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Objective:To determine the rate and severity of short- and long-term morbidity in very low birth weight infants treated before and after the implementation of a change in clinical practice designed to avoid hyperoxia.Methods:Analysis of a prospectively collected database of all infants

Objective:To determine the rate and severity of short- and long-term morbidity in very low birth weight infants treated before and after the implementation of a change in clinical practice designed to avoid hyperoxia.Methods:Analysis of a prospectively collected database of all infants 1250 g admitted to two Emory University NICU's from January 2000 to December 2004. A change in practice was instituted in January 2003 with the objective of avoiding hyperoxia in preterm infants with target O2 saturation (SpO2) at 93 to 85% (Period II). Before the change in practice, SpO2 high alarms were set at 100% and low alarms at 92% (Period I). Statistical analysis included bivariate analyses and multivariate logistic regression comparing outcomes between the two periods.Results:From January 2000 to December 2004, 502 infants met enrollment criteria and 202 (40%) were born in period II, after change in SpO2 targets. Birth weight, gestational age and survival were similar between both periods. The rates for any retinopathy of prematurity, supplemental oxygen at 36 weeks post-conceptional age and the use of steroids for chronic lung disease were significantly lower in the infants born in Period II. There was no difference in the rates of necrotizing enterocolitis, intraventricular hemorrhage and periventricular leukomalacia. At 18 months corrected age (CA), the infants treated during Period II had a higher Mental Developmental Index (MDI) scores (80.2±18.3 vs 89.2±18.5; P 0.02) and similar Psychomotor Developmental Index (PDI) scores (83.9±18.6 vs 89.4±17.2; P 0.08) than those treated during Period I. The proportion of infants with an MDI or a PDI less than 70 was similar between the periods.Conclusions:The change in practice to avoid hyperoxia is associated with a significant decrease in neonatal morbidity and does not have a detrimental effect on developmental outcomes at 18 months CA.Journal of Perinatology (2006) 26, 700–705. doi:10.1038/sj.jp.7211608; published online 12 October 2006 [ABSTRACT FROM AUTHOR]

Importance: Maternal milk feeding of extremely preterm infants during the birth hospitalization has been associated with better neurodevelopmental outcomes compared with preterm formula. For infants receiving no or minimal maternal milk, it is unknown whether donor human milk conveys similar neurodevelopmental advantages vs preterm formula., Objective: To determine if nutrient-fortified, pasteurized donor human milk improves neurodevelopmental outcomes at 22 to 26 months' corrected age compared with preterm infant formula among extremely preterm infants who received minimal maternal milk., Design, Setting, and Participants: Double-blind, randomized clinical trial conducted at 15 US academic medical centers within the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants younger than 29 weeks 0 days' gestation or with a birth weight of less than 1000 g were enrolled between September 2012 and March 2019., Intervention: Preterm formula or donor human milk feeding from randomization to 120 days of age, death, or hospital discharge., Main Outcomes and Measures: The primary outcome was the Bayley Scales of Infant and Toddler Development (BSID) cognitive score measured at 22 to 26 months' corrected age; a score of 54 (score range, 54-155; a score of ≥85 indicates no neurodevelopmental delay) was assigned to infants who died between randomization and 22 to 26 months' corrected age. The 24 secondary outcomes included BSID language and motor scores, in-hospital growth, necrotizing enterocolitis, and death., Results: Of 1965 eligible infants, 483 were randomized (239 in the donor milk group and 244 in the preterm formula group); the median gestational age was 26 weeks (IQR, 25-27 weeks), the median birth weight was 840 g (IQR, 676-986 g), and 52% were female. The birthing parent's race was self-reported as Black for 52% (247/478), White for 43% (206/478), and other for 5% (25/478). There were 54 infants who died prior to follow-up; 88% (376/429) of survivors were assessed at 22 to 26 months' corrected age. The adjusted mean BSID cognitive score was 80.7 (SD, 17.4) for the donor milk group vs 81.1 (SD, 16.7) for the preterm formula group (adjusted mean difference, -0.77 [95% CI, -3.93 to 2.39], which was not significant); the adjusted mean BSID language and motor scores also did not differ. Mortality (death prior to follow-up) was 13% (29/231) in the donor milk group vs 11% (25/233) in the preterm formula group (adjusted risk difference, -1% [95% CI, -4% to 2%]). Necrotizing enterocolitis occurred in 4.2% of infants (10/239) in the donor milk group vs 9.0% of infants (22/244) in the preterm formula group (adjusted risk difference, -5% [95% CI, -9% to -2%]). Weight gain was slower in the donor milk group (22.3 g/kg/d [95% CI, 21.3 to 23.3 g/kg/d]) compared with the preterm formula group (24.6 g/kg/d [95% CI, 23.6 to 25.6 g/kg/d])., Conclusions and Relevance: Among extremely preterm neonates fed minimal maternal milk, neurodevelopmental outcomes at 22 to 26 months' corrected age did not differ between infants fed donor milk or preterm formula., Trial Registration: ClinicalTrials.gov Identifier: NCT01534481.

Objective: Extremely preterm (EP) impairment rates are likely underestimated using the Bayley III norm-based thresholds scores and may be better assessed relative to concurrent healthy term reference (TR) infants born in the same hospital., Study Design: Blinded, certified examiners in the Neonatal Research Network (NRN) evaluated EP survivors and a sample of healthy TR infants recruited near the 2-year assessment age., Results: We assessed 1452 EP infants and 183 TR infants. TR-based thresholds showed higher overall EP impairment than Bayley norm-based thresholds (O.R. = 1.86; [95% CI 1.56-2.23], especially for severe impairment (36% vs. 24%; p ≤ 0.001). Difficulty recruiting TR patients at 2 years extended the study by 14 months and affected their demographics., Conclusion: Impairment rates among EP infants appear to be substantially underestimated from Bayley III norms. These rates may be best assessed by comparison with healthy term infants followed with minimal attrition from birth in the same centers., Gov Id: Term Reference (under the Generic Database Study): NCT00063063., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

To support decision-making in the primary care medical home, this clinical report links preterm birth and perinatal complications to early childhood developmental disability risks. It consolidates extensive contemporary outcome research from 2005 onward into an easy-to-use framework and stratifies prematurity and NICU experiences by degree of risk for developmental impairments. This framework informs and prioritizes point-of-care screening and surveillance strategies for pediatricians caring for children born preterm, guides additional assessment and referral for appropriate therapies, and offers opportunities for reassurance (when applicable) in office settings., (Copyright © 2023 by the American Academy of Pediatrics.)

Objectives: To assess variability in continuation of antiseizure medication (ASM) at discharge and to evaluate if continuation of ASM at discharge is associated with death or disability among infants with hypoxic-ischaemic encephalopathy (HIE) and seizures., Design: Retrospective study of infants enrolled in three National Institute of Child Health and Human Development Neonatal Research Network Trials of therapeutic hypothermia., Setting: 22 US centres., Patients: Infants with HIE who survived to discharge and had clinical or electrographic seizures treated with ASM., Exposures: ASM continued or discontinued at discharge., Outcomes: Death or moderate-to-severe disability at 18-22 months, using trial definitions. Multivariable logistic regression evaluated the association between continuation of ASM at discharge and the primary outcome, adjusting for severity of HIE, hypothermia trial treatment arm, use of electroencephalogram, discharge on gavage feeds, Apgar Score at 5 min, birth year and centre., Results: Of 302 infants included, 61% were continued on ASMs at discharge (range 13%-100% among 22 centres). Electroencephalogram use occurred in 92% of the cohort. Infants with severe HIE comprised 24% and 22% of those discharged with and without ASM, respectively. The risk of death or moderate-to-severe disability was greater for infants continued on ASM at discharge, compared with those infants discharged without ASM (44% vs 28%, adjusted OR 2.14; 95% CI 1.13 to 4.05)., Conclusions: In infants with HIE and seizures, continuation of ASM at discharge varies substantially among centres and may be associated with a higher risk of death or disability at 18-22 months of age., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Bronchopulmonary dysplasia is a prevalent complication after extremely preterm birth. Inflammation with mechanical ventilation may contribute to its development. Whether hydrocortisone treatment after the second postnatal week can improve survival without bronchopulmonary dysplasia and without adverse neurodevelopmental effects is unknown., Methods: We conducted a trial involving infants who had a gestational age of less than 30 weeks and who had been intubated for at least 7 days at 14 to 28 days. Infants were randomly assigned to receive either hydrocortisone (4 mg per kilogram of body weight per day tapered over a period of 10 days) or placebo. Mandatory extubation thresholds were specified. The primary efficacy outcome was survival without moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age, and the primary safety outcome was survival without moderate or severe neurodevelopmental impairment at 22 to 26 months of corrected age., Results: We enrolled 800 infants (mean [±SD] birth weight, 715±167 g; mean gestational age, 24.9±1.5 weeks). Survival without moderate or severe bronchopulmonary dysplasia at 36 weeks occurred in 66 of 398 infants (16.6%) in the hydrocortisone group and in 53 of 402 (13.2%) in the placebo group (adjusted rate ratio, 1.27; 95% confidence interval [CI], 0.93 to 1.74). Two-year outcomes were known for 91.0% of the infants. Survival without moderate or severe neurodevelopmental impairment occurred in 132 of 358 infants (36.9%) in the hydrocortisone group and in 134 of 359 (37.3%) in the placebo group (adjusted rate ratio, 0.98; 95% CI, 0.81 to 1.18). Hypertension that was treated with medication occurred more frequently with hydrocortisone than with placebo (4.3% vs. 1.0%). Other adverse events were similar in the two groups., Conclusions: In this trial involving preterm infants, hydrocortisone treatment starting on postnatal day 14 to 28 did not result in substantially higher survival without moderate or severe bronchopulmonary dysplasia than placebo. Survival without moderate or severe neurodevelopmental impairment did not differ substantially between the two groups. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01353313.)., (Copyright © 2022 Massachusetts Medical Society.)

Objective: This study evaluates the 24-month follow-up for the NICHD Neonatal Research Network (NRN) Inositol for Retinopathy Trial., Study Design: Bayley Scales of Infants Development-III and a standardized neurosensory examination were performed in infants enrolled in the main trial. Moderate/severe NDI was defined as BSID-III Cognitive or Motor composite score <85, moderate or severe cerebral palsy, blindness, or hearing loss that prevents communication despite amplification were assessed., Results: Primary outcome was determined for 605/638 (95%). The mean gestational age was 25.8 ± 1.3 weeks and mean birthweight was 805 ± 192 g. Treatment group did not affect the risk for the composite outcome of death or survival with moderate/severe NDI (60% vs 56%, p = 0.40)., Conclusions: Treatment group did not affect the risk of death or survival with moderate/severe NDI. Despite early termination, this study represents the largest RCT of extremely preterm infants treated with myo-inositol with neurodevelopmental outcome data., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Objective: To determine if preterm infants with surgical necrotizing enterocolitis (sNEC) or spontaneous intestinal perforation (SIP) with short bowel syndrome (SBS) have worse neurodevelopmental and growth outcomes than those with sNEC/SIP without SBS, and those with no necrotizing enterocolitis, SIP, or SBS., Study Design: We undertook a retrospective analysis of prospectively collected data from infants born between 22 and 26 weeks of gestation in the National Institute of Child Health and Human Development Neonatal Research Network centers from January 1, 2008, to December 31, 2016. Survivors were assessed at 18-26 months corrected age by standardized neurologic examination and Bayley Scales of Infant and Toddler Development, Third Edition. The primary outcome was moderate-severe neurodevelopmental impairment. Growth was assessed using World Health Organization z-score standards. Adjusted relative risks were estimated using modified Poisson regression models., Results: Mortality was 32%, 45%, and 21% in the 3 groups, respectively. Eighty-nine percent of survivors were seen at 18-26 months corrected age. Moderate-severe neurodevelopmental impairment was present in 77% of children with SBS compared with 62% with sNEC/SIP without SBS (adjusted relative risk, 1.22; 95% CI, 1.02-1.45; P = .03) and 44% with no necrotizing enterocolitis, SIP, or SBS (adjusted relative risk, 1.60; 95% CI, 1.37-1.88; P < .001). Children with SBS had lowcognitive, language, and motor scores than children with sNEC/SIP without SBS. At follow-up, length and head circumference z-scores remained more than 1 SD below the mean for children with SBS., Conclusions: Preterm infants with sNEC/SIP and SBS had increased risk of adverse neurodevelopmental outcomes at 18-26 months corrected age and impaired growth compared with peers with sNEC/SIP without SBS or without any of these conditions., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: The objectives of this study are to determine whether abnormalities on neonatal cranial ultrasound (CUS) are associated with minor motor abnormalities at 2 years' corrected age (CA) and to assess functional outcomes and resource utilization among children with minor motor abnormalities., Methods: Infants born at <27 weeks in the National Institute of Child Health and Human Development Neonatal Research Network between January 1, 2010, and December 31, 2014, who underwent neuroimaging with CUS at both <28 days and ≥28 days and were evaluated at 18 to 26 months' CA, were included. Follow-up included Bayley-3, neuromotor examination, Gross Motor Function Classification System (GMFCS) level, and parent questionnaires about special services and resource needs. Children were classified by the most severe motor abnormality at 18 to 26 months' CA as follows: none, minor, or major motor function abnormality. Minor motor abnormalities were defined as any of the following: (1) Bayley-3 motor composite, fine motor score, or gross motor score 1 to 2 SDs below the test normative means; (2) mild abnormalities of axial or extremity motor skills on standardized neuromotor examination; or (3) GMFCS level 1., Results: A total of 809 (35%) of 2306 children had minor motor function abnormalities alone. This did not increase substantially with CUS findings (no intraventricular hemorrhage [IVH]: 37%, grade I IVH: 32%, grade II IVH: 38%, grade III/IV IVH: 30%, isolated ventriculomegaly: 33%, and cystic periventricular leukomalacia: 24%). The adjusted odds of minor axial and upper extremity function abnormalities and GMFCS level 1 were significantly higher in children with more severe CUS findings. Children with minor motor abnormalities had increased resource utilization and evidence of functional impairment compared with those without motor function abnormalities., Conclusion: Minor motor abnormalities at 2 years' CA are common and cannot be predicted by neonatal CUS abnormalities alone. Minor motor abnormalities are associated with higher resource utilization and evidence of functional impairment. These findings have important implications for early counseling and follow-up planning for extremely preterm infants.

Background: Preterm birth is a risk factor for elevated blood pressure in childhood and the development of hypertension and cardiometabolic disease in adulthood; however, mechanisms for the development of both are poorly understood. Rapid weight gain early in childhood may serve as a driver directly and indirectly through cortisol levels found to be elevated in early childhood in individuals born preterm., Objectives: The objective of this pilot study was to examine the effect sizes of the relationships between weight gain and blood pressure in toddlers born very preterm. A secondary aim was to note any mediating effect of cortisol on the relationships between weight gain and blood pressure., Methods: A cross-sectional design with a convenience sample of 36 toddlers who were born very preterm was used to examine the relationships between postnatal weight gain, cortisol, and blood pressure at follow-up., Results: Many of the participants experienced rapid weight gain in the first 12 months of life. Mean systolic and diastolic readings were 94 and 56.6, respectively. Diastolic blood pressure readings were obtained from 23 participants, and the majority were elevated. Weight gain was associated with diastolic blood pressure with a medium effect size. A mediating role with cortisol was not supported., Discussion: Although findings need to be validated in a larger sample, the blood pressure elevations in this sample were alarming. If readings continue to amplify as these children age, the fact that elevations are already present during the toddler period could indicate more significant cardiovascular disease in adulthood for this population. Rapid weight gain in early life may be a driver for elevated blood pressure even during early childhood in individuals born preterm.

Objective: To assess the frequency of gastrostomy tube (GT) placement in extremely low birth weight (ELBW) infants, associated comorbidities, and long-term outcomes., Study Design: Analysis of ELBW infants from 25 centers enrolled in the National Institute of Child Health and Human Development Neonatal Research Network's Generic Database and Follow-up Registry from 2006 to 2012. Frequency of GT placement before 18-22 months, demographic and medical factors associated with GT placement, and associated long-term outcomes at 18-22 months of corrected age were described. Associations between GT placement and neonatal morbidities and long-term outcomes were assessed with logistic regression after adjustment for center and common co-variables., Results: Of the 4549 ELBW infants included in these analyses, 333 (7.3%) underwent GT placement; 76% had the GT placed postdischarge. Of infants with GTs, 11% had birth weights small for gestational age, 77% had bronchopulmonary dysplasia, and 29% severe intraventricular hemorrhage or periventricular leukomalacia. At follow-up, 56% of infants with a GT had weight <10th percentile, 61% had neurodevelopmental impairment (NDI), and 55% had chronic breathing problems. After adjustment, small for gestational age, bronchopulmonary dysplasia, intraventricular hemorrhage/periventricular leukomalacia, poor growth, and NDI were associated with GT placement. Thirty-two percent of infants with GTs placed were taking full oral feeds at follow-up., Conclusions: GT placement is common in ELBW infants, particularly among those with severe neonatal morbidities. GT placement in this population was associated with poor growth, NDI, and chronic respiratory and feeding problems at follow-up. The frequency of GT placement postneonatal discharge indicates the need for close nutritional follow-up of ELBW infants., Trial Registration: ClinicalTrials.gov: NCT00063063., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective(s): Investigate associations between 18 and 22-month corrected age hand function, adverse findings on serial cranial ultrasound (CUS) and near-term brain MRI (ntMRI), and Bayley-III scores in extremely preterm (EPT) toddlers., Study Design: Cohort analysis of Neonatal Research Network SUPPORT NEURO data. Associations between brain abnormalities, hand function, and Bayley-III scores were examined using chi-square and generalized linear mixed effect model analyses., Results: A total of 433 children were included. Sixteen percent had hand function deficits; these were associated with late CUS (p < 0.001) abnormalities, white matter abnormality (WMA) on ntMRI (p < 0.001), and Bayley-III scores. Six percent had CP. Fourteen percent of children without and 50% of those with CP had hand function abnormalities., Conclusions: Late CUS findings and severity of WMA were significantly associated with hand function deficits. Hand function deficits were nearly three times more common than CP and may be a useful marker of early brain insult and predictor of preterm birth effects on development.

Necrotizing enterocolitis is a serious complication of prematurity that is associated with an increased risk for adverse neurodevelopmental outcome secondary to a complex relationship between various morbidities that increase the risk for central nervous system injury. Affected infants are exposed to a variety of circulating cytokines known to be associated with white matter injury. These infants also have an increased risk of secondary blood stream infections and nutritional compromise., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Invasive candidiasis is an important cause of sepsis in extremely low birth weight infants (ELBW, < 1000 g), is often fatal, and frequently results in neurodevelopmental impairment (NDI) among survivors. We sought to assess the antifungal minimum inhibitory concentration (MIC) distribution for Candida in ELBW infants and evaluate the association between antifungal resistance and death or NDI., Methods: This was a secondary analysis of a National Institute of Child Health and Human Development Neonatal Research Network study. MIC values were determined for fluconazole, amphotericin B and micafungin. NDI was assessed at 18-22 months adjusted age using the Bayley Scales of Infant Development. An infant was defined as having a resistant Candida isolate if ≥ 1 positive cultures from normally sterile sites (blood, cerebrospinal fluid, or urine) were resistant to ≥ 1 antifungal agent. In addition to resistance status, we categorized fungal isolates according to MIC values (low and high). The association between death/NDI and MIC level was determined using logistic regression, controlling for gestational age and Bayley Scales of Infant Development (II or III)., Results: Among 137 ELBW infants with IC, MICs were determined for 308 isolates from 110 (80%) infants. Three Candida isolates from 3 infants were resistant to fluconazole. None were resistant to amphotericin B or micafungin. No significant difference in death, NDI, or death/NDI between groups with low and high MICs was observed., Conclusions: Antifungal resistance was rare among infecting Candida isolates, and MIC level was not associated with increased risk of death or NDI in this cohort of ELBW infants.

Background and Objectives: Children born extremely preterm are at risk for cognitive difficulties and disability. The relative prognostic value of neonatal brain MRI and cranial ultrasound (CUS) for school-age outcomes remains unclear. Our objectives were to relate near-term conventional brain MRI and early and late CUS to cognitive impairment and disability at 6 to 7 years among children born extremely preterm and assess prognostic value., Methods: A prospective study of adverse early and late CUS and near-term conventional MRI findings to predict outcomes at 6 to 7 years including a full-scale IQ (FSIQ) <70 and disability (FSIQ <70, moderate-to-severe cerebral palsy, or severe vision or hearing impairment) in a subgroup of Surfactant Positive Airway Pressure and Pulse Oximetry Randomized Trial enrollees. Stepwise logistic regression evaluated associations of neuroimaging with outcomes, adjusting for perinatal-neonatal factors., Results: A total of 386 children had follow-up. In unadjusted analyses, severity of white matter abnormality and cerebellar lesions on MRI and adverse CUS findings were associated with outcomes. In full regression models, both adverse late CUS findings (odds ratio [OR] 27.9; 95% confidence interval [CI] 6.0-129) and significant cerebellar lesions on MRI (OR 2.71; 95% CI 1.1-6.7) remained associated with disability, but only adverse late CUS findings (OR 20.1; 95% CI 3.6-111) were associated with FSIQ <70. Predictive accuracy of stepwise models was not substantially improved with the addition of neuroimaging., Conclusions: Severe but rare adverse late CUS findings were most strongly associated with cognitive impairment and disability at school age, and significant cerebellar lesions on MRI were associated with disability. Near-term conventional MRI did not substantively enhance prediction of severe early school-age outcomes., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Objectives: Evaluate the spectrum of neurodevelopmental outcome in a contemporary cohort of extremely preterm infants. We hypothesize that the rate of severe neurodevelopmental impairment (NDI) decreases over time., Methods: Retrospective analysis of neurodevelopmental outcome of preterm infants ≤27 weeks' gestational age (GA) from a Neonatal Research Network center that completed neurodevelopmental follow-up assessments between April 1, 2011, and January 1, 2015. The Bayley Scales of Infant Development-III (BSID III) and a standardized neurosensory examination were performed between 18 and 26 months' adjusted age. Outcome measures were neurologic examination diagnoses, BSID III cognitive and motor scores, sensory impairment, and the composite outcome of NDI, based on the BSID III cognitive score (analyzed by using a cutoff of <85 or <70), BSID III motor score of <70, moderate or severe cerebral palsy (CP), bilateral blindness, and hearing impairment., Results: Two thousand one hundred and thirteen infants with a mean GA of 25.0 ± 1.0 weeks and mean birth weight of 760 ± 154 g were evaluated. The 11% lost to follow-up were less likely to have private insurance, late-onset sepsis, or severe intraventricular hemorrhage. Neurologic examination results were normal in 59%, suspect abnormal in 19%, and definitely abnormal in 22%. Severe CP decreased 43% whereas mild CP increased 13% during the study. The rate of moderate to severe NDI decreased from 21% to 16% when using the BSID III cognitive cutoff of <70 ( P = .07) or from 34% to 31% when using the BSID III cognitive cutoff of <85 ( P = .67)., Conclusions: Extremely preterm children are at risk for NDI. Over time, the rate of moderate to severe NDI did not differ, but the rates of severe CP decreased, and mild CP increased., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Importance: Studies of cranial ultrasonography and early childhood outcomes among cohorts of extremely preterm neonates have linked periventricular-intraventricular hemorrhage and cystic periventricular leukomalacia with adverse neurodevelopmental outcomes. However, the association between nonhemorrhagic ventriculomegaly and neurodevelopmental and behavioral outcomes is not fully understood., Objective: To characterize the outcomes of extremely preterm neonates younger than 27 weeks' gestational age who experienced nonhemorrhagic ventriculomegaly that was detected prior to 36 weeks' postmenstrual age., Design, Setting, and Participants: This longitudinal observational study was conducted at 16 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants born prior to 27 weeks' gestational age in any network facility between July 1, 2006, and June 30, 2011, were included if they had a cranial ultrasonogram performed prior to 36 weeks' postmenstrual age. Comparisons were made between those with ventriculomegaly and those with normal cranial sonograms. Data analysis was completed from August 2013 to August 2017., Main Outcomes and Measures: The main outcome was neurodevelopmental impairment, defined as a Bayley Scales of Infant and Toddler Development III cognitive score less than 70, moderate/severe cerebral palsy, a Gross Motor Function Classification System score of level 2 or more, vision impairment, or hearing impairment. Secondary outcomes included Bayley Scales of Infant and Toddler Development III subscores, components of neurodevelopmental impairment, behavioral outcomes, and death/neurodevelopmental impairment. Logistic regression was used to evaluate the association of ventriculomegaly with adverse outcomes while controlling for potentially confounding variables and center differences as a random effect. Linear regression was used similarly for continuous outcomes., Results: Of 4193 neonates with ultrasonography data, 300 had nonhemorrhagic ventriculomegaly (7%); 3045 had normal cranial ultrasonograms (73%), 775 had periventricular-intraventricular hemorrhage (18.5%), and 73 had cystic periventricular leukomalacia (1.7%). Outcomes were available for 3008 of 3345 neonates with ventriculomegaly or normal scans (90%). Compared with normal cranial ultrasonograms, ventriculomegaly was associated with lower gestational age, male sex, and bronchopulmonary dysplasia, late-onset sepsis, meningitis, necrotizing enterocolitis, and stage 3 retinopathy of prematurity. After adjustment, neonates with ventriculomegaly had higher odds of neurodevelopmental impairment (odds ratio [OR], 3.07; 95% CI, 2.13-4.43), cognitive impairment (OR, 3.23; 95% CI, 2.09-4.99), moderate/severe cerebral palsy (OR, 3.68; 95% CI, 2.08-6.51), death/neurodevelopmental impairment (OR, 2.17; 95% CI, 1.62-2.91), but not death alone (OR, 1.09; 95% CI, 0.76-1.57). Behavioral outcomes did not differ., Conclusions and Relevance: Nonhemorrhagic ventriculomegaly is associated with increased odds of neurodevelopmental impairment among extremely preterm neonates.

Background: Limited data are available evaluating language outcomes of preterm infants in early childhood. Furthermore, the relationship between language outcomes, medical morbidities and developmental trajectory in early infancy is unclear., Aims: The goal of this study was to evaluate language outcomes among extremely low birth weight (ELBW) infants at 30months adjusted age (AA)., Study Design: The Bayley Scales of Infant Development II and the Peabody Picture Vocabulary Test or Expressive One Word Picture Vocabulary Test/Receptive One Word Picture Vocabulary Test were administered at 30months AA to a prospective cohort of ELBW infants who participated in the NICHD Neonatal Network Glutamine Trial and Neurodevelopmental Follow-Up Study. A standardized history and physical examination and query regarding feeding behaviors were performed at 18months AA and 30months AA., Results: Of the 467 infants evaluated, 55% had receptive language delay at 30months with 23% having severe delays. Fewer (26%) had expressive language delays, with 16% of those being severe delays. Non-English speaking infants had poorer performance on all language measures compared to English-speaking infants. Forty-seven percent of the cohort required assistance with feeds at 18months. These children were more likely to have language delay at the 30month assessment compared to infants who could feed themselves., Conclusions: ELBW infants are at risk of language delay in early childhood. Additional research is needed to further explore the relationship between early predictors of language delay and the use of monolingual language assessments in non-English speaking patients with a history of prematurity., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Extremely preterm infants are at risk for neurodevelopmental impairment (NDI). Early cranial ultrasound (CUS) is usual practice, but near-term brain MRI has been reported to better predict outcomes. We prospectively evaluated MRI white matter abnormality (WMA) and cerebellar lesions, and serial CUS adverse findings as predictors of outcomes at 18 to 22 months' corrected age., Methods: Early and late CUS, and brain MRI were read by masked central readers, in a large cohort (n = 480) of infants <28 weeks' gestation surviving to near term in the Neonatal Research Network. Outcomes included NDI or death after neuroimaging, and significant gross motor impairment or death, with NDI defined as cognitive composite score <70, significant gross motor impairment, and severe hearing or visual impairment. Multivariable models evaluated the relative predictive value of neuroimaging while controlling for other factors., Results: Of 480 infants, 15 died and 20 were lost. Increasing severity of WMA and significant cerebellar lesions on MRI were associated with adverse outcomes. Cerebellar lesions were rarely identified by CUS. In full multivariable models, both late CUS and MRI, but not early CUS, remained independently associated with NDI or death (MRI cerebellar lesions: odds ratio, 3.0 [95% confidence interval: 1.3-6.8]; late CUS: odds ratio, 9.8 [95% confidence interval: 2.8-35]), and significant gross motor impairment or death. In models that did not include late CUS, MRI moderate-severe WMA was independently associated with adverse outcomes., Conclusions: Both late CUS and near-term MRI abnormalities were associated with outcomes, independent of early CUS and other factors, underscoring the relative prognostic value of near-term neuroimaging., (Copyright © 2015 by the American Academy of Pediatrics.)

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., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: Little is known about how very low birth weight (VLBW) affects survival and morbidities among infants with trisomy 13 (T13) or trisomy 18 (T18). We examined the care plans for VLBW infants with T13 or T18 and compared their risks of mortality and neonatal morbidities with VLBW infants with trisomy 21 and VLBW infants without birth defects., Methods: Infants with birth weight 401 to 1500 g born or cared for at a participating center of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network during the period 1994-2009 were studied. Poisson regression models were used to examine risk of death and neonatal morbidities among infants with T13 or T18., Results: Of 52,262 VLBW infants, 38 (0.07%) had T13 and 128 (0.24%) had T18. Intensity of care in the delivery room varied depending on whether the trisomy was diagnosed before or after birth. The plan for subsequent care for the majority of the infants was to withdraw care or to provide comfort care. Eleven percent of infants with T13 and 9% of infants with T18 survived to hospital discharge. Survivors with T13 or T18 had significantly increased risk of patent ductus arteriosus and respiratory distress syndrome compared with infants without birth defects. No infant with T13 or T18 developed necrotizing enterocolitis., Conclusions: In this cohort of liveborn VLBW infants with T13 or T18, the timing of trisomy diagnosis affected the plan for care, survival was poor, and death usually occurred early.

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., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Aim: The aim of this study was to better understand the impact of non-English language spoken in the home on measures of cognition, language and behaviour in toddlers born extremely preterm., Methods: Eight hundred and fifty children born at <28 weeks of gestational ages were studied. 427 male and 423 female participants from three racial/ethnic groups (White, Black and Hispanic) were evaluated at 18-22 months adjusted for age using the Bayley Scales of Infant Development third edition and the Brief Infant Toddler Social Emotional Assessment (BITSEA). Children whose primary language was Spanish (n = 98) were compared with children whose primary language was English (n = 752), using multivariable regression adjusted for medical and psychosocial factors., Results: Cognitive scores were similar between groups; however, receptive, expressive and composite language scores were lower for children whose primary language was Spanish. These differences remained significant after adjustment for medical and socio-economic factors. Spanish-speaking children scored worse on the BITSEA competence and problem scores using univariate analysis, but not after adjustment for medical and socio-economic factors., Conclusion: Our finding that preterm children whose primary language was Spanish had similar cognitive but lower language scores than those whose primary language was English suggests that using English language-based testing tools may introduce bias against non-English-speaking children born preterm., (©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Objective: To evaluate the relationship between abnormal feeding patterns and language performance on the Bayley Scales of Infant Development-Third Edition at 18-22 months adjusted age among a cohort of extremely premature infants., Study Design: This is a descriptive analysis of 1477 preterm infants born ≤ 26 weeks gestation or enrolled in a clinical trial between January 1, 2006 and March 18, 2008 at a National Institute of Child Health and Human Development Neonatal Research Network center who completed the 18-month neurodevelopmental follow-up assessment. At 18-22 months adjusted age, a comprehensive neurodevelopmental evaluation was performed by certified examiners including the Receptive and Expressive Language Subscales of the Bayley Scales of Infant Development-Third Edition and a standardized adjusted age feeding behaviors and nutritional intake. Data were analyzed using bivariate and multilevel linear and logistic regression modeling., Results: Abnormal feeding behaviors were reported in 193 (13%) of these infants at 18-22 months adjusted age. Abnormal feeding patterns, days of mechanical ventilation, hearing impairment, and Gross Motor Functional Classification System level ≥ 2 each independently predicted lower composite language scores., Conclusions: At 18 months adjusted age, premature infants with a history of feeding difficulties are more likely to have language delay. Neuromotor impairment and days of mechanical ventilation are both important risk factors associated with these outcomes., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objective: Birth defects (BDs) are an important cause of infant mortality and disproportionately occur among low birth weight infants. We determined the prevalence of BDs in a cohort of very low birth weight (VLBW) infants cared for at the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) centers over a 10-year period and examined the relationship between anomalies, neonatal outcomes, and surgical care., Methods: Infant and maternal data were collected prospectively for infants weighing 401 to 1500 g at NRN sites between January 1, 1998, and December 31, 2007. Poisson regression models were used to compare risk of outcomes for infants with versus without BDs while adjusting for gestational age and other characteristics., Results: A BD was present in 1776 (4.8%) of the 37 262 infants in our VLBW cohort. Yearly prevalence of BDs increased from 4.0% of infants born in 1998 to 5.6% in 2007, P < .001. Mean gestational age overall was 28 weeks, and mean birth weight was 1007 g. Infants with BDs were more mature but more likely to be small for gestational age compared with infants without BDs. Chromosomal and cardiovascular anomalies were most frequent with each occurring in 20% of affected infants. Mortality was higher among infants with BDs (49% vs 18%; adjusted relative risk: 3.66 [95% confidence interval: 3.41-3.92]; P < .001) and varied by diagnosis. Among those surviving >3 days, more infants with BDs underwent major surgery (48% vs 13%, P < .001)., Conclusions: Prevalence of BDs increased during the 10 years studied. BDs remain an important cause of neonatal morbidity and mortality among VLBW infants.

Background: Previous results from our trial of early treatment with continuous positive airway pressure (CPAP) versus early surfactant treatment in infants showed no significant difference in the outcome of death or bronchopulmonary dysplasia. A lower (vs. higher) target range of oxygen saturation was associated with a lower rate of severe retinopathy but higher mortality. We now report longer-term results from our prespecified hypotheses., Methods: Using a 2-by-2 factorial design, we randomly assigned infants born between 24 weeks 0 days and 27 weeks 6 days of gestation to early CPAP with a limited ventilation strategy or early surfactant administration and to lower or higher target ranges of oxygen saturation (85 to 89% or 91 to 95%). The primary composite outcome for the longer-term analysis was death before assessment at 18 to 22 months or neurodevelopmental impairment at 18 to 22 months of corrected age., Results: The primary outcome was determined for 1234 of 1316 enrolled infants (93.8%); 990 of the 1058 surviving infants (93.6%) were evaluated at 18 to 22 months of corrected age. Death or neurodevelopmental impairment occurred in 27.9% of the infants in the CPAP group (173 of 621 infants), versus 29.9% of those in the surfactant group (183 of 613) (relative risk, 0.93; 95% confidence interval [CI], 0.78 to 1.10; P=0.38), and in 30.2% of the infants in the lower-oxygen-saturation group (185 of 612), versus 27.5% of those in the higher-oxygen-saturation group (171 of 622) (relative risk, 1.12; 95% CI, 0.94 to 1.32; P=0.21). Mortality was increased with the lower-oxygen-saturation target (22.1%, vs. 18.2% with the higher-oxygen-saturation target; relative risk, 1.25; 95% CI, 1.00 to 1.55; P=0.046)., Conclusions: We found no significant differences in the composite outcome of death or neurodevelopmental impairment among extremely premature infants randomly assigned to early CPAP or early surfactant administration and to a lower or higher target range of oxygen saturation. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Heart, Lung, and Blood Institute; SUPPORT ClinicalTrials.gov number, NCT00233324.).

Prematurely born infants are at increased risk for infection throughout their hospitalization. Various developmentally regulated processes involving the central nervous and respiratory systems may be disrupted by the proinflammatory state associated with infection, resulting in an increased risk for death, chronic lung disease, and adverse neurodevelopmental outcome. This review summarizes the current understanding of the long-term impact of infection and/or inflammation in preterm infants, including the risks associated with perinatal infection, early-onset sepsis, late-onset sepsis, and necrotizing enterocolitis., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Little is known about the outcomes of extremely low birth weight (ELBW) preterm infants with congenital heart defects (CHDs). The aim of this study was to assess the mortality, morbidity, and early childhood outcomes of ELBW infants with isolated CHD compared with infants with no congenital defects. Participants were 401-1,000 g infants cared for at National Institute of Child Health and Human Development Neonatal Research Network centers between January 1, 1998, and December 31, 2005. Neonatal morbidities and 18-22 months' corrected age outcomes were assessed. Neurodevelopmental impairment (NDI) was defined as moderate to severe cerebral palsy, Bayley II mental or psychomotor developmental index <70, bilateral blindness, or hearing impairment requiring aids. Poisson regression models were used to estimate relative risks for outcomes while adjusting for gestational age, small-for-gestational-age status, and other variables. Of 14,457 ELBW infants, 110 (0.8 %) had isolated CHD, and 13,887 (96 %) had no major birth defect. The most common CHD were septal defects, tetralogy of Fallot, pulmonary valve stenosis, and coarctation of the aorta. Infants with CHD experienced increased mortality (48 % compared with 35 % for infants with no birth defect) and poorer growth. Surprisingly, the adjusted risks of other short-term neonatal morbidities associated with prematurity were not significantly different. Fifty-seven (52 %) infants with CHD survived to 18-22 months' corrected age, and 49 (86 %) infants completed follow-up. A higher proportion of surviving infants with CHD were impaired compared with those without birth defects (57 vs. 38 %, p = 0.004). Risk of death or NDI was greater for ELBW infants with CHD, although 20 % of infants survived without NDI.

Objectives: To compare 18- to 22-month cognitive scores and neurodevelopmental impairment (NDI) in 2 time periods using the National Institute of Child Health and Human Development's Neonatal Research Network assessment of extremely low birth weight infants with the Bayley Scales of Infant Development, Second Edition (Bayley II) in 2006-2007 (period 1) and using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley III), with separate cognitive and language scores, in 2008-2011 (period 2)., Study Design: Scores were compared with bivariate analysis, and regression analyses were run to identify differences in NDI rates., Results: Mean Bayley III cognitive scores were 11 points higher than mean Bayley II cognitive scores. The NDI rate was reduced by 70% (from 43% in period 1 to 13% in period 2; P < .0001). Multivariate analyses revealed that Bayley III contributed to a decreased risk of NDI by 5 definitions: cognitive score <70 and <85, cognitive or language score <70; cognitive or motor score <70, and cognitive, language, or motor score <70 (P < .001)., Conclusion: Whether the Bayley III is overestimating cognitive performance or whether it is a more valid assessment of emerging cognitive skills than the Bayley II is uncertain. Because the Bayley III identifies significantly fewer children with disability, it is recommended that all extremely low birth weight infants be offered early intervention services at the time of discharge from the neonatal intensive care unit, and that Bayley scores be interpreted with caution., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Background: Information on cytokine profiles in fungal sepsis (FS), an important cause of mortality in extremely low birthweight (ELBW) infants, is lacking. We hypothesized that cytokine profiles in the first 21 d of life in ELBW infants with FS differ from those with bacterial sepsis (BS) or no sepsis (NS)., Methods: In a secondary analysis of the National Institute of Child Health and Human Development Cytokine study, three groups were defined-FS (≥1 episode of FS), BS (≥1 episode of BS without FS), and NS. Association between 11 cytokines assayed in dried blood spots obtained on days 0-1, 3 ± 1, 7 ± 2, 14 ± 3, and 21 ± 3 and sepsis group was explored., Results: Of 1,066 infants, 89 had FS and 368 had BS. As compared with BS, FS was more likely to be associated with lower birthweight, vaginal delivery, patent ductus arteriosus, postnatal steroids, multiple central lines, longer respiratory support and hospital stay, and higher mortality (P < 0.05). Analyses controlling for covariates showed significant group differences over time for interferon-γ (IFN-γ), interleukin (IL)-10, IL-18, transforming growth factor-β (TGF-β), and tumor necrosis factor-α (TNF-α) (P < 0.05)., Conclusion: Significant differences in profiles for IFN-γ, IL-10, IL-18, TGF-β, and TNF-α in FS, BS, or NS in this hypothesis-generating secondary study require validation in rigorously designed prospective studies and may have implications for diagnosis and treatment.

Objective: To evaluate the relationship of race/ethnicity to Cognitive and Language scores on the Bayley Scales of Infant and Toddler Development, Third Edition in extremely preterm toddlers (<28 + 0 weeks' estimated gestational age)., Study Design: This cohort study included extremely preterm toddlers seen at Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers evaluated at 18-22 months adjusted age from 3 race/ethnic groups (white, black, and Hispanic white). Multivariate regression modeling was used to identify race/ethnic differences, after adjusting for medical and psychosocial factors., Results: The study population comprised 369 whites, 352 blacks, and 144 Hispanic whites. Cognitive scores differed among the 3 groups on unadjusted analysis (P ≤ .001), but not after adjusting for medical and psychosocial factors (P = .13). Language scores differed on adjusted and unadjusted analyses. Whites scored higher than blacks and Hispanic whites, and blacks scored higher than Hispanic whites., Conclusions: A combination of medical variables and primary caretaker education accounted for differences in Bayley Scales of Infant and Toddler Development, Third Edition Cognitive scores among the 3 groups. Black and Hispanic white toddlers had lower Language scores than whites, even after adjustment. Early intervention should be targeted to these identified risk factors. Assessment of early language development in minority children may be warranted., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Background: We previously reported early results of a randomized trial of whole-body hypothermia for neonatal hypoxic-ischemic encephalopathy showing a significant reduction in the rate of death or moderate or severe disability at 18 to 22 months of age. Long-term outcomes are now available., Methods: In the original trial, we assigned infants with moderate or severe encephalopathy to usual care (the control group) or whole-body cooling to an esophageal temperature of 33.5°C for 72 hours, followed by slow rewarming (the hypothermia group). We evaluated cognitive, attention and executive, and visuospatial function; neurologic outcomes; and physical and psychosocial health among participants at 6 to 7 years of age. The primary outcome of the present analyses was death or an IQ score below 70., Results: Of the 208 trial participants, primary outcome data were available for 190. Of the 97 children in the hypothermia group and the 93 children in the control group, death or an IQ score below 70 occurred in 46 (47%) and 58 (62%), respectively (P=0.06); death occurred in 27 (28%) and 41 (44%) (P=0.04); and death or severe disability occurred in 38 (41%) and 53 (60%) (P=0.03). Other outcome data were available for the 122 surviving children, 70 in the hypothermia group and 52 in the control group. Moderate or severe disability occurred in 24 of 69 children (35%) and 19 of 50 children (38%), respectively (P=0.87). Attention-executive dysfunction occurred in 4% and 13%, respectively, of children receiving hypothermia and those receiving usual care (P=0.19), and visuospatial dysfunction occurred in 4% and 3% (P=0.80)., Conclusions: The rate of the combined end point of death or an IQ score of less than 70 at 6 to 7 years of age was lower among children undergoing whole-body hypothermia than among those undergoing usual care, but the differences were not significant. However, hypothermia resulted in lower death rates and did not increase rates of severe disability among survivors. (Funded by the National Institutes of Health and the Eunice Kennedy Shriver NICHD Neonatal Research Network; ClinicalTrials.gov number, NCT00005772.).

Background: Candidiasis carries a significant risk of death or neurodevelopmental impairment (NDI) in extremely low birth weight infants (ELBW; <1000 g). We sought to determine the impact of candiduria in ELBW preterm infants., Methods: Our study was a secondary analysis of the Neonatal Research Network study Early Diagnosis of Nosocomial Candidiasis. Follow-up assessments included Bayley Scales of Infant Development examinations at 18-22 months of corrected age. Risk factors were compared between groups using exact tests and general linear modeling. Death, NDI, and death or NDI were compared using generalized linear mixed modeling., Results: Of 1515 infants enrolled, 34 (2.2%) had candiduria only. Candida was isolated from blood only (69 of 1515 [4.6%]), cerebrospinal fluid (CSF) only (2 of 1515 [0.1%]), other sterile site only (not urine, blood, or CSF; 4 of 1515 [0.3%]), or multiple sources (28 of 1515 [2%]). Eleven infants had the same Candida species isolated in blood and urine within 3 days; 3 (27%) had a positive urine culture result first. Most urine isolates were Candida albicans (21 of 34 [62%]) or Candida parapsilosis (7 of 34 [29%]). Rate of death or NDI was greater among those with candiduria (50%) than among those with suspected but not proven infection (32%; odds ratio, 2.5 [95% confidence interval, 1.2-5.3]) after adjustment. No difference in death and death or NDI was noted between infants with candiduria and those with candidemia., Conclusions: These findings provide compelling evidence that ELBW infants with candiduria are at substantial risk of death or NDI. Candiduria in ELBW preterm infants should prompt a systemic evaluation (blood, CSF, and abdominal ultrasound) for disseminated Candida infection and warrants treatment.

Unlabelled: Premature infants have a disproportionately increased risk for brain injury based on several mechanisms including intraventricular hemorrhage, ischemia and the vulnerability of developing neuronal progenitor cells. Injury to the developing brain often results in neurologic abnormalities that can be correlated with a structural lesion; however more subtle injury may result in disruption of critical neural pathways. There also appears to be an important relationship between brain injury in the cortex and the growth and developing cerebellum. Although the survival rate for premature has improved over the past decade, researchers remain concerned about the risk for adverse neurocognitive functioning in these early childhood, including an increased risk for cerebral palsy, cognitive impairment, speech and language delay and sensory dysfunction., Learning Outcomes: After this activity, the learner will be able to (1) identify potential causes of brain injury in the premature infant, (2) understand that the maturational process for the human brain continues throughout gestation, (3) identify risk factors for adverse neurocognitive functioning in premature infants, and (4) identify abnormalities on central nervous system neuroimaging studies that correlate with an increased risk for adverse neurodevelopmental outcome in premature infants.

Prevention of neurologic injury to the fetus through skilled and attentive care during the peripartum period is designed to identify signs of fetal distress so that appropriate obstetric interventions can occur. The impact of mode of delivery on neurologic outcome varies depending on the clinical indication for cesarean delivery and the associated maternal and fetal conditions. This review summarizes current knowledge of the impact of mode of delivery on long-term neurologic outcome.

Objective: We aimed to evaluate neurodevelopmental and growth outcomes among extremely low birth weight infants who had severe intraventricular hemorrhage that required shunt insertion compared with infants without shunt insertion., Methods: Infants who were born in 1993-2002 with birth weights of 401 to 1000 g were enrolled in a very low birth weight registry at medical centers that participate in the National Institute of Child Health and Human Development Neonatal Research Network, and returned for follow-up at 18 to 22 months' corrected age were studied. Eighty-two percent of survivors completed follow-up, and 6161 children were classified into 5 groups: group 1, no intraventricular hemorrhage/no shunt (n = 5163); group 2, intraventricular hemorrhage grade 3/no shunt (n = 459); group 3, intraventricular hemorrhage grade 3/shunt (n = 103); group 4, intraventricular hemorrhage grade 4/no shunt (n = 311); and group 5, intraventricular hemorrhage grade 4/shunt (n = 125). Group comparisons were evaluated with chi(2) and Wilcoxon tests, and regression models were used to compare outcomes after adjustment for covariates., Results: Children with severe intraventricular hemorrhage and shunts had significantly lower scores on the Bayley Scales of Infant Development IIR compared with children with no intraventricular hemorrhage and with children with intraventricular hemorrhage of the same grade and no shunt. Infants with shunts were at increased risk for cerebral palsy and head circumference at the <10th percentile at 18 months' adjusted age. Greatest differences were observed between children with shunts and those with no intraventricular hemorrhage on these outcomes., Conclusions: This large cohort study suggests that extremely low birth weight children with severe intraventricular hemorrhage that requires shunt insertion are at greatest risk for adverse neurodevelopmental and growth outcomes at 18 to 22 months compared with children with and without severe intraventricular hemorrhage and with no shunt. Long-term follow-up is needed to determine whether adverse outcomes persist or improve over time.

Objectives: We hypothesized that inhaled nitric oxide (iNO) would not decrease death or neurodevelopmental impairment (NDI) in infants enrolled in the National Institute of Child Health and Human Development Preemie iNO Trial (PiNO) trial, nor improve neurodevelopmental outcomes in the follow-up group., Study Design: Infants <34 weeks of age, weighing <1500 g, with severe respiratory failure were enrolled in the multicenter, randomized, controlled trial. NDI at 18 to 22 months corrected age was defined as: moderate to severe cerebral palsy (CP; Mental Developmental Index or Psychomotor score Developmental Index <70), blindness, or deafness., Results: Of 420 patients enrolled, 109 who received iNO (52%) and 98 who received placebo (47%) died. The follow-up rate in survivors was 90%. iNO did not reduce death or NDI (78% versus 73%; relative risk [RR], 1.07; 95% CI, 0.95-1.19), or NDI or Mental Developmental Index <70 in the follow-up group. Moderate-severe CP was slightly higher with iNO (RR, 2.41; 95% CI, 1.01-5.75), as was death or CP in infants weighing <1000 g (RR, 1.22; 95% CI, 1.05-1.43)., Conclusions: In this extremely ill cohort, iNO did not reduce death or NDI or improve neurodevelopmental outcomes. Routine iNO use in premature infants should be limited to research settings until further data are available.

There is very limited information about the developmental outcome of the late preterm infant. The developing brain is vulnerable to injury during this very active and important stage of fetal brain development; therefore, it is important to carefully monitor the neurologic outcome of these infants. This article discusses gestational brain development and complications of late preterm birth that contribute to the overall risk of brain injury.

Context: Neonatal infections are frequent complications of extremely low-birth-weight (ELBW) infants receiving intensive care., Objective: To determine if neonatal infections in ELBW infants are associated with increased risks of adverse neurodevelopmental and growth sequelae in early childhood., Design, Setting, and Participants: Infants weighing 401 to 1000 g at birth (born in 1993-2001) were enrolled in a prospectively collected very low-birth-weight registry at academic medical centers participating in the National Institute of Child Health and Human Development Neonatal Research Network. Neurodevelopmental and growth outcomes were assessed at a comprehensive follow-up visit at 18 to 22 months of corrected gestational age and compared by infection group. Eighty percent of survivors completed the follow-up visit and 6093 infants were studied. Registry data were used to classify infants by type of infection: uninfected (n = 2161), clinical infection alone (n = 1538), sepsis (n = 1922), sepsis and necrotizing enterocolitis (n = 279), or meningitis with or without sepsis (n = 193)., Main Outcome Measures: Cognitive and neuromotor development, neurologic status, vision and hearing, and growth (weight, length, and head circumference) were assessed at follow-up., Results: The majority of ELBW survivors (65%) had at least 1 infection during their hospitalization after birth. Compared with uninfected infants, those in each of the 4 infection groups were significantly more likely to have adverse neurodevelopmental outcomes at follow-up, including cerebral palsy (range of significant odds ratios [ORs], 1.4-1.7), low Bayley Scales of Infant Development II scores on the mental development index (ORs, 1.3-1.6) and psychomotor development index (ORs, 1.5-2.4), and vision impairment (ORs, 1.3-2.2). Infection in the neonatal period was also associated with impaired head growth, a known predictor of poor neurodevelopmental outcome., Conclusions: This large cohort study suggests that neonatal infections among ELBW infants are associated with poor neurodevelopmental and growth outcomes in early childhood. Additional studies are needed to elucidate the pathogenesis of brain injury in infants with infection so that novel interventions to improve these outcomes can be explored.