Department of Obstetrics and Gynaecology, Center for Reproductive Medicine, Amsterdam UMC, Amsterdam, The Netherlands.
Cochrane Gynaecology and Fertility Satellite, Amsterdam, The Netherlands.
Hum Reprod Update. 2024 Mar 1;30(2):133-152. doi: 10.1093/humupd/dmad030.
BACKGROUND: Pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more likely to experience preterm birth and their neonates are more likely to be stillborn or admitted to a neonatal unit. The World Health Organization declared in May 2023 an end to the coronavirus disease 2019 (COVID-19) pandemic as a global health emergency. However, pregnant women are still becoming infected with SARS-CoV-2 and there is limited information available regarding the effect of SARS-CoV-2 infection in early pregnancy on pregnancy outcomes. OBJECTIVE AND RATIONALE: We conducted this systematic review to determine the prevalence of early pregnancy loss in women with SARS-Cov-2 infection and compare the risk to pregnant women without SARS-CoV-2 infection. SEARCH METHODS: Our systematic review is based on a prospectively registered protocol. The search of PregCov19 consortium was supplemented with an extra electronic search specifically on pregnancy loss in pregnant women infected with SARS-CoV-2 up to 10 March 2023 in PubMed, Google Scholar, and LitCovid. We included retrospective and prospective studies of pregnant women with SARS-CoV-2 infection, provided that they contained information on pregnancy losses in the first and/or second trimester. Primary outcome was miscarriage defined as a pregnancy loss before 20 weeks of gestation, however, studies that reported loss up to 22 or 24 weeks were also included. Additionally, we report on studies that defined the pregnancy loss to occur at the first and/or second trimester of pregnancy without specifying gestational age, and for second trimester miscarriage only when the study presented stillbirths and/or foetal losses separately from miscarriages. Data were stratified into first and second trimester. Secondary outcomes were ectopic pregnancy (any extra-uterine pregnancy), and termination of pregnancy. At least three researchers independently extracted the data and assessed study quality. We calculated odds ratios (OR) and risk differences (RDs) with corresponding 95% CI and pooled the data using random effects meta-analysis. To estimate risk prevalence, we performed meta-analysis on proportions. Heterogeneity was assessed by I2. OUTCOMES: We included 120 studies comprising a total of 168 444 pregnant women with SARS-CoV-2 infection; of which 18 233 women were in their first or second trimester of pregnancy. Evidence level was considered to be of low to moderate certainty, mostly owing to selection bias. We did not find evidence of an association between SARS-CoV-2 infection and miscarriage (OR 1.10, 95% CI 0.81-1.48; I2 = 0.0%; RD 0.0012, 95% CI -0.0103 to 0.0127; I2 = 0%; 9 studies, 4439 women). Miscarriage occurred in 9.9% (95% CI 6.2-14.0%; I2 = 68%; 46 studies, 1797 women) of the women with SARS CoV-2 infection in their first trimester and in 1.2% (95% CI 0.3-2.4%; I2 = 34%; 33 studies; 3159 women) in the second trimester. The proportion of ectopic pregnancies in women with SARS-CoV-2 infection was 1.4% (95% CI 0.02-4.2%; I2 = 66%; 14 studies, 950 women). Termination of pregnancy occurred in 0.6% of the women (95% CI 0.01-1.6%; I2 = 79%; 39 studies; 1166 women). WIDER IMPLICATIONS: Our study found no indication that SARS-CoV-2 infection in the first or second trimester increases the risk of miscarriages. To provide better risk estimates, well-designed studies are needed that include pregnant women with and without SARS-CoV-2 infection at conception and early pregnancy and consider the association of clinical manifestation and severity of SARS-CoV-2 infection with pregnancy loss, as well as potential confounding factors such as previous pregnancy loss. For clinical practice, pregnant women should still be advised to take precautions to avoid risk of SARS-CoV-2 exposure and receive SARS-CoV-2 vaccination.
背景:感染严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)的孕妇更有可能早产,其新生儿更有可能死产或被送入新生儿病房。世界卫生组织于 2023 年 5 月宣布,将新型冠状病毒病(COVID-19)大流行作为一项全球卫生紧急事件结束。然而,孕妇仍在感染 SARS-CoV-2,关于早期妊娠期间 SARS-CoV-2 感染对妊娠结局的影响,目前信息有限。
目的和理由:我们进行了这项系统评价,以确定感染 SARS-CoV-2 的孕妇早期妊娠丢失的发生率,并比较感染 SARS-CoV-2 的孕妇与未感染 SARS-CoV-2 的孕妇的风险。
检索方法:我们的系统评价是基于一个预先注册的方案进行的。在 PregCov19 联盟的搜索基础上,我们还专门在 PubMed、Google Scholar 和 LitCovid 中进行了额外的电子搜索,以获取截至 2023 年 3 月 10 日孕妇感染 SARS-CoV-2 与妊娠丢失相关的研究。我们纳入了有 SARS-CoV-2 感染的孕妇的回顾性和前瞻性研究,只要它们包含了第一和/或第二孕期妊娠丢失的信息。主要结局为流产,定义为妊娠 20 周前的妊娠丢失,但也包括报道至 22 或 24 周的妊娠丢失。此外,我们还报告了定义妊娠丢失发生在第一和/或第二孕期而未具体指定孕周的研究,以及仅报告第二孕期流产且未分别报告死产和/或胎儿丢失的研究。数据分层为第一和第二孕期。次要结局为异位妊娠(任何子宫外妊娠)和终止妊娠。至少有 3 位研究人员独立提取数据并评估研究质量。我们使用随机效应荟萃分析计算了比值比(OR)和风险差异(RD)及其对应的 95%置信区间(CI),并对比例进行荟萃分析以估计风险流行率。我们使用 I2 评估了异质性。
结果:我们纳入了 120 项研究,共纳入了 168444 名感染 SARS-CoV-2 的孕妇;其中 18233 名孕妇处于第一或第二孕期。证据水平被认为是低到中度确定性,主要是由于选择偏倚。我们没有发现 SARS-CoV-2 感染与流产之间存在关联的证据(OR 1.10,95%CI 0.81-1.48;I2 = 0.0%;RD 0.0012,95%CI -0.0103 至 0.0127;I2 = 0%;9 项研究,4439 名妇女)。感染 SARS-CoV-2 的孕妇中,第一孕期流产的发生率为 9.9%(95%CI 6.2-14.0%;I2 = 68%;46 项研究,1797 名妇女),第二孕期流产的发生率为 1.2%(95%CI 0.3-2.4%;I2 = 34%;33 项研究,3159 名妇女)。感染 SARS-CoV-2 的孕妇中异位妊娠的比例为 1.4%(95%CI 0.02-4.2%;I2 = 66%;14 项研究,950 名妇女)。终止妊娠的发生率为 0.6%(95%CI 0.01-1.6%;I2 = 79%;39 项研究,1166 名妇女)。
更广泛的影响:我们的研究没有发现证据表明感染 SARS-CoV-2 的第一或第二孕期会增加流产的风险。为了提供更好的风险估计,需要设计良好的研究,包括感染 SARS-CoV-2 的孕妇和未感染 SARS-CoV-2 的孕妇,以及考虑 SARS-CoV-2 感染的临床表现和严重程度与妊娠丢失的关联,以及潜在的混杂因素,如既往妊娠丢失。对于临床实践,仍应建议孕妇采取预防措施,避免 SARS-CoV-2 暴露,并接种 SARS-CoV-2 疫苗。