Randomized placebo-controlled trial of a 42-day tapering course of dexamethasone to reduce the duration of ventilator dependency in very low birth weight infants: outcome of study participants at 1-year adjusted age.

OBJECTIVE: Ventilator-dependent preterm infants are often treated with a prolonged tapering course of dexamethasone to decrease the risk and severity of chronic lung disease. The objective of this study was to assess the effect of this therapy on developmental outcome at 1 year of age. METHODS: Study participants were 118 very low birth weight infants who, at 15 to 25 days of life, were not weaning from assisted ventilation and were then enrolled in a randomized, placebo-controlled, double-blind trial of a 42-day tapering course of dexamethasone. Infants were examined at 1 year of age, adjusted for prematurity, by a pediatrician and a child psychologist. A physical and neurologic examination was performed, and the Bayley Scales of Infant Development were administered. All examiners were blind to treatment group. RESULTS: Groups were similar in terms of birth weight, gestational age, gender, and race. A higher percentage of dexamethasone recipients had major intracranial abnormalities diagnosed by ultrasonography (21% vs 11%). Group differences were not found for Bayley Mental Development Index (median [range] for dexamethasone-treated group, 94 [50-123]; for placebo group, 90 [28-117]) or Psychomotor Development Index Index (median [range]) for dexamethasone-treated group, 78 (50-109); for placebo-treated group, 81 [28-117]). More dexamethasone-treated infants had cerebral palsy (25% vs 7%) and abnormal neurologic examination findings (45% vs 16%). In stratified analyses, adjusted for major cranial ultrasound abnormalities, these associations persisted (OR values for cerebral palsy, 5.3; 95% CI: 1.3-21.4; OR values for neurologic abnormality 3.6; 95% CI: 1.2-11.0). CONCLUSIONS: A 42-day tapering course of dexamethasone was associated with an increased risk of cerebral palsy. Possible explanations include an adverse effect of this therapy on brain development and/or improved survival of infants who either already have neurologic injury or who are at increased risk for such injury.

Jumping translocation with partial duplications and triplications of chromosomes 7 and 15.

We report a 2-year-old female with seizures, mild dysmorphic features and a jumping translocation involving chromosome 15 that results in multiple cell lines with partial duplications and triplications of chromosomes 7 and 15. Fluorescent in situ hybridization (FISH) and chromosome microdissection were used to identify the complex nature of the jumping translocation. Interstitial telomeres were observed at the jumping translocation sites. The jumping chromosome rearrangement was also found to have a partial duplication of 7p as demonstrated by chromosome microdissection. Despite these partial duplications and triplications of chromosomes 7 and 15, the child does not have major birth defects. She does have mild sensorimotor delays. A review of non-Robertsonian jumping translocations is provided.

Trends in mortality and cerebral palsy in a geographically based cohort of very low birth weight neonates born between 1982 to 1994.

OBJECTIVE: To analyze whether the increasing survival of very low birth weight infants during the 1980s and 1990s has increased the risk of cerebral palsy among survivors. METHODS: The study cohort consisted of 2076 consecutively born infants, with birth weights of 500 to 1500 g and no major anomaly, born July 1, 1982, through June 30, 1994, to residents of a 17-county region in North Carolina. These infants had a mean birth weight of 1096 g (standard deviation, 251 g) and a mean gestational age of 29 weeks (standard deviation, 3 weeks). One thousand five hundred sixty-eight infants (76%) survived to 1 year adjusted age, at which point 1282 infants (82%) were examined at our medical center. The diagnosis of cerebral palsy was made only if the examining pediatrician and a pediatric physical therapist agreed on the diagnosis. To analyze trends across time, the Cochran-Armitage chi2 test and logistic regression were applied to data for infants categorized into six 2-year epochs according to year of birth. RESULTS: Mortality did not change significantly through 1990, and then began to decrease in 1990 to 1994. During the study period, mortality decreased from 36.8% between 1982 and 1984, to 13.8% between 1992 and 1994. The prevalence of cerebral palsy among survivors was constant from 1982 to 1988 (11.3%), decreased slightly from 1988 to 1990 (9.2%), and was lowest in 1990 to 1994 (5.2%). These secular trends in mortality and cerebral palsy risk remained significant when adjusted for gestational age, gender, and race. When adjusted for surfactant use, the trend in mortality was no longer significant, whereas the trend in cerebral palsy risk persisted. CONCLUSIONS: The increasing survival of very low birth weight infants in the 1980s and 1990s has not resulted in an increased prevalence of cerebral palsy among survivors.

Intrauterine infection and the risk of cerebral palsy in very low-birthweight infants.

Very low-birthweight infants constitute more than one-quarter of all new cases of cerebral palsy. We performed a case-control study of associations between antenatal maternal infection and cerebral palsy in very low-birthweight infants. Cases and controls were selected from a cohort of 1238 consecutive infants who: (1) had birthweights between 500 and 1500 g and no major congenital anomaly; (2) were born 1 January 1986 to 31 December 1993 to a mother residing in 1 of 17 counties in north-west North Carolina; and (3) were delivered at the only tertiary obstetric referral centre in those same 17 counties. A total of 984 of these infants (79%) survived to 1 year of age (adjusted for degree of prematurity) and were scheduled for a multidisciplinary examination; 815 (83%) came as scheduled. Excluding two cases attributable to post-neonatal events, 62 cases of cerebral palsy were identified. Controls were the two infants, without cerebral palsy, born closest in time to each case. Medical records were reviewed by a nurse who was not aware of which subjects were cases. Among possible markers of intra-amniotic infection, those associated most strongly with cerebral palsy were chorioamnionitis diagnosed by an obstetrician (odds ratio [OR] adjusted for gestational age [95% confidence limits] = 2.6 [1.0, 6.5]), antepartum maternal temperature > 37.8 degrees C (OR = 2.6 [1.1, 6.0]), uterine tenderness (OR = 2.6 [0.8, 9.3]), maternal receipt of antibiotics (OR = 2.2 [1.0, 4.7]) and neonatal sepsis in the first week of life (OR = 2.9 [0.9, 8.9]). All of these associations were stronger for diplegia than the other clinical subtypes of cerebral palsy. The association with chorioamnionitis and spastic diplegia persisted when adjusted for maternal magnesium sulphate receipt, maternal betamethasone receipt, method of delivery (vaginal vs. abdominal), acidosis on the neonate's initial arterial blood gas, systolic blood pressure < 30 mmHg and the diagnosis of major neonatal neurosonographic abnormality.

Prenatal events and the risk of cerebral palsy in very low birth weight infants.

The purpose of this study was to analyze associations between prenatal factors and cerebral palsy in a geographically based cohort of very low birth weight infants. Cases (n = 80) and controls had birth weights of 500-1,500 g and were born in 1978-1989, to a resident of one of 17 counties in northwest North Carolina. Medical records were reviewed for data about prenatal and neonatal factors. Associations were analyzed separately for three clinical forms of spastic cerebral palsy (hemiplegia, diplegia, and quadriplegia) and for cerebral palsy with and without antecedent major cranial ultrasound abnormalities. The following factors were associated most strongly with an increased risk of cerebral palsy: multiple gestation, chorioamnionitis, maternal antibiotics, antepartum vaginal bleeding, and labor lasting less than 4 hours. Preeclampsia and delivery without labor were associated with a decreased risk. Evidence of confounding was found for each of these associations, except for those with chorioamnionitis and labor lasting less than 4 hours. The association with chorioamnionitis was stronger for diplegia (compared with hemiplegia and quadriplegia) and for cerebral palsy without major cranial ultrasound abnormalities. Associations with antepartum vaginal bleeding (increased risk) and preeclampsia (decreased risk) were stronger for cerebral palsy occurring with major cranial ultrasound abnormality.

Survival and developmental disability in infants with birth weights of 501 to 800 grams, born between 1979 and 1994.

OBJECTIVE: Because the survival rate has increased for extremely low birth weight neonates, many have raised the concern that the rate of developmental disability among survivors will also increase. To address this concern, we analyzed changes over time in survival and major neurosensory impairment in a sample of extremely low birth weight infants born between July 1, 1979, and June 30, 1994. METHODS: The study sample included 513 infants with birth weights of 501 to 800 g who were cared for in either of the two neonatal intensive care units that serve a 17-county region in northwest North Carolina and who were born to mothers residing in that region. At 1 year of age (corrected for gestation), survivors were examined by a pediatrician and were tested using the Bayley Scales of Infant Development. Major neurosensory impairment was defined as cerebral palsy, a Bayley Mental Developmental Index <68, or blindness. A total of 209/216 (97%) of survivors were examined at 1 year of age. Epoch of birth was defined as follows: epoch 1, July 1, 1979 to June 30, 1984; epoch 2, July 1, 1984 to June 30, 1989; and epoch 3, July 1, 1989 to June 30, 1994. RESULTS: Survival rates for epochs 1, 2, and 3 were, respectively, 24/120 (20%), 63/175 (36%), and 129/218 (59%). In contrast, the proportions with a major neurosensory impairment did not increase over time; rates for successive epochs were 6/24 (25%), 17/61 (28%), and 26/124 (21%). Rates of cerebral palsy were 3/24 (13%), 12/61 (20%), and 9/124 (7%); rates of delayed mental development were 4/24 (17%), 12/61 (20%), and 17/124 (14%); and rates of blindness were 2/24 (8%), 0/62, and 5/124 (4%), respectively. CONCLUSIONS: This analysis suggests that the increasing survival of extremely low birth weight neonates since the late 1970s has not resulted in an increased rate of major developmental problems identifiable at 1 year of age.

Molecular cytogenetic analysis of a duplication Xp in a male: further delineation of a possible sex influencing region on the X chromosome.

We describe a male infant with severe mental retardation and autism with a duplication of the short arm of the X chromosome. Chromosome painting confirmed the origin of this X duplication. Molecular cytogenetic analysis with fluorescence in situ hybridization (FISH) identified one copy of the zinc finger protein on the X chromosome (ZFX) and two copies of the steroid sulfatase gene (STS), further delineating the breakpoints. Based on cytogenetic and molecular comparisons of cases from the literature of sex-reversal in dup(X),Y patients and our patient, we suggest that a possible secondary sex-influencing gene involved in the regulation of sex determination or testis morphogenesis is present at the distal Xp21.1 to p21.2 region.

Follow-up of preterm infants treated with dexamethasone for chronic lung disease.

OBJECTIVE: To study the outcome of prolonged treatment with dexamethasone sodium phosphate in preterm infants who depend on assisted ventilation. DESIGN: Longitudinal follow-up using historic controls. SETTING: Regional intensive care nursery. PARTICIPANTS: Sixty-one very-low-birth-weight infants treated with a 42-day course of dexamethasone and 61 historic controls matched for birth weight, gestational age, race, and sex. All 122 subjects required assisted ventilation for at least 15 days. INTERVENTION: Infants were given dexamethasone sodium phosphate at a dose of 0.5 mg/kg per day. The dose was then tapered over 42 days. MEASUREMENTS/MAIN RESULTS: Infants treated with dexamethasone received assisted ventilation for a median of 33 days; controls, a median of 47 days (P < .05). One hundred infants survived; 94 were examined at age 1 year. The two groups were similar with respect to the proportions hospitalized for respiratory infection in the first year of life and the proportions with weight, length, and head circumference below the fifth percentile. Rates of cerebral palsy were also similar between the two groups, as were median Bayley Mental and Psychomotor developmental index scores. CONCLUSIONS: Dexamethasone treatment was associated with fewer days of assisted ventilation, but not with improved outcome at age 1 year. More assessment should be made of dexamethasone's effect on long-term outcome before dexamethasone becomes widely used in preterm infants who depend on assisted ventilation.

Serum bilirubin levels, intracranial hemorrhage, and the risk of developmental problems in very low birth weight neonates.

To study whether elevated levels of bilirubin in the neonatal period increase the risk of developmental problems for very low birth weight neonates, the investigators used data from a geographically based sample of 495 very low birth weight neonates, born January 1, 1985, to December 31, 1989, who survived to 1 year of adjusted age. Maximum neonatal bilirubin levels were found in medical records. A developmental problem was defined as either cerebral palsy or a Bayley Mental Developmental Index of less than 68 at 1 year adjusted age. Potentially confounding factors were controlled using logistic regression. To control for the effects of intracranial abnormalities (eg, intraventricular hemorrhage), separate logistic regression analyses were carried out for three strata, defined according to the results of cranial ultrasonography. In these analyses, the following odds ratios (with 95% confidence limits) were found for the association of maximum neonatal bilirubin concentration and developmental problems: for subjects without intracranial abnormalities, 0.9 (0.7, 1.9); for subjects with uncomplicated intracranial hemorrhage, 1.5 (0.8, 2.5); for subjects with complicated intracranial hemorrhage or intraparenchymal echo-densities, 1.2 (0.4, 3.6). In summary, in analyses controlled for confounding factors, maximum neonatal bilirubin level was not consistently associated with the risk of developmental problems identifiable at 1 year.

Appropriateness of intrapartum fetal heart rate management and risk of cerebral palsy.

Cerebral palsy affects 2 in 1000 infants in the United States, and the intrapartum period is frequently scrutinized as the etiologic source. In a matched group of 49 infants with cerebral palsy at 1 year of age and 49 controls, no difference in the incidence of inappropriate intrapartum fetal heart rate pattern management was detected. This supports the conclusions of others that the intrapartum period is an infrequent source of cerebral palsy.