Practice parameter: neuroimaging of the neonate: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society.

OBJECTIVE: The authors reviewed available evidence on neonatal neuroimaging strategies for evaluating both very low birth weight preterm infants and encephalopathic term neonates. IMAGING FOR THE PRETERM NEONATE: Routine screening cranial ultrasonography (US) should be performed on all infants of <30 weeks' gestation once between 7 and 14 days of age and should be optimally repeated between 36 and 40 weeks' postmenstrual age. This strategy detects lesions such as intraventricular hemorrhage, which influences clinical care, and those such as periventricular leukomalacia and low-pressure ventriculomegaly, which provide information about long-term neurodevelopmental outcome. There is insufficient evidence for routine MRI of all very low birth weight preterm infants with abnormal results of cranial US. IMAGING FOR THE TERM INFANT: Noncontrast CT should be performed to detect hemorrhagic lesions in the encephalopathic term infant with a history of birth trauma, low hematocrit, or coagulopathy. If CT findings are inconclusive, MRI should be performed between days 2 and 8 to assess the location and extent of injury. The pattern of injury identified with conventional MRI may provide diagnostic and prognostic information for term infants with evidence of encephalopathy. In particular, basal ganglia and thalamic lesions detected by conventional MRI are associated with poor neurodevelopmental outcome. Diffusion-weighted imaging may allow earlier detection of these cerebral injuries. RECOMMENDATIONS: US plays an established role in the management of preterm neonates of <30 weeks' gestation. US also provides valuable prognostic information when the infant reaches 40 weeks' postmenstrual age. For encephalopathic term infants, early CT should be used to exclude hemorrhage; MRI should be performed later in the first postnatal week to establish the pattern of injury and predict neurologic outcome.

Longitudinal growth of hospitalized very low birth weight infants.

BACKGROUND: The interpretation of growth rates for very low birth weight infants is obscured by limited data, recent changes in perinatal care, and the uncertain effects of multiple therapies. OBJECTIVES: To develop contemporary postnatal growth curves for very low birth weight preterm infants and to relate growth velocity to birth weight, nutritional practices, fetal growth status (small- or appropriate-for-gestational-age), and major neonatal morbidities (chronic lung disease, nosocomial infection or late-onset infection, severe intraventricular hemorrhage, and necrotizing enterocolitis). DESIGN: Large, multicenter, prospective cohort study. METHODS: Growth was prospectively assessed for 1660 infants with birth weights between 501 to 1500 g admitted by 24 hours of age to 1 of the 12 National Institute of Child Health and Human Development Neonatal Research Network centers between August 31, 1994 and August 9, 1995. Infants were included if they survived >7 days (168 hours) and were free of major congenital anomalies. Anthropometric measures (body weight, length, head circumference, and midarm circumference) were performed from birth until discharge, transfer, death, age 120 days, or a body weight of 2000 g. To obtain representative data, nutritional practices were not altered by the study protocol. RESULTS: Postnatal growth curves suitable for clinical and research use were constructed for body weight, length, head circumference, and midarm circumference. Once birth weight was regained, weight gain (14.4-16.1 g/kg/d) approximated intrauterine rates. However, at hospital discharge, most infants born between 24 and 29 weeks of gestation had not achieved the median birth weight of the reference fetus at the same postmenstrual age. Gestational age, race, and gender had no effect on growth within 100-g birth weight strata. Appropriate-for-gestational age infants who survived to hospital discharge without developing chronic lung disease, severe intraventricular hemorrhage, necrotizing enterocolitis, or late onset-sepsis gained weight faster than comparable infants with those morbidities. More rapid weight gain was also associated with a shorter duration of parenteral nutrition providing at least 75% of the total daily fluid volume, an earlier age at the initiation of enteral feedings, and an earlier age at achievement of full enteral feedings. CONCLUSIONS: These growth curves may be used to better understand postnatal growth, to help identify infants developing illnesses affecting growth, and to aid in the design of future research. They should not be taken as optimal. Randomized clinical trials should be performed to evaluate whether different nutritional management practices will permit birth weight to be regained earlier and result in more rapid growth, more appropriate body composition, and improved short- and long-term outcomes.

Persistent pulmonary hypertension of the newborn in the era before nitric oxide: practice variation and outcomes.

OBJECTIVES: In the era before widespread use of inhaled nitric oxide, to determine the prevalence of persistent pulmonary hypertension (PPHN) in a multicenter cohort, demographic descriptors of the population, treatments used, the outcomes of those treatments, and variation in practice among centers. STUDY DESIGN: A total of 385 neonates who received >/=50% inspired oxygen and/or mechanical ventilation and had documented evidence of PPHN (2D echocardiogram or preductal or postductal oxygen difference) were tracked from admission at 12 Level III neonatal intensive care units. Demographics, treatments, and outcomes were documented. RESULTS: The prevalence of PPHN was 1.9 per 1000 live births (based on 71 558 inborns) with a wide variation observed among centers (.43-6.82 per 1000 live births). Neonates with PPHN were admitted to the Level III neonatal intensive care units at a mean of 12 hours of age (standard deviation: 19 hours). Wide variations in the use of all treatments studied were found at the centers. Hyperventilation was used in 65% overall but centers ranged from 33% to 92%, and continuous infusion of alkali was used in 75% overall, with a range of 27% to 93% of neonates. Other frequently used treatments included sedation (94%; range: 77%-100%), paralysis (73%; range: 33%-98%), and inotrope administration (84%; range: 46%-100%). Vasodilator drugs, primarily tolazoline, were used in 39% (range: 13%-81%) of neonates. Despite the wide variation in practice, there was no significant difference in mortality among centers. Mortality was 11% (range: 4%-33%). No specific therapy was clearly associated with a reduction in mortality. To determine whether the therapies were equivalent, neonates treated with hyperventilation were compared with those treated with alkali infusion. Hyperventilation reduced the risk of extracorporeal membrane oxygenation without increasing the use of oxygen at 28 days of age. In contrast, the use of alkali infusion was associated with increased use of extracorporeal membrane oxygenation (odds ratio: 5.03, compared with those treated with hyperventilation) and an increased use of oxygen at 28 days of age. CONCLUSIONS: Hyperventilation and alkali infusion are not equivalent in their outcomes in neonates with PPHN. Randomized trials are needed to evaluate the role of these common therapies.

Indications for operation in acute necrotizing enterocolitis of the neonate.

A study to evaluate criteria for operation was carried out in 61 infants with acute necrotizing enterocolitis (NEC). A total of 10 clinical, roentgenographic, and laboratory criteria were considered. Each proposed operative criterion was correlated with the documented presence or absence of intestinal gangrene in these infants. Indications for operation verified by this study were (1) pneumoperitoneum, (2) paracentesis findings positive for gangrenous intestine, (3) erythema of the abdominal wall, (4) a fixed abdominal mass, and (5) a persistently dilated loop of intestine on serial abdominal radiographs. The first two signs occurred frequently; the latter three were rare. Operative indications which proved to be invalid in this study were (1) clinical deterioration, (2) persistent abdominal tenderness, (3) profuse lower gastrointestinal hemorrhage, (4) the roentgenographic finding of gasless abdomen with ascites, and (5) severe thrombocytopenia. Twenty-four of the infants were operated on. The mortality rate among the infants operated on after free intestinal perforation had occurred (64%) was double that of infants operated on for intestinal gangrene without perforation (30%). Paracentesis may identify infants with intestinal gangrene prior to the development of perforation and may permit advantagenous timing of operation. This analysis of the frequency and reliability of proposed operative criteria may aid the surgical decision.

Antenatal corticosteroids in pregnancies complicated by preterm premature rupture of membranes.

In 1994, the National Institutes of Health Consensus Development Conference on Antenatal Steroids recommended corticosteroids between 24 and 30-32 weeks' gestation in pregnancies complicated by preterm premature rupture of membranes (PROM). Since the Consensus Conference, the use of antenatal corticosteroids has increased to approximately 60% of potential treatment candidates. Some of the remaining 40% of pregnant candidates may go untreated because of concern that corticosteroids could increase the risk of neonatal infection. Using decision-analysis techniques, we compared the potential benefit of antenatal corticosteroids in reducing the incidence of severe intraventricular hemorrhage with the potential risk of increasing the rate of neonatal sepsis. Our analysis indicates that the benefit of a small decrease in severe intraventricular hemorrhage outweighs the potential harm of a large increase in the rate of neonatal sepsis. Therefore, we support the Consensus Conference panel's recommendation that antenatal corticosteroids be used in pregnancies complicated by preterm PROM.

Sex differences in outcomes of very low birthweight infants: the newborn male disadvantage.

OBJECTIVE: To determine the differences in short term outcome of very low birthweight infants attributable to sex. METHODS: Boys and girls weighing 501-1500 g admitted to the 12 centres of the National Institute of Child Health and Human Development Neonatal Research Network were compared. Maternal information and perinatal data were collected from hospital records. Infant outcome was recorded at discharge, at 120 days of age if the infant was still in hospital, or at death. Best obstetric estimate based on the last menstrual period, standard obstetric factors, and ultrasound were used to assign gestational age in completed weeks. Data were collected on a cohort that included 3356 boys and 3382 girls, representing all inborn births from 1 May 1991 to 31 December 1993. RESULTS: Mortality for boys was 22% and that for girls 15%. The prenatal and perinatal data indicate few differences between the sex groups, except that boys were less likely to have been exposed to antenatal steroids (odds ratio (OR) = 0.80) and were less stable after birth, as reflected in a higher percentage with lower Apgar scores at one and five minutes and the need for physical and pharmacological assistance. In particular, boys were more likely to have been intubated (OR = 1.16) and to have received resuscitation medication (OR = 1.40). Boys had a higher risk (OR > 1.00) for most adverse neonatal outcomes. Although pulmonary morbidity predominated, intracranial haemorrhage and urinary tract infection were also more common. CONCLUSIONS: Relative differences in short term morbidity and mortality persist between the sexes.

Predicting the future for newborns requiring intensive care.

When intensive care for newborns was introduced thirty years ago its primary goal was to improve the rates of survival of sick and premature infants. Medicine has been successful in attaining this goal; however, as more infants survive, the cost of intensive care and the additional cost of services and care for handicapped survivors continue to escalate. In order to curb the increasing cost of newborn intensive care, heightened initiatives directed at the prevention of premature births will be necessary.

Impact of antenatal corticosteroid therapy in very low birth weight infants on chronic lung disease and other morbidities of prematurity.

OBJECTIVE: To assess the effect of antenatal corticosteroids on very low birth weight (VLBW) infants through 36 weeks' postconceptional age. STUDY DESIGN: Data were collected prospectively on all VLBW (< or = 1500 gm) infants (n = 670) admitted to a single newborn intensive care unit from 1991 to 1996. Mortality rate and the frequency of medical morbidities attributable to prematurity were compared between VLBW infants who received antenatal corticosteroid therapy and those who did not. RESULTS: Antenatal steroid therapy was associated with a significantly lower rate of mortality (p = 0.02) and of mortality due to respiratory causes (p = 0.01). Although the frequency of chronic lung disease (oxygen requirement at 36 weeks' postconceptional age) was not significantly different between the groups (p = 0.48), the frequency of infants surviving without chronic lung disease was significantly greater in the steroid-exposed group (p = 0.02). There were no significant differences between the groups in the frequency of sepsis, necrotizing enterocolitis, length of hospital stay, or retinopathy of prematurity requiring surgery. CONCLUSION: In our study, antenatal corticosteroid therapy was associated with a beneficial effect on mortality and respiratory morbidity for VLBW infants and was not associated with any known increased risks.

Use of the Ages and Stages Questionnaire and Bayley Scales of Infant Development-II in neurodevelopmental follow-up of extremely low birth weight infants.

OBJECTIVE: For infants born with extremely low birth weight (ELBW), we examined the (1) correlation between results on the Ages and Stages Questionnaire (ASQ) and the Bayley Scales of Infant Development-II (BSID-II) at 18 to 22 months corrected age; (2) degree to which earlier ASQ assessments predict later BSID-II results; (3) impact of ASQ use on follow-up study return rates. STUDY DESIGN: ASQ data were collected at 4, 8, 12 and 18 to 22 months corrected age. The BSID-II was completed at 18 to 22 months corrected age. ASQ and BSID-II 18 to 22 month sensitivity and specificity were examined. Ability of earlier ASQs to predict later BSID-II scores was examined through linear regression analyses. RESULT: ASQ sensitivity and specificity at 18 to 22 months were 73 and 65%, respectively. Moderate correlation existed between earlier ASQ and later BSID-II results. CONCLUSION: For extremely low birth weight infant assessment, the ASQ cannot substitute for the BSID-II, but seems to improve tracking success.

The very low birthweight infant: incidence and significance of low Apgar scores, "asphyxia," and morbidity. Findings at delivery.

Cord blood gas determinations were made on arterial and venous blood from 78 babies weighing less than 2000 gm at birth, including 52 weighing 1500 gm or less. Correlations were made with Apgar scores and intrapartum events as well as with birthweight (BW) and gestational age (GA). Significant differences were seen between mean BW, GA, and Apgar scores for survivors versus nonsurvivors but only BW and GA were found to affect mortality. The incidence of low Apgar scores, which was high, was inversely related to BW and GA. Correlations between cord blood gases and Apgar scores were poor, most newborns showing normal gases irrespective of Apgar scores. The authors conclude that the term "asphyxia" is an overused explanation for low Apgar scores among very low birthweight babies; they believe it should be reserved for those depressed states proved to be associated with disturbed respiratory physiology.

Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm.

We have performed brain scanning by computed tomography on 46 consecutive live-born infants whose birth weights were less than 1,500 gm; 20 of them had evidence of cerebral intraventricular hemorrhage. Nine of the 29 infants who survived had IVH. Four grades of IVH were identified. Grade I and II lesions resolved spontaneously, but there was prominence of the interhemispheric fissue on CT of the infants at six months of age. Hydrocephalus developed in infants with Grade III and IV lesions. Seven of the surviving infants with IVH did not have clinical evidence of hemorrhage. There were no significant differences between the infants with and without IVH in birth weight, gestational age, one- and five-minute Apgar scores, or the need for resuscitation at birth or for subsequent respiratory assistance.

Intraventricular hemorrhage and hydrocephalus in premature newborns: a prospective study with CT.

In a prospective study, 100 premature infants were studied with computed tomography (CT) brain scans within the first week of life. In 44 of these,hemorrhages originated from the subependymal germinal matrix, and ranged in severity from isolated germinal matrix hemorrhages to blood-filled, dilated ventricles with extension of hemorrhage into the brain parenchyma. A system of grading the severity of hemorrhage was developed. Grades I and II hemorrhages resolved spontaneously and grades III and IV were associated with progressive hydrocephalus. Asymptomatic hemorrhages that would not have been diagnosed on clinical grounds were detected by CT. This study offers a clearer understanding of the true incidence and natural history of cerebroventricular hemorrhage and associated hydrocephalus in premature neonates and may clarify etiologic factors and identify children at risk for subsequent neurologic abnormalities.

Autoregulation of cerebral blood flow in the preterm fetal lamb.

The purpose of the present study was to determine if autoregulation of cerebral blood flow (CBF) is present in the preterm fetal lamb and, if present, to measure the range of mean arterial blood pressure over which autoregulation exists. Thirty-seven measurements of CBF were made in seven preterm fetal lambs (118-122 days gestation) over a mean carotid arterial blood pressure (CBP) range of 18-90 mm Hg. CBF was measured by the radionuclide-labeled microsphere technique. CBP was altered by graduated inflation of balloons placed around the brachiocephalic trunk and the aortic isthmus. To eliminate the effects of reflex changes in heart rate, the carotid sinus and aortic nerve were ablated bilaterally. CBF was linearly related to mean CBP from 18-45 mm Hg, constant over a mean CBP of 45-80 mm Hg, and again linear from 80-90 mm Hg. Resting mean CBP (normotension) was 53.8 +/- 1.9 mm Hg during the control period and 51.7 +/- 0.8 mm Hg during the equilibration periods. This study demonstrates that although autoregulation of CBF is intact in the preterm fetal lamb, the range is narrowed compared to the term lamb and resting mean CBP lies close to the lower limit of autoregulation.

Relationship of cerebral intraventricular hemorrhage and early childhood neurologic handicaps.

The outcome in 198 surviving very-low-birth-weight (less than 1501 gm) infants with and without cerebral intraventricular hemorrhage was compared to determine whether CVH is associated with early childhood developmental or neuromotor handicaps. Major handicaps were noted in 10% of the infants without and 28% of the infants with CVH. Among the infants with CVH, a major handicap was present in 9% with grade 1, 11% with grade 2, 36% with grade 3, and 76% with grade 4 CVH. Infants with posthemorrhagic hydrocephalus had the same incidence of major handicaps (59%) as did comparable infants with no hydrocephalus (57%). Our data indicate that grades 1 and 2 CVH do not increase an infant's risk for major handicaps, and there is a direct relationship of grades 3 and 4 CVH and major handicaps.

Quantification of neonatal cerebral ventricular volume by real-time ultrasonography. In vivo validation of the cylindrical coordinate method.

Posthemorrhagic ventricular dilation is a common clinical problem in preterm infants who have incurred an intraventricular hemorrhage. Presently there are no clinically applicable methods to follow quantitatively the progression of ventricular dilation at bedside. We describe the in vivo validation of a method to measure ventricular volume using bedside real-time cranial ultrasonography. Six infants undergoing either serial lumbar punctures or cerebral ventricular reservoir taps for posthemorrhagic hydrocephalus were studied. The cerebrospinal fluid (CSF) volume removed ranged from 5.5 mL to 30 mL. A strong correlation was found (r2 = 0.84) between the volume of CSF removed by reservoir tap and the change in ventricular volume calculated by the ultrasound method, whereas the correlation between the volume of CSF removed at lumbar puncture and the change in ventricular volume calculated by the ultrasound method was not as strong (r2 = 0.70). Limitations and sources of error in the method are discussed. We conclude that this procedure is accurate and offers a quantitative method to follow longitudinally posthemorrhagic progressive ventricular dilation.

Relationship of intravenous sodium bicarbonate infusions and cerebral intraventricular hemorrhage.

The incidence of cerebral intraventricular hemorrhage was determined by computed tomography in 100 infants with birth weights less than or equal to 1,500 gm. A comparison of IVH with serum sodium concentrations and the amount of intravenous sodium bicarbonate administered did not reveal a significant relationship. Analysis of the method of infusion of sodium bicarbonate indicated that the rapid infusion of hyperosmolar (M to M/12) sodium bicarbonate is associated with a significantly increased incidence of IVH.

Posthemorrhagic hydrocephalus in low-birth-weight infants: treatment by serial lumbar punctures.

We have performed weekly computed tomographic brain scans on 28 surviving low-birth-weight infants with cerebral intraventricular hemorrhage and acute ventricular dilatation. Evolving hydrocephalus was observed in 15 infants. Twelve of the 15 infants were treated by removing large volumes of cerebrospinal fluid with serial lumbar punctures. Arrest in the progression of hydrocephalus was evident in 11 of the 12. Clinical hydrocephalus requiring surgical intervention occurred in one of the treated infants and in all three untreated infants. No complications of serial lumbar punctures were noted, whereas shunt-related morbidity was 100%. Our results suggest that serial lumbar punctures are effective in arresting the development of posthemorrhagic hydrocephalus.

Long-term follow-up of bronchopulmonary dysplasia.

We observed 10 children with bronchopulmonary dysplasia, evaluated initially by cardiac catheterization (mean age 18 months), for an average of 4.4 years. Age at last evaluation averaged 5.8 years; subjects reside in and around Albuquerque, N.M. (altitude 5000 ft). At initial cardiac catheterization, mean pulmonary artery pressure was 40 mm Hg, pulmonary vascular resistance index 8.9 units, and intrapulmonary shunt fraction was high; pulmonary wedge angiograms were normal. Over the period of follow-up the group has done poorly. Four of the 10 continue to receive home oxygen therapy, but none requires inotropic or diuretic therapy; four children have marked developmental or motor delays. Nine of 10 patients have abnormalities of respiratory function on spirometric testing. Four patients underwent recatheterization because of clinical indications; two had large atrial level left-to-right shunts not found on initial study. Reductions in pulmonary artery pressure (55 to 37 mm Hg) and pulmonary vascular resistance (11.9 to 7.8 units) occurred between the two studies in these four patients (average study interval 4.0 years); the still elevated levels of pressure and resistance fell further in response to 40% O2 administration. Pulmonary wedge angiograms were abnormal in each restudied patient. Although not uniformly bleak, the long-term outlook for children with severe bronchopulmonary dysplasia is diverse and guarded.