Relation of body mass index to frequency of recurrent preterm birth in women treated with 17-alpha hydroxyprogesterone caproate.

The standard weekly dose of 17-alpha hydroxyprogesterone caproate (17OHP-C; 250 mg/wk) to reduce the risk of recurrent preterm birth was adopted without regard to patient characteristics. We examined the relationship between prepregnancy body mass index (BMI) and gestational age at birth after 17OHP-C prophylaxis. We hypothesized that rates of births before 32, 35, and 37 weeks of gestation would be increased in women with a BMI of 25 kg/m(2) or greater. A retrospective cohort study was conducted from a deidentified database of women treated with 17OHP-C for prior spontaneous preterm birth. The frequency of recurrent preterm delivery before 32, 35, and 37 weeks of gestation was investigated for women with a BMI less than 25 kg/m(2) compared with women with a BMI of 25 kg/m(2) or greater. The adjusted relative risk of preterm delivery was estimated through a modified Poisson regression approach. Of 390 women who met inclusion criteria, 60 (15.4%) delivered before 32 weeks, 89 (22.8%) before 35 weeks, and 156 (40.0%) before 37 weeks. A total of 174 women had a BMI less than 25 kg/m(2) (mean [SD], 21.2 [2.5]) and 216 had a BMI of 25 kg/m(2) or greater (mean [SD], 33.5 [6.7]). Risk of birth before 32 weeks was 1.7 times higher on average (adjusted relative risk, 1.7; 95% confidence interval, 1.05-2.77) in overweight women than in women with a BMI less than 25 kg/m(2), adjusting for age, race, smoking, and short cervix. There was no difference in the risk of preterm birth before 35 or 37 weeks. Among pregnant women receiving 17OHP-C prophylaxis for a prior preterm birth, recurrent preterm birth before 32 weeks was significantly more common in those women whose prepregnancy BMI was 25 kg/m(2) or greater than in women with BMI less than 25 kg/m(2). This observation is consistent with pharmacological studies suggesting that dosing regimens of 17OHP-C may affect efficacy.

Co AL ，Walker HC ，Hade EM ，Iams JD ... -  《-》

Does 17-alpha hydroxyprogesterone caproate prevent recurrent preterm birth in obese women?

We sought to determine if maternal weight or body mass index (BMI) modifies the effectiveness of 17-alpha hydroxyprogesterone caproate (17OHP-C). We performed a secondary analysis of the Maternal-Fetal Medicine Units Network Trial for the Prevention of Recurrent Preterm Delivery by 17-Alpha Hydroxyprogesterone Caproate. Binomial regression models were estimated to determine the relative risk (RR) of preterm birth (PTB) in women randomized to 17OHP-C vs placebo according to BMI category and maternal weight. Adjusted models considered inclusion of potential confounders. In all, 443 women with complete data were included. 17OHP-C is effective in preventing PTB <37 weeks only in women with prepregnancy BMI <30 kg/m(2) (RR, 0.54; 95% confidence interval, 0.43-0.68). Above this BMI threshold there is a nonsignificant trend toward an increased risk of PTB (RR, 1.55; 95% confidence interval, 0.83-2.89) with 17OHP-C treatment. When analyzing by maternal weight, a similar threshold is observed at 165 lb, above which 17OHP-C is no longer effective. The effectiveness of 17OHP-C is modified by maternal weight and BMI, and treatment does not appear to reduce the rate of PTB in women who are obese or have a weight >165 lb. This finding may be due to subtherapeutic serum levels in women with increased BMI or weight. Studies of adjusted-dose 17OHP-C in women who are obese or who weigh >165 lb are warranted, and current recommendations regarding the uniform use of 17OHP-C regardless of maternal BMI and weight may deserve reassessment.

Heyborne KD ，Allshouse AA ，Carey JC 《-》

Rates of recurrent preterm birth by maternal body habitus in women receiving 17α-hydroxyprogesterone caproate.

Timofeev J ，Feghali M ，Boyle A ，Istwan N ，Rhea D ，Driggers RW ... -  《-》

Predictors of response to 17-alpha hydroxyprogesterone caproate for prevention of recurrent spontaneous preterm birth.

Prematurity is the leading cause of neonatal morbidity and death among nonanomalous neonates in the United States. Intramuscular 17-alpha hydroxyprogesterone caproate injections reduce the risk of recurrent prematurity by approximately one third. Unfortunately, prophylactic 17-alpha hydroxyprogesterone caproate is not always effective, and one-third of high-risk women will have a recurrent preterm birth, despite 17-alpha hydroxyprogesterone caproate therapy. The reasons for this variability in response are unknown. Previous investigators have examined the influence of a variety of factors on 17-alpha hydroxyprogesterone caproate response but have analyzed data that used a fixed outcome of term delivery to define progesterone response. We hypothesized that the demographics, history, and pregnancy course among women who deliver at a similar gestational age with 17-alpha hydroxyprogesterone caproate for recurrent spontaneous preterm birth prevention differs when compared with those women who deliver later with 17-alpha hydroxyprogesterone caproate and that these associations could be refined by the use of a contemporary definition of 17-alpha hydroxyprogesterone caproate "responder." This was a planned secondary analysis of a prospective, multicenter, longitudinal study of women with ≥1 previous documented singleton spontaneous preterm birth at <37 weeks gestation. Data were collected at 3 prespecified gestational age epochs during pregnancy. All women who were included in this analysis received 17-alpha hydroxyprogesterone caproate during the studied pregnancy. We classified women as a 17-alpha hydroxyprogesterone caproate responder or nonresponder by calculating the difference in delivery gestational age between the 17-alpha hydroxyprogesterone caproate-treated pregnancy and her earliest spontaneous preterm birth. Responders were defined as those with pregnancy that extended ≥3 weeks later with 17-alpha hydroxyprogesterone caproate, compared with the delivery gestational age of their earliest previous spontaneous preterm birth. Data were analyzed with the use of chi-square test, t-test, and logistic regression. One hundred fifty-five women met the inclusion criteria. The 118 responders delivered later on average (37.7 weeks gestation) than the 37 nonresponders (33.5 weeks gestation; P < .001). Among responders, 32% (38/118 women) had a recurrent spontaneous preterm birth. Demographics (age, race/ethnicity, education, and parity) were similar between groups. In the regression model, the gestational age of the previous spontaneous preterm birth (odds ratio, 0.68; 95% confidence interval, 0.56-0.82; P < .001), vaginal bleeding/abruption in the current pregnancy (odds ratio, 0.24; 95% confidence interval, 0.06-0.88; P = .031), and first-degree family history of spontaneous preterm birth (odds ratio, 0.37; 95% confidence interval, 0.15-0.88; P = .024) were associated with response to 17-alpha hydroxyprogesterone caproate. Because women with a penultimate preterm pregnancy were more likely to be 17-alpha hydroxyprogesterone caproate nonresponders, we performed an additional limited analysis examining only the 130 women whose penultimate pregnancy was preterm. In regression models, the results were similar to those in the main cohort. Several historic and current pregnancy characteristics define women who are at risk for recurrent preterm birth at a similar gestational age, despite 17-alpha hydroxyprogesterone caproate therapy. These data should be studied prospectively in larger cohorts and combined with genetic and environmental data to identify women who are most likely to benefit from this intervention.

Manuck TA ，Esplin MS ，Biggio J ，Bukowski R ，Parry S ，Zhang H ，Huang H ，Varner MW ，Andrews W ，Saade G ，Sadovsky Y ，Reddy UM ，Ilekis J ，Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Genomics and Proteomics Network for Preterm Birth Research (GPN-PBR) ... -  《-》

17 alpha-hydroxyprogesterone caproate does not prolong pregnancy or reduce the rate of preterm birth in women at high risk for preterm delivery and a short cervix: a randomized controlled trial.

The objective of the study was to evaluate the efficacy of 17 alpha-hydroxyprogesterone caproate (17OHP-C) in prolonging gestation in patients with a short cervix and other risk factors for preterm delivery, such as previous preterm birth, cervical surgery, uterine anomalies, or prenatal diethylstilbestrol (DES) exposure. This open-label, multicenter, randomized controlled trial included asymptomatic singleton pregnancies from 20(+0) through 31(+6) weeks of gestation with a cervical length less than 25 mm and a history of preterm delivery or cervical surgery or uterine malformation or prenatal DES exposure. Randomization assigned them to receive (or not) 500 mg of intramuscular 17OHP-C weekly until 36 weeks. The primary outcome was time from randomization to delivery. After enrolling 105 patients, an interim analysis demonstrated the lack of efficacy of 17OHP-C in prolonging pregnancy. The study was discontinued because of futility. The groups were similar for maternal age, body mass index, parity, gestational age at inclusion, history of uterine anomalies, DES syndrome, previous preterm delivery or midtrimester abortion, and cervical length at randomization. The enrollment-to-delivery interval did not differ between patients allocated to 17OHP-C (n = 51) and those allocated to the control group (n = 54) (median [interquartile range] time to delivery: 77 [54-103] and 74 [52-99] days, respectively). The rate of preterm delivery less than 37 (45% vs 44%, P > .99), less than 34 (24% vs 30%, P = .51), or less than 32 (14% vs 20%, P = .44) weeks was similar in patients allocated to 17OHP-C and those in the control group. 17OHP-C did not prolong pregnancy in women with singleton gestations, a sonographic short cervix, and other risk factors of preterm delivery (prior history, uterine malformations, cervical surgery, or prenatal DES exposure).

Winer N ，Bretelle F ，Senat MV ，Bohec C ，Deruelle P ，Perrotin F ，Connan L ，Vayssière C ，Langer B ，Capelle M ，Azimi S ，Porcher R ，Rozenberg P ，Groupe de Recherche en Obstétrique et Gynécologie ... -  《-》