Discharging Medically Complex Infants with Supplemental Nasogastric Tube Feeds: Impact on Neonatal Intensive Care Unit Length of Stay and Prevention of Gastrostomy Tubes.

OBJECTIVE: The aim of this study is to evaluate the feasibility, safety, and efficacy of discharge with supplemental nasogastric tube (NGT) feeds in medically complex infants. STUDY DESIGN: Cohort study of 400 infants enrolled in the Transitional Medical Home (TMH) program at Duke University Level IV neonatal intensive care unit from January 2013 to 2017. RESULTS: Among 400 infants enrolled in the TMH, 57 infants were discharged with an NGT. A total of 45 infants with a variety of diagnoses and comorbidities were included in final analysis. Among 45 infants, 5 obtained a gastrostomy tube (GT) postdischarge. Median (25-75th percentile) length of use of NGT in 40 infants was 12 days (4-37). Excluding four outliers who used NGT for ≥140 days, the median length of use was 8 days (3-24). This extrapolates to a median of 288 hospital days saved for the remaining 36 infants. There were only three emergency room visits related to parental concern for incorrect NGT placement. There was no statistically significant difference in percent oral feeding predischarge or growth in first month postdischarge between infants who orally fed versus those who obtained GTs. CONCLUSION: Discharge with supplemental NGT feeds is safe and feasible utilizing a standardized protocol and close postdischarge follow-up. This practice can decrease length of stay and prevent need for GT. KEY POINTS: · Discharge with nasogastric tube (NGT) supplementation is safe.. · Discharge with NGT supplementation decreases cost.. · Discharge with NGT can decrease neonatal intensive care unit length of stay.. · Medical home model facilitates safe discharge..

Survival and Neurodevelopmental Outcomes among Periviable Infants.

BACKGROUND: Data reported during the past 5 years indicate that rates of survival have increased among infants born at the borderline of viability, but less is known about how increased rates of survival among these infants relate to early childhood neurodevelopmental outcomes. METHODS: We compared survival and neurodevelopmental outcomes among infants born at 22 to 24 weeks of gestation, as assessed at 18 to 22 months of corrected age, across three consecutive birth-year epochs (2000-2003 [epoch 1], 2004-2007 [epoch 2], and 2008-2011 [epoch 3]). The infants were born at 11 centers that participated in the National Institute of Child Health and Human Development Neonatal Research Network. The primary outcome measure was a three-level outcome - survival without neurodevelopmental impairment, survival with neurodevelopmental impairment, or death. After accounting for differences in infant characteristics, including birth center, we used multinomial generalized logit models to compare the relative risk of survival without neurodevelopmental impairment, survival with neurodevelopmental impairment, and death. RESULTS: Data on the primary outcome were available for 4274 of 4458 infants (96%) born at the 11 centers. The percentage of infants who survived increased from 30% (424 of 1391 infants) in epoch 1 to 36% (487 of 1348 infants) in epoch 3 (P<0.001). The percentage of infants who survived without neurodevelopmental impairment increased from 16% (217 of 1391) in epoch 1 to 20% (276 of 1348) in epoch 3 (P=0.001), whereas the percentage of infants who survived with neurodevelopmental impairment did not change significantly (15% [207 of 1391] in epoch 1 and 16% [211 of 1348] in epoch 3, P=0.29). After adjustment for changes in the baseline characteristics of the infants over time, both the rate of survival with neurodevelopmental impairment (as compared with death) and the rate of survival without neurodevelopmental impairment (as compared with death) increased over time (adjusted relative risks, 1.27 [95% confidence interval {CI}, 1.01 to 1.59] and 1.59 [95% CI, 1.28 to 1.99], respectively). CONCLUSIONS: The rate of survival without neurodevelopmental impairment increased between 2000 and 2011 in this large cohort of periviable infants. (Funded by the National Institutes of Health and others; ClinicalTrials.gov numbers, NCT00063063 and NCT00009633 .).

Genetic variation in dopamine neurotransmission and motor development of infants born extremely-low-birthweight.

AIM: To determine if genetic variation associated with decreased dopamine neurotransmission predicts a decrease in motor development in a convenience cohort study of infants born extremely-low-birthweight (ELBW). METHOD: Four hundred and ninety-eight infants born ELBW had genome-wide genotyping and a neurodevelopmental evaluation at 18 to 22 months of age, corrected for preterm birth. A polygenic risk score (PRS) was created to combine into one predictor variable the hypothesized influences on motor development of alleles at seven independent single nucleotide polymorphisms previously associated with relative decreases in both dopamine neurotransmission and motor learning, by summing the number of alleles present in each infant (range=0-14). The motor development outcome was the Psychomotor Development Index (PDI) of the Bayley Scales of Infant Development, Second Edition. The linear regression models were adjusted for seven clinical and four genetic ancestry covariates. The mean PRS of infants with cerebral palsy (CP) was compared to those without CP. RESULTS: PRS was inversely related to PDI (p=0.011). Each 1-point increase in PRS resulted in an average decrease in PDI of 1.37 points. Patients with CP did not have a greater mean PRS than those without (p=0.67), both with and without adjustment for covariates. INTERPRETATION: Genetic variation that favors a decrease in dopamine neurotransmission predisposes to a decrease in motor development in infants born ELBW, but not to the diagnosis of CP. WHAT THIS PAPER ADDS: Genetic variation in dopamine neurotransmission was associated with a decrease in motor development in infants born at an extremely-low-birthweight. It does not predispose to the diagnosis of cerebral palsy.

Gastrostomy Tube Feeding in Extremely Low Birthweight Infants: Frequency, Associated Comorbidities, and Long-term Outcomes.

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.

Use of a Midliner Positioning System for Prevention of Dolichocephaly in Preterm Infants.

PURPOSE: The purpose of this study was to determine effectiveness of a midliner positioning system (MPS, Tortle Midliner) for preventing dolichocephaly. METHODS: This was a nonrandomized, prospective study of 30 premature infants (study cohort, SC) using an MPS compared with a retrospective study cohort (RSC) of 65 infants who received standard of care intervention. RESULTS: RSC baseline cranial index (CI) of 80% and final CI of 77% significantly decreased over an average 5.5 weeks (P < .0001). The SC baseline CI and the final CI were both 79% over an average 5.7 weeks, indicating no significant difference between CI measures (P = .6). Gestational age, birth weight, reflux, time on continuous positive airway pressure, and time in a supine position were not associated with dolichocephaly. CONCLUSIONS: The SC developed less cranial molding (ie, had greater CI), compared with the RSC. A larger randomized study is needed to recommend routine use of MPS for prevention and/or treatment of cranial molding in premature infants.

Dolichocephaly in Preterm Infants: Prevalence, Risk Factors, and Early Motor Outcomes.

Objective The purpose of this study was to determine when dolichocephaly develops in preterm infants, to establish factors that contribute to its development, and to determine its association with adverse motor outcomes. Study Design This study was a retrospective review of data collected from preterm infants born at < 32 weeks' gestation. The cranial index was measured by a physical therapist (PT) at three time points during hospitalization. Demographic data, neonatal morbidities, and motor outcomes at outpatient follow-up were collected. Results Overall, 54% of infants developed dolichocephaly during hospitalization. The presence of dolichocephaly was highest in infants between 32 and 34 weeks' postmenstrual age (PMA) (39%). Birth weight, gestational age, bronchopulmonary dysplasia, gastroesophageal reflux disease, and severe intraventricular hemorrhage were not associated with dolichocephaly. Infants with dolichocephaly at 32 to 34 weeks' PMA were more likely to either be receiving PT services or be referred to PT services by outpatient follow-up (p = 0.05). Conclusion The presence of dolichocephaly was highest in infants between 32 and 34 weeks' PMA and was associated with increased need for PT services in early infancy. Findings support early developmental intervention at < 32 weeks' PMA to prevent and/or treat cranial molding deformity and improve early motor outcomes.

Neurodevelopmental outcomes in the early CPAP and pulse oximetry trial.

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.).

Childhood outcomes after hypothermia for neonatal encephalopathy.

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.).

Poorer neurodevelopmental outcomes associated with cystoid macular edema identified in preterm infants in the intensive care nursery.

PURPOSE: To evaluate the association between cystoid macular edema (CME) observed in very preterm infants and developmental outcomes at 18 to 24 months corrected age. DESIGN: Cohort study. PARTICIPANTS: Infants born at or less than 1500 g or at or less than 30 weeks postmenstrual age who underwent screening for retinopathy of prematurity (ROP) in an intensive care nursery. METHODS: Bedside handheld spectral-domain optical coherence tomography (SD OCT; Envisu, Bioptigen, Inc, Research Triangle Park, NC) imaging was obtained from preterm infants who were being screened for ROP and graded for presence of CME, central foveal thickness (CFT), inner nuclear layer thickness, and foveal-to-parafoveal thickness ratio. At 18 to 24 months corrected age, the children were assessed with the Bayley Scales of Infant and Toddler Development, Third Edition. MAIN OUTCOME MEASURES: Scores on the Bayley cognitive, language, and motor subscales. RESULTS: Among 77 children with SD OCT imaging, 53 were evaluated with the Bayley Scales. Compared with children who did not have CME as infants (n=22), the mean score for children who had CME (n=31) was 7.3 points (95% confidence interval [CI], -15.5 to 0.9; P=0.08) lower on the cognitive subscale, 14.1 points (95% CI, -22.7 to -5.5; P=0.002) lower for the language subscale, and 11.5 points (95% CI, -21.6 to -1.3; P=0.03) lower for the motor subscale. Differences were maintained after adjusting for gestational age and birth weight. Severity of CME, as assessed by foveal-to-parafoveal thickness ratio, within the CME group correlated with poorer cognitive (R2=0.16, P=0.03) and motor (R2=0.15, P=0.03) development. CONCLUSIONS: Cystoid macular edema observed on SD OCT in very preterm infants screened for ROP is associated with poorer language and motor skills at 18 to 24 months corrected age. Evaluation of the retina with SD-OCT may serve as an indicator of neurodevelopmental health for very preterm infants in the intensive care nursery.

Feasibility of autologous cord blood cells for infants with hypoxic-ischemic encephalopathy.

OBJECTIVE: To assess feasibility and safety of providing autologous umbilical cord blood (UCB) cells to neonates with hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: We enrolled infants in the intensive care nursery who were cooled for HIE and had available UCB in an open-label study of non-cyropreserved autologous volume- and red blood cell-reduced UCB cells (up to 4 doses adjusted for volume and red blood cell content, 1-5 × 10(7) cells/dose). We recorded UCB collection and cell infusion characteristics, and pre- and post-infusion vital signs. As exploratory analyses, we compared cell recipients' hospital outcomes (mortality, oral feeds at discharge) and 1-year survival with Bayley Scales of Infant and Toddler Development, 3rd edition scores ≥85 in 3 domains (cognitive, language, and motor development) with cooled infants who did not have available cells. RESULTS: Twenty-three infants were cooled and received cells. Median collection and infusion volumes were 36 and 4.3 mL. Vital signs including oxygen saturation were similar before and after infusions in the first 48 postnatal hours. Cell recipients and concurrent cooled infants had similar hospital outcomes. Thirteen of 18 (74%) cell recipients and 19 of 46 (41%) concurrent cooled infants with known 1-year outcomes survived with scores >85. CONCLUSIONS: Collection, preparation, and infusion of fresh autologous UCB cells for use in infants with HIE is feasible. A randomized double-blind study is needed.

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.

Evaluation of optic nerve development in preterm and term infants using handheld spectral-domain optical coherence tomography.

PURPOSE: To evaluate effects of prematurity on early optic nerve (ON) development and the usefulness of ON parameters as indicators of central nervous system (CNS) development and pathology. DESIGN: Prospective, cross-sectional, longitudinal study. PARTICIPANTS: Forty-four preterm infants undergoing retinopathy of prematurity (ROP) screening and 52 term infants. METHODS: We analyzed ON from portable handheld spectral-domain optical coherence tomography (SD-OCT) images (Bioptigen, Inc, Research Triangle Park, NC) of 44 preterm and 52 term infants. The highest-quality ON scan from either eye was selected for quantitative analysis. Longitudinal analysis was performed at 31-36 weeks and 37-42 weeks postmenstrual age (PMA). Preterm ON parameters also were assessed for correlation with indicators of cognitive, language, and motor development and CNS pathology. MAIN OUTCOME MEASURES: Vertical cup diameter (vCD), vertical disc diameter (vDD), vertical cup-to-disc ratio (vCDR), cup depth, and indicators of neurocognitive development and CNS pathology. RESULTS: At 37-42 weeks PMA, preterm infants had larger vCD and vCDR than term infants (908 vs. 700 µm [P<0.001] and 0.68 vs. 0.53 µm [P<0.001], respectively), whereas cup depth and vDD were not significantly different. Longitudinal changes (n = 26 preterm eyes; mean interval, 4.7 weeks) in vDD and in vCDR were an increase of 74 µm (P = 0.008) and decrease of 0.05 (P = 0.015), respectively. In preterm infants (n = 44), periventricular leukomalacia was associated with larger vCD (1084 vs. 828 µm; P = 0.005) and vCDR (0.85 vs. 0.63; P<0.001), posthemorrhagic hydrocephalus was associated with shallower cup (331 vs. 456 µm; P = 0.030), and clinical magnetic resonance imaging was associated with larger vCDR (0.73 vs. 0.64; P = 0.023). In 23 preterm infants with Bayley Scales of Infant Development scores, larger vCDR was associated with lower cognitive scores (P = 0.049). CONCLUSIONS: This is the first analysis of ON parameters in premature infants using SD-OCT. It demonstrated that by age of term birth, vCD and vCDR are larger in preterm infants who were screened for ROP than in term infants. In this prospective pilot study, ON parameters in these preterm infants associate weakly with CNS pathology and future cognitive development. Future prospective studies with larger numbers are necessary before further conclusions can be made.

Apolipoprotein E genotype and outcome in infants with hypoxic-ischemic encephalopathy.

BACKGROUND: Adults with the apolipoprotein E (APOE) gene alleles e4 and e2 are at high risk of poor neurological outcome after brain injury. The e4 allele has been associated with cerebral palsy (CP), and the e2 allele has been associated with worse neurological outcome with congenital heart disease. This study was done to test the hypothesis that the APOE genotype is associated with outcome among neonates who survive after hypoxic-ischemic encephalopathy (HIE). METHODS: We conducted a cohort study of infants who survived HIE and had 18-22 mo standardized neurodevelopmental evaluations to assess associations between disability and the APOE genotypes e3/e3, e4/-, and e2/-. RESULTS: A total of 139 survivors were genotyped. Of these, 86 (62%) were of the e3/e3, 41 (29%) were of the e4/-, and 14 (10%) were of the e2/- genotypes. One hundred and twenty-nine infants had genotype and follow-up data; 26% had moderate or severe disabilities. Disability prevalence was 30 and 19% among those with and without the e3/e3 genotype, 25 and 26% among those with and without the e2 allele, and 18 and 29% among those with and without the e4 allele, respectively. None of the differences were statistically significant. CP prevalence was also similar among genotype groups. CONCLUSION: Disability was not associated with the APOE genotype in this cohort of HIE survivors.

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.

Are outcomes of extremely preterm infants improving? Impact of Bayley assessment on outcomes.

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.

Genetic predictors of severe intraventricular hemorrhage in extremely low-birthweight infants.

OBJECTIVE: To test associations between grades 3 or 4 (severe) intraventricular hemorrhage (IVH) and single nucleotide polymorphisms (SNPs) associated with coagulation, inflammation, angiogenesis, and organ development in an exploratory study. STUDY DESIGN: Extremely low-birthweight (ELBW) infants enrolled in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network's (NRN) Cytokines Study were included if they had cranial ultrasound (CUS) and genotyping data available in the NRN Anonymized DNA Repository and Database. Associations between SNPs and IVH severity were tested with multivariable logistic regression analysis. RESULT: One hundred thirty-nine infants with severe IVH and 687 infants with grade 1 or 0 IVH were included. One thousand two hundred seventy-nine SNPs were genotyped. Thirteen were preliminarily associated with severe IVH including five related to central nervous system (CNS) neuronal and neurovascular development. CONCLUSION: Genetic variants for CNS neuronal and neurovascular development may be associated with severe IVH in premature infants.

Neurodevelopmental outcome of preterm infants enrolled in myo-inositol randomized controlled trial.

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.

Care of the Neonatal Intensive Care Unit Graduate after Discharge.

Premature and critically ill term infants are often discharged from the neonatal intensive care unit (NICU) with ongoing medical problems, including respiratory problems; growth, nutrition and feeding problems; and neurologic injury. At discharge, they may also be dependent on technology such as supplemental oxygen, tracheostomy, mechanical ventilation, feeding tube, and monitors. Primary care physicians must have special knowledge and understanding of the medical complications of NICU graduates to coordinate post-discharge care. We examine the most common post-discharge medical problems in premature and critically ill term infants and inform the primary care provider about expected outcomes and possible new problems.

Outcomes of preterm infants treated with hypothermia for hypoxic-ischemic encephalopathy.

BACKGROUND: Therapeutic hypothermia reduces the risk of death, or moderate to severe neurodevelopmental impairment (NDI) in term infants with hypoxic-ischemic encephalopathy (HIE). Reports of its safety and efficacy in preterm infants are scarce. OBJECTIVE: Report short and long-term outcomes of preterm infants with HIE who received therapeutic hypothermia. METHODS: A retrospective cohort analysis of all preterm infants <36 weeks' gestation with HIE who received whole body hypothermia in a single center from January 2007 to April 2015. The primary outcome was death or moderate to severe NDI defined by moderate or severe cerebral palsy, severe hearing or visual impairment, or cognitive score < 85 on the Bayley Scales of Infant Development III (BSID III) at 18-24 months' adjusted age. RESULTS: 30 infants with a median gestational age and birthweight of 35 weeks' (range; 33-35) and 2575 g (1850-4840) and a median first postnatal blood pH of 6.81 (6.58-7.14). Complications included coagulopathy (50%), early clinical seizures (43.3%), arterial hypotension (40%), persistent metabolic acidosis (37%) and thrombocytopenia (20%). Four infants died before or soon after discharge (18.2%). Eighteen surviving infants (69.2%) had follow up data; 7 of them had moderate to severe NDI (38.9%). Cognitive, motor and language mean composite BSID III scores were 84 (54-110), 83 (46-118), and 78 (46-112). Death or moderate to severe NDI occurred in 11/22 (50%) infants with known outcomes. CONCLUSION: Large randomized trials on efficacy and safety are needed in this highly vulnerable population as the incidence of complications and the combined outcome of death and NDI is concerning.