A multicenter randomized masked comparison trial of synthetic surfactant versus calf lung surfactant extract in the prevention of neonatal respiratory distress syndrome.

OBJECTIVE: To compare the efficacy and safety of a synthetic surfactant (Exosurf Neonatal, Burroughs Wellcome Co) and a surfactant extract of calf lung lavage (Infasurf, IND #27,169, ONY, Inc) in the prevention of neonatal respiratory distress syndrome (RDS). DESIGN AND SETTING: Ten-center randomized masked comparison trial. PATIENTS: Premature infants (n = 871) <29 weeks gestational age by best obstetric estimate. INTERVENTIONS: Infants were randomly assigned to a course of treatment with Exosurf Neonatal (n = 438) or Infasurf (n = 433) at birth, and if still intubated, at 12 and 24 hours of age. Crossover treatment was allowed within 72 hours of age if severe respiratory failure (defined as two consecutive a/A PO2 ratios

Does surfactant therapy prolong dying? Age at in-hospital death of extremely premature babies.

We reviewed medical records of inborn babies of < 30 gestational weeks who died before hospital discharge to identify the cause of death and age at death. We compared all surfactant-treated babies born during the first 19 months of our experience in a phase III trial of exogenous surfactant prophylaxis of respiratory distress syndrome with all untreated babies born during the 19 months immediately preceding the surfactant trial. The two groups were virtually identical in birth weight and gestational age. Mortality in all gestational age groups declined by half after the initiation of surfactant treatment. The mean age at death did not change significantly. Cases of early or late mortality did not change between the two periods. Exogenous surfactant prophylaxis does not significantly prolong the lives of extremely premature babies who are destined to die before hospital discharge.

A multicenter randomized, masked comparison trial of natural versus synthetic surfactant for the treatment of respiratory distress syndrome.

OBJECTIVE: To compare the efficacy and safety of two surfactant preparations in the treatment of respiratory distress syndrome (RDS). METHODS: We conducted a randomized, masked comparison trial at 21 centers. Infants with RDS who were undergoing mechanical ventilation were eligible for treatment with two doses of either a synthetic (Exosurf) or natural (Infasurf) surfactant if the ratio of arterial to alveolar partial pressure of oxygen was less than or equal to 0.22. Crossover treatment was allowed within 96 hours of age if severe respiratory failure (defined as two consecutive arterial/alveolar oxygen tension ratios < or = 0.10) persisted after two doses of the randomly assigned surfactant. Four primary outcome measures of efficacy (the incidence of pulmonary air leak (< or = 7 days); the severity of RDS; the incidence of death from RDS; and the incidence of survival without bronchopulmonary dysplasia (BPD) at 28 days after birth) were compared by means of linear regression techniques. RESULTS: The primary analysis of efficacy was performed in 1033 eligible infants and an analysis of safety outcomes in the 1126 infants who received study surfactant. Preentry demographic characteristics and respiratory status were similar for the two treatment groups, except for a small but significant difference in mean gestational age (0.5 week) that favored the infasurf treatment group. Pulmonary air leak (< or = 7 days) occurred in 21% of Exosurf- and 11% of infasurf-treated infants (adjusted relative risk, 0.53; 95% confidence interval, 0.40 to 0.71; p < or = 0.0001). During the 72 hours after the initial surfactant treatment, the average fraction of inspired oxygen (+/-SEM) was 0.47 +/- 0.01 for Exosurf- and 0.39 +/- 0.01 for infasurf-treated infants (difference, 0.08; 95% confidence interval, 0.06 to 0.10; p < 0.0001); the average mean airway pressure (+/-SEM) was 8.6 +/- 0.1 cm H2O; for Exosurf- and 7.2 +/- 0.1 cm H2O for Infasurf-treated infants (difference, 1.4 cm H2O; 95% confidence interval, 1.0 to 1.8 cm H2O; p < 0.0001). The incidences of RDS-related death, total respiratory death, death to discharge, and survival without bronchopulmonary dysplasia at 28 days after birth did not differ. The number of days of more than 30% inspired oxygen and of assisted ventilation, but not the duration of hospitalization, were significantly lower in Infasurf-treated infants. CONCLUSION: Compared with Exosurf, Infasurf provided more effective therapy for RDS as assessed by significant reductions in the severity of respiratory disease and in the incidence of air leak complications.

Hematochezia associated with the use of hypertonic sodium polystyrene sulfonate enemas in premature infants.

The onset of hematochezia with the use of sodium polystyrene sulfonate enemas in an index case prompted us to review our experience with the use of such enemas in neonates. Sodium polystyrene sulfonate enemas were used in 20 of 2317 patients. Of these 20 patients, four (20%) had evidence of hematochezia temporally related to the use of the enemas. No episodes of such bleeding occurred in infants who were older than 29 weeks of gestation or larger than 1250 gm birth weight. In one case an autopsy performed within 2 days of the enemas showed extensive vascular congestion within the mucosa and submucosa with focal areas of hemorrhage. Approximately 20% sorbitol (1098 mOsm/L) was the vehicle for suspension of the sodium polystyrene sulfonate. On the basis of evidence regarding similar morbidities in adults, we are concerned that the hyperosmolar suspending agent, sorbitol, may be the cause of such pathologic conditions in the colon of susceptible infants.

Congenital chest wall mesenchymal hamartoma.

The case of an infant with mesenchymal hamartoma of the chest wall is presented, and the role of conservative diagnostic and therapeutic intervention is emphasized. A large mass that involved the right hemithorax and chest wall was detected in utero on routine ultrasonographic studies and diagnosed as mesenchymal hamartoma by percutaneous fine needle biopsy at 4 days after birth. The mass did not enlarge after birth, but surgical debulking was necessary at 1 month because of progressive respiratory compromise. Tumor regrowth was noted over the ensuing 8 months, and a second debulking at 9 months has been followed by a 6-year interval without evidence of recurrence.

Prophylactic administration of calf lung surfactant extract is more effective than early treatment of respiratory distress syndrome in neonates of 29 through 32 weeks' gestation.

OBJECTIVE: Although numerous trials have demonstrated the efficacy of exogenous surfactant for prophylaxis or treatment of neonatal respiratory distress syndrome (RDS), optimum timing of administration remains controversial. One previous study showed that administration of calf lung surfactant extract immediately following birth, to neonates born before 30 weeks postconceptional age, was preferable to delaying administration until after development of RDS. The current study was designed to test a similar hypothesis for babies born between 29 and 32 weeks gestational age. DESIGN: One thousand three hundred ninety-eight neonates with obstetric estimates of 29 through 32 weeks' gestation were randomized to receive CLSE at birth or to wait until development of mild RDS. After exclusions for malformations and other factors, data from 1248 were analyzed. RESULTS: Prophylaxis was associated with less development of moderate RDS (7% vs 12%), less need for retreatment (5% vs 9%), less need for mechanical ventilation or supplemental oxygen during the first 4 days, and fewer deaths or less requirement for supplemental oxygen at 28 days (5% vs 9%). Although 1-minute Apgar scores were significantly lower in the prophylaxis group, the difference disappeared by the 5-minute score and there was no difference in the incidence of asphyxia-related complications. Sixty percent of the neonates assigned to early treatment received endotracheal intubation and 43% received calf lung surfactant extract at a median age of 1.5 hours. When data were analyzed by gestational age and birth weight subgroups, most of the differences could be attributable to babies born at 30 weeks or less or weighing less than 1500 g, probably because of the higher incidence of surfactant deficiency in this more immature subgroup.

Osteochondrodysplasia in Fryns syndrome.

Various skeletal abnormalities have been identified in roentgenograms of persons with Fryns syndrome, but to our knowledge, no histopathologic description of bone or cartilage has been published. We describe disordered endochondral and intramembranous bone formation in a premature female infant with Fryns syndrome. This infant and a full sibling (ie, had same set of parents) with Fryns syndrome in addition exhibited delayed ossification of the basiocciput and of cervical vertebral bodies, also previously undescribed in Fryns syndrome. These findings expand the spectrum of Fryns syndrome to include osteochondrodysplasia.

Clinical evaluation of a new chest tube used in neonates.

We report preliminary experience with a newly designed chest tube (JCT), for evacuation of neonatal pneumothorax. The catheter has a unique pigtail confirguration at the distal end, intended to simplify placement and minimize chest wall and lung trauma by reduced tube size and depth and insertion. Thirty-eight JCTs were placed in neonates with pneumothoraces. Neonates' birth weights ranged from 400 to 3,595 grams. All 38 tubes immediately relieved clinical signs of pneumothoraces. Thirty-five (92%) tubes immediately fully evacuated the pneumothoraces as evidences on chest radiograph. Twelve pneumothoraces partially reoccurred at a mean of 24 hours following JCT placement. These tubes were either irrigated or replaced. This newly configured chest tube functions effectively in the treatment of neonatal pneumothorax.

Neonatal back transport: clinical outcomes.

The convalescent course of 55 infants transported from a Level III hospital back to the community hospitals from which they were originally transported was compared with the course of 58 infants who convalesced in the tertiary center nurseries. The events in their prenatal course and acute neonatal course were similar, thus making comparisons of their convalescent course possible. Weight gain was greater among the transported infants for infants with birth weights greater than or equal to 2,000 g and comparable if birth weight was less than 2,000 g. Transported infants received fewer transfusions than their nontransported counterparts. Tolerance of feedings, the occurrence of apnea and bradycardia, and use and discontinuance of supplemental oxygen were similar in both groups. Major new health problems occurred in 27% of all subjects, 20% of transported infants and 32% of nontransported infants. Readmission to the tertiary center or a change in status to more intensive care in the tertiary center occurred in 10% of all infants, 7% of transported and 14% of nontransported infants. It was concluded that convalescing infants often presented new clinical problems, in similar numbers and severity whether convalescing in the tertiary center or after back transport to community hospitals. Community hospital care givers were considered alert to these new problems and to have provided appropriate care, including retransfer to the tertiary center when necessary.

Home phototherapy treatment of neonatal jaundice.

A home phototherapy program for healthy, term newborns with hyperbilirubinemia (n = 62) was implemented, and results were compared prospectively with a group of term neonates who met enrollment criteria but were treated in-hospital (n = 55). The purpose of the study was to prospectively assess the feasibility, safety, and effectiveness of home phototherapy in treating uncomplicated neonatal jaundice. Infants were required to be greater than 24 hours old and to weigh at least 2,270 g (5 lb). Enrolling physicians were instructed to select infants whose clinical diagnoses and bilirubin levels allowed an adequate margin of error for a trial of home phototherapy and whose parents were capable of managing the added responsibilities of home therapy. At the time the phototherapy equipment was delivered and set up in their home, parents received extensive instruction, including how to record pertinent ongoing data on a home flow sheet. Serum bilirubin levels were measured at least daily. The preponderant diagnosis listed by enrolling physicians was "physiologic jaundice." No parent reported significant complications, and no infant required rehospitalization. Bilirubin levels decreased as rapidly in the home group as in the hospitalized control group, and duration of treatment averaged 2.8 days. About $18,000 was saved by treating these 62 infants at home compared with in-hospital costs in our community. We found home phototherapy to be a feasible, safe, and effective alternative to in-hospital phototherapy for otherwise healthy, jaundiced infants with motivated and capable parents.

Total population estimate of newborn special-care bed needs.

In 1977, 7% of the 38,855 infants born in Utah were estimated to have required a total of 27,439 special-care hospital days. About half (53%) were mildly ill; their average length of stay was 4.6 days, or 24% of the total hospital-days. Another 20% of the infants had intermediate illness, with a 12-day average stay, or 23% of the total hospital-days. The remaining 27% of the infants required intensive care and used 53% of the total hospital-days; their average length of stay was 20 days. As a total population, the state's 38,855 births generated a need for two beds per 1,000 annual live births in special-care facilities. The estimated bed need was: mild illness (Level I), 0.5 beds per 1,000 annual live births; intermediate illness (Level II), 0.5 beds per 1,000 annual live births; and intense illness (Level III), one bed per 1,000 annual live births. Results are based on the assumption that nonstudy births, 30% of the total, have needs proportionate to study births. The following considerations are necessary to extrapolate these bed needs to other populations: convalescence of intensely ill babies may require that up to 50% of their bed needs may be shifted to intermediate care; compliance with criteria for transport to the next level of care may not be 100% as assumed in the study, thus redistributing bed needs; census characteristically fluctuates in special-care nurseries (study results are reported for an unchanging daily census); and the low birth rate of a population is intimately related to the bed needs.

Neonatal back-transport. Cost-effectiveness.

This study examines the cost-effectiveness of returning previously ill neonates to community hospitals after treatment in a tertiary center, a concept known as "back-transport." The authors compared the charges for medical care during convalescence of a group of back-transported infants (BT infants; n = 20) with a similar group of infants who remained in a tertiary center for convalescence (NT infants; n = 20). The total charges for convalescent care (inpatient plus transport charges) for 20 representative BT infants was $61,840, compared with $68,240 for 20 matched NT infants, an average savings of $320 per BT infant. The average daily bed charge and charges for laboratory tests and medications were significantly less for BT infants compared with NT infants, and these reductions offset the transport charges for BT infants. The authors conclude that back transport decreases the charges for medical care for most infants. Therefore, the decision to back-transport an individual infant usually can be based on factors other than cost.

Back transport of neonates: improved efficiency of tertiary nursery bed utilization.

Neonatal back transport is defined as the return of previously critically ill neonates from Level III newborn intensive care units to Level II and Level I nurseries for intermediate and/or convalescing care. During 1980, 172 infants (65% of eligible infants) were back transported from a Level III nursery to both Level I and Level II community hospitals. Infants who were returned to Level II hospitals tended to be smaller at the time of transfer, were less frequently nipple fed, and more frequently required oxygen supplementation compared with infants returned to Level I hospitals. Back transport permitted physicians to defer 3,892 days of hospitalization for these infants to community hospitals, an equivalent savings of approximately ten hospital beds at full occupancy. This resulted in a 44% reduction in the need for services in the newborn intensive care unit. Back transport is an efficient means of dealing with overcrowding of Level III nurseries.

Effectiveness of chest tube evacuation of pneumothorax in neonates.

This is a retrospective review of the effectiveness of 149 chest tubes placed in attempts to evacuate 91 pneumothoraces among 57 infants. Forty-four percent of initial evacuation attempts were ineffective; 42% of total chest tubes throughout the clinical courses were ineffective. The largest number of these ineffective chest tubes lay posterior in the pleural cavity. Fifty-six percent of posterior tubes were ineffective whereas only 4% of anterior tubes were ineffective. Other causes for failure included tubes which had perforated the lung, diaphragm, or mediastinum or were lying subcutaneously. On some occasions, chest tubes were mistakenly used to evacuate intrathoracic air which was actually a pulmonary pseudocyst or pneumomediastinum. Two thoracostomy sites were chosen: the superior and lateral. Eighty-five percent of chest tubes inserted through the superior approach lay anteriorly in the pleural cavity whereas only 47% of the laterally inserted tubes lay anteriorly. Superior thoracostomy tubes were significantly more effective than lateral tubes because of their more frequent anterior location. There were also fewer complications with superior thoracostomy tubes. Whereas only 10% of superiorly inserted tubes encroached upon the mediastinum, 32% of lateral tubes did so. To be effective, chest tubes should be placed anteriorly in the pleural space; this location is more often achieved via the superior thoracostomy approach.

Functional residual capacity and severity of respiratory distress syndrome in infants.

Infants with respiratory distress syndrome (RDS) have insufficient surfactant systems and decreased functional residual capacity (FRC). This study attempts to relate FRC with severity of disease course. Measurements were made on 36 newborn infants with clinically diagnosed RDS. All infants were intubated and breathing on continuous positive airway pressure (CPAP) at the time studied. Infant CPAP levels were adjusted to 10 cm H2O; then FRC and arterial blood gas measurements were made. The infants were grouped according to their FRC per birth weight (BW). Volumes larger than or equal to 2 SD (larger than or equal to 42 ml/kg) of normal term infants not on CPAP were placed in the "large FRC" group. Volumes within +/- 2 SD (15-41 ml/kg) were in the "medium FRC: group, and infants smaller than or equal to 2 SD (< 14 ml/kg) of normal were in the "small FRC" group. The severity of RDS disease course was judged by the time duration the infants were managed on CPAP and FIO2 > 0.21 and by the maximum CPAP and FIO2 levels used. Twelve infants (33%) had small FRC, 18 (50%) medium FRC, and 6 (17%) large FRC. The time duration the infants with large FRC were on CPAP was significantly less than infants with medium FRC and the medium FRC group time was less than the small FRC group. The time duration on increased FIO2 and maximum FIO2 level used on the large FRC group was less than the medium and small FRC groups. Thus, FRC/BW appears related to the severity of RDS disease course. It is possible that the infants with FRC/BW larger than or equal to 42 ml/kg had pneumonia and were misdiagnosed as RDS. If so, FRC monitoring could have assisted in their diagnosis. BW and gestational ages of the groups were not different. Thus, variables other than these two play an important role in the degree of atelectasis occurring in infants with RDS. In patient management, where frequent changes in airway pressure and FIO2 are made, knowing the FRC/BW as well as blood gas values could aid the clinician in his choice of CPAP and FIO2 levels.

A method of estimating the functional residual capacity of infants with respiratory distress syndrome.

This report describes and evaluates a new method of estimating the functional residual capacity (FRC) of newborn infants receiving continuous positive airway pressure (CPAP). Standard nitrogen washout methods of measuring lung volume are time consuming, frequently interfere with patient care, and may be hazardous to prematurely born infants. The authors are using a four-breath nitrogen washout technique to estimate the FRC of infants. The method was evaluated using: (1) a mechanical lung model, and (2) results from 32 newborn infants with RDS. The actual volume of the mechanical lung model was 21.6 ml and the estimated volume was 21.4 +/- 2.3 (SD) n = 13. Using different volumes in the mechanical lung model and comparing with estimated FRCs yielded a correlation coefficient of 0.96 (n = 15). Comparing the FRC of infants determined by standard nitrogen washout with the estimated FRC yielded a correlation coefficient of 0.92, n = 145. Thus, the results of the two methods are in good agreement. The new method reduces the period of breathing pure oxygen from several minutes to just a few seconds, thus, decreasing the dangers of absorption atelectasis and oxygen toxicity. The new system also lends itself well to micro-processor automation.

Fetal hydantoin syndrome, neuroblastoma, and hemorrhagic disease in a neonate.

This is the first patient report of maternal ingestion of anticonvulsants associated with the triad of fetal hydantoin syndrome, neuroblastoma, and hemorrhagic disease. The neuroblastoma, a neural crest tumor, is the fourth of such origin reported after in utero exposure to phenytoin, suggesting that phenytoin is a transplacental carcinogen. Infants of epileptic mothers receiving anticonvulsants should be closely examined at birth for the fetal hydantoin syndrome and monitored for hemorrhagic problems. The neural crest tumor may be found at birth or later in childhood.