Adverse neonatal outcomes following in utero antipsychotic exposure remain unclear.

This systematic review and meta-analysis aimed to investigate associations between in utero first-and second-generation antipsychotic exposure and various neonatal outcomes. The primary outcome was small for gestational age. Secondary outcomes included other birth weight-related measures, prematurity and neonatal outcomes.

MEDLINE, EMBASE, CENTRAL, ICTRP, and ClinicalTrials.gov were searched for on 8 th July 2023. Two reviewers independently selected studies reporting associations between exposure and neonatal outcomes (all designs were eligible, no language or time restriction) and extracted data. ROBINS-I was used for risk of bias assessment. Meta-analyses were performed. Measures of association were odds ratios and mean differences.

Thirty-one observational studies were included. Regarding small for gestational age<10 th percentile, meta-analysis was only performed for second-generation antipsychotics and showed no evidence for an association (OR 1.31 [95%CI 0.83; 2.07]; I²=46%; phet=0.13, n=4 studies). First-generation antipsychotics were associated with an increased risk of small for gestational age<3 rd percentile (OR 1.37 [95%CI 1.02; 1.83]; I²=60%; phet=0.04, n=5) and a lower mean birthweight (MD -135g [95%CI -203; -66]; I²=53%; phet=0.07, n=5). Second-generation antipsychotics were associated with large for gestational age>97 th percentile (OR 1.56 [95%CI 1.31; 1.87]; I²=4%; phet=0.37, n=4) and Apgar score <7 (OR 1.64 [95%CI 1.09; 2.47]; I²=47%; phet=0.13, n=4). Both types of antipsychotics were associated with increased risks of preterm birth and neonatal hospitalization.

Despite potential confounding in the studies, this systematic review and meta-analysis showed that newborns of mothers using antipsychotics during pregnancy are potentially at risk of adverse neonatal outcomes.