Risk of intrauterine growth retardation, malformations and other birth outcomes in children after topical use of corticosteroid in pregnancy. Population-based case-control study of teratogenic potential of corticosteroids. The effect of a single remote course versus weekly courses of antenatal corticosteroids on functional residual capacity in preterm infants: a randomized trial. First trimester exposure to corticosteroids and oral clefts. Maternal corticosteroid use and orofacial clefts. The effect of antenatal corticosteroid therapy on pregnancies complicated by premature rupture of membranes. [Value of prenatal corticotherapy in the prevention of hyaline membrane disease in premature infants. Randomized prospective study]. Multiple versus single courses of antenatal corticosteroids for preterm birth: a pilot study. Prospective randomized study of corticosteroids in the management of premature rupture of the membranes and the premature gestation.
Topical corticosteroids are frequently used drugs, but little is known of the exposure during pregnancy and birth outcome.
                In a population-based follow-up study restricted to primigravida women, we examined the risk of low birth weight, malformations and other birth outcomes following pregnancy upon exposure to topical corticosteroids. We compared the offspring of 363 women exposed to topical corticosteroids during pregnancy with 9263 controls, who received no prescriptions at all.
                The prevalence of malformations was 2.9% among 170 infants exposed during the first trimester and 3.6% among the controls. Adjusted odds ratios for low birth weight, malformations and preterm delivery among women receiving weak/medium strong corticosteroids were 0.7 (95% CI 0.17-2.85), 0.93 (95% CI 0.23-3.80) and 1.04 (95% CI 0.56-1.92), respectively, and adjusted odds ratios for strong/very strong corticosteroids were 1.23 (95% CI 0.45-3.37), 0.56 (95% CI 0.14-2.28) and 0.99 (95% CI 0.54-1.84), respectively.
                The study showed no increased risk of low birth weight, malformations or preterm delivery in the offspring of women exposed to topical corticosteroid during pregnancy. The teratogenic potential of oral and topical corticosteroid treatment during pregnancy was evaluated in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1994. Corticosteroid tablet pregnancy exposure was 1.55% among 20,830 malformed cases and 1.41% among 35,727 healthy control births (P = 0.2). Corticosteroid ointment pregnancy exposure was 0.35% among malformed and 0.33% among control births (P = 0.7). The absolute risk of oral and ointment corticosteroid treatment was low in pregnancy and particularly in the second and third months of gestation, i.e., in the critical period for major congenital abnormalities. The adjusted odds ratio and the analysis of case-control pairs did not show any association between the rate of different congenital abnormalities and the corticosteroid treatment in the second and third months of gestation. Thus, treatments with corticosteroids in pregnancy do not appear to noticeably increase the risk of congenital abnormalities in humans. There are no randomized data on the effect of repeat courses of corticosteroids during pregnancy on newborn pulmonary function. Our objective was to compare the effect of a single remote course of antenatal steroids (AS) with weekly courses of AS on functional residual capacity (FRC) and respiratory compliance in preterm infants.
                Pregnant women 25 to 33 weeks' gestation, who remained undelivered 1 week after their first course of antenatal corticosteroids (two 12-mg doses of betamethasone) were randomized to weekly courses of corticosteroids versus weekly placebo until delivery or 34 weeks' gestation. FRC was measured with the nitrogen washout technique and respiratory compliance with the single breath occlusion technique within 48 hours of life.
                Thirty-seven infants (mean gestational age at delivery approximately 32.5 weeks) were studied. Maternal and infant demographics were similar. There was no significant difference in FRC (28.5 vs 27.5 mL/kg) or respiratory compliance between the infants who received a single remote course of antenatal corticosteroids and those who received weekly courses of corticosteroids until delivery. There was no significant difference in admission head circumference or birth weights between the groups.
                Our results demonstrate that weekly repetitive courses of AS do not significantly increase FRC or respiratory compliance in preterm infants when compared with a single remote course of steroids given at a mean gestational age of 29 weeks. The possible association between oral cleft in the newborn and maternal exposure to corticoids during pregnancy is still controversial. The aim of this study was to test this association by a case-control analysis using the large multicentric MADRE database.
                The MADRE database is a collection of information on malformed infants with a history of maternal first-trimester drug exposure. Nine malformation registries participate in the data collection. Cases were defined as infants presenting with a cleft palate or cleft lip, and exposure was defined by the use of corticosteroids during the first trimester of pregnancy.
                After 12 years of data collection, the database includes data on 11,150 malformed infants. A slight association is observed between exposure to corticoids for systemic use and the occurrence of cleft lip with or without cleft palate (OR, 2.59; 95% CI, 1.18-5.67).
                If the observed association is real, an interpretation is suggested, based on a likely interaction between corticosteroids and environmental dioxins. It is indeed possible that human fetuses may become sensitive to the teratogenic effect of corticosteroids when they are exposed in utero to environmental pesticides as well.
                Copyright 2003 Wiley-Liss, Inc. The purpose of this study was to examine whether maternal corticosteroid use during pregnancy is associated with delivering an infant with an orofacial cleft.
                This study included data on deliveries from the National Birth Defects Prevention Study, which is a population-based case-control study. Exposures were assessed by telephone interviews for mothers of 1141 cases with cleft lip +/- cleft palate (CLP), 628 with cleft palate (CP), and 4143 controls.
                Mothers of 33 infants with CLP (2.9%), mothers of 6 infants with CP (1.0%), and 72 control subjects (1.7%) reported corticosteroid use from 4 weeks before through 12 weeks after conception. The crude odds ratio for "any" vs "no" use was 1.7 (95% CI, 1.1-2.6) for CLP and 0.5 (0.2-1.3) for CP. When analyzed by route of administration and medication components, odds ratios for CLP tended to be elevated, and odds ratios for CP tended to be close to 1.
                Our results suggest a moderately increased risk of CLP among women who use corticosteroids during early pregnancy. This study was carried out to examine the effect of antenatal corticosteroid therapy on pregnancies complicated by premature rupture of membranes (PROMs). For this purpose, 139 patients with a singleton pregnancy (27-34 weeks of gestation) complicated by PROMs were evaluated prospectively during the period January 1997 to February 1999 at two Jordanian military hospitals (Prince Rhashed and Prince Zaid). Patients were allocated into two groups; Group 1 included 72 patients treated with dexamethsone (24 mg divided into 4 doses 12 hours apart), and Group 2 which included 67 patients whoreceived no treatment (control group). All women were examined clinically and the diagnosis of PROMs was demonstrated using vaginal speculum, nitrazine paper examination and ultrasonography. All neonates were evaluated clinically, radiologically, and by laboratory investigations. Pearson's Chi-square and Fisher's exact tests were used to assess the significance of differences between the two study groups. Respiratory distress syndrome (RDS), necrotizing enterocolitis (NEC), intraventricular haemorrhage (IVH), and days of hospital stay were significantly reduced in premature infants of the corticosteroid treated women compared with the controls (p<0.04, p<0.04, p<0.04, and p<0.05, respectively). The perinatal mortality was significantly decreased among the corticosteroid treated group in the gestational subgroups 31-32 and 33-34 weeks (p<0.04), and in all birth weight subgroups (p<0.03). RDS was statistically a significant factor which resulted in increased perinatal mortality in the control group (p=0.02). Regarding the occurrence of postpartum endometritis there was a statistically significant increase among the corticosteroid treated group compared with the controls (p<0.04). Conclusion: Antenatal corticosteroid therapy in pregnancies complicated by PROMs has a positive influencing effect on premature infants between 31 and 34 weeks of gestation, decreasing significantly the perinatal morbidity and mortality. It should be used with particular relevance to the developing world where surfactant is not available or where neonatal intensive care units are lacking. 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. (1) To determine the feasibility of a multicentre, randomized, double-masked, placebo-controlled trial to investigate the effects of multiple courses of antenatal corticosteroids (ACS), more than 7 days following the initial course of ACS therapy, on perinatal or neonatal mortality or neonatal morbidity. (2) To determine the risk of complications that would require discontinuation of ACS therapy. (3) To determine if multiple courses of ACS have an effect on the concentrations of plasma cortisol and adrenocorticotropin hormone (ACTH) in cord blood and in maternal blood immediately following delivery, compared to a single course of ACS.
                Women at 24 to 30 weeks' gestation, at continued increased risk of preterm birth 7 or more days following a single course of ACS, were randomized to receive weekly courses of betamethasone or placebo until 33 weeks' gestation or delivery.
                Women were recruited at two hospitals in Toronto from 01 September 1999 to 31 August 2000. Of the 78 women who were approached and were eligible for the study, 12 (15%) were recruited and 66 (85%) refused to participate. Of the 66 refusals, 38 (58%) did not feel their physicians were supportive of the study, 10 (15%) did not want to be randomized, and 4 (6%) had other personal reasons for refusing to enter the trial. Fourteen women (21%) had physicians who did not allow them to join the study. The lack of physician support was due to concerns related to the potential adverse effects of multiple courses of ACS. There were no complications requiring discontinuation of ACS. Plasma cortisol and ACTH concentrations in cord and maternal blood taken after delivery were not significantly different between ACS and placebo groups.
                A multicentre randomized controlled trial is required to determine the benefits and risks of multiple versus a single course of ACS. If the study protocols are supported by physicians and their patients, a multicentre randomized controlled trial is feasible. A prospective randomized study involving patients with premature rupture of the membranes between the twenty-eighth week and the thirty-fourth week of pregnancy was conducted. Patients with chorioamnionitis, advanced labor, and fetal distress, as well as those with mature lecithin/sphingomyelin ratios and/or Gram stains positive for bacteria, were delivered immediately. The remaining patients were randomized. One group received betamethasone. Tocolytic agents were used in this group when necessary. After 48 hours all patients given corticosteroids (CS group) were delivered). The second group was managed expectantly (EM group) and were delivered only when spontaneous labor or infection occurred. A total of 160 patients were randomized, 80 in each group. Maternal outcome, including chorioamnionitis and cesarean section rates, was not different; however, the endometritis rate was significantly higher in the CS group (p less than 0.05). Neonatal outcome did not differ in mean birth weights, perinatal death rates, neonatal infections, or incidences of respiratory distress. The frequency of prolonged hospital stay (greater than 4 weeks) was higher in the neonates in the CS group (p less than 0.01). The conclusion is that corticosteroids and active management in patients with premature rupture of the membranes and premature gestations do not decrease the incidence of respiratory distress syndrome or perinatal mortality and may aggravate certain infectious complications.
Currently limited and inconclusive data are unable to detect an association between topical corticosteroids and congenital abnormality, preterm delivery, or stillbirth. The current evidence shows no statistically significant difference between pregnant women who use and those who do not use topical corticosteroids. However, there does appear to be an association of very potent topical corticosteroids with low birthweight. Cohort studies with comprehensive outcome measures, assessment of effects of corticosteroid potency and dose, application methods, and reasons for giving them, and a very large sample size are needed.