Association between placental metal exposure and NICU Network Neurobehavioral Scales (NNNS) profiles in the Rhode Island Child Health Study (RICHS)

Abstract

BACKGROUND AND AIM: Exposure to even low levels of toxic metals has been linked to cognitive and behavioral deficits in children. Our prior work has demonstrated the placenta’s role in programming newborn health, and that placenta function can be affected by metals exposures. In this study, we hypothesized that placental trace metals can lead to poor neurobehavioral performance and so assessed the associations between placental toxic trace metals, cadmium, manganese, and lead, and neurobehavioral performance indicated through the NNNS in newborns. METHODS: A hospital-based birth cohort, RICHS enrolled infants 37 weeks gestation and oversampled for infants born either small or large for gestational age (n= 840). Placental tissue was collected within 2 hours of birth, and 24 metals’, metalloids’, and nutrient elements’ concentrations were determined using inductively couple plasma mass spectrometry. NNNS assessment was carried out by certified psychometrists from 24-72 hours after birth (n=625). Latent profile analysis (LPA) was used to define neurobehavior profiles based on 12 NNNS summary scales. Multinomial regression was used to examine the association between placental metals concentrations and neurobehavioral profile membership controlled for confounders (infant sex, maternal age, race, BMI, education status and tobacco smoking during pregnancy). RESULTS:The optimal LPA fit was a 5-profile model. The 12 NNNS summary scores were significantly different across the five profiles. Adjusted models showed that a doubling of placental cadmium concentration was associated with a 2.4 fold increased odds of newborns belonging to the atypical neurobehavioral profile compared to the typical performing profile (95%CI: [1.4, 3.4]). Participants with detectable placental lead levels also had increased odds of belonging to the atypical profile (OR: 3.4, 95%CI: [2.1, 4.8]). CONCLUSIONS:Placental toxic heavy metals including cadmium and lead were associated with atypical neurobehavioral performance at birth and provided additional evidence of the importance of the placenta in newborn health. KEYWORDS: heavy metals, children's environmental health, neurodevelopmental outcomes, environmental epidemiology