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OBJECTIVE: To examine the cost effects of a single dose (5 ml/kg) of a protein-free synthetic surfactant (Exosurf) as therapy for neonatal respiratory distress syndrome, for both rescue and prophylactic therapy. RESEARCH DESIGN: Nonblinded, randomized clinical trials of both rescue and prophylactic therapy. Regression analyses were used to control for the independent effects of sex, multiple birth, delivery method, birth weight, and surfactant therapy. SETTING: The prophylactic trial was conducted at a university medical center only; the rescue trial also included a tertiary community hospital. PATIENTS: Prophylaxis was administered immediately after birth to 36 infants (38 control subjects) with birth weights between 700 and 1350 gm. Rescue therapy was administered at 4 to 24 hours of age to 53 infants (51 control subjects) with established respiratory distress syndrome and birth weights > or = 650 gm (no upper limit). Infants in the prophylactic trial were not eligible for the rescue trial. RESULTS: For the rescue trial, there was a $16,600 reduction in average hospital costs (p = 0.18), which was larger than the cost of the surfactant ($450 to $900), yielding a probable net savings. For the prophylactic trial, hospital costs were larger for treated infants versus control subjects who weighed less than about 1100 gm at birth and lower for treated infants versus control subjects who weighed more than 1100 gm at birth (p < 0.05). For the prophylactic sample, the result was an average cost per life saved of $71,500. CONCLUSIONS: Single-dose rescue surfactant therapy is probably a cost-effective therapy because it produced a lower mortality rate for the same (and probably lower) expenditure. Single-dose prophylactic therapy for smaller infants (< or = 1350 gm) appeared to yield a reduction in mortality rate for a small additional cost. The use of multiple-dose therapy in infants who do not respond to initial therapy may alter the effects described above to either increase or decrease the observed cost-effectiveness of surfactant therapy. Regardless, surfactant therapy will remain a cost-effective method of reducing mortality rates, relative to other commonly used health care interventions.

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Neurophysiologic and behavioral assessments of auditory function were performed on 224 very low birth weight (less than or equal to 1500 gm) infants requiring intensive care in the nursery. The subjects were studied prospectively from 36 weeks to 4 years of age, as available for follow-up. To classify them according to their neonatal status, we applied a principal components analysis to a number of variables representative of the extent of illness and of patient care in early postnatal life. The subjects were then divided into neonatal status quartiles and evaluated for hearing outcome. All those with sensorineural hearing loss fell exclusively into the lowest neonatal status quartile. Sensorineural hearing loss was statistically associated (1) with greater amounts of furosemide administration for longer durations and in combination with aminoglycoside antibiotics and (2) with more episodes of low pH, hypoxemia, or both, higher total bilirubin levels, and substantially lower neonatal status scores. Birth weight, gestational age, highest creatinine level, Apgar score, and aminoglycosides alone were not systematically related to hearing capacity. Subjects in the lowest neonatal status quartile also had a considerably higher incidence of middle ear disorders, characterized by elevated thresholds and prolonged auditory brain stem-response latencies reflective of conductive hearing loss. We conclude that protracted illness and its associated treatment, independently of specific diagnostic categories, constitute important risk factors for permanent hearing loss and for transient hearing loss in early life.

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Using only skin surface blood gas measurements, we calculated the ventilatory response to inhaled carbon dioxide from changes in skin surface PCO2 (PSCO2). This new method is based on the fact that if CO2 elimination is nearly constant, the change in alveolar ventilation from one steady state level to another is inversely proportional to the change in PSCO2. From this we derived a ventilatory ratio (VR) for 0%, 2%, and 4% CO2 breathing. A ventilatory response slope is then calculated from the three VR values, and is similar to a standard CO2 response slope. We serially studied 20 infants (28 to 40 weeks gestation) 2 to 9 weeks of age. Ten infants had serious apnea, ten did not. The infants breathed each test gas for 8 to 10 minutes during quiet sleep with skin surface electrodes attached. Infants with apnea were studied before and after apneic spells resolved. We found that apneic infants had a significantly reduced VR slope compared with that in the nonapneic infants, regardless of age. When apnea disappeared, the ventilatory ratio slope always increased into the range measured in nonapneic infants. In nonapneic infants the ventilatory ratio slope significantly increased with postnatal age. We conclude that infants with serious apnea have a reduced ventilatory response to CO2 and that the resolution of apnea is associated with the development of a normal CO2 response.

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