Carmel T Collins

Impact of fatty acid status on growth and neurobehavioural development in humans

Many studies have been conducted to investigate the effect of n-3 long-chain polyunsaturated fatty acid (LCPUFA) supplementation during the perinatal period on the growth and neurobehavioural development of young children. Most of these intervention trials have involved infants from high-income countries, and a significant proportion have investigated supplementation of infant formulas. Generally, supplementation of infant formula for preterm rather than term infants has demonstrated more consistent, positive effects on aspects of neurobehavioural development, while the growth of both term and preterm infants appears unaffected by LCPUFA supplementation. Maternal n-3 LCPUFA supplementation during pregnancy has consistently resulted in modest increases in birth size, and the most recent study suggests that this is also true from women from low-income environments. The effect of maternal supplementation on global neurobehavioural outcomes for children born at term remains unclear, although n-3 LCPUFA supplementation of women expressing milk for their preterm infants does improve their performance on tests of global neurodevelopment. Further work is required to determine whether dietary n-3 LCPUFA is neuroprotective for children from disadvantaged or low-income backgrounds.

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.

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.

An evaluation of Midwifery Group Practice: Part II: Women’s satisfaction

BACKGROUND Midwifery Group Practice (MGP) is a continuity of midwifery care model for women of all levels of pregnancy risk available at a tertiary metropolitan hospital in Australia. This paper presents Part II of the demonstration study exploring the effectiveness of MGP, and reports on womens satisfaction with the model of care. METHODS A Maternal Satisfaction Questionnaire was developed and sent to all women (n=120) enrolled in MGP over a three-month period. The questionnaire comprised two open-ended questions asking women to list up to three things they liked and did not like about MGP, and a structured section exploring levels of satisfaction through a five-point Likert response format. The open-ended questions were analysed using qualitative content analysis, and analysis of the structured part of the questionnaire was undertaken by comparing mean scores of satisfaction ranging from -2 (very negative attitudes) to +2 (very positive attitudes). RESULTS Of the 120 women who were sent a Maternal Satisfaction Questionnaire, 84 returned their questionnaire (70% response rate). Three overarching themes were identified in the content analysis of open-ended questions, namely: Continuity of care; Accessibility; and Personal and professional attributes of the midwife. Analysis of the structured part of the questionnaire showed that women were satisfied with the care they received in MGP, as indicated by positive scores on all questions. CONCLUSIONS Women being cared for in MGP are satisfied with their care.

Acupuncture to induce labor: a randomized controlled trial.

OBJECTIVE: To estimate the clinical effectiveness of acupuncture to induce labor. METHODS: This study was a randomized controlled trial of acupuncture compared with sham acupuncture. Women who were scheduled for a postterm induction with a singleton pregnancy and cephalic presentation were eligible for the study. Women received two acupuncture or sham acupuncture sessions over a 2-day period before the planned medical/pharmacological induction. The principal primary outcomes related to the need for induction methods and time from the administration of the intervention to delivery. RESULTS: Three hundred sixty-four women were randomly assigned to the trial (treatment n=181 and control n=183). Women did not differ in their need for induction methods between groups: prostaglandin induction: relative risk (RR) 1.20, 95% confidence interval (CI) 0.96–1.51, P=.11; artificial rupture of membranes only: RR 0.93, 95% CI 0.72–1.20, P=.57; oxytocin only: RR 0.89, 95% CI 0.60–1.32, P=.55; artificial rupture of membranes plus oxytocin: RR 0.87, 95% CI 0.57–1.33, P=.52; prostaglandins, artificial rupture of membranes, and oxytocin: RR 0.84, 95% CI 0.37–1.91, P=.68. The median time from acupuncture to delivery was 68.6 hours (interquartile range 53.9–79.5) compared with 65 hours (interquartile range 49.3–76.3) for women in the control group. CONCLUSION: Two sessions of manual acupuncture, using local and distal acupuncture points, administered 2 days before a scheduled induction of labor did not reduce the need for induction methods or the duration of labor for women with a postterm pregnancy. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, www.anzctr.org.au, ACTRN12606000494538 LEVEL OF EVIDENCE: I

Neurodevelopmental outcomes at 7 years’ corrected age in preterm infants who were fed high-dose docosahexaenoic acid to term equivalent: a follow-up of a randomised controlled trial

Objective To determine if improvements in cognitive outcome detected at 18 months’ corrected age (CA) in infants born <33 weeks’ gestation receiving a high-docosahexaenoic acid (DHA) compared with standard-DHA diet were sustained in early childhood. Design Follow-up of a multicentre randomised controlled trial. Randomisation was stratified for sex, birth weight (<1250 vs ≥1250 g) and hospital. Setting Five Australian tertiary hospitals from 2008 to 2013. Participants 626 of the 657 participants randomised between 2001 and 2005 were eligible to participate. Interventions High-DHA (≈1% total fatty acids) enteral feeds compared with standard-DHA (≈0.3% total fatty acids) from age 2–4 days until term CA. Primary outcome Full Scale IQ of the Wechsler Abbreviated Scale of Intelligence (WASI) at 7 years CA. Prespecified subgroup analyses based on the randomisation strata (sex, birth weight) were conducted. Results 604 (92% of the 657 originally randomised) consented to participate (291 high-DHA, 313 standard-DHA). To address missing data in the 604 consenting participants (22 for primary outcome), multiple imputation was performed. The Full Scale IQ was not significantly different between groups (high-DHA 98.3, SD 14.0, standard-DHA 98.5, SD 14.9; mean difference adjusted for sex, birthweight strata and hospital −0.3, 95% CI −2.9 to 2.2; p=0.79). There were no significant differences in any secondary outcomes. In prespecified subgroup analyses, there was a significant sex by treatment interaction on measures of parent-reported executive function and behaviour. Scores were within the normal range but girls receiving the high-DHA diet scored significantly higher (poorer outcome) compared with girls receiving the standard-DHA diet. Conclusions Supplementing the diets of preterm infants with a DHA dose of approximately 1% total fatty acids from days 2–4 until term CA showed no evidence of benefit at 7 years’ CA. Trial registration number Australian New Zealand Clinical Trials Registry: ACTRN12606000327583.

Neurodevelopmental Outcomes of Preterm Infants Fed High-Dose Docosahexaenoic Acid : A Randomized Controlled Trial

Infants born before 33 weeks’ gestation are at high risk of developmental disorders and learning disabilities. An inadequate endogenous supply of docosahexaenoic acid (DHA), a major brain lipid, may contribute to this poor developmental outcome. Trials evaluating the possible benefit of dietary DHA on the neurodevelopment of preterm infants have been inconclusive. This randomized, double-blind, controlled trial was designed to evaluate the long-term efficacy of a high-dose DHA enteral feed on the neurodevelopment of preterm infants born at less than 33 weeks’ gestation. A total of 657 infants were randomized to receive an enteral feed containing 1% total fatty acids (high-DHA group, n = 322) or a standard feed containing 0.3% total fatty acids (standard-DHA group, n = 335) from day 2 to 4 of life until term corrected age. The data were stratified by birth weight ( 1250 g) and infant gender. At 18 months follow-up, neurodevelopment was assessed using the Bayley Mental Development Index (MDI). In the whole study group, no difference was found in the unadjusted MDI scores of the children receiving high versus standard DHA feeds (mean difference: 1.9, 95% CI:-1.0–4.7), or among boys in the high versus standard feed groups. Adjustment for confounding variables did not change these results. However, girls receiving high-DHA feeds had significantly higher MDI scores than those receiving standard-DHA feeds (unadjusted mean difference: 4.7; 95% CI: 0.5–8.8, P = 0.03; adjusted mean difference: 4.5; 95% CI: 0.5–8.5, P = 0.03). Although ingestion of a high-DHA dose does not increase the MDI scores of all preterm infants born before 33 weeks, it was associated with an increase of MDI scores among girls. These data suggest that future trials with higher doses should be considered.

Pre- and post-term growth in pre-term infants supplemented with higher-dose DHA: A randomised controlled trial

The effect of the dietary n-3 long-chain PUFA, DHA (22 : 6n-3), on the growth of pre-term infants is controversial. We tested the effect of higher-dose DHA (approximately 1 % dietary fatty acids) on the growth of pre-term infants to 18 months corrected age compared with standard feeding practice (0·2-0·3 % DHA) in a randomised controlled trial. Infants born < 33 weeks gestation (n 657) were randomly allocated to receive breast milk and/or formula with higher DHA or standard DHA according to a concealed schedule stratified for sex and birth-weight ( < 1250 and ≥ 1250 g). The dietary arachidonic acid content of both diets was constant at approximately 0·4 % total fatty acids. The intervention was from day 2 to 5 of life until the infants expected date of delivery (EDD). Growth was assessed at EDD, and at 4, 12 and 18 months corrected age. There was no effect of higher DHA on weight or head circumference at any age, but infants fed higher DHA were 0·7 cm (95 % CI 0·1, 1·4 cm; P = 0·02) longer at 18 months corrected age. There was an interaction effect between treatment and birth weight strata for weight (P = 0·01) and length (P = 0·04). Higher DHA resulted in increased length in infants born weighing ≥ 1250 g at 4 months corrected age and in both weight and length at 12 and 18 months corrected age. Our data show that DHA up to 1 % total dietary fatty acids does not adversely affect growth.

Carbohydrate intake is the main determinant of growth in infants born <33 weeks' gestation when protein intake is adequate.

OBJECTIVE We investigated the relative contribution of macronutrients to postnatal growth in preterm infants born <33 wk of gestation. METHODS An audit of daily parenteral and enteral intakes of protein, carbohydrate, fat, energy, and growth (daily weight, weekly length, and head circumference) from birth to discharge home in 138 infants at <33 wk of gestation admitted to an Australian tertiary hospital was done. A mixed-model analysis of variance with random effects (slope and intercept) for subject and controlling for time, sex, gestational age, and total energy was used to determine the relative contribution of macronutrients to growth. RESULTS A higher energy intake (kilocalories per day) had a positive influence on growth. With total energy held constant, the contribution of carbohydrate to total energy had a positive relation to weight, length, and head circumference gains; protein had no relation and fat was negatively associated. For every 1% increase in energy from carbohydrate, there was a 2.3-g/d increase in weight (95% confidence interval 1.6-3.0, P < 0.0001), a 0.013-cm/d increase in length (95% confidence interval 0.003-0.022, P = 0.007), and a 0.015-cm/d increase in head circumference (95% confidence interval 0.009-0.022, P < 0.0001). CONCLUSION A re-examination of the macronutrient balance in the diet of preterm infants is required in relation to optimizing growth.

Docosahexaenoic Acid and Bronchopulmonary Dysplasia in Preterm Infants

BACKGROUND Studies in animals and in humans have suggested that docosahexaenoic acid (DHA), an n‐3 long‐chain polyunsaturated fatty acid, might reduce the risk of bronchopulmonary dysplasia, but appropriately designed trials are lacking. METHODS We randomly assigned 1273 infants born before 29 weeks of gestation (stratified according to sex, gestational age [<27 weeks or 27 to <29 weeks], and center) within 3 days after their first enteral feeding to receive either an enteral emulsion providing DHA at a dose of 60 mg per kilogram of body weight per day or a control (soy) emulsion without DHA until 36 weeks of postmenstrual age. The primary outcome was bronchopulmonary dysplasia, defined on a physiological basis (with the use of oxygen‐saturation monitoring in selected infants), at 36 weeks of postmenstrual age or discharge home, whichever occurred first. RESULTS A total of 1205 infants survived to the primary outcome assessment. Of the 592 infants assigned to the DHA group, 291 (49.1% by multiple imputation) were classified as having physiological bronchopulmonary dysplasia, as compared with 269 (43.9%) of the 613 infants assigned to the control group (relative risk adjusted for randomization strata, 1.13; 95% confidence interval [CI], 1.02 to 1.25; P=0.02). The composite outcome of physiological bronchopulmonary dysplasia or death before 36 weeks of postmenstrual age occurred in 52.3% of the infants in the DHA group and in 46.4% of the infants in the control group (adjusted relative risk, 1.11; 95% CI, 1.00 to 1.23; P=0.045). There were no significant differences between the two groups in the rates of death or any other neonatal illnesses. Bronchopulmonary dysplasia based on a clinical definition occurred in 53.2% of the infants in the DHA group and in 49.7% of the infants in the control group (P=0.06). CONCLUSIONS Enteral DHA supplementation at a dose of 60 mg per kilogram per day did not result in a lower risk of physiological bronchopulmonary dysplasia than a control emulsion among preterm infants born before 29 weeks of gestation and may have resulted in a greater risk. (Funded by the Australian National Health and Medical Research Council and others; Australian New Zealand Clinical Trials Registry number, ACTRN12612000503820.)