Plasticity is a consequence of environmental exposures during critical life periods affecting physiological systems orchestrating underlying developmental processes. The autonomic nervous system (ANS) is a putative key regulatory system vulnerable to perinatal environmental programming toward trajectories of enhanced pediatric and adult disease risk. Epidemiological studies that examine candidate environmental factors that program the ANS starting in utero and explore putative underlying mechanisms are scarce. While environmental influences are diverse, factors gaining attention with respect to fetal programming and autonomic disruption include particulate air pollution and maternal diet (e.g., oxidant/antioxidant balance). While these factors have generally been considered independently, evolving theory underscores the importance of studying their integrated effects. Biological mechanisms responsible for adverse outcomes associated with particulate pollution include ANS imbalance and the induction of oxidative stress is thought to have a central role. Air pollution effects on the mother during pregnancy may disrupt fetal-placental oxidant/antioxidant balance with implications for the developing ANS. Dietary factors may play a modulating role on effects of air pollutants. This investigative team leveraged the Harvard Programming of Intergenerational Stress Mechanisms (PRISM) study, a prenatal urban cohort, to add nutritional measures to study and examine associations among prenatal short-term (7-day mean) and chronic exposure to ambient particulate pollution [PM2.5, black carbon (BC) as a marker of traffic-related particles] and autonomic function in 6-month old infants. ANS phenotyping is indexed through a neuroendocrinologial approach analyzing salivary ?-amylase levels during basal ambulatory conditions and following an in-laboratory stressor. An electrophysiological approach is also employed to analyze ANS reactivity [indexed by respiratory sinus arrhythmia (RSA)] in response to the same in-laboratory stressor. Secondly, associations among long- and short- term prenatal ambient particulate pollution, biomarkers of oxidative stress (F2-isoprostanes) will be examined in maternal prenatal urine and cord blood, and infant autonomic functioning to explore whether associations between prenatal pollution and infant autonomic balance are mediated through enhanced oxidative stress. Finally, ambient particulate pollution will be examined on ANS functioning in 6-month olds to see if the effects are modified by maternal prenatal dietary factors that may protect the infant from oxidative stress [e.g., ?-3 fatt acids and antioxidant micronutrients (e.g., vitamins C and E and flavonoids)] ascertained using a triad approach incorporating a food frequency questionnaire (FFQ), dietary records obtained twice during pregnancy, and select maternal serum/plasma biomarkers ascertained prenatally.

Public Health Relevance

Our findings will provide insight into the possible role of particulate air pollution and prenatal maternal diet in the programming of autonomic balance. Given the generalized integration of autonomic nervous system (ANS) functioning (e.g., involvement in the regulation of cardiovascular functioning as well as modulation of the immune system, inflammation, and metabolism), disruption of autonomic balance in early development may have broad long- term health implications. Identifying specific chemical and nutritional programming agents that are amenable to intervention, and understanding the mechanisms by which they exert their effects during developmentally sensitive periods, may enhance our understanding of the origins of many disorders and suggest more efficacious preventative strategies.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Exploratory/Developmental Grants (R21)
Project #
Application #
Study Section
Special Emphasis Panel (ZES1-LWJ-J (DI))
Program Officer
Gray, Kimberly A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Icahn School of Medicine at Mount Sinai
Schools of Medicine
New York
United States
Zip Code
Brunst, Kelly J; Enlow, Michelle Bosquet; Kannan, Srimathi et al. (2014) Effects of Prenatal Social Stress and Maternal Dietary Fatty Acid Ratio on Infant Temperament: Does Race Matter? Epidemiology (Sunnyvale) 4: