Lisa G. Smithers

The effect of maternal omega-3 (n-3) LCPUFA supplementation during pregnancy on early childhood cognitive and visual development: a systematic review and meta-analysis of randomized controlled trials

BACKGROUND Maternal fish consumption during pregnancy has been positively associated with cognitive and visual abilities in the offspring, leading to the hypothesis that maternal omega-3 (n-3) long-chain PUFA (LCPUFA) supplementation improves childrens neurologic and visual development. OBJECTIVE The objective was to evaluate the effect of maternal omega-3 LCPUFA supplementation in pregnancy on neurologic and visual development in the offspring. DESIGN Five electronic databases were searched. Human randomized controlled trials that supplemented the maternal diet with omega-3 LCPUFAs during pregnancy, or pregnancy and lactation, and that assessed either neurologic or visual development of the offspring were included. Trial quality was assessed, and the results of eligible trials were compared in meta-analyses. RESULTS Eleven RCTs involving 5272 participants were included in the review. Most trials had methodologic limitations. No differences in standardized psychometric test scores for cognitive, language, or motor development were observed between the LCPUFA-supplemented and control groups, except for cognitive scores in 2-5-y-old children, in whom supplementation resulted in higher Developmental Standard Scores (mean difference: 3.92; 95% CI: 0.77, 7.08; n = 156; P = 0.01). However, this effect was from 2 trials with a high risk of bias. Because of the variety of visual assessments and age ranges, it was not possible to combine studies with visual outcomes in a meta-analysis, although 6 of the 8 assessments in 5 trials reported no difference between the supplemented and control groups. CONCLUSION The evidence does not conclusively support or refute that omega-3 LCPUFA supplementation in pregnancy improves cognitive or visual development.

Characterizing whole diets of young children from developed countries and the association between diet and health: a systematic review

Early childhood is an important nutritional period that involves the transition from a milk-based diet to ordinary foods. A systematic review was conducted of studies that applied whole-of-diet analysis of children aged 1-5 years to examine associations between diet and nutrition, health, and development. Literature searches identified 40 articles using dietary indices, principal component analysis, or cluster analysis. Reports that applied indices (n = 23, 18 indices) were cross-sectional, and most measured diet quality or variety. Articles reporting principal component or cluster analyses (n =17) described between two and six dietary patterns, and most identified healthy, unhealthy, and traditional patterns. In cross-sectional analyses, mixed associations were found between index or pattern scores and nutrient intake (n = 10), nutritional biomarkers (n = 1), and anthropometry (n = 10). Five reports from two birth cohorts showed healthier dietary patterns were associated with better lean mass, cognition, and behavior, but not with bone mass or body mass index at later ages. Few studies have characterized the diets of children under 5 years of age and linked diet with health. Given the limited evidence, research establishing the predictive validity of whole-of-diet methods in childhood is needed.

Associations between dietary patterns at 6 and 15 months of age and sociodemographic factors

BACKGROUND/OBJECTIVES:Data from the Avon Longitudinal Study of Parents and Children (ALSPAC) have previously shown that dietary patterns are observable by 3 years. However, it is not clear when dietary patterns emerge. We aimed to describe dietary patterns in early life and their associations with maternal and infant sociodemographic characteristics.SUBJECTS/METHODS:Principal component analysis was applied to diet questionnaires of ALSPAC participants at 6 months (n=7052) and 15 months (n=5610) to extract dietary patterns. The sociodemographic factors associated with dietary patterns were investigated using regression analyses.RESULTS:Four dietary patterns were extracted at both 6 and 15 months. A traditional-style pattern characterized by home-prepared meats, vegetables and desserts, a second pattern characterized by ready-prepared baby foods and a third pattern characterized by discretionary foods such as biscuits, sweets and crisps were identified at both ages. At 6 months, the fourth pattern was characterized predominantly by breastfeeding and at 15 months, by contemporary-style foods including herbs, legumes, nuts, raw fruit and vegetables. Higher maternal age and education, number of siblings and lower body mass index (BMI) was associated with higher scores on the breastfeeding or meat, vegetables and desserts patterns, whereas higher discretionary food pattern scores were associated with younger maternal age, lower education, higher BMI and more siblings. Associations between sociodemographic factors and the ready-prepared baby food pattern scores were inconsistent across ages.CONCLUSIONS:Dietary patterns emerge from infancy and are associated with sociodemographic characteristics.

The effect of dairy foods on CHD: a systematic review of prospective cohort studies

There is interest in the degree to which fats in dairy foods contribute to CHD. We undertook a systematic review to investigate the effect of dairy consumption on CHD using prospective cohort studies. A systematic search of electronic databases identified studies relating dairy food intake in adulthood to episodes or death from CHD, IHD and myocardial infarction. Included studies were assessed for quality based on study methodology, validity of dietary assessment, success of follow-up, standardised assessment of CHD, IHD or myocardial infarction end points and appropriateness of statistical adjustment. Data from twelve cohorts involving >280,000 subjects were included. Most studies had follow-up of >80 %, adjusted statistically for three or more confounders and used standard criteria to determine end points. About half the studies used a validated FFQ, administered the FFQ more than once or had follow-up of >20 years. Fewer than half the studies involved subjects representative of the general population. Four of the twelve cohorts found no association between dairy intake and CHD. Eight studies reported varying relationships between different dairy foods and CHD or differential associations based on race, sex or over time. Although dairy foods contribute to the SFA composition of the diet, this systematic review could find no consistent evidence that dairy food consumption is associated with a higher risk of CHD. This could be due to the limited sensitivity of the dietary assessment methods to detect an effect of a single food in a mixed diet on complex clinical outcomes.

Role of long-chain polyunsaturated fatty acids in neurodevelopment and growth.

There has been intense interest in the role of the n-3 long-chain polyunsaturated fatty acid (LCPUFA) docosahexaenoic acid (DHA, 22:6n-3), in growth and development of infants. In 2009, there are at least twelve published randomized controlled trials (RCT) assessing the effects of LCPUFA supplementation of infant formula for preterm infants and seventeen RCTs involving formula-fed term infants. In addition, at least five RCTs have investigated the effect of DHA supplementation during pregnancy and/or lactation on infant and early child development. Collectively, the published literature has demonstrated no harm of dietary LCPUFA for infants regardless of whether they are born preterm or at term. However, developmental benefit is more consistently observed in infants born preterm. This may be explained by the fact that DHA accretion to neural tissues peaks during the fetal brain growth spurt in the last trimester of pregnancy. Infants born preterm are denied the full gestation period to accumulate DHA and are at risk of incomplete DHA accumulation. New research is focused on the timing and dose of DHA supplementation needed to optimize developmental outcomes.

Feeding preterm infants milk with a higher dose of docosahexaenoic acid than that used in current practice does not influence language or behavior in early childhood: a follow-up study of a randomized controlled trial

BACKGROUND The visual and mental development of preterm infants improved after feeding them milk enriched with docosahexaenoic acid (DHA) in amounts matching the fetal accretion rate. OBJECTIVE The objective was to evaluate whether feeding preterm infants milk with a higher DHA content than that used in current practice influences language or behavior in early childhood. DESIGN This was a follow-up study in a subgroup of infants enrolled in the DINO (Docosahexaenoic acid for the Improvement in Neurodevelopmental Outcome) trial. In a double-blind randomized controlled trial, infants born at <33 wk of gestation were fed milk containing 1% of total fatty acids as DHA (higher-DHA group) or approximately 0.3% DHA (control group) until reaching full-term equivalent age. The longer-term effects of the intervention on language, behavior, and temperament were measured by using the MacArthur Communicative Development Inventory (MCDI) at 26-mo corrected age, the Strengths and Difficulties Questionnaire (SDQ), and the Short Temperament Scale for Children (STSC) between 3- and 5-y corrected age. RESULTS Mean (+/-SD) MCDI scores did not differ significantly (adjusted P = 0.8) between the higher-DHA group (308 +/- 179, n = 60) and the control group (316 +/- 192, n = 67) per the Vocabulary Production subscale. Composite scores on the SDQ and STSC did not differ between the higher-DHA group and the control group [SDQ Total Difficulties: higher-DHA group (10.3 +/- 6.0, n = 61), control group (9.5 +/- 5.5, n = 64), adjusted P = 0.5; STSC score: higher-DHA group (3.1 +/- 0.7, n = 61), control group (3.0 +/- 0.7, n = 64), adjusted P = 0.3]. CONCLUSIONS Feeding preterm infants milk containing 3 times the standard amount of DHA did not result in any clinically meaningful change to language development or behavior when assessed in early childhood. Whether longer-term effects of dietary DHA supplementation can be detected remains to be assessed. This trial was registered with the Australia and New Zealand Clinical Trial Registry at www.anzctr.org.au as 12606000327583.

Effect of two doses of docosahexaenoic acid (DHA) in the diet of preterm infants on infant fatty acid status: results from the DINO Trial

Formula supplemented with docosahexaenoic acid (DHA) improves retinal function of preterm infants but the optimal dose is unknown. In a randomized controlled trial we examined the effect of increasing the DHA concentration of human milk and formula on circulating fatty acids of preterm infants. Infants born <33 weeks gestation were fed high-DHA milk (1% total fat as DHA) or standard-DHA milk (0.2-0.3% DHA) until reaching their estimated due date (EDD). Milk arachidonic acid (AA) concentration was approximately 0.5% for both groups. At EDD, erythrocyte membrane phospholipid DHA was elevated in the high-DHA group compared with standard-DHA (mean+/-SD, high-DHA 6.8+/-1.2, standard-DHA 5.2+/-0.7, p<0.0005) but AA was lower (high-DHA 14.9+/-1.3, standard-DHA 16.0+/-1.2, p<0.0005). Feeding preterm infants human milk and formula with 1% DHA raises but does not saturate erythrocyte phospholipids with DHA. Milk exceeding 1% DHA may be required to increase DHA status to levels seen in term infants.

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.

Maternal supplementation with docosahexaenoic acid during pregnancy does not affect early visual development in the infant: a randomized controlled trial

BACKGROUND The docosahexaenoic acid (DHA) intake of pregnant women is lower than estimates of the DHA accretion by the fetus, and recommendations were made to increase the DHA intake of pregnant women. OBJECTIVE The objective of this study was to determine whether the supplementation of pregnant women with DHA improved the visual acuity of infants at 4 mo. DESIGN We conducted a blinded assessment of a subset of healthy, full-term infants born to women enrolled in a double-blind, randomized controlled trial called the DHA for Maternal and Infant Outcomes (DOMInO) trial. Women were randomly assigned to consume DHA-rich fish-oil capsules (≈800 mg DHA/d in the treatment group) or vegetable oil capsules (control group) from midpregnancy to delivery. The primary outcome was the sweep visual evoked potential (VEP) acuity at 4 mo. The VEP latency at 4 mo was a secondary outcome. RESULTS Mean (±SD) VEP acuity did not differ between treatment and control groups [treatment group: 8.37 ± 2.11 cycles per degree (cpd), n = 89; control group: 8.55 ± 1.86 cpd, n = 93; P = 0.55]. VEP latencies also did not differ between groups. Irrespective of the group, maternal smoking in pregnancy was independently associated with poorer VEP acuity in the infant. CONCLUSIONS DHA supplementation in women with singleton pregnancies does not enhance infant visual acuity in infants at 4 mo of age. Visual acuity in infancy is adversely associated with maternal smoking in pregnancy. This trial was registered at www.anzctr.org.au as ACTRN12606000327583. The DOMInO trial was registered at www.anzctr.org.au as ACTRN12605000569606.

Effect of fatty acid structure on neutrophil adhesion, degranulation and damage to endothelial cells

Neutrophils have been implicated in ischaemic heart disease, unstable angina pectoris and acute myocardial infarction. Alterations in dietary levels of specific 18- and 20-carbon polyunsaturated fatty acids have significant clinical benefits in cardiovascular disease. However, to date there has been no concerted effort to identify the structural basis for polyunsaturated fatty acid-induced alterations in key neutrophil functions. We have investigated the influence of fatty acid structure and involvement of lipoxygenase/cyclooxygenase pathways on fatty acid-induced neutrophil functions. When neutrophils were incubated with 18-carbon fatty acids containing one to four double bonds (10-33 mumol/l), a significant increase in adherence and release of specific granule constituents occurred compared with control cells. In general, as the number of double bonds in the 18-carbon fatty acid increased, so did its ability to stimulate these functions. There was less stimulation of adherence and specific granule release by 18:3(n-3) than its isomer 18:3(n-6). Smaller effects were seen on azurophilic granule release. A further increase in adherence and degranulation was observed with increasing carbon chain length (20:3(n-6) and 20:4(n-6)). Differences were found in the ability of isomers of 20:3 to stimulate neutrophil function. Of the fatty acids tested only 20:4(n-6) was able to induce significant neutrophil-mediated endothelial detachment. Introduction of either internal hydroperoxy or hydroxyl groups into 20:4(n-6) abolished its adherence stimulating activity and considerably reduced its ability to stimulate release of both specific and azurophilic granules. Preincubation of neutrophils with either lipoxygenase (caffeic acid) or cyclooxygenase (indomethacin) inhibitors had no effect on 20:4(n-6) stimulated function. These studies show that the number and position of double bonds, carbon chain length and oxidation state can be critical to the neutrophil stimulatory properties of these fatty acids.