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In a randomized trial to determine whether oral vitamin E reduced stages III and IV bronchopulmonary dysplasia (BPD) by 50%, 268 infants were randomly allocated, after stratification by birth weight and severity of disease, to receive vitamin E 25 units or an indistinguishable placebo. The experimental (E) group and the control (C) group were similar in weight, gestational ages, Apgar scores, severity of illness, and initial oxygen and ventilator exposure. Serum vitamin E levels were significantly different within 48 h of administration and remained well above normal adult levels from the first week of life in the experimental group. There was no difference in the rates of early death, BPD at 28 days, or mortality from BPD. Severity was similar and no difference was seen in the incidence of necrotizing enterocolitis or sepsis. There was no evidence that vitamin E supplementation offered protection against chronic lung disease in infants less than 1,500 g birth weight.
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PMID:Failure of supplementation with vitamin E to prevent bronchopulmonary dysplasia in infants less than 1,500 g birth weight. 204 36

Fifty-six neonates with enterococcal septicemia in a single hospital from 1977 through 1986 were studied. The incidence was low and constant until 1983, when an increase, attributable to infections in infants older than 7 days of age (late-onset), was noted. These infants were more premature (mean gestational age 29.5 vs 36.9 weeks) and had lower birth weights (mean 1250 vs 2700 g) than those with early-onset enterococcal sepsis, and in most the infections were characterized by a nosocomial origin. Infants with early-onset infection had a mild illness with respiratory distress typical of other etiologic agents or diarrhea without focal infection. By contrast, late-onset enterococcal sepsis was heralded by severe apnea, bradycardia, circulatory collapse, and increased ventilatory requirements. Focal infections, including scalp abscess or catheter-related infection (23% each), meningitis or pneumonia (15% each), were common. Rapid clinical improvement and clearance of bacteremia resulted from therapy with an aminoglycoside and either ampicillin or vancomycin, but only if abscesses were drained and intravascular catheters were removed. Mortality rates for early-onset, late-onset, and necrotizing enterocolitis-associated infection were 6, 8, and 17%, respectively. Enterococcus is a frequent cause of late-onset septicemia in premature neonates, and empiric therapy should include appropriate antimicrobial agents.
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PMID:Enterococcal sepsis in neonates: features by age at onset and occurrence of focal infection. 210 74

Premature infants demonstrate hypoglobulinemia and are at increased risk for serious infections. Although a cause-and-effect relation between low serum IgG levels and neonatal infections has not been established, prophylaxis of such severe infections may be possible by replacement of antibody with intravenous immunoglobulin (IVIG). For success, IVIG must provide specific antibodies to neonatal pathogens and reach therapeutic serum IgG target levels. Pilot investigations have demonstrated that IVIG reduces the incidence of bacterial sepsis among premature infants. Infants received IVIG every 2 weeks (or more frequently) until they weighed 2,000 g. Serum IgG levels were monitored after each dose so that the dose could be adjusted to achieve a target IgG level greater than 700 mg/dL. The observation that infection among placebo-treated patients occurred when the serum IgG level declined to less than 400 mg/dL suggests the importance of achieving a target level. In our preliminary analysis, the IVIG used did not reduce the incidence of infection with respiratory syncytial virus (RSV) and rotavirus or of necrotizing enterocolitis. That the lot of IVIG used did not contain significant antibody to RSV or rotavirus emphasizes the importance of pathogen-specific antibody. Because of the preliminary nature of these results and the potential for undetermined short-term and long-term sequelae, we do not recommend the indiscriminant use of IVIG for prevention or treatment of neonatal infections.
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PMID:Targeted immunoglobulin therapy for the prevention of neonatal infections. 211 35

From 1979 to 1986, 82 infants underwent surgical treatment for necrotizing enterocolitis (NEC), with 36 deaths. The records of 30 of the 36 infants who died were available for review. Fungal colonization and sepsis, the sites of infection, and timing of diagnosis and therapy were determined. Sixteen of 30 (53%) neonates had no evidence of fungus. Six (20%) were colonized with Candida species. Eight (27%) had fungal sepsis, with two of these eight found only at necropsy. Positive fungal blood cultures were a late finding. In only four of the six patients with positive blood cultures were the results known in time to initiate treatment with amphotericin B. Two of these four babies received less than 2 days of amphotericin B treatment prior to death. Fungal sepsis is a significant lethal factor in the surgical mortality of NEC. Vigorous efforts at earlier diagnosis are mandatory.
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PMID:The hidden mortality in surgically treated necrotizing enterocolitis: fungal sepsis. 212 15

A 93% survival rate was achieved in 80 neonates treated for gastroschisis between 1979 and 1986. Uncomplicated gastroschisis occurred in 70 infants (88%); 51% underwent staged silo reduction and 49% had primary fascial closure. Gastroschisis associated with intestinal atresia or volvulus was present in 10 neonates (12%), half of whom had a residual jejunoileum between 10 and 55 cm. Major postoperative complications included gastrointestinal problems (infarction, obstruction, and prolonged dysfunction), wound infection, and catheter-associated difficulties (sepsis, infiltration, and malposition). Three of the six deaths were related to associated conditions (extreme prematurity, trisomy 13, and multiple anomalies) and three were caused by intraoperative hemorrhage, necrotizing enterocolitis, and extensive short-bowel syndrome. No statistical difference in morbidity, mortality, and length of hospitalization was demonstrated between infants treated by silo reduction and primary closure. Safe management of gastroschisis should include an individualized assessment of visceroabdominal disproportion and degree of intraabdominal tension. Vigilant expectation of potentially life-threatening complications is required to decrease postoperative morbidity, irrespective of the technique of abdominal wall closure.
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PMID:An individualized approach to the management of gastroschisis. 213 18

Congenital tuberculosis is a rare disease, difficult to be correctly diagnosed from clinical manifestations alone without maternal tuberculous history. In this article we report a neonate who exhibited abdominal distension and bloody diarrhea simulating neonatal sepsis and necrotizing enterocolitis. Exploratory laparatomy was performed for the markedly distended abdomen and deteriorated condition. Calcified lymph nodes over mesentery and spleen were found, and biopsy was done to show caseous tubercles. However, this neonate deteriorated rapidly and died one day after operation. Autopsy revealed generalized discrete miliary tubercles over the lungs, liver, spleen, pancreas, adrenal glands, thyroid and lymph nodes.
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PMID:Congenital tuberculosis: a case report. 216 75

A randomized, double-blind study to determine the effect of intramuscular vitamin E on mortality and intracranial hemorrhage (ICH) was performed. One hundred forty-nine neonates with birth weights less than or equal to 1000 g and less than or equal to 24 hours of age were grouped by weight (501 to 750 g and 751 to 1000 g) and randomized to treatment or control. The treatment group received intramuscular injections of vitamin E (dl-alpha-tocopherol) on days 1, 2, 4, and 6 of life. The control group received intramuscular injections of placebo on the same schedule. All neonates initially received oral vitamin E (100 mg/kg/day dl-alpha-tocopheryl acetate), which was subsequently adjusted to keep serum levels at 0.5 to 3.5 mg/dL. Ultrasonographic examinations of the head were performed as possible on days 1, 5 to 7, and 12 to 14. Hemorrhage was defined as mild if less than or equal to grade II ICH, or severe if grade III or IV. No significant differences in neonatal or total hospital mortality between groups were found. However, all ICH, as well as severe ICH, were significantly less in the vitamin E-treated 501 to 750-g subgroup (all ICH: 60% vs 29%; severe ICH: 32% vs 4%). When survivors were analyzed separately, a significant decrease in severe ICH was seen in the vitamin E-treated neonates (25% vs 5%). Necrotizing enterocolitis and sepsis did not occur more frequently in the neonates treated with intramuscular injections of vitamin E. Other than two cases of mild induration at injection sites, no deleterious side effects of treatment were identified. Vitamin E may have a role in the prevention of severe ICH in premature neonates weighing between 501 and 750 g.
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PMID:Effect of intramuscular vitamin E on mortality and intracranial hemorrhage in neonates of 1000 grams or less. 217 50

A multicenter, prospective randomized controlled trial was performed comparing the efficacy of a single intratracheal dose of modified bovine surfactant extract (Survanta, 100 mg/kg, Abbott Laboratory, North Chicago, IL) with air placebo in preventing respiratory distress syndrome. Infants were enrolled if they were estimated to be between 24 and 30 weeks' gestation, weighed between 750 and 1250 g, and were intubated and stabilized within 15 minutes after birth. A total of 160 infants were treated (79 with surfactant, 81 with air placebo) between 4 and 37 minutes after birth (median time 12 minutes). Of these, 5 infants were excluded from the final analysis. The 72-hour average values for the arterial-alveolar oxygen ratio, fraction of inspired oxygen, and mean airway pressure were calculated from the area under the curve of scheduled values measured throughout 72 hours. Clinical status was classified using five ordered categories (no supplemental oxygen or assisted ventilation, supplemental oxygen only, continuous positive airway pressure or assisted ventilation with intermittent mandatory ventilation less than or equal to 6 breaths/min, assisted ventilation with intermittent mandatory ventilation greater than 6 breaths/min, death). Chest radiographs at 24 hours were graded for severity of respiratory distress syndrome. Infants receiving Survanta had less severe radiographic changes at 24 hours of age and decreased average fraction of inspired oxygen (31% vs 42%, P = .002) compared with control infants. No differences were noted in the average arterial-alveolar oxygen ratio, mean airway pressure, or clinical status on days 7 and 28. A beneficial effect was noted in the incidence of pneumothorax (P = .057) and an increase was noted in the incidence of necrotizing enterocolitis (P = .052). No differences in incidence of patent ductus arteriosus, intraventricular hemorrhage, sepsis, or bronchopulmonary dysplasia were seen. According to results of a secondary analysis, there was improvement in the fraction of inspired oxygen and a greater number of survivors without bronchopulmonary dysplasia in the subgroup of infants weighing less than 1000 g who were treated with surfactant. It was concluded that a single dose of Survanta given shortly after birth resulted in decreased severity of chest radiographic findings 24 hours after treatment and improved oxygenation during 72 hours after treatment, but did not improve other acute measures of disease severity or clinical status later in the neonatal period. The group at highest risk for respiratory distress syndrome (infants with birth weights between 750 and 999 g) may benefit the most from preventive therapy.
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PMID:Multicenter trial of single-dose modified bovine surfactant extract (Survanta) for prevention of respiratory distress syndrome. Ross Collaborative Surfactant Prevention Study Group. 218 76

We performed a case-control study to determine whether fetuses delivered prematurely because of pregnancy complications (primarily pregnancy-associated hypertensive disease) had a different neonatal course than that of those born after either spontaneous preterm labor or after premature rupture of the membranes. Two case-control populations were matched by gestational age at delivery, fetal sex, and race. There was no perinatal survival advantage in babies delivered from "stressed" pregnancies. Selected neonatal morbidities were generally similar, but there was an increased incidence of necrotizing enterocolitis in babies born after preterm labor and a higher incidence of both necrotizing enterocolitis and neonatal sepsis after premature rupture of the membranes. We conclude that a "stressed" pregnancy confers a negligible survival advantage to the fetus.
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PMID:Is indicated or spontaneous preterm delivery more advantageous for the fetus? 220 74

The effects of a single dose of surfactant TA were assessed in premature neonates (birth weight 750 to 1749 g) with respiratory distress syndrome (RDS) in a multicenter, double-blind, randomized clinical trial. Only neonates with surfactant deficiency and without ultrasonographic evidence of intracranial hemorrhage greater than or equal to grade II were enrolled. Fifty-four patients received surfactant (100 mg of phospholipid per kilogram of body weight) and 46 patients received an air placebo within 8 hours of life. Treatment with this surfactant resulted in a significant reduction in the severity of RDS with a concomitant increase in the proportion of neonates with mild disease. The frequency of pulmonary interstitial emphysema and of pneumothorax was significantly lower in treated neonates compared with control neonates (2% vs 26%, P = .0008, and 7% vs 39%, P = .0004, respectively). The frequency of intracranial hemorrhage was significantly lower in the surfactant group compared with the control group (20% vs 54%, P = .0008) and was also reduced for the smallest neonates in the surfactant group (13% vs 73%, P = .00008). When categorized according to severity of intracranial hemorrhage and severity of bronchopulmonary dysplasia, the surfactant group was at a significant advantage (adjusted Cochran-Mantel-Haenszel X2 = 10.72, P less than .001 and X2 = 4.43, P = .036, respectively). The proportion of neonates surviving without intracranial hemorrhage and/or bronchopulmonary dysplasia was 63% in the surfactant group vs 26% in the control group (P = .0004); as for the smallest neonates, it was 58% in the surfactant group vs 4% in the control group (P = .0002). There were no differences between the groups with respect to the frequency of patent ductus arteriosus (46% vs 37%), pulmonary hemorrhage (6% vs 7%), necrotizing enterocolitis (0% vs 2%), sepsis (4% vs 2%), retinopathy of prematurity (13% vs 22%), or death (15% vs 22%). It is concluded that treatment with the single-dose surfactant regimen used in this study reduces the severity of respiratory distress during the 48 hours after treatment and decreases the major pulmonary morbidity and intracranial hemorrhage in premature neonates with RDS. Further studies are needed to determine whether (1) treatment at birth or as soon as after RDS is diagnosed and (2) the use of multiple dose of this surfactant would result in any additional benefits.
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PMID:Surfactant replacement therapy with a single postventilatory dose of a reconstituted bovine surfactant in preterm neonates with respiratory distress syndrome: final analysis of a multicenter, double-blind, randomized trial and comparison with similar trials. The Surfactant-TA Study Group. 223 30


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