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. 2024 Dec 2;7(12):e2451117.
doi: 10.1001/jamanetworkopen.2024.51117.

Lithium Use During Pregnancy in 14 Countries

Felix Wittström  1 , Carolyn E Cesta  1 , Brian T Bateman  2 , Marie Bendix  3   4   5 , Mette Bliddal  6   7 , Adrienne Y L Chan  8   9 , Yongtai Cho  10 , Eun-Young Choi  10 , Jacqueline M Cohen  11 , Sarah Donald  12 , Mika Gissler  13   14   15 , Alys Havard  16   17 , Sonia Hernandez-Diaz  18 , Krista F Huybrechts  19 , Bianca Kollhorst  20 , Edward Chia-Cheng Lai  21 , Maarit K Leinonen  13   22 , Brian M H Li  21 , Kenneth K C Man  9   23   24   25 , Vanessa W S Ng  9 , Lianne Parkin  12 , Laura Pazzagli  26 , Lotte Rasmussen  6 , Ran S Rotem  27   28 , Tania Schink  20   29 , Ju-Young Shin  10 , Duong T Tran  16 , Ian C K Wong  8   9   23   30 , Helga Zoega  17   31 , Johan Reutfors  1
Affiliations

Lithium Use During Pregnancy in 14 Countries

Felix Wittström et al. JAMA Netw Open. .

Abstract

Importance: In pregnancy, the benefits of lithium treatment for relapse prevention in psychiatric conditions must be weighed against potential teratogenic effects. Currently, there is a paucity of information on how and when lithium is used by pregnant women.

Objective: To examine lithium use in the perinatal period.

Design, setting, and participants: This cohort study used individual-level data of pregnancies from January 1, 2000, to December 31, 2021, in Australia, Denmark, Finland, Germany, Hong Kong, Iceland, Israel, New Zealand, Norway, South Korea, Sweden, Taiwan, the UK, and 2 cohorts in the US. Analyses were performed from September 1 to November 30, 2023.

Exposures: The prevalence of lithium use as the proportion of pregnancies with at least 1 prescription fill or prescription within 3 months before pregnancy until childbirth was estimated using a common protocol. Lithium use during pregnancy by trimester and in the 3 months before and after pregnancy was examined.

Main outcomes and measures: Comparison of prevalence between the first and last 3-year periods of available data.

Results: Among 21 659 454 pregnancies from all collaborating sites, the prevalence of lithium use ranged from 0.07 per 1000 pregnancies in Hong Kong to 1.56 per 1000 in the US publicly insured population. Lithium use increased per 1000 pregnancies in 10 populations (Australia [0.60 to 0.74], Denmark [0.09 to 0.51], Finland [0.10 to 0.29], Iceland [0.24 to 0.99], Israel [0.25 to 0.37], Norway [0.24 to 0.47], South Korea [0.30 to 0.44], Sweden [0.42 to 1.07], the UK [0.07 to 0.10], and Taiwan [0.15 to 0.19]), remained stable in 4 populations (Germany [0.17 to 0.16], Hong Kong [0.06 to 0.06], and the publicly [1.50 to 1.34] and commercially [0.38 to 0.36] insured US populations), and decreased in 1 population (New Zealand [0.54 to 0.39]). Use of lithium decreased with each trimester of pregnancy, while prevalence of postpartum use was similar to prepregnancy levels. The proportion of lithium use in the second trimester compared with the prepregnancy period ranged from 2% in South Korea to 80% in Denmark.

Conclusions and relevance: Prevalence of lithium use in pregnant women over the past 2 decades varied markedly between populations. Patterns of use before, during, and after pregnancy suggest that many women discontinued lithium use during pregnancy and reinitiated treatment after childbirth, with large variations between countries. These findings underscore the need for internationally harmonized guidelines, specifically for psychiatric conditions among pregnant women that may benefit from lithium treatment.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr. Wittström reported participation in research projects partially or fully funded by pharmaceutical companies, all with funds paid to the employer outside the submitted work. Dr Cesta reported participation in research projects funded by pharmaceutical companies, all with funds paid to the employer outside the submitted work. Dr Bendix reported receiving postdoctoral grant funding from the Söderström-Königska-Foundation outside the submitted work. Dr Cohen reported receiving grant funding from the Research Council of Norway and ADHD Research Network outside the submitted work. Dr Donald reported receiving grant funding from the New Zealand Health Research Council and the Australian National Health and Medical Research Council (NHMRC) outside the submitted work. Dr Havard reported receiving grant funding from University of New South Wales (UNSW) outside the submitted work. Dr Huybrechts reported receiving grant funding to institution from UCB and Takeda Pharmaceutical Company Limited outside the submitted work. Mrs Kollhorst reported her employer conducts postauthorization safety studies financed by the pharmaceutical industry outside the submitted work. Dr Leinonen reported participation in research projects partially or fully funded by pharmaceutical companies, all with funds paid to the employer outside the submitted work. Dr Man reported receiving funding from the CW Maplethorpe Fellowship and grant funding from European Commission Horizon 2020, the UK National Institute for Health and Care Research, the Research Grant Council, Hong Kong, and the Hong Kong Innovation and Technology Commission outside the submitted work. Dr Ng reported receiving personal fees from OCUS Innovation (HK) Limited outside the submitted work. Dr Rasmussen reported participation in research projects funded by Novo Nordisk A/S, with funds paid to the employer outside the submitted work. Dr Schink reported her employer conducts postauthorization safety studies financed by the pharmaceutical industry outside the submitted work. Dr Shin reported receiving grant funding from the Ministry of Food and Drug Safety, the Ministry of Health and Welfare, the National Research Foundation, SK Bioscience, Yuhan Corporation, and Pfizer Inc outside the submitted work. Dr. Wong reports research funding from Amgen Inc, BMS, Pfizer Inc, Janssen Global Services LLC, Bayer AG, GSK, Novartis AG, the Hong Kong Research Grants Council of the Government of the Hong Kong SAR, the Hong Kong Health and Medical Research Fund, the National Institute for Health Research in England, the European Commission, and the Australian NHMRC, consulting fees from IQVIA and World Health Organization, payment for expert testimony for Appeal Court of Hong Kong, and serving as a nonexecutive director of Jacobson Medical in Hong Kong, Advance Data Analytics for Medical Science Limited (HK), Asia Medicine Regulatory Affairs (AMERA) Services Limited, and OCUS Innovation Limited (HK, Ireland and UK) and a former director of Therakind in England outside of the submitted work. Dr Zoega reported receiving grant funding from UNSW during the conduct of the study. Dr Reutfors reported participation in research projects partially or fully funded by pharmaceutical companies, all with funds paid to the employer outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Prevalence of Lithium Use Over Time
Lithium use in the pregnancy period is defined as at least 1 prescription fill from 90 days before the last menstrual period until birth. Prevalence of use is shown as a 3-year moving average. MAX indicates Medicaid Analytic eXtract–Transformed Medicaid Statistical Information System Analytic Files.
Figure 2.
Figure 2.. Prevalence of Lithium Use Before, During, and After Pregnancy
The scales on the y-axes differ (panel O [US MAX; Medicaid Analytic eXtract–Transformed Medicaid Statistical Information System Analytic Files] ranges from 0 to 1.5) and are not directly comparable to the other panels. Prepregnancy indicates up to 90 days before the last menstrual period (LMP); first trimester, up to 97 days after LMP; second trimester, between 98 and 202 days after LMP; third trimester, more than 203 days after LMP until birth; and postpartum, up to 90 days after birth. aData on lithium use for the postpartum period were not available.
See this image and copyright information in PMC

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