Theophylline toxicokinetics in premature newborns.

BACKGROUND: While cytochrome P4501A2 is the primary pathway for theophylline (aminophylline ethylenediamine) metabolism in adults, it is developmentally immature in the newborn. OBJECTIVE: To report the developmental differences in theophylline toxicokinetics of neonates. DESIGN: Case series. Three premature neonates received inadvertent intravenous overdoses of theophylline for apnea of prematurity while in newborn intensive care. Maximum serum concentrations ranged from 55 to 123 mg/L. Theophylline-derived caffeine levels plateaued at 8.4 to 13 mg/L and did not decline during the sampling period. All newborns experienced sinus tachycardia and agitation. Sequential theophylline and caffeine serum levels were obtained periodically for 62 to 100 hours. In contrast to older children and adults, in whom theophylline disposition follows zero-order kinetics at high concentrations, a monoexponential function best described theophylline elimination in the premature newborn, with half-lives ranging from 24.7 to 36.5 hours and estimated clearance from 0.02 to 0.05 L/kg per hour. These values are consistent with those previously reported in neonates. All patients were treated with supportive care without invasive procedures. No seizures or apparent sequelae occurred. CONCLUSION: Developmental differences in the balance between nonrenal (ie, metabolic) and renal elimination pathways produce the unique toxicokinetics of theophylline in the neonate.

Prevalence of prematurity, low birthweight, and asphyxia as perinatal risk factors in a current population of children with cerebral palsy.

To test the hypothesis that increasing survival of infants at highest risk for long-term neurological sequelae has strengthened the associations between perinatal events and subsequent cerebral palsy (CP), we compared the prevalence rates for prematurity, low birthweight, congenital malformations, and perinatal asphyxia from a current population of children with CP with those reported nearly 30 years ago by the National Collaborative Perinatal Project (NCPP, 1959-1966) of the National Institute of Neurologic and Communicative Disorders and Stroke. Although we saw no differences in the proportion of children who were born prematurely, we did find a significant shift in the birthweight and gestational age distribution, with a nearly threefold greater prevalence of births less than 1501 g in our population (31.1% and 95% confidence interval [CI] of 20.6 to 41.7% vs 9.1% and 95% CI of 5.0 to 13.2%). Nearly half (43.5%) of these very low birthweight infants had evidence of brain injury (intraventricular hemorrhage), a diagnosis not commonly recognized in the NCPP. On the other hand, birth asphyxia and congenital malformations occurred no more frequently in our population than that reported earlier. Furthermore, the majority (60%) of full-term infants who develop CP continue to be the products of normal pregnancies and have no perinatal events that may have caused their neurological impairment. The increasing prevalence of births less than 1501 g among children with CP may well reflect the improving survival of very small infants over the last 30 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Endotracheal administration of tolazoline in hypoxia-induced pulmonary hypertension.

STUDY OBJECTIVE: To compare the pulmonary and systemic vascular responses to intravenously (IV) and endotracheally (ET) administered tolazoline (Tz) in newborn lambs with hypoxia-induced pulmonary hypertension. DESIGN: Randomized, controlled study design. METHODS: Twenty lambs, 2 to 7 days of age, were anesthetized, intubated, and surgically catheterized for continuous physiologic monitoring and cardiac output measurements using radiolabeled microspheres. After a postoperative stabilization period, the lambs were ventilated with a hypoxic gas mixture which was titrated to increase mean pulmonary artery pressure (MPAP) 30% to 50% above baseline. Each animal was randomly assigned to receive either IV-Tz (2 mg/kg), ET-Tz (4 mg/kg), or ET-saline (Sal, control group). RESULTS: ET-Tz significantly (P < .05) reduced MPAP, PVRI (pulmonary vascular resistance index), MPAP/mean artery pressure (MAP) and PVRI/systemic vascular resistance index (SVRI), but not SVRI. IV-Tz lowered (P < .05) MPAP, PVRI, and PVRI/SVRI but also produced significant reductions in MAP and SVRI while only transiently decreasing MPAP/MAP: MPAP/MAP and PVRI/SVRI ratios were consistently lower in the ET-Tz animals than either the IV-Tz or ET-Sal animals. CONCLUSIONS: Our results suggest that ET-Tz produced a more selective pulmonary vascular response than IV-Tz and may warrant further investigation for potential clinical applications.

Perinatal factors associated with early-onset intracranial hemorrhage in premature infants. A prospective study.

Serial ultrasound examinations were performed on 40 consecutive newborn infants less than 35 weeks' gestational age. Fifteen of 17 infants with intracranial hemorrhage (ICH) had evidence of hemorrhage on the first ultrasound examination (mean age, 1.9 +/- 0.2 hours post partum). Comparing the clinical course of these 15 infants with age- and weight-matched non-hemorrhage controls showed a significant association between the occurrence of early ICH and the pattern of labor. There was no correlation between ICH and the mode of delivery, the use of sodium bicarbonate, volume administration, or the initial BP. In nine of the 15 infants with early-onset ICH, the hemorrhage progressed in severity during the first three postpartum days in association with increasing ventilatory requirements. The results of this study suggest that the course of labor may be a precipitating factor in the onset and evolution of early ICH.

Estimated blood volumes in polycythemic neonates as a function of birth weight.

This prospective study was designed to test the correlation of blood volume per kilogram of body weight with birthweight in polycythemic neonates. One hundred and sixty-four neonates with venous hematocrits of 65% or greater were treated with partial exchange transfusion. Follow-up venous hematocrits were obtained, and BV/kg was estimated for each infant based on the exchange volume used and the observed change in hematocrit. Birth weight ranged from 1,210 to 5,080 gm. Individual blood volume estimates ranged from 44 to 176 ml/kg, with a mean of 88.4 +/- 23.5 ml/kg. There was a highly significant negative linear correlation of BV/kg with birth weight (P less than 0.001), the regression line intersecting 100 ml/kg at 2,000 gm and 70 ml/kg at 4,500 gm. This correlation has clinical application in the management of polycythemic neonates with partial exchange transfusion. A nomogram is provided for estimating BV/kg in polycythemic neonates based on birth weight.

An analysis of air transport results in the sick newborn II. Antenatal and neonatal referrals.

The neonatal intensive-care unit at Fitzsimons Army Medical Center admits approximately 350 infants each year. At least half of these infants are referred, and, since 1973, there has been a steady increase in antenatal referrals. In 1975, in utero referrals exceeded neonatal referrals. The entire perinatal population of two referring hospitals was retrospectively evaluated in order to compare neonatal and in utero transfers. The neonatal transfers had higher-than-predicted mortality rate, while the in utero referrals had not only lower-than-predicted mortality rate, but the survivors had a shorter hospital stay. The combined neonatal/perinatal regionalization program resulted in a perinatal mortality rate of eight and 7.6 per 1,000 births in the two hospitals during the study period.

An analysis of air transport results in the sick newborn infant: Part I. The transport team.

Regionalization of neonatal intensive care has necessitated air transport of the critically ill infant in sparsely populated areas. All newborn air transports to four Denver area newborn intensive-care units over a 14-month period were reviewed. An emergency-care nurse and a neonatal intensive-care nurse provided the basic transport team with physician assistance in selected cases. Infants were evaluated and stabilized at the referring hospital before moving the infant. The transports were analyzed for the type of air craft utilized, reason for referral, and mortality. The results indicate that prior planning will permit the use of the most appropriate aircraft and transport team. When using well-trained transport personnel, the presence of a physician may be limited to specific situations without adversely affecting overall neonatal mortality.