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Miller J.,Womens and Childrens Health Research Institute | Miller J.,University of Adelaide | Makrides M.,Womens and Childrens Health Research Institute | Makrides M.,University of Adelaide | And 9 more authors.
American Journal of Clinical Nutrition | Year: 2012

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. © 2012 American Society for Nutrition.


Smithers L.G.,Womens and Childrens Health Research Institute | Smithers L.G.,Flinders Medical Center | Smithers L.G.,University of Adelaide | Smithers L.G.,Flinders University | And 14 more authors.
American Journal of Clinical Nutrition | Year: 2010

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 ≈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. © 2010 American Society for Nutrition.


Collins C.T.,Womens and Childrens Health Research Institute | Collins C.T.,University of Adelaide | Makrides M.,Womens and Childrens Health Research Institute | Makrides M.,University of Adelaide | And 11 more authors.
British Journal of Nutrition | Year: 2011

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•20•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 infant's 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. © 2011 The Authors.


Belfort M.B.,Childrens Hospital Boston | Rifas-Shiman S.L.,Harvard University | Sullivan T.,University of Adelaide | Collins C.T.,University of Adelaide | And 9 more authors.
Pediatrics | Year: 2011

OBJECTIVE: To identify sensitive periods of postnatal growth for preterm infants relative to neurodevelopment at 18 months' corrected age. PATIENTS AND METHODS: We studied 613 infants born at <33 weeks'gestation who participated in the DHA for Improvement of Neurodevelopmental Outcome trial. We calculated linear slopes of growth in weight, length, BMI, and head circumference from 1 week of age to term (40 weeks' postmenstrual age), term to 4 months, and 4 to 12 months, and we estimated their associations with Bayley Scales of Infant Development, 2nd Edition, Mental (MDI) and Psychomotor (PDI) Development Indexes in linear regression. RESULTS: The median gestational age was 30 (range: 2-33) weeks. Mean ± SD MDI was 94 ± 16, and PDI was 93 ± 16. From 1 week to term, greater weight gain (2.4 MDI points per z score [95% confidence interval (CI): 0.8 -3.9]; 2.7 PDI points [95% CI: 1.2-.2]), BMI gain (1.7 MDI points [95% CI: 0.4 -3.1]; 2.5 PDI points [95% CI: 1.2-3.9]), and head growth (1.4 MDI points [95% CI: -0.0 -2.8]; 2.5 PDI points [95% CI: 1.2-3.9]) were associated with higher scores. From term to 4 months, greater weight gain (1.7 points [95% CI: 0.2-3.1]) and linear growth (2.0 points [95% CI: 0.7-3.2]), but not BMI gain, were associated with higher PDI. From 4 to 12 months, none of the growth measures was associated with MDI or PDI score. CONCLUSIONS: In preterm infants, greater weight and BMI gain to term were associated with better neurodevelopmental outcomes. After term, greater weight gain was also associated with better outcomes, but increasing weight out of proportion to length did not confer additional benefit. Copyright © 2011 by the American Academy of Pediatrics.


Manley B.J.,Royal Womens Hospital | Manley B.J.,Murdoch Childrens Research Institute | Manley B.J.,University of Melbourne | Makrides M.,Womens and Childrens Health Research Institute | And 11 more authors.
Pediatrics | Year: 2011

BACKGROUND: Docosahexaenoic acid (DHA) has been associated with downregulation of inflammatory responses. OBJECTIVE: To report the effect of DHA supplementation on long-term atopic and respiratory outcomes in preterm infants. METHODS: This study is a multicenter, randomized controlled trial comparing the outcomes for preterm infants <33 weeks' gestation who consumed expressed breast milk from mothers taking either tuna oil (high-DHA diet) or soy oil (standard-DHA) capsules. Data collected included incidence of bronchopulmonary dysplasia (BPD) and parental reporting of atopic conditions over the first 18 months of life. RESULTS: Six hundred fifty-seven infants were enrolled (322 to high-DHA diet, 335 to standard), and 93.5% completed the 18-month follow-up. There was a reduction in BPD in boys (relative risk [RR]: 0.67 [95% confidence interval (CI): 0.47-0.96]; P = .03) and in all infants with a birth weight of <1250 g (RR: 0.75 [95% CI: 0.57-0.98]; P = .04). There was no effect on duration of respiratory support, admission length, or home oxygen requirement. There was a reduction in reported hay fever in all infants in the high-DHA group at either 12 or 18 months (RR: 0.41 [95% CI: 0.18-0.91]; P = .03) and at either 12 or 18 months in boys (RR: 0.15 [0.03-0.64]; P = .01). There was no effect on asthma, eczema, or food allergy. CONCLUSIONS: DHA supplementation for infants of <33 weeks' gestation reduced the incidence of BPD in boys and in all infants with a birth weight of <1250 g and reduced the incidence of reported hay fever in boys at either 12 or 18 months. Copyright © 2011 by the American Academy of Pediatrics.

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