase 12-month contraception prescribing and lead to greater patient-centered care. Evidence shows that providers and pharmacists are not necessarily aware of laws that require 12-month supply coverage and routinely prescribe smaller supplies.6,7,9 For clinicians in states that have these laws (FIGURE 1), we urge you to provide as full a supply of contraceptives as possible as this approach is both evidence based and patient centered. Although this study shows the benefit of universal system change to the EMR, individual clinicians also must be sure to modify personal order preferences. In addition, pharmacists can play an important role by updating policies that comply with these laws and by increasing pharmacy stocks of contraception supplies.7 For those living in states that do not currently have these laws, we encourage you to reach out to your legislators to advocate for similar laws as the data show clear medical and cost benefits for patients and society.

 Continue to: Pharmacist prescription of  hormonal contraception is safe and promotes continuation...

 

 

Pharmacist prescription of  hormonal contraception is safe and promotes continuation

Rodriguez MI, Skye M, Edelman AB, et al. Association of pharmacist prescription and 12-month contraceptive continuation rates. Am J Obstet Gynecol. 2021;225:647.e1-647.e9.

Patients often face difficulty obtaining both new and timely refills of self-administered contraception.10,11 To expand contraception access, Oregon became the first state (in 2016) to enact legislation to authorize direct pharmacist prescribing of hormonal contraceptives.12 Currently, 17 states and the District of Columbia have protocols for pharmacist prescribing privileges (FIGURE 2), and proposed legislation is pending in another  14 states.10,12 These protocols vary, but basic processes include screening, documentation, monitoring, and referrals when necessary. Typically, protocols require a pharmacist to review a patient’s medical history, pregnancy status, medication use, and blood pressure, followed by contraceptive counseling.10 Pharmacies are generally located in the community they serve, have extended hours, and usually do not require an appointment.8,13,14

Pharmacist prescribing increases the number of new contraceptive users, and pharmacists are more likely to prescribe a 6-month or longer supply of contraceptives compared with clinicians.8,13,15 Also, pharmacist prescribing is safe, with adherence rates to the CDC’s US Medical Eligibility Criteria for Contraceptive Use similar to those of prescriptions provided by a clinician.13

Authors of a recent multi-state study further assessed the impact of pharmacist prescribing by evaluating 12-month continuation and perfect use rates.

Study design

Rodriguez and colleagues evaluated the results of a 1-year prospective cohort study conducted in 2019 that included 388 participants who sought contraception in California, Colorado, Hawaii, and Oregon. All these states had laws permitting pharmacist prescribing and 12-month supply of hormonal contraception. Participants received prescriptions directly from a pharmacist at 1 of 139 pharmacies (n = 149) or filled a prescription provided by a clinician (n = 239). The primary outcomes were continuation of an effective method and perfect use of contraception across 12 months.

Participant demographics were similar between the 2 groups except for education and insurance status. Participants who received a prescription from a clinician reported higher levels of education. A greater proportion of uninsured participants received a prescription from a pharmacist (11%) compared with from a clinician (3%).

Contraceptive continuation rates

Participants were surveyed 3 times during the 12-month study about their current contraceptive method, if they had switched methods, or if they had any missed days  of contraception. 

Overall, 340 participants (88%) completed a full 12 months of follow-up. Continuation rates were similar between the 2 groups: 89% in the clinician-prescribed and 90% in the pharmacist-prescribed group (P=.86). Participants in the 2 groups also reported similar rates of perfect use (no missed days: 54% and 47%, respectively [P=.69]).  Additionally, the authors reported that  29 participants changed from a tier 2 (pill, patch, ring, injection) to a tier 1 (intrauterine device or implant) method during follow-up, with no difference in switch rates for participants who received care from a clinician (10%) or a pharmacist (7%).

WHAT THIS EVIDENCE MEANS FOR PRACTICE

Patients have difficulties in obtaining both an initial contraceptive prescription and refills in time to avoid breaks in coverage.16 Pharmacist prescription of contraception is a proven strategy to increase access to contraception for new users or to promote continuation among current users. This practice is evidence based, decreases unintended pregnancy rates, and is safe.8,13,15,17

Promoting universal pharmacist prescribing is even more important given the overruling of Roe v Wade. With abortion restrictions, many family planning clinics that also play a vital role in providing contraception will close. Most states that are limiting abortion care (FIGURE 3) are the same states without pharmacist-prescribing provisions (FIGURE 2). As patient advocates, we need to continue to support this evidence-based practice in states where it is available and push legislators in states where it is not. Pharmacists should receive support to complete the training and certification needed to not only provide this service but also to receive appropriate reimbursements. Restrictions, such as requiring patients to be 18 years or older or to have prior consultation with a physician, should be limited as these are not necessary to provide self-administered contraception safely. Clinicians and pharmacists should inform patients, in states where this is available, that they can access initial or refill prescriptions at their local pharmacy if that is more convenient or their preference. Clinicians who live in states without these laws can advocate for their community by encouraging their legislators to pass laws that allow this evidence-based practice.

Continue to: LNG 52 mg IUD demonstrates  efficacy and safety through 8 years of use... 

 

 

LNG 52 mg IUD demonstrates  efficacy and safety through 8 years of use 

Creinin MD, Schreiber CA, Turok DK, et al. Levonorgestrel 52 mg intrauterine system efficacy and safety through 8 years of use. Am J Obstet Gynecol. 2022;S00029378(22)00366-0.

Given the potential difficulty accessing contraceptive and abortion services due to state restrictions, patients may be more motivated to maintain long-acting reversible contraceptives for maximum periods of time. The LNG 52 mg IUD was first marketed as a 5-year product, but multiple studies suggested that it had potential longer duration of efficacy and safety.18,19 The most recent clinical trial report shows that the LNG 52 mg IUD has at least 8 years of efficacy  and safety.

Evidence supports 8 years’ use

The ACCESS IUS (A Comprehensive Contraceptive Efficacy and Safety Study of an IUS) phase 3 trial was designed to assess the safety and efficacy of a LNG 52 mg IUD (Liletta) for up to 10 years of use. The recent publication by Creinin and colleagues extends the available data from this study from 6 to 8 years.

Five-hundred and sixty-nine participants started year 7; 478 completed year 7 and 343 completed year 8 by the time the study was discontinued. Two pregnancies occurred in year 7 and no pregnancies occurred in year 8. One of the pregnancies in year 7 was determined by ultrasound examination to have implantation on day 4 after LNG IUD removal. According to the FDA, any pregnancy that occurs within 7 days of discontinuation is included as on-treatment, whereas the European Medicines Agency (EMA) has a 2-day cutoff. Over 8 years,  11 pregnancies occurred. The cumulative life-table pregnancy rate in the primary efficacy population through year 8 was 1.32% (95% confidence interval [CI],  0.69–2.51) under FDA rules and 1.09% (95% CI,  0.56–2.13) according to EMA guidance.

Absence of bleeding/spotting rates and adverse events

Rates of absence of bleeding/spotting remained relatively stable in years 7 and 8 at around 40%, similar to the rates during years 3 to 8 (FIGURE 4). Overall, only 2.6% of participants discontinued LNG IUD use because of bleeding problems, with a total of 4 participants discontinuing for this reason in years 7 and 8. Expulsion rates remained low at a rate of approximately 0.5% in years 7 and 8. Vulvovaginal infections were the most common adverse effect during year 7–8 of use. These findings are consistent with those found at  6 years.20

 

WHAT THIS EVIDENCE MEANS FOR PRACTICE
As abortion and contraception services become more difficult to access, patients may be more motivated to initiate or maintain an intrauterine device for longer. The ACCESS IUS trial provides contemporary data that are generalizable across the US population. Clinicians should educate patients about the efficacy, low incidence of new adverse events, and the steady rate at which patients experience absence of bleeding/spotting. The most recent data analysis supports continued use of LNG 52 mg IUD products for up to 8 years with an excellent extended safety profile. While some providers may express concern that patients may experience more bleeding with prolonged use, this study demonstrated low discontinuation rates due to bleeding in years 7 and 8. Perforations were diagnosed only during the first year, meaning that they most likely are related to the insertion process. Additionally, in this long-term study, expulsions occurred most frequently in the first year after placement. This study, which shows that the LNG IUD can continue to be used for longer than before, is important because it means that many patients will need fewer removals and reinsertions over their lifetime, reducing a patient’s risks and discomfort associated with these procedures. Sharing these data is important, as longer LNG IUD retention may reduce burdens faced by patients who desire long-acting reversible contraception.
References
  1. Kirstein M, Jones RK, Philbin J. One month post-Roe: at least 43 abortion clinics across 11 states have stopped offering abortion care. Guttmacher Institute. July 28, 2022. Accessed September 14, 2022. https://www.guttmacher.org /article/2022/07/one-month-post-roe-least-43-abortion-clinics-across -11-states-have-stopped-offering
  2. Foster DG, Hulett D, Bradsberry M, et al. Number of oral contraceptive pill packages dispensed and subsequent unintended pregnancies. Obstet Gynecol. 2011;117:566-572.
  3. Foster DG, Parvataneni R, de Bocanegra HT, et al. Number of oral contraceptive pill packages dispensed, method continuation, and costs. Obstet Gynecol. 2006;108:1107-114.
  4. Niu F, Cornelius J, Aboubechara N, et al. Real world outcomes related to providing an annual supply of short-acting hormonal contraceptives. Contraception. 2022;107:58-61.
  5. Curtis KM, Jatlaoui TC, Tepper NK, et al. US selected practice recommendations for contraceptive use, 2016. MMWR Recomm Rep. 2016;65:1-66.
  6. Women’s sexual and reproductive health services: key findings from the 2017 Kaiser Women’s Health Survey. KFF: Kaiser Family Foundation. March 13, 2018. Accessed September 14, 2022. https://www.kff.org/womens-health-policy /issue-brief/womens-sexual-and-reproductive-health-services-key-findings -from-the-2017-kaiser-womens-health-survey/
  7. Nikpour G, Allen A, Rafie S, et al. Pharmacy implementation of a new law allowing year-long hormonal contraception supplies. Pharmacy (Basel). 2020;8:E165.
  8. Rodriguez MI, Edelman AB, Skye M, et al. Association of pharmacist prescription with dispensed duration of hormonal contraception. JAMA Netw Open. 2020;3:e205252.
  9. Insurance coverage of contraceptives. Guttmacher Institute. Updated August 1, 2022. Accessed September 14, 2022. https://www.guttmacher.org/state-policy /explore/insurance-coverage-contraceptives
  10. Chim C, Sharma P. Pharmacists prescribing hormonal contraceptives: a status update. US Pharm. 2021;46:45-49.
  11. Rodriguez MI, Hersh A, Anderson LB, et al. Association of pharmacist prescription of hormonal contraception with unintended pregnancies and Medicaid costs. Obstet Gynecol. 2019;133:1238-1246.
  12. Pharmacist-prescribed contraceptives. Guttmacher Institute. Updated August 1, 2022. Accessed September 14, 2022. https://www.guttmacher.org/state -policy/explore/pharmacist-prescribed-contraceptives
  13. Anderson L, Hartung DM, Middleton L, et al. Pharmacist provision of hormonal contraception in the Oregon Medicaid population. Obstet Gynecol. 2019;133:1231-1237.
  14. Rodriguez MI, Edelman AB, Skye M, et al. Reasons for and experience in obtaining pharmacist prescribed contraception. Contraception. 2020;102:259-261.
  15. Rodriguez MI, Manibusan B, Kaufman M, et al. Association of pharmacist prescription of contraception with breaks in coverage. Obstet Gynecol. 2022;139:781-787.
  16. Pittman ME, Secura GM, Allsworth JE, et al. Understanding prescription adherence: pharmacy claims data from the Contraceptive CHOICE Project. Contraception. 2011;83:340-345.
  17. Rodriguez MI, Skye M, Edelman AB, et al. Association of pharmacist prescription and 12-month contraceptive continuation rates. Am J Obstet Gynecol. 2021;225:647.e1-647.e9.
  18. Secura GM, Allsworth JE, Madden T, et al. The Contraceptive CHOICE Project: reducing barriers to long-acting reversible contraception. Am J Obstet Gynecol. 2010;203:115.e1-7.
  19. Rowe P, Farley T, Peregoudov A, et al. Safety and efficacy in parous women of a 52-mg levonorgestrel-medicated intrauterine device: a 7-year randomized comparative study with the TCu380A. Contraception. 2016;93:498-506.
  20. Westhoff CL, Keder LM, Gangestad A, et al. Six-year contraceptive efficacy and continued safety of a levonorgestrel 52 mg intrauterine system. Contraception. 2020;101:159-161.
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Author and Disclosure Information

Jewel Brown, MD

Dr. Brown is a Complex Family Planning Fellow, Department of Obstetrics and Gynecology, University of California, Davis, Sacramento.

Mitchell D. Creinin, MD

Dr. Creinin is Professor and Director of the Complex Family Planning Fellowship, Department of Obstetrics and Gynecology, University of California, Davis, Sacramento.

Dr. Creinin reports that he has received speaking honorarium from Mayne and Organon, serves on an Advisory Board for Gedeon Richter, GlaxoSmithKline, OLIC, and Organon, and is a consultant for Estetra SPRL, FHI 360, Mayne, and Medicines360. Dr. Brown reports no financial relationships relevant to this article.

The Department of Obstetrics and Gynecology, University of California, Davis, receives contraceptive research funding for Dr. Creinin from Chemo Research SL, Evofem, Medicines360, Merck, Sebela, NIH/NICHD, and the Society of Family Planning.

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Author and Disclosure Information

Jewel Brown, MD

Dr. Brown is a Complex Family Planning Fellow, Department of Obstetrics and Gynecology, University of California, Davis, Sacramento.

Mitchell D. Creinin, MD

Dr. Creinin is Professor and Director of the Complex Family Planning Fellowship, Department of Obstetrics and Gynecology, University of California, Davis, Sacramento.

Dr. Creinin reports that he has received speaking honorarium from Mayne and Organon, serves on an Advisory Board for Gedeon Richter, GlaxoSmithKline, OLIC, and Organon, and is a consultant for Estetra SPRL, FHI 360, Mayne, and Medicines360. Dr. Brown reports no financial relationships relevant to this article.

The Department of Obstetrics and Gynecology, University of California, Davis, receives contraceptive research funding for Dr. Creinin from Chemo Research SL, Evofem, Medicines360, Merck, Sebela, NIH/NICHD, and the Society of Family Planning.

Author and Disclosure Information

Jewel Brown, MD

Dr. Brown is a Complex Family Planning Fellow, Department of Obstetrics and Gynecology, University of California, Davis, Sacramento.

Mitchell D. Creinin, MD

Dr. Creinin is Professor and Director of the Complex Family Planning Fellowship, Department of Obstetrics and Gynecology, University of California, Davis, Sacramento.

Dr. Creinin reports that he has received speaking honorarium from Mayne and Organon, serves on an Advisory Board for Gedeon Richter, GlaxoSmithKline, OLIC, and Organon, and is a consultant for Estetra SPRL, FHI 360, Mayne, and Medicines360. Dr. Brown reports no financial relationships relevant to this article.

The Department of Obstetrics and Gynecology, University of California, Davis, receives contraceptive research funding for Dr. Creinin from Chemo Research SL, Evofem, Medicines360, Merck, Sebela, NIH/NICHD, and the Society of Family Planning.

Article PDF
Article PDF

 

On June 24, 2022, the US Supreme Court ruled in Dobbs v Jackson to overturn the landmark Roe v Wade decision, deeming that abortion is not protected by statutes that provide the right to privacy, liberty, or autonomy. With this historic ruling, other rights founded on the same principles, including the freedom to use contraception, may be called into question in the future. Clinics that provide abortion care typically play a vital role in providing contraception services. Due to abortion restriction across the country, many of these clinics are predicted to close and many have already closed. Within one month of the Dobbs decision, 43 clinics in 11 states had shut their doors to patients, reducing access to basic contraception services.1 It is more important now than ever that clinicians address barriers and lead the effort to improve and ensure that patients have access to contraceptive services.

In this Update, we review recent evidence that may help aid patients in obtaining contraception more easily and for longer periods of time. We review strategies demonstrated to improve contraceptive access, including how to increase prescribing rates of 1-year contraceptive supplies and pharmacist-prescribed contraception. We also review new data on extended use of the levonorgestrel 52 mg intrauterine device (LNG 52 mg IUD).

 

One-year prescribing of  hormonal contraception  decreases an access barrier

Uhm S, Chen MJ, Cutler ED, et al. Twelve-month prescribing of contraceptive pill, patch, and ring before and after a standardized electronic medical record order change. Contraception. 2021;103:60-63.

Providing a 1-year supply of self-administered contraception can lead to higher likelihood of continued use and is associated with reduced cost, unintended pregnancy, and abortion rates.2-4 Although some patients may not use a full year’s supply of pills, rings, or patches under such programs, the lower rates of unintended pregnancy result in significant cost savings as compared with the unused contraceptives.2,3 Accordingly, the Centers for Disease Control and Prevention (CDC) advises dispensing a 1-year supply of self-administered hormonal contraception.5 Insurance coverage and providers’ prescribing practices can be barriers to patients obtaining a year’s supply of hormonal contraception. Currently, 18 states and the District of Columbia legally require insurers to cover a 12-month supply of prescription contraceptives (FIGURE 1). Despite these laws and the CDC recommendation, studies show that most people continue to receive only a 1- to 3-month supply.6-8 One strategy to increase the number of 1-year supplies of self-administered contraception is institutional changes to default prescription orders.

Study design

In California, legislation enacted in January 2017 required commercial and medical assistance health plans to cover up to  12 months of US Food and Drug Administration (FDA)-approved self-administered hormonal contraceptives dispensed at 1 time as prescribed or requested. To better serve patients, a multidisciplinary team from the University of California Davis Health worked with the institution’s pharmacy to institute an electronic medical record (EMR) default order change from dispensing 1-month with refills to dispensing 12-month quantities for all combined and progestin-only pills, patches, and rings on formulary.

After this EMR order change in December 2019, Uhm and colleagues conducted a retrospective pre-post study using outpatient prescription data that included nearly  5,000 contraceptive pill, patch, and ring prescriptions over an 8-month period. They compared the frequency of 12-month prescriptions for each of these methods 4 months before and 4 months after the default order change. They compared the proportion of 12-month prescriptions by prescriber department affiliation and by clinic location. Department affiliation was categorized as obstetrics-gynecology or non–obstetrics-gynecology. Clinic location was categorized as medical center campus or community clinics.

Increase in 12-month prescriptions

The authors found an overall increase in 12-month prescriptions, from 11% to 27%, after the EMR order change. Prescribers at the medical center campus clinics more frequently ordered a 12-month supply compared with prescribers at community clinics both before (33% vs 4%, respectively) and after (53% vs 19%, respectively) the EMR change. The only group of providers without a significant increase in 12-month prescriptions was among obstetrics-gynecology providers at community clinics (4% before  vs 6% after).

The system EMR change modified only the standard facility order settings and did not affect individual favorite orders, which may help explain the differences in prescribing practices. While this study found an increase in 12-month prescriptions, there were no data on the actual number of supplies a patient received or  on reimbursement.

 

WHAT THIS EVIDENCE MEANS FOR PRACTICE
The study by Uhm and colleagues showed that making a relatively simple change to default EMR orders can increase 12-month contraception prescribing and lead to greater patient-centered care. Evidence shows that providers and pharmacists are not necessarily aware of laws that require 12-month supply coverage and routinely prescribe smaller supplies.6,7,9 For clinicians in states that have these laws (FIGURE 1), we urge you to provide as full a supply of contraceptives as possible as this approach is both evidence based and patient centered. Although this study shows the benefit of universal system change to the EMR, individual clinicians also must be sure to modify personal order preferences. In addition, pharmacists can play an important role by updating policies that comply with these laws and by increasing pharmacy stocks of contraception supplies.7 For those living in states that do not currently have these laws, we encourage you to reach out to your legislators to advocate for similar laws as the data show clear medical and cost benefits for patients and society.

 Continue to: Pharmacist prescription of  hormonal contraception is safe and promotes continuation...

 

 

Pharmacist prescription of  hormonal contraception is safe and promotes continuation

Rodriguez MI, Skye M, Edelman AB, et al. Association of pharmacist prescription and 12-month contraceptive continuation rates. Am J Obstet Gynecol. 2021;225:647.e1-647.e9.

Patients often face difficulty obtaining both new and timely refills of self-administered contraception.10,11 To expand contraception access, Oregon became the first state (in 2016) to enact legislation to authorize direct pharmacist prescribing of hormonal contraceptives.12 Currently, 17 states and the District of Columbia have protocols for pharmacist prescribing privileges (FIGURE 2), and proposed legislation is pending in another  14 states.10,12 These protocols vary, but basic processes include screening, documentation, monitoring, and referrals when necessary. Typically, protocols require a pharmacist to review a patient’s medical history, pregnancy status, medication use, and blood pressure, followed by contraceptive counseling.10 Pharmacies are generally located in the community they serve, have extended hours, and usually do not require an appointment.8,13,14

Pharmacist prescribing increases the number of new contraceptive users, and pharmacists are more likely to prescribe a 6-month or longer supply of contraceptives compared with clinicians.8,13,15 Also, pharmacist prescribing is safe, with adherence rates to the CDC’s US Medical Eligibility Criteria for Contraceptive Use similar to those of prescriptions provided by a clinician.13

Authors of a recent multi-state study further assessed the impact of pharmacist prescribing by evaluating 12-month continuation and perfect use rates.

Study design

Rodriguez and colleagues evaluated the results of a 1-year prospective cohort study conducted in 2019 that included 388 participants who sought contraception in California, Colorado, Hawaii, and Oregon. All these states had laws permitting pharmacist prescribing and 12-month supply of hormonal contraception. Participants received prescriptions directly from a pharmacist at 1 of 139 pharmacies (n = 149) or filled a prescription provided by a clinician (n = 239). The primary outcomes were continuation of an effective method and perfect use of contraception across 12 months.

Participant demographics were similar between the 2 groups except for education and insurance status. Participants who received a prescription from a clinician reported higher levels of education. A greater proportion of uninsured participants received a prescription from a pharmacist (11%) compared with from a clinician (3%).

Contraceptive continuation rates

Participants were surveyed 3 times during the 12-month study about their current contraceptive method, if they had switched methods, or if they had any missed days  of contraception. 

Overall, 340 participants (88%) completed a full 12 months of follow-up. Continuation rates were similar between the 2 groups: 89% in the clinician-prescribed and 90% in the pharmacist-prescribed group (P=.86). Participants in the 2 groups also reported similar rates of perfect use (no missed days: 54% and 47%, respectively [P=.69]).  Additionally, the authors reported that  29 participants changed from a tier 2 (pill, patch, ring, injection) to a tier 1 (intrauterine device or implant) method during follow-up, with no difference in switch rates for participants who received care from a clinician (10%) or a pharmacist (7%).

WHAT THIS EVIDENCE MEANS FOR PRACTICE

Patients have difficulties in obtaining both an initial contraceptive prescription and refills in time to avoid breaks in coverage.16 Pharmacist prescription of contraception is a proven strategy to increase access to contraception for new users or to promote continuation among current users. This practice is evidence based, decreases unintended pregnancy rates, and is safe.8,13,15,17

Promoting universal pharmacist prescribing is even more important given the overruling of Roe v Wade. With abortion restrictions, many family planning clinics that also play a vital role in providing contraception will close. Most states that are limiting abortion care (FIGURE 3) are the same states without pharmacist-prescribing provisions (FIGURE 2). As patient advocates, we need to continue to support this evidence-based practice in states where it is available and push legislators in states where it is not. Pharmacists should receive support to complete the training and certification needed to not only provide this service but also to receive appropriate reimbursements. Restrictions, such as requiring patients to be 18 years or older or to have prior consultation with a physician, should be limited as these are not necessary to provide self-administered contraception safely. Clinicians and pharmacists should inform patients, in states where this is available, that they can access initial or refill prescriptions at their local pharmacy if that is more convenient or their preference. Clinicians who live in states without these laws can advocate for their community by encouraging their legislators to pass laws that allow this evidence-based practice.

Continue to: LNG 52 mg IUD demonstrates  efficacy and safety through 8 years of use... 

 

 

LNG 52 mg IUD demonstrates  efficacy and safety through 8 years of use 

Creinin MD, Schreiber CA, Turok DK, et al. Levonorgestrel 52 mg intrauterine system efficacy and safety through 8 years of use. Am J Obstet Gynecol. 2022;S00029378(22)00366-0.

Given the potential difficulty accessing contraceptive and abortion services due to state restrictions, patients may be more motivated to maintain long-acting reversible contraceptives for maximum periods of time. The LNG 52 mg IUD was first marketed as a 5-year product, but multiple studies suggested that it had potential longer duration of efficacy and safety.18,19 The most recent clinical trial report shows that the LNG 52 mg IUD has at least 8 years of efficacy  and safety.

Evidence supports 8 years’ use

The ACCESS IUS (A Comprehensive Contraceptive Efficacy and Safety Study of an IUS) phase 3 trial was designed to assess the safety and efficacy of a LNG 52 mg IUD (Liletta) for up to 10 years of use. The recent publication by Creinin and colleagues extends the available data from this study from 6 to 8 years.

Five-hundred and sixty-nine participants started year 7; 478 completed year 7 and 343 completed year 8 by the time the study was discontinued. Two pregnancies occurred in year 7 and no pregnancies occurred in year 8. One of the pregnancies in year 7 was determined by ultrasound examination to have implantation on day 4 after LNG IUD removal. According to the FDA, any pregnancy that occurs within 7 days of discontinuation is included as on-treatment, whereas the European Medicines Agency (EMA) has a 2-day cutoff. Over 8 years,  11 pregnancies occurred. The cumulative life-table pregnancy rate in the primary efficacy population through year 8 was 1.32% (95% confidence interval [CI],  0.69–2.51) under FDA rules and 1.09% (95% CI,  0.56–2.13) according to EMA guidance.

Absence of bleeding/spotting rates and adverse events

Rates of absence of bleeding/spotting remained relatively stable in years 7 and 8 at around 40%, similar to the rates during years 3 to 8 (FIGURE 4). Overall, only 2.6% of participants discontinued LNG IUD use because of bleeding problems, with a total of 4 participants discontinuing for this reason in years 7 and 8. Expulsion rates remained low at a rate of approximately 0.5% in years 7 and 8. Vulvovaginal infections were the most common adverse effect during year 7–8 of use. These findings are consistent with those found at  6 years.20

 

WHAT THIS EVIDENCE MEANS FOR PRACTICE
As abortion and contraception services become more difficult to access, patients may be more motivated to initiate or maintain an intrauterine device for longer. The ACCESS IUS trial provides contemporary data that are generalizable across the US population. Clinicians should educate patients about the efficacy, low incidence of new adverse events, and the steady rate at which patients experience absence of bleeding/spotting. The most recent data analysis supports continued use of LNG 52 mg IUD products for up to 8 years with an excellent extended safety profile. While some providers may express concern that patients may experience more bleeding with prolonged use, this study demonstrated low discontinuation rates due to bleeding in years 7 and 8. Perforations were diagnosed only during the first year, meaning that they most likely are related to the insertion process. Additionally, in this long-term study, expulsions occurred most frequently in the first year after placement. This study, which shows that the LNG IUD can continue to be used for longer than before, is important because it means that many patients will need fewer removals and reinsertions over their lifetime, reducing a patient’s risks and discomfort associated with these procedures. Sharing these data is important, as longer LNG IUD retention may reduce burdens faced by patients who desire long-acting reversible contraception.

 

On June 24, 2022, the US Supreme Court ruled in Dobbs v Jackson to overturn the landmark Roe v Wade decision, deeming that abortion is not protected by statutes that provide the right to privacy, liberty, or autonomy. With this historic ruling, other rights founded on the same principles, including the freedom to use contraception, may be called into question in the future. Clinics that provide abortion care typically play a vital role in providing contraception services. Due to abortion restriction across the country, many of these clinics are predicted to close and many have already closed. Within one month of the Dobbs decision, 43 clinics in 11 states had shut their doors to patients, reducing access to basic contraception services.1 It is more important now than ever that clinicians address barriers and lead the effort to improve and ensure that patients have access to contraceptive services.

In this Update, we review recent evidence that may help aid patients in obtaining contraception more easily and for longer periods of time. We review strategies demonstrated to improve contraceptive access, including how to increase prescribing rates of 1-year contraceptive supplies and pharmacist-prescribed contraception. We also review new data on extended use of the levonorgestrel 52 mg intrauterine device (LNG 52 mg IUD).

 

One-year prescribing of  hormonal contraception  decreases an access barrier

Uhm S, Chen MJ, Cutler ED, et al. Twelve-month prescribing of contraceptive pill, patch, and ring before and after a standardized electronic medical record order change. Contraception. 2021;103:60-63.

Providing a 1-year supply of self-administered contraception can lead to higher likelihood of continued use and is associated with reduced cost, unintended pregnancy, and abortion rates.2-4 Although some patients may not use a full year’s supply of pills, rings, or patches under such programs, the lower rates of unintended pregnancy result in significant cost savings as compared with the unused contraceptives.2,3 Accordingly, the Centers for Disease Control and Prevention (CDC) advises dispensing a 1-year supply of self-administered hormonal contraception.5 Insurance coverage and providers’ prescribing practices can be barriers to patients obtaining a year’s supply of hormonal contraception. Currently, 18 states and the District of Columbia legally require insurers to cover a 12-month supply of prescription contraceptives (FIGURE 1). Despite these laws and the CDC recommendation, studies show that most people continue to receive only a 1- to 3-month supply.6-8 One strategy to increase the number of 1-year supplies of self-administered contraception is institutional changes to default prescription orders.

Study design

In California, legislation enacted in January 2017 required commercial and medical assistance health plans to cover up to  12 months of US Food and Drug Administration (FDA)-approved self-administered hormonal contraceptives dispensed at 1 time as prescribed or requested. To better serve patients, a multidisciplinary team from the University of California Davis Health worked with the institution’s pharmacy to institute an electronic medical record (EMR) default order change from dispensing 1-month with refills to dispensing 12-month quantities for all combined and progestin-only pills, patches, and rings on formulary.

After this EMR order change in December 2019, Uhm and colleagues conducted a retrospective pre-post study using outpatient prescription data that included nearly  5,000 contraceptive pill, patch, and ring prescriptions over an 8-month period. They compared the frequency of 12-month prescriptions for each of these methods 4 months before and 4 months after the default order change. They compared the proportion of 12-month prescriptions by prescriber department affiliation and by clinic location. Department affiliation was categorized as obstetrics-gynecology or non–obstetrics-gynecology. Clinic location was categorized as medical center campus or community clinics.

Increase in 12-month prescriptions

The authors found an overall increase in 12-month prescriptions, from 11% to 27%, after the EMR order change. Prescribers at the medical center campus clinics more frequently ordered a 12-month supply compared with prescribers at community clinics both before (33% vs 4%, respectively) and after (53% vs 19%, respectively) the EMR change. The only group of providers without a significant increase in 12-month prescriptions was among obstetrics-gynecology providers at community clinics (4% before  vs 6% after).

The system EMR change modified only the standard facility order settings and did not affect individual favorite orders, which may help explain the differences in prescribing practices. While this study found an increase in 12-month prescriptions, there were no data on the actual number of supplies a patient received or  on reimbursement.

 

WHAT THIS EVIDENCE MEANS FOR PRACTICE
The study by Uhm and colleagues showed that making a relatively simple change to default EMR orders can increase 12-month contraception prescribing and lead to greater patient-centered care. Evidence shows that providers and pharmacists are not necessarily aware of laws that require 12-month supply coverage and routinely prescribe smaller supplies.6,7,9 For clinicians in states that have these laws (FIGURE 1), we urge you to provide as full a supply of contraceptives as possible as this approach is both evidence based and patient centered. Although this study shows the benefit of universal system change to the EMR, individual clinicians also must be sure to modify personal order preferences. In addition, pharmacists can play an important role by updating policies that comply with these laws and by increasing pharmacy stocks of contraception supplies.7 For those living in states that do not currently have these laws, we encourage you to reach out to your legislators to advocate for similar laws as the data show clear medical and cost benefits for patients and society.

 Continue to: Pharmacist prescription of  hormonal contraception is safe and promotes continuation...

 

 

Pharmacist prescription of  hormonal contraception is safe and promotes continuation

Rodriguez MI, Skye M, Edelman AB, et al. Association of pharmacist prescription and 12-month contraceptive continuation rates. Am J Obstet Gynecol. 2021;225:647.e1-647.e9.

Patients often face difficulty obtaining both new and timely refills of self-administered contraception.10,11 To expand contraception access, Oregon became the first state (in 2016) to enact legislation to authorize direct pharmacist prescribing of hormonal contraceptives.12 Currently, 17 states and the District of Columbia have protocols for pharmacist prescribing privileges (FIGURE 2), and proposed legislation is pending in another  14 states.10,12 These protocols vary, but basic processes include screening, documentation, monitoring, and referrals when necessary. Typically, protocols require a pharmacist to review a patient’s medical history, pregnancy status, medication use, and blood pressure, followed by contraceptive counseling.10 Pharmacies are generally located in the community they serve, have extended hours, and usually do not require an appointment.8,13,14

Pharmacist prescribing increases the number of new contraceptive users, and pharmacists are more likely to prescribe a 6-month or longer supply of contraceptives compared with clinicians.8,13,15 Also, pharmacist prescribing is safe, with adherence rates to the CDC’s US Medical Eligibility Criteria for Contraceptive Use similar to those of prescriptions provided by a clinician.13

Authors of a recent multi-state study further assessed the impact of pharmacist prescribing by evaluating 12-month continuation and perfect use rates.

Study design

Rodriguez and colleagues evaluated the results of a 1-year prospective cohort study conducted in 2019 that included 388 participants who sought contraception in California, Colorado, Hawaii, and Oregon. All these states had laws permitting pharmacist prescribing and 12-month supply of hormonal contraception. Participants received prescriptions directly from a pharmacist at 1 of 139 pharmacies (n = 149) or filled a prescription provided by a clinician (n = 239). The primary outcomes were continuation of an effective method and perfect use of contraception across 12 months.

Participant demographics were similar between the 2 groups except for education and insurance status. Participants who received a prescription from a clinician reported higher levels of education. A greater proportion of uninsured participants received a prescription from a pharmacist (11%) compared with from a clinician (3%).

Contraceptive continuation rates

Participants were surveyed 3 times during the 12-month study about their current contraceptive method, if they had switched methods, or if they had any missed days  of contraception. 

Overall, 340 participants (88%) completed a full 12 months of follow-up. Continuation rates were similar between the 2 groups: 89% in the clinician-prescribed and 90% in the pharmacist-prescribed group (P=.86). Participants in the 2 groups also reported similar rates of perfect use (no missed days: 54% and 47%, respectively [P=.69]).  Additionally, the authors reported that  29 participants changed from a tier 2 (pill, patch, ring, injection) to a tier 1 (intrauterine device or implant) method during follow-up, with no difference in switch rates for participants who received care from a clinician (10%) or a pharmacist (7%).

WHAT THIS EVIDENCE MEANS FOR PRACTICE

Patients have difficulties in obtaining both an initial contraceptive prescription and refills in time to avoid breaks in coverage.16 Pharmacist prescription of contraception is a proven strategy to increase access to contraception for new users or to promote continuation among current users. This practice is evidence based, decreases unintended pregnancy rates, and is safe.8,13,15,17

Promoting universal pharmacist prescribing is even more important given the overruling of Roe v Wade. With abortion restrictions, many family planning clinics that also play a vital role in providing contraception will close. Most states that are limiting abortion care (FIGURE 3) are the same states without pharmacist-prescribing provisions (FIGURE 2). As patient advocates, we need to continue to support this evidence-based practice in states where it is available and push legislators in states where it is not. Pharmacists should receive support to complete the training and certification needed to not only provide this service but also to receive appropriate reimbursements. Restrictions, such as requiring patients to be 18 years or older or to have prior consultation with a physician, should be limited as these are not necessary to provide self-administered contraception safely. Clinicians and pharmacists should inform patients, in states where this is available, that they can access initial or refill prescriptions at their local pharmacy if that is more convenient or their preference. Clinicians who live in states without these laws can advocate for their community by encouraging their legislators to pass laws that allow this evidence-based practice.

Continue to: LNG 52 mg IUD demonstrates  efficacy and safety through 8 years of use... 

 

 

LNG 52 mg IUD demonstrates  efficacy and safety through 8 years of use 

Creinin MD, Schreiber CA, Turok DK, et al. Levonorgestrel 52 mg intrauterine system efficacy and safety through 8 years of use. Am J Obstet Gynecol. 2022;S00029378(22)00366-0.

Given the potential difficulty accessing contraceptive and abortion services due to state restrictions, patients may be more motivated to maintain long-acting reversible contraceptives for maximum periods of time. The LNG 52 mg IUD was first marketed as a 5-year product, but multiple studies suggested that it had potential longer duration of efficacy and safety.18,19 The most recent clinical trial report shows that the LNG 52 mg IUD has at least 8 years of efficacy  and safety.

Evidence supports 8 years’ use

The ACCESS IUS (A Comprehensive Contraceptive Efficacy and Safety Study of an IUS) phase 3 trial was designed to assess the safety and efficacy of a LNG 52 mg IUD (Liletta) for up to 10 years of use. The recent publication by Creinin and colleagues extends the available data from this study from 6 to 8 years.

Five-hundred and sixty-nine participants started year 7; 478 completed year 7 and 343 completed year 8 by the time the study was discontinued. Two pregnancies occurred in year 7 and no pregnancies occurred in year 8. One of the pregnancies in year 7 was determined by ultrasound examination to have implantation on day 4 after LNG IUD removal. According to the FDA, any pregnancy that occurs within 7 days of discontinuation is included as on-treatment, whereas the European Medicines Agency (EMA) has a 2-day cutoff. Over 8 years,  11 pregnancies occurred. The cumulative life-table pregnancy rate in the primary efficacy population through year 8 was 1.32% (95% confidence interval [CI],  0.69–2.51) under FDA rules and 1.09% (95% CI,  0.56–2.13) according to EMA guidance.

Absence of bleeding/spotting rates and adverse events

Rates of absence of bleeding/spotting remained relatively stable in years 7 and 8 at around 40%, similar to the rates during years 3 to 8 (FIGURE 4). Overall, only 2.6% of participants discontinued LNG IUD use because of bleeding problems, with a total of 4 participants discontinuing for this reason in years 7 and 8. Expulsion rates remained low at a rate of approximately 0.5% in years 7 and 8. Vulvovaginal infections were the most common adverse effect during year 7–8 of use. These findings are consistent with those found at  6 years.20

 

WHAT THIS EVIDENCE MEANS FOR PRACTICE
As abortion and contraception services become more difficult to access, patients may be more motivated to initiate or maintain an intrauterine device for longer. The ACCESS IUS trial provides contemporary data that are generalizable across the US population. Clinicians should educate patients about the efficacy, low incidence of new adverse events, and the steady rate at which patients experience absence of bleeding/spotting. The most recent data analysis supports continued use of LNG 52 mg IUD products for up to 8 years with an excellent extended safety profile. While some providers may express concern that patients may experience more bleeding with prolonged use, this study demonstrated low discontinuation rates due to bleeding in years 7 and 8. Perforations were diagnosed only during the first year, meaning that they most likely are related to the insertion process. Additionally, in this long-term study, expulsions occurred most frequently in the first year after placement. This study, which shows that the LNG IUD can continue to be used for longer than before, is important because it means that many patients will need fewer removals and reinsertions over their lifetime, reducing a patient’s risks and discomfort associated with these procedures. Sharing these data is important, as longer LNG IUD retention may reduce burdens faced by patients who desire long-acting reversible contraception.
References
  1. Kirstein M, Jones RK, Philbin J. One month post-Roe: at least 43 abortion clinics across 11 states have stopped offering abortion care. Guttmacher Institute. July 28, 2022. Accessed September 14, 2022. https://www.guttmacher.org /article/2022/07/one-month-post-roe-least-43-abortion-clinics-across -11-states-have-stopped-offering
  2. Foster DG, Hulett D, Bradsberry M, et al. Number of oral contraceptive pill packages dispensed and subsequent unintended pregnancies. Obstet Gynecol. 2011;117:566-572.
  3. Foster DG, Parvataneni R, de Bocanegra HT, et al. Number of oral contraceptive pill packages dispensed, method continuation, and costs. Obstet Gynecol. 2006;108:1107-114.
  4. Niu F, Cornelius J, Aboubechara N, et al. Real world outcomes related to providing an annual supply of short-acting hormonal contraceptives. Contraception. 2022;107:58-61.
  5. Curtis KM, Jatlaoui TC, Tepper NK, et al. US selected practice recommendations for contraceptive use, 2016. MMWR Recomm Rep. 2016;65:1-66.
  6. Women’s sexual and reproductive health services: key findings from the 2017 Kaiser Women’s Health Survey. KFF: Kaiser Family Foundation. March 13, 2018. Accessed September 14, 2022. https://www.kff.org/womens-health-policy /issue-brief/womens-sexual-and-reproductive-health-services-key-findings -from-the-2017-kaiser-womens-health-survey/
  7. Nikpour G, Allen A, Rafie S, et al. Pharmacy implementation of a new law allowing year-long hormonal contraception supplies. Pharmacy (Basel). 2020;8:E165.
  8. Rodriguez MI, Edelman AB, Skye M, et al. Association of pharmacist prescription with dispensed duration of hormonal contraception. JAMA Netw Open. 2020;3:e205252.
  9. Insurance coverage of contraceptives. Guttmacher Institute. Updated August 1, 2022. Accessed September 14, 2022. https://www.guttmacher.org/state-policy /explore/insurance-coverage-contraceptives
  10. Chim C, Sharma P. Pharmacists prescribing hormonal contraceptives: a status update. US Pharm. 2021;46:45-49.
  11. Rodriguez MI, Hersh A, Anderson LB, et al. Association of pharmacist prescription of hormonal contraception with unintended pregnancies and Medicaid costs. Obstet Gynecol. 2019;133:1238-1246.
  12. Pharmacist-prescribed contraceptives. Guttmacher Institute. Updated August 1, 2022. Accessed September 14, 2022. https://www.guttmacher.org/state -policy/explore/pharmacist-prescribed-contraceptives
  13. Anderson L, Hartung DM, Middleton L, et al. Pharmacist provision of hormonal contraception in the Oregon Medicaid population. Obstet Gynecol. 2019;133:1231-1237.
  14. Rodriguez MI, Edelman AB, Skye M, et al. Reasons for and experience in obtaining pharmacist prescribed contraception. Contraception. 2020;102:259-261.
  15. Rodriguez MI, Manibusan B, Kaufman M, et al. Association of pharmacist prescription of contraception with breaks in coverage. Obstet Gynecol. 2022;139:781-787.
  16. Pittman ME, Secura GM, Allsworth JE, et al. Understanding prescription adherence: pharmacy claims data from the Contraceptive CHOICE Project. Contraception. 2011;83:340-345.
  17. Rodriguez MI, Skye M, Edelman AB, et al. Association of pharmacist prescription and 12-month contraceptive continuation rates. Am J Obstet Gynecol. 2021;225:647.e1-647.e9.
  18. Secura GM, Allsworth JE, Madden T, et al. The Contraceptive CHOICE Project: reducing barriers to long-acting reversible contraception. Am J Obstet Gynecol. 2010;203:115.e1-7.
  19. Rowe P, Farley T, Peregoudov A, et al. Safety and efficacy in parous women of a 52-mg levonorgestrel-medicated intrauterine device: a 7-year randomized comparative study with the TCu380A. Contraception. 2016;93:498-506.
  20. Westhoff CL, Keder LM, Gangestad A, et al. Six-year contraceptive efficacy and continued safety of a levonorgestrel 52 mg intrauterine system. Contraception. 2020;101:159-161.
References
  1. Kirstein M, Jones RK, Philbin J. One month post-Roe: at least 43 abortion clinics across 11 states have stopped offering abortion care. Guttmacher Institute. July 28, 2022. Accessed September 14, 2022. https://www.guttmacher.org /article/2022/07/one-month-post-roe-least-43-abortion-clinics-across -11-states-have-stopped-offering
  2. Foster DG, Hulett D, Bradsberry M, et al. Number of oral contraceptive pill packages dispensed and subsequent unintended pregnancies. Obstet Gynecol. 2011;117:566-572.
  3. Foster DG, Parvataneni R, de Bocanegra HT, et al. Number of oral contraceptive pill packages dispensed, method continuation, and costs. Obstet Gynecol. 2006;108:1107-114.
  4. Niu F, Cornelius J, Aboubechara N, et al. Real world outcomes related to providing an annual supply of short-acting hormonal contraceptives. Contraception. 2022;107:58-61.
  5. Curtis KM, Jatlaoui TC, Tepper NK, et al. US selected practice recommendations for contraceptive use, 2016. MMWR Recomm Rep. 2016;65:1-66.
  6. Women’s sexual and reproductive health services: key findings from the 2017 Kaiser Women’s Health Survey. KFF: Kaiser Family Foundation. March 13, 2018. Accessed September 14, 2022. https://www.kff.org/womens-health-policy /issue-brief/womens-sexual-and-reproductive-health-services-key-findings -from-the-2017-kaiser-womens-health-survey/
  7. Nikpour G, Allen A, Rafie S, et al. Pharmacy implementation of a new law allowing year-long hormonal contraception supplies. Pharmacy (Basel). 2020;8:E165.
  8. Rodriguez MI, Edelman AB, Skye M, et al. Association of pharmacist prescription with dispensed duration of hormonal contraception. JAMA Netw Open. 2020;3:e205252.
  9. Insurance coverage of contraceptives. Guttmacher Institute. Updated August 1, 2022. Accessed September 14, 2022. https://www.guttmacher.org/state-policy /explore/insurance-coverage-contraceptives
  10. Chim C, Sharma P. Pharmacists prescribing hormonal contraceptives: a status update. US Pharm. 2021;46:45-49.
  11. Rodriguez MI, Hersh A, Anderson LB, et al. Association of pharmacist prescription of hormonal contraception with unintended pregnancies and Medicaid costs. Obstet Gynecol. 2019;133:1238-1246.
  12. Pharmacist-prescribed contraceptives. Guttmacher Institute. Updated August 1, 2022. Accessed September 14, 2022. https://www.guttmacher.org/state -policy/explore/pharmacist-prescribed-contraceptives
  13. Anderson L, Hartung DM, Middleton L, et al. Pharmacist provision of hormonal contraception in the Oregon Medicaid population. Obstet Gynecol. 2019;133:1231-1237.
  14. Rodriguez MI, Edelman AB, Skye M, et al. Reasons for and experience in obtaining pharmacist prescribed contraception. Contraception. 2020;102:259-261.
  15. Rodriguez MI, Manibusan B, Kaufman M, et al. Association of pharmacist prescription of contraception with breaks in coverage. Obstet Gynecol. 2022;139:781-787.
  16. Pittman ME, Secura GM, Allsworth JE, et al. Understanding prescription adherence: pharmacy claims data from the Contraceptive CHOICE Project. Contraception. 2011;83:340-345.
  17. Rodriguez MI, Skye M, Edelman AB, et al. Association of pharmacist prescription and 12-month contraceptive continuation rates. Am J Obstet Gynecol. 2021;225:647.e1-647.e9.
  18. Secura GM, Allsworth JE, Madden T, et al. The Contraceptive CHOICE Project: reducing barriers to long-acting reversible contraception. Am J Obstet Gynecol. 2010;203:115.e1-7.
  19. Rowe P, Farley T, Peregoudov A, et al. Safety and efficacy in parous women of a 52-mg levonorgestrel-medicated intrauterine device: a 7-year randomized comparative study with the TCu380A. Contraception. 2016;93:498-506.
  20. Westhoff CL, Keder LM, Gangestad A, et al. Six-year contraceptive efficacy and continued safety of a levonorgestrel 52 mg intrauterine system. Contraception. 2020;101:159-161.
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Disjointed states of America: The medical is political

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Mon, 10/17/2022 - 21:48

Like many of you, I am an obstetrician-gynecologist who provides full-spectrum reproductive health care. Our jobs demand great intimacy—we are with patients as they meet their first born, learn of a miscarriage diagnosis, or decide to end their pregnancy. I have performed an uncomplicated, joyful vaginal delivery, then within an hour rushed a different patient’s gurney to the intensive care unit as she became acutely hypotensive and hypoxic, developing ARDS after a stillbirth. The care we provide is uniquely personal, and in that, has become deeply political. We have spent a long time here—news pundits, members of our family, even us—viewing abortion and reproductive health as something innately political. Although abortion is at the forefront of legislative interference and politicization, more than 1,300 abortion restrictions have been passed in the United States since Roe v Wade in 1973. It is not the only medical care affected by political interference.1 The United States ranks last in maternal mortality among industrialized nations, and Black women are more than twice as likely to die.2 As we grapple with the fallout of the Dobbs v Jackson Women’s Health Organization opinion and begin to recognize how fractured medical care has become—based on zip code—we should take stock of the way legislation and politics have already dictated reproductive health care. Abortion is the salient example, but state policy and legislation have unjustly been determining medical care available to women and other patients on a broader scale for decades. Here are just a few examples.

Postpartum care

The postpartum period is critical for maternal health; it is the time period in which many comorbidities emerge, including hypertensive disorders, postpartum thyroiditis, and mood disorders. Fifty percent of maternal deaths in the United States occur postpartum. Despite the importance of this care, Medicaid coverage for longer than 60 days postpartum varies greatly state to state. After the Affordable Care Act was implemented, it was assumed that all states would expand their Medicaid programs to include parents in their coverage plans beyond the guaranteed 60 days, negating the need for a specific postpartum coverage time period. However, the 2012 Supreme Court decision in National Federation of Independent Business v Sebelius allowed states to opt out of Medicaid expansion.3 In many states, postpartum patients lose their Medicaid insurance after 60 days if they do not meet the stringent income criteria.

The income level that makes patients ineligible for Medicaid coverage at day 61 postpartum varies widely. In Maryland, a patient can extend their Medicaid coverage for 12 months postpartum if their family of 4 earns less than $73,260 annually (264% of the federal poverty level). However, in Mississippi, an income of more than $6,936 per year for a family of 4 (approximately 25% of the federal poverty level) renders mothers who are 61 days postpartum ineligible for Medicaid coverage.4 Thus, many low-income postpartum patients (who are at twice the risk of maternal mortality as affluent patients) find themselves without access to this critical care depending on the decisions of their state legislatures.5 The American Rescue Plan Act of 2021 (known as the COVID-19 Stimulus Package) included a provision that allows states to expand their postpartum Medicaid coverage from 60 days to 12 months; currently, 10 additional states are planning to expand postpartum Medicaid for 12 months. While encouraging, 14 states still have not announced plans to utilize this provision or apply for a waiver to extend Medicaid coverage in the postpartum period.6

 

 

Treatment for substance use

Drug overdose is a leading cause of pregnancy-related death from unintentional causes.7 Overdose deaths in the general population climbed between 2020 and 2021, reaching historic highs of more than 100,000 deaths in a 12-month period.8 Given the impact of substance use and overdose on maternal mortality, health systems should be maximizing efforts to respond to this public health crisis by implementing effective screening and treatment interventions and establishing clinics and hospitals as safe places to seek care. However, many states have criminalized substance use in pregnant patients and mandate that clinicians report patients who use substances, creating an ethical dilemma for clinicians seeking to screen and treat patients for substance use disorder. Twenty-three states consider substance use in pregnancy to be child abuse, and 3 states consider substance use in pregnancy to be grounds for civil commitment. In Wisconsin, a patient can be detained against their will for the duration of the pregnancy. Twenty-five states require health care professionals to report suspected substance abuse in pregnancy to child protective services or a similar state office.9 Even when universal substance use screening is implemented, it has disparate impact on patients of color; Black women who screened positive for substance use in pregnancy were more likely to be reported to child protective services than their White counterparts.10 The criminalization of pregnant bodies does not lead to improvements in individual, community, or public health, it infringes on the ethical principle of bodily autonomy and puts clinicians at odds with what is best for their patients.

Gender-affirming care

Gender-affirming care is supported by major medical organizations and reduces the risk of depression and suicidality in transgender youth.11 Despite this evidence, several states have passed legislation restricting or banning this care, criminalizing the doctors who provide it. Idaho’s house of representatives passed House Bill 675,12 which would make providing gender-affirming care a felony, punishable by up to a life sentence. This would extend to parents trying to access care for their children as well as clinicians.

Although abortion is the medical care most conspicuously manipulated by politics and legislation, it is far from the only example. No area of medicine will be untouched by eliminating access to reproductive health care and by the regulation and criminalization of health care workers who provide it. This is a sea change, although state legislative interference and disparities in reproductive health care have been a tocsin of such change for years. We can no longer afford to believe there is a separation between politics and medicine; this directly interferes with our Hippocratic oath to do no harm. A politician in Ohio should not decide whether or not a 13-year-old patient should have to carry a pregnancy to term; the house of representatives in Idaho should not put someone’s transgender child at increased risk of depression and suicidality by making their medical care a felony. Colleagues in Texas should not be punishable by life in prison for providing abortion care.13 As a physician, I cannot stand by when, facing a maternal mortality crisis, state politicians decide whether a patient living below the poverty line should have access to postpartum care.

I am neither a politician nor a legal scholar. I am a physician who takes care of people in this intimate and powerful space of healing and support between doctor and patient. What should we do? We need to come together to find the answers. We need to vote if we haven’t before. And we need to vote differently if we have elected lawmakers who politicize and dangerously interfere with medicine, the well-being of our patients, and our ability to carry out our duty as physicians in our patients’ best interests. We need to tell our stories—to each other, to our newspapers, to our neighbors, and to our legislatures. If we are leading organizations, we can use the power held in our institutions to commit to providing care to the fullest extent possible, commit to protecting our clinicians providing evidence-based care, and encourage legislators who use medicine as a political bargaining chip to reverse course. Medicine is not an apolitical field, and we can no longer uphold that paradigm. Our patients lives, and our livelihood as healers and caretakers, depends on our collective action against it. ●

Acknowledgement

The author would like to thank Lauren Sobel, DO, MPH, for her contributions to a presentation on this subject.

References
  1. Nash E, Ephross P. State policy trends at midyear 2022: with Roe about to be overturned, some states double down on abortion restrictions. Guttmacher Institute. June 22, 2022. https://live. guttmacher.org/article/2022/06/state-policy -trends-midyear-2022-roe-about-be-overturnedsome-states-double-down. Accessed September 12, 2022.
  2. Declercq E, Zephyrin L. Maternal mortality in the United States: a primer. Commonwealth Fund; 2020. https://www.commonwealthfund .org/publications/issue-brief-report/2020 /dec/maternal-mortality-united-states-primer. Accessed September 12, 2022.
  3. Santa Clara Law Digital Communications website. Supreme Court of the United States. National Federation of Independent Business v Sebelius. (2012). Patient Protection and Affordable Care Act Litigation. 333. https://digitalcommons.law.scu.edu /aca/333. Accessed September 13, 2022.
  4. Ranji U, Salganicoff A, Gomez I. Postpartum coverage extension in the American Rescue Plan Act of 2021. San Francisco, CA: Kaiser Family Foundation; 2021.
  5. Singh GK, Lee H. Trends and racial/ethnic, socioeconomic, and geographic disparities in maternal mortality from indirect obstetric causes in the United States, 1999-2017. Int J MCH AIDS. 2021;10:43.
  6. Kaiser Family Foundation. Medicaid Postpartum Coverage Extension Tracker. https://www.kff. org/medicaid/issue-brief/medicaid-postpartum -coverage-extension-tracker/. Accessed September 7, 2022.
  7. Mehta PK, Bachhuber MA, Hoffman R, et al. Deaths from unintentional injury, homicide, and suicide during or within 1 year of pregnancy in Philadelphia. Am J Public Health. 2016;106: 2208-2210.
  8. O’Donnell J, Tanz LJ, Gladden RM, et al. Trends in and characteristics of drug overdose deaths involving illicitly manufactured fentanyls— United States, 2019–2020. MMWR Morb Mortal Wkly Rep. 2021;70:1740.
  9. State laws and policies: substance use during pregnancy. Guttmacher Institute. https://www .guttmacher.org/state-policy/explore/substance -use-during-pregnancy. August 1, 2022. Accessed September 13, 2022.
  10. Roberts S, Nuru-Jeter A. Universal screening for alcohol and drug use and racial disparities in child protective services reporting. J Behav Health Serv Res. 2012;39;3-16.
  11. Tordoff DM, Wanta JW, Collin, et al. (2022). Mental health outcomes in transgender and nonbinary youths receiving gender-affirming care. JAMA Network Open. 2022;5:e220978. doi: 10.1001/jamanetworkopen.2022.0978.
  12. House Bill 675. Idaho Legislature web site. https:// legislature.idaho.gov/sessioninfo/2022/legislation/h0675/. Accessed September 9, 2022.
  13. Simon S. New Texas trigger law makes abortion a felony. NPR. August 27, 2022. https://www.npr. org/2022/08/27/1119795665/new-texas-trigger -law-makes-abortion-a-felony. Accessed September 13, 2022. 
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Like many of you, I am an obstetrician-gynecologist who provides full-spectrum reproductive health care. Our jobs demand great intimacy—we are with patients as they meet their first born, learn of a miscarriage diagnosis, or decide to end their pregnancy. I have performed an uncomplicated, joyful vaginal delivery, then within an hour rushed a different patient’s gurney to the intensive care unit as she became acutely hypotensive and hypoxic, developing ARDS after a stillbirth. The care we provide is uniquely personal, and in that, has become deeply political. We have spent a long time here—news pundits, members of our family, even us—viewing abortion and reproductive health as something innately political. Although abortion is at the forefront of legislative interference and politicization, more than 1,300 abortion restrictions have been passed in the United States since Roe v Wade in 1973. It is not the only medical care affected by political interference.1 The United States ranks last in maternal mortality among industrialized nations, and Black women are more than twice as likely to die.2 As we grapple with the fallout of the Dobbs v Jackson Women’s Health Organization opinion and begin to recognize how fractured medical care has become—based on zip code—we should take stock of the way legislation and politics have already dictated reproductive health care. Abortion is the salient example, but state policy and legislation have unjustly been determining medical care available to women and other patients on a broader scale for decades. Here are just a few examples.

Postpartum care

The postpartum period is critical for maternal health; it is the time period in which many comorbidities emerge, including hypertensive disorders, postpartum thyroiditis, and mood disorders. Fifty percent of maternal deaths in the United States occur postpartum. Despite the importance of this care, Medicaid coverage for longer than 60 days postpartum varies greatly state to state. After the Affordable Care Act was implemented, it was assumed that all states would expand their Medicaid programs to include parents in their coverage plans beyond the guaranteed 60 days, negating the need for a specific postpartum coverage time period. However, the 2012 Supreme Court decision in National Federation of Independent Business v Sebelius allowed states to opt out of Medicaid expansion.3 In many states, postpartum patients lose their Medicaid insurance after 60 days if they do not meet the stringent income criteria.

The income level that makes patients ineligible for Medicaid coverage at day 61 postpartum varies widely. In Maryland, a patient can extend their Medicaid coverage for 12 months postpartum if their family of 4 earns less than $73,260 annually (264% of the federal poverty level). However, in Mississippi, an income of more than $6,936 per year for a family of 4 (approximately 25% of the federal poverty level) renders mothers who are 61 days postpartum ineligible for Medicaid coverage.4 Thus, many low-income postpartum patients (who are at twice the risk of maternal mortality as affluent patients) find themselves without access to this critical care depending on the decisions of their state legislatures.5 The American Rescue Plan Act of 2021 (known as the COVID-19 Stimulus Package) included a provision that allows states to expand their postpartum Medicaid coverage from 60 days to 12 months; currently, 10 additional states are planning to expand postpartum Medicaid for 12 months. While encouraging, 14 states still have not announced plans to utilize this provision or apply for a waiver to extend Medicaid coverage in the postpartum period.6

 

 

Treatment for substance use

Drug overdose is a leading cause of pregnancy-related death from unintentional causes.7 Overdose deaths in the general population climbed between 2020 and 2021, reaching historic highs of more than 100,000 deaths in a 12-month period.8 Given the impact of substance use and overdose on maternal mortality, health systems should be maximizing efforts to respond to this public health crisis by implementing effective screening and treatment interventions and establishing clinics and hospitals as safe places to seek care. However, many states have criminalized substance use in pregnant patients and mandate that clinicians report patients who use substances, creating an ethical dilemma for clinicians seeking to screen and treat patients for substance use disorder. Twenty-three states consider substance use in pregnancy to be child abuse, and 3 states consider substance use in pregnancy to be grounds for civil commitment. In Wisconsin, a patient can be detained against their will for the duration of the pregnancy. Twenty-five states require health care professionals to report suspected substance abuse in pregnancy to child protective services or a similar state office.9 Even when universal substance use screening is implemented, it has disparate impact on patients of color; Black women who screened positive for substance use in pregnancy were more likely to be reported to child protective services than their White counterparts.10 The criminalization of pregnant bodies does not lead to improvements in individual, community, or public health, it infringes on the ethical principle of bodily autonomy and puts clinicians at odds with what is best for their patients.

Gender-affirming care

Gender-affirming care is supported by major medical organizations and reduces the risk of depression and suicidality in transgender youth.11 Despite this evidence, several states have passed legislation restricting or banning this care, criminalizing the doctors who provide it. Idaho’s house of representatives passed House Bill 675,12 which would make providing gender-affirming care a felony, punishable by up to a life sentence. This would extend to parents trying to access care for their children as well as clinicians.

Although abortion is the medical care most conspicuously manipulated by politics and legislation, it is far from the only example. No area of medicine will be untouched by eliminating access to reproductive health care and by the regulation and criminalization of health care workers who provide it. This is a sea change, although state legislative interference and disparities in reproductive health care have been a tocsin of such change for years. We can no longer afford to believe there is a separation between politics and medicine; this directly interferes with our Hippocratic oath to do no harm. A politician in Ohio should not decide whether or not a 13-year-old patient should have to carry a pregnancy to term; the house of representatives in Idaho should not put someone’s transgender child at increased risk of depression and suicidality by making their medical care a felony. Colleagues in Texas should not be punishable by life in prison for providing abortion care.13 As a physician, I cannot stand by when, facing a maternal mortality crisis, state politicians decide whether a patient living below the poverty line should have access to postpartum care.

I am neither a politician nor a legal scholar. I am a physician who takes care of people in this intimate and powerful space of healing and support between doctor and patient. What should we do? We need to come together to find the answers. We need to vote if we haven’t before. And we need to vote differently if we have elected lawmakers who politicize and dangerously interfere with medicine, the well-being of our patients, and our ability to carry out our duty as physicians in our patients’ best interests. We need to tell our stories—to each other, to our newspapers, to our neighbors, and to our legislatures. If we are leading organizations, we can use the power held in our institutions to commit to providing care to the fullest extent possible, commit to protecting our clinicians providing evidence-based care, and encourage legislators who use medicine as a political bargaining chip to reverse course. Medicine is not an apolitical field, and we can no longer uphold that paradigm. Our patients lives, and our livelihood as healers and caretakers, depends on our collective action against it. ●

Acknowledgement

The author would like to thank Lauren Sobel, DO, MPH, for her contributions to a presentation on this subject.

Like many of you, I am an obstetrician-gynecologist who provides full-spectrum reproductive health care. Our jobs demand great intimacy—we are with patients as they meet their first born, learn of a miscarriage diagnosis, or decide to end their pregnancy. I have performed an uncomplicated, joyful vaginal delivery, then within an hour rushed a different patient’s gurney to the intensive care unit as she became acutely hypotensive and hypoxic, developing ARDS after a stillbirth. The care we provide is uniquely personal, and in that, has become deeply political. We have spent a long time here—news pundits, members of our family, even us—viewing abortion and reproductive health as something innately political. Although abortion is at the forefront of legislative interference and politicization, more than 1,300 abortion restrictions have been passed in the United States since Roe v Wade in 1973. It is not the only medical care affected by political interference.1 The United States ranks last in maternal mortality among industrialized nations, and Black women are more than twice as likely to die.2 As we grapple with the fallout of the Dobbs v Jackson Women’s Health Organization opinion and begin to recognize how fractured medical care has become—based on zip code—we should take stock of the way legislation and politics have already dictated reproductive health care. Abortion is the salient example, but state policy and legislation have unjustly been determining medical care available to women and other patients on a broader scale for decades. Here are just a few examples.

Postpartum care

The postpartum period is critical for maternal health; it is the time period in which many comorbidities emerge, including hypertensive disorders, postpartum thyroiditis, and mood disorders. Fifty percent of maternal deaths in the United States occur postpartum. Despite the importance of this care, Medicaid coverage for longer than 60 days postpartum varies greatly state to state. After the Affordable Care Act was implemented, it was assumed that all states would expand their Medicaid programs to include parents in their coverage plans beyond the guaranteed 60 days, negating the need for a specific postpartum coverage time period. However, the 2012 Supreme Court decision in National Federation of Independent Business v Sebelius allowed states to opt out of Medicaid expansion.3 In many states, postpartum patients lose their Medicaid insurance after 60 days if they do not meet the stringent income criteria.

The income level that makes patients ineligible for Medicaid coverage at day 61 postpartum varies widely. In Maryland, a patient can extend their Medicaid coverage for 12 months postpartum if their family of 4 earns less than $73,260 annually (264% of the federal poverty level). However, in Mississippi, an income of more than $6,936 per year for a family of 4 (approximately 25% of the federal poverty level) renders mothers who are 61 days postpartum ineligible for Medicaid coverage.4 Thus, many low-income postpartum patients (who are at twice the risk of maternal mortality as affluent patients) find themselves without access to this critical care depending on the decisions of their state legislatures.5 The American Rescue Plan Act of 2021 (known as the COVID-19 Stimulus Package) included a provision that allows states to expand their postpartum Medicaid coverage from 60 days to 12 months; currently, 10 additional states are planning to expand postpartum Medicaid for 12 months. While encouraging, 14 states still have not announced plans to utilize this provision or apply for a waiver to extend Medicaid coverage in the postpartum period.6

 

 

Treatment for substance use

Drug overdose is a leading cause of pregnancy-related death from unintentional causes.7 Overdose deaths in the general population climbed between 2020 and 2021, reaching historic highs of more than 100,000 deaths in a 12-month period.8 Given the impact of substance use and overdose on maternal mortality, health systems should be maximizing efforts to respond to this public health crisis by implementing effective screening and treatment interventions and establishing clinics and hospitals as safe places to seek care. However, many states have criminalized substance use in pregnant patients and mandate that clinicians report patients who use substances, creating an ethical dilemma for clinicians seeking to screen and treat patients for substance use disorder. Twenty-three states consider substance use in pregnancy to be child abuse, and 3 states consider substance use in pregnancy to be grounds for civil commitment. In Wisconsin, a patient can be detained against their will for the duration of the pregnancy. Twenty-five states require health care professionals to report suspected substance abuse in pregnancy to child protective services or a similar state office.9 Even when universal substance use screening is implemented, it has disparate impact on patients of color; Black women who screened positive for substance use in pregnancy were more likely to be reported to child protective services than their White counterparts.10 The criminalization of pregnant bodies does not lead to improvements in individual, community, or public health, it infringes on the ethical principle of bodily autonomy and puts clinicians at odds with what is best for their patients.

Gender-affirming care

Gender-affirming care is supported by major medical organizations and reduces the risk of depression and suicidality in transgender youth.11 Despite this evidence, several states have passed legislation restricting or banning this care, criminalizing the doctors who provide it. Idaho’s house of representatives passed House Bill 675,12 which would make providing gender-affirming care a felony, punishable by up to a life sentence. This would extend to parents trying to access care for their children as well as clinicians.

Although abortion is the medical care most conspicuously manipulated by politics and legislation, it is far from the only example. No area of medicine will be untouched by eliminating access to reproductive health care and by the regulation and criminalization of health care workers who provide it. This is a sea change, although state legislative interference and disparities in reproductive health care have been a tocsin of such change for years. We can no longer afford to believe there is a separation between politics and medicine; this directly interferes with our Hippocratic oath to do no harm. A politician in Ohio should not decide whether or not a 13-year-old patient should have to carry a pregnancy to term; the house of representatives in Idaho should not put someone’s transgender child at increased risk of depression and suicidality by making their medical care a felony. Colleagues in Texas should not be punishable by life in prison for providing abortion care.13 As a physician, I cannot stand by when, facing a maternal mortality crisis, state politicians decide whether a patient living below the poverty line should have access to postpartum care.

I am neither a politician nor a legal scholar. I am a physician who takes care of people in this intimate and powerful space of healing and support between doctor and patient. What should we do? We need to come together to find the answers. We need to vote if we haven’t before. And we need to vote differently if we have elected lawmakers who politicize and dangerously interfere with medicine, the well-being of our patients, and our ability to carry out our duty as physicians in our patients’ best interests. We need to tell our stories—to each other, to our newspapers, to our neighbors, and to our legislatures. If we are leading organizations, we can use the power held in our institutions to commit to providing care to the fullest extent possible, commit to protecting our clinicians providing evidence-based care, and encourage legislators who use medicine as a political bargaining chip to reverse course. Medicine is not an apolitical field, and we can no longer uphold that paradigm. Our patients lives, and our livelihood as healers and caretakers, depends on our collective action against it. ●

Acknowledgement

The author would like to thank Lauren Sobel, DO, MPH, for her contributions to a presentation on this subject.

References
  1. Nash E, Ephross P. State policy trends at midyear 2022: with Roe about to be overturned, some states double down on abortion restrictions. Guttmacher Institute. June 22, 2022. https://live. guttmacher.org/article/2022/06/state-policy -trends-midyear-2022-roe-about-be-overturnedsome-states-double-down. Accessed September 12, 2022.
  2. Declercq E, Zephyrin L. Maternal mortality in the United States: a primer. Commonwealth Fund; 2020. https://www.commonwealthfund .org/publications/issue-brief-report/2020 /dec/maternal-mortality-united-states-primer. Accessed September 12, 2022.
  3. Santa Clara Law Digital Communications website. Supreme Court of the United States. National Federation of Independent Business v Sebelius. (2012). Patient Protection and Affordable Care Act Litigation. 333. https://digitalcommons.law.scu.edu /aca/333. Accessed September 13, 2022.
  4. Ranji U, Salganicoff A, Gomez I. Postpartum coverage extension in the American Rescue Plan Act of 2021. San Francisco, CA: Kaiser Family Foundation; 2021.
  5. Singh GK, Lee H. Trends and racial/ethnic, socioeconomic, and geographic disparities in maternal mortality from indirect obstetric causes in the United States, 1999-2017. Int J MCH AIDS. 2021;10:43.
  6. Kaiser Family Foundation. Medicaid Postpartum Coverage Extension Tracker. https://www.kff. org/medicaid/issue-brief/medicaid-postpartum -coverage-extension-tracker/. Accessed September 7, 2022.
  7. Mehta PK, Bachhuber MA, Hoffman R, et al. Deaths from unintentional injury, homicide, and suicide during or within 1 year of pregnancy in Philadelphia. Am J Public Health. 2016;106: 2208-2210.
  8. O’Donnell J, Tanz LJ, Gladden RM, et al. Trends in and characteristics of drug overdose deaths involving illicitly manufactured fentanyls— United States, 2019–2020. MMWR Morb Mortal Wkly Rep. 2021;70:1740.
  9. State laws and policies: substance use during pregnancy. Guttmacher Institute. https://www .guttmacher.org/state-policy/explore/substance -use-during-pregnancy. August 1, 2022. Accessed September 13, 2022.
  10. Roberts S, Nuru-Jeter A. Universal screening for alcohol and drug use and racial disparities in child protective services reporting. J Behav Health Serv Res. 2012;39;3-16.
  11. Tordoff DM, Wanta JW, Collin, et al. (2022). Mental health outcomes in transgender and nonbinary youths receiving gender-affirming care. JAMA Network Open. 2022;5:e220978. doi: 10.1001/jamanetworkopen.2022.0978.
  12. House Bill 675. Idaho Legislature web site. https:// legislature.idaho.gov/sessioninfo/2022/legislation/h0675/. Accessed September 9, 2022.
  13. Simon S. New Texas trigger law makes abortion a felony. NPR. August 27, 2022. https://www.npr. org/2022/08/27/1119795665/new-texas-trigger -law-makes-abortion-a-felony. Accessed September 13, 2022. 
References
  1. Nash E, Ephross P. State policy trends at midyear 2022: with Roe about to be overturned, some states double down on abortion restrictions. Guttmacher Institute. June 22, 2022. https://live. guttmacher.org/article/2022/06/state-policy -trends-midyear-2022-roe-about-be-overturnedsome-states-double-down. Accessed September 12, 2022.
  2. Declercq E, Zephyrin L. Maternal mortality in the United States: a primer. Commonwealth Fund; 2020. https://www.commonwealthfund .org/publications/issue-brief-report/2020 /dec/maternal-mortality-united-states-primer. Accessed September 12, 2022.
  3. Santa Clara Law Digital Communications website. Supreme Court of the United States. National Federation of Independent Business v Sebelius. (2012). Patient Protection and Affordable Care Act Litigation. 333. https://digitalcommons.law.scu.edu /aca/333. Accessed September 13, 2022.
  4. Ranji U, Salganicoff A, Gomez I. Postpartum coverage extension in the American Rescue Plan Act of 2021. San Francisco, CA: Kaiser Family Foundation; 2021.
  5. Singh GK, Lee H. Trends and racial/ethnic, socioeconomic, and geographic disparities in maternal mortality from indirect obstetric causes in the United States, 1999-2017. Int J MCH AIDS. 2021;10:43.
  6. Kaiser Family Foundation. Medicaid Postpartum Coverage Extension Tracker. https://www.kff. org/medicaid/issue-brief/medicaid-postpartum -coverage-extension-tracker/. Accessed September 7, 2022.
  7. Mehta PK, Bachhuber MA, Hoffman R, et al. Deaths from unintentional injury, homicide, and suicide during or within 1 year of pregnancy in Philadelphia. Am J Public Health. 2016;106: 2208-2210.
  8. O’Donnell J, Tanz LJ, Gladden RM, et al. Trends in and characteristics of drug overdose deaths involving illicitly manufactured fentanyls— United States, 2019–2020. MMWR Morb Mortal Wkly Rep. 2021;70:1740.
  9. State laws and policies: substance use during pregnancy. Guttmacher Institute. https://www .guttmacher.org/state-policy/explore/substance -use-during-pregnancy. August 1, 2022. Accessed September 13, 2022.
  10. Roberts S, Nuru-Jeter A. Universal screening for alcohol and drug use and racial disparities in child protective services reporting. J Behav Health Serv Res. 2012;39;3-16.
  11. Tordoff DM, Wanta JW, Collin, et al. (2022). Mental health outcomes in transgender and nonbinary youths receiving gender-affirming care. JAMA Network Open. 2022;5:e220978. doi: 10.1001/jamanetworkopen.2022.0978.
  12. House Bill 675. Idaho Legislature web site. https:// legislature.idaho.gov/sessioninfo/2022/legislation/h0675/. Accessed September 9, 2022.
  13. Simon S. New Texas trigger law makes abortion a felony. NPR. August 27, 2022. https://www.npr. org/2022/08/27/1119795665/new-texas-trigger -law-makes-abortion-a-felony. Accessed September 13, 2022. 
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Viral threats to the fetus and mother: Parvovirus and varicella

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We review 2 important viral infections in this article. One, parvovirus, poses a major threat to the fetus. The second, varicella, poses less risk to the fetus but significantly greater risk to the mother. We focus on the epidemiology, clinical presentation, diagnosis, and management of each infection.

Parvovirus infection and its risks to the fetus

CASE #1 Pregnant teacher exposed to fifth disease

A 28-year-old primigravid woman at 16 weeks’ gestation works as an elementary school teacher. Over the past 3 weeks, she has been exposed to 4 children who had fifth disease. She now requests evaluation because she has malaise, arthralgias, myalgias, fever of 38.2°C, and a fine lacelike erythematous rash on her trunk, arms, and cheeks.

  • What is the most likely diagnosis?
  • What diagnostic tests are indicated?
  • Is her fetus at risk?

Epidemiology of parvovirus

Parvovirus B19 is a small, single-stranded DNA virus. It is highly contagious and is transmitted primarily by respiratory droplets. Transmission also can occur via infected blood, for example, through a blood transfusion. The incubation period is 10 to 20 days. Among adults, the individuals at greatest risk for infection are those who have close contact with young children, such as parents, day-care workers, and elementary school teachers. With sustained exposure in the household or classroom, the risk of seroconversion approaches 50%.1 Approximately 50% to 60% of reproductive-aged women have evidence of prior infection, and immunity is usually lifelong.

 

Clinical manifestations

The classic presentation of parvovirus infection is erythema infectiosum, also called fifth disease. This condition is characterized by a “slapped cheek” facial rash, malaise, myalgias, arthralgias, and low-grade fever. A fine lacelike rash often develops over the torso. In adults, the characteristic rash may be absent, and the most common presentation is a flu-like illness with joint pains.1,2 In children and in adults with an underlying hemoglobinopathy, parvovirus can cause transient aplastic crisis, and patients present with signs of a severe anemia, such as dyspnea, pallor, and fatigue.

Although parvovirus infection usually poses no serious risk in otherwise healthy children and adults, it can cause major fetal injury when the pregnant woman is infected early in pregnancy. The principal manifestation of fetal infection is hydrops. Hydrops primarily results when the virus crosses the placenta and attaches to the P antigen on the surface of red cell progenitors in the fetal marrow, causing an aplastic anemia with resultant high-output congestive heart failure. The virus also may directly injure the fetal myocardium, thus exacerbating heart failure. Other manifestations of congenital parvovirus include thrombocytopenia and hepatitis.3

The severity of fetal injury is inversely proportional to the gestational age at the time of maternal infection. When primary maternal infection occurs in the first trimester, the frequency of fetal hydrops is 5% to 10%. If infection develops in weeks 13 to 20, the risk of hydrops decreases to 5% or less. If infection develops beyond week 20, the incidence of fetal hydrops is 1% or lower.2

Continue to: Diagnostic steps...

 

 

Diagnostic steps

Appropriate diagnostic evaluation for a pregnant woman with exposure to parvovirus or clinical manifestations suggestive of parvovirus infection is outlined in FIGURE 1.

If infection is confirmed, serial ultrasound monitoring should be performed on a weekly to biweekly basis for 8 to 12 weeks, as delineated in FIGURE 2. Extended surveillance is necessary because the incubation period in the fetus is longer than that in the mother.


As the fetus develops anemia, peripheral tissues become hypoxic, leading to reflex peripheral vasoconstriction and increased cardiac output. At the same time, reduction in the number of fetal red blood cells decreases blood viscosity. The combination of these changes results in an increase in blood flow to the fetal brain, which can be detected by measuring the peak systolic velocity of flow in the middle cerebral artery (MCA PSV) with Doppler ultrasound imaging (FIGURE 3). The increase in MCA PSV parallels the decrease in fetal hematocrit and precedes the development of hydrops. In fact, signs of fetal hydrops do not usually develop until the fetal hematocrit falls to 15 to 20 vol%.

 

Management may necessitate intrauterine transfusion

Although some cases of fetal hydrops may resolve spontaneously, most authors agree that intrauterine transfusion is essential. In most instances, only a single intrauterine transfusion is necessary. In some fetuses, however, the infection is so prolonged and the anemia so severe that 2 to 3 transfusions may be required.

Infants who survive the intrauterine transfusion usually have an excellent long-term prognosis. However, isolated case reports have documented neurologic morbidity and prolonged transfusion-dependent anemia.4 In light of these reports, we recommend that a third trimester ultrasound exam be performed to assess fetal growth and evaluate the anatomy of the fetal brain. For the fetus with abnormal intracranial findings on ultrasonography, fetal magnetic resonance imaging is indicated.5

CASE #1 Diagnosis is probable parvovirus

The most likely diagnosis in this case is erythema infectiosum. This diagnosis can be confirmed by identifying positive immunogloblulin M (IgM) antibody and by detecting parvovirus in the maternal serum by polymerase chain reaction. Given the gestational age of 16 weeks, the risk of serious fetal injury should be less than 5%. Nevertheless, serial ultrasound examinations should be performed to assess for signs of fetal anemia.

Varicella exposure in pregnancy

CASE #2 Pregnant woman exposed to chickenpox has symptoms

Two weeks ago, a 32-year-old woman (G3P2002) at 24 weeks’ gestation was exposed to a neighbor’s child who had chickenpox. The patient has no history of natural infection or vaccination. She now has a fever of 38.6°C, malaise, headache, and a diffuse pruritic vesicular rash on her trunk and extremities. She also is experiencing a dry cough and mild dyspnea.

  • What diagnostic tests are indicated?
  • What treatment is indicated?
  • What risk does this condition pose to the fetus?

Epidemiology of varicella

Varicella (chickenpox) is caused by the DNA varicella-zoster virus, an organism that is a member of the herpesvirus family. The disease occurs predominantly in children, and the infection is transmitted by respiratory droplets and by direct contact. Its incubation period is short (10–14 days), and it is highly contagious. More than 90% of susceptible close contacts will become infected after exposure to the index case. Like other herpesviruses, the varicella virus can establish a latent infection and then become manifest years later as herpes zoster (shingles).5,6

Continue to: Clinical manifestations...

 

 

Clinical manifestations

Patients with varicella usually have prodromal symptoms and signs that include malaise, fatigue, arthralgias, myalgias, and a low-grade fever. Varicella’s pathognomonic manifestation is a pruritic, macular rash that starts on the face and trunk and then spreads centripetally to the extremities. The lesions typically appear in “crops” and evolve through several distinct phases: macule, papule, vesicle, pustule, ulcer, and crust.5

In children, varicella is manifest almost entirely by mucocutaneous lesions. In adults, however, 2 serious and potentially life-threatening complications can occur. Approximately 1% of infected adults develop encephalitis and about 20% develop viral pneumonia, often accompanied by a severe superimposed bacterial pneumonia.5

When maternal infection develops in the first half of pregnancy, approximately 2% of fetuses will have evidence of congenital infection, usually manifested by circular, constricting scars on the extremities. These lesions typically occur in a dermatomal distribution. Spontaneous abortion and fetal death in utero also have been reported, but fortunately they are quite rare. When maternal infection occurs beyond 20 weeks of gestation, fetal injury is very uncommon.7

Interestingly, when maternal infection occurs at the time of delivery or shortly thereafter (from 5 days before until 2 days after delivery), neonatal varicella may develop. This infection may take 3 forms: disseminated mucocutaneous lesions, a deep-seated visceral infection, or severe pneumonia. In the era before the ready availability of antiviral agents, the case fatality rate from neonatal varicella was approximately 30%.5

 

Diagnosis is clinical

The diagnosis of varicella usually is established on the basis of clinical examination. It can be confirmed by identification of anti–varicella-zoster IgM.

Management includes assessing immunity

If a patient is seen for a preconception appointment, ask her whether she has ever had varicella or been vaccinated for this disease. If she is uncertain, a varicella-zoster immunoglobulin G (IgG) titer should be ordered. If the IgG titer is negative, denoting susceptibility to infection, the patient should be vaccinated before she tries to conceive (see below).8

If a patient has not had a preconception appointment and now presents for her first prenatal appointment, she should be asked about immunity to varicella. If she is uncertain, a varicella-zoster IgG assay should be obtained. Approximately 75% of patients who are uncertain about immunity will, in fact, be immune. Those who are not immune should be counseled to avoid exposure to individuals who may have varicella, and they should be targeted for vaccination immediately postpartum.5,9

If a susceptible pregnant patient has been exposed to an individual with varicella, she should receive 1 of 2 regimens within 72 to 96 hours to minimize the risk of maternal infection.5,9,10 One option is intramuscular varicella-zoster immune globulin (VariZIG), 125 U/10 kg body weight, with a maximum dose of 625 U (5 vials). The distributor of this agent is FFF Enterprises in Temucula, California (telephone: 800-843-7477). A company representative will assess the patient’s eligibility and deliver the drug within 24 hours if the patient is considered eligible. An alternative prophylactic regimen is oral acyclovir, 800 mg 5 times daily for 7 days, or oral valacyclovir, 1,000 mg 3 times daily for 7 days.

If, despite prophylaxis, the pregnant woman becomes infected, she should immediately be treated with 1 of the oral antiviral regimens described above. If she has evidence of encephalitis, pneumonia, or severe disseminated mucocutaneous infection, or if she is immunosuppressed, she should be hospitalized and treated with intravenous acyclovir, 10 mg/kg infused over 1 hour every 8 hours for 10 days.

Ultrasonography is the most valuable test to identify fetal infection. Key findings that suggest congenital varicella are fetal growth restriction, microcephaly, ventriculomegaly, echogenic foci in the liver, and limb abnormalities. There is no proven therapy for congenital varicella.

When a patient has varicella at the time of delivery, she should be isolated from her infant until all lesions have crusted over. In addition, the neonate should be treated with either VariZIG or an antiviral agent.5,9

Prevention with varicella vaccine

The varicella vaccine (Varivax) is a live-virus vaccine that is highly immunogenic. The vaccine is now part of the routine childhood immunization sequence. Children ages 1 to 12 years require only a single dose of the vaccine. Individuals older than 12 years of age require 2 doses, administered 4 to 6 weeks apart. The vaccine should not be administered during pregnancy. It also should not be administered to individuals who are severely immunocompromised, are receiving high-dose systemic steroids, have untreated tuberculosis, or have an allergy to neomycin, which is a component of the vaccine. The vaccine does not pose a risk to the breastfeeding infant.11

CASE #2 Hospitalization is recommended for this patient

The patient in this case developed acute varicella pneumonia as a result of her exposure to the neighbor’s child. The diagnosis can be confirmed by demonstrating a positive varicella-zoster IgM and by obtaining a chest x-ray that identifies the diffuse patchy infiltrates characteristic of viral pneumonia. Because this is such a potentially serious illness, the patient should be hospitalized and treated with intravenous acyclovir or valacyclovir. Antibiotics such as ceftriaxone and azithromycin may be indicated to treat superimposed bacterial pneumonia. Given the later gestational age, the fetus is at low risk for serious injury. ●

References
  1. Valeur-Jensen AK, Pedersen CB, Westergaard T, et al. Risk factors for parvovirus B19 infection in pregnancy. JAMA. 1999;281:1099-1105.
  2. Harger JH, Adler SP, Koch WC, et al. Prospective evaluation of 618 pregnant women exposed to parvovirus B19: risks and symptoms. Obstet Gynecol. 1998;91:413-420.
  3. Melamed N, Whittle W, Kelly EN, et al. Fetal thrombocytopenia in pregnancies with fetal human parvovirus-B19 infection. Am J Obstet Gynecol. 2015;212:793.e1-8.
  4. Nagel HTC, de Haan TR, Vandenbussche FPH, et al. Long-term outcome after fetal transfusion for hydrops associated with parvovirus B19 infection. Obstet Gynecol. 2007;109:42-47.
  5. Duff P. Maternal and fetal infections. In: Resnik R, Lockwood CJ, Moore TR, et al (eds). Creasy & Resnik’s Maternal-Fetal Medicine: Principles and Practice. 8th ed. Elsevier; 2019:911-912.
  6. Cohen JI. Herpes zoster. N Engl J Med. 2013;369:255-263.
  7. Enders G, Miller E, Cradock-Watson J, et al. Consequences of varicella and herpes zoster in pregnancy: prospective study of 1739 cases. Lancet. 1994;343:1548-1551.
  8. Duff P. Varicella in pregnancy: five priorities for clinicians. Infect Dis Obstet Gynecol. 1994;1:163-165.
  9. Marin M, Guris D, Chaves SS, et al; Advisory Committee on Immunization Practices, Centers for Disease Control and Prevention. Prevention of varicella. MMWR Recommend Rep. 2007;56(RR-4):1-40.
  10. Swamy GK, Dotters-Katz SK. Safety and varicella outcomes after varicella zoster immune globulin administration in pregnancy. Am J Obstet Gynecol. 2019;221:655-656.
  11. Duff P. Varicella vaccine. Infect Dis Obstet Gynecol. 1996;4:63-65.
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We review 2 important viral infections in this article. One, parvovirus, poses a major threat to the fetus. The second, varicella, poses less risk to the fetus but significantly greater risk to the mother. We focus on the epidemiology, clinical presentation, diagnosis, and management of each infection.

Parvovirus infection and its risks to the fetus

CASE #1 Pregnant teacher exposed to fifth disease

A 28-year-old primigravid woman at 16 weeks’ gestation works as an elementary school teacher. Over the past 3 weeks, she has been exposed to 4 children who had fifth disease. She now requests evaluation because she has malaise, arthralgias, myalgias, fever of 38.2°C, and a fine lacelike erythematous rash on her trunk, arms, and cheeks.

  • What is the most likely diagnosis?
  • What diagnostic tests are indicated?
  • Is her fetus at risk?

Epidemiology of parvovirus

Parvovirus B19 is a small, single-stranded DNA virus. It is highly contagious and is transmitted primarily by respiratory droplets. Transmission also can occur via infected blood, for example, through a blood transfusion. The incubation period is 10 to 20 days. Among adults, the individuals at greatest risk for infection are those who have close contact with young children, such as parents, day-care workers, and elementary school teachers. With sustained exposure in the household or classroom, the risk of seroconversion approaches 50%.1 Approximately 50% to 60% of reproductive-aged women have evidence of prior infection, and immunity is usually lifelong.

 

Clinical manifestations

The classic presentation of parvovirus infection is erythema infectiosum, also called fifth disease. This condition is characterized by a “slapped cheek” facial rash, malaise, myalgias, arthralgias, and low-grade fever. A fine lacelike rash often develops over the torso. In adults, the characteristic rash may be absent, and the most common presentation is a flu-like illness with joint pains.1,2 In children and in adults with an underlying hemoglobinopathy, parvovirus can cause transient aplastic crisis, and patients present with signs of a severe anemia, such as dyspnea, pallor, and fatigue.

Although parvovirus infection usually poses no serious risk in otherwise healthy children and adults, it can cause major fetal injury when the pregnant woman is infected early in pregnancy. The principal manifestation of fetal infection is hydrops. Hydrops primarily results when the virus crosses the placenta and attaches to the P antigen on the surface of red cell progenitors in the fetal marrow, causing an aplastic anemia with resultant high-output congestive heart failure. The virus also may directly injure the fetal myocardium, thus exacerbating heart failure. Other manifestations of congenital parvovirus include thrombocytopenia and hepatitis.3

The severity of fetal injury is inversely proportional to the gestational age at the time of maternal infection. When primary maternal infection occurs in the first trimester, the frequency of fetal hydrops is 5% to 10%. If infection develops in weeks 13 to 20, the risk of hydrops decreases to 5% or less. If infection develops beyond week 20, the incidence of fetal hydrops is 1% or lower.2

Continue to: Diagnostic steps...

 

 

Diagnostic steps

Appropriate diagnostic evaluation for a pregnant woman with exposure to parvovirus or clinical manifestations suggestive of parvovirus infection is outlined in FIGURE 1.

If infection is confirmed, serial ultrasound monitoring should be performed on a weekly to biweekly basis for 8 to 12 weeks, as delineated in FIGURE 2. Extended surveillance is necessary because the incubation period in the fetus is longer than that in the mother.


As the fetus develops anemia, peripheral tissues become hypoxic, leading to reflex peripheral vasoconstriction and increased cardiac output. At the same time, reduction in the number of fetal red blood cells decreases blood viscosity. The combination of these changes results in an increase in blood flow to the fetal brain, which can be detected by measuring the peak systolic velocity of flow in the middle cerebral artery (MCA PSV) with Doppler ultrasound imaging (FIGURE 3). The increase in MCA PSV parallels the decrease in fetal hematocrit and precedes the development of hydrops. In fact, signs of fetal hydrops do not usually develop until the fetal hematocrit falls to 15 to 20 vol%.

 

Management may necessitate intrauterine transfusion

Although some cases of fetal hydrops may resolve spontaneously, most authors agree that intrauterine transfusion is essential. In most instances, only a single intrauterine transfusion is necessary. In some fetuses, however, the infection is so prolonged and the anemia so severe that 2 to 3 transfusions may be required.

Infants who survive the intrauterine transfusion usually have an excellent long-term prognosis. However, isolated case reports have documented neurologic morbidity and prolonged transfusion-dependent anemia.4 In light of these reports, we recommend that a third trimester ultrasound exam be performed to assess fetal growth and evaluate the anatomy of the fetal brain. For the fetus with abnormal intracranial findings on ultrasonography, fetal magnetic resonance imaging is indicated.5

CASE #1 Diagnosis is probable parvovirus

The most likely diagnosis in this case is erythema infectiosum. This diagnosis can be confirmed by identifying positive immunogloblulin M (IgM) antibody and by detecting parvovirus in the maternal serum by polymerase chain reaction. Given the gestational age of 16 weeks, the risk of serious fetal injury should be less than 5%. Nevertheless, serial ultrasound examinations should be performed to assess for signs of fetal anemia.

Varicella exposure in pregnancy

CASE #2 Pregnant woman exposed to chickenpox has symptoms

Two weeks ago, a 32-year-old woman (G3P2002) at 24 weeks’ gestation was exposed to a neighbor’s child who had chickenpox. The patient has no history of natural infection or vaccination. She now has a fever of 38.6°C, malaise, headache, and a diffuse pruritic vesicular rash on her trunk and extremities. She also is experiencing a dry cough and mild dyspnea.

  • What diagnostic tests are indicated?
  • What treatment is indicated?
  • What risk does this condition pose to the fetus?

Epidemiology of varicella

Varicella (chickenpox) is caused by the DNA varicella-zoster virus, an organism that is a member of the herpesvirus family. The disease occurs predominantly in children, and the infection is transmitted by respiratory droplets and by direct contact. Its incubation period is short (10–14 days), and it is highly contagious. More than 90% of susceptible close contacts will become infected after exposure to the index case. Like other herpesviruses, the varicella virus can establish a latent infection and then become manifest years later as herpes zoster (shingles).5,6

Continue to: Clinical manifestations...

 

 

Clinical manifestations

Patients with varicella usually have prodromal symptoms and signs that include malaise, fatigue, arthralgias, myalgias, and a low-grade fever. Varicella’s pathognomonic manifestation is a pruritic, macular rash that starts on the face and trunk and then spreads centripetally to the extremities. The lesions typically appear in “crops” and evolve through several distinct phases: macule, papule, vesicle, pustule, ulcer, and crust.5

In children, varicella is manifest almost entirely by mucocutaneous lesions. In adults, however, 2 serious and potentially life-threatening complications can occur. Approximately 1% of infected adults develop encephalitis and about 20% develop viral pneumonia, often accompanied by a severe superimposed bacterial pneumonia.5

When maternal infection develops in the first half of pregnancy, approximately 2% of fetuses will have evidence of congenital infection, usually manifested by circular, constricting scars on the extremities. These lesions typically occur in a dermatomal distribution. Spontaneous abortion and fetal death in utero also have been reported, but fortunately they are quite rare. When maternal infection occurs beyond 20 weeks of gestation, fetal injury is very uncommon.7

Interestingly, when maternal infection occurs at the time of delivery or shortly thereafter (from 5 days before until 2 days after delivery), neonatal varicella may develop. This infection may take 3 forms: disseminated mucocutaneous lesions, a deep-seated visceral infection, or severe pneumonia. In the era before the ready availability of antiviral agents, the case fatality rate from neonatal varicella was approximately 30%.5

 

Diagnosis is clinical

The diagnosis of varicella usually is established on the basis of clinical examination. It can be confirmed by identification of anti–varicella-zoster IgM.

Management includes assessing immunity

If a patient is seen for a preconception appointment, ask her whether she has ever had varicella or been vaccinated for this disease. If she is uncertain, a varicella-zoster immunoglobulin G (IgG) titer should be ordered. If the IgG titer is negative, denoting susceptibility to infection, the patient should be vaccinated before she tries to conceive (see below).8

If a patient has not had a preconception appointment and now presents for her first prenatal appointment, she should be asked about immunity to varicella. If she is uncertain, a varicella-zoster IgG assay should be obtained. Approximately 75% of patients who are uncertain about immunity will, in fact, be immune. Those who are not immune should be counseled to avoid exposure to individuals who may have varicella, and they should be targeted for vaccination immediately postpartum.5,9

If a susceptible pregnant patient has been exposed to an individual with varicella, she should receive 1 of 2 regimens within 72 to 96 hours to minimize the risk of maternal infection.5,9,10 One option is intramuscular varicella-zoster immune globulin (VariZIG), 125 U/10 kg body weight, with a maximum dose of 625 U (5 vials). The distributor of this agent is FFF Enterprises in Temucula, California (telephone: 800-843-7477). A company representative will assess the patient’s eligibility and deliver the drug within 24 hours if the patient is considered eligible. An alternative prophylactic regimen is oral acyclovir, 800 mg 5 times daily for 7 days, or oral valacyclovir, 1,000 mg 3 times daily for 7 days.

If, despite prophylaxis, the pregnant woman becomes infected, she should immediately be treated with 1 of the oral antiviral regimens described above. If she has evidence of encephalitis, pneumonia, or severe disseminated mucocutaneous infection, or if she is immunosuppressed, she should be hospitalized and treated with intravenous acyclovir, 10 mg/kg infused over 1 hour every 8 hours for 10 days.

Ultrasonography is the most valuable test to identify fetal infection. Key findings that suggest congenital varicella are fetal growth restriction, microcephaly, ventriculomegaly, echogenic foci in the liver, and limb abnormalities. There is no proven therapy for congenital varicella.

When a patient has varicella at the time of delivery, she should be isolated from her infant until all lesions have crusted over. In addition, the neonate should be treated with either VariZIG or an antiviral agent.5,9

Prevention with varicella vaccine

The varicella vaccine (Varivax) is a live-virus vaccine that is highly immunogenic. The vaccine is now part of the routine childhood immunization sequence. Children ages 1 to 12 years require only a single dose of the vaccine. Individuals older than 12 years of age require 2 doses, administered 4 to 6 weeks apart. The vaccine should not be administered during pregnancy. It also should not be administered to individuals who are severely immunocompromised, are receiving high-dose systemic steroids, have untreated tuberculosis, or have an allergy to neomycin, which is a component of the vaccine. The vaccine does not pose a risk to the breastfeeding infant.11

CASE #2 Hospitalization is recommended for this patient

The patient in this case developed acute varicella pneumonia as a result of her exposure to the neighbor’s child. The diagnosis can be confirmed by demonstrating a positive varicella-zoster IgM and by obtaining a chest x-ray that identifies the diffuse patchy infiltrates characteristic of viral pneumonia. Because this is such a potentially serious illness, the patient should be hospitalized and treated with intravenous acyclovir or valacyclovir. Antibiotics such as ceftriaxone and azithromycin may be indicated to treat superimposed bacterial pneumonia. Given the later gestational age, the fetus is at low risk for serious injury. ●

 

 

We review 2 important viral infections in this article. One, parvovirus, poses a major threat to the fetus. The second, varicella, poses less risk to the fetus but significantly greater risk to the mother. We focus on the epidemiology, clinical presentation, diagnosis, and management of each infection.

Parvovirus infection and its risks to the fetus

CASE #1 Pregnant teacher exposed to fifth disease

A 28-year-old primigravid woman at 16 weeks’ gestation works as an elementary school teacher. Over the past 3 weeks, she has been exposed to 4 children who had fifth disease. She now requests evaluation because she has malaise, arthralgias, myalgias, fever of 38.2°C, and a fine lacelike erythematous rash on her trunk, arms, and cheeks.

  • What is the most likely diagnosis?
  • What diagnostic tests are indicated?
  • Is her fetus at risk?

Epidemiology of parvovirus

Parvovirus B19 is a small, single-stranded DNA virus. It is highly contagious and is transmitted primarily by respiratory droplets. Transmission also can occur via infected blood, for example, through a blood transfusion. The incubation period is 10 to 20 days. Among adults, the individuals at greatest risk for infection are those who have close contact with young children, such as parents, day-care workers, and elementary school teachers. With sustained exposure in the household or classroom, the risk of seroconversion approaches 50%.1 Approximately 50% to 60% of reproductive-aged women have evidence of prior infection, and immunity is usually lifelong.

 

Clinical manifestations

The classic presentation of parvovirus infection is erythema infectiosum, also called fifth disease. This condition is characterized by a “slapped cheek” facial rash, malaise, myalgias, arthralgias, and low-grade fever. A fine lacelike rash often develops over the torso. In adults, the characteristic rash may be absent, and the most common presentation is a flu-like illness with joint pains.1,2 In children and in adults with an underlying hemoglobinopathy, parvovirus can cause transient aplastic crisis, and patients present with signs of a severe anemia, such as dyspnea, pallor, and fatigue.

Although parvovirus infection usually poses no serious risk in otherwise healthy children and adults, it can cause major fetal injury when the pregnant woman is infected early in pregnancy. The principal manifestation of fetal infection is hydrops. Hydrops primarily results when the virus crosses the placenta and attaches to the P antigen on the surface of red cell progenitors in the fetal marrow, causing an aplastic anemia with resultant high-output congestive heart failure. The virus also may directly injure the fetal myocardium, thus exacerbating heart failure. Other manifestations of congenital parvovirus include thrombocytopenia and hepatitis.3

The severity of fetal injury is inversely proportional to the gestational age at the time of maternal infection. When primary maternal infection occurs in the first trimester, the frequency of fetal hydrops is 5% to 10%. If infection develops in weeks 13 to 20, the risk of hydrops decreases to 5% or less. If infection develops beyond week 20, the incidence of fetal hydrops is 1% or lower.2

Continue to: Diagnostic steps...

 

 

Diagnostic steps

Appropriate diagnostic evaluation for a pregnant woman with exposure to parvovirus or clinical manifestations suggestive of parvovirus infection is outlined in FIGURE 1.

If infection is confirmed, serial ultrasound monitoring should be performed on a weekly to biweekly basis for 8 to 12 weeks, as delineated in FIGURE 2. Extended surveillance is necessary because the incubation period in the fetus is longer than that in the mother.


As the fetus develops anemia, peripheral tissues become hypoxic, leading to reflex peripheral vasoconstriction and increased cardiac output. At the same time, reduction in the number of fetal red blood cells decreases blood viscosity. The combination of these changes results in an increase in blood flow to the fetal brain, which can be detected by measuring the peak systolic velocity of flow in the middle cerebral artery (MCA PSV) with Doppler ultrasound imaging (FIGURE 3). The increase in MCA PSV parallels the decrease in fetal hematocrit and precedes the development of hydrops. In fact, signs of fetal hydrops do not usually develop until the fetal hematocrit falls to 15 to 20 vol%.

 

Management may necessitate intrauterine transfusion

Although some cases of fetal hydrops may resolve spontaneously, most authors agree that intrauterine transfusion is essential. In most instances, only a single intrauterine transfusion is necessary. In some fetuses, however, the infection is so prolonged and the anemia so severe that 2 to 3 transfusions may be required.

Infants who survive the intrauterine transfusion usually have an excellent long-term prognosis. However, isolated case reports have documented neurologic morbidity and prolonged transfusion-dependent anemia.4 In light of these reports, we recommend that a third trimester ultrasound exam be performed to assess fetal growth and evaluate the anatomy of the fetal brain. For the fetus with abnormal intracranial findings on ultrasonography, fetal magnetic resonance imaging is indicated.5

CASE #1 Diagnosis is probable parvovirus

The most likely diagnosis in this case is erythema infectiosum. This diagnosis can be confirmed by identifying positive immunogloblulin M (IgM) antibody and by detecting parvovirus in the maternal serum by polymerase chain reaction. Given the gestational age of 16 weeks, the risk of serious fetal injury should be less than 5%. Nevertheless, serial ultrasound examinations should be performed to assess for signs of fetal anemia.

Varicella exposure in pregnancy

CASE #2 Pregnant woman exposed to chickenpox has symptoms

Two weeks ago, a 32-year-old woman (G3P2002) at 24 weeks’ gestation was exposed to a neighbor’s child who had chickenpox. The patient has no history of natural infection or vaccination. She now has a fever of 38.6°C, malaise, headache, and a diffuse pruritic vesicular rash on her trunk and extremities. She also is experiencing a dry cough and mild dyspnea.

  • What diagnostic tests are indicated?
  • What treatment is indicated?
  • What risk does this condition pose to the fetus?

Epidemiology of varicella

Varicella (chickenpox) is caused by the DNA varicella-zoster virus, an organism that is a member of the herpesvirus family. The disease occurs predominantly in children, and the infection is transmitted by respiratory droplets and by direct contact. Its incubation period is short (10–14 days), and it is highly contagious. More than 90% of susceptible close contacts will become infected after exposure to the index case. Like other herpesviruses, the varicella virus can establish a latent infection and then become manifest years later as herpes zoster (shingles).5,6

Continue to: Clinical manifestations...

 

 

Clinical manifestations

Patients with varicella usually have prodromal symptoms and signs that include malaise, fatigue, arthralgias, myalgias, and a low-grade fever. Varicella’s pathognomonic manifestation is a pruritic, macular rash that starts on the face and trunk and then spreads centripetally to the extremities. The lesions typically appear in “crops” and evolve through several distinct phases: macule, papule, vesicle, pustule, ulcer, and crust.5

In children, varicella is manifest almost entirely by mucocutaneous lesions. In adults, however, 2 serious and potentially life-threatening complications can occur. Approximately 1% of infected adults develop encephalitis and about 20% develop viral pneumonia, often accompanied by a severe superimposed bacterial pneumonia.5

When maternal infection develops in the first half of pregnancy, approximately 2% of fetuses will have evidence of congenital infection, usually manifested by circular, constricting scars on the extremities. These lesions typically occur in a dermatomal distribution. Spontaneous abortion and fetal death in utero also have been reported, but fortunately they are quite rare. When maternal infection occurs beyond 20 weeks of gestation, fetal injury is very uncommon.7

Interestingly, when maternal infection occurs at the time of delivery or shortly thereafter (from 5 days before until 2 days after delivery), neonatal varicella may develop. This infection may take 3 forms: disseminated mucocutaneous lesions, a deep-seated visceral infection, or severe pneumonia. In the era before the ready availability of antiviral agents, the case fatality rate from neonatal varicella was approximately 30%.5

 

Diagnosis is clinical

The diagnosis of varicella usually is established on the basis of clinical examination. It can be confirmed by identification of anti–varicella-zoster IgM.

Management includes assessing immunity

If a patient is seen for a preconception appointment, ask her whether she has ever had varicella or been vaccinated for this disease. If she is uncertain, a varicella-zoster immunoglobulin G (IgG) titer should be ordered. If the IgG titer is negative, denoting susceptibility to infection, the patient should be vaccinated before she tries to conceive (see below).8

If a patient has not had a preconception appointment and now presents for her first prenatal appointment, she should be asked about immunity to varicella. If she is uncertain, a varicella-zoster IgG assay should be obtained. Approximately 75% of patients who are uncertain about immunity will, in fact, be immune. Those who are not immune should be counseled to avoid exposure to individuals who may have varicella, and they should be targeted for vaccination immediately postpartum.5,9

If a susceptible pregnant patient has been exposed to an individual with varicella, she should receive 1 of 2 regimens within 72 to 96 hours to minimize the risk of maternal infection.5,9,10 One option is intramuscular varicella-zoster immune globulin (VariZIG), 125 U/10 kg body weight, with a maximum dose of 625 U (5 vials). The distributor of this agent is FFF Enterprises in Temucula, California (telephone: 800-843-7477). A company representative will assess the patient’s eligibility and deliver the drug within 24 hours if the patient is considered eligible. An alternative prophylactic regimen is oral acyclovir, 800 mg 5 times daily for 7 days, or oral valacyclovir, 1,000 mg 3 times daily for 7 days.

If, despite prophylaxis, the pregnant woman becomes infected, she should immediately be treated with 1 of the oral antiviral regimens described above. If she has evidence of encephalitis, pneumonia, or severe disseminated mucocutaneous infection, or if she is immunosuppressed, she should be hospitalized and treated with intravenous acyclovir, 10 mg/kg infused over 1 hour every 8 hours for 10 days.

Ultrasonography is the most valuable test to identify fetal infection. Key findings that suggest congenital varicella are fetal growth restriction, microcephaly, ventriculomegaly, echogenic foci in the liver, and limb abnormalities. There is no proven therapy for congenital varicella.

When a patient has varicella at the time of delivery, she should be isolated from her infant until all lesions have crusted over. In addition, the neonate should be treated with either VariZIG or an antiviral agent.5,9

Prevention with varicella vaccine

The varicella vaccine (Varivax) is a live-virus vaccine that is highly immunogenic. The vaccine is now part of the routine childhood immunization sequence. Children ages 1 to 12 years require only a single dose of the vaccine. Individuals older than 12 years of age require 2 doses, administered 4 to 6 weeks apart. The vaccine should not be administered during pregnancy. It also should not be administered to individuals who are severely immunocompromised, are receiving high-dose systemic steroids, have untreated tuberculosis, or have an allergy to neomycin, which is a component of the vaccine. The vaccine does not pose a risk to the breastfeeding infant.11

CASE #2 Hospitalization is recommended for this patient

The patient in this case developed acute varicella pneumonia as a result of her exposure to the neighbor’s child. The diagnosis can be confirmed by demonstrating a positive varicella-zoster IgM and by obtaining a chest x-ray that identifies the diffuse patchy infiltrates characteristic of viral pneumonia. Because this is such a potentially serious illness, the patient should be hospitalized and treated with intravenous acyclovir or valacyclovir. Antibiotics such as ceftriaxone and azithromycin may be indicated to treat superimposed bacterial pneumonia. Given the later gestational age, the fetus is at low risk for serious injury. ●

References
  1. Valeur-Jensen AK, Pedersen CB, Westergaard T, et al. Risk factors for parvovirus B19 infection in pregnancy. JAMA. 1999;281:1099-1105.
  2. Harger JH, Adler SP, Koch WC, et al. Prospective evaluation of 618 pregnant women exposed to parvovirus B19: risks and symptoms. Obstet Gynecol. 1998;91:413-420.
  3. Melamed N, Whittle W, Kelly EN, et al. Fetal thrombocytopenia in pregnancies with fetal human parvovirus-B19 infection. Am J Obstet Gynecol. 2015;212:793.e1-8.
  4. Nagel HTC, de Haan TR, Vandenbussche FPH, et al. Long-term outcome after fetal transfusion for hydrops associated with parvovirus B19 infection. Obstet Gynecol. 2007;109:42-47.
  5. Duff P. Maternal and fetal infections. In: Resnik R, Lockwood CJ, Moore TR, et al (eds). Creasy & Resnik’s Maternal-Fetal Medicine: Principles and Practice. 8th ed. Elsevier; 2019:911-912.
  6. Cohen JI. Herpes zoster. N Engl J Med. 2013;369:255-263.
  7. Enders G, Miller E, Cradock-Watson J, et al. Consequences of varicella and herpes zoster in pregnancy: prospective study of 1739 cases. Lancet. 1994;343:1548-1551.
  8. Duff P. Varicella in pregnancy: five priorities for clinicians. Infect Dis Obstet Gynecol. 1994;1:163-165.
  9. Marin M, Guris D, Chaves SS, et al; Advisory Committee on Immunization Practices, Centers for Disease Control and Prevention. Prevention of varicella. MMWR Recommend Rep. 2007;56(RR-4):1-40.
  10. Swamy GK, Dotters-Katz SK. Safety and varicella outcomes after varicella zoster immune globulin administration in pregnancy. Am J Obstet Gynecol. 2019;221:655-656.
  11. Duff P. Varicella vaccine. Infect Dis Obstet Gynecol. 1996;4:63-65.
References
  1. Valeur-Jensen AK, Pedersen CB, Westergaard T, et al. Risk factors for parvovirus B19 infection in pregnancy. JAMA. 1999;281:1099-1105.
  2. Harger JH, Adler SP, Koch WC, et al. Prospective evaluation of 618 pregnant women exposed to parvovirus B19: risks and symptoms. Obstet Gynecol. 1998;91:413-420.
  3. Melamed N, Whittle W, Kelly EN, et al. Fetal thrombocytopenia in pregnancies with fetal human parvovirus-B19 infection. Am J Obstet Gynecol. 2015;212:793.e1-8.
  4. Nagel HTC, de Haan TR, Vandenbussche FPH, et al. Long-term outcome after fetal transfusion for hydrops associated with parvovirus B19 infection. Obstet Gynecol. 2007;109:42-47.
  5. Duff P. Maternal and fetal infections. In: Resnik R, Lockwood CJ, Moore TR, et al (eds). Creasy & Resnik’s Maternal-Fetal Medicine: Principles and Practice. 8th ed. Elsevier; 2019:911-912.
  6. Cohen JI. Herpes zoster. N Engl J Med. 2013;369:255-263.
  7. Enders G, Miller E, Cradock-Watson J, et al. Consequences of varicella and herpes zoster in pregnancy: prospective study of 1739 cases. Lancet. 1994;343:1548-1551.
  8. Duff P. Varicella in pregnancy: five priorities for clinicians. Infect Dis Obstet Gynecol. 1994;1:163-165.
  9. Marin M, Guris D, Chaves SS, et al; Advisory Committee on Immunization Practices, Centers for Disease Control and Prevention. Prevention of varicella. MMWR Recommend Rep. 2007;56(RR-4):1-40.
  10. Swamy GK, Dotters-Katz SK. Safety and varicella outcomes after varicella zoster immune globulin administration in pregnancy. Am J Obstet Gynecol. 2019;221:655-656.
  11. Duff P. Varicella vaccine. Infect Dis Obstet Gynecol. 1996;4:63-65.
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Dietary sodium and potassium consumption and cardiovascular health

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Hypertension is a prevalent medical problem among US women, with a higher prevalence among Black women, than among White, Hispanic, or Asian women (TABLE 1).1 Among US women aged 55 to 64 years, approximately 50% have hypertension or are taking a hypertension medicine.1 Hypertension is an important risk factor for cardiovascular disease, including stroke, coronary heart disease, heart failure, atrial fibrillation, and peripheral vascular disease.1,2 In a study of 1.3 million people, blood pressure (BP) ≥ 130/80 mm Hg was associated with an increased risk of a cardiovascular event, including myocardial infarction and stroke.2 Excessive sodium intake is an important risk factor for developing hypertension.3 In 2015–2016, 87% of US adults consumed >2,300 mg/d of sodium,4 an amount that is considered excessive.1 Less well known is the association between low potassium intake and hypertension. This editorial reviews the evidence that diets high in sodium and low in potassium contribute to the development of hypertension and cardiovascular disease.

Sodium and potassium dueling cations

Many cohort studies report that diets high in sodium and low in potassium are associated with hypertension and an increased risk of cardiovascular disease. For example, in a cohort of 146,000 Chinese people, high sodium and low potassium intake was positively correlated with higher BP.5 In addition, the impact of increasing sodium intake or decreasing potassium intake was greater for people with a BMI ≥24 kg/m2, than people with a BMI <24 kg/m2. In a cohort of 11,095 US adults, high sodium and low potassium intake was associated with an increased risk of hypertension.6

In a study of 13,696 women, high potassium intake was associated with lower BP in participants with either a low or high sodium intake.7 In addition, over a 19-year follow up, higher potassium intake was associated with a lower risk of cardiovascular events.7 Comparing the highest (5,773 mg/d) vs lowest (2,783 mg/d) tertile of potassium intake, the decreased risk of a cardiovascular event was 0.89 (95% confidence interval [CI], 0.83–0.95).7

In a meta-analysis of data culled from 6 cohort studies, 10,709 adults with a mean age of 52 years, 54% of whom identified as women, were followed for a median of 8.8 years.8 Each adult contributed at least two 24-hour urine samples for measurement of sodium and potassium content. (Measurement of sodium and potassium in multiple 24-hour urine specimens from the same participant is thought to be the best way to assess sodium and potassium consumption.) The primary outcome was a cardiovascular event, including heart attack, stroke, or undergoing coronary revascularization procedures. In this study increasing consumption of sodium was associated with an increase in cardiovascular events, and increasing consumption of potassium was associated with a decrease in cardiovascular events. The hazard ratio for a cardiovascular event comparing high versus low consumption of sodium was 1.60 (95% CI, 1.19–2.14), and comparing high versus low consumption of potassium was 0.69 (95% CI, 0.51–0.91) (TABLE 2).8

Continue to: Clinical trial data on decreasing Na and/or increasing K consumption on CV outcomes...

 

 

Clinical trial data on decreasing Na and/or increasing K consumption on CV outcomes

Building on the cohort studies reporting that diets high in sodium and low in potassium are associated with hypertension and cardiovascular disease, clinical trials report that decreasing dietary sodium intake reduces BP and the risk of a cardiovascular event. For example, in a meta-analysis of 85 clinical trials studying the link between sodium and BP, the investigators concluded that there was a linear relationship between sodium intake and BP, with larger reductions in sodium intake associated with greater reductions in BP, down to a daily sodium intake of 1,000 to 1,500 mg.9 The effect of sodium reduction on BP was greatest in study participants with higher BP at baseline.

In a cluster-randomized clinical trial in China, people living in 600 villages were assigned to a control group, continuing to use sodium chloride in their food preparation or an experimental intervention, replacing sodium chloride with a substitute product containing 75% sodium chloride and 25% potassium chloride by weight.10 The inclusion criteria included people ≥60 years of age with high BP or a history of stroke. The mean duration of follow-up was 4.7 years. Half of the participants were female. A total of 73% of the participants had a history of stroke and 88% had hypertension. In this study, the rate of death was lower in the group that used the salt substitute than in the group using sodium chloride (39 vs 45 deaths per 1,000 person-years; rate ratio (RR) 0.88; 95% CI, 0.82–0.95, P<.001). The rate of major cardiovascular events (nonfatal stroke, nonfatal acute coronary syndrome or death from vascular causes) was decreased in the group that used salt substitute compared with the group using sodium chloride (49 vs 56 events per 1,000 person-years, rate ratio (RR), 0.87; 95% CI, 0.80–0.94; P<.001). Similarly, the rate of stroke was decreased in the group that used salt substitute compared with the group using sodium chloride (29 vs 34 events per 1,000 person-years; rate ratio (RR), 0.86; 95% CI, 0.77–0.96; P = .006). This study shows that by decreasing sodium intake and increasing potassium, cardiovascular outcomes are improved in people at high risk for a cardiovascular event.10 People with kidney disease or taking medications that decrease renal excretion of potassium should consult with their health care provider before using potassium chloride containing salt substitutes.

What is your daily intake of sodium and potassium?

Almost all packaged prepared foods have labels indicating the amount of sodium in one serving. Many packaged foods also report the amount of potassium in one serving. Many processed foods contain high amounts of sodium and low amounts of potassium. Processed and ultra-processed foods are a major dietary source of sodium.11 In contrast to processed foods, fresh fruits, vegetables, and milk have high quantities of potassium and low amounts of sodium. As an example, a major brand of canned chicken broth has 750 mg of sodium and 40 mg of potassium per one-half cup, a ratio of sodium to potassium of 19:1. By contrast, canned red kidney beans have 135 mg of sodium and 425 mg of potassium in one-half cup, a ratio of sodium to potassium of 1:3. Patients can better understand their daily sodium and potassium intake by reading the food labels. Calculating a sodium to potassium ratio for a food may help people better understand their salt intake and identify foods associated with positive health outcomes.

The optimal target for daily consumption of sodium and potassium is controversial (TABLE 2). The mean daily intakes of sodium and potassium in the United States are approximately 3,380 mg and 2,499 mg,respectively.12 The American College of Cardiology (ACC) recommends that an optimal diet contains <1,500 mg/d of sodium, a stringent target.1 If that target is unattainable, people should at least aim for a 1,000 mg/d-reduction in their current sodium intake.1 The World Health Organization strongly recommends that adults consume <2,000 mg/d of sodium.13 The National Academy of Science recommends adults seeking to reduce the risk of cardiovascular disease consume <2,300 mg/d of sodium.14 The top dietary sources of sodium include deli meat, pizza, burritos and tacos, soups, savory snacks (chips, crackers, popcorn), fried poultry, burgers, and eggs.15

The optimal target for daily consumption of potassium is controversial. The ACC recommends that an optimal diet contains 3,500–5,000 mg/d of potassium.1 The World Health Organization recommends that adults consume >3,510 mg/d of potassium.16 The top dietary sources of potassium include milk, fruit, vegetables, coffee, savory snacks (chips, crackers, popcorn), fruit juice, white potatoes, deli meats, burritos, and tacos.15 The foods with the greatest amount of potassium include banana, avocado, acorn squash, spinach, sweet potatoes, salmon, apricots, grapefruit, broccoli, and white beans. People with kidney disease or those who are taking medications that interfere with renal excretion of potassium should consult with their health care provider before adding more potassium to their diet.

The ACC also recommends1:

  • Maintaining an optimal weight (a 1-kg reduction in weight is associated with a 1-mm Hg reduction in BP).
  • Eating a healthy diet rich in fruits, vegetables, whole grains, and low-fat dairy products with reduced saturated and total fat.
  • Regular aerobic physical activity 90 to 150 min/wk.
  • Moderation in alcohol consumption, with men limiting consumption ≤ 2 drinks/d and women limiting consumption to ≤ 1 drink/d.
  • Smoking cessation.

Most adults in the US have too much sodium and too little potassium in their daily diet. Diets high in sodium and low in potassium increase the risk of hypertension. In turn, this increases the risk of cardiovascular disease, including myocardial infarction and stroke. Many personal choices and societal factors contribute to our current imbalanced and unhealthy diet, rich in sodium and deficient in potassium. Our best approach to improve health and reduce cardiovascular disease is to guide people to modify unhealthy lifestyle behaviors.17 For patients who are ready to change, a counseling intervention using the 5 A’s (including assess risk behaviors, advise change, agree on goals/action plan, assist with treatment, and arrange follow-up) has been shown to result in improved dietary choices, increased physical activity, and reduced use of tobacco products.18

Sodium intake and pregnancy-associated hypertension: Is there a link?

Two randomized clinical trials completed in the 1990s, comparing a low-sodium and a standard diet, showed no effect of reducing sodium intake by 32% and 57% on the risk of developing preeclampsia.1,2 Based on these 2 studies, a Cochrane review concluded that during pregnancy salt consumption should remain a matter of personal preference.3 Three recent observational studies report a relationship between sodium intake and the risk of developing pregnancy-associated hypertension.

In a study of 66,651 singleton pregnancies in the Danish Birth Cohort, participants with the greatest daily sodium intake, ranging from 3,520 to 7,520 mg/d had a 54% increased risk of developing gestational hypertension (95% confidence interval [CI], 16%–104%) and a 20% increased risk of developing preeclampsia (95% CI, 1%–42%).4 Another cohort study also reported that elevated sodium chloride intake was associated with an increased risk of developing preeclampsia.5 In one study, among patients with preeclampsia, those with lower urinary sodium to potassium ratio were less likely to develop severe preeclampsia.6 In a pregnant rat model, high salt intake is associated with a severe increase in blood pressure, the development of proteinuria, and an increase in circulating plasma soluble fmslike tyrosine-kinase 1 (sFlt-1)—changes also seen in preeclampsia.7 Pregnancy associated hypertension may not be as “salt sensitive” as chronic hypertension.

Future research could explore the effect of dietary sodium and potassium intake on the risk of developing severe hypertension during pregnancy in patients with chronic hypertension.

References

1. Knuist M, Bonsel GJ, Zondervan HA, et al. Low sodium diet and pregnancy-induced hypertension, a multicenter randomised controlled trial. Brit J Obstet Gynecol. 1998;105:430-434.

2. van der Maten GD, van Raaij JMA, Visman L, et al. Low-sodium in pregnancy: effects on blood pressure and maternal nutritional status. Brit J Nutr. 1997;77:703-720.

3. Duley L, Henderson-Smart DJ, Meher S. Altered dietary salt for preventing pre-eclampsia, and its complications. Cochrane Database Syst Rev. 2005;CD005548.

4. Arvizu, M, Bjerregaard AA, Madsen MTB, et al. Sodium intake during pregnancy, but not other diet recommendations aimed at preventing cardiovascular disease, is positively related to risk of hypertensive disorders of pregnancy. J Nutr. 2020;150:159-166.

5. Birukov A, Andersen LB, Herse F, et al. Aldosterone, salt and potassium intakes as predictors of pregnancy outcome, including preeclampsia. Hypertension. 2019;74:391-398.

6. Yilmaz ZV, Akkas E, Turkmen GG, et al. Dietary sodium and potassium intake were associated with hypertension, kidney damage and adverse perinatal outcome in pregnant women with preeclampsia. Hypertension Preg. 2017;36:77-83.

7. Gillis EE, Williams JM, Garrett MR, et al. The Dahl salt-sensitive rat is a spontaneous model of superimposed preeclampsia. Am J Physiol Regul Integr Comp Physiol. 2015;309:R62-70.

References
  1. Whelton PK, Carey RM, Aronow WS, et al. ACC/ AHA/AAPA/ABC/ACPM/AGS/APHA/ASH/ ASPC/NMA/PCNA guideline for the prevention, detection, evaluation and management of high blood pressure in adults: Executive Summary: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2018;138:e426-e483.
  2. Flint AC, Conell C, Ren X, et al. Effect of systolic and diastolic blood pressure on cardiovascular outcomes. N Engl J Med. 2019;381:243-251.
  3. Aljuraiban G, Jose AP, Gupta P, et al. Sodium intake, health implications and the role of population-level strategies. Nutr Rev. 2021;79:351-359.
  4. Clarke LS, Overwyk K, Bates M, et al. Temporal trends in dietary sodium intake among adults aged ≥ 19 years--United States 2003-2016. MMWR. 2021;70:1478-1482.
  5. Guo X, Zhang M, Li C, et al. Association between urinary sodium and potassium excretion and blood pressure among non-hypertensive adults-China, 2018-2019. China CDC Wkly. 2022;4:522-526.
  6. Li M, Yan S, Li X, et al. Association between blood pressure and dietary intakes of sodium and potassium among US adults using quantile regression analysis NHANES 2007-2014. J Hum Hypertens. 2020;34:346-354.
  7. Wouda RD, Boekholdt SM, Khaw KT, et al. Sex-specific associations between potassium intake, blood pressure and cardiovascular outcomes: the EPIC-Norfolk study. Europ Heart J. 2022, Epub July 21.
  8. Ma Y, He, Sun Q, et al. 24-hour urinary sodium and potassium excretion and cardiovascular risk. N Engl J Med. 2022;386:252-263.
  9. Filippini T, Malavolti M, Whelton PK, et al. Blood pressure effects of sodium reduction: dose-response meta-analysis of experimental studies. Circulation. 2021;143:1542-1567.
  10. Neal B, Wu Y, Feng X, et al. Effect of salt substitution on cardiovascular events. N Engl J Med. 2021;385:1067-1077.
  11. Monteiro CA, Cannon G, Moubarac JC, et al. The U.N. decade of nutrition: The NOVA food classification and the trouble with ultra-processing. Public Health Nutr. 2018;51:5-17.
  12. Nutrient intakes; From foods and beverages. Gender and Ag. WWEIA Data Tables. US Department of Health and Human Services, US Department of Agriculture. Web address Table 1. https://www .ars.usda.gov/ARSUserFiles/80400530/pdf /usual/Usual_Intake_gender_WWEIA_2015 _2018.pdf.
  13. WHO. Guideline: Sodium intake for adults and children. Geneva. World Health Organization (WHO), 2012. https://www.who.int /publications/i/item/9789241504836.
  14. National Academies of Sciences, Engineering and Medicine 2019. Dietary Reference Intakes for Sodium and Potassium. Washington DC: The National Academies Press. https://doi .org/10.17226/25353.
  15. Woodruff RC, Zhao L, Ahuja JKC, et al. Top food category contributors to sodium and potassium intake-United States 2015-2016. MMWR. 2020;69:1064-1069.
  16. WHO. Guideline: Potassium intake for adults and children. Geneva. World Health Organization (WHO), 2012. https://www.who.int /publications/i/item/9789241504829.
  17. Li Y, Pan A, Wang DD, et al. Impact of healthy lifestyle factors on life expectancies in the US population. Circulation. 2018;138:345-355.
  18. US Preventive Services Task Force. Behavioral counseling interventions to promote a healthy diet and physical activity for cardiovascular disease prevention in adults without cardiovascular disease risk factors. JAMA. 2022;328:367-374.
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Hypertension is a prevalent medical problem among US women, with a higher prevalence among Black women, than among White, Hispanic, or Asian women (TABLE 1).1 Among US women aged 55 to 64 years, approximately 50% have hypertension or are taking a hypertension medicine.1 Hypertension is an important risk factor for cardiovascular disease, including stroke, coronary heart disease, heart failure, atrial fibrillation, and peripheral vascular disease.1,2 In a study of 1.3 million people, blood pressure (BP) ≥ 130/80 mm Hg was associated with an increased risk of a cardiovascular event, including myocardial infarction and stroke.2 Excessive sodium intake is an important risk factor for developing hypertension.3 In 2015–2016, 87% of US adults consumed >2,300 mg/d of sodium,4 an amount that is considered excessive.1 Less well known is the association between low potassium intake and hypertension. This editorial reviews the evidence that diets high in sodium and low in potassium contribute to the development of hypertension and cardiovascular disease.

Sodium and potassium dueling cations

Many cohort studies report that diets high in sodium and low in potassium are associated with hypertension and an increased risk of cardiovascular disease. For example, in a cohort of 146,000 Chinese people, high sodium and low potassium intake was positively correlated with higher BP.5 In addition, the impact of increasing sodium intake or decreasing potassium intake was greater for people with a BMI ≥24 kg/m2, than people with a BMI <24 kg/m2. In a cohort of 11,095 US adults, high sodium and low potassium intake was associated with an increased risk of hypertension.6

In a study of 13,696 women, high potassium intake was associated with lower BP in participants with either a low or high sodium intake.7 In addition, over a 19-year follow up, higher potassium intake was associated with a lower risk of cardiovascular events.7 Comparing the highest (5,773 mg/d) vs lowest (2,783 mg/d) tertile of potassium intake, the decreased risk of a cardiovascular event was 0.89 (95% confidence interval [CI], 0.83–0.95).7

In a meta-analysis of data culled from 6 cohort studies, 10,709 adults with a mean age of 52 years, 54% of whom identified as women, were followed for a median of 8.8 years.8 Each adult contributed at least two 24-hour urine samples for measurement of sodium and potassium content. (Measurement of sodium and potassium in multiple 24-hour urine specimens from the same participant is thought to be the best way to assess sodium and potassium consumption.) The primary outcome was a cardiovascular event, including heart attack, stroke, or undergoing coronary revascularization procedures. In this study increasing consumption of sodium was associated with an increase in cardiovascular events, and increasing consumption of potassium was associated with a decrease in cardiovascular events. The hazard ratio for a cardiovascular event comparing high versus low consumption of sodium was 1.60 (95% CI, 1.19–2.14), and comparing high versus low consumption of potassium was 0.69 (95% CI, 0.51–0.91) (TABLE 2).8

Continue to: Clinical trial data on decreasing Na and/or increasing K consumption on CV outcomes...

 

 

Clinical trial data on decreasing Na and/or increasing K consumption on CV outcomes

Building on the cohort studies reporting that diets high in sodium and low in potassium are associated with hypertension and cardiovascular disease, clinical trials report that decreasing dietary sodium intake reduces BP and the risk of a cardiovascular event. For example, in a meta-analysis of 85 clinical trials studying the link between sodium and BP, the investigators concluded that there was a linear relationship between sodium intake and BP, with larger reductions in sodium intake associated with greater reductions in BP, down to a daily sodium intake of 1,000 to 1,500 mg.9 The effect of sodium reduction on BP was greatest in study participants with higher BP at baseline.

In a cluster-randomized clinical trial in China, people living in 600 villages were assigned to a control group, continuing to use sodium chloride in their food preparation or an experimental intervention, replacing sodium chloride with a substitute product containing 75% sodium chloride and 25% potassium chloride by weight.10 The inclusion criteria included people ≥60 years of age with high BP or a history of stroke. The mean duration of follow-up was 4.7 years. Half of the participants were female. A total of 73% of the participants had a history of stroke and 88% had hypertension. In this study, the rate of death was lower in the group that used the salt substitute than in the group using sodium chloride (39 vs 45 deaths per 1,000 person-years; rate ratio (RR) 0.88; 95% CI, 0.82–0.95, P<.001). The rate of major cardiovascular events (nonfatal stroke, nonfatal acute coronary syndrome or death from vascular causes) was decreased in the group that used salt substitute compared with the group using sodium chloride (49 vs 56 events per 1,000 person-years, rate ratio (RR), 0.87; 95% CI, 0.80–0.94; P<.001). Similarly, the rate of stroke was decreased in the group that used salt substitute compared with the group using sodium chloride (29 vs 34 events per 1,000 person-years; rate ratio (RR), 0.86; 95% CI, 0.77–0.96; P = .006). This study shows that by decreasing sodium intake and increasing potassium, cardiovascular outcomes are improved in people at high risk for a cardiovascular event.10 People with kidney disease or taking medications that decrease renal excretion of potassium should consult with their health care provider before using potassium chloride containing salt substitutes.

What is your daily intake of sodium and potassium?

Almost all packaged prepared foods have labels indicating the amount of sodium in one serving. Many packaged foods also report the amount of potassium in one serving. Many processed foods contain high amounts of sodium and low amounts of potassium. Processed and ultra-processed foods are a major dietary source of sodium.11 In contrast to processed foods, fresh fruits, vegetables, and milk have high quantities of potassium and low amounts of sodium. As an example, a major brand of canned chicken broth has 750 mg of sodium and 40 mg of potassium per one-half cup, a ratio of sodium to potassium of 19:1. By contrast, canned red kidney beans have 135 mg of sodium and 425 mg of potassium in one-half cup, a ratio of sodium to potassium of 1:3. Patients can better understand their daily sodium and potassium intake by reading the food labels. Calculating a sodium to potassium ratio for a food may help people better understand their salt intake and identify foods associated with positive health outcomes.

The optimal target for daily consumption of sodium and potassium is controversial (TABLE 2). The mean daily intakes of sodium and potassium in the United States are approximately 3,380 mg and 2,499 mg,respectively.12 The American College of Cardiology (ACC) recommends that an optimal diet contains <1,500 mg/d of sodium, a stringent target.1 If that target is unattainable, people should at least aim for a 1,000 mg/d-reduction in their current sodium intake.1 The World Health Organization strongly recommends that adults consume <2,000 mg/d of sodium.13 The National Academy of Science recommends adults seeking to reduce the risk of cardiovascular disease consume <2,300 mg/d of sodium.14 The top dietary sources of sodium include deli meat, pizza, burritos and tacos, soups, savory snacks (chips, crackers, popcorn), fried poultry, burgers, and eggs.15

The optimal target for daily consumption of potassium is controversial. The ACC recommends that an optimal diet contains 3,500–5,000 mg/d of potassium.1 The World Health Organization recommends that adults consume >3,510 mg/d of potassium.16 The top dietary sources of potassium include milk, fruit, vegetables, coffee, savory snacks (chips, crackers, popcorn), fruit juice, white potatoes, deli meats, burritos, and tacos.15 The foods with the greatest amount of potassium include banana, avocado, acorn squash, spinach, sweet potatoes, salmon, apricots, grapefruit, broccoli, and white beans. People with kidney disease or those who are taking medications that interfere with renal excretion of potassium should consult with their health care provider before adding more potassium to their diet.

The ACC also recommends1:

  • Maintaining an optimal weight (a 1-kg reduction in weight is associated with a 1-mm Hg reduction in BP).
  • Eating a healthy diet rich in fruits, vegetables, whole grains, and low-fat dairy products with reduced saturated and total fat.
  • Regular aerobic physical activity 90 to 150 min/wk.
  • Moderation in alcohol consumption, with men limiting consumption ≤ 2 drinks/d and women limiting consumption to ≤ 1 drink/d.
  • Smoking cessation.

Most adults in the US have too much sodium and too little potassium in their daily diet. Diets high in sodium and low in potassium increase the risk of hypertension. In turn, this increases the risk of cardiovascular disease, including myocardial infarction and stroke. Many personal choices and societal factors contribute to our current imbalanced and unhealthy diet, rich in sodium and deficient in potassium. Our best approach to improve health and reduce cardiovascular disease is to guide people to modify unhealthy lifestyle behaviors.17 For patients who are ready to change, a counseling intervention using the 5 A’s (including assess risk behaviors, advise change, agree on goals/action plan, assist with treatment, and arrange follow-up) has been shown to result in improved dietary choices, increased physical activity, and reduced use of tobacco products.18

Sodium intake and pregnancy-associated hypertension: Is there a link?

Two randomized clinical trials completed in the 1990s, comparing a low-sodium and a standard diet, showed no effect of reducing sodium intake by 32% and 57% on the risk of developing preeclampsia.1,2 Based on these 2 studies, a Cochrane review concluded that during pregnancy salt consumption should remain a matter of personal preference.3 Three recent observational studies report a relationship between sodium intake and the risk of developing pregnancy-associated hypertension.

In a study of 66,651 singleton pregnancies in the Danish Birth Cohort, participants with the greatest daily sodium intake, ranging from 3,520 to 7,520 mg/d had a 54% increased risk of developing gestational hypertension (95% confidence interval [CI], 16%–104%) and a 20% increased risk of developing preeclampsia (95% CI, 1%–42%).4 Another cohort study also reported that elevated sodium chloride intake was associated with an increased risk of developing preeclampsia.5 In one study, among patients with preeclampsia, those with lower urinary sodium to potassium ratio were less likely to develop severe preeclampsia.6 In a pregnant rat model, high salt intake is associated with a severe increase in blood pressure, the development of proteinuria, and an increase in circulating plasma soluble fmslike tyrosine-kinase 1 (sFlt-1)—changes also seen in preeclampsia.7 Pregnancy associated hypertension may not be as “salt sensitive” as chronic hypertension.

Future research could explore the effect of dietary sodium and potassium intake on the risk of developing severe hypertension during pregnancy in patients with chronic hypertension.

References

1. Knuist M, Bonsel GJ, Zondervan HA, et al. Low sodium diet and pregnancy-induced hypertension, a multicenter randomised controlled trial. Brit J Obstet Gynecol. 1998;105:430-434.

2. van der Maten GD, van Raaij JMA, Visman L, et al. Low-sodium in pregnancy: effects on blood pressure and maternal nutritional status. Brit J Nutr. 1997;77:703-720.

3. Duley L, Henderson-Smart DJ, Meher S. Altered dietary salt for preventing pre-eclampsia, and its complications. Cochrane Database Syst Rev. 2005;CD005548.

4. Arvizu, M, Bjerregaard AA, Madsen MTB, et al. Sodium intake during pregnancy, but not other diet recommendations aimed at preventing cardiovascular disease, is positively related to risk of hypertensive disorders of pregnancy. J Nutr. 2020;150:159-166.

5. Birukov A, Andersen LB, Herse F, et al. Aldosterone, salt and potassium intakes as predictors of pregnancy outcome, including preeclampsia. Hypertension. 2019;74:391-398.

6. Yilmaz ZV, Akkas E, Turkmen GG, et al. Dietary sodium and potassium intake were associated with hypertension, kidney damage and adverse perinatal outcome in pregnant women with preeclampsia. Hypertension Preg. 2017;36:77-83.

7. Gillis EE, Williams JM, Garrett MR, et al. The Dahl salt-sensitive rat is a spontaneous model of superimposed preeclampsia. Am J Physiol Regul Integr Comp Physiol. 2015;309:R62-70.

 

Hypertension is a prevalent medical problem among US women, with a higher prevalence among Black women, than among White, Hispanic, or Asian women (TABLE 1).1 Among US women aged 55 to 64 years, approximately 50% have hypertension or are taking a hypertension medicine.1 Hypertension is an important risk factor for cardiovascular disease, including stroke, coronary heart disease, heart failure, atrial fibrillation, and peripheral vascular disease.1,2 In a study of 1.3 million people, blood pressure (BP) ≥ 130/80 mm Hg was associated with an increased risk of a cardiovascular event, including myocardial infarction and stroke.2 Excessive sodium intake is an important risk factor for developing hypertension.3 In 2015–2016, 87% of US adults consumed >2,300 mg/d of sodium,4 an amount that is considered excessive.1 Less well known is the association between low potassium intake and hypertension. This editorial reviews the evidence that diets high in sodium and low in potassium contribute to the development of hypertension and cardiovascular disease.

Sodium and potassium dueling cations

Many cohort studies report that diets high in sodium and low in potassium are associated with hypertension and an increased risk of cardiovascular disease. For example, in a cohort of 146,000 Chinese people, high sodium and low potassium intake was positively correlated with higher BP.5 In addition, the impact of increasing sodium intake or decreasing potassium intake was greater for people with a BMI ≥24 kg/m2, than people with a BMI <24 kg/m2. In a cohort of 11,095 US adults, high sodium and low potassium intake was associated with an increased risk of hypertension.6

In a study of 13,696 women, high potassium intake was associated with lower BP in participants with either a low or high sodium intake.7 In addition, over a 19-year follow up, higher potassium intake was associated with a lower risk of cardiovascular events.7 Comparing the highest (5,773 mg/d) vs lowest (2,783 mg/d) tertile of potassium intake, the decreased risk of a cardiovascular event was 0.89 (95% confidence interval [CI], 0.83–0.95).7

In a meta-analysis of data culled from 6 cohort studies, 10,709 adults with a mean age of 52 years, 54% of whom identified as women, were followed for a median of 8.8 years.8 Each adult contributed at least two 24-hour urine samples for measurement of sodium and potassium content. (Measurement of sodium and potassium in multiple 24-hour urine specimens from the same participant is thought to be the best way to assess sodium and potassium consumption.) The primary outcome was a cardiovascular event, including heart attack, stroke, or undergoing coronary revascularization procedures. In this study increasing consumption of sodium was associated with an increase in cardiovascular events, and increasing consumption of potassium was associated with a decrease in cardiovascular events. The hazard ratio for a cardiovascular event comparing high versus low consumption of sodium was 1.60 (95% CI, 1.19–2.14), and comparing high versus low consumption of potassium was 0.69 (95% CI, 0.51–0.91) (TABLE 2).8

Continue to: Clinical trial data on decreasing Na and/or increasing K consumption on CV outcomes...

 

 

Clinical trial data on decreasing Na and/or increasing K consumption on CV outcomes

Building on the cohort studies reporting that diets high in sodium and low in potassium are associated with hypertension and cardiovascular disease, clinical trials report that decreasing dietary sodium intake reduces BP and the risk of a cardiovascular event. For example, in a meta-analysis of 85 clinical trials studying the link between sodium and BP, the investigators concluded that there was a linear relationship between sodium intake and BP, with larger reductions in sodium intake associated with greater reductions in BP, down to a daily sodium intake of 1,000 to 1,500 mg.9 The effect of sodium reduction on BP was greatest in study participants with higher BP at baseline.

In a cluster-randomized clinical trial in China, people living in 600 villages were assigned to a control group, continuing to use sodium chloride in their food preparation or an experimental intervention, replacing sodium chloride with a substitute product containing 75% sodium chloride and 25% potassium chloride by weight.10 The inclusion criteria included people ≥60 years of age with high BP or a history of stroke. The mean duration of follow-up was 4.7 years. Half of the participants were female. A total of 73% of the participants had a history of stroke and 88% had hypertension. In this study, the rate of death was lower in the group that used the salt substitute than in the group using sodium chloride (39 vs 45 deaths per 1,000 person-years; rate ratio (RR) 0.88; 95% CI, 0.82–0.95, P<.001). The rate of major cardiovascular events (nonfatal stroke, nonfatal acute coronary syndrome or death from vascular causes) was decreased in the group that used salt substitute compared with the group using sodium chloride (49 vs 56 events per 1,000 person-years, rate ratio (RR), 0.87; 95% CI, 0.80–0.94; P<.001). Similarly, the rate of stroke was decreased in the group that used salt substitute compared with the group using sodium chloride (29 vs 34 events per 1,000 person-years; rate ratio (RR), 0.86; 95% CI, 0.77–0.96; P = .006). This study shows that by decreasing sodium intake and increasing potassium, cardiovascular outcomes are improved in people at high risk for a cardiovascular event.10 People with kidney disease or taking medications that decrease renal excretion of potassium should consult with their health care provider before using potassium chloride containing salt substitutes.

What is your daily intake of sodium and potassium?

Almost all packaged prepared foods have labels indicating the amount of sodium in one serving. Many packaged foods also report the amount of potassium in one serving. Many processed foods contain high amounts of sodium and low amounts of potassium. Processed and ultra-processed foods are a major dietary source of sodium.11 In contrast to processed foods, fresh fruits, vegetables, and milk have high quantities of potassium and low amounts of sodium. As an example, a major brand of canned chicken broth has 750 mg of sodium and 40 mg of potassium per one-half cup, a ratio of sodium to potassium of 19:1. By contrast, canned red kidney beans have 135 mg of sodium and 425 mg of potassium in one-half cup, a ratio of sodium to potassium of 1:3. Patients can better understand their daily sodium and potassium intake by reading the food labels. Calculating a sodium to potassium ratio for a food may help people better understand their salt intake and identify foods associated with positive health outcomes.

The optimal target for daily consumption of sodium and potassium is controversial (TABLE 2). The mean daily intakes of sodium and potassium in the United States are approximately 3,380 mg and 2,499 mg,respectively.12 The American College of Cardiology (ACC) recommends that an optimal diet contains <1,500 mg/d of sodium, a stringent target.1 If that target is unattainable, people should at least aim for a 1,000 mg/d-reduction in their current sodium intake.1 The World Health Organization strongly recommends that adults consume <2,000 mg/d of sodium.13 The National Academy of Science recommends adults seeking to reduce the risk of cardiovascular disease consume <2,300 mg/d of sodium.14 The top dietary sources of sodium include deli meat, pizza, burritos and tacos, soups, savory snacks (chips, crackers, popcorn), fried poultry, burgers, and eggs.15

The optimal target for daily consumption of potassium is controversial. The ACC recommends that an optimal diet contains 3,500–5,000 mg/d of potassium.1 The World Health Organization recommends that adults consume >3,510 mg/d of potassium.16 The top dietary sources of potassium include milk, fruit, vegetables, coffee, savory snacks (chips, crackers, popcorn), fruit juice, white potatoes, deli meats, burritos, and tacos.15 The foods with the greatest amount of potassium include banana, avocado, acorn squash, spinach, sweet potatoes, salmon, apricots, grapefruit, broccoli, and white beans. People with kidney disease or those who are taking medications that interfere with renal excretion of potassium should consult with their health care provider before adding more potassium to their diet.

The ACC also recommends1:

  • Maintaining an optimal weight (a 1-kg reduction in weight is associated with a 1-mm Hg reduction in BP).
  • Eating a healthy diet rich in fruits, vegetables, whole grains, and low-fat dairy products with reduced saturated and total fat.
  • Regular aerobic physical activity 90 to 150 min/wk.
  • Moderation in alcohol consumption, with men limiting consumption ≤ 2 drinks/d and women limiting consumption to ≤ 1 drink/d.
  • Smoking cessation.

Most adults in the US have too much sodium and too little potassium in their daily diet. Diets high in sodium and low in potassium increase the risk of hypertension. In turn, this increases the risk of cardiovascular disease, including myocardial infarction and stroke. Many personal choices and societal factors contribute to our current imbalanced and unhealthy diet, rich in sodium and deficient in potassium. Our best approach to improve health and reduce cardiovascular disease is to guide people to modify unhealthy lifestyle behaviors.17 For patients who are ready to change, a counseling intervention using the 5 A’s (including assess risk behaviors, advise change, agree on goals/action plan, assist with treatment, and arrange follow-up) has been shown to result in improved dietary choices, increased physical activity, and reduced use of tobacco products.18

Sodium intake and pregnancy-associated hypertension: Is there a link?

Two randomized clinical trials completed in the 1990s, comparing a low-sodium and a standard diet, showed no effect of reducing sodium intake by 32% and 57% on the risk of developing preeclampsia.1,2 Based on these 2 studies, a Cochrane review concluded that during pregnancy salt consumption should remain a matter of personal preference.3 Three recent observational studies report a relationship between sodium intake and the risk of developing pregnancy-associated hypertension.

In a study of 66,651 singleton pregnancies in the Danish Birth Cohort, participants with the greatest daily sodium intake, ranging from 3,520 to 7,520 mg/d had a 54% increased risk of developing gestational hypertension (95% confidence interval [CI], 16%–104%) and a 20% increased risk of developing preeclampsia (95% CI, 1%–42%).4 Another cohort study also reported that elevated sodium chloride intake was associated with an increased risk of developing preeclampsia.5 In one study, among patients with preeclampsia, those with lower urinary sodium to potassium ratio were less likely to develop severe preeclampsia.6 In a pregnant rat model, high salt intake is associated with a severe increase in blood pressure, the development of proteinuria, and an increase in circulating plasma soluble fmslike tyrosine-kinase 1 (sFlt-1)—changes also seen in preeclampsia.7 Pregnancy associated hypertension may not be as “salt sensitive” as chronic hypertension.

Future research could explore the effect of dietary sodium and potassium intake on the risk of developing severe hypertension during pregnancy in patients with chronic hypertension.

References

1. Knuist M, Bonsel GJ, Zondervan HA, et al. Low sodium diet and pregnancy-induced hypertension, a multicenter randomised controlled trial. Brit J Obstet Gynecol. 1998;105:430-434.

2. van der Maten GD, van Raaij JMA, Visman L, et al. Low-sodium in pregnancy: effects on blood pressure and maternal nutritional status. Brit J Nutr. 1997;77:703-720.

3. Duley L, Henderson-Smart DJ, Meher S. Altered dietary salt for preventing pre-eclampsia, and its complications. Cochrane Database Syst Rev. 2005;CD005548.

4. Arvizu, M, Bjerregaard AA, Madsen MTB, et al. Sodium intake during pregnancy, but not other diet recommendations aimed at preventing cardiovascular disease, is positively related to risk of hypertensive disorders of pregnancy. J Nutr. 2020;150:159-166.

5. Birukov A, Andersen LB, Herse F, et al. Aldosterone, salt and potassium intakes as predictors of pregnancy outcome, including preeclampsia. Hypertension. 2019;74:391-398.

6. Yilmaz ZV, Akkas E, Turkmen GG, et al. Dietary sodium and potassium intake were associated with hypertension, kidney damage and adverse perinatal outcome in pregnant women with preeclampsia. Hypertension Preg. 2017;36:77-83.

7. Gillis EE, Williams JM, Garrett MR, et al. The Dahl salt-sensitive rat is a spontaneous model of superimposed preeclampsia. Am J Physiol Regul Integr Comp Physiol. 2015;309:R62-70.

References
  1. Whelton PK, Carey RM, Aronow WS, et al. ACC/ AHA/AAPA/ABC/ACPM/AGS/APHA/ASH/ ASPC/NMA/PCNA guideline for the prevention, detection, evaluation and management of high blood pressure in adults: Executive Summary: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2018;138:e426-e483.
  2. Flint AC, Conell C, Ren X, et al. Effect of systolic and diastolic blood pressure on cardiovascular outcomes. N Engl J Med. 2019;381:243-251.
  3. Aljuraiban G, Jose AP, Gupta P, et al. Sodium intake, health implications and the role of population-level strategies. Nutr Rev. 2021;79:351-359.
  4. Clarke LS, Overwyk K, Bates M, et al. Temporal trends in dietary sodium intake among adults aged ≥ 19 years--United States 2003-2016. MMWR. 2021;70:1478-1482.
  5. Guo X, Zhang M, Li C, et al. Association between urinary sodium and potassium excretion and blood pressure among non-hypertensive adults-China, 2018-2019. China CDC Wkly. 2022;4:522-526.
  6. Li M, Yan S, Li X, et al. Association between blood pressure and dietary intakes of sodium and potassium among US adults using quantile regression analysis NHANES 2007-2014. J Hum Hypertens. 2020;34:346-354.
  7. Wouda RD, Boekholdt SM, Khaw KT, et al. Sex-specific associations between potassium intake, blood pressure and cardiovascular outcomes: the EPIC-Norfolk study. Europ Heart J. 2022, Epub July 21.
  8. Ma Y, He, Sun Q, et al. 24-hour urinary sodium and potassium excretion and cardiovascular risk. N Engl J Med. 2022;386:252-263.
  9. Filippini T, Malavolti M, Whelton PK, et al. Blood pressure effects of sodium reduction: dose-response meta-analysis of experimental studies. Circulation. 2021;143:1542-1567.
  10. Neal B, Wu Y, Feng X, et al. Effect of salt substitution on cardiovascular events. N Engl J Med. 2021;385:1067-1077.
  11. Monteiro CA, Cannon G, Moubarac JC, et al. The U.N. decade of nutrition: The NOVA food classification and the trouble with ultra-processing. Public Health Nutr. 2018;51:5-17.
  12. Nutrient intakes; From foods and beverages. Gender and Ag. WWEIA Data Tables. US Department of Health and Human Services, US Department of Agriculture. Web address Table 1. https://www .ars.usda.gov/ARSUserFiles/80400530/pdf /usual/Usual_Intake_gender_WWEIA_2015 _2018.pdf.
  13. WHO. Guideline: Sodium intake for adults and children. Geneva. World Health Organization (WHO), 2012. https://www.who.int /publications/i/item/9789241504836.
  14. National Academies of Sciences, Engineering and Medicine 2019. Dietary Reference Intakes for Sodium and Potassium. Washington DC: The National Academies Press. https://doi .org/10.17226/25353.
  15. Woodruff RC, Zhao L, Ahuja JKC, et al. Top food category contributors to sodium and potassium intake-United States 2015-2016. MMWR. 2020;69:1064-1069.
  16. WHO. Guideline: Potassium intake for adults and children. Geneva. World Health Organization (WHO), 2012. https://www.who.int /publications/i/item/9789241504829.
  17. Li Y, Pan A, Wang DD, et al. Impact of healthy lifestyle factors on life expectancies in the US population. Circulation. 2018;138:345-355.
  18. US Preventive Services Task Force. Behavioral counseling interventions to promote a healthy diet and physical activity for cardiovascular disease prevention in adults without cardiovascular disease risk factors. JAMA. 2022;328:367-374.
References
  1. Whelton PK, Carey RM, Aronow WS, et al. ACC/ AHA/AAPA/ABC/ACPM/AGS/APHA/ASH/ ASPC/NMA/PCNA guideline for the prevention, detection, evaluation and management of high blood pressure in adults: Executive Summary: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2018;138:e426-e483.
  2. Flint AC, Conell C, Ren X, et al. Effect of systolic and diastolic blood pressure on cardiovascular outcomes. N Engl J Med. 2019;381:243-251.
  3. Aljuraiban G, Jose AP, Gupta P, et al. Sodium intake, health implications and the role of population-level strategies. Nutr Rev. 2021;79:351-359.
  4. Clarke LS, Overwyk K, Bates M, et al. Temporal trends in dietary sodium intake among adults aged ≥ 19 years--United States 2003-2016. MMWR. 2021;70:1478-1482.
  5. Guo X, Zhang M, Li C, et al. Association between urinary sodium and potassium excretion and blood pressure among non-hypertensive adults-China, 2018-2019. China CDC Wkly. 2022;4:522-526.
  6. Li M, Yan S, Li X, et al. Association between blood pressure and dietary intakes of sodium and potassium among US adults using quantile regression analysis NHANES 2007-2014. J Hum Hypertens. 2020;34:346-354.
  7. Wouda RD, Boekholdt SM, Khaw KT, et al. Sex-specific associations between potassium intake, blood pressure and cardiovascular outcomes: the EPIC-Norfolk study. Europ Heart J. 2022, Epub July 21.
  8. Ma Y, He, Sun Q, et al. 24-hour urinary sodium and potassium excretion and cardiovascular risk. N Engl J Med. 2022;386:252-263.
  9. Filippini T, Malavolti M, Whelton PK, et al. Blood pressure effects of sodium reduction: dose-response meta-analysis of experimental studies. Circulation. 2021;143:1542-1567.
  10. Neal B, Wu Y, Feng X, et al. Effect of salt substitution on cardiovascular events. N Engl J Med. 2021;385:1067-1077.
  11. Monteiro CA, Cannon G, Moubarac JC, et al. The U.N. decade of nutrition: The NOVA food classification and the trouble with ultra-processing. Public Health Nutr. 2018;51:5-17.
  12. Nutrient intakes; From foods and beverages. Gender and Ag. WWEIA Data Tables. US Department of Health and Human Services, US Department of Agriculture. Web address Table 1. https://www .ars.usda.gov/ARSUserFiles/80400530/pdf /usual/Usual_Intake_gender_WWEIA_2015 _2018.pdf.
  13. WHO. Guideline: Sodium intake for adults and children. Geneva. World Health Organization (WHO), 2012. https://www.who.int /publications/i/item/9789241504836.
  14. National Academies of Sciences, Engineering and Medicine 2019. Dietary Reference Intakes for Sodium and Potassium. Washington DC: The National Academies Press. https://doi .org/10.17226/25353.
  15. Woodruff RC, Zhao L, Ahuja JKC, et al. Top food category contributors to sodium and potassium intake-United States 2015-2016. MMWR. 2020;69:1064-1069.
  16. WHO. Guideline: Potassium intake for adults and children. Geneva. World Health Organization (WHO), 2012. https://www.who.int /publications/i/item/9789241504829.
  17. Li Y, Pan A, Wang DD, et al. Impact of healthy lifestyle factors on life expectancies in the US population. Circulation. 2018;138:345-355.
  18. US Preventive Services Task Force. Behavioral counseling interventions to promote a healthy diet and physical activity for cardiovascular disease prevention in adults without cardiovascular disease risk factors. JAMA. 2022;328:367-374.
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Type 2 Diabetes in Adolescents: We Must Do Better

Article Type
Changed
Fri, 10/28/2022 - 11:11

 

Type 2 diabetes (T2D) has become a noncommunicable pandemic. Approximately 14.7% of the US adult population has diabetes.1 Additionally, nearly 25% of the geriatric population has diabetes and nearly 50% has prediabetes.2 Needless to say, most practices, regardless of specialty, see many patients with diabetes. We have made major advances in diabetes treatments, yet diabetes mellitus is still the leading cause of legal blindness, nontraumatic amputation, and end-stage renal disease requiring dialysis.3 

 

While the prevalence of diabetes in adults is concerning, what is even more startling is the significant increase of T2D within the pediatric population. It was not too long ago that we considered T2D an “adult-only” disease. Now, 24% of children with diabetes have T2D, and 18% of adolescents have prediabetes.4,5 This is not the end of the story. Recent studies have identified that the earlier you are diagnosed with T2D, the less responsive you are to diabetes treatments—and the disease will progress more rapidly to complications. 
 

We know that pediatric patients are not little adults. There are important physiologic and metabolic differences in our younger patients. The RISE study found that adolescents have lower insulin sensitivity than adults.4,6 The pancreatic beta cells are more responsive at first and there is less clearance by the liver, which may indeed make insulin resistance worse. Finally, pancreatic beta cell function declines more rapidly in adolescents than in adults.4,6 These physiologic changes can be even worse during puberty. The hormonal changes seen in puberty accelerate and amplify insulin secretion and worsen insulin resistance, which can result in hyperglycemia in those at risk.7,8

 

The other complicating factor is the rapid rise in obesity in Americans. While childhood obesity is not quite at adult levels, it is a major risk factor for adult obesity. The prevalence of obesity in childhood was recently estimated to be 19.7% and is still on the rise.9 Obesity can be diabetogenic as we see an increase in visceral obesity. This triggers an inflammatory response that leads to worsening systemic insulin resistance and lipotoxicity from elevated circulating free fatty acids.8 

 

Lifestyle and behavioral factors are also important in adolescents with T2D. While they are more independent than younger children, they are still largely dependent on the foods that are available in their home. Family food choices have a major impact on our youth. Further, the foods that our adolescents eat outside the home are more likely to be fast food or ultra-processed foods, which have been shown to contribute to obesity and T2D. 

 

Family history is a strong predictor of risk for T2D. In the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) cohort, 89.4% of pediatric participants had a first-degree relative or grandparent with T2D.10 This highlights the importance of both genetic risk and living environment as risks for T2D. 

 

The American Diabetes Association recommends that all children with specific risk factors be screened for diabetes starting at the age 10 years or at puberty, whichever comes first.11 The screening tests recommended for diabetes are currently the same as for adults, yet there are few data supporting this regimen. To diagnose diabetes, you can use any of the following screening tests: fasting glucose, glucose tolerance, or glycated hemoglobin (HbA1c).1 

 

Risk Factors That Should Prompt Diabetes Screening11

Screening is recommended in children who are overweight (≥85%) or obese (≥95%) and who also have ≥1 of the following risk factors:

  • Family history of T2D in a first- or second-degree relative
  • Maternal history of gestational diabetes
  • Low birth weight for gestational age
  • Physical signs of insulin resistance or related conditions (eg, hypertension, dyslipidemia, polycystic ovary syndrome)
  • High-risk race/ethnicity (Native American, African American, Pacific Islander, Latino)



 

Diagnostic Criteria for Diabetes Mellitus11

 

Testing method

Normal range

Pre-diabetes

Diabetes mellitus

Fasting glucose

<100 mg/dL

100-125 mg/dL

≥126 mg/dL

2-hour glucose tolerance test

<140 mg/dL

140-199 mg/dL

≥200 mg/dL

HbA1c

<5.7%

5.7%-6.4%

≥6.5%

 

A childhood or adolescent T2D diagnosis should be taken seriously and communicated to the patient and family in a timely manner. Treatment should start immediately. There are several factors that make managing T2D in adolescents more challenging. Children do not control key aspects of their life, including nutrition and, often, free time activity. There are a lot of social pressures to be “normal,” and having a chronic disease will definitely make the child feel “different” and potentially feel socially isolated. There are high rates of mood disorders in children with diabetes, which can make self-management even harder.12

 

As mentioned above, treatment should begin immediately upon diagnosis. This is because T2D in younger people tends to be more progressive and less responsive to treatment options, and patients are much more likely to develop.1,13,14 These same complications can be seen in adult patients, but in younger patients they develop earlier in the disease; specifically, renal and neurologic complications occur at even higher rates.14 

 

The initial treatment should include both family-based therapeutic lifestyle changes (ie, nutrition, physical activity intervention) and medication.11 There are fewer US Food and Drug Administration–approved medication options for children and adolescents, and those treatments that have been approved are less durable in this population. 

 

Metformin and insulin are the most-used medications, but their initiation is often delayed, as therapeutic lifestyle change is tried first. This has not been shown to be an effective strategy and may even undermine the value of therapeutic lifestyle change if the family is told later that medication may still need to be added. 

 

Recent studies have shown the benefit of select glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as important therapeutic tools to treat T2D in adolescence. Dulaglutide, exenatide, and liraglutide have been shown to be safe and effective in trials for adolescents with T2D.15-17 These agents reduce glucose and body weight and may be important tools to help reduce extra glycemic risks (eg, cardiovascular disease, kidney disease), but they have not been studied for this purpose yet. 

 

Further, there is good support for the use of bariatric surgery for adolescents. While this is a relatively new treatment option, early and mid-term results are favorable compared with medication-based strategies.18 Further studies are needed to determine the long-term benefits.

 

Take home points:

 

  1. T2D is becoming increasingly common in our youth.
  2. T2D, when diagnosed earlier in life, is more progressive, less responsive to treatment options, and associated with earlier complications.
  3. New studies support the use of novel therapies such as GLP-1 RAs and metabolic surgery in this age group.

 

Dr. Shubrook and Dr. Antonia M. Molinari have written a comprehensive review on treatment options and current guidelines for the management of T2D in the pediatric population, which can supply further information.19 

 

References

  1. National and state diabetes trends 2021. Centers for Disease Control and Prevention. Accessed September 26, 2022. https://www.cdc.gov/diabetes/library/reports/reportcard/national-state-diabetes-trends.html

  2. National diabetes statistics report. Centers for Disease Control and Prevention. Accessed September 26, 2022. https://www.cdc.gov/diabetes/data/statistics-report/index.html 

  3. National diabetes statistics report. Estimates of diabetes and its burden in the United States. Centers for Disease Control and Prevention. Accessed September 26, 2022. https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf 

  4. RISE Consortium. Metabolic contrasts between youth and adults with impaired glucose tolerance or recently diagnosed type 2 diabetes: I. Observations using the hyperglycemic clamp. Diabetes Care. 2018;41(8):1696-1706. doi:10.2337/dc18-0244

  5. Andes LJ, Cheng YJ, Rolka DB, Gregg EW, Imperatore G. Prevalence of prediabetes among adolescents and young adults in the United States, 2005-2016. JAMA Pediatr. 2020;174:e194498. doi:10.1001/jamapediatrics.2019.4498

  6. RISE Consortium. Metabolic contrasts between youth and adults with impaired glucose tolerance or recently diagnosed type 2 diabetes: II. Observations using the oral glucose tolerance test. Diabetes Care. 2018;41(8):1707-1716. doi:10.2337/dc18-0243.

  7. Cree-Green M, Triolo TM, Nadeau KJ. Etiology of insulin resistance in youth with type 2 diabetes. Curr Diab Rep. 2013;13(1):81-88. doi:10.1007/s11892-012-0341-0

  8. Goran MI, Gower BA. Longitudinal study on pubertal insulin resistance. Diabetes. 2001;50(11):2444-2450. doi:10.2337/diabetes.50.11.2444

  9. Childhood obesity facts. Centers for Disease Control and Prevention. Accessed October 3, 2022. https://www.cdc.gov/obesity/data/childhood.html 

  10. Copeland KC, Zeitler P, Geffner M, et al. Characteristics of adolescents and youth with recent-onset type 2 diabetes: the TODAY cohort at baseline. J Clin Endocrinol Metab. 2011;96(1):159-167. doi:10.1210/jc.2010-1642

  11. Arslanian S, Bacha F, Grey M, Marcus MD, White NH, Zeitler P. Evaluation and management of youth-onset type 2 diabetes: a position statement by the American Diabetes Association. Diabetes Care. 2018;41(12):2648-2668. doi:10.2337/dci18-0052

  12. Anderson BJ, Edelstein S, Abramson NW, et al. Depressive symptoms and quality of life in adolescents with type 2 diabetes: baseline data from the TODAY study. Diabetes Care. 2011;34(10):2205-2207. doi:10.2337/dc11-0431

  13. TODAY Study Group. Treatment options for type 2 diabetes in adolescents and youth: a study of the comparative efficacy of metformin alone or in combination with rosiglitazone or lifestyle intervention in adolescents with type 2 diabetes. Pediatr Diabetes. 2007;8(2):74-87. doi:10.1111/j.1399-5448.2007.00237.x

  14. Dart AB, Martens PJ, Rigatto C, Brownell MD, Dean HJ, Sellers EA. Earlier onset of complications in youth with type 2 diabetes. Diabetes Care. 2014;37(2):436-443. doi:10.2337/dc13-0954

  15. Arslanian SA, Hannon T, Zeitler P et al. Once-weekly dulaglutide for the treatment of youths with type 2 diabetes. N Engl J Med. 2022;387(5):433-443. doi:10.1056/NEJMoa2204601

  16. Tamborlane WV, Barrientos-Pérez M, Fainberg U, et al. Liraglutide in children and adolescents with type 2 diabetes. N Engl J Med. 2019;381(7):637-646. doi:10.1056/NEJMoa1903822

  17. Tamborlane WV, Bishai R, Geller D, et al. Once-weekly exenatide in youth with type 2 diabetes. Diabetes Care. 2022;45(8):1833-1840. doi:10.2337/dc21-2275

  18. Inge TH, Laffel LM, Jenkins TM, et al. Comparison of surgical and medical therapy for type 2 diabetes in severely obese adolescents. JAMA Pediatr. 2018;172(5):452-460. doi:10.1001/jamapediatrics.2017.5763

  19. Molinari AM, Shubrook JH. Treatment options and current guidelines of care for pediatric type 2 diabetes patients: a narrative review. J Osteopath Med. 2021;121(4):431-440. doi:10.1515/jom-2020-0172

 

Author and Disclosure Information

 

Jay H. Shubrook, DO

Professor, Primary Care Diabetologist

Touro University California, College of Osteopathic Medicine

Vallejo, CA

Dr. Shubrook has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Abbott, AstraZeneca, Bayer, Eli Lilly and Company, and Novo Nordisk.

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Author and Disclosure Information

 

Jay H. Shubrook, DO

Professor, Primary Care Diabetologist

Touro University California, College of Osteopathic Medicine

Vallejo, CA

Dr. Shubrook has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Abbott, AstraZeneca, Bayer, Eli Lilly and Company, and Novo Nordisk.

Author and Disclosure Information

 

Jay H. Shubrook, DO

Professor, Primary Care Diabetologist

Touro University California, College of Osteopathic Medicine

Vallejo, CA

Dr. Shubrook has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Abbott, AstraZeneca, Bayer, Eli Lilly and Company, and Novo Nordisk.

 

Type 2 diabetes (T2D) has become a noncommunicable pandemic. Approximately 14.7% of the US adult population has diabetes.1 Additionally, nearly 25% of the geriatric population has diabetes and nearly 50% has prediabetes.2 Needless to say, most practices, regardless of specialty, see many patients with diabetes. We have made major advances in diabetes treatments, yet diabetes mellitus is still the leading cause of legal blindness, nontraumatic amputation, and end-stage renal disease requiring dialysis.3 

 

While the prevalence of diabetes in adults is concerning, what is even more startling is the significant increase of T2D within the pediatric population. It was not too long ago that we considered T2D an “adult-only” disease. Now, 24% of children with diabetes have T2D, and 18% of adolescents have prediabetes.4,5 This is not the end of the story. Recent studies have identified that the earlier you are diagnosed with T2D, the less responsive you are to diabetes treatments—and the disease will progress more rapidly to complications. 
 

We know that pediatric patients are not little adults. There are important physiologic and metabolic differences in our younger patients. The RISE study found that adolescents have lower insulin sensitivity than adults.4,6 The pancreatic beta cells are more responsive at first and there is less clearance by the liver, which may indeed make insulin resistance worse. Finally, pancreatic beta cell function declines more rapidly in adolescents than in adults.4,6 These physiologic changes can be even worse during puberty. The hormonal changes seen in puberty accelerate and amplify insulin secretion and worsen insulin resistance, which can result in hyperglycemia in those at risk.7,8

 

The other complicating factor is the rapid rise in obesity in Americans. While childhood obesity is not quite at adult levels, it is a major risk factor for adult obesity. The prevalence of obesity in childhood was recently estimated to be 19.7% and is still on the rise.9 Obesity can be diabetogenic as we see an increase in visceral obesity. This triggers an inflammatory response that leads to worsening systemic insulin resistance and lipotoxicity from elevated circulating free fatty acids.8 

 

Lifestyle and behavioral factors are also important in adolescents with T2D. While they are more independent than younger children, they are still largely dependent on the foods that are available in their home. Family food choices have a major impact on our youth. Further, the foods that our adolescents eat outside the home are more likely to be fast food or ultra-processed foods, which have been shown to contribute to obesity and T2D. 

 

Family history is a strong predictor of risk for T2D. In the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) cohort, 89.4% of pediatric participants had a first-degree relative or grandparent with T2D.10 This highlights the importance of both genetic risk and living environment as risks for T2D. 

 

The American Diabetes Association recommends that all children with specific risk factors be screened for diabetes starting at the age 10 years or at puberty, whichever comes first.11 The screening tests recommended for diabetes are currently the same as for adults, yet there are few data supporting this regimen. To diagnose diabetes, you can use any of the following screening tests: fasting glucose, glucose tolerance, or glycated hemoglobin (HbA1c).1 

 

Risk Factors That Should Prompt Diabetes Screening11

Screening is recommended in children who are overweight (≥85%) or obese (≥95%) and who also have ≥1 of the following risk factors:

  • Family history of T2D in a first- or second-degree relative
  • Maternal history of gestational diabetes
  • Low birth weight for gestational age
  • Physical signs of insulin resistance or related conditions (eg, hypertension, dyslipidemia, polycystic ovary syndrome)
  • High-risk race/ethnicity (Native American, African American, Pacific Islander, Latino)



 

Diagnostic Criteria for Diabetes Mellitus11

 

Testing method

Normal range

Pre-diabetes

Diabetes mellitus

Fasting glucose

<100 mg/dL

100-125 mg/dL

≥126 mg/dL

2-hour glucose tolerance test

<140 mg/dL

140-199 mg/dL

≥200 mg/dL

HbA1c

<5.7%

5.7%-6.4%

≥6.5%

 

A childhood or adolescent T2D diagnosis should be taken seriously and communicated to the patient and family in a timely manner. Treatment should start immediately. There are several factors that make managing T2D in adolescents more challenging. Children do not control key aspects of their life, including nutrition and, often, free time activity. There are a lot of social pressures to be “normal,” and having a chronic disease will definitely make the child feel “different” and potentially feel socially isolated. There are high rates of mood disorders in children with diabetes, which can make self-management even harder.12

 

As mentioned above, treatment should begin immediately upon diagnosis. This is because T2D in younger people tends to be more progressive and less responsive to treatment options, and patients are much more likely to develop.1,13,14 These same complications can be seen in adult patients, but in younger patients they develop earlier in the disease; specifically, renal and neurologic complications occur at even higher rates.14 

 

The initial treatment should include both family-based therapeutic lifestyle changes (ie, nutrition, physical activity intervention) and medication.11 There are fewer US Food and Drug Administration–approved medication options for children and adolescents, and those treatments that have been approved are less durable in this population. 

 

Metformin and insulin are the most-used medications, but their initiation is often delayed, as therapeutic lifestyle change is tried first. This has not been shown to be an effective strategy and may even undermine the value of therapeutic lifestyle change if the family is told later that medication may still need to be added. 

 

Recent studies have shown the benefit of select glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as important therapeutic tools to treat T2D in adolescence. Dulaglutide, exenatide, and liraglutide have been shown to be safe and effective in trials for adolescents with T2D.15-17 These agents reduce glucose and body weight and may be important tools to help reduce extra glycemic risks (eg, cardiovascular disease, kidney disease), but they have not been studied for this purpose yet. 

 

Further, there is good support for the use of bariatric surgery for adolescents. While this is a relatively new treatment option, early and mid-term results are favorable compared with medication-based strategies.18 Further studies are needed to determine the long-term benefits.

 

Take home points:

 

  1. T2D is becoming increasingly common in our youth.
  2. T2D, when diagnosed earlier in life, is more progressive, less responsive to treatment options, and associated with earlier complications.
  3. New studies support the use of novel therapies such as GLP-1 RAs and metabolic surgery in this age group.

 

Dr. Shubrook and Dr. Antonia M. Molinari have written a comprehensive review on treatment options and current guidelines for the management of T2D in the pediatric population, which can supply further information.19 

 

 

Type 2 diabetes (T2D) has become a noncommunicable pandemic. Approximately 14.7% of the US adult population has diabetes.1 Additionally, nearly 25% of the geriatric population has diabetes and nearly 50% has prediabetes.2 Needless to say, most practices, regardless of specialty, see many patients with diabetes. We have made major advances in diabetes treatments, yet diabetes mellitus is still the leading cause of legal blindness, nontraumatic amputation, and end-stage renal disease requiring dialysis.3 

 

While the prevalence of diabetes in adults is concerning, what is even more startling is the significant increase of T2D within the pediatric population. It was not too long ago that we considered T2D an “adult-only” disease. Now, 24% of children with diabetes have T2D, and 18% of adolescents have prediabetes.4,5 This is not the end of the story. Recent studies have identified that the earlier you are diagnosed with T2D, the less responsive you are to diabetes treatments—and the disease will progress more rapidly to complications. 
 

We know that pediatric patients are not little adults. There are important physiologic and metabolic differences in our younger patients. The RISE study found that adolescents have lower insulin sensitivity than adults.4,6 The pancreatic beta cells are more responsive at first and there is less clearance by the liver, which may indeed make insulin resistance worse. Finally, pancreatic beta cell function declines more rapidly in adolescents than in adults.4,6 These physiologic changes can be even worse during puberty. The hormonal changes seen in puberty accelerate and amplify insulin secretion and worsen insulin resistance, which can result in hyperglycemia in those at risk.7,8

 

The other complicating factor is the rapid rise in obesity in Americans. While childhood obesity is not quite at adult levels, it is a major risk factor for adult obesity. The prevalence of obesity in childhood was recently estimated to be 19.7% and is still on the rise.9 Obesity can be diabetogenic as we see an increase in visceral obesity. This triggers an inflammatory response that leads to worsening systemic insulin resistance and lipotoxicity from elevated circulating free fatty acids.8 

 

Lifestyle and behavioral factors are also important in adolescents with T2D. While they are more independent than younger children, they are still largely dependent on the foods that are available in their home. Family food choices have a major impact on our youth. Further, the foods that our adolescents eat outside the home are more likely to be fast food or ultra-processed foods, which have been shown to contribute to obesity and T2D. 

 

Family history is a strong predictor of risk for T2D. In the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) cohort, 89.4% of pediatric participants had a first-degree relative or grandparent with T2D.10 This highlights the importance of both genetic risk and living environment as risks for T2D. 

 

The American Diabetes Association recommends that all children with specific risk factors be screened for diabetes starting at the age 10 years or at puberty, whichever comes first.11 The screening tests recommended for diabetes are currently the same as for adults, yet there are few data supporting this regimen. To diagnose diabetes, you can use any of the following screening tests: fasting glucose, glucose tolerance, or glycated hemoglobin (HbA1c).1 

 

Risk Factors That Should Prompt Diabetes Screening11

Screening is recommended in children who are overweight (≥85%) or obese (≥95%) and who also have ≥1 of the following risk factors:

  • Family history of T2D in a first- or second-degree relative
  • Maternal history of gestational diabetes
  • Low birth weight for gestational age
  • Physical signs of insulin resistance or related conditions (eg, hypertension, dyslipidemia, polycystic ovary syndrome)
  • High-risk race/ethnicity (Native American, African American, Pacific Islander, Latino)



 

Diagnostic Criteria for Diabetes Mellitus11

 

Testing method

Normal range

Pre-diabetes

Diabetes mellitus

Fasting glucose

<100 mg/dL

100-125 mg/dL

≥126 mg/dL

2-hour glucose tolerance test

<140 mg/dL

140-199 mg/dL

≥200 mg/dL

HbA1c

<5.7%

5.7%-6.4%

≥6.5%

 

A childhood or adolescent T2D diagnosis should be taken seriously and communicated to the patient and family in a timely manner. Treatment should start immediately. There are several factors that make managing T2D in adolescents more challenging. Children do not control key aspects of their life, including nutrition and, often, free time activity. There are a lot of social pressures to be “normal,” and having a chronic disease will definitely make the child feel “different” and potentially feel socially isolated. There are high rates of mood disorders in children with diabetes, which can make self-management even harder.12

 

As mentioned above, treatment should begin immediately upon diagnosis. This is because T2D in younger people tends to be more progressive and less responsive to treatment options, and patients are much more likely to develop.1,13,14 These same complications can be seen in adult patients, but in younger patients they develop earlier in the disease; specifically, renal and neurologic complications occur at even higher rates.14 

 

The initial treatment should include both family-based therapeutic lifestyle changes (ie, nutrition, physical activity intervention) and medication.11 There are fewer US Food and Drug Administration–approved medication options for children and adolescents, and those treatments that have been approved are less durable in this population. 

 

Metformin and insulin are the most-used medications, but their initiation is often delayed, as therapeutic lifestyle change is tried first. This has not been shown to be an effective strategy and may even undermine the value of therapeutic lifestyle change if the family is told later that medication may still need to be added. 

 

Recent studies have shown the benefit of select glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as important therapeutic tools to treat T2D in adolescence. Dulaglutide, exenatide, and liraglutide have been shown to be safe and effective in trials for adolescents with T2D.15-17 These agents reduce glucose and body weight and may be important tools to help reduce extra glycemic risks (eg, cardiovascular disease, kidney disease), but they have not been studied for this purpose yet. 

 

Further, there is good support for the use of bariatric surgery for adolescents. While this is a relatively new treatment option, early and mid-term results are favorable compared with medication-based strategies.18 Further studies are needed to determine the long-term benefits.

 

Take home points:

 

  1. T2D is becoming increasingly common in our youth.
  2. T2D, when diagnosed earlier in life, is more progressive, less responsive to treatment options, and associated with earlier complications.
  3. New studies support the use of novel therapies such as GLP-1 RAs and metabolic surgery in this age group.

 

Dr. Shubrook and Dr. Antonia M. Molinari have written a comprehensive review on treatment options and current guidelines for the management of T2D in the pediatric population, which can supply further information.19 

 

References

  1. National and state diabetes trends 2021. Centers for Disease Control and Prevention. Accessed September 26, 2022. https://www.cdc.gov/diabetes/library/reports/reportcard/national-state-diabetes-trends.html

  2. National diabetes statistics report. Centers for Disease Control and Prevention. Accessed September 26, 2022. https://www.cdc.gov/diabetes/data/statistics-report/index.html 

  3. National diabetes statistics report. Estimates of diabetes and its burden in the United States. Centers for Disease Control and Prevention. Accessed September 26, 2022. https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf 

  4. RISE Consortium. Metabolic contrasts between youth and adults with impaired glucose tolerance or recently diagnosed type 2 diabetes: I. Observations using the hyperglycemic clamp. Diabetes Care. 2018;41(8):1696-1706. doi:10.2337/dc18-0244

  5. Andes LJ, Cheng YJ, Rolka DB, Gregg EW, Imperatore G. Prevalence of prediabetes among adolescents and young adults in the United States, 2005-2016. JAMA Pediatr. 2020;174:e194498. doi:10.1001/jamapediatrics.2019.4498

  6. RISE Consortium. Metabolic contrasts between youth and adults with impaired glucose tolerance or recently diagnosed type 2 diabetes: II. Observations using the oral glucose tolerance test. Diabetes Care. 2018;41(8):1707-1716. doi:10.2337/dc18-0243.

  7. Cree-Green M, Triolo TM, Nadeau KJ. Etiology of insulin resistance in youth with type 2 diabetes. Curr Diab Rep. 2013;13(1):81-88. doi:10.1007/s11892-012-0341-0

  8. Goran MI, Gower BA. Longitudinal study on pubertal insulin resistance. Diabetes. 2001;50(11):2444-2450. doi:10.2337/diabetes.50.11.2444

  9. Childhood obesity facts. Centers for Disease Control and Prevention. Accessed October 3, 2022. https://www.cdc.gov/obesity/data/childhood.html 

  10. Copeland KC, Zeitler P, Geffner M, et al. Characteristics of adolescents and youth with recent-onset type 2 diabetes: the TODAY cohort at baseline. J Clin Endocrinol Metab. 2011;96(1):159-167. doi:10.1210/jc.2010-1642

  11. Arslanian S, Bacha F, Grey M, Marcus MD, White NH, Zeitler P. Evaluation and management of youth-onset type 2 diabetes: a position statement by the American Diabetes Association. Diabetes Care. 2018;41(12):2648-2668. doi:10.2337/dci18-0052

  12. Anderson BJ, Edelstein S, Abramson NW, et al. Depressive symptoms and quality of life in adolescents with type 2 diabetes: baseline data from the TODAY study. Diabetes Care. 2011;34(10):2205-2207. doi:10.2337/dc11-0431

  13. TODAY Study Group. Treatment options for type 2 diabetes in adolescents and youth: a study of the comparative efficacy of metformin alone or in combination with rosiglitazone or lifestyle intervention in adolescents with type 2 diabetes. Pediatr Diabetes. 2007;8(2):74-87. doi:10.1111/j.1399-5448.2007.00237.x

  14. Dart AB, Martens PJ, Rigatto C, Brownell MD, Dean HJ, Sellers EA. Earlier onset of complications in youth with type 2 diabetes. Diabetes Care. 2014;37(2):436-443. doi:10.2337/dc13-0954

  15. Arslanian SA, Hannon T, Zeitler P et al. Once-weekly dulaglutide for the treatment of youths with type 2 diabetes. N Engl J Med. 2022;387(5):433-443. doi:10.1056/NEJMoa2204601

  16. Tamborlane WV, Barrientos-Pérez M, Fainberg U, et al. Liraglutide in children and adolescents with type 2 diabetes. N Engl J Med. 2019;381(7):637-646. doi:10.1056/NEJMoa1903822

  17. Tamborlane WV, Bishai R, Geller D, et al. Once-weekly exenatide in youth with type 2 diabetes. Diabetes Care. 2022;45(8):1833-1840. doi:10.2337/dc21-2275

  18. Inge TH, Laffel LM, Jenkins TM, et al. Comparison of surgical and medical therapy for type 2 diabetes in severely obese adolescents. JAMA Pediatr. 2018;172(5):452-460. doi:10.1001/jamapediatrics.2017.5763

  19. Molinari AM, Shubrook JH. Treatment options and current guidelines of care for pediatric type 2 diabetes patients: a narrative review. J Osteopath Med. 2021;121(4):431-440. doi:10.1515/jom-2020-0172

 

References

  1. National and state diabetes trends 2021. Centers for Disease Control and Prevention. Accessed September 26, 2022. https://www.cdc.gov/diabetes/library/reports/reportcard/national-state-diabetes-trends.html

  2. National diabetes statistics report. Centers for Disease Control and Prevention. Accessed September 26, 2022. https://www.cdc.gov/diabetes/data/statistics-report/index.html 

  3. National diabetes statistics report. Estimates of diabetes and its burden in the United States. Centers for Disease Control and Prevention. Accessed September 26, 2022. https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf 

  4. RISE Consortium. Metabolic contrasts between youth and adults with impaired glucose tolerance or recently diagnosed type 2 diabetes: I. Observations using the hyperglycemic clamp. Diabetes Care. 2018;41(8):1696-1706. doi:10.2337/dc18-0244

  5. Andes LJ, Cheng YJ, Rolka DB, Gregg EW, Imperatore G. Prevalence of prediabetes among adolescents and young adults in the United States, 2005-2016. JAMA Pediatr. 2020;174:e194498. doi:10.1001/jamapediatrics.2019.4498

  6. RISE Consortium. Metabolic contrasts between youth and adults with impaired glucose tolerance or recently diagnosed type 2 diabetes: II. Observations using the oral glucose tolerance test. Diabetes Care. 2018;41(8):1707-1716. doi:10.2337/dc18-0243.

  7. Cree-Green M, Triolo TM, Nadeau KJ. Etiology of insulin resistance in youth with type 2 diabetes. Curr Diab Rep. 2013;13(1):81-88. doi:10.1007/s11892-012-0341-0

  8. Goran MI, Gower BA. Longitudinal study on pubertal insulin resistance. Diabetes. 2001;50(11):2444-2450. doi:10.2337/diabetes.50.11.2444

  9. Childhood obesity facts. Centers for Disease Control and Prevention. Accessed October 3, 2022. https://www.cdc.gov/obesity/data/childhood.html 

  10. Copeland KC, Zeitler P, Geffner M, et al. Characteristics of adolescents and youth with recent-onset type 2 diabetes: the TODAY cohort at baseline. J Clin Endocrinol Metab. 2011;96(1):159-167. doi:10.1210/jc.2010-1642

  11. Arslanian S, Bacha F, Grey M, Marcus MD, White NH, Zeitler P. Evaluation and management of youth-onset type 2 diabetes: a position statement by the American Diabetes Association. Diabetes Care. 2018;41(12):2648-2668. doi:10.2337/dci18-0052

  12. Anderson BJ, Edelstein S, Abramson NW, et al. Depressive symptoms and quality of life in adolescents with type 2 diabetes: baseline data from the TODAY study. Diabetes Care. 2011;34(10):2205-2207. doi:10.2337/dc11-0431

  13. TODAY Study Group. Treatment options for type 2 diabetes in adolescents and youth: a study of the comparative efficacy of metformin alone or in combination with rosiglitazone or lifestyle intervention in adolescents with type 2 diabetes. Pediatr Diabetes. 2007;8(2):74-87. doi:10.1111/j.1399-5448.2007.00237.x

  14. Dart AB, Martens PJ, Rigatto C, Brownell MD, Dean HJ, Sellers EA. Earlier onset of complications in youth with type 2 diabetes. Diabetes Care. 2014;37(2):436-443. doi:10.2337/dc13-0954

  15. Arslanian SA, Hannon T, Zeitler P et al. Once-weekly dulaglutide for the treatment of youths with type 2 diabetes. N Engl J Med. 2022;387(5):433-443. doi:10.1056/NEJMoa2204601

  16. Tamborlane WV, Barrientos-Pérez M, Fainberg U, et al. Liraglutide in children and adolescents with type 2 diabetes. N Engl J Med. 2019;381(7):637-646. doi:10.1056/NEJMoa1903822

  17. Tamborlane WV, Bishai R, Geller D, et al. Once-weekly exenatide in youth with type 2 diabetes. Diabetes Care. 2022;45(8):1833-1840. doi:10.2337/dc21-2275

  18. Inge TH, Laffel LM, Jenkins TM, et al. Comparison of surgical and medical therapy for type 2 diabetes in severely obese adolescents. JAMA Pediatr. 2018;172(5):452-460. doi:10.1001/jamapediatrics.2017.5763

  19. Molinari AM, Shubrook JH. Treatment options and current guidelines of care for pediatric type 2 diabetes patients: a narrative review. J Osteopath Med. 2021;121(4):431-440. doi:10.1515/jom-2020-0172

 

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Nick Burwick, MD, discusses important takeaways that he gathered from the AVAHO 2022 meeting in San Diego. In keeping with this year's theme of self-care in cancer care, the keynote speaker, 'Patient Lee' Tomlinson, made a big impact on Dr Burwick with a motivational message about practicing compassion for not only your patients, but also for yourself. This theme continued with Dr Fay Hlubocky's presentation on resources available for self-care.

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Nick Burwick, MD, discusses important takeaways that he gathered from the AVAHO 2022 meeting in San Diego. In keeping with this year's theme of self-care in cancer care, the keynote speaker, 'Patient Lee' Tomlinson, made a big impact on Dr Burwick with a motivational message about practicing compassion for not only your patients, but also for yourself. This theme continued with Dr Fay Hlubocky's presentation on resources available for self-care.

Dr Burwick also appreciated the multidisciplinary aspects of this year's AVAHO meeting that showcased the range of VA Whole Health options, the implementation of the Schwartz Rounds, and a diverse group of cancer care providers.

Nick Burwick, MD, discusses important takeaways that he gathered from the AVAHO 2022 meeting in San Diego. In keeping with this year's theme of self-care in cancer care, the keynote speaker, 'Patient Lee' Tomlinson, made a big impact on Dr Burwick with a motivational message about practicing compassion for not only your patients, but also for yourself. This theme continued with Dr Fay Hlubocky's presentation on resources available for self-care.

Dr Burwick also appreciated the multidisciplinary aspects of this year's AVAHO meeting that showcased the range of VA Whole Health options, the implementation of the Schwartz Rounds, and a diverse group of cancer care providers.

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AVAHO 2022: The Necessity of Self-care in Cancer Care

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Bernadette Heron, PharmD, summarizes the offerings at the AVAHO 2022 meeting, from the standard sharing of updates across disciplines and specialties to the more specific focus on the role of self-care in cancer care.

Importantly, Dr Heron underscores the connection between the concept of self-care and the implements required for its realization in the clinical setting, resulting in an assortment of tools that practitioners can draw on as they continue the conversation that drives the evolution of cancer care. 

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Bernadette Heron, PharmD, summarizes the offerings at the AVAHO 2022 meeting, from the standard sharing of updates across disciplines and specialties to the more specific focus on the role of self-care in cancer care.

Importantly, Dr Heron underscores the connection between the concept of self-care and the implements required for its realization in the clinical setting, resulting in an assortment of tools that practitioners can draw on as they continue the conversation that drives the evolution of cancer care. 

Bernadette Heron, PharmD, summarizes the offerings at the AVAHO 2022 meeting, from the standard sharing of updates across disciplines and specialties to the more specific focus on the role of self-care in cancer care.

Importantly, Dr Heron underscores the connection between the concept of self-care and the implements required for its realization in the clinical setting, resulting in an assortment of tools that practitioners can draw on as they continue the conversation that drives the evolution of cancer care. 

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