Mode of delivery in pregnancies complicated by preeclampsia with very low birth weight infants.

The aims of this study were to examine data from an institution at which the goal has been to pursue vaginal delivery in patients with a preterm gestation and preeclampsia and to test the hypothesis that labor does not increase the risk of poor outcome for the preterm infant of a mother with preeclampsia. An analysis of all singleton infants born live who weighed 1500 gm or less and who were born to mothers with preeclampsia or eclampsia from 1975 to 1990 was undertaken. The infants who were delivered by cesarean section without labor and with a reassuring fetal assessment were compared with the infants who went through labor. Of 116 women with singleton pregnancies with preeclampsia and an infant who weighed 1500 gm or less, 54.3% were delivered by cesarean section without labor, 31.0% because of nonreassuring fetal assessment and 23.3% (group 1) because of other indications. Of the patients allowed to labor (group 2), 47.2% had cesarean sections because of fetal intolerance of labor and 32.1% were delivered vaginally. Of the patients who were delivered vaginally, 75% had an unfavorable Bishop's score at the outset of the induction. There was no significant difference between groups 1 and 2 for a number of immediate and long-term outcome variables except for a lower incidence of respiratory distress syndrome in the infants who went through labor. On the basis of these limited data a trial of labor should be considered in carefully selected women with preeclampsia who have very-low-birth-weight infants.

Cost effects of surfactant therapy for neonatal respiratory distress syndrome.

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.

Initial clinical trial of EXOSURF, a protein-free synthetic surfactant, for the prophylaxis and early treatment of hyaline membrane disease.

EXOSURF is a protein-free surfactant composed of 85% dipalmitoylphosphatidylcholine, 9% hexadecanol, and 6% tyloxapol by weight. A single dose of 5 mL of EXOSURF per kilogram body weight, which gave 67 mg of dipalmitoylphosphatidylcholine per kilogram body weight, or 5 mL/kg air was given intratracheally in each of two controlled trials: at birth to neonates 700 through 1350 g (the prophylactic trial, n = 74) or at 4 to 24 hours after birth to neonates greater than 650 g who had hyaline membrane disease severe enough to require mechanical ventilation (the rescue trial, n = 104). In both studies, time-averaged inspired oxygen concentrations and mean airway pressures during the 72 hours after entry decreased significantly (P less than .05) in the treated neonates when compared with control neonates. Thirty-six percent of the treated neonates in the rescue study had an incomplete response to treatment or relapsed within 24 hours, suggesting the need for retreatment in some neonates. In the rescue trial, risk-adjusted survival increased significantly in the treated group. There were no significant differences in intracranial hemorrhages, chronic lung disease, or symptomatic patent ductus arteriosus between control and treated infants in either trial.

Outcome of very-low-birth-weight infants exposed to beta-sympathomimetics in utero.

In this study we examined neonatal and early childhood outcomes after intrauterine exposure to beta-sympathomimetic agents on infants with birth weights less than or equal to 1500 gm. The hospital courses and anthropomorphic, developmental, and neurologic development of 201 infants exposed to one or more beta-sympathomimetic agents (isoxsuprine, 33; ritodrine, 70; terbutaline, 43; combination, 55) were analyzed and compared with those of 130 control infants of similar birth weight. One hundred and seventy-seven infants had follow-up to 1 year of age, 101 to age 3, and 58 to age 4. When treatments consisting of a single beta-sympathomimetic or no treatment were compared, there were no statistically significant overall differences found in growth and development or in most of the short-term measures of infant well-being. However, significant overall differences with no evidence of confounding by time-related effects were found for the following; mortality, none greater than terbutaline; maximum positive inspiratory pressure when respiratory distress syndrome was present, none greater than terbutaline; neonatal trauma, terbutaline greater than ritodrine. Other differences were found in conjunction with evidence of time-related confounding, or within specific time intervals. It should be noted that these differences are not necessarily due to effects of the different treatments, as the data are observational.

Stridor and gastroesophageal reflux in infants.

A relation was found between persistent stridor and gastroesophageal reflux in seven infants, aged 6 weeks to 6 months. Stridor began at 11 days to 2 months of age, and four of the seven infants had transient hypercarbia on at least one occasion before study. Only one had a history of frequent vomiting; three had recurrent pneumonia. Midesophageal pH, chest and abdominal movement, exhaled carbon dioxide partial pressure, and heart rate of six of the infants were recorded for 4 to 12 hours as they slept. Esophageal pH of the seventh infant was recorded for 24 hours. In the six completely studied infants, there were persistent increases of greater than 10 mm Hg in exhaled carbon dioxide level (three infants), of greater than 10 breaths per minute in respiratory rate (four infants), and in retractions and stridor (six infants) 5 to 20 minutes after onset of reflux. Stridor improved with medical management in 48 hours (five of five infants) and disappeared in 3 weeks (three of five infants) to 2 months (one of five infants). One of these medically treated infants subsequently was treated by Nissen gastric fundoplication because of a recurrence of persistent and severe stridor. Three infants had antireflux surgery, and in two of these stridor disappeared in 48 hours. In the third infant stridor disappeared 3 weeks after surgery. Based on this experience, reflux occasionally causes stridor, probably because of acute inflammation of the upper airway. If structural anomalies are ruled out, infants with severe stridor should be examined for gastroesophageal reflux.

Neonatal status and hearing loss in high-risk infants.

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.

Very low birth weight infants at 8 and 11 years of age: role of neonatal illness and family status.

The intellectual and educational status of 108 children with very low birth weight (less than or equal to 1,500 g), born from 1965 to 1978, was evaluated and tested on standard tests (eight children with severe handicaps were excluded) at 8 years of age. Fifty-seven were further evaluated at 11 years of age. Six categorical outcomes were defined a priori, based on the Wechsler Intelligence Scale for Children-Revised IQ and discrepancies between Verbal and Performance scores and Bender Gestalt Test score. Proportions at 8 years of age were: 4.6% very low IQ (below 70), 13.9% low IQ (70 to 84), and, for those with IQ greater than 84, 12.0% language disability, 12.0% performance disability, 21.4% visual-motor disability, and 36.1% normal. Learning disabilities, determined by discrepancies between IQ and Wide Range Achievement Test scores, included 16.7% of all children. Outcome proportions at 11 years of age were essentially comparable to those at 8 years of age; outcome constancy was present in 52.6%. Ratings of neonatal illness and parent education level strongly influenced the likelihood of outcome at 8 years of age. When ratings were dichotomized (ie, low v high neonatal illness and low v high parent education), the level of neonatal illness primarily influenced the likelihood of normal outcome, whereas the level of parent education influenced the degree of severity of the disability.

Neonatal status: an objective scoring method for identifying infants at risk for poor outcome.

The likelihood of sustaining neurological, sensory or cognitive deficits is considerably greater for very low birthweight (VLBW) infants who require intensive care in early postnatal life than those without major neonatal illness. Identifying which, if any, medical events are responsible for an adverse outcome is most difficult in the face of multiple concurrent complications. In this research, a principal components analysis was performed in order to arrive at a set of orthogonal variables which succinctly described clinical involvement in the nursery. With this procedure, a single hypothetical factor depicting neonatal status (NS) was computed. Principal component scores were then generated for NS and assigned to 252 VLBW (less than 1500 g) infants. These subjects were followed prospectively from birth to 4 years of age. Standardized measures of neurological, sensory and intellectual function were regularly administered. Neonatal status was shown to be significantly correlated with the various test results and predictive of long-term development. When subjects were divided into quartiles with respect to NS, a specific subgroup was identified as "at high risk" for poor outcome. Those subjects falling into the lower quartile incurred more neurological abnormalities persisting beyond the first year. They also suffered a higher incidence of intracranial hemorrhage and sensori-neural hearing loss. In addition, the lower 25%, as a group, scored well below all others on traditional tests of mental ability. These differences were sustained throughout infancy and early childhood and could not be attributed to a number of demographic variables including sex, gestational age, birthweight, Apgar scores or parental educational level.

An acute reduction in the fraction of inspired oxygen increases airway constriction in infants with chronic lung disease.

Infants with chronic lung disease have acute episodes of hypoxemia that are often accompanied by wheezing. To test whether a sudden reduction in FIO2 might increase airway obstruction in such infants, we measured the flow-volume relationship, O2 saturation, and skin-surface CO2 tension in 19 sedated infants, 11 with chronic lung disease, and 8 control infants, before and during 10 min of continuous hypoxemia. In the infants with chronic lung disease, a 20 to 25% reduction in FIO2 caused acute hypoxemia (O2 saturation, 77 +/- 8%) and an associated decrease in mid-expiratory flow from 103 +/- 55 to 69 +/- 37 ml/s (mean +/- SD; p less than 0.05) in the absence of a significant change in tidal volume or skin-surface CO2 tension. In the infants without lung disease, breathing 17% O2 led to a significant increase in minute ventilation (26 +/- 25%; p = 0.05), but there was no consistent change in mid-expiratory flow. To further study the effects of an acute reduction in FIO2 on pulmonary function in infants with chronic lung disease, we measured lung mechanics in 6 infants and end-expiratory lung volume in 5. Baseline lung resistance was high (49 +/- 35 cm/l/s) and increased by 55 +/- 30% (p less than 0.05) in response to hypoxemia. Baseline dynamic lung compliance was low (2.5 +/- 1.5 ml/cm) and decreased by 24 +/- 10% (p less than 0.05). Functional residual capacity increased from 26 +/- 13 to 33 +/- 14 ml/kg (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Developmental outcome following posthemorrhagic hydrocephalus in preterm infants. Comparison of twins discordant for hydrocephalus.

The mental development and neurologic outcome of four sets of preterm twins, in whom one infant within each pair developed posthemorrhagic hydrocephalus during the neonatal period, were assessed. Each hydrocephalic infant presented with signs of increased intracranial pressure and required placement of a ventriculoperitoneal shunt. Three of the four hydrocephalic infants required revision or replacement of the shunt during the first year. The four nonhydrocephalic infants had normal neurologic outcomes. All four hydrocephalic infants had some neurologic abnormalities on follow-up examination. Neurologic abnormalities were transient in one infant and persistent in three others, each of whom showed evidence of mild right hemiparesis. Within each twin pair, developmental rates and mental test scores were strikingly similar throughout infancy and early childhood. Two of the twin pairs have undergone psychological assessments at 8 and 11 years of age. Relatively lower IQ scores were obtained for the hydrocephalic child in each twin pair at these ages.

Lung function in prematurely delivered rabbits treated with a synthetic surfactant.

We treated prematurely delivered rabbit pups with the synthetic surfactant that has been named Exosurf. By weight, Exosurf is 61.8% dipalmitoylphosphatidylcholine, 6.8% hexadecanol, 4.6% tyloxapol, and 26.7% NaCl. This simple mixture, suspended at 15 mg lipid X ml-1 water, has appropriate in vitro characteristics for a lung surfactant substitute. As determined by static pressure volume relationships performed after 30 min ventilation, lungs treated with Exosurf accepted significantly more gas at maximal inflation (36 versus 15 ml X kg-1 body weight) and had significantly greater volumes during deflation that did saline-treated control lungs; lungs treated with natural rabbit surfactant (SAM) had significantly larger volumes at maximal inflation (65 versus 35 ml X kg-1) and during deflation than did the Exosurf-treated lungs. After 30 min of ventilation with oxygen and fixation at 10 cm H2O pressure, the ratio of air space to tissue space was determined by a point-counting technique, and mean linear intercepts were measured for air spaces. Exosurf-treated lungs were intermediate between SAM and saline-treated lungs in both measurements. With positive pressure ventilation to maintain a tidal volume of 6.5 to 7.5 ml X kg-1, total compliance was significantly greater and inspiratory pressure significantly lower in both SAM- and Exosurf-treated animals than in saline-treated control animals, although the lungs of the SAM-treated animals were more compliant than the lungs of animals treated with Exosurf. During the first minute of positive pressure ventilation, lungs treated with SAM or Exosurf expanded equally rapidly, both expanding more rapidly than the saline-treated lungs.(ABSTRACT TRUNCATED AT 250 WORDS)

Is chronic lung disease in low birth weight infants preventable? A survey of eight centers.

Chronic lung disease in prematurely born infants, defined as the need for increased inspired oxygen at 28 days of age, was thought to be more common in some institutions than in others. To test this hypothesis, we surveyed the experience in the intensive care nurseries at Columbia and Vanderbilt Universities, the Universities of Texas at Dallas, Washington at Seattle, and California at San Francisco, the Brigham and Women's Hospital in Boston, Texas Children's Hospital in Houston, and Mt Sinai Hospital in Toronto. The survey included 1,625 infants with birth weights of 700 to 1,500 g. We confirmed the relationship of risk to low birth weight, white race, and male sex. Significant differences in the incidence of chronic lung disease were found between institutions even when birth weight, race, and sex were taken into consideration through a multivariate logistic regression analysis. Columbia had one of the best outcomes for low birth weight infants and the lowest incidence of chronic lung disease.

Estimation of ventilatory response to carbon dioxide in newborn infants using skin surface blood gas electrodes.

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.

Esophageal spasm associated with apnea and bradycardia in an infant.

A newborn infant was found to have diffuse esophageal spasm in association with apnea and bradycardia. This association has not been physiologically documented before. The infant's condition improved after the administration of glycopyrrolate, an anticholinergic agent. It is speculated that the association of esophageal spasm and bradycardia may be mediated by the vagus.

Changes in phospholipid composition of lung surfactant during development in the fetal lamb.

The lung surfactant isolated from pulmonary fluid of fetal sheep changes both in amount and composition during gestation. Total phosphatidylcholine (PC) and its most surface-active components, disaturated PC, are present at very low levels 3-4 weeks prior to term and rise to adult levels 3-4 days before birth. The acidic phospholipids appear with a different time course. Phosphatidylserine reaches elevated levels about 21 days before birth. Phosphatidylinositol begins to increase at about 130 days of gestation. Phosphatidylglycerol is not a component (less than 1%) of the surfactant in this fetal lung fluid. At term, phosphatidylinositol is the major acidic phospholipid found in these fluids.

Inhibition of breathing movements in fetal sheep by prostaglandins.

We studied the effects of infusions (duration 13.4 +/- 2.9 h) of prostaglandins (PG) on fetal breathing movements (FBM) in 12 fetal sheep at 122-141 days gestation. We gave similar doses (1.1 +/- 0.7 microgram . kg-1 . min-1) of PGE2 (8 studies), PGF2 alpha (5 studies), and cyclic endoperoxide analogues (6 studies). During control periods (304 h), incidence of FBM was 41%; this decreased during every infusion. With PGE2, incidence of FBM markedly decreased to 9.8% of control (P less than 0.001). With the other agents the decrease was less profound; incidence of FBM with PGF2 alpha was 63.7% of control and with endoperoxide analogues 69.4% of control (P less than 0.05 for both). During infusions there were no changes in fetal heart rate, arterial blood pressure, pH, or blood gas tensions. In three fetuses (5 infusions) with electrocorticogram recordings, incidence of low-voltage fast activity was unchanged from control values. Inhibition of FBM by PGE2, combined with previous results showing stimulation of FBM by PG synthetase inhibitors, suggests that endogenous PG may inhibit breathing movements in utero and that a change in PG metabolism may contribute to the change in control of breathing at birth.

Developmental profiles for the brainstem auditory evoked potential.

Brainstem auditory evoked potentials (BAEP's) were recorded from 641 subjects in eleven age groups ranging from birth through adulthood, including three levels of prematurity, in order to establish an age-specific normative data base. The amplitude and latency values for waves 1-6, interwave differences for 3-1, 5-3, 5-1 and the amplitude ratios for 5/3 and 5/1 were then converted to percentile scores to permit construction of age-related BAEP profile report forms. Visual inspection of the printed output reveals the proportion of subjects falling above and below a given individual across all BAEP measures. This simple format is useful for general screening purposes as well as plotting maturational changes in healthy or high risk infants.

An intercostal retractometer for estimation of intrapleural pressure changes in infants.

An intercostal retractometer was developed for estimation of intrapleural pressure changes in infants. It consists of a flat reference plate which floats over the interspace and is attached to the skin by a flexible plastic film. The pressure inside the device is measured with a strain gauge. The volume inside the device is adjusted, so that the intercostal space is brought to a condition of flatness and pressure changes in the device correlate linearly with intrapleural pressure changes. The retractometer is calibrated against overall intrapleural pressure changes by matching its output to changes in airway pressure during occlusion of the airway. The calibration factor is qualitatively proportional to the thickness of the subcutaneous tissue. Retractometer and intrapleural pressures were simultaneously measured in two infant rhesus monkeys with small pneumothoraces. Esophageal and retractometer pressures were compared in seven preterm infants with an average weight of 1345 g. The device estimated the monkeys' intrapleural pressure changes to within 1.2 cmH2O and the human preterm infants' esophageal pressure changes to within 1.3 cmH2O (95% confidence limits of a linear regression).