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Neonatal outcome following maternal infection with SARS-CoV-2 in Germany: COVID-19-Related Obstetric and Neonatal Outcome Study (CRONOS)
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  1. Nadine Mand1,
  2. Antonella Iannaccone2,
  3. Ann-Carolin Longardt3,
  4. Matthias Hutten4,
  5. Lars Mense5,
  6. Peter Oppelt6,
  7. Rolf Felix Maier1,
  8. Ulrich Pecks7,
  9. Mario Rüdiger5
  10. on behalf of the CRONOS Network
    1. 1Department of Pediatrics, Philipps University of Marburg, Marburg, Germany
    2. 2Department of Obstetrics, University of Duisburg-Essen, Essen, Germany
    3. 3Department of Pediatrics, Christian-Albrechts-University of Kiel, Kiel, Germany
    4. 4Department of Pediatrics, Maastricht University, Maastricht, The Netherlands
    5. 5Department of Pediatrics, University of Dresden, Dresden, Germany
    6. 6Department of Obstetrics, Johannes Kepler University Linz, Linz, Austria
    7. 7Department of Obstetrics, Christian-Albrechts-University of Kiel, Kiel, Germany
    1. Correspondence to Dr Nadine Mand, Pediatrics, University of Marburg, Marburg, 35043, Germany; mandn{at}staff.uni-marburg.de

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    SARS-CoV-2 infections in pregnant women and the consequences for their offspring are summarised in various reviews,1 2 but data on the impact of time of SARS-CoV-2 infection during pregnancy on neonatal morbidity are still inconclusive.3 4

    CRONOS (COVID-19-Related Obstetric and Neonatal Outcome Study) is a prospective German registry enrolling pregnant women with confirmed SARS-CoV-2 infection during their pregnancy.5 SARS-CoV-2 infection is defined as detection of viral RNA by PCR testing or detection of maternal SARS-CoV-2 antibodies. Neonatal infection is defined as detection of viral RNA by PCR testing of a nasopharyngeal/oropharyngeal or rectal swab.

    For the present analysis, time of maternal infection was categorised into ‘early’ or ‘late’ if women tested positive for SARS-CoV-2 more or less than 2 weeks prior to delivery, respectively. Data obtained between 3 April and 27 November 2020 were analysed, using 74 hospitals (73 German and 1 Austrian) comprising approximately 20% of German births.

    Within the study period 435 newborns were entered into the registry, 4 (0.9%) of which were stillbirths. From the 431 live births, 261 (60.6%) were born to mothers with a late SARS-CoV-2 infection and 163 (37.8%) were born to mothers with an early infection. In 7 (1.6%) cases time of SARS-CoV-2 detection was unclear (table 1).

    Table 1

    Maternal characteristics by time of positive SARS-CoV-2 infection (n=7 with undetermined time of diagnosis)

    We found no significant difference in neonatal outcome with regard to time of maternal infection (table 2). There was no decrease in birth weight or increase in congenital malformations in infants of mothers with early infection. Neither the rate of caesarean section (37.4% vs 37.9%, n.s.) nor the rate of prematurity (14.9% vs 10.4%, n.s.) differed between the two groups. Prevalence of neonatal intensive care unit (NICU) admission (15.4% vs 12.5%, n.s.) or need for ventilatory support (58.8% vs 41.2%, p=0.07) was not affected by time of maternal SARS-CoV-2 infection. Thus, recent maternal SARS-CoV-2 seems not to increase the risk of neonatal pulmonary infection. Despite maternal infection majority of infants were rooming-in (overall 85.5%) and fed with mother’s milk (overall 92.8%). Our data support the recommendation of rooming-in and feeding with maternal breastmilk as long as the mother’s illness does not prevent her from caring for her infant.

    Table 2

    Neonatal characteristics by time of positive SARS-CoV-2 PCR (only live births)

    Within the group of late maternal infection, nine infants (4.5%) tested positive for SARS-CoV-2. Of these, seven infants tested positive during their first 48 hours of life, all were asymptomatic. Two infants tested positive more than 48 hours postnatally, and one infant was admitted to the NICU requiring mechanical ventilation, which is rarely seen as a complication of neonatal SARS-CoV-2 infection.

    Short-term follow-up of 187 infants was favourable, with all but one with signs of a metabolic disorder appearing well. No infant was reported to require rehospitalisation after birth.

    Overall, our report of 431 infants born to women infected with SARS-CoV-2 during their pregnancy shows low neonatal morbidity. Only 2.8% had a positive SARS-CoV-2 PCR in their postnatal period. Time of maternal SARS-CoV-2 infection seems not to affect neonatal outcome; however, further data on the impact of long COVID-19 are needed.

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    • Collaborators Alexander Hein, Sven Kehl, Julia Kornes, Corinna Keil, Maria Delius, Magdalena Jegen, Babett Ramsauer, Dietmar Schlembach, Bastian Riebe, Michael Abou-Dakn, Ute Schaefer-Graf, Charlotte Engelbrecht, Teresa-Mira Gruber, Lars Hellmeyer, Claudia Laesser, Charlotte Rohlwink, Cosmin Paul Sarac, Mirjam Kunze, Maike Manz, Angela Lihs, Michael Bohlmann, Elsa Hollatz-Galuschki, Janine Zöllkau, Cahit Birdir, Katharina Lang, Christine Morfeld, Constantin Kaisenberg, Marketa Vasku, Lena Anthuber, Gentiana Ibrahimi, Hendrik Veldink, Parnian Parvanta, Anke Reitter, Sara Fill Malfertheiner, Martin Berghaeuser, Verena Haeffner, Monika Palz-Fleige, Tanja Ruebelmann, Nadja Hirschfeld, Marina Sourouni, Christian Enzensberger, Bernhard Bungert, Sven Seeger, Marek Struck, Claudia Roll, Sirma Supcun, Joannis Kyvernitakis, Ines Erhardt, Tamina Rawnaq, Gunnar Schwennicke, Ina Rühl, Carolin Kladt, Anja Leonhardt, Vincent Winkler, Jeannette Teeuwen-Mutter, Frank Reister, Seliger Gregor, Asimina Kartsiouni, Christian Schindlbeck, Tamme Goecke, Katharina Freienstein, Irmgard Drost, Joachim Zucker-Reimann, Stefan Schmidt, Sönke Ebert.

    • Contributors NM designed and conducted the analyses reported in this study and wrote the manuscript. UP contributed significantly to the design of these analyses. A-CL, MH, LM, RFM, UP and MR all contributed significantly to the final draft of this manuscript by discussing the results and their interpretations and by revising earlier drafts. IA and PO provided significant data for the analysis. UP and MR are the principal investigators of the CRONOS Network.

    • Funding The CRONOS Network received funding from CAU/UKSH, DGPM, Krumme-Stiftung Kiel and the German Society of Diabetes.

    • Provenance and peer review Not commissioned; internally peer reviewed.

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