Department of Obstetrics and Gynaecology, The Fertility Clinic, Copenhagen University Hospital Hvidovre, DK-2650 Hvidovre, Denmark.
Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.
Hum Reprod. 2021 Jan 1;36(1):40-47. doi: 10.1093/humrep/deaa311.
Does maternal infection with severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) in first trimester pregnancy have an impact on the fetal development as measured by nuchal translucency thickness and pregnancy loss?
Nuchal translucency thickness at the first trimester scan was not significantly different in pregnant women with versus without SARS-CoV-2 infection in early pregnancy and there was no significantly increased risk of pregnancy loss in women with SARS-CoV-2 infection in the first trimester.
Pregnant women are more vulnerable to viral infections. Previous coronavirus epidemics have been associated with increased maternal morbidity, mortality and adverse obstetric outcomes. Currently, no evidence exists regarding possible effects of SARS-CoV-2 in first trimester pregnancies.
STUDY DESIGN, SIZE, DURATION: Cohort study of 1019 women with a double test taken between 17 February and 23 April 2020, as a part of the combined first trimester risk assessment, and 36 women with a first trimester pregnancy loss between 14 April and 21 May 2020, prior to the double test. The study period was during the first SARS-CoV-2 epidemic wave in Denmark.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Cohort 1 included pregnant women with a double test taken within the study period. The excess serum from each double test was analyzed for SARS-CoV-2 antibodies. Results were correlated to the nuchal translucency thickness and the number of pregnancy losses before or at the time of the first trimester scan. Cohort 2 included women with a pregnancy loss before the gestational age for double test sample. Serum from a blood test taken the day the pregnancy loss was identified was analyzed for SARS-CoV-2 antibodies. The study was conducted at a public university hospital serving ∼12% of pregnant women and births in Denmark. All participants in the study provided written informed consent.
Eighteen (1.8%) women had SARS-CoV-2 antibodies in the serum from the double test suggestive of SARS-CoV-2 infection in early pregnancy. There was no significant difference in nuchal translucency thickness for women testing positive for previous SARS-CoV-2 infection (n = 16) versus negative (n = 966) (P = 0.62). There was no significantly increased risk of pregnancy loss for women with antibodies (n = 1) (OR 3.4, 0.08-24.3 95% CI, P = 0.27). None of the women had been hospitalized due to SARS-CoV-2 infection. None of the women with pregnancy loss prior to the double test (Cohort 2) had SARS-CoV-2 antibodies.
LIMITATIONS, REASONS FOR CAUTION: These results may only apply to similar populations and to patients who do not require hospitalization due to SARS-CoV-2 infection. A limitation of the study is that only 1.8% of the study population had SARS-CoV-2 antibodies suggestive of previous infection.
Maternal SARS-CoV-2 infection had no effect on the nuchal translucency thickness and there was no significantly increased risk of pregnancy loss for women with SARS-CoV-2 infection in first trimester pregnancy. Evidence concerning COVID-19 in pregnancy is still limited. These data indicate that infection with SARS-CoV-2 in not hospitalized women does not pose a significant threat in first trimester pregnancies. Follow-up studies are needed to establish any risk to a fetus exposed to maternal SARS-CoV-2 infection.
STUDY FUNDING/COMPETING INTEREST(S): Prof. H.S.N. and colleagues received a grant from the Danish Ministry of Research and Education for research of COVID-19 among pregnant women. The Danish government was not involved in the study design, data collection, analysis, interpretation of data, writing of the report or decision to submit the paper for publication. A.I., J.O.-L., J.B.-R., D.M.S., J.E.-F. and E.R.H. received funding from a Novo Nordisk Foundation (NNF) Young Investigator Grant (NNF15OC0016662) and a Danish National Science Foundation Center Grant (6110-00344B). A.I. received a Novo Scholarship. J.O.-L. is funded by an NNF Pregraduate Fellowship (NNF19OC0058982). D.W. is funded by the NNF (NNF18SA0034956, NNF14CC0001, NNF17OC0027594). A.M.K. is funded by a grant from the Rigshospitalet's research fund. H.S.N. has received speaker's fees from Ferring Pharmaceuticals, Merck Denmark A/S and Ibsa Nordic (outside the submitted work). N.l.C.F. has received a grant from Gedeon Richter (outside the submitted work). A.M.K. has received speaker's fee from Merck (outside the submitted work). The other authors did not report any potential conflicts of interest.
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在妊娠早期感染严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)是否会影响胎儿发育,表现为颈项透明层厚度和妊娠丢失?
在妊娠早期感染 SARS-CoV-2 的孕妇中,颈项透明层厚度在首次产前检查时并无显著差异,且在妊娠早期感染 SARS-CoV-2 的孕妇中,妊娠丢失的风险无显著增加。
孕妇更容易受到病毒感染。以前的冠状病毒流行与产妇发病率、死亡率和不良产科结局增加有关。目前,尚无关于 SARS-CoV-2 在妊娠早期可能产生的影响的证据。
研究设计、规模、持续时间:对 1019 名在 2020 年 2 月 17 日至 4 月 23 日期间进行双次检测的孕妇进行队列研究,这是联合进行的首次产前检查风险评估的一部分,另外对 36 名在 4 月 14 日至 5 月 21 日之间进行首次产前检查时发生妊娠丢失的孕妇进行队列研究。研究期间正值丹麦的 SARS-CoV-2 首次流行期间。
参与者/材料、设置、方法:队列 1 包括在研究期间进行双次检测的孕妇。从每次双次检测的多余血清中分析 SARS-CoV-2 抗体。结果与颈项透明层厚度和首次产前检查时或之前的妊娠丢失数量相关。队列 2 包括在双次检测样本采集前妊娠丢失的孕妇。在确定妊娠丢失的当天采集血样,分析 SARS-CoV-2 抗体。该研究在一所为丹麦约 12%的孕妇和分娩提供服务的公立大学医院进行。所有参与研究的参与者均提供了书面知情同意书。
18 名(1.8%)孕妇的双次检测血清中存在 SARS-CoV-2 抗体,提示其在妊娠早期感染了 SARS-CoV-2。在 SARS-CoV-2 感染检测呈阳性的孕妇(n=16)与阴性的孕妇(n=966)中,颈项透明层厚度无显著差异(P=0.62)。在有抗体的孕妇(n=1)中,妊娠丢失的风险无显著增加(OR 3.4,0.08-24.3,95%CI,P=0.27)。无孕妇因 SARS-CoV-2 感染而住院。在未进行双次检测的妊娠丢失孕妇(队列 2)中,均未检测到 SARS-CoV-2 抗体。
局限性、谨慎的原因:这些结果可能仅适用于类似人群和因 SARS-CoV-2 感染无需住院的患者。该研究的一个局限性是,只有 1.8%的研究人群有 SARS-CoV-2 抗体,提示以前感染过。
在妊娠早期感染 SARS-CoV-2 的孕妇中,SARS-CoV-2 感染对颈项透明层厚度无影响,且有 SARS-CoV-2 感染的孕妇妊娠丢失的风险无显著增加。关于 COVID-19 对妊娠的影响的证据仍然有限。这些数据表明,未住院的 SARS-CoV-2 感染孕妇对胎儿没有显著威胁。需要进一步的随访研究来确定母体 SARS-CoV-2 感染对暴露胎儿的任何风险。
研究资金/利益冲突:Prof. H.S.N.及其同事获得了丹麦研究和教育部的一项研究 COVID-19 对孕妇影响的拨款。丹麦政府未参与研究设计、数据收集、分析、对数据的解释、撰写报告或决定提交论文供发表。A.I.、J.O.-L.、J.B.-R.、D.M.S.、J.E.-F.和 E.R.H.获得了 Novo Nordisk 基金会(NNF)青年研究员资助(NNF15OC0016662)和丹麦国家科学基金会中心资助(6110-00344B)。A.I.获得了 Novo 奖学金。J.O.-L.由 NNF 研究生奖学金资助(NNF19OC0058982)。D.W.由 NNF 资助(NNF18SA0034956、NNF14CC0001、NNF17OC0027594)。A.M.K.获得了 Rigshospitalet 研究基金的资助。H.S.N.曾担任 Ferring 制药公司、默克丹麦公司和 Ibsa Nordic 公司的演讲嘉宾(在提交的工作之外)。N.l.C.F.获得了 Gedeon Richter 的资助(在提交的工作之外)。A.M.K.担任 Merck 公司的演讲嘉宾(在提交的工作之外)。其他作者未报告任何潜在的利益冲突。
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