Enteral feeding during indomethacin and ibuprofen treatment of a patent ductus arteriosus.

OBJECTIVE: To test the hypothesis that infants who are just being introduced to enteral feedings will advance to full enteral nutrition at a faster rate if they receive "trophic" (15 mL/kg/d) enteral feedings while receiving indomethacin or ibuprofen treatment for patent ductus arteriosus. STUDY DESIGN: Infants were eligible for the study if they were 23(1/7)-30(6/7) weeks' gestation, weighed 401-1250 g at birth, received maximum enteral volumes ≤60 mL/kg/d, and were about to be treated with indomethacin or ibuprofen. A standardized "feeding advance regimen" and guidelines for managing feeding intolerance were followed at each site (N = 13). RESULTS: Infants (N = 177, 26.3 ± 1.9 weeks' mean ± SD gestation) were randomized at 6.5 ± 3.9 days to receive "trophic" feeds ("feeding" group, n = 81: indomethacin 80%, ibuprofen 20%) or no feeds ("fasting [nil per os]" group, n = 96: indomethacin 75%, ibuprofen 25%) during the drug administration period. Maximum daily enteral volumes before study entry were 14 ± 15 mL/kg/d. After drug treatment, infants randomized to the "feeding" arm required fewer days to reach the study's feeding volume end point (120 mL/kg/d). Although the enteral feeding end point was reached at an earlier postnatal age, the age at which central venous lines were removed did not differ between the 2 groups. There were no differences between the 2 groups in the incidence of infection, necrotizing enterocolitis, spontaneous intestinal perforation, or other neonatal morbidities. CONCLUSION: Infants required less time to reach the feeding volume end point if they were given "trophic" enteral feedings when they received indomethacin or ibuprofen treatments.

Risk of cranial ultrasound abnormalities in very-low-birth-weight infants conceived with assisted reproductive techniques.

OBJECTIVE: To evaluate risks of cranial ultrasound abnormalities among very-low-birth-weight (VLBW) infants conceived with fertility therapy (ovulation induction only or with assisted reproductive techniques [ART]) and of multiple gestation pregnancies. STUDY DESIGN: The incidences of cranial ultrasound abnormalities in 1473 VLBW infants conceived with and without fertility therapy and born of multiple versus singleton pregnancies were compared, using logistic regression models. RESULTS: Infants conceived with ART were less likely to have intraventricular hemorrhage (IVH). Twins and triplets had risks of cranial ultrasound abnormalities similar to those of singletons. Twins and triplets conceived with ART were at lower risk of IVH. CONCLUSION: VLBW infants conceived with ART do not appear to be at increased risk of cranial ultrasound abnormalities. Likewise, twins and triplets were not at increased risk of these abnormalities.

Hypothermia for hypoxic-ischemic encephalopathy.

We are entering an era in which hypothermia will be used in combination with other novel neuroprotective interventions. The targeting of multiple sites in the cascade leading to brain injury may prove to be a more effective treatment strategy after hypoxic-ischemic encephalopathy in newborn infants than hypothermia alone.

Variables associated with the early failure of nasal CPAP in very low birth weight infants.

OBJECTIVE: To identify risk factors and neonatal outcomes associated with the early failure of "bubble" nasal continuous positive airway pressure (CPAP) in very low birth weight (VLBW) infants with respiratory distress syndrome (RDS). STUDY DESIGN: Following resuscitation and stabilization at delivery, a cohort of 261 consecutively inborn infants (birth weight < or = 1250 g) was divided into three groups based on the initial respiratory support modality and outcome at 72 hours of age: "ventilator-started" group, "CPAP-failure" group, and "CPAP-success" group. RESULTS: CPAP was successful in 76% of infants < or = 1250 g birth weight and 50% of infants < or = 750 g birth weight. In analyses adjusted for postmenstrual age (PMA) and small for gestational age (SGA), CPAP failure was associated with need for positive pressure ventilation (PPV) at delivery, alveolar-arterial oxygen tension gradient (A-a DO2) >180 mmHg on the first arterial blood gas (ABG), and severe RDS on the initial chest x-ray (adjusted odds ratio [95% CI] = 2.37 [1.02, 5.52], 2.91 [1.30, 6.55] and 6.42 [2.75, 15.0], respectively). The positive predictive value of these variables ranged from 43% to 55%. In analyses adjusted for PMA and severe RDS, rates of mortality and common premature morbidities were higher in the CPAP-failure group than in the CPAP-success group. CONCLUSION: Although several variables available near birth were strongly associated with early CPAP failure, they proved weak predictors of failure. A prospective controlled trial is needed to determine if extremely premature spontaneously breathing infants are better served by initial management with CPAP or mechanical ventilation.

Factors associated with microcephaly at school age in a very-low-birthweight population.

The neonatal predictors of microcephaly, defined as a head circumference <5th centile in children born preterm, has not been systematically assessed. Children were drawn from the Developmental Epidemiology Network (DEN) cohort of very low-birthweight children (VLBW: 500-1500g) born from 1991 to 1993 at three sites in the USA. Neurological assessments were carried out among 198 singleton children (mean age 6 years 8 months, SD 0.5 years). Ninety-six children (48.5%) were male. Microcephaly was observed in 30 children (15%) and, using multivariate analysis, it was found to be associated with gestational age <26 weeks and bronchopulmonary dysplasia (BPD). Sonography-defined white-matter damage (WMD, i.e. echolucency or echodensities) was not associated with increased odds of microcephaly, while occurrence of intraventricular hemorrhage (IVH) was in univariate but not multivariate analysis. In analyses that excluded children with IVH/WMD, odds of microcephaly increased in dose-related fashion according to number of days on ventilator: >5 days, OR=4.5; 95%CI=1.4 to 15; >10 days, OR=5.7; 95%CI=1.7 to 19; >15 days OR=8.3; 95% CI=2.3 to 29.2. Among children without BPD, microcephaly was not associated with differences in IQ, while IQ scores among children with BPD or any ventilation were disproportionately lower among those with microcephaly. In multivariate analyses predicting IQ at age 7 years, microcephaly was found to modify the association between neonatal lung disease and IQ.

Systemic hypotension and white-matter damage in preterm infants.

This study was designed to test the hypothesis that systemic hypotension during the first postnatal week increases the risk of ultrasonographic echolucency in the white matter of preterm infants (< or = 28 weeks' gestation) while adjusting for confounders. From a study base of 1607 very-low-birthweight neonates (500 to 1500 g), a subsample of 243 preterm infants (122 females; < or = 28 weeks' gestation) was selected for echolucency and data collection prospectively for the entire first postnatal week. Data analyses were performed separately for the first 24 hours of life, for the interval from the end of the first 24 hours to the end of the fourth postnatal day, and for days 5, 6, and 7. Systemic hypotension was defined as the mean arterial blood pressure in the lowest quartile for the infant's week of gestational age. Protocol cranial ultrasounds were those obtained closest to days 1, 7, and 21. A committee of sonologists classified the infants as having either echolucency (echolucency group) or not (control group). Systemic hypotension during the first week of life appeared to be associated with echolucency in univariable analyses but the association did not persist after adjustment for potential confounders. Detailed summaries of 13 previous studies, the majority of which did not show an association between systemic hypotension and white-matter damage, are presented. In sum, these results do not support the hypothesis that systemic hypotension contributes to echolucency among preterm infants.