The largest study ever to examine the risk of birth defects in babies exposed to lithium provides valuable information.

As lithium is a first-line treatment for bipolar disorder, women with the condition considering pregnancy have long called for better research information on the risks of taking it during pregnancy and now an international consortium spanning six countries has conducted a meta-analysis to try to provide some answers. They pooled results from 727 lithium-exposed pregnancies compared to a control group of 21,397 pregnancies in mothers with a mood disorder who were not taking lithium.

Researchers found that the risk of birth defects in lithium-exposed infants was lower than previously thought, because previous studies had not looked at large enough populations. Yet they found an elevated risk of major congenital malformations in foetuses after exposure to lithium in the first trimester (7.4% compared to 4.3%).  In addition, risk for hospital readmission shortly after birth was nearly doubled in lithium-exposed babies compared to the unexposed group (27.5 percent versus 14.3 percent). However, lithium exposure was not associated with pregnancy complications or other delivery outcomes, such as pre-eclampsia, preterm birth, gestational diabetes, or low birth weight. 

Researchers from the Netherlands, UK, USA, Denmark, Sweden and Canada combined their data to investigate the association between in-utero lithium exposure and the risk of a broad set of maternal and perinatal outcomes. The resultant meta-analysis has a number of strengths methodologically and presents the most reliable evidence so far that there is an increased risk of congenital malformations attributable to lithium use specifically in the first trimester of pregnancy, though the results suggest that the absolute risk of malformations throughout the 9 months of pregnancy is much smaller than those reported in earlier studies.

The study, which was published in The Lancet Psychiatry, will be of great interest to women with bipolar taking lithium who are thinking about the safest way to approach pregnancy.  The overall findings are reassuring and the fact that the risk is specifically associated with the first trimester may encourage some women to consider stopping, replacing or decreasing their lithium dosage in the first 3 months.

‘Women should be informed on malformation risk in first-trimester exposed infants, but also about very high relapse risks for mental illness both during pregnancy and during the postpartum period,’ said the study's senior author, Veerle Bergink, MD, PhD, Professor of Psychiatry and of Obstetrics, Gynaecology, and Reproductive Science, Mount Sinai, NY, USA.

‘Given the well-documented effectiveness of lithium in reducing relapse in the perinatal period, some important clinical considerations are either to continue lithium in a lower dose during the first trimester or to restart lithium after the first trimester or immediately postpartum.’

1. Ref: Trine Munk-Olsen et al. Maternal and infant outcomes associated with lithium use in pregnancy: an international collaborative meta-analysis of six cohort studies. The Lancet Psychiatry, 2018; DOI: 10.1016/S2215-0366(18)30180-9

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