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.

First-trimester assessment of the fetal palate: a novel application of the Volume NT algorithm.

We describe a new technique that can facilitate the first-trimester examination of the fetal palate using the Volume NT algorithm (Samsung Medison, Seoul, Korea), a program that automatically detects the exact midsagittal plane of the head and is primarily designed for semiautomatic measurement of the nuchal translucency thickness. Three-dimensional (3D) data sets from the fetal face were captured with Volume NT and subsequently reformatted with the Oblique View software to obtain orthogonal views of the primary and secondary palate in coronal and axial planes, respectively. By testing this method in selected 3D data sets obtained retrospectively (n = 12) and prospectively (n = 28), we were able to extract clinically acceptable views of the fetal palate in all cases. This preliminary report shows that with this new 3D automation development, early evaluation of the fetal palate is feasible and reproducible and could be easily incorporated into the first-trimester sonographic protocol once its ability to detect abnormal cases is demonstrated.

Effects of maternal docosahexaenoic acid supplementation on brain development and neurodevelopmental outcomes of breastfed preterm neonates: protocol for a follow-up at preschool age of a randomised clinical trial (MOBYDIckPS).

INTRODUCTION: Docosahexaenoic acid (DHA), an omega-3 fatty acid, is important for brain development with possible implications in neurodevelopmental outcomes. In the two-arm, randomised, double-blind, placebo-controlled Maternal Omega-3 Supplementation to Reduce Bronchopulmonary Dysplasia in Very Preterm Infants trial, very preterm infants (<29 weeks' gestation) were supplemented in high doses of DHA or placebo until they reached 36 weeks' postmenstrual age. We propose a long-term neurodevelopmental follow-up of these children. This protocol details the follow-up at 5 years of age, which aims to (1) confirm our long-term recruitment capacity and (2) determine the spectrum of neurodevelopmental outcomes at preschool age following neonatal DHA supplementation. METHODS AND ANALYSIS: This long-term follow-up involves children (n=194) born to mothers (n=170) randomised to DHA (n=85) or placebo (n=85) from the five sites in Quebec when they will be 5 years' corrected age. The primary outcome measure is related to the long-term recruitment capacity, which we determined as successful if 75% (±10%, 95% CI) of the eligible children consent to the 5-year follow-up study. Interviews with mothers will be conducted to assess various aspects of neurodevelopment at preschool age (executive functions, behavioural problems, global development and health-related quality of life), evaluated with standardised neurodevelopmental questionnaires. In addition, a semistructured interview conducted in a subset of the mothers will be used to determine their acceptability and identify barriers and enablers to their eventual participation to the next phase of the trial. This follow-up study will require approximately 22 months to be completed. ETHICS AND DISSEMINATION: This study was approved by the CHU de Québec-Université Laval Research Ethics Board (MP-20-2022-5926). Mothers will provide informed consent before participating in this study. Findings will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT02371460.

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.

Review of the antenatal and postnatal use of steroids.

Antenatal and postnatal corticosteroids play an extremely important role in the management of premature infants. The antenatal administration of steroids has been universally implemented. They have not only been shown to reduce the incidence and severity of respiratory distress syndrome (RDS), but also have an impact on the incidence of intraventricular hemorrhage (IVH), patent ductus arteriosus (PDA), necrotizing enterocolitis (NEC), and possibly retinopathy of prematurity (ROP) by reducing the need for supplemental oxygen due to improved lung function. The postnatal use of dexamethasone in ventilated infants has been adopted with caution, as there have been several reports of long-term neurodevelopmental complications with this therapy. Hence, changes in dosage and indications and the search for alternative therapies has emerged. Hydrocortisone appears to be a good alternative, with reassuring long-term evaluations thus far.

Risk factors and correlates of neonatal growth velocity in extremely low gestational age newborns: the ELGAN Study.

OBJECTIVES: To identify maternal and infant characteristics associated with reduced growth velocity (GV) in extremely premature newborns. METHODS: We evaluated 1,187 infants born between 23 and 27 weeks' gestation at 14 institutions between 2002 and 2004 who survived until day 28 to identify the maternal and infant characteristics associated with a GV and caloric intake in the lowest quartile. RESULTS: Newborns in the lowest gestational age and low birth weight categories, as well as those with intrauterine growth restriction, or high SNAP-II received relatively fewer kcal/kg/day than their peers without these risk factors, but were not at increased risk of being in the lowest GV quartile. Newborns with bacteremia, patent ductus arteriosus, retinopathy of prematurity stage 3-5, or pulmonary illness received fewer calories, as did those who received medications or blood transfusions. However, in a multivariable model adjusting for confounders, only ventilator dependence on day 7 (OR 2.2, 95% CI 1.5-3.2), early persistent pulmonary dysfunction (OR 1.8, 95% CI 1.3-2.5), and postnatal exposure to dexamethasone (OR 2.8, 95% CI 1.2-6.5) were associated with an increased risk of being in the lowest GV quartile. In this model, low caloric intake was not associated with low GV (OR 1.3, 95% CI 0.9-1.9). CONCLUSION: Variables associated with severe pulmonary disease convey more information about the risk of reduced GV during the first 28 postnatal days than does low caloric intake.