Understanding risk in complex environments underscores potential fallacy of generalizing across populations: Added value of longitudinal measurement and integrated analytical methods

• In Event: Effects of Environmental Exposures on Birth and Early developmental Outcomes

Abstract

Introduction: Preterm birth has been linked to neurodevelopmental delay in multiple studies, suggesting reducing the risk for preterm birth could improve neurodevelopmental outcomes. Populations with multiple socioeconomic disparities, environmental exposures, and infrastructure gaps, however, highlights the importance of more holistic assessments. Work in Indigenous communities exposed to mine waste containing as many as 20 metals in various combinations has allowed us to test existing theories and develop a broader picture of risks. Comprehensive neurodevelopmental exposures have identified verbal delays in up to 40% of participants at 4 years of age, without either cognitive or spatial delay. Recent work in our group has shown that clusters of metal mixture exposures created up to a 3-fold increase in the likelihood of preterm birth. To the extent that preterm birth alone leads to developmental delay, would these early exposures leading to an increased likelihood of preterm birth also increase the likelihood of observed verbal delays in early childhood?

Study Population: Participants (N = 104) were children from a larger cohort (n=1000) who had reached 4 years of age, completed an early childhood clinical neurodevelopmental assessment, and whose mothers had complete metals biomonitoring data during pregnancy.

Methods: Participating mothers completed a variety of surveys during the prenatal period and provided blood and urine specimens at enrollment and delivery. Twenty-five metals were measured in blood and urine to determine metal mixture exposures. Newborn gestational age at delivery was obtained from medical records. A battery of neurodevelopmental assessments and clinical consensus diagnoses were done at age 4, +/- 6 mos by a clinical team and Navajo bilingual field staff. Scores on the Differential Ability Scale (DAS) were examined to assess the relationships of metal-mixture exposure and preterm birth to verbal development. Clusters derived from supervised clustering of 25 metals using the PReMiuM Package (R) with preterm birth as an outcome were evaluated against DAS verbal performance using regression analysis. Direct evaluation of preterm birth as a predictor of verbal delay was also examined.

Results: No relationship between verbal performance and either exposure clusters or preterm birth was found. In addition, supervised clustering of verbal performance using PReMiuM showed no alternate patterns of metal mixtures directly linked to verbal delays. Ongoing work is examining contribution of a variety of SES factors, as well as micronutrients on verbal development both alone and in combination with the ongoing metal exposures.
Conclusions: Although preterm birth itself has been found to predict neurodevelopmental delays in multiple studies, the verbal delays identified in our cohort did not show a predictive relationship with either preterm birth directly, or with exposure variables associated with preterm birth. Ongoing work is investigating the integrated influences of socioeconomic stressors and nutritional status, with exposure and appropriate methods to unravel the complex contributions from these multiple risk factors on verbal development. The relationships between exposures and preterm birth were strong in this cohort, underscoring the importance of longitudinal assessments and integrated analyses of the full range of factors influencing development to identify avenues for greatest impact to improve these outcomes.

Authors

• Johnnye Lewis
  Presenting Author

• Li Luo, University of New Mexico

• Debra MacKenzie