Docosahexaenoic Acid and Bronchopulmonary Dysplasia in Preterm Infants

Published on Mar 29, 2017in The New England Journal of Medicine91.253
· DOI :10.1056/NEJMOA1611942
Carmel T Collins23
Estimated H-index: 23
(University of Adelaide),
Maria Makrides70
Estimated H-index: 70
(University of Adelaide)
+ 21 AuthorsRobert A. Gibson80
Estimated H-index: 80
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Abstract
BackgroundStudies 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. MethodsWe 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. ResultsA 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)...
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20092.47JAMA
12 Authors (Maria Makrides, ..., Philip Ryan)
References30
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#1Carmel T Collins (University of Adelaide)H-Index: 23
#2Robert A. Gibson (University of Adelaide)H-Index: 80
Last. Victor Samuel Rajadurai (NUS: National University of Singapore)H-Index: 16
view all 9 authors...
Background Bronchopulmonary dysplasia (BPD) is a major cause of mortality and long-term respiratory and neurological morbidity in very preterm infants. While survival rates of very preterm infants have increased over the past two decades there has been no decrease in the rate of BPD in surviving infants. Evidence from animal and human studies has suggested potential benefits of docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid, in the prevention of chronic lung disease. Th...
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Background: Parenteral nutrition is central to the care of very immature infants. Current international recommendations favor higher amino acid intakes and fish oil–containing lipid emulsions. Objective: The aim of this trial was to compare 1) the effects of high [immediate recommended daily intake (Imm-RDI)] and low [incremental introduction of amino acids (Inc-AAs)] parenteral amino acid delivery within 24 h of birth on body composition and 2) the effect of a multicomponent lipid emulsion cont...
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#1Lisa N Yelland (University of Adelaide)H-Index: 24
#2Maria Makrides (University of Adelaide)H-Index: 70
Last. Robert A. Gibson (University of Adelaide)H-Index: 80
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Randomised controlled trials are the ideal way to assess the effects of interventions. Small trials are useful for generating pilot data to determine samples sizes for larger trials, but can produce unreliable or biased results if they are considered in their own right. We investigate the impact of small sample sizes due to either inadequate recruitment targets or high attrition rates on the results of fatty acid intervention trials. Data from our large trial of DHA supplementation during pregna...
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#1Brenda B. Poindexter (IU: Indiana University)H-Index: 46
#2Rui Feng (UPenn: University of Pennsylvania)H-Index: 39
Last. Alan H. Jobe (Cincinnati Children's Hospital Medical Center)H-Index: 101
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Rationale: Bronchopulmonary dysplasia is the most common morbidity of prematurity, but the validity and utility of commonly used definitions have been questioned.Objectives: To compare three commonly used definitions of bronchopulmonary dysplasia in a contemporary prospective, multicenter observational cohort of extremely preterm infants.Methods: At 36 weeks postmenstrual age, the following definitions of bronchopulmonary dysplasia were applied to surviving infants with and without imputation: n...
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#1Carmel Collins (University of Adelaide)H-Index: 2
#2Thomas Sullivan (University of Adelaide)H-Index: 41
Last. Robert A. Gibson (University of Adelaide)H-Index: 80
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Abstract Thirty one infants born less than 30 weeks׳ gestational age were randomised to receive either 40 ( n =11), 80 ( n =9) or 120 ( n =11) mg/kg/day of docosahexaenoic acid (DHA) respectively as an emulsion, via the feeding tube, commenced within 4 days of the first enteral feed. Twenty three infants were enroled in non-randomised reference groups; n =11 who had no supplementary DHA and n =12 who had maternal DHA supplementation. All levels of DHA in the emulsion were well tolerated with no ...
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#1Lotte Lauritzen (UCPH: University of Copenhagen)H-Index: 43
#2Mary Fewtrell (UCL: University College London)H-Index: 71
Last. Carlo Agostoni (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico)H-Index: 71
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Arachidonic acid (AA) is supplied together with docosahexaenoic acid (DHA) in infant formulas, but we have limited knowledge about the effects of supplementation with either of these long-chain polyunsaturated fatty acids (LCPUFA) on growth and developmental outcomes. AA is present in similar levels in breast milk throughout the world, whereas the level of DHA is highly diet dependent. Autopsy studies show similar diet-dependent variation in brain DHA, whereas AA is little affected by intake. Ea...
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#1Ge Liu (University of Adelaide)H-Index: 7
#2Beverly S. Muhlhausler (University of Adelaide)H-Index: 41
Last. Robert A. Gibson (University of Adelaide)H-Index: 80
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Abstract Conventional assays of omega-3 long chain polyunsaturated fatty acid (n-3 LCPUFA) status in humans involve venous blood collection and expensive, multi-step processes that limit their usefulness as screening tools. This study aimed to develop a capillary dried blood spot (DBS) system capable of protecting n-3 LCPUFA from oxidation for up to 2 months at room temperature (20–25°C). We demonstrated that a DBS system comprising both an antioxidant and chelating agent on silica-gel coated pa...
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#1Dorota Pawlik (Jagiellonian University Medical College)H-Index: 13
#2Ryszard Lauterbach (Jagiellonian University Medical College)H-Index: 16
Last. Michael P. Sherman (MU: University of Missouri)H-Index: 39
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Background: Preliminary studies suggest that fish-oil lipid emulsion given parenterally to very preterm infants reduces the severity of retinopathy (ROP) and cholestasis. Methods: Infants weighing <1250 g at birth were randomly allocated to 2 groups: an experimental group of 60 infants that received an intravenous (IV) soybean, olive oil, and fish oil emulsion, and a control group of 70 infants that was given a parenteral soybean and olive oil emulsion. Plasma and erythrocyte concentrations of d...
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#1Ola Hjalmarson (University of Gothenburg)H-Index: 15
#2Hrolfur Brynjarsson (University of Gothenburg)H-Index: 3
Last. Kenneth Sandberg (University of Gothenburg)H-Index: 14
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Bronchopulmonary dysplasia (BPD), defined as protracted neonatal hypoxaemia, is considered a risk factor for respiratory disease in adulthood. The relationship between this diagnosis and the actual lung injury appearing in very immature infants is, however, unknown.
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#1Markus Velten (The Research Institute at Nationwide Children's Hospital)H-Index: 22
#2Rodney D. Britt (OSU: Ohio State University)H-Index: 16
Last. Lynette K. Rogers (OSU: Ohio State University)H-Index: 32
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The preterm infant is often exposed to maternal and neonatal inflammatory stimuli and is born with immature lungs, resulting in a need for oxygen therapy. Nutritional intervention with docosahexaenoic acid (DHA; 6.3 g/kg of diet) has been shown to attenuate inflammation in various human diseases. Previous studies demonstrated that maternal DHA supplementation during late gestation and lactation attenuated hyperoxic lung injury in newborn mouse pups. In the present studies, we tested the hypothes...
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Cited By68
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#1Andrew S H Tsai (NUS: National University of Singapore)H-Index: 8
#2Hung-Da Chou (CGU: Chang Gung University)
Last. Wei-Chi Wu (CGU: Chang Gung University)H-Index: 25
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The incidence of retinopathy of prematurity (ROP) continues to rise due to the improved survival of very low birth weight infants in developed countries. This epidemic is also fueled by increased survival of preterm babies with variable use of oxygen and a lack of ROP awareness and screening services in resource-limited regions. Improvements in technology and a basic understanding of the disease pathophysiology have changed the way we screen and manage ROP, educate providers and patients, and im...
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#1Hélène Fougère (Laval University)
#2Jean-François Bilodeau (Laval University)H-Index: 16
Last. Bruno Piedboeuf (Laval University)H-Index: 27
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Preterm infants are deficient in long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), a fatty acid (FA) associated with an increase in bronchopulmonary dysplasia (BPD). In two previous randomized control trials, DHA supplementation did not reduce the risk of BPD. We examined the breast milk FA profile, collected 14 days after birth, of mothers who delivered before 29 weeks of gestation and who were supplemented with DHA-rich algae oil or a placebo within 72 h after birt...
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Retinopathy of prematurity is defined as retinal abnormalities that occur during development as a consequence of disturbed oxygen conditions and nutrient supply after preterm birth. Both neuronal maturation and retinal vascularization are impaired, leading to the compensatory but uncontrolled retinal neovessel growth. Current therapeutic interventions target the hypoxia-induced neovessels but negatively impact retinal neurons and normal vessels. Emerging evidence suggests that metabolic disturba...
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#6Anders Nilsson (University of Gothenburg)H-Index: 22
Importance null Supplementing preterm infants with long-chain polyunsaturated fatty acids (LC-PUFA) has been inconsistent in reducing the severity and incidence of retinopathy of prematurity (ROP). Furthermore, few studies have measured the long-term serum lipid levels after supplementation. null Objective null To assess whether ROP severity is associated with serum levels of LC-PUFA, especially docosahexaenoic acid (DHA) and arachidonic acid (AA), during the first 28 postnatal days. null Design...
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#2Marwa Adel Ahmed (Ain Shams University)H-Index: 1
Last. Nagwa Ali Sabri (Ain Shams University)H-Index: 9
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Abstract null null Introduction null Preterm neonates have under-developed immune-regulatory system; consequently, there is a risk for developing chronic inflammation. Necrotizing enterocolitis (NEC) is an acute devastating neonatal intestinal inflammatory disorder. Due to the obscure multifactorial etiology, early diagnosis and effective treatment of NEC are limited. Consequently, effective strategies in the prevention of NEC, including nutritional approaches, are critically needed. The current...
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#1Thomas SullivanH-Index: 41
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Randomized trials involving independent and paired observations occur in many areas of health research, for example in paediatrics, where studies can include infants from both single and twin births. Multiple imputation (MI) is often used to address missing outcome data in randomized trials, yet its performance in trials with independent and paired observations, where design effects can be less than or greater than one, remains to be explored. Using simulated data and through application to a tr...
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#2Pavel Goriacko (Montefiore Medical Center)H-Index: 3
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Background Parenteral nutrition (PN) is crucial for the improvement of long-term outcomes in very low birth weight (VLBW) neonates. Lipid injectable emulsions are a key component of PN, as they contain essential fatty acids and provide energy critical for brain growth. Prolonged administration increases risk of intestinal failure-associated liver disease, including cholestasis, and other complications. Methods This is a retrospective, quasi-experimental cohort study of 215 VLBW neonates. The pri...
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#1I-Lun Chen (CGU: Chang Gung University)H-Index: 3
#2Chih-Hsing Hung (CGU: Chang Gung University)
Last. Hsin-Chun Huang (CGU: Chang Gung University)H-Index: 15
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Neurodevelopmental morbidities developed more commonly in low-birth-weight premature infants. We sought to determine the effects of different lipid emulsions on the neurodevelopmental outcomes of children born prematurely. This retrospective cross-sectional study had two intervention legs, Lipofundin® MCT/LCT (LIPO) versus Smoflipid® (SMOF), which are mainly differentiated by fish oil. Data of premature neonates born between 2001 and 2015 from the research database of Chang Gung Memorial Hospita...
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#1Christina D’Agrosa (SUNY Downstate Medical Center)H-Index: 3
#2Charles L. Cai (SUNY Downstate Medical Center)H-Index: 9
Last. Kay D. Beharry (SUNY: State University of New York System)H-Index: 19
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BACKGROUND Neonatal intermittent hypoxia (IH) results in oxidative distress in preterm infants with immature antioxidant systems, contributing to lung injury. Coenzyme Q10 (CoQ10) and fish oil protect against oxidative injury. We tested the hypothesis that CoQ10 is more effective than fish oil for prevention of IH-induced lung injury in neonatal rats. METHODS Newborn rats were exposed to two clinically relevant IH paradigms at birth (P0): (1) 50% O2 with brief hypoxia (12% O2); or (2) room air (...
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Adequate supply of long-chain polyunsaturated fatty acids (LCPUFAs) is of great importance for neonates, especially preterm infants. In particular, n-3 LCPUFAs and n-6 LCPUFAs play a key role in brain development, immune regulation, and disease prevention. Lack of LCPUFAs may lead to neurodevelopmental impairment, affect the development of neonatal immune system, and result in neonatal diseases. This article reviews related research advances in the physiological function of LCPUFAs and its effec...
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