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Docosahexaenoic and Arachidonic Acid Supplementation of Toddlers Born Preterm Does Not Affect Short-Term Growth or Adiposity.

ABSTRACT: BACKGROUND:Dietary DHA intake among US toddlers is low. Healthy physical growth is an important objective for the clinical care of children born preterm. OBJECTIVES:The aim of the trial was to examine the effects of supplementing toddlers born preterm with DHA and arachidonic acid (AA) for 180 d on growth and adiposity. METHODS:Omega Tots, a randomized placebo-controlled trial, was conducted between April 2012 and March 2017. Children born at <35 wk gestation who were 10-16 mo in corrected age were assigned to receive daily oral supplements of DHA and AA (200 mg each, "DHA + AA") or corn oil (placebo) for 180 d. Prespecified secondary outcomes included weight, length, head circumference, mid-upper arm circumference, triceps and subscapular skinfolds, BMI, and their respective z scores, and body fat percentage, which were measured at baseline and trial completion. Mixed-effects regression was used to compare the change in outcomes between the DHA + AA and placebo groups, controlling for baseline values. RESULTS:Among 377 children included in the analysis (median corrected age = 15.7 mo, 48.3% female), 348 (92.3%) had growth or adiposity data at baseline and trial end. No statistically significant differences between the DHA + AA and placebo groups in growth or adiposity outcomes were observed. For instance, the change in weight-for-age z scores was 0.1 for the DHA + AA group and 0.0 for the placebo group (effect size = 0.01, P = 0.99). However, post-hoc subgroup analyses revealed a statistically significant interaction between treatment group and sex, suggesting somewhat slower linear growth for females assigned to the DHA + AA group compared with the placebo group. CONCLUSIONS:Among toddlers born preterm, daily supplementation with DHA + AA for 180 d resulted in no short-term differences in growth or adiposity compared with placebo. If DHA supplementation is implemented after the first year of life, it can be expected to have no effect on short-term growth or adiposity. This trial is registered with clinicaltrials.gov as NCT02199808.

SUBMITTER: Ingol TT

PROVIDER: S-EPMC7443757 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Docosahexaenoic and Arachidonic Acid Supplementation of Toddlers Born Preterm Does Not Affect Short-Term Growth or Adiposity.

Ingol Taniqua T TT Li Rui R Boone Kelly M KM Rausch Joseph J Klebanoff Mark A MA Turner Abigail Norris AN Yeates Keith O KO Nelin Mary Ann MA Sheppard Kelly W KW Keim Sarah A SA

The Journal of nutrition 20191201 12

<h4>Background</h4>Dietary DHA intake among US toddlers is low. Healthy physical growth is an important objective for the clinical care of children born preterm.<h4>Objectives</h4>The aim of the trial was to examine the effects of supplementing toddlers born preterm with DHA and arachidonic acid (AA) for 180 d on growth and adiposity.<h4>Methods</h4>Omega Tots, a randomized placebo-controlled trial, was conducted between April 2012 and March 2017. Children born at <35 wk gestation who were 10-16 ...[more]

PMID: 31187863

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Project description:STUDY OBJECTIVES:This secondary analysis characterized sleep patterns for toddlers born preterm and tested effects of docosahexaenoic acid (DHA)+ arachidonic acid (AA) supplementation on children's caregiver-reported sleep. Exploratory analyses tested whether child sex, birth weight, and caregiver depressive symptomatology were moderators of the treatment effect. METHODS:Omega Tots was a single-site 180-day randomized (1:1), double-blinded, placebo-controlled trial. Children (n = 377) were age 10 to 16 months at enrollment, born at less than 35 weeks' gestation, assigned to 180 days of daily 200 mg DHA + 200 mg AA supplementation or placebo (400 mg corn oil), and followed after the trial ended to age 26 to 32 months. Caregivers completed a sociodemographic profile and questionnaires about their depressive symptomatology (Center for Epidemiologic Studies Depression Scale) and the child's sleep (Brief Infant Sleep Questionnaire). Analyses compared changes in sleep between the DHA+AA and placebo groups, controlling for baseline scores. Exploratory post hoc subgroup analyses were conducted. RESULTS:Eighty-one percent (ntx = 156; nplacebo = 150) of children had 180-day trial outcome data; 68% (ntx = 134; nplacebo = 122) had postintervention outcome data. Differences in change between the DHA+AA and placebo groups after 180 days of supplementation were not statistically significant for the entire cohort. Male children (difference in nocturnal sleep change = 0.44, effect size = 0.26, P = .04; sleep problems odds ratio = 0.36, 95% confidence interval = 0.15, 0.82) and children of depressed caregivers (difference in nocturnal sleep change = 1.07, effect size = 0.65, P = .006; difference in total sleep change = 1.10, effect size = 0.50, P = .04) assigned to the treatment group showed improvements in sleep, compared to placebo. CONCLUSIONS:Although there is no evidence of an overall effect of DHA+AA supplementation on child sleep, exploratory post hoc analyses identified important subgroups of children born preterm who may benefit. Future research including larger samples is warranted. CLINICAL TRIAL REGISTRATION:Registry: ClinicalTrials.gov; Identifier: NCT01576783. CITATION:Boone KM, Rausch J, Pelak G, Li R, Turner AN, Klebanoff MA, Keim SA. Docosahexaenoic acid and arachidonic acid supplementation and sleep in toddlers born preterm: secondary analysis of a randomized clinical trial. J Clin Sleep Med. 2019;15(9):1197-1208.

Project description:Importance:Intake of dietary docosahexaenoic acid (DHA) among toddlers is low. Supplementation may benefit developmental outcomes of toddlers who were born preterm. Objective:To determine whether 6 months of daily DHA supplementation improves developmental outcomes of toddlers who were born preterm. Design, Setting, and Participants:A randomized, fully masked, placebo-controlled trial was conducted from April 26, 2012, to March 24, 2017, at a large US pediatric academic center with 9 neonatal intensive care units. Children born at less than 35 weeks' gestation who were 10 to 16 months corrected age underwent 6 months of intervention. Of 2363 children assessed, 982 were eligible, 605 declined, and 377 enrolled and were randomized. Analyses were according to intent to treat. Interventions:One-to-one allocation to receive daily microencapsulated DHA, 200 mg, and arachidonic acid (AA), 200 mg (DHA+AA), or microencapsulated corn oil (placebo). Main Outcomes and Measures:The primary outcome specified a priori was Bayley Scales of Infant and Toddler Development, third edition (Bayley-III), cognitive composite score at 16 to 22 months corrected age. Secondary outcomes were Bayley-III language and motor composite scores and Infant Behavior Questionnaire-Revised and Early Childhood Behavior Questionnaire effortful control and activity level scores. Subgroup analyses defined a priori were by income, sex, and birth weight. Results:Among 377 children randomized and included in the analysis (182 girls and 195 boys; median corrected age, 15.7 months), 338 children (89.7%) had complete data on the primary outcome. Bayley-III cognitive scores did not differ between the DHA+AA and placebo groups (difference in change, 0.5 [95% CI, -1.8 to 2.8]; effect size, 0.05; P?=?.66). Assignment to the DHA+AA group had a small to medium negative effect on Bayley-III language scores among children with lower birth weights (eg, a child with a birth weight of 1000 g assigned to receive DHA+AA experienced a 4.1-point relative decrease, while a child assigned to placebo did not; P?=?.03 for interaction). Supplementation had a similar negative effect on effortful control scores among children with annual household incomes greater than $35?000 (difference in change, -0.3 [95% CI, -0.4 to -0.1]; effect size, -0.37; P?=?.01). Bayley-III motor scores and activity level scores were unaffected. Conclusions and Relevance:Daily supplementation with 200 mg of DHA and 200 mg of AA for 6 months resulted in no improvement in cognitive development and early measures of executive function vs placebo, and may have resulted in negative effects on language development and effortful control in certain subgroups of children. These findings do not support DHA supplementation in the second year of life for children who are born preterm. Trial Registration:ClinicalTrials.gov Identifier: NCT01576783.

Project description:INTRODUCTION: Herein, we expand our previous work on the effects of long chain polyunsaturated fatty acids (LC-PUFA) on the murine hepatic transcriptome using novel statistical and bioinformatic approaches for evaluating microarray data. The analyses focuses on key differences in the transcriptomic response that will influence metabolism following consumption of FUNG (rich in 20:4n6), FISH (rich in 20:5n3, 22:5n3, and 22:6n3) and COMB, the combination of the two. RESULTS: Using a variance-stabilized F-statistic, 371 probe sets (out of 13 K probe sets in the Affymetrix Mu11K chip set) were changed by dietary treatment (P < 0.001). Relative to other groups, COMB had unique affects on murine hepatic transcripts involved in cytoskeletal and carbohydrate metabolism; whereas FUNG affected amino acid metabolism via CTNB1 signaling. All three diets affected transcripts linked to apoptosis and cell proliferation, with evidence FISH may have increased apoptosis and decreased cell proliferation via various transcription factors, kinases, and phosphatases. The three diets affected lipid transport, lipoprotein metabolism, and bile acid metabolism through diverse pathways. Relative to other groups, FISH activated cyps that form hydroxylated fatty acids known to affect vascular tone and ion channel activity. FA synthesis and delta 9 desaturation were down regulated by COMB relative to other groups, implying that a FA mixture of 20:4n6, 20:5n3, and 22:6n3 is most effective at down regulating synthesis, via INS1, SREBP, PPAR alpha, and TNF signaling. Heme synthesis and the utilization of heme for hemoglobin production were likely affected by FUNG and FISH. Finally, relative to other groups, FISH increased numerous transcripts linked to combating oxidative such as peroxidases, an aldehyde dehydrogenase, and heat shock proteins, consistent with the major LC-PUFA in FISH (20:5n3, 22:5n3, 22:6n3) being more oxidizable than the major fatty acids in FUNG (20:4n6). CONCLUSION: Distinct transcriptomic, signaling cascades, and predicted affects on murine liver metabolism have been elucidated for 20:4n6-rich dietary oils, 22:6n3-rich oils, and a surprisingly distinct set of genes were affected by the combination of the two. Our results emphasize that the balance of dietary n6 and n3 LC-PUFA provided for infants and in nutritional and neutraceutical applications could have profoundly different affects on metabolism and cell signaling, beyond that previously recognized.

Project description:Background: Human milk contains both arachidonic acid (ARA) and docosahexaenoic acid (DHA). Supplementation of infant formula with ARA and DHA results in fatty acid (FA) profiles, neurodevelopmental outcomes, and immune responses in formula-fed infants that are more like those observed in breastfed infants. Consequently, ARA and DHA have been historically added together to infant formula. This study investigated the impact of ARA or DHA supplementation alone or in combination on tissue FA incorporation, immune responses, and neurodevelopment in the young pig. Methods: Male pigs (N = 48 total) received one of four dietary treatments from postnatal day (PND) 2-30. Treatments targeted the following ARA/DHA levels (% of total FA): CON (0.00/0.00), ARA (0.80/0.00), DHA (0.00/0.80), and ARA+DHA (0.80/0.80). Plasma, red blood cells (RBC), and prefrontal cortex (PFC) were collected for FA analysis. Blood was collected for T cell immunophenotyping and to quantify a panel of immune outcomes. Myelin thickness in the corpus callosum was measured by transmission electron microscopy and pig movement was measured by actigraphy. Results: There were no differences in formula intake or growth between dietary groups. DHA supplementation increased brain DHA, but decreased ARA, compared with all other groups. ARA supplementation increased brain ARA compared with all other groups but did not affect brain DHA. Combined supplementation increased brain DHA levels but did not affect brain ARA levels compared with the control. Pigs fed ARA or ARA+DHA exhibited more activity than those fed CON or DHA. Diet-dependent differences in activity suggested pigs fed ARA had the lowest percent time asleep, while those fed DHA had the highest. No differences were observed for immune or myelination outcomes. Conclusion: Supplementation with ARA and DHA did not differentially affect immune responses, but ARA levels in RBC and PFC were reduced when DHA was provided without ARA. Supplementation of either ARA or DHA alone induced differences in time spent asleep, and ARA inclusion increased general activity. Therefore, the current data support the combined supplementation with both ARA and DHA in infant formula and raise questions regarding the safety and nutritional suitability of ARA or DHA supplementation individually.

Dataset Information

Docosahexaenoic and Arachidonic Acid Supplementation of Toddlers Born Preterm Does Not Affect Short-Term Growth or Adiposity.

Publications

Docosahexaenoic and Arachidonic Acid Supplementation of Toddlers Born Preterm Does Not Affect Short-Term Growth or Adiposity.

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