Objective To examine the effect of early initiation of caffeine therapy on neonatal outcomes and characterized the use of caffeine therapy in very-low-birth-weight (VLBW) infants. Study design We analyzed a cohort of 62,056 VLBW infants discharged between 1997 and 2010 who received caffeine. We compared outcomes between infants receiving early caffeine therapy (initial dose <3 days of life) and late caffeine therapy (initial dose ≥3 days of life) through propensity scoring using baseline and early clinical variables. The primary outcome was the association between the timing of caffeine initiation and the incidence of bronchopulmonary dysplasia (BPD) or death. Results We propensity score-matched 29,070 VLBW infants in a 1:1 ratio. Of infants receiving early caffeine therapy, 3681 (27.6%) died or developed BPD compared with 4591 (34.0%) infants receiving late caffeine therapy (odds ratio [OR]=0.74; 99% confidence interval 0.69–0.80). The incidence of BPD was lower in infants receiving early caffeine (early, 23.1%; late, 30.7%; OR=0.68; 0.63–0.73), and the incidence of death was higher (early, 4.5%; late, 3.7%; OR=1.23; 1.05–1.43). Infants receiving early caffeine therapy had decreased treatment of a patent ductus arteriosus (OR=0.60; 0.55–0.65) and a shorter duration of mechanical ventilation (mean difference of 6 days; P<0.001). Conclusions Early caffeine initiation is associated with a decreased incidence of BPD. Randomized trials are needed to determine the efficacy and safety of early caffeine prophylaxis in VLBW infants.

BACKGROUND: Exogenous surfactants to treat respiratory distress syndrome (RDS) are approved for tracheal instillation only; this requires intubation, often followed by positive pressure ventilation to promote distribution. Aerosol delivery offers a safer alternative, but clinical studies have had mixed results. We hypothesized that efficient aerosolization of a surfactant with low viscosity, early in the course of RDS, could reduce the need for intubation and instillation of liquid surfactant. METHODS: A prospective, multicenter, randomized, unblinded comparison trial of aerosolized calfactant (Infasurf) in newborns with signs of RDS that required noninvasive respiratory support. Calfactant was aerosolized by using a Solarys nebulizer modified with a pacifier adapter; 6 mL/kg (210 mg phospholipid/kg body weight) were delivered directly into the mouth. Infants in the aerosol group received up to 3 treatments, at least 4 hours apart. Infants in the control group received usual care, determined by providers. Infants were intubated and given instilled surfactant for persistent or worsening respiratory distress, at their providers’ discretion. RESULTS: Among 22 NICUs, 457 infants were enrolled; gestation 23 to 41 (median 33) weeks and birth weight 595 to 4802 (median 1960) grams. In total, 230 infants were randomly assigned to aerosol; 225 received 334 treatments, starting at a median of 5 hours. The rates of intubation for surfactant instillation were 26% in the aerosol group and 50% in the usual care group (P &lt; .0001). Respiratory outcomes up to 28 days of age were no different. CONCLUSIONS: In newborns with early, mild to moderate respiratory distress, aerosolized calfactant at a dose of 210 mg phospholipid/kg body weight reduced intubation and surfactant instillation by nearly one-half.

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Background Most children who are exposed to large quantities of alcohol in utero do not develop fetal alcohol syndrome (FAS). Population-based prospective data on the risk of developing components of fetal alcohol spectrum disorders (FASD), however, are limited. Methods This was a prospective cohort study of 9,628 women screened during their first prenatal appointment in Chile, which identified 101 who consumed at least 4 drinks/d (exposed) matched with 101 women with no reported alcohol consumption during pregnancy (unexposed). Detailed alcohol consumption data were collected during the pregnancy. Children were evaluated up to 8.5 years of age by clinicians masked to exposure status. Results One or more functional central nervous system abnormalities were present in 44.0% (22/50) of the exposed children compared to 13.6% (6/44) of the unexposed (p = 0.002). Growth restriction was present in 27.2% (25/92) of the exposed and 12.5% (12/96) of the unexposed (p = 0.02). Abnormal facial features were present in 17.3% (14/81) of the exposed children compared to 1.1% (1/89) of the unexposed children (p = 0.0002) by direct examination. Of the 59 exposed children with data available to detect at least 1 abnormality, 12 (20.3%) had no abnormalities. Binge drinking from conception to recognition of pregnancy (OR = 1.48 per day, 95% CI: 1.15 to 1.91, p = 0.002) and after recognition of pregnancy (OR= 1.41 per day, 95% CI: 1.01 to 1.95, p = 0.04) and total number of drinks consumed per week from conception to recognition of pregnancy (OR = 1.02 per drink, 95% CI: 1.01 to 1.04, p = 0.0009) were significantly associated with abnormal child outcome. Conclusions After exposure to heavy alcohol consumption during pregnancy, 80% of children had 1 or more abnormalities associated with alcohol exposure. Patterns of alcohol use that posed the greatest risk of adverse outcomes were binge drinking and high total weekly intake. Functional neurologic impairment occurred most frequently and may be the only sign to alert physicians to prenatal alcohol exposure.