Trimester of maternal SARS-CoV-2 infection differentially predicts newborn size in the COVID-19 Mother Baby Outcomes (COMBO) cohort

Margaret H Kyle; Presley Nichols; Lerzan Coskun; William Fifer; Amara Finch; Morgan R Firestein; Dympna Gallagher; Cynthia Gyamfi-Bannerman; Rachel Marsh; Isabelle Mollicone; Catherine Monk; Mirella Mourad; Jennifer Woo Baidal; Sharon Oberfield; Melissa S Stockwell; Ilene Fennoy; Dani Dumitriu

doi:10.1038/s41390-025-03909-1

Trimester of maternal SARS-CoV-2 infection differentially predicts newborn size in the COVID-19 Mother Baby Outcomes (COMBO) cohort

Pediatr Res. 2025 May 31. doi: 10.1038/s41390-025-03909-1. Online ahead of print.

Authors

Margaret H Kyle^{1

2}, Presley Nichols³, Lerzan Coskun⁴, William Fifer^{4

5}, Amara Finch⁶, Morgan R Firestein⁵, Dympna Gallagher⁷, Cynthia Gyamfi-Bannerman⁸, Rachel Marsh⁵, Isabelle Mollicone⁹, Catherine Monk^{5

10}, Mirella Mourad¹⁰, Jennifer Woo Baidal¹¹, Sharon Oberfield³, Melissa S Stockwell^{1

12}, Ilene Fennoy³, Dani Dumitriu^{13

14}

Affiliations

¹ Division of Child and Adolescent Health, Department of Pediatrics, Columbia University Irving Medical Center and NewYork-Presbyterian Hospital, New York, USA.
² Division of Developmental Neuroscience, Department of Psychiatry, Columbia University Irving Medical Center, New York, USA.
³ Division of Pediatric Endocrinology Diabetes and Metabolism, Department of Pediatrics, Columbia University Irving Medical Center and NewYork-Presbyterian Hospital, New York, USA.
⁴ Department of Pediatrics, Columbia University Irving Medical Center and NewYork-Presbyterian Hospital, New York, USA.
⁵ Department of Psychiatry, Columbia University Irving Medical Center, New York, USA.
⁶ Department of Pediatrics, University of Utah, Salt Lake City, USA.
⁷ New York Nutrition Obesity Research Center, Department of Medicine, Institute of Human Nutrition, Columbia University Irving Medical Center, New York, USA.
⁸ Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California at San Diego, La Jolla, USA.
⁹ Barnard College, New York, USA.
¹⁰ Department of Obstetrics and Gynecology, Columbia University Irving Medical Center and NewYork-Presbyterian Hospital, New York, USA.
¹¹ Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Columbia University Irving Medical Center and NewYork-Presbyterian Hospital, New York, USA.
¹² Department of Population and Family Health, Mailman School of Public Health, Columbia University Irving Medical Center, New York, USA.
¹³ Division of Child and Adolescent Health, Department of Pediatrics, Columbia University Irving Medical Center and NewYork-Presbyterian Hospital, New York, USA. idd2001@columbia.edu.
¹⁴ Division of Developmental Neuroscience, Department of Psychiatry, Columbia University Irving Medical Center, New York, USA. idd2001@columbia.edu.

PMID: 40450140
DOI: 10.1038/s41390-025-03909-1

Abstract

Background: In-utero exposures affect the developing fetus differentially and may manifest as growth and body size differences. We examined associations between maternal SARS-CoV-2 infection and newborn body size at a large medical center in New York City.

Methods: Between 3/22/2020 and 10/31/2020, birth outcomes for 544 newborns exposed to SARS-CoV-2 in utero and 3325 unexposed newborns were collected through retrospective chart review as part of the COVID-19 Mother Baby Outcomes (COMBO) Initiative. Data were also abstracted for 560 newborns born in February 2020 as a pre-pandemic comparison group. Growth outcomes at 6-10 weeks of life were available for a subset of 865 newborns followed in our hospital system.

Results: Newborns exposed to SARS-CoV-2 during the first trimester had significantly smaller birth weight, length, head circumference (HC) and earlier gestational age (GA) at birth than unexposed or second-to-third trimester exposed newborns. Mediation analysis found that GA mediated the relationship between first trimester SARS-CoV-2 exposure and body size at birth.

Conclusion: Maternal SARS-CoV-2 infection during the first trimester is associated with smaller body size at birth and this association is largely mediated by earlier GA. Size differences at birth can predict later adverse cardiometabolic and neurodevelopmental outcomes, warranting prospective analysis in this cohort.

Impact: Using data obtained through universal SARS-CoV-2 testing at a large, urban medical center, maternal SARS-CoV-2 infection during pregnancy was associated with newborn size. Previous literature shows that SARS-CoV-2 does not tend to cause severe respiratory disease in infants and that vertical transmission to the fetus is unlikely. However, maternal SARS-CoV-2 infection during pregnancy is associated with increased occurrence of pre-term delivery. This study contributes to the literature by showing that timing of maternal SARS-CoV-2 infection, specifically during the first trimester of pregnancy, predicts smaller newborn body size and that this relationship is mediated by earlier gestational age (GA) at birth.