Congenital hepatic arteriovenous malformation: an unusual cause of neonatal persistent pulmonary hypertension.

Congenital hepatic arteriovenous malformations are rare anomalies, which typically present in infancy with congestive heart failure, anemia, and hepatomegaly. Morbidity and mortality is high if the condition is not recognized and treated promptly. Hepatic arteriovenous malformation associated with persistent pulmonary hypertension of the newborn has been reported in two cases in the literature. We report a neonate who was referred for management of persistent pulmonary hypertension and was subsequently diagnosed with a large hepatic arteriovenous malformation. He underwent coil embolization following which pulmonary hypertension resolved.

EEG abnormalities in survivors of neonatal ECMO: its role as a predictor of neurodevelopmental outcome.

The incidence and site of electroencephalogram (EEG) abnormalities and the efficacy of post-ECMO EEG as a predictor of neurodevelopmental outcome was evaluated in survivors of neonatal extracorporeal membrane oxygenation (ECMO). All survivors of neonatal ECMO with an EEG performed prior to their discharge were included if they had at least 12 months of follow-up. The neurodevelopmental outcome was reported as normal, suspect, and abnormal on the basis of neurological examination and the scores on Bayley Scales of Infant Development or McCarthy Scale of Children's Abilities. EEG abnormalities were noted in 31 (70%) of 44 infants. The distribution of EEG abnormalities was not significantly different for right and left hemispheres. The incidence of abnormal neurodevelopmental outcome was similar in infants with a normal or an abnormal EEG (3 of 13 vs. 7 of 31; p = 0.8). EEG abnormalities had no correlation with neurodevelopmental outcome. We conclude that the high incidence of EEG abnormalities and their lack of correlation with neurodevelopmental outcome would suggest that these abnormalities do not represent permanent brain injury and a single EEG performed after decannulation from ECMO is not helpful in identifying infants at risk of subsequent abnormal neurodevelopmental outcome.

Identifying at risk infants following neonatal extracorporeal membrane oxygenation.

OBJECTIVE: To identify infants at risk of death and abnormal neurodevelopmental outcome following extracorporeal membrane oxygenation (ECMO) in the neonatal period. METHODS: The medical records of 82 neonates treated with ECMO were reviewed to evaluate risk of death. All survivors were followed by neurologic examinations and tested using the Bayley Scales of Infant Development or McCarthy Scale of Children's Abilities, and risk for abnormal neurodevelopmental outcome was assessed. RESULTS: The overall survival was 91% (75 of 82). The mean gestational age and birth weight of nonsurvivors were lower than those of survivors (37 +/- 1 weeks vs 40 +/- 0 weeks; 2734 +/- 230 vs 3325 +/- 69 gm, p < 0.05). Infants who were lost to follow-up (16%) did not differ from those with follow-up in demographic variables or clinical indicators of illness severity. Thirty-five of 63 infants (56%) with follow-up had normal neurodevelopmental outcome. Risk of abnormal outcome was higher in infants requiring assisted ventilation for > or = 15 days (relative risk [RR] 5.5; 95% confidence interval [CI] 2.0 to 14.8), supplemental oxygenation for > or = 22 days (RR 3.1; 95% CI 1.3 to 7.6), and black race (RR 8.9; 95% CI 1.3 to 62.9). None of the neuroimaging studies accurately predicted the neurodevelopmental outcome of these infants. CONCLUSION: We conclude that ECMO in critically ill infants is associated with good survival. The need for prolonged respiratory support may help in identifying infants at risk for abnormal neurodevelopmental outcome.

Antenatal phenobarbital therapy and neonatal outcome. I: Effect on intracranial hemorrhage.

OBJECTIVE: To evaluate the effect of antenatal phenobarbital (PB) therapy on neonatal intracranial hemorrhage (ICH) in preterm infants. DESIGN: Prospective, randomized, controlled trial. SETTING: Single institution study. SUBJECTS AND INTERVENTIONS: Women in preterm labor ( < 35 weeks' gestation) were assigned to control and treatment groups. The treatment group received 10 mg/kg (maximum, 1000 mg) PB intravenously, followed by 100 mg orally daily, until delivery. Neonates did not receive PB after birth. Head sonograms were performed on days 3, 7, and 14 and at discharge. Hemorrhage was classified as mild, moderate, or severe by a single reader. OUTCOME MEASURES: Incidence of neonatal ICH in all infants, infants weighing less than 1250 g, and infants of multiple gestations. RESULTS: The study population comprised 110 women, 60 in the control group and 50 in the PB group. Neonates in the control group (n = 74, including 10 pairs of twins and 2 sets of triplets) were comparable to those in the treatment group (n = 62, including 7 pairs of twins, 1 set of triplets, and 1 set of quadruplets) regarding birth weight, gestational age, and other clinical risk factors for ICH. There was a trend for the incidence of any grade of hemorrhage to be lower in the PB group (22% [14 of 62]) compared with the control group (35% [26 of 74]). Moderate and severe hemorrhages were significantly lower in the PB group (1.6% [1 of 62]) compared with the control group (9.4% [7 of 74]). Among infants weighing less than 1250 g, overall ICH was lower in the PB group (23% [6 of 26]) compared with the control group (51% [18 of 35]). Among multiple-gestation infants, overall ICH was 4.7% (1 of 21) in the PB group, compared with 31% (8 of 26) in the control group. CONCLUSIONS: Antenatal PB therapy results in a significant decrease in moderate and severe ICH in infants born at less than 35 weeks' gestation. Antenatal PB therapy also resulted in a decrease in the incidence of all grades of ICH in infants weighing less than 1250 g and infants born of multiple gestations.

Characterization of superior sagittal sinus blood flow velocity using color flow Doppler in neonates and infants.

The objective of the investigation was to determine what effect intracranial pathology has on alterations of superior sagittal sinus blood flow, and to determine the role of color flow Doppler imaging of the superior sagittal sinus in the diagnosis of intracranial pathology in the neonate and infant. One hundred examinations were performed prospectively in 96 patients. The velocity was determined with an angle correction at 30-60 degrees and was obtained with and without gentle transducer compression. Superior sagittal sinus thrombosis was identified in two patients by the absence of flow. Multiple t-tests for independent measures showed no clinically significant differences between flow velocities with regard to intracranial hemorrhage, ventriculomegaly, extracorporeal membrane oxygenation therapy or prematurity. The authors conclude that color flow Doppler can accurately diagnose superior sagittal sinus thrombosis and may be used to screen high risk neonates such as those with thrombosis elsewhere or those treated with extracorporeal membrane oxygenation. No clinically significant associations were found between superior sagittal sinus flow velocity and any of the parameters evaluated in this study.

Post extracorporeal membrane oxygenation single photon emission computed tomography (SPECT) as a predictor of neurodevelopmental outcome.

OBJECTIVE: To determine the incidence and site of single photon emission computed tomography scan (SPECT) abnormalities in survivors of neonatal extracorporeal membrane oxygenation and to evaluate the efficacy of SPECT scan as a predictor of neurodevelopmental outcome in these infants. SETTING: Tertiary care neonatal intensive care unit in Detroit, MI. PATIENT POPULATION: Survivors of neonatal extracorporeal membrane oxygenation who had a SPECT scan of the brain performed after decannulation and before their discharge from the neonatal intensive care unit were included if they had at least 12 months of follow-up in our developmental assessment clinic. OUTCOME MEASURES: The neurological outcome was reported as normal, suspect, and abnormal on the basis of neurological examination and developmental milestones. The developmental outcome was assessed by Bayley mental development index or McCarthy general cognitive index scores. RESULTS: A total of 59 patients met study criteria. SPECT scan abnormalities were noted in 45 (76%) infants. Global hypoperfusion was the most frequent abnormality followed closely by bilateral focal perfusion defects. The distribution of perfusion abnormalities was not significantly different for right and left hemispheres. Among 14 infants with normal SPECT scans, 13 infants had normal neurological outcome and all had a normal developmental outcome. Of the 45 infants with an abnormal SPECT scan, 7 infants had an abnormal neurological outcomes and 4 infants had an abnormal developmental outcome. SPECT scan abnormalities had no significant correlation with neurodevelopmental outcome of these infants. CONCLUSION: Although a normal SPECT scan was more likely to predict a normal neurodevelopmental outcome, an abnormal SPECT scan did not predict an abnormal outcome in these infants.

Feasibility of invasive monitoring of intracranial pressure in term neonates.

Seven term neonates with encephalopathy resulting from asphyxia and/or intracranial hemorrhage underwent invasive monitoring of intracranial pressure through the epidural or intracerebral space. The average age (in hours) at insertion of the monitor was 27 h in the 3 neonates with asphyxia and 70 h in the 4 neonates with hemorrhage. Intracranial hypertension was noted in 6 neonates. The management of the hypertension included hyperventilation followed by mannitol for pressures that were sustained above 20 mmHg and pentobarbital for pressures above 30 mmHg. The duration of the hypertension varied in 5 neonates from 4 to 72 h, while in the remaining neonates, the pressure remained elevated until death at 70 h. All 4 survivors with intracranial hemorrhage have minimal neuromotor deficits on follow up and 2 survivors with asphyxia have cognitive deficits and are microcephalic. From this small series, it appears that in the management of term neonates with intracranial hemorrhage, monitoring of intracranial pressure should be considered.

Acute neonatal morbidity and long-term central nervous system sequelae of perinatal asphyxia in term infants.

Twenty-eight term neonates with severe perinatal asphyxia were referred to a tertiary neonatal intensive care unit (NICU). The morbidity of asphyxia included involvement of the pulmonary (n = 24 infants), central nervous system (n = 22), renal (n = 15), cardiac (n = 14), metabolic (n = 13) and hematologic (n = 10) systems. The majority of neonates had more than three organ systems involved. Twenty-four neonates survived the neonatal course and at NICU discharge all system effects other than the central nervous system had resolved. At 5 years (60 months), 14 children had a normal neurologic examination, 9 had spastic quadriplegia and one had hemiplegia. Nine children had a McCarthy General Cognitive Index (GCI) greater than or equal to 84, 3 had a GCI between 68 and 83 and 12 scored less than 67. Neonatal seizures, renal problems, microcephaly at 3 months, and post-neonatal seizures were associated with an abnormal neurologic outcome or a GCI less than 67. A neurologic examination during the first year of life may reveal whether children with birth asphyxia will be relatively normal at age 5 years or whether they will show considerable delay.

Outcome after posthemorrhagic ventriculomegaly in comparison with mild hemorrhage without ventriculomegaly.

The neurodevelopmental sequelae in 33 low birth weight neonates with moderate or severe hemorrhage and ventriculomegaly (VM group) and in 39 neonates with mild hemorrhage only (non-VM group) were evaluated prospectively. Both groups were comparable in birth weight, gestational age, and socioeconomic status. Ventriculoperitoneal shunts were inserted in 23 of the 33 VM group infants at a mean age of 26 days. Eighty-two shunt revisions were performed, for obstruction (71 revisions) or infection (11 revisions), in 18 of the 23 children. At a mean age of 50 months, 19 of 33 children in the VM group had sequelae; 14 children had moderate or severe neurologic deficits, and 5 children had mild sequelae. In the non-VM group, only 3 of 39 children had deficits, all of which were mild (p less than 0.05). In the VM group, 19 of 33 children had mental developmental delay in comparison with 8 of 39 in the non-VM group (p less than 0.05), and 17 of 33 children in the VM group had motor developmental delay in comparison with 5 of 39 in the non-VM group (p less than 0.01). Within the VM group, the number of children with neurodevelopmental sequelae did not differ significantly among the 23 children with shunts, in comparison with the 10 who did not require shunting. Among the children with shunts, a higher incidence of sequelae occurred when lack of ventricular decompression was noted immediately after shunt insertion (p less than 0.005) and when shunt infections occurred (p less than 0.01). The most important predictor of mental and motor outcome in the group with shunts was lack of ventricular decompression immediately after shunt insertion. We speculate that, in some infants, loss of brain tissue, cerebral atrophy, or both may occur before insertion of the ventriculoperitoneal shunt, even when the shunt is inserted early.

Ultrasonographic findings (CNS, thorax, abdomen) in infants undergoing extracorporeal oxygenation therapy.

Extracorporeal membrane oxygenation (ECMO) has been performed on 45 neonates at the Children's Hospital of Michigan in a 39-month period. Ultrasound evaluation of these patients prior to and during ECMO therapy has demonstrated abnormalities in the central nervous system including intracranial hemorrhage (21), extra-axial fluid collections (5), and ventricular enlargement (2). Ultrasonic evaluation of the thoracic cavity in 12 infants revealed pleural fluid in 8. There were seven children with varying types of peritoneal fluid. Two children had visceral abnormalities - 1 with liver hemorrhage and 1 with hydronephrosis found prior to ECMO. Most of these findings could not have been diagnosed without ultrasound and may lead directly to alterations in clinical management. Ultrasound is an extension of physical examination which is important in hour-by-hour clinical care of patients on ECMO.

Hemorrhagic complications during extracorporeal membrane oxygenation: prevention and treatment.

Hemorrhage related to systemic heparinization is the major complication of extracorporeal membrane oxygenation (ECMO). Intracranial hemorrhage (ICH) is the most devastating complication. ICH developed in 13 of our 25 ECMO patients (52%). Six died, six survived with normal neurologic function, and one is severely impaired. In nine of 13 patients (69%) ECMO was discontinued when serial cranial ultrasounds showed progressive ICH. Seizures developed in six infants while receiving ECMO, and ICH developed in all. There is a correlation between hypertension and ICH. A hypertension index (hours systolic BP greater than 90/hours receiving ECMO) was 0.1 +/- 0.12 for infants without ICH and 0.37 +/- 0.28 for infants with ICH (P less than .05). ICH developed in 79% of the patients with an index greater than 0.1. Twenty neck explorations were required in the first 20 patients for incisional bleeding (mean blood loss, 21.9 +/- 18.0 mL/kg/d). We now use fibrin glue following cannulation and have done only one neck exploration in the last five patients (mean blood loss, 2.8 +/- 2.2 mL/kg/d, P less than .05). Endobronchial bleeding has responded to phenylephrine lavage and increased positive end-expiratory pressure. We have controlled pleural space bleeding with topical thrombin. None of the hemorrhagic complications encountered correlate with the activated clotting time or the amount of heparin used. There is an increased risk of hemorrhage associated with platelet counts less than 100,000/microL for 75% of a day (P less than .05) so that aggressive platelet transfusion remains important in preventing hemorrhagic complications during ECMO.

Antenatal phenobarbital for the prevention of neonatal intracerebral hemorrhage.

Forty-six pregnant women less than 35 weeks of gestation were enrolled in a prospective randomized controlled study evaluating the effects of antenatal phenobarbital on neonatal intracerebral hemorrhage. The women were randomly assigned to control (n = 22) or treatment (n = 24) groups; the treatment group received 500 mg of phenobarbital intravenously. The time interval between the dose of phenobarbital and delivery was 5.5 +/- 4.8 hours (mean +/- SD). The infants in the control group (n = 23) and those in the phenobarbital-treated group (n = 25) were comparable regarding birth weight, gestational age, and other obstetric and neonatal risk factors associated with intracerebral hemorrhage. The incidence of intracerebral hemorrhage was 56.5% (13 of 23 infants) in the control group and 32% (eight of 25 infants) in the phenobarbital-treated group (p = 0.08). Moderate or severe hemorrhage was diagnosed in six of 13 control infants and in none of the phenobarbital-treated infants (p less than 0.01). The mortality rate was significantly lower in the phenobarbital-treated group (two of 25 infants) than in the control group (eight of 23 infants; p less than 0.05). Our study suggests that antenatal phenobarbital administration results in a decrease in mortality and in the severity of intracerebral hemorrhage in the preterm neonate.

Analysis of the effects of applying federal diagnosis-related grouping (DRG) guidelines to a population of high-risk newborn infants.

Length of stay data collected for high-risk newborn infants admitted to a tertiary care children's hospital neonatal unit over a 6-year period were compared with mean and outlier lengths of stay published in the Federal Register as part of a proposed system for prospective payment of hospital cost by diagnosis-related groupings (DRGs). We found that the classification system for newborns markedly underestimated the number of days required for the treatment of these infants. The use of the geometric mean instead of the arithmetic mean as the measure of central tendency was a significant contributor to the discrepancy, especially in those subgroups with bimodal frequency distributions of lengths of stay. Another contributor to the discrepancy was the lack of inborn patients in the children's hospital cohort. The system of prospective payments, as outlined, does not take into account several factors that have a strong influence on length of stay such as birth weight (which requires more than three divisions to serve as an effective predictor), surgery, outborn status, and ventilation. Implementation of the system described in the Federal Register would severely discourage tertiary care referral hospitals from providing neonatal intensive care.

Intracranial hemorrhage in the hypoxic-ischemic infant: ultrasound demonstration of unusual complications.

Seven neonates (four preterm and three term) with severe hypoxic-ischemic parenchymal brain changes are presented to illustrate the kinds of parenchymal lesions demonstrable on ultrasound, to show the similarity of parenchymal lesions in preterm and term infants, and to correlate the severe neurologic deficits with the parenchymal changes. The lesions demonstrated are periventricular leukomalacia, large-vessel infarction, isolated parenchymal hemorrhage, multiple cystic encephalomalacia, and parenchymal atrophy. Parenchymal changes should be sought in such infants during any stage of their disease.

Effect of prophylactic phenobarbital on intraventricular hemorrhage in high-risk infants.

Forty-two premature infants less than 24 hours of age, with normal admission echoencephalograms, were randomly assigned to control or phenobarbital treatment groups. Infants in the treated group received two loading doses of 10 mg/kg of phenobarbital 12 hours apart, followed by a maintenance dose of 2.5 mg/kg every 12 hours for 6 days. Serial echoencephalograms were obtained in both groups. The groups were comparable with regard to birth weight, gestational age, and potential risk factors for subependymal-intraventricular hemorrhage. Ten infants (48%) in each group developed hemorrhage. The hemorrhages in the phenobarbital-treated group were significantly less severe than those in the control group. The phenobarbital-treated infants who bled, however, were also significantly larger and more mature than control infants who bled. The results of this study indicate no effect of phenobarbital on the incidence of subependymal-intraventricular hemorrhage, but a possible beneficial effect on the severity of hemorrhage.

Acute cardiovascular effects of indomethacin in anesthetized newborn dogs.

Cardiac output and regional blood flow distribution were measured in 14 newborn dogs before and 90 min following 0.3 mg/kg of indomethacin and in 4 control animals who received buffer alone using the Radioactive Microsphere Reference Organ Technique. Indomethacin produced no significant change in cardiac output or blood flow to the gastrointestinal tract or kidney. There were no changes in cerebral blood flow in animals over 4 days of age. However, in 3 of 8 puppies less than 3 days of age, indomethacin resulted in a 47% fall in cerebral blood flow. In newborn dogs, indomethacin in the dose employed had no deleterious effects on cardiac output and, with the possible exception of the cerebral circulation, on blood flow distribution.

Sonographic classification of intracranial hemorrhage. A prognostic indicator of mortality, morbidity, and short-term neurologic outcome.

Sixty-two neonates diagnosed to have periventricular-intraventricular hemorrhage were classified by sonographic findings as follows: mild, confined to the subependymal region or accompanied by a small amount of blood in the normal-sized lateral ventricle (10); moderate, intermediate amount of blood in the enlarged lateral ventricle (26); and severe, hemorrhage filling the entire ventricle forming a cast (12) or intraventricular hemorrhage with an intracerebral extension (14). Twenty-six of 35 surviving neonates had posthemorrhagic hydrocephalus, and 11 infants required shunt insertion. The survival rate of neonates with periventricular-intraventricular hemorrhage and the incidence of posthemorrhagic hydrocephalus correlated with the severity of the hemorrhage (P less than 0.05). The highest mortality rate was seen in the group with ventricular casts. All surviving neonates with casts developed hydrocephalus. All surviving neonates with intracerebral hemorrhage developed porencephaly. The severity of the hemorrhage correlated with short-term neurologic outcome (P less than 0.05), the group most severely affected being the one with intracerebral extension of hemorrhage. The severity of the hemorrhage also correlated with abnormal ventricular size by sonography on follow-up (P less than 0.05). However, posthemorrhagic hydrocephalus and abnormal ventricular size on follow-up did not correlate with neurologic outcome in the moderate and severe hemorrhage groups.