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The use of hydroxychloroquine in pregnancy and its effect on perinatal outcomes in a population with autoimmune abnormalities

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Abstract

Objective

This study was conducted to analyse the medication indications of hydroxychloroquine (HCQ) and to explore the clinical characteristics and perinatal outcomes of pregnancy in women with autoimmune abnormalities. The value of HCQ against placental dysfunction–related pregnancy outcomes in people with autoimmune abnormalities was also explored.

Methods

① To collect HCQ application cases during pregnancy who were hospitalized and delivered from 2016 to 2020. The classification and distribution of HCQ indications were analysed. The characteristics of cases and pregnancy outcomes were discussed. ② To include pregnancy combined with autoimmune abnormalities population during the period. Demographic information, clinical characteristics, classification, medication time frame, and pregnancy outcomes were discussed.

Results

① There were 741 cases of HCQ use during pregnancy. Classification by drug indication was as follows: 257 cases (34.68%) had clear indications for autoimmune diseases. There were 359 controversial cases, as follows: 140 (18.89%) cases of antiphospholipid syndrome and 219 (29.55%) cases of autoantibody-positive cases who had no clear drug indication and also used HCQ during pregnancy. No indications were found for 125 cases (16.87%), without autoimmune abnormalities and empirical medication of HCQ during pregnancy. ② In 853 pregnancies with autoimmune abnormalities, women with systemic lupus erythematosus, Sjögren's syndrome, rheumatoid arthritis, and undifferentiated connective tissue disease had clear indications for HCQ. The proportions of HCQ applied during pregnancy were 86.67%, 85.71%, 73.53%, and 75.00%. The start of medication before pregnancy only accounted for 74.44%, 65.31%, 64.71%, and 43.38%. ③ Medication indicated antiphospholipid syndrome and simple autoantibody-positive cases in the controversial population. The proportions of cases in which HCQ was used during pregnancy were 74.47% (140/188) and 64.79% (219/338). Application of HCQ during pregnancy significantly reduced pre-eclampsia (19.8% vs. 8.91%, P < 0.001), early-onset pre-eclampsia (7.78% vs. 2.51%, P = 0.007), and pregnancy loss during the middle and late pregnancy stages (2.99% vs. 0.56%, P = 0.036) in this controversial population.

Conclusion

Empirical, over-indicated, or even no indications usage of HCQ in pregnancy is common. The strength of standardized and specialist management are needed in populations with clear HCQ indications. HCQ-indicated controversial population should avoid overdiagnosis and guard against the potential risks of combined anticoagulation and glucocorticoid therapy. The incidence of placental dysfunction diseases in people with autoimmune abnormalities increases. HCQ application may alleviate the incidence of adverse pregnancy outcomes in this population.

Key Points

•The incidence of placental dysfunction diseases in people with autoimmune abnormalities increases.

•Our work have discovered the unique value of HCQ in improving placental dysfunction diseases in autoimmune abnormal cases, not just in AID such as SLE, SS, UTCD, and RA.

•HCQ is a potential drug option for autoimmune abnormalities to improve placental function, by providing synergistic prevention and treatment of these disorders, not just single target of antispasmodic, anti-hypertensive, and circulatory improvement.

•Empirical, over-indicated, or even no indications usage of HCQ in pregnancy is common. However, the strength of standardized and specialist management are needed in populations with clear HCQ indications.

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Data availability

The data that support the findings of this study are available from Third Hospital of Peking University but restrictions apply to the availability of these data, which were used under licence for the current study, and so are not publicly available. However, data are available from the corresponding author on reasonable request and with permission of Third Hospital of Peking University.

Abbreviations

HCQ:

Hydroxychloroquine

AID:

Autoimmune diseases

SLE:

Systemic lupus erythematosus

APS:

Antiphospholipid syndrome

SS:

Sjögren’s syndrome

RA:

Rheumatoid arthritis

UTCD:

Undifferentiated connective tissue disease

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Acknowledgements

Special thanks to Prof. Jiuliang Zhao, Department of Rheumatology and Immunology, Peking Union Medical College Hospital, for his professional guidance on the study design and expert discussion. Special thanks to Lin Zeng, associate professor of the Clinical Epidemiological Research Center of Peking University Third Hospital, and M.D. Wen Zhang and M.D. Huifeng Shi from Department of Obstetrics and Gynecology for the guidance on statistical methods of this study.

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Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, Peking University Third Hospital, 49 North Garden Rd, Haidian District, 100191, Beijing, People’s Republic of China

    Shenglong Ye, Xueqing Zhao, Yuanying Liu, Yue Ma & Yongqing Wang

  2. Department of Rheumatology and Immunology, Peking University Third Hospital, 49 North Garden Rd, Haidian District, 100191, Beijing, People’s Republic of China

    Jinxia Zhao

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Contributions

Yongqing Wang, Jinxia Zhao, and Shenglong Ye contributed to conception and study design. Shenglong Ye wrote the main manuscript text. Xueqing Zhao, Yuanying Liu, and Yue Ma participated in collecting and analysing the data. All the authors had full access to all of the data in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis. All the authors read and approved the final manuscript.

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Correspondence to Yongqing Wang or Jinxia Zhao.

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Ethics approval

This study was approved by the ethics committee and Institutional Review Board of the Third Hospital of Peking University, People’s Republic of China (2022 No. 203–01).

This study is a retrospective study, the records and data did not include potential patient identifying information, and the project did not involve any commercial interests. Therefore, an exemption from informed consent of this study was approved.

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Ye, S., Zhao, X., Liu, Y. et al. The use of hydroxychloroquine in pregnancy and its effect on perinatal outcomes in a population with autoimmune abnormalities. Clin Rheumatol 42, 1137–1150 (2023). https://doi.org/10.1007/s10067-022-06462-y

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