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. 2025 Jan 1;64(1):117-125.
doi: 10.1093/rheumatology/keae168.

Hydroxychloroquine in lupus or rheumatoid arthritis pregnancy and risk of major congenital malformations: a population-based cohort study

Ngoc V Nguyen  1 , Elisabet Svenungsson  2 , Annica Dominicus  1 , Maria Altman  1 , Karin Hellgren  1 , Julia F Simard  1   3   4 , Elizabeth V Arkema  1
Affiliations

Hydroxychloroquine in lupus or rheumatoid arthritis pregnancy and risk of major congenital malformations: a population-based cohort study

Ngoc V Nguyen et al. Rheumatology (Oxford). .

Abstract

Objectives: To assess the infant risk of major congenital malformations (MCM) associated with first-trimester exposure to hydroxychloroquine (HCQ) among mothers with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA).

Methods: This population-based cohort study utilized Swedish nationwide registers and included all singleton births (2006-2021) among individuals with prevalent SLE or RA in Sweden. The exposure was filling ≥1 HCQ prescription during the first trimester. The outcome was infant MCM within 1 year of birth. Inverse probability of treatment weighting was applied to adjust for potential confounders (e.g. maternal smoking, body mass index, pregestational diabetes and corticosteroids). Modified Poisson regression models with robust variance were used to estimate risk ratios (RR) and 95% CI.

Results: We included 1007 births (453 exposed) and 2500 births (144 exposed) in the SLE and RA cohorts, respectively. The MCM risks in the SLE overall cohort, exposed and unexposed groups were 3.6%, 3.7% and 3.4%, respectively. The corresponding figures in the RA cohort were 4.4%, 5.6% and 4.3%, respectively. The adjusted RRs (95% CI) were 1.29 (0.65, 2.56) in the SLE cohort, 1.32 (0.56, 3.13) in the RA cohort and 1.30 (0.76, 2.23) in the pooled analysis. The adjusted risk difference (exposed vs unexposed) was small (0.9% in SLE and 1.3% in RA). Sensitivity analyses examining different exposure and outcome windows yielded similar findings.

Conclusion: First-trimester exposure to HCQ was not associated with a significantly increased risk of MCM. HCQ's benefits may outweigh the risks in managing SLE or RA during pregnancy.

Keywords: autoimmune disease; hydroxychloroquine; inverse probability of treatment weighting; major congenital malformations; rheumatoid arthritis; systemic lupus erythematosus.

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Figures

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Graphical abstract
Figure 1.
Figure 1.
Adjusted RRs and 95% CIs of the HCQ–MCM association in SLE and RA cohorts. Main analysis: exposure window from LMP to LMP + 90. Sensitivity analysis: exposure window LMP − 90 to LMP + 90. HCQ: hydroxychloroquine; LMP: last menstrual period date; MCM: major congenital malformation; RR: risk ratio
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