The Effect of a Preconception Nutrition Supplement on One Carbon Metabolites (P24-028-19)

Abstract Objectives Studies in both animals and humans have shown that maternal dietary restriction and supplementation of one carbon (1C) metabolites (methyl donors), such as methionine and choline, can impact offspring growth, insulin resistance, and DNA methylation. However, there has been limited longitudinal research of 1C metabolite concentrations over the reproduction cycle of human pregnancy. The purpose of this study was to investigate if 1C metabolite concentrations change prior to and during pregnancy and if a preconception lipid-based nutrition supplement (LNS) influences such changes. Methods This study was a secondary analysis as part of the Women First study (clinicaltrials.gov, NCT01883193), a large, randomized controlled trial investigating whether the timing of maternal LNS initiation would impact fetal growth and development. The study arms were supplementation at least 3 months prior to conception (Arm 1), supplementation at ∼12 weeks of gestation (Arm 2), or no supplementation (Arm 3). Dried blood spot (DBS) cards were collected at study enrollment prior to conception, and at 12 and 34 weeks gestation. A targeted 1C metabolite assay (27 metabolites) was performed on a subset of DBS samples from Guatemalan women (n = 134) at each time point using liquid chromatography/tandem mass spectrometry. Longitudinal analyses were performed using linear mixed modeling to investigate the influence of time and LNS on these metabolites. Results The concentrations of two metabolites were changed by intervention status: asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA). Twenty-one of 27 metabolites significantly changed from preconception and across gestation after correcting for multiple testing using the Bonferroni correction (P < 0.00185). Conclusions Preconception LNS significantly decreased the level of ADMA, a metabolite which has been implicated in intrauterine growth restriction and preeclampsia. More work is needed to determine whether this intervention could influence development of these conditions. Funding Sources Bill & Melinda Gates Foundation, National Institutes of Health.

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Maternal Characteristics Affect Fetal Growth Response to Maternal Supplements in the Women First Preconception Trial (WF) (P10-017-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz034.p10-017-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Michael Hambidge ◽

Carla Bann ◽

Elizabeth McClure ◽

Jamie Westcott ◽

Ana Garces ◽

...

Keyword(s):

Fetal Growth ◽

Maternal Nutrition ◽

Secondary Analysis ◽

Effect Modifier ◽

Mixed Effect ◽

Maternal Characteristics ◽

Funding Sources ◽

Effect Regression ◽

Female Effect ◽

Gates Foundation

Abstract Objectives Determine if maternal characteristics modified newborn anthropometric outcomes in the WF trial (ClinicalTrials.gov NCT01883193). Methods Secondary analysis included combined data for all 1465 maternal infant dyads in WF sites in Guatemala, India, and Pakistan who had 1st trimester ultrasounds and newborn anthropometry with the three WF arms maintained: Arm 1 commenced a comprehensive nutrition supplement ≥3 months prior to conception; Arm 2 commenced the same supplement in the 1st trimester, and Arm 3 received no trial supplements. Maternal characteristics included were: baseline, BMI, hemoglobin, age, education, SES, and parity plus newborn sex. Newborn outcomes were Z-scores for length (LAZ), weight (WAZ), and weight-to-length ratio (WLRZ). Mixed effect regression models were fit for each outcome, including treatment arm, effect modifier, and treatment arm x effect modifier interaction as predictors and controlling for study site, maternal characteristics, and newborn sex. Results Parity, anemia and newborn sex were significant effect modifiers favoring para 0 vs para ≥1, anemia vs non anemia, and newborn male vs female. Effect of Arm 1 vs 3 was significantly larger for para 0 vs ≥1 women on length and weight (Table). Arm 2 vs 3 was not associated with improvements for para 0 in weight (P = 0.273) or WLRZ (P = 0.710). Arms 1 and 2 (vs 3) were associated with significantly higher length, weight, and WLRZ for anemic women. For parity and anemia, effect sizes for Arm 1 were greater than for Arm 2 for WAZ and WLZ (P < 0.05), but not LAZ. Arm 1 and 2 were associated with significantly higher weight and WLRZ for male vs female newborn. Conclusions In diverse low resource populations, impaired fetal growth (weight and length) is substantially improved in nulliparous and in anemic women but minimally or not at all in parous and in non-anemic women. Correction of weight decrements is most pronounced with improvement in maternal nutrition commencing prior to conception. Funding Sources Bill & Melinda Gates Foundation; NIH, NICHD and ODS. Supporting Tables, Images and/or Graphs

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Differential DNA Methylation of Human Metastable Epialleles in Guatemalan Infants at Birth Due to Timing of a Maternal Lipid-Based Nutrition Supplement and Pre-Pregnancy BMI (P11-139-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz048.p11-139-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Sarah Borengasser ◽

Audrey Hendricks ◽

Purevsuren Jambal ◽

Stephanie Gilley ◽

Alexandra Palacios ◽

...

Keyword(s):

Dna Methylation ◽

National Institutes Of Health ◽

Base Pairs ◽

Significance Level ◽

Maternal Nutritional Status ◽

Funding Sources ◽

Nutrition Supplement ◽

Gates Foundation ◽

Independent Effects

Abstract Objectives Human metastable epialleles (MEs) are specific regions that are systemically methylated (lack tissue specificity), stable over time, and variably expressed between individuals. DNA methylation (DNAme) of MEs have been previously reported to be altered by maternal nutritional status at the time of conception. Here, we examined DNAme of MEs from a subset of Guatemalan mother/infant dyads as part of the Women First study, an international RCT that tested whether timing of a daily lipid-based nutrition supplement (LNS) improved birth length. The 3 study arms are: women consumed LNS ≥ 3 months prior to conception until delivery (Arm 1, N = 45); women consumed the same LNS commencing at 12 weeks gestation until delivery (Arm 2, N = 45); or no LNS (Arm 3, N = 44). The purpose of this study was to test if the timing of maternal LNS and pre-pregnancy BMI (ppBMI, BMI range = 20.1 – 38.4 kg/m2) led to differential DNAme of MEs in infants at birth. Methods Bisulfite-converted DNAme libraries were constructed using NimbleGen SeqCap Epi CpGiant probes from amnion tissue collected at birth. Individuals were sequenced via 2 × 150 paired end reads using the Illumina NovaSeq sequencer. Subjects that passed quality control (131/142 subjects) were used in subsequent statistical analyses. A linear model was used to test for the interaction between maternal LNS and ppBMI on infant DNAme for each base pair site within 296 previously identified candidate ME regions. The number of methylated base pairs per region ranged from 1 – 737. A significance level adjusting for the 296 regions was set at P ≤ 0.000169. Results We identified 6 ME regions with significant interactions, demonstrating differential ME DNAme due to intervention arm was dependent on ppBMI values. Our analyses also identified 3 CpGs associated with ppBMI regardless of LNS status and 1 CpG associated with LNS regardless of ppBMI suggesting a role for independent effects of maternal LNS and ppBMI on ME DNAme. Conclusions Our findings indicate that timing of maternal LNS and ppBMI contribute to DNAme of candidate MEs in infants at birth, suggesting epigenetic influences due to in utero exposures. Future analyses will identify genes associated with changes in ME DNAme and the role of DNAme on infant growth. Funding Sources Bill & Melinda Gates Foundation and National Institutes of Health.

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Mapping the Metabolic Profiles of Long-Term Vegetable, Fruit, and Fruit Juice Consumption

Current Developments in Nutrition ◽

10.1093/cdn/nzaa052_056 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 787-787

Author(s):

Fenglei Wang ◽

Yi Wan ◽

Oana Zeleznik ◽

Megu Baden ◽

You Wu ◽

...

Keyword(s):

Multiple Testing ◽

Fruit Juice ◽

Health Study ◽

P Value ◽

Metabolic Profiles ◽

Funding Sources ◽

Liquid Chromatography Tandem Mass ◽

Study Population ◽

Metabolic Signatures

Abstract Objectives The aim of this study was to explore the metabolic profiles, including both named metabolites and unknown peaks detected in the metabolomics measurement, that are related to long-term vegetable, fruit, and fruit juice consumption. Methods The study population for exploration included 5270 participants and for replication included 4216 participants in the Nurses’ Health Study (NHS), NHSII, and Health Professionals Follow-Up Study. Plasma metabolic profiling was conducted by liquid chromatography-tandem mass spectrometry. Long-term vegetable, fruit, and fruit juice consumption was estimated from food-frequency questionnaires. We included 332 named metabolites and 2561 unknown peaks in the exploration analysis. Partial Spearman correlation analyses were used to assess the associations of vegetable, fruit, and fruit juice consumption with individual metabolites. We further identified metabolic signatures using machine learning models. Results We observed a panel of named metabolites and unknown peaks that were significantly associated with long-term vegetable, fruit, and fruit juice consumption (P value < 0.05 after adjusting for multiple testing). Several unknown peaks exhibited a comparable correlation (partial Spearman rho > 0.4) with fruit juice, especially orange juice consumption, relative to the named metabolites. Metabolic signatures, comprised of 78, 104, and 41 named metabolites, were robustly correlated with total vegetable, total fruit, and total fruit juice consumption, respectively (Pearson r = 0.27–0.37 between the signature and dietary consumption in exploration samples, and 0.24–0.27 in replication samples). Adding unknown peaks into the metabolic signature strengthened the Pearson r by 17.7% for total vegetable, 9.5% for total fruit, and 5.3% for total fruit juice consumption. Conclusions Using plasma metabolomics platform, we identified metabolic profiles, including named metabolites and unknown peaks, that reflect long-term vegetable, fruit, and fruit juice consumption, respectively. Funding Sources None.

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Effects of Different Strategies for Delivering Supplemental Zinc on Selected Fecal Markers of Environmental Enteric Dysfunction Among Young Laotian Children (P04-012-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz051.p04-012-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Cited By ~ 1

Author(s):

Guy-Marino Hinnouho ◽

K Ryan Wessells ◽

Maxwell Barffour ◽

Somphou Sayasone ◽

Charles Arnold ◽

...

Keyword(s):

Controlled Trial ◽

Geometric Mean ◽

Physical Growth ◽

Linear Regression Models ◽

Double Blind ◽

Funding Sources ◽

Supplemental Zinc ◽

Zinc Supplements ◽

Gates Foundation ◽

The Impact

Abstract Objectives To assess the impact of different strategies for delivering supplemental zinc on fecal myeloperoxidase (MPO), neopterin (NEO) and calprotectin (CAL) among young Laotian children and explore modifying effects of MPO, CAL and NEO on growth Methods In a double-blind controlled trial, children 6–23 mo of age were randomized to receive either daily preventive zinc tablets (PZ; 7 mg/d), daily micronutrient powder sachets (MNP; containing 10 mg zinc and 14 other micronutrients), therapeutic zinc supplements for diarrhea treatment (TZ; 20 mg/d for 10 days) or daily placebo powder and followed for ∼36 weeks. Stool samples were collected at baseline and endline. Fecal MPO, NEO and CAL were determined in a randomly selected sub-sample of 720 children using commercially available ELISA kits. Linear regression models were used to assess main and modifying effects while controlling for baseline value, age and district Results The baseline prevalence of stunting was 39.3%, and there was no overall treatment effect on physical growth in the parent trial. At endline, geometric mean fecal MPO, NEO and CAL concentrations did not differ among the 4 groups (all P > 0.23). There was an effect modification by baseline concentrations of NEO and CAL on endline stunting (p for interaction = 0.01 and 0.02, respectively). Among children in the lowest quintile of NEO concentrations, there was a trend towards a higher stunting prevalence at endline in the TZ [47.1% (35.6, 58.7)] and the MNP [45.3% (32.7, 57.9)] groups compared to the PZ [33.6% (21.0, 46.3)] and the control [33.9% (22.8, 44.9)] groups. Similar results were found among children in the lowest quintile of CAL concentrations. Moreover, baseline concentration of CAL, modified the impact of the interventions on weight-for-height z-scores (WHZ) (p for interaction = 0.074). Among children in the lowest quintile of CAL concentrations, there was a trend towards a higher WHZ at endline in the MNP [−0.57 (−0.73, −0.42)] and TZ [−0.68 (−0.86, −0.51)] groups compared to the control [−0.79 (−0.97, −0.61)] and the PZ [−0.88 (−1.05, −0.72)] groups. Conclusions In this population of young Laotian children PZ, MNP and TZ had no overall impact on EED or growth, but intestinal function modified the growth response to supplementation suggesting its potential role in the pathways of growth impairment. Funding Sources Funded by the Bill & Melinda Gates Foundation, Nutrition International and the Mathile Institute for the Advancement of Human Nutrition.

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