For many environmental exposures the most sensitive period of risk for later child health is pregnancy and the perinatal period, and these exposures are best ascertained from maternal self-report, biological specimens and objective environmental data collected during pregnancy and immediately after birth. This study will examine this sensitive period, measuring environmental contaminants, nutritional factors and inflammation in some 2,000 mother infant pairs in the context of their social and psychological environment. We have two cohorts totaling nearly 1,000 women enrolled, interviewed and sampled early in pregnancy (most before 14 weeks) with biological specimens archived, and are now expanding the larger of our two cohorts to a statewide probability sample of Michigan hospitals and clinics to enroll 1,000 more pregnancies. We are in contact with more than 84% of our extant cohort members. We will use newborn dried blood spots (NDBS) from the Michigan Neonatal Biobank to further quantify environmental exposures, examine epigenomic changes, and, by accessing both the child's and the mother's newborn spots, study environmental effects across generations. In Flint, MI we will examine the effects of recent water contamination on fetus and child. We will focus on three important exposures in pregnancy. First, we will determine the effects of persistent organic pollutants (POPs) and heavy metals on cognitive outcomes. We hypothesize that the effects of these toxins will be mediated by epigenetic changes measured on NDBS, and will be amplified by grant-maternal exposure (measured on mother's blood spot when she was a newborn). We hypothesize that recent in utero lead exposure in Flint, MI, as assessed in NDBS, and in the shed teeth of exposed children, will also be associated with impaired cognitive outcomes. Second, we will assess the effect of maternal nutritional and weight status in pregnancy on cognitive outcomes and childhood obesity, with a special focus on low pregnancy iodine and/or iron status, agents interfering with thyroid iodine uptake (perchlorate, thiocyanate), abnormal thyroid hormone function and pregnancy-related weight changes. Finally, we will assess the effects of pregnancy viral infection and maternal obesity on perinatal outcomes and behavior related to the autism spectrum. The effects of viral infections and maternal obesity are hypothesized to be mediated by increased placental and neonatal inflammation. The infant gut microbiome will also be assessed, as we anticipate that it may be a pathway linking both nutritional factors and pregnancy inflammation to adverse child health outcomes.

Public Health Relevance

Many important problems in child health and development may result from a mother's diet, her infections, and chemicals in her environment while she was pregnant. We plan to study 2,000 pregnancies in detail by interviewing women in pregnancy and by saving specimens such as blood, urine and placenta. We will then assess the child's health and development in relation to these factors, to learn what changes might be made during a woman's pregnancy that could prevent later problems in child health and development.

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
Exploratory/Developmental Cooperative Agreement Phase II (UH3)
Project #
5UH3OD023285-04
Application #
9772565
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Laessig, Susan Alison
Project Start
2016-09-21
Project End
2023-08-31
Budget Start
2019-09-01
Budget End
2020-08-31
Support Year
4
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Michigan State University
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824
Ruden, Douglas M; Bolnick, Alan; Awonuga, Awoniyi et al. (2018) Effects of Gravity, Microgravity or Microgravity Simulation on Early Mammalian Development. Stem Cells Dev 27:1230-1236
Slawinski, Brooke L; Talge, Nicole; Ingersoll, Brooke et al. (2018) Maternal cytomegalovirus sero-positivity and autism symptoms in children. Am J Reprod Immunol 79:e12840
Paneth, Nigel; Monk, Catherine (2018) The importance of cohort research starting early in life to understanding child health. Curr Opin Pediatr 30:292-296
Jamesdaniel, Samson; Rosati, Rita; Westrick, Judy et al. (2018) Chronic lead exposure induces cochlear oxidative stress and potentiates noise-induced hearing loss. Toxicol Lett 292:175-180
Montrose, Luke; Padmanabhan, Vasantha; Goodrich, Jaclyn M et al. (2018) Maternal levels of endocrine disrupting chemicals in the first trimester of pregnancy are associated with infant cord blood DNA methylation. Epigenetics 13:301-309
Sen, Arko; Gurdziel, Katherine; Liu, Jenney et al. (2017) Smooth, an hnRNP-L Homolog, Might Decrease Mitochondrial Metabolism by Post-Transcriptional Regulation of Isocitrate Dehydrogenase (Idh) and Other Metabolic Genes in the Sub-Acute Phase of Traumatic Brain Injury. Front Genet 8:175
Qu, Wen; Gurdziel, Katherine; Pique-Regi, Roger et al. (2017) Identification of Splicing Quantitative Trait Loci (sQTL) in Drosophila melanogaster with Developmental Lead (Pb2+) Exposure. Front Genet 8:145
Racicot, Karen; VanOeveren, Sarah; Alberts, Art (2017) Viral Hijacking of Formins in Neurodevelopmental Pathologies. Trends Mol Med 23:778-785
Qu, Wen; Cingolani, Pablo; Zeeberg, Barry R et al. (2017) A Bioinformatics-Based Alternative mRNA Splicing Code that May Explain Some Disease Mutations Is Conserved in Animals. Front Genet 8:38
Racicot, Karen; Mor, Gil (2017) Risks associated with viral infections during pregnancy. J Clin Invest 127:1591-1599