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OBJECTIVE:To study the impact of neonatal sepsis on the long-term neurodevelopmental outcome in very low birth weight (VLBW) infants. STUDY DESIGN: Systematic review and meta-analysis of observational studies comparing neurodevelopmental outcomes in VLBW infants exposed to culture-proven sepsis in the neonatal period with similar infants without sepsis. RESULT: Seventeen studies involving 15 331 infants were included in the meta-analysis. Sepsis in VLBW infants was associated with an increased risk of one or more long-term neurodevelopmental impairments (odds ratio (OR) 2.09; 95% confidence interval (CI) 1.65 to 2.65) including cerebral palsy (CP; OR 2.09; 95% CI 1.78 to 2.45). Heterogeneity (I 2 ¼ 36.9%; P ¼ 0.06) between the studies was significant and related to variations in patient characteristics, causative pathogens and follow-up methods. Sensitivity analyses based on study design, follow-up rate and year of birth were not significantly different from the overall analysis. CONCLUSION: The meta-analysis suggests that sepsis in VLBW infants is associated with a worse neurodevelopmental outcome including higher incidence of CP.

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 MEASURESThe 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.

We prospectively evaluated risk factors for early-onset neonatal (EON) sepsis in a case-control study among inborn patients at the Aga Khan University Medical Centre in Karachi between 1990-1993. A total of 38 cases with blood culture proven bacterial sepsis were identified within 72 hr of birth (prevalence 5.6 of 1000 live births) and matched with two consecutive gender matched births with no complications. The most common isolates were Staphylococcus aureus (18%), group B Streptococci (13%), and Klebsiella pneumoniae (13%). Univariate analysis of maternal risk factors revealed a significant association between maternal urinary tract infection (UTI) (odds ratio [OR]20, 95% confidence interval [CI]2.4-166.9), maternal pyrexia (P < 0.0001), vaginal discharge (P < 0.05), vaginal examinations during labor (P = 0.03), and EON sepsis. The infected newborns also had significantly lower apgar scores at birth (P < 0.0001) and a significantly greater number were intubated at birth (Fisher's exact test P = 0.04). Infected newborn infants were transferred out of the labor room earlier than noninfected controls and significantly fewer received exclusive breastfeeds (OR 0.33, 95% CI 0.1-0.8). Our data suggest the possibility that both vertical transmission from the mother as well as postnatal acquisition of infection from the environment may be of importance in the pathogenesis of EON sepsis in Karachi. Preventive measures should focus at recognition of high-risk infants, strict asepsis during labor, and early institution of exclusive breastfeeding.

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, g, h, i on behalf of the investigators of the Canadian Neonatal Network (CNN) and the Canadian Neonatal Follow-up Network (CNFUN) BACKGROUND: Although caffeine use for apnea of prematurity is well studied, the long-term safety and benefit of routine early caffeine administration has not been explored. Our objective was to determine the association between early (within 2 days of birth) versus late caffeine exposure and neurodevelopmental outcomes in preterm infants. METHODS: Infants of <29 weeks' gestation born between April 2009 and September 2011 and admitted to Canadian Neonatal Network units and then assessed at Canadian Neonatal Follow-up Network centers were studied. Neonates who received caffeine were divided into early-(received within 2 days of birth) and late-caffeine (received after 2 days of birth) groups. The primary outcome was significant neurodevelopmental impairment, defined as cerebral palsy, or a Bayley Scales of Infant and Toddler Development, Third Edition composite score of <70 on any component, hearing aid or cochlear implant, or bilateral visual impairment at 18 to 24 months' corrected age. RESULTS: Of 2108 neonates who were eligible, 1545 were in the early-caffeine group and 563 were in the late-caffeine group. Rates of bronchopulmonary dysplasia, patent ductus arteriosus, and severe neurologic injury were lower in the early-caffeine group than in the late-caffeine group. Significant neurodevelopmental impairment (adjusted odds ratio 0.68 [95% confidence interval 0.50-0.94]) and odds of Bayley Scales of Infant and Toddler Development, Third Edition cognitive scores of <85 (adjusted odds ratio 0.67 [95% confidence interval 0.47-0.95]) were lower in the early-caffeine group than in the late-caffeine group. Propensity score-based matched-pair analyses revealed lower odds of cerebral palsy and hearing impairment only. CONCLUSIONS: Early caffeine therapy is associated with better neurodevelopmental outcomes compared with late caffeine therapy in preterm infants born at <29 weeks' gestation.