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HCV pregnancy increase suggests need for broader screening
Hepatitis C virus (HCV) infection among women giving birth increased 89% from 1.8 cases per 1,000 live births in 2009 to 3.4 cases in 2014, translating to about 35 infants exposed to the virus per day in the United States in 2014, according to the May 11 Morbidity and Mortality Weekly Report.
The highest rate in 2014 was in West Virginia, with 22.6 cases per 1,000 live births. The lowest was in Hawaii, with 0.7 cases.
“The prevalence of maternal HCV infection appears to have increased sharply in the United States. ... Ensuring that women of childbearing age have access to HCV testing and treatment and consideration of universal screening among women of reproductive age residing in areas with high HCV prevalence might mitigate risk and prevent transmission,” said investigators led by Stephen Patrick, MD, of the division of neonatology at Vanderbilt University, Nashville (MMWR. 2017;66[18]:470-3).
Both the Centers for Disease Control and Prevention and the American College of Obstetricians and Gynecologists recommend selective screening of pregnant women at high risk for HCV infection, including intravenous drug users and long-term hemodialysis patients.
“These data might inform expansion of the definition of women at risk.” Generally, about 6% of infants will pick up HCV from their mother during delivery. Screening and treating women of childbearing could reduce the risk, the investigators said.
The analysis was based on U.S. birth certificate data. Risk factors were identified using Tennessee birth certificates.
Hepatitis C virus (HCV) infection among women giving birth increased 89% from 1.8 cases per 1,000 live births in 2009 to 3.4 cases in 2014, translating to about 35 infants exposed to the virus per day in the United States in 2014, according to the May 11 Morbidity and Mortality Weekly Report.
The highest rate in 2014 was in West Virginia, with 22.6 cases per 1,000 live births. The lowest was in Hawaii, with 0.7 cases.
“The prevalence of maternal HCV infection appears to have increased sharply in the United States. ... Ensuring that women of childbearing age have access to HCV testing and treatment and consideration of universal screening among women of reproductive age residing in areas with high HCV prevalence might mitigate risk and prevent transmission,” said investigators led by Stephen Patrick, MD, of the division of neonatology at Vanderbilt University, Nashville (MMWR. 2017;66[18]:470-3).
Both the Centers for Disease Control and Prevention and the American College of Obstetricians and Gynecologists recommend selective screening of pregnant women at high risk for HCV infection, including intravenous drug users and long-term hemodialysis patients.
“These data might inform expansion of the definition of women at risk.” Generally, about 6% of infants will pick up HCV from their mother during delivery. Screening and treating women of childbearing could reduce the risk, the investigators said.
The analysis was based on U.S. birth certificate data. Risk factors were identified using Tennessee birth certificates.
Hepatitis C virus (HCV) infection among women giving birth increased 89% from 1.8 cases per 1,000 live births in 2009 to 3.4 cases in 2014, translating to about 35 infants exposed to the virus per day in the United States in 2014, according to the May 11 Morbidity and Mortality Weekly Report.
The highest rate in 2014 was in West Virginia, with 22.6 cases per 1,000 live births. The lowest was in Hawaii, with 0.7 cases.
“The prevalence of maternal HCV infection appears to have increased sharply in the United States. ... Ensuring that women of childbearing age have access to HCV testing and treatment and consideration of universal screening among women of reproductive age residing in areas with high HCV prevalence might mitigate risk and prevent transmission,” said investigators led by Stephen Patrick, MD, of the division of neonatology at Vanderbilt University, Nashville (MMWR. 2017;66[18]:470-3).
Both the Centers for Disease Control and Prevention and the American College of Obstetricians and Gynecologists recommend selective screening of pregnant women at high risk for HCV infection, including intravenous drug users and long-term hemodialysis patients.
“These data might inform expansion of the definition of women at risk.” Generally, about 6% of infants will pick up HCV from their mother during delivery. Screening and treating women of childbearing could reduce the risk, the investigators said.
The analysis was based on U.S. birth certificate data. Risk factors were identified using Tennessee birth certificates.
FROM MMWR
Lower-dose aluminum hydroxide–adjuvanted polio vaccine noninferior to standard IPV
Aluminum hydroxide–adjuvanted vaccines with reduced doses of inactivated polio vaccine (IPV-Al) were noninferior to standard inactivated poliovirus vaccine (IPV) in a large trial in the Dominican Republic, said Luis Rivera, MD, of the Hospital Maternidad Nuestra Señora de la Altagracia, Santo Domingo, Dominican Republic, and his associates.
If these findings are replicated in phase III trials and regulatory approval follows, such vaccines could be low-cost replacements for standard IPV and oral poliovirus vaccines in low-resource countries, the study authors suggested.
In this phase II, blinded, randomized trial with three investigational IPV-Al groups and one IPV group, the vaccines were given at 6 weeks, 10 weeks, 14 weeks, and 18 weeks to 823 infants who had not previously received any polio vaccination. The three new IPV-Al vaccines all proved to be noninferior to IPV for poliovirus types 1, 2, and 3.
For 1/10 IPV-Al, the seroconversion rates for the different poliovirus types were 98.5% (type 1), 94.6% (type 2), and 99.5% (type 3), compared with 100% (type 1), 98.5% (type 2), and 100% (type 3) for IPV.
This and the results from other studies “have paved the way for further clinical investigations of IPV-Al in phase III trials,” Dr. Rivera and his associates wrote.
“The low frequency of adverse events in this phase II trial suggests that a safety evaluation is not necessarily justified,” they concluded.
The Bill & Melinda Gates Foundation funded the study. The authors had no disclosures.
Read more in the Lancet Infectious Diseases (2017 Apr 25. doi: 10.1016/S1473-3099(17)30177-9).
Aluminum hydroxide–adjuvanted vaccines with reduced doses of inactivated polio vaccine (IPV-Al) were noninferior to standard inactivated poliovirus vaccine (IPV) in a large trial in the Dominican Republic, said Luis Rivera, MD, of the Hospital Maternidad Nuestra Señora de la Altagracia, Santo Domingo, Dominican Republic, and his associates.
If these findings are replicated in phase III trials and regulatory approval follows, such vaccines could be low-cost replacements for standard IPV and oral poliovirus vaccines in low-resource countries, the study authors suggested.
In this phase II, blinded, randomized trial with three investigational IPV-Al groups and one IPV group, the vaccines were given at 6 weeks, 10 weeks, 14 weeks, and 18 weeks to 823 infants who had not previously received any polio vaccination. The three new IPV-Al vaccines all proved to be noninferior to IPV for poliovirus types 1, 2, and 3.
For 1/10 IPV-Al, the seroconversion rates for the different poliovirus types were 98.5% (type 1), 94.6% (type 2), and 99.5% (type 3), compared with 100% (type 1), 98.5% (type 2), and 100% (type 3) for IPV.
This and the results from other studies “have paved the way for further clinical investigations of IPV-Al in phase III trials,” Dr. Rivera and his associates wrote.
“The low frequency of adverse events in this phase II trial suggests that a safety evaluation is not necessarily justified,” they concluded.
The Bill & Melinda Gates Foundation funded the study. The authors had no disclosures.
Read more in the Lancet Infectious Diseases (2017 Apr 25. doi: 10.1016/S1473-3099(17)30177-9).
Aluminum hydroxide–adjuvanted vaccines with reduced doses of inactivated polio vaccine (IPV-Al) were noninferior to standard inactivated poliovirus vaccine (IPV) in a large trial in the Dominican Republic, said Luis Rivera, MD, of the Hospital Maternidad Nuestra Señora de la Altagracia, Santo Domingo, Dominican Republic, and his associates.
If these findings are replicated in phase III trials and regulatory approval follows, such vaccines could be low-cost replacements for standard IPV and oral poliovirus vaccines in low-resource countries, the study authors suggested.
In this phase II, blinded, randomized trial with three investigational IPV-Al groups and one IPV group, the vaccines were given at 6 weeks, 10 weeks, 14 weeks, and 18 weeks to 823 infants who had not previously received any polio vaccination. The three new IPV-Al vaccines all proved to be noninferior to IPV for poliovirus types 1, 2, and 3.
For 1/10 IPV-Al, the seroconversion rates for the different poliovirus types were 98.5% (type 1), 94.6% (type 2), and 99.5% (type 3), compared with 100% (type 1), 98.5% (type 2), and 100% (type 3) for IPV.
This and the results from other studies “have paved the way for further clinical investigations of IPV-Al in phase III trials,” Dr. Rivera and his associates wrote.
“The low frequency of adverse events in this phase II trial suggests that a safety evaluation is not necessarily justified,” they concluded.
The Bill & Melinda Gates Foundation funded the study. The authors had no disclosures.
Read more in the Lancet Infectious Diseases (2017 Apr 25. doi: 10.1016/S1473-3099(17)30177-9).
FROM THE LANCET INFECTIOUS DISEASES
Novel evaluation, treatment of NAS decreases medication use
AT PAS 2017
SAN FRANCISCO – A nonpharmacologic approach to neonatal abstinence syndrome (NAS) appears to reduce the use of morphine and may shorten hospital stay, compared with the conventional evaluation that looks at symptoms of opioid withdrawal, a study showed.
“If you focus on the well-being of these infants rather than a list of symptoms, you are much less likely to start medication. Our approach inherently destigmatizes the parents of these infants by allowing them to focus on the same things that any other parent focuses on,” said Matthew Lipshaw, MD, a pediatrician at Yale–New Haven (Conn.) Children’s Hospital.
The novel approach aims instead to avoid drug use. According to Dr. Lipshaw, the nonintrusive approach “assesses infants’ ability to function as infants during their withdrawal.” The approach provides a low-stimulation environment featuring rooming-in by mothers, and frequent feeding of their infants. Dubbed ESC, the approach gauges the ability of an infant to eat 1 ounce or more or breastfeed well, sleep undisturbed for an hour or longer, and be consolable within 10 minutes.
The ESC approach replaced the FNASS at Yale–New Haven Children’s Hospital in 2013. While patient management decisions since then have been based on ESC, FNASS scores have continued to be collected every 2-6 hours. This provided the researchers with the means to conduct a head-to-head comparison of the two systems on the same patients.
The records of 50 consecutive newborns born from March 2014 to August 2015 who had been exposed to opioids for at least 30 days prior to birth were reviewed. The primary outcome was the proportion of infants treated with morphine. Secondary outcomes included disagreements between the two approaches on a daily basis, seizures, 30-day readmissions, and need for more intensive care.
The neonates (56%, female) were mostly white. All were born at greater than 36 weeks’ gestation. Opioid exposure was methadone in 80% of cases and buprenorphine in 14%, with the remaining 6% exposed to hydrocodone, Percocet (acetaminophen/oxycodone), and/or OxyContin (oxycodone).
Morphine was started in 6 (12%) of the 50 patients. If the FNASS protocol had been followed, 31 (62%) of the infants would have been started on morphine (P less than .01). Over a span of 296 hospital days, when the ESC protocol was used, morphine was not used 87% of the time, morphine use was increased 3% of the time, use was decreased 7% of the time, and use was maintained 3% of the time. If decisions had been made based on the FNASS protocol, the frequency of nonuse, increased use, decreased use, and maintained use of morphine would have been 53%, 26%, 12%, and 10%, respectively (all P less than .01).
The use of morphine was less than the FNASS recommendation on 78 days (26% of the total days). Moreover, the FNASS scores on the days following the decreased use of morphine were lower by an average of 0.9 points and were decreased in 69% of cases. The ESC protocol led to greater morphine use than recommended by the FNASS protocol on only 2 days. Both times, the FNASS score was increased the following day.
No adverse events occurred during the study.
“These findings are significant because nearly all institutions use the Finnegan score to guide management, and most research has used Finnegan-based medication thresholds to evaluate new medical therapies. Our point is that if you base your assessment on function, many of these infants may not need medication at all. We have had dramatic reductions in length of stay, which allows these infants to get home and minimize the interruption in this crucial period for maternal-child bonding in these high-risk patients,” Dr. Lipshaw said at the Pediatric Academic Societies meeting.
So far, only the Boston Medical Center has implemented the new system. This does not surprise Dr. Lipshaw: “Most places have been using a symptom-based approach for decades. It requires major buy in from physicians and nurses who have been doing things differently for a long time.”
He said is not deterred, however, and pointed to ongoing efforts by colleagues at Yale–New Haven Hospital and Boston Medical Center that are underway that could led to the ESC’s use in a network of hospitals in New Hampshire and Vermont.
The study was sponsored by Yale–New Haven Children’s Hospital and was not funded. Dr. Lipshaw reported having no relevant financial disclosures.
AT PAS 2017
SAN FRANCISCO – A nonpharmacologic approach to neonatal abstinence syndrome (NAS) appears to reduce the use of morphine and may shorten hospital stay, compared with the conventional evaluation that looks at symptoms of opioid withdrawal, a study showed.
“If you focus on the well-being of these infants rather than a list of symptoms, you are much less likely to start medication. Our approach inherently destigmatizes the parents of these infants by allowing them to focus on the same things that any other parent focuses on,” said Matthew Lipshaw, MD, a pediatrician at Yale–New Haven (Conn.) Children’s Hospital.
The novel approach aims instead to avoid drug use. According to Dr. Lipshaw, the nonintrusive approach “assesses infants’ ability to function as infants during their withdrawal.” The approach provides a low-stimulation environment featuring rooming-in by mothers, and frequent feeding of their infants. Dubbed ESC, the approach gauges the ability of an infant to eat 1 ounce or more or breastfeed well, sleep undisturbed for an hour or longer, and be consolable within 10 minutes.
The ESC approach replaced the FNASS at Yale–New Haven Children’s Hospital in 2013. While patient management decisions since then have been based on ESC, FNASS scores have continued to be collected every 2-6 hours. This provided the researchers with the means to conduct a head-to-head comparison of the two systems on the same patients.
The records of 50 consecutive newborns born from March 2014 to August 2015 who had been exposed to opioids for at least 30 days prior to birth were reviewed. The primary outcome was the proportion of infants treated with morphine. Secondary outcomes included disagreements between the two approaches on a daily basis, seizures, 30-day readmissions, and need for more intensive care.
The neonates (56%, female) were mostly white. All were born at greater than 36 weeks’ gestation. Opioid exposure was methadone in 80% of cases and buprenorphine in 14%, with the remaining 6% exposed to hydrocodone, Percocet (acetaminophen/oxycodone), and/or OxyContin (oxycodone).
Morphine was started in 6 (12%) of the 50 patients. If the FNASS protocol had been followed, 31 (62%) of the infants would have been started on morphine (P less than .01). Over a span of 296 hospital days, when the ESC protocol was used, morphine was not used 87% of the time, morphine use was increased 3% of the time, use was decreased 7% of the time, and use was maintained 3% of the time. If decisions had been made based on the FNASS protocol, the frequency of nonuse, increased use, decreased use, and maintained use of morphine would have been 53%, 26%, 12%, and 10%, respectively (all P less than .01).
The use of morphine was less than the FNASS recommendation on 78 days (26% of the total days). Moreover, the FNASS scores on the days following the decreased use of morphine were lower by an average of 0.9 points and were decreased in 69% of cases. The ESC protocol led to greater morphine use than recommended by the FNASS protocol on only 2 days. Both times, the FNASS score was increased the following day.
No adverse events occurred during the study.
“These findings are significant because nearly all institutions use the Finnegan score to guide management, and most research has used Finnegan-based medication thresholds to evaluate new medical therapies. Our point is that if you base your assessment on function, many of these infants may not need medication at all. We have had dramatic reductions in length of stay, which allows these infants to get home and minimize the interruption in this crucial period for maternal-child bonding in these high-risk patients,” Dr. Lipshaw said at the Pediatric Academic Societies meeting.
So far, only the Boston Medical Center has implemented the new system. This does not surprise Dr. Lipshaw: “Most places have been using a symptom-based approach for decades. It requires major buy in from physicians and nurses who have been doing things differently for a long time.”
He said is not deterred, however, and pointed to ongoing efforts by colleagues at Yale–New Haven Hospital and Boston Medical Center that are underway that could led to the ESC’s use in a network of hospitals in New Hampshire and Vermont.
The study was sponsored by Yale–New Haven Children’s Hospital and was not funded. Dr. Lipshaw reported having no relevant financial disclosures.
AT PAS 2017
SAN FRANCISCO – A nonpharmacologic approach to neonatal abstinence syndrome (NAS) appears to reduce the use of morphine and may shorten hospital stay, compared with the conventional evaluation that looks at symptoms of opioid withdrawal, a study showed.
“If you focus on the well-being of these infants rather than a list of symptoms, you are much less likely to start medication. Our approach inherently destigmatizes the parents of these infants by allowing them to focus on the same things that any other parent focuses on,” said Matthew Lipshaw, MD, a pediatrician at Yale–New Haven (Conn.) Children’s Hospital.
The novel approach aims instead to avoid drug use. According to Dr. Lipshaw, the nonintrusive approach “assesses infants’ ability to function as infants during their withdrawal.” The approach provides a low-stimulation environment featuring rooming-in by mothers, and frequent feeding of their infants. Dubbed ESC, the approach gauges the ability of an infant to eat 1 ounce or more or breastfeed well, sleep undisturbed for an hour or longer, and be consolable within 10 minutes.
The ESC approach replaced the FNASS at Yale–New Haven Children’s Hospital in 2013. While patient management decisions since then have been based on ESC, FNASS scores have continued to be collected every 2-6 hours. This provided the researchers with the means to conduct a head-to-head comparison of the two systems on the same patients.
The records of 50 consecutive newborns born from March 2014 to August 2015 who had been exposed to opioids for at least 30 days prior to birth were reviewed. The primary outcome was the proportion of infants treated with morphine. Secondary outcomes included disagreements between the two approaches on a daily basis, seizures, 30-day readmissions, and need for more intensive care.
The neonates (56%, female) were mostly white. All were born at greater than 36 weeks’ gestation. Opioid exposure was methadone in 80% of cases and buprenorphine in 14%, with the remaining 6% exposed to hydrocodone, Percocet (acetaminophen/oxycodone), and/or OxyContin (oxycodone).
Morphine was started in 6 (12%) of the 50 patients. If the FNASS protocol had been followed, 31 (62%) of the infants would have been started on morphine (P less than .01). Over a span of 296 hospital days, when the ESC protocol was used, morphine was not used 87% of the time, morphine use was increased 3% of the time, use was decreased 7% of the time, and use was maintained 3% of the time. If decisions had been made based on the FNASS protocol, the frequency of nonuse, increased use, decreased use, and maintained use of morphine would have been 53%, 26%, 12%, and 10%, respectively (all P less than .01).
The use of morphine was less than the FNASS recommendation on 78 days (26% of the total days). Moreover, the FNASS scores on the days following the decreased use of morphine were lower by an average of 0.9 points and were decreased in 69% of cases. The ESC protocol led to greater morphine use than recommended by the FNASS protocol on only 2 days. Both times, the FNASS score was increased the following day.
No adverse events occurred during the study.
“These findings are significant because nearly all institutions use the Finnegan score to guide management, and most research has used Finnegan-based medication thresholds to evaluate new medical therapies. Our point is that if you base your assessment on function, many of these infants may not need medication at all. We have had dramatic reductions in length of stay, which allows these infants to get home and minimize the interruption in this crucial period for maternal-child bonding in these high-risk patients,” Dr. Lipshaw said at the Pediatric Academic Societies meeting.
So far, only the Boston Medical Center has implemented the new system. This does not surprise Dr. Lipshaw: “Most places have been using a symptom-based approach for decades. It requires major buy in from physicians and nurses who have been doing things differently for a long time.”
He said is not deterred, however, and pointed to ongoing efforts by colleagues at Yale–New Haven Hospital and Boston Medical Center that are underway that could led to the ESC’s use in a network of hospitals in New Hampshire and Vermont.
The study was sponsored by Yale–New Haven Children’s Hospital and was not funded. Dr. Lipshaw reported having no relevant financial disclosures.
Key clinical point: Evaluation and treatment of neonatal abstinence syndrome that focuses on feeding, quality of sleep, and ability to be consoled significantly reduces morphine use, compared with the established system.
Major finding: The novel ESC approach decreased morphine use, compared with the established FNASS approach (3% vs. 26%, P less than .01).
Data source: A retrospective examination of patient medical records.
Disclosures: The study was sponsored by Yale–New Haven Children’s Hospital and was not funded. Dr. Lipshaw reported having no relevant financial disclosures.
UTI predictors identified in infants under 3 months of age
SAN FRANCISCO – Serum leukocytosis, pyuria, and urine leukocyte esterase have been identified as predictors of urinary tract infection (UTI) in infants younger than 90 days of age, with males being more likely to develop UTI than females.
The chance of the infection declined in older infants.
“Really young infants have a less well developed immune system, which may increase their susceptibility to UTIs,” said Sarah Berman, DO, a pediatric resident at Winthrop-University Hospital, Mineola, N.Y.
In 2011, the American Academy of Pediatrics issued “Urinary Tract Infection: Clinical Practice Guidelines for the Diagnosis and Management of the Initial UTI in Febrile Infants and Children 2 to 24 Months” (Pediatrics. 2011. doi: 10.1542/peds.2011-1330) concerning the diagnosis and management of the presence of bacteria in urine – a possible warning sign of UTI, but the AAP guidelines did not consider infants in the first 2 months of life.
To address this gap, the Winthrop-University Hospital researchers reviewed the medical records for all infants younger than 90 days of age diagnosed with UTI, fever, or viral illness from the beginning of 2009 to September 2015. Residence in neonatal intensive care, known congenital abnormalities, and prior antibiotic use were grounds for exclusion. Standard growth-based definitions of UTI and bacteriuria were used.
Of the 315 mainly white or Hispanic patients, 73 had a diagnosis of UTI and 261 did not. Both groups had the same mean age of 45 days. Fever within 24 hours of admission was more prevalent in those without UTI than those with (57% vs. 41%; P = .035). Those with UTI were significantly more likely (all P lesser than .001) to display serum leukocytosis (35% vs. 12%), pyuria (71% vs. 12%), and urine detection of leukocyte esterase (87% vs. 14%) and nitrite (19% vs. 0%).
In a univariate analysis, factors that were associated with UTI included serum leukocytosis, white blood cells in the urine, and urine leukocyte esterase, with fever within 24 hours of admission associated with reduced chance of UTI. A multivariate analysis that accounted for age, gender, and gestational age identified serum leukocytosis, pyruria, urine leukocyte esterase, and male sex as predictors of UTI, with increased odds ratio of 6.25, 3.19, 28, and 3.88, respectively.
The reduced likelihood of UTI in those who developed a fever within 24 hours of admission held up in the multivariate analysis (odds ratio 0.34).
Validation of the findings will require a prospective study, which is in the planning stage. If the findings bear out, the result could be improved diagnosis of UTI from birth onward, according to Dr. Berman.
Dr. Berman reported having no relevant financial disclosures.
SAN FRANCISCO – Serum leukocytosis, pyuria, and urine leukocyte esterase have been identified as predictors of urinary tract infection (UTI) in infants younger than 90 days of age, with males being more likely to develop UTI than females.
The chance of the infection declined in older infants.
“Really young infants have a less well developed immune system, which may increase their susceptibility to UTIs,” said Sarah Berman, DO, a pediatric resident at Winthrop-University Hospital, Mineola, N.Y.
In 2011, the American Academy of Pediatrics issued “Urinary Tract Infection: Clinical Practice Guidelines for the Diagnosis and Management of the Initial UTI in Febrile Infants and Children 2 to 24 Months” (Pediatrics. 2011. doi: 10.1542/peds.2011-1330) concerning the diagnosis and management of the presence of bacteria in urine – a possible warning sign of UTI, but the AAP guidelines did not consider infants in the first 2 months of life.
To address this gap, the Winthrop-University Hospital researchers reviewed the medical records for all infants younger than 90 days of age diagnosed with UTI, fever, or viral illness from the beginning of 2009 to September 2015. Residence in neonatal intensive care, known congenital abnormalities, and prior antibiotic use were grounds for exclusion. Standard growth-based definitions of UTI and bacteriuria were used.
Of the 315 mainly white or Hispanic patients, 73 had a diagnosis of UTI and 261 did not. Both groups had the same mean age of 45 days. Fever within 24 hours of admission was more prevalent in those without UTI than those with (57% vs. 41%; P = .035). Those with UTI were significantly more likely (all P lesser than .001) to display serum leukocytosis (35% vs. 12%), pyuria (71% vs. 12%), and urine detection of leukocyte esterase (87% vs. 14%) and nitrite (19% vs. 0%).
In a univariate analysis, factors that were associated with UTI included serum leukocytosis, white blood cells in the urine, and urine leukocyte esterase, with fever within 24 hours of admission associated with reduced chance of UTI. A multivariate analysis that accounted for age, gender, and gestational age identified serum leukocytosis, pyruria, urine leukocyte esterase, and male sex as predictors of UTI, with increased odds ratio of 6.25, 3.19, 28, and 3.88, respectively.
The reduced likelihood of UTI in those who developed a fever within 24 hours of admission held up in the multivariate analysis (odds ratio 0.34).
Validation of the findings will require a prospective study, which is in the planning stage. If the findings bear out, the result could be improved diagnosis of UTI from birth onward, according to Dr. Berman.
Dr. Berman reported having no relevant financial disclosures.
SAN FRANCISCO – Serum leukocytosis, pyuria, and urine leukocyte esterase have been identified as predictors of urinary tract infection (UTI) in infants younger than 90 days of age, with males being more likely to develop UTI than females.
The chance of the infection declined in older infants.
“Really young infants have a less well developed immune system, which may increase their susceptibility to UTIs,” said Sarah Berman, DO, a pediatric resident at Winthrop-University Hospital, Mineola, N.Y.
In 2011, the American Academy of Pediatrics issued “Urinary Tract Infection: Clinical Practice Guidelines for the Diagnosis and Management of the Initial UTI in Febrile Infants and Children 2 to 24 Months” (Pediatrics. 2011. doi: 10.1542/peds.2011-1330) concerning the diagnosis and management of the presence of bacteria in urine – a possible warning sign of UTI, but the AAP guidelines did not consider infants in the first 2 months of life.
To address this gap, the Winthrop-University Hospital researchers reviewed the medical records for all infants younger than 90 days of age diagnosed with UTI, fever, or viral illness from the beginning of 2009 to September 2015. Residence in neonatal intensive care, known congenital abnormalities, and prior antibiotic use were grounds for exclusion. Standard growth-based definitions of UTI and bacteriuria were used.
Of the 315 mainly white or Hispanic patients, 73 had a diagnosis of UTI and 261 did not. Both groups had the same mean age of 45 days. Fever within 24 hours of admission was more prevalent in those without UTI than those with (57% vs. 41%; P = .035). Those with UTI were significantly more likely (all P lesser than .001) to display serum leukocytosis (35% vs. 12%), pyuria (71% vs. 12%), and urine detection of leukocyte esterase (87% vs. 14%) and nitrite (19% vs. 0%).
In a univariate analysis, factors that were associated with UTI included serum leukocytosis, white blood cells in the urine, and urine leukocyte esterase, with fever within 24 hours of admission associated with reduced chance of UTI. A multivariate analysis that accounted for age, gender, and gestational age identified serum leukocytosis, pyruria, urine leukocyte esterase, and male sex as predictors of UTI, with increased odds ratio of 6.25, 3.19, 28, and 3.88, respectively.
The reduced likelihood of UTI in those who developed a fever within 24 hours of admission held up in the multivariate analysis (odds ratio 0.34).
Validation of the findings will require a prospective study, which is in the planning stage. If the findings bear out, the result could be improved diagnosis of UTI from birth onward, according to Dr. Berman.
Dr. Berman reported having no relevant financial disclosures.
AT PAS 17
Key clinical point: Pyuria, urine leukocyte esterase, and serum leukocytosis appear to be predictors of urinary tract infection in infants younger than 90 days of age.
Major finding: A multivariate analysis identified serum leukocytosis, pyruria, and urine leukocyte esterase as predictors of UTI, with increased odds ratio of 6.25, 3.19, and 28, respectively.
Data source: Retrospective analysis of medical records from one hospital.
Disclosures: Dr. Berman reported having no relevant financial disclosures.
Breastfeeding among factors that modify neonatal abstinence syndrome
SAN FRANCISCO – The good news of a prospective, multicenter study presented at the Pediatric Academic Societies meeting was that neonates who were breastfed were less likely to require neonatal abstinence syndrome (NAS) treatment and displayed milder symptoms.
The study also identified other risk factors associated with the need for NAS treatment and the severity of NAS.
“These findings are important because many of these risk factors are modifiable. Prenatal care providers strive to provide the best treatments for both the mother and the fetus. Our findings regarding the association of NAS with some maternal drug exposures can be shared with opiate-dependent mothers during general counseling about tobacco and illicit use in pregnancy and in counseling about NAS,” explained Megan Stover, MD, a fellow in maternal-fetal medicine and genetics at Tufts Medical Center in Boston.
The current standard of care for opioid-dependent pregnant women is medication-assisted treatment with either methadone or buprenorphine. The intervention can be effective in curbing continued opioid abuse and preventing relapse. However, for many of their unborn children, the damage has already been done.
The scope of the problem in the United States is staggering. Between 2004 and 2013, there was a fourfold to fivefold increase in the rate of admissions to neonatal intensive care units (NICUs) for NAS. “It has been estimated that, every minute in the United States, one neonate will require treatment for NAS,” said Dr. Stover. The glum reality for the Tufts researchers is that 50%-80% of opiate-exposed infants will require treatment for NAS. The aim is to reduce this rate.
Dr. Stover was part of a study conducted at hospitals on the U.S. East Coast that aimed to clarify factors before and after birth that were associated with NAS. The enrolled mothers had been treated during their third trimester or following admission for birth for opioid dependence or had received an opioid for relief of chronic pain. They had given birth to their child at term.
Neonates who were born prematurely or who had comorbidities judged to be significant were not part of the analyses. Of the 306 neonates included, 52% required treatment for NAS and 48% did not. The two groups were similar in age of the mother and for neonatal characteristics of gestational age, sex, ethnicity, and body measurements at birth. The severity of NAS was gauged in two ways. One was the number of days of treatment required to free the neonates from the opioid-induced symptoms, with less than 10 days indicating mild NAS, greater than 30 days indicating severe NAS, and the intervening days indicating moderate NAS. Severe NAS also was indicated by the use of two or more medications.
There was good news. Neonates were significantly less likely to require NAS treatment if they were breastfed exclusively, compared with formula fed babies (15% vs 67%; P less than .0001). NAS was usually mild in breastfed babies and often severe in formula-fed babies (P less than .002).
“Our findings regarding the favorable outcomes seen with breastfeeding support recent research regarding the influence of nonpharmacologic approaches to the prevention and management of NAS, namely that more soothing environments, like those outside the NICU, may be more optimal settings for infants undergoing surveillance for NAS,” said Dr. Stover.
Neonatal treatment was more prevalent for women whose opioid substitution therapy involved methadone (54% vs 28% of untreated neonates; P less than .0001). When therapy used buprenorphine, 62% of the neonates did not display NAS. The drug used for substitution therapy had no effect on the length of treatment of the neonates.
“Our data regarding methadone exposure [versus buprenorphine] adds to a growing literature surrounding more favorable neonatal effects seen with this opiate maintenance agent over methadone,” commented Dr. Stover.
NAS treatment was more prevalent for mothers who smoked during pregnancy, compared with those who did not (76% vs 42%; P equal to .02), and for maternal use of illicit drugs (50% vs 34%; P equal to .002), with no effect on length of neonatal treatment.
Maternal psychiatric diagnosis was associated with neonatal NAS (P equal to .03), as was prescription benzodiazepine use in the third trimester of pregnancy (P equal to .02). Benzodiazepine use did not influence the length of treatment. However, maternal alprazolam use did, as it was associated with more severe NAS (P less than .001). Use of selective serotonin reuptake inhibitor during pregnancy was also associated with more severe NAS (P equal to 0.01).
The researchers are currently sifting through the genetic data gathered in the study. The goal is to combine the clinical and genetic data to create a risk score that will be used to tailor care before birth and in the early weeks following birth.
The study was sponsored by Tufts Medical Center and was funded by National Institute on Drug Abuse. Dr. Stover reported having no relevant financial disclosures.
SAN FRANCISCO – The good news of a prospective, multicenter study presented at the Pediatric Academic Societies meeting was that neonates who were breastfed were less likely to require neonatal abstinence syndrome (NAS) treatment and displayed milder symptoms.
The study also identified other risk factors associated with the need for NAS treatment and the severity of NAS.
“These findings are important because many of these risk factors are modifiable. Prenatal care providers strive to provide the best treatments for both the mother and the fetus. Our findings regarding the association of NAS with some maternal drug exposures can be shared with opiate-dependent mothers during general counseling about tobacco and illicit use in pregnancy and in counseling about NAS,” explained Megan Stover, MD, a fellow in maternal-fetal medicine and genetics at Tufts Medical Center in Boston.
The current standard of care for opioid-dependent pregnant women is medication-assisted treatment with either methadone or buprenorphine. The intervention can be effective in curbing continued opioid abuse and preventing relapse. However, for many of their unborn children, the damage has already been done.
The scope of the problem in the United States is staggering. Between 2004 and 2013, there was a fourfold to fivefold increase in the rate of admissions to neonatal intensive care units (NICUs) for NAS. “It has been estimated that, every minute in the United States, one neonate will require treatment for NAS,” said Dr. Stover. The glum reality for the Tufts researchers is that 50%-80% of opiate-exposed infants will require treatment for NAS. The aim is to reduce this rate.
Dr. Stover was part of a study conducted at hospitals on the U.S. East Coast that aimed to clarify factors before and after birth that were associated with NAS. The enrolled mothers had been treated during their third trimester or following admission for birth for opioid dependence or had received an opioid for relief of chronic pain. They had given birth to their child at term.
Neonates who were born prematurely or who had comorbidities judged to be significant were not part of the analyses. Of the 306 neonates included, 52% required treatment for NAS and 48% did not. The two groups were similar in age of the mother and for neonatal characteristics of gestational age, sex, ethnicity, and body measurements at birth. The severity of NAS was gauged in two ways. One was the number of days of treatment required to free the neonates from the opioid-induced symptoms, with less than 10 days indicating mild NAS, greater than 30 days indicating severe NAS, and the intervening days indicating moderate NAS. Severe NAS also was indicated by the use of two or more medications.
There was good news. Neonates were significantly less likely to require NAS treatment if they were breastfed exclusively, compared with formula fed babies (15% vs 67%; P less than .0001). NAS was usually mild in breastfed babies and often severe in formula-fed babies (P less than .002).
“Our findings regarding the favorable outcomes seen with breastfeeding support recent research regarding the influence of nonpharmacologic approaches to the prevention and management of NAS, namely that more soothing environments, like those outside the NICU, may be more optimal settings for infants undergoing surveillance for NAS,” said Dr. Stover.
Neonatal treatment was more prevalent for women whose opioid substitution therapy involved methadone (54% vs 28% of untreated neonates; P less than .0001). When therapy used buprenorphine, 62% of the neonates did not display NAS. The drug used for substitution therapy had no effect on the length of treatment of the neonates.
“Our data regarding methadone exposure [versus buprenorphine] adds to a growing literature surrounding more favorable neonatal effects seen with this opiate maintenance agent over methadone,” commented Dr. Stover.
NAS treatment was more prevalent for mothers who smoked during pregnancy, compared with those who did not (76% vs 42%; P equal to .02), and for maternal use of illicit drugs (50% vs 34%; P equal to .002), with no effect on length of neonatal treatment.
Maternal psychiatric diagnosis was associated with neonatal NAS (P equal to .03), as was prescription benzodiazepine use in the third trimester of pregnancy (P equal to .02). Benzodiazepine use did not influence the length of treatment. However, maternal alprazolam use did, as it was associated with more severe NAS (P less than .001). Use of selective serotonin reuptake inhibitor during pregnancy was also associated with more severe NAS (P equal to 0.01).
The researchers are currently sifting through the genetic data gathered in the study. The goal is to combine the clinical and genetic data to create a risk score that will be used to tailor care before birth and in the early weeks following birth.
The study was sponsored by Tufts Medical Center and was funded by National Institute on Drug Abuse. Dr. Stover reported having no relevant financial disclosures.
SAN FRANCISCO – The good news of a prospective, multicenter study presented at the Pediatric Academic Societies meeting was that neonates who were breastfed were less likely to require neonatal abstinence syndrome (NAS) treatment and displayed milder symptoms.
The study also identified other risk factors associated with the need for NAS treatment and the severity of NAS.
“These findings are important because many of these risk factors are modifiable. Prenatal care providers strive to provide the best treatments for both the mother and the fetus. Our findings regarding the association of NAS with some maternal drug exposures can be shared with opiate-dependent mothers during general counseling about tobacco and illicit use in pregnancy and in counseling about NAS,” explained Megan Stover, MD, a fellow in maternal-fetal medicine and genetics at Tufts Medical Center in Boston.
The current standard of care for opioid-dependent pregnant women is medication-assisted treatment with either methadone or buprenorphine. The intervention can be effective in curbing continued opioid abuse and preventing relapse. However, for many of their unborn children, the damage has already been done.
The scope of the problem in the United States is staggering. Between 2004 and 2013, there was a fourfold to fivefold increase in the rate of admissions to neonatal intensive care units (NICUs) for NAS. “It has been estimated that, every minute in the United States, one neonate will require treatment for NAS,” said Dr. Stover. The glum reality for the Tufts researchers is that 50%-80% of opiate-exposed infants will require treatment for NAS. The aim is to reduce this rate.
Dr. Stover was part of a study conducted at hospitals on the U.S. East Coast that aimed to clarify factors before and after birth that were associated with NAS. The enrolled mothers had been treated during their third trimester or following admission for birth for opioid dependence or had received an opioid for relief of chronic pain. They had given birth to their child at term.
Neonates who were born prematurely or who had comorbidities judged to be significant were not part of the analyses. Of the 306 neonates included, 52% required treatment for NAS and 48% did not. The two groups were similar in age of the mother and for neonatal characteristics of gestational age, sex, ethnicity, and body measurements at birth. The severity of NAS was gauged in two ways. One was the number of days of treatment required to free the neonates from the opioid-induced symptoms, with less than 10 days indicating mild NAS, greater than 30 days indicating severe NAS, and the intervening days indicating moderate NAS. Severe NAS also was indicated by the use of two or more medications.
There was good news. Neonates were significantly less likely to require NAS treatment if they were breastfed exclusively, compared with formula fed babies (15% vs 67%; P less than .0001). NAS was usually mild in breastfed babies and often severe in formula-fed babies (P less than .002).
“Our findings regarding the favorable outcomes seen with breastfeeding support recent research regarding the influence of nonpharmacologic approaches to the prevention and management of NAS, namely that more soothing environments, like those outside the NICU, may be more optimal settings for infants undergoing surveillance for NAS,” said Dr. Stover.
Neonatal treatment was more prevalent for women whose opioid substitution therapy involved methadone (54% vs 28% of untreated neonates; P less than .0001). When therapy used buprenorphine, 62% of the neonates did not display NAS. The drug used for substitution therapy had no effect on the length of treatment of the neonates.
“Our data regarding methadone exposure [versus buprenorphine] adds to a growing literature surrounding more favorable neonatal effects seen with this opiate maintenance agent over methadone,” commented Dr. Stover.
NAS treatment was more prevalent for mothers who smoked during pregnancy, compared with those who did not (76% vs 42%; P equal to .02), and for maternal use of illicit drugs (50% vs 34%; P equal to .002), with no effect on length of neonatal treatment.
Maternal psychiatric diagnosis was associated with neonatal NAS (P equal to .03), as was prescription benzodiazepine use in the third trimester of pregnancy (P equal to .02). Benzodiazepine use did not influence the length of treatment. However, maternal alprazolam use did, as it was associated with more severe NAS (P less than .001). Use of selective serotonin reuptake inhibitor during pregnancy was also associated with more severe NAS (P equal to 0.01).
The researchers are currently sifting through the genetic data gathered in the study. The goal is to combine the clinical and genetic data to create a risk score that will be used to tailor care before birth and in the early weeks following birth.
The study was sponsored by Tufts Medical Center and was funded by National Institute on Drug Abuse. Dr. Stover reported having no relevant financial disclosures.
AT PAS 2017
Key clinical point: Clinical factors associated with the need for treatment of neonatal abstinence syndrome and for its severity were identified.
Major finding: Breastfeeding was also associated with less severe NAS (P equal to .0003).
Data source: Prospective cohort analysis as part of a multisite trial.
Disclosures: The study was sponsored by Tufts Medical Center and was funded by the National Institute on Drug Abuse. Dr. Stover reported having no relevant financial disclosures.
Buprenorphine is an alternative to morphine in treating NAS
SAN FRANCISCO – The phase III, single-center Blinded Buprenorphine or Neonatal Morphine Solution (BBORN) clinical trial has established the efficacy of buprenorphine as an alternative to morphine for treatment of newborns with neonatal abstinence syndrome (NAS).
The strategy cuts the treatment time needed to relieve the withdrawal symptoms of the infants by nearly half, the researchers reported. The study results, presented at the Pediatric Academic Societies meeting, were simultaneously published in the New England Journal of Medicine (2017. doi: 10.1056/NEJMoa1614835).
“For those infants who ultimately require pharmacologic treatment, the BBORN trial demonstrated that buprenorphine has similar safety and improved efficacy in length of treatment and length of stay compared to morphine, which is used in 80% of neonatal intensive care units,” said Walter K. Kraft, MD, of Thomas Jefferson University, Philadelphia,.
In the trial, 63 term infants (greater than and equal to 37 weeks of gestation) exposed to opioids prior to birth and who displayed signs of NAS were randomized to receive sublingual buprenorphine or oral morphine. Prior exposure to benzodiazepine in the 30 days before birth, medical or neurologic illness, and elevated bilirubin were grounds for exclusion.
The primary endpoint was the length of treatment needed to deal with the withdrawal symptoms. Secondary endpoints included length of hospitalization, need for supplementary treatment with phenobarbital, and safety.
The groups were comparable at baseline, with the exception of median gestational age in the buprenorphine group (38.5 vs. 39.0 weeks, P = .03). Most of the infants were white. Almost all mothers were on maintenance methadone therapy and almost all were current smokers. Thirty-three infants were randomized to receive buprenorphine. Three withdrew and were treated with open-label morphine. Thirty infants received morphine, with two withdrawing to the open-label treatment.
Those receiving buprenorphine displayed significantly shorter median duration of treatment (15 vs. 28 days) and median length of hospital stay (21 vs. 33 days) (both P less than .001). The use of supplemental phenobarbital was similar in both groups.
Occurrence of adverse events was similar, with 13 events in 7 infants in the buprenorphine group and 10 events in 8 infants in the morphine group. One serious event occurred in each group; neither was treatment related.
“The trial only proves that buprenorphine works but does not answer how. We suspect a long half-life is a part of the answer, though methadone also has a long half-life. We have not compared buprenorphine to methadone for treatment of infants with neonatal abstinence syndrome. We conjecture that as a partial agonist, weaning may be smoother. In our trial, it was a shorter wean time, rather than quicker control of symptoms, in which buprenorphine was more effective than morphine. Buprenorphine has effects on other receptors, but it is very unclear if this added to efficacy relative to morphine,” explained Dr. Kraft.
“Regarding mechanism, it is believed that the somatic (as opposed to the drug craving) symptoms of opiate withdrawal in the adult arise from areas of the brainstem called the locus coeruleus and periaqueductal gray, which express opiate receptors. These areas are undergoing major developmental changes in utero and at the time of birth. Therefore, although we hypothesize that the withdrawal symptoms in the infants are likely arising from the same regions, it has not been proven, and is actually something we are investigating in rodent models,” explained the study’s main author, Michelle Ehrlich, MD, of Icahn School of Medicine at Mount Sinai, New York.
While the trial’s findings presented at PAS 17 are an advance in the armamentarium of care for NAS, the researchers are adamant that the approach should not be seen as a stand-alone treatment.
“I would stress than an approach to treatment of neonatal abstinence syndrome most importantly be multidisciplinary and use a uniform institutional protocol. For example, there should be standardization of Finnegan scoring with continuous quality improvement. All babies should have nonpharmacologic treatment of breastfeeding, rooming in, and minimization of excessive stimuli,” explained Dr. Kraft.
Next steps include clarifying the pharmacokinetics to optimize the dose, and to assess the influence of buprenorphine on neurobehavior. “We suspect the mechanism of action to be similar to that of adults. However, how the biology of neonatal abstinence syndrome differs from opioid withdrawal of adults is not known and [is] an area in need of more investigation. We did collect pharmacokinetic samples, and these data are currently being analyzed,” said Dr. Kraft.
Thomas Jefferson University sponsored the study, which was funded by the National Institute on Drug Abuse. Dr. Kraft reported serving as an unpaid consultant to Chiesi Farmaceutici S.p.A. Dr. Ehrlich disclosed receipt of buprenorphine from Indivior for the study and grants from NIDA.
SAN FRANCISCO – The phase III, single-center Blinded Buprenorphine or Neonatal Morphine Solution (BBORN) clinical trial has established the efficacy of buprenorphine as an alternative to morphine for treatment of newborns with neonatal abstinence syndrome (NAS).
The strategy cuts the treatment time needed to relieve the withdrawal symptoms of the infants by nearly half, the researchers reported. The study results, presented at the Pediatric Academic Societies meeting, were simultaneously published in the New England Journal of Medicine (2017. doi: 10.1056/NEJMoa1614835).
“For those infants who ultimately require pharmacologic treatment, the BBORN trial demonstrated that buprenorphine has similar safety and improved efficacy in length of treatment and length of stay compared to morphine, which is used in 80% of neonatal intensive care units,” said Walter K. Kraft, MD, of Thomas Jefferson University, Philadelphia,.
In the trial, 63 term infants (greater than and equal to 37 weeks of gestation) exposed to opioids prior to birth and who displayed signs of NAS were randomized to receive sublingual buprenorphine or oral morphine. Prior exposure to benzodiazepine in the 30 days before birth, medical or neurologic illness, and elevated bilirubin were grounds for exclusion.
The primary endpoint was the length of treatment needed to deal with the withdrawal symptoms. Secondary endpoints included length of hospitalization, need for supplementary treatment with phenobarbital, and safety.
The groups were comparable at baseline, with the exception of median gestational age in the buprenorphine group (38.5 vs. 39.0 weeks, P = .03). Most of the infants were white. Almost all mothers were on maintenance methadone therapy and almost all were current smokers. Thirty-three infants were randomized to receive buprenorphine. Three withdrew and were treated with open-label morphine. Thirty infants received morphine, with two withdrawing to the open-label treatment.
Those receiving buprenorphine displayed significantly shorter median duration of treatment (15 vs. 28 days) and median length of hospital stay (21 vs. 33 days) (both P less than .001). The use of supplemental phenobarbital was similar in both groups.
Occurrence of adverse events was similar, with 13 events in 7 infants in the buprenorphine group and 10 events in 8 infants in the morphine group. One serious event occurred in each group; neither was treatment related.
“The trial only proves that buprenorphine works but does not answer how. We suspect a long half-life is a part of the answer, though methadone also has a long half-life. We have not compared buprenorphine to methadone for treatment of infants with neonatal abstinence syndrome. We conjecture that as a partial agonist, weaning may be smoother. In our trial, it was a shorter wean time, rather than quicker control of symptoms, in which buprenorphine was more effective than morphine. Buprenorphine has effects on other receptors, but it is very unclear if this added to efficacy relative to morphine,” explained Dr. Kraft.
“Regarding mechanism, it is believed that the somatic (as opposed to the drug craving) symptoms of opiate withdrawal in the adult arise from areas of the brainstem called the locus coeruleus and periaqueductal gray, which express opiate receptors. These areas are undergoing major developmental changes in utero and at the time of birth. Therefore, although we hypothesize that the withdrawal symptoms in the infants are likely arising from the same regions, it has not been proven, and is actually something we are investigating in rodent models,” explained the study’s main author, Michelle Ehrlich, MD, of Icahn School of Medicine at Mount Sinai, New York.
While the trial’s findings presented at PAS 17 are an advance in the armamentarium of care for NAS, the researchers are adamant that the approach should not be seen as a stand-alone treatment.
“I would stress than an approach to treatment of neonatal abstinence syndrome most importantly be multidisciplinary and use a uniform institutional protocol. For example, there should be standardization of Finnegan scoring with continuous quality improvement. All babies should have nonpharmacologic treatment of breastfeeding, rooming in, and minimization of excessive stimuli,” explained Dr. Kraft.
Next steps include clarifying the pharmacokinetics to optimize the dose, and to assess the influence of buprenorphine on neurobehavior. “We suspect the mechanism of action to be similar to that of adults. However, how the biology of neonatal abstinence syndrome differs from opioid withdrawal of adults is not known and [is] an area in need of more investigation. We did collect pharmacokinetic samples, and these data are currently being analyzed,” said Dr. Kraft.
Thomas Jefferson University sponsored the study, which was funded by the National Institute on Drug Abuse. Dr. Kraft reported serving as an unpaid consultant to Chiesi Farmaceutici S.p.A. Dr. Ehrlich disclosed receipt of buprenorphine from Indivior for the study and grants from NIDA.
SAN FRANCISCO – The phase III, single-center Blinded Buprenorphine or Neonatal Morphine Solution (BBORN) clinical trial has established the efficacy of buprenorphine as an alternative to morphine for treatment of newborns with neonatal abstinence syndrome (NAS).
The strategy cuts the treatment time needed to relieve the withdrawal symptoms of the infants by nearly half, the researchers reported. The study results, presented at the Pediatric Academic Societies meeting, were simultaneously published in the New England Journal of Medicine (2017. doi: 10.1056/NEJMoa1614835).
“For those infants who ultimately require pharmacologic treatment, the BBORN trial demonstrated that buprenorphine has similar safety and improved efficacy in length of treatment and length of stay compared to morphine, which is used in 80% of neonatal intensive care units,” said Walter K. Kraft, MD, of Thomas Jefferson University, Philadelphia,.
In the trial, 63 term infants (greater than and equal to 37 weeks of gestation) exposed to opioids prior to birth and who displayed signs of NAS were randomized to receive sublingual buprenorphine or oral morphine. Prior exposure to benzodiazepine in the 30 days before birth, medical or neurologic illness, and elevated bilirubin were grounds for exclusion.
The primary endpoint was the length of treatment needed to deal with the withdrawal symptoms. Secondary endpoints included length of hospitalization, need for supplementary treatment with phenobarbital, and safety.
The groups were comparable at baseline, with the exception of median gestational age in the buprenorphine group (38.5 vs. 39.0 weeks, P = .03). Most of the infants were white. Almost all mothers were on maintenance methadone therapy and almost all were current smokers. Thirty-three infants were randomized to receive buprenorphine. Three withdrew and were treated with open-label morphine. Thirty infants received morphine, with two withdrawing to the open-label treatment.
Those receiving buprenorphine displayed significantly shorter median duration of treatment (15 vs. 28 days) and median length of hospital stay (21 vs. 33 days) (both P less than .001). The use of supplemental phenobarbital was similar in both groups.
Occurrence of adverse events was similar, with 13 events in 7 infants in the buprenorphine group and 10 events in 8 infants in the morphine group. One serious event occurred in each group; neither was treatment related.
“The trial only proves that buprenorphine works but does not answer how. We suspect a long half-life is a part of the answer, though methadone also has a long half-life. We have not compared buprenorphine to methadone for treatment of infants with neonatal abstinence syndrome. We conjecture that as a partial agonist, weaning may be smoother. In our trial, it was a shorter wean time, rather than quicker control of symptoms, in which buprenorphine was more effective than morphine. Buprenorphine has effects on other receptors, but it is very unclear if this added to efficacy relative to morphine,” explained Dr. Kraft.
“Regarding mechanism, it is believed that the somatic (as opposed to the drug craving) symptoms of opiate withdrawal in the adult arise from areas of the brainstem called the locus coeruleus and periaqueductal gray, which express opiate receptors. These areas are undergoing major developmental changes in utero and at the time of birth. Therefore, although we hypothesize that the withdrawal symptoms in the infants are likely arising from the same regions, it has not been proven, and is actually something we are investigating in rodent models,” explained the study’s main author, Michelle Ehrlich, MD, of Icahn School of Medicine at Mount Sinai, New York.
While the trial’s findings presented at PAS 17 are an advance in the armamentarium of care for NAS, the researchers are adamant that the approach should not be seen as a stand-alone treatment.
“I would stress than an approach to treatment of neonatal abstinence syndrome most importantly be multidisciplinary and use a uniform institutional protocol. For example, there should be standardization of Finnegan scoring with continuous quality improvement. All babies should have nonpharmacologic treatment of breastfeeding, rooming in, and minimization of excessive stimuli,” explained Dr. Kraft.
Next steps include clarifying the pharmacokinetics to optimize the dose, and to assess the influence of buprenorphine on neurobehavior. “We suspect the mechanism of action to be similar to that of adults. However, how the biology of neonatal abstinence syndrome differs from opioid withdrawal of adults is not known and [is] an area in need of more investigation. We did collect pharmacokinetic samples, and these data are currently being analyzed,” said Dr. Kraft.
Thomas Jefferson University sponsored the study, which was funded by the National Institute on Drug Abuse. Dr. Kraft reported serving as an unpaid consultant to Chiesi Farmaceutici S.p.A. Dr. Ehrlich disclosed receipt of buprenorphine from Indivior for the study and grants from NIDA.
AT PAS 17
Key clinical point:
Major finding: Buprenorphine reduced median length of treatment (15 vs. 28 days, P less than .001) and median length of stay (21 vs. 34.5 days, P less than .001), compared with morphine.
Data source: Double-blind, double-dummy, single-site, randomized clinical trial (NCT01452789).
Disclosures: Thomas Jefferson University sponsored the study, which was funded by the National Institute on Drug Abuse. Dr. Kraft reported serving as an unpaid consultant to Chiesi Farmaceutici S.p.A. Dr. Ehrlich disclosed receipt of buprenorphine from Indivior for the study and grants from NIDA.
Constipation implicated as an indicator of Helicobacter pylori infection
SAN FRANCISCO – Infants refractory constipation and chronic abdominal pain should be tested for the presence of Helicobacter pylori infection. Just relying on the detection of antigen to H. pylori in stool may not be a definitive indicator of the bacterial infection; endoscopic biopsy is a more specific test, according to study findings presented at the Pediatric Academic Societies meeting.
“Our study highlights that constipation seems to be prevalent among children who test positive for H. pylori in stool. No other predominant symptom was found to be related to H. pylori infection,” said Ayesha Baig, MD, a third-year resident at Brookdale University Hospital and Medical Center in Brooklyn, N.Y.
Gastritis that results from H. pylori infection in the mucous membrane lining the stomach is extremely common in children and adolescents. Yet, diagnosis remains challenging, with disagreement about the hallmark symptoms to look for in making the diagnosis.
The researchers retrospectively examined the medical records of patients aged 2-18 years who had been treated for chronic abdominal pain at the hospital’s gastrointestinal clinic between late 2013 and mid-2016. One aim was to see if there was a predominant symptom in patients in whom H. pylori infection had been proven by the detection of antibody to the bacteria in stool and/or in an endoscopic biopsy. Other aims were to identify a relationship between symptoms and the two methods of detecting H. pylori, and to see if symptoms varied with age. Other gastrointestinal disorders were not considered.
The majority (60%) of the 91 patients were male. Most were African American. Their mean age was 10-12 years.
The presence of nausea, vomiting, diarrhea, constipation, blood in stool, and prior history of use of proton pump inhibitors were compared in those testing positive and negative for H. pylori.
Of the patients who were constipated, 72% tested positive for H. pylori in stool and 28% of tested positive for H. pylori in endoscopic biopsy. In patients testing positive for H. pylori based on the presence of antigen in the stool, about 40% tested negative using endoscopic biopsy.
Age was irrelevant concerning biopsy results and symptoms.
“A proportion of patients who tested positive for H. pylori stool antigen tested negative for H. pylori using endoscopic biopsy, which is a higher-specificity method. Our study indicated that stool antigen alone is not a definitive indicator for treating H. pylori,” said Dr. Baig.
The influence of empiric treatment is still an open question that needs examination.
Dr. Baig reported having no relevant financial disclosures.
*This article was updated on 5/24/2017.
SAN FRANCISCO – Infants refractory constipation and chronic abdominal pain should be tested for the presence of Helicobacter pylori infection. Just relying on the detection of antigen to H. pylori in stool may not be a definitive indicator of the bacterial infection; endoscopic biopsy is a more specific test, according to study findings presented at the Pediatric Academic Societies meeting.
“Our study highlights that constipation seems to be prevalent among children who test positive for H. pylori in stool. No other predominant symptom was found to be related to H. pylori infection,” said Ayesha Baig, MD, a third-year resident at Brookdale University Hospital and Medical Center in Brooklyn, N.Y.
Gastritis that results from H. pylori infection in the mucous membrane lining the stomach is extremely common in children and adolescents. Yet, diagnosis remains challenging, with disagreement about the hallmark symptoms to look for in making the diagnosis.
The researchers retrospectively examined the medical records of patients aged 2-18 years who had been treated for chronic abdominal pain at the hospital’s gastrointestinal clinic between late 2013 and mid-2016. One aim was to see if there was a predominant symptom in patients in whom H. pylori infection had been proven by the detection of antibody to the bacteria in stool and/or in an endoscopic biopsy. Other aims were to identify a relationship between symptoms and the two methods of detecting H. pylori, and to see if symptoms varied with age. Other gastrointestinal disorders were not considered.
The majority (60%) of the 91 patients were male. Most were African American. Their mean age was 10-12 years.
The presence of nausea, vomiting, diarrhea, constipation, blood in stool, and prior history of use of proton pump inhibitors were compared in those testing positive and negative for H. pylori.
Of the patients who were constipated, 72% tested positive for H. pylori in stool and 28% of tested positive for H. pylori in endoscopic biopsy. In patients testing positive for H. pylori based on the presence of antigen in the stool, about 40% tested negative using endoscopic biopsy.
Age was irrelevant concerning biopsy results and symptoms.
“A proportion of patients who tested positive for H. pylori stool antigen tested negative for H. pylori using endoscopic biopsy, which is a higher-specificity method. Our study indicated that stool antigen alone is not a definitive indicator for treating H. pylori,” said Dr. Baig.
The influence of empiric treatment is still an open question that needs examination.
Dr. Baig reported having no relevant financial disclosures.
*This article was updated on 5/24/2017.
SAN FRANCISCO – Infants refractory constipation and chronic abdominal pain should be tested for the presence of Helicobacter pylori infection. Just relying on the detection of antigen to H. pylori in stool may not be a definitive indicator of the bacterial infection; endoscopic biopsy is a more specific test, according to study findings presented at the Pediatric Academic Societies meeting.
“Our study highlights that constipation seems to be prevalent among children who test positive for H. pylori in stool. No other predominant symptom was found to be related to H. pylori infection,” said Ayesha Baig, MD, a third-year resident at Brookdale University Hospital and Medical Center in Brooklyn, N.Y.
Gastritis that results from H. pylori infection in the mucous membrane lining the stomach is extremely common in children and adolescents. Yet, diagnosis remains challenging, with disagreement about the hallmark symptoms to look for in making the diagnosis.
The researchers retrospectively examined the medical records of patients aged 2-18 years who had been treated for chronic abdominal pain at the hospital’s gastrointestinal clinic between late 2013 and mid-2016. One aim was to see if there was a predominant symptom in patients in whom H. pylori infection had been proven by the detection of antibody to the bacteria in stool and/or in an endoscopic biopsy. Other aims were to identify a relationship between symptoms and the two methods of detecting H. pylori, and to see if symptoms varied with age. Other gastrointestinal disorders were not considered.
The majority (60%) of the 91 patients were male. Most were African American. Their mean age was 10-12 years.
The presence of nausea, vomiting, diarrhea, constipation, blood in stool, and prior history of use of proton pump inhibitors were compared in those testing positive and negative for H. pylori.
Of the patients who were constipated, 72% tested positive for H. pylori in stool and 28% of tested positive for H. pylori in endoscopic biopsy. In patients testing positive for H. pylori based on the presence of antigen in the stool, about 40% tested negative using endoscopic biopsy.
Age was irrelevant concerning biopsy results and symptoms.
“A proportion of patients who tested positive for H. pylori stool antigen tested negative for H. pylori using endoscopic biopsy, which is a higher-specificity method. Our study indicated that stool antigen alone is not a definitive indicator for treating H. pylori,” said Dr. Baig.
The influence of empiric treatment is still an open question that needs examination.
Dr. Baig reported having no relevant financial disclosures.
*This article was updated on 5/24/2017.
AT PAS 17
Key clinical point:
Major finding: Seventy-two percent and 28% of patients who were constipated tested positive for H. pylori in stool and in endoscopic biopsy, respectively.
Data source: Retrospective case-control study from a single medical center.
Disclosures: Dr. Baig reported having no relevant financial disclosures.
Periconception smoking found to affect birth defect risk
SAN DIEGO – Smoking during the period of fetal organogenesis, during the first trimester of pregnancy, is associated with increased risk of some birth defects, results from a large retrospective analysis demonstrated.
Ms. Perry, a second-year medical student at the University of Cincinnati and her associates conducted a population-based retrospective cohort analysis of 1,436,036 live births in Ohio during 2006-2015. They compared the rates of major defects between births to nonsmoking mothers and those who smoked only during the 3-month preconception period and not in the first trimester; and in the preconception period plus throughout the first trimester. They used multivariate logistic regression to quantify the relationship between smoking and birth defects after adjustment for maternal race, age, pregestational diabetes, and socioeconomic factors.
The researchers observed that 23.3% of women smoked during pregnancy; 6.0% during preconception only and 17.3% smoked through the first trimester, as well. Smoking during the preconception period only, even without first trimester exposure, was associated with a 40% increased risk of gastroschisis (adjusted risk ratio, 1.4), but no other individual birth defects. However, smoking through the first trimester was associated with a modest but significantly increased risk of several defects, including gastroschisis (adjusted RR, 1.9), limb reduction (adjusted RR, 1.6), congenital diaphragmatic hernia (adjusted RR, 1.4), and cleft palate (adjusted RR, 1.2), even after adjustment for coexisting factors.
“It was surprising to see that, even when women stop smoking when they find out they are pregnant, and therefore are not smoking during the period of fetal organogenesis, there is still an increased risk of some congenital birth defects to the fetus,” Ms. Perry said. “My hope is that this study serves as a launching point for future research and public health efforts. It’s important to encourage smoking cessation in women of reproductive age, whether pregnant or not. Furthermore, it’s valuable to be able to explain to patients that along with adverse effects to their own health, smoking even before conception poses a risk to the fetus.”
She acknowledged certain limitations of the study, including its observational design. “There could exist unmeasurable influences that we were unable to adjust for,” Ms. Perry said. She reported having no financial disclosures.
SAN DIEGO – Smoking during the period of fetal organogenesis, during the first trimester of pregnancy, is associated with increased risk of some birth defects, results from a large retrospective analysis demonstrated.
Ms. Perry, a second-year medical student at the University of Cincinnati and her associates conducted a population-based retrospective cohort analysis of 1,436,036 live births in Ohio during 2006-2015. They compared the rates of major defects between births to nonsmoking mothers and those who smoked only during the 3-month preconception period and not in the first trimester; and in the preconception period plus throughout the first trimester. They used multivariate logistic regression to quantify the relationship between smoking and birth defects after adjustment for maternal race, age, pregestational diabetes, and socioeconomic factors.
The researchers observed that 23.3% of women smoked during pregnancy; 6.0% during preconception only and 17.3% smoked through the first trimester, as well. Smoking during the preconception period only, even without first trimester exposure, was associated with a 40% increased risk of gastroschisis (adjusted risk ratio, 1.4), but no other individual birth defects. However, smoking through the first trimester was associated with a modest but significantly increased risk of several defects, including gastroschisis (adjusted RR, 1.9), limb reduction (adjusted RR, 1.6), congenital diaphragmatic hernia (adjusted RR, 1.4), and cleft palate (adjusted RR, 1.2), even after adjustment for coexisting factors.
“It was surprising to see that, even when women stop smoking when they find out they are pregnant, and therefore are not smoking during the period of fetal organogenesis, there is still an increased risk of some congenital birth defects to the fetus,” Ms. Perry said. “My hope is that this study serves as a launching point for future research and public health efforts. It’s important to encourage smoking cessation in women of reproductive age, whether pregnant or not. Furthermore, it’s valuable to be able to explain to patients that along with adverse effects to their own health, smoking even before conception poses a risk to the fetus.”
She acknowledged certain limitations of the study, including its observational design. “There could exist unmeasurable influences that we were unable to adjust for,” Ms. Perry said. She reported having no financial disclosures.
SAN DIEGO – Smoking during the period of fetal organogenesis, during the first trimester of pregnancy, is associated with increased risk of some birth defects, results from a large retrospective analysis demonstrated.
Ms. Perry, a second-year medical student at the University of Cincinnati and her associates conducted a population-based retrospective cohort analysis of 1,436,036 live births in Ohio during 2006-2015. They compared the rates of major defects between births to nonsmoking mothers and those who smoked only during the 3-month preconception period and not in the first trimester; and in the preconception period plus throughout the first trimester. They used multivariate logistic regression to quantify the relationship between smoking and birth defects after adjustment for maternal race, age, pregestational diabetes, and socioeconomic factors.
The researchers observed that 23.3% of women smoked during pregnancy; 6.0% during preconception only and 17.3% smoked through the first trimester, as well. Smoking during the preconception period only, even without first trimester exposure, was associated with a 40% increased risk of gastroschisis (adjusted risk ratio, 1.4), but no other individual birth defects. However, smoking through the first trimester was associated with a modest but significantly increased risk of several defects, including gastroschisis (adjusted RR, 1.9), limb reduction (adjusted RR, 1.6), congenital diaphragmatic hernia (adjusted RR, 1.4), and cleft palate (adjusted RR, 1.2), even after adjustment for coexisting factors.
“It was surprising to see that, even when women stop smoking when they find out they are pregnant, and therefore are not smoking during the period of fetal organogenesis, there is still an increased risk of some congenital birth defects to the fetus,” Ms. Perry said. “My hope is that this study serves as a launching point for future research and public health efforts. It’s important to encourage smoking cessation in women of reproductive age, whether pregnant or not. Furthermore, it’s valuable to be able to explain to patients that along with adverse effects to their own health, smoking even before conception poses a risk to the fetus.”
She acknowledged certain limitations of the study, including its observational design. “There could exist unmeasurable influences that we were unable to adjust for,” Ms. Perry said. She reported having no financial disclosures.
AT ACOG 2017
Key clinical point:
Major finding: Smoking during only the preconception period was associated with a 40% increased risk of gastroschisis (adjusted RR, 1.4), while smoking during the first trimester of pregnancy was associated with a significantly increased risk of gastroschisis (adjusted RR, 1.9) and several other birth defects.
Data source: A retrospective cohort analysis of 1,436,036 live births in Ohio during 2006-2015.
Disclosures: Ms. Perry reported having no financial disclosures.
Maternal antidepressants unrelated to autism in offspring
Maternal use of antidepressants during pregnancy is unrelated to autism spectrum disorder in the offspring, according to two separate, population-level cohort studies that used sophisticated statistical techniques to account for numerous confounding factors.
Both studies were reported online April 18 in JAMA.
Some previous studies have reported a possible link between in utero exposure to antidepressants, particularly SSRIs, and autism. But they had limited ability to control for key confounders, notably the mother’s underlying depression.
Overall, 1.1% of these children were diagnosed as having autism spectrum disorder. This prevalence is consistent with current population estimates, indicating that few if any cases of the disorder were missed, said Dr. Brown of Women’s College Research Institute in Toronto and the division of epidemiology, University of Toronto, and her associates.
In initial, unadjusted analyses of the data, the risk of autism was higher in exposed than in nonexposed children. However, that association disappeared once the data were adjusted to account for numerous potential confounders.
Further analysis comparing the exposed children with their unexposed siblings also found that after adjusting for confounding factors, prenatal exposure to antidepressants did not affect the risk of developing autism. In addition, this lack of association also was found in the subgroup of children whose mothers took antidepressants shortly before but not during pregnancy.
Taken together, these findings “suggest that confounding by indication for the medication may explain previously observed associations between in utero serotonergic antidepressant exposure and autism spectrum disorder,” Dr. Brown and her associates said (JAMA. 2017 Apr 18. doi: 10.1001.jama.2017.3415). In the other study, Ayesha C. Sujan and her associates analyzed data in several nationwide Swedish registries to examine whether first trimester exposure to any antidepressants raised the risk of a range of neurodevelopmental problems, including autism. This study involved 1,580,629 offspring, including 22,544 (1.4%) whose mothers took antidepressants during the first trimester.
As with Dr. Brown’s study, the initial unadjusted analysis showed an association between antidepressant exposure and autism, but that association disappeared once the data were adjusted to account for confounding factors. In the final data analysis, first trimester exposure was associated with preterm birth (odds ratio, 1.34) but not with small-for-gestational-age size (OR, 1.01), autism spectrum disorder (hazard ratio, 0.83), or attention deficit/hyperactivity disorder (HR, 0.99), said Ms. Sujan of the department of psychological and brain sciences, Indiana University, Bloomington, and her associates.
“These results are consistent with the hypothesis that genetic factors, familial environmental factors, or both, account for the population-wide associations between first-trimester antidepressant exposure and these outcomes,” they noted (JAMA. 2017 Apr 18. doi: 10.1001/jama.2017.3413).
These two studies add to the growing literature suggesting that any association between prenatal antidepressant exposure and autism spectrum disorder may not be causal.
Both reports should reassure both parents and clinicians.
And regardless of whether any such association reflects antidepressant effects, the mother’s underlying mental health, or other factors, efforts should focus on promoting optimal child health in ways that harness the child’s inherent developmental plasticity.
Tim F. Oberlander, MD, is in the division of developmental pediatrics at the University of British Columbia and at the British Columbia Children’s Hospital Research Institute, both in Vancouver. Lonnie Zwaigenbaum, MD, is in the department of pediatrics at the University of Alberta, Edmonton. They reported having no relevant financial disclosures. These remarks were excerpted from an editorial accompanying the two reports (JAMA. 2017;317[15]:1533-4).
These two studies add to the growing literature suggesting that any association between prenatal antidepressant exposure and autism spectrum disorder may not be causal.
Both reports should reassure both parents and clinicians.
And regardless of whether any such association reflects antidepressant effects, the mother’s underlying mental health, or other factors, efforts should focus on promoting optimal child health in ways that harness the child’s inherent developmental plasticity.
Tim F. Oberlander, MD, is in the division of developmental pediatrics at the University of British Columbia and at the British Columbia Children’s Hospital Research Institute, both in Vancouver. Lonnie Zwaigenbaum, MD, is in the department of pediatrics at the University of Alberta, Edmonton. They reported having no relevant financial disclosures. These remarks were excerpted from an editorial accompanying the two reports (JAMA. 2017;317[15]:1533-4).
These two studies add to the growing literature suggesting that any association between prenatal antidepressant exposure and autism spectrum disorder may not be causal.
Both reports should reassure both parents and clinicians.
And regardless of whether any such association reflects antidepressant effects, the mother’s underlying mental health, or other factors, efforts should focus on promoting optimal child health in ways that harness the child’s inherent developmental plasticity.
Tim F. Oberlander, MD, is in the division of developmental pediatrics at the University of British Columbia and at the British Columbia Children’s Hospital Research Institute, both in Vancouver. Lonnie Zwaigenbaum, MD, is in the department of pediatrics at the University of Alberta, Edmonton. They reported having no relevant financial disclosures. These remarks were excerpted from an editorial accompanying the two reports (JAMA. 2017;317[15]:1533-4).
Maternal use of antidepressants during pregnancy is unrelated to autism spectrum disorder in the offspring, according to two separate, population-level cohort studies that used sophisticated statistical techniques to account for numerous confounding factors.
Both studies were reported online April 18 in JAMA.
Some previous studies have reported a possible link between in utero exposure to antidepressants, particularly SSRIs, and autism. But they had limited ability to control for key confounders, notably the mother’s underlying depression.
Overall, 1.1% of these children were diagnosed as having autism spectrum disorder. This prevalence is consistent with current population estimates, indicating that few if any cases of the disorder were missed, said Dr. Brown of Women’s College Research Institute in Toronto and the division of epidemiology, University of Toronto, and her associates.
In initial, unadjusted analyses of the data, the risk of autism was higher in exposed than in nonexposed children. However, that association disappeared once the data were adjusted to account for numerous potential confounders.
Further analysis comparing the exposed children with their unexposed siblings also found that after adjusting for confounding factors, prenatal exposure to antidepressants did not affect the risk of developing autism. In addition, this lack of association also was found in the subgroup of children whose mothers took antidepressants shortly before but not during pregnancy.
Taken together, these findings “suggest that confounding by indication for the medication may explain previously observed associations between in utero serotonergic antidepressant exposure and autism spectrum disorder,” Dr. Brown and her associates said (JAMA. 2017 Apr 18. doi: 10.1001.jama.2017.3415). In the other study, Ayesha C. Sujan and her associates analyzed data in several nationwide Swedish registries to examine whether first trimester exposure to any antidepressants raised the risk of a range of neurodevelopmental problems, including autism. This study involved 1,580,629 offspring, including 22,544 (1.4%) whose mothers took antidepressants during the first trimester.
As with Dr. Brown’s study, the initial unadjusted analysis showed an association between antidepressant exposure and autism, but that association disappeared once the data were adjusted to account for confounding factors. In the final data analysis, first trimester exposure was associated with preterm birth (odds ratio, 1.34) but not with small-for-gestational-age size (OR, 1.01), autism spectrum disorder (hazard ratio, 0.83), or attention deficit/hyperactivity disorder (HR, 0.99), said Ms. Sujan of the department of psychological and brain sciences, Indiana University, Bloomington, and her associates.
“These results are consistent with the hypothesis that genetic factors, familial environmental factors, or both, account for the population-wide associations between first-trimester antidepressant exposure and these outcomes,” they noted (JAMA. 2017 Apr 18. doi: 10.1001/jama.2017.3413).
Maternal use of antidepressants during pregnancy is unrelated to autism spectrum disorder in the offspring, according to two separate, population-level cohort studies that used sophisticated statistical techniques to account for numerous confounding factors.
Both studies were reported online April 18 in JAMA.
Some previous studies have reported a possible link between in utero exposure to antidepressants, particularly SSRIs, and autism. But they had limited ability to control for key confounders, notably the mother’s underlying depression.
Overall, 1.1% of these children were diagnosed as having autism spectrum disorder. This prevalence is consistent with current population estimates, indicating that few if any cases of the disorder were missed, said Dr. Brown of Women’s College Research Institute in Toronto and the division of epidemiology, University of Toronto, and her associates.
In initial, unadjusted analyses of the data, the risk of autism was higher in exposed than in nonexposed children. However, that association disappeared once the data were adjusted to account for numerous potential confounders.
Further analysis comparing the exposed children with their unexposed siblings also found that after adjusting for confounding factors, prenatal exposure to antidepressants did not affect the risk of developing autism. In addition, this lack of association also was found in the subgroup of children whose mothers took antidepressants shortly before but not during pregnancy.
Taken together, these findings “suggest that confounding by indication for the medication may explain previously observed associations between in utero serotonergic antidepressant exposure and autism spectrum disorder,” Dr. Brown and her associates said (JAMA. 2017 Apr 18. doi: 10.1001.jama.2017.3415). In the other study, Ayesha C. Sujan and her associates analyzed data in several nationwide Swedish registries to examine whether first trimester exposure to any antidepressants raised the risk of a range of neurodevelopmental problems, including autism. This study involved 1,580,629 offspring, including 22,544 (1.4%) whose mothers took antidepressants during the first trimester.
As with Dr. Brown’s study, the initial unadjusted analysis showed an association between antidepressant exposure and autism, but that association disappeared once the data were adjusted to account for confounding factors. In the final data analysis, first trimester exposure was associated with preterm birth (odds ratio, 1.34) but not with small-for-gestational-age size (OR, 1.01), autism spectrum disorder (hazard ratio, 0.83), or attention deficit/hyperactivity disorder (HR, 0.99), said Ms. Sujan of the department of psychological and brain sciences, Indiana University, Bloomington, and her associates.
“These results are consistent with the hypothesis that genetic factors, familial environmental factors, or both, account for the population-wide associations between first-trimester antidepressant exposure and these outcomes,” they noted (JAMA. 2017 Apr 18. doi: 10.1001/jama.2017.3413).
FROM JAMA
Key clinical point: Maternal use of antidepressants during pregnancy is unrelated to autism spectrum disorder in offspring.
Major finding: Prenatal exposure to antidepressants was not associated with small-for-gestational-age size (OR, 1.01), autism spectrum disorder (HR, 0.83), or attention deficit/hyperactivity disorder (HR, 0.99).
Data source: Two separate retrospective cohort studies involving 35,906 births in Canada and 1,580,629 in Sweden.
Disclosures: Dr. Brown’s study was supported by the Institute for Clinical Evaluative Sciences and the Ontario Ministry of Health and Long-Term Care. Dr. Brown and her associates reported having no relevant financial disclosures. Dr. Sujan’s study was supported by the U.S. National Institute of Mental Health, the National Institute on Drug Abuse, the National Science Foundation, and others. Dr. Sujan reported having no relevant financial disclosures; her associates reported ties to numerous industry sources.
Universal preterm birth screening not ready for prime time
Two screens to predict spontaneous preterm birth in low-risk women, which were rapidly adapted into clinical practice despite a lack of supportive evidence, proved to have little predictive value in a large cohort study.
Transvaginal ultrasound examination for short cervical length and quantitative cervicovaginal swabbing for fetal fibronectin are routinely used to predict spontaneous preterm birth. To assess the accuracy of both screens individually and in combination, researchers analyzed data for women participating in the prospective multicenter Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b). They focused on 9,410 nulliparous women with singleton pregnancies who were followed at eight clinical centers across the country. In addition to regular pregnancy visits, these women underwent both screening procedures at approximately 12 weeks, 19 weeks, and 28 weeks.
Both screens had relatively low sensitivity and low positive predictive value, regardless of when they were performed, which threshold values were used, and whether the results were considered individually or in combination (JAMA. 2017;317[10]:1047-56).
Transvaginal cervical length at 22-30 weeks’ gestation was the most accurate predictor of spontaneous preterm birth before 37 weeks, outperforming fetal fibronectin assessment alone. However, with a threshold of 25 mm or less – the most commonly used clinical cutoff – cervical length screening identified just 23.3% of spontaneous preterm births before 37 weeks. Use of that same threshold at 16-22 weeks – the most common time for screening in clinical practice – identified just 8% of subsequent spontaneous preterm births. The addition of fetal fibronectin did not increase the predictive performance of cervical length alone, according to the findings.
The researchers cited the low incidence of short cervix (1% at 16-22 weeks) as a potential reason why the ultrasound screen was not useful. “Using the most conservative threshold of 25 mm or less in the most common time for clinical screening (16-22 weeks’ gestation), 247 women would need to be screened to identify 1 case of spontaneous preterm birth,” the researchers wrote. Using a transvaginal cervical length of 15 mm or less during the same time period, the number needed to screen rose to 680 to identify a single case of spontaneous preterm birth.
These findings do not support the routine use of these two screens among nulliparous women with singleton pregnancies, the researchers wrote. Screening procedures with relatively poor predictive values “may sometimes be useful if they are inexpensive, lack serious adverse effects, and address a serious condition for which an effective intervention exists. Neither of these tests, alone or in combination, meets all of these criteria,” they added.
The Eunice Kennedy Shriver National Institute of Child Health and Human Development supported the study. Dr. Esplin reported holding a patent for serum markers of preterm birth and ties to Sera Prognostics and Clinical Innovations. One of his coauthors reported ties to Natera, Sequenom, Illumina, March of Dimes, Ariosa Diagnostics/Roche, KellBenx, and LabCorp.
The report by Esplin and colleagues is important for at least two reasons. First, this large and well-executed prospective study provides compelling data that two popular screening modalities, either alone or in combination, do not accurately predict which women will deliver preterm. Second, this report provides provocative insights as to how medical practice determined through consensus, rather than reproducible evidence, contributes to the narrative in the United States regarding the cost and quality of health care.
In 2012, the publications committee of the Society for Maternal-Fetal Medicine provided a consensus clinical guideline for use of progesterone for the prevention of preterm birth. The guideline indicated that vaginal progesterone was beneficial for women at low risk for preterm birth who were discovered to have short cervical length during an ultrasound examination. This recommendation raised the issue of universal testing for short cervix in women such as those screened in the study by Esplin and colleagues. The authors of the clinical guideline, which was reaffirmed in 2016, stated that “cervical length screening in singleton gestations without prior preterm birth cannot yet be universally mandated. Nonetheless, implementation of such a screening strategy can be viewed as reasonable, and can be considered by individual practitioners.” Similarly, one of the recommendations – although based on limited or inconsistent scientific evidence – promulgated by the American College of Obstetricians and Gynecologists in its 2012 Practice Bulletin on Prediction and Prevention of Preterm Birth, and also reaffirmed in 2016, stated that “although this document does not mandate universal cervical length screening in women without a prior preterm birth, this screening strategy may be considered.”
The important study by Esplin and colleagues should serve to temper the use of two controversial screening approaches. While it is gratifying that such research takes place, that research should have preceded the adoption of this screening strategy into practice.
Steven L. Bloom, MD, and Kenneth J. Leveno, MD, are in the department of ob.gyn. at the University of Texas Southwestern Medical Center, Dallas. They reported having no relevant financial disclosures. These comments are excerpted from an editorial ( JAMA. 2017;317[10]:1025-26).
The report by Esplin and colleagues is important for at least two reasons. First, this large and well-executed prospective study provides compelling data that two popular screening modalities, either alone or in combination, do not accurately predict which women will deliver preterm. Second, this report provides provocative insights as to how medical practice determined through consensus, rather than reproducible evidence, contributes to the narrative in the United States regarding the cost and quality of health care.
In 2012, the publications committee of the Society for Maternal-Fetal Medicine provided a consensus clinical guideline for use of progesterone for the prevention of preterm birth. The guideline indicated that vaginal progesterone was beneficial for women at low risk for preterm birth who were discovered to have short cervical length during an ultrasound examination. This recommendation raised the issue of universal testing for short cervix in women such as those screened in the study by Esplin and colleagues. The authors of the clinical guideline, which was reaffirmed in 2016, stated that “cervical length screening in singleton gestations without prior preterm birth cannot yet be universally mandated. Nonetheless, implementation of such a screening strategy can be viewed as reasonable, and can be considered by individual practitioners.” Similarly, one of the recommendations – although based on limited or inconsistent scientific evidence – promulgated by the American College of Obstetricians and Gynecologists in its 2012 Practice Bulletin on Prediction and Prevention of Preterm Birth, and also reaffirmed in 2016, stated that “although this document does not mandate universal cervical length screening in women without a prior preterm birth, this screening strategy may be considered.”
The important study by Esplin and colleagues should serve to temper the use of two controversial screening approaches. While it is gratifying that such research takes place, that research should have preceded the adoption of this screening strategy into practice.
Steven L. Bloom, MD, and Kenneth J. Leveno, MD, are in the department of ob.gyn. at the University of Texas Southwestern Medical Center, Dallas. They reported having no relevant financial disclosures. These comments are excerpted from an editorial ( JAMA. 2017;317[10]:1025-26).
The report by Esplin and colleagues is important for at least two reasons. First, this large and well-executed prospective study provides compelling data that two popular screening modalities, either alone or in combination, do not accurately predict which women will deliver preterm. Second, this report provides provocative insights as to how medical practice determined through consensus, rather than reproducible evidence, contributes to the narrative in the United States regarding the cost and quality of health care.
In 2012, the publications committee of the Society for Maternal-Fetal Medicine provided a consensus clinical guideline for use of progesterone for the prevention of preterm birth. The guideline indicated that vaginal progesterone was beneficial for women at low risk for preterm birth who were discovered to have short cervical length during an ultrasound examination. This recommendation raised the issue of universal testing for short cervix in women such as those screened in the study by Esplin and colleagues. The authors of the clinical guideline, which was reaffirmed in 2016, stated that “cervical length screening in singleton gestations without prior preterm birth cannot yet be universally mandated. Nonetheless, implementation of such a screening strategy can be viewed as reasonable, and can be considered by individual practitioners.” Similarly, one of the recommendations – although based on limited or inconsistent scientific evidence – promulgated by the American College of Obstetricians and Gynecologists in its 2012 Practice Bulletin on Prediction and Prevention of Preterm Birth, and also reaffirmed in 2016, stated that “although this document does not mandate universal cervical length screening in women without a prior preterm birth, this screening strategy may be considered.”
The important study by Esplin and colleagues should serve to temper the use of two controversial screening approaches. While it is gratifying that such research takes place, that research should have preceded the adoption of this screening strategy into practice.
Steven L. Bloom, MD, and Kenneth J. Leveno, MD, are in the department of ob.gyn. at the University of Texas Southwestern Medical Center, Dallas. They reported having no relevant financial disclosures. These comments are excerpted from an editorial ( JAMA. 2017;317[10]:1025-26).
Two screens to predict spontaneous preterm birth in low-risk women, which were rapidly adapted into clinical practice despite a lack of supportive evidence, proved to have little predictive value in a large cohort study.
Transvaginal ultrasound examination for short cervical length and quantitative cervicovaginal swabbing for fetal fibronectin are routinely used to predict spontaneous preterm birth. To assess the accuracy of both screens individually and in combination, researchers analyzed data for women participating in the prospective multicenter Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b). They focused on 9,410 nulliparous women with singleton pregnancies who were followed at eight clinical centers across the country. In addition to regular pregnancy visits, these women underwent both screening procedures at approximately 12 weeks, 19 weeks, and 28 weeks.
Both screens had relatively low sensitivity and low positive predictive value, regardless of when they were performed, which threshold values were used, and whether the results were considered individually or in combination (JAMA. 2017;317[10]:1047-56).
Transvaginal cervical length at 22-30 weeks’ gestation was the most accurate predictor of spontaneous preterm birth before 37 weeks, outperforming fetal fibronectin assessment alone. However, with a threshold of 25 mm or less – the most commonly used clinical cutoff – cervical length screening identified just 23.3% of spontaneous preterm births before 37 weeks. Use of that same threshold at 16-22 weeks – the most common time for screening in clinical practice – identified just 8% of subsequent spontaneous preterm births. The addition of fetal fibronectin did not increase the predictive performance of cervical length alone, according to the findings.
The researchers cited the low incidence of short cervix (1% at 16-22 weeks) as a potential reason why the ultrasound screen was not useful. “Using the most conservative threshold of 25 mm or less in the most common time for clinical screening (16-22 weeks’ gestation), 247 women would need to be screened to identify 1 case of spontaneous preterm birth,” the researchers wrote. Using a transvaginal cervical length of 15 mm or less during the same time period, the number needed to screen rose to 680 to identify a single case of spontaneous preterm birth.
These findings do not support the routine use of these two screens among nulliparous women with singleton pregnancies, the researchers wrote. Screening procedures with relatively poor predictive values “may sometimes be useful if they are inexpensive, lack serious adverse effects, and address a serious condition for which an effective intervention exists. Neither of these tests, alone or in combination, meets all of these criteria,” they added.
The Eunice Kennedy Shriver National Institute of Child Health and Human Development supported the study. Dr. Esplin reported holding a patent for serum markers of preterm birth and ties to Sera Prognostics and Clinical Innovations. One of his coauthors reported ties to Natera, Sequenom, Illumina, March of Dimes, Ariosa Diagnostics/Roche, KellBenx, and LabCorp.
Two screens to predict spontaneous preterm birth in low-risk women, which were rapidly adapted into clinical practice despite a lack of supportive evidence, proved to have little predictive value in a large cohort study.
Transvaginal ultrasound examination for short cervical length and quantitative cervicovaginal swabbing for fetal fibronectin are routinely used to predict spontaneous preterm birth. To assess the accuracy of both screens individually and in combination, researchers analyzed data for women participating in the prospective multicenter Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b). They focused on 9,410 nulliparous women with singleton pregnancies who were followed at eight clinical centers across the country. In addition to regular pregnancy visits, these women underwent both screening procedures at approximately 12 weeks, 19 weeks, and 28 weeks.
Both screens had relatively low sensitivity and low positive predictive value, regardless of when they were performed, which threshold values were used, and whether the results were considered individually or in combination (JAMA. 2017;317[10]:1047-56).
Transvaginal cervical length at 22-30 weeks’ gestation was the most accurate predictor of spontaneous preterm birth before 37 weeks, outperforming fetal fibronectin assessment alone. However, with a threshold of 25 mm or less – the most commonly used clinical cutoff – cervical length screening identified just 23.3% of spontaneous preterm births before 37 weeks. Use of that same threshold at 16-22 weeks – the most common time for screening in clinical practice – identified just 8% of subsequent spontaneous preterm births. The addition of fetal fibronectin did not increase the predictive performance of cervical length alone, according to the findings.
The researchers cited the low incidence of short cervix (1% at 16-22 weeks) as a potential reason why the ultrasound screen was not useful. “Using the most conservative threshold of 25 mm or less in the most common time for clinical screening (16-22 weeks’ gestation), 247 women would need to be screened to identify 1 case of spontaneous preterm birth,” the researchers wrote. Using a transvaginal cervical length of 15 mm or less during the same time period, the number needed to screen rose to 680 to identify a single case of spontaneous preterm birth.
These findings do not support the routine use of these two screens among nulliparous women with singleton pregnancies, the researchers wrote. Screening procedures with relatively poor predictive values “may sometimes be useful if they are inexpensive, lack serious adverse effects, and address a serious condition for which an effective intervention exists. Neither of these tests, alone or in combination, meets all of these criteria,” they added.
The Eunice Kennedy Shriver National Institute of Child Health and Human Development supported the study. Dr. Esplin reported holding a patent for serum markers of preterm birth and ties to Sera Prognostics and Clinical Innovations. One of his coauthors reported ties to Natera, Sequenom, Illumina, March of Dimes, Ariosa Diagnostics/Roche, KellBenx, and LabCorp.
FROM JAMA
Key clinical point:
Major finding: With a threshold of transvaginal cervical length of 25 mm or less at 16-22 weeks’ gestation, 247 women would need to be screened to identify one case of spontaneous preterm birth before 37 weeks’ gestation.
Data source: A prospective multicenter observational cohort study involving 9,410 nulliparous women across the United States.
Disclosures: The Eunice Kennedy Shriver National Institute of Child Health and Human Development supported the study. Dr. Esplin reported holding a patent for serum markers of preterm birth and ties to Sera Prognostics and Clinical Innovations. An associate reported ties to Natera, Sequenom, Illumina, March of Dimes, Ariosa Diagnostics/Roche, KellBenx, and LabCorp.