Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, ME, 02115, USA.
Roux Institute at Northeastern University, 100 Fore St, Portland, ME, 04101, USA.
BMC Pregnancy Childbirth. 2022 Oct 18;22(1):775. doi: 10.1186/s12884-022-05101-3.
Studies of preterm delivery after COVID-19 are often subject to selection bias and do not distinguish between early vs. late infection in pregnancy, nor between spontaneous vs. medically indicated preterm delivery. This study aimed to estimate the risk of preterm birth (overall, spontaneous, and indicated) after COVID-19 during pregnancy, while considering different levels of disease severity and timing.
Pregnant and recently pregnant people who were tested for or clinically diagnosed with COVID-19 during pregnancy enrolled in an international internet-based cohort study between June 2020 and July 2021. We used several analytic approaches to minimize confounding and immortal time bias, including multivariable regression, time-to-delivery models, and a case-time-control design.
Among 14,264 eligible participants from 70 countries who did not report a pregnancy loss before 20 gestational weeks, 5893 had completed their pregnancies and reported delivery information; others were censored at time of their last follow-up. Participants with symptomatic COVID-19 before 20 weeks' gestation had no increased risk of preterm delivery compared to those testing negative, with adjusted risks of 10.0% (95% CI 7.8, 12.0) vs. 9.8% (9.1, 10.5). Mild COVID-19 later in pregnancy was not clearly associated with preterm delivery. In contrast, severe COVID-19 after 20 weeks' gestation led to an increase in preterm delivery compared to milder disease. For example, the risk ratio for preterm delivery comparing severe to mild/moderate COVID-19 at 35 weeks was 2.8 (2.0, 4.0); corresponding risk ratios for indicated and spontaneous preterm delivery were 3.7 (2.0, 7.0) and 2.3 (1.2, 3.9), respectively.
Severe COVID-19 late in pregnancy sharply increased the risk of preterm delivery compared to no COVID-19. This elevated risk was primarily due to an increase in medically indicated preterm deliveries, included preterm cesarean sections, although an increase in spontaneous preterm delivery was also observed. In contrast, mild or moderate COVID-19 conferred minimal risk, as did severe disease early in pregnancy.
关于 COVID-19 后早产的研究往往受到选择偏倚的影响，并且不能区分妊娠早期与晚期感染、自发性与医学指征性早产。本研究旨在估计 COVID-19 孕妇的早产（总体、自发性和医学指征性）风险，同时考虑不同疾病严重程度和时间的影响。
在 2020 年 6 月至 2021 年 7 月期间，参加一项国际互联网队列研究的孕妇和近期孕妇，对其进行了 COVID-19 的检测或临床诊断。我们使用了多种分析方法来最小化混杂和不朽时间偏倚，包括多变量回归、分娩时间模型和病例时间对照设计。
在来自 70 个国家的 14264 名符合条件且在 20 孕周前未报告妊娠丢失的参与者中，有 5893 名完成了妊娠并报告了分娩信息；其余参与者在最后一次随访时被截尾。与阴性检测结果相比，20 孕周前出现有症状 COVID-19 的孕妇早产风险没有增加，调整后的风险分别为 10.0%（95%CI 7.8，12.0）和 9.8%（9.1，10.5）。妊娠晚期轻度 COVID-19 与早产无明显关联。相比之下，20 孕周后严重 COVID-19 导致早产风险增加，与轻度疾病相比。例如，将严重 COVID-19 与轻度/中度 COVID-19 相比，35 孕周早产的风险比为 2.8（2.0，4.0）；相应的早产风险比为 3.7（2.0，7.0）和 2.3（1.2，3.9）。
妊娠晚期严重 COVID-19 与无 COVID-19 相比，显著增加了早产风险。这种风险升高主要归因于医学指征性早产的增加，包括早产剖宫产，尽管也观察到自发性早产的增加。相比之下，轻度或中度 COVID-19 风险较小，妊娠早期的严重疾病也是如此。
