Chambers Christina D, Johnson Diana L, Xu Ronghui, Luo Yunjun, Felix Robert, Fine Minh, Lessard Chloe, Adam Margaret P, Braddock Stephen R, Robinson Luther K, Burke Leah, Jones Kenneth Lyons
University of California San Diego.
University of Washington, Seattle.
Arthritis Rheumatol. 2022 Apr;74(4):711-724. doi: 10.1002/art.42015. Epub 2022 Mar 10.
Findings from previous small studies have been reassuring regarding the safety of treatment with hydroxychloroquine (HCQ) during pregnancy. In one recent study, it was demonstrated that the frequency of major birth defects was increased in women who had received HCQ at a dose of ≥400 mg/day during pregnancy. This study was undertaken to examine pregnancy outcomes among women following the use of HCQ.
The study cohort comprised pregnant women who were prospectively enrolled in the MotherToBaby/Organization of Teratology Information Specialists Autoimmune Diseases in Pregnancy Study and were receiving treatment with HCQ. For the control groups, disease-matched women without HCQ exposure and healthy women were randomly selected from the same source, with subject matching using a 1:1 ratio. Data were collected through interviews, medical records, and dysmorphology examinations. Pregnancy outcome measures included the presence or absence of major and minor birth defects, rates of spontaneous abortion, rates of preterm delivery, and infant growth measures.
Between 2004 and 2018, 837 pregnant women met the criteria for study inclusion, including 279 women exposed to HCQ during pregnancy and 279 women in each unexposed control group. Sixty pregnant women (7.2%) were lost to follow-up. Among the women with live births, major birth defects occurred as a pregnancy outcome in 20 (8.6%) of 232 women with HCQ exposure in the first trimester, compared to 19 (7.4%) of 256 disease-matched unexposed controls (odds ratio [OR] 1.18, 95% confidence interval [95% CI] 0.61-2.26) and 13 (5.4%) of 239 healthy controls (adjusted OR 0.76, 95% CI 0.28-2.05). Risks did not differ in women who were receiving an HCQ dose of ≥400 mg/day. No pattern of birth defects was identified. There were no differences in the rates of spontaneous abortion or preterm delivery between groups. Occurrence of infant growth deficiencies did not differ in the HCQ-exposed group compared to the disease-matched unexposed control group, except in the infant's head circumference at birth (adjusted OR 1.85, 95% CI 1.07-3.20).
In this study, there was no evidence of an increased risk of structural birth defects or other adverse outcomes among women receiving HCQ during pregnancy, with the exception of infant head circumference at birth. For pregnant women being treated with HCQ, these findings are reassuring.
既往小型研究的结果显示孕期使用羟氯喹（HCQ）治疗是安全的，令人安心。在最近一项研究中，已证实孕期接受≥400mg/日剂量HCQ治疗的女性中，严重出生缺陷的发生率有所增加。本研究旨在探讨使用HCQ后女性的妊娠结局。
研究队列包括前瞻性纳入母婴健康研究/致畸信息专家组织孕期自身免疫性疾病研究且正在接受HCQ治疗的孕妇。对于对照组，从同一来源随机选取未接触HCQ的疾病匹配女性和健康女性，按1:1比例进行对象匹配。通过访谈、病历和畸形学检查收集数据。妊娠结局指标包括是否存在严重和轻微出生缺陷、自然流产率、早产率以及婴儿生长指标。
2004年至2018年期间，837名孕妇符合研究纳入标准，其中包括279名孕期接触HCQ的女性以及每个未接触对照组中的279名女性。60名孕妇（7.2%）失访。在活产女性中，孕早期接触HCQ的232名女性中有20名（8.6%）出现严重出生缺陷这一妊娠结局，相比之下，256名疾病匹配的未接触对照组中有19名（7.4%）（优势比[OR]1.18，95%置信区间[95%CI]0.61 - 2.26），239名健康对照组中有13名（5.4%）（校正OR 0.76，95%CI 0.28 - 2.05）。接受≥400mg/日剂量HCQ治疗的女性风险无差异。未发现出生缺陷模式。各组之间自然流产率或早产率无差异。与疾病匹配的未接触对照组相比，HCQ暴露组婴儿生长发育不足的发生率无差异，但出生时婴儿头围除外（校正OR 1.85，95%CI 1.07 - 3.20）。
在本研究中，没有证据表明孕期接受HCQ治疗的女性出现结构出生缺陷或其他不良结局的风险增加，但出生时婴儿头围除外。对于接受HCQ治疗的孕妇，这些发现令人安心。
