Early prophylactic inhaled beclomethasone in infants less than 1250 g for the prevention of chronic lung disease.

OBJECTIVE: Inflammation plays an important role in the development of chronic lung disease (CLD), which has become a major cause of morbidity in surviving infants less than 1250 g at birth. The authors hypothesized that the progression of this inflammation and, therefore, the establishment of CLD would be decreased with the use of early prophylactic inhaled corticosteroids. Short, and long term respiratory and neurodevelopmental outcomes were also examined. DESIGN: A double-blind, randomized placebo controlled trial. SETTING: Level-III neonatal intensive care unit. POPULATION STUDIED: Sixty infants less than 1250 g at birth, diagnosed with respiratory distress syndrome and requiring ventilatory support at 72 h of age were enrolled in the study. INTERVENTION: Infants enrolled received either placebo or beclomethasone diproprionate by a metered dose inhaler, which was used in-line with the ventilator circuit while the infant was ventilated and then via a spacer until 28 days of age. RESULTS: Thirty infants were given beclomethasone and 30 were given placebo. There were two deaths in each group. Among the surviving infants, the frequency of moderate-to-severe CLD was 17% in each study group. Mean time to extubation was not different for beclomethasone compared with placebo at 16.4 and 12.5 days (P=0.12), respectively. The requirement for intravenous corticosteroids was lower in the beclomethasone-treated group (RR 0.67, 95% CI 0.43 to 1.04), although this difference was not statistically significant. The incidence of growth failure, infection and intraventricular hemmorhage did not differ between the two groups. Long term outcomes were not different with respect to the incidence of respiratory re-admissions, cerebral palsy, developmental delay, blindness or deafness. CONCLUSIONS: Early treatment with inhaled beclomethasone diproprionate did not reduce the incidence of CLD or decrease the duration of mechanical ventilation. The decrease in intravenous corticosteroid use was not statistically significant. Long term outcome was not affected.

Causes and consequences of recent increases in preterm birth among twins.

OBJECTIVE: To examine the causes and consequences of the recent increase in preterm birth among twins. METHODS: We studied all twin births among residents of the province of Nova Scotia, Canada, between 1988 and 1997. Rates of preterm birth, preterm labor induction, preterm cesarean, small-for-gestational age (SGA), respiratory distress syndrome (RDS), stillbirth, perinatal mortality, and infant mortality were compared between past and more recent years. Changes in perinatal mortality were examined using logistic regression to adjust for the effects of other determinants. RESULTS: The study included 2516 twin births (73 stillbirths and 2443 live births). The rate of preterm birth increased from 42.3% in 1988-1992 to 48.2% of twin live births in 1993-1997 (14% increase, P =.04). Twin live births born after preterm labor induction increased from 3.5% in 1988-1989 to 8.6% in 1996-1997 (P for trend =.007). Of live births between 34 and 36 weeks' gestation, the proportion born SGA decreased from 17.5% in 1988-1992 to 9.2% in 1993-1997 (P =.005). Over the same period, rates of prophylactic maternal steroid therapy increased substantially and rates of RDS declined. Perinatal mortality rates among pregnancies reaching 34 weeks decreased from 12.9 per 1000 total births in 1988-1992 to 4.2 per 1000 total births in 1993-1997 (P =.05). CONCLUSION: Increases in preterm labor induction appear to be responsible for the recent increase in preterm birth among twins. These changes have been accompanied by decreases in perinatal morbidity and mortality among twin pregnancies that reach 34 weeks' gestation.

Hypomandibular faciocranial dysostosis: another case and review.

We report on a third case of hypomandibular faciocranial dysostosis and review the literature. Manifestations include craniosynostosis, prominent eyes, deficient midface and zygomatic arches, short nose with anteverted nares, protruding lower face, minute oral aperture, persistent buccopharyngeal membrane, and severe mandibular hypoplasia. In contrast to coronal synostosis found in the 2 earlier cases, our patient had multiple sutural synostosis. The 2 affected sibs reported earlier suggest the possibility of autosomal recessive inheritance. However, gonadal mosaicism for a dominant mutation or an undetected microdeletion must also be considered at this early stage in the delineation of this disorder.

Auditory brain stem responses to air- and bone-conducted clicks in the audiological assessment of at-risk infants.

Auditory brain stem responses (ABRs) to air- and bone-conducted clicks were used to assess the auditory status of 170 at-risk neonates. During the perinatal period, 20.6% (35/170 cases) of the at-risk infants failed ABRs to air-conducted clicks at 30 dB nHL in at least one ear. Ear-specific results indicated an initial failure rate of 15.0% (51/340 ears). Approximately two-thirds (32/51 ears) of these initial failures showed purely conductive deficits, whereas the remaining one-third (19/51 ears) involved suspected sensorineural components. Follow-up audiological evaluations were performed for 87.1% (148 cases) of these at-risk infants at 4 mo and/or 1 yr corrected age. Based on the initial tests and follow-up assessments, the tentative operating characteristics of ABRs to both air- and bone-conducted clicks for identification of sensorineural deficits in at-risk neonates were calculated. It was found that the ABR to bone-conducted clicks yielded better specificity, predictive value of positive results, and overall efficiency. It is suggested that the ABR to bone-conducted stimuli should be viewed as a valuable addition in the assessment of cochlear reserve in infants who fail a newborn auditory screening to air-conducted stimuli.

Effect of high-dose vitamin D supplementation on radiographically detectable bone disease of very low birth weight infants.

To test the hypothesis that high-dose vitamin D2 supplementation would result in a lower incidence of radiographically detectable bone disease, we randomly assigned 40 very low birth weight infants to a control group who received vitamin D2 in a dosage of 400 IU/day and 41 to an experimental group who received a dosage of 2000 IU/day. After 6 weeks, radiographs from all infants were scored blindly for degree of radiographic bone disease, and serum osteocalcin and 25-hydroxyvitamin D levels were measured. Mean vitamin D intake was 360 +/- 141 (SD) IU/day in the control group and 2170 +/- 144 (SD) IU/day in the experimental group. Median 6-week serum 25-hydroxyvitamin D levels were 24 ng/ml (range 3 to 60 ng/ml) in the control group and 68 ng/ml (range 9 to 150 ng/ml) in the experimental group (p less than 0.001). Overall, 20% of the infants had evidence of moderate radiographic bone disease and only 2% were severely affected. The radiographic bone score (median = 2.5) and serum osteocalcin concentration (mean = 21.7 +/- 8.7 ng/ml) in the control subjects did not differ significantly from those in the experimental group (median bone score = 2.0; mean osteocalcin level = 24.1 +/- 7.9 ng/ml). Although there may be a subset of very low birth weight infants who would benefit from high doses of vitamin D, we conclude that no generalized clinical improvement can be attributed to this regimen alone.

Drug errors and incidents in a neonatal intensive care unit. A quality assurance activity.

We prospectively examined the causes of medication errors and incidents in a level 3 neonatal intensive care unit for a 2-year period. There were 313 incidents in 23,307 patient days (13.4 incidents per 1000 patient days). The relative risk of incidents was greater in more intensive levels of care. The two most common causes of incidents were neglecting to give a medication on schedule (n = 52) and nonregulation of an intravenous infusion (n = 32). Twenty percent of orders made by physicians that were in error resulted in serious incidents compared with only 6% of all other causes.

Effect of timing of cerebral ultrasonography on the prediction of later neurodevelopmental outcome in high-risk preterm infants.

To determine the predictive value of cranial ultrasonographic examination in high-risk preterm infants at different postnatal ages, we scanned 110 infants less than or equal to 32 weeks gestational age at 1, 2, 3, and 6 weeks postnatal ages and at 40 weeks postconceptional age (PCA). Cranial abnormalities detected by ultrasonography at each postnatal age of examination were classified as minor (periventricular superolateral echogenicity with or without intraventricular hemorrhage, grades 1 to 3) or major (cystic periventricular leukomalacia with or without intraventricular hemorrhage, grade 4) and correlated with neurodevelopmental outcome determined by 1 year of age. Major abnormalities detected by ultrasonography were present in four infants at 1 week, four at 2 weeks, eight at 3 weeks, and 11 infants at 6 weeks and 40 weeks PCA, respectively. Nineteen infants (17%) had moderate to severe functional handicaps defined as cerebral palsy, cognitive or visual deficit, or deafness. The positive and negative predictive values of ultrasound examinations, with regard to later neurodevelopmental outcome, improved with increasing postnatal age at examination and was best at 40 weeks PCA. Negative results of ultrasound study at 40 weeks PCA most correctly predicted satisfactory outcome. Although only 58% of moderately to severely handicapped infants were correctly identified by ultrasound examination at 40 weeks PCA, all infants with major ultrasonographic abnormalities at 40 weeks PCA had moderate or severe handicap. Our data demonstrate that the timing of cerebral ultrasonography is important in the prediction of later neurodevelopmental outcome in high-risk preterm infants.

Preterm birth at 23 to 26 weeks' gestation: is active obstetric management justified?

To determine if active perinatal management was justified in preterm deliveries at less than or equal to 26 weeks' gestation, the outcome (survival and short- and long-term morbidity) of 43 infants (group I) born between 23 and 26 weeks' gestation was compared with that of 17 infants (group II) born at 27 weeks' gestation. Of the 12 surviving infants in group I (survival 28%), 11 were ventilated (median = 50 days), eight had moderate to severe bronchopulmonary dysplasia, and four had mild retrolental fibroplasia. At follow-up, two infants had physical disabilities with moderate to severe functional impairment, one had a minor disability, and nine had normal neurodevelopment. In contrast, of the 13 surviving infants in group II (survival 76%), nine were ventilated (median = 8 days), six had moderate to severe bronchopulmonary dysplasia, and six had mild RLF. At follow-up, one infant had a physical disability with moderate to severe functional impairment, four had minor disabilities, and eight had normal development. Perinatal factors that positively influenced survival in the two groups combined included active perinatal management, antenatal steroids, female sex, and absence of clinical chorioamnionitis and asphyxia. Although group I infants had a significantly higher mortality rate (p less than 0.05) and required a longer duration of ventilation (p less than 0.05), no differences in the incidence of postnatal complications or long-term morbidity at 2 to 4 years of age were evident between the two groups.