Mary P. Bedard

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.

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.

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.

Experience with caspofungin in the treatment of persistent fungemia in neonates

OBJECTIVE:To review our experience of caspofungin in the treatment of persistent candidemia in the neonatal intensive care unit.STUDY DESIGN:This was a retrospective chart review on 13 infants in whom caspofungin was added to conventional antifungals (amphotericin B and/or fluconazole or flucytosine) for the treatment of refractory candidemia.RESULTS:A total of 12 infants were preterm (gestational age, 24 to 28 weeks) and one was term; the median birth weight was 800 g (range, 530 to 5600 g). Candidemia (Candida albicans in five, C. parapsilosis in six, C. albicans and C. parapsilosis in one and C. tropicalis in one) persisted despite 6 to 30 days of conventional antifungal therapy. After the addition of caspofungin, sterilization of blood cultures was achieved in 11 infants at the median time of 3 days (range, 1 to 21 days). Adverse events included thrombophlebitis (one patient), hypokalemia (two patients) and elevation of liver enzymes (four patients). Three infants had a second episode of candidemia and seven patients died.CONCLUSION:Caspofungin may be an efficacious addition for treatment of candidemia refractory to conventional antifungal therapy. This drug should be further investigated in neonates.

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.

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.

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° and was obtained with and without gentle transducer compression. Superior sagittal sinus thrombosis was identified in two patients by the absence of flow. Multiplet-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.

Ultrasonographic findings (CNS, Thorax, Abdomen) in infants undergoing extracorporeal oxygenation therapy

Extracorporeal membrane oxygenation (ECMO) has been performed on 45 neonates at the Childrens 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.

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.

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 ≥15 days (relative risk [RR] 5.5; 95% confidence interval [CI] 2.0 to 14.8), supplemental oxygenation for ≥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.