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

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.

PMID: 40184958
PMCID: PMC12085287
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

L E Gyllenhammer et al. Psychoneuroendocrinology. 2025 Jul.

. 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.

PMID: 40184958
PMCID: PMC12085287
DOI: 10.1016/j.psyneuen.2025.107450

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.

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Conflict of interest statement

Declaration of Competing Interest none

Figures

**Figure 1:**
Greater maternal allostatic load (AL) in pregnancy significantly associated with higher offspring (a, b) % total body fat (%FM), and (c, d) % abdominal fat from (%AbFM) birth to early childhood. There was no significant interaction with child age, so the relationship was consistent across birth to early childhood (figures a and c display %fat at each child measure, and figures b and d display the mean across all time points, which represents the final model). Figures b and d display the additional sensitivity analyses, which excluded pregnant moms with obesity from the analyses. After excluding women with pre-pregnancy obesity (n=14), maternal allostatic load remained significantly associated with offspring total and abdominal adiposity (p<0.05). We note that the models were run with AL as a continuous measure, but are presented as mean split of high/low AL for visualization purposes. Data are mean ±SEM. *** p<0.001, **p<0.01, *p<0.05; AL=allostatic load, NW= normal weight, OW= overweight.

**Figure 2:**
Greater maternal allostatic load (AL) in pregnancy significantly associated with higher offspring (a, b) insulin resistance (log₁₀HOMA-IR), and (c, d) fasting insulin in early childhood. There was no relationship between maternal AL and child fasting glucose (e, f). In figures a, c, and e, the dotted grey line indicates the regression line for the sensitivity analyses, which excluded pregnant moms with obesity from the analyses. In figures b, d and f, the sensitivity analyses are represented by additional box plots, outlined in grey. After excluding women with pre-pregnancy obesity (n=14), maternal allostatic load remained significantly associated with childhood HOMA-IR and fasting insulin (p<0.05). We note that models were run with AL as a continuous measure (figures a, c, e), but are additionally presented as mean split of high/low AL for visualization purposes (figures b, d, f). Data are mean ±SEM. *p<0.05; AL=allostatic load, NW= normal weight, OW= overweight, OB= obesity.

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

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

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