alpha1-Proteinase inhibitor therapy for the prevention of chronic lung disease of prematurity: a randomized, controlled trial. A three-day course of dexamethasone therapy to prevent chronic lung disease in ventilated neonates: a randomized trial. Early postnatal dexamethasone for the prevention of chronic lung disease in high-risk preterm infants. Aggressive or expectant management for patients with severe preeclampsia between 28-34 weeks' gestation: a randomized controlled trial. Randomized trial of a parenting intervention for very preterm infants: outcome at 2 years. Preterm infants born at less than 31 weeks' gestation have improved growth in cycled light compared with continuous near darkness. Open randomised controlled trial of inhaled nitric oxide and early dexamethasone in high risk preterm infants. Randomised trial of effect of delayed intravenous lipid administration on chronic lung disease in preterm neonates. Prophylaxis against early adrenal insufficiency to prevent chronic lung disease in premature infants.
An imbalance between increased neutrophil elastase and a decreased antiprotease shield has been suggested as a factor contributing to the development of chronic lung disease (CLD). We hypothesized that administration of alpha1-proteinase inhibitor (A1PI), also known as alpha1-antitrypsin, to premature neonates would prevent CLD.
                A randomized, placebo-controlled, prospective study of A1PI supplementation was performed. Neonates <24 hours of age with birth weights 600-1000 g on respiratory support, and 1001-1250 g with respiratory distress syndrome (RDS) were eligible. Intravenous A1PI (60 mg/kg) or placebo was infused on days 0, 4, 7, and 14. Primary outcome was CLD in survivors, defined as the need for supplemental oxygen on day 28.
                A total of 106 patients were recruited. There were no significant differences between groups in birth weight or incidence of RDS. The incidence of CLD in survivors was lower in the treated group, but the difference did not reach statistical significance (relative risk [RR], 0.79; confidence interval [CI], 0.60-1.02). This beneficial trend persisted at 36 weeks corrected gestational age (RR, 0.48; CI, 0.23-1.00). The incidence of pulmonary hemorrhage was lower in the treated group (RR, 0.22; CI, 0.05-0.98). Other complications were not significantly different between groups.
                In this, the first trial of a protease inhibitor for the prevention of CLD in premature infants, the infusions were well-tolerated. A1PI therapy may impede the development of CLD and appears to reduce the incidence of pulmonary hemorrhage in some neonates born prematurely. Although several trials of early dexamethasone therapy have been completed to determine if such therapy would reduce mortality and chronic lung disease (CLD) in infants with respiratory distress, optimal duration and side effects of such therapy remain unknown.
                The purpose of this study was: 1) to determine if a 3-day course of early dexamethasone therapy would reduce CLD and increase survival without CLD in neonates who received surfactant therapy for respiratory distress syndrome and 2) to determine adverse effects associated with such therapy.
                This was a prospective multicenter randomized trial comparing a 3-day course of dexamethasone therapy beginning at 24 to 48 hours of life to placebo therapy. Two hundred forty-one neonates (dexamethasone n = 118, placebo n = 123), who weighed between 500 g and 1500 g, received surfactant therapy, and were at significant risk for CLD or death using a model to predict CLD or death at 24 hours of life, were enrolled in the trial. Infants randomized to receive early dexamethasone were given 6 doses of dexamethasone at 12-hour intervals beginning at 24 to 48 hours of life. The primary outcomes compared were survival without CLD and CLD. CLD was defined by the need for supplemental oxygen at the gestational age of 36 weeks. Complication rates and adverse effects of study drug therapy were also compared.
                Neonates randomized to early dexamethasone treatment were more likely to survive without CLD (RR: 1.3; 95% CI: 1.03, 1.7) and were less likely to develop CLD (RR: 0.6; CI: 0.3, 0. 98). Mortality rates were not significantly different. Subsequent dexamethasone therapy use was less in early dexamethasone-treated neonates (RR: 0.8; CI: 0.7, 0.96). Very early (</=7 days of life) intestinal perforations were more common among dexamethasone-treated neonates (8% vs 1%).
                We conclude that an early 3-day course of dexamethasone therapy increases survival without CLD, reduces CLD, and reduces late dexamethasone therapy in high-risk, low birth weight infants who receive surfactant therapy for respiratory distress syndrome. Potential benefits of early dexamethasone therapy at the dosing schedule used in this trial need to be weighed against the risk for early intestinal perforation. The purpose of this study was to evaluate the effect of early administration of dexamethasone on the incidence of chronic lung disease (CLD) in high risk preterm infants and to evaluate the side effects of the early steroid administration.
                Randomised clinical trial.
                Neonatal intensive care unit.
                50 infants at high risk of CLD were randomly assigned after 72 h of life to the dexamethasone group (n = 25) or to the control group (n = 25). The treated infants received dexamethasone intravenously from the 4th day of life for 7 days (0.5 mg/kg per day for the first 3 days, 0.25 mg/kg per day for the next 3 days and 0.125 mg/kg per day on the 7th day). The control group received no steroid treatment.
                The incidence of CLD at 28 days of life and at 36 weeks' postconceptional age was significantly lower in the dexamethasone group than in the control group (p < 0.001). Moreover, infants in the dexamethasone group remained intubated and required oxygen therapy for a shorter period than those in the control group (p < 0.001). Hyperglycaemia, hypertension, growth failure and mainly hypertrophy of the left ventricle were the transient side effects associated with early steroid administration.
                Early dexamethasone administration may be useful in preventing CLD, but its use should prudently be restricted to preterm infants at high risk of CLD. Fifty-eight women with severe preeclampsia between 28-34 weeks' gestation qualified for a randomized controlled trial to establish whether elective delivery 48 hours after administration of betamethasone (aggressive-management group) or delivery later as indicated by maternal or fetal condition (expectant-management group) was more beneficial to maternal and fetal outcome. Twenty women who qualified were not randomized because they developed maternal or fetal indications necessitating delivery within 48 hours; these newborns developed most of the complications. Expectant management was not associated with an increase in maternal complications, but it significantly prolonged the gestational age (mean 7.1 days; P less than .05), reduced the number of neonates requiring ventilation (P less than .05), and reduced the number of neonatal complications (P less than .05). To determine the efficacy of a neonatal parenting intervention for improving development in very preterm infants.
                A cluster-randomized, controlled trial with a cross-over design and washout period was conducted in 6 neonatal centers. Two hundred thirty-three babies <32 weeks' gestation were recruited (intervention = 112; control = 121). Intervention families received weekly Parent Baby Interaction Programme (PBIP) sessions during neonatal intensive care unit admission and up to 6 weeks after discharge. Control families received standard care. All 195 infants remaining in the study at 24 months' corrected age were assessed by psychologists blinded to group allocation.
                There was no significant difference in Mental Development Index (-0.9 points; 95% CI, -5.0, 3.2) or Psychomotor Development Index (2.5; -3.3, 8.4) scores between the intervention and control groups and no significant effect of intervention on Mental Development Index or Psychomotor Development Index scores for subgroups dichotomized by gestational age (<28 weeks/> or =28 weeks), parity (1st/other child) or mother's cohabiting status (supported/unsupported).
                There was no effect of PBIP on infant development at 2 years' corrected age. Parenting interventions may be better delivered after discharge or targeted for preterm infants with high biological and social risk. Our purpose was to evaluate the benefits of cycled light (CL) versus near darkness (ND) on health in preterm infants born at <31 weeks' gestational age.
                Randomized, interventional study comparing infants receiving (1) CL from birth, (2) CL at 32 weeks' postconceptional age (PCA), and (3) CL at 36 weeks' PCA in transition for discharge home. Statistical significance was assessed with segmented mixed general linear models, analysis of covariance, general estimating equations, chi(2), and Fisher's exact procedure.
                Infants receiving CL at birth and 32 weeks' PCA gained weight faster than infants not receiving CL until 36 weeks' PCA. There were no differences among the groups in length of hospitalization stay or number of ventilator days, but the power was low for these variables.
                These findings suggest that CL has significant weight gain benefits over ND, and there are no short-term advantages of ND over cycled light for health in preterm infants. To determine whether treatment with inhaled nitric oxide (NO) and/or dexamethasone reduces the incidence of chronic lung disease (CLD) and/or death in high risk preterm infants.
                Infants below 32 weeks of gestation were recruited at 96 hours of age if they were deemed to be at high risk of developing CLD. Infants were randomly assigned to one of four treatment groups using a factorial design: (1) 5-20 parts per million inhaled NO for 72 hours; (2) 0.5-1 mg/kg/day intravenous dexamethasone for 6 days; (3) both drugs together; (4) continued conventional management.
                Forty two infants were randomised: 10 infants received inhaled NO alone; 11 dexamethasone alone; 10 both treatments; and 11 neither treatment. There was no difference in the combined incidence of CLD and/or death before discharge from hospital between either infants treated with inhaled NO and controls (RR 1.05, 95% CI 0.84-1.25), or those treated with dexamethasone and controls (RR 0.95, 95% CI 0.79-1.18).
                At 96 hours of age, neither treatment with inhaled NO nor dexamethasone prevented CLD or death. A recent sevenfold increase in the annual incidence of chronic neonatal lung disease (CNLD) on an intensive care unit was attributed to the early administration of intravenous lipid (IVL) in ventilated preterm neonates. When logistic regression was used to eliminate other confounding variables, early delivery of IVL was independently associated with an eight-fold increase in the likelihood of CNLD. Consequently, we designed a prospective study to detect a halving of the incidence of CNLD by delaying IVL administration from 5 days (as is routine practice) to 14 days. Sixty-four parenterally fed preterm neonates weighing < 1,500 g at birth were randomised to receive IVL either on day 5 or day 14. Analysis was by intention to treat, since several infants in the latter group required no parenteral nutrition by day 14. Our results showed that the relative risk (95% confidence interval) of CNLD at 28 postnatal days was 1.15 (0.81-1.62); at 36 weeks postconception, it was 1.08 (0.59-1.99). A study population of > 2,000 would be required to determine whether these relative risks were significantly different from 1. BACKGROUND. Many extremely low birth weight infants (<1000 g) show biochemical evidence of adrenal insufficiency in the first week of life, correlating with subsequent development of chronic lung disease (CLD).
                We conducted a randomized, double-masked, placebo-controlled pilot study to test whether early treatment with low-dose hydrocortisone for 12 days (1 mg/kg/day for 9 days followed by.5 mg/kg/day for 3 days), begun before 48 hours of life, would increase the likelihood of survival without CLD.
                Forty patients were enrolled at two centers. Birth weight and gestation were similar for treatment and placebo groups: 732 +/- 135 g versus 770 +/- 135 g and 25.2 +/- 1.3 weeks versus 25.4 +/- 1.5 weeks. More infants treated with hydrocortisone achieved study success, defined as survival without supplemental oxygen at 36 weeks' postconception (12/20 [60%] vs 7/20 [35%]). Lower birth weight, histologic chorioamnionitis, and preeclampsia were significant risk factors, whereas study center, prenatal steroids, sex, and ethnicity were not significant. Hydrocortisone treatment decreased days on >40% oxygen, days on >25% oxygen, days on ventilator, and oxygen at discharge. Among infants exposed to chorioamnionitis, hydrocortisone treatment also was associated with increased enteral intake during the first month of life and with increased weight at 36 weeks' postconception. Five treated infants and 6 placebo infants developed sepsis; 3 in each group died.
                First, early treatment with low-dose hydrocortisone in this population of extremely low birth weight infants increased the likelihood of survival without CLD. Second, the benefit was particularly apparent in infants with chorioamnionitis. Third, a larger multicenter trial is needed to verify the primary outcome and to better evaluate risks and benefits.
Prophylactic administration of a1PI did not reduce the risk of CLD at 36 weeks or long term adverse developmental outcomes in preterm neonates.