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Reproductive

The impact of prenatal nutrition interventions including balanced energy protein supplementation on maternal metabolomic profiles in rural Amhara, Ethiopia Unmesha Roy Paladhi* Unmesha Roy Paladhi Nebiyou Fasil Sophie Driker Firehiwot Workneh Kalkidan Yibeltal Alemayehu Worku Yemane Berhane Anne CC Lee

Background
Prenatal nutritional supplementation with balanced energy protein and micronutrients may prevent adverse birth outcomes yet the impacts of such interventions on the maternal metabolome during pregnancy is understudied.

Methods
In a cluster randomized clinical effectiveness trial in Amhara, Ethiopia, we randomized 12 health centers to provide an Enhanced Nutrition Package (ENP: iodized salt, iron folic acid, and for women with mid-upper arm circumference <23cm, a micronutrient fortified balanced-energy protein [BEP]) or routine nutrition care (iron folic acid only). We enrolled pregnant women at <24 weeks gestation and collected maternal whole blood at enrollment and a 3rd-trimester follow-up visit via volumetric absorptive microsampling. We conducted untargeted metabolomics analysis via rapid liquid chromatography-mass spectroscopy. Using logistic regression models, we identified the maternal metabolites that differed between women on ENP vs. non-ENP in trimester 3, post-intervention. Non-singleton births were excluded from these analyses.

Results
From 284 pregnant women, we collected 448 samples (63 in trimester 1, 212 in trimester 2, 173 in trimester 3) and conducted complete case analysis on the post-intervention trimester 3 samples. From the total 38,668 metabolites found in the women, 504 were identified and matched to known metabolites in trimester 3 of which 1 – n-acetylglutamine – was significantly negatively associated with the nutrition package group (FDR<0.1) compared to routine care. Among the subset of women taking BEP, 19 metabolites were identified; they were more likely to have higher levels of acetylaspartic acid and lower levels of 22:6 cholesterol ester compared to those not taking BEP.

Conclusions
Women receiving the nutrition intervention package had lower levels of n-acetylglutamine, which has a role in removing ammonia from the body. Women consuming BEP had higher acetylaspartic acid, which is linked to fetal neuronal development.

Funding Sources: Bill & Melinda Gates Foundation