Data_Sheet_1_Maternal and Fetal Outcomes After Interferon Exposure During Pregnancy: A Systematic Review With Meta-Analysis.docx

Interferon (IFN) treatment is widely applied in viral hepatitis and multiple myeloproliferative diseases. However, there is considerable controversy on how to deal with unintended pregnancy during IFN treatment, even selective termination is suggested by hepatologists. To settle this clinical dilemma, we conducted a systematic review to retrieve all published articles involving IFN exposure during pregnancy up until March 31, 2021. Only 8 case reports that were relevant with outcomes of pregnant women with viral hepatitis exposed to IFN-α were retrieved, and 17 studies reporting pregnancy outcomes after exposure to type I IFNs involving 3,543 pregnancies were eligible for meta-analysis. No birth defect was reported in the case reports of pregnant women with viral hepatitis. The meta-analysis showed that risks of pregnancy outcomes and birth defects were not increased after exposure to IFN-α. Further comprehensive meta-analysis concerning the IFN-α and IFN-β exposure demonstrated that the risks of live birth (OR 0.89, 95% CI: 0.62–1.27), spontaneous abortion (OR 1.09, 95% CI: 0.73–1.63), stillbirth (OR 1.38, 95% CI: 0.51–3.72), preterm delivery (OR 1.24, 95% CI: 0.85–1.81), and maternal complications (OR 0.72, 95% CI: 0.38–1.38) were not increased in patients exposed to IFNs. The pooled estimates of live birth, spontaneous abortion, stillbirth, preterm delivery, and maternal complications were 85.2, 9.4, 0, 7.5, and 6.5%, respectively. Importantly, the risk of birth defects was not increased (OR 0.68, 95% CI: 0.39–1.20) after IFN exposure, with a pooled rate of 0.51%. Therefore, IFN exposure does not increase the prevalence of spontaneous abortion, stillbirth, preterm delivery, and birth defects. Clinical decision should be made after weighing up all the evidence.

干扰素（IFN）治疗在病毒性肝炎和多种骨髓增殖性疾病中应用广泛。然而，关于如何处理干扰素治疗期间的不孕问题存在诸多争议，甚至有肝病学专家建议选择性终止妊娠。为解决这一临床难题，本研究进行了系统综述，旨在检索至2021年3月31日为止所有关于妊娠期间暴露于干扰素的已发表文章。共检索到8篇与病毒性肝炎孕妇暴露于IFN-α相关联的病例报告，以及17项涉及3,543例妊娠的I型干扰素暴露后妊娠结果研究，符合荟萃分析条件。病例报告中未报告病毒性肝炎孕妇的出生缺陷。荟萃分析显示，暴露于IFN-α后，妊娠结果和出生缺陷的风险并未增加。进一步针对IFN-α和IFN-β暴露的全面荟萃分析表明，对于接受IFN治疗的病人，活产（OR 0.89，95% CI：0.62–1.27）、自然流产（OR 1.09，95% CI：0.73–1.63）、死产（OR 1.38，95% CI：0.51–3.72）、早产（OR 1.24，95% CI：0.85–1.81）和母体并发症（OR 0.72，95% CI：0.38–1.38）的风险并未增加。活产、自然流产、死产、早产和母体并发症的汇总估计率分别为85.2%、9.4%、0%、7.5%和6.5%。值得注意的是，暴露于干扰素后，出生缺陷的风险并未增加（OR 0.68，95% CI：0.39–1.20），汇总发生率为0.51%。因此，干扰素暴露并未增加自然流产、死产、早产和出生缺陷的发病率。临床决策应在权衡所有证据后作出。