Exploration of Hydroxychloroquine to Improve Perinatal Outcomes in Women with Isolated Non-Specific Auto-Antibody Positivity During Pregnancy

Objective: This study aimed to investigate the effect of hydroxychloroquine (HCQ) application during pregnancy on perinatal outcomes in cases of combined non-specific auto-antibodies. Methods: A retrospective cohort study was carried out. Cases of pregnancy combined with isolated auto-antibody positivity at Peking University Third Hospital from 2016 to 2020 were included. HCQ use during pregnancy was defined as the primary exposure. The impact of HCQ on perinatal outcomes was explored through univariate and multivariate analyses, and stratified analyses of its effects were conducted according to prophylactic anticoagulation use and medication duration. Results: A total of 338 cases were included, accounting for 39.62% (338/853) of pregnancies with autoimmune abnormalities during the same period. Univariate analysis of the overall population showed that HCQ use during pregnancy was associated with a significantly lower incidence of pre-eclampsia (9.13% vs. 25.53%), early-onset pre-eclampsia (1.37% vs. 10.08%), and small for gestational age (SGA) (12.07% vs. 22.88%). In the subgroup without anticoagulation, both multivariate and univariate analyses revealed that HCQ was associated with markedly lower rates of pre-eclampsia (0% vs. 36.67%, p = 0.004), early-onset pre-eclampsia (0% vs. 15.00%, p = 0.046), and SGA (0% vs. 28.33%, p = 0.006), and a significantly longer pregnancy gestational age with a higher birth weight. The timing of HCQ initiation showed no significant impact on adverse pregnancy outcomes. Conclusions: HCQ use during pregnancy is associated with favorable perinatal outcomes among women with isolated non-specific auto-antibody positivity, especially in those not receiving anticoagulation. Strengthened clinical evaluation and careful risk–benefit assessment are warranted to avoid unnecessary interventions.