Betamethasone - systemic use

Additional information

Pharmacokinetics and dosing

Healthy adults (2 men, 6 women) receiving betamethasone 8 mg i.v. and betamethasone phosphate 10.6 mg i.v. showed no apparent sex difference in any pharmacokinetic parameter. Body weight did not affect AUC or half-life [3].

Effects

No studies with a clinically relevant sex analysis regarding the effect of betamethasone have been found, except for use during pregnancy. In pregnancy, corticosteroid can be used to encourage fetal lung maturation where premature delivery is expected [4] as immature lung development can lead to respiratory distress syndrome (RDS) [5]. A systematic review and meta-analysis, including four studies using betamethasone and four studies using dexamethasone (in total 1109 boys, 968 girls), found no difference in the reduction of RDS between girls and boys (relative risk 0.57 vs. 0.50). However, all four trials with betamethasone showed a benefit only for boys, while all four trials with dexamethasone showed benefit only in girls [6]. In contrast to this, other studies [7, 8] have shown a beneficial response to betamethasone only in girls. One possible explanation to these contradictory findings may be heterogeneous groups with different average gestational ages and birth weights in the studies [6-8].

Adverse effects

A large meta-analysis of corticosteroid-induced osteoporosis in adults showed that oral corticosteroid treatment with doses above 5 mg/day (of prednisolone or equivalent) reduced bone mineral density and increased the risk of fracture during treatment, irrespective of age, sex, or underlying disease (66 studies with 2891 patients with BMD measures, 71.5% women and 23 studies with 558 with fractures in corticosteroid users, and 244 235 corticosteroid users with fractures in the General Practice Research Database) [1]. However, a study not included in the meta-analysis, retrospectively analyzed the population attributable risk of fracture in a cohort using oral corticosteroids (8192 men, 12034 women). Compared to the general population, corticosteroids users had a higher risk of fracture (RR 1.90), and women had a higher risk than men (RR 2.13) [2]. Another meta-analysis of glucocorticoid therapy in children (in total 287 patients with BMD measure, and 37 819 with fractures) showed corticosteroid use to be associated with reduced spine bone mineral density and no sex difference in the risk for fracture were seen [3].

Reproductive health issues

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).

Other information

There has been concern that prenatal use of corticosteroids to increase lung maturation in premature infants is associated with long term effects, such as cognitive deficits [4]. A cross-sectional study evaluated children (117 boys, 105 girls) born to women at risk of preterm delivery   treated with synthetic betamethasone or dexamethasone as a single course during pregnancy. Cognitive testing was performed when the children were at age 8-11 years old along with a structured interview with the mothers. Boys born to women with a pathologic pregnancy with or without receiving glucocorticoid scored lower IQ than controls. No differences in IQ scores between groups were seen in girls [9]. A study of individuals aged 20-22 years (43 men, 38 women) who had antenatally been exposed to one course betamethasone for prevention of neonatal respiratory distress syndrome showed no effect on cognitive functioning [10]. Another observational study of long-term effects of antenatal corticosteroid use (betamethasone or dexamethasone) showed that boys had a higher risk of epilepsy than girls (OR 1.74 vs. 0.50). Children were followed up until their ninth birthday [11].The effect of betamethasone on fetal heart rate and behavior in preterm twin pregnancy was analyzed in 18 pregnant women receiving 12 mg of betamethasone i.m. Betamethasone decreased basal fetal heart rate and body and breathing movements. The response in one fetus was highly associated with that in the co-twin, and independent of sex [7].