Neurodevelopmental Consequences With In Utero Exposure to Lithium, Antipsychotics

human fetus
human fetus
Investigators examined long-term consequences in offspring in patients taking lithium and antipsychotics during pregnancy.

Although preclinical studies suggest that in utero exposure to lithium or antipsychotics may have long-term, adverse neurodevelopment effects, there is a lack of high-quality clinical studies on the subject, according to results published in European Child & Adolescent Psychiatry.

The researchers performed a systematic search of Embase, Medline, Web of Science, PsycINFO, Cochrane, and Google Scholar. Inclusion criteria included studies that investigated the neurodevelopment of offspring exposed to lithium or antipsychotics during gestation. The researchers selected 73 studies for qualitative synthesis and 3 for quantitative synthesis.

According to the results, 93% of preclinical studies found that prenatal exposure to antipsychotics or lithium had 1 or more adverse effects on neurodevelopment or behavior.

Researchers only found 3 clinical cohort studies that investigated how lithium exposure during gestation affected offspring; all 3 studies reported normal development.

Among clinical studies that investigated antipsychotic exposure during gestation, 66% found a transient delay in neurodevelopment among offspring. After exposure to antipsychotics in utero, the estimated relative risk of developing neuromotor deficits was 1.63 (95% CI, 1.22–2.19; I2 =0%).

Most of the included studies compared children with exposure to antipsychotics or lithium with children from the unaffected population. The researchers noted this does not allow for the correction of potential influences such as genetic predisposition or parental psychiatric illness.

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“In particular, improved clinical studies will require prospective designs with longer follow-up periods and more extensive assessments, including validated measures of child development, in order to offer more substantiated evidence-based advice to women with bipolar disorder or psychotic disorders regarding the risks and benefits of pharmacotherapy during pregnancy,” the researchers wrote.


Poels EMP, Schrijver L, Kamperman AM, et al. Long-term neurodevelopmental consequences of intrauterine exposure to lithium and antipsychotics: a systematic review and meta-analysis [published online June 11, 2018]. Eur Child Adolesc Psychiatry. doi:10.1007/s00787-018-1177-1