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Maternal and infant outcomes associated with lithium use in pregnancy

Munk-Olsen, Trine, Liu, Xiaoqin, Viktorin, Alexander, Brown, Hilary K., Florio, Arianna Di, D'Onofrio, Brian M., Gomes, Tara, Howard, Louise M., Khalifeh, Hind, Krohn, Holly, Larsson, Henrik, Lichtenstein, Paul, Taylor, Clare L., Kamp, Inge Van, Wesseloo, Richard, Meltzer-Brody, Samantha, Vigod, Simone N. and Bergink, Veerle 2018. Maternal and infant outcomes associated with lithium use in pregnancy. Lancet Psychiatry 5 (8) , pp. 644-652. 10.1016/S2215-0366(18)30180-9

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Abstract

Background Concerns about teratogenicity and offspring complications limit use of lithium in pregnancy. We aimed to investigate the association between in-utero lithium exposure and risk of pregnancy complications, delivery outcomes, neonatal morbidity and congenital malformations. Methods Meta-analysis of primary data analyzed using a shared protocol. Six study sites participated: Denmark, Canada, Netherlands, Sweden, UK, and US, totaling 727 lithium-exposed pregnancies compared to 21,397 reference pregnancies in mothers with a mood disorder, but unexposed to lithium. Main outcome measures included: (1) pregnancy complications, (2) delivery outcomes, (3) neonatal readmission to hospital within 28 days of birth, and (4) congenital malformations (major malformations and cardiac malformations). Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were generated using logistic regression models. Site-specific prevalence rates and ORs were pooled using random-effects meta-analytic models. Findings Lithium exposure was not associated with any of the pre-defined pregnancy complications or delivery outcomes. There was an increased risk for neonatal readmission in lithium exposed (27·5%) versus reference group (14·3%) (Pooled aOR1·62; 95% CI: 1·12–2·33). Lithium exposure during first trimester was associated with increased risk of major malformations (7·4% versus 4·3%; pooled aOR 1·71, 95% CI: 1·07–2·72). Similarly, more lithium exposed children had major cardiac malformations, albeit not stasticially significant (2·1% versus 1·6%; pooled aOR 1·54, 95% CI: 0·64–3·70). Limitations in our study include: Serum lithium 5 levels were not available, hence no analyses related to dose-response effects could be performed, and residual confounding from e.g. substance abuse cannot be ruled out. Interpretation Treatment decisions must weigh the potential for increased risks, considering both effct sizes and the precision of the estimates, in particular associated with first-trimester lithium use against its effectiveness at reducing relapse.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: Elsevier: Lancet
ISSN: 2215-0366
Date of First Compliant Deposit: 1 May 2018
Date of Acceptance: 30 April 2018
Last Modified: 03 Oct 2018 01:36
URI: http://orca-mwe.cf.ac.uk/id/eprint/111114

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