Prenatal Docosahexaenoic Acid Supplementation Research Articles

The Effect of Prenatal Docosahexaenoic Acid Supplementation on Offspring Fat Mass and Distribution at 24 Months Old

BackgroundExcessive gestational weight gain (GWG) is related to increased offspring fat accrual, and increased fat mass (FM) is related to obesity development. Prenatal DHA supplementation has been linked to lower levels of offspring FM; however, conflicting data exist. ObjectivesThis study aimed to determine if there is a protective effect of prenatal DHA supplementation on offspring fat accrual and adipose tissue deposition at 24 mo in offspring born to females who gain excessive weight compared with nonexcessive weight during pregnancy. We also explored if the effect of DHA dose on FM differed by offspring sex. MethodsInfants born to females who participated in the Assessment of DHA on Reducing Early Preterm Birth randomized controlled trial (ADORE) were recruited. In ADORE, females were randomly assigned to either a high or low prenatal DHA supplement. Offspring body composition and adipose tissue distribution were measured using dual-energy x-ray absorptiometry (DXA). GWG was categorized as excessive or not excessive based on clinical guidelines. ResultsFor total FM, there was a significant main effect for the DHA dose (P = 0.03); however, the dose by GWG status was nonsignificant (P = 0.44). Therefore, a higher prenatal DHA dose was related to greater offspring FM (622.9 g greater) and unrelated to GWG status. When investigating a DHA dose by sex effect, a significant main effect for DHA dose (P = 0.01) was detected for central FM. However, no interaction was detected (P = 0.98), meaning that both boys and girls had greater central FM if their mother was assigned to the higher DHA dose. ConclusionsGreater prenatal DHA supplementation was associated with greater offspring FM and adipose tissue distribution at 24 mo. It will be important to understand if these effects persist into childhood.This trial was registered at clinicaltrials.gov as NCT03310983.

Maternal and Offspring Fatty Acid Desaturase Variants, Prenatal DHA Supplementation, and Dietary n–6:n–3 Fatty Acid Ratio in Relation to Cardiometabolic Health in Mexican Children

BackgroundSingle-nucleotide polymorphisms (SNPs) in fatty acid desaturase (FADS) genes may modify dietary fatty acid requirements and influence cardiometabolic health (CMH). ObjectivesWe evaluated the role of selected variants in maternal and offspring FADS genes on offspring CMH at the age of 11 y and assessed interactions of genotype with diet quality and prenatal docosahexaenoic acid (DHA) supplementation. MethodsWe used data from offspring (n = 203) born to females who participated in a randomized controlled trial of DHA supplementation (400 mg/d) from midgestation to delivery. We generated a metabolic syndrome (MetS) score from body mass index, high-density lipoprotein cholesterol, triglycerides, systolic blood pressure, and fasting glucose and identified 6 distinct haplotypes from 5 offspring FADS SNPs. Dietary n–6 (ω–6):n–3 fatty acid ratios were derived from 24-h recall data (n = 141). We used generalized linear models to test associations of offspring diet and FADS haplotypes with MetS score and interactions of maternal and offspring FADS SNP rs174602 with prenatal treatment group and dietary n–6:n–3 ratio on MetS score. ResultsAssociations between FADS haplotypes and MetS score were null. Offspring SNP rs174602 did not modify the association of prenatal DHA supplementation with MetS score. Among children with TT or TC genotype for SNP rs174602 (n = 88), those in the highest n–6:n–3 ratio tertile (>8.61) had higher MetS score relative to the lowest tertile [<6.67) (Δ= 0.36; 95% confidence interval (CI): 0.03, 0.69]. Among children with CC genotype (n = 53), those in the highest n–6:n–3 ratio tertile had a lower MetS score relative to the lowest tertile (Δ= –0.23; 95% CI: –0.61, 0.16). ConclusionsThere was evidence of an interaction of offspring FADS SNP rs174602 with current dietary polyunsaturated fatty acid intake, but not with prenatal DHA supplementation, on MetS score. Further studies may help to determine the utility of targeted supplementation strategies and dietary recommendations based on genetic profile.

Effects of prenatal docosahexaenoic acid supplementation on offspring cardiometabolic health at 11 years differs by maternal single nucleotide polymorphism rs174602: follow-up of a randomized controlled trial in Mexico

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.

Growth and adiposity in newborns study (GAINS): The influence of prenatal DHA supplementation protocol

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; NCT 02626299) 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 registration: ClinicalTrials.gov ID: NCT03310983

Maternal FADS2 single nucleotide polymorphism modified the impact of prenatal docosahexaenoic acid (DHA) supplementation on child neurodevelopment at 5 years: Follow-up of a randomized clinical trial

Variability 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. To assess if maternal FADS2 single nucleotide polymorphisms (SNPs) modified the effect of prenatal DHA on offspring development at 5 years. We 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 400mg/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). Maternal 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). Maternal 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.

The Influence of Prenatal DHA Supplementation on Individual Domains of Behavioral Functioning in School-Aged Children: Follow-Up of a Randomized Controlled Trial.

Docosahexaenoic acid (DHA) accumulates in the fetal brain during pregnancy and is thought to have a role in supporting neurodevelopment. We conducted a multicenter, double-blind, randomized controlled trial in women with a singleton pregnancy who were <21 weeks’ gestation at trial entry. Women were provided with 800 mg DHA/day or a placebo supplement from trial entry until birth. When children reached seven years of age, we invited parents to complete the Strengths and Difficulties Questionnaire (SDQ), the Behavior Rating Inventory of Executive Function (BRIEF), and the Conners 3rd Edition Attention-Deficit Hyperactivity Disorder (ADHD) Index to assess child behavior and behavioral manifestations of executive dysfunction. There were 543 parent–child pairs (85% of those eligible) that participated in the follow-up. Scores were worse in the DHA group than the placebo group for the BRIEF Global Executive, Behavioral Regulation and Metacognition Indexes, and the Shift, Inhibit, Monitor, Working Memory, and Organization of Materials scales, as well as for the Conners 3 ADHD index, and the SDQ Total Difficulties score, Hyperactivity/Inattention score, and Peer Relationship Problems score. In this healthy, largely term-born sample of children, prenatal DHA supplementation conferred no advantage to childhood behavior, and instead appeared to have an adverse effect on behavioral functioning, as assessed by standardized parental report scales.

The influence of DHA supplementation during pregnancy on language development across childhood: Follow-up of a randomised controlled trial

Numerous randomised controlled trials have explored the effect of docosahexaenoic acid (DHA) supplementation in early life on neurodevelopment, with some suggested positive effects on language. Australian women with a singleton pregnancy <21 weeks’ gestation were randomised to receive 800 mg DHA/day or a placebo until birth. A sample of 726 children (all n=96 born preterm, random sample of n=630 born at term) were invited to undergo assessments of language, academic, and language-based cognitive abilities at 1.5, four and seven years of age. No group differences were detected for any group comparison. Exploratory analyses for sex by treatment interactions revealed a possible adverse effect of DHA supplementation on the language of females at 1.5 years but no effects on outcomes at four or seven years. Taken as a whole, evidence of an effect of prenatal DHA supplementation on language abilities across childhood is negligible and could be a chance finding.

Prenatal docosahexaenoic acid supplementation has long-term effects on childhood behavioral and brain responses during performance on an inhibitory task

ABSTRACT Introduction: Offsprings from a prenatal docosahexaenoic acid (DHA) supplementation trial, in which pregnant women were assigned to placebo or 600mg DHA/day, were followed to determine the effect of prenatal DHA supplementation on the behavior and brain function at 5.5 years (n=81 placebo, n=86 supplemented). Methods: Event-related potentials (ERP) were recorded during a visual task requiring a button press (Go) to frequent target stimuli and response inhibition to the rare stimuli (No-Go). Univariate ANOVAs were used to test differences between group and sex for behavioral measures. ERP differences were tested using a three-way mixed-design multivariate analysis of variance (MANOVA). Results: There was a significant sex × group interaction for hit rate and errors of omission; there was no difference between males and females in the placebo group, but DHA males outperformed DHA females. Males overall and the placebo group made more errors requiring response inhibition; DHA females were significantly better than placebo females and DHA males. ERP P2 amplitude was larger in the DHA group. A significant N2 amplitude condition effect was observed in females and DHA group males, but not in placebo group males. Discussion: Prenatal DHA supplementation improved inhibitory performance overall, especially for females in the DHA group, possibly accounting for their conservative behavior during Go trials. Development of brain regions responsible for visual processing may be sensitive to maternal DHA status, evidenced by greater P2 amplitude. Males may benefit more from maternal DHA supplementation, indicated by the N2 condition effect seen only in males in the DHA group.

The Kansas University DHA Outcomes Study (KUDOS) clinical trial: long-term behavioral follow-up of the effects of prenatal DHA supplementation

Docosahexaenoic 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. Our objective was to evaluate the efficacy of the prenatal supplementation on both global and granular longitudinal assessments of cognitive and behavioral development. In 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. Although 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. Although 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.

Effect of Prenatal Docosahexaenoic Acid Supplementation on Blood Pressure in Children With Overweight Condition or Obesity

The blood pressure-lowering property of docosahexaenoic acid (DHA) in children and adults is known, and an observational study from the Netherlands has linked higher intrauterine DHA exposure to lower childhood blood pressure. However, the association of prenatal intake of DHA supplement with childhood blood pressure has not been evaluated in randomized clinical trials. To determine the effect of DHA supplementation during pregnancy on childhood blood pressure. This prespecified secondary analysis of the Kansas University DHA Outcome Study (KUDOS), a phase 3, double-blind, randomized, placebo-controlled clinical trial was conducted at several local hospitals in the Kansas City, Kansas, metropolitan area. Pregnant women (n = 350) were enrolled in the KUDOS trial between January 10, 2006, and November 17, 2009, and were followed up until their children were 18 months of age. During pregnancy, the women received either 3 capsules per day of placebo or 600 mg per day of DHA from a mean (SD) of 14.5 (3.7) weeks' (all before 20 weeks) gestation until birth. The parents of 190 children consented to additional follow-up of their children until 6 years, which ended April 29, 2016. Study personnel involved in testing were blind to the randomization until all children had completed the trial. Data analysis was performed from May 23, 2017, to July 10, 2018. Pregnant women were assigned to either 600 mg per day of DHA or a placebo that was half soy and half corn oil. Both placebo and DHA were provided in 3 capsules per day. Childhood blood pressure was a planned secondary outcome of a study powered to measure cognitive development. The hypothesis was that DHA would lower blood pressure prior to data analysis. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured at 4, 4.5, 5, 5.5, and 6 years and were analyzed for possible covariates using mixed models to generate a final model. In total, 171 children (88 [51.5%] female) were included in this analysis. Of these children, 89 (52.0%) were randomized to the DHA group and 82 (47.9%) to the placebo group. A statistically significant interaction was found between treatment (placebo or DHA) and child weight status (5-year body mass index ≤85th or >85th percentile) for both SBP and DBP. Children who were overweight or obese whose mothers received placebo during pregnancy had higher SBP and DBP compared with children who were overweight or obese whose mothers received DHA (mean [SE] SBP, 104.28 [1.37] mm Hg vs 100.34 [1.02] mm Hg; DBP, 64.7 [1.23] mm Hg vs 59.76 [0.91] mm Hg). No differences in the SBP and DBP were found between children who were overweight or obese whose mothers received DHA and children who were not overweight or obese. In the mixed model analysis, the child's age at blood pressure measurement and the maternal prepregnancy body mass index were the only other statistically significant variables (child age, SBP: F = 7.385; P = .001; DBP: F = 7.39; P = .001; prepregnancy BMI, SBP: r = 0.284; P = .001; DBP: r = 0.216; P = .01). Maternal docosahexaenoic acid intake during pregnancy appeared to mitigate the association between childhood overweight condition or obesity and blood pressure. ClinicalTrials.gov Identifier: NCT02487771.

Effect of omega-3 fatty acids supplementation during pregnancy on lung function in preschoolers: a clinical trial

ABSTRACTRationale: Prenatal omega-3 fatty acids improve alveolarization, diminish inflammation, and improve pulmonary growth, but it is unclear whether these outcomes translate into improved postnatal lung function. Objective: We assessed the effect of prenatal supplementation with docosahexaenoic acid (DHA) on offspring lung function through 60 months of age. Methods: We included a cohort of 772 Mexican preschoolers whose mothers participated in a clinical trial (NCT00646360) of supplementation with DHA or a placebo from week 18–22 of gestation through delivery. Measurements: The children were followed after birth and anthropometric measurements and forced oscillation tests were performed at 36, 48, and 60 months of age. The effect of DHA was tested using a longitudinal mixed effect models. Results: Overall, mean (Standard Deviation) of the measurements of respiratory system resistance and respiratory system reactance at 6, 8, and 10 Hz during follow up period were 11.3 (2.4), 11.1 (2.4), 10.3 (2.2) and –5.2 (1.6), –4.8 (1.7), –4.6 (1.6), respectively. There were no significant differences in pulmonary function by treatment group. DHA did not affect the average lung function or the trajectories through 60 months. Conclusions: Prenatal DHA supplementation did not influence pulmonary function in this cohort of Mexican preschoolers.

Intrauterine DHA exposure and child body composition at 5 y: exploratory analysis of a randomized controlled trial of prenatal DHA supplementation

Observational 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. This 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). At 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. Change 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. Change 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.

Yogurt consumption during pregnancy and preterm delivery in Mexican women: A prospective analysis of interaction with maternal overweight status.

Preterm delivery is an important cause of perinatal morbidity and mortality, often precipitated by maternal infection or inflammation. Probiotic-containing foods, such as yogurt, may reduce systemic inflammatory responses. We sought to evaluate whether yogurt consumption during pregnancy is associated with decreased preterm delivery. We studied 965 women enrolled at midpregnancy into a clinical trial of prenatal docosahexaenoic acid supplementation in Mexico. Yogurt consumption during the previous 3months was categorized as ≥5, 2-4, or <2cups per week. Preterm delivery was defined as delivery of a live infant before 37weeks gestation. We used logistic regression to evaluate the association between prenatal yogurt consumption and preterm delivery and examined interaction with maternal overweight status. In this population, 25.4%, 34.2%, and 40.4% of women reported consuming ≥5, 2-4, and <2cups of yogurt per week, respectively. The prevalence of preterm delivery was 8.9%. Differences in preterm delivery were non-significant across maternal yogurt consumption groups; compared with women reporting <2cups of yogurt per week, those reporting 2-4cups of yogurt per week had adjusted odds ratio (aOR) for preterm delivery of 0.81 (95% confidence interval, CI [.46, 1.41]), and those reporting ≥5cups of yogurt per week had aOR of 0.94 (95% CI [.51, 1.72]). The association between maternal yogurt consumption and preterm delivery differed significantly for nonoverweight women compared with overweight women (p for interaction=.01). Compared with nonoverweight women who consumed <2cups of yogurt per week, nonoverweight women who consumed ≥5cups of yogurt per week had aOR for preterm delivery of 0.24 (95% CI [.07, .89]). Among overweight women, there was no significant association. In this population, there was no overall association between prenatal yogurt consumption and preterm delivery. However, there was significant interaction with maternal overweight status; among nonoverweight women, higher prenatal yogurt consumption was associated with reduced preterm delivery.

Seven-Year Follow-up of Children Born to Women in a Randomized Trial of Prenatal DHA Supplementation

The sale of prenatal supplements with docosahexaenoic acid (DHA) continues to increase, despite little evidence of benefit to offspring neurodevelopment.1 We randomized pregnant women to receive 800 mg of DHA daily or a placebo during the last half of pregnancy and found no group differences in cognitive, language, and motor development at 18 months of age, although secondary analyses revealed less cognitive delay but lower language scores in the DHA group.2 At 4 years of age there was no benefit of DHA supplementation in general intelligence, language, and executive functioning, and a possible negative effect on parent-rated behavior and executive functioning.3 This follow-up was designed to evaluate the effect of prenatal DHA on intelligence quotient (IQ) at 7 years, the earliest age at which adult performance can be indicated.

Prenatal Docosahexaenoic Acid Supplementation Does Not Affect Nonfasting Serum Lipid and Glucose Concentrations of Offspring at 4 Years of Age in a Follow-Up of a Randomized Controlled Clinical Trial in Mexico

Docosahexaenoic acid (DHA) has regulatory effects on lipid and glucose metabolism. Differences in DHA availability during specific developmental windows may program metabolic changes. We investigated the effects of maternal DHA supplementation during pregnancy on the nonfasting serum lipid and glucose concentrations of offspring at 4 y of age. We used data from the Prenatal Omega-3 Fatty Acid Supplementation, Growth, and Development trial, a double-blind randomized controlled trial conducted in Mexico. Pregnant women were supplemented daily with 400 mg DHA or placebo from 18-22 wk of gestation to delivery. The primary outcomes of the trial were offspring growth and neurological development. Nonfasting blood samples were obtained from the offspring at 4 y of age. We analyzed serum total, HDL, non-HDL, and LDL cholesterol; the total-to-HDL cholesterol ratio; apolipoprotein B (apoB); triglycerides; glucose; and insulin as secondary outcomes and compared their concentrations between treatment groups. Data from 524 offspring were available. The women were compliant with the intervention based on pill counts and changes in cord blood and breast milk DHA concentrations. None of the between-group differences (DHA compared with placebo), adjusted for maternal height and time since last food intake, were significant (P range 0.27-0.83). Means (95% CIs) were as follows: total cholesterol (TC), 1.73 mg/dL (-2.63, 6.09 mg/dL); HDL cholesterol, 0.66 mg/dL (-1.07, 2.39 mg/dL); non-HDL cholesterol, 1.77 mg/dL (-1.83, 5.37 mg/dL); LDL cholesterol, 1.62 mg/dL (-2.21, 5.45 mg/dL); TC:HDL ratio, 0.01 (-0.09, 0.11); apoB, -0.15 mg/dL (-2.78, 2.48 mg/dL); triglycerides, 0.21 mg/dL (-10.93, 10.52 mg/dL); glucose, -0.67 mg/dL (-2.46, 1.11 mg/dL); and insulin, 0.62 μU/mL (-0.88, 2.11 μU/mL). Prenatal DHA supplementation does not affect nonfasting serum lipid and glucose concentrations of offspring at 4 y of age. This trial was registered at clinicaltrials.gov as NCT00646360.

Dietary patterns of early childhood and maternal socioeconomic status in a unique prospective sample from a randomized controlled trial of Prenatal DHA Supplementation.

BackgroundDietary habits established in early childhood and maternal socioeconomic status (SES) are important, complex, interrelated factors that influence a child’s growth and development. The aim of this study was to define the major dietary patterns in a cohort of young US children, construct a maternal SES index, and evaluate their associations.MethodsThe diets of 190 children from a randomized, controlled trial of prenatal supplementation of docosahexaenoic acid (DHA) were recorded at 6-mo intervals from 2-4.5 years by 24-h dietary recall. Hierarchical cluster analysis of age-adjusted, average daily intake of 24 food and beverage groups was used to categorize diet. Unrotated factor analysis generated an SES score from maternal race, ethnicity, age, education, and neighborhood income.ResultsWe identified two major dietary patterns: “Prudent” and “Western.” The 85 (45%) children with a Prudent diet consumed more whole grains, fruit, yogurt and low-fat milk, green and non-starchy vegetables, and nuts and seeds. Conversely, those with a Western diet had greater intake of red meat, discretionary fat and condiments, sweet beverages, refined grains, French fries and potato chips, eggs, starchy vegetables, processed meats, chicken and seafood, and whole-fat milk. Compared to a Western diet, a Prudent diet was associated with one standard deviation higher maternal SES (95% CI: 0.80 to 1.30).ConclusionsWe found two major dietary patterns of young US children and defined a single, continuous axis of maternal SES that differed strongly between groups. This is an important first step to investigate how child diet, SES, and prenatal DHA supplementation interact to influence health outcomes.Trial registration NCT00266825. Prospectively registered on December 15, 2005Electronic supplementary materialThe online version of this article (doi:10.1186/s12887-016-0729-0) contains supplementary material, which is available to authorized users.

Effect of prenatal DHA supplementation on the infant epigenome: results from a randomized controlled trial.

BackgroundEvidence 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 utilized 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/day) 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.ResultsThere 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.ConclusionMaternal 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 point the way for future studies.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12605000569606 and ACTRN12611001127998 Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0281-7) contains supplementary material, which is available to authorized users.

Omega-3 Fatty Acids and Maternal and Child Health: An Updated Systematic Review.

To update a prior systematic review on the effects of omega-3 fatty acids (n-3 FA) on maternal and child health and to assess the evidence for their effects on, and associations with, additional outcomes. MEDLINE®, Embase®, the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Centre for Agriculture and Biosciences (CAB) Abstracts from 2000 to August 2015; eligible studies from the original report; and relevant systematic reviews. We included randomized controlled trials (RCTs) of any defined dose of n-3 FA (or combination) compared to placebo, any other n-3 FA, or alternative dose with an outcome of interest conducted in pregnant or breastfeeding women or neonates (preterm or term). We also included prospective observational studies that analyzed the association between baseline n-3 FA intake or biomarker level and followup outcomes. Postnatal interventions began within a week of birth for term infants and within a week of beginning enteral or oral feeding for preterm infants. Standard methods were used for data abstraction and analysis, according to the Evidence-based Practice Center Methods Guide. We identified 4,275 potentially relevant titles from our searches, of which 95 RCTs and 48 observational studies met the inclusion criteria. Risk of bias was a concern with both RCTs and observational studies. Outcomes for which evidence was sufficient to draw a conclusion are summarized here with the Strength of Evidence (SoE). (Outcomes for which the evidence was insufficient to draw a conclusion are summarized in Appendix G of the report.). Most studies in this report examined the effects of fish oil (or other combinations of DHA and EPA) supplements on pregnant or breastfeeding women or the effects of infant formula fortified with DHA plus AA. As with the original report, with the exception of small increases in birth weight and length of gestation,n-3 FA supplementation or fortification has no consistent evidence of effects on peripartum maternal or infant health outcomes. No effects of n-3 FA were seen on gestational hypertension, peripartum depression, or postnatal growth. Apparent effects of n-3 FA supplementation were inconsistent across assessment methods and followup times for outcomes related to infant visual acuity, cognitive development and prevention of allergy and asthma. Future RCTs need to assess standardized preparations of n-3 and n-6 FA, using a select group of clinically important outcomes, on populations with baseline n-3 FA intakes typical of those of most western populations.

Prenatal DHA supplementation and infant attention.

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. 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. 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. The findings support with the suggestion that prenatal DHA may positively affect infants' attention and regulation of state.

The effect of prenatal docosahexaenoic acid supplementation on infant outcomes in African American women living in low-income environments: A randomized, controlled trial

ImportanceAfrican American women living in urban, low-income environments are at high risk for poor nutrition during pregnancy and birth complications. ObjectiveTo test the effectiveness of prenatal docosahexaenoic acid (DHA) supplementation on birth outcomes and infant development in a sample of African American women with Medicaid insurance and living in the city of Pittsburgh. DesignThe Nutrition and Pregnancy Study (NAPS) is a double-blind, randomized controlled trial of prenatal DHA supplementation conducted between 2012 and 2014. SettingParticipants were recruited from obstetric clinics at the University of Pittsburgh Medical Center. ParticipantsSixty-four pregnant, African American women were enrolled at 16–21 weeks of gestation and randomized to either 450mg/day of DHA (22:6n-3)(n=43) or a soybean placebo (n=21). Four women (6.3%) withdrew from the study: two participants from each study arm; complete data were obtained for 49 infants (76.5%) at the 3-month assessment. InterventionsSupplementation with DHA or placebo continued from the beginning of enrollment through delivery. Main outcome and measuresData on birth outcomes were collected from medical records. At approximately 3 months post-partum, mothers brought their infants to the laboratory where the Bayley Scales of Infant Development (BSID-III) were administered and cortisol response to the Face-to-Face Still-Face (FFSF) paradigm was assessed. ResultsInfants of mothers who received DHA supplementation had higher birth weight (3.174g versus 2.890g) than infants of mothers receiving placebo (F [2.40]=6.09, p=0.018, eta=0.36), and were more likely to have a 1-min Apgar score greater than 8 (OR=5.99 [95% CI=1.25–28.75], p=0.025). Infants of mothers who received DHA compared with infants of mothers receiving placebo had lower levels of cortisol in response to the FFSF paradigm (F [1.32]=5.36, p=0.018, eta=0.36). None of the scores on the BSID-III differed as a function of active supplement versus placebo. ConclusionsInfants of women living in urban, low-income environments who received DHA supplementation had more optimal birth outcomes and more modulated cortisol response to a stressor. DHA supplementation may be effective in attenuating the negative effects of prenatal stress on offspring development.