NOURISH: Nutrition and Outcomes of Reproductive Injury and Stillbirth related Harms

Placental dysfunction causes more than half of preventable stillbirths in the United States. Placental dysfunction also causes preeclampsia, fetal growth restriction, and gestational diabetes, which can represent near misses for stillbirth. Stillbirths can be prevented by identifying pregnancies at increased risk and using increased fetal monitoring and sometimes early delivery before stillbirth occurs. Current ways of assessing pregnancy risk misses the majority of people who go on to have a stillbirth. Existing biomarkers of placental health fail to detect most placental dysfunction occurring later in pregnancy. Focus on nutritional health and allostatic load could improve pregnancy risk assessment, as they are both associated with cardiometabolic risk factors for placental dysfunction. Allostatic load is the inflammatory state caused by chronic exposures to stress, such as racism. Assessing allostatic load and maternal nutrition helps address inequities in stillbirth. Dietary intake represents a potentially modifiable risk factor and thus a target for intervention to improve pregnancy health. To reduce the incidence of stillbirth, we must improve 1) our understanding of how allostatic load contributes to placental dysfunction, and 2) the role of nutrition in placental dysfunction. Without this knowledge, we are limited in assessing pregnancy risk and identifying impactful interventions to prevent stillbirth. Our long-term goal is to improve prediction and prevention of stillbirth. We propose rigorous evaluation of the impact of allostatic load and perinatal nutrition on placental dysfunction. The main objective of this project is to identify the effect of allostatic load and dietary patterns on pregnancy outcomes and placental health. The secondary objective is to advance the field of placental biology using novel assessments of placental function in order to improve detection of placental dysfunction during pregnancy. Aim 1: Measure incremental benefit of adding allostatic load biomarkers to classic placental biomarkers in predicting risk of clinical placental dysfunction. Aim 2: Determine the association between perinatal nutrition (ultra-processed food consumption and Healthy Eating Index) and clinical placental dysfunction. Aim 3: Determine association between key biomarkers of placental health and allostatic load and novel measures of placental tissue function and stress. To test these aims, we will enroll 495 pregnant participants prior to 14 weeks' gestation and following them prospectively through pregnancy. We will conduct dietary assessments and serial blood draws to assess allostatic load, cardiometabolic, and placental biomarkers at three time points; two prenatal ultrasound assessments of fetal and placental development; and placental histology, exosome, and trophoblastic functional evaluations to determine the role of allostatic load and nutritional contributors in placental dysfunction. This work has the potential to reduce preventable stillbirth through better risk assessment and improved placental health. Project Number: 1UG1HD119576-01 | Fiscal Year: 2025 | NIH Institute/Center: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Principal Investigator: Karen Gibbins (+1 co-PI) | Institution: OREGON HEALTH & SCIENCE UNIVERSITY, PORTLAND, OR | Award Amount: $1,330,985 | Activity Code: UG1 | Study Section: Special Emphasis Panel[ZHD1 DSR-L (50)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1UG1HD11957601