By: Geraldine Ciaccio, PharmD Candidate c/o 2025
Pregnant women treated with antidepressants may no longer have to endure the worry that their medications will harm their newborn. Previous studies have shown a correlation between the use of antidepressants in pregnant patients and the prevalence of various birth defects, including cardiac defects, anencephaly, and gastroschisis, in their children. These birth defects occurred 2 to 3.5 times more frequently among infants of women treated with paroxetine or fluoxetine early in pregnancy.1 However, a recent cohort study by Suarez et al. yielded different results, concluding that exposure to certain antidepressants in pregnancy does not increase the risk of developmental disorders in children.2
On October 3, 2022, the Journal of the American Medical Association (JAMA) published the results of this cohort study, which evaluated the correlation of antidepressant use in pregnancy and neurodevelopmental disorders (NDDs) in children.2 The subjects in this group were studied during synaptogenesis, the period of fetal development when the synapses between neurons are formed. This period ranges from week 19 until delivery and is essential for the formation of neuronal connectivity. NDDs evaluated in this study included autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), developmental speech/language disorder, developmental coordination disorder, intellectual disability, and behavioral disorder.2 Using Medicaid Analytic eXtract (MAX) and the IBM MarketScan Research Database (MarketScan), a total of 3.18 million pregnancies were evaluated, following children from birth until diagnosis of NDD, disenrollment, death, or end of study (maximum of 14 years). Of this total, 145,702 pregnancies had maternal antidepressant-exposure.2
The unexposed group was defined as having no antidepressant dispensed from 90 days prior to pregnancy start through one day prior to delivery.2 The exposed group was defined as pregnant individuals having at least one dispensed antidepressant from 127 days after week 19 of gestation to delivery. The exposed group was further divided by which class of medications were taken, including selective serotonin receptor inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants. The five most common antidepressants used included sertraline, fluoxetine, bupropion, citalopram, and escitalopram.2
The most common neurodevelopmental outcome assessed was ADHD. In the exposed group, the cumulative incidence of ADHD at age 12 was 33.3% (95% CI 32.2% to 34.5%) in the MAX database and 17.6% (95% CI 15.8% to 19.5%) in the MarketScan database.2 In the unexposed group, the cumulative incidence of ADHD at age 12 was 20.3% (95% CI 20.0% to 20.5%) in the MAX database and 9.6% (95% CI 9.3% to 10.0%) in the MarketScan database.2 Another common neurodevelopmental outcome assessed was ASD. In the exposed group, cumulative incidence of ASD at age 12 was 4.1% (95% CI 3.5% to 4.7%) in the MAX database and 2.9% (95% CI 2.4% to 3.6%) in the MarketScan database. In the unexposed group, the cumulative incidence of ASD was 2.1% (95% CI 2.0% to 2.1%) in the MAX database and 1.6% (95% CI 1.4% to 1.7%) in the MarketScan database.2 These incidence rates for neurodevelopmental outcomes were higher among children of women with antidepressant exposure during pregnancy than in those of unexposed women, suggesting a correlation between antidepressant use in pregnancy and neurodevelopmental disorders in children.
However, the investigators took the crude data and made adjustments for potential confounders, including demographics, indications for antidepressant prescribing, mental health diagnoses, lifestyle factors, other medication use, comorbidities, and adequate level of prenatal care.2 After these adjustments, the analysis showed no association between antidepressant use in pregnancy and neurodevelopmental outcomes. For example, unadjusted hazard ratios (HRs) for all NDD outcomes suggested an increased risk in children of women exposed to antidepressants during pregnancy compared to those of unexposed women. These unadjusted HRs ranged from 1.32 for specific learning disorders to 2.02 for ADHD.2 Once adjusted for confounders, HRs ranged from 1.01 for specific learning disorders to 1.20 for ADHD. Similarly, the HRs for data from the unexposed group were consistent with the adjusted results for all NDD outcomes.2 Compared to the crude analysis, the adjusted results support the idea that an increased risk of neurodevelopmental disorders is correlated with various factors associated with antidepressant use during pregnancy, rather than the use of the antidepressant itself.2
Sandy LaMotte from CNN interviewed study investigator Elizabeth Suarez, who acknowledged the contradicting results of previous studies on this topic, but believed her study provides clarity “due to our large population size and careful study design.” 3 These results express reassurance for pregnant individuals who struggle with mental health, and clinicians are aiming to remove the negative connotations associated with antidepressant use in this patient population. CNN was also able to interview Dr. Tiffany Moore Simas, a member of the Committee on Clinical Practice Guidelines on Obstetrics for the American College of Obstetricians and Gynecologists, who claimed that “one in five perinatal individuals will experience a mental health condition.” 3 She stressed the importance of allowing pregnant individuals to care for themselves by stating that “healthy babies need healthy mothers.” 3
Overall, the results of the cohort study by Suarez et al. support the idea that antidepressant medications on their own do not increase the risk of NDDs in children. The crude results do provide insight that screening for NDDs may be beneficial in children birthed by mothers who took antidepressants during pregnancy. Antidepressant use during pregnancy is still a strong indicator of the risk of NDDs in children.2 Ultimately, early screening and intervention can improve outcomes for children at risk for NDDs.
References
- Reefhuis J, Devine O, Friedman JM, Louik C, Honein MA; National Birth Defects Prevention Study. Specific SSRIs and birth defects: Bayesian analysis to interpret new data in the context of previous reports. BMJ. 2015;351:h3190. doi: 10.1136/bmj.h3190.
- Suarez EA, Bateman BT, Hernández-Díaz S, et al. Association of Antidepressant Use During Pregnancy With Risk of Neurodevelopmental Disorders in Children. JAMA Intern Med. 2022;182(11):1149-60. doi: 10.1001/jamainternmed.2022.4268
- LaMotte S. Pregnant and taking antidepressants? Don’t worry about neurodevelopment harm, study says. CNN. https://www.cnn.com/2022/10/04/health/pregnancy-antidepressant-use-wellness/index.html. Published 10/04/2022.
