Placental Functional Genomics and Newborn Neurobehavioral Performance

• In Event: 2-123 - The Placenta and Child Development

Integrative Statement

Introduction: The placenta represents a unique endocrine and metabolic organ, in addition to its roles in nutrient, water, waste, and gas exchange, and through these myriad functions supports the proper development of the fetus, including the development of the fetal brain. These critical functions of the placenta can be affected by environmental signals during pregnancy, and genomic features including gene expression or epigenetic regulation can be used as markers of those perturbations. Imprinted genes are a specific class of genes under exquisite, allele-specific control, which play critical roles in growth and neurobehavioral development and which are particularly important in the placenta.
Hypothesis: Genomic features, specifically imprinted gene expression in the placenta are associated with neurobehavioral health assessed using the NICU Network Neurobehavioral Scales (NNNS).
Study Population: We examined these hypotheses in the Rhode Island Child Health Study, a birth cohort of healthy term infants oversampled for small and large for gestational age birth from Women and Infants Hospital in Providence, RI.
Methods: Placenta parenchyma samples were collected within 2 hours of birth in a standardized fashion, and stored in RNAlater until processed for RNA extraction. Imprinted gene expression was assessed in the placental RNA using a Nanostring nCounter custom gene panel targeting all known and predicted human imprinted genes. Neurobehavioral performance was assessed using the NNNS at least 24 hours after birth but before discharge by a trained psychometrist. The NNNS summary scores were used to develop unique profiles of neurobehavior, and associations between imprinted gene expression and these NNNS profiles were examined using machine-learning methods followed by logistic regression controlled for confounders collected through medical records abstraction and maternal questionnaire
Results: We have identified a specific panel of 10 imprinted genes (DLX5, DHCR24, VTRNA2-1, PHLDA2, NPAP1, FAM50B, GNAS-AS1, PAX8-AS1, SHANK2, and COPG2IT1) whose expression could distinguish between newborn neurobehavioral profiles derived from the NNNS. Infants whose placenta exhibited one profile of coordinated expression of these genes had a 2-fold increase risk movement quality in the lowest decile (OR 2.1, 95% CI 1.2, 3.4) and greater than 6-fold increased risk for demonstrating signs of physiologic stress or abstinence behaviors (OR 6.8, 95% CI 3.1, 15.2). A number of these imprinted genes have also been linked to environmental perturbations and birth weight. These results suggest the integrated nature and central importance of imprinted genes within the placenta and their potentially important role in neurobehavioral development particularly regarding neurological development.

Author

• Carmen J. Marsit, Emory University, Rollins School of Public Health
  Presenting Author