Maternal nutritional status modifies heat-associated growth restriction in women with chronic malnutrition

Authors: SHANKAR, KARTIK - University Of Colorado; SUMERA, ALI - Aga Khan University; Ruebel, Meghan; JESSANI, SALEEM - Aga Khan University; BORENGASSER, SARAH - University Of Colorado; GILLEY, STEPANIE - University Of Colorado; PUREVSUREN, JAMBAL - University Of Colorado; DEAUNABAH, YAZZA - University Of Colorado; WEAVER, NICHOLAS - University Of Colorado; KEMP, JENNIFER - University Of Colorado; WESTCOTT, JAMIE - University Of Colorado; HENDRICKS, AUDREY - University Of Colorado; SALEEM, SARAH - Aga Khan University; GOLDENBERG, ROBERT - Columbia University; HAMBIDGE,, K MICHAEL - University Of Colorado; KREBS, NANCY - University Of Colorado

Submitted to: Proceedings of the National Academy of Sciences-Nexus
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/20/2022
Publication Date: 1/27/2023
Citation: Shankar, K., Sumera, A., Ruebel, M., Jessani, S., Borengasser, S., Gilley, S., Purevsuren, J., Deaunabah, Y., Weaver, N., Kemp, J., Westcott, J., Hendricks, A., Saleem, S., Goldenberg, R., Hambidge,, K., Krebs, N. 2023. Maternal nutritional status modifies heat-associated growth restriction in women with chronic malnutrition. Proceedings of the National Academy of Sciences-Nexus. 2(1):309. https://doi.org/10.1093/pnasnexus/pgac309.
DOI: https://doi.org/10.1093/pnasnexus/pgac309

Interpretive Summary: There is emerging evidence that rising outdoor temperatures can be harmful to both mother and infant health. We also know that poor dietary intake (decreased intake of macronutrient and micronutrients) of the mother in addition to heat stress can lead to reduced growth of the baby. In this study, researchers found that women exposed to an excessive outdoor temperature during the first trimester of their pregnancy were associated with babies that were shorter in length and head size at birth, and these effects were reduced when women received micronutrient supplementation before and during pregnancy. The mothers exposed to excessive temperatures also showed alterations to placenta gene expression (the organ that provides nutrients and oxygen to the baby during pregnancy) and metabolites. Although more studies are needed, these findings show that improving the diet of the mother through micronutrient supplementation may provide protective effects to the baby against rising outdoor temperatures.

Technical Abstract: Rapid changes in the global climate are deepening existing health disparities from resource scarcity and malnutrition. In particular rising ambient temperatures represent an imminent risk to pregnant women and infants. Both maternal malnutrition and heat stress during pregnancy contribute to poor fetal growth, the leading cause of diminished child development in low-resource settings. However, studies explicitly examining interactions between these two important environmental factors are lacking. We leveraged maternal and neonatal anthropometry data from a randomized controlled trial focused on improving preconception maternal nutrition (Women First Preconception Nutrition trial) conducted in Thatta Pakistan, where both nutritional deficits and heat stress are prevalent. Multiple linear regression of ambient temperature and neonatal anthropometry at birth (n = 459) showed a negative association between daily maximal temperatures in the first trimester and z-scores of birth length (LGAZ) and head circumference (HCGAZ). Placental mRNA-sequencing and protein analysis showed transcriptomic changes in protein translation, ribosomal proteins and mTORC1 signalling components in term placenta exposed to excessive heat in the first trimester. Targeted metabolomic analysis indicated ambient temperature associated alterations in maternal circulation with decreases in choline concentrations. Notably, negative impacts of heat on birth length were mitigated in women randomized to comprehensive maternal nutritional supplementation (MNS) before pregnancy suggesting potential interactions between heat stress and nutritional status of the mother. Collectively the findings bridge critical gaps in our current understanding of how maternal nutrition may provide resilience against adverse effects of heat stress in pregnancy.