Prenatal DHA supplementation and infant attention.
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ABSTRACT: Background
Results of randomized trials on the effects of prenatal docosahexaenoic acid (DHA) on infant cognition are mixed, but most trials have used global standardized outcomes, which may not be sensitive to effects of DHA on specific cognitive domains.Methods
Women were randomized to 600 mg/d DHA or a placebo for the last two trimesters of pregnancy. Infants of these mothers were then followed on tests of visual habituation at 4, 6, and 9 mo of age.Results
DHA supplementation did not affect look duration or habituation parameters but infants of supplemented mothers maintained high levels of sustained attention (SA) across the first year; SA declined for the placebo group. The supplemented group also showed significantly reduced attrition on habituation tasks, especially at 6 and 9 mo.Conclusion
The findings support with the suggestion that prenatal DHA may positively affect infants' attention and regulation of state.
SUBMITTER: Colombo J
PROVIDER: S-EPMC5164926 | biostudies-literature | 2016 Nov
REPOSITORIES: biostudies-literature
Publications
Prenatal DHA supplementation and infant attention.
Colombo John J Gustafson Kathleen M KM Gajewski Byron J BJ Shaddy D Jill DJ Kerling Elizabeth H EH Thodosoff Jocelynn M JM Doty Tasha T Brez Caitlin C CC Carlson Susan E SE
Pediatric research 20160630 5
<h4>Background</h4>Results of randomized trials on the effects of prenatal docosahexaenoic acid (DHA) on infant cognition are mixed, but most trials have used global standardized outcomes, which may not be sensitive to effects of DHA on specific cognitive domains.<h4>Methods</h4>Women were randomized to 600 mg/d DHA or a placebo for the last two trimesters of pregnancy. Infants of these mothers were then followed on tests of visual habituation at 4, 6, and 9 mo of age.<h4>Results</h4>DHA supplem ...[more]
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Project description:Evidence is accumulating that nutritional exposures in utero can influence health outcomes in later life. Animal studies and human epidemiological studies have implicated epigenetic modifications as playing a key role in this process, but there are limited data from large well-controlled human intervention trials. This study utilised a large double-blind randomized placebo-controlled trial to test whether a defined nutritional exposure in utero, in this case docosahexaenoic acid (DHA), could alter the infant epigenome. Pregnant mothers consumed DHA-rich fish oil (800 mg DHA/d) or placebo supplements from 20 weeks’ gestation to delivery. Blood spots were collected from the children at birth (n=991) and blood leukocytes at 5 years (n=667). Global DNA methylation was measured in all samples and Illumina HumanMethylation450K BeadChip arrays were used for genome-wide methylation profiling in a subset of 369 children at birth and 65 children at 5 years. There were no differences in global DNA methylation levels between the DHA and control group either at birth or at 5 years, but we identified 21 differentially methylated regions (DMRs) at birth, showing small DNA methylation differences (<5%) between the treatment groups, some of which seemed to persist until 5 years. The number of DMRs at birth was greater in males (127 DMRs) and in females (72 DMRs) separately, indicating a gender-specific effect. In conclusion, maternal DHA supplementation during the second half of pregnancy had small effects on DNA methylation of infants. While the potential functional significance of these changes remains to be determined, these findings further support the role of epigenetic modifications in developmental programming in humans, and points the way for future studies.
2018-02-06 | GSE89278 | GEO
Project description:BackgroundDocosahexanoic acid (DHA) is an important constituent of the brain. Evidence from well-designed intervention trials of the long-term benefits of increasing DHA intake during pregnancy has been sparse.ObjectiveWe evaluated global cognition, behavior, and attention at age 5 y in the offspring of Mexican women who participated in a randomized controlled trial of prenatal DHA supplementation.DesignA total of 1094 women were randomly assigned to receive 400 mg of either DHA or placebo/d from 18 to 22 wk of pregnancy until delivery. We assessed cognitive development and behavioral and executive functioning, including attention, in 797 offspring at age 5 y (82% of 973 live births) with the use of the McCarthy Scales of Children's Abilities (MSCA), the parental scale of the Behavioral Assessment System for Children, Second Edition (BASC-2), and the Conners' Kiddie Continuous Performance Test (K-CPT). We compared the groups on raw scores, T-scores, and standardized scores, as appropriate. We examined heterogeneity by the quality of the home environment, maternal intelligence, and socioeconomic status.ResultsThere were no group differences for MSCA scores (P > 0.05), but the positive effect of the home environment at 12 mo on general cognitive abilities was attenuated in the DHA group compared with in the placebo group (P-interaction < 0.05). There were no differences between groups on the BASC-2. On the K-CPT, offspring in the DHA group showed improved mean ± SD T-scores compared with those of the placebo group for omissions (DHA: 47.6 ± 10.3; placebo: 49.6 ± 11.2; P < 0.01) with no differences (P > 0.05) for the other K-CPT scores or of the proportion who were clinically at risk of attention deficit hyperactivity disorders after Bonferroni correction for multiple comparisons.ConclusionPrenatal exposure to DHA may contribute to improved sustained attention in preschool children. This trial was registered at clinicaltrials.gov as NCT00646360.
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Project description:BackgroundAlthough DHA (22:6n-3) is critical for fetal development, results from randomized controlled trials (RCTs) of prenatal DHA supplementation report inconsistent effects on offspring health. Variants in fatty acid desaturase (FADS) genes that regulate the conversion of n-3 and n-6 essential fatty acids into their biologically active derivatives may explain this heterogeneity.ObjectivesWe investigated the effect of prenatal DHA supplementation on the offspring metabolome at age 3 mo and explored differences by maternal FADS single-nucleotide polymorphism (SNP) rs174602.MethodsData were obtained from a double-blind RCT in Mexico [POSGRAD (Prenatal Omega-3 Fatty Acid Supplementation and Child Growth and Development)] in which women (18-35 y old) received DHA (400 mg/d) or placebo from mid-gestation until delivery. Using high-resolution MS with LC, untargeted metabolomics was performed on 112 offspring plasma samples. Discriminatory metabolic features were selected via linear regression (P < 0.05) with false discovery rate (FDR) correction (q = 0.2). Interaction by SNP rs174602 was assessed using 2-factor ANOVA. Stratified analyses were performed, where the study population was grouped into carriers (TT, TC; n = 70) and noncarriers (CC; n = 42) of the minor allele. Pathway enrichment analysis was performed with Mummichog (P < 0.05).ResultsAfter FDR correction, there were no differences in metabolic features between infants whose mothers received prenatal DHA (n = 58) and those whose mothers received placebo (n = 54). However, we identified 343 differentially expressed features in the interaction analysis after FDR correction. DHA supplementation positively enriched amino acid and aminosugars metabolism pathways and decreased fatty acid metabolism pathways among offspring of minor allele carriers and decreased metabolites within the tricarboxylic acid cycle and galactose metabolism pathways among offspring of noncarriers.ConclusionsOur findings demonstrate differences in infant metabolism in response to prenatal DHA supplementation by maternal SNP rs174602 and further support the need to incorporate genetic analysis of FADS polymorphisms into DHA supplementation trials.This trial was registered at clinicaltrials.gov as NCT00646360.
| S-EPMC8562085 | biostudies-literature
Project description: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.
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Project description:BackgroundObesity and central fat mass (FM) accrual drive disease development and are related to greater morbidity and mortality. Excessive gestational weight gain (GWG) increases fetal fat accretion resulting in greater offspring FM across the lifespan. Studies associate greater maternal docosahexaenoic acid (DHA) levels with lower offspring FM and lower visceral adipose tissue during childhood, however, most U.S. pregnant women do not consume an adequate amount of DHA. We will determine if prenatal DHA supplementation is protective for body composition changes during infancy and toddlerhood in offspring exposed to excessive GWG.Methods and designInfants born to women who participated in the Assessment of DHA on Reducing Early Preterm Birth randomized controlled trial (ADORE; NCT02626299) will be invited to participate. Women were randomized to either a high 1000 mg or low 200 mg daily prenatal DHA supplement starting in the first trimester of pregnancy. Offspring body composition and adipose tissue distribution will be measured at 2 weeks, 6 months, 12 months, and 24 months using dual energy x-ray absorptiometry. Maternal GWG will be categorized as excessive or not excessive based on clinical guidelines.DiscussionEffective strategies to prevent obesity development are lacking. Exposures during the prenatal period are important in the establishment of the offspring phenotype. However, it is largely unknown which exposures can be successfully targeted to have a meaningful impact. This study will determine if prenatal DHA supplementation modifies the relationship between maternal weight gain and offspring FM and FM distribution at 24 months of age.Ethics and disseminationThe University of Kansas Medical Center Institutional Review Board (IRB) approved the study protocol (STUDY00140895). The results of the trial will be disseminated at conferences and in peer reviewed publications.Trial registrationClinicalTrials.gov ID: NCT03310983.
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Project description:BackgroundObservational studies find associations between maternal docosahexaenoic acid (DHA) and greater fat-free mass and lower percentage of body fat, but randomized trials of prenatal DHA supplementation have not found significant intent-to-treat effects on childhood body composition.ObjectiveThis study sought to explore associations between intrauterine DHA exposure and body composition and size at 5 y in the offspring of women who participated in a randomized trial of prenatal DHA supplementation (corn and soybean oil placebo or 600 mg/d).DesignAt 5 y, body composition was measured by air displacement plethysmography in 154 offspring of women who had participated in the Kansas University DHA Outcomes Study and who had red blood cell (RBC) phospholipid (PL) fatty acids assessed at enrollment and delivery. We used linear regression models to analyze the relation among 3 indicators of intrauterine DHA exposure-1) intent-to-treat (placebo or DHA), 2) maternal RBC PL DHA status at delivery, and 3) change in maternal DHA (delivery minus enrollment)-and 6 outcomes of interest: 5-y fat mass, fat-free mass, percentage of body fat, height, weight, and body mass index z score.ResultsChange in maternal RBC PL DHA correlated with higher fat-free mass (r = 0.21, P = 0.0088); the association was unchanged after adjustment for maternal, perinatal, and childhood dietary factors. Intent-to-treat and DHA status at delivery showed positive trends with fat-free mass that were not statistically significant. There was no evidence relating intrauterine DHA exposure to any other body composition measure.ConclusionsChange in maternal DHA status during pregnancy was related to higher offspring 5-y fat-free mass. The other 2 indicators of intrauterine exposure to DHA suggested a trend for higher offspring 5-y fat-free mass. Our findings agree with an earlier observational study from the United Kingdom. This trial was registered at clinicaltrials.gov as NCT00266825.
| S-EPMC5972598 | biostudies-literature
Project description:BackgroundDocosahexaenoic acid (DHA) is a long-chain polyunsaturated fatty acid that has been linked to improved vision and cognition in postnatal feeding studies and has been consistently associated with reduction of early preterm birth in prenatal supplementation trials. This is a report of the first long-term follow-up of infants from mothers receiving prenatal DHA supplementation in a US cohort.ObjectiveOur objective was to evaluate the efficacy of the prenatal supplementation on both global and granular longitudinal assessments of cognitive and behavioral development.MethodsIn a randomized double-blind clinical trial, mothers received either 600 mg/d of DHA or a placebo beginning at 14.5 weeks of gestation and capsules were provided until delivery. Children from those pregnancies were followed by cognitive and behavioral assessments administered from 10 mo through 6 y of age. From 301 mothers in the initial study, ∼200 infants completed the longitudinal schedule.ResultsAlthough this intervention had been shown to reduce high-risk pregnancies and improve visual attention in infants during the first year, only a few positive long-term effects of prenatal DHA supplementation emerged from analyses of this follow-up. Increases in maternal blood DHA during pregnancy were related to verbal and full scale intelligence quotient (IQ) scores at 5 and 6 y, but these effects disappeared after controlling for SES. Maternal blood DHA concentrations at delivery were unrelated to outcomes, although maternal DHA at enrollment was related to productive vocabulary at 18 mo.ConclusionsAlthough prenatal DHA supplementation substantially reduced early preterm birth and improved visual attention in infancy in this sample, no consistent long-term benefits were observed into childhood. Increases in maternal blood DHA concentration in pregnancy were related to higher IQs but this effect was confounded with SES and disappeared when SES was statistically controlled. This trial was registered at http://www.clinicaltrials.gov as NCT00266825 and NCT02487771.
| S-EPMC6499507 | biostudies-literature
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.
| S-EPMC9437984 | biostudies-literature
Project description:ObjectiveTo determine the effect of prenatal maternal vitamin D supplementation on infant vitamin D status in a tropical region where vitamin D supplementation is not routine.DesignA prospective observational follow-up of a randomized trial.SettingMaternal-child health facility in Dhaka, Bangladesh (23°N).SubjectsInfants born to pregnant women (n 160) randomized to receive 875 µg (35 000 IU) cholecalciferol (vitamin D3) per week (VD) or placebo (PL) during the third trimester were followed from birth until 6 months of age (n 115). Infant serum 25-hydroxyvitamin D concentration (25(OH)D) was measured at <1, 2, 4 and 6 months of age.ResultsMean infant 25(OH)D was higher in the VD v. PL group at <1 month of age (mean (sd): 80 (20) nmol/l v. 22 (18) nmol/l; P<0·001), but the difference was attenuated by 2 months (52 (19) nmol/l v. 40 (23) nmol/l; P=0·05). Groups were similar at 4 months (P=0·40) and 6 months (n 72; P=0·26). In the PL group, mean infant 25(OH)D increased to 78 (95 % CI 67, 88) nmol/l by 6 months of age (n 34). 25(OH)D was higher with infant formula-feeding and higher in summer v. winter.ConclusionsPrenatal third-trimester vitamin D supplementation (875 µg (35 000 IU)/week) significantly ameliorated infant vitamin D status during the neonatal period when the risk of vitamin D deficiency is greatest. Further research is warranted to determine factors that contribute to the rise in 25(OH)D during the first 6 months of life among breast-fed infants in this setting.
| S-EPMC10261491 | biostudies-literature