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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Neurodevelopmental assessment of the young child: the state of the art.

A wide variety of tests are available to assess the central nervous system (CNS) function of the toddler and preschool-aged child. These tests vary as to function; qualities and abilities tapped; facility with which they can be learned, administered, and scored; availability of test materials and manuals or training videos; and strength of standardization and validation data. Some were developed to screen development of large numbers of children. Others were developed to evaluate a child for diagnosis of disability or delineation of a child's strengths and weaknesses. Some broadly screen or assess multiple aspects of development, while some focus on specific abilities. A limitation of all these tests is that they tap only a small portion of a child's abilities at a given point in time. Administration of a variety of different tests provides a more complete evaluation of a child's abilities. Tests that can follow a child's development over time tap into the continuum of human development. The ability to measure various aspects of CNS functional development is a first step in addressing our greatest challenge, how to promote and support a child's development.

Assessment of gestational age and neuromaturation.

Neuromaturation is the functional development of the central nervous system (CNS). It is by its very nature a dynamic process, a continuous interaction between the genome and first the intrauterine environment, then the extrauterine environment. Understanding neuromaturation and being able to measure it is fundamental to infant neurodevelopmental assessment. Fetal and preterm neuromaturation has become easier to observe with the advent of prenatal ultrasonography and neonatal intensive care units. A number of measures of degree of fetal maturation have been developed and used to estimate gestational age (GA) at birth. The most reliable measures of GA are prenatal measures, especially from the first trimester. Postnatal GA measurements tend to be least accurate at the extremes of gestation, that is, in extremely preterm and post-term infants. Observations of measures of neuromaturation in infants born to mothers with pregnancy complications, including intrauterine growth restriction, multiple gestation, and chronic hypertension, have led to the discovery that stressed pregnancies may accelerate fetal pulmonary and CNS maturation. This acceleration of neuromaturation does not occur before 30 weeks' gestation and has a cost with respect to cognitive limitations manifested in childhood. The ability to measure fetal and preterm neuromaturation provides an assessment of neurodevelopmental progress that can be used to reassure parents or identify at risk infants who would benefit from limited comprehensive follow-up and early intervention services. In addition, measures of neuromaturation have the potential to provide insight into mechanisms of CNS injury and recovery, much-needed early feedback in intervention or treatment trials and a measure of early CNS function for research into the relationships between CNS structure and function.

Are histopathologic chorioamnionitis and funisitis associated with metabolic acidosis in the preterm fetus?

OBJECTIVE: Perinatal infection increases the risk of neonatal neurologic injury. Our objective is to determine whether histologically confirmed chorioamnionitis and funisitis is associated with fetal metabolic acidosis. STUDY DESIGN: This is a retrospective cohort study of all infants 34 weeks or less born at a single tertiary hospital admitted to the neonatal intensive care unit (NICU) between April 1999 and September 2002. Maternal and neonatal records and placental pathology reports were reviewed. RESULTS: There were 392 infants at 23 to 34 weeks' gestational age admitted to the NICU during this period of whom 354 had placental pathology reported; 259 infants had umbilical cord gases available. These neonates were placed into 3 groups: group 1 (208 infants) had no signs of placental infection, group 2 (59 infants) had isolated chorioamnionitis, and group 3 (87 infants) had both chorioamnionitis and funisitis. The gestational age (30.2 +/- 2.8, 28.3 +/- 3.4, 27.8 +/- 2.8 weeks, P < .01) and birth weight (1358 +/- 520, 1242 +/- 547, 1103 +/- 381 g, P < .01) were significantly higher in group 1. There was an increase in neurologic morbidity in groups 2 and 3 (25.2%, 34.4%, 43.7%), which was not significant when corrected for gestational age. Groups 2 and 3 had a small but significant increase in umbilical arterial pH (7.25 +/- 0.10, 7.29 +/- 0.10, 7.30 +/- 0.08, P < .01) and base excess (-3.5 +/- 3.6, -2.2 +/- 3.6, -2.3 +/- 2.7 mmol/L, P = .02). When a single pathologist reviewed all placentas with any inflammation and staged them on the basis of the degree of the fetal inflammatory response, no relationship was found between the degree of fetal inflammation and umbilical arterial pH (stage 1, 7.27 +/- 0.09; stage 2, 7.30 +/- 0.09; stage 3, 7.30 +/- 0.08; P = .41) or base excess (stage 1, -2.82 +/- 3.47 mmol/L; stage 2, -1.95 +/- 3.17 mmol/L; stage 3, -2.23 +/- 3.07 mmol/L; P = .62). When stepwise multiple linear regression was performed, neither histologic chorioamnionitis nor histologic funisitis were associated with a change in umbilical cord pH or base excess. CONCLUSION: Intrauterine infection, as confirmed by histologic chorioamnionitis and funisitis, is not associated with fetal metabolic acidosis. Intrauterine infection may represent a nonhypoxic form of encephalopathy that produces neurologic morbidity by a mechanism independent of hypoxia-ischemia leading to metabolic acidosis.

Neonatal cerebral white matter injury in preterm infants is associated with culture positive infections and only rarely with metabolic acidosis.

OBJECTIVE: Neonatal cerebral white matter injury represents a major precursor for neurological impairment and cerebral palsy. Our objective was to identify risk factors associated with its development. STUDY DESIGN: This retrospective case-control study of all births between 23 and 34 weeks gestation at a single university hospital between May 1994 and September 2001 identified 150 cases with white matter injury characterized by periventricular leukomalacia or ventricular dilatation from white matter atrophy that were chromosomally normal and did not have other congenital anomalies. Cases were matched to controls without brain injury by the next delivery within 7 days of their gestational age. RESULTS: There were small differences between controls and cases in gestational age (27.5 +/- 2.7, 27.4 +/- 2.6 weeks, P = .01) and birth weight (1053 +/- 402, 966 +/- 285 g, P = .002) that were statistically but not clinically significant. There was no difference in the percentage of controls and cases delivered by cesarean (45%, 49%, P = .64). There were no differences between controls and cases in umbilical arterial pH (7.27 +/- 0.11, 7.25 +/- 0.15, P = .19), base excess (-2.1 +/- 2.7, -3.0 +/- 4.1 mmol/L, P = .28), pH less than 7.0 (2/122 [2%], 3/107 [3%], P = 1.0), or base excess less than -12 mmol/L (4/121 [3%], 6/106 [6%], P = .75). The cases had a significant increase in positive blood (19%, 29%, P = .036), cerebrospinal fluid (6%, 17%, P = .002), and tracheal (9%, 22%, P = .003) cultures during the neonatal period. Conditional logistic regression showed a significant association among multiple gestations ( P = .02), intraventricular hemorrhage ( P < .001), and positive tracheal cultures ( P = .02) with cerebral white matter injury. CONCLUSION: Culture-positive infection was associated with an increased risk of cerebral white matter injury in preterm neonates. Intrapartum hypoxia-ischemia as manifested by metabolic acidosis was rarely associated with white matter injury and was not different from the incidence in premature neonates without injury.

Preterm outcomes research: a critical component of neonatal intensive care.

While early preterm outcome studies described the lives of preterm survivors to justify the efforts required to save them, subsequent studies demonstrated their increased incidence of cerebral palsy, mental retardation, sensory impairments, minor neuromotor dysfunction, language delays, visual-perceptual disorders, learning disability and behavior problems compared to fullterm controls. Because infants born at the lower limit of viability require the most resources and have the highest incidence of neurodevelopmental disability, there is concern that resources have gone primarily to neonatal intensive care and are not available for meeting the followup, health, educational and emotional needs of these fragile infants and their families. Despite many methodological concerns, preterm outcome studies have provided insight into risk factors for and causes of CNS injury in preterm infants. Nevertheless, it remains difficult to predict neurodevelopmental outcome for individual preterm infants. Perinatal and neonatal risk factors are inadequate proxies for neurodevelopmental disability. Recent randomized controlled trials with one to five year neurodevelopmental followup have provided valuable information about perinatal and neonatal treatments. Recognizing adverse longterm neurodevelopmental effects of pharmacological doses of postnatal steroids is a sobering reminder of the need for longterm neurodevelopmental followup in all neonatal randomized controlled trials. Ongoing longterm preterm neurodevelopmental studies, analysis of changes in outcomes over time and among centers, and evaluation of the longterm safety, efficacy and effectiveness of many perinatal and neonatal management strategies and proposed neuroprotective agents are all necessary for further medical and technological advances in neonatal intensive care.