Effective primary prevention requires knowledge of modifiable antecedents of disease risk. Obesity, autonomic dysregulation, and HPA axis dysregulation are risk factors for cardiovascular and metabolic (cardiometabolic) disorders. Their prevalence in populations of all ages is increasing, including among young children. Converging evidence traces the origins of cardiometabolic risk back to the intrauterine and early postnatal period of life, supporting the concept of developmental programming of health and disease. Maternal excess weight and excess stress exposure are emerging as important gestational environment factors that affect offspring development and are plausible contributors to later disease. Previous research has been primarily cross-sectional or retrospective and/or has assessed limited systems for prenatal effects. The proposed research expands this research by capitalizing on an existing control trial of a prenatal intervention to reduce maternal stress and excessive weight gain during gestation to examine the effects of intrauterine exposures on subsequent child cardiometabolic risk. We propose to follow 168 offspring of women in the trial from birth until 4 years age, with longitudinal assessments of cardiometabolic risk factors (adiposity, autonomic and HPA axis dysregulation) and their developmental trajectories. We will evaluate the effects of the intervention (Aim 1), as well as the effects of individual-level variation in prenatal stress and weight gain (Aim 2), on newborn and child outcomes that are likely early drivers of cardiovascular disease risk. The span of assessments allows us to separate the effects of prenatal from postnatal influences and examine important developmental trajectories; and assessment of other exposures will reduce confounding and provide clues about pathways and further targets of intervention. Preliminary data from the prenatal intervention suggest it reduces stress and weight gain in mothers and data from our offspring pilot study provide initial support for our hypotheses, showing maternal improvements in stress and weight gain predicted improved indices of offspring adiposity and neurobehavioral regulation.
The SPECIFIC AIMS are to: 1) Test whether offspring born to mothers in the intervention have more favorable cardiometabolic outcomes (lower levels of: adiposity, autonomic dysregulation, and HPA-axis dysregulation) at birth and over the first 4 years of life, relative to offspring in the control group. 2) Examine across the full sample of 168 mother-infant dyads (controlling for treatment group) whether: a) Cardiometabolic risk outcomes, at birth and over the first 4 years of life, are more adverse in offspring from mothers with greater adiposity and/or stress during pregnancy. b) Adverse cardiometabolic outcomes are heightened in offspring from mothers with higher levels of both weight and stress (synergistic effects). Animal models provide support for such associations, but this interactive effect on offspring cardiometabolic risk outcomes has not yet been tested in human studies.

Public Health Relevance

Risk factors for cardiometabolic disease can develop in utero, and children's anthropometric and physiologic development in early life plays an important role in later disease development. This research will 1) test whether a novel prenatal intervention to reduce maternal excessive weight and stress during pregnancy reduces cardiometabolic risk in the offspring and 2) identify prenatal factors that contribute to the development of disease risk i offspring. Findings will inform interventions to reduce disease in mothers and children and may lead to effective prevention efforts.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Psychosocial Risk and Disease Prevention Study Section (PRDP)
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Nicastro, Holly L
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University of California San Francisco
Internal Medicine/Medicine
Schools of Medicine
San Francisco
United States
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