Association of Maternal Prepregnancy Body Mass Index With Fetal Growth and Neonatal Thalamic Brain Connectivity Among Adolescent and Young Women

Abstract

Importance: Higher maternal prepregnancy body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is associated with adverse long-term outcomes for offspring, including obesity, poorer cognitive and social abilities, and increased risk of psychiatric disorders. Less clear is whether higher maternal BMI disrupts fetal growth and brain development.

Objective: To investigate the association of maternal prepregnancy BMI with fetal growth and neonatal functional connectivity.

Design, setting, and participants: This prospective longitudinal cohort study was conducted from 2012 to 2017. Participants included nulliparous pregnant adolescent and young adult women, aged 14 to 19 years who were recruited in the second trimester through Columbia University Irving Medical Center and Weill Cornell Medical College. Women received routine prenatal care and had no major health problems at the time of recruitment. Data were analyzed from January 2018 to March 2020.

Exposures: Maternal prepregnancy BMI.

Main outcomes and measures: The main outcomes were fetal growth, measured as estimated fetal weight, and neonatal functional connectivity, measured using magnetic resonance imaging. Prepregnancy BMI and fetal ultrasonographic measurements were obtained from electronic health record review. Resting-state brain imaging data were acquired in infants within the first month of postnatal life. Functional connectivity was measured using intrinsic functional distribution and seed-based methods.

Results: Among 129 women recruited, 105 had ultrasonographic data from at least 2 points and were included in analyses. The mean (SD) age at delivery was 17.82 (1.31) years. Maternal prepregnancy BMI was positively associated with the slope of estimated fetal weight (β = 0.668; 95% CI, 0.163 to 1.175; P = .01) but not with fetal head circumference (β = -0.004; 95% CI, -0.024 to 0.016; P = .70). In a subsample of 45 infants with magnetic resonance imaging data, maternal prepregnancy BMI was positively correlated with global connectivity in the left thalamus. Using this thalamic region as a seed, higher maternal BMI was associated with greater local thalamic (both hemispheres) and lower frontothalamic connectivity.

Conclusions and relevance: These results suggest that maternal prepregnancy BMI was associated with the development of regulation of body weight and thalamic functional brain connectivity in offspring even during fetal development.

Figure 1.. Associations of Prepregnancy Body Mass Index (BMI) With Growth Curve of Estimated Fetal Weight (EFW) and Fetal Head Circumference (HC)

A and C, Dots indicate individual data points; line, trend. Unadj. indicates unadjusted. B and D, Lines indicate median; boxes, interquartile range; whiskers, the minimum and maximum excluding any outliers; dots, potential outliers.

Figure 2.. Associations of Prepregnancy Body Mass Index (BMI) and Whole Brain Connectivity

Higher maternal prepregnancy BMI using the intrinsic connectivity distribution was associated with stronger connectivity between the left thalamus and the whole brain. The scatterplot visualizes the distribution of the observed data points for mean infant connectivity in the left thalamic region plotted against prepregnancy BMI.

Figure 3.. Thalamic Seed-Based Connectivity

The left thalamic seed demonstrates greater local connectivity with the bilateral thalamus. The thalamic seed also demonstrated reduced connectivity with the right ventrolateral prefrontal cortex (vlPFC) and left dorsolateral prefrontal cortex (dlPFC) regions.

Figure 4.. Mediation Model With Prepregnancy Body Mass Index (BMI), Estimated Fetal Weight, and Neonatal Thalamic Connectivity

^aP < .001.