Karl Kuban

Developmental and Neurologic Status of Children after Heart Surgery with Hypothermic Circulatory Arrest or Low-Flow Cardiopulmonary Bypass

Background Deep hypothermia with either total circulatory arrest or low-flow cardiopulmonary bypass is used to support vital organs during heart surgery in infants. We compared the developmental and neurologic sequelae of these two strategies one year after surgery. Methods Infants with D-transposition of the great arteries who underwent an arterial-switch operation were randomly assigned to a method of support consisting predominantly of circulatory arrest or a method consisting predominantly of low-flow bypass. Developmental and neurologic evaluations and magnetic resonance imaging (MRI) were performed at one year of age. Results Of the 171 patients enrolled in the study, 155 were evaluated. After adjustment for the presence or absence of a ventricular septal defect, the infants assigned to circulatory arrest, as compared with those assigned to low-flow bypass, had a lower mean score on the Psychomotor Development Index of the Bayley Scales of Infant Development (a 6.5-point deficit, P = 0.01) and a hig...

A comparison of the perioperative neurologic effects of hypothermic circulatory arrest versus low-flow cardiopulmonary bypass in infant heart surgery

Background Hypothermic circulatory arrest is a widely used support technique during heart surgery in infants, but its effects on neurologic outcome have been controversial. An alternative method, low-flow cardiopulmonary bypass, maintains continuous cerebral circulation but may increase exposure to known pump-related sources of brain injury, such as embolism or inadequate cerebral perfusion. Methods We compared the incidence of perioperative brain injury after deep hypothermia and support consisting predominantly of total circulatory arrest with the incidence after deep hypothermia and support consisting predominantly of low-flow cardiopulmonary bypass in a randomized, single-center trial. The criteria for eligibility included a diagnosis of transposition of the great arteries with an intact ventricular septum or a ventricular septal defect and a planned arterial-switch operation before the age of three months. Results Of 171 patients with D-transposition of the great arteries, 129 (66 of whom were assign...

Developmental and Neurological Status of Children at 4 Years of Age After Heart Surgery With Hypothermic Circulatory Arrest or Low-Flow Cardiopulmonary Bypass

BACKGROUNDnIt is not known whether developmental and neurological outcomes in the preschool period differ depending on whether the predominant vital organ support strategy used in infant heart surgery was total circulatory arrest (CA) or low-flow cardiopulmonary bypass.nnnMETHODS AND RESULTSnInfants with D-transposition of the great arteries who underwent an arterial-switch operation were randomly assigned to a support method consisting predominantly of CA or low-flow cardiopulmonary bypass. Developmental and neurological status were evaluated blindly at 4 years of age in 158 of 163 eligible children (97%). Neither IQ scores nor overall neurological status were significantly associated with either treatment group or duration of CA. The CA group scored lower on tests of motor function (gross motor, P=0.01; fine motor, P=0.03) and had more severe speech abnormalities (oromotor apraxia, P=0.007). Seizures in the perioperative period, detected either clinically or by continuous electroencephalographic monitoring, were associated with lower mean IQ scores (12.6 and 7.7 points, respectively) and increased risk of neurological abnormalities (odds ratios, 8.4 and 5.6, respectively). The performance of the full cohort was below expectations in several domains, including IQ, expressive language, visual-motor integration, motor function, and oromotor control.nnnCONCLUSIONSnUse of CA to support vital organs during open heart surgery in infancy is associated, at the age of 4 years, with worse motor coordination and planning but not with lower IQ or with worse overall neurological status.

Maternal Toxemia Is Associated With Reduced Incidence of Germinal Matrix Hemorrhage in Premature Babies

To evaluate prenatal and perinatal risk factors for development of germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH), we conducted a prospective epidemiologic study of 449 babies whose birth weight was less than 1501 grams. This study permitted us to test our previously generated hypothesis that babies born to mothers with preeclampsia were at substantially reduced risk of developing GMH-IVH. Seventy-two (16%) of the babies in this population developed GMH-IVH. One (2.5%) of the 40 mothers with a diagnosis of preeclampsia and 71 (17.4%) of 409 mothers without preeclampsia gave birth to babies who developed GMH-IVH. GMH-IVH was seen in 6/107 (5.6%) of babies born to women with hypertension including 4/69 (5.8%) of babies born to women with pregnancy-induced hypertension, compared to 66/352 (18.8%) of babies born to mothers who did not have hypertension. Only 7.3% (8/108) of babies born to women who had proteinuria had GMH-IVH, compared to 18.3% (64/350) of babies whose mothers did not have proteinuria. GMH-IVH was seen in 5/89 (5.6%) of babies whose mothers had both hypertension and proteinuria, whereas 63/332 (19%) of babies born to mothers who lacked both factors, developed GMH-IVH. In stepwise logistic regression analysis, these significant findings were not explained by the presence of labor, postnatal acidemia, need for intubation, antenatal administration of steroids, birth weight, or gestational age. In addition, we found that maternal receipt of magnesium sulfate was associated with diminished risk of GMH-IVH even in those babies born to mothers who apparently did not have preeclampsia. We postulate that the association of preeclampsia and GVH-IVH may be related to prostaglandin effects. Reduced maternal, placental, and umbilical prostaglandin I2 (PGI2) values are characteristic of women with preeclampsia. Thus, babies born to mothers with preeclampsia may have a physiologic state similar to those having received indomethacin, a cyclooxygenase blocker that causes diminished PGI2 levels and an effective GMH-IVH prophylactic agent. We conclude that early third-trimester maternal preeclampsia/toxemia is associated with reduced risk of GMH-IVH in the preterm newborn. (J Child Neurol 1992;7:70-76).

Relation of Seizures After Cardiac Surgery in Early Infancy to Neurodevelopmental Outcome

BACKGROUNDnThe outcome of infants who have transient seizures after open heart surgery has not been studied. Using the database of the Boston Circulatory Arrest Study involving 171 children with D-transposition of the great arteries, we explored the relationship between early postoperative clinical and EEG seizures and neurodevelopmental outcomes at ages 1 and 2 1/2 years.nnnMETHODS AND RESULTSnAt 1 year, children returned for developmental and neurological evaluations and MRI. Parent-completed developmental questionnaires were collected at 2 1/2 years of age. At 1 year, children with early postoperative seizures had lower Psychomotor Development Index (motor function) scores (clinical seizures: 12.9 mean difference [MD]; 95% confidence interval [CI], 2.2 to 23.6; P=.02; EEG seizures: 13.3 MD; 95% CI, 6.8 to 19.7; P<.001). Mental Developmental Index scores of children with clinical or EEG seizures were also lower, but the differences were not statistically significant. Infants with seizures were more likely to have an abnormal neurological examination (clinical seizures: 78% versus 31%; P=.008; EEG seizures: 58% versus 34%; P=.04). Children with EEG seizures were more likely to have MRI abnormalities (43% versus 13%, P=.002). At age 2 1/2, children with EEG seizures had lower scores in several areas of function.nnnCONCLUSIONSnIn infants undergoing the arterial switch operation for correction of D-transposition of the great arteries, transient postoperative clinical and EEG seizures were associated with worse neurodevelopmental outcomes at ages 1 and 2 1/2 years as well as neurological and MRI abnormalities at 1 year of age. The occurrence of such seizures may provide an early sign of brain injury with neurological and developmental sequelae.

Hydration during the first days of life and the risk of bronchopulmonary dysplasia in low birth weight infants

We conducted a case-control study of antecedents of bronchopulmonary dysplasia (BPD) in 223 infants enrolled in a prospective, randomized clinical trial of phenobarbital prophylaxis for intracranial hemorrhage. The trial took place at three Boston neonatal intensive care units between June 1981 and April 1984. The 76 babies with BPD had radiographic evidence of the condition and required oxygen therapy for 28 days or more. All 147 control babies survived until day 28 of life without meeting either of these criteria for BPD. Compared with control infants, those with BPD received greater quantities of total, crystalloid, and colloid fluids per kilogram per day in the first 4 days of life. In addition, infants with BPD generally had a net weight gain in the first 4 days of life in contrast to the normal pattern of weight loss seen in control infants. Finally, the infants with BPD were more likely to be given a clinical diagnosis of patent ductus arteriosus and to have received furosemide on days 3 and 4 of life. From these observations we infer that early postnatal phenomena such as excessive fluid therapy may be important in the pathogenesis of BPD.

Rate of bronchopulmonary dysplasia as a function of neonatal intensive care practices

Some differences among neonatal intensive care units (NICUs) in incidence of bronchopulmonary dysplasia may reflect variations in medical care practices. After adjusting for differences in the inherent risk of bronchopulmonary dysplasia among 223 infants of less than 1751 gm birth weight who were admitted to three Harvard-affiliated NICUs, we used multivariate analysis to explore the extent to which medical care practices during the first days of life varied with the rate of bronchopulmonary dysplasia. In our analyses, variables were grouped by three major hypotheses: oxygen toxicity, barotrauma, and fluid overload. The NICU designated 1 (the one with the highest rate of bronchopulmonary dysplasia) used much higher than expected colloidal volumes during the first 4 days of life; in contrast, in the NICU designated 3 (the one with the lowest rate of bronchopulmonary dysplasia), infants consistently received lower than expected amounts of colloidal solution. Signs of patent ductus arteriosus were also much more frequent than expected during this time at NICU 1; rates were much lower than predicted at NICU 2 and were near predicted values at NICU 3. Maximum inspired oxygen fraction during the first 4 days varied significantly in a direction inconsistent with the oxygen toxicity hypothesis. Maximum arterial oxygen tension was significantly less than expected at the hospital with the lowest rate of bronchopulmonary dysplasia (NICU 3). None of six medical care practices indicating potential for barotrauma varied with NICU expect for positive end-expiratory pressure, which varied in a direction suggesting a protective effect against bronchopulmonary dysplasia. These findings agree best with the hypothesis that differences in hydration during the first days of life account for some of the difference among NICUs in bronchopulmonary dysplasia occurrence.

Behaviour at eight years in children with surgically corrected transposition: The Boston Circulatory Arrest Trial

Uncertainty exists regarding the degree to which infants with congenitally malformed hearts are at risk of behavioural disorders in childhood. Data was collected as part of a randomized clinical trial involving 155 children with surgically corrected transposition (concordant atrioventricular and ventriculo-arterial connections or alignments). As infants, they underwent the arterial switch operation, involving deep hypothermia with predominantly total circulatory arrest or predominantly low-flow continuous cardiopulmonary bypass as the method of providing support to the vital organs. Parents completed the Child Behavior Checklist when the patients were aged 4 and 8 years, and the Connors Parent Rating Scale at the age of 8 years. When the children were aged 8, teachers completed the Teachers Report Form and the Connors Teacher Rating Scale. In the cohort as a whole, the frequencies of behavioural problems identified by both parents and teachers were elevated, particularly on the scales for competence of the Child Behavior Checklist, and the Adaptive scales of the Teachers Report Form. Approximately 1 in 5 patients had scores for Total Problem Behavior in the range of clinical concern on both the Child Behavior Checklist and the Teachers Report Form. Few differences were found, however, according to the method of operative treatment. Postoperative seizures were associated with social and attention problems. Children experiencing academic problems at the age of 8 showed a larger increase in behavioural problems between the ages of 4 and 8 than did children making adequate academic progress. Children with congenitally malformed hearts who underwent reparative surgery in infancy using a strategy of severe haemodilution and alpha stat are at increased risk of behavioural problems in middle childhood.

Labor and Deliver Characteristics and the Risk of Germinal Matrix Hemorrhage in Low Birth Weight Infants

To assess the influence of labor and delivery events on the risk of germinal matrix hemorrhage in preterm newborns, we conducted a review of data collected on 449 babies who weighed 1.5 kg or less. Babies delivered vaginally were more likely to have germinal matrix hemorrhage than were babies delivered abdominally (odds ratio, 2.5; 95% confidence interval, 1.4,3.3). Among babies delivered vaginally, the risk of germinal matrix hemorrhage was increased by 39% if labor lasted more than 12 hours. Among babies delivered abdominally, the occurrence of any labor was accompanied by a 150% increased risk of germinal matrix hemorrhage. The only indication for abdominal delivery associated with an increased risk of germinal matrix hemorrhage was impending amnionitis (odds ratio, 2.6; 95% confidence interval, 1.2,5.7), whereas the only indication associated with a decreased risk was preeclampsia (odds ratio, 0.2; 95% confidence interval, 0.6). Epidural and local anesthesia were associated with a reduced risk of germinal matrix hemorrhage among babies delivered abdominally. We conclude that delivery practices, or their indications, appear to influence the risk of germinal matrix hemorrhage in low birth weight babies. (J Child Neurol 1991;6:35-40).

Systemic hypotension and white‐matter damage in preterm infants

This study was designed to test the hypothesis that systemic hypotension during the first postnatal week increases the risk of ultrasonographic echolucency in the white matter of preterm infants (< or = 28 weeks gestation) while adjusting for confounders. From a study base of 1607 very-low-birthweight neonates (500 to 1500 g), a subsample of 243 preterm infants (122 females; < or = 28 weeks gestation) was selected for echolucency and data collection prospectively for the entire first postnatal week. Data analyses were performed separately for the first 24 hours of life, for the interval from the end of the first 24 hours to the end of the fourth postnatal day, and for days 5, 6, and 7. Systemic hypotension was defined as the mean arterial blood pressure in the lowest quartile for the infants week of gestational age. Protocol cranial ultrasounds were those obtained closest to days 1, 7, and 21. A committee of sonologists classified the infants as having either echolucency (echolucency group) or not (control group). Systemic hypotension during the first week of life appeared to be associated with echolucency in univariable analyses but the association did not persist after adjustment for potential confounders. Detailed summaries of 13 previous studies, the majority of which did not show an association between systemic hypotension and white-matter damage, are presented. In sum, these results do not support the hypothesis that systemic hypotension contributes to echolucency among preterm infants.