Maternal allostatic load in pregnancy is prospectively associated with child adiposity and metabolic function across infancy and early childhood

L E Gyllenhammer; J M Rasmussen; K L Lindsay; W-P Chen; D Gillen; K E Boyle; C Buss; S Entringer; P D Wadhwa

doi:10.1016/j.psyneuen.2025.107450

Maternal allostatic load in pregnancy is prospectively associated with child adiposity and metabolic function across infancy and early childhood

Psychoneuroendocrinology. 2025 Jul:177:107450. doi: 10.1016/j.psyneuen.2025.107450. Epub 2025 Mar 26.

Authors

L E Gyllenhammer¹, J M Rasmussen², K L Lindsay³, W-P Chen⁴, D Gillen⁴, K E Boyle⁵, C Buss⁶, S Entringer⁶, P D Wadhwa⁷

Affiliations

¹ Development, Health and Disease Research Program, University of California, School of Medicine, Irvine, CA, USA; Department of Pediatrics, University of California, School of Medicine, Irvine, CA, USA. Electronic address: lgyllenh@uci.edu.
² Development, Health and Disease Research Program, University of California, School of Medicine, Irvine, CA, USA; Department of Pediatrics, University of California, School of Medicine, Irvine, CA, USA.
³ Department of Pediatrics, University of California, School of Medicine, Irvine, CA, USA; Susan Samueli Integrative Health Institute, University of California Irvine, CA, USA; Department of Population Health and Disease Prevention, UCI Program in Public Health, University of California, Irvine, CA, USA.
⁴ Department of Statistics, University of California, Irvine, Irvine, CA, USA.
⁵ Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Lifecourse Epidemiology of Adiposity and Diabetes Center, Aurora, CO, USA.
⁶ Development, Health and Disease Research Program, University of California, School of Medicine, Irvine, CA, USA; Department of Pediatrics, University of California, School of Medicine, Irvine, CA, USA; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Institute of Medical Psychology, Berlin, Germany.
⁷ Development, Health and Disease Research Program, University of California, School of Medicine, Irvine, CA, USA; Department of Pediatrics, University of California, School of Medicine, Irvine, CA, USA; Department of Psychiatry and Human Behavior, University of California, School of Medicine, Irvine, CA, USA; Department of Obstetrics and Gynecology, University of California, School of Medicine, Irvine, CA, USA; Department of Epidemiology, University of California, School of Medicine, Irvine, CA, USA.

Abstract

Background: Empirical evidence suggests that the origins of obesity and metabolic dysfunction can be traced to stress-related exposures in prenatal life. The aim of the present study was to examine the prospective association of a composite, multi-system measure of maternal biological stress in pregnancy -- allostatic load (AL) -- with offspring adiposity and insulin resistance across infancy and early childhood.

Methods: In N = 55 mother-child dyads, maternal allostatic load was operationalized as a latent variable representing the following components: pre-pregnancy BMI, cortisol, interleukin-6, C-reactive protein, homeostasis model assessment of insulin resistance (HOMA-IR), free fatty acids, and systolic/diastolic blood pressure. Offspring percent total (%FM) and abdominal (%AbFM) fat were quantified with dual-energy X-ray absorptiometry at birth (newborn), 6-mo, and ∼5 yrs age, and HOMA-IR was quantified at ∼5 yrs age. Generalized estimating equation modeling was used to estimate effects of maternal AL on serial (repeated) measures of child adiposity, and linear regression was used to estimate effects on child HOMA-IR. A priori model covariates included maternal race and ethnicity, socioeconomic status, infant feeding practices, child age, and sex.

Results: Maternal AL was positively associated with child %FM and %AbFM before as well as after adjustment for key maternal and offspring covariates (%FM: adjusted β=0.38, p = 0.0074; %AbFM: adjusted β=0.37, p = 0.0013). Maternal AL also was positively associated with child insulin resistance (adjusted β= 0.011, p = 0.0324).

Conclusion: Our findings suggest that exposure to a higher biological stress milieu during prenatal development predisposes towards elevated early life adiposity and insulin resistance in early childhood, a proximate cause of type 2 diabetes and cardiometabolic disease. Collectively, these results provide evidence that a multi-systems approach to quantify early life exposures is useful in prospectively predicting variation in childhood adiposity and metabolic function.

Keywords: Adipose; Allostatic load; Childhood obesity; Fetal programming; Insulin resistance; Stress.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Adiposity* / physiology
Adult
Allostasis* / physiology
Body Mass Index
Child
Child, Preschool
Female
Humans
Hydrocortisone / analysis
Hydrocortisone / metabolism
Infant
Infant, Newborn
Insulin Resistance / physiology
Male
Mothers
Pediatric Obesity / metabolism
Pregnancy
Prenatal Exposure Delayed Effects* / metabolism
Prenatal Exposure Delayed Effects* / physiopathology
Prospective Studies
Stress, Psychological / metabolism
Stress, Psychological / physiopathology

Substances

Hydrocortisone

Abstract

Publication types

MeSH terms

Substances

Grants and funding