The effects of parenteral fish oil on neurodevelopment in preterm infants: A narrative review.

OBJECTIVE: This narrative review aimed to summarize studies assessing the effects of parenteral fish oil on neurodevelopment in preterm infants. METHODS: PubMed was searched (July 1985 to October 2023). We reviewed randomized controlled trials, and observational studies assessing intravenous lipid emulsion with fish oil in preterm infants (born less than 37 weeks' gestation), that reported long-term neurodevelopmental outcomes. RESULTS: We identified four publications relating to three randomized controlled trials in addition to four cohort studies. Study designs and outcomes were heterogenous and precluded meta-analyses. Results of trials were null for a selection of neurodevelopmental outcomes, however possible benefits of parenteral fish oil supplementation for neurodevelopment was reported in three cohort studies. Certainty of the evidence is hindered by methodological limitations of available trials and observational studies. CONCLUSIONS: Further research is required to firmly establish the effects of parenteral fish oil on preterm neurodevelopment.

Subgroup analyses of a randomized trial of DHA supplementation for infants born preterm with assessments of cognitive development up to 7-years of age: What happens in infants born <29 weeks' gestation?

A recent trial showed that high-dose docosahexaenoic acid (high-DHA) supplementation of infants born <29 weeks' gestation improves intelligence quotient (IQ) at five years' corrected age. However, this finding has not been detected by other trials of DHA, which either did not measure IQ or included more mature infants. We analyzed the subgroup of 204 infants born <29 weeks' from our earlier randomized trial of high-DHA (∼1 % total fatty acids) or standard-DHA (∼ 0.3 % total fatty acids). Participants were assessed for cognition at 18 months, and IQ and behavior at seven years' corrected age. No group differences were detected for mean cognitive, IQ or behavior scores. At 18 months, 18.8 % of children in the high-DHA group had a cognitive score <85, compared with 31.1 % of children in the standard-DHA group, but at seven years there was no difference. Although an underpowered post-hoc subgroup analysis, this study provides limited support to recommendations that infants born <29 weeks' gestation require supplemental DHA.

ISSFAL statement number 7 - Omega-3 fatty acids during pregnancy to reduce preterm birth.

Globally, preterm birth is the leading cause of death in children under the age of 5 years and survivors may suffer life-long consequences. Following many years of investigation, there is strong evidence that a proportion of preterm births can be prevented by increasing maternal dietary omega-3 long chain polyunsaturated fatty acid (LCPUFA) intake during pregnancy. This Statement provides a synthesis of contemporary evidence on the role of omega-3 LCPUFA on prevention of preterm birth and is designed to provide fatty acid-specific knowledge and guidance for medical practitioners, midwives, health services, professional bodies and policy makers to consider for their contextual situations. The evidence synthesis, which underpins this statement, is based on the 2018 Cochrane systematic review with supplemental evidence from RCTs completed since that time as well as other systematic reviews. Heterogeneity between studies was explored to understand how the effect of omega-3 supplementation may vary in different population groups and by dose and type of omega-3 supplementation. Most trials were conducted in upper-middle or high-income countries and the evidence are most applicable in those settings. The evidence synthesis confirmed that omega-3 LCPUFA, particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have an important role to play in determining gestational length in singleton pregnancies. Adequate intake of omega-3 LCPUFA in early pregnancy, consistent with existing nutritional guidelines, is associated with a lower risk of preterm and early preterm births for women with singleton pregnancies. Therefore, women with adequate omega-3 intakes in early pregnancy should maintain these intakes. Women who are low in omega-3 fatty acids will benefit most from omega-3 LCPUFA supplementation to reduce their risk of early birth. In such cases supplementation with a total of about 1000 mg of DHA plus EPA is effective at reducing risk of early birth, preferably with supplementation commencing before 20 weeks' gestation.

Effect of omega-3 lcpufa supplementation on maternal fatty acid and oxylipin concentrations during pregnancy.

INTRODUCTION: Omega-3 long chain polyunsaturated fatty acids (LCPUFA) have been associated with a reduction in risk for preterm birth. However, there is limited understanding of how fatty acids and their bioactive derivatives (oxylipins) change over the course of pregnancy. Here we document the changes in concentration of fatty acids and oxylipins during pregnancy and how fatty acid status and oxylipin concentrations are affected by supplementation with omega-3 LCPUFA. We also investigate the degree to which fatty acid and oxylipin changes across pregnancy are influenced by baseline omega-3 status. MATERIALS AND METHODS: We profiled the fatty acids in all lipids in dried blood spots (total blood fatty acids) by gas chromatography and free (unesterified) fatty acids and their associated oxylipins in separate dried blood spot samples by LC-MS-MS collected from a random sample of 1263 women with a singleton pregnancy who participated in the ORIP (Omega-3 fats to Reduce the Incidence of Prematurity) trial. ORIP is a double-blind, randomized controlled trial involving 5544 participants and designed to determine the effect of supplementing the diets of pregnant women with omega-3 LCPUFA on the incidence of early preterm birth. Maternal whole blood finger prick samples were collected at baseline (~14 weeks gestation) and at completion of the study intervention period (34 weeks gestation). RESULTS: The concentration of most total and free polyunsaturated fatty acids and their associated oxylipins declined over the course of pregnancy. Omega-3 LCPUFA supplementation increased total DHA and 7-HDHA and mitigated the decline in free DHA, 4-HDHA and 14-HDHA. The intervention had minimal or no effect on free EPA, LA, AA and their associated oxylipins. Omega-3 LCPUFA supplementation in women with higher omega-3 status at baseline was associated with a significant increase in 7-HDHA and 4-HDHA between the treatment and control whereas there were no differences between groups in 7-HDHA and 4-HDHA in women with intermediate or lower baseline omega-3 status. CONCLUSION: Our data suggest a differential response with or without omega-3 supplementation for DHA and DHA-derived oxylipins, which may have an important role to play in modulating pregnancy duration. Further work is needed to understand their role, which may allow us to better tailor omega-3 supplementation for preterm birth prevention.

Omega-3 fatty acid supplementation in pregnancy-baseline omega-3 status and early preterm birth: exploratory analysis of a randomised controlled trial.

OBJECTIVE: To identify a polyunsaturated fatty acid (PUFA) biomarker able to detect which women with singleton pregnancies are most likely to benefit from omega-3 supplementation to reduce their risk of early preterm birth. DESIGN: Exploratory analysis of a randomised controlled trial. SETTING: Six Australian hospitals. POPULATION: Women with a singleton pregnancy enrolled in the ORIP trial. METHODS: Using maternal capillary whole blood collected ~14 weeks' gestation, the fatty acids in total blood lipids were quantified using gas chromatography. Interaction tests examined whether baseline PUFA status modified the effect of omega-3 supplementation on birth outcomes. MAIN OUTCOME MEASURE: Early preterm birth (<34 weeks' gestation). RESULTS: A low total omega-3 PUFA status in early pregnancy was associated with a higher risk of early preterm birth. Among women with a total omega-3 status ≤4.1% of total fatty acids, omega-3 supplementation substantially reduced the risk of early preterm birth compared with control (0.73 versus 3.16%; relative risk = 0.23, 95% confidence interval [CI] 0.07-0.79). Conversely, women with higher total omega-3 status in early pregnancy were at lower risk of early preterm birth. Supplementing women with a baseline status above 4.9% increased early preterm birth (2.20 versus 0.97%; relative risk = 2.27, 95% CI 1.13-4.58). CONCLUSIONS: Women with singleton pregnancies and low total omega-3 PUFA status early in pregnancy have an increased risk of early preterm birth and are most likely to benefit from omega-3 supplementation to reduce this risk. Women with higher total omega-3 status are at lower risk and additional omega-3 supplementation may increase their risk. TWEETABLE ABSTRACT: Low total omega-3 fat status helps identify which women benefit from extra omega-3 to reduce early prematurity.

Exposure to maternal cafeteria diets during the suckling period has greater effects on fat deposition and Sterol Regulatory Element Binding Protein-1c (SREBP-1c) gene expression in rodent offspring compared to exposure before birth.

BACKGROUND: While the adverse metabolic effects of exposure to obesogenic diets during both the prenatal and early postnatal period are well established, the relative impact of exposure during these separate developmental windows remains unclear. This study aimed to assess the relative contribution of exposure to a maternal cafeteria diet during pregnancy and lactation on body weight, fat mass and expression of lipogenic and adipokine genes in the offspring. METHODS: Wistar rats were fed either a control chow (Control, n = 14) or obesogenic cafeteria diet (CAF, n = 12) during pregnancy and lactation. Pups were cross-fostered to another dam in either the same or different dietary group within 24 h of birth. Body weight, body fat mass and expression of lipogenic and adipokine genes in subcutaneous and visceral adipose tissues were determined in offspring at weaning and 3 weeks post-weaning. RESULTS: Offspring suckled by CAF dams had a lower body weight (P < 0.05), but ~ 2-fold higher percentage body fat at weaning than offspring suckled by Control dams (P < 0.01), independent of whether they were born to a Control or CAF dam. At 6 weeks of age, after all offspring were weaned onto standard chow, males and females suckled by CAF dams remained lighter (P < 0.05) than offspring suckled by Control dams, but the percentage fat mass was no longer different between groups. Sterol Regulatory Element Binding Protein-1c (SREBP-1c) mRNA expression was ~ 25% lower in offspring suckled by cafeteria dams in males at weaning (P < 0.05) and in females at 6 weeks of age (P < 0.05). Exposure to a cafeteria diet during the suckling period alone also resulted in increased adipocyte Peroxisome Proliferator Activated Receptor-γ (PPAR-γ) mRNA expression in females, and adiponectin and leptin mRNA expression in both sexes at weaning. CONCLUSIONS: The findings from this study point to the critical role of the suckling period for deposition of adipose tissue in rodents, and the potential role of altered adipocyte gene expression in mediating these effects.

The effect of maternal DHA supplementation on body fat mass in children at 7 years: follow-up of the DOMInO randomized controlled trial.

BACKGROUND: Animal studies have suggested that an increased supply of omega-3 long chain polyunsaturated fatty acids (LCPUFA), in particular docosahexaenoic acid (DHA), during the perinatal period can prevent later excess body fat mass. However, previous human studies have produced inconsistent findings, and few have assessed potential effects beyond 6 years of age. OBJECTIVE: To evaluate the effect of supplementing women in the second half of pregnancy with omega-3 LCPUFA, chiefly as DHA, on the percentage body fat of children at 7 years of age, as assessed by two methods: air displacement plethysmography (BOD POD) and bioelectrical impedance spectroscopy (BIS). DESIGN: A time-restricted follow up at 7 years of age of children born to mothers enrolled in DOMInO (DHA to Optimise Maternal Infant Outcome) randomized controlled trial, in which women took either high-DHA tuna oil (800mg/day DHA) or placebo capsules from 20 weeks' gestation to delivery, at Adelaide-based centers. Primary outcomes were the percentage body fat at 7 years of age as assessed by both BOD POD and BIS. Weight, height, waist/hip circumferences and BMI were also recorded. RESULTS: A total of 252 DOMInO children (n=135 males, n=117 females) completed the follow up study. There were no differences between the DHA and placebo groups in percentage body fat as assessed by either BOD POD [adjusted mean difference: -0.35, 95% CI: -1.46, 2.16; P=0.71] or BIS [adjusted mean difference: 0.64, 95% CI: -0.99, 2.27; P=0.44]. BMI z-scores were also similar between groups [adjusted mean difference: 0.18, 95% CI: -0.10, 0.45; P=0.21]. There were also no differences in height, weight or waist and hip circumference between the DHA and placebo groups at 7 years of age. CONCLUSION: DHA supplementation in the second half of pregnancy has no effect on childhood growth or fat mass at 7 years of age, supporting findings from follow ups of the DOMInO children at 3 and 5 years.

DNA methylation in blood from neonatal screening cards and the association with BMI and insulin sensitivity in early childhood.

BACKGROUND/OBJECTIVES: There is increasing evidence that metabolic diseases originate in early life, and epigenetic changes have been implicated as key drivers of this early life programming. This led to the hypothesis that epigenetic marks present at birth may predict an individual's future risk of obesity and type 2 diabetes. In this study, we assessed whether epigenetic marks in blood of newborn children were associated with body mass index (BMI) and insulin sensitivity later in childhood. SUBJECTS/METHODS: DNA methylation was measured in neonatal blood spot samples of 438 children using the Illumina Infinium 450 k BeadChip. Associations were assessed between DNA methylation at birth and BMI z-scores, body fat mass, fasting plasma glucose, insulin and homeostatic model assessment of insulin resistance (HOMA-IR) at age 5 years, as well as birth weight, maternal BMI and smoking status. RESULTS: No individual methylation sites at birth were associated with obesity or insulin sensitivity measures at 5 years. DNA methylation in 69 genomic regions at birth was associated with BMI z-scores at age 5 years, and in 63 regions with HOMA-IR. The methylation changes were generally small (<5%), except for a region near the non-coding RNA nc886 (VTRNA2-1) where a clear link between methylation status at birth and BMI in childhood was observed (P=0.001). Associations were also found between DNA methylation, maternal smoking and birth weight. CONCLUSIONS: We identified a number of DNA methylation regions at birth that were associated with obesity or insulin sensitivity measurements in childhood. These findings support the mounting evidence on the role of epigenetics in programming of metabolic health. Whether many of these small changes in DNA methylation are causally related to the health outcomes, and of clinical relevance, remains to be determined, but the nc886 region represents a promising obesity risk marker that warrants further investigation.

Predicting the effect of maternal docosahexaenoic acid (DHA) supplementation to reduce early preterm birth in Australia and the United States using results of within country randomized controlled trials.

The DHA to Optimize Mother Infant Outcome (DOMInO) and Kansas DHA Outcomes Study (KUDOS) were randomized controlled trials that supplemented mothers with 800 and 600mg DHA/day, respectively, or a placebo during pregnancy. DOMInO was conducted in Australia and KUDOS in the United States. Both trials found an unanticipated and statistically significant reduction in early preterm birth (ePTB; i.e., birth before 34 weeks gestation). However, in each trial, the number of ePTBs were small. We used a novel Bayesian approach to estimate statistically derived low, moderate or high risk for ePTB, and to test for differences between the DHA and placebo groups. In both trials, the model predicted DHA would significantly reduce the expected proportion of deliveries in the high risk group under the trial conditions of the parent studies. Among the next 300,000 births in Australia we estimated that 1112 ePTB (95% credible interval 51-2189) could be avoided by providing DHA. And in the USA we estimated that 106,030 ePTB (95% credible interval 6400 to 175,700) could be avoided with DHA.

Effect of a maternal cafeteria diet on the fatty acid composition of milk and offspring red blood cells.

Previous studies have demonstrated that exposure to a maternal cafeteria diet during the lactation period alone produces detrimental effects to offspring metabolic health comparable to exposure during the entire perinatal period. The present study used a rodent model to assess the effect of a maternal cafeteria diet on the fat content and fatty acid composition of the dams' milk, and to determine the degree to which this was related to the fatty acid status of offspring on postnatal day 1 (PND1), weaning and 3 weeks post-weaning onto a standard rodent diet. As expected, omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) content of both the milk and pup red blood cells (RBCs) was lower in the cafeteria (CAF) group on PND1. At 2 weeks post-partum, milk produced by CAF dams had a higher total fat, saturated fat and n-6 PUFA content, however these differences were modest in comparison with the differences in maternal intake between groups. Offspring suckled by CAF dams had a lower n-3 LCPUFA and n-6 PUFA status at weaning and higher trans fatty acid levels at both weaning and 6 weeks of age. These findings indicate that the fat content and fatty acid composition of the dam's milk is altered by exposure to a cafeteria diet. While it appears that the dam has a significant capacity to buffer the transfer of most dietary lipids into the milk, the trans fatty acids in particular appear to be readily transferred, resulting in persistent increases in trans fatty acid status of the offspring after weaning. The potential physiological implications of this warrants further examination.

Maternal characteristics influence response to DHA during pregnancy.

We explored the degree to which maternal and offspring outcomes resulting from consuming prenatal docosahexaenoic acid (DHA, 800mg/day) in a clinical trial were influenced by maternal characteristics. Among non-smokers, women who received DHA had heavier babies (adjusted mean difference (MD)=99g 95% CI 45-153, p<0.01; interaction p=0.01) and fewer low birth weight babies than control women (adjusted relative risk=0.43 95% CI 0.25-0.74, p<0.01; interaction p=0.01). From women who had not completed further education, children in the DHA group had higher cognitive scores at 18 months compared with control children (adjusted MD=3.15 95% CI 0.93-5.37, p=0.01; interaction p<0.01). Conversely, the children of women who completed further education in the DHA group had lower language scores than control children (adjusted MD -2.82 95% CI -4.90 to -0.73, p=0.01; interaction p=0.04). Our results support the notion that responsiveness to prenatal DHA may depend on the characteristics of specific population subgroups.

A dose response randomised controlled trial of docosahexaenoic acid (DHA) in preterm infants.

Thirty one infants born less than 30 weeks׳ gestational age were randomised to receive either 40 (n=11), 80 (n=9) or 120 (n=11) mg/kg/day of docosahexaenoic acid (DHA) respectively as an emulsion, via the feeding tube, commenced within 4 days of the first enteral feed. Twenty three infants were enroled in non-randomised reference groups; n=11 who had no supplementary DHA and n=12 who had maternal DHA supplementation. All levels of DHA in the emulsion were well tolerated with no effect on number of days of interrupted feeds or days to full enteral feeds. DHA levels in diets were directly related to blood DHA levels but were unrelated to arachidonic acid (AA) levels. All randomised groups and the maternal supplementation reference group prevented the drop in DHA levels at study end that was evident in infants not receiving supplementation. Australian New Zealand Clinical Trials Registry: ACTRN12610000382077.

The effect of modifying dietary LA and ALA intakes on omega-3 long chain polyunsaturated fatty acid (n-3 LCPUFA) status in human adults: a systematic review and commentary.

This paper presents a systematic review of human studies investigating the effect of altering dietary omega-3 polyunsaturated fatty acid (n-3 PUFA) alpha-linolenic acid (ALA) and omega-6 polyunsaturated fatty acid (n-6 PUFA) linoleic acid (LA) intakes on n-3 long-chain polyunsaturated fatty acid (LCPUFA) status in adult humans. The results suggest that it is possible to increase n-3 LCPUFA status by reducing LA and/or increasing ALA intake in humans, although decreasing LA intake to below 2.5%E may be required to specifically increase levels of the n-3 LCPUFA docosahexaenoic acid (DHA). The majority of studies in this area to date have been relatively poor in quality, which limits the ability to draw robust conclusions, and we present a series of recommendations to improve the quality of future studies in fatty acid nutrition in humans.

Heterogeneity in cord blood DHA concentration: towards an explanation.

This paper aimed to identify the dietary and non-dietary determinants of docosahexaenoic acid (DHA) levels in umbilical cord blood at delivery. DHA was measured in cord blood plasma phospholipids of 1571 participants from the DOMInO (DHA to Optimize Mother Infant Outcome) randomized controlled trial. Socioeconomic, lifestyle and clinical data relating to the mother and current pregnancy were obtained from all women and their relationships with cord blood DHA assessed. DHA concentrations in the cord plasma phospholipids at delivery covered a 3-4 fold range in both control and DHA groups. The total number of DHA-rich intervention supplement capsules consumed over the course of pregnancy and gestational age at delivery individually explained 21% and 16% respectively of the variation in DHA abundance in the cord blood plasma phospholipids at delivery, but no other clinical or life-style factors explored in this study could account for >2% of the variation. Indeed, more than 65% of the variation remained unaccounted for even when all factors were included in the analysis. These data suggest that factors other than maternal DHA intake have an important role in determining cord blood DHA concentrations at delivery, and may at least partially explain the variation in the response of infants to maternal DHA supplementation reported in published trials.

A low omega-6 polyunsaturated fatty acid (n-6 PUFA) diet increases omega-3 (n-3) long chain PUFA status in plasma phospholipids in humans.

This study aimed to determine the effect of reducing the dietary linoleic acid (LA) intake from ~5% to <2.5% energy (%E) on n-3 long chain PUFA (LCPUFA) status in humans. Thirty-six participants followed a <2.5%E LA diet for 4 weeks. Nutrient intakes were estimated from diet diaries and blood samples were collected for assessment of fatty acid composition in plasma and erythrocyte phospholipids. LA intakes were reduced from 4.6%E to 2%E during the low LA intervention (P<0.001) while n-3 LCPUFA intakes were unchanged. LA and total n-6 PUFA content of plasma and erythrocyte phospholipids were significantly reduced after the low LA diet phase (P<0.001). The n-3 LCPUFA content of plasma phospholipids was significantly increased after the low LA diet compared to baseline (6.22% vs. 5.53%, P<0.001). These data demonstrate that reducing LA intake for 4 weeks increases n-3 LCPUFA status in humans in the absence of increased n-3 LCPUFA intake.

U-shaped relationship between tissue docosahexaenoic acid and atrial fibrillation following cardiac surgery.

BACKGROUND/OBJECTIVES: Randomised controlled trials (RCTs) evaluating the effect of fish oil supplementation on postoperative atrial fibrillation (POAF) following cardiac surgery have produced mixed results. In this study, we examined relationships between levels of red blood cell (RBC) n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) and the incidence of POAF. SUBJECTS/METHODS: We used combined data (n=355) from RCTs conducted in Australia and Iceland. The primary end point was defined as POAF lasting >10 min in the first 6 days following surgery. The odds ratios (ORs) for POAF were compared between quintiles of preoperative RBC n-3 LC-PUFA levels by multivariable logistic regression. RESULTS: Subjects with RBC docosahexaenoic acid (DHA) in the fourth quintile, comprising a RBC DHA range of 7.0-7.9%, had the lowest incidence of POAF. Subjects in the lowest and highest quintiles had significantly higher risk of developing POAF compared with those in the fourth quintile (OR=2.36: 95% CI; 1.07-5.24 and OR=2.45: 95% CI; 1.16-5.17, respectively). There was no association between RBC eicosapentaenoic acid levels and POAF incidence. CONCLUSIONS: The results suggest a 'U-shaped' relationship between RBC DHA levels and POAF incidence. The possibility of increased risk of POAF at high levels of DHA suggests an upper limit for n-3 LC-PUFAs in certain conditions.

Effect of dietary canola oil on long-chain omega-3 fatty acid content in broiler hearts.

Young and healthy broilers are susceptible to sudden death syndrome (SDS), which is caused by cardiac arrhythmia. The long-chain 'fish-type' omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have cardioprotective anti-arrhythmic effects in animals and humans. Raising the cardiac level of EPA and DHA in chickens may protect against SDS. However, fish oil as a source of EPA and DHA in poultry feed is costly and introduces undesirable properties to the meat. Whilst omega-3 vegetable oils, such as canola oil, are cheaper and do not have a strong odour, they contain the short-chain fatty acid α-linolenic acid, which requires conversion to EPA and DHA after ingestion. We investigated the capacity for dietary canola oil to elevate cardiac EPA and DHA in broilers. Broilers were fed with diets containing either 3% canola oil or tallow, which is currently used in some commercial feeds. Upon completion of a 42 day feeding trial, canola oil significantly increased EPA and EPA + DHA in heart phospholipids relative to tallow. The elevation in cardiac EPA and EPA + DHA may provide anti-arrhythmic effects and protect against SDS in poultry. This proof-of-concept biochemical study suggests that a larger study to assess the clinical outcome of SDS may be warranted.

Randomized controlled trial of fish oil supplementation in pregnancy on childhood allergies.

BACKGROUND: Diets high in n-3 long chain polyunsaturated fatty acids (LCPUFA) may modulate the development of IgE-mediated allergic disease and have been proposed as a possible allergy prevention strategy. The aim of this study was to determine whether n-3 LCPUFA supplementation of pregnant women reduces IgE-mediated allergic disease in their children. METHODS: Follow-up of children (n = 706) at hereditary risk of allergic disease in the Docosahexaenoic Acid to Optimise Mother Infant Outcome randomized controlled trial. The intervention group (n = 368) was randomly allocated to receive fish oil capsules (providing 900 mg of n-3 LCPUFA daily) from 21 weeks' gestation until birth; the control group (n = 338) received matched vegetable oil capsules without n-3 LCPUFA. The diagnosis of allergic disease was made during medical assessments at 1 and 3 years of age. RESULTS: No differences were seen in the overall percentage of children with IgE-mediated allergic disease in the first 3 years of life between the n-3 LCPUFA and control groups (64/368 (17.3%) vs 76/338 (22.6%); adjusted relative risk 0.78; 95% CI 0.58-1.06; P = 0.11). Eczema was the most common allergic disease; 13.8% of children in the n-3 LCPUFA group had eczema with sensitization compared with 19.0% in the control group (adjusted relative risk 0.75; 95% CI 0.53-1.05; P = 0.10). CONCLUSIONS: Overall, n-3 LCPUFA supplementation during pregnancy did not significantly reduce IgE-associated allergic disease in the first 3 years of life. Further studies should examine whether the nonsignificant reductions in IgE-associated allergies are of clinical and public health significance.

Dietary and ontogenic regulation of fatty acid desaturase and elongase expression in broiler chickens.

Effects of diet and ontogeny on the expression of fatty acid desaturases and elongases were examined in broiler chickens. In Study 1, 120 day-old male chicks received one of six diets with LA:ALA ranging from 46:4 to 16:34, for 33 days. Total n-6 PUFA decreased, and n-3 PUFA increased in response to a decrease in the dietary LA:ALA. FADS1, FADS2, ELOVL2 and ELOVL5 mRNAs were highest (P<0.05) in birds fed lower LA:ALA diets. In Study 2, 60 day-old male chicks were fed a basal diet, and liver samples were collected on day of hatch, and on days 2, 7, 14, 21 and 35 post-hatch. Total n-6 and n-3 PUFA increased (P<0.01) from days 7 to days 21. FADS1, FADS2 and ELOVL2 mRNAs generally increased (P<0.01) with age. These findings provide evidence for the dietary and developmental regulation of PUFA metabolism in broiler chickens.