Long-term neurodevelopmental consequences of intrauterine exposure to lithium and antipsychotics: a systematic review and meta-analysis

Abstract

Lithium and antipsychotics are often prescribed to treat bipolar disorder or psychotic disorders in women of childbearing age. Little is known about the consequences of these medications during pregnancy for the developing child. The objective of this article is to systematically review findings from preclinical and clinical studies that have examined the neurodevelopmental consequences of intrauterine exposure to lithium and antipsychotics. A systematic search was performed in Embase, Medline, Web of Science, PsychINFO, Cochrane, and Google Scholar. Clinical and experimental studies were selected if they investigated neurodevelopment of offspring exposed to lithium or antipsychotics during gestation. Quality of clinical and preclinical studies was assessed by the Newcastle–Ottawa Scale and the SYRCLE’s risk of Bias tool, respectively. In total, 73 studies were selected for qualitative synthesis and three studies were selected for quantitative synthesis. Of preclinical studies, 93% found one or more adverse effects of prenatal exposure to antipsychotics or lithium on neurodevelopment or behaviour. Only three clinical cohort studies have investigated the consequences of lithium exposure, all of which reported normal development. In 66% of clinical studies regarding antipsychotic exposure, a transient delay in neurodevelopment was observed. The relative risk for neuromotor deficits after in utero exposure to antipsychotics was estimated to be 1.63 (95% CI 1.22–2.19; I2 = 0%). Preclinical studies suggest long-term adverse neurodevelopmental consequences of intrauterine exposure to either lithium or antipsychotics. However, there is a lack of high-quality clinical studies. Interpretation is difficult, since most studies have compared exposed children with their peers from the unaffected population, which did not allow correction for potential influences regarding genetic predisposition or parental psychiatric illness.Electronic supplementary materialThe online version of this article (10.1007/s00787-018-1177-1) contains supplementary material, which is available to authorized users.

Comparative psychopharmacology of autism and psychotic-affective disorders suggests new targets for treatment

“…Effects of prenatal antipsychotic use during pregnancy on autism risk are largely unknown, due to a paucity of relevant quality data [262, 263]; one study [264] reported increased head circumference, an autism-associated trait, in neonates prenatally exposed to the antipsychotics olanzapine and/or clozapine, but birth weight and length, which are also commonly higher in autism, were not affected.…”

Lithium Exposure During Pregnancy and the Postpartum Period: A Systematic Review and Meta-Analysis of Safety and Efficacy Outcomes

“…Aside from lithium teratogenicity, neonatal toxicity events may occur in offspring exposed to lithium during labor, including the so-called floppy baby syndrome (characterized by cyanosis and hypotonicity), neonatal hypothyroidism, and nephrogenic diabetes insipidus (9). Nonetheless, the appraisal of the risk for long-term adverse neurodevelopmental consequences of intrauterine exposure to lithium is hampered by the fact that most studies have compared exposed children with children from unaffected populations, which did not allow for correction of the potential influence of genetic predisposition or parental psychiatric illness (10).…”

Lithium during pregnancy and after delivery: a review

“…Prenatal exposure to lithium may therefore have consequences on development and health outcomes well beyond infancy. Indeed, results from preclinical studies in mice, rats and zebrafish show neurodevelopmental deficits (Poels et al 2018). Clinical data are scarce, four small clinical cohort studies have investigated long term neurodevelopmental outcomes.…”