Maternal High-Dose DHA Supplementation and Neurodevelopment at 18-22 Months of Preterm Children.

OBJECTIVES: To determine whether maternal supplementation with high-dose docosahexaenoic acid (DHA) in breastfed, very preterm neonates improves neurodevelopmental outcomes at 18 to 22 months' corrected age (CA). METHODS: Planned follow-up of a randomized, double-blind, placebo-controlled, multicenter trial to compare neurodevelopmental outcomes in breastfed, preterm neonates born before 29 weeks' gestational age (GA). Lactating mothers were randomized to receive either DHA-rich algae oil or a placebo within 72 hours of delivery until 36 weeks' postmenstrual age. Neurodevelopmental outcomes were assessed with the Bayley Scales of Infant and Toddler Development third edition (Bayley-III) at 18 to 22 months' CA. Planned subgroup analyses were conducted for GA (<27 vs ≥27 weeks' gestation) and sex. RESULTS: Among the 528 children enrolled, 457 (86.6%) had outcomes available at 18 to 22 months' CA (DHA, N = 234, placebo, N = 223). The mean differences in Bayley-III between children in the DHA and placebo groups were -0.07 (95% confidence interval [CI] -3.23 to 3.10, P = .97) for cognitive score, 2.36 (95% CI -1.14 to 5.87, P = .19) for language score, and 1.10 (95% CI -2.01 to 4.20, P = .49) for motor score. The association between treatment and the Bayley-III language score was modified by GA at birth (interaction P = .07). Neonates born <27 weeks' gestation exposed to DHA performed better on the Bayley-III language score, compared with the placebo group (mean difference 5.06, 95% CI 0.08-10.03, P = .05). There was no interaction between treatment group and sex. CONCLUSIONS: Maternal DHA supplementation did not improve neurodevelopmental outcomes at 18 to 22 months' CA in breastfed, preterm neonates, but subgroup analyses suggested a potential benefit for language in preterm neonates born before 27 weeks' GA.

Use of SMOF lipid emulsion in very preterm infants does not affect the incidence of bronchopulmonary dysplasia-free survival.

BACKGROUND: We aim to assess whether the docosahexaenoic acid (DHA)-containing lipid emulsion (LE) SMOFlipid 20% (Fresenius Kabi Canada Ltd) is associated with bronchopulmonary dysplasia (BPD)-free survival at 36 weeks' postmenstrual age in very preterm infants. METHODS: This cohort study is nested in the MOBYDIck randomized clinical trial (NCT02371460), which investigated the effect of maternal DHA supplementation on BPD-free survival in breastfed very preterm infants born between 23 0/7 and 28 6/7 weeks' gestation in 16 Canadian neonatal intensive care units (2015-2018). Parenteral SMOF-LE was given to the infants according to the sites' routine care protocols. Relative risks (RRs) were estimated using a modified Poisson regression model with generalized estimating equations taking into account recruitment site, multiple birth, DHA supplementation, birth weight, sex, and gestational age. RESULTS: Among 528 infants (mean gestational age, 26.5 weeks [SD, 1.6]), 272 received SMOF-LE. Overall, 56.7% of the infants in the SMOF-LE group and 59.7% infants in the non-SMOF-LE group survived without BPD (adjusted RR, 0.94 [95% CI, 0.77-1.14]; P = 0.51). BPD rates were 39.3% in the SMOF-LE group vs 34.1% in the non-SMOF-LE group (adjusted RR, 1.10 [95% CI, 0.82-1.47]; P = 0.53). Severe BPD rates were 31.8% in the SMOF-LE group vs 28.8% in the non-SMOF-LE group (adjusted P = 0.59). Mortality was not significantly different between the SMOF-LE (6.7%) and non-SMOF-LE groups (9.5%; adjusted P = 0.40). CONCLUSION: In very preterm infants, intravenous DHA-containing SMOF-LE during the neonatal period was not associated with BPD-free survival.

Effect of Maternal Docosahexaenoic Acid Supplementation on Very Preterm Infant Growth: Secondary Outcome of a Randomized Clinical Trial.

INTRODUCTION: The aim of the study was to determine the effect of a maternal docosahexaenoic acid (DHA) supplementation during lactation, compared with a placebo, on the neonatal growth profile of breastfed very preterm infants. METHODS: Preterm infants' growth profile, growth velocity from birth to 36 weeks' postmenstrual age (PMA), and growth at 36 weeks' PMA were pre-specified secondary outcomes of a randomized placebo-controlled trial conducted in 16 Canadian neonatal intensive care units (2015-2018). Lactating mothers who delivered before 29 weeks' gestation were given 1.2 g of DHA daily or a placebo within 72 h of delivery and up to 36 weeks' PMA. Analyses were performed using a linear regression model with generalized estimating equations. RESULTS: 461 mothers and their 528 infants (DHA, N = 273; placebo, N = 255) were included with mean gestational age of 26.5 weeks (standard deviation [SD] = 1.6); 275 (52.1%) were males; mean birth weight was 895 g (SD = 240). DHA interaction with sex was significant on weight profile (interaction p < 0.001), weight velocity (interaction p = 0.05), and weight at 36 weeks' PMA (interaction p = 0.02). Females in the DHA group gained more weight compared to the placebo group (mean difference [MD], 52.6 g [95% confidence interval [CI]: 24.5-80.8], p < 0.001). Weight velocity was significantly higher in females of the DHA group (MD, 3.4 g/kg/day [95% CI: 0.6-6.2], p = 0.02). At 36 weeks' PMA, the weight of males in the DHA group was significantly smaller (MD, -88.9 g [95% CI: -166.2 to -11.6], p = 0.02). CONCLUSION: DHA positively affected female infants' neonatal weight profile and velocity and negatively affected male infants' weight at 36 weeks' PMA.

Effect of Maternal Docosahexaenoic Acid Supplementation on Bronchopulmonary Dysplasia-Free Survival in Breastfed Preterm Infants: A Randomized Clinical Trial.

Importance: Maternal docosahexaenoic acid (DHA) supplementation may prevent bronchopulmonary dysplasia, but evidence remains inconclusive. Objective: To determine whether maternal DHA supplementation during the neonatal period improves bronchopulmonary dysplasia-free survival in breastfed infants born before 29 weeks of gestation. Design, Setting, and Participants: Superiority, placebo-controlled randomized clinical trial at 16 Canadian neonatal intensive care units (June 2015-April 2018 with last infant follow-up in July 2018). Lactating women who delivered before 29 weeks of gestation were enrolled within 72 hours of delivery. The trial intended to enroll 800 mothers, but was stopped earlier. Interventions: There were 232 mothers (273 infants) assigned to oral capsules providing 1.2 g/d of DHA from randomization to 36 weeks' postmenstrual age and 229 mothers (255 infants) assigned to placebo capsules. Main Outcomes and Measures: The primary outcome was bronchopulmonary dysplasia-free survival in infants at 36 weeks' postmenstrual age. There were 22 secondary outcomes, including mortality and bronchopulmonary dysplasia. Results: Enrollment was stopped early due to concern for harm based on interim data from this trial and from another trial that was published during the course of this study. Among 461 mothers and their 528 infants (mean gestational age, 26.6 weeks [SD, 1.6 weeks]; 253 [47.9%] females), 375 mothers (81.3%) and 523 infants (99.1%) completed the trial. Overall, 147 of 268 infants (54.9%) in the DHA group vs 157 of 255 infants (61.6%) in the placebo group survived without bronchopulmonary dysplasia (absolute difference, -5.0% [95% CI, -11.6% to 2.6%]; relative risk, 0.91 [95% CI, 0.80 to 1.04], P = .18). Mortality occurred in 6.0% of infants in the DHA group vs 10.2% of infants in the placebo group (absolute difference, -3.9% [95% CI, -6.8% to 1.4%]; relative risk, 0.61 [95% CI, 0.33 to 1.13], P = .12). Bronchopulmonary dysplasia occurred in 41.7% of surviving infants in the DHA group vs 31.4% in the placebo group (absolute difference, 11.5% [95% CI, 2.3% to 23.2%]; relative risk, 1.36 [95% CI, 1.07 to 1.73], P = .01). Of 22 prespecified secondary outcomes, 19 were not significantly different. Conclusions and Relevance: Among breastfed preterm infants born before 29 weeks of gestation, maternal docosahexaenoic acid supplementation during the neonatal period did not significantly improve bronchopulmonary dysplasia-free survival at 36 weeks' postmenstrual age compared with placebo. Study interpretation is limited by early trial termination. Trial Registration: ClinicalTrials.gov Identifier: NCT02371460.

Newborn Bilirubin Screening for Preventing Severe Hyperbilirubinemia and Bilirubin Encephalopathy: A Rapid Review.

According to the 2004 American Academy of Pediatrics guideline on the management of hyperbilirubinemia, every newborn should be assessed for the risk of developing severe hyperbilirubinemia with the help of predischarge total serum bilirubin or transcutaneous bilirubin measurements and/or assessments of clinical risk factors. The aim of this rapid review is 1) to review the evidence for 1) predicting and preventing severe hyperbilirubinemia and bilirubin encephalopathy, 2) determining the efficacy of home/community treatments (home phototherapy) in the prevention of severe hyperbilirubinemia, and 3) non-invasive/transcutaneous methods for estimating serum bilirubin level. METHODS: In this rapid review, studies were identified through the Medline database. The main outcomes of interest were severe hyperbilirubinemia and encephalopathy. A subset of articles was double screened and all articles were critically appraised using the SIGN and AMSTAR checklists. This review investigated if systems approach is likely to reduce the occurrence of severe hyperbilirubinemia. RESULTS: Fifty-two studies met the inclusion criteria. Included studies assessed the association between bilirubin measurement early in neonatal life and the subsequent development of severe hyperbilirubinemia and chronic bilirubin encephalopathy/kernicterus. It was observed that, highest priority should be given to (i) universal bilirubin screening programs; (ii) implementation of community and midwife practice; (iii) outreach to communities for education of prospective parents; and (iv) development of clinical pathways to monitor, evaluate and track infants with severe hyperbilirubinemia. CONCLUSIONS: We found substantial observational evidence that severe hyperbilirubinemia can be accurately predicted and prevented through universal bilirubin screening. So far, there is no evidence of any harm.

Minimizing blood loss and the need for transfusions in very premature infants.

Reducing blood loss and the need for blood transfusions in extremely preterm infants is part of effective care. Delayed cord clamping is well supported by the evidence and is recommended for infants who do not immediately require resuscitation. Cord milking may be an alternative to delayed cord clamping; however, more research is needed to support its use. In view of concerns regarding the increased risk for cognitive delay, clinicians should avoid using hemoglobin transfusion thresholds lower than those tested in clinical trials. Higher transfusion volumes (15 mL/kg to 20 mL/kg) may decrease exposure to multiple donors. Erythropoietin is not recommended for routine use due to concerns about retinopathy of prematurity. Elemental iron supplementation (2 mg/kg/day to 3 mg/kg/day once full oral feeds are achieved) is recommended to prevent later iron deficiency anemia. Noninvasive monitoring (eg, for carbon dioxide, bilirubin) and point-of-care testing reduce the need for blood sampling. Clinicians should strive to order the minimal amount of blood sampling required for safe patient care, and cluster samplings to avoid unnecessary skin breaks.

Dans le cadre des soins efficaces aux très grands prématurés, il est important de limiter les pertes de sang et les transfusions. Le report du clampage du cordon, bien soutenu par les données probantes, est recommandé pour les nouveau-nés qui n'ont pas besoin d'une réanimation immédiate. La traite du cordon peut le remplacer, mais plus de recherches s'imposent pour en confirmer l'intérêt. Lorsqu'ils transfusent, les cliniciens doivent éviter de recourir à des seuils d'hémoglobine inférieurs à ceux qui sont utilisés lors des essais cliniques, en raison des craintes quant à l'augmentation du risque de retard cognitif. De plus gros volumes de transfusion (15 mL/kg à 20 mL/kg) peuvent réduire l'exposition à de multiples donneurs. L'utilisation systématique d'érythropoïétine n'est pas recommandée à cause du risque connexe de rétinopathie des prématurés. Les suppléments de fer élémentaire (de 2 mg/kg/jour à 3 mg/kg/jour une fois l'alimentation orale établie) sont recommandés pour prévenir une anémie ferriprive plus tard. Le monitorage non invasif (p. ex., dioxyde de carbone, bilirubine) et les tests au point de service réduisent les prélèvements de sang. Les cliniciens devraient demander le moins de prélèvements nécessaires pour prodiguer des soins sécuritaires aux patients et les regrouper pour éviter de transpercer la peau inutilement.

Omega-3 long-chain polyunsaturated fatty acids for extremely preterm infants: a systematic review.

BACKGROUND AND OBJECTIVE: Omega-3 long chain polyunsaturated fatty acid (LCPUFA) exposure can be associated with reduced neonatal morbidities. We systematically review the evidence for the benefits of omega-3 LCPUFAs for reducing neonatal morbidities in extremely preterm infants. METHODS: Data sources were PubMed, Embase, Center for Reviews and Dissemination, and the Cochrane Register of Controlled Trials. Original studies were selected that included infants born at <29 weeks' gestation, those published until May 2013, and those that evaluated the relationship between omega-3 LCPUFA supplementation and major adverse neonatal outcomes. Data were extracted on study design and outcome. Effect estimates were pooled. RESULTS: Of the 1876 studies identified, 18 randomized controlled trials (RCTs) and 6 observational studies met the defined criteria. No RCT specifically targeted a population of extremely preterm infants. Based on RCTs, omega-3 LCPUFA was not associated with a decreased risk of bronchopulmonary dysplasia in infants overall (pooled risk ratio [RR] 0.97, 95% confidence interval [CI] 0.82-1.13], 12 studies, n = 2809 infants); however, when considering RCTs that include only infants born at ≤32 weeks' gestation, a trend toward a reduction in the risk of bronchopulmonary dysplasia (pooled RR 0.88, 95% CI 0.74-1.05, 7 studies, n = 1156 infants) and a reduction in the risk of necrotizing enterocolitis (pooled RR 0.50, 95% CI 0.23-1.10, 5 studies, n = 900 infants) was observed with LCPUFA. CONCLUSIONS: Large-scale interventional studies are required to determine the clinical benefits of omega-3 LCPUFA, specifically in extremely preterm infants, during the neonatal period.