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.
Objectives Lithium is an effective treatment for bipolar disorder, also during pregnancy to prevent the recurrence of episodes in the perinatal period. Little is known about the neuropsychological development of lithium‐exposed offspring. The current study was designed to investigate neuropsychological functioning in lithium‐exposed children with the aim to provide further knowledge on the long‐term effects of lithium use during pregnancy. Methods Participants were offspring of women with a diagnosis of bipolar spectrum disorder, aged 6–14 years. In total, 99 children participated in the study, 56 were exposed to lithium in utero and 43 were not exposed to lithium. Neuropsychological tests were administered, including the Snijders‐Oomen Nonverbal Intelligence Test and the NEPSY‐II‐NL assessment. Linear and negative binomial regression models were used to investigate the association between prenatal lithium exposure and neuropsychological functioning. In secondary analyses, the association between lithium blood level during pregnancy and neuropsychological functioning was assessed. Additionally, norm scores and percentiles for task outcomes were calculated. Results Lithium use during pregnancy was associated with the total number of mistakes made on the Auditory Attention task, but not statistically significant after full adjustment for potential confounding factors. No association between prenatal lithium exposure and IQ was found. Also, no relationship between lithium blood level during pregnancy and neuropsychological functioning was found after adjustment for potential confounders. Task outcomes in both groups were comparable to the general population. Conclusion In this study, we found no evidence for significantly altered neuropsychological functioning of lithium‐exposed children at the age of 6–14 years, when compared to non‐lithium‐exposed controls.
Objective: Antipsychotics are increasingly prescribed in pregnancy, yet little is known about potential long-term developmental effects on children. In this study, we investigated the effect of prenatal antipsychotic exposure on neurodevelopmental functioning in school-aged children.Methods: We performed a cross-sectional neurodevelopmental assessment of 91 children aged 6-14 years whose mothers had severe mental illness and were either exposed or unexposed to antipsychotic medication during pregnancy.Neurodevelopmental outcomes were assessed using validated neurodevelopmental assessment instruments to examine the child's IQ and global cognitive functioning, and the presence of any psychiatric disorders and/or learning problems in the child was assessed by parental report.Results: No statistically significant associations were found between antipsychotic exposure during pregnancy and either adverse neurodevelopmental outcomes (IQ, neuropsychological function), likelihood of psychiatric diagnosis, or learning problems based on parental report. Analyses were likely limited in power to detect subtler differences in neurodevelopmental functioning because of small sample size and heterogeneity of the sample. Conclusions: In this exploratory cohort study, intrauterine exposure to antipsychotics was not associated with any adverse effect on IQ or neurodevelopmental functioning in a cohort of school-aged children (6-14 years).
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