In utero exposure to antidepressant medication and neonatal and child outcomes: a systematic review

Acta Psychiatr Scand. 2020 Jan;141(1):21-33. doi: 10.1111/acps.13120. Epub 2019 Nov 15.


Objective: The aim of this study is to systematically review published studies, reporting outcomes to offspring following in utero exposure to antidepressant medications, which used an untreated depressed comparison group.

Methods: OVID, Scopus, EBSCO Collections, the Cochrane Library and Web of Science databases were searched for relevant publications published between January 1950 and May 2018 and a total of 188 potentially eligible studies were identified.

Results: Following review, 16 primary studies were eligible for inclusion. Antidepressant exposure was associated with an increased risk of lower gestational age, preterm birth, but not low birthweight or being small for gestational age compared to untreated depression. There is some evidence that congenital defects are associated with antidepressant use, particularly between cardiac defects and paroxetine use. There is conflicting evidence regarding neurodevelopment in offspring, with some reports of increased incidence of autistic spectrum disorders and depression, but also reports of no problems when measuring emotional symptoms, peer problems, conduct problems and hyperactivity-inattention scores.

Conclusion: When compared with an untreated depressed group, antidepressant exposure was associated with adverse outcomes at birth, while there is insufficient data to determine whether the association between antidepressants and congenital defects or developmental disorders is a true association. However, although we compared treated vs. untreated depression there still may be residual confounding as an untreated depressed group is likely to have less severe depression.

Keywords: adverse drug event; antidepressant; in utero exposure; pharmacovigilance; pregnancy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Antidepressive Agents / therapeutic use*
  • Attention Deficit Disorder with Hyperactivity / epidemiology
  • Autism Spectrum Disorder / epidemiology
  • Child
  • Conduct Disorder / epidemiology
  • Congenital Abnormalities / epidemiology*
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / epidemiology
  • Female
  • Gestational Age
  • Heart Defects, Congenital / epidemiology
  • Humans
  • Infant, Newborn
  • Neurodevelopmental Disorders / epidemiology*
  • Paroxetine / therapeutic use
  • Pregnancy
  • Pregnancy Complications / drug therapy*
  • Premature Birth / epidemiology*
  • Prenatal Exposure Delayed Effects / epidemiology
  • Risk Factors


  • Antidepressive Agents
  • Paroxetine