Understanding the effects of docosahexaenoic acid (DHA) supplementation during pregnancy on multiple outcomes from the DOMInO trial

Title, Abstract and Keywords in English and French. French title: Comprendre les effets de la supplémentation en acide docosahexaénoïque (DHA) pendant la grossesse sur de multiples paramètres à partir de l’étude DOMIn0.Docosahexaenoic acid (DHA) has been postulated to extend the period of gestation, increase birth weight, enhance neurodevelopment and reduce the risk of allergic disease. Because of its large sample size and relatively broad inclusion criteria, the DOMInO (DHA to Optimise Mother Infant Outcome) trial offers the opportunity to explore the effect of prenatal DHA supplementation of multiple outcomes. Overall, the DOMInO trial showed that prenatal DHA supplementation increases the length of gestation, reduces the risk of early preterm and low birth weight, has little or no effect on maternal postpartum depression and early childhood neurodevelopment but reduces the risk of atopic eczema and sensitisation in the first year of life. The clinical utility of prenatal DHA supplementation of reducing early birth is important and requires further investigation. = Il a été envisagé que l’acide docosahexaénoïque (DHA) puisse prolonger la période de gestation, augmenter le poids de naissance, renforcer le développement neurologique et réduire le risque de maladie allergique. En raison de la grande taille de son échantillon et de critères d’inclusion relativement larges, l’étude DOMInO (DHA to Optimise Mother Infant Outcome) offre l’occasion d’explorer l’effet d’une supplémentation prénatale en DHA sur de multiples paramètres. Dans l’ensemble, l’étude DOMInO a montré que la supplémentation prénatale en DHA augmente la durée de la gestation, réduit le risque de prématurité précoce et de faible poids de naissance, a peu ou pas d’effet sur la dépression maternelle post-partum et sur le développement neurologique durant la petite enfance, mais réduit le risque d’eczéma atopique et de sensibilisation dans la première année de la vie. L’utilité clinique d’une supplémentation prénatale en DHA afin de réduire les naissances avant terme est importante et nécessite une enquête plus approfondie.Maria Makride

Several new catalysts for reduction of oxygen in fuel cells

Test results prove nickel carbide or nitride, nickel-cobalt carbide, titanium carbide or nitride, and intermetallic compounds of the transition or noble metals to be efficient electrocatalysts for oxygen reduction in alkaline electrolytes in low temperature fuel cells

Effects of Early Diet on Childhood Allergy

Merryn Netting and Maria Makride

Dietary alpha-linolenic acid enhances omega-3 long chain polyunsaturated fatty acid levels in chicken tissues

The effects of enriching broiler chicken diets with a vegetable source of n−3 fat in the form of alpha- linolenic acid (ALA, 18:3n−3) on the accumulation of n−3 long chain polyunsaturated fatty acids (LCPUFA) in chicken meat were investigated. Sixty unsexed one-day-old broiler chickens (Cobb 500) were randomly allocated to one of six diets (n=10 birds/diet) for 4 weeks. The ALA levels varied from 1 to 8% energy (%en) while the level of the n−6 fatty acid linoleic acid (LA, 18:2n−6) was held to less than 5%en in all diets. At harvest (day 28) the levels of n−3 LCPUFA including eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) in breast and thigh meat increased in a curvilinear manner as dietary ALA increased, reaching 4- to 9-fold above the levels seen in control birds. In contrast, arachidonic acid (AA) was reduced in response to increasing dietary ALA

Importance of adequate sample sizes in fatty acid intervention trials

Abstract not availableLisa N. Yelland, Maria Makrides, Andrew J. McPhee, Julie Quinlivan, Robert A. Gibso

LCPUFAs as conditionally essential nutrients for very low birth weight and low birth weight infants. metabolic, functional, and clinical outcomes - how much is enough?

Preterm infants are denied the rapid accumulation of docosahexaenoic acid (DHA) occurring during the third trimester in utero. The potential benefit of long-chain polyunsaturated fatty acids (LCPUFAs) has generated interest over the last 3 decades. Early intervention trials assessed the effects of supplementing infant formulas lacking DHA with concentrations equivalent to LCPUFA in milk of women from Westernized societies, leading to the inclusion of LCPUFA by the year 2000. Recently attention has been on determining the optimal dose of DHA and on whether there is in advantage in matching the higher doses of late pregnancy.Maria Makrides, Ricardo Uau

Steady-state kinetic characterization of the mouse B0AT1 sodium-dependent neutral amino acid transporter

The members of the neurotransmitter transporter family SLC6A exhibit a high degree of structural homology; however differences arise in many aspects of their transport mechanisms. In this study we report that mouse B0AT1 (mouse Slc6a19) mediates the electrogenic transport of a broad range of neutral amino acids but not of the chemically similar substrates transported by other SLC6A family members. Cotransport of L-Leu and Na+ generates a saturable, reversible, inward current with Michaelis-Menten kinetics (Hill coefficient ~1) yielding a K0.5 for L-Leu of 1.16mM and for Na+ of 16mM at a holding potential of −50mV. Changing the membrane voltage influences both substrate binding and substrate translocation. Li+ can substitute partially for Na+ in the generation of L-Leu-evoked inward currents, whereas both Cl− and H+ concentrations influence its magnitude. The simultaneous measurement of charge translocation and L-Leu uptake in the same cell indicates that B0AT1 transports one Na+ per neutral amino acid. This appears to be accomplished by an ordered, simultaneous mechanism, with the amino acid binding prior to the Na+, followed by the simultaneous translocation of both co-substrates across the plasma membrane. From this kinetic analysis, we conclude that the relatively constant [Na+] along the renal proximal tubule both drives the uptake of neutral amino acids via B0AT1 thermodynamically and ensures that, upon binding, these are translocated efficiently into the cel

Comparison of dichotomized and distributional approaches in rare event clinical trial design: a fixed Bayesian design

Accepted 14 July 2016This research was motivated by our goal to design an efficient clinical trial to compare two doses of docosahexaenoic acid supplementation for reducing the rate of earliest preterm births (ePTB) and/or preterm births (PTB). Dichotomizing continuous gestational age (GA) data using a classic binomial distribution will result in a loss of information and reduced power. A distributional approach is an improved strategy to retain statistical power from the continuous distribution. However, appropriate distributions that fit the data properly, particularly in the tails, must be chosen, especially when the data are skewed. A recent study proposed a skew-normal method. We propose a three-component normal mixture model and introduce separate treatment effects at different components of GA. We evaluate operating characteristics of mixture model, beta-binomial model, and skew-normal model through simulation. We also apply these three methods to data from two completed clinical trials from the USA and Australia. Finite mixture models are shown to have favorable properties in PTB analysis but minimal benefit for ePTB analysis. Normal models on log-transformed data have the largest bias. Therefore we recommend finite mixture model for PTB study. Either finite mixture model or beta-binomial model is acceptable for ePTB study.Yang Lei, Susan Carlson, Lisa N. Yelland, Maria Makrides, Robert Gibson and Byron J. Gajewsk

Can we identify women who initiate and then prematurely cease breastfeeding? An Australian multicentre cohort study

Background: Health authorities recommend 6 months of fully breastfeeding and continuation of breastfeeding for at least a year. Many women initiate breastfeeding in hospital but discontinue before the six-month period, and therefore do not optimise the public health benefits. The aim of this study was to determine whether these women could be identified at hospital discharge, to enable targeted interventions. Methods: A secondary analysis of women who intended to breastfeed and were enrolled in a large randomized trial was undertaken. Women were enrolled in the antenatal period and antenatal, delivery and six month postnatal questionnaires were completed. Univariate and multivariate analyses were undertaken to determine the variables associated with early cessation of breastfeeding within six months, compared to women who continued to breastfeed. Results: Of 2148 women who initiated breastfeeding in hospital, 877 continued to breastfed either partially (N = 262) or fully (N = 615) until six months postpartum and 1271 ceased breastfeeding early. Median breastfeeding duration in women who ceased early was 3+6 weeks (IQR 1+1 to 11+2 weeks). In multivariate analysis, factors that were significantly associated with early cessation of breastfeeding were maternal factors of lower education (less than 12 years of schooling, no completion of further education), smoking (pre-pregnancy or during pregnancy), and newborn factors of preterm birth and low birthweight (all p \u3c 0.01). These variables correctly identify 83% of women. Conclusion: We can identify women who initiate and then prematurely discontinue breastfeeding prior to hospital discharge. Evaluation of additional interventions to support longer duration of breastfeeding in women at risk of ceasing prematurely is needed