A randomized, controlled trial of antepartum thyrotropin-releasing hormone and betamethasone in the prevention of respiratory disease in preterm infants. Collaborative trial of prenatal thyrotropin-releasing hormone and corticosteroids for prevention of respiratory distress syndrome. Collaborative Santiago Surfactant Group. Respiratory disease in very-low-birthweight infants after prenatal thyrotropin-releasing hormone and glucocorticoid. TRH Study Group. Risk of respiratory distress syndrome after prenatal dexamethasone treatment. Postnatal triiodothyronine replacement and respiratory distress syndrome of the preterm infant. Failure of early postnatal dexamethasone to prevent chronic lung disease in infants with respiratory distress syndrome. Postnatal thyroxine administration for idiopathic respiratory distress syndrome in preterm infants. Corticosteroid therapy for prevention of respiratory distress syndrome in severe preeclampsia. [Value of prenatal corticotherapy in the prevention of hyaline membrane disease in premature infants. Randomized prospective study].
The objective was to investigate whether the addition of thyrotropin-releasing hormone to antepartum betamethasone further reduces the incidence of respiratory disease in preterm infants.
                A randomized, placebo-controlled, double-blind trial of antepartum thyrotropin-releasing hormone (400 micrograms given intravenously four times) and betamethasone (5 mg given intramuscularly four times) was conducted in 378 mothers likely to be delivered between 24 and 32.6 weeks' gestation. Statistical analysis was by relative risk, chi 2, t tests, and multiple logistic regression analysis.
                Four hundred five live-born infants were delivered. In infants without lethal abnormalities delivered between 24 hours and 10 days from entry (n = 175) the incidence of respiratory distress syndrome was reduced from 52% to 31% (relative risk 0.61, 95% confidence interval 0.41 to 0.89) and that of severe respiratory distress syndrome from 42% to 20% (relative risk 0.48, 95% confidence interval 0.29 to 0.78) in the placebo and thyrotropin-releasing hormone groups, respectively. The number of deaths fell from 14 to one (relative risk 0.08, 95% confidence interval 0.01 to 0.63). The incidence of chronic lung disease was not significantly different, but that of an adverse outcome (chronic lung disease or death by 36 weeks' gestation) fell from 29% in the placebo group to 16% with thyrotropin-releasing hormone (relative risk 0.55, 95% confidence interval 0.31 to 0.99).
                The addition of thyrotropin-releasing hormone to antepartum glucocorticoid treatment reduces the incidence of respiratory distress syndrome and improves survival in preterm infants. Our purpose was to determine whether adding antenatal thyrotropin-releasing hormone to prenatal corticosteroids reduces the frequency of respiratory distress syndrome.
                A randomized, multicenter, double-blind, placebo-controlled trial was conducted of thyrotropin-releasing hormone (400 micrograms intravenously every 8 hours four times) in women with singleton pregnancies < 33 weeks of gestation who received antenatal betamethasone (12 mg intramuscularly every 24 hours two times). Neonates weighing < 1.0 kg received prophylactic surfactant and those above that weight received rescue therapy.
                One hundred ninety women received thyrotropin-releasing hormone and 180 were given placebo. There were no differences in the frequency of respiratory distress syndrome (relative risk 1.17 [95% confidence interval 0.93 to 1.48]), use of oxygen at age 28 days (1.14 [0.80 to 1.62]), or neonatal mortality (1.05 [0.79 to 1.38]). Air leaks were more frequent in the thyrotropin-releasing hormone group (1.57 [1.23 to 2.01]).
                The combination of antenatal thyrotropin-releasing hormone and corticosteroids does not reduce the frequency of respiratory distress syndrome or improve the outcome of preterm neonates compared with the use of corticosteroids alone. Although prenatal glucocorticoid treatment reduces neonatal respiratory morbidity, respiratory distress syndrome and chronic lung disease (CLD) develop in many very-low-birthweight infants despite therapy. To investigate the effect of additional prenatal treatment with thyrotropin-releasing hormone (TRH), we did a multicentre, blinded, randomised trial. 404 women with threatened preterm delivery at less than 32 weeks' gestation received betamethasone plus TRH (4 doses of 400 micrograms 8-hourly) or betamethasone plus placebo. 103 infants who were fully treated and of less than 1500 g birthweight were evaluated during the neonatal period. TRH treatment (55 infants) did not affect the total incidence of respiratory distress syndrome (47% vs 58% in controls) or of severe respiratory distress syndrome (13% vs 25% in controls, p = 0.11). CLD (defined as requirement for supplemental oxygen at 28 days after birth) developed in significantly fewer TRH-treated infants (18% vs 44% of controls, p less than 0.01). The unadjusted relative risk of CLD with TRH therapy was 0.40 (95% CI 0.26-0.80, p less than 0.05), and this was not materially changed after adjustment for potentially modifying variables. There were significantly fewer adverse outcomes, defined as death or continuing oxygen requirement, in the TRH group than in the steroid-alone group both at 28 days and when infants reached 36 weeks' postconceptional age. The incidence of other complications of prematurity was similar in the two groups. Prenatal TRH reduces the incidence of chronic lung disease among betamethasone-treated infants. A prospective double-blind randomized clinical trial was carried out to determine whether glucocorticoid treatment reduces the risk of respiratory distress syndrome (RDS) in prematurely born infants. There were 127 infants born to 122 mothers who received either steroid (dexamethasone phosphate) or placebo. No differences between groups occurred in risk factors for RDS (eg, prepartum asphyxia, male sex, cesarean section). When those who received a full course of dexamethasone therapy were compared with those who received placebo, a significant reduction was found in risk, severity, and deaths due to RDS. An increased incidence of infection in mothers treated with steroid was evident, particularly after premature rupture of membranes. We conclude that steroids are effective in reducing risk of RDS, but safer and more efficacious approaches for the prevention of RDS should be sought. Improvements in the management of respiratory distress syndrome (RDS) include pre- and postnatal stimulation of pulmonary maturity, and triiodothyronine (T3) is believed to influence directly surfactant production. Its circulating levels are low in premature infants with RDS probably due to a low thyroxine T4-T3 hepatic conversion mechanism. While a state of hypotriiodothyroninemia exists at birth, we studied the influence of postnatal intravenous T3 administration on the course of RDS in preterm infants of less than 32 weeks' gestation. Fifty preterm infants with RDS were studied (mean gestational age 30.4 +/- 1.2 weeks and birth weight 1,180 +/- 220 g). They were at random assigned to treatment with 50 micrograms L-T3 (Thyrotardin) or to the control group. Mortality rate, peak oxygen concentrations, duration of artificial ventilation and development of major complications of RDS were the criteria to estimate the influence of T3 treatment on RDS. We failed to detect a statistically significant difference between the two groups in all of the mentioned criteria except for FiO2 concentrations required to maintain PaO2 between 50 and 60 mm Hg (p less than 0.05). These observations suggest a relative beneficial effect of T3 replacement on the course of RDS in preterm infants of less than 32 weeks of gestation. To study the effect of early postnatal dexamethasone (days 1-3) on the incidence and severity of chronic lung disease in preterm infants with respiratory distress syndrome.
                A multicentre, randomised, placebo controlled, blinded study was carried out in 18 neonatal intensive care units in Israel. The primary outcome measure was survival to discharge without requirement for supplemental oxygen therapy beyond 28 days of life. The secondary outcome measures were requirement for mechanical ventilation at 3 and 7 days, duration of ventilation or oxygen therapy, need for subsequent steroids for established chronic lung disease and incidence of major morbidities.
                The study consisted of 248 infants (dexamethasone n = 132; placebo n = 116). No differences were found in the outcome variables except for a reduction in requirement for mechanical ventilation at age 3 days in treated infants (dexamethasone 44%, placebo 67%; P = 0.001). Gastrointestinal haemorrhage, hypertension, and hyperglycaemia were more common in treated infants, but no life threatening complications, such as gastrointestinal perforation, were encountered.
                These data do no support the routine use of early postnatal steroids, but may justify further study in a selected, high risk group of infants. Thirty-six preterm infants of less than 34 weeks of gestation with idiopathic respiratory distress syndrome (IRDS) were studied. Eighteen of them were treated with intravenous thyroxine (T4) and compared with 18 control prematures to evaluate the effect of postnatal T4 administration on the course of IRDS. After treatment, serum T4 levels were similar to those of healthy term infants. No statistically significant effect on mortality rate, duration of mechanical ventilation (p greater than 0.3), need of high oxygen environment (p greater than 0.05) and development of bronchopulmonary dysplasia (p greater than 0.2) was observed between the two groups. These observations show that postnatal use of T4 does not carry any benefit for preterm infants with IRDS. The objective of the study was to determine the efficacy and side effects of corticosteroid therapy for pregnant women with severe preeclampsia in the prevention of respiratory distress syndrome in their premature neonates.
                A prospective double-blind randomized trial enrolled 218 pregnant women with severe preeclampsia and gestational age between 26 and 34 weeks. One hundred ten received betamethasone (12 mg administered intramuscularly, repeated after 24 hours and then once a week) and 108 received placebo. Relative risks and 95% confidence intervals of respiratory distress syndrome and other neonatal and maternal complications were calculated for corticosteroid use.
                Frequency of respiratory distress syndrome was significantly reduced in the corticosteroid group (23%) with respect to the placebo group (43%), with a relative risk of 0.53 (95% confidence interval 0.35-0. 82). Relative risks of intraventricular hemorrhage, patent ductus arteriosus, and perinatal infection were significantly decreased in the corticosteroid group: 0.35 (95% confidence interval 0.15-0.86), 0.27 (95% confidence interval 0.08-0.95), and 0.39 (95% confidence interval 0.39-0.97), respectively. There was no significant difference in the frequency of stillbirth, but the neonatal mortality rate was lower in the corticosteroid group (14%) than in the placebo group (28%), with a relative risk of 0.5 (95% confidence interval 0.28-0.89). There was increased risk of gestational diabetes but of no other maternal complication after corticosteroid therapy, and mean blood pressures were similar in the 2 groups.
                Antenatal corticosteroid therapy with betamethasone for acceleration of fetal lung maturity is a safe and efficient treatment in patients with severe preeclampsia at between 26 and 34 weeks' gestation. The aim of the study was to determine the feasibility, the cost and the effects of antenatal maternal corticosteroid treatment on preventing respiratory distress syndrome in premature neonates of our population.
                Between January, 1, 1998 and June, 31, 1999, 118 pregnant women at 26-34 weeks' gestation and at a high risk of premature delivery, were prospectively randomized in 2 groups: group 1 received intramusculary 24 mg of betamethasone (12 mg every 24 hours), group 2 didn't receive antenatal corticosteroids. At birth, premature neonates were systematically examined by a neonatologist.
                131 premature neonates were born (63 from group 1, 68 from group 2). The incidence and the degree of severity of respiratory distress syndrome, appeared substancially reduced (4.8% vs 27.9%) by the use of antenatal corticosteroids. Moreover, neonatal mortality due to respiratory distress syndrome was statistically less in group 1 than in group 2 (22.9% vs 57%). There was no significant difference in the occurrence of maternal or neonatal corticosteroid complications such as infection between treated group and control subjects. We estimated a potential annual savings of 21 thousands tunisian dinars, when the cost implications for antenatal corticosteroid therapy were estimated to 2 thousands tunisian dinars.
                Maternal administration of corticosteroids before preterm delivery results in a decrease in the incidence and severity of respiratory distress syndrome and a decrease in neonatal mortality rate among premature neonates born to treated versus untreated mothers at 26-34 weeks' gestation; added to an annual savings estimated to 21 thousands tunisian dinars.
There is no evidence from controlled clinical trials that postnatal thyroid hormone treatment reduces the severity of respiratory distress syndrome, neonatal morbidity or mortality in preterm infants with respiratory distress syndrome.