Accelerated Longitudinal Weight Gain Among Infants With In Utero COVID-19 Exposure

Abstract

Context: Since the initial outbreak of coronavirus disease 2019 (COVID-19), a novel population of children with in utero exposure to maternal infection has emerged whose health outcomes are largely unknown.

Objective: To compare longitudinal growth trajectories among infants with vs without in utero COVID-19 exposure.

Methods: We conducted a longitudinal cohort study leveraging a prospectively enrolled perinatal biorepository among 149 infants with in utero COVID-19 exposure and 127 unexposed controls. Weight, length, and body mass index (BMI) were abstracted from health records at 0, 2, 6, and 12 months and standardized using World Health Organization growth charts. Analyses were adjusted for maternal age, ethnicity, parity, insurance, and BMI as well as infant sex, birthdate, and breastfeeding.

Results: Infants with in utero COVID-19 exposure vs controls exhibited differential trajectories of weight and BMI, but not length, z-score over the first year of life (study group × time interaction, P < .0001 for weight and BMI). Infants born to mothers with prenatal COVID-19 had lower BMI z-score at birth (effect size: -0.35, 95% CI -0.66 to -0.03) and greater gain in BMI z-score from birth to 12 months (effect size: 0.53, 95% CI 0.06 to 0.99). Birth weight z-score mediated a significant proportion of the relationship between COVID-19 exposure and postnatal growth (estimate ± SE, 32 ± 14%, P = .02).

Conclusion: Infants with in utero COVID-19 exposure exhibited lower birth weight and accelerated weight gain in the first year of life, which may be harbingers of downstream cardiometabolic pathology. Further studies are needed to delineate cardiometabolic sequelae among this emerging global population.

Keywords: BMI; COVID-19; fetal programming; growth; in utero.

Figure 1.

Participant selection. All infants in our study were born before June 1, 2021 to mothers with or at risk for prenatal COVID-19 who had participated in the MGB COVID-19 Perinatal Biorepository at MGH. Following the exclusion of individuals for the reasons delineated, a total of 149 infants with in utero COVID-19 exposure and 127 infants without known COVID-19 exposure were eligible for inclusion. Figure was created with BioRender.com.

Figure 2.

Longitudinal BMI z-score trajectories among infants with versus without in utero COVID-19 exposure. (A) Individuals born to mothers with vs without prenatal COVID-19 were found to have distinct BMI z-score trajectories over the first year of life with a linear mixed effects model. (B) As our primary endpoint, infants with in utero COVID-19 exposure demonstrated a greater change in BMI z-score from birth to 12 months than in unexposed controls using a 2-sample t-test. (C) The unadjusted differential change between groups in BMI z-score from birth to 12 months persisted in a linear regression model adjusting for maternal age at delivery, ethnicity, parity, insurance status, and earliest BMI during pregnancy as well as infant sex, date of birth, and any history of breastfeeding. Mean and SE of the mean (SEM), mean and SD, and effect size with 95% CI are shown in (A), (B), and (C), respectively.

Figure 3.

Birth weight z-score as a predictor of change in BMI z-score from birth to 12 months. (A) In the overall sample, birth weight z-score was inversely associated with change in BMI z-score over the first year of life, irrespective of study group. Linear regression with 95% confidence interval is shown. (B) A path model diagram depicts the results of a mediation analysis for the effect of in utero COVID-19 exposure on change in BMI z-score over 12 months as mediated by birth weight z-score. Total Effect C represents the effect of exposure status on change in BMI z-score with no mediators in the model. Direct Effect C′ represents the effect of exposure status on change in BMI z-score when birth weight z-score is included as a mediator in the model. Indirect Effect AB represents the effect of exposure status on change in BMI z-score through birth weight z-score. β-Coefficients are shown with asterisks used to denote P < .05. Figure was created with BioRender.com.