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.

Waning Immunity Against Respiratory Syncytial Virus During the Coronavirus Disease 2019 Pandemic.

Health jurisdictions have seen a near-disappearance of respiratory syncytial virus (RSV) during the first year of the coronavirus disease 2019 (COVID-19) pandemic. Over this corresponding period, we report a reduction in RSV antibody levels and live virus neutralization in sera from women of childbearing age and infants between May to June 2020 and February to June 2021, in British Columbia (BC), Canada. This supports that antibody immunity against RSV is relatively short-lived and that maintaining optimal antibody levels in infants requires repeated maternal viral exposure. Waning immunity may explain the interseasonal resurgence of RSV cases observed in BC and other countries.

Association of umbilical cord blood gas values with mortality and severe neurologic injury in preterm neonates <29 weeks' gestation: a national cohort study.

BACKGROUND: Umbilical cord arterial and venous blood gas values reflect the acid-base balance status of a newborn at birth. Derangement in these values has been linked to poor neonatal outcomes in term and late preterm neonates; however, the utility of these values in preterm neonates of <29 weeks' gestation is unclear. OBJECTIVE: This study aimed to determine the associations of umbilical cord arterial and venous blood gas values with neonatal mortality and severe neurologic injury in extremely preterm neonates and to identify the cutoff values associated with 2.5-fold increases or decreases in the posttest probabilities of outcomes. STUDY DESIGN: This was a retrospective cohort study of neonates who were born at 23+0 to 28+6 weeks' gestation between January 1, 2018 and December 31, 2019, and who were admitted to neonatal units in Canada. EXPOSURE: Various cut-offs of umbilical cord blood gas values and lactate values were studied. MAIN OUTCOMES AND MEASURES: The main outcomes were mortality before discharge from the neonatal unit and severe neurologic injury defined as grade 3 or 4 periventricular or intraventricular hemorrhage or periventricular leukomalacia. The outcome rates were calculated for various cutoff values of umbilical cord blood gas parameters and were adjusted for birthweight, gestational age, sex, and multiple births. Likelihood ratios were calculated to derive posttest probabilities. RESULTS: A total of 1040 and 1217 neonates had analyzable umbilical cord arterial and venous blood gas values, respectively. In the cohort, the mean (standard deviation) gestational age was 26.5 (1.5) weeks, the mean birthweight was 936 (215) g, the prevalence of mortality was 10% (105/1040), and the prevalence of severe neurologic injury was 9% (92/1016). An umbilical cord arterial pH of ≤7.1 and base excess of ≤-12 mmol/L were associated with >2.5-fold higher posttest probability of mortality, and an umbilical cord arterial or venous lactate value of <3 was associated with a 2.5-fold lower posttest probability of mortality. An umbilical cord arterial lactate value of <3 was associated with a lower posttest probability of severe neurological injury. CONCLUSION: In preterm neonates of <29 weeks' gestation, low umbilical cord arterial pH and high umbilical cord arterial base excess values were associated with a clinically important increase in the posttest probability of mortality, whereas low umbilical cord arterial or venous lactate values were associated with a decrease in the posttest probability of mortality.

Rates and Determinants of Mother's Own Milk Feeding in Infants Born Very Preterm.

OBJECTIVES: To examine rates and determinants of mother's own milk (MOM) feeding at hospital discharge in a cohort of infants born very preterm within the Canadian Neonatal Network (CNN). STUDY DESIGN: This was a population-based cohort study of infants born at <33 weeks of gestation and admitted to neonatal intensive care units (NICUs) participating in the CNN between January 1, 2015, and December 31, 2018. We examined the rates and determinants of MOM use at discharge home among the participating NICUs. We used multivariable logistic regression analysis to identify independent determinants of MOM feeding. RESULTS: Among the 6404 infants born very preterm and discharged home during the study period, 4457 (70%) received MOM or MOM supplemented with formula. Rates of MOM feeding at discharge varied from 49% to 87% across NICUs. Determinants associated with MOM feeding at discharge were gestational age 29-32 weeks compared with <26 weeks (aOR 1.56, 95% CI 1.25-1.93), primipara mothers (aOR 2.12, 95% CI 1.86-2.42), maternal diabetes (aOR 0.79, 95% CI 0.66-0.93), and maternal smoking (aOR 0.27, 95% CI 0.19-0.38). Receipt of MOM by day 3 of age was the major predictor of breast milk feeding at discharge (aOR 3.61, 95% CI 3.17-4.12). CONCLUSIONS: Approximately two-thirds of infants born very preterm received MOM at hospital discharge, and rates varied across NICUs. Supporting mothers to provide breast milk in the first 3 days after birth may be associated with improved MOM feeding rates at discharge.

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.

A Comparison of Strategies for Managing the Umbilical Cord at Birth in Preterm Infants.

OBJECTIVE: To evaluate the rates of practice, and the associations between different cord management strategies at birth (delayed cord clamping [DCC], umbilical cord milking [UCM], and early cord clamping [ECC]) and mortality or major morbidity, rates of blood transfusion, and peak serum bilirubin in a large national cohort of very preterm infants. STUDY DESIGN: We retrospectively studied preterm infants <33 weeks of gestation admitted to the Canadian Neonatal Network between January 2015 and December 2017. Patients who received ECC (<30 seconds), UCM, or DCC (≥30 seconds) were compared. Multiple generalized linear/quantile logistic regression models were used. RESULTS: Of 12 749 admitted infants, 9729 were included; 4916 (50.5%) received ECC, 394 (4.1%) UCM, and 4419 (45.4%) DCC. After adjustment for potential confounders identified between groups in univariate analyses, the odds of mortality or major morbidity were higher in the ECC group when compared with UCM group (aOR, 1.18; 95% CI, 1.03-1.35). Mortality and intraventricular hemorrhage were associated with ECC as compared with DCC (aOR, 1.6 [95% CI, 1.22-2.1] and aOR, 1.29 [95% CI, 1.19-1.41], respectively). The odds of severe intraventricular hemorrhage were higher with UCM compared with DCC (aOR, 1.38; 95% CI, 1.05-1.81). Rates of blood transfusion were higher with ECC compared with UCM and DCC (aOR, 1.67 [95% CI, 1.31-2.14] and aOR, 1.68 [95% CI, 1.35-2.09], respectively), although peak serum bilirubin levels were not significantly different. CONCLUSIONS: Both DCC and UCM were associated with better short-term outcomes than ECC; however, the odds of severe intraventricular hemorrhage were higher with UCM compared with DCC.

Duration of Initial Empirical Antibiotic Therapy and Outcomes in Very Low Birth Weight Infants.

: media-1vid110.1542/5984244681001PEDS-VA_2018-2286Video Abstract BACKGROUND: Overuse of antibiotics can facilitate antibiotic resistance and is associated with adverse neonatal outcomes. We studied the association between duration of antibiotic therapy and short-term outcomes of very low birth weight (VLBW) (<1500 g) infants without culture-proven sepsis. METHODS: We included VLBW infants admitted to NICUs in the Canadian Neonatal Network between 2010-2016 who were exposed to antibiotics but did not have culture-proven sepsis in the first week. Antibiotic exposure was calculated as the number of days an infant received antibiotics in the first week of life. Composite primary outcome was defined as mortality or any major morbidity (severe neurologic injury, retinopathy of prematurity, necrotizing enterocolitis, chronic lung disease, or hospital-acquired infection). RESULTS: Of the 14 207 included infants, 21% (n = 2950), 38% (n = 5401), and 41% (n = 5856) received 0, 1 to 3, and 4 to 7 days of antibiotics, respectively. Antibiotic exposure for 4 to 7 days was associated with higher odds of the composite outcome (adjusted odds ratio 1.24; 95% confidence interval [CI] 1.09-1.41). Each additional day of antibiotic use was associated with 4.7% (95% CI 2.6%-6.8%) increased odds of composite outcome and 7.3% (95% CI 3.3%-11.4%) increased odds in VLBW infants at low risk of early-onset sepsis (born via cesarean delivery, without labor and without chorioamnionitis). CONCLUSIONS: Prolonged empirical antibiotic exposure within the first week after birth in VLBW infants is associated with increased odds of the composite outcome. This practice is a potential target for antimicrobial stewardship.

Head Growth Trajectory and Neurodevelopmental Outcomes in Preterm Neonates.

OBJECTIVES: To evaluate the association between head growth (HG) during neonatal and postdischarge periods and neurodevelopmental outcomes of preterm neonates of <29 weeks gestational age. METHODS: We conducted a retrospective cohort study of infants <29 weeks gestationalage admitted between 2009 and 2011 to participating Canadian Neonatal Networkunits and followed by Canadian Neonatal Follow-Up Network clinics. Differences in head circumference (ΔHC) z score were calculated for 3 time periods, which include admission to discharge, discharge to follow-up at 16-36 months, and admission to follow-up. These were categorized in 1 reference group (ΔHC z score between -1 and +1) and 4 study groups (ΔHC z score of <-2, between -2 to -1, +1 to +2, and >+2). Neurodevelopmental outcomes were compared with the reference group. RESULTS: 1973 infants met the inclusion criteria. Poor HG occurred frequently during the NICU admission (ΔHC z score <-2 in 24% infants versus 2% infants post-discharge) with a period of "catch-up" growth postdischarge. Significant neurodevelopmental impairment was higher in infants with the poorest HG from admission to follow-up (adjusted odds ratio 2.18, 95% confidence interval 1.50-3.15), specifically cognitive and motor delays. Infants with poor initial HG and catch-up postdischarge have a lower adjusted odds ratio of significant neurodevelopmental impairment (0.35, 95% CI 0.16-0.74). Infants with poor HG received a longer duration of parenteral nutrition and mechanical ventilation and had poor weight gain. CONCLUSIONS: Poor HG during the neonatal and postdischarge periods was associated with motor and cognitive delays at 16 to 36 months.

Nil-per-os days and necrotizing enterocolitis in extremely preterm infants.

OBJECTIVE: This study aims to evaluate the association between nil-per-os (NPO) days and development of necrotizing enterocolitis (NEC) in extremely preterm neonates (<29 weeks gestational age). STUDY DESIGN: A case-control study of 234 extremely preterm neonates who developed stage II or III NEC and 467 matched control infants admitted to participating sites in the Canadian Neonatal Network between 2010 and 2011 was conducted. The number and percentage of NPO days before the development of NEC was compared with the equivalent period in control infants using logistic regression. RESULTS: Infants with NEC were NPO on average 5.6 days (28% of days before NEC) versus 3.7 days (19% of equivalent days; p < 0.01) among controls. NEC cases required more days of inotropic support, antibiotic use, and had higher rates of patent ductus arteriosus (PDA). After adjusting for inotrope use, PDA, antibiotics, and severity of illness, for each additional NPO day the adjusted odds for NEC increased by 1.08 (95% confidence interval: 1.04-1.12). CONCLUSION: Among extremely preterm neonates, those who developed NEC were NPO for a longer period of time than control infants who were NEC-free. We speculate that delayed initiation or interruption of feeding may be a potent risk factor for NEC.