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

Rapid changes in the global climate are deepening existing health disparities from resource scarcity and malnutrition. 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 and head circumference. Placental mRNA-sequencing and protein analysis showed transcriptomic changes in protein translation, ribosomal proteins, and mTORC1 signaling 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 in part mitigated in women randomized to comprehensive maternal nutritional supplementation 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.

Case report: Cystic fibrosis with kwashiorkor: A rare presentation in the era of universal newborn screening.

Background: Universal newborn screening changed the way medical providers think about the presentation of cystic fibrosis (CF). Before implementation of universal screening, it was common for children with CF to present with failure to thrive, nutritional deficiencies, and recurrent infections. Now, nearly all cases of CF are diagnosed by newborn screening shortly after birth before significant symptoms develop. Therefore, providers often do not consider this illness in the setting of a normal newborn screen. Newborn screening significantly decreases the risk of complications in early childhood, yet definitive testing should be pursued if a patient with negative newborn screening presents with symptoms consistent with CF, including severe failure to thrive, metabolic alkalosis due to significant salt losses, or recurrent respiratory infections. Case presentation: We present a case of a 6-month-old infant male with kwashiorkor, severe edema, multiple vitamin deficiencies, hematemesis secondary to coagulopathy, and diffuse erythematous rash, all secondary to severe pancreatic insufficiency. His first newborn screen had an immunoreactive trypsinogen (IRT) value below the state cut-off value, so additional testing was not performed, and his growth trajectory appeared reassuring. He was ultimately diagnosed with CF by genetic testing and confirmatory sweat chloride testing, in the setting of his parents being known CF carriers and his severe presentation being clinically consistent with CF. Acutely, management with supplemental albumin, furosemide, potassium, and vitamin K was initiated to correct the presenting hypoalbuminemia, edema, and coagulopathy. Later, pancreatic enzyme supplementation and additional vitamins and minerals were added to manage ongoing deficiencies from pancreatic insufficiency. With appropriate treatment, his vitamin deficiencies and edema resolved, and his growth improved. Conclusion: Due to universal newborn screening, symptomatic presentation of CF is rare and presentation with kwashiorkor is extremely rare in resource-rich communities. The diagnosis of CF was delayed in our patient because of a normal newborn screen and falsely reassuring growth, which after diagnosis was determined to be secondary to severe edematous malnutrition. This case highlights that newborn screening is a useful but imperfect tool. Clinicians should continue to have suspicion for CF in the right clinical context, even in the setting of normal newborn screen results.

Longitudinal Changes of One-Carbon Metabolites and Amino Acid Concentrations during Pregnancy in the Women First Maternal Nutrition Trial.

BACKGROUND: Maternal dietary restriction and supplementation of one-carbon (1C) metabolites can impact offspring growth and DNA methylation. However, longitudinal research of 1C metabolite and amino acid (AA) concentrations over the reproductive cycle of human pregnancy is limited. OBJECTIVE: To investigate longitudinal 1C metabolite and AA concentrations prior to and during pregnancy and the effects of a small-quantity lipid-based nutrition supplement (LNS) containing >20 micronutrients and prepregnancy BMI (ppBMI). METHODS: This study was an ancillary study of the Women First Trial (NCT01883193, clinicaltrials.gov) focused on a subset of Guatemalan women (n = 134), 49% of whom entered pregnancy with a BMI ≥25 kg/m2. Ninety-five women received LNS during pregnancy (+LNS group), while the remainder did not (-LNS group). A subset of women from the Pakistan study site (n = 179) were used as a replication cohort, 124 of whom received LNS. Maternal blood was longitudinally collected on dried blood spot (DBS) cards at preconception, and at 12 and 34 wk gestation. A targeted metabolomics assay was performed on DBS samples at each time point using LC-MS/MS. Longitudinal analyses were performed using linear mixed modeling to investigate the influence of time, LNS, and ppBMI. RESULTS: Concentrations of 23 of 27 metabolites, including betaine, choline, and serine, changed from preconception across gestation after application of a Bonferroni multiple testing correction (P < 0.00185). Sixteen of those metabolites showed similar changes in the replication cohort. Asymmetric and symmetric dimethylarginine were decreased by LNS in the participants from Guatemala. Only tyrosine was statistically associated with ppBMI at both study sites. CONCLUSIONS: Time influenced most 1C metabolite and AA concentrations with a high degree of similarity between the 2 diverse study populations. These patterns were not significantly altered by LNS consumption or ppBMI. Future investigations will focus on 1C metabolite changes associated with infant outcomes, including DNA methylation. This trial was registered at clinicaltrials.gov as NCT01883193.