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PTSD symptoms in women tied to worse heart, brain health
TOPLINE:
METHODOLOGY:
- Researchers conducted a cross-sectional study of 274 women (mean age, 59 years) participating in the MsBrain study of menopause and brain health.
- As part of the study, the women completed the PTSD Checklist–Civilian Version and underwent physical and neuropsychological testing, as well as carotid artery ultrasonography and brain MRI.
- Outcomes of interest were associations of PTSD symptoms with carotid intima media thickness (IMT), brain white matter hyperintensity volume (WMHV), and cognition, assessed in linear regression models.
- Interactions by APOEε4 were assessed; covariates included age, race/ethnicity, education, and CVD risk factors.
TAKEAWAY:
- Higher PTSD symptoms were associated with greater carotid IMT (P = .03); associations of PTSD symptoms with neurocognitive outcomes varied significantly by APOEε4 status.
- Among APOEε4 carriers, PTSD symptoms were associated with greater whole-brain WMHV (P = .009), periventricular WMHV (P = .02), deep WMHV (P = .01), and frontal WMHV (P = .04) in multivariable models.
- APOEε4 carriers with PTSD symptoms also had poorer cognition, specifically attention and working memory (P = .02), semantic fluency (P = .01), perceptual speed (P = .002) and processing speed (P = .002), in multivariable models.
IN PRACTICE:
“This study sheds important insight on the implications of PTSD symptoms to women’s cardiovascular and neurocognitive health. Our findings indicate that the APOEε4 genotype may identify a group of women with PTSD symptoms at particular risk for poor neurocognitive health,” the authors wrote.
SOURCE:
The study, with first author Rebecca Thurston, PhD, of the department of psychiatry, University of Pittsburgh, was published online in JAMA Network Open.
LIMITATIONS:
No diagnostic clinical interviews were conducted, and PTSD treatment was not assessed. All participants identified as cisgender, and most were non-Hispanic Black or White. The study was observational and cross-sectional, precluding assertions about directionality or causality.
DISCLOSURES:
The study was funded by the National Institutes of Health, the University of Pittsburgh Clinical and Translational Science Institute, and the University of Pittsburgh Small Molecule Biomarker Core. Dr. Thurston reported receiving personal fees from Astellas Pharma, Bayer, Hello Therapeutics, Vira Health, and Happify Health outside the submitted work.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Researchers conducted a cross-sectional study of 274 women (mean age, 59 years) participating in the MsBrain study of menopause and brain health.
- As part of the study, the women completed the PTSD Checklist–Civilian Version and underwent physical and neuropsychological testing, as well as carotid artery ultrasonography and brain MRI.
- Outcomes of interest were associations of PTSD symptoms with carotid intima media thickness (IMT), brain white matter hyperintensity volume (WMHV), and cognition, assessed in linear regression models.
- Interactions by APOEε4 were assessed; covariates included age, race/ethnicity, education, and CVD risk factors.
TAKEAWAY:
- Higher PTSD symptoms were associated with greater carotid IMT (P = .03); associations of PTSD symptoms with neurocognitive outcomes varied significantly by APOEε4 status.
- Among APOEε4 carriers, PTSD symptoms were associated with greater whole-brain WMHV (P = .009), periventricular WMHV (P = .02), deep WMHV (P = .01), and frontal WMHV (P = .04) in multivariable models.
- APOEε4 carriers with PTSD symptoms also had poorer cognition, specifically attention and working memory (P = .02), semantic fluency (P = .01), perceptual speed (P = .002) and processing speed (P = .002), in multivariable models.
IN PRACTICE:
“This study sheds important insight on the implications of PTSD symptoms to women’s cardiovascular and neurocognitive health. Our findings indicate that the APOEε4 genotype may identify a group of women with PTSD symptoms at particular risk for poor neurocognitive health,” the authors wrote.
SOURCE:
The study, with first author Rebecca Thurston, PhD, of the department of psychiatry, University of Pittsburgh, was published online in JAMA Network Open.
LIMITATIONS:
No diagnostic clinical interviews were conducted, and PTSD treatment was not assessed. All participants identified as cisgender, and most were non-Hispanic Black or White. The study was observational and cross-sectional, precluding assertions about directionality or causality.
DISCLOSURES:
The study was funded by the National Institutes of Health, the University of Pittsburgh Clinical and Translational Science Institute, and the University of Pittsburgh Small Molecule Biomarker Core. Dr. Thurston reported receiving personal fees from Astellas Pharma, Bayer, Hello Therapeutics, Vira Health, and Happify Health outside the submitted work.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Researchers conducted a cross-sectional study of 274 women (mean age, 59 years) participating in the MsBrain study of menopause and brain health.
- As part of the study, the women completed the PTSD Checklist–Civilian Version and underwent physical and neuropsychological testing, as well as carotid artery ultrasonography and brain MRI.
- Outcomes of interest were associations of PTSD symptoms with carotid intima media thickness (IMT), brain white matter hyperintensity volume (WMHV), and cognition, assessed in linear regression models.
- Interactions by APOEε4 were assessed; covariates included age, race/ethnicity, education, and CVD risk factors.
TAKEAWAY:
- Higher PTSD symptoms were associated with greater carotid IMT (P = .03); associations of PTSD symptoms with neurocognitive outcomes varied significantly by APOEε4 status.
- Among APOEε4 carriers, PTSD symptoms were associated with greater whole-brain WMHV (P = .009), periventricular WMHV (P = .02), deep WMHV (P = .01), and frontal WMHV (P = .04) in multivariable models.
- APOEε4 carriers with PTSD symptoms also had poorer cognition, specifically attention and working memory (P = .02), semantic fluency (P = .01), perceptual speed (P = .002) and processing speed (P = .002), in multivariable models.
IN PRACTICE:
“This study sheds important insight on the implications of PTSD symptoms to women’s cardiovascular and neurocognitive health. Our findings indicate that the APOEε4 genotype may identify a group of women with PTSD symptoms at particular risk for poor neurocognitive health,” the authors wrote.
SOURCE:
The study, with first author Rebecca Thurston, PhD, of the department of psychiatry, University of Pittsburgh, was published online in JAMA Network Open.
LIMITATIONS:
No diagnostic clinical interviews were conducted, and PTSD treatment was not assessed. All participants identified as cisgender, and most were non-Hispanic Black or White. The study was observational and cross-sectional, precluding assertions about directionality or causality.
DISCLOSURES:
The study was funded by the National Institutes of Health, the University of Pittsburgh Clinical and Translational Science Institute, and the University of Pittsburgh Small Molecule Biomarker Core. Dr. Thurston reported receiving personal fees from Astellas Pharma, Bayer, Hello Therapeutics, Vira Health, and Happify Health outside the submitted work.
A version of this article first appeared on Medscape.com.
Low-dose aspirin provokes no flares in patients with IBD during pregnancy
, shows new research presented in October at the American College of Gastroenterology (ACG) Annual Scientific Meeting.
Low-dose aspirin is recommended for pregnant women who are at risk of hypertensive disorders, such as eclampsia, preeclampsia, and gestational diabetes, said Uma Mahadevan, MD, AGAF, a gastroenterologist and director of the University of California, San Francisco Colitis and Crohn’s Disease Center, who presented the research at the meeting. Regular nonsteroidal anti-inflammatory drug use has been associated with increased disease activity in patients with inflammatory bowel disease (IBD), but the impact of low-dose aspirin on IBD during pregnancy has not been well studied, she said.
The study, which was conducted between January 2013 and December 2022 at a single clinic, included 325 women (mean age 34 years) with IBD who had at least one pregnancy. Of these, 53% had ulcerative colitis and 47% had Crohn’s disease. The primary outcome was IBD flare during pregnancy or within 6 months postpartum. Flares were defined as an IBD-related hospitalization and/or surgery, new initiation of IBD therapy, elevated level of fecal calprotectin greater than 150 micrograms per milligram, or new active endoscopic disease.
A total of 95 patients (29%) used low-dose aspirin during pregnancy; 59 took 81 mg and 36 took 162 mg. The cumulative flare rate was similar between patients who took low-dose aspirin and those who did not (24% vs. 26%, P = .83). However, patients who took low-dose aspirin were significantly more likely than were those who did not to experience preterm birth, younger gestational age at delivery, and cesarean delivery (22.1% vs. 6.1%, 38 weeks vs. 39 weeks, 51% vs. 27%, respectively, P < .01 for all).
Overall rates of hypertensive disorders of pregnancy were similar between the low-dose aspirin and non–low-dose aspirin groups (22% vs. 19%, respectively, P = .59), but individuals on low-dose aspirin were more likely to experience preeclampsia than were those not on low-dose aspirin (11.6% vs 4.3%, P = .03).
The study findings support the benefits of aspirin for pregnant women at increased risk for these conditions. “Pregnant patients with IBD should be offered low-dose aspirin without concern for increased risk of flares,” Dr. Mahadevan said.
“This is a very practical study with high relevance in our everyday management of IBD patients,” Shannon Chang, MD, a specialist in IBD with NYU Langone Health, said in an interview. “Having this study helps us understand the risk of increased IBD activity in the setting of aspirin use during pregnancy.”
Dr. Chang was not surprised by the findings. “Since the [ACOG] guidelines changed several years ago, there have been more and more patients with IBD who have taken aspirin during their pregnancies and the results of this study seem to match what we see in clinical practice,” she said. “This study will help us counsel our patients on the safety of aspirin use during pregnancy, and the findings will also be useful for discussions with our obstetrics colleagues who may seek guidance on the safety of aspirin [use] in our pregnant IBD patients.”
The study received no outside funding. Dr. Mahadevan disclosed relationships with AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Gilead, Janssen, Pfizer, Prometheus Biosciences, Protagonist Therapeutics, Rani Therapeutics, Roivant, and Takeda. Dr. Chang disclosed serving as a consultant for Pfizer, AbbVie, and BMS.
, shows new research presented in October at the American College of Gastroenterology (ACG) Annual Scientific Meeting.
Low-dose aspirin is recommended for pregnant women who are at risk of hypertensive disorders, such as eclampsia, preeclampsia, and gestational diabetes, said Uma Mahadevan, MD, AGAF, a gastroenterologist and director of the University of California, San Francisco Colitis and Crohn’s Disease Center, who presented the research at the meeting. Regular nonsteroidal anti-inflammatory drug use has been associated with increased disease activity in patients with inflammatory bowel disease (IBD), but the impact of low-dose aspirin on IBD during pregnancy has not been well studied, she said.
The study, which was conducted between January 2013 and December 2022 at a single clinic, included 325 women (mean age 34 years) with IBD who had at least one pregnancy. Of these, 53% had ulcerative colitis and 47% had Crohn’s disease. The primary outcome was IBD flare during pregnancy or within 6 months postpartum. Flares were defined as an IBD-related hospitalization and/or surgery, new initiation of IBD therapy, elevated level of fecal calprotectin greater than 150 micrograms per milligram, or new active endoscopic disease.
A total of 95 patients (29%) used low-dose aspirin during pregnancy; 59 took 81 mg and 36 took 162 mg. The cumulative flare rate was similar between patients who took low-dose aspirin and those who did not (24% vs. 26%, P = .83). However, patients who took low-dose aspirin were significantly more likely than were those who did not to experience preterm birth, younger gestational age at delivery, and cesarean delivery (22.1% vs. 6.1%, 38 weeks vs. 39 weeks, 51% vs. 27%, respectively, P < .01 for all).
Overall rates of hypertensive disorders of pregnancy were similar between the low-dose aspirin and non–low-dose aspirin groups (22% vs. 19%, respectively, P = .59), but individuals on low-dose aspirin were more likely to experience preeclampsia than were those not on low-dose aspirin (11.6% vs 4.3%, P = .03).
The study findings support the benefits of aspirin for pregnant women at increased risk for these conditions. “Pregnant patients with IBD should be offered low-dose aspirin without concern for increased risk of flares,” Dr. Mahadevan said.
“This is a very practical study with high relevance in our everyday management of IBD patients,” Shannon Chang, MD, a specialist in IBD with NYU Langone Health, said in an interview. “Having this study helps us understand the risk of increased IBD activity in the setting of aspirin use during pregnancy.”
Dr. Chang was not surprised by the findings. “Since the [ACOG] guidelines changed several years ago, there have been more and more patients with IBD who have taken aspirin during their pregnancies and the results of this study seem to match what we see in clinical practice,” she said. “This study will help us counsel our patients on the safety of aspirin use during pregnancy, and the findings will also be useful for discussions with our obstetrics colleagues who may seek guidance on the safety of aspirin [use] in our pregnant IBD patients.”
The study received no outside funding. Dr. Mahadevan disclosed relationships with AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Gilead, Janssen, Pfizer, Prometheus Biosciences, Protagonist Therapeutics, Rani Therapeutics, Roivant, and Takeda. Dr. Chang disclosed serving as a consultant for Pfizer, AbbVie, and BMS.
, shows new research presented in October at the American College of Gastroenterology (ACG) Annual Scientific Meeting.
Low-dose aspirin is recommended for pregnant women who are at risk of hypertensive disorders, such as eclampsia, preeclampsia, and gestational diabetes, said Uma Mahadevan, MD, AGAF, a gastroenterologist and director of the University of California, San Francisco Colitis and Crohn’s Disease Center, who presented the research at the meeting. Regular nonsteroidal anti-inflammatory drug use has been associated with increased disease activity in patients with inflammatory bowel disease (IBD), but the impact of low-dose aspirin on IBD during pregnancy has not been well studied, she said.
The study, which was conducted between January 2013 and December 2022 at a single clinic, included 325 women (mean age 34 years) with IBD who had at least one pregnancy. Of these, 53% had ulcerative colitis and 47% had Crohn’s disease. The primary outcome was IBD flare during pregnancy or within 6 months postpartum. Flares were defined as an IBD-related hospitalization and/or surgery, new initiation of IBD therapy, elevated level of fecal calprotectin greater than 150 micrograms per milligram, or new active endoscopic disease.
A total of 95 patients (29%) used low-dose aspirin during pregnancy; 59 took 81 mg and 36 took 162 mg. The cumulative flare rate was similar between patients who took low-dose aspirin and those who did not (24% vs. 26%, P = .83). However, patients who took low-dose aspirin were significantly more likely than were those who did not to experience preterm birth, younger gestational age at delivery, and cesarean delivery (22.1% vs. 6.1%, 38 weeks vs. 39 weeks, 51% vs. 27%, respectively, P < .01 for all).
Overall rates of hypertensive disorders of pregnancy were similar between the low-dose aspirin and non–low-dose aspirin groups (22% vs. 19%, respectively, P = .59), but individuals on low-dose aspirin were more likely to experience preeclampsia than were those not on low-dose aspirin (11.6% vs 4.3%, P = .03).
The study findings support the benefits of aspirin for pregnant women at increased risk for these conditions. “Pregnant patients with IBD should be offered low-dose aspirin without concern for increased risk of flares,” Dr. Mahadevan said.
“This is a very practical study with high relevance in our everyday management of IBD patients,” Shannon Chang, MD, a specialist in IBD with NYU Langone Health, said in an interview. “Having this study helps us understand the risk of increased IBD activity in the setting of aspirin use during pregnancy.”
Dr. Chang was not surprised by the findings. “Since the [ACOG] guidelines changed several years ago, there have been more and more patients with IBD who have taken aspirin during their pregnancies and the results of this study seem to match what we see in clinical practice,” she said. “This study will help us counsel our patients on the safety of aspirin use during pregnancy, and the findings will also be useful for discussions with our obstetrics colleagues who may seek guidance on the safety of aspirin [use] in our pregnant IBD patients.”
The study received no outside funding. Dr. Mahadevan disclosed relationships with AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Gilead, Janssen, Pfizer, Prometheus Biosciences, Protagonist Therapeutics, Rani Therapeutics, Roivant, and Takeda. Dr. Chang disclosed serving as a consultant for Pfizer, AbbVie, and BMS.
FROM ACG 2023
Risks quantified in medically optimized pregnancy with lupus
SAN DIEGO – In pregnant women with systemic lupus erythematosus (SLE), those with ill-timed pregnancies had poorer pregnancy outcomes, including preeclampsia and preterm birth.
Women with autoimmune conditions are at an increased risk for pregnancy complications, including pregnancy loss, preterm delivery, and increased need for cesarean delivery, said Catherine Sims, MD, a rheumatologist at Duke Health in Durham, N.C., who is focused on reproductive rheumatology. “The natural question, both clinically and from a research perspective, is: ‘What can we do in order to mitigate or minimize these complications?’ ” she said during a presentation at the annual meeting of the American College of Rheumatology.
While research suggests that patients who plan their pregnancies during times of well-controlled disease have the “best chances of improved pregnancy outcomes,” Dr. Sims and colleagues wanted to quantify how planning for pregnancy affected reproductive outcomes.
Dr. Sims recruited pregnant women with SLE and assessed if the women were medically optimized for pregnancy, if the pregnancy was intended, or both. Intended pregnancy was assessed by using a validated self-reported survey called the London Measure of Unplanned Pregnancy. Pregnant women were considered “medically optimized” for pregnancy if they were not on teratogenic medication, had continued pregnancy-compatible SLE medications, and had a urine protein-creatinine ratio of less than 1 gram in the 6 months prior to or during the first trimester. Intended pregnancies that were medically optimized were classified as “well timed.”
Of the 115 women enrolled in the study, about half had well-timed pregnancies, 20% were neither intended nor medically optimized, 17% were not intended but medically optimized, and 13% were intended but not medically optimized.
Women with ill-timed pregnancy – either not medically optimized and/or unintended – were generally younger and more likely to be single, on Medicare or Medicaid, and on income of less than $50,000 per year.
Ill-timed pregnancies had higher rates of mycophenolate exposure and higher physician-reported SLE disease activity. While patient-reported SLE activity was higher in patients who were not personally ready for pregnancy, in patients who had an intended pregnancy, there was no difference in self-reported SLE activity between those that were medically optimized and those not medically optimized.
“About a third of our patients are actually underestimating their true disease activity level when they are preparing for pregnancy,” Dr. Sims said. For example, while persistent proteinuria in a patient would drive up physician assessment of disease activity, the patient may not be experiencing any symptoms and is unaware of her condition.
In terms of pregnancy outcomes, women with unintended pregnancies had a 2.5 times higher incidence of preeclampsia, compared with those with intended pregnancies. Patients with unplanned pregnancies were also significantly more likely to experience stillbirth.
Women who were not medically optimized for pregnancy were three times as likely to experience preterm birth and preeclampsia compared with those with optimized pregnancies.
These outcomes drive home the importance of optimizing patients for pregnancy, Dr. Sims said, and effectively communicating this importance to patients, especially when they might not be perceiving their disease activity.
The study’s findings show providers “what we thought we knew, which is that there are some patients that are not as aware of their risk,” commented Lisa R. Sammaritano, MD, Hospital for Special Surgery, New York, who moderated the session where the research was presented. “It brings home the importance of counselling our patients about contraception [as well as] the importance of planning.”
Dr. Sims added that it is “crucial” to make this information easily accessible and digestible to patients. One important resource she mentioned is the HOP-STEP program, which stands for Healthy Outcomes in Pregnancy with SLE Through Education of Providers. The program, directed by researchers at Duke University, is designed to improve pregnancy planning in people with lupus. Direct-to-patient resources are key, she said, as patients can often be nervous to ask about pregnancy planning during appointments.
“They won’t want to bring a pregnancy with me in clinic because they’re afraid I’m just going to say, ‘don’t do it,’ ” Dr. Sims said. “But we are making decisions with the patient. Our patients are not asking for permission, but telling us what they want, and we need to meet them where they are at.”
A version of this article appeared on Medscape.com.
SAN DIEGO – In pregnant women with systemic lupus erythematosus (SLE), those with ill-timed pregnancies had poorer pregnancy outcomes, including preeclampsia and preterm birth.
Women with autoimmune conditions are at an increased risk for pregnancy complications, including pregnancy loss, preterm delivery, and increased need for cesarean delivery, said Catherine Sims, MD, a rheumatologist at Duke Health in Durham, N.C., who is focused on reproductive rheumatology. “The natural question, both clinically and from a research perspective, is: ‘What can we do in order to mitigate or minimize these complications?’ ” she said during a presentation at the annual meeting of the American College of Rheumatology.
While research suggests that patients who plan their pregnancies during times of well-controlled disease have the “best chances of improved pregnancy outcomes,” Dr. Sims and colleagues wanted to quantify how planning for pregnancy affected reproductive outcomes.
Dr. Sims recruited pregnant women with SLE and assessed if the women were medically optimized for pregnancy, if the pregnancy was intended, or both. Intended pregnancy was assessed by using a validated self-reported survey called the London Measure of Unplanned Pregnancy. Pregnant women were considered “medically optimized” for pregnancy if they were not on teratogenic medication, had continued pregnancy-compatible SLE medications, and had a urine protein-creatinine ratio of less than 1 gram in the 6 months prior to or during the first trimester. Intended pregnancies that were medically optimized were classified as “well timed.”
Of the 115 women enrolled in the study, about half had well-timed pregnancies, 20% were neither intended nor medically optimized, 17% were not intended but medically optimized, and 13% were intended but not medically optimized.
Women with ill-timed pregnancy – either not medically optimized and/or unintended – were generally younger and more likely to be single, on Medicare or Medicaid, and on income of less than $50,000 per year.
Ill-timed pregnancies had higher rates of mycophenolate exposure and higher physician-reported SLE disease activity. While patient-reported SLE activity was higher in patients who were not personally ready for pregnancy, in patients who had an intended pregnancy, there was no difference in self-reported SLE activity between those that were medically optimized and those not medically optimized.
“About a third of our patients are actually underestimating their true disease activity level when they are preparing for pregnancy,” Dr. Sims said. For example, while persistent proteinuria in a patient would drive up physician assessment of disease activity, the patient may not be experiencing any symptoms and is unaware of her condition.
In terms of pregnancy outcomes, women with unintended pregnancies had a 2.5 times higher incidence of preeclampsia, compared with those with intended pregnancies. Patients with unplanned pregnancies were also significantly more likely to experience stillbirth.
Women who were not medically optimized for pregnancy were three times as likely to experience preterm birth and preeclampsia compared with those with optimized pregnancies.
These outcomes drive home the importance of optimizing patients for pregnancy, Dr. Sims said, and effectively communicating this importance to patients, especially when they might not be perceiving their disease activity.
The study’s findings show providers “what we thought we knew, which is that there are some patients that are not as aware of their risk,” commented Lisa R. Sammaritano, MD, Hospital for Special Surgery, New York, who moderated the session where the research was presented. “It brings home the importance of counselling our patients about contraception [as well as] the importance of planning.”
Dr. Sims added that it is “crucial” to make this information easily accessible and digestible to patients. One important resource she mentioned is the HOP-STEP program, which stands for Healthy Outcomes in Pregnancy with SLE Through Education of Providers. The program, directed by researchers at Duke University, is designed to improve pregnancy planning in people with lupus. Direct-to-patient resources are key, she said, as patients can often be nervous to ask about pregnancy planning during appointments.
“They won’t want to bring a pregnancy with me in clinic because they’re afraid I’m just going to say, ‘don’t do it,’ ” Dr. Sims said. “But we are making decisions with the patient. Our patients are not asking for permission, but telling us what they want, and we need to meet them where they are at.”
A version of this article appeared on Medscape.com.
SAN DIEGO – In pregnant women with systemic lupus erythematosus (SLE), those with ill-timed pregnancies had poorer pregnancy outcomes, including preeclampsia and preterm birth.
Women with autoimmune conditions are at an increased risk for pregnancy complications, including pregnancy loss, preterm delivery, and increased need for cesarean delivery, said Catherine Sims, MD, a rheumatologist at Duke Health in Durham, N.C., who is focused on reproductive rheumatology. “The natural question, both clinically and from a research perspective, is: ‘What can we do in order to mitigate or minimize these complications?’ ” she said during a presentation at the annual meeting of the American College of Rheumatology.
While research suggests that patients who plan their pregnancies during times of well-controlled disease have the “best chances of improved pregnancy outcomes,” Dr. Sims and colleagues wanted to quantify how planning for pregnancy affected reproductive outcomes.
Dr. Sims recruited pregnant women with SLE and assessed if the women were medically optimized for pregnancy, if the pregnancy was intended, or both. Intended pregnancy was assessed by using a validated self-reported survey called the London Measure of Unplanned Pregnancy. Pregnant women were considered “medically optimized” for pregnancy if they were not on teratogenic medication, had continued pregnancy-compatible SLE medications, and had a urine protein-creatinine ratio of less than 1 gram in the 6 months prior to or during the first trimester. Intended pregnancies that were medically optimized were classified as “well timed.”
Of the 115 women enrolled in the study, about half had well-timed pregnancies, 20% were neither intended nor medically optimized, 17% were not intended but medically optimized, and 13% were intended but not medically optimized.
Women with ill-timed pregnancy – either not medically optimized and/or unintended – were generally younger and more likely to be single, on Medicare or Medicaid, and on income of less than $50,000 per year.
Ill-timed pregnancies had higher rates of mycophenolate exposure and higher physician-reported SLE disease activity. While patient-reported SLE activity was higher in patients who were not personally ready for pregnancy, in patients who had an intended pregnancy, there was no difference in self-reported SLE activity between those that were medically optimized and those not medically optimized.
“About a third of our patients are actually underestimating their true disease activity level when they are preparing for pregnancy,” Dr. Sims said. For example, while persistent proteinuria in a patient would drive up physician assessment of disease activity, the patient may not be experiencing any symptoms and is unaware of her condition.
In terms of pregnancy outcomes, women with unintended pregnancies had a 2.5 times higher incidence of preeclampsia, compared with those with intended pregnancies. Patients with unplanned pregnancies were also significantly more likely to experience stillbirth.
Women who were not medically optimized for pregnancy were three times as likely to experience preterm birth and preeclampsia compared with those with optimized pregnancies.
These outcomes drive home the importance of optimizing patients for pregnancy, Dr. Sims said, and effectively communicating this importance to patients, especially when they might not be perceiving their disease activity.
The study’s findings show providers “what we thought we knew, which is that there are some patients that are not as aware of their risk,” commented Lisa R. Sammaritano, MD, Hospital for Special Surgery, New York, who moderated the session where the research was presented. “It brings home the importance of counselling our patients about contraception [as well as] the importance of planning.”
Dr. Sims added that it is “crucial” to make this information easily accessible and digestible to patients. One important resource she mentioned is the HOP-STEP program, which stands for Healthy Outcomes in Pregnancy with SLE Through Education of Providers. The program, directed by researchers at Duke University, is designed to improve pregnancy planning in people with lupus. Direct-to-patient resources are key, she said, as patients can often be nervous to ask about pregnancy planning during appointments.
“They won’t want to bring a pregnancy with me in clinic because they’re afraid I’m just going to say, ‘don’t do it,’ ” Dr. Sims said. “But we are making decisions with the patient. Our patients are not asking for permission, but telling us what they want, and we need to meet them where they are at.”
A version of this article appeared on Medscape.com.
AT ACR 2023
‘Smart’ stethoscope spots peripartum cardiomyopathy
in a large study of obstetric patients in Nigeria.
Demilade A. Adedinsewo, MD, MPH, from Mayo Clinic, Jacksonville, Fla., reported these findings from the Screening for Pregnancy Related Heart Failure in Nigeria (SPEC-AI Nigeria) trial in a press briefing and in a late-breaking trial session at the annual scientific sessions of the American Heart Association.
“The key takeaway,” Dr. Adedinsewo said in an interview, “is recognizing that a simple, low-impact tool like a digital stethoscope can dramatically improve the diagnosis of a life-threatening condition, and we can treat it. A large proportion of the women will recover; if we identify them early and treat them appropriately, we can reduce the risk of dying.”
If the device predicted low ejection fraction, the patient went on to have an echocardiogram to confirm cardiomyopathy, defined as a left ventricular ejection fraction (LVEF) <50%.
Peripartum cardiomyopathy was detected in 4% of the women who were screened with this tool, compared with 1.8% of those who received usual care, which included a traditional ECG.
“I believe that the control arm also has about 4% of cardiomyopathy cases, but because they didn’t have the same screening and echo, we’re missing them,” Dr. Adedinsewo said.
Diagnosis of peripartum cardiomyopathy is challenging, she noted, owing to overlap of common symptoms in pregnancy, such as lower-extremity swelling, fatigue, and shortness of breath with mild activity, which are also cardinal symptoms of heart failure.
“We were really impressed by the effectiveness of the tool, looking at how accurate it was when it comes to the sensitivity,” she added. She noted that the digital stethoscope correctly identified 92% of women with LVEF < 50% and 100% of those with LVEF < 40%.
This was the first large, clinical trial to evaluate an AI intervention in pregnancy. The investigators used a portable, battery-operated device that yielded AI results in real time.
Nigeria has the highest rate of pericardium cardiomyopathy of any country. However, one study showed a 16-fold higher rate of cardiomyopathy among African American women, compared with White women in the United States, Dr. Adedinsewo noted. “It will be important to identify who we should be screening to identify more cases,” she said.
A digital stethoscope that provides an ECG is currently available, but the algorithm that powers detection of cardiomyopathy is not yet commercially available.
Findings ‘absolutely startling’
The study discussant in the press briefing, Alexander Tarlochan Singh Sandhu, MD, from Stanford (Calif.) University congratulated the authors on this “valuable study that uses AI tools to solve a real health problem.”
Finding that 4% of the women in the intervention arm had reduced ejection fraction is “absolutely startling,” he said, “and speaks to how important improving our diagnosis in this space is.
“Where the burden of disease is high, a tool like this can be so incredibly valuable,” he said. He noted that the investigators identified 2% more patients with peripartum cardiomyopathy.
“This is an example of the potential of AI tools that can actually improve access to care and improve quality of care in resource-limited settings,” he said. “We need to move to understanding how to implement this into subsequent care [and] figure out what the next steps are to improve their outcomes.”
“The main takeaway is that, in areas where there is a very high prevalence of a morbid condition, a prescreening tool like this may be helpful” for diagnosis, the assigned discussant in the session, Marco Perez, MD, also from Stanford University, told this news organization.
The number of women needed to screen to detect peripartum cardiomyopathy by echocardiography alone is 1 in 23 in Nigeria and 1 in 970 in the United States, he said.
With an AI tool such as this one (sensitivity, 92%; specificity, 80%), the number needed to screen would be 1 in 5.7 in Nigeria and 1 in 194 in the United States, he estimates on the basis of incidence data.
“Because it is so common in Nigeria, a screening method makes a lot of sense,” Dr. Perez said. “The big question that remains is, what is the best screening modality?
“Certainly, this tool helped in bringing down the number of echoes needed to find a case, from the mid 20s down to about 5 or 6, so it certainly does seem to be helpful.”
However, the investigators did not say whether this tool is better than a clinical review of ECG or an AI analysis of ECG alone. It’s not clear whether the phonocardiogram component is significant in conjunction with the ECG component.
Nevertheless, “In a place where there’s a very high prevalence of peripartum cardiomyopathy, like Haiti, like Nigeria, doing something like this makes a lot of sense.
“For the U.S. and the rest of the world, where the prevalence is much lower, even with a tool like this you still would need to do a lot of echoes to find one case, and that may end up not being cost-effective. You would need to screen 200 women with echo to find one case.”
AI-guided screening study
Nigeria has the highest reported incidence of peripartum cardiomyopathy mortality (1 in 100 live births) and the highest number of maternal deaths.
In the United States, where rates of peripartum cardiomyopathy are much lower, maternal deaths are nevertheless higher than in other developed countries and have trended up over the past 3 decades; cardiomyopathy is a key contributor.
The investigators enrolled 1,195 women who were pregnant or had given birth in the past 12 months. The patients were from six teaching hospitals in Nigeria (two in the north and four in the south). They were randomly assigned in a 1:1 ratio to the intervention group (587) or the control group (608).
In the intervention group, clinicians used a smart stethoscope to record a phonocardiogram and a single-lead ECG reading in the V2 position and in an angled position on the patient’s chest wall and to record an ECG from the patient’s fingers. The recordings were sent to a Bluetooth-enabled mobile device (tablet or smartphone), which displayed the phonocardiogram and ECG images and that indicated whether the ejection fraction was normal or low. All patients in the intervention group received an echocardiogram.
In the control group, patients received usual care plus a traditional ECG. They were not required to have an echocardiogram because undergoing an echocardiogram is not part of usual care; however, they could receive an echocardiogram if the ECG suggested that they might need further testing.
The mean age of all the patients was 31 years, and all were Black. At study entry, 73% were pregnant, and 26% were post partum. They had similar comorbidities.
The primary outcome, cardiomyopathy (LVEF <50%) was detected in 24 of 587 patients (4.1%) in the intervention group and in 11 of 608 patients (1.8%) in the control group (odds ratio, 2.3; 95% confidence interval, 1.1-4.8; P = .02).
For the detection of LVEF <50%, the sensitivity was 92% and the specificity was 80%. For the detection of LVEF <40% (a secondary outcome), the sensitivity was 100% and the specificity was 79%.
Dr. Adedinsewo is supported by the Mayo Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) Program, which is funded by the National Institutes of Health. The trial was funded by Mayo Clinic (Centers for Digital Health and Community Health and Engagement Research) and in part by the Mayo Clinic BIRCWH Program. Portable ECG, phonocardiogram recordings, and AI predictions using the digital stethoscope were extracted by the Eko Health team and were sent to the coordinating center for analysis. Eko Health had no role in study design, data collection, data analysis, or data interpretation.
A version of this article appeared on Medscape.com.
in a large study of obstetric patients in Nigeria.
Demilade A. Adedinsewo, MD, MPH, from Mayo Clinic, Jacksonville, Fla., reported these findings from the Screening for Pregnancy Related Heart Failure in Nigeria (SPEC-AI Nigeria) trial in a press briefing and in a late-breaking trial session at the annual scientific sessions of the American Heart Association.
“The key takeaway,” Dr. Adedinsewo said in an interview, “is recognizing that a simple, low-impact tool like a digital stethoscope can dramatically improve the diagnosis of a life-threatening condition, and we can treat it. A large proportion of the women will recover; if we identify them early and treat them appropriately, we can reduce the risk of dying.”
If the device predicted low ejection fraction, the patient went on to have an echocardiogram to confirm cardiomyopathy, defined as a left ventricular ejection fraction (LVEF) <50%.
Peripartum cardiomyopathy was detected in 4% of the women who were screened with this tool, compared with 1.8% of those who received usual care, which included a traditional ECG.
“I believe that the control arm also has about 4% of cardiomyopathy cases, but because they didn’t have the same screening and echo, we’re missing them,” Dr. Adedinsewo said.
Diagnosis of peripartum cardiomyopathy is challenging, she noted, owing to overlap of common symptoms in pregnancy, such as lower-extremity swelling, fatigue, and shortness of breath with mild activity, which are also cardinal symptoms of heart failure.
“We were really impressed by the effectiveness of the tool, looking at how accurate it was when it comes to the sensitivity,” she added. She noted that the digital stethoscope correctly identified 92% of women with LVEF < 50% and 100% of those with LVEF < 40%.
This was the first large, clinical trial to evaluate an AI intervention in pregnancy. The investigators used a portable, battery-operated device that yielded AI results in real time.
Nigeria has the highest rate of pericardium cardiomyopathy of any country. However, one study showed a 16-fold higher rate of cardiomyopathy among African American women, compared with White women in the United States, Dr. Adedinsewo noted. “It will be important to identify who we should be screening to identify more cases,” she said.
A digital stethoscope that provides an ECG is currently available, but the algorithm that powers detection of cardiomyopathy is not yet commercially available.
Findings ‘absolutely startling’
The study discussant in the press briefing, Alexander Tarlochan Singh Sandhu, MD, from Stanford (Calif.) University congratulated the authors on this “valuable study that uses AI tools to solve a real health problem.”
Finding that 4% of the women in the intervention arm had reduced ejection fraction is “absolutely startling,” he said, “and speaks to how important improving our diagnosis in this space is.
“Where the burden of disease is high, a tool like this can be so incredibly valuable,” he said. He noted that the investigators identified 2% more patients with peripartum cardiomyopathy.
“This is an example of the potential of AI tools that can actually improve access to care and improve quality of care in resource-limited settings,” he said. “We need to move to understanding how to implement this into subsequent care [and] figure out what the next steps are to improve their outcomes.”
“The main takeaway is that, in areas where there is a very high prevalence of a morbid condition, a prescreening tool like this may be helpful” for diagnosis, the assigned discussant in the session, Marco Perez, MD, also from Stanford University, told this news organization.
The number of women needed to screen to detect peripartum cardiomyopathy by echocardiography alone is 1 in 23 in Nigeria and 1 in 970 in the United States, he said.
With an AI tool such as this one (sensitivity, 92%; specificity, 80%), the number needed to screen would be 1 in 5.7 in Nigeria and 1 in 194 in the United States, he estimates on the basis of incidence data.
“Because it is so common in Nigeria, a screening method makes a lot of sense,” Dr. Perez said. “The big question that remains is, what is the best screening modality?
“Certainly, this tool helped in bringing down the number of echoes needed to find a case, from the mid 20s down to about 5 or 6, so it certainly does seem to be helpful.”
However, the investigators did not say whether this tool is better than a clinical review of ECG or an AI analysis of ECG alone. It’s not clear whether the phonocardiogram component is significant in conjunction with the ECG component.
Nevertheless, “In a place where there’s a very high prevalence of peripartum cardiomyopathy, like Haiti, like Nigeria, doing something like this makes a lot of sense.
“For the U.S. and the rest of the world, where the prevalence is much lower, even with a tool like this you still would need to do a lot of echoes to find one case, and that may end up not being cost-effective. You would need to screen 200 women with echo to find one case.”
AI-guided screening study
Nigeria has the highest reported incidence of peripartum cardiomyopathy mortality (1 in 100 live births) and the highest number of maternal deaths.
In the United States, where rates of peripartum cardiomyopathy are much lower, maternal deaths are nevertheless higher than in other developed countries and have trended up over the past 3 decades; cardiomyopathy is a key contributor.
The investigators enrolled 1,195 women who were pregnant or had given birth in the past 12 months. The patients were from six teaching hospitals in Nigeria (two in the north and four in the south). They were randomly assigned in a 1:1 ratio to the intervention group (587) or the control group (608).
In the intervention group, clinicians used a smart stethoscope to record a phonocardiogram and a single-lead ECG reading in the V2 position and in an angled position on the patient’s chest wall and to record an ECG from the patient’s fingers. The recordings were sent to a Bluetooth-enabled mobile device (tablet or smartphone), which displayed the phonocardiogram and ECG images and that indicated whether the ejection fraction was normal or low. All patients in the intervention group received an echocardiogram.
In the control group, patients received usual care plus a traditional ECG. They were not required to have an echocardiogram because undergoing an echocardiogram is not part of usual care; however, they could receive an echocardiogram if the ECG suggested that they might need further testing.
The mean age of all the patients was 31 years, and all were Black. At study entry, 73% were pregnant, and 26% were post partum. They had similar comorbidities.
The primary outcome, cardiomyopathy (LVEF <50%) was detected in 24 of 587 patients (4.1%) in the intervention group and in 11 of 608 patients (1.8%) in the control group (odds ratio, 2.3; 95% confidence interval, 1.1-4.8; P = .02).
For the detection of LVEF <50%, the sensitivity was 92% and the specificity was 80%. For the detection of LVEF <40% (a secondary outcome), the sensitivity was 100% and the specificity was 79%.
Dr. Adedinsewo is supported by the Mayo Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) Program, which is funded by the National Institutes of Health. The trial was funded by Mayo Clinic (Centers for Digital Health and Community Health and Engagement Research) and in part by the Mayo Clinic BIRCWH Program. Portable ECG, phonocardiogram recordings, and AI predictions using the digital stethoscope were extracted by the Eko Health team and were sent to the coordinating center for analysis. Eko Health had no role in study design, data collection, data analysis, or data interpretation.
A version of this article appeared on Medscape.com.
in a large study of obstetric patients in Nigeria.
Demilade A. Adedinsewo, MD, MPH, from Mayo Clinic, Jacksonville, Fla., reported these findings from the Screening for Pregnancy Related Heart Failure in Nigeria (SPEC-AI Nigeria) trial in a press briefing and in a late-breaking trial session at the annual scientific sessions of the American Heart Association.
“The key takeaway,” Dr. Adedinsewo said in an interview, “is recognizing that a simple, low-impact tool like a digital stethoscope can dramatically improve the diagnosis of a life-threatening condition, and we can treat it. A large proportion of the women will recover; if we identify them early and treat them appropriately, we can reduce the risk of dying.”
If the device predicted low ejection fraction, the patient went on to have an echocardiogram to confirm cardiomyopathy, defined as a left ventricular ejection fraction (LVEF) <50%.
Peripartum cardiomyopathy was detected in 4% of the women who were screened with this tool, compared with 1.8% of those who received usual care, which included a traditional ECG.
“I believe that the control arm also has about 4% of cardiomyopathy cases, but because they didn’t have the same screening and echo, we’re missing them,” Dr. Adedinsewo said.
Diagnosis of peripartum cardiomyopathy is challenging, she noted, owing to overlap of common symptoms in pregnancy, such as lower-extremity swelling, fatigue, and shortness of breath with mild activity, which are also cardinal symptoms of heart failure.
“We were really impressed by the effectiveness of the tool, looking at how accurate it was when it comes to the sensitivity,” she added. She noted that the digital stethoscope correctly identified 92% of women with LVEF < 50% and 100% of those with LVEF < 40%.
This was the first large, clinical trial to evaluate an AI intervention in pregnancy. The investigators used a portable, battery-operated device that yielded AI results in real time.
Nigeria has the highest rate of pericardium cardiomyopathy of any country. However, one study showed a 16-fold higher rate of cardiomyopathy among African American women, compared with White women in the United States, Dr. Adedinsewo noted. “It will be important to identify who we should be screening to identify more cases,” she said.
A digital stethoscope that provides an ECG is currently available, but the algorithm that powers detection of cardiomyopathy is not yet commercially available.
Findings ‘absolutely startling’
The study discussant in the press briefing, Alexander Tarlochan Singh Sandhu, MD, from Stanford (Calif.) University congratulated the authors on this “valuable study that uses AI tools to solve a real health problem.”
Finding that 4% of the women in the intervention arm had reduced ejection fraction is “absolutely startling,” he said, “and speaks to how important improving our diagnosis in this space is.
“Where the burden of disease is high, a tool like this can be so incredibly valuable,” he said. He noted that the investigators identified 2% more patients with peripartum cardiomyopathy.
“This is an example of the potential of AI tools that can actually improve access to care and improve quality of care in resource-limited settings,” he said. “We need to move to understanding how to implement this into subsequent care [and] figure out what the next steps are to improve their outcomes.”
“The main takeaway is that, in areas where there is a very high prevalence of a morbid condition, a prescreening tool like this may be helpful” for diagnosis, the assigned discussant in the session, Marco Perez, MD, also from Stanford University, told this news organization.
The number of women needed to screen to detect peripartum cardiomyopathy by echocardiography alone is 1 in 23 in Nigeria and 1 in 970 in the United States, he said.
With an AI tool such as this one (sensitivity, 92%; specificity, 80%), the number needed to screen would be 1 in 5.7 in Nigeria and 1 in 194 in the United States, he estimates on the basis of incidence data.
“Because it is so common in Nigeria, a screening method makes a lot of sense,” Dr. Perez said. “The big question that remains is, what is the best screening modality?
“Certainly, this tool helped in bringing down the number of echoes needed to find a case, from the mid 20s down to about 5 or 6, so it certainly does seem to be helpful.”
However, the investigators did not say whether this tool is better than a clinical review of ECG or an AI analysis of ECG alone. It’s not clear whether the phonocardiogram component is significant in conjunction with the ECG component.
Nevertheless, “In a place where there’s a very high prevalence of peripartum cardiomyopathy, like Haiti, like Nigeria, doing something like this makes a lot of sense.
“For the U.S. and the rest of the world, where the prevalence is much lower, even with a tool like this you still would need to do a lot of echoes to find one case, and that may end up not being cost-effective. You would need to screen 200 women with echo to find one case.”
AI-guided screening study
Nigeria has the highest reported incidence of peripartum cardiomyopathy mortality (1 in 100 live births) and the highest number of maternal deaths.
In the United States, where rates of peripartum cardiomyopathy are much lower, maternal deaths are nevertheless higher than in other developed countries and have trended up over the past 3 decades; cardiomyopathy is a key contributor.
The investigators enrolled 1,195 women who were pregnant or had given birth in the past 12 months. The patients were from six teaching hospitals in Nigeria (two in the north and four in the south). They were randomly assigned in a 1:1 ratio to the intervention group (587) or the control group (608).
In the intervention group, clinicians used a smart stethoscope to record a phonocardiogram and a single-lead ECG reading in the V2 position and in an angled position on the patient’s chest wall and to record an ECG from the patient’s fingers. The recordings were sent to a Bluetooth-enabled mobile device (tablet or smartphone), which displayed the phonocardiogram and ECG images and that indicated whether the ejection fraction was normal or low. All patients in the intervention group received an echocardiogram.
In the control group, patients received usual care plus a traditional ECG. They were not required to have an echocardiogram because undergoing an echocardiogram is not part of usual care; however, they could receive an echocardiogram if the ECG suggested that they might need further testing.
The mean age of all the patients was 31 years, and all were Black. At study entry, 73% were pregnant, and 26% were post partum. They had similar comorbidities.
The primary outcome, cardiomyopathy (LVEF <50%) was detected in 24 of 587 patients (4.1%) in the intervention group and in 11 of 608 patients (1.8%) in the control group (odds ratio, 2.3; 95% confidence interval, 1.1-4.8; P = .02).
For the detection of LVEF <50%, the sensitivity was 92% and the specificity was 80%. For the detection of LVEF <40% (a secondary outcome), the sensitivity was 100% and the specificity was 79%.
Dr. Adedinsewo is supported by the Mayo Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) Program, which is funded by the National Institutes of Health. The trial was funded by Mayo Clinic (Centers for Digital Health and Community Health and Engagement Research) and in part by the Mayo Clinic BIRCWH Program. Portable ECG, phonocardiogram recordings, and AI predictions using the digital stethoscope were extracted by the Eko Health team and were sent to the coordinating center for analysis. Eko Health had no role in study design, data collection, data analysis, or data interpretation.
A version of this article appeared on Medscape.com.
FROM AHA 2023
Maternal depressive symptoms may start at pregnancy
, new research suggests.
The analysis of more than 11,000 pregnant women with depressive symptoms from seven prospective cohorts in Canada, the United Kingdom, and Singapore suggests that depressive symptoms (low, mild, or high levels) start sooner and last longer than is commonly thought.
The term “postnatal depression” is “at odds with existing scientific literature and the experience of clinicians who treat mental disorders in the context of obstetric practice,” said Michael J. Meaney, PhD, professor at McGill University, Montreal, and director of the Translational Neuroscience Program at the Agency for Science, Technology and Research (A*STAR), Singapore.
“Although we anticipated that the prenatal period would be the primary time of onset and that symptom levels would be largely stable, I was nevertheless surprised at how this pattern was so universal across so many studies,” he said in an interview. “In truth, we saw very little evidence for a postnatal onset.”
This suggests that depressive symptoms start earlier than previously thought, and “that the relevant clinical settings for prevention are those treating women in routine health care, including family medicine,” he added.
Start screening sooner
The investigators examined the course and stability of self-reported depressive symptoms at multiple time points across the perinatal period among 11,563 pregnant women in seven cohorts from the United Kingdom, Canada, and Singapore. Participants’ mean age was 29 years; 87.6% were White, 4.9% were East Asian, and 2.6% were Southeast Asian.
The analysis tracked depressive symptoms from preconception through pregnancy to 2 years after childbirth. Three groups of mothers were identified in each cohort on the basis of their level of depressive symptoms (low, mild, or high) as assessed by the Edinburgh Postnatal Depression Scale (EPDS) or the Center for Epidemiological Studies Depression (CES-D).
The team found that all mothers within and across all cohorts had stable trajectories of maternal depressive symptoms from pregnancy onward. Trajectories for mothers who passed clinically validated cutoffs for “probable” depression also showed stable trajectories from pregnancy into the postnatal period.
“Taken together, these findings suggest that maternal depressive symptom levels in community-based cohort studies are apparent during pregnancy and remain stable into the postnatal period,” the authors write. “The results point to the early antenatal period as a timepoint for the identification of stable trajectories of maternal depressive symptoms. Public health policies should emphasize the early antenatal period as the optimal timing for interventions targeting maternal depressive symptoms.”
The findings, they note, “underscore the American Psychiatric Association’s recent approach in renaming postpartum depression as peripartum depression.”
Furthermore, a recent paper of the group’s findings details that depressive symptoms may often predate conception.
“Our findings should serve to universally align practice to prenatal screening,” even though depression screening often takes place in a mid-gestational visit during the second trimester, Dr. Meaney said. “Our findings and those on the effects on child development strongly suggest the timing of the screening must be advanced into the first confirmation of pregnancy.”
Depression is likely worse in the United States
Catherine Monk, PhD, chief of the Division of Women’s Mental Health and professor of medical psychology at Columbia University, Vagelos College of Physicians and Surgeons, New York, said in an interview that the results of the study “amplify similar research findings and the experience of most perinatal clinicians: Depression is stable from pregnancy onwards.”
Dr. Monk, who was not involved in the research, said that “as the authors note, the common focus on postpartum depression misses the months of prior suffering and an opportunity for earlier intervention.” Dr. Monk said she would have liked the results to have been examined further by race and ethnicity and socioeconomic factors. “Also, the combined sample does not include a U.S. cohort. This is significant as the U.S. has the highest maternal morbidity and mortality rate of developed nations, and some reports identify mental health factors as the number-one cause of maternal mortality.”
“Given the tremendous economic, racial, and ethnic inequities in health care – the lack of any kind of health justice – it is quite possible that in the U.S., depression that starts in pregnancy worsens over time, at least for some demographic groups,” Dr. Monk said. “Rates of depression, levels of depression, and the course of it during the peripartum period may be even more dire [in the U.S.] than what is represented in this article.” “What should be practice-changing about this article, and so many others demonstrating the persistent and often high levels of life-threatening depression during pregnancy, is the need for mental health providers to advocate for changes to the low rates of insurance reimbursement that push providers away from accepting insurance and into private practice, making access to affordable mental care nearly impossible for most,” she concluded.
This study was supported by the Singapore Institute for Clinical Sciences, Agency for Science, Technology, and Research; the Toxic Stress Network of the JPB Foundation; the Hope for Depression Research Foundation; and the Jacob’s Foundation. Dr. Meaney and Dr. Monk report no conflicts of interest.
A version of this article appeared on Medscape.com.
, new research suggests.
The analysis of more than 11,000 pregnant women with depressive symptoms from seven prospective cohorts in Canada, the United Kingdom, and Singapore suggests that depressive symptoms (low, mild, or high levels) start sooner and last longer than is commonly thought.
The term “postnatal depression” is “at odds with existing scientific literature and the experience of clinicians who treat mental disorders in the context of obstetric practice,” said Michael J. Meaney, PhD, professor at McGill University, Montreal, and director of the Translational Neuroscience Program at the Agency for Science, Technology and Research (A*STAR), Singapore.
“Although we anticipated that the prenatal period would be the primary time of onset and that symptom levels would be largely stable, I was nevertheless surprised at how this pattern was so universal across so many studies,” he said in an interview. “In truth, we saw very little evidence for a postnatal onset.”
This suggests that depressive symptoms start earlier than previously thought, and “that the relevant clinical settings for prevention are those treating women in routine health care, including family medicine,” he added.
Start screening sooner
The investigators examined the course and stability of self-reported depressive symptoms at multiple time points across the perinatal period among 11,563 pregnant women in seven cohorts from the United Kingdom, Canada, and Singapore. Participants’ mean age was 29 years; 87.6% were White, 4.9% were East Asian, and 2.6% were Southeast Asian.
The analysis tracked depressive symptoms from preconception through pregnancy to 2 years after childbirth. Three groups of mothers were identified in each cohort on the basis of their level of depressive symptoms (low, mild, or high) as assessed by the Edinburgh Postnatal Depression Scale (EPDS) or the Center for Epidemiological Studies Depression (CES-D).
The team found that all mothers within and across all cohorts had stable trajectories of maternal depressive symptoms from pregnancy onward. Trajectories for mothers who passed clinically validated cutoffs for “probable” depression also showed stable trajectories from pregnancy into the postnatal period.
“Taken together, these findings suggest that maternal depressive symptom levels in community-based cohort studies are apparent during pregnancy and remain stable into the postnatal period,” the authors write. “The results point to the early antenatal period as a timepoint for the identification of stable trajectories of maternal depressive symptoms. Public health policies should emphasize the early antenatal period as the optimal timing for interventions targeting maternal depressive symptoms.”
The findings, they note, “underscore the American Psychiatric Association’s recent approach in renaming postpartum depression as peripartum depression.”
Furthermore, a recent paper of the group’s findings details that depressive symptoms may often predate conception.
“Our findings should serve to universally align practice to prenatal screening,” even though depression screening often takes place in a mid-gestational visit during the second trimester, Dr. Meaney said. “Our findings and those on the effects on child development strongly suggest the timing of the screening must be advanced into the first confirmation of pregnancy.”
Depression is likely worse in the United States
Catherine Monk, PhD, chief of the Division of Women’s Mental Health and professor of medical psychology at Columbia University, Vagelos College of Physicians and Surgeons, New York, said in an interview that the results of the study “amplify similar research findings and the experience of most perinatal clinicians: Depression is stable from pregnancy onwards.”
Dr. Monk, who was not involved in the research, said that “as the authors note, the common focus on postpartum depression misses the months of prior suffering and an opportunity for earlier intervention.” Dr. Monk said she would have liked the results to have been examined further by race and ethnicity and socioeconomic factors. “Also, the combined sample does not include a U.S. cohort. This is significant as the U.S. has the highest maternal morbidity and mortality rate of developed nations, and some reports identify mental health factors as the number-one cause of maternal mortality.”
“Given the tremendous economic, racial, and ethnic inequities in health care – the lack of any kind of health justice – it is quite possible that in the U.S., depression that starts in pregnancy worsens over time, at least for some demographic groups,” Dr. Monk said. “Rates of depression, levels of depression, and the course of it during the peripartum period may be even more dire [in the U.S.] than what is represented in this article.” “What should be practice-changing about this article, and so many others demonstrating the persistent and often high levels of life-threatening depression during pregnancy, is the need for mental health providers to advocate for changes to the low rates of insurance reimbursement that push providers away from accepting insurance and into private practice, making access to affordable mental care nearly impossible for most,” she concluded.
This study was supported by the Singapore Institute for Clinical Sciences, Agency for Science, Technology, and Research; the Toxic Stress Network of the JPB Foundation; the Hope for Depression Research Foundation; and the Jacob’s Foundation. Dr. Meaney and Dr. Monk report no conflicts of interest.
A version of this article appeared on Medscape.com.
, new research suggests.
The analysis of more than 11,000 pregnant women with depressive symptoms from seven prospective cohorts in Canada, the United Kingdom, and Singapore suggests that depressive symptoms (low, mild, or high levels) start sooner and last longer than is commonly thought.
The term “postnatal depression” is “at odds with existing scientific literature and the experience of clinicians who treat mental disorders in the context of obstetric practice,” said Michael J. Meaney, PhD, professor at McGill University, Montreal, and director of the Translational Neuroscience Program at the Agency for Science, Technology and Research (A*STAR), Singapore.
“Although we anticipated that the prenatal period would be the primary time of onset and that symptom levels would be largely stable, I was nevertheless surprised at how this pattern was so universal across so many studies,” he said in an interview. “In truth, we saw very little evidence for a postnatal onset.”
This suggests that depressive symptoms start earlier than previously thought, and “that the relevant clinical settings for prevention are those treating women in routine health care, including family medicine,” he added.
Start screening sooner
The investigators examined the course and stability of self-reported depressive symptoms at multiple time points across the perinatal period among 11,563 pregnant women in seven cohorts from the United Kingdom, Canada, and Singapore. Participants’ mean age was 29 years; 87.6% were White, 4.9% were East Asian, and 2.6% were Southeast Asian.
The analysis tracked depressive symptoms from preconception through pregnancy to 2 years after childbirth. Three groups of mothers were identified in each cohort on the basis of their level of depressive symptoms (low, mild, or high) as assessed by the Edinburgh Postnatal Depression Scale (EPDS) or the Center for Epidemiological Studies Depression (CES-D).
The team found that all mothers within and across all cohorts had stable trajectories of maternal depressive symptoms from pregnancy onward. Trajectories for mothers who passed clinically validated cutoffs for “probable” depression also showed stable trajectories from pregnancy into the postnatal period.
“Taken together, these findings suggest that maternal depressive symptom levels in community-based cohort studies are apparent during pregnancy and remain stable into the postnatal period,” the authors write. “The results point to the early antenatal period as a timepoint for the identification of stable trajectories of maternal depressive symptoms. Public health policies should emphasize the early antenatal period as the optimal timing for interventions targeting maternal depressive symptoms.”
The findings, they note, “underscore the American Psychiatric Association’s recent approach in renaming postpartum depression as peripartum depression.”
Furthermore, a recent paper of the group’s findings details that depressive symptoms may often predate conception.
“Our findings should serve to universally align practice to prenatal screening,” even though depression screening often takes place in a mid-gestational visit during the second trimester, Dr. Meaney said. “Our findings and those on the effects on child development strongly suggest the timing of the screening must be advanced into the first confirmation of pregnancy.”
Depression is likely worse in the United States
Catherine Monk, PhD, chief of the Division of Women’s Mental Health and professor of medical psychology at Columbia University, Vagelos College of Physicians and Surgeons, New York, said in an interview that the results of the study “amplify similar research findings and the experience of most perinatal clinicians: Depression is stable from pregnancy onwards.”
Dr. Monk, who was not involved in the research, said that “as the authors note, the common focus on postpartum depression misses the months of prior suffering and an opportunity for earlier intervention.” Dr. Monk said she would have liked the results to have been examined further by race and ethnicity and socioeconomic factors. “Also, the combined sample does not include a U.S. cohort. This is significant as the U.S. has the highest maternal morbidity and mortality rate of developed nations, and some reports identify mental health factors as the number-one cause of maternal mortality.”
“Given the tremendous economic, racial, and ethnic inequities in health care – the lack of any kind of health justice – it is quite possible that in the U.S., depression that starts in pregnancy worsens over time, at least for some demographic groups,” Dr. Monk said. “Rates of depression, levels of depression, and the course of it during the peripartum period may be even more dire [in the U.S.] than what is represented in this article.” “What should be practice-changing about this article, and so many others demonstrating the persistent and often high levels of life-threatening depression during pregnancy, is the need for mental health providers to advocate for changes to the low rates of insurance reimbursement that push providers away from accepting insurance and into private practice, making access to affordable mental care nearly impossible for most,” she concluded.
This study was supported by the Singapore Institute for Clinical Sciences, Agency for Science, Technology, and Research; the Toxic Stress Network of the JPB Foundation; the Hope for Depression Research Foundation; and the Jacob’s Foundation. Dr. Meaney and Dr. Monk report no conflicts of interest.
A version of this article appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Breast milk liquid biopsy under study for early-stage breast cancer detection
Breast cancer has a worse prognosis when diagnosed during pregnancy or postpartum. Methods for early detection are needed, as evidenced every day in the multidisciplinary unit for treating pregnancy-associated breast cancer, which operates within the breast unit at the Vall d’Hebron University Hospital in Barcelona.
The team working in this field is led by Cristina Saura, PhD, who is also head of the Breast Cancer Group at the Vall d’Hebron Institute of Oncology (VHIO). The results of a study recently published in Cancer Discovery show, for the first time, that breast milk from breast cancer patients contains circulating tumor DNA that can be detected by a liquid biopsy of the milk.
Dr. Saura explained in an interview why they began to pursue this research, which, in one sense, fell into their laps. “In this case, it arose from the concerns of a breast cancer patient who was diagnosed while pregnant with her third daughter. She was actually the one who came up with the idea for the project. She was worried that she had transmitted the tumor through her breast milk to her second daughter while breastfeeding. She had been breastfeeding for a long time and had stretched it out until shortly before she was diagnosed with breast cancer. So she brought us a sample of breast milk that she had stored in her freezer.
“So, thanks to her, that’s where our project started. Though we knew that breast cancer is not transmitted through breast milk, we decided to test the sample and look for markers that could help our research. In the end, when we analyzed the patient’s breast milk, we found DNA with the same mutation that was present in her tumor,” explained Dr. Saura. She noted that the breast milk they analyzed had been frozen for more than a year before the patient’s cancer diagnosis.
In terms of methodology, Ana Vivancos, PhD, head of the VHIO cancer genomics group and also one of the authors of the study, explained that they used two techniques to analyze the breast milk and blood samples: next-generation sequencing and droplet digital polymerase chain reaction. These methods confirmed the presence of ctDNA in the breast milk.
High-sensitivity genomic panel
“We were able to detect tumor mutations in milk samples from 13 of the 15 patients with breast cancer who were tested, while circulating tumor DNA was detected in only one of all the blood samples that were collected at the same time,” said Dr. Vivancos. “The samples from the two patients for whom no mutation was detected were discovered to be colostrum that had been collected during the first few hours of lactation.”
As a next step to make this finding practically useful, the research team designed a genomic panel using next-generation sequencing as a potential method for early detection of breast cancer. “We’ve developed a panel that uses hybrid capture chemistry and unique molecular identifiers that ensure better sensitivity during next-generation sequencing. The panel has been calibrated, based on the existing literature, to detect the genes that are most frequently mutated in breast cancer in young women under 45 years old.”
According to Dr. Vivancos, the sensitivity of this panel exceeds 70%. This means that for all the patient samples analyzed using this panel, 7 out of 10 cases are detected with 100% specificity.
“In practice, the panel design allows us to detect mutations in more than 95% of breast cancer cases in women under 45 years old. noted Dr. Vivancos.
As for this unresolved need, Dr. Saura explained that there is currently no system or tool available to allow early suspicion of breast tumors in pregnant women prior to diagnosis. “That’s exactly the goal of this research: to screen for breast cancer in women who have just given birth. Now, it needs to be validated in a larger group of women in a clinical trial.”
More direct contact with tumor cells
In Dr. Saura’s opinion, in Spain, just like taking a small blood sample from newborns in a heel-prick test to rule out metabolic diseases, milk samples could be taken from women who give birth to rule out or diagnose breast cancer.
As to the potential advantages that breast milk liquid biopsy could have over similar techniques like blood liquid biopsy, Dr. Vivancos pointed to the results of her study: “We have seen that breast milk liquid biopsy was positive for the presence of circulating tumor DNA in 87% of cases, whereas blood only revealed the presence of this marker in 8% of cases. This difference indicates that breast milk is a biofluid that is in more direct contact with tumor cells and therefore will be more informative in earlier stages.”
Dr. Saura explained that the data does not lie when it comes to these tumors in pregnant or postpartum women. “In general, they tend to have a worse prognosis because, in most cases, they are diagnosed in advanced stages. Furthermore, it is typically assumed that the physiological changes in the breasts during gestation and lactation, which are considered to be normal, may hide a developing tumor. The fact is that postpartum breast cancer, understood to be the 10 years after delivery, accounts for 40%-45% of breast cancer cases diagnosed before age 45.”
The researchers plan to continue this project. “Our next step to confirm the usefulness of breast milk as a new tool for liquid biopsy for early detection of breast cancer during the postpartum period is to perform this noninvasive test in thousands of women,” said Dr. Saura.
Goal: Standardize the test as a screening method
“Based on the results we’ve published, we’re starting a study aimed at collecting breast milk samples from 5,000 healthy women around the world who became pregnant at age 40 or older, or who got pregnant at any age and carry mutations that increase their risk of breast cancer,” Dr. Saura added.
When asked when they expect to have preliminary results from this new study, Dr. Saura stated that it’s not yet possible to say exactly when. “We’re still waiting for funding to continue this project, but we continue performing analyses on a case-by-case basis. Of course, if we detect any abnormalities in these women, we will follow the established protocol to confirm diagnosis and start treatment if necessary.”
When asked whether it is reasonable to expect breast milk liquid biopsy to become normalized as a screening method for women of childbearing age who have a history or risk factors for developing breast cancer, Dr. Vivancos said, “That’s the scenario we see in the future and what we wish to contribute toward by providing scientific evidence to make it a reality.”
“For now, our goal is to validate whether circulating tumor DNA can be detected by breast milk liquid biopsy even before breast cancer can be diagnosed using conventional imaging techniques. If we can validate these preliminary results, we will be able to detect breast cancer early using a noninvasive test like breast milk liquid biopsy,” explained Saura.
Lastly, and in view of the issues that are still unresolved when it comes to the detection and treatment of breast cancer during pregnancy, Dr. Saura highlighted the emotional impact that a diagnosis of pregnancy-related cancer has on women and on those close to them. “But the first thing they need to know is that diagnosis is not necessarily synonymous with termination of the pregnancy. On the contrary, this tumor can be treated during pregnancy, since surgery can be performed at any time, and chemotherapy can be started in the second trimester. Proof of this is the 72 children who have been born under these circumstances in the past 20 years at the Vall d’Hebrón University Hospital. This hospital is a pioneer in Spain thanks to its multidisciplinary program for education and specific follow-up with women who have been diagnosed with a breast tumor during pregnancy.”
Dr. Saura and Dr. Vivancos reported no relevant financial relationships.
This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.
Breast cancer has a worse prognosis when diagnosed during pregnancy or postpartum. Methods for early detection are needed, as evidenced every day in the multidisciplinary unit for treating pregnancy-associated breast cancer, which operates within the breast unit at the Vall d’Hebron University Hospital in Barcelona.
The team working in this field is led by Cristina Saura, PhD, who is also head of the Breast Cancer Group at the Vall d’Hebron Institute of Oncology (VHIO). The results of a study recently published in Cancer Discovery show, for the first time, that breast milk from breast cancer patients contains circulating tumor DNA that can be detected by a liquid biopsy of the milk.
Dr. Saura explained in an interview why they began to pursue this research, which, in one sense, fell into their laps. “In this case, it arose from the concerns of a breast cancer patient who was diagnosed while pregnant with her third daughter. She was actually the one who came up with the idea for the project. She was worried that she had transmitted the tumor through her breast milk to her second daughter while breastfeeding. She had been breastfeeding for a long time and had stretched it out until shortly before she was diagnosed with breast cancer. So she brought us a sample of breast milk that she had stored in her freezer.
“So, thanks to her, that’s where our project started. Though we knew that breast cancer is not transmitted through breast milk, we decided to test the sample and look for markers that could help our research. In the end, when we analyzed the patient’s breast milk, we found DNA with the same mutation that was present in her tumor,” explained Dr. Saura. She noted that the breast milk they analyzed had been frozen for more than a year before the patient’s cancer diagnosis.
In terms of methodology, Ana Vivancos, PhD, head of the VHIO cancer genomics group and also one of the authors of the study, explained that they used two techniques to analyze the breast milk and blood samples: next-generation sequencing and droplet digital polymerase chain reaction. These methods confirmed the presence of ctDNA in the breast milk.
High-sensitivity genomic panel
“We were able to detect tumor mutations in milk samples from 13 of the 15 patients with breast cancer who were tested, while circulating tumor DNA was detected in only one of all the blood samples that were collected at the same time,” said Dr. Vivancos. “The samples from the two patients for whom no mutation was detected were discovered to be colostrum that had been collected during the first few hours of lactation.”
As a next step to make this finding practically useful, the research team designed a genomic panel using next-generation sequencing as a potential method for early detection of breast cancer. “We’ve developed a panel that uses hybrid capture chemistry and unique molecular identifiers that ensure better sensitivity during next-generation sequencing. The panel has been calibrated, based on the existing literature, to detect the genes that are most frequently mutated in breast cancer in young women under 45 years old.”
According to Dr. Vivancos, the sensitivity of this panel exceeds 70%. This means that for all the patient samples analyzed using this panel, 7 out of 10 cases are detected with 100% specificity.
“In practice, the panel design allows us to detect mutations in more than 95% of breast cancer cases in women under 45 years old. noted Dr. Vivancos.
As for this unresolved need, Dr. Saura explained that there is currently no system or tool available to allow early suspicion of breast tumors in pregnant women prior to diagnosis. “That’s exactly the goal of this research: to screen for breast cancer in women who have just given birth. Now, it needs to be validated in a larger group of women in a clinical trial.”
More direct contact with tumor cells
In Dr. Saura’s opinion, in Spain, just like taking a small blood sample from newborns in a heel-prick test to rule out metabolic diseases, milk samples could be taken from women who give birth to rule out or diagnose breast cancer.
As to the potential advantages that breast milk liquid biopsy could have over similar techniques like blood liquid biopsy, Dr. Vivancos pointed to the results of her study: “We have seen that breast milk liquid biopsy was positive for the presence of circulating tumor DNA in 87% of cases, whereas blood only revealed the presence of this marker in 8% of cases. This difference indicates that breast milk is a biofluid that is in more direct contact with tumor cells and therefore will be more informative in earlier stages.”
Dr. Saura explained that the data does not lie when it comes to these tumors in pregnant or postpartum women. “In general, they tend to have a worse prognosis because, in most cases, they are diagnosed in advanced stages. Furthermore, it is typically assumed that the physiological changes in the breasts during gestation and lactation, which are considered to be normal, may hide a developing tumor. The fact is that postpartum breast cancer, understood to be the 10 years after delivery, accounts for 40%-45% of breast cancer cases diagnosed before age 45.”
The researchers plan to continue this project. “Our next step to confirm the usefulness of breast milk as a new tool for liquid biopsy for early detection of breast cancer during the postpartum period is to perform this noninvasive test in thousands of women,” said Dr. Saura.
Goal: Standardize the test as a screening method
“Based on the results we’ve published, we’re starting a study aimed at collecting breast milk samples from 5,000 healthy women around the world who became pregnant at age 40 or older, or who got pregnant at any age and carry mutations that increase their risk of breast cancer,” Dr. Saura added.
When asked when they expect to have preliminary results from this new study, Dr. Saura stated that it’s not yet possible to say exactly when. “We’re still waiting for funding to continue this project, but we continue performing analyses on a case-by-case basis. Of course, if we detect any abnormalities in these women, we will follow the established protocol to confirm diagnosis and start treatment if necessary.”
When asked whether it is reasonable to expect breast milk liquid biopsy to become normalized as a screening method for women of childbearing age who have a history or risk factors for developing breast cancer, Dr. Vivancos said, “That’s the scenario we see in the future and what we wish to contribute toward by providing scientific evidence to make it a reality.”
“For now, our goal is to validate whether circulating tumor DNA can be detected by breast milk liquid biopsy even before breast cancer can be diagnosed using conventional imaging techniques. If we can validate these preliminary results, we will be able to detect breast cancer early using a noninvasive test like breast milk liquid biopsy,” explained Saura.
Lastly, and in view of the issues that are still unresolved when it comes to the detection and treatment of breast cancer during pregnancy, Dr. Saura highlighted the emotional impact that a diagnosis of pregnancy-related cancer has on women and on those close to them. “But the first thing they need to know is that diagnosis is not necessarily synonymous with termination of the pregnancy. On the contrary, this tumor can be treated during pregnancy, since surgery can be performed at any time, and chemotherapy can be started in the second trimester. Proof of this is the 72 children who have been born under these circumstances in the past 20 years at the Vall d’Hebrón University Hospital. This hospital is a pioneer in Spain thanks to its multidisciplinary program for education and specific follow-up with women who have been diagnosed with a breast tumor during pregnancy.”
Dr. Saura and Dr. Vivancos reported no relevant financial relationships.
This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.
Breast cancer has a worse prognosis when diagnosed during pregnancy or postpartum. Methods for early detection are needed, as evidenced every day in the multidisciplinary unit for treating pregnancy-associated breast cancer, which operates within the breast unit at the Vall d’Hebron University Hospital in Barcelona.
The team working in this field is led by Cristina Saura, PhD, who is also head of the Breast Cancer Group at the Vall d’Hebron Institute of Oncology (VHIO). The results of a study recently published in Cancer Discovery show, for the first time, that breast milk from breast cancer patients contains circulating tumor DNA that can be detected by a liquid biopsy of the milk.
Dr. Saura explained in an interview why they began to pursue this research, which, in one sense, fell into their laps. “In this case, it arose from the concerns of a breast cancer patient who was diagnosed while pregnant with her third daughter. She was actually the one who came up with the idea for the project. She was worried that she had transmitted the tumor through her breast milk to her second daughter while breastfeeding. She had been breastfeeding for a long time and had stretched it out until shortly before she was diagnosed with breast cancer. So she brought us a sample of breast milk that she had stored in her freezer.
“So, thanks to her, that’s where our project started. Though we knew that breast cancer is not transmitted through breast milk, we decided to test the sample and look for markers that could help our research. In the end, when we analyzed the patient’s breast milk, we found DNA with the same mutation that was present in her tumor,” explained Dr. Saura. She noted that the breast milk they analyzed had been frozen for more than a year before the patient’s cancer diagnosis.
In terms of methodology, Ana Vivancos, PhD, head of the VHIO cancer genomics group and also one of the authors of the study, explained that they used two techniques to analyze the breast milk and blood samples: next-generation sequencing and droplet digital polymerase chain reaction. These methods confirmed the presence of ctDNA in the breast milk.
High-sensitivity genomic panel
“We were able to detect tumor mutations in milk samples from 13 of the 15 patients with breast cancer who were tested, while circulating tumor DNA was detected in only one of all the blood samples that were collected at the same time,” said Dr. Vivancos. “The samples from the two patients for whom no mutation was detected were discovered to be colostrum that had been collected during the first few hours of lactation.”
As a next step to make this finding practically useful, the research team designed a genomic panel using next-generation sequencing as a potential method for early detection of breast cancer. “We’ve developed a panel that uses hybrid capture chemistry and unique molecular identifiers that ensure better sensitivity during next-generation sequencing. The panel has been calibrated, based on the existing literature, to detect the genes that are most frequently mutated in breast cancer in young women under 45 years old.”
According to Dr. Vivancos, the sensitivity of this panel exceeds 70%. This means that for all the patient samples analyzed using this panel, 7 out of 10 cases are detected with 100% specificity.
“In practice, the panel design allows us to detect mutations in more than 95% of breast cancer cases in women under 45 years old. noted Dr. Vivancos.
As for this unresolved need, Dr. Saura explained that there is currently no system or tool available to allow early suspicion of breast tumors in pregnant women prior to diagnosis. “That’s exactly the goal of this research: to screen for breast cancer in women who have just given birth. Now, it needs to be validated in a larger group of women in a clinical trial.”
More direct contact with tumor cells
In Dr. Saura’s opinion, in Spain, just like taking a small blood sample from newborns in a heel-prick test to rule out metabolic diseases, milk samples could be taken from women who give birth to rule out or diagnose breast cancer.
As to the potential advantages that breast milk liquid biopsy could have over similar techniques like blood liquid biopsy, Dr. Vivancos pointed to the results of her study: “We have seen that breast milk liquid biopsy was positive for the presence of circulating tumor DNA in 87% of cases, whereas blood only revealed the presence of this marker in 8% of cases. This difference indicates that breast milk is a biofluid that is in more direct contact with tumor cells and therefore will be more informative in earlier stages.”
Dr. Saura explained that the data does not lie when it comes to these tumors in pregnant or postpartum women. “In general, they tend to have a worse prognosis because, in most cases, they are diagnosed in advanced stages. Furthermore, it is typically assumed that the physiological changes in the breasts during gestation and lactation, which are considered to be normal, may hide a developing tumor. The fact is that postpartum breast cancer, understood to be the 10 years after delivery, accounts for 40%-45% of breast cancer cases diagnosed before age 45.”
The researchers plan to continue this project. “Our next step to confirm the usefulness of breast milk as a new tool for liquid biopsy for early detection of breast cancer during the postpartum period is to perform this noninvasive test in thousands of women,” said Dr. Saura.
Goal: Standardize the test as a screening method
“Based on the results we’ve published, we’re starting a study aimed at collecting breast milk samples from 5,000 healthy women around the world who became pregnant at age 40 or older, or who got pregnant at any age and carry mutations that increase their risk of breast cancer,” Dr. Saura added.
When asked when they expect to have preliminary results from this new study, Dr. Saura stated that it’s not yet possible to say exactly when. “We’re still waiting for funding to continue this project, but we continue performing analyses on a case-by-case basis. Of course, if we detect any abnormalities in these women, we will follow the established protocol to confirm diagnosis and start treatment if necessary.”
When asked whether it is reasonable to expect breast milk liquid biopsy to become normalized as a screening method for women of childbearing age who have a history or risk factors for developing breast cancer, Dr. Vivancos said, “That’s the scenario we see in the future and what we wish to contribute toward by providing scientific evidence to make it a reality.”
“For now, our goal is to validate whether circulating tumor DNA can be detected by breast milk liquid biopsy even before breast cancer can be diagnosed using conventional imaging techniques. If we can validate these preliminary results, we will be able to detect breast cancer early using a noninvasive test like breast milk liquid biopsy,” explained Saura.
Lastly, and in view of the issues that are still unresolved when it comes to the detection and treatment of breast cancer during pregnancy, Dr. Saura highlighted the emotional impact that a diagnosis of pregnancy-related cancer has on women and on those close to them. “But the first thing they need to know is that diagnosis is not necessarily synonymous with termination of the pregnancy. On the contrary, this tumor can be treated during pregnancy, since surgery can be performed at any time, and chemotherapy can be started in the second trimester. Proof of this is the 72 children who have been born under these circumstances in the past 20 years at the Vall d’Hebrón University Hospital. This hospital is a pioneer in Spain thanks to its multidisciplinary program for education and specific follow-up with women who have been diagnosed with a breast tumor during pregnancy.”
Dr. Saura and Dr. Vivancos reported no relevant financial relationships.
This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.
FROM CANCER DISCOVERY
Can a Mediterranean diet reduce breast cancer recurrence?
TOPLINE:
However, women at high risk for recurrence who made the greatest improvements in their diet quality demonstrated a 41% lower risk for recurrence, compared with peers who made the fewest improvements.
METHODOLOGY:
- A growing body of evidence suggests that a better dietary quality may improve survival among patients with breast cancer, but whether diet impacts breast cancer–specific mortality remains controversial.
- To better understand the relationship between diet and breast cancer outcomes, investigators recruited 1,542 women with breast cancer who had undergone surgical resection in the past 5 years and were considered high risk for recurrence.
- All women received general recommendations for cancer prevention, while the intervention group received active support to adhere to a macro–Mediterranean-style diet, which encourages mainly consuming whole grains, legumes, and high-fiber vegetables and discourages eating foods high in saturated and trans fats, processed meats, and foods and beverages high in sugar.
- Diet was assessed at baseline, 1 year, and every few months in subsequent years via food frequency diaries. Compliance with dietary recommendations for the whole cohort was assessed using a dietary index developed for the trial.
- In addition to diet, women in the diet intervention group were encouraged to maintain moderate to intense physical activity – 30 minutes, on average, each day – and received pedometers to track steps, aiming for 10,000 per day.
TAKEAWAY:
- Over 5 years of follow-up, the rate of breast cancer recurrence did not differ between women in the diet intervention group and those in the control group. Overall, 95 of 769 women in the intervention group and 98 of 773 in the control group had a breast cancer recurrence (hazard ratio, 0.99).
- When evaluating outcomes in the entire cohort, looking at everyone’s level of compliance with dietary recommendations, women who adhered the most to the dietary guidelines had a 41% lower recurrence risk compared with women who adhered the least (HR, 0.59).
- The greatest protective effect among women who demonstrated high compliance occurred in those with ER-positive cancers (HR, 0.42) and those with ER-positive cancers who received tamoxifen (HR, 0.30).
IN PRACTICE:
This intervention trial “did not confirm the hypothesis that a comprehensive dietary modification reduces breast cancer recurrence and metastases,” but when looking at compliance to the Mediterranean diet overall, the analysis did find “a significantly better prognosis” for women with the best adherence.
SOURCE:
The study, with first author Franco Berrino, MD, PhD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, was published online in Clinical Cancer Research.
LIMITATIONS:
The study relied on self-reported dietary data. No dietary instrument was used to estimate nutrient intake and the dietary index developed for the trial remains unvalidated.
DISCLOSURES:
The study was supported by the Italian Department of Health, the Associazione Italiana per la Ricerca sul Cancro, and the Vita e Salute Foundation. The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
TOPLINE:
However, women at high risk for recurrence who made the greatest improvements in their diet quality demonstrated a 41% lower risk for recurrence, compared with peers who made the fewest improvements.
METHODOLOGY:
- A growing body of evidence suggests that a better dietary quality may improve survival among patients with breast cancer, but whether diet impacts breast cancer–specific mortality remains controversial.
- To better understand the relationship between diet and breast cancer outcomes, investigators recruited 1,542 women with breast cancer who had undergone surgical resection in the past 5 years and were considered high risk for recurrence.
- All women received general recommendations for cancer prevention, while the intervention group received active support to adhere to a macro–Mediterranean-style diet, which encourages mainly consuming whole grains, legumes, and high-fiber vegetables and discourages eating foods high in saturated and trans fats, processed meats, and foods and beverages high in sugar.
- Diet was assessed at baseline, 1 year, and every few months in subsequent years via food frequency diaries. Compliance with dietary recommendations for the whole cohort was assessed using a dietary index developed for the trial.
- In addition to diet, women in the diet intervention group were encouraged to maintain moderate to intense physical activity – 30 minutes, on average, each day – and received pedometers to track steps, aiming for 10,000 per day.
TAKEAWAY:
- Over 5 years of follow-up, the rate of breast cancer recurrence did not differ between women in the diet intervention group and those in the control group. Overall, 95 of 769 women in the intervention group and 98 of 773 in the control group had a breast cancer recurrence (hazard ratio, 0.99).
- When evaluating outcomes in the entire cohort, looking at everyone’s level of compliance with dietary recommendations, women who adhered the most to the dietary guidelines had a 41% lower recurrence risk compared with women who adhered the least (HR, 0.59).
- The greatest protective effect among women who demonstrated high compliance occurred in those with ER-positive cancers (HR, 0.42) and those with ER-positive cancers who received tamoxifen (HR, 0.30).
IN PRACTICE:
This intervention trial “did not confirm the hypothesis that a comprehensive dietary modification reduces breast cancer recurrence and metastases,” but when looking at compliance to the Mediterranean diet overall, the analysis did find “a significantly better prognosis” for women with the best adherence.
SOURCE:
The study, with first author Franco Berrino, MD, PhD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, was published online in Clinical Cancer Research.
LIMITATIONS:
The study relied on self-reported dietary data. No dietary instrument was used to estimate nutrient intake and the dietary index developed for the trial remains unvalidated.
DISCLOSURES:
The study was supported by the Italian Department of Health, the Associazione Italiana per la Ricerca sul Cancro, and the Vita e Salute Foundation. The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
TOPLINE:
However, women at high risk for recurrence who made the greatest improvements in their diet quality demonstrated a 41% lower risk for recurrence, compared with peers who made the fewest improvements.
METHODOLOGY:
- A growing body of evidence suggests that a better dietary quality may improve survival among patients with breast cancer, but whether diet impacts breast cancer–specific mortality remains controversial.
- To better understand the relationship between diet and breast cancer outcomes, investigators recruited 1,542 women with breast cancer who had undergone surgical resection in the past 5 years and were considered high risk for recurrence.
- All women received general recommendations for cancer prevention, while the intervention group received active support to adhere to a macro–Mediterranean-style diet, which encourages mainly consuming whole grains, legumes, and high-fiber vegetables and discourages eating foods high in saturated and trans fats, processed meats, and foods and beverages high in sugar.
- Diet was assessed at baseline, 1 year, and every few months in subsequent years via food frequency diaries. Compliance with dietary recommendations for the whole cohort was assessed using a dietary index developed for the trial.
- In addition to diet, women in the diet intervention group were encouraged to maintain moderate to intense physical activity – 30 minutes, on average, each day – and received pedometers to track steps, aiming for 10,000 per day.
TAKEAWAY:
- Over 5 years of follow-up, the rate of breast cancer recurrence did not differ between women in the diet intervention group and those in the control group. Overall, 95 of 769 women in the intervention group and 98 of 773 in the control group had a breast cancer recurrence (hazard ratio, 0.99).
- When evaluating outcomes in the entire cohort, looking at everyone’s level of compliance with dietary recommendations, women who adhered the most to the dietary guidelines had a 41% lower recurrence risk compared with women who adhered the least (HR, 0.59).
- The greatest protective effect among women who demonstrated high compliance occurred in those with ER-positive cancers (HR, 0.42) and those with ER-positive cancers who received tamoxifen (HR, 0.30).
IN PRACTICE:
This intervention trial “did not confirm the hypothesis that a comprehensive dietary modification reduces breast cancer recurrence and metastases,” but when looking at compliance to the Mediterranean diet overall, the analysis did find “a significantly better prognosis” for women with the best adherence.
SOURCE:
The study, with first author Franco Berrino, MD, PhD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, was published online in Clinical Cancer Research.
LIMITATIONS:
The study relied on self-reported dietary data. No dietary instrument was used to estimate nutrient intake and the dietary index developed for the trial remains unvalidated.
DISCLOSURES:
The study was supported by the Italian Department of Health, the Associazione Italiana per la Ricerca sul Cancro, and the Vita e Salute Foundation. The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Bipolar disorder may raise risk of polycystic ovarian syndrome
Previous studies suggest that the prevalence of polycystic ovarian syndrome (PCOS) is higher in bipolar disorder (BD) patients compared with individuals not diagnosed with BD, wrote Jieyu Liu, PhD, of the Second Xiangya Hospital of Central South University, Hunan, China, and colleagues.
However, studies have been limited to drug-treated BD patients, and data on the effects of BD on the development of PCOS are limited, they said. Data from previous studies also indicate that serum testosterone levels, serum androstenedione levels, and polycystic ovarian morphology (PCOM) are increased in BD patients compared with women without BD.
In a study published in the Journal of Affective Disorders, the researchers recruited 72 BD patients on long-term medication, 72 drug-naive patients, and 98 healthy controls between March 2022 and November 2022.
PCOM was assessed using ≥ 8 MHz transvaginal transducers to determine the number of follicles and ovarian volume. PCOS was then defined using the Rotterdam criteria, in which patients met two of three qualifications: oligoovulation or anovulation; hyperandrogenemia; or PCOM (excluding other endocrine diseases).
In a multivariate analysis, drug-naive women with BD had significantly higher rates of PCOS compared with healthy controls (odds ratio 3.02). The drug-naive BD patients also had a greater prevalence of oligoamenorrhea compared with healthy controls (36.36% vs. 12.12%) and higher levels of anti-mullerian hormone, luteinizing hormone, and follicle stimulating hormone compared to the controls.
A further regression analysis showed that those on long-term valproate treatment had the highest risk (OR 3.89) and the prevalence of PCOS was significantly higher among patients treated with valproate compared with drug-naive patients (53.3% vs. 30.6%). Younger age and the presence of insulin resistance also were associated with increased risk of PCOS (OR 0.37 and OR 1.73, respectively).
“Unexpectedly, no significant differences in serum androgen levels, including TT, FAI, androstenedione, and [dehydroepiandrosterone sulfate] levels, were observed between drug-naive BD patients and the HCs,” the researchers wrote in their discussion. This difference may stem from multiple causes including demographic variables, inclusion of PCOM as a diagnostic criterion, and the impact of genetic and environmental factors, they said.
The findings were limited by several factors including the small study population, which prevented conclusions of causality and comparison of the effects of different mood stabilizers on PCOS, the researchers noted. Other limitations included the relatively homogeneous population from a single region in China, and the inability to account for the effects of diet and lifestyle.
More research is needed to explore the impact of mediations, but the results suggest that BD patients are susceptible to PCOS; therefore, they should evaluate their reproductive health before starting any medication, and review reproductive health regularly, the researchers concluded.
The study was supported by the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose.
Previous studies suggest that the prevalence of polycystic ovarian syndrome (PCOS) is higher in bipolar disorder (BD) patients compared with individuals not diagnosed with BD, wrote Jieyu Liu, PhD, of the Second Xiangya Hospital of Central South University, Hunan, China, and colleagues.
However, studies have been limited to drug-treated BD patients, and data on the effects of BD on the development of PCOS are limited, they said. Data from previous studies also indicate that serum testosterone levels, serum androstenedione levels, and polycystic ovarian morphology (PCOM) are increased in BD patients compared with women without BD.
In a study published in the Journal of Affective Disorders, the researchers recruited 72 BD patients on long-term medication, 72 drug-naive patients, and 98 healthy controls between March 2022 and November 2022.
PCOM was assessed using ≥ 8 MHz transvaginal transducers to determine the number of follicles and ovarian volume. PCOS was then defined using the Rotterdam criteria, in which patients met two of three qualifications: oligoovulation or anovulation; hyperandrogenemia; or PCOM (excluding other endocrine diseases).
In a multivariate analysis, drug-naive women with BD had significantly higher rates of PCOS compared with healthy controls (odds ratio 3.02). The drug-naive BD patients also had a greater prevalence of oligoamenorrhea compared with healthy controls (36.36% vs. 12.12%) and higher levels of anti-mullerian hormone, luteinizing hormone, and follicle stimulating hormone compared to the controls.
A further regression analysis showed that those on long-term valproate treatment had the highest risk (OR 3.89) and the prevalence of PCOS was significantly higher among patients treated with valproate compared with drug-naive patients (53.3% vs. 30.6%). Younger age and the presence of insulin resistance also were associated with increased risk of PCOS (OR 0.37 and OR 1.73, respectively).
“Unexpectedly, no significant differences in serum androgen levels, including TT, FAI, androstenedione, and [dehydroepiandrosterone sulfate] levels, were observed between drug-naive BD patients and the HCs,” the researchers wrote in their discussion. This difference may stem from multiple causes including demographic variables, inclusion of PCOM as a diagnostic criterion, and the impact of genetic and environmental factors, they said.
The findings were limited by several factors including the small study population, which prevented conclusions of causality and comparison of the effects of different mood stabilizers on PCOS, the researchers noted. Other limitations included the relatively homogeneous population from a single region in China, and the inability to account for the effects of diet and lifestyle.
More research is needed to explore the impact of mediations, but the results suggest that BD patients are susceptible to PCOS; therefore, they should evaluate their reproductive health before starting any medication, and review reproductive health regularly, the researchers concluded.
The study was supported by the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose.
Previous studies suggest that the prevalence of polycystic ovarian syndrome (PCOS) is higher in bipolar disorder (BD) patients compared with individuals not diagnosed with BD, wrote Jieyu Liu, PhD, of the Second Xiangya Hospital of Central South University, Hunan, China, and colleagues.
However, studies have been limited to drug-treated BD patients, and data on the effects of BD on the development of PCOS are limited, they said. Data from previous studies also indicate that serum testosterone levels, serum androstenedione levels, and polycystic ovarian morphology (PCOM) are increased in BD patients compared with women without BD.
In a study published in the Journal of Affective Disorders, the researchers recruited 72 BD patients on long-term medication, 72 drug-naive patients, and 98 healthy controls between March 2022 and November 2022.
PCOM was assessed using ≥ 8 MHz transvaginal transducers to determine the number of follicles and ovarian volume. PCOS was then defined using the Rotterdam criteria, in which patients met two of three qualifications: oligoovulation or anovulation; hyperandrogenemia; or PCOM (excluding other endocrine diseases).
In a multivariate analysis, drug-naive women with BD had significantly higher rates of PCOS compared with healthy controls (odds ratio 3.02). The drug-naive BD patients also had a greater prevalence of oligoamenorrhea compared with healthy controls (36.36% vs. 12.12%) and higher levels of anti-mullerian hormone, luteinizing hormone, and follicle stimulating hormone compared to the controls.
A further regression analysis showed that those on long-term valproate treatment had the highest risk (OR 3.89) and the prevalence of PCOS was significantly higher among patients treated with valproate compared with drug-naive patients (53.3% vs. 30.6%). Younger age and the presence of insulin resistance also were associated with increased risk of PCOS (OR 0.37 and OR 1.73, respectively).
“Unexpectedly, no significant differences in serum androgen levels, including TT, FAI, androstenedione, and [dehydroepiandrosterone sulfate] levels, were observed between drug-naive BD patients and the HCs,” the researchers wrote in their discussion. This difference may stem from multiple causes including demographic variables, inclusion of PCOM as a diagnostic criterion, and the impact of genetic and environmental factors, they said.
The findings were limited by several factors including the small study population, which prevented conclusions of causality and comparison of the effects of different mood stabilizers on PCOS, the researchers noted. Other limitations included the relatively homogeneous population from a single region in China, and the inability to account for the effects of diet and lifestyle.
More research is needed to explore the impact of mediations, but the results suggest that BD patients are susceptible to PCOS; therefore, they should evaluate their reproductive health before starting any medication, and review reproductive health regularly, the researchers concluded.
The study was supported by the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose.
FROM THE JOURNAL OF AFFECTIVE DISORDERS
False-positive mammography results and risk for cancer death
False-positive mammography results are common, but
Women with a false-positive mammography result had 61% greater risk of developing breast cancer and an 84% greater risk of dying of breast cancer, compared with those who did not have a false-positive result.
However, the investigators also found that the risk for breast cancer varied by individual characteristics such as age and breast density.
The analysis provides clues about which patients with false-positive mammography results will go on to develop breast cancer and “can be used to develop individualized risk-based breast cancer screening,” said the investigators, led by Xinhe Mao, MSc, of Karolinska Institute, Stockholm.
The findings were published online in JAMA Oncology.
About 11% of women in the United States and 2.5% in Europe will receive a false-positive result after a single mammography screening, and previous research shows that these women have a higher risk of developing breast cancer, compared with women without false-positive results. Still, whether this risk for breast cancer varies by individual characteristics and whether an association between a false-positive mammography result and mortality exists remain unclear.
To assess long-term outcomes after a false-positive result, the study investigators compared 45,213 women who had a false-positive mammography result between 1991 and 2017 with 452,130 controls matched for age, calendar year of mammography, and screening history. These data came from the Stockholm Mammography Screening program and Swedish nationwide registers. The analysis also included 1,113 women with a false-positive result and 11,130 matched controls with information on mammographic breast density from the Karolinska Mammography Project for Risk Prediction of Breast Cancer study.
Among women with a false-positive result, the 20-year cumulative breast cancer incidence was 11.3% compared with 7.3% among those without a false-positive (adjusted hazard ratio, 1.61).
Breast cancer risk was higher in older women – those aged 60-75 years (HR, 2.02) – vs younger women aged 40-49 years (HR, 1.38). Breast cancer risk was also higher among women with less dense breasts (HR, 4.65) vs more dense breasts (HR, 1.60) and those who underwent a biopsy during recall (HR, 1.77) vs those who did not (HR, 1.51).
After a false-positive result, cancers were more likely to occur on the ipsilateral side to the false-positive result (HR, 1.92) versus the contralateral (HR, 1.28) and were more common during the first 4 years of follow-up (HR, 2.57 in the first 2 years and 1.93 between 2 and 4 years). No statistical differences were observed based on tumor characteristics, aside from tumor size (HR, 1.78 for tumors ≥ 20 mm vs. 1.47 for smaller tumors).
The prognosis of patients with breast cancer did not differ on the basis of whether they had false-positive results before diagnosis (HR, 1.05 for a false-positive result versus no false-positive result; 95% CI, 0.89-1.25).
This study is the first to show that “women with a false-positive result are at increased risk of death from breast cancer,” Ms. Mao and colleagues concluded. This finding is “most probably associated with the increased breast cancer incidence,” given that the prognosis of patients with breast cancer was similar among those who had a false-positive result versus those who did not.
The authors noted that the increased risk for breast cancer after a false-positive result could suggest that false positives indicate the presence of small tumors that were missed or generally indicate a higher risk for breast cancer. Other factors, such as hormones or genetics, may be at play as well, but would need to be investigated in further studies, Ms. Mao and colleagues noted.
When individualizing surveillance after a false-positive result, age and breast density should be considered, the authors explained. Clinicians may also want to provide more intensive surveillance in the years after a false-positive result as well as education to patients about the risks associated with a false-positive result.
Overall, the findings indicate that clinicians “ should stress the importance of continued screening in women with false-positive results, given their higher risk of cancer, especially within the first 5 or so years after a false-positive result,” Diana L. Miglioretti, PhD, professor and division chief of biostatistics at the University of California, Davis, said in an interview.
Dr. Miglioretti, who has led research on false-positive mammography results and approaches to reduce false positives, noted that “this is a very important study confirming prior work by the Breast Cancer Surveillance Consortium showing individuals with false-positive screening mammography results are at increased risk of developing breast cancer in the future.”
The new evidence demonstrated an increased risk for death from breast cancer in patients who have a false-positive result is particularly worrisome because some studies suggest that women with false-positive results are less likely to return for screening, perhaps because of their negative experience, Dr. Miglioretti said.
However, her own research has shown that providing immediate screening mammography interpretation and same-day diagnostic workup to individuals who have not had a mammogram in the past 5 years and to younger women could prevent 40% of people from needing to return for diagnostic workup later and potentially reduce time to diagnosis for those with cancer.
It is “important that radiology facilities find ways to reduce false-positive results and the anxiety associated with these results,” Dr. Miglioretti said.
This study was supported by grants from the Swedish Research Council, the Swedish Cancer Society, the Stockholm County Council, and FORTE. Ms. Mao is supported by a grant from the China Scholarship Council. Dr. Miglioretti received funding from PCORI and NCI and royalties from Elsevier.
A version of this article first appeared on Medscape.com.
False-positive mammography results are common, but
Women with a false-positive mammography result had 61% greater risk of developing breast cancer and an 84% greater risk of dying of breast cancer, compared with those who did not have a false-positive result.
However, the investigators also found that the risk for breast cancer varied by individual characteristics such as age and breast density.
The analysis provides clues about which patients with false-positive mammography results will go on to develop breast cancer and “can be used to develop individualized risk-based breast cancer screening,” said the investigators, led by Xinhe Mao, MSc, of Karolinska Institute, Stockholm.
The findings were published online in JAMA Oncology.
About 11% of women in the United States and 2.5% in Europe will receive a false-positive result after a single mammography screening, and previous research shows that these women have a higher risk of developing breast cancer, compared with women without false-positive results. Still, whether this risk for breast cancer varies by individual characteristics and whether an association between a false-positive mammography result and mortality exists remain unclear.
To assess long-term outcomes after a false-positive result, the study investigators compared 45,213 women who had a false-positive mammography result between 1991 and 2017 with 452,130 controls matched for age, calendar year of mammography, and screening history. These data came from the Stockholm Mammography Screening program and Swedish nationwide registers. The analysis also included 1,113 women with a false-positive result and 11,130 matched controls with information on mammographic breast density from the Karolinska Mammography Project for Risk Prediction of Breast Cancer study.
Among women with a false-positive result, the 20-year cumulative breast cancer incidence was 11.3% compared with 7.3% among those without a false-positive (adjusted hazard ratio, 1.61).
Breast cancer risk was higher in older women – those aged 60-75 years (HR, 2.02) – vs younger women aged 40-49 years (HR, 1.38). Breast cancer risk was also higher among women with less dense breasts (HR, 4.65) vs more dense breasts (HR, 1.60) and those who underwent a biopsy during recall (HR, 1.77) vs those who did not (HR, 1.51).
After a false-positive result, cancers were more likely to occur on the ipsilateral side to the false-positive result (HR, 1.92) versus the contralateral (HR, 1.28) and were more common during the first 4 years of follow-up (HR, 2.57 in the first 2 years and 1.93 between 2 and 4 years). No statistical differences were observed based on tumor characteristics, aside from tumor size (HR, 1.78 for tumors ≥ 20 mm vs. 1.47 for smaller tumors).
The prognosis of patients with breast cancer did not differ on the basis of whether they had false-positive results before diagnosis (HR, 1.05 for a false-positive result versus no false-positive result; 95% CI, 0.89-1.25).
This study is the first to show that “women with a false-positive result are at increased risk of death from breast cancer,” Ms. Mao and colleagues concluded. This finding is “most probably associated with the increased breast cancer incidence,” given that the prognosis of patients with breast cancer was similar among those who had a false-positive result versus those who did not.
The authors noted that the increased risk for breast cancer after a false-positive result could suggest that false positives indicate the presence of small tumors that were missed or generally indicate a higher risk for breast cancer. Other factors, such as hormones or genetics, may be at play as well, but would need to be investigated in further studies, Ms. Mao and colleagues noted.
When individualizing surveillance after a false-positive result, age and breast density should be considered, the authors explained. Clinicians may also want to provide more intensive surveillance in the years after a false-positive result as well as education to patients about the risks associated with a false-positive result.
Overall, the findings indicate that clinicians “ should stress the importance of continued screening in women with false-positive results, given their higher risk of cancer, especially within the first 5 or so years after a false-positive result,” Diana L. Miglioretti, PhD, professor and division chief of biostatistics at the University of California, Davis, said in an interview.
Dr. Miglioretti, who has led research on false-positive mammography results and approaches to reduce false positives, noted that “this is a very important study confirming prior work by the Breast Cancer Surveillance Consortium showing individuals with false-positive screening mammography results are at increased risk of developing breast cancer in the future.”
The new evidence demonstrated an increased risk for death from breast cancer in patients who have a false-positive result is particularly worrisome because some studies suggest that women with false-positive results are less likely to return for screening, perhaps because of their negative experience, Dr. Miglioretti said.
However, her own research has shown that providing immediate screening mammography interpretation and same-day diagnostic workup to individuals who have not had a mammogram in the past 5 years and to younger women could prevent 40% of people from needing to return for diagnostic workup later and potentially reduce time to diagnosis for those with cancer.
It is “important that radiology facilities find ways to reduce false-positive results and the anxiety associated with these results,” Dr. Miglioretti said.
This study was supported by grants from the Swedish Research Council, the Swedish Cancer Society, the Stockholm County Council, and FORTE. Ms. Mao is supported by a grant from the China Scholarship Council. Dr. Miglioretti received funding from PCORI and NCI and royalties from Elsevier.
A version of this article first appeared on Medscape.com.
False-positive mammography results are common, but
Women with a false-positive mammography result had 61% greater risk of developing breast cancer and an 84% greater risk of dying of breast cancer, compared with those who did not have a false-positive result.
However, the investigators also found that the risk for breast cancer varied by individual characteristics such as age and breast density.
The analysis provides clues about which patients with false-positive mammography results will go on to develop breast cancer and “can be used to develop individualized risk-based breast cancer screening,” said the investigators, led by Xinhe Mao, MSc, of Karolinska Institute, Stockholm.
The findings were published online in JAMA Oncology.
About 11% of women in the United States and 2.5% in Europe will receive a false-positive result after a single mammography screening, and previous research shows that these women have a higher risk of developing breast cancer, compared with women without false-positive results. Still, whether this risk for breast cancer varies by individual characteristics and whether an association between a false-positive mammography result and mortality exists remain unclear.
To assess long-term outcomes after a false-positive result, the study investigators compared 45,213 women who had a false-positive mammography result between 1991 and 2017 with 452,130 controls matched for age, calendar year of mammography, and screening history. These data came from the Stockholm Mammography Screening program and Swedish nationwide registers. The analysis also included 1,113 women with a false-positive result and 11,130 matched controls with information on mammographic breast density from the Karolinska Mammography Project for Risk Prediction of Breast Cancer study.
Among women with a false-positive result, the 20-year cumulative breast cancer incidence was 11.3% compared with 7.3% among those without a false-positive (adjusted hazard ratio, 1.61).
Breast cancer risk was higher in older women – those aged 60-75 years (HR, 2.02) – vs younger women aged 40-49 years (HR, 1.38). Breast cancer risk was also higher among women with less dense breasts (HR, 4.65) vs more dense breasts (HR, 1.60) and those who underwent a biopsy during recall (HR, 1.77) vs those who did not (HR, 1.51).
After a false-positive result, cancers were more likely to occur on the ipsilateral side to the false-positive result (HR, 1.92) versus the contralateral (HR, 1.28) and were more common during the first 4 years of follow-up (HR, 2.57 in the first 2 years and 1.93 between 2 and 4 years). No statistical differences were observed based on tumor characteristics, aside from tumor size (HR, 1.78 for tumors ≥ 20 mm vs. 1.47 for smaller tumors).
The prognosis of patients with breast cancer did not differ on the basis of whether they had false-positive results before diagnosis (HR, 1.05 for a false-positive result versus no false-positive result; 95% CI, 0.89-1.25).
This study is the first to show that “women with a false-positive result are at increased risk of death from breast cancer,” Ms. Mao and colleagues concluded. This finding is “most probably associated with the increased breast cancer incidence,” given that the prognosis of patients with breast cancer was similar among those who had a false-positive result versus those who did not.
The authors noted that the increased risk for breast cancer after a false-positive result could suggest that false positives indicate the presence of small tumors that were missed or generally indicate a higher risk for breast cancer. Other factors, such as hormones or genetics, may be at play as well, but would need to be investigated in further studies, Ms. Mao and colleagues noted.
When individualizing surveillance after a false-positive result, age and breast density should be considered, the authors explained. Clinicians may also want to provide more intensive surveillance in the years after a false-positive result as well as education to patients about the risks associated with a false-positive result.
Overall, the findings indicate that clinicians “ should stress the importance of continued screening in women with false-positive results, given their higher risk of cancer, especially within the first 5 or so years after a false-positive result,” Diana L. Miglioretti, PhD, professor and division chief of biostatistics at the University of California, Davis, said in an interview.
Dr. Miglioretti, who has led research on false-positive mammography results and approaches to reduce false positives, noted that “this is a very important study confirming prior work by the Breast Cancer Surveillance Consortium showing individuals with false-positive screening mammography results are at increased risk of developing breast cancer in the future.”
The new evidence demonstrated an increased risk for death from breast cancer in patients who have a false-positive result is particularly worrisome because some studies suggest that women with false-positive results are less likely to return for screening, perhaps because of their negative experience, Dr. Miglioretti said.
However, her own research has shown that providing immediate screening mammography interpretation and same-day diagnostic workup to individuals who have not had a mammogram in the past 5 years and to younger women could prevent 40% of people from needing to return for diagnostic workup later and potentially reduce time to diagnosis for those with cancer.
It is “important that radiology facilities find ways to reduce false-positive results and the anxiety associated with these results,” Dr. Miglioretti said.
This study was supported by grants from the Swedish Research Council, the Swedish Cancer Society, the Stockholm County Council, and FORTE. Ms. Mao is supported by a grant from the China Scholarship Council. Dr. Miglioretti received funding from PCORI and NCI and royalties from Elsevier.
A version of this article first appeared on Medscape.com.
FROM JAMA ONCOLOGY
Vasculitis confers higher risk for adverse pregnancy outcomes
SAN DIEGO – Pregnancy in patients with vasculitis had a higher risk for preterm delivery and preeclampsia/eclampsia – especially those with small-vessel vasculitis – compared with the general obstetric population, in a large analysis of administrative claims data presented at the American College of Rheumatology annual meeting.
“We suspect that there is a relationship between the increased risk of these serious hypertensive disorders and preterm delivery, given the higher risk of medically indicated preterm delivery,” one the of the study authors, Audra Horomanski, MD, said in an interview prior to her presentation in a plenary session at the meeting.
Limited data exist on the risks of pregnancy in patients with systemic vasculitis, according to Dr. Horomanski, a rheumatologist who directs the Stanford Vasculitis Clinic at Stanford (Calif.) University. “The majority of what we do know comes from relatively small cohort studies,” she said. “This is the first U.S., nationwide database study looking at the risk of preterm delivery and other adverse pregnancy outcomes.”
Drawing on administrative claims data from private health insurance providers, Dr. Horomanski and her colleagues identified all pregnancies regardless of outcome for patients with and without vasculitis from 2007 to 2021. They defined vasculitis as ≥ 2 ICD-coded outpatient visits or ≥ 1 ICD-coded inpatient visit occurring before the estimated last menstrual period (LMP), and they further categorized vasculitis by vessel size: large, medium, small, and variable, based on Chapel Hill Consensus Conference criteria. For a referent population, they included patients without vasculitis or other rheumatic disease, defined as no ICD-coded outpatient or inpatient visits for vasculitis, systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, or juvenile idiopathic arthritis before LMP or during pregnancy. Next, the researchers described pregnancy outcomes in patients with vasculitis compared with the referent population, and explored pregnancy characteristics and complications in patients with vasculitis stratified by parity (nulliparous vs. multiparous).
Dr. Horomanski reported results from 665 pregnancies in 527 patients with vasculitis and 4,209,034 pregnancies in 2,932,379 patients from the referent population. Patients with vasculitis had higher rates of spontaneous abortion (21% vs. 19%), elective termination (6% vs. 5%), ectopic and molar pregnancy (4% vs. 3%), and preterm delivery (13% vs. 6%). Approximately 12% of pregnancies among patients with vasculitis were complicated by preeclampsia. Multiparous pregnancies had a slightly higher frequency of preterm delivery than did nulliparous pregnancies (14% vs. 13%) and were more often comorbid with gestational diabetes (11% vs. 6%) and prepregnancy hypertension (23% vs. 13%). Patients with small-vessel vasculitis had higher frequencies of spontaneous abortion, preterm delivery, and comorbidities among vasculitis subtypes.
“I was surprised that vasculitis patients were less likely to be diagnosed with gestational hypertension compared to the general population, but more likely to be diagnosed with preeclampsia/eclampsia,” Dr. Horomanski added. “It raises questions about whether vasculitis patients are more likely to be diagnosed with more serious hypertensive disorders of pregnancy due to their underlying systemic disease or due to the perceptions of the treating clinicians.”
She acknowledged certain limitations of the study, including the fact that it lacked information on race and ethnicity and was limited to privately insured individuals. This “suggests that we are likely missing patients with disabilities and those who are uninsured, both groups that may be at higher risk for adverse pregnancy outcomes,” she said. “We also have no information on disease activity or flare events which may contribute to these outcomes, particularly medically indicated preterm delivery. There is also a risk of misclassification due to the use of claims data and ICD coding. This misclassification may impact vasculitis diagnoses, parity, and early pregnancy losses.”
Despite the limitations, she said that the work “highlights the value of large database analysis as a complement to prior cohort studies to further clarify this complex picture. Overall, this information is valuable for the counseling of vasculitis patients considering pregnancy and for creating a plan to monitor for pregnancy complications.”
Lindsay S. Lally, MD, a rheumatologist with Hospital for Special Surgery in New York, who was asked to comment on the study, characterized the findings as “important in how many women with vasculitis and vasculitis pregnancies were identified. These data are a start at heightening our awareness about potential complications these women may experience during pregnancy. This study should help inform our family planning conversations with our vasculitis patients. Discussing potential reproductive risks, which are likely mediated by the disease itself, as well as the treatments that we prescribe, is important to help our vasculitis patients make informed decisions.”
Dr. Lally noted that an ongoing project through the Vasculitis Clinical Research Consortium includes a prospective registry of pregnant women with vasculitis, which asks pregnant patients to enter information throughout their pregnancy. “These studies will ultimately help optimize care of our vasculitis patients during pregnancy, ensuring the best outcomes for mother and baby,” she said.
Dr. Horomanski disclosed that she has received research support from Principia, BeiGene, Gilead, and the National Institutes of Health. Dr. Lally reported having no relevant financial relationships.
A version of this article appeared on Medscape.com.
SAN DIEGO – Pregnancy in patients with vasculitis had a higher risk for preterm delivery and preeclampsia/eclampsia – especially those with small-vessel vasculitis – compared with the general obstetric population, in a large analysis of administrative claims data presented at the American College of Rheumatology annual meeting.
“We suspect that there is a relationship between the increased risk of these serious hypertensive disorders and preterm delivery, given the higher risk of medically indicated preterm delivery,” one the of the study authors, Audra Horomanski, MD, said in an interview prior to her presentation in a plenary session at the meeting.
Limited data exist on the risks of pregnancy in patients with systemic vasculitis, according to Dr. Horomanski, a rheumatologist who directs the Stanford Vasculitis Clinic at Stanford (Calif.) University. “The majority of what we do know comes from relatively small cohort studies,” she said. “This is the first U.S., nationwide database study looking at the risk of preterm delivery and other adverse pregnancy outcomes.”
Drawing on administrative claims data from private health insurance providers, Dr. Horomanski and her colleagues identified all pregnancies regardless of outcome for patients with and without vasculitis from 2007 to 2021. They defined vasculitis as ≥ 2 ICD-coded outpatient visits or ≥ 1 ICD-coded inpatient visit occurring before the estimated last menstrual period (LMP), and they further categorized vasculitis by vessel size: large, medium, small, and variable, based on Chapel Hill Consensus Conference criteria. For a referent population, they included patients without vasculitis or other rheumatic disease, defined as no ICD-coded outpatient or inpatient visits for vasculitis, systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, or juvenile idiopathic arthritis before LMP or during pregnancy. Next, the researchers described pregnancy outcomes in patients with vasculitis compared with the referent population, and explored pregnancy characteristics and complications in patients with vasculitis stratified by parity (nulliparous vs. multiparous).
Dr. Horomanski reported results from 665 pregnancies in 527 patients with vasculitis and 4,209,034 pregnancies in 2,932,379 patients from the referent population. Patients with vasculitis had higher rates of spontaneous abortion (21% vs. 19%), elective termination (6% vs. 5%), ectopic and molar pregnancy (4% vs. 3%), and preterm delivery (13% vs. 6%). Approximately 12% of pregnancies among patients with vasculitis were complicated by preeclampsia. Multiparous pregnancies had a slightly higher frequency of preterm delivery than did nulliparous pregnancies (14% vs. 13%) and were more often comorbid with gestational diabetes (11% vs. 6%) and prepregnancy hypertension (23% vs. 13%). Patients with small-vessel vasculitis had higher frequencies of spontaneous abortion, preterm delivery, and comorbidities among vasculitis subtypes.
“I was surprised that vasculitis patients were less likely to be diagnosed with gestational hypertension compared to the general population, but more likely to be diagnosed with preeclampsia/eclampsia,” Dr. Horomanski added. “It raises questions about whether vasculitis patients are more likely to be diagnosed with more serious hypertensive disorders of pregnancy due to their underlying systemic disease or due to the perceptions of the treating clinicians.”
She acknowledged certain limitations of the study, including the fact that it lacked information on race and ethnicity and was limited to privately insured individuals. This “suggests that we are likely missing patients with disabilities and those who are uninsured, both groups that may be at higher risk for adverse pregnancy outcomes,” she said. “We also have no information on disease activity or flare events which may contribute to these outcomes, particularly medically indicated preterm delivery. There is also a risk of misclassification due to the use of claims data and ICD coding. This misclassification may impact vasculitis diagnoses, parity, and early pregnancy losses.”
Despite the limitations, she said that the work “highlights the value of large database analysis as a complement to prior cohort studies to further clarify this complex picture. Overall, this information is valuable for the counseling of vasculitis patients considering pregnancy and for creating a plan to monitor for pregnancy complications.”
Lindsay S. Lally, MD, a rheumatologist with Hospital for Special Surgery in New York, who was asked to comment on the study, characterized the findings as “important in how many women with vasculitis and vasculitis pregnancies were identified. These data are a start at heightening our awareness about potential complications these women may experience during pregnancy. This study should help inform our family planning conversations with our vasculitis patients. Discussing potential reproductive risks, which are likely mediated by the disease itself, as well as the treatments that we prescribe, is important to help our vasculitis patients make informed decisions.”
Dr. Lally noted that an ongoing project through the Vasculitis Clinical Research Consortium includes a prospective registry of pregnant women with vasculitis, which asks pregnant patients to enter information throughout their pregnancy. “These studies will ultimately help optimize care of our vasculitis patients during pregnancy, ensuring the best outcomes for mother and baby,” she said.
Dr. Horomanski disclosed that she has received research support from Principia, BeiGene, Gilead, and the National Institutes of Health. Dr. Lally reported having no relevant financial relationships.
A version of this article appeared on Medscape.com.
SAN DIEGO – Pregnancy in patients with vasculitis had a higher risk for preterm delivery and preeclampsia/eclampsia – especially those with small-vessel vasculitis – compared with the general obstetric population, in a large analysis of administrative claims data presented at the American College of Rheumatology annual meeting.
“We suspect that there is a relationship between the increased risk of these serious hypertensive disorders and preterm delivery, given the higher risk of medically indicated preterm delivery,” one the of the study authors, Audra Horomanski, MD, said in an interview prior to her presentation in a plenary session at the meeting.
Limited data exist on the risks of pregnancy in patients with systemic vasculitis, according to Dr. Horomanski, a rheumatologist who directs the Stanford Vasculitis Clinic at Stanford (Calif.) University. “The majority of what we do know comes from relatively small cohort studies,” she said. “This is the first U.S., nationwide database study looking at the risk of preterm delivery and other adverse pregnancy outcomes.”
Drawing on administrative claims data from private health insurance providers, Dr. Horomanski and her colleagues identified all pregnancies regardless of outcome for patients with and without vasculitis from 2007 to 2021. They defined vasculitis as ≥ 2 ICD-coded outpatient visits or ≥ 1 ICD-coded inpatient visit occurring before the estimated last menstrual period (LMP), and they further categorized vasculitis by vessel size: large, medium, small, and variable, based on Chapel Hill Consensus Conference criteria. For a referent population, they included patients without vasculitis or other rheumatic disease, defined as no ICD-coded outpatient or inpatient visits for vasculitis, systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, or juvenile idiopathic arthritis before LMP or during pregnancy. Next, the researchers described pregnancy outcomes in patients with vasculitis compared with the referent population, and explored pregnancy characteristics and complications in patients with vasculitis stratified by parity (nulliparous vs. multiparous).
Dr. Horomanski reported results from 665 pregnancies in 527 patients with vasculitis and 4,209,034 pregnancies in 2,932,379 patients from the referent population. Patients with vasculitis had higher rates of spontaneous abortion (21% vs. 19%), elective termination (6% vs. 5%), ectopic and molar pregnancy (4% vs. 3%), and preterm delivery (13% vs. 6%). Approximately 12% of pregnancies among patients with vasculitis were complicated by preeclampsia. Multiparous pregnancies had a slightly higher frequency of preterm delivery than did nulliparous pregnancies (14% vs. 13%) and were more often comorbid with gestational diabetes (11% vs. 6%) and prepregnancy hypertension (23% vs. 13%). Patients with small-vessel vasculitis had higher frequencies of spontaneous abortion, preterm delivery, and comorbidities among vasculitis subtypes.
“I was surprised that vasculitis patients were less likely to be diagnosed with gestational hypertension compared to the general population, but more likely to be diagnosed with preeclampsia/eclampsia,” Dr. Horomanski added. “It raises questions about whether vasculitis patients are more likely to be diagnosed with more serious hypertensive disorders of pregnancy due to their underlying systemic disease or due to the perceptions of the treating clinicians.”
She acknowledged certain limitations of the study, including the fact that it lacked information on race and ethnicity and was limited to privately insured individuals. This “suggests that we are likely missing patients with disabilities and those who are uninsured, both groups that may be at higher risk for adverse pregnancy outcomes,” she said. “We also have no information on disease activity or flare events which may contribute to these outcomes, particularly medically indicated preterm delivery. There is also a risk of misclassification due to the use of claims data and ICD coding. This misclassification may impact vasculitis diagnoses, parity, and early pregnancy losses.”
Despite the limitations, she said that the work “highlights the value of large database analysis as a complement to prior cohort studies to further clarify this complex picture. Overall, this information is valuable for the counseling of vasculitis patients considering pregnancy and for creating a plan to monitor for pregnancy complications.”
Lindsay S. Lally, MD, a rheumatologist with Hospital for Special Surgery in New York, who was asked to comment on the study, characterized the findings as “important in how many women with vasculitis and vasculitis pregnancies were identified. These data are a start at heightening our awareness about potential complications these women may experience during pregnancy. This study should help inform our family planning conversations with our vasculitis patients. Discussing potential reproductive risks, which are likely mediated by the disease itself, as well as the treatments that we prescribe, is important to help our vasculitis patients make informed decisions.”
Dr. Lally noted that an ongoing project through the Vasculitis Clinical Research Consortium includes a prospective registry of pregnant women with vasculitis, which asks pregnant patients to enter information throughout their pregnancy. “These studies will ultimately help optimize care of our vasculitis patients during pregnancy, ensuring the best outcomes for mother and baby,” she said.
Dr. Horomanski disclosed that she has received research support from Principia, BeiGene, Gilead, and the National Institutes of Health. Dr. Lally reported having no relevant financial relationships.
A version of this article appeared on Medscape.com.
AT ACR 2023