Andrew J. McPhee

Antenatal lifestyle advice for women who are overweight or obese: LIMIT randomised trial

Objective To determine the effect of antenatal dietary and lifestyle interventions on health outcomes in overweight and obese pregnant women. Design Multicentre randomised trial. We utilised a central telephone randomisation server, with computer generated schedule, balanced variable blocks, and stratification for parity, body mass index (BMI) category, and hospital. Setting Three public maternity hospitals across South Australia. Participants 2212 women with a singleton pregnancy, between 10+0 and 20+0 weeks’ gestation, and BMI ≥25. Interventions 1108 women were randomised to a comprehensive dietary and lifestyle intervention delivered by research staff; 1104 were randomised to standard care and received pregnancy care according to local guidelines, which did not include such information. Main outcome measures Incidence of infants born large for gestational age (birth weight ≥90th centile for gestation and sex). Prespecified secondary outcomes included birth weight >4000 g, hypertension, pre-eclampsia, and gestational diabetes. Analyses used intention to treat principles. Results 2152 women and 2142 liveborn infants were included in the analyses. The risk of the infant being large for gestational age was not significantly different in the two groups (lifestyle advice 203/1075 (19%) v standard care 224/1067 (21%); adjusted relative risk 0.90, 95% confidence interval 0.77 to 1.07; P=0.24). Infants born to women after lifestyle advice were significantly less likely to have birth weight above 4000 g (lifestyle advice 164/1075 (15%) v standard care 201/1067 (19%); 0.82, 0.68 to 0.99; number needed to treat (NNT) 28, 15 to 263; P=0.04). There were no differences in maternal pregnancy and birth outcomes between the two treatment groups. Conclusions For women who were overweight or obese, the antenatal lifestyle advice used in this study did not reduce the risk delivering a baby weighing above the 90th centile for gestational age and sex or improve maternal pregnancy and birth outcomes. Trial registration Australian and New Zealand Clinical Trials Registry (ACTRN12607000161426).

Limiting weight gain in overweight and obese women during pregnancy to improve health outcomes: the LIMIT randomised controlled trial

BackgroundObesity is a significant global health problem, with the proportion of women entering pregnancy with a body mass index greater than or equal to 25 kg/m2 approaching 50%. Obesity during pregnancy is associated with a well-recognised increased risk of adverse health outcomes both for the woman and her infant, however there is more limited information available regarding effective interventions to improve health outcomes.The aims of this randomised controlled trial are to assess whether the implementation of a package of dietary and lifestyle advice to overweight and obese women during pregnancy to limit gestational weight gain is effective in improving maternal, fetal and infant health outcomes.Methods/DesignDesign: Multicentred randomised, controlled trial.Inclusion Criteria: Women with a singleton, live gestation between 10+0-20+0 weeks who are obese or overweight (defined as body mass index greater than or equal to 25 kg/m2), at the first antenatal visit.Trial Entry & Randomisation: Eligible, consenting women will be randomised between 10+0 and 20+0 weeks gestation using a central telephone randomisation service, and randomisation schedule prepared by non-clinical research staff with balanced variable blocks. Stratification will be according to maternal BMI at trial entry, parity, and centre where planned to give birth.Treatment Schedules: Women randomised to the Dietary and Lifestyle Advice Group will receive a series of inputs from research assistants and research dietician to limit gestational weight gain, and will include a combination of dietary, exercise and behavioural strategies.Women randomised to the Standard Care Group will continue to receive their pregnancy care according to local hospital guidelines, which does not currently include routine provision of dietary, lifestyle and behavioural advice.Outcome assessors will be blinded to the allocated treatment group.Primary Study Outcome: infant large for gestational age (defined as infant birth weight ≥ 90th centile for gestational age).Sample Size: 2,180 women to detect a 30% reduction in large for gestational age infants from 14.40% (p = 0.05, 80% power, two-tailed).DiscussionThis is a protocol for a randomised trial. The findings will contribute to the development of evidence based clinical practice guidelines.Trial RegistrationAustralian and New Zealand Clinical Trials Registry ACTRN12607000161426

Effects of birthweight and oxygen supplementation on lung function in late childhood in children of very low birth weight

Impaired respiratory function has been found frequently in ex‐premature children, but it is unclear which specific factors influence this impairment the most. The aim of this study was to determine the importance of the contributions of birth weight, gestational age, neonatal respiratory disease, and its treatment on subsequent childhood lung function at age 11 years in a cohort of children of very low birth weight (VLBW; ≤1,500 g). Detailed clinical histories were recorded, and lung function was measured in 60% (102 children) of surviving VLBW infants born 1981/1982, and compared with 82 matched control children (birth weight >2,000 g) of similar age.

Late-onset infections of infants in neonatal units

Objective: To examine regional variations in the incidence of late‐onset neonatal infections in Australian and New Zealand neonatal units.

The effects of antenatal dietary and lifestyle advice for women who are overweight or obese on maternal diet and physical activity: the LIMIT randomised trial

BackgroundOverweight and obesity is a significant health concern during pregnancy. Our aim was to investigate the effect of providing antenatal dietary and lifestyle advice to women who are overweight or obese on components of maternal diet and physical activity.MethodsWe conducted a randomised controlled trial, in which pregnant women with a body mass index ≥25 kg/m2, and singleton gestation between 10+0 to 20+0 weeks were recruited and randomised to Lifestyle Advice (involving a comprehensive dietary and lifestyle intervention over their pregnancy) or Standard Care. Within the intervention group, we conducted a nested randomised trial in which a subgroup of women were further randomised to receive access to supervised group walking sessions in addition to the standard information presented during the intervention contacts (the Walking group) or standard information only.The outcome measures were maternal dietary intake, (including food groups, macronutrient and micronutrient intake, diet quality (using the Healthy Eating Index; HEI), dietary glycaemic load, and glycaemic index) and maternal physical activity. Women completed the Harvard Semi-Structured Food Frequency Questionnaire, and the Short Questionnaire to Assess Health-enhancing Physical Activity (SQUASH), at trial entry, 28 and 36 weeks’ gestational age, and 4 months postpartum.Analyses were performed on an intention-to-treat basis, using linear mixed effects models with adjustment for the stratification variables.ResultsWomen randomised to Lifestyle Advice demonstrated a statistically significant increase in the number of servings of fruit and vegetables consumed per day, as well as increased consumption of fibre, and reduced percentage energy intake from saturated fats (P < 0.05 for all). Maternal HEI was significantly improved at both 28 (73.35 ± 6.62 versus 71.86 ± 7.01; adjusted difference in means 1.58; 95% CI 0.89 to 2.27; P < 0.0001) and 36 (72.95 ± 6.82 versus 71.17 ± 7.69; adjusted difference in means 1.77; 95% CI 1.01 to 2.53; P < 0.0001) weeks. There were no differences in dietary glycaemic index or glycaemic load. Women randomised to Lifestyle Advice also demonstrated greater total physical activity (adjusted difference in means 359.76 metabolic equivalent task units (MET) minutes/week; 95% CI 74.87 to 644.65; P = 0.01) compared with women receiving Standard Care. The supervised walking group was poorly utilised.ConclusionsFor women who are overweight or obese, antenatal lifestyle advice improves maternal diet and physical activity during pregnancy.Please see related articles: http://www.biomedcentral.com/1741-7015/12/163 and http://www.biomedcentral.com/1741-7015/12/201.Trial registrationAustralian and New Zealand Clinical Trials Registry (http://ACTRN12607000161426)

Effect of increasing protein content of human milk fortifier on growth in preterm infants born at <31 wk gestation: a randomized controlled trial

BACKGROUND Preterm human milk-fed infants often experience suboptimal growth despite the use of human milk fortifier (HMF). The extra protein supplied in fortifiers may be inadequate to meet dietary protein requirements for preterm infants. OBJECTIVE We assessed the effect of human milk fortified with a higher-protein HMF on growth in preterm infants. DESIGN This is a randomized controlled trial in 92 preterm infants born at <31 wk gestation who received maternal breast milk that was fortified with HMF containing 1.4 g protein/100 mL (higher-protein group) or 1.0 g protein/100 mL (current practice) until discharge or estimated due date, whichever came first. The HMFs used were isocaloric and differed only in the amount of protein or carbohydrate. Length, weight, and head-circumference gains were assessed over the study duration. RESULTS Length gains did not differ between the higher- and standard-protein groups (mean difference: 0.06 cm/wk; 95% CI: -0.01, 0.12 cm/wk; P = 0.08). Infants in the higher-protein group achieved a greater weight at study end (mean difference: 220 g; 95% CI: 23, 419 g; P = 0.03). Secondary analyses showed a significant reduction in the proportion of infants who were less than the 10th percentile for length at the study end in the higher-protein group (risk difference: 0.186; 95% CI: 0.370, 0.003; P = 0.047). CONCLUSIONS A higher protein intake results in less growth faltering in human milk-fed preterm infants. It is possible that a higher-protein fortifier than used in this study is needed. This trial was registered with the Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au/) as ACTRN12606000525583.

Plasma cytokines and markers of endothelial activation increase after packed red blood cell transfusion in the preterm infant

Background:Transfusion of packed red blood cells (PRBCs) saves lives in the neonatal critical care setting and is one of the most common interventions in the preterm infant. The number and volume of PRBC transfusions are associated with several major neonatal morbidities, although a direct causal link between transfusion and major neonatal morbidity is still to be proven. Transfusion-related immunomodulation (TRIM) may underlie these adverse outcomes, yet it has received little attention in the high-risk preterm infant.Methods:One transfusion event was studied in infants ≤28 wk gestation between 2 and 6 wk postnatal age (n = 28). Plasma inflammatory cytokines and markers of endothelial activation were measured in the infants before and 2–4 h after transfusion, as well as in the donor pack.Results:Median (range) age at transfusion was 18 (14–39) days with the pretransfusion hemoglobin level at 9.8 (7.4–10.2) g/dl. Interleukin (IL)-1β (P = 0.01), IL-8 (P = <0.001), tumor necrosis factor-α (P = 0.008), and monocyte chemoattractant protein (P = 0.01) were increased after transfusion. A similar elevation in markers of endothelial activation was seen after transfusion with increased plasma macrophage inhibitory factor (P = 0.005) and soluble intracellular adhesion molecule-1 (P = <0.001).Conclusion:Production of inflammatory cytokines and immunoactivation of the endothelium observed after the transfusion of PRBCs in the preterm infant may be a manifestation of TRIM. The implications of this emerging phenomenon within the preterm neonatal population warrant further investigation.

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.

The effects of antenatal dietary and lifestyle advice for women who are overweight or obese on neonatal health outcomes: the LIMIT randomised trial

BackgroundOverweight and obesity during pregnancy represents a considerable health burden. While research has focused on interventions to limit gestational weight gain, there is little information describing their impact on neonatal health. Our aim was to investigate the effect on a range of pre-specified secondary neonatal outcomes of providing antenatal dietary and lifestyle advice to women who are overweight or obese.MethodsWe report a range of pre-specified secondary neonatal outcomes from a large randomised trial in which antenatal dietary and lifestyle advice was provided to women who were overweight or obese. Pregnant women were eligible for participation with a body mass index of 25 kg/m2 or over, and singleton gestation between 10+0 and 20+0 weeks. Outcome measures included gestational age at birth; Apgar score below 7 at 5 minutes of age; need for resuscitation at birth; birth weight above 4.5 kg or below 2.5 kg; birth weight, length and head circumference (and Z-scores); admission to the nursery; respiratory distress syndrome; and postnatal length of stay. Data relating to the primary outcome (large for gestational age infants defined as birth weight above the 90th centile) and birth weight above 4 kg have been reported previously. Analyses used intention-to-treat principles.ResultsIn total, 2,142 infants were included in the analyses. Infants born to women following lifestyle advice were significantly less likely to have birth weight above 4.5 kg (2.15% versus 3.69%; adjusted risk ratio (aRR) = 0.59; 95% confidence interval (CI) 0.36 to 0.98; P = 0.04), or respiratory distress syndrome (1.22% versus 2.57%; aRR = 0.47; 95% CI 0.24 to 0.90; P = 0.02), particularly moderate or severe disease, and had a shorter length of postnatal hospital stay (3.94 ± 7.26 days versus 4.41 ± 9.87 days; adjusted ratio of means 0.89; 95% CI 0.82 to 0.97; P = 0.006) compared with infants born to women who received Standard Care.ConclusionsFor women who are overweight or obese, antenatal dietary and lifestyle advice has health benefits for infants, without an increase in the risk of harm. Continued follow-up into childhood will be important to assess the longer-term effects of a reduction in high infant birth weight on risk of child obesity.Please see related articles: http://www.biomedcentral.com/1741-7015/12/161 and http://www.biomedcentral.com/1741-7015/12/201.Clinical trial registrationAustralian and New Zealand Clinical Trials Registry (http://ACTRN12607000161426)

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.