Micaela Della Torre

Betamethasone in Pregnancy: Influence of maternal body weight and multiple gestation on pharmacokinetics

OBJECTIVE The goals of the study were to estimate the pharmacokinetic parameters of standard dose betamethasone in a large obstetrics population and evaluate the effect of maternal body size and multiple gestation on the pharmacokinetic parameters and their observed variability. STUDY DESIGN This was a prospective pharmacokinetic study. Liquid chromatography mass spectrometry was used to measure betamethasone plasma concentrations. Pharmacokinetic parameters and significant clinical covariates were estimated with mixed effect modeling. Bootstrap analysis confirmed validity of the model. RESULTS Two hundred seventy-four blood samples from 77 patients were obtained. The greatest effect on pharmacokinetic variability was observed with maternal lean body weight (LBW). The relationship between the pharmacokinetic parameters and LBW remained linear over a wide range of maternal body sizes. Multiple gestations did not affect the pharmacokinetic parameters. CONCLUSION Individualization of betamethasone dosing by maternal LBW reduces variability in drug exposure. Mutiple gestations do not require betamethasone dosing adjustment, because pharmacokinetics are the same as singleton gestations.

Cervical cerclage for singleton pregnant patients on vaginal progesterone with progressive cervical shortening

BACKGROUND: Premature cervical ripening plays a significant role in spontaneous preterm birth. Vaginal progesterone is the recommended treatment in singleton pregnancy with incidental short cervix. There is lack of evidence on whether it is beneficial to reinforce the cervix with cerclage when the cervical length becomes progressively shortened <10 mm while on vaginal progesterone. OBJECTIVE: Our aims are to determine whether cerclage with vaginal progesterone will: (1) reduce the overall spontaneous preterm birth rate, (2) prolong pregnancy latency, and (3) improve neonatal outcomes compared to vaginal progesterone alone. STUDY DESIGN: This was a retrospective cohort study at the University of Illinois at Chicago of all women with singleton pregnancy on vaginal progesterone for incidental short cervix, cervical length <20 mm. Only those with progressive cervical length shortening <10 mm who delivered at the University of Illinois at Chicago from January 2013 through December 2016 were included. The decision to perform cerclage was based on individual physician preference. Demographic data; information on serial cervical length status; medical, obstetric, and social history; cerclage vs no cerclage; and neonatal outcomes were compared. RESULTS: A total of 310 women with incidental short cervix on vaginal progesterone were identified, and of these, 75 had progressive shortening cervical length <10 mm and met inclusion criteria. Among the women with extremely shortened cervical length <10 mm, 36 women (48%) had cervical cerclage plus vaginal progesterone, and 39 women (52%) continued on vaginal progesterone alone. The baseline characteristics, mean cervical length (5.06 vs 5.52 mm), and mean gestational age at diagnosis of extreme short cervix (21.5 vs 21.3 weeks) were similar between women who received cerclage vs those who did not, respectively. The mean gestational age at delivery was significantly greater for those with cerclage (34 weeks and 3 days vs 27 weeks and 2 days; P < .001). The rate of spontaneous preterm birth at <37, 35, 32, 28, and 24 weeks were significantly lower in the cerclage group: 44.1% vs 84.2%, 38.2% vs 81.6%, 23.5% vs 78.9%, 14.7% vs 63.2%, and 11.8% vs 39.5%, respectively. The rate of spontaneous preterm birth <37 weeks remained significant after controlling for confounders (relative risk, 0.11; 95% confidence interval, 0.03–0.41; P < .001). The average pregnancy latency was 14 weeks in the cerclage combined with vaginal progesterone group compared to vaginal progesterone alone group. Neonatal intensive care unit admission and development of respiratory distress syndrome were significantly lower in the cerclage group compared to vaginal progesterone alone group: 13 (36.1%) vs 23 (65.7%) (relative risk, 0.55; 95% confidence interval, 0.34–0.90; P = .018) and 8 (22.2%) vs 17 (43.6%) (relative risk, 0.59; 95% confidence interval, 0.29–0.90; P = .027), respectively. Neonates of women with cerclage were also significantly less likely to develop necrotizing enterocolitis or experience neonatal death. CONCLUSION: Our study showed that cerclage plus vaginal progesterone in women with extremely shortened cervix significantly decreased overall spontaneous preterm birth rates, prolonged pregnancy latency by 2‐fold, and decreased the overall neonatal morbidity and mortality.