Julie Y. Lo

Prevention of preterm birth in triplets using 17 alpha-hydroxyprogesterone caproate: A randomized controlled trial

OBJECTIVE: To assess whether 17 alpha-hydroxyprogesterone caproate reduces the rate of preterm birth in women carrying triplets. METHODS: We performed this randomized, double-blinded, placebo-controlled trial in 14 centers. Healthy women with triplets were randomly assigned to weekly intramuscular injections of either 250 mg of 17 alpha-hydroxyprogesterone caproate or matching placebo, starting at 16–20 weeks and ending at delivery or 35 weeks of gestation. The primary study outcome was delivery or fetal loss before 35 weeks. RESULTS: One hundred thirty-four women were assigned, 71 to 17 alpha-hydroxyprogesterone caproate and 63 to placebo; none were lost to follow-up. Baseline demographic data were similar in the two groups. The proportion of women experiencing the primary outcome (a composite of delivery or fetal loss before 35 0/7 weeks) was similar in the two treatment groups: 83% of pregnancies in the 17 alpha-hydroxyprogesterone caproate group and 84% in the placebo group, relative risk 1.0, 95% confidence interval 0.9–1.1. The lack of benefit of 17 alpha-hydroxyprogesterone caproate was evident regardless of the conception method or whether a gestational age cutoff for delivery was set at 32 or 28 weeks. CONCLUSION: Treatment with 17 alpha-hydroxyprogesterone caproate did not reduce the rate of preterm birth in women with triplet gestations. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00099164 LEVEL OF EVIDENCE: I

Loop electrosurgical excision procedure and risk of preterm birth

OBJECTIVE: To examine whether preterm birth is related to the loop electrosurgical excision procedure (LEEP) itself or intrinsic to the women undergoing the procedure. METHODS: Rates of preterm birth, defined as births before 37 weeks of gestation, as well as causes were analyzed in women undergoing LEEP before or after an index pregnancy. These rates were compared with the general obstetric population. RESULTS: A total of 241,701 women were delivered of singletons at Parkland Hospital between January 1992 and May 2008; of these women, 511 previously had undergone LEEP and another 842 underwent LEEP after the index pregnancy. When compared with the general obstetric population, no increased risk of preterm birth was observed for either group. This was true regardless of the reason for preterm birth. Likewise, there was no increased risk of delivery before 34 weeks or between 34 and 36 weeks of gestation. CONCLUSION: No association was observed between LEEP and preterm birth in women undergoing the procedure before or after an index pregnancy. LEVEL OF EVIDENCE: II

Second trimester cervical length and risk of preterm birth in women with twin gestations treated with 17-α hydroxyprogesterone caproate

Objective. To compare rates of preterm birth before 35 weeks based on cervical length measurement at 16–20 weeks in women with twin gestations who received 17-α hydroxyprogesterone caproate (17OHPC) or placebo. Methods. This is a secondary analysis of a randomised, double-blind, placebo-controlled trial of twin gestations exposed to 17OHPC or placebo. Baseline transvaginal ultrasound evaluation of cervical length was performed prior to treatment assignment at 16–20 weeks. Cervical length measurements were categorised according to the 10th, 25th, 50th and 75th percentiles in the women studied. The effect of 17OHPC administration in women with a short (25th percentile) and long (75th percentile) cervix was evaluated. Results. Of 661 twin gestations studied, 221 (33.4%) women enrolled at 11 centers underwent cervical length measurement. The 10th, 25th, 50th, 75th percentiles for cervical length at 16–20 weeks were 32, 36, 40 and 44 mm, respectively. The risk of preterm birth <35 weeks was increased in women with a cervical length <25th percentile (55.8 vs. 36.9%, p = 0.02). However, a cervical length >75th percentile at this gestational age interval was not protective for preterm birth (36.5 vs. 42.9%, p = 0.42). Administration of 17OHPC did not reduce preterm birth before 35 weeks among those with either a short or a long cervix (64.3 vs. 45.8%, p = 0.18 and 38.1 vs. 35.5%, p = 0.85, respectively). Conclusion. Women with twin gestations and a cervical length below the 25th percentile at 16–20 weeks had higher rates of preterm birth. In this subgroup of women, 17 OHPC did not prevent preterm birth before 35 weeks gestation. A cervical length above the 75th percentile at 16–20 weeks did not significantly reduce the risk of preterm birth in this high risk population.

Weekly compared with daily blood glucose monitoring in women with diet-treated gestational diabetes.

OBJECTIVE: To estimate whether daily blood glucose self-monitoring reduces macrosomia when compared with weekly office testing in women with gestational diabetes. METHODS: Between January 1991 and December 1997, standard treatment at our hospital for women with diet-treated gestational diabetes included routine office monitoring of fasting blood glucose. Beginning in January 1998, blood glucose self-monitoring (four times daily) became the standard management. Women with diet-treated gestational diabetes who underwent routine office-based monitoring of fasting glucose values were compared with similar women who used blood glucose self-monitoring. The outcomes of interest were birthweight at or above 4,000 g and large for gestational age (LGA) in relation to the method of blood glucose self-monitoring. RESULTS: A total of 315 women used daily blood glucose self-monitoring, and they were compared with 675 women with weekly office-based glucose testing. Women with daily blood glucose self-monitoring had fewer macrosomic (29.5% compared with 21.9%, P=.013) and LGA neonates (34.4% compared with 23.1%, P≤.001) and gained significantly less weight (median 0.56, interquartile range 0.22–1.08 lb per week compared with 0.74, interquartile range 0.33–1.17 lb per week, P=.009). CONCLUSION: Daily blood glucose self-monitoring, compared with weekly office-based testing, is associated with a reduction in the incidence of macrosomia. LEVEL OF EVIDENCE: II

Relationship between 17-hydroxyprogesterone caproate concentrations and gestational age at delivery in twin gestation

OBJECTIVE We sought to evaluate in women with twin gestation the relationship between 17-hydroxyprogesterone caproate (17-OHPC) concentration and gestational age at delivery and select biomarkers of potential pathways of drug action. STUDY DESIGN Blood was obtained between 24-28 weeks (epoch 1) and 32-35 weeks (epoch 2) in 217 women with twin gestation receiving 17-OHPC or placebo. Gestational age at delivery and concentrations of 17-OHPC, 17-hydroxyprogesterone, progesterone, C-reactive protein (CRP), and corticotrophin-releasing hormone were assessed. RESULTS Women with higher concentrations of 17-OHPC delivered at earlier gestational ages than women with lower concentrations (P < .001). Women receiving 17-OHPC demonstrated significantly higher (P = .005) concentrations of CRP in epoch 1 than women receiving placebo but CRP values were similar in epoch 2 in both groups. A highly significant (P < .0001) positive relationship was observed between 17-OHPC concentration and progesterone and 17-hydroxyprogesterone concentrations at both epochs. Corticotropin-releasing hormone concentrations did not differ by treatment group. CONCLUSION 17-OHPC may adversely impact gestational age at delivery in women with twin gestation.

Maternal 25-Hydroxyvitamin D and Preterm Birth in Twin Gestations

OBJECTIVE: To assess whether there was an independent association between maternal 25-hydroxyvitamin D concentrations at 24–28 weeks of gestation and preterm birth in a multicenter U.S. cohort of twin pregnancies. METHODS: Serum samples from women who participated in a clinical trial of 17 &agr;-hydroxyprogesterone caproate for the prevention of preterm birth in twin gestations (2004–2006) were assayed for 25-hydroxyvitamin D concentrations using liquid chromatography tandem mass spectrometry (n=211). Gestational age was determined early in pregnancy using a rigorous algorithm. Preterm birth was defined as delivery of the first twin or death of either twin at less than 35 weeks of gestation. RESULTS: The mean serum 25-hydroxyvitamin D concentration was 82.7 nmol/L (standard deviation 31.5); 40.3% of women had concentrations less than 75 nmol/L. Preterm birth at less than 35 weeks of gestation occurred in 49.4% of women with 25-hydroxyvitamin D concentrations less than 75 nmol/L compared with 26.2% among those with concentrations of 75 nmol/L or more (P<.001). After adjustment for maternal race and ethnicity, study site, parity, prepregnancy body mass index, season, marital status, education, gestational age at blood sampling, smoking status, and 17 &agr;-hydroxyprogesterone caproate treatment, maternal 25-hydroxyvitamin D concentration of 75 nmol/L or more was associated with a 60% reduction in the odds of preterm birth compared with concentrations less than 75 nmol/L (adjusted odds ratio [OR] 0.4, 95% confidence interval [CI] 0.2–0.8). A similar protective association was observed when studying preterm birth at less than 32 weeks of gestation (OR 0.2, 95% CI 0.1–0.6) and after confounder adjustment. CONCLUSIONS: Late second-trimester maternal 25-hydroxyvitamin D concentrations less than 75 nmol/L are associated with an increase in the risk of preterm birth in this cohort of twin pregnancies. LEVEL OF EVIDENCE: II

Diet-treated gestational diabetes mellitus: comparison of early vs routine diagnosis

OBJECTIVE The purpose of this study was to compare pregnancy outcomes in women with diet-treated gestational diabetes mellitus (GDM) that was diagnosed at < 24 weeks of gestation to those women who received the diagnosis at > or = 24 weeks of gestation. STUDY DESIGN This was a retrospective cohort study of 2596 women with diet-treated GDM who delivered between December 1999 and June 2005 at Parkland Hospital. Women with risk factors for GDM underwent immediate glucose screening; women without risk factors underwent universal glucose screening between 24 and 28 weeks of gestation. Women with diet-treated GDM that was diagnosed at < 24 weeks of gestation (n = 339; 13.1%) were compared with those women who received the diagnosis at > or = 24 weeks of gestation. RESULTS Women with an earlier diagnosis of diet-treated GDM were at increased risk of preeclampsia and the delivery of large infants. Even after adjustment for differences in maternal characteristics and glycemic control, the risk of preeclampsia persisted (odds ratio, 2.4; 95% CI, 1.5, 3.8). CONCLUSION Women with an early diagnosis of diet-treated GDM have a 2-fold increased risk of preeclampsia.

Prediction of diabetes recurrence in women with class A1 (diet-treated) gestational diabetes.

We sought to evaluate the likelihood of recurrent diabetes in women with a prior history of diet-treated (class A(1)) gestational diabetes mellitus (GDM). In a retrospective cohort analysis, nulliparous women diagnosed based upon National Diabetes Data Group criteria with diet-treated GDM who had recurrent diabetes in a subsequent pregnancy were compared with those who did not have recurrent diabetes. The probability of recurrent diabetes was calculated using maternal age at first pregnancy, interpregnancy interval, and body mass index (BMI) during the subsequent pregnancy. Three hundred forty-four nulliparous women with diet-treated GDM had a subsequent delivery in our database. One hundred thirty-seven (40%) had recurrent diabetes. Women with a history of GDM were more likely to have recurrent diabetes if they were heavier (193 versus 173 lbs; P < 0.001; BMI 35.7 versus 32.2; P < 0.001) and waited longer between pregnancies (2.9 versus 2.4 years, P = 0.02). Age, interpregnancy interval, and BMI can be used to predict diabetes recurrence in pregnant women with a history of GDM.

Ruptured membranes at term: randomized, double-blind trial of oral misoprostol for labor induction

OBJECTIVE To determine if oral misoprostol can replace oxytocin for labor stimulation in women with ruptured membranes at term and without evidence of labor. METHODS Nulliparous women at 36 to 41 6/7 weeks with a singleton, cephalic-presenting fetus and ruptured membranes without evidence of labor were randomized to receive oral misoprostol (100 μg) or a placebo every 4 hours for a maximum of two doses. Intravenous oxytocin was initiated if active labor had not ensued within 8 hours of the initial study drug dose. RESULTS Fifty-one women were randomized to oral misoprostol and 51 women to the placebo. Misoprostol reduced the use of oxytocin stimulation of labor from 90% to 37% (P < .001) and was associated with approximately a 7-hour shorter elapsed time in the labor unit. Uterine hyperactivity, defined as six or more contractions in 10 minutes without fetal heart rate decelerations, occurred in 25% of women randomized to misoprostol. However, uterine hyperactivity associated with fetal heart rate decelerations occurred in only three (6%) women, none of whom required emergency cesarean delivery. Route of delivery and infant outcomes were not related to misoprostol use. CONCLUSION Oral misoprostol (100 μg) given in a maximum of two doses 4 hours apart significantly reduced the use of oxytocin in the management of women with ruptured membranes without labor at term.

Accuracy of Sonographic Chorionicity Classification in Twin Gestations

To evaluate the accuracy of sonographic classification of chorionicity in a large cohort of twins and investigate which factors may be associated with sonographic accuracy.