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Effect of Maternal Docosahexaenoic Acid (DHA) Supplementation on Offspring Neurodevelopment at 12 Months in India: A Randomized Controlled Trial.

ABSTRACT: Intake of dietary docosahexaenoic acid (DHA 22:6n-3) is very low among Indian pregnant women. Maternal supplementation during pregnancy and lactation may benefit offspring neurodevelopment. We conducted a double-blind, randomized, placebo-controlled trial to test the effectiveness of supplementing pregnant Indian women (singleton gestation) from ?20 weeks through 6 months postpartum with 400 mg/d algal DHA compared to placebo on neurodevelopment of their offspring at 12 months. Of 3379 women screened, 1131 were found eligible; 957 were randomized. The primary outcome was infant neurodevelopment at 12 months, assessed using the Development Assessment Scale for Indian Infants (DASII). Both groups were well balanced on sociodemographic variables at baseline. More than 72% of women took >90% of their assigned treatment. Twenty-five serious adverse events (SAEs), none related to the intervention, (DHA group = 16; placebo = 9) were noted. Of 902 live births, 878 were followed up to 12 months; the DASII was administered to 863 infants. At 12 months, the mean development quotient (DQ) scores in the DHA and placebo groups were not statistically significant (96.6 ± 12.2 vs. 97.1 ± 13.0, p = 0.60). Supplementing mothers through pregnancy and lactation with 400 mg/d DHA did not impact offspring neurodevelopment at 12 months of age in this setting.

SUBMITTER: Khandelwal S

PROVIDER: S-EPMC7600740 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Effect of Maternal Docosahexaenoic Acid (DHA) Supplementation on Offspring Neurodevelopment at 12 Months in India: A Randomized Controlled Trial.

Khandelwal Shweta S Kondal Dimple D Chaudhry Monica M Patil Kamal K Swamy Mallaiah Kenchaveeraiah MK Metgud Deepa D Jogalekar Sandesh S Kamate Mahesh M Divan Gauri G Gupta Ruby R Prabhakaran Dorairaj D Tandon Nikhil N Ramakrishnan Usha U Stein Aryeh D AD

Nutrients 20201003 10

Intake of dietary docosahexaenoic acid (DHA 22:6n-3) is very low among Indian pregnant women. Maternal supplementation during pregnancy and lactation may benefit offspring neurodevelopment. We conducted a double-blind, randomized, placebo-controlled trial to test the effectiveness of supplementing pregnant Indian women (singleton gestation) from ≤20 weeks through 6 months postpartum with 400 mg/d algal DHA compared to placebo on neurodevelopment of their offspring at 12 months. Of 3379 women scr ...[more]

PMID: 33023067

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Project description:BACKGROUND:Evidence suggests a strong association between nutrition during the first 1000 days (conception to 2 years of life) and cognitive development. Maternal docosahexaenoic acid (DHA) supplementation has been suggested to be linked with cognitive development of their offspring. DHA is a structural component of human brain and retina, and can be derived from marine algae, fatty fish and marine oils. Since Indian diets are largely devoid of such products, plasma DHA levels are low. We are testing the effect of pre- and post-natal DHA maternal supplementation in India on infant motor and mental development, anthropometry and morbidity patterns. METHODS:DHANI is a double-blinded, parallel group, randomized, placebo controlled trial supplementing 957 pregnant women aged 18-35 years from ?20 weeks gestation through 6 months postpartum with 400 mg/d algal-derived DHA or placebo. Data on the participant's socio-demographic profile, anthropometric measurements and dietary intake are being recorded at baseline. The mother-infant dyads are followed through age 12 months. The primary outcome variable is infant motor and mental development quotient at 12 months of age evaluated by Development Assessment Scale in Indian Infants (DASII). Secondary outcomes are gestational age, APGAR scores, and infant anthropometry. Biochemical indices (blood and breast-milk) from mother-child dyads are being collected to estimate changes in DHA levels in response to supplementation. All analyses will follow the intent-to-treat principle. Two-sample t test will be used to test unadjusted difference in mean DASII score between placebo and DHA group. Adjusted analyses will be performed using multiple linear regression. DISCUSSION:Implications for maternal and child health and nutrition in India: DHANI is the first large pre- and post-natal maternal dietary supplementation trial in India. If the trial finds substantial benefit, it can serve as a learning to scale up the DHA intervention in the country. TRIAL REGISTRATION:The trial is retrospectively registered at clinicaltrials.gov ( NCT01580345 , NCT03072277 ) and ctri.nic.in ( CTRI/2013/04/003540 , CTRI/2017/08/009296 ).

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:Rationale: Docosahexaenoic acid (DHA) in cell membrane may influence breast cancer (BC) patients' prognosis, affecting tumor cells sensitivity to chemo- and radio-therapy and likely modulating inflammation. The possibility of identifying BC patients presenting with low DHA levels and/or low ability of DHA incorporation into cell membrane might help to treat this condition. Methods: We enrolled BC patients and healthy controls, recording their seafood dietary intake. DHA in form of algal oil was administered for 10 consecutive days (2 g/day). Blood samples were collected at baseline (T0) and after 10 days of supplementation (T1) to assess DHA, omega-3 index, as the sum of DHA + eicosapentaenoic acid (EPA), in red blood cells (RBC) membranes and plasma tumor necrosis factor-alpha and interleukin-6 levels. Pre- and post-treatment fatty acid profiles were obtained by gas-chromatography. Parametric and non-parametric tests were performed, as appropriate, and P-value < 0.05 was considered statistically significant. Results: Forty-three women were studied, divided into 4 groups: 11 patients with BRCA1/2 gene mutation (M group), 12 patients with familiar positive history for BC (F group), 10 patients with sporadic BC (S group), and 10 healthy controls (C group). DHA and omega-3 index increased from T0 to T1 in the 3 groups of BC patients and in controls (P < 0.001). No difference was found in DHA incorporation between each group of BC patients and between patients and controls, except for M group, which incorporated higher DHA levels with respect to controls (β = 0.42; P = 0.03). No association was documented between cytokines levels and DHA and omega-3 index at baseline and after DHA supplementation. Independent of the presence of BC, women considered as "good seafood consumers" showed at baseline DHA and omega-3 index higher with respect to "low seafood consumers" (P = 0.04; P = 0.007, respectively). After supplementation, the increase in DHA levels was greater in "low seafood consumers" with respect to "good seafood consumers" (P < 0.0001). Conclusion: DHA supplementation was associated with increased DHA levels and omega-3 index in RBC membranes of BC cancer patients, independent of the type of BC presentation, and in controls. BRCA1/2 mutation, as well as low seafood consuming habits in both BC patients and healthy controls, seem to be associated with greater ability of DHA incorporation. Larger samples of BC patients are necessary to confirm our observation.

Dataset Information

Effect of Maternal Docosahexaenoic Acid (DHA) Supplementation on Offspring Neurodevelopment at 12 Months in India: A Randomized Controlled Trial.

Publications

Effect of Maternal Docosahexaenoic Acid (DHA) Supplementation on Offspring Neurodevelopment at 12 Months in India: A Randomized Controlled Trial.

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