BACKGROUND AND OBJECTIVE: Evidence from randomized controlled trials in early infancy suggest that prenatal supplementation with Ω-3 (n-3) long-chain polyunsaturated fatty acids (LCPUFA) reduces the incidence of allergic disease characterized by an immunoglobulin E (IgE) response. We aimed to determine whether protective effects were evident in the 6-year-old offspring of women supplemented with n-3 rich fish oil during pregnancy.

Our systematic review and meta-analysis was suggestive of benefits of increased n-3 LC-PUFAs in the maternal diet and outcomes of childhood allergic disease. However, due to the inconsistency in results, the hypothesis linking maternal n-3 LC-PUFA intake to childhood allergic disease cannot unequivocally be confirmed or rejected.

In addition to providing nutritional and bioactive factors necessary for infant development, human breast milk contains bacteria that contribute to the establishment of commensal microbiota in the infant. However, the composition of this bacterial community differs considerably between studies. We hypothesised that bacterial DnA extraction methodology from breast milk samples are a substantial contributor to these inter-study differences. We tested this hypothesis by applying five widely employed methodologies to a mock breast milk sample and four individual human breast milk samples. Significant differences in DNA yield and purity were observed between methods (P < 0.05). Microbiota composition, assessed by 16S rRNA gene amplicon sequencing, also differed significantly with extraction methodology (P < 0.05), including in the contribution of contaminant signal. Concerningly, many of the bacterial taxa identified here as contaminants have been reported as components of the breast milk microbiome in other studies. These findings highlight the importance of using stringent, well-validated, DNA extraction methodologies for analysis of the breast milk microbiome, and exercising caution interpreting microbiota data from low-biomass contexts. In addition to nutrients and bioactive components, human breast milk contains bacteria 1 , commonly referred to as the breast milk microbiome. These bacterial populations are thought to contribute to the establishment of commensal bacterial communities in the infant, as well as supporting the maturation of the gut, and development of the immune system 1,2. The potential importance of microbes introduced with breast milk on early-life development has led to increasing efforts to accurately define them. Early culture-and PCR-based methods, predominantly reported the presence of members of the Staphylococcus, Streptococcus, Lactobacillus and Bifidobacterium genera 3-12. More recently, 16S rRNA gene amplicon sequencing has become an increasingly popular approach to characterising the bacterial content of breast milk samples 13-33. By enabling the detection of species that are refractory to standard culture methodologies, as well as providing insight into the relative abundance of constitutive bacteria, 16S rRNA gene sequencing offers substantial analytical advantages. However, the composition of the breast milk microbiome reported in sequencing-based studies varies substantially. For example, while two studies have described a "core" human breast milk microbiome (bacteria that are present in all samples analysed) from healthy mothers, consisting of 7 and 9 taxa respectively, only three of these taxa were present in both (Propionibacterium, Staphylococcus, and Streptococcus) 27,34. Notably, many of the other bacterial taxa often reported as part of the breast milk microbiome, including

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.

BackgroundRandomized controlled trials of prenatal omega (ω-3) long chain polyunsaturated fatty acid (LCPUFA) supplementation are suggestive of some protective effects on allergic sensitization and symptoms of allergic disease in childhood. Due to the nature of the atopic march, investigation of any effects of this prenatal intervention may be most informative when consistently assessed longitudinally during childhood.MethodsFollow-up of children (n = 706) with familial risk of allergy from the Docosahexaenoic Acid to Optimize Mother Infant Outcome (DOMInO) trial. The intervention group received fish oil capsules (900 mg of ω-3 LCPUFA) daily from <21 weeks’ gestation until birth; the control group received vegetable oil capsules without ω-3 LCPUFA. This new longitudinal analysis reports previously unpublished data collected at 1 and 3 years of age. The allergic disease symptom data at 1, 3 and 6 years of age were consistently reported by parents using the "International Study of Asthma and Allergies in Childhood" (ISAAC) questionnaire. Sensitization was determined by skin prick test to age specific, common allergen extracts.ResultsChanges over time in symptoms of allergic disease with sensitization (IgE-mediated) and sensitization did not differ between the groups; interaction p = 0.49, p = 0.10, respectively. Averaged across the 1, 3 and 6-year assessments, there were no significant effects of prenatal ω-3 LCPUFA supplementation on IgE-mediated allergic disease symptoms (adjusted relative risk 0.88 (95% CI 0.69, 1.12), p = 0.29) or sensitization (adjusted relative risk 0.97 (95% CI 0.82, 1.15), p = 0.76). Sensitization patterns to common allergens were consistent with the atopic march, with egg sensitization at 1 year strongly associated with house dust mite sensitization at 6 years, (p < 0.0001).DiscussionAlthough there is some evidence to suggest that maternal supplementation with 900mg ω-3 LCPUFA has a protective effect on early symptoms of allergic disease and sensitization in the offspring, we did not observe any differences in the progression of disease over time in this longitudinal analysis. Further investigation into the dose and timing of ω-3 LCPUFA supplementation, including long-term follow up of children using consistent outcome reporting, is essential to determine whether this intervention may be of benefit as a primary prevention strategy for allergic disease.ConclusionMaternal supplementation with 900 mg of ω-3 LCPUFA did not change the progression of IgE-mediated allergic disease symptoms or sensitization throughout childhood from 1 to 6 years.Trial registrationAustralian New Zealand Clinical Trials Registry (ACTRN); DOMInO trial ACTRN12605000569606, early childhood allergy follow up ACTRN12610000735055 and 6-year allergy follow up ACTRN12615000498594.

BACKGROUND Previous studies have suggested that maternal supplementation with n−3 long-chain polyunsaturated fatty acids may reduce the incidence of preterm delivery but may also prolong gestation beyond term; however, more data are needed regarding the role of n−3 long-chain polyunsaturated fatty acids in pregnancy. METHODS We performed a multicenter, double-blind, randomized trial in which women who were pregnant with single or multiple fetuses were assigned to receive either fish-oil capsules that contained 900 mg of n−3 long-chain polyunsaturated fatty acids (n−3 group) or vegetable-oil capsules that contained trace n−3 long-chain polyunsaturated fatty acids (control group) daily, beginning before 20 weeks of gestation and continuing to 34 weeks of gestation or delivery, whichever occurred first. The primary outcome was early preterm delivery, defined as delivery before 34 completed weeks of gestation. Other pregnancy and neonatal outcomes were also assessed. RESULTS A total of 5544 pregnancies in 5517 women were randomly assigned at six centers in Australia; 5486 pregnancies were included in the primary analysis. Early preterm delivery occurred in the case of 61 of 2734 pregnancies (2.2%) in the n−3 group and 55 of 2752 pregnancies (2.0%) in the control group; the between-group difference was not significant (adjusted relative risk, 1.13; 95% confidence interval [CI], 0.79 to 1.63; P = 0.50). There were no significant differences between the groups in the incidence of interventions in post-term (>41 weeks of gestation) deliveries, in adverse events, or in other pregnancy or neonatal outcomes, except that a higher percentage of infants born to women in the n−3 group than in the control group were very large for gestational age at birth (adjusted relative risk, 1.30; 95% CI, 1.02 to 1.65). Percentages of serious adverse events did not differ between the groups. Minor gastrointestinal disturbances were more commonly reported in the n−3 group than in the control group. CONCLUSIONS Supplementation with n−3 long-chain polyunsaturated fatty acids from early pregnancy (<20 weeks of gestation) until 34 weeks of gestation did not result in a lower incidence of early preterm delivery or a higher incidence of interventions in post-term deliveries than control.

No abstract

R. (2019). A randomized trial of prenatal n-3 fatty acid supplementation and preterm delivery. R. (2019) A randomized trial of prenatal n-3 fatty acid supplementation and preterm delivery.