Hypocapnia and other ventilation-related risk factors for cerebral palsy in low birth weight infants.

Ventilatory management patterns in very low birth weight newborns, particularly iatrogenic hypocapnia, have occasionally been implicated in perinatal brain damage. However, such relationships have not been explored in large representative populations. To examine the risk of disabling cerebral palsy in mechanically ventilated very low birth weight infants in relation to hypocapnia and other ventilation-related variables, we conducted a population-based prospective cohort study of 1105 newborns with birth weights of 500-2000 g born in New Jersey from mid-1984 through 1987, among whom 777 of 902 survivors (86%) had at least one neurodevelopmental assessment at age 2 y or older. Six hundred fifty-seven of 777 assessed survivors (85%), of whom 400 had been mechanically ventilated, had blood gases obtained during the neonatal period. Hypocapnia was defined as the highest quintile of cumulative exposure to arterial PCO(2) levels <35 mm Hg during the neonatal period. Disabling cerebral palsy was diagnosed in six of 257 unventilated newborns (2.3%), 30 of 320 ventilated newborns without hypocapnia (9.4%), and 22 of 80 ventilated newborns with hypocapnia (27.5%). Two additional ventilatory risk factors for disabling cerebral palsy were found-hyperoxia and prolonged duration of ventilation. In a multivariate analysis, each of the three ventilatory variables independently contributed a 2- to 3-fold increase in risk of disabling cerebral palsy. These risks were additive. Although duration of mechanical ventilation in very low birth weight newborns likely represents severity of illness, both hypocapnia and hyperoxia are largely controlled by ventilatory practice. Avoidance of arterial PCO(2) levels <35 mm Hg and arterial PO(2) levels >60 mm Hg in mechanically ventilated very low birth weight infants would seem prudent.

Comparison of management strategies for extreme prematurity in New Jersey and the Netherlands: outcomes and resource expenditure.

OBJECTIVE: To quantify differences in resource expenditure in the perinatal period and long-term outcome of extremely premature infants who received systematically different approaches to neonatal intensive care. METHODS: Perinatal management, mortality, prevalence of disabling cerebral palsy (DCP), and resource expenditure of 2 population-based inception cohorts of extremely premature infants born in the mid-1980s were compared. Electronic fetal monitoring, tocolysis, cesarean section delivery, and assisted ventilation were used to characterize management approaches. Participants included all live births at 23 to 26 weeks' gestation in a 3-county area of central New Jersey (NJ) from 1984 to 1987 (N = 146) and throughout the Netherlands (NETH) in 1983 (N = 142). Mortality and the prevalence of DCP were the primary outcomes. Numbers of hospital days with and without assisted ventilation were the measures of resource expenditure. RESULTS: Electronic fetal monitoring (100% vs 38%), cesarean section (28% vs 6%), and assisted ventilation (95% vs 64%) were all more commonly used in NJ than in NETH. Ten percent of NJ deaths occurred without assisted ventilation, compared with 45% of Dutch deaths. A total of 1820 ventilator days were expended per 100 live births in NJ, compared with 448 in NETH. The increase in the number of nonventilator days (3174 vs 2265 days per 100 live births) did not reach statistical significance. Survival to age 2 (46 vs 22%) and the prevalence of DCP among survivors (17.2 vs 3.4%) were significantly greater in NJ at age 2 than in NETH at age 5. CONCLUSIONS: Near universal initiation of intensive care in NJ, compared with selective initiation of intensive care in NETH, was associated with 24.1 additional survivors per 100 live births, 7.2 additional cases of DCP per 100 live births, and a cost of 1372 additional ventilator days per 100 live births.

A quantitative review of mortality and developmental disability in extremely premature newborns.

OBJECTIVES: To summarize the literature on mortality rates and prevalences of major neurodevelopmental disabilities and to examine trends of these outcomes over time in extremely premature neonates. DATA SOURCES: MEDLINE was used to search the English literature for studies published since 1970 reporting on both mortality and disability in infants born at or before 26 weeks' gestation (extremely immature [EI] cohort), with a birth weight of 800 g or less (extremely small [ES] cohort), or subgroups of these. STUDY SELECTION: Studies were included in the analysis if all of the following were reported: mortality; direct examination of 75% or more of the survivors; and the proportion of patients with at least 1 of the following disabilities: cerebral palsy, mental retardation, blindness, and deafness. Studies reporting cohorts included as a subset of cohorts in another study were excluded. Forty-two studies providing mortality and disability data for 20 cohorts of 4116 EI infants and 38 cohorts of 4345 ES infants born after 1972 met the inclusion criteria. DATA EXTRACTION: Data were abstracted from all studies that met these criteria by two of us (J.M.L. and D.E.W.), independently; the data were then cross-checked to ensure accuracy. RESULTS: Survival averaged 41% for EI infants and 30% for ES infants, and it increased significantly with time. In contrast to mortality, the prevalences of major neurodevelopmental disabilities among survivors have not changed over time. The most common major disability was mental retardation, found in 14% of EI and ES survivors. Cerebral palsy was found in 12% of EI survivors and 8% of ES survivors, blindness was found in 8% of EI and ES survivors, and deafness was found in 3% of EI and ES survivors. Overall, 22% of EI survivors and 24% of ES survivors were classified as having at least 1 major disability. Each 100 EI or ES livebirths yielded 7 children with major disabilities; this prevalence was correlated with survival across cohorts. CONCLUSIONS: The prevalence of disabilities had not changed among EI or ES survivors with increasing survival. However, increasing survival of these infants has resulted in a steadily increasing prevalence of children with disabilities.

The use of methylphenidate in Michigan.

OBJECTIVE: To describe the epidemiologic findings associated with the use of methylphenidate hydrochloride among children aged 0 to 19 years in Michigan. DESIGN: A population-based data set of all prescriptions filed with the Michigan Triplicate Prescription Program during February and March 1992 was analyzed, maintaining complete anonymity. SETTING: State of Michigan. PARTICIPANTS: All patients receiving a prescription for methylphenidate who are residents of Michigan, and all physicians prescribing methylphenidate. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Descriptive data. RESULTS: Eleven of 1000 Michigan residents between the ages of 0 and 19 years received a prescription for methylphenidate during the study period. Eighty-four percent were boys. Boys aged 10 or 11 years received more prescriptions for methylphenidate than any other age group--43 per 1000. The number of children receiving prescriptions for methylphenidate ranged from 2.5 to 28 per 1000. The range for boys aged 10 or 11 years was from 9.6 to 117 per 1000. Primary care physicians wrote 84% of all prescriptions; pediatricians wrote 59% of the prescriptions for patients younger than 20 years old. Half of the prescriptions written by pediatricians were written by 5% of the pediatricians in the state. CONCLUSIONS: Michigan has been among the states with the highest per capita consumption of methylphenidate for the past 10 years. The major use of methylphenidate is for treatment of attention deficit hyperactivity disorder. The number of boys in Michigan aged 10 or 11 years who were treated with methylphenidate was similar to the national prevalence of the disorder, 3% to 5%. A tenfold variation was noted in the percentage of children medicated when the data were analyzed by county. Relatively few pediatricians account for the largest proportion of prescriptions. Future studies are needed to link the use of methylphenidate with diagnostic and treatment considerations in attention deficit hyperactivity disorder.