Neonatal inflammation and its association with asthma and obesity in late childhood among individuals born extremely preterm.

BACKGROUND: Asthma and obesity are frequent outcomes among individuals born extremely preterm and are associated with decreased lifespan. Neonatal inflammation is associated with chronic neurodevelopmental disorders; however, it is less studied in association with other later childhood chronic disorders in this population. METHODS: Fourteen hospitals in 5 U.S. states enrolled 1506 infants born before 28 weeks of gestation in the Extremely Low Gestational Age Newborn cohort in 2004-2014. Neonatal blood spots were collected on postnatal days 1, 7, 14, 21, and 28, and used to measure 14 inflammation-related proteins. Associations were evaluated between high (top quartile) levels of proteins and two chronic health disorders at ages 10 and 15 years: physician-diagnosed asthma and obesity (body mass index ≥95th percentile). RESULTS: Few associations were found between high levels of 14 inflammation-related proteins, either on a single day or on multiple days, and either asthma or obesity. Similarly, few associations were found in analyses stratified by sex or presence/absence of prenatal inflammation. CONCLUSIONS: In extremely preterm newborns, systemic elevations of inflammation-related proteins during the neonatal period were not associated with childhood asthma and obesity outcomes at 10 or 15 years of age. IMPACT: In the large multi-center Extremely Low Gestational Age Newborn (ELGAN) cohort, sustained elevation of neonatal levels of inflammation-related proteins was not consistently associated with asthma or obesity outcomes at 10 or 15 years of age. This finding contrasts with reported associations of perinatal inflammation with obesity at 2 years and neurodevelopmental disorders at 2-15 years in the ELGANs, suggesting that unlike neurodevelopment, peripubertal obesity and asthma may be driven by later childhood exposures. Future research on perinatal mechanisms of childhood asthma and obesity should account for both fetal and later exposures and pathways in addition to inflammation at birth.

Prenatal tobacco smoke exposure and neurological impairment at 10 years of age among children born extremely preterm: a prospective cohort.

OBJECTIVE: To determine the association between prenatal tobacco smoke exposure and neurological impairment at 10 years of age among children born extremely preterm (<28 weeks of gestation). DESIGN: The Extremely Low Gestational Age Newborn (ELGAN) Study, a prospective cohort. SETTING: Ten-year follow-up of extremely preterm infants born at 14 US hospitals between 2002 and 2004. METHODS: Prenatal tobacco smoke exposure was defined as a mother's report at enrolment of active (i.e. maternal) and passive smoking during pregnancy. Poisson regression with generalized estimating equations was used. Models adjusted for mother's age, race/ethnicity, education, insurance, pre-pregnancy body mass index, US region, multiple gestation and infant's sex; and in sensitivity analysis, gestational age at delivery and clinical subtype of preterm birth, given their classification as intermediate and non-confounding variables. MAIN OUTCOMES: Neurological impairment at 10 years, epilepsy, cerebral palsy and cognitive impairment. RESULTS: Of 1200 ELGAN study survivors, 856 were assessed at 10 years of age with neurological outcomes, of whom 14% (118/856) had active tobacco exposure during pregnancy and 24% (207/852) had passive tobacco exposure. Compared with children who were not exposed prenatally to tobacco, children exposed to active tobacco use during pregnancy had a higher risk of epilepsy (14% versus 5%; adjusted relative risk: 1.68, 95% CI 1.45-1.92). This risk remained after adjustment for gestational age at delivery and clinical subtype of preterm birth. Prenatal tobacco smoke exposure was not associated with other assessed neurological outcomes, including cerebral palsy and multiple measures of cognitive impairment. CONCLUSIONS: Among children born extremely preterm, prenatal active tobacco smoke exposure was associated with an increased risk of epilepsy at 10 years of life. TWEETABLE ABSTRACT: Among infants born before 28 weeks of gestation, prenatal active tobacco smoke exposure was associated with an increased risk of epilepsy at 10 years of life.

Lesion environments direct transplanted neural progenitors towards a wound repair astroglial phenotype in mice.

Neural progenitor cells (NPC) represent potential cell transplantation therapies for CNS injuries. To understand how lesion environments influence transplanted NPC fate in vivo, we derived NPC expressing a ribosomal protein-hemagglutinin tag (RiboTag) for transcriptional profiling of transplanted NPC. Here, we show that NPC grafted into uninjured mouse CNS generate cells that are transcriptionally similar to healthy astrocytes and oligodendrocyte lineages. In striking contrast, NPC transplanted into subacute CNS lesions after stroke or spinal cord injury in mice generate cells that share transcriptional, morphological and functional features with newly proliferated host astroglia that restrict inflammation and fibrosis and isolate lesions from adjacent viable neural tissue. Our findings reveal overlapping differentiation potentials of grafted NPC and proliferating host astrocytes; and show that in the absence of other interventions, non-cell autonomous cues in subacute CNS lesions direct the differentiation of grafted NPC towards a naturally occurring wound repair astroglial phenotype.

Injectable polypeptide hydrogels via methionine modification for neural stem cell delivery.

Injectable hydrogels with tunable physiochemical and biological properties are potential tools for improving neural stem/progenitor cell (NSPC) transplantation to treat central nervous system (CNS) injury and disease. Here, we developed injectable diblock copolypeptide hydrogels (DCH) for NSPC transplantation that contain hydrophilic segments of modified l-methionine (Met). Multiple Met-based DCH were fabricated by post-polymerization modification of Met to various functional derivatives, and incorporation of different amino acid comonomers into hydrophilic segments. Met-based DCH assembled into self-healing hydrogels with concentration and composition dependent mechanical properties. Mechanical properties of non-ionic Met-sulfoxide formulations (DCHMO) were stable across diverse aqueous media while cationic formulations showed salt ion dependent stiffness reduction. Murine NSPC survival in DCHMO was equivalent to that of standard culture conditions, and sulfoxide functionality imparted cell non-fouling character. Within serum rich environments in vitro, DCHMO was superior at preserving NSPC stemness and multipotency compared to cell adhesive materials. NSPC in DCHMO injected into uninjured forebrain remained local and, after 4 weeks, exhibited an immature astroglial phenotype that integrated with host neural tissue and acted as cellular substrates that supported growth of host-derived axons. These findings demonstrate that Met-based DCH are suitable vehicles for further study of NSPC transplantation in CNS injury and disease models.

Early human milk feeding is associated with a lower risk of necrotizing enterocolitis in very low birth weight infants.

BACKGROUND: Necrotizing enterocolitis (NEC) is a frequent cause of mortality and morbidity in very low birth weight (VLBW) infants. Human milk (HM) feeding has been associated with lower risk of NEC. However, mothers of VLBW infants often experience insufficient milk production, resulting in mixed feedings of HM and formula. Moreover, medical complications often limit the volume of feeding they can be given. OBJECTIVE: To determine if high proportions of (50% or greater) HM enteral feeding within the first 14 days of life are protective against NEC. METHOD: This was a prospective cohort study of VLBW infants who were grouped according to the HM proportion of enteral feeding in the first 14 days: <50% (low human milk, LHM, n=46) and > or =50% (high human milk, HHM, n=156). The outcome of interest was development of NEC (Bell stage 2 or 3). Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) and to assess potential confounding due to perinatal risk factors. RESULT: Two hundred and two infants were studied. Confirmed NEC occurred in 5/46 (10.6%) of the LHM group, as compared with 5/156 (3.2%) of the HHM. Gestational age was the only perinatal factor associated with risk of NEC. After adjustment for gestational age, HHM was associated with a lower risk of NEC ((OR=0.17, 95% CI: 0.04 to 0.68), P=0.01). CONCLUSION: Enteral feeding containing at least 50% HM in the first 14 days of life was associated with a sixfold decrease in the odds of NEC.

Early postnatal illness severity scores predict neurodevelopmental impairments at 10 years of age in children born extremely preterm.

OBJECTIVE: A neonatal illness severity score, The Score for Neonatal Acute Physiology-II (SNAP-II), predicts neurodevelopmental impairments at two years of age among children born extremely preterm. We sought to evaluate to what extent SNAP-II is predictive of cognitive and other neurodevelopmental impairments at 10 years of age. STUDY DESIGN: In a cohort of 874 children born before 28 weeks of gestation, we prospectively collected clinical, physiologic and laboratory data to calculate SNAP-II for each infant. When the children were 10 years old, examiners who were unaware of the child's medical history assessed neurodevelopmental outcomes, including neurocognitive, gross motor, social and communication functions, diagnosis and treatment of seizures or attention deficit hyperactivity disorder (ADHD), academic achievement, and quality of life. We used logistic regression to adjust for potential confounders. RESULTS: An undesirably high SNAP-II (⩾30), present in 23% of participants, was associated with an increased risk of cognitive impairment (IQ, executive function, language ability), adverse neurological outcomes (epilepsy, impaired gross motor function), behavioral abnormalities (attention deficit disorder and hyperactivity), social dysfunction (autistic spectrum disorder) and education-related adversities (school achievement and need for educational supports. In analyses that adjusted for potential confounders, Z-scores ⩽-1 on 11 of 18 cognitive outcomes were associated with SNAP-II in the highest category, and 6 of 18 were associated with SNAP-II in the intermediate category. Odds ratios and 95% confidence intervals ranged from 1.4 (1.01, 2.1) to 2.1 (1.4, 3.1). Similarly, 2 of the 8 social dysfunctions were associated with SNAP-II in the highest category, and 3 of 8 were associated with SNAP-II in the intermediate category. Odds ratios and 95% confidence intervals were slightly higher for these assessments, ranging from 1.6 (1.1, 2.4) to 2.3 (1.2, 4.6). CONCLUSION: Among very preterm newborns, physiologic derangements present in the first 12 postnatal hours are associated with dysfunctions in several neurodevelopmental domains at 10 years of age. We are unable to make inferences about causality.

Volume guarantee pressure support ventilation in extremely preterm infants and neurodevelopmental outcome at 18 months.

OBJECTIVE: Compared with pressure-controlled ventilation (PCV), volume-targeted ventilation is associated with decreased neonatal complications, including the combined outcome of death or bronchopulmonary dysplasia. However, little is known about its effect on neurodevelopmental outcome. We evaluated the hypothesis that as compared with PCV, volume-targeted ventilation reduces the risk of the combined outcome of neurodevelopmental impairment or death in very low birth weight infants. STUDY DESIGN: We studied a cohort of extremely preterm infants managed with either volume guarantee pressure support ventilation (VGPSV; n=135) or PCV (n=135). Infants were evaluated at 18 months adjusted age with a standardized neurological examination and the Bayley Scales of Infant and Toddler Development-third edition. Logistic regression models were used to evaluate the association of ventilation mode and neurodevelopmental outcome. RESULT: Rates of pulmonary interstitial emphysema (odds ratio 0.6; 95% confidence limits: 0.4, 0.8), hypotension (odds ratio: 0.7; 95% confidence limits: 0.5, 0.9) and mortality (odds ratio 0.45; 95% confidence limits: 0.22, 0.9) were lower among infants treated with VGPSV. The infants in the VGPSV group had a significantly shorter duration on mechanical ventilation compared with infants in the PCV group (log-rank test P<0.01). Seventy percent (155/221) of survivors were evaluated at 18 months adjusted age. A trend towards benefit for the combined outcome of death or neurodevelopmental impairment was seen in the VGPSV group but did not reach statistical significance (odds ratio: 0.59; 95% confidence limits: 0.32, 1.08). CONCLUSION: VGPSV was associated with a decreased risk of short-term complications but not long-term developmental impairment in this modest-sized cohort.

Serum bilirubin levels, intracranial hemorrhage, and the risk of developmental problems in very low birth weight neonates.

To study whether elevated levels of bilirubin in the neonatal period increase the risk of developmental problems for very low birth weight neonates, the investigators used data from a geographically based sample of 495 very low birth weight neonates, born January 1, 1985, to December 31, 1989, who survived to 1 year of adjusted age. Maximum neonatal bilirubin levels were found in medical records. A developmental problem was defined as either cerebral palsy or a Bayley Mental Developmental Index of less than 68 at 1 year adjusted age. Potentially confounding factors were controlled using logistic regression. To control for the effects of intracranial abnormalities (eg, intraventricular hemorrhage), separate logistic regression analyses were carried out for three strata, defined according to the results of cranial ultrasonography. In these analyses, the following odds ratios (with 95% confidence limits) were found for the association of maximum neonatal bilirubin concentration and developmental problems: for subjects without intracranial abnormalities, 0.9 (0.7, 1.9); for subjects with uncomplicated intracranial hemorrhage, 1.5 (0.8, 2.5); for subjects with complicated intracranial hemorrhage or intraparenchymal echo-densities, 1.2 (0.4, 3.6). In summary, in analyses controlled for confounding factors, maximum neonatal bilirubin level was not consistently associated with the risk of developmental problems identifiable at 1 year.

Trends in mortality and cerebral palsy in a geographically based cohort of very low birth weight neonates born between 1982 to 1994.

OBJECTIVE: To analyze whether the increasing survival of very low birth weight infants during the 1980s and 1990s has increased the risk of cerebral palsy among survivors. METHODS: The study cohort consisted of 2076 consecutively born infants, with birth weights of 500 to 1500 g and no major anomaly, born July 1, 1982, through June 30, 1994, to residents of a 17-county region in North Carolina. These infants had a mean birth weight of 1096 g (standard deviation, 251 g) and a mean gestational age of 29 weeks (standard deviation, 3 weeks). One thousand five hundred sixty-eight infants (76%) survived to 1 year adjusted age, at which point 1282 infants (82%) were examined at our medical center. The diagnosis of cerebral palsy was made only if the examining pediatrician and a pediatric physical therapist agreed on the diagnosis. To analyze trends across time, the Cochran-Armitage chi2 test and logistic regression were applied to data for infants categorized into six 2-year epochs according to year of birth. RESULTS: Mortality did not change significantly through 1990, and then began to decrease in 1990 to 1994. During the study period, mortality decreased from 36.8% between 1982 and 1984, to 13.8% between 1992 and 1994. The prevalence of cerebral palsy among survivors was constant from 1982 to 1988 (11.3%), decreased slightly from 1988 to 1990 (9.2%), and was lowest in 1990 to 1994 (5.2%). These secular trends in mortality and cerebral palsy risk remained significant when adjusted for gestational age, gender, and race. When adjusted for surfactant use, the trend in mortality was no longer significant, whereas the trend in cerebral palsy risk persisted. CONCLUSIONS: The increasing survival of very low birth weight infants in the 1980s and 1990s has not resulted in an increased prevalence of cerebral palsy among survivors.

Randomized placebo-controlled trial of a 42-day tapering course of dexamethasone to reduce the duration of ventilator dependency in very low birth weight infants: outcome of study participants at 1-year adjusted age.

OBJECTIVE: Ventilator-dependent preterm infants are often treated with a prolonged tapering course of dexamethasone to decrease the risk and severity of chronic lung disease. The objective of this study was to assess the effect of this therapy on developmental outcome at 1 year of age. METHODS: Study participants were 118 very low birth weight infants who, at 15 to 25 days of life, were not weaning from assisted ventilation and were then enrolled in a randomized, placebo-controlled, double-blind trial of a 42-day tapering course of dexamethasone. Infants were examined at 1 year of age, adjusted for prematurity, by a pediatrician and a child psychologist. A physical and neurologic examination was performed, and the Bayley Scales of Infant Development were administered. All examiners were blind to treatment group. RESULTS: Groups were similar in terms of birth weight, gestational age, gender, and race. A higher percentage of dexamethasone recipients had major intracranial abnormalities diagnosed by ultrasonography (21% vs 11%). Group differences were not found for Bayley Mental Development Index (median [range] for dexamethasone-treated group, 94 [50-123]; for placebo group, 90 [28-117]) or Psychomotor Development Index Index (median [range]) for dexamethasone-treated group, 78 (50-109); for placebo-treated group, 81 [28-117]). More dexamethasone-treated infants had cerebral palsy (25% vs 7%) and abnormal neurologic examination findings (45% vs 16%). In stratified analyses, adjusted for major cranial ultrasound abnormalities, these associations persisted (OR values for cerebral palsy, 5.3; 95% CI: 1.3-21.4; OR values for neurologic abnormality 3.6; 95% CI: 1.2-11.0). CONCLUSIONS: A 42-day tapering course of dexamethasone was associated with an increased risk of cerebral palsy. Possible explanations include an adverse effect of this therapy on brain development and/or improved survival of infants who either already have neurologic injury or who are at increased risk for such injury.

Randomized placebo-controlled trial of a 42-Day tapering course of dexamethasone to reduce the duration of ventilator dependency in very low birth weight infants.

OBJECTIVE: To assess the effect on duration of ventilator dependency of a 42-day tapering course of dexamethasone in very low birth weight neonates. METHODS: Infants (N = 118) were assigned randomly, within birth weight/gender strata, to treatment with either a 42-day tapering course of dexamethasone or an equal volume of saline as placebo. Entry criteria were 1) birth weight <1501 g; 2) age between 15 and 25 days; 3) <10% decrease in ventilator settings for 24 hours and FIO2 >/=0.3; 4) absence of patent ductus arteriosus, sepsis, major congenital malformation, congenital heart disease; and 5) no evidence of maternal HIV or hepatitis B infection. The dosage schedule was 0.25 mg/kg bid for 3 days, then 0.15 mg/kg bid for 3 days, then a 10% reduction in the dose every 3 days until a dose of 0.1 mg/kg had been given for 3 days, from which time a dose of 0.1 mg/kg qod was continued until 42 days after entry. The primary endpoint was the number of days on assisted ventilation after study entry. Secondary outcomes of interest included days on supplemental oxygen, days of hospitalization, and potential adverse effects, such as infection, gastrointestinal bleeding, left ventricular hypertrophy, and severe retinopathy of prematurity. RESULTS: Infants in the dexamethasone- and placebo-treated groups were similar in terms of baseline attributes, including birth weight, gestational age, gender, race, and ventilator settings at entry. Infants treated with dexamethasone were on assisted ventilation and supplemental oxygen for fewer days after study entry (median days on ventilator, 5th and 95th percentiles, 13 [1-64] vs 25 [6-104]; days on oxygen, 59 [6-247] vs 100 [11-346]). No differences were found in risk of death, infection, or severe retinopathy. In subgroup analyses, the association of dexamethasone with more rapid weaning from the ventilator was weaker among infants enrolled before the 16th day of life, infants with chest radiographs showing cystic changes and/or hyperinflation, and infants requiring an FIO2 >/=0.7 or a peak inspiratory pressure >/=19 at study entry. CONCLUSIONS: A 42-day tapering course of dexamethasone decreases the duration of ventilator and oxygen dependency in very low birth weight infants and is not associated with an increased risk of short-term adverse effects.

Costs and benefits of respiratory syncytial virus immunoglobulin to prevent hospitalization for lower respiratory tract illness in very low birth weight infants.

BACKGROUND: Respiratory syncytial virus immunoglobulin intravenous (RSV-IGIV) has been shown to reduce the risk of lower respiratory illness (LRI) hospitalization in preterm infants and infants with bronchopulmonary dysplasia (BPD). The purpose of this analysis was to estimate the economic costs and benefits of prophylaxis with RSV-IGIV in these groups. METHODS: The analysis was performed from a payer's perspective and therefore included only costs and cost savings that would be realized by an insurer. Estimates of the direct costs of prophylaxis and the risk and cost of LRI hospitalization were based on data about preterm very low birth weight infants cared for at our medical center. Estimates of the reduction in risk of LRI hospitalization associated with RSV-IGIV were based on data from a randomized trial (the PREVENT Study). RESULTS: The range of cost for a five-dose course of RSV-IGIV was estimated to be $3280 to $8800 for infants weighing 1.2 to 10.0 kg at the time of the initial dose. Risks of LRI hospitalization were estimated to be 12, 17 and 28%, respectively, for preterm infants without BPD, with mild BPD and with moderate to severe BPD. Estimates of duration and per diem cost of LRI hospitalizations were, respectively, 5 days and $971. The estimated net cost of prophylaxis per infant ranged between $5415 for a 6-kg infant without BPD to $1689 for an infant with BPD and age < or =3 months. CONCLUSIONS: The cost of RSV-IGIV typically exceeds the cost of hospitalizations prevented by several thousand dollars. Cost minus benefit is lower for infants with BPD and infants 3 months of age or younger.

Gastroesophageal reflux in very low birth weight infants: association with chronic lung disease and outcomes through 1 year of age.

OBJECTIVE: To analyze the association between chronic lung disease (CLD) and clinically diagnosed gastroesophageal reflux (GER) in very low birth weight (VLBW) infants, and between GER and outcomes at 1 year adjusted age. METHODS: A total of 375 consecutively born VLBW infants with CLD and 345 gestational age-matched controls were studied. Records were reviewed to ascertain which infants were diagnosed with GER (based on clinical suspicion or confirmatory tests) and which infants had delayed growth or development at 1 year adjusted age. RESULTS: Infants with CLD were treated for GER more frequently than controls (CLD: 27% versus controls: 9%; p < 0.0001). Among infants with CLD, those with and without GER were comparable in terms of the days on supplemental oxygen [124 (64 to 93) vs 121 (47 to 394)] and the proportion with cystic changes on chest radiograph (44% vs 47%). Comparing outcomes at 1 year for infants with and without GER, no differences were found in the rates of Bayley Mental Developmental and Psychomotor Developmental Indices of < 70, cerebral palsy, and measurements below the 10th percentile. CONCLUSION: Among VLBW infants, an association exists between CLD and GER, although this association might be due to greater diagnostic suspicion in infants with CLD. In VLBW infants, GER does not appear to increase the risk of delayed growth or development.

Association between the severity of chronic lung disease and first-year outcomes of very low birth weight infants.

OBJECTIVE: The objective of this study was to determine if there is an association between the severity of chronic lung disease in very low birth weight infants (as assessed by the duration of supplemental oxygen requirements in the neonatal period) and first-year neurodevelopmental, sensory, and growth outcomes as well as duration of neonatal hospitalization and first-year hospital readmissions. STUDY DESIGN: Retrospective chart review with matched subject groups. METHODS: The subjects of this study were very low birth weight infants born between 1987 and 1991 in a 17-county perinatal region of North Carolina. Infants were categorized into one of three groups on the basis of duration of supplemental oxygen requirements. Infants who were breathing room air by 28 days were classified as having no chronic lung disease; infants who required supplemental oxygen at 28 days but not at 36 weeks postmenstrual age were classified as having mild chronic lung disease; and infants who required supplemental oxygen at 36 weeks postmenstrual age were classified as having severe chronic lung disease. Infants were matched for birth weight, sex, and race. The matched groups (n = 174) were compared with respect to the incidence of first year adverse neurodevelopmental and sensory outcomes, growth patterns, and hospital readmissions during the first year. Results were analyzed with general linear models and logistic regression analyses. RESULTS: The incidence of any adverse neurodevelopmental or sensory outcome increased as severity of chronic lung disease increased from none (3.6%) to mild (21.4%) to severe (31.6%, p < 0.001). Growth patterns were similar in infants with no and mild chronic lung disease, but infants with severe chronic lung disease were significantly lighter (p < 0.01) and shorter (p < 0.005) at 40 weeks postmenstrual age and significantly lighter at 1 year adjusted age (p < 0.05). The duration of the initial hospitalization increased with chronic lung disease severity (p < 0.001). Infants with severe chronic lung disease were readmitted to the hospital significantly more often (p < 0.005) than infants with no chronic lung disease or mild chronic lung disease. CONCLUSIONS: Very low birth weight infants who required supplemental oxygen at or beyond 28 days were at increased risk for adverse neurodevelopmental and sensory outcomes, but only those infants who continued to require supplemental oxygen at 36 weeks were at increased risk for poor growth and readmission to the hospital.

Antecedents of cerebral palsy in very low-birth weight infants.

Research from the last two decades provides directions for efforts to prevent CP in VLBW infants. The pathogenesis of CP seems to involve factors operating both during pregnancy and in the neonatal period. The most important prenatal factor appears to be intrauterine infection. Perinatal infection and other risk factors, such as the death of a co-twin, placental abruption, and cerebral ischemia, could trigger a cytokine cascade resulting in damage to the developing brain. The low frequency of intrauterine infection in mothers with preeclampsia might explain the apparent protective effect of this disorder. If the brain damage attributed to intrauterine infection and other risk factors involves cytokines as intermediates, then blockade of the proinflammatory cascade or promotion of endogenous inhibitors might prevent CP. Other potentially preventive strategies include corticosteroids given to mothers (but not those given to neonates) and thyroid hormone.

Antenatal steroid exposure and pulmonary outcomes in adolescents born with very low birth weight.

OBJECTIVE: To compare asthma history and pulmonary function in adolescents born prematurely with very low birth weight with and without antenatal steroid exposure. STUDY DESIGN: We studied 188 fourteen-year olds (94 exposed, 84 male). We used parent report to ascertain asthma and asthma-related symptoms and spirometry to assess pulmonary function. Steroid-exposed and -unexposed groups were compared using Mann-Whitney U-tests (continuous variables), χ(2) analysis (categorical variables) and logistic regression (multivariate analyses). RESULT: The steroid-exposed group had greater prevalence of larger airway obstruction (35% vs 21%), and steroid-exposed adolescents with birth weights <1000 g had 4.5-fold higher odds of larger airway obstruction. Wheezing in the past 12 months was two times as prevalent in steroid-exposed adolescents with birth weights between 1000 and 1500 g. CONCLUSION: Antenatal steroid exposure does not provide long-term benefits for pulmonary outcomes in adolescents born prematurely with very low birth weight in the era of surfactant therapy.

Brain wave maturation and neurodevelopmental outcome in extremely low gestational age neonates.

OBJECTIVE: Infants born at extremely low gestational ages are at high risk for developmental impairments. Early predictors of these impairments are useful for both clinicians and researchers. Our objective was to assess the correlation between the rate of brain wave maturation as measured by serial amplitude-integrated electroencephalograms (aEEGs) and scores on standardized measures of infant development in extremely low gestational age neonates. STUDY DESIGN: This was a prospective observational study of 65 infants born before 28 weeks' gestational age who were assessed with an aEEG monthly between 28 and 36 weeks' postmenstrual age and with the Bayley Scales of Infant and Toddler Development-III at 18 to 22 months adjusted age. We analyzed the correlation between the rate of brain wave maturation on aEEG and Bayley Scales of Infant and Toddler Development-III Cognitive and Motor Scales. RESULT: The mean rate of brain wave maturation was 0.83 (±0.36) points per week. Brain wave maturation was not correlated with either the Cognitive or Motor Scale (adjusted regression coefficients for Cognitive and Motor Scales were 1.61 (s.e.: 4.20; P=0.70) and 2.39 (s.e.: 4.62; P=0.61), respectively. CONCLUSION: Among extremely preterm infants, the rate of maturational changes in brain wave characteristics between 28 and 36 weeks' postmenstrual age is not predictive of developmental abilities at 18 to 22 months adjusted age.

Efficacy of phototherapy devices and outcomes among extremely low birth weight infants: multi-center observational study.

OBJECTIVE: Evaluate the efficacy of phototherapy (PT) devices and the outcomes of extremely premature infants treated with those devices. STUDY DESIGN: This substudy of the National Institute of Child Health and Human Development Neonatal Research Network PT trial included 1404 infants treated with a single type of PT device during the first 24±12 h of treatment. The absolute (primary outcome) and relative decrease in total serum bilirubin (TSB) and other measures were evaluated. For infants treated with one PT type during the 2-week intervention period (n=1223), adjusted outcomes at discharge and 18 to 22 months corrected age were determined. RESULT: In the first 24 h, the adjusted absolute (mean (±s.d.)) and relative (%) decrease in TSB (mg dl(-1)) were: light-emitting diodes (LEDs) -2.2 (±3), -22%; Spotlights -1.7 (±2), -19%; Banks -1.3 (±3), -8%; Blankets -0.8 (±3), -1%; (P<0.0002). Some findings at 18 to 22 months differed between groups. CONCLUSION: LEDs achieved the greatest initial absolute reduction in TSB but were similar to Spots in the other performance measures. Long-term effects of PT devices in extremely premature infants deserve rigorous evaluation.

Motor cortical functional geometry in cerebral palsy and its relationship to disability.

OBJECTIVE: To investigate motor cortical map patterns in children with diplegic and hemiplegic cerebral palsy (CP), and the relationships between motor cortical geometry and motor function in CP. METHODS: Transcranial magnetic stimulation (TMS) was used to map motor cortical representations of the first dorsal interosseus (FDI) and tibialis anterior (TA) muscles in 13 children with CP (age 9-16 years, 6 males.) The Gross Motor Function Measure (GMFM) and Melbourne upper extremity function were used to quantify motor ability. RESULTS: In the hemiplegic participants (N = 7), the affected (right) FDI cortical representation was mapped on the ipsilateral (N = 4), contralateral (N = 2), or bilateral (N = 1) cortex. Participants with diplegia (N = 6) showed either bilateral (N = 2) or contralateral (N = 4) cortical hand maps. The FDI and TA motor map center-of-gravity mediolateral location ranged from 2-8 cm and 3-6 cm from the midline, respectively. Among diplegics, more lateral FDI representation locations were associated with lower Melbourne scores, i.e. worse hand motor function (Spearman's rho = -0.841, p = 0.036). CONCLUSIONS: Abnormalities in TMS-derived motor maps cut across the clinical classifications of hemiplegic and diplegic CP. The lateralization of the upper and lower extremity motor representation demonstrates reorganization after insults to the affected hemispheres of both diplegic and hemiplegic children. SIGNIFICANCE: The current study is a step towards defining the relationship between changes in motor maps and functional impairments in CP. These results suggest the need for further work to develop improved classification schemes that integrate clinical, radiologic, and neurophysiologic measures in CP.