Neonatal and Childhood Outcomes in Offspring of Pregnant Women Using Antidepressant Medications: A Critical Review of Current Meta‐Analyses

Abstract

This article reviewed the results of 21 recent meta‐analyses examining the relationship between maternal use of antidepressants during pregnancy and negative outcomes in newborns and children. PubMed was searched for meta‐analyses published in English between January 1, 2011, and November 30, 2019, by using combinations of the keywords pregnancy, antidepressants, review, meta‐analysis, selective serotonin reuptake inhibitors, selective serotonin‐norepinephrine reuptake inhibitors, tricyclic antidepressants, neonatal outcomes, autism spectrum disorders, attention deficit hyperactivity disorder (ADHD), preterm birth, low birth weight, spontaneous abortion, persistent pulmonary hypertension, infant, newborn, children, and offspring. The present review included a total of 21 relevant meta‐analyses that met the inclusion criteria. Most of the meta‐analyses reported that compared to non‐users, the risks of preterm birth, low birth weight, spontaneous abortion, persistent pulmonary hypertension, autism spectrum disorders, and ADHD in offspring of antidepressant users were significantly higher. Some meta‐analyses also noted that the elevated risks were no longer statistically significant when pregnant women with psychiatric diagnoses treated with an antidepressant were compared with control patients who remained untreated. Although this review of current meta‐analyses suggests a moderately increased risk of neonatal and childhood outcomes assessed with maternal use of antidepressants, it is difficult to ascertain whether these outcomes are independent of underlying maternal psychiatric disorders.

A systematic review of the biological, social, and environmental determinants of intellectual disability in children and adolescents

“…What is not understood is the mechanism underlying these findings. There is much recent research investigating relationships between antidepressant medications and ASD ( 94 , 95 ) but despite the positive associations, a causal link has not been firmly substantiated. Much less is known about such a relationship with ID ( 96 ).…”

Association of Antidepressant Use During Pregnancy With Risk of Neurodevelopmental Disorders in Children

“…8 Results have largely been conflicting, and whether antidepressant exposure increases the risk of these childhood disorders remains controversial. 8 It is possible that confounding by indication of antidepressants for severe depression and by genetic and environmental factors associated with NDDs in children can explain the observed associations. 9 Moreover, few studies have considered other specific diagnosed NDDs outside of small, hospital-or clinicbased settings.…”

Psychotropic medication in pregnancy and lactation and early development of exposed children

“…A moderately increased risk of neonatal and childhood outcomes in children (e.g., preterm birth, low birth weight or autism) exposed to antidepressants in utero was reported, although some meta‐analyses outlined that these increased risks of complication were no longer significant when compared to a group of untreated depressed mother–child pairs. Thus, the author of this review article including 21 meta‐analyses concluded that it is difficult to disentangle whether underlying mechanisms are related to medication or maternal psychiatric disorders 24 . In contrast, Xing and colleagues concluded in their meta‐analysis (including 48 cohort and 6 case–control studies) that children exposed to antidepressants during pregnancy had increased risks of preterm birth, low birth weight and admissions to neonatal intensive care units compared with newborns of depressed but unmedicated mothers.…”

“…Thus, the author of this review article including 21 meta-analyses concluded that it is difficult to disentangle whether underlying mechanisms are related to medication or maternal psychiatric disorders. 24 In contrast, Xing and colleagues concluded in their meta-analysis (including 48 cohort and 6 case-control studies) that children exposed to antidepressants during pregnancy had increased risks of preterm birth, low birth weight and admissions to neonatal intensive care units compared with newborns of depressed but unmedicated mothers. Risks of spontaneous abortions, low APGAR scores at 5 min or neonatal convulsions were higher when mothers were treated with antidepressant medication during pregnancy compared to newborns of healthy mothers.…”