Perinatal health effects of herbicides exposures in the United States: the Heartland Study, a Midwestern birth cohort study

Document Type

Journal Article

Publication Date



BMC public health








Birth cohort; Glyphosate; Herbicides; Reproductive impacts


BACKGROUND: The objective of the Heartland Study is to address major knowledge gaps concerning the health effects of herbicides on maternal and infant health. To achieve this goal, a two-phased, prospective longitudinal cohort study is being conducted. Phase 1 is designed to evaluate associations between biomarkers of herbicide concentration and pregnancy/childbirth outcomes. Phase 2 is designed to evaluate potential associations between herbicide biomarkers and early childhood neurological development. METHODS: People (target enrollment of 2,000) who are seeking prenatal care, are ages 18 or older, and are ≤ 20 + 6 weeks gestation will be eligible for recruitment. The Heartland Study will utilize a combination of questionnaire data and biospecimen collections to meet the study objectives. One prenatal urine and buccal sample will be collected per trimester to assess the impact of herbicide concentration levels on pregnancy outcomes. Infant buccal specimens will be collected post-delivery. All questionnaires will be collected by trained study staff and clinic staff will remain blinded to all individual level research data. All data will be stored in a secure REDCap database. Hospitals in the agriculturally intensive states in the Midwestern region will be recruited as study sites. Currently participating clinical sites include Indiana University School of Medicine- affiliated Hospitals in Indianapolis, Indiana; Franciscan Health Center in Indianapolis, Indiana; Gundersen Lutheran Medical Center in La Crosse, Wisconsin, and University of Iowa in Iowa City, Iowa. An anticipated 30% of the total enrollment will be recruited from rural areas to evaluate herbicide concentrations among those pregnant people residing in the rural Midwest. Perinatal outcomes (e.g. birth outcomes, preterm birth, preeclampsia, etc.) will be extracted by trained study teams and analyzed for their relationship to herbicide concentration levels using appropriate multivariable models. DISCUSSION: Though decades of study have shown that environmental chemicals may have important impacts on the health of parents and infants, there is a paucity of prospective longitudinal data on reproductive impacts of herbicides. The recent, rapid increases in herbicide use across agricultural regions of the United States necessitate further research into the human health effects of these chemicals, particularly in pregnant people. The Heartland Study provides an invaluable opportunity to evaluate health impacts of herbicides during pregnancy and beyond. TRIAL REGISTRATION: The study is registered at, NCT05492708 with initial registration and release 05 August, 2022.