Neonatal outcomes after in utero exposure to antipsychotics: a systematic review and meta-analysis

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 8th 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 < 10th 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]; I-2=46%; p(het)=0.13, n = 4 studies). First-generation antipsychotics were associated with an increased risk of small for gestational age < 3rd percentile (OR 1.37 [95%CI 1.02; 1.83]; I-2=60%; p(het)=0.04, n = 5) and a lower mean birthweight (MD -135 g [95%CI -203; -66]; I-2=53%; p(het)=0.07, n = 5). Second-generation antipsychotics were associated with large for gestational age > 97th percentile (OR 1.56 [95%CI 1.31; 1.87]; I-2=4%; p(het)=0.37, n = 4) and Apgar score < 7 (OR 1.64 [95%CI 1.09; 2.47]; I-2=47%; p(het)=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. Data sources: MEDLINE, EMBASE, CENTRAL, ICTRP, ClinicalTrials.gov. Prospero Registration Number CRD42023401805.