TOPLINE

Continuing selective serotonin reuptake inhibitors (SSRIs) during pregnancy is associated with impaired neonatal adaptation, including lower Apgar scores and increased meconium-stained amniotic fluid, but not with severe complications or NICU admission. Using a target trial emulation framework with electronic health records (EHR) from 1014 pregnancies, researchers found no statistically significant associations with life-threatening complications or major congenital anomalies.

METHODOLOGY

• Study researchers used a target trial emulation framework with EHR from a single academic center in the US (Vanderbilt University Medical Center, Nashville) to compare neonatal outcomes between pregnancies with SSRI continuation versus discontinuation from 2006 to 2022.
• A total of 1014 pregnancies (mean maternal age, 30.3 years) were included in the early-pregnancy trial examining nonanomaly outcomes with first- or second-trimester exposure, and 807 pregnancies (mean maternal age, 30.4 years) in the periconception trial assessing congenital anomalies with first-trimester exposure.
• Participants were women with singleton pregnancies who had SSRI use within 2 years before conception and at least one prenatal visit during the first trimester (periconception trial) or during the first or second trimester (early-pregnancy trial).
• Outcome measures included Apgar scores, meconium in amniotic fluid, NICU admission, preterm birth, birth weight, respiratory distress, feeding problems, hypoglycemia, hypothermia, pulmonary hypertension, cesarean delivery, and congenital anomalies.
• Analysis used inverse probability weighting with overlap weights to adjust for baseline covariates including maternal age, delivery year, race, insurance type, marital status, gravida, smoking status, BMI, Charlson Comorbidity Index score, number of health care visits, substance use disorder, and depression diagnosis frequency.

TAKEAWAY

• SSRI continuation during pregnancy was associated with lower Apgar scores at 1 minute (mean difference, -0.39; 95% CI, -0.60 to -0.18) and at 5 minutes (mean difference, -0.28; 95% CI, -0.42 to -0.13) compared with discontinuation.
• Continuation was associated with increased risk for meconium in amniotic fluid (odds ratio [OR], 1.73; 95% CI, 1.22-2.45) compared with discontinuation.
• No significant associations were found for congenital anomalies (OR, 1.09; 95% CI, 0.63-1.90), though the authors noted this result should be interpreted with caution given limited sample size.
• No differences were found for NICU admission (OR, 1.23; 95% CI, 0.82-1.83), preterm birth, birth weight, respiratory distress, feeding problems, hypoglycemia, hypothermia, pulmonary hypertension, or cesarean delivery after adjustment.

IN PRACTICE

“In this cohort study, SSRI continuation during pregnancy was associated with impaired neonatal adaptation but not with severe complications or NICU admission. These findings highlight the importance of appropriate comparator selection to minimize confounding and illustrate how target trial emulation can improve causal inference in studies of medication safety during pregnancy,” the authors of the study wrote.

SOURCE

The study was led by Layla Aref and Lisa Bastarache, MS, Department of Biomedical Informatics, Vanderbilt University Medical Center. It was published online on July 13 in JAMA Network Open.

LIMITATIONS

SSRI exposure was defined using prescription records, which do not confirm adherence or continuous exposure throughout the third trimester, and exposure misclassification may underestimate outcomes associated with late-pregnancy exposure. The requirement for continuous enrollment through delivery excluded miscarriages, so findings reflect associations among live births and do not account for pregnancy loss as a competing event. Restricting analyses to individuals with prepregnancy SSRI use may limit generalizability. Patient Health Questionnaire-9 scores were available for only about 10% of patients, limiting adjustment for depression severity, and residual confounding by indication may persist despite adjustment for proxy measures. Stringent inclusion criteria reduced sample size, limiting power to detect associations with rare outcomes including congenital anomalies and preventing stratified analyses by SSRI type or dosage.

DISCLOSURES

This study received support from the National Library of Medicine (R01LM010685), the National Heart, Lung, and Blood Institute (K08HL143051, R01HL158556), and the Biodevelopmental Origins of Lung Disease Center. Sherwin Shirazi, MS, disclosed receiving grants from the National Institutes of Health during the conduct of the study. Jennifer M.S. Sucre, PhD, disclosed receiving grants from the National Institutes of Health during the conduct of the study. Lisa Bastarache, MS, disclosed receiving royalties from Nashville Biosciences outside the submitted work. No other disclosures were reported.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.