SARS-CoV-2 in first trimester pregnancy: a cohort study

Author:

la Cour Freiesleben N12,Egerup P3,Hviid K V R3,Severinsen E R3,Kolte A M24,Westergaard D356,Fich Olsen L3,Prætorius L1,Zedeler A1,Christiansen A -M H3,Nielsen J R3,Bang D7,Berntsen S1,Ollé-López J8,Ingham A8,Bello-Rodríguez J8,Storm D M8,Ethelberg-Findsen J8,Hoffmann E R8,Wilken-Jensen C3,Jørgensen F S29,Westh H27,Jørgensen H L210,Nielsen H S1234

Affiliation:

1. Department of Obstetrics and Gynaecology, The Fertility Clinic, Copenhagen University Hospital Hvidovre, DK-2650 Hvidovre, Denmark

2. Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark

3. Department of Obstetrics and Gynaecology, Copenhagen University Hospital Hvidovre, DK-2650 Hvidovre, Denmark

4. The Recurrent Pregnancy Loss Unit, The Capital Region, Copenhagen University Hospitals Rigshospitalet & Hvidovre Hospital, Denmark

5. Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, DK-2200 Copenhagen, Denmark

6. Methods and Analysis, Statistics Denmark, DK-2100, Copenhagen, Denmark

7. Department of Clinical Microbiology, Copenhagen University Hospital Hvidovre, DK-2650 Hvidovre, Denmark

8. DNRF Center for Chromosome Stability (CCS), Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark

9. Fetal Medicine Unit, Department of Obstetrics and Gynaecology, Copenhagen University Hospital Hvidovre, DK-2650 Hvidovre, Denmark

10. Department of Clinical Biochemistry, Copenhagen University Hospital Hvidovre, DK-2650 Hvidovre, Denmark

Abstract

Abstract STUDY QUESTION 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? SUMMARY ANSWER 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. WHAT IS KNOWN ALREADY 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. MAIN RESULTS AND THE ROLE OF CHANCE 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. WIDER IMPLICATION OF THE FINDINGS 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. TRIAL REGISTRATION NUMBER N/A

Funder

Danish Ministry of Research and Education for research of COVID-19

Novo Nordisk Foundation

Danish National Science Foundation Center

NNF Pregraduate Fellowship

NNF

Publisher

Oxford University Press (OUP)

Subject

Obstetrics and Gynecology,Rehabilitation,Reproductive Medicine

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