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In Utero Exposure to SARS-CoV-2 May Increase the Risk of Cardiometabolic Disease

Key findings

  • This study examined for the first time the association of in utero SARS-CoV-2 exposure with weight, length, and body mass index (BMI) over the first year of life
  • A group of 149 infants exposed in utero exhibited lower birth weight, lower birth BMI, and accelerated postnatal weight gain compared with 127 unexposed infants born during the same period of March 2020 to May 2021
  • A growing body of evidence suggests growth trajectories in early life are key predictors of long-term obesity and cardiometabolic disease
  • Children who had in utero exposure to SARS-CoV-2 may need close monitoring throughout their lives

The global population of children with in utero exposure to maternal SARS-CoV-2 infection may reach hundreds of millions over the next five years. This is a pressing concern because fetal programming may influence growth patterns in early life and modulate the health of offspring in childhood and adulthood, particularly with regard to risk of obesity and cardiometabolic disease.

Massachusetts General Hospital researchers conducted the first study of how in utero exposure to SARS-CoV-2 infection is associated with birth anthropometrics of neonates and growth during the first year of life. In The Journal of Clinical Endocrinology & Metabolism, they conclude such children may need close monitoring for adverse cardiometabolic outcomes throughout the life course.

The authors are Mollie W. Ockene, a clinical researcher in the Metabolism Unit at Mass General, Lindsay T. Fourman, MD, an endocrinologist in the Unit, Andrea Edlow, MD, MSc, a maternal–fetal medicine specialist in the Department of Obstetrics and Gynecology, and colleagues.


Early in the COVID-19 pandemic, physicians at Mass General Brigham (MGB) rapidly established the MGB COVID-19 Perinatal Biorepository to bank clinical data and biospecimens from mothers with or at risk of SARS-CoV-2 infection and their neonates.

The current analysis of the biorepository focused on 149 babies born between March 2020 and May 2021. They were compared with 127 babies born during the same period who had no known exposure to maternal SARS-CoV-2 infection during pregnancy. All babies were born to women who were unvaccinated during pregnancy.

Measurements at Birth

Infants born to mothers with prenatal SARS-CoV-2 infection exhibited two relatively modest but statistically significant differences from unexposed controls:

  • Birth weight z-score: −0.006 vs. 0.36 (P=0.006)
  • Body mass index (BMI) z-score: −0.19 vs. 0.22 (P=0.004)

A z-score is the number of standard deviations from the mean. These differences persisted in multivariable analyses. The two groups did not differ significantly in birth length z-score.

Growth Trajectories

The primary outcome measure was the change in BMI z-score from birth to age 12 months. Compared with the controls, infants with prenatal SARS-CoV-2 exposure had a steeper rise in z-score over the first year of life (0.62 vs. −0.05; P=0.001). In an adjusted model, this change remained significantly higher (effect size, 0.53; 95% CI, 0.06–0.99).

By 12 months there was no significant difference between the groups in BMI z-score.

Relationship of Birth Weight to Growth

Regardless of study group, lower birth weight z-score was associated with a greater change in BMI z-score from birth to 12 months (r = −0.49; P<0.0001). In a mediation analysis, birth weight z-score explained an estimated 32% of the effect of COVID-19 exposure on change in BMI z-score over the first year of life.

This finding suggests that maternal SARS-CoV-2 infection may impair the ability of a fetus to achieve its full growth potential in utero and predisposes to postnatal "catch-up" growth.

Implications for the Clinic

Catch-up growth, a biologic response to a period of growth restriction, trades improved short-term survival for an increased risk of chronic comorbidities. Reduced birth weight followed by accelerated weight gain may confer a "double hit" with respect to cardiometabolic disease risk, and children exhibiting this growth pattern may need monitoring throughout their lives.

This study also highlights the importance of preventing prenatal SARS-CoV-2 infection, including the need for indoor masking and vaccination/boosting before or during pregnancy.

Learn more about the Metabolism Unit

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Related topics


Researchers at Mass General are studying the effects of SARS-CoV-2 infection and mRNA vaccines in pregnant and lactating individuals, as well as neonates.


LydiaL. Shook, MD, Andrea G. Edlow, MD, MSc, and colleagues observed that maternal obesity was more immune-activating in the male than female placenta. They also observed sexual dimorphism in placental lipid transfer. These findings may explain sex differences in cardiometabolic disease risk in obesity-exposed offspring.