Leo Pevzner

Effects of Maternal Obesity on Duration and Outcomes of Prostaglandin Cervical Ripening and Labor Induction

OBJECTIVE: To estimate the effect of maternal body mass index (BMI) on progress and outcomes of prostaglandin labor induction. METHODS: This study was a secondary analysis of data collected during the Misoprostol Vaginal Insert Trial, a multisite, double-blind, randomized trial of women requiring cervical ripening before induction of labor. The duration, characteristics, and outcomes of labor were analyzed after stratification by BMI categories. Multivariable regression analysis was performed on all outcomes of interest, adjusting for race, parity, and treatment group allocation. RESULTS: One thousand two hundred seventy-three patients were stratified according to BMI categories, with 418 study participants classified as lean (BMI less than 30), 644 as obese (BMI 30–39.9), and 211 as extremely obese (BMI 40 or higher). The incidence of cesarean delivery increased from 21.3% in the BMI less than 30 group to 29.8% in the BMI 30–39.9 group (odds ratio [OR] 1.57, 95% confidence interval [CI] 1.18–2.1, P=.002) and 36.5% in the BMI 40 or higher group (OR 2.12, 95% CI 1.47–3.06, P<.001). Median dose and duration of predelivery oxytocin in the lean group (2.6 units and 6.5 hours) was significantly lower than for women in either the obese (3.5 units and 7.7 hours) or the extremely obese (5.0 units and 8.5 hours) group. Median time to delivery was significantly longer in the BMI 40 or higher (27.0 hours) and BMI 30–39.9 (24.9 hours) groups compared with the BMI less than 30 (22.7 hours) group (P<.001). The relationship between maternal obesity and adverse labor and delivery outcomes persisted in a multivariable analysis that adjusted for race, parity, and treatment group allocation. CONCLUSION: Duration of labor, oxytocin requirements, and cesarean delivery rates are significantly higher with increasing maternal obesity in prostaglandin-induced women. LEVEL OF EVIDENCE: II

Effects of maternal obesity on tissue concentrations of prophylactic cefazolin during cesarean delivery.

OBJECTIVE: To estimate the adequacy of antimicrobial activity of preoperative antibiotics at the time of cesarean delivery as a function of maternal obesity. METHODS: Twenty-nine patients scheduled for cesarean delivery were stratified according to body mass index (BMI) category, with 10 study participants classified as lean (BMI less than 30), 10 as obese (BMI 30–39.9), and nine as extremely obese (BMI 40 or higher). All patients were given a dose of 2 g cefazolin 30–60 minutes before skin incision. Antibiotic concentrations from adipose samples, collected after skin incision and before skin closure, along with myometrial and serum samples, were analyzed with microbiological agar diffusion assay. RESULTS: Cefazolin concentrations within adipose tissue obtained at skin incision were inversely proportional to maternal BMI (r=−0.67, P<.001). The mean adipose concentration was 9.4 plus or minus 2.7 micrograms/g in the lean group of women compared with 6.4 plus or minus 2.3 micrograms/g in the obese group (P=.009) and 4.4 plus or minus 1.2 micrograms/g in the extremely obese group (P<.001). Although all specimens demonstrated therapeutic cefazolin levels for gram-positive cocci (greater than 1 microgram/g), a considerable portion of obese and extremely obese did not achieve minimal inhibitory concentrations of greater than 4 micrograms/g for Gram-negative rods in adipose samples at skin incision (20% and 33.3%, respectively) or closure (20.0% and 44.4%, respectively). No significant difference in cefazolin concentration was observed in mean closure adipose, myometrial, or serum specimens across the BMI categories. CONCLUSION: Pharmacokinetic analysis suggests that present antibiotic prophylaxis dosing may fail to provide adequate antimicrobial coverage in obese patients during cesarean delivery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00980486. LEVEL OF EVIDENCE: II

Cardiotocographic abnormalities associated with misoprostol and dinoprostone cervical ripening and labor induction.

OBJECTIVE To characterize the incidence and timing of cardiotocographic (CTG) abnormalities associated with misoprostol and dinoprostone vaginal inserts during labor induction. STUDY DESIGN This was a secondary analysis of data collected during the misoprostol vaginal insert (MVI) trial, a multi-site, double-masked, randomized trial of women requiring cervical ripening before induction of labor. The timing, incidence and clinical outcomes associated with CTG abnormalities were analyzed among three study groups. RESULTS 1308 subjects were randomized to receive dinoprostone pessary, misoprostol 50 mcg (MVI 50) or 100 mcg (MVI 100) vaginal insert. 6.8% of MVI 50-treated women had a uterine contractile abnormality (hyperstimulation, hypertonus and/or tachysystole) while the study drug was in situ, compared to 17.4% with dinoprostone insert (p<0.001) and 17.3% with MVI 100 (p<0.001). There was no significant difference in incidence of fetal heart rate (FHR) abnormalities that occurred with the study drug-11.2% with dinoprostone, compared to 9.9% with MVI 50 and 10.7% with MVI 100. Cardiotocographic (CTG) abnormalities while the study drug was in situ occurred later in women treated with MVI 50 (7.5h [6.2-9.8]) compared to dinoprostone (5.5h [4.2-6.6], p=0.003) and MVI 100 (7.0 h [5.7-7.9], p=0.13). Eight participants in MVI 50 group underwent cesarean section secondary to a CTG event that was initially noted with the study drug in situ, compared to eight dinoprostone-treated participants and 16 in the MVI 100 group, but these differences were not statistically significant. CONCLUSION Cardiotocographic abnormalities were less frequent and occurred after longer exposure with MVI 50 than MVI 100 or dinoprostone. Clinical outcomes were similar among the groups.

Retention of dinoprostone vaginal insert beyond 12 hours for induction of labor.

We evaluate the likelihood of cesarean delivery and identify risks of retaining a sustained-release dinoprostone vaginal insert beyond 12 hours. In a secondary analysis of outcomes, data were collected during a large, randomized trial comparing different sustained-release prostaglandin vaginal inserts for labor induction. Outcomes were compared between cases in whom the dinoprostone insert was removed early (within 12 hours) or late (12 to 24 hours). A total of 431 subjects had the dinoprostone vaginal insert in place for 12 to 24 hours ( N = 226, 52.4%) or within 12 hours ( N = 205, 47.6%). Insert removal for labor complications was less frequent in the late group than in the early group (5.8% versus 21.5%; P ≤ 0.001). Abnormal uterine contractility patterns were less common in the late than early group (25.2% versus 37.6%; P = 0.03). Rates of cesarean delivery during the first hospitalization were similar for late and early groups (25.0% versus 29.2%; P = 0.33). Percentages of infants requiring immediate attention or intensive care were low and similar between groups. Sustained-release intravaginal dinoprostone left in place beyond 12 hours did not increase the risks of intrapartum complications, cesarean delivery, or immediate adverse neonatal events.