Multiple Gestation as a Risk Factor for SARS-CoV-2-Associated Adverse Maternal Outcome: Data From the COVID-19 Related Obstetric and Neonatal Outcome Study (CRONOS)
Authors: Sourouni Marina , Germeyer Ariane , Feißt Manuel , Balzer Alexandra , Köster Helen , Minte Annemarie , Brüggmann Dörthe , Kohll Celine , Reinhardt Kristin , Möginger Michaela , Leonhardt Anja , Banz-Jansen Constanze , Bohlmann Michael , Fröhlich Christiane , Backes Clara , Hager Dietrich , Kaup Lisa , Hollatz-Galuschki Elsa , Engelbrecht Charlotte , Markfeld-Erol Filiz , Hagenbeck Carsten , Schäffler Hening , Winkler Jennifer , Stubert Johannes , Rathberger Katharina , Lüber Laura , Hertlein Linda , Machill Antonia , Richter Manuela , Berghäuser Martin , Weigel Michael , Morgen Mirjam , Horn Nora , Jakubowski Peter , Riebe Bastian , Ramsauer Babett , Sczesny Robert , Schäfer-Graf Ute Margaretha , Schrey Susanne , Kehl Sven , Lastinger Julia , Seeger Sven , Parchmann Olaf , Iannaccone Antonella , Rohne Jens , Gattung Luise , Morfeld Christine A. , Abou-Dakn Michael , Schmidt Markus , Glöckner Michaela , Jebens Anja , Sondern Kathleen Marie , Pecks Ulrich , Schmitz Ralf , Möllers Mareike 
Published: November 2023

Studies have shown that pregnant women with COVID-19 have a higher risk of intensive
care unit admission and invasive mechanical ventilation support than non-pregnant women.
Pregnancy-associated physiological changes in respiratory function may contribute to the
elevated risk. Alteration in lung volumes and capacities are attributed to the mechanical
impediment caused by the growing fetus. Multiple pregnancies may therefore compromise
functional lung capacity earlier than singleton pregnancies and contribute to severe
respiratory symptoms of COVID-19.

A total of 5514 women with a symptomatic SARS-CoV-2 infection during pregnancy
registered in the COVID-19 Related Obstetric and Neonatal Outcome Study were included. The
COVID-19-related adverse maternal outcomes were compared in 165 multiple versus 5349
singleton pregnancies. Combined adverse maternal outcome was defined as presence of
COVID-19-related hospitalization and/or pneumonia and/or oxygen administration and/or
transfer to ICU and/or death. Multivariate logistic regression was used to estimate the odds
ratios and 95% confidence intervals were calculated.

The frequency of dyspnea, likelihood of developing dyspnea in a defined pregnancy week
and duration of the symptomatic phase of the COVID-19 infection did not differ between the
two groups. On average, COVID-19-related combined adverse outcome occurred earlier during
pregnancy in women expecting more than one child than in singleton pregnancies. The overall
incidence of singular and combined COVID-19-associated adverse maternal outcomes was not
significantly different between groups. However, regression analysis revealed that multiple
gestation, preconceptional BMI > 30 kg/m2 and gestational age correlated
significantly with an increased risk of combined adverse maternal outcome. Conversely,
maternal age and medically assisted reproduction were not significant risk factors for
combined adverse maternal outcome.

Our data show that multiple gestation alone is a risk factor for COVID-19-associated
combined adverse maternal outcome. Moreover, severe courses of COVID-19 in women expecting
more than one child are observed earlier in pregnancy than in singleton pregnancies.