Association between betamethasone levels and respiratory distress syndrome in preterm births: A prospective cohort study

Abstract

The recommended fixed dosage of betamethasone for pregnancies at risk of preterm birth was determined in the 1970s, regardless of gestational age (GA), number of fetuses, and maternal weight. We aimed to examine the association between maternal and neonatal betamethasone serum levels and neonatal respiratory distress syndrome (RDS) and to examine whether levels correlate with maternal weight, GA, or number of fetuses. A prospective study was conducted at a single academic medical center between August 2016 and February 2019. Women received betamethasone and delivered between 28+0 and 34+6 weeks were included. Maternal serum levels (MSLs), and neonatal serum levels (NSLs) of betamethasone at delivery were analyzed using Corticosteroid enzyme‐linked immunosorbent assay kit. RDS was diagnosed according to clinical and radiographic findings. We assumed that the sensitivity of NSLs to detect RDS is 95%; hence, 150 neonates were needed (power 80%, alpha 0.05). Overall, 124 women were included; including 96 (77.4%) singletons, 26 (21.0%) twins, and 2 (1.6%) triplets, corresponding to 154 neonates. RDS was diagnosed in 35 neonates (22.7%). After adjusting for GA, time elapsed from the last dose, and number of doses, NSLs were associated with RDS (relative risk: 0.97, 95% confidence interval: 0.94–0.99, p = 0.011). A level of 6.00 ng/ml predicted RDS with a sensitivity of 80.0% and specificity of 64.7%. Adjusted MSLs were not associated with RDS. Both maternal and neonatal serum levels were not associated with the number of fetuses and maternal weight. In conclusion, NSLs are associated with RDS whereas MSLs are not.

Minimal physiologically‐based hybrid model of pharmacokinetics in pregnant women: Application to antenatal corticosteroids

“…Petersen et al 32 reported C f p ∕ C m p = 0.28 for BET with no time dependence and the first observation recorded at 1 h after the last dose. Similar findings for BET with C f p ∕ C m p = 0.37were reported by Ballard et al 33 A recent study by Zafran et al 34 in women dosed with BET-PA reports the value of C f p ∕ C m p = 0.72 for BET calculated as the ratio of mean values. The twofold difference from previous values might be explained by a relatively large between-subject variability of C f p and C m p in their study.…”