Prenatal Exposure to Psychotropics and Analgesics on Cognitive, Linguistic and Educational Outcomes – a Systematic Review with Focus on Validity and Reliability of Outcome Measures

Abstract

Abstract Objective: To provide an overview of the observational studies on cognitive, linguistic, and educational outcomes following prenatal exposure to psychotropics and analgesics, including reporting of outcome measure validity and reliability. Study design: We searched four databases, MEDLINE, Embase, PsycINFO, and PubMed from inception to July 2022. We included all original studies involving participants less than 18 years old, who were prenatally exposed to psychotropics and/or analgesics with cognitive, linguistic, and/or educational outcomes. Results: 68 studies were identified. Most studies (47%) focused on the effects of prenatal exposure to antiepileptics on child cognition. Valproate showed a consistently increased risk of neurodevelopmental disorders, whereas the results for other medications were sparse and conflicting. Neurodevelopmental outcomes were measured by psychometric assessments in 62 studies and by diagnostic codes in health care registries in six studies. Only 29 of the 62 studies (46.8%) using psychometric measures mentioned the psychometric properties of the instruments used. In studies using diagnostic outcome measures, only one study reported positive predictive values and performed a sensitivity analysis to address outcome misclassification. Conclusion: Except for valproate, there is a concerning lack of studies on the impact of prenatal exposure to psychotropics and analgesics on cognitive, linguistic, and educational outcomes. Regardless of whether psychometric measures or diagnostic codes were used, most studies lacked a robust assessment of outcome measures, which threatens their validity and interpretability. Future studies on long-term prenatal medication safety need to focus on the accuracy of neurodevelopmental outcome measures.