The effect of prenatal lithium exposure on the neuropsychological development of the child

Eline M P Poels; Lisanne Schrijver; Tonya J H White; Sabine J Roza; Milan G Zarchev; Hilmar Bijma; Adriaan Honig; Inge L van Kamp; Witte J G Hoogendijk; Astrid M Kamperman; Veerle Bergink

doi:10.1111/bdi.13133

The effect of prenatal lithium exposure on the neuropsychological development of the child

Bipolar Disord. 2022 May;24(3):310-319. doi: 10.1111/bdi.13133. Epub 2021 Oct 5.

Authors

Affiliations

¹ Department of Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands.
² Department of Psychiatry, Reinier van Arkel, 's-Hertogenbosch, The Netherlands.
³ Department of Child and Adolescent Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁴ Department of Obstetrics and Gynaecology, Division of Obstetrics and Prenatal Medicine, Erasmus University Medical Centre Rotterdam, Rotterdam, The Netherlands.
⁵ Department of Psychiatry, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands.
⁶ Department of Psychiatry, VU Medical Centre, Amsterdam, The Netherlands.
⁷ Department of Obstetrics, Leiden University Medical Center, Leiden, The Netherlands.
⁸ Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.

Abstract

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.

Keywords: bipolar disorder; cognition; fetal exposure; intelligence quotient; lithium; neuropsychological development; offspring; pregnancy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bipolar Disorder* / drug therapy
Child
Child Development
Female
Humans
Intelligence Tests
Lithium / therapeutic use
Neuropsychological Tests
Pregnancy
Prenatal Exposure Delayed Effects* / chemically induced
Prenatal Exposure Delayed Effects* / epidemiology
Prenatal Exposure Delayed Effects* / psychology

Substances

Lithium