Randomized trial of azithromycin to eradicate Ureaplasma respiratory colonization in preterm infants: 2-year outcomes.

BACKGROUND: To assess the potential impact of azithromycin treatment in the first week following birth on 2-year outcomes in preterm infants with and without Ureaplasma respiratory colonization who participated in a double-blind, placebo-controlled randomized controlled trial. METHODS: Respiratory morbidity was assessed at NICU discharge and at 6, 12, and 22-26 months corrected age using pulmonary questionnaires. Comprehensive neurodevelopmental assessments were completed between 22 and 26 months corrected age. The primary and secondary composite outcomes were death or severe respiratory morbidity and death or moderate-severe neurodevelopmental impairment, respectively, at 22-26 months corrected age. RESULTS: One hundred and twenty-one randomized participants (azithromycin, N = 60; placebo, N = 61) were included in the intent-to-treat analysis. There were no significant differences in death or serious respiratory morbidity (34.8 vs 30.4%, p = 0.67) or death or moderate-severe neurodevelopmental impairment (47 vs 33%, p = 0.11) between the azithromycin and placebo groups. Among all trial participants, tracheal aspirate Ureaplasma-positive infants experienced a higher frequency of death or serious respiratory morbidity at 22-26 months corrected age (58%) than tracheal aspirate Ureaplasma-negative infants (34%) or non-intubated infants (21%) (p = 0.028). CONCLUSIONS: We did not observe strong evidence of a difference in long-term pulmonary and neurodevelopment outcomes in preterm infants treated with azithromycin in the first week of life compared to placebo. IMPACT: No strong evidence of a difference in long-term pulmonary and neurodevelopment outcomes was identified at 22-26 months corrected age in infants treated with azithromycin in the first week of life compared to placebo. The RCT is the first study of 2-year pulmonary and neurodevelopmental outcomes of azithromycin treatment in ELGANs. Provides evidence that ELGANs with lower respiratory tract Ureaplasma have the most frequent serious respiratory morbidity in the first 2 years of life, suggesting that a Phase III trial of azithromycin to prevent BPD targeting this population is warranted.

Preschool Language Outcomes following Perinatal Hypoxic-Ischemic Encephalopathy in the Age of Therapeutic Hypothermia.

Early studies following perinatal hypoxic-ischemic encephalopathy (HIE) suggested expressive language deficits and academic difficulties, but there is only limited detailed study of language development in this population since the widespread adoption of therapeutic hypothermia (TH). Expressive and receptive language testing was performed as part of a larger battery with 45 children with a mean age of 26 months following perinatal HIE treated with TH. Overall cohort outcomes as well as the effects of gender, estimated household income, initial pH and base excess, and pattern of injury on neonatal brain MRI were assessed. The cohort overall demonstrated expressive language subscore, visual-reception subscore, and early learning composite scores significantly below test norms, with relative sparing of receptive language subscores. Poorer expressive language manifested as decreased vocabulary size and shorter utterances. Expressive language subscores showed a significant gender effect, and estimated socioeconomic status showed a significant effect on both receptive and expressive language subscores. Initial blood gas markers and modified Sarnat scoring did not show a significant effect on language subscores. Binarized MRI abnormality predicted a significant effect on both receptive and expressive language subscores; the presence of specific cortical/subcortical abnormalities predicted receptive language deficits. Overall, the language development profile of children following HIE in the era of hypothermia shows a relative strength in receptive language. Gender and socioeconomic status predominantly predict expressive language deficits; abnormalities detectable on MRI predominantly predict receptive language deficits.

Recommendations for the design of therapeutic trials for neonatal seizures.

Although seizures have a higher incidence in neonates than any other age group and are associated with significant mortality and neurodevelopmental disability, treatment is largely guided by physician preference and tradition, due to a lack of data from well-designed clinical trials. There is increasing interest in conducting trials of novel drugs to treat neonatal seizures, but the unique characteristics of this disorder and patient population require special consideration with regard to trial design. The Critical Path Institute formed a global working group of experts and key stakeholders from academia, the pharmaceutical industry, regulatory agencies, neonatal nurse associations, and patient advocacy groups to develop consensus recommendations for design of clinical trials to treat neonatal seizures. The broad expertise and perspectives of this group were invaluable in developing recommendations addressing: (1) use of neonate-specific adaptive trial designs, (2) inclusion/exclusion criteria, (3) stratification and randomization, (4) statistical analysis, (5) safety monitoring, and (6) definitions of important outcomes. The guidelines are based on available literature and expert consensus, pharmacokinetic analyses, ethical considerations, and parental concerns. These recommendations will ultimately facilitate development of a Master Protocol and design of efficient and successful drug trials to improve the treatment and outcome for this highly vulnerable population.

Factors affecting early childhood growth in hypoxic-ischemic encephalopathy treated with hypothermia.

INTRODUCTION: There is an extensive body of research regarding neurological outcomes following neonatal hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia (TH), with limited data on growth outcomes. We examined perinatal characteristics associated with postnatal growth in this population. METHODS: Convenience cohort of 66 infants with HIE who underwent TH and participated in follow-up at 24 months of age were included. Regression modeling including perinatal anthropomorphics, markers of HIE, and systemic injury was used to evaluate growth at 24 months. RESULTS: Birth head circumference was associated with weight (p = 0.036). MRI severity, pH at admission and birth head circumference were associated with height (p = 0.043, p = 0.015 and p = 0.043 respectively). MRI severity and length of intubation were associated with head circumference (p = 0.038 and p < 0.001 respectively). CONCLUSION: There was a significant association between specific early factors and growth at 24 months among infants with HIE treated with TH.

Glial fibrillary acidic protein as a biomarker for periventricular white matter injury.

OBJECTIVE: Periventricular white matter injury (PWMI), a precursor of cerebral palsy, traditionally is not diagnosed until 6 weeks of life by head ultrasound scanning. We sought to determine whether early neonatal glial fibrillary acidic protein (GFAP) levels could identify PWMI in low birthweight (<2500 g) infants. STUDY DESIGN: Each case with PWMI on head ultrasound scanning at 6 weeks of life from April 2009 to April 2011 was matched by gestational age and mode of delivery to 2 subsequent neonates with a normal head ultrasound scan. GFAP was measured in cord blood at birth, at neonatal intensive care unit admission, and on days 1-4 of life. RESULTS: During this 2-year period, 21 cases with PWMI with gestational age 27.4 ± 3.3 weeks were compared with 42 control infants. The incidence of cesarean delivery was 61.9% in both groups. GFAP was not significantly different in cord blood or at neonatal intensive care unit admission but was significantly elevated on day 1 (median, 5-95%; 0, 0-0.98 ng/mL cases; 0, 0-0.06 ng/mL control infants; P = .03), day 2 (0, 0-1.21 ng/mL; 0, 0-0.05 ng/mL, respectively; P = .02), day 3 (0.05, 0-0.33 ng/mL; 0, 0-0.04 ng/mL, respectively; P = .004), and day 4 (0.02, 0-1.03 ng/mL; 0, 0-0.05 ng/mL, respectively; P < .001). The odds of the development of PWMI significantly increased with increasing levels of GFAP from day 1-4 of life when adjustment was made for preeclampsia, antenatal steroid administration, and neonatal chronic lung disease. CONCLUSION: The ability to predict PWMI with a blood test for GFAP shortly after birth opens the possibility for rapid identification of infants for early intervention and provides a benchmark for the qualification of new therapies to improve neurodevelopmental outcomes.

Extrauterine neuromaturation of low risk preterm infants.

The objective of the study was to follow neuromaturation in preterm infants. From serial exams in 90 low risk very low birthweight infants, each infant's Maturity Scores (the sum of tone, reflex, and response items) were plotted against postmenstrual age (PMA) when examined. Each infant's estimated line of best fit provides two descriptors of that infant's neuromaturation: slope (Individual Maturity Slope) and y-value (Predicted Maturity Score at 32-wk PMA). We found that Maturity Scores increased with PMA; 96% had correlation coefficients >0.8. Mean Actual and Predicted Maturity Scores at 32-wk PMA were 60 and 58, respectively, in 65 infants. When stratified by gestational age, Mean Actual Maturity Score at 30-wk PMA were 50 whether infants were 1 or several weeks old when examined. Therefore, low risk preterm infants demonstrated individual variability in rate of neuromaturation. Tone, reflexes, and responses nonetheless emerged in a predictable pattern, whether neuromaturation was intrauterine or extrauterine. This unique tool that measures preterm neuromaturation requires expertise but no technology. It has an exciting potential for providing insight into how emerging central nervous system function and structure influence each other, as well as how the central nervous system recovers from injury.

Early neurodevelopmental outcome in preterm posthemorrhagic ventricular dilatation and hydrocephalus: Neonatal ICU Network Neurobehavioral Scale and imaging predict 3-6-month motor quotients and Capute Scales.

OBJECTIVE: Brain injury remains a serious complication of prematurity. Almost half of infants with severe intraventricular hemorrhage (IVH) develop posthemorrhagic ventricular dilatation (PHVD) and 20% need surgery for posthemorrhagic hydrocephalus (PHH). This population is associated with an increased risk of later neurodevelopmental disability, but there is uncertainty about which radiological and examination features predict later disability. In this study the authors sought to devise and describe a novel combination of neurobehavioral examination and imaging for prediction of neurodevelopmental disability among preterm infants with PHVD and PHH. METHODS: The study patients were preterm infants (< 36 weeks gestation) with IVH and PHVD, with or without PHH. Ventricular index (VI), anterior horn width (AHW), thalamooccipital distance (TOD), ventricle/brain (V/B) ratio, and resistive indices (RIs) were recorded on the head ultrasound (HUS) just prior to surgery, or the HUS capturing the worst PHVD when surgery was not indicated. The posterior fossa was assessed with MRI. Neonatal ICU Network Neurobehavioral Scale (NNNS) examinations were performed at term age equivalent for each infant. A neurodevelopmental assessment using the Capute Scales (Capute Cognitive Adaptive Test [CAT] scores and Capute Clinical Linguistic Auditory Milestone Scale [CLAMS] scores) and a motor quotient (MQ) assessment were performed between 3 and 6 months of age corrected for degree of prematurity (corrected age). MQs < 50 reflect moderate to severe delays in early motor milestone attainment, CAT scores < 85 reflect delays in early visual and problem-solving abilities, and CLAMS scores < 85 reflect delays in early language. RESULTS: Twenty-one infants underwent assessments that included imaging and NNNS examinations, Capute Scales assessments, and MQs. NNNS nonoptimal reflexes (NOR) and hypertonicity subscores and AHW were associated with MQs < 50: NOR subscore OR 2.46 (95% CI 1.15-37.6, p = 0.034), hypertonicity subscore OR 1.68 (95% CI 1.04-3.78, p = 0.037), and AHW OR 1.13 (95% CI 1.01-1.39, p = 0.041). PVHI, cystic changes, and neurosurgical intervention were associated with CAT scores < 85: PVHI OR 9.2 (95% CI 1.2-73.2, p = 0.037); cystic changes OR 12.0 (95% CI 1.0-141.3, p = 0.048), and neurosurgical intervention OR 11.2 (95% CI 1.0-120.4, p = 0.046). Every 1-SD increase in the NOR subscore was associated with an increase in odds of a CAT score < 85, OR 4.0 (95% CI 1.0-15.0, p = 0.044). Worse NNNS NOR subscores were associated with early language delay: for a 1-SD increase in NOR subscore, there was an increase in the odds of a CLAMS score < 85, OR 19.5 (95% CI 1.3-303, p = 0.034). CONCLUSIONS: In former preterm children with severe IVH and PHVD, neonatal neurological examination findings and imaging features are associated with delays at 3-6 months in motor milestones, visual and problem-solving abilities, and language.

The Relationship Between Clinical Imaging and Neurobehavioral Assessment in Posthemorrhagic Ventricular Dilation of Prematurity.

Introduction: Neonatal intraventricular hemorrhage (IVH) and subsequent posthemorrhagic ventricular dilation and hydrocephalus of prematurity are associated with brain injury and neurodevelopmental impairment in the preterm population. Neuroimaging assesses cerebral injury and guides neurosurgical intervention; however, the relationship of head ultrasound (HUS) and magnetic resonance imaging (MRI) parameters to neonatal exams in this group has not been well described. The NICU Network Neurobehavioral Scale (NNNS) is a reproducible, highly reliable battery with motor and cognitive domain scores. Objective: To evaluate the relationship between neonatal neurobehavioral findings on the NNNS and measures of ventricular dilation and associated brain injury on HUS and MRI. Materials and Methods: Neonates with IVH and ventricular dilatation with and without posthemorrhagic hydrocephalus were enrolled. NNNS exams were performed at approximately term age equivalent. HUS indices were measured on the last HUS before initial neurosurgical procedure or that with worst ventriculomegaly if no intervention. The posterior fossa was assessed with MRI at term. Descriptive statistics including medians, interquartile ranges, means, and percentages were performed. Correlations were estimated using Pearson's method. Results: 28 patients had NNNS and HUS, and 18 patients also had an MRI. Ventricle size measures for the cohort were significantly above normal. Motor and cognitive subscores on the NNNS exam varied from established baseline scores for postmenstrual age. Children who required neurosurgical intervention had higher ventricle/brain ratios and worse NNNS habituation scores. Ventricle sizes were modestly correlated with motor abnormalities (0.24-0.59); larger anterior horn width correlated with nonoptimal reflexes, hypertonicity and hypotonicity. Ventricle sizes were modestly correlated with cognitive scores (-0.44 to 0.27); larger ventricular index correlated with worse attention. Periventricular hemorrhagic infarction correlated with worse habituation. Conclusion: For this cohort of preterm infants with IVH, surgical intervention for posthemorrhagic hydrocephalus correlated with both larger degrees of ventriculomegaly and worse NNNS exams. Findings on both HUS and MRI correlated with motor and cognitive abnormalities on neonatal neurobehavioral exam, suggesting that larger neonatal ventricle sizes and white matter injury have detectable correlates on exam. The NNNS exam provides important additional information when assessing posthemorrhagic ventricular dilation and hydrocephalus of prematurity.

Quality of life of caregivers of very low-birthweight infants.

BACKGROUND: The health and developmental outcomes of very low-birthweight infants are unpredictable over the first year of life. This uncertainty may have meaningful consequences for parents' quality of life. The objective of this study was to explore the quality of life of caregivers of these infants. METHODS: Primary caregivers of very low-birthweight infants, 12 to 18 months old, who had been cared for in an inner-city hospital were enrolled in the study. Primary caregivers of full-term infants of the same age served as a comparison group. During a telephone survey, participants answered questions about their quality of life, mental and physical health, living arrangements, and child's health. RESULTS: Eighty-three caregivers of very low-birthweight infants and 84 caregivers of full-term infants were enrolled in the study. Demographic characteristics of the caregivers were similar between the groups. Forty-five percent of caregivers of very low-birthweight infants reported that their child had an ongoing medical problem compared with 23 percent of caregivers of full-term infants. Both groups of caregivers reported significant physical and mental health problems. Caregivers of very low-birthweight infants reported higher quality of life than did caregivers of full-term infants, but the difference did not reach statistical significance. CONCLUSIONS: Although very low-birthweight infants had poorer health and required significantly more health care resources than full-term infants, caregivers' quality of life did not differ between the two groups. Caregivers of both groups of infants reported substantial mental and physical health problems but perceived good quality of life. These data will aid parents, physicians, and policy makers as they struggle to make decisions concerning care of high-risk, costly, very low-birthweight infants.

Preterm neuroimaging and neurodevelopmental outcome: a focus on intraventricular hemorrhage, post-hemorrhagic hydrocephalus, and associated brain injury.

Intraventricular hemorrhage in the setting of prematurity remains the most common cause of acquired hydrocephalus. Neonates with progressive post-hemorrhagic hydrocephalus are at risk for adverse neurodevelopmental outcomes. The goal of this review is to describe the distinct and often overlapping types of brain injury in the preterm neonate, with a focus on neonatal hydrocephalus, and to connect injury on imaging to neurodevelopmental outcome risk. Head ultrasound and magnetic resonance imaging findings are described separately. The current state of the literature is imprecise and we end the review with recommendations for future radiologic and neurodevelopmental research.

Association of prematurity and neonatal infection with neurologic morbidity in very low birth weight infants.

OBJECTIVE: To identify risk factors predictive of neurologic morbidity in very low birth weight (VLBW) infants. METHODS: This is a case-control study of all infants weighing 1500 g or less admitted to a single tertiary neonatal intensive care unit between April 1999 and December 2001. The case group were those neonates with neurologic morbidity including intraventricular hemorrhage, seizures, hydrocephalus, and periventricular leukomalacia. The control group were those without neurologic morbidity. Wilcoxon rank-sum, Fisher exact test, chi(2), and univariate and stepwise multiple logistic regression were performed, with P < 0.05 considered significant. RESULTS: Of 213 VLBW infants, 77 had neurologic morbidity: 61 had intraventricular hemorrhage, eight had seizures, 13 had hydrocephalus, and nine had periventricular leukomalacia. Several infants had more than one morbidity. Gestational age (odds ratio [OR] 0.95; 95% confidence interval [CI] 0.94, 0.96; P <.005), birth weight (OR 0.62; 95% CI 0.49, 0.79; P <.005), and neonatal infection (OR 1.36; 95% CI 1.17, 1.58; P <.005) were highly associated with neurologic morbidity. There was no difference in mean umbilical arterial cord pH (7.25 +/- 0.15, 7.28 +/- 0.09, P =.45) or base excess (-3.8 +/- 4.8 mEq/L, -2.3 +/- 3.0, P =.10). Only three of 52 infants (5.8%) in the case group had an umbilical arterial pH of less than 7. CONCLUSION: Prematurity and neonatal infection were the dominant factors associated with neurologic morbidity in VLBW infants. Intrapartum acidosis occurred in less than 6% of those with neurologic morbidity.

Outcomes of preterm infants: morbidity replaces mortality.

Over the last 50 years in the United States a rising preterm birth rate, a progressive decrease in preterm mortality, and a lowering of the limit of viability have made preterm birth a significant public health problem. Neuromaturation, the functional development of the central nervous system (CNS), is a dynamic process that promotes and shapes CNS structural development. This article reviews preterm outcomes, recognizing that multiple factors influence neuromaturation and lead to a range of neurodevelopmental disabilities, dysfunctions, and altered CNS processing. Ways to protect preterm infants and support their growth and development in and beyond intensive care are examined.

Inhaled nitric oxide in preterm infants: a systematic review.

CONTEXT: Studies of the efficacy of inhaled nitric oxide (iNO) to prevent or treat respiratory failure in preterm infants have had variable and contradictory findings. OBJECTIVES: To systematically review the evidence on the use of iNO in infants born at ≤ 34 weeks' gestation who receive respiratory support. METHODS: Medline, Embase, the Cochrane Central Register of Controlled Studies, PsycInfo, ClinicalTrials.gov, and proceedings of the 2009 and 2010 Pediatric Academic Societies meetings were searched in June 2010. Additional studies from reference lists of eligible articles, relevant reviews, and technical experts were considered. Two investigators independently screened search results and abstracted data from eligible articles. We focus here on mortality, bronchopulmonary dysplasia (BPD), the composite outcome of death or BPD, and neurodevelopmental impairment. RESULTS: Fourteen randomized controlled trials, 7 follow-up studies, and 1 observational study were eligible for inclusion. Mortality rates in the NICU did not differ for infants treated with iNO compared with controls (risk ratio [RR]: 0.97 [95% confidence interval (CI): 0.82-1.15]). BPD at 36 weeks for iNO and control groups also did not differ for survivors (RR: 0.93 [95% CI: 0.86-1.003]). A small difference was found in favor of iNO in the composite outcome of death or BPD (RR: 0.93 [95% CI: 0.87-0.99]). There was no evidence to suggest a difference in the incidence of cerebral palsy (RR: 1.36 [95% CI: 0.88-2.10]), neurodevelopmental impairment (RR: 0.91 [95% CI: 0.77-1.12]), or cognitive impairment (RR: 0.72 [95% CI: 0.35-1.45]). CONCLUSIONS: There was a 7% reduction in the risk of the composite outcome of death or BPD at 36 weeks for infants treated with iNO compared with controls but no reduction in death alone or BPD. There is currently no evidence to support the use of iNO in preterm infants with respiratory failure outside the context of rigorously conducted randomized clinical trials.

Preterm birth: Transition to adulthood.

Preterm birth is associated with greater difficulty with transitions from childhood to adolescence to adulthood. Adolescents and young adults born preterm have higher rates of cerebral palsy, intellectual disability, cognitive impairment, learning disability, executive dysfunction, attention deficit disorder, and social-emotional difficulties than their peers born fullterm. Compared to individuals born fullterm, more preterm survivors have major neurodevelopmental or psychiatric disability and need financial supports and societal resources. Neuroimaging studies of adolescents and adults born preterm report higher rates of brain injury, differences in regional brain structure, and different brain circuits than in those born fullterm. Making the transition to adulthood is more difficult for young adults who were born preterm than their peers born fullterm, in that fewer complete high school and higher education, find and keep meaningful employment, and live independently from their parents. As a group, they do not tend to be risk-takers, and they have lower rates of alcohol abuse, use of illicit drugs, and criminal offenses than do their peers. Despite their many challenges, the majority of adults born preterm function well, form personal relationships, integrate well into their community, and are as satisfied with their quality of life as are their peers. Concerns regarding current preterm infants, with more extremely preterm survivors, overwhelming our medical, educational, and societal resources should serve as an impetus for research on prevention of preterm births and brain injury, as well as how to support and promote their ongoing neuromaturation and recovery from injury.

Inhaled nitric oxide in preterm infants.

OBJECTIVES: To systematically review the evidence on the use of inhaled nitric oxide (iNO) in preterm infants born at or before 34 weeks gestation age who receive respiratory support. DATA SOURCES: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Studies (CENTRAL) and PsycInfo in June 2010. We also searched the proceedings of the 2009 and 2010 Pediatric Academic Societies Meeting and ClinicalTrials.gov. We identified additional studies from reference lists of eligible articles and relevant reviews, as well as from technical experts. REVIEW METHODS: Questions were developed in collaboration with technical experts, including the chair of the upcoming National Institutes of Health Office of Medical Applications of Research Consensus Development Conference. We limited our review to randomized controlled trials (RCTs) for the question of survival or occurrence of bronchopulmonary dysplasia (BPD) and for the question on short-term risks. All study designs were considered for long-term pulmonary or neurodevelopmental outcomes, and for questions about whether outcomes varied by subpopulation or by intervention characteristics. Two investigators independently screened search results, and abstracted data from eligible articles. RESULTS: We identified a total of 14 RCTs, reported in 23 articles, and eight observational studies. Mortality rates in the NICU did not differ for infants treated with iNO versus those not treated with iNO (RR 0.97 (95% CI 0.82, 1.15)). BPD at 36 weeks for iNO and control groups also did not differ (RR 0.93 (0.86, 1.003) for survivors). A small difference was found between iNO and control infants in the composite outcome of death or BPD (RR 0.93 (0.87, 0.99)). There was inconsistent evidence about the risk of brain injury from individual RCTs, but meta-analyses showed no difference between iNO and control groups. We found no evidence of differences in other short term risks. There was no evidence to suggest a difference in the incidence of cerebral palsy (RR 1.36 (0.88, 2.10)), neurodevelopmental impairment (RR 0.91 (0.77, 1.12)), or cognitive impairment (RR 0.72 (0.35, 1.45)). Evidence was limited on whether the effect of iNO varies by subpopulation or by characteristics of the therapy (timing, dose and duration, mode of delivery, or concurrent therapies). CONCLUSIONS: There was a seven percent reduction in the risk of the composite outcome of death or BPD at 36 weeks PMA for infants treated with iNO compared to controls, but no reduction in death or BPD alone. Further studies are needed to explore particular subgroups of infants and to assess long term outcomes including function in childhood. There is currently no evidence to support the use of iNO in preterm infants with respiratory failure outside the context of rigorously conducted randomized clinical trials.

Intervention at the border of viability: perspective over a decade.

OBJECTIVE: To investigate prenatal management and outcome of infants born at the border of viability during 2 periods, 2001 to 2003 (late epoch) and 1993 to 1995 (early epoch). DESIGN: Cohort study. SETTING: Single academic, high-risk perinatal referral center. PARTICIPANTS: All 160 women admitted to labor and delivery with a live fetus who delivered at an estimated gestational age of 220/7 weeks to 246/7 weeks. MAIN OUTCOME MEASURES: Prenatal management and time between maternal admission and delivery or death of the fetus, infant resuscitation efforts, neonatal intensive care unit interventions, time of death, and morbidities in survivors. RESULTS: Mothers in both epochs were of similar age, race, and duration of pregnancy at hospital admission. Compared with the early epoch, women during the late epoch were more likely to be transported to a higher level of care (relative risk [RR], 2.01; 95% confidence interval [CI], 1.58-2.57) and receive sonographic surveillance (RR, 1.48; 95% CI, 1.07-2.04), antibiotics (RR, 1.60; 95% CI, 1.10-2.33), and antenatal steroids (RR, 1.61; 95% CI, 1.22-2.12). Life-sustaining interventions were provided for infants admitted to the neonatal intensive care unit more frequently during the late epoch than the early epoch, including high-frequency ventilation (RR, 3.57; 95% CI, 1.93-6.61), chest tubes (RR, 1.44; 95% CI, 1.06-1.94), dopamine administration (RR, 2.49; 95% CI, 1.24-4.97), and steroid administration for blood pressure support (RR, 2.18; 95% CI, 1.60-2.92). Gestational age-specific mortality was the same in the 2 epochs. CONCLUSIONS: More interventions were provided for infants born at 22 to 24 weeks' gestation in the late epoch than the early epoch. Despite these changes in management, there has been no reduction in mortality in more than a decade.

Neurodevelopmental outcomes of preterm infants.

PURPOSE OF REVIEW: Preterm birth is emerging as a major public health problem in the USA. Improvements in preterm birth and survival rates translate to increasing numbers of preterm survivors, and many develop motor, cognitive and sensory impairments. RECENT FINDINGS: The review discusses the recently reported prevalence of neurodevelopmental disabilities in preterm survivors, in addition to studies of factors associated with neurodevelopmental outcome. SUMMARY: A 2007 report from the Institute of Medicine emphasizes preterm birth as an increasingly common complex condition with multiple risk factors resulting from multiple gene-environmental interactions, leading to birth before 37 weeks gestation, neonatal complications and a disproportionately high contribution to neurodevelopmental disability rates. The increased risk of cerebral palsy with decreasing gestational age categories is well documented, but recent studies highlight the range and severity of cognitive, sensory, language, visual-perceptual, attention and learning deficits in very preterm children. Combined with increasingly sophisticated neuroimaging studies to identify perinatal risk factors, neurodevelopmental follow-up of neonatal intensive care unit trials offers the potential to really improve our understanding of how the preterm brain develops, is injured and recovers from injuries. Knowledge of what influences neurodevelopmental outcomes is key to developing better treatment strategies.

Summary proceedings from the bronchopulmonary dysplasia group.

Despite improvements in neonatal care, bronchopulmonary dysplasia (BPD) continues to occur in approximately one third of newborns who have birth weights of <1000 g and contributes to significant morbidity in this population. Gaps in knowledge about the prevention and treatment of BPD remain, resulting in unintended short- and long-term sequelae. In addition to chronic lung disease, preterm newborns with BPD are more likely to develop language delay, cerebral palsy, and cognitive impairments compared with preterm newborns without BPD. The pulmonary group identified 3 critical needs to enhance the design of clinical trials in neonates with BPD: (1) identify the stages of BPD; (2) define BPD more clearly; and (3) identify subtypes of BPD patients. The group determined that trials are needed for 3 areas of BPD: (1) prevention of BPD; (2) treatment of evolving BPD; and (3) treatment of established BPD. The severity of BPD is defined as mild, moderate, and severe, and subgroups among those with BPD are described. Here we identify gaps in basic science and pharmacologic knowledge that hamper investigators' ability to conduct effective BPD clinical trials and provide a list of drugs to be studied in BPD trials. Priorities for drug-class evaluation by stage of BPD are given. The pulmonary group proposes a BPD clinical-trials framework that varies according to the different stages of BPD and describes characteristics of the overall design for BPD clinical trials. Finally, we discuss trial-design issues that are common to all neonatal studies.