Maternal Pre-pregnancy body mass index is associated with fetal growth, neonatal brain connectivity, and toddler adaptive skills

• In Event: Associations Between Prenatal Biological Environmental Factors and Brain Development in Infancy

Abstract

Background: Higher maternal pre-pregnancy body mass index (BMI) is associated with obesity, poorer cognition and social abilities, and increased risk of psychiatric disorders in offspring. However, potential mediators of these outcomes, such as early brain development, are largely unknown. Furthermore, behavioral antecedents of the BMI-related psychiatric outcomes are poorly characterized. The current study investigates the association of maternal pre-pregnancy BMI with fetal growth, functional connectivity of the neonatal brain, and toddler adaptive skills.

Methods: One hundred and five 3rd trimester pregnant women, aged 14 to 19, were enrolled in the 2nd trimester and completed psychosocial and physical assessments, including metabolic, dietary, and nutrient information. Their pre-pregnancy BMI and fetal growth indices via ultrasound were determined from chart review. They received routine prenatal care and had no major health problems. For 45 neonates, resting-state functional MRI were acquired and standard preprocessing was performed. Intrinsic connectivity distribution (ICD) was performed to measure global connectivity on the voxel level. Controlling for infant sex and age at scan, linear regression was used to relate pre-pregnancy BMI to neonatal ICD. Post-hoc seed connectivity was performed to explore which specific connections most likely contributed to the ICD findings. Participants completed the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), Adaptive Skills scale at 14-months.

Results: All neonates were appropriate for gestational age (birthweight: 3206.9±461.3 kg, gestational at birth: 39.3±1.3 weeks) and were scanned at 42.5±1.7 weeks postmenstrual age. The majority of participants were male (61.1%). Maternal pre-pregnancy BMI correlated positively with the slope of estimated fetal weight (beta=0.67, 95% CI:0.16,1.18, p=0.011), but not with fetal head circumference (beta=-0.004, 95% CI:-0.02,0.02, p=0.6973). A positive correlation between pre-pregnancy BMI and global neonatal connectivity in the left thalamus was observed. Maternal pre-pregnancy BMI and global thalamic connectivity inversely correlated with total monounsaturated fat consumption (r=-0.37, p=0.054; r=-0.37, p=0.04, respectively). Using the thalamic region as a seed, higher pre-pregnancy BMI was associated with greater local thalamic connectivity and lower fronto-thalamic connectivity. Maternal pre-pregnancy BMI also correlated positively with BSID- III Self-Direction (r=0.73, p=<0.0001), Communication (r=0.49, p=0.02), and Socialization (r=0.62, p=0.005) scales at 14 months. Estimated fetal growth was associated with a different index of social abilities (Leisure: r=0.48, p=0.01).

Conclusions: Our finding is similar to adult human studies using resting state imaging data and with rodent electrophysiological studies that report an association of BMI with thalamic connectivity, and it is consistent with recent findings suggesting thalamic involvement in food intake, weight control, and reward processing. We observed this association of BMI with thalamic connectivity, but extended it across generations. These results suggest that maternal pre-pregnancy BMI is involved in the development of regulation of body weight and thalamic functional brain connectivity in offspring even during fetal development. This study begins to set the stage for future intervention studies to determine whether improving maternal pre-pregnancy BMI may influence fetal brain development to optimize circuit development in areas key to regulating nutrient intake and satiety signals and subsequently support optimal long-term infant cognitive, social, and behavioral capacities.

Authors

• Marisa N. Spann, Columbia University
  Non-Presenting Author

• Dustin Scheinost, Yale School of Medicine
  Presenting Author

• Catherine Monk, Columbia University Irving Medical Center
  Non-Presenting Author

• Bradley S. Peterson, Children’s Hospital Los Angeles
  Non-Presenting Author