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Prenatal Maternal Docosahexaenoic Acid (DHA) Supplementation and Newborn Anthropometry in India: Findings from DHANI.

ABSTRACT: Long-chain omega-3 fatty acid status during pregnancy may influence newborn anthropometry and duration of gestation. Evidence from high-quality trials from low- and middle-income countries (LMICs) is limited. We conducted a double-blind, randomized, placebo-controlled trial among 957 pregnant women (singleton gestation, 14-20 weeks' gestation at enrollment) in India to test the effectiveness of 400 mg/day algal docosahexaenoic acid (DHA) compared to placebo provided from enrollment through delivery. Among 3379 women who were screened, 1171 were found eligible; 957 were enrolled and were randomized. The intervention was two microencapsulated algal DHA (200 × 2 = 400 mg/day) or two microencapsulated soy and corn oil placebo tablets to be consumed daily from enrollment (≤20 weeks) through delivery. The primary outcome was newborn anthropometry (birth weight, length, head circumference). Secondary outcomes were gestational age and 1 and 5 min Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) score. The groups (DHA; n = 478 and placebo; n = 479) were well balanced at baseline. There were 902 live births. Compliance with the intervention was similar across groups (DHA: 88.5%; placebo: 87.1%). There were no significant differences between DHA and placebo groups for birth weight (2750.6 ± 421.5 vs. 2768.2 ± 436.6 g, p = 0.54), length (47.3 ± 2.0 vs. 47.5 ± 2.0 cm, p = 0.13), or head circumference (33.7 ± 1.4 vs. 33.8 ± 1.4 cm, p = 0.15). The mean gestational age at delivery was similar between groups (DHA: 38.8 ± 1.7 placebo: 38.8 ± 1.7 wk, p = 0.54) as were APGAR scores at 1 and 5 min. Supplementing mothers through pregnancy with 400 mg/day DHA did not impact the offspring's birthweight, length, or head circumference.

SUBMITTER: Khandelwal S

PROVIDER: S-EPMC7996222 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionMaternal-infant equilibrium occurs when cord blood docosahexaenoic acid (DHA) is less than or equal to maternal DHA at delivery. Equilibrium may be an indicator of sufficient DHA for optimal fetal and infant neurodevelopment. The purpose of this study was to test the effect of maternal DHA supplementation on equilibrium status and fetal neurodevelopment.MethodsWomen enrolled between 12 and 20 weeks gestation and were randomized to 200 or 800 mg DHA/day until delivery. Maternal red blood cell (RBC) phospholipids were measured at enrollment, 32 weeks, delivery, and in cord blood at delivery. Fetal neurodevelopment was measured at 32 and 36 weeks gestation. Intent-to-treat analyses were conducted to test differences in equilibrium status by group. Fetal outcomes were assessed by equilibrium status and group.ResultsThree hundred women enrolled and 262 maternal-infant dyads provided blood samples at delivery. No maternal-infant dyads with maternal RBC-DHA ≤ 6.96% at delivery achieved equilibrium. The incidence of equilibrium was significantly higher in the 800 mg group. There was no effect of maternal group or equilibrium status on fetal neurodevelopment.ConclusionThe significance of maternal-infant DHA equilibrium remains unknown. Ongoing research will test the effect of treatment group, equilibrium, and nutrient status on infant behavior and brain function.ImpactPregnant women who received a higher dose of docosahexaenoic acid (DHA) were more likely to achieve maternal-infant DHA equilibrium at delivery. Equilibrium status had no effect on fetal neurodevelopment in this sample. While DHA is crucial for early life neurodevelopment, the significance of achieving maternal-infant equilibrium above the lower threshold is uncertain. There is a lower threshold of maternal DHA status where maternal-infant DHA equilibrium never occurs. The lack of equilibrium associated with low maternal DHA status may indicate insufficient maternal status for optimal placental transfer.

Project description:BackgroundVariability in the FADS2 gene, which codifies the Delta-6 Desaturases and modulates the conversion of essential n-3 and n-6 fatty acids into long-chain polyunsaturated fatty acids, might modify the impact of prenatal supplementation with n-3 docosahexaenoic acid (DHA) on neurodevelopment.ObjectiveTo assess if maternal FADS2 single nucleotide polymorphisms (SNPs) modified the effect of prenatal DHA on offspring development at 5 years.DesignWe conducted a post-hoc interaction analysis of the POSGRAD randomized controlled trial (NCT00646360) of prenatal supplementation with algal-DHA where 1094 pregnant women originally randomized to 400 mg/day of preformed algal DHA or a placebo from gestation week 18-22 through delivery. In this analysis, we included offspring with information on maternal genotype and neurodevelopment at 5 years (DHA = 316; Control = 306) and used generalized linear models to assess interactions between FADS2 SNPs rs174602 or rs174575 and prenatal DHA on neurodevelopment at 5 years measured with McCarthy Scales of Children's Abilities (MSCA).ResultsMaternal and offspring characteristics were similar between groups. At baseline, mean (±standard deviation) maternal age was 26 ± 5 years and schooling was 12 ± 4 years. Forty-six percent (46%) of the children were female. Maternal minor allele frequencies were 0.37 and 0.33 for SNPs rs174602 and rs174575, respectively. There were significant variations by SNP rs174602 and intervention group (p for interactions <0.05) where children in the intervention group had higher MSCA scores on the quantitative (DHA: mean ± SEM = 22.6 ± 0.9 vs. Control = 19.1 ± 0.9, mean difference (Δ) = 3.45; p = 0.01) and memory (DHA = 27.9 ± 1.1 vs. Control = 23.7 ± 1.1, Δ = 4.26; p = 0.02) scales only among offspring of TT (minor allele homozygotes).ConclusionsMaternal FADS2 SNP rs174602 modified the effect of prenatal DHA on cognitive development at 5 years. Variations in the genetic make-up of target populations could be an important factor to consider for prenatal DHA supplementation interventions.

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.

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Prenatal Maternal Docosahexaenoic Acid (DHA) Supplementation and Newborn Anthropometry in India: Findings from DHANI.

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