SARS-CoV-2-Infektion in der Schwangerschaft und Auftreten von angeborenen Fehlbildungen – Besteht ein Zusammenhang? Auswertung von 8032 Schwangerschaften aus dem CRONOS-Register

Zusammenfassung

Hintergrund/ Fragestellung Aufgrund einzelner Fallberichte untersuchte das COVID-19 Related Obstetric and Neonatal Outcome Study (CRONOS)-Register, gefördert durch die Deutsche Gesellschaft für Perinatalmedizin (DGPM), mit welcher Wahrscheinlichkeit eine in der Früh-Schwangerschaft aufgetretene SARS-CoV-2-Infektion der Mutter Embryopathien und/oder Fetopathien verursacht.

Material/Methode Das CRONOS-Register erfasste an über 130 beteiligten Kliniken von April 2020 bis Februar 2023 insgesamt 8032 Frauen mit nachweislicher SARS-CoV-2-Infektion in der Schwangerschaft. Sowohl mütterliche als auch kindliche Daten wurden dokumentiert und es erfolgte eine anonymisierte, deskriptive Auswertung der multizentrischen Daten.

Ergebnisse Unter 7142 vollständig dokumentierten Schwangerschaften (inklusive postnataler Daten) kam es bei 140 Feten zu einer angeborenen Fehlbildung. 8,57% der Mütter hatten eine SARS-COV-2-Infektion im 1. Trimenon und 36,43% im 2. Trimenon. 66 Fehlbildungen (47,14%) wurden erst nach der maternalen SARS-CoV-2-Infektion diagnostiziert. Es zeigte sich in der untersuchten Kohorte eine Gesamtprävalenz angeborener Fehlbildungen von 1,96%. Die im EUROCAT (European network of population-based registries for the epidemiological surveillance of congenital anomalies)-Register vor der Pandemie im Zeitraum 2017–2019 angegebene Prävalenz lag bei 2,39%.

Diskussion Die multizentrisch erhobenen Daten zeigen, dass eine mütterliche SARS-CoV-2-Infektion in der Frühschwangerschaft nicht mit einem erhöhten Fehlbildungsrisiko einhergeht.

Abstract

Background Based on single case reports, the COVID-19 Related Obstetric and Neonatal Outcome Study (CRONOS) registry, sponsored by the German Society for Perinatal Medicine (DGPM), investigated the likelihood that SARS-CoV-2 infections of the mother in (early) pregnancy cause embryopathies and/or fetopathies.

Material/Methods The CRONOS registry enrolled a total of 8032 women with confirmed SARS-CoV-2 infection during pregnancy at more than 130 participating hospitals from April 2020 to February 2023. Both maternal and fetal data were documented and the anonymized multicenter data were analyzed.

Results Of 7142 fully documented pregnancies (including postnatal data), 140 showed congenital malformations. 8.57% of the mothers had had a SARS-CoV-2-infection in the 1st trimester and 36.43% in the 2nd trimester. In 66 cases with congenital malformations (47.14%), the malformation was only detected after the diagnosis of a maternal SARS-CoV-2 infection. The overall prevalence of congenital malformations in this cohort was 1.96%, compared to a prevalence of 2.39% reported in the EUROCAT (European network of population-based registries for the epidemiological surveillance of congenital anomalies) pre-pandemic registry between 2017–2019.

Discussion Our multicenter data argue against a link between maternal SARS-CoV-2 infection in early pregnancy and congenital malformation.

Schlüsselwörter

Coronavirus - COVID-19 - Fehlbildungen - Embryopathie - Fetopathie - CRONOS-Register

Key words

Coronavirus - COVID-19 - malformations - embryopathy - fetopathy - CRONOS-registry

Publication History

Received: 27 July 2023

Accepted after revision: 05 November 2023

Article published online:
08 February 2024

• Literatur

• 1 WHO. Coronavirus (COVID-19) Dashboard with Vaccination Data. Available online https://covid19whoint/ (accessed on 10 July 2023)
• 2 Docherty AB, Harrison EM, Green CA. et al. Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study. Bmj 2020; 369: m1985 DOI: 10.1136/bmj.m1985.
• 3 Stanczyk P, Jachymski T, Sieroszewski P. COVID-19 during pregnancy, delivery and postpartum period based on EBM. Ginekol Pol 2020; 91: 417-423 DOI: 10.5603/gp.2020.0106.
• 4 Selim M, Mohamed S, Abdo M. et al. Is COVID-19 Similar in Pregnant and Non-Pregnant Women?. Cureus 2020; 12: e8888 DOI: 10.7759/cureus.8888.
• 5 Di Mascio D, Sen C, Saccone G. et al. Risk factors associated with adverse fetal outcomes in pregnancies affected by Coronavirus disease 2019 (COVID-19): a secondary analysis of the WAPM study on COVID-19. J Perinat Med 2020; 48: 950-958 DOI: 10.1515/jpm-2020-0355.
• 6 Sahu AK, Sreepadmanabh M, Rai M. et al. SARS-CoV-2: phylogenetic origins, pathogenesis, modes of transmission, and the potential role of nanotechnology. Virusdisease 2021; 32: 1-12 DOI: 10.1007/s13337-021-00653-y.
• 7 Vousden N, Bunch K, Morris E. et al. The incidence, characteristics and outcomes of pregnant women hospitalized with symptomatic and asymptomatic SARS-CoV-2 infection in the UK from March to September 2020: A national cohort study using the UK Obstetric Surveillance System (UKOSS). PLoS One 2021; 16: e0251123 DOI: 10.1371/journal.pone.0251123.
• 8 Pecks U, Kuschel B, Mense L. et al. Pregnancy and SARS-CoV-2 Infection in Germany-the CRONOS Registry. Dtsch Arztebl Int 2020; 117: 841-842 DOI: 10.3238/arztebl.2020.0841.
• 9 Knight M, Bunch K, Vousden N. et al. Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study. Bmj 2020; 369: m2107 DOI: 10.1136/bmj.m2107.
• 10 Thompson JL, Nguyen LM, Noble KN. et al. COVID-19-related disease severity in pregnancy. Am J Reprod Immunol 2020; 84: e13339 DOI: 10.1111/aji.13339.
• 11 Vivanti AJ, Vauloup-Fellous C, Prevot S. et al. Transplacental transmission of SARS-CoV-2 infection. Nat Commun 2020; 11: 3572 DOI: 10.1038/s41467-020-17436-6.
• 12 Fenizia C, Biasin M, Cetin I. et al. Analysis of SARS-CoV-2 vertical transmission during pregnancy. Nat Commun 2020; 11: 5128 DOI: 10.1038/s41467-020-18933-4.
• 13 Pulinx B, Kieffer D, Michiels I. et al. Vertical transmission of SARS-CoV-2 infection and preterm birth. Eur J Clin Microbiol Infect Dis 2020; 39: 2441-2445 DOI: 10.1007/s10096-020-03964-y.
• 14 Morhart P, Mardin C, Rauh M. et al. Maternal SARS-CoV-2 infection during pregnancy: possible impact on the infant. Eur J Pediatr 2022; 181: 413-418 DOI: 10.1007/s00431-021-04221-w.
• 15 Heidarzadeh M, Taheri M, Mazaheripour Z. et al. The incidence of congenital anomalies in newborns before and during the Covid-19 pandemic. Ital J Pediatr 2022; 48: 174 DOI: 10.1186/s13052-022-01368-6.
• 16 Calvert C, Carruthers J, Denny C. et al. A population-based matched cohort study of early pregnancy outcomes following COVID-19 vaccination and SARS-CoV-2 infection. Nat Commun 2022; 13: 6124 DOI: 10.1038/s41467-022-33937-y.
• 17 Platform. CT-ReDM. Available online https://www.castoredc.com/ (accessed on 10 July 2023)
• 18 Lee KS, Choi YJ, Cho J. et al. Environmental and Genetic Risk Factors of Congenital Anomalies: an Umbrella Review of Systematic Reviews and Meta-Analyses. J Korean Med Sci 2021; 36: e183 DOI: 10.3346/jkms.2021.36.e183.
• 19 Dolk H, Damase-Michel C, Morris JK. et al. COVID-19 in pregnancy-what study designs can we use to assess the risk of congenital anomalies in relation to COVID-19 disease, treatment and vaccination?. Paediatr Perinat Epidemiol 2022; 36: 493-507 DOI: 10.1111/ppe.12840.
• 20 DeSilva M, Munoz FM, McMillan M. et al. Congenital anomalies: Case definition and guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine 2016; 34: 6015-6026 DOI: 10.1016/j.vaccine.2016.03.047.
• 21 Barron S. Anencephaly: An Ongoing Investigation in Washington State. Am J Nurs 2016; 116: 60-66 DOI: 10.1097/01.NAJ.0000481286.16720.6e.
• 22 Edwards MJ. Review: Hyperthermia and fever during pregnancy. Birth Defects Res A Clin Mol Teratol 2006; 76: 507-516 DOI: 10.1002/bdra.20277.
• 23 Munteanu O, Cirstoiu MM, Filipoiu FM. et al. The etiopathogenic and morphological spectrum of anencephaly: a comprehensive review of literature. Rom J Morphol Embryol 2020; 61: 335-343 DOI: 10.47162/RJME.61.2.03.
• 24 Massimo M, Barelli C, Moreno C. et al. Haemorrhage of human foetal cortex associated with SARS-CoV-2 infection. Brain 2023; 146: 1175-1185 DOI: 10.1093/brain/awac372.
• 25 Martínez-Varea A, Desco-Blay J, Monfort S. et al. Transitory Fetal Skin Edema in a Pregnant Patient with a Mild SARS-CoV-2 Infection. Case Reports in Obstetrics and Gynecology 2021; 2021: 5552877 DOI: 10.1155/2021/5552877.
• 26 Popescu DE, Cioca A, Muresan C. et al. A Case of COVID-19 Pregnancy Complicated with Hydrops Fetalis and Intrauterine Death. Medicina (Kaunas) 2021; 57 DOI: 10.3390/medicina57070667.
• 27 Cribiu FM, Erra R, Pugni L. et al. Severe SARS-CoV-2 placenta infection can impact neonatal outcome in the absence of vertical transmission. J Clin Invest 2021; 131 DOI: 10.1172/JCI145427.
• 28 Sharps MC, Hayes DJL, Lee S. et al. A structured review of placental morphology and histopathological lesions associated with SARS-CoV-2 infection. Placenta 2020; 101: 13-29 DOI: 10.1016/j.placenta.2020.08.018.
• 29 Linehan L, O'Donoghue K, Dineen S. et al. SARS-CoV-2 placentitis: An uncommon complication of maternal COVID-19. Placenta 2021; 104: 261-266 DOI: 10.1016/j.placenta.2021.01.012.
• 30 Menter T, Tzankov A, Bruder E. [Impact of SARS-CoV-2/COVID-19 on the placenta]. Pathologe 2021; 42: 591-597 DOI: 10.1007/s00292-021-00952-7.
• 31 Duppers AL, Bohnhorst B, Bultmann E. et al. Severe fetal brain damage subsequent to acute maternal hypoxemic deterioration in COVID-19. Ultrasound Obstet Gynecol 2021; 58: 490-491 DOI: 10.1002/uog.23744.
• 32 Gurol-Urganci I, Jardine JE, Carroll F. et al. Maternal and perinatal outcomes of pregnant women with SARS-CoV-2 infection at the time of birth in England: national cohort study. Am J Obstet Gynecol 2021; 225: 522-522 e511-e521 DOI: 10.1016/j.ajog.2021.05.016.
• 33 Allotey J, Stallings E, Bonet M. et al. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis. Bmj 2020; 370: m3320 DOI: 10.1136/bmj.m3320.
• 34 Wei SQ, Bilodeau-Bertrand M, Liu S. et al. The impact of COVID-19 on pregnancy outcomes: a systematic review and meta-analysis. Cmaj 2021; 193: E540-e548 DOI: 10.1503/cmaj.202604.