Risk of Poor Neonatal Adaptation Syndrome Among Infants Exposed to Second-Generation Atypical Antipsychotics Compared to Antidepressants: Results From the National Pregnancy Registry for Psychiatric Medications.

Objective: While poor neonatal adaptation syndrome (PNAS) has been particularly well described among infants exposed to antidepressants, specifically selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), this is not the case for second-generation antipsychotics (SGAs). In 2011, the US Food and Drug Administration (FDA) issued a drug safety warning regarding fetal antipsychotic exposure and risk for PNAS and extrapyramidal symptoms (EPS). The primary objective of this study was to examine the risk for PNAS among infants exposed to SGAs compared to SSRI/SNRI-exposed infants, leveraging the prospective, longitudinal design of the National Pregnancy Registry for Psychiatric Medications (NPRPM).Methods: The NPRPM is a prospective pharmacovigilance program in which pregnant women, aged 18-45 years, are enrolled and followed prospectively. Medical records were systematically reviewed and data abstracted using a checklist of PNAS and EPS symptoms specifically outlined in the FDA drug safety warning. The two study groups included infants exposed to an SGA during pregnancy and infants exposed to an SSRI/SNRI during pregnancy. The primary outcome was the presence of at least one or more PNAS symptoms during the first month of life. Other neonatal outcomes following exposure to the medication of interest, including preterm birth, neonatal intensive care unit (NICU) admission, rates of EPS, and whether infants were discharged home with their mothers, are also reported.Results: Of the 2,145 women enrolled in this study as of December 16, 2020, a total of 373 women and their infants (n = 384) were eligible for inclusion (n = 193 SGA-exposed infants and 191 SSRI/SNRI-exposed infants). Among SGA-exposed infants, 32.6% (63/193) experienced at least 1 PNAS sign compared to 34.6% of infants (66/191) in the SSRI/SNRI-exposed group. The majority of infants in each group showed no symptoms of PNAS. No differences were observed between the two groups with respect to rates of preterm birth, NICU admission, prevalence of EPS, and timing of infants being discharged home with their mothers.Conclusions: PNAS symptomatology was comparable among infants exposed prenatally to an SGA or to an SSRI/SNRI. These preliminary findings provide an estimated risk of PNAS among infants exposed to SGAs of roughly 30%. Interestingly, these findings are also consistent with estimates in the literature of PNAS in SSRI/SNRI-exposed infants, suggesting a possible common pathway underlying this phenomenon.Trial Registration: ClinicalTrials.gov identifier: NCT01246765.

Neurobehavioral follow-up of children exposed to selective serotonin reuptake inhibitors in utero.

BACKGROUND: Systematic data regarding long-term neurobehavioral effects of maternal antidepressant use during pregnancy are sparse. The aim of this study was to evaluate the impact of gestational exposure to antidepressants on later neurodevelopmental function. METHODS: This study describes a cohort of mother-child dyads (44 mothers, 54 children) in which maternal depressive symptoms and medication exposures were prospectively collected across pregnancy and the postpartum period. Children age 6 to 17 were assessed using validated instruments across domains of childhood behavior and executive memory and functioning. RESULTS: No associations were found between maternal use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy and atypical neurodevelopment of children. Borderline clinical or clinical ranges of internalizing symptoms were associated with exposure to a higher maternal depressive symptom burden during pregnancy compared with those in the normal range. Compared with age- and sex-matched controls, the SSRI-exposed group showed superior performance on executive function tasks; findings did not demonstrate elevated risk for abnormal neurodevelopment in children age 6 to 17 exposed to SSRIs in utero. Deviations from the norm were instead associated with higher in utero exposure to maternal depression burden. CONCLUSIONS: This study highlights the need for rigorous studies of long-term outcomes after fetal antidepressant exposure.

Correction. Reproductive Safety of Second-Generation Antipsychotics: Updated Data From the Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics.

This corrects the article DOI: 10.4088/JCP.20m13745.

Reproductive Safety of Second-Generation Antipsychotics: Updated Data From the Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics.

Objective: Second-generation antipsychotics (SGAs) are prescribed for a wide range of indications in women of reproductive age. The National Pregnancy Registry for Atypical Antipsychotics (NPRAA) was established to determine the risk of major malformations among infants exposed to these medications during the first trimester relative to a comparison group of unexposed infants of mothers with histories of psychiatric morbidity.Methods: Women, aged 18-45 years, with histories of psychiatric illness were prospectively followed through pregnancy and during the postpartum period. Pediatric and maternal medical records were obtained and screened for evidence of major malformations. Potential cases were adjudicated by a dysmorphologist who was blinded to drug exposure.. Recruitment to the Registry, which is based at the Ammon-Pinizzotto Center for Women's Mental Health at Massachusetts General Hospital (MGH), includes nationwide provider referral, self-referral, and advertisement through the MGH Center for Women's Mental Health website.Results: As of April 9, 2020, 1,906 women had enrolled, including 889 in the exposure group and 1,017 controls. A total of 1,311 women completed the study and were eligible for inclusion in the analysis. Medical records were obtained for 81.3% of participants. Among 640 live births in the exposure group, 16 (2.50%) had confirmed major malformations reported, and among 704 live births in the control group, 14 (1.99%) had confirmed major malformations reported. The estimated odds ratio for major malformations comparing exposed and unexposed infants was 1.48 (95% CI, 0.625-3.517).Conclusions: Data from the Registry assessing SGAs as a class indicate that they are unlikely to have a major teratogenic effect. These findings provide pertinent information for women and their health care providers regarding decisions about atypical antipsychotic use during pregnancy.Trial Registration: ClinicalTrails.gov identifier: NCT01246765.

Reproductive safety of aripiprazole: data from the Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics.

Aripiprazole has become one of the most commonly prescribed psychotropics, making a more comprehensive understanding of its reproductive safety profile a priority. The goal of the current analysis was to determine the risk of major malformations in infants exposed during the first trimester of pregnancy to aripiprazole compared to infants whose mothers had psychiatric diagnoses but did not use an atypical antipsychotic during pregnancy. The National Pregnancy Registry for Atypical Antipsychotics is a prospective pharmacovigilance program in which pregnant women are enrolled and interviewed during pregnancy and the postpartum period. Medical records are assessed to confirm presence or absence of major malformations. Pregnant women ages 18-45 with psychiatric diagnoses are enrolled. As of April 2020, N = 848 women who had delivered infants were eligible for analyses. A total of 158 women with first trimester exposure to aripiprazole were compared to 690 controls. For 163 infants born to women in the exposed group, seven major malformations were confirmed (4.29%), compared to fourteen of the 690 unexposed infants (1.99%). The unadjusted odds ratio for major malformations between aripiprazole-exposed and unexposed infants was 2.21 (95% confidence interval [CI] = (0.88, 5.57) The adjusted odds ratio for major malformations was 1.35 (95% confidence interval [CI] = (0.43, 4.20). After adjustment for confounding variables, the risk of major malformations after first trimester exposure to aripiprazole was not significant compared to controls. While these results are reassuring, they are limited by relatively small numbers of participants. Future analyses with larger numbers are expected to provide more of a complete and precise reproductive safety profile regarding aripiprazole use during pregnancy. Trial registration: clinicaltrials.gov NCT01246765.

The impact of obesity on pregnancy outcomes among women with psychiatric disorders: Results from a prospective pregnancy registry.

OBJECTIVE: Obesity is associated with an increased risk of adverse pregnancy outcomes. As individuals with psychiatric disorders are at a higher risk of obesity than the general population, we aimed to examine the effect of obesity on neonatal and maternal outcomes in this population. METHODS: Pregnant women with psychiatric disorders were enrolled in the Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications (NCT01246765) and followed prospectively until 6 months postpartum. Pre-pregnancy body mass index was used to categorize participants as normal-weight, overweight, and obese to assess comparative risk of adverse outcomes. RESULTS: Within our sample of 584 participants (N = 252 normal-weight; N = 170 overweight; N = 162 obese), obesity was not significantly associated with higher risk for birth defects (OR: 3.19; 95% CI:0.79,12.95; p = 0.10; unadjusted due to the rarity of this outcome in the sample). After adjustment, women with obesity were at higher risk for gestational diabetes (p = 0.011; OR:3.23; 95% CI:1.30,7.98), as were women in the overweight BMI category (p = 0.003; OR:3.77; 95% CI:1.58,9.00). Among women with obesity, there was a tendency for a higher C-section rate (p = 0.07) compared to women in the normal-weight BMI category. Other outcomes were not significantly different among groups. CONCLUSIONS: Peripartum complications associated with obesity are common among women with psychiatric illness; thus, it is important to develop antenatal weight management interventions for this population.