The Joint Effects of Prenatal Pesticide Exposure and Psychosocial Factors on Epigenetic Age Trajectories and Child Psychopathology in a South African Birth Cohort

Pregnancy is a critical period for neurodevelopment, with the developing fetus particularly
vulnerable to environmental toxicants and maternal psychosocial stressors. Prenatal
pesticide exposure, an established neurotoxicant, has been linked to an increased risk of
child psychopathology, including anxiety, mood disorders, and Attention-deficit/
hyperactivity disorder. Preliminary studies indicate that the harmful effects of
environmental toxins are exacerbated by psychosocial stressors, which lower the
developing brain's threshold for neurotoxicity. This issue is particularly pronounced in low-resource settings, defined as areas with limited access to health services or infrastructure,
and experience high burden of co-occurring exposures. However, little is known about
how psychosocial stressors may exacerbate the harmful effects of pesticide exposures on
child psychopathology. Epigenetic age acceleration, a biomarker of biological aging, is
proposed as a mechanism underlying the impact of combined environmental and
psychosocial exposures on behavioral outcomes. This study aims to investigate the joint
effects of prenatal pesticide exposure and psychosocial factors on trajectories of
epigenetic age acceleration and subsequent child psychopathology. Utilizing advanced
environmental mixture methods, the study will leverage longitudinal data from the
Drakenstein Child Health Study (DCHS), a birth cohort from a low-resource setting. Aim
1: Investigate the joint effects of prenatal urinary pesticide metabolite levels and
psychosocial factors on child psychopathology at 6.5 years of age. We hypothesize that
these joint effects will be associated with increased child psychopathology and that their
magnitude will exceed the individual effects of pesticides or psychosocial factors. Aim 2:
Assess the joint effects of prenatal urinary pesticide metabolite levels and psychosocial
factors on longitudinal changes in epigenetic age acceleration at 1, 3, and 5 years of age.
We hypothesize that these joint exposures will affect the trajectories of epigenetic age
acceleration. Aim 3: Determine the relationship between epigenetic age acceleration
trajectories and child psychopathology at 6.5 years of age and explore whether epigenetic
age acceleration mediates the association between prenatal exposures and child
psychopathology. We hypothesize that changes in epigenetic age acceleration will be
associated with increased psychopathology and that epigenetic age acceleration will
mediate the effects of joint exposures on child psychopathology. This research will
enhance our understanding of how environmental toxicants and psychosocial stressors
interact during a sensitive developmental period, particularly in communities that
experience high burden of exposure. The findings could inform early detection and
prevention strategies to improve child brain health outcomes.

Grant Number: 1F31ES037540-01
NIH Institute/Center: NIH
Principal Investigator: Sarina Abrishamcar