Effect of dexamethasone therapy on the neonatal ductus arteriosus.

Patent ductus arteriosus (PDA) is believed to be a contributing factor in the etiopathogenesis of bronchopulmonary dysplasia (BPD). We studied the effects of early dexamethasone therapy on persistent ductal patency and the role of PDA in the etiopathogenesis of BPD during the course of a randomized double-blind trial of dexamethasone to prevent BPD. Infants, who weighed between 700 and 999 g, had severe RDS, and had been given surfactant, were randomized to receive a 12-day course of dexamethasone (n = 13) or placebo (n = 17) starting within the first 12 hours of postnatal life. The diagnosis of PDA was made clinically and was confirmed by cardiac ultrasound. The incidence of clinically significant ductus in infants who weighed less than 1000 g was 23% in the dexamethasone-treated group, as compared with 59% in infants who were given placebo. This difference was marginally significant, p = 0.05, odds ratio 0.21, 95% confidence interval 0.04-1.05. None of the infants in the dexamethasone group had recurrence of PDA after indomethacin therapy as compared with three infants in the placebo group. Dexamethasone significantly reduced the number of days infants required ventilator and supplemental oxygen as compared with infants who received placebo. Dexamethasone, as compared with placebo, also reduced the incidence of BPD, p = 0.025, odds ratio 0.08, 95% confidence interval 0.01-0.58. Dexamethasone may reduce the incidence of PDA in premature infants who weigh less than 1000 g at birth and thereby reduce the incidence of BPD.

Ophthalmological morbidity in very-low-birthweight infants with bronchopulmonary dysplasia.

This study was undertaken to determine the relationship between retinopathy of prematurity, ocular sequelae of retinopathy, and bronchopulmonary dysplasia in infants weighing < 1250 g at birth prior to the introduction of steroid therapy for chronic lung disease. Ophthalmological data from 67 infants (22 with severe bronchopulmonary dysplasia and 45 controls) who were enrolled prospectively in an early intervention program were analyzed. The infants had two or more eye examinations prior to discharge and a follow-up examination at 12 to 18 months postconceptual age. The incidence of any retinopathy of prematurity was 33%, and severe retinopathy was 25%. Infants with severe bronchopulmonary dysplasia were 1.7 times more likely to develop any retinopathy and 1.8 times more likely to develop severe retinopathy than controls. The incidence of ocular sequelae, was 45%. Infants with any retinopathy had a 2.3 odds of developing sequelae, and infants with severe retinopathy had a 2.64 odds ratio. When adjusted for bronchopulmonary dysplasia, the odds ratio for developing sequelae was 1.36 in infants with any retinopathy and 1.27 in those with severe retinopathy. The predictors of retinopathy were lower birthweight and gestational age, acidosis, and hypoxemia. Bronchopulmonary dysplasia per se has an adverse effect on ophthalmologic morbidity. Evaluation of the adverse effect of any therapy for chronic lung disease on retinopathy of prematurity should make adjustments for the underlying lung disease.

A prospective randomized trial of feeding methods in very low birth weight infants.

OBJECTIVE: To test the hypothesis that very low birth weight infants fed by continuous nasogastric gavage (CNG) would achieve full enteral feedings (100 kcal/kg/d) at an earlier postnatal age and have less feeding intolerance (FI) than infants fed by intermittent bolus gavage (IBG). METHODS: Eighty infants were stratified by birth weight (700 to 1000 g and 1001 to 1250 g) and randomized into CNG or IBG feeding groups. CNG infants were comparable with IBG in birth weight, gestational age, sex, race, and day of onset of feeding (5.7 +/- 2.1 days vs 5.6 +/- 2.2 days, respectively). Feedings were given as undiluted Similac Special Care formula (Ross Laboratories, Columbus, OH) via a specific protocol designed for each 50 to 100 g birth weight category. Feedings were advanced isoenergetically by a maximum of 25 mL/kg/d until an endpoint of 100/kcal/kg/d for at least 48 hours was reached. An infant whose feedings were withheld for >12 hours based on predetermined criteria was considered to have an episode of FI. RESULTS: Infants in the CNG group reached full enteral feeding at 17.1 +/- 8.9 days compared with 15.5 +/- 5.5 days in the IBG group; these were not statistically different. Secondary outcome variables such as days to regain birth weight (CNG, 12.6 +/- 5 days vs IBG, 12.5 +/- 3.7 days), days to reach discharge weight of 2040 g (CNG, 60 +/- 13.4 days vs IBG, 62 +/- 13.6 days), and number of episodes of FI were not significantly different between feeding methods. FI was primarily associated with birth weight

A controlled trial of dexamethasone to prevent bronchopulmonary dysplasia in surfactant-treated infants.

BACKGROUND: Surfactant therapy now has a well-established role in the treatment of neonates with respiratory distress syndrome but has failed to reduce the incidence of bronchopulmonary dysplasia (BPD). We conducted a double-blind, placebo-controlled trial to test the hypothesis that dexamethasone therapy given during the first 12 days of life to very low birth weight infants would be synergistic to surfactant in preventing BPD. METHODS: Seventy surfactant-pretreated infants (700-1500 g) who had severe respiratory distress syndrome (a/A ratio, 0.18 +/- 0.10; mean airway pressure, 11.1 +/- 1.9 cm H2O; fraction of inspired oxygen, 0.81 +/- 0.22) were enrolled to receive a 12-day course of dexamethasone (n = 36) or saline placebo (n = 34) starting within the first 12 hours after birth. The starting dose of dexamethasone was 0.5 mg/kg per day, and it was tapered progressively. RESULTS: Ventilator variables at 5 to 14 days were significantly improved in those infants who received dexamethasone compared with those who received the placebo. The effect seem to be more marked in infants weighting less than 1250 g at birth. Significantly more infants could be extubated by 14 days of age in the dexamethasone group (26 of 32 vs 14 of 32). Dexamethasone therapy reduced the incidence of BPD at 28 days (odds ratio, 0.1; 95% confidence interval, 0.03 to 0.3) and eliminated BPD at 36 weeks' postconceptional age. Dexamethasone-treated infants had greater weight loss at 14 days (12.9 +/- 6.4% vs 3.7 +/- 8.6%, respectively) and higher blood pressures from days 3 to 10. However, no differences were seen in time to regain birth weight, hypertension (1 infant in each group), or incidence of intraventricular hemorrhage. CONCLUSIONS: We found an additive effect between dexamethasone and surfactant in improving pulmonary status and reducing the incidence of BPD. Compared with the placebo, dexamethasone therapy was more effective in reducing the incidence of BPD in surfactant-pretreated very low birth weight infants.

Nebulized furosemide in infants with bronchopulmonary dysplasia.

The effects of 0.1 mg, 0.25 mg, 0.50 mg, and 1.0 mg of nebulized furosemide per kilogram of body weight on pulmonary functions were studied in eight preterm infants with bronchopulmonary dysplasia who were supported by mechanical ventilation. Doses of 1 mg/kg significantly improved lung compliance (51% at 2 hours after nebulization), pulmonary resistance (28% at 1 hour), and tidal volume (43% at 1 hour), starting as early as 30 minutes after the dose; the effect lasted for at least 4 hours in many of the infants and was not associated with diuresis or renal side effects.

Measles antibody titers in early infancy.

OBJECTIVE: To determine the prevalence of measles seronegativity among infants younger than 6 months and to ascertain their serologic response to measles vaccine. DESIGN: Cross-sectional measles antibody survey during the 1989 measles epidemic in Chicago, Ill. SETTING: Inner-city perinatal center. PARTICIPANTS: Two hundred three infants younger than 6 months who had been admitted to the neonatal intensive care unit at birth; 130 (64%) of these infants were premature. Transplacental antibody transfer was evaluated in a subset of 89 mother-newborn pairs. INTERVENTION: Administration of measles monovalent vaccine to seronegative infants. MEASUREMENTS/RESULTS: Measles IgG antibody was measured using indirect fluorescent assay. At birth, 19 (38%) of 50 neonates born at less than 37 weeks' gestation had antibody titers that were twofold to fourfold lower than those of their mothers compared with three (8%) of 39 neonates born at more than 37 weeks' gestation (P < .01). Of the 203 study infants, fewer than 4% were seronegative at birth, while 74% of these infants aged 4 to 5 months were seronegative. Univariate logistic regression analysis indicated that the independent variables related to seronegativity were as follows: gestational age at birth (P = .007), chronological age (P < .001), history of having received three or more packed red blood cell transfusions (P < .001), and maternal age at delivery (P = .001). Multiple logistic regression analysis confirmed the association of seronegativity with chronological age (P < .001), gestational age (P < .02) and maternal age at delivery (P < .001). Seroconversion following administration of the measles vaccine was documented in 11 (79%) of 14 infants. CONCLUSION: A significant proportion of 4- to 5-month-old infants who had been admitted to the neonatal intensive care unit at birth lack measurable measles antibody; this population should be taken into account when strategies to control measles are considered.

Evaluation of the relationship between cocaine and intraventricular hemorrhage.

To evaluate the relationship of cocaine to intraventricular hemorrhage in preterm (< or = 37 weeks gestation) infants, the charts of infants admitted to an intensive care nursery over a 2-year period were reviewed. Data were extracted regarding intrauterine exposure to cocaine, head ultrasonography, and specific independent variables: gestational age, 5-minute Apgar score, and the presence of pneumothorax. These variables were classified into high-, moderate-, and low-risk groups for the development of intraventricular hemorrhage. Analysis was done using chi-square, Mantel-Haentzel tests, crude odds ratio with 95% tests, crude odds ratio with 95% confidence intervals, and stepwise multiple logistic regression analysis. Intraventricular hemorrhage developed in 24 (22%) cocaine-exposed infants versus 49 (20%) nonexposed infants. Thirteen (12%) infants exposed to cocaine developed grades I to II and 11 (10%) developed grades III to IV intraventricular hemorrhage. The figures in the nonexposed infants were 29 (12%) and 20 (8%), respectively. Intraventricular hemorrhage was more likely to occur in infants who belonged to the high-risk groups: gestational age < or = 30 weeks, 5-minute Apgar score < or = 5, and the presence of pneumothorax. Pneumothorax was the single most significant factor associated with intraventricular hemorrhage grades III to IV. Intrauterine exposure to cocaine does not seem to influence the prevalence or severity of intraventricular hemorrhage in the preterm infant.

Management of asymptomatic neonates with prolonged rupture of membranes.

Guidelines for management of asymptomatic term and preterm neonates born to mothers with prolonged rupture of membranes (PROM) have not been clearly established. A survey was conducted to identify current management practice of neonatologists in midwestern states and to find if there is consensus among physicians with regard to management of PROM without chorioamnionitis, with chorioamnionitis but without treatment prior to delivery, and with intrapartum maternal antibiotic therapy prior to delivery. One hundred thirty seven responses to the questionnaire were received. Management of asymptomatic at risk neonates varied in different clinical scenarios. Preterm neonates were screened (94% vs 82%, p < 0.001) and treated (64% vs 41%, p < 0.001) more often than term babies. In the absence of maternal symptoms of chorioamnionitis, term neonates were usually observed or treated based on screening test results. With maternal symptoms, 94% of physicians ordered screening test. Prematurity and perceived severity of maternal illness significantly influenced the decision to treat routinely irrespective of screening test results. Physicians favour routine treatment of infants born to mothers who had received intrapartum antibiotic therapy; opinion was divided about management of term asymptomatic infant born to mothers with chorioamnionitis without intrapartum antibiotic therapy. Lumbar punctures were not routinely done for term or preterm neonates prior to antibiotic therapy. Further studies are needed to answer questions regarding the benefits and risks of routine therapy of high risk neonates vs routine clinical observation and selective therapy of only infants who develop symptoms.

Endocarditis in neonatal intensive care unit.

The clinical spectrum of infective endocarditis (IE) in infants is examined in four infants between 3 and 9 months of age. None of the patients had signs of IE; all four had an anatomically normal heart. Echocardiograms showed echo-dense vegetations in the left side of heart in three cases and in the right side in one. Three of the four patients recovered after the episode of endocarditis. Three of the four patients had necrotizing enterocolitis in the neonatal period. The important predisposing factor was the presence of indwelling central catheter for intravenous nutrition. Unlike previously reported cases, coagulase-negative Staphylococci and Enterococci were important causative organisms in this high-risk nursery population.

Ontogeny of stool passage in low birth weight infants < or = 1500 grams.

The onset of stool passage, timing of transition to yellow stools and the pattern of stooling frequency over the first 4 weeks were studied in infants < 1500 g at birth. The time of passage of the first stool (median, 19) correlated with birth weight and gestational age but not with presence or severity of respiratory distress; fourteen percent passed stool after 1st 48 hours. Transition to yellow occurred at 17.6 +/- 6.4 days and was related to the onset of feeding and birth weight. Stooling frequency was similar in Wk 2 as Wk 1, increased in Wk 3 and plateaued on Wk 4. Volume of feeding/day increased each week over that of preceding week but stooling frequency was not related to the increased volume or any of the other variables.

Early postnatal dexamethasone therapy in premature infants with severe respiratory distress syndrome: a double-blind, controlled study.

To determine whether early (less than or equal to 12 hours) postnatal dexamethasone therapy would facilitate removal of the endotracheal tube and improve outcome in premature infants with severe respiratory distress syndrome, we conducted a double-blind, controlled study of 57 infants whose birth weights were less than 2000 gm. The placebo (n = 29) and treated (n = 28) groups were comparable in birth weight (mean +/- SD: 1273 +/- 323 vs 1318 +/- 359 gm), gestational age (30.1 +/- 2.1 vs 30.8 +/- 2.7 weeks), postnatal age (8.7 +/- 3.1 vs 8.5 +/- 3.1 hours), and pulmonary function at the start of the study. The dose of dexamethasone was 1.0 mg/kg/day for 3 days and then was progressively decreased for 12 days. Infants in the dexamethasone group had significantly higher pulmonary compliance, tidal volume, and minute ventilation, and required lower mean airway pressure for ventilation than infants in the placebo group. The endotracheal tube was successfully removed from more infants in the dexamethasone group (16/28 vs 8/29; p less than 0.025). Nineteen infants (65%) in the placebo group and 11 (39%) in the dexamethasone group (p less than 0.05) had lung injuries. Dexamethasone therapy was associated with a temporary increase in blood pressure and plasma glucose concentration and a delay in somatic growth. We conclude that early postnatal dexamethasone therapy improves pulmonary status, facilitates removal of the endotracheal tube, and minimizes lung injuries in premature infants with severe respiratory distress syndrome.

Maternal and cord serum glycosylated protein in neonatal macrosomia and correlation with birth weight.

Maternal glycosylated hemoglobin and glycosylated protein and cord glycosylated protein were measured at delivery in 20 normal mothers of 20 macrosomic neonates over 4000 g (group I) and compared with values in two groups of mother/infant pairs: 20 normal/20 appropriate for gestational age (group II) and nine diabetic mothers/ten neonates (group III). Infants in group I, by design, weighed more (mean +/- SD 4403 +/- 337 g) than those in group II (2902 +/- 278 g) or group III (3365 +/- 898 g) (P less than .001). There was no significant difference in weight between group II and group III infants. Birth weight ratio was greater (P less than .001) in group I than in group II or group III (1.39 +/- 0.1, 0.9 +/- 0.08, and 1.08 +/- 0.25, respectively); group III infants had a higher birth weight ratio (P less than .05) than those in group II. Hematocrit (%) was higher (P less than .05) in group III (62 +/- 3) than in group I (59 +/- 5) or group II (57 +/- 6) infants. Glycosylated hemoglobin values were similar in all three groups. Mean serum glycosylated protein was higher (P less than .001) in group III (13.8 +/- 2%) than in group I (10 +/- 2%) or group II (9.8 +/- 2.5%) mothers. Cord glycosylated protein was also higher (P less than .001) in group III (12.3 +/- 1.9%) than in group I (9 +/- 1.3%) or group II (8.6 +/- 1.7%) neonates.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma amino acid patterns in very low birth weight infants during parenteral nutrition.

Plasma amino acids were measured in eight very low birth weight infants (less than or equal to 1000 gm) before and after infusion of parenteral alimentations with Freamine III. Significant elevation in serum threonine, valine, isoleucine, methionine, serine, proline, glycine and ornithine was noted after twenty four hours of infusion. On the other hand, significant decreases in taurine and tyrosine levels were noted. Our study suggests that current solution is not optimal for premature neonates and the amount of protein administered during the first week in infants weighing less than or equal to 1000 gm should be decreased from the recommended 2.5-3.0 gm/kg/day.

Metabolic rate and energy balance in infants with bronchopulmonary dysplasia.

To determine energy use and growth of infants with bronchopulmonary dysplasia (BPD), we studied metabolic rate and energy balance in five infants with stage III-IV BPD (birth weight 1309 +/- 530 gm, gestational age 32 +/- 3 weeks, postnatal age 59.8 +/- 14.2 days) and in five control infants (birth weight 1540 +/- 213 gm, gestational age 33 +/- 2 weeks, postnatal age 42.0 +/- 4.2 days). Infants with BPD had significantly lower energy intake but higher energy expenditure than did control infants. Weight gain and energy cost of growth were significantly less in BPD infants than in control infants, as were urine output and output/intake ratio. We conclude that infants with BPD (1) absorbed caloric intake as well as did normal control infants, (2) had low energy intake and high energy expenditure, resulting in poor weight gain, and (3) had low energy cost of growth, suggesting an alteration in composition of tissue gain, with relatively high water content.

Indomethacin therapy in premature infants with patent ductus arteriosus--determination of therapeutic plasma levels.

To determine the therapeutic range of plasma indomethacin levels for ductus closure, we evaluated the ductus response and renal side effects on two therapeutic regimens using different dosage; regimen I received 0.3 mg/kg q 24 h for a maximum of 3 doses, and regimen II received 0.1, 0.2 and 0.3 mg/kg at 24-hour intervals, for a maximum of 3 doses if needed. Infants in regimen I had significantly higher plasma indomethacin and higher ductus response rate than infants in regimen II. Urine output (U/O) was comparable between the regimens, but serum sodium was lower in regimen I than in regimen II. In both regimens, U/O and serum sodium return to normal by 72 h. The plasma indomethacin levels at 12 h after 1 dose correlated significantly with ductus response and hyponatremia. There appeared to be a minimal level of plasma indomethacin above which U/O decreased; with a plasma level greater than 170 ng/ml the majority (greater than 97%) of infants showed a decrease in U/O. While there was a 50% or greater chance that ductus would close when the plasma levels reached 600 ng/ml or more, a great proportion of infants would also develop renal side effects. Thus, a safe therapeutic range of plasma indomethacin appeared to be very narrow. However, when the dose of indomethacin is increased to optimize constrictive response, there is no significant increase in incidence and severity of renal adverse effects. In view of the transient nature of renal side effects, they should not hinder indomethacin therapy if ductus closure is indicated.

Chest physiotherapy in preterm infants with RDS in the first 24 hours of life.

To evaluate if chest physiotherapy is beneficial to premature infants with respiratory distress syndrome (RDS) during the first 24 hours of life, 20 infants were randomly assigned to two groups; 10 infants in Group I received routine chest physiotherapy and suction, and 10 infants in Group II received suction only. The birth weight, gestational age, postnatal age, Apgar scores, blood gases, acid-base status, and ventilatory requirements prior to study were comparable between the two groups. There were no significant differences between the groups in the amount of endotracheal secretions removed, the PO2/FIO2 ratio, blood gases, and pH during the study. The incidence of patent ductus arteriosus (PDA), bronchopulmonary dysplasia (BPD), Grade I and II intraventricular hemorrhage (IVH), and mortality was comparable. However, five of 10 Group I and zero of 10 Group II infants developed Grade III or IV IVH (P less than 0.05).

Indomethacin therapy in infants with advanced postnatal age and patent ductus arteriosus.

A trial of intravenous indomethacin therapy was performed on 11 premature infants whose postnatal age was 8 weeks or more (mean 65.3 days). In an attempt to maintain the desired plasma level, indomethacin was given at a dosage of 0.3 mg/kg, at 8-hour intervals (total dose 0.9 mg/kg) for a total of 3 doses. In spite of desirable plasma indomethacin levels (which ranged from 280-870 ng/ml) and area under the curve (24.1 micrograms/hr/ml), calculated from time 0 to 24 hrs after the initial dose, none of the infants responded to indomethacin with ductus closure. There were a transient significant decrease in urine output, creatinine clearance, and fractional excretion of sodium. The present study confirms the clinical impression that Indomethacin is ineffective for the closure of ductus arteriosus in infants with advanced postnatal age.