Umbilical Cord Milking vs Delayed Cord Clamping and Associations with In-Hospital Outcomes among Extremely Premature Infants.

OBJECTIVE: To compare in-hospital outcomes after umbilical cord milking vs delayed cord clamping among infants <29 weeks of gestation. STUDY DESIGN: Multicenter retrospective study of infants born <29 weeks of gestation from 2016 to 2018 without congenital anomalies who received active treatment at delivery and were exposed to umbilical cord milking or delayed cord clamping. The primary outcome was mortality or severe (grade III or IV) intraventricular hemorrhage (IVH) by 36 weeks of postmenstrual age (PMA). Secondary outcomes assessed at 36 weeks of PMA were mortality, severe IVH, any IVH or mortality, and a composite of mortality or major morbidity. Outcomes were assessed using multivariable regression, incorporating mortality risk factors identified a priori, confounders, and center. A prespecified, exploratory analysis evaluated severe IVH in 2 gestational age strata, 22-246/7 and 25-286/7 weeks. RESULTS: Among 1834 infants, 23.6% were exposed to umbilical cord milking and 76.4% to delayed cord clamping. The primary outcome, mortality or severe IVH, occurred in 21.1% of infants: 28.3% exposed to umbilical cord milking and 19.1% exposed to delayed cord clamping, with an aOR that was similar between groups (aOR 1.45, 95% CI 0.93, 2.26). Infants exposed to umbilical cord milking had higher odds of severe IVH (19.8% umbilical cord milking vs 11.8% delayed cord clamping, aOR 1.70 95% CI 1.20, 2.43), as did the 25-286/7 week stratum (14.8% umbilical cord milking vs 7.4% delayed cord clamping, aOR 1.89 95% CI 1.22, 2.95). Other secondary outcomes were similar between groups. CONCLUSIONS: This analysis of extremely preterm infants suggests that delayed cord clamping is the preferred practice for placental transfusion, as umbilical cord milking exposure was associated with an increase in the adverse outcome of severe IVH. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00063063.

Outcomes Following Post-Hemorrhagic Ventricular Dilatation among Infants of Extremely Low Gestational Age.

OBJECTIVE: To assess outcomes following post-hemorrhagic ventricular dilatation (PHVD) among infants born at ≤26 weeks of gestation. STUDY DESIGN: Observational study of infants born April 1, 2011, to December 31, 2015, in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network and categorized into 3 groups: PHVD, intracranial hemorrhage without ventricular dilatation, or normal head ultrasound. PHVD was treated per center practice. Neurodevelopmental impairment at 18-26 months was defined by cerebral palsy, Bayley Scales of Infant and Toddler Development, 3rd edition, cognitive or motor score <70, blindness, or deafness. Multivariable logistic regression examined the association of death or impairment, adjusting for neonatal course, center, maternal education, and parenchymal hemorrhage. RESULTS: Of 4216 infants, 815 had PHVD, 769 had hemorrhage without ventricular dilatation, and 2632 had normal head ultrasounds. Progressive dilatation occurred among 119 of 815 infants; the initial intervention in 66 infants was reservoir placement and 53 had ventriculoperitoneal shunt placement. Death or impairment occurred among 68%, 39%, and 28% of infants with PHVD, hemorrhage without dilatation, and normal head ultrasound, respectively; aOR (95% CI) were 4.6 (3.8-5.7) PHVD vs normal head ultrasound scan and 2.98 (2.3-3.8) for PHVD vs hemorrhage without dilatation. Death or impairment was more frequent with intervention for progressive dilatation vs no intervention (80% vs 65%; aOR 2.2 [1.38-3.8]). Death or impairment increased with parenchymal hemorrhage, intervention for PHVD, male sex, and surgery for retinopathy; odds decreased with each additional gestational week. CONCLUSIONS: PHVD was associated with high rates of death or impairment among infants with gestational ages ≤26 weeks; risk was further increased among those with progressive ventricular dilation requiring intervention.

Association between Policy Changes for Oxygen Saturation Alarm Settings and Neonatal Morbidity and Mortality in Infants Born Very Preterm.

OBJECTIVE: To determine the impact of policy changes for pulse oximetry oxygen saturation (SpO2) alarm limits on neonatal mortality and morbidity among infants born very preterm. STUDY DESIGN: This was a retrospective cohort study of infants born very preterm in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants were classified based on treatment at a hospital with an SpO2 alarm policy change and study epoch (before vs after policy change). We used a generalized linear mixed model to determine the effect of hospital group and epoch on the primary outcomes of mortality and severe retinopathy of prematurity (ROP) and secondary outcomes of necrotizing enterocolitis, bronchopulmonary dysplasia, and any ROP. RESULTS: There were 3809 infants in 10 hospitals with an SpO2 alarm policy change and 3685 infants in 9 hospitals without a policy change. The nature of most policy changes was to narrow the SpO2 alarm settings. Mortality was lower in hospitals without a policy change (aOR 0.63; 95% CI 0.50-0.80) but did not differ between epochs in policy change hospitals. The odds of bronchopulmonary dysplasia were greater for hospitals with a policy change (aOR 1.65; 95% CI 1.36-2.00) but did not differ for hospitals without a policy change. Severe ROP and necrotizing enterocolitis did not differ between epochs for either group. The adjusted odds of any ROP were lower in recent years in both hospital groups. CONCLUSIONS: Changing SpO2 alarm policies was not associated with reduced mortality or increased severe ROP among infants born very preterm.

Discordance in Antenatal Corticosteroid Use and Resuscitation Following Extremely Preterm Birth.

OBJECTIVE: To describe discordance in antenatal corticosteroid use and resuscitation following extremely preterm birth and its relationship with infant survival and neurodevelopment. STUDY DESIGN: A multicenter cohort study of 4858 infants 22-26 weeks of gestation born 2006-2011 at 24 US hospitals participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, with follow-up through 2013. Survival and neurodevelopmental outcomes were available at 18-22 months of corrected age for 4576 (94.2%) infants. We described antenatal interventions, resuscitation, and infant outcomes. We modeled the effect on infant outcomes of each hospital increasing antenatal corticosteroid exposure for resuscitated infants born at 22-24 weeks of gestation to rates observed at 25-26 weeks of gestation. RESULTS: Discordant antenatal corticosteroid use and resuscitation, where one and not the other occurred, were more frequent for births at 22 and 23 but not 24 weeks (rate ratio [95% CI] at 22 weeks: 1.7 [1.3-2.2]; 23 weeks: 2.6 [2.2-3.2]; 24 weeks: 1.0 [0.8-1.2]) when compared with 25-26 weeks. Among infants resuscitated at 23 weeks, adjusting each hospital's rate of antenatal corticosteroid use to the average at 25-26 weeks (89.2%) was projected to increase infant survival by 7.1% (95% CI 5.4-8.8%) and survival without severe impairment by 6.4% (95% CI 4.7-8.1%). No significant change in outcomes was projected for infants resuscitated at 22 weeks, where few (n = 22) resuscitated infants received antenatal corticosteroids. CONCLUSIONS: Infants born at 23 weeks were more frequently resuscitated without antenatal corticosteroids than other extremely preterm infants. When resuscitation is intended, consistent provision of antenatal corticosteroids may increase infant survival and survival without impairment. TRIAL REGISTRATION: ClinicalTrials.govNCT00063063 (Generic Database) and NCT00009633 (Follow-Up Study).

Weaning of Moderately Preterm Infants from the Incubator to the Crib: A Randomized Clinical Trial.

OBJECTIVE: To assess whether length of hospital stay is decreased among moderately preterm infants weaned from incubator to crib at a lower vs higher weight. STUDY DESIGN: This trial was conducted in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants with gestational ages 29-33 weeks, birthweight <1600 g, and in an incubator were randomly assigned to a weaning weight of 1600 or 1800 g. Within 60 to 100 g of weaning weight, the incubator temperature was decreased by 1.0°C to 1.5°C every 24 hours until 28.0°C. The infants were weaned to the crib following stable temperature at 36.5°C to 37.4°C for 8 to 12 hours. Clothing and bedcoverings were standardized. The primary outcome was length of hospital stay from birth to discharge; secondary outcomes included length of stay and growth velocity from weaning to discharge. Adverse events were monitored. RESULTS: Of 1565 infants screened, 885 were eligible, and 366 enrolled-187 to the 1600-g and 179 to the 1800-g group. Maternal and neonatal characteristics did not differ among weight groups. Length of hospital stay was a median of 43 days in the lower and 41 days in the higher weight group (P = .12). Growth velocity from completion of weaning to discharge was higher in the lower weight group, 13.7 g/kg/day vs 12.8 g/kg/day (P = .005). Groups did not differ in adverse events. CONCLUSIONS: Among moderately preterm neonates, weaning from incubator to crib at a lower weight did not decrease length of stay, but was safe and was accompanied by higher weight gain after weaning. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02160002.

Antecedents and Outcomes of Abnormal Cranial Imaging in Moderately Preterm Infants.

OBJECTIVES: To describe the frequency and findings of cranial imaging in moderately preterm infants (born at 290/7-336/7 weeks of gestation) across centers, and to examine the association between abnormal imaging and clinical characteristics. STUDY DESIGN: We used data from the Neonatal Research Network Moderately Preterm Registry, including the most severe early (≤28 days) and late (>28 days) cranial imaging. Stepwise logistic regression and CART analysis were performed after adjustment for gestational age, antenatal steroid use, and center. RESULTS: Among 7021 infants, 4184 (60%) underwent cranial imaging. These infants had lower gestational ages and birth weights and higher rates of small for gestational age, outborn birth, cesarean delivery, neonatal resuscitation, and treatment with surfactant, compared with those without imaging (P < .0001). Imaging abnormalities noted in 15% of the infants included any intracranial hemorrhage (13.2%), grades 3-4 intracranial hemorrhage (1.7%), cystic periventricular leukomalacia (2.6%), and ventriculomegaly (6.6%). Histologic chorioamnionitis (OR, 1.47; 95% CI, 1.19-1.83), gestational age (0.95; 95% CI, 0.94-0.97), antenatal steroids (OR, 0.55; 95% CI, 0.41-0.74), and cesarean delivery (OR, 0.66; 95% CI, 0.53-0.81) were associated with abnormal imaging. The center with the highest rate of cranial imaging, compared with the lowest, had a higher risk of abnormal imaging (OR, 2.08; 95% CI, 1.10-3.92). On the classification and regression-tree model, cesarean delivery, center, antenatal steroids, and chorioamnionitis, in that order, predicted abnormal imaging. CONCLUSION: Among the 60% of moderately preterm infants with cranial imaging, 15% had intracranial hemorrhage, cystic periventricular leukomalacia or late ventriculomegaly. Further correlation of imaging and long-term neurodevelopmental outcomes in moderately preterm infants is needed.

Delivery Room Resuscitation and Short-Term Outcomes in Moderately Preterm Infants.

OBJECTIVES: To describe the frequency and extent of delivery room resuscitation and evaluate the association of delivery room resuscitation with neonatal outcomes in moderately preterm (MPT) infants. STUDY DESIGN: This was an observational cohort study of MPT infants delivered at 290/7 to 336/7 weeks' gestational age (GA) enrolled in the Neonatal Research Network MPT registry. Infants were categorized into 5 groups based on the highest level of delivery room intervention: routine care, oxygen and/or continuous positive airway pressure, bag and mask ventilation, endotracheal intubation, and cardiopulmonary resuscitation including chest compressions and/or epinephrine use. The association of antepartum and intrapartum risk factors and discharge outcomes with the intensity of resuscitation was evaluated. RESULTS: Of 7014 included infants, 1684 (24.0%) received routine care and no additional resuscitation, 2279 (32.5%) received oxygen or continuous positive airway pressure, 1831 (26.1%) received bag and mask ventilation, 1034 (14.7%) underwent endotracheal intubation, and 186 (2.7%) received cardiopulmonary resuscitation. Among the antepartum and intrapartum factors, increasing GA, any exposure to antenatal steroids and prolonged rupture of membranes decreased the likelihood of receipt of all levels of resuscitation. Infants who were small for GA (SGA) had increased risk of delivery room resuscitation. Among the neonatal outcomes, respiratory support at 28 days, days to full oral feeds and length of stay were significantly associated with the intensity of delivery room resuscitation. Higher intensity of resuscitation was associated with increased risk of mortality. CONCLUSIONS: The majority of MPT infants receive some level of delivery room resuscitation. Increased intensity of delivery room interventions was associated with prolonged respiratory and nutritional support, increased mortality, and a longer length of stay.

Admission Temperature and Associated Mortality and Morbidity among Moderately and Extremely Preterm Infants.

OBJECTIVE: To evaluate the temperature distribution among moderately preterm (MPT, 29-33 weeks) and extremely preterm (EPT, <29 weeks) infants upon neonatal intensive care unit (NICU) admission in 2012-2013, the change in admission temperature distribution for EPT infants between 2002-2003 and 2012-2013, and associations between admission temperature and mortality and morbidity for both MPT and EPT infants. STUDY DESIGN: Prospectively collected data from 18 centers in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network were used to examine NICU admission temperature of inborn MPT and EPT infants. Associations between admission temperature and mortality and morbidity were determined by multivariable logistic regression. EPT infants from 2002-2003 and 2012-2013 were compared. RESULTS: MPT and EPT cohorts consisted of 5818 and 3213 infants, respectively. The distribution of admission temperatures differed between the MPT vs EPT (P < .01), including the percentage <36.5°C (38.6% vs 40.9%), 36.5°C-37.5°C (57.3% vs 52.9%), and >37.5°C (4.2% vs 6.2%). For EPT infants in 2012-2013 compared with 2002-2003, the percentage of temperatures between 36.5°C and 37.5°C more than doubled and the percentage of temperatures >37.5°C more than tripled. Admission temperature was inversely associated with in-hospital mortality. CONCLUSIONS: Low and high admission temperatures are more frequent among EPT than MPT infants. Compared with a decade earlier, fewer EPT infants experience low admission temperatures but more have elevated temperatures. In spite of a change in distribution of NICU admission temperature, an inverse association between temperature and mortality risk persists.

Association between Use of Prophylactic Indomethacin and the Risk for Bronchopulmonary Dysplasia in Extremely Preterm Infants.

OBJECTIVE: To assess the association between prophylactic indomethacin and bronchopulmonary dysplasia (BPD) in a recent, large cohort of extremely preterm infants. STUDY DESIGN: Retrospective cohort study using prospectively collected data for infants with gestational ages < 29 weeks or birth weights of 401-1000 g born between 2008 and 2012 at participating hospitals of the National Institute of Child Health and Human Development Neonatal Research Network. Infants treated with indomethacin in the first 24 hours of life were compared with those who were not. Study outcomes were BPD, defined as use of supplemental oxygen at 36 weeks postmenstrual age among survivors to that time point, death, and the composite of death or BPD. Prespecified subgroup analyses were performed. RESULTS: Prophylactic indomethacin use varied by hospital. Treatment of a patent ductus arteriosus after the first day of life was less common among 2587 infants who received prophylactic indomethacin compared with 5244 who did not (21.0% vs 36.1%, P < .001). After adjustment for potential confounders, use of prophylactic indomethacin was not associated with higher or lower odds of BPD (OR 0.89, 95% CI 0.72-1.10), death (OR 0.80, 95% CI 0.64-1.01), or death or BPD (OR 0.87, 95% CI 0.71-1.05). The only evidence of subgroup effects associated with prophylactic indomethacin were lower odds of death among infants with birth weights above the 10th percentile and those who were not treated for a patent ductus arteriosus after the first day of life. CONCLUSIONS: Prophylactic indomethacin was not associated with either reduced or increased risk for BPD or death. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00063063.

Patterns of Oxygenation, Mortality, and Growth Status in the Surfactant Positive Pressure and Oxygen Trial Cohort.

OBJECTIVE: To characterize actual achieved patterns of oxygenation in infants born appropriate vs small for gestational age (SGA) randomized to a lower (85-89%) vs higher (91%-95%) oxygen saturation target in the Surfactant Positive Pressure and Oxygen Trial. To determine the association between achieved oxygen saturation levels and survival in infants born appropriate vs SGA enrolled in the Surfactant Positive Pressure and Oxygen Trial. STUDY DESIGN: Median oxygen saturation and intermittent hypoxemia events (<80%, 20 seconds-5 minutes) were documented in 1054 infants of 240/7-276/7 weeks of gestation while receiving supplemental oxygen during the first 3 days of life. RESULTS: Lower target infants who were small for gestational age had the lowest oxygen saturation and highest incidence of intermittent hypoxemia during the first 3 days of life. The lowest quartile of oxygen saturation (≤92%) during the first 3 days of life was associated with lower 90-day survival for both infants born appropriate and SGA. An increased incidence of intermittent hypoxemia events during the first 3 days of life was associated with lower 90-day survival only in infants born SGA. CONCLUSION: Lower achieved oxygen saturation during the first 3 days of life was associated with lower 90-day survival in extremely preterm infants. Infants born SGA had enhanced vulnerability to lower oxygen saturation targets as evidenced by lower achieved oxygen saturation and an association between increased intermittent hypoxemia events and lower survival. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00233324.

Growth Outcomes of Preterm Infants Exposed to Different Oxygen Saturation Target Ranges from Birth.

OBJECTIVE: To test whether infants randomized to a lower oxygen saturation (peripheral capillary oxygen saturation [SpO2]) target range while on supplemental oxygen from birth will have better growth velocity from birth to 36 weeks postmenstrual age (PMA) and less growth failure at 36 weeks PMA and 18-22 months corrected age. STUDY DESIGN: We evaluated a subgroup of 810 preterm infants from the Surfactant, Positive Pressure, and Oxygenation Randomized Trial, randomized at birth to lower (85%-89%, n = 402, PMA 26 ± 1 weeks, birth weight 839 ± 186 g) or higher (91%-95%, n = 408, PMA 26 ± 1 weeks, birth weight 840 ± 191 g) SpO2 target ranges. Anthropometric measures were obtained at birth, postnatal days 7, 14, 21, and 28; then at 32 and 36 weeks PMA; and 18-22 months corrected age. Growth velocities were estimated with the exponential method and analyzed with linear mixed models. Poor growth outcome, defined as weight <10th percentile at 36 weeks PMA and 18-22 months corrected age, was compared across the 2 treatment groups by the use of robust Poisson regression. RESULTS: Growth outcomes including growth at 36 weeks PMA and 18-22 months corrected age, as well as growth velocity were similar in the lower and higher SpO2 target groups. CONCLUSION: Targeting different oxygen saturation ranges between 85% and 95% from birth did not impact growth velocity or reduce growth failure in preterm infants.

Respiratory outcomes of the surfactant positive pressure and oximetry randomized trial (SUPPORT).

OBJECTIVE: To explore the early childhood pulmonary outcomes of infants who participated in the National Institute of Child Health and Human Development's Surfactant Positive Airway Pressure and Pulse Oximetry Randomized Trial (SUPPORT), using a factorial design that randomized extremely preterm infants to lower vs higher oxygen saturation targets and delivery room continuous positive airway pressure (CPAP) vs intubation/surfactant. STUDY DESIGN: The Breathing Outcomes Study, a prospective secondary study to the Surfactant Positive Airway Pressure and Pulse Oximetry Randomized Trial, assessed respiratory morbidity at 6-month intervals from hospital discharge to 18-22 months corrected age (CA). Two prespecified primary outcomes-wheezing more than twice per week during the worst 2-week period and cough longer than 3 days without a cold-were compared for each randomized intervention. RESULTS: One or more interviews were completed for 918 of the 922 eligible infants. The incidences of wheezing and cough were 47.9% and 31.0%, respectively, and did not differ between the study arms of either randomized intervention. Infants randomized to lower vs higher oxygen saturation targets had a similar risk of death or respiratory morbidity (except for croup and treatment with oxygen or diuretics at home). Infants randomized to CPAP vs intubation/surfactant had fewer episodes of wheezing without a cold (28.9% vs 36.5%; P<.05), respiratory illnesses diagnosed by a doctor (47.7% vs 55.2%; P<.05), and physician or emergency room visits for breathing problems (68.0% vs 72.9%; P<.05) by 18-22 months CA. CONCLUSION: Treatment with early CPAP rather than intubation/surfactant is associated with less respiratory morbidity by 18-22 months CA. Longitudinal assessment of pulmonary morbidity is necessary to fully evaluate the potential benefits of respiratory interventions for neonates.

Developmental outcomes of very preterm infants with tracheostomies.

OBJECTIVES: To evaluate the neurodevelopmental outcomes of very preterm (<30 weeks) infants who underwent tracheostomy. STUDY DESIGN: Retrospective cohort study from 16 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network over 10 years (2001-2011). Infants who survived to at least 36 weeks (N = 8683), including 304 infants with tracheostomies, were studied. Primary outcome was death or neurodevelopmental impairment (NDI; a composite of ≥1 of developmental delay, neurologic impairment, profound hearing loss, severe visual impairment) at a corrected age of 18-22 months. Outcomes were compared using multiple logistic regression. We assessed the impact of timing by comparing outcomes of infants who underwent tracheostomy before and after 120 days of life. RESULTS: Tracheostomies were associated with all neonatal morbidities examined and with most adverse neurodevelopmental outcomes. Death or NDI occurred in 83% of infants with tracheostomies and 40% of those without (OR adjusted for center 7.0, 95% CI 5.2-9.5). After adjustment for potential confounders, odds of death or NDI remained higher (OR 3.3, 95% CI 2.4-4.6), but odds of death alone were lower (OR 0.4, 95% CI 0.3-0.7) among infants with tracheostomies. Death or NDI was lower in infants who received their tracheostomies before, rather than after, 120 days of life (aOR 0.5, 95% CI 0.3-0.9). CONCLUSIONS: Tracheostomy in preterm infants is associated with adverse developmental outcomes and cannot mitigate the significant risk associated with many complications of prematurity. These data may inform counseling about tracheostomy in this vulnerable population.

Superior mesenteric artery blood flow velocities following medical treatment of a patent ductus arteriosus.

We examined superior mesenteric artery blood flow velocity in response to feeding in infants randomized to trophic feeds (n = 16) or nil per os (n = 18) during previous treatment for patent ductus arteriosus. Blood flow velocity increased earlier in the fed infants, but was similar in the 2 groups at 30 minutes after feeding.

Neurodevelopmental outcome of extremely low birth weight infants with Candida infection.

OBJECTIVE: Candida remains an important cause of late-onset infection in preterm infants. Mortality and neurodevelopmental outcome of extremely low birth weight (ELBW) infants enrolled in the Candida study were evaluated based on infection status. STUDY DESIGN: ELBW infants born at Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) centers between March 2004 and July 2007 who were screened for suspected sepsis were eligible for inclusion in the Candida study. Primary outcome data for neurodevelopmental impairment (NDI) or death were available for 1317 of the 1515 infants (87%) enrolled in the Candida study. The Bayley Scales of Infant Development-II or -III was administered at 18 months' adjusted age. A secondary comparison was performed with 864 infants enrolled in the NRN Generic Database during the same cohort who were never screened for sepsis and therefore not eligible for the Candida study. RESULTS: Among ELBW infants enrolled in the Candida study, 31% with Candida and 31% with late-onset non-Candida sepsis had NDI at 18 months. Infants with Candida sepsis and/or meningitis had an increased risk of death and were more likely to have the composite outcome of death and/or NDI compared with uninfected infants in adjusted analysis. Compared with infants in the NRN registry never screened for sepsis, overall risk for death were similar but those with Candida infection were more likely to have NDI (OR 1.83, 95% CI 1.01-3.33, P = .047). CONCLUSIONS: In this cohort of ELBW infants, those with infection and/or meningitis were at increased risk for death and/or NDI. This risk was highest among those with Candida sepsis and/or meningitis.

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.

Outcomes of small for gestational age infants born at <27 weeks' gestation.

OBJECTIVE: To determine whether small for gestational age (SGA) infants born at <27 weeks gestational age (GA) are at increased risk for mortality, morbidity, and growth and neurodevelopmental impairment at 18-22 months corrected age. STUDY DESIGN: This was a retrospective cohort study from National Institute of Child Health and Human Development Neonatal Research Network's Generic Database and Follow-Up Studies. Infants born at <27 weeks GA between January 2006 and July 2008 were included. SGA was defined as birth weight <10th percentile for GA based on Olsen growth curves. Infants with birth weight ≥ 10th percentile for GA were classified as non-SGA. Maternal and infant characteristics, neonatal outcomes, and neurodevelopmental data were compared in SGA and non-SGA infants. Neurodevelopmental impairment was defined as any of the following: cognitive score <70 on the Bayley Scales of Infant Development III, moderate or severe cerebral palsy, bilateral hearing loss (with and without amplification), or blindness (bilateral vision <20/200). Logistic regression analysis was applied to evaluate the associations between SGA status and death or neurodevelopmental impairment. RESULTS: The SGA group comprised 385 infants; the non-SGA group, 2586 infants. Compared with mothers of non-SGA infants, mothers of SGA infants were more likely to have a high school education, prenatal care, cesarean delivery, pregnancy-induced hypertension, and antenatal corticosteroid exposure. Compared with non-SGA infants, SGA infants had higher mortality and were more likely to have postnatal growth failure, prolonged mechanical ventilation, and postnatal steroid use. SGA status was associated with increased risk of death or neurodevelopmental impairment (OR, 3.91; 95% CI, 2.91-5.25; P < .001). CONCLUSION: SGA status in infants born at <27 weeks GA is associated with an increased likelihood of postnatal steroid use, mortality, growth failure, and neurodevelopmental impairment at 18-22 months corrected age.

Late-onset sepsis in very low birth weight infants from singleton and multiple-gestation births.

OBJECTIVES: To describe and compare the incidence of late-onset sepsis (LOS) and demographic and clinical characteristics associated with LOS in very low birth weight (VLBW) infants from singleton and multiple births, and to examine the heritability of susceptibility to LOS among VLBW twins by comparing same-sex and unlike-sex twin pairs. STUDY DESIGN: The study group comprised infants with birth weight 401-1500 g seen at clinical centers of the Eunice Kennedy Shriver National Institute of Child and Human Development Neonatal Research Network between 2002 and 2008. Only the first episode of LOS was included in our analysis. Stepwise logistic regression models were fitted separately for singleton and multiple pregnancies to examine the maternal and neonatal factors associated with LOS. LOS due solely to gram-negative bacteria in singleton and multiple pregnancies was also examined in separate models. The heritability of LOS was estimated by examining the concordance of LOS in twins from same-sex and unlike-sex pairs. RESULTS: LOS occurred in 25.0% (3797 of 15,178) of singleton and 22.6% (1196 of 5294) of multiple-birth VLBW infants. Coagulase-negative staphylococci were the most common infecting organisms, accounting for 53.2% of all LOS episodes in singletons and 49.2% in multiples. Escherichia coli and Klebsiella species were the most commonly isolated gram-negative organisms, and Candida albicans was the most commonly isolated fungus. Concordance of LOS did not differ significantly between same-sex and unlike-sex twin pairs. CONCLUSION: LOS remains a common problem in VLBW infants. The incidence of LOS is similar for singleton and multiple-birth infants. The similar concordance of LOS in same-sex and unlike-sex twin pairs provides no evidence that susceptibility to LOS among VLBW infants is genetically determined.

Low oxygen saturation target range is associated with increased incidence of intermittent hypoxemia.

OBJECTIVE: To test the hypothesis that preterm infants randomized to a low vs high O(2) saturation target range have a higher incidence of intermittent hypoxemia. STUDY DESIGN: A subcohort of 115 preterm infants with high resolution pulse oximetry enrolled in the Surfactant, Positive Pressure, and Oxygenation Randomized Trial were randomized to low (85%-89%) or high (91%-95%) O(2) saturation target ranges. Oxygen saturation was monitored until 36 weeks postmenstrual age or until the infant was breathing room air without respiratory support for ≥72 hours. RESULTS: The low target O(2) saturation group had a higher rate of intermittent hypoxemia (≤80% for ≥10 seconds and ≤3 minutes) prior to 12 days and beyond 57 days of life (P < .05). The duration shortened (P < .0001) and the severity increased (P < .0001) with increasing postnatal age with no differences between target saturation groups. The higher rate of intermittent hypoxemia events in the low target group was associated with a time interval between events of <1 minute. CONCLUSION: A low O(2) saturation target was associated with an increased rate of intermittent hypoxemia events that was dependent on postnatal age. The duration and severity of events was comparable between target groups. Further investigation is needed to assess the role of intermittent hypoxemia and their timing on neonatal morbidity.