Neonatal outcome and adaption after in utero exposure to antidepressants: A systematic review and meta-analysis

Major depressive disorder (MDD) and anxiety disorders are both common and especially challenging during pregnancy. Considering possible risks of intrauterine drug exposure of the child, the role of psychopharmacological treatment is ambiguous and various negative obstetric outcomes were inconsistently associated with medication. Consequently, a critical examination of peri- and postnatal phenomena associated with intrauterine exposure to antidepressants based on serotonin reuptake inhibition (SRI) and subsumed under the term "poor neonatal adaptation syndrome" (PNAS) is urgently called for.

A comprehensive literature search was conducted, revealing a total number of 33 relevant studies and 69 individual outcomes among 3025 screened studies. Seventeen outcomes allowed meta-analytic evaluation (random effects model). Measures for heterogeneity (I² ) and contour-enhanced funnel plots were generated.

Single studies showed increased risks for deficits in neurological functioning and autonomous adaptation in SRI exposed infants. Meta-analytical evaluation showed increased symptom occurrence or severity in exposed neonates for low APGAR scores, birth weight, size for gestational age, preterm delivery, neuromuscular and autonomous regulation, and higher rates of admission to specialized care. Mostly, increased risk after SRI exposure was supported by comparison to unexposed infants born to mothers diagnosed with depression.

Whereas statistically significant evidence for various effects of intrauterine exposure to SRI was found, the clinical relevance remains unresolved because of inherently low data quality in this research domain and insufficiently defined samples and outcomes. More systematic research under ethical considerations is required to improve multiprofessional counseling in the many women dealing with MDD during pregnancy and the peripartum.