Dataset Information

Prenatal Docosahexaenoic Acid Supplementation and Offspring Development at 18 Months: Randomized Controlled Trial.

ABSTRACT:

Objective

We evaluated the effects of prenatal docosahexaenoic acid (DHA) supplementation on offspring development at 18 months of age.

Design

Randomized placebo double-blind controlled trial.

Settings

Cuernavaca, Mexico.

Participants and methods

We followed up offspring (n = 730; 75% of the birth cohort) of women in Mexico who participated in a trial of DHA supplementation during the latter half of pregnancy. We assessed the effect of the intervention on child development and the potential modifying effects of gravidity, gender, SES, and quality of the home environment.

Interventions or main exposures

400 mg/day of algal DHA.

Outcome measures

Child development at 18 months of age measured using the Spanish version of the Bayley Scales of Infant Development-II. We calculated standardized psychomotor and mental development indices, and behavior rating scale scores.

Results

Intent-to-treat differences (DHA-control) were: Psychomotor Developmental Index -0.90 (95% CI: -2.35, 0.56), Mental Developmental Index -0.26 (95% CI: -1.63, 1.10) and Behavior Rating Scale -0.01 (95% CI: -0.95, 0.94). Prenatal DHA intake attenuated the positive association between home environment and psychomotor development index observed in the control group (p for interaction = 0.03) suggesting potential benefits for children living in home environments characterized by reduced caregiver interactions and opportunities for early childhood stimulation.

Conclusions

Prenatal DHA supplementation in a population with low intakes of DHA had no effects on offspring development at 18 months of age although there may be some benefit for infants from poor quality home environments.

Trial registration

Clinicaltrials.gov NCT00646360.

SUBMITTER: Ramakrishnan U

PROVIDER: S-EPMC4532364 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Prenatal Docosahexaenoic Acid Supplementation and Offspring Development at 18 Months: Randomized Controlled Trial.

Ramakrishnan Usha U Stinger Amanda A DiGirolamo Ann M AM Martorell Reynaldo R Neufeld Lynnette M LM Rivera Juan A JA Schnaas Lourdes L Stein Aryeh D AD Wang Meng M

PloS one 20150811 8

<h4>Objective</h4>We evaluated the effects of prenatal docosahexaenoic acid (DHA) supplementation on offspring development at 18 months of age.<h4>Design</h4>Randomized placebo double-blind controlled trial.<h4>Settings</h4>Cuernavaca, Mexico.<h4>Participants and methods</h4>We followed up offspring (n = 730; 75% of the birth cohort) of women in Mexico who participated in a trial of DHA supplementation during the latter half of pregnancy. We assessed the effect of the intervention on child devel ...[more]

PMID: 26262896

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Project description:BackgroundThere is limited evidence regarding long-term effects of prenatal docosahexaenoic acid (DHA) supplementation on offspring cardiometabolic health (CMH). Inconsistent results may be attributable to variants of fatty acid desaturase (FADS) genes.ObjectiveWe aimed to evaluate the effect of prenatal DHA supplementation on offspring CMH and investigate effect modification by maternal FADS2 single nucleotide polymorphism (SNP) rs174602.MethodsWe used follow-up data from a double-blind, randomized controlled trial in Mexico in which pregnant females received 400 mg/d of algal DHA or placebo from midgestation until delivery. The study sample included 314 offspring with data at age 11 y and maternal FADS genetic data (DHA: n = 160; Placebo: n = 154). We derived a Metabolic Syndrome (MetS) score from body mass index, HDL, triglycerides, fasting glucose concentrations, and systolic blood pressure. Generalized linear models were used to evaluate the effect of the intervention on offspring MetS score and test interactions between treatment group and genotype, adjusting for maternal, offspring, and household factors.ResultsOffspring MetS score did not differ significantly by treatment group. We observed evidence of effect modification by maternal SNP rs174602 (P = 0.001); offspring of maternal TT genotype who received DHA had lower MetS score relative to the placebo group (DHA (mean ± standard error of the mean (SEM)): -0.21 ± 0.11, n = 21; Placebo: 0.05 ± 0.11, n = 23; Δ= -0.26 (95% CI: -0.55, 0.04), P = 0.09); among CC maternal genotype carriers, offspring of mothers who received DHA had higher MetS score (0.18 ± 0.06, n = 62) relative to the placebo group (-0.05 ± 0.06, n = 65, Δ=0.24 (0.06, 0.41), P < 0.01).ConclusionThe effect of prenatal DHA supplementation on offspring MetS score differed by maternal FADS SNP rs174602. These findings further support incorporating genetic analysis of FADS polymorphisms in DHA supplementation trials.Clinical trial detailsThis trial was registered at clinicaltrials.gov as NCT00646360.

Project description:Abstract Objectives To assess if maternal fatty acid desaturase (FADS) single nucleotide polymorphism (SNP) rs174602 modifies the effect of prenatal DHA supplementation on the offspring metabolome at age 3 months. Methods Data were obtained from POSGRAD, a double-blind randomized controlled trial in Mexico in which 1094 women received 400 mg/day of algal DHA or a placebo (corn and soy oil) from mid-gestation until delivery. Genotyping was performed using maternal blood samples collected from women at baseline. Using liquid chromatography with high-resolution mass spectrometry, untargeted metabolomics was performed on plasma samples obtained from a random subsample of 112 offspring of POSGRAD participants at 3 months of age. Discriminatory metabolic features were selected via linear regression (P < 0.05); false discovery rate (FDR) was controlled for using the Benjamini-Hochberg method (q = 0.2). Analyses were adjusted for infant sex. Effect modification by FADS SNP rs174602 was assessed using two-way analysis of variance. Pathway enrichment analysis was performed with Mummichog (P < 0.05). Subgroup analyses were performed by rs174602, where the study population was grouped into carriers (TT, TC; n = 70) and non-carriers (CC; n = 42) of the minor allele. Results We identified 279 metabolic features that differed significantly between infants whose mothers received prenatal DHA (n = 59) versus placebo (n = 53); however, zero features remained significant after FDR correction. In the DHA * SNP rs174602 interaction analysis, following FDR correction, 346 differentially expressed features were identified. In the subgroup analysis, positively enriched fatty acid metabolism and decreased amino acid and vitamin B3 metabolism pathways were seen among carriers in the DHA group compared to placebo, whereas differentially enriched TCA cycle and omega-6 fatty acid metabolism pathways were observed by treatment group among non-carriers. Conclusions Maternal SNP rs174602 modified the effect of prenatal DHA supplementation on the infant metabolome at 3 months of age, particularly with regards to fatty acid metabolism. These findings provide additional support for the suggestion that differences in FADS genotype may explain inconsistent results observed across DHA supplementation trials. Funding Sources NIH, Nutricia Foundation, Laney Graduate School, and Conacyt, Mexico.

Project description:BackgroundDietary methyl donors (e.g., choline) support the activity of the phosphatidylethanolamine N-methyltransferase (PEMT) pathway, which generates phosphatidylcholine (PC) molecules enriched in DHA that are exported from the liver and made available to extrahepatic tissues.ObjectivesThis study investigated the effect of prenatal choline supplementation on biomarkers of DHA status among pregnant participants consuming supplemental DHA.MethodsPregnant participants (n = 30) were randomly assigned to receive supplemental choline intakes of 550 mg/d [500 mg/d d0-choline + 50 mg/d deuterium-labeled choline (d9-choline); intervention] or 25 mg/d (25 mg/d d9-choline; control) from gestational week (GW) 12-16 until delivery. All participants received a daily 200-mg DHA supplement and consumed self-selected diets. Fasting blood samples were obtained at baseline, GW 20-24, and GW 28-32; maternal/cord blood was obtained at delivery. Mixed-effects linear models were used to assess the impact of prenatal choline supplementation on maternal and newborn DHA status.ResultsCholine supplementation (550 vs. 25 mg/d) did not achieve a statistically significant intervention × time interaction for RBC PC-DHA (P = 0.11); a significant interaction was observed for plasma PC-DHA and RBC total DHA, with choline supplementation yielding higher levels (+32-38% and +8-11%, respectively) at GW 28-32 (P < 0.05) and delivery (P < 0.005). A main effect of choline supplementation on plasma total DHA was also observed (P = 0.018); its interaction with time was not significant (P = 0.068). Compared with controls, the intervention group exhibited higher (P = 0.007; main effect) plasma enrichment of d3-PC (d3-PC/total PC). Moreover, the ratio of d3-PC to d9-PC was higher (+50-67%; P < 0.001) in the choline intervention arm (vs. control) at GW 20-24, GW 28-32, and delivery.ConclusionsPrenatal choline supplementation improves hepatic DHA export and biomarkers of DHA status by bolstering methyl group supply for PEMT activity among pregnant participants consuming supplemental DHA. This trial is registered at www.clinicaltrials.gov as NCT03194659.

Dataset Information

Prenatal Docosahexaenoic Acid Supplementation and Offspring Development at 18 Months: Randomized Controlled Trial.

Objective

Design

Settings

Participants and methods

Interventions or main exposures

Outcome measures

Results

Conclusions

Trial registration

Publications

Prenatal Docosahexaenoic Acid Supplementation and Offspring Development at 18 Months: Randomized Controlled Trial.

Similar Datasets

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