A single very early dexamethasone dose improves respiratory and cardiovascular adaptation in preterm infants.

OBJECTIVES: To test the hypothesis that a single dose of dexamethasone given soon after delivery to infants <28 weeks' gestation leads to improved cardiopulmonary adaptation in the first week and lowers the risk of significant intraventricular hemorrhage. METHODS: In a prospective, blinded, placebo-controlled study, we randomly assigned 70 infants <28 weeks' gestation who were born in the hospital to receive dexamethasone (0.2 mg/kg) (n = 37) or normal saline solution (n = 33) within 2 hours of delivery. After an interim analysis showed that the incidence of intraventricular hemorrhage was much lower than expected, enrollment was stopped and we limited our analysis to a comparison of ventilator settings, blood pressure, and pressor use during the first 7 days. RESULTS: Clinical characteristics of the groups were comparable at study entry. Ventilator weaning occurred more rapidly in the patients who received dexamethasone: their intermittent mandatory ventilation rate was significantly lower on days 1 through 6, and their peak inspiratory pressure was lower on days 3 through 7 compared with the control group. Mean blood pressures were higher in the dexamethasone group within 12 hours and remained higher through day 5, but the use of pressors was not different. Fewer infants in the dexamethasone group received indomethacin to treat a patent ductus arteriosus (22% vs 47%, P <.03). CONCLUSION: Dexamethasone given within 2 hours of delivery to preterm infants <28 weeks' gestation resulted in lower ventilator settings and higher mean blood pressures during the first 7 days. Fewer infants required indomethacin to treat a patent ductus arteriosus.

Comparison of the effect of three doses of a synthetic surfactant on the alveolar-arterial oxygen gradient in infants weighing > or = 1250 grams with respiratory distress syndrome. American Exosurf Neonatal Study Group II.

The effect of a 50% increment or decrement in the recommended 5 ml/kg dose of a commercially available surfactant (Exosurf Neonatal) on the alveolar-arterial oxygen gradient was investigated in a multicenter, double-blind, placebo-controlled rescue trial conducted at 15 hospitals in the United States. Two doses of three different volumes (2.5, 5.0, and 7.5 ml/kg) were compared with two 5.0 ml/kg doses of air in 281 infants weighing > or = 1250 gm who had respiratory distress syndrome requiring mechanical ventilation and an arterial/alveolar oxygen ratio < 0.22. The first dose was given between 2 and 24 hours of age, and the second dose was given 12 hours later to all infants who still required mechanical ventilation. Infants were stratified at entry by gender and the magnitude of the arterial/alveolar oxygen ratio. The air placebo arm of the study was terminated early when reductions in mortality rates were proved in another rescue trial of this surfactant in infants with the same birth weights. For the first 48 hours, administration of a 2.5 ml/kg dose of surfactant provided less improvement in the alveolar-arterial oxygen gradient than doses of 5.0 and 7.5 ml/kg, which were equivalent. Similar results were observed in mean airway pressure (p < 0.05). There were no significant differences among the three dosage groups in mortality rate, air leak, bronchopulmonary dysplasia, and other complications of prematurity. There were no pulmonary hemorrhages in any group. Reflux of surfactant occurred more frequently in the 5.0 and 7.5 ml/kg groups. These results indicate that more sustained improvements in oxygenation are provided, with equal safety, by the standard two 5.0 ml/kg rescue doses of this surfactant than by the 2.5 ml/kg dose. No further benefit is gained from two larger doses given 12 hours apart.

Effects of nimodipine on brain blood flow following acute brain ischemia in the newborn piglet.

We examined the effect of the calcium channel blocker nimodipine on postischemic hypoperfusion in the newborn piglet brain. A severe pneumothorax (SP) was induced by injecting air into the right thorax until the mean arterial blood pressure fell to 25% of baseline and was maintained for 4 min. Blood flow was immediately reduced 70-90% from baseline in each brain region during SP. In untreated animals postischemic hypoperfusion existed at 60 min, following recovery from SP with regional brain blood flow reduced 20-30% from baseline. Nimodipine infusion after SP prevented postischemic hypoperfusion in all brain regions and increased blood flows by as much as 40% above baseline in midbrain and brainstem structures. Nimodipine infusion began after severe brain ischemia prevented postischemic hypoperfusion and enhanced brain blood flow in this model.

Association of pneumothorax and hypotension with intraventricular haemorrhage.

To test the hypothesis that acute hypotension resulting from pneumothorax would be associated with severe brain injury (grade 3 or 4 intraventricular haemorrhage), 67 very low birthweight (VLBW) infants of 32 weeks' gestation or less with respiratory distress syndrome and pneumothorax were studied. Thirty six had pneumothorax associated with systemic hypotension and 31 had pneumothorax with normal blood pressure. The groups were similar in gestational age and severity of their respiratory distress syndrome. Thirty two of 36 of infants with pneumothorax associated with hypotension (89%) had grade 3 or 4 intraventricular haemorrhage. This percentage was significantly greater than the percentage for infants with pneumothorax and normal blood pressure (three of 31, 10%). The risk ratio for grade 3 or 4 intraventricular haemorrhage for infants with pneumothorax associated with hypotension was 9.8 compared with neonates with pneumothorax and normal blood pressure. These observations are consistent with the hypothesis that systemic hypotension and cerebral hypoperfusion are important factors leading to intraventricular haemorrhage in VLBW infants.

Neonatologists judge the "Baby Doe" regulations.

The federal regulations now in effect governing the treatment of severely handicapped infants--the so-called Baby Doe regulations--are based on the 1984 amendments to the Child Abuse Prevention and Treatment Act; these regulations require that, except under certain specified conditions, all newborns receive maximal life-prolonging treatment. We sent questionnaires to the 1007 members of the Perinatal Pediatrics Section of the American Academy of Pediatrics to determine their views on the Baby Doe regulations and on whether the regulations had affected their practices; 494 of the members (49 percent) responded. Of the respondents, 76 percent believed that the current regulations were not necessary to protect the rights of handicapped infants; 66 percent believed that the regulations interfered with parents' right to determine what course of action was in the best interest of their children; and 60 percent believed that the regulations did not allow adequate consideration of infants' suffering. In responding to the three hypothetical cases of severely handicapped newborns, up to 32 percent of the respondents said that maximal life-prolonging treatment was not in the best interests of the infants described but that the Baby Doe regulations required such treatment. The responding neonatologists' concerns about the current Baby Doe regulations were similar to those expressed by the United States Supreme Court in rejecting an earlier set of Baby Doe regulations. This similarity suggests that the current Baby Doe regulations should be reevaluated.

Meconium pleuritis: cytologic diagnosis in a neonate with perforated sigmoid colon and diaphragmatic hernia.

Meconium pleuritis developed in a neonate with a perforation of the sigmoid colon, through a diaphragmatic defect. The meconium released in the abdomen communicated with the right pleural space. The association of these defects is unusual, and the cytologic diagnosis of meconium pleuritis has not been previously reported.

Gallbladder distention in ill preterm infants.

Four ill preterm infants each had a severely dilated gallbladder that was detected as a right-upper-quadrant abdominal mass. In each infant, the diagnosis was suspected on physical examination and confirmed by ultrasound study. One extremely premature infant with respiratory distress syndrome died, and at autopsy, the gallbladder and biliary tree showed no abnormalities, except for severe gallbladder distention. In the other three infants, distention of the gallbladder resolved spontaneously.

Delayed cerebral development in twins with congenital hyperthyroidism.

Twins had congenital hyperthyroidism and delayed cerebral development manifested as ventriculomegaly, increased space in the interhemispheric fissure, and an exaggerated gyral pattern on cranial computed tomographic scans. At 3 1/2 years of age, both children had delayed development. Fetal and neonatal hyperthyroidism may interfere with normal brain growth and maturation with both neuranatomic and developmental sequelae.

Plasma prostaglandin E2 and F2 alpha in preterm infants: association with respiratory distress syndrome and patent ductus arteriosus.

In order to determine if prostaglandin values correlate with gestational age, birth weight, postnatal age, or respiratory distress syndrome (RDS), we determined plasma prostaglandin F2 alpha (PGF2 alpha) and prostaglandin E2 (PGE2) by specific radioimmunoassay in 34 samples from 27 preterm infants. Neither prostaglandin correlated with gestational age or with birth weight. PGF2 alpha decreased (p less than 0.3) with postnatal age. Values for PGF2 alpha and PGE2 in each sample varied together (p less than .01) but only PGF2 alpha increased (p less than .09) in infants with RDS. The highest PGF2 alpha values occurred in infants with severe RDS, including four infants with patent ductus arteriosus (PDA). In contrast, plasma PGE2 was not elevated in infants with RDS or PDA.

Brain prostaglandins E2 and F2 alpha following neonatal asphyxia in the guinea pig.

In this study, the effects of (1) asphyxia and (2) asphyxiation followed by resuscitation on brain levels of prostaglandins E2 and F2 alpha were evaluated in 2-day-old guinea pigs. Asphyxiation in a nitrogen atmosphere for either 3 min or 3 min 40 s did not alter brain PGF2 alpha levels but after 3 min 40 s of asphyxia, brain PGE2 levels were significantly elevated from control values. When asphyxiation was followed by resuscitation with 95% O2 and 5% CO2, brain PGF2 alpha levels rose significantly while PGE2 levels were not different from nonasphyxiated control values. Pretreatment of animals with indomethacin lowered brain levels of both prostaglandins below nonasphyxiated control levels and prevented any asphyxiation or resuscitation-induced rise in brain prostaglandin levels. Also, animals which were asphyxiated, resuscitated, and sacrificed 1 day after asphyxiation had brain prostaglandin levels which were not different from levels in nonasphyxiated control animals. These studies demonstrate a significant rise in brain PGF2 alpha levels following resuscitation from acute total asphyxia. We speculate that the resuscitation-induced rise in brain PGF2 alpha may contribute to restriction of cerebral blood flow in the postasphyxial period through its action as a vasoconstrictive agent.

Neonatal respiratory syncytial virus infection.

Respiratory syncytial virus infections are thought to be uncommon in the first month of life. During a community outbreak, we prospectively studied such infection in our neonatal units. Of 82 neonates studied, 66 were hospitalized for six days or longer, and 23 (35 per cent) acquired this virus. Four infants died, two unexpectedly. Infected infants had a significantly shorter gestation and birth weight. Illness was often atypical, with nonspecific signs, especially in infants under three weeks of age, who had significantly less lower-respiratory-tract involvement and lower quantities of virus in their nasal washes. The titer of virus shed correlated with the infants' postnatal, but not gestational, age. Infection was also acquired by 34 per cent of the staff, who appeared to be important in the spread of the virus. These findings suggest that respiratory syncytial virus may readily infect neonates, but the disease may be atypical and may be overlooked.