Hydroxychloroquine and teratogenic risk in pregnancy in systemic autoimmune diseases: A systematic narrative review

Hydroxychloroquine (HCQ) is increasingly prescribed during pregnancy to manage systemic autoimmune diseases (SAD) such as systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Its use has been consistently associated with improved foetal outcomes and a reduced risk of maternal disease flares. Despite growing and consistent evidence supporting its safety in pregnancy, some clinicians express concerns about potential teratogenicity. This systematic narrative review aims to consolidate the current literature and critically evaluate the evidence regarding the teratogenic safety of HCQ during pregnancy.

To systematically review and critically appraise the potential teratogenic risk of HCQ during pregnancy, based on available human data from women with SAD.

We conducted a systematic narrative review following PRISMA 2020 guidelines. PubMed/MEDLINE and EMBASE were searched up to April 2025 for randomized trials, cohort studies, and case-control studies reporting congenital malformations after in utero exposure to HCQ. Risk of bias was assessed using RoB 2 and ROBINS-I tools. Due to clinical and methodological heterogeneity, findings were synthesized narratively without quantitative pooling.

Fourteen studies including 4797 HCQ-exposed pregnancies were identified. Across randomized, prospective, and large population-based observational studies, HCQ exposure was not consistently associated with an increased risk of major congenital malformations, and no specific pattern of anomalies was observed. A single large population-based study reported a modest, dose-dependent increase in risk at daily doses ≥400 mg; however, absolute risk differences were small, no consistent malformation phenotype emerged, and findings were not replicated in other large cohorts. Minor congenital anomalies were inconsistently reported and showed no coherent association with HCQ exposure.

The available evidence does not support an increased teratogenic risk associated with HCQ use during pregnancy in women with systemic autoimmune diseases. When weighed against the established risks of uncontrolled maternal disease, continuation of HCQ at standard doses appears justified. Integration of epidemiological data with current mechanistic evidence further supports the biological plausibility of fetal safety.