Betamethasone

BackgroundThe Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study (MACS) showed no benefit in the reduction of major neonatal mortality/morbidity or neurodevelopment at 2 and 5 years of age. Using the data from the randomized controlled trial and its follow-up, the aim of this study was to evaluate the association between gestational ages at birth in children exposed to single versus multiple courses of antenatal corticosteroid (ACS) therapy in utero and outcomes at 5 years of age.MethodA total of 1719 children, with the breakdown into groupings of ResultsGestational age at birth was strongly associated with the primary outcome, p ConclusionPreterm birth (Trial registrationThis study has been registered at (identifier NCT00187382).

Dermatitis herpetiformis (DH) is an inflammatory disease of the skin, considered the specific cutaneous manifestation of celiac disease (CD). Both DH and CD occur in gluten-sensitive individuals, share the same Human Leukocyte Antigen (HLA) haplotypes (DQ2 and DQ8), and improve following the administration of a gluten-free diet. Moreover, almost all DH patients show typical CD alterations at the small bowel biopsy, ranging from villous atrophy to augmented presence of intraepithelial lymphocytes, as well as the generation of circulating autoantibodies against tissue transglutaminase (tTG). Clinically, DH presents with polymorphic lesions, including papules, vesicles, and small blisters, symmetrically distributed in typical anatomical sites including the extensor aspects of the limbs, the elbows, the sacral regions, and the buttocks. Intense pruritus is almost the rule. However, many atypical presentations of DH have also been reported. Moreover, recent evidence suggested that DH is changing. Firstly, some studies reported a reduced incidence of DH, probably due to early recognition of CD, so that there is not enough time for DH to develop. Moreover, data from Japanese literature highlighted the absence of intestinal involvement as well as of the typical serological markers of CD (i.e., anti-tTG antibodies) in Japanese patients with DH. Similar cases may also occur in Caucasian patients, complicating DH diagnosis. The latter relies on the combination of clinical, histopathologic, and immunopathologic findings. Detecting granular IgA deposits at the dermal-epidermal junction by direct immunofluorescence (DIF) from perilesional skin represents the most specific diagnostic tool. Further, assessing serum titers of autoantibodies against epidermal transglutaminase (eTG), the supposed autoantigen of DH, may also serve as a clue for the diagnosis. However, a study from our group has recently demonstrated that granular IgA deposits may also occur in celiac patients with non-DH inflammatory skin diseases, raising questions about the effective role of eTG IgA autoantibodies in DH and suggesting the need of revising diagnostic criteria, conceivably emphasizing clinical aspects of the disease along with DIF. DH usually responds to the gluten-free diet. Topical clobetasol ointment or dapsone may be also applied to favor rapid disease control. Our review will focus on novel pathogenic insights, controversies, and management aspects of DH.

BackgroundAntenatal steroids are standard of care for women who are at risk of preterm delivery; however, antenatal steroid dosing and formulation have not been evaluated adequately. The standard clinical 2-dose treatment with betamethasone-acetate+betamethasone-phosphate is more effective than 2 doses of betamethasone-phosphate for the induction of lung maturation in preterm fetal sheep. We hypothesized that the slowly released betamethasone-acetate component induces similar lung maturation to betamethasone-phosphate+betamethasone-acetate with decreased dose and fetal exposure.ObjectiveThe purpose of this study was to investigate pharmacokinetics and fetal lung maturation of antenatal betamethasone-acetate in preterm fetal sheep.Study designGroups of 10 singleton-pregnant ewes received 1 or 2 intramuscular doses 24 hours apart of 0.25 mg/kg/dose of betamethasone-phosphate+betamethasone-acetate (the standard of care dose) or 1 intramuscular dose of 0.5 mg/kg, 0.25 mg/kg, or 0.125 mg/kg of betamethasone-acetate. Fetuses were delivered 48 hours after the first injection at 122 days of gestation (80% of term) and ventilated for 30 minutes, with ventilator settings, compliance, vital signs, and blood gas measurements recorded every 10 minutes. After ventilation, we measured static lung pressure-volume curves and sampled the lungs for messenger RNA measurements. Other groups of pregnant ewes and fetuses were catheterized and treated with intramuscular injections of betamethasone-phosphate 0.125 mg/kg, betamethasone-acetate 0.125 mg/kg, or betamethasone-acetate 0.5 mg/kg. Maternal and fetal betamethasone concentrations in plasma were measured for 24 hours.ResultsAll betamethasone-treated groups had increased messenger RNA expression of surfactant proteins A, B, and C, ATP-binding cassette subfamily A member 3, and aquaporin-5 compared with control animals. Treatment with 1 dose of intramuscular betamethasone-acetate 0.125mg/kg improved dynamic and static lung compliance, gas exchange, and ventilation efficiency similarly to the standard treatment of 2 doses of 0.25 m/kg of betamethasone-acetate+betamethasone-phosphate. Betamethasone-acetate 0.125 mg/kg resulted in lower maternal and fetal peak plasma concentrations and decreased fetal exposure to betamethasone compared with betamethasone-phosphate 0.125 mg/kg.ConclusionA single dose of betamethasone-acetate results in similar fetal lung maturation as the 2-dose clinical formulation of betamethasone-phosphate+betamethasone-acetate with decreased fetal exposure to betamethasone. A lower dose of betamethasone-acetate may be an effective alternative to induce fetal lung maturation with less risk to the fetus.

ImportanceAlthough betamethasone reduces complications of prematurity, it can cause maternal hyperglycemia and neonatal hypoglycemia. Metformin effectively treats maternal hyperglycemia and has been shown to decrease neonatal hypoglycemia in women with gestational diabetes.ObjectiveTo evaluate the impact of metformin treatment after betamethasone administration on maternal glycemic control and the incidence of neonatal hypoglycemia in preterm infants.Design, setting, and participantsThis multicenter, open-label randomized clinical trial was conducted from July 1, 2020, to June 30, 2024, at 3 medical centers in Israel. Pregnant women receiving betamethasone from 24.0 to 36.5 gestational weeks due to increased preterm delivery risk were studied. Women with diabetes were excluded.InterventionsParticipants were randomized to metformin (425 mg 3 times daily before meals and 850-1700 mg at 10 pm) or no treatment. The treatment lasted up to 48 hours after the first betamethasone dose. Capillary glucose was measured before meals (preprandial), 90 minutes after starting meals (postprandial), and at 10 pm.Main outcome and measureThe primary end points were the mean maternal glucose values up to 48 hours from first betamethasone injection and the rate of neonatal hypoglycemia in preterm deliveries (ResultsA total of 169 women (mean [SD] age, 29.7 [5.4] years), including 84 with 48 preterm infants in the metformin group and 85 with 58 preterm neonates in the control group, were included in the study. Mean (SD) maternal total and postprandial glucose values were significantly lower in the metformin group (121 [15] vs 127 [17] mg/dL; P = .01; and 129 [22] vs 138 [26] mg/dL; P = .009, respectively). Neonatal hypoglycemia rate was lower in the metformin group (10 [21%] vs 23 [40%]; P = .04; relative risk, 0.53; 95% CI, 0.28-0.99). Mild adverse effects, mostly gastrointestinal, were reported by 12 women (14%).Conclusions and relevanceIn this randomized clinical trial, metformin was safe and effective in preventing betamethasone-induced maternal hyperglycemia and neonatal hypoglycemia. Metformin should be considered as a treatment option for women who receive antenatal corticosteroids to prevent their related adverse effects.Trial registrationClinicalTrials.gov Identifier: NCT04332393.