Prior Spontaneous Preterm Birth Research Articles

Prior Ultrasound-Indicated Cerclage

INTRODUCTION: To evaluate pregnancy outcomes of women with a history of ultrasound-indicated cerclage for a short cervix who in subsequent pregnancy either were followed by transvaginal ultrasound cervical length screening or received a history-indicated cerclage. METHODS: Retrospective cohort study was performed from 1993 to 2012 involving women with an index singleton pregnancy and history of ultrasound-indicated cerclage. Prior ultrasound-indicated cerclage was defined as cerclage placed for cervical length less than 25 mm before 24 weeks of gestation in women at high risk for preterm birth. At our institution, women with a history of ultrasound-indicated cerclage were managed in their subsequent pregnancy either by transvaginal ultrasound cervical length screening or by history-indicated cerclage, at the physician's discretion (Fig. 1). In the transvaginal ultrasound cervical length group, if cervical length became less than 25 mm before 24 weeks of gestation, an ultrasound-indicated cerclage was performed. In the history-indicated cerclage group, history-indicated cerclage was placed at approximately 12–15 weeks of gestation. Primary outcome was spontaneous preterm birth at less than 35 weeks (Table 1).RESULTS: Twenty-eight women met the inclusion criteria. Of these 28 women, 13 were in the transvaginal ultrasound cervical length group and 15 in the history-indicated cerclage group. Demographics were similar in both the groups, except earliest gestational age of prior spontaneous preterm birth (Table 1). The odds of spontaneous preterm birth at less than 35 weeks of gestation for the two groups was similar (odds ratio 0.54, 95% confidence interval 0.04–6.77). Secondary outcomes were also similar in two groups except birth weight (Table 1). CONCLUSION: Women with prior ultrasound-indicated cerclage have similar outcomes if they are managed in the next pregnancy by either transvaginal ultrasound cervical length screening and ultrasound-indicated cerclage placement if cervical length is less than 25 mm before 24 weeks of gestation or by history-indicated cerclage. Our study results are limited by small sample size. There are currently no other studies evaluating this clinical dilemma.

Implementation of a Universal Cervical Length Screening Program for the Prevention of Preterm Birth

The objective of this article is to evaluate the implementation and acceptability of a universal cervical length (CL) screening program for prediction and prevention of preterm birth (PTB). We performed a prospective observational study to evaluate the implementation and acceptability of a universal CL screening program. Between January 1, 2012, and December 31, 2012, women with singleton gestations, without a cerclage or prior spontaneous PTB, were offered transvaginal ultrasound (TVU) for CL between 18(0/7) and 23(6/7) weeks' gestation. Sonographers and medical staff received education before implementation. Intervention for a short CL was interpreted according to a standard protocol. On June 1, 2012, our program was modified from "opt-in" to "opt-out." SPSS 20.0 (released 2011, IBM statistics for Windows version 20, IBM Corp., Armonk, NY) was used for analysis. Over 12 months, 1,484 (87%) of 1,706 eligible women were offered CL screening, and 1,119 (75%) were actually screened. Women were more likely to accept CL screening if they were nulliparous versus multiparous (83 vs. 68%, p < 0.001) and if the sonographer was female versus male (83 vs. 42%, p < 0.001). Implementation of an "opt-out" protocol did not increase the overall number of women accepting CL screening compared with an "opt-in" approach (76 vs. 75%, p = 0.81) CONCLUSION: Universal CL screening can be feasibly implemented and is acceptable to most women.

771: Can cervical length and obstetric history identify asymptomatic women at low risk for preterm birth after a previous preterm birth: a re-analysis of individual patient data

Women with a prior spontaneous preterm birth (PSPTB) are considered to be at high risk for recurrent preterm birth. We investigated whether cervical length (CL) and details of their PSPTB could stratify women into risk groups and identify a subgroup at low risk for recurrent preterm birth.

795: Clinical presentation of prior preterm delivery as a risk factor for subsequent cervical shortening

While it is known that women with a prior spontaneous preterm birth are at increased risk for short cervical length in a subsequent pregnancy, there is little evidence regarding whether a particular clinical presentation during an index pregnancy - premature rupture of membranes (PPROM), preterm labor, or painless cervical dilatation in the absence of contractions - places women at higher or lower risk for short cervix in a subsequent pregnancy.

Proteomic analysis of cervical vaginal fluid proteins among women in recurrent preterm labor

Objective: Proteomic analysis of four cervical-vaginal fluid (CVF) proteins to identify biomarkers of recurrent preterm birth (rPTB) in at-risk women prior to onset of preterm labor.Methods: Nested case control study from 2007 to 2011 of women with prior spontaneous preterm birth(s) (PTB) who underwent serial CVF sampling. Mass spectrometry analysis was used and ELISA analysis was performed to validate candidates.Results: 108 patients were enrolled and 10 cases and 20 gestational age matched controls were analyzed after exclusions. Of 748 CVF proteins identified, 72 had statistically significant (p < 0.05) expression differences and 38 were highly differentially expressed (p < 0.01). Four candidate proteins were abundant and involved in immune/inflammatory response, but ELISA analysis did not confirm altered expression patterns.Conclusion: The lack of confirmation of potential biomarkers identified by mass spectrometry and ELISA demonstrates the challenges of validating PTB biomarkers and suggests that a panel of biomarkers would improve the predictive value of CVF testing.

Relationship between 17-alpha hydroxyprogesterone caproate concentration and spontaneous preterm birth

17-alpha hydroxyprogesterone caproate 250 mg weekly reduces recurrent spontaneous preterm birth in women with a prior spontaneous preterm birth by 33%. The dose is not based on pharmacologic considerations. A therapeutic concentration has not been determined hampering any attempt to optimize treatment. This study evaluated the relationship between 17-alpha hydroxyprogesterone caproate plasma concentrations and the rate of spontaneous preterm birth in women with singleton gestation. A single blood sample was obtained between 25 and 28 weeks' gestation from 315 women with a spontaneous preterm birth who participated in a placebo-controlled, prospective, randomized clinical trial evaluating the benefit of omega-3 supplementation in reducing preterm birth. All women in the parent study received 17-alpha hydroxyprogesterone caproate and 434 received omega-3 supplementation and 418 received a placebo. Plasma from 315 consenting women was analyzed for 17-alpha hydroxyprogesterone caproate concentration. There were no differences between placebo and omega-3 supplemented groups in demographic variables, outcomes or in mean 17-alpha hydroxyprogesterone caproate concentration. Plasma concentrations of 17-alpha hydroxyprogesterone caproate ranged from 3.7-56 ng/mL. Women with plasma concentrations of 17-alpha hydroxyprogesterone caproate in the lowest quartile had a significantly higher risk of spontaneous preterm birth (P= .03) and delivered at significantly earlier gestational ages (P= .002) than did women in the second to fourth quartiles. The lowest preterm birth rates were seen when median 17-alpha hydroxyprogesterone caproate concentrations exceeded 6.4 ng/mL. Low plasma 17-alpha hydroxyprogesterone caproate concentration is associated with an increased risk of spontaneous preterm birth. This finding validates efficacy of this treatment but suggests that additional studies are needed to determine the optimal dosage.

Vaginal Progesterone, Cerclage or Cervical Pessary for Preventing Preterm Birth in Asymptomatic Singleton Pregnant Women With a History of Preterm Birth and a Sonographic Short Cervix

A major effort to decrease preterm birth rates is directed at preventing recurrent spontaneous preterm birth in singleton pregnancies. Shortened cervical length is one predictor of spontaneous preterm birth, and cervical pessary and cerclage are often used. This study was undertaken to compare the outcomes in women with a singleton pregnancy and history of preterm birth and sonographic short cervix, managed with cerclage, vaginal progesterone, or cervical pessary. The 3 cohorts of asymptomatic women had a singleton pregnancy, a history of at least 1 spontaneous preterm birth at less than 34 weeks, and a short cervix on ultrasonography. Cohort A included 142 women (United States) initially treated with cerclage (with or without 17α-hydroxyprogesterone caproate); cohort B comprised 59 women (United Kingdom) treated with vaginal progesterone followed by cerclage in cases of progressive cervical shortening, and cohort C had 42 women from Spain treated with cervical pessary. Women in cohort A had 1 prior spontaneous preterm birth and received cerclage when the cervical length was less than 25 mm. Management after cerclage followed standard protocols, and the cerclage suture was removed at 37 weeks’ gestation. For cohort B, short cervix was defined as 30.5 mm at 16 weeks’ gestation and 24.5 mm at 23 weeks’ gestation. Women were prescribed 200 mg vaginal progesterone. If additional significant cervical shortening was noted after treatment began, ultrasound-indicated cerclage was performed. In cohort C, serial transvaginal scans of the cervix started at 16 weeks’ gestation and continued at 1- to 4-weekly intervals. The pessary was removed at 37 weeks. Outcomes assessed included preterm births before 37, 34, and 28 weeks’ gestation; cesarean delivery; perinatal losses; and serious neonatal morbidity. The demographic characteristics of the 3 cohorts were similar but with slight differences in ethnicity/race among the groups. In cohort A, 38% of women also indicated an intent to receive weekly injections of 17α-hydroxyprogesterone caproate. Seven women (12%) in cohort B had rescue treatment because of progressive cervical shortening; 6 had cerclage, and 1 had a cervical pessary. The 3 groups did not differ significantly in the number of preterm births at less than 37 weeks (44%, 46%, and 45% for cohorts A, B, and C, respectively) or in rates of cesarean delivery (30%, 20%, and 24%, respectively). Fewer preterm births before 34 and 28 weeks’ gestation occurred in group C, but differences were not statistically significant except for births at less than 34 weeks in cohort B compared with cohort C (32% vs 12%; relative risk [RR], 2.70; 95% CI, 1.10–6.67). In comparing only the women with cervical length of less than 25 mm, regardless of gestational age, the difference between cohorts B and C was not statistically significant (RR, 2.21; 95% CI, 0.83–5.89). Neonatal deaths and serious neonatal morbidity were rare, and the 3 groups did not differ significantly. The available treatments for women with short cervix carry similar rates of effectiveness. Other than the higher incidence of preterm birth at less than 34 weeks’ gestation in cohort B compared with cohort C, no other comparisons were statistically significant. Without randomized cohorts and long-term safety data, the decision regarding which treatment options to choose should consider the preferences of the patient and clinician. International collaborations should be undertaken to investigate these treatments in adequately powered randomized trials that include low- and high-risk women.

Change in Mononuclear Leukocyte Responsiveness in Midpregnancy and Subsequent Preterm Birth

To estimate the associations of change in immune response with preterm delivery, omega-3 supplementation, and fish diet. This was an ancillary study to a randomized trial of omega-3 fatty acid supplementation for the prevention of recurrent preterm birth. In vitro maternal peripheral blood mononuclear leukocyte production of the anti-inflammatory cytokine, interleukin-10, and the proinflammatory cytokine, tumor necrosis factor-α, in response to stimulation with lipopolysaccharide, was measured at 16-22 weeks of gestation (baseline) and again at 25-28 weeks of gestation (follow-up) among women with prior spontaneous preterm birth. Changes in concentrations from baseline to follow-up ([INCREMENT]) were compared separately among groups defined by gestational age category at delivery, fish diet history, and omega-3 compared with placebo treatment assignment with Kruskal-Wallis tests. Interleukin-10 [INCREMENT] differed by gestational age category among 292 women with paired assays. Concentrations increased less in women delivering between 35 and 36 6/7 weeks of gestation (48.9 pg/mL) compared with women delivering at term (159.3 pg/mL) and decreased by 65.2 pg/mL in women delivering before 35 weeks of gestation (P=.01). Tumor necrosis factor-α Δ also differed by gestational age category among 319 women, but the pattern was inconsistent. Those delivering between 35 and 36 6/7 weeks of gestation exhibited decreased concentrations of tumor necrosis factor-α at follow-up compared with baseline (-356.0 pg/mL); concentrations increased among women delivering before 35 weeks of gestation and those delivering at term, 132.1 and 86.9 pg/mL (P=.03). Interleukin-10 Δ and tumor necrosis factor-α Δ were unaffected by either omega-3 supplementation or fish diet. Recurrent preterm birth was associated with decreased peripheral blood mononuclear leukocyte production of interleukin-10 in response to a stimulus during the second trimester. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00135902. II.

The Rebirth of Progesterone in the Prevention of Preterm Labor

To evaluate data since 2003 on the efficacy and safety of progesterone supplementation in the prevention of preterm labor. A MEDLINE and Ovid database search (January 2003-September 2012) was performed using the search terms preterm, progesterone, and 17α-hydroxyprogesterone caproate. All relevant abstracts were reviewed. For efficacy and safety data, the search was limited to randomized, double-blind, placebo-controlled trials with the primary outcome of preterm delivery, fetal loss, or neonatal morbidity or mortality. Quality of the studies was assessed using the CONSORT (Consolidated Standards of Reporting Trials) guidelines for reporting parallel-group randomized trials. Eleven articles were selected for review. Preterm birth, prior to 37 weeks' gestation, remains the leading cause of neonatal morbidity and mortality in the US due to lack of treatment options. Recently, the use of progesterone to prevent preterm labor, deemed decades ago to be ineffective, has been reexamined. Progesterone formulations and dosage regimens varied greatly between studies. In patients with prior preterm birth or shortened cervix shown on transvaginal ultrasound, progesterone appears efficacious in reducing the rate of preterm birth. However, this benefit was not demonstrated in multiple-gestation pregnancies. Overall, progesterone was well tolerated and appeared safe for mother and fetus. More studies are needed to confirm the dosage regimen and population that will benefit most from progesterone. Progesterone appears to be safe and efficacious in reducing the risk of preterm birth in a select group of high-risk women with prior spontaneous preterm births and those with an ultrasound-confirmed short cervix. Women with multiple gestations do not benefit from progesterone supplementation.

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

Objective: To examine the influence of maternal pre-pregnancy body mass index (BMI) on the rates of recurrent spontaneous preterm birth (SPTB) in women receiving 17α-hydroxyprogesterone caproate (17P).Methods: Retrospective analysis of a cohort of 6253 women with a singleton gestation and prior SPTB enrolled in 17P home administration program between 16.0 and 26.9 weeks. Data were grouped by pre-pregnancy BMI (lean <18.5 kg/m2, normal 18.5–24.9 kg/m2, overweight 25–29.9 kg/m2 and obese ≥30.0 kg/m2). Delivery outcomes were compared using χ2 and Kruskal–Wallis tests with statistical significance set at p < 0.05.Results: SPTB<28 weeks was significantly lower in normal weight women. Rates of recurrent SPTB<37 weeks were highest in the group with BMI<18.5 kg/m2. Lean gravidas were younger, more likely to smoke, and less likely to be African–American than those with normal or increased BMI. In logistic regression, after controlling for race and prior preterm birth <28 weeks, the risk of SPTB<37 weeks decreased 2% for every additional 1 kg/m2 increase in BMI.Conclusions: Recurrent spontaneous preterm delivery<37 weeks in patients on 17P is more common in lean women (BMI<18.5 kg/m2), and less common in obese women (BMI ≥30 kg/m2) suggesting that the current recommended dosing of 17 P is adequate for women with higher BMI.

Vaginal progesterone, cerclage or cervical pessary for preventing preterm birth in asymptomatic singleton pregnant women with a history of preterm birth and a sonographic short cervix

To compare the outcome of pregnancy in cohorts of women with singleton pregnancy and history of preterm birth and sonographic short cervix managed with different treatment protocols, namely cerclage, vaginal progesterone or cervical pessary. This was a comparison of three management protocols for women with singleton pregnancy and a high risk of preterm birth because of a prior spontaneous preterm birth before 34 weeks and a shortened cervical length detected by transvaginal ultrasound. The study included 142 women who were initially treated with cerclage (USA), 59 with vaginal progesterone (UK) and 42 with cervical pessary (Spain). Perinatal outcomes were compared between the three cohorts. There were no statistically significant differences in perinatal losses, neonatal morbidity and preterm births among the three groups, apart from a higher rate of preterm birth before 34 weeks' gestation after treatment with vaginal progesterone in comparison with treatment with cervical pessary (32% vs 12%; relative risk (RR) = 2.70; 95% CI, 1.10-6.67). When only the subgroups of women with cervical length < 25 mm, irrespective of gestational age, were compared, the difference between these two cohorts was not statistically significant (RR = 2.21; 95% CI, 0.83-5.89). Cerclage, vaginal progesterone and pessary appear to have similar effectiveness as management strategies in women with singleton pregnancy, previous spontaneous preterm birth and short cervix. Direct randomized comparisons of these strategies, or combinations thereof, are needed to determine optimal management.

503: Implementation of a universal cervical length surveillance program for prediction of preterm birth

503 Implementation of a universal cervical length surveillance program for prediction of preterm birth Kelly Orzechowski, Sara Nicholas, Stuart Weiner, Jason Baxter, Vincenzo Berghella Thomas Jefferson University Hospital, Obstetrics & Gynecology, Philadelphia, PA OBJECTIVE: To evaluate factors associated with successful implementation of a universal cervical length (CL) screening program for prediction of preterm birth. STUDY DESIGN: We performed a retrospective cohort study to evaluate the acceptability of universal CL screening program for the prediction of preterm birth (PTB) between January 1, 2012 and June 30, 2012. Women with singleton gestations undergoing obstetric ultrasounds between 18 0/7-23 6/7 weeks were eligible for CL screening. Patients with prior spontaneous PTB were excluded. CL measurements were always performed in a uniform fashion with transvaginal ultrasound and the results were interpreted according to a standard protocol (Figure). Sonographers and medical staff received education prior to implementation and appointment times were extended by 10 minutes. Patients received educational handouts at check-in. On June 1, 2012, our program was modified from “opt-in” to “opt-out” in attempt to improve patient acceptance rates. Independent samples Mann-Whitney U, Chi-square, and independent samples t-tests were performed using SPSS 20.0. RESULTS: During the study period, 733 (82%) of 898 eligible patients were offered CL screening. Women were more likely to accept CL screening if they were nulliparous and if the sonographer was female. Implementation of an “opt-out” CL screening program significantly increased the percentage of women screened (Table). Among 561 women who accepted CL screening, 9 (1.6%) had a CL 25mm and 6 (1%) had a CL 20mm and were offered vaginal progesterone. CONCLUSION: Universal CL screening is acceptable to most women and is feasible to implement on a large scale. Patient education is necessary to achieve optimal rates of acceptance. An “Opt-out” screening approach increases acceptance rates. 504 Does cervical conization increase the risk of a sonographic short cervix in the second trimester of pregnancy? Kelly Orzechowski, Sara Nicholas, Vincenzo Berghella Thomas Jefferson University Hospital, Obstetrics & Gynecology, Philadelphia, PA OBJECTIVE: To evaluate whether prior cervical conization increases the incidence of a sonographic short cervix in the second trimester of pregnancy. STUDY DESIGN: We conducted a retrospective cohort study from January 1, 2012 to June 30, 2012 involving women with singleton gestations between 18 0/7-23 6/7 weeks undergoing universal cervical length (CL) screening with transvaginal ultrasound for prediction of preterm birth. Women with a prior spontaneous preterm birth and those receiving prenatal care at outside institutions were excluded. History of cervical conization including cold knife conization (CKC) and Loop Electrosurgical Excision Procedure (LEEP) was determined by review of the prenatal record. The primary outcomes were mean CL measurement and the incidence of a short cervix (CL 20mm) among women with and without prior cervical conization. Independent samples Mann-Whitney U, Chi-square, and independent samples t-tests were performed using SPSS 20.0. RESULTS: During the study period, 527 women underwent second trimester CL screening, and of those, 33 (6.2%) had a documented history of prior conization (4 CKC and 29 LEEP). Demographic characteristics between the groups are shown in the Table. The mean midtrimester cervical length in women with prior cervical conizations was significantly shorter compared to women without a history of conization (39mm vs. 43mm, p 0.012). Women with prior conization also had a significantly higher incidence of CL 25mm (6% vs. 1%, p 0.046) as well as a non-significant higher incidence of CL 20mm. CONCLUSION: In a universal CL screening program, women with prior cervical conizations have shorter second trimester cervical lengths and a higher incidence of short cervix compared to women without such a history. Universal CL screening algorithm Demographics and outcomes of a universal CL screening program

529: Cervical cerclage, progesterone supplementation, and spontaneous preterm birth

Women with a prior spontaneous preterm birth (SPTB) and/or prior or current cervical insufficiency may be candidates for both supplementation with 17-alpha hydroxyprogesterone caproate (17P) and cervical cerclage placement. However, the relationship between the simultaneous use of these interventions and SPTB is uncertain. We sought to examine pregnancy outcomes among women with cerclage with and without 17P.

619: A history of prior preeclampsia is a major risk factor for preterm birth

major risk factor for preterm birth Brendan Connealy, Carlos Carreno, Benjamin Kase, Laura Hart, Sean Blackwell, Baha Sibai University of Texas Health Science Center Houston, Obstetrics, Gynecology, and Reproductive Sciences, Houtson, TX OBJECTIVE: Women with prior preeclampsia are considered at increased risk for adverse pregnancy outcomes (recurrent preeclampsia, fetal growth restriction, abruptio placentae). Limited data exists to describe an association between prior preeclampsia and spontaneous preterm birth (SPTB). Our objective is to evaluate the frequency of SPTB in women with prior preeclampsia and describe neonatal outcomes in these infants compared those with indicated preterm birth (IPTB). STUDY DESIGN: This is a secondary analysis of data in women with prior preeclampsia enrolled in a multicenter randomized trial of low dose aspirin for preeclampsia prevention. Inclusion criteria were women with history of prior preeclampsia, and live fetus. Women with preexisting medical disorders were excluded. Indications for delivery were categorized as SPTB (PTL or PPROM) and IPTB. Primary outcomes were rates of SPTB and IPTB by GA. Composite respiratory morbidity and NICU admission were compared between groups. Chi square and t test were used to establish a difference between the study groups. RESULTS: Of the 606 pregnancies studied, 142 (23%) delivered at 37 weeks. Of those delivered preterm, 47% were due to SPTB and 53% were IPTB. The table below summarizes the frequency of PTB by subtype and GA. There were no significant differences in rates of SPTB or IPTB, or in the rates of composite neonatal morbidity, between the GA groups. There were 14 perinatal deaths (2.3%): of which the majority (13) were at 34 weeks. Additionally, there were no differences in NICU admission between the groups. CONCLUSION: Women with prior preeclampsia have a substantially high rate of preterm birth with almost half being spontaneous and nearly two-thirds occurring in the late preterm. We recommend that prior preeclampsia should be considered a risk factor for both IPTB and SPTB with the potential for early intervention to improve perinatal outcome. 620 Timing of adverse neonatal outcomes in pregnancies complicated by preeclampsia and small for gestational age births in a cohort of high-risk pregnancies Cande Ananth, Jaclyn Coletta-Lucas, Ronald Wapner Columbia University Medical Center, Department of Obstetrics and Gynecology, New York, NY OBJECTIVE: In a group of high-risk women with underlying medical conditions predisposing to preeclampsia and small for gestational age (SGA), the timing of delivery is often based on a worsening maternal condition. We evaluated the risk of adverse neonatal outcomes in early intervention compared to spontaneous delivery. STUDY DESIGN: We performed a secondary analysis of data from the Maternal-Fetal Medicine Units network of a randomized controlled trial of aspirin to prevent preeclampsia in high-risk women (those with chronic hypertension, insulin-dependent diabetes mellitus and women with previous preeclampsia). The trial resulted in no benefit of aspirin on the risk of preeclampsia. We examined risks of adverse composite neonatal outcomes (perinatal death, respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage, retinopathy of prematurity, patent ductus arteriosus, pulmonary hypertension, neonatal seizures, admission to the neonatal intensive care unit and 5-minute Apgar 5) in relation to preeclampsia and small for gestational age (SGA, birthweight 10% for gestational age). Odds ratio (OR) and 95% confidence interval (CI) were estimated from logistic regression models after adjusting for potential confounders. RESULTS: Of the 1,787 women in the high-risk trial, the overall risk of composite neonatal outcome was 29.3%. The risk of composite outcome was higher in the SGA-only and preeclampsia (with or without SGA) groups, but this association was evident only at preterm gestations (Table). Among infants that were SGA (only), the risk of neonatal morbidity was dramatically higher among women that had a spontaneous rather than indicated preterm birth. CONCLUSION: In a group of women at high-risk for preeclampsia, appropriately timed obstetrical interventions at preterm gestations, relative to spontaneous preterm birth, is associated with reduced risk of neonatal morbidity.

Association between body mass index and pregnancy outcome in a randomized trial of cerclage for short cervix.

To evaluate whether increasing body mass index (BMI) alters the efficacy of ultrasound-directed cerclage in women with a history of preterm birth. This was a planned secondary analysis of a multicenter trial in which women with a singleton gestation and prior spontaneous preterm birth (17 to 33 + 6 weeks' gestation) were screened for a short cervix by serial transvaginal ultrasound evaluations between 16 and 22 + 6 weeks. Women with a short cervix (cervical length < 25 mm) were randomly assigned to cerclage or not. Linear and logistic regression were used to assess the relationship between BMI and continuous and categorical variables, respectively. Overall, in the screened women (n = 986), BMI was not associated with cervical length (P = 0.68), gestational age at delivery (P = 0.12) or birth at < 35 weeks (P = 0.68). For the cerclage group (n = 148), BMI had no significant effect. For the no-cerclage group (n = 153), BMI was associated with a decrease in gestational age at delivery, with an estimated slope of - 0.14 weeks per kg/m(2) (P = 0.03; including adjustment for cervical length). This result was driven primarily by several women with BMI > 47 kg/m(2) . In women at high risk for recurrent preterm birth, BMI was not associated with cervical length or gestational age at birth. BMI did not appear to adversely affect ultrasound-indicated cerclage.

Vitamin D status and recurrent preterm birth: a nested case-control study in high-risk women.

To determine whether vitamin D status is associated with recurrent preterm birth, and any interactions between vitamin D levels and fish consumption. A nested case-control study, using data from a randomised trial of omega-3 fatty acid supplementation to prevent recurrent preterm birth. Fourteen academic health centres in the USA. Women with prior spontaneous preterm birth. In 131 cases (preterm delivery at <35 weeks of gestation) and 134 term controls, we measured serum 25-hydroxyvitamin D [25(OH)D] concentrations by liquid chromatography-tandem mass spectrometry (LC-MS) from samples collected at baseline (16-22 weeks of gestation). Logistic regression models controlled for study centre, maternal age, race/ethnicity, number of prior preterm deliveries, smoking status, body mass index, and treatment. Recurrent preterm birth at <37 and <32 weeks of gestation. The median mid-gestation serum 25(OH)D concentration was 67 nmol/l, and 27% had concentrations of <50 nmol/l. Serum 25(OH)D concentration was not significantly associated with preterm birth (OR 1.33; 95% CI 0.48-3.70 for lowest versus highest quartiles). Likewise, comparing women with 25(OH)D concentrations of 50 nmol/l, or higher, with those with <50 nmol/l generated an odds ratio of 0.80 (95% CI 0.38-1.69). Contrary to our expectation, a negative correlation was observed between fish consumption and serum 25(OH)D concentration (-0.18, P < 0.01). In a cohort of women with a prior preterm birth, vitamin D status at mid-pregnancy was not associated with recurrent preterm birth.

Universal Cervical Length Screening for Prediction and Prevention of Preterm Birth

Universal transvaginal ultrasound (TVU) cervical length (CL) screening represent a step forward in the campaign against preterm birth (PTB). Transvaginal ultrasound CL is a safe, acceptable, reproducible, and accurate screening test, with potentially widespread availability given its feasibility. For this screening to be effective, the ultrasounds should be done with proper TVU technique and with continuing quality assurance. Clinicians should refrain from screening different populations, at different gestational ages, and from stretching the definition of short CL to include measurements above 25 mm. A single TVU CL measurement at about 18 to 24 6/7 weeks can be offered to all singleton gestations. About 2% to 5% of these women will demonstrate a TVU CL of 20 mm or less and should be offered vaginal progesterone, either 200-mg suppository or 90-mg gel daily, until 36 weeks, being counseled that this intervention has been associated with about 45% decrease in PTB and neonatal benefits. Serial TVU CL measurements, about every 2 weeks and weekly if CL is 25 to 29 mm, can be offered between about 16 and 23 6/7 weeks to singleton gestations with a prior spontaneous PTB. In the 40% of these women who will develop a short TVU CL of less than 25 mm, cerclage should be offered, as it is associated with a significant 30% reduction in the risk of PTB less than 35 weeks and a 36% reduction in composite perinatal mortality and morbidity. Transabdominal CL screening has not been sufficiently studied and cannot be recommended. Results from just 1 trial offer promise for pessary as another effective intervention, which cannot be recommended yet until results are confirmed with another trial. Transvaginal ultrasound CL in multiples cannot be recommended yet, given lack of effective interventions in this population.

Progestogens for Preterm Birth Prevention

We systematically reviewed the effectiveness of progestogens for prevention of preterm birth among women with prior spontaneous preterm birth, multiple gestations, preterm labor, short cervix, or other indications. We searched MEDLINE and EMBASE databases for English language articles published from January 1966 to October 2011. We excluded publications that were not randomized controlled trials or had fewer than 20 participants, identifying 34 publications, of which 19 contained data for Bayesian meta-analysis. Two reviewers independently extracted data and assigned overall quality ratings based on predetermined criteria. Among women with prior preterm birth and a singleton pregnancy (five randomized controlled trials), progestogen treatment decreased the median risk of preterm birth by 22% (relative risk [RR] 0.78, 95% Bayesian credible interval 0.68-0.88) and neonatal death by 42% (RR 0.58, 95% Bayesian credible interval 0.27-0.98). The evidence suggests progestogen treatment does not prevent prematurity (RR 1.02, 95% Bayesian credible interval 0.87-1.17) or neonatal death (RR 1.44, 95% Bayesian credible interval 0.46-3.18) in multiple gestations. Limited evidence suggests progestogen treatment may prevent prematurity in women with preterm labor (RR 0.62, 95% Bayesian credible interval 0.47-0.79) and short cervix (RR 0.52, 95% Bayesian credible interval 0.36-0.70). Across indications, evidence about maternal, fetal, or neonatal health outcomes, other than reducing preterm birth and neonatal mortality, is inconsistent, insufficient, or absent. Progestogens prevent preterm birth when used in singleton pregnancies for women with a prior preterm birth. In contrast, evidence suggests lack of effectiveness for multiple gestations. Evidence supporting all other uses is insufficient to guide clinical care. Overall, clinicians and patients lack longer-term information to understand whether intervention has the ultimately desired outcome of preventing morbidity and promoting normal childhood development.

Cerclage for the prevention of preterm birth in high risk women receiving intramuscular 17-α-hydroxyprogesterone caproate

Objective: To assess cerclage benefit in women with short cervix also receiving 17-α-hydroxyprogesterone caproate (17P) to prevent recurrent preterm birth (PTB). Methods: Secondary analysis of a multicenter trial of ultrasound-indicated cerclage for shortened cervical length (CL). Women with prior spontaneous PTB at 16–33 6/7 weeks, singleton gestation and CL < 25 mm between 16 and 22 6/7 weeks were counseled on use of 17P and randomized to cerclage or no cerclage. Outcomes of women who received 17P were analyzed by randomization group. Primary outcome was PTB < 35 weeks. Results: 99 women received 17P: 47 cerclage; 52 no cerclage. Rates of PTB < 35 weeks were similar, 30% for cerclage and 38% for no cerclage (aOR 0.64 (0.27–1.52)). In women with CL < 15 mm, PTB < 35 weeks was reduced for the cerclage group (17% vs. 75%, p = 0.02). However, this difference was nullified after controlling for total progesterone doses received (p = 0.40). Conclusions: Cerclage was shown not to offer additional benefit for the prevention of recurrent PTB in women with short CL < 25 mm receiving 17P, but the sample size is insufficient for a definite conclusion given the 36% nonsignificant decrease in the odds of PTB < 35 weeks. Cerclage may further offer substantial benefit to women with very short CL < 15 mm and further study is needed.

Treatment Options and Recommendations to Reduce Preterm Births in Women With Short Cervix

Premature shortening of the cervix, or short cervix, is the most predictive risk factor for preterm birth. Results of clinical studies of interventions to prevent preterm birth have shown that identifying at-risk women on the basis of cervical length versus obstetric history alone improves the likelihood of timely interventions with cervical cerclage or progesterone supplementation, improving outcomes. Debate continues over the use of cerclage; however, results of a meta-analysis of randomized controlled trials provide evidence to support its use in women who have history of prior preterm birth and who develop short cervix before 24 weeks' gestation. Results of the recent PREGNANT trial, consistent with the earlier Fetal Medicine Foundation study, support the use of vaginal progesterone for prevention of preterm birth. In women identified by transvaginal ultrasound to have short cervix (10-20 mm) in midtrimester, daily vaginal progesterone gel reduced the risk of preterm birth before 33 weeks' gestation by 45% and before 28 weeks' gestation by 50%. Occurrence of any morbidity and mortality event also was significantly reduced by 43%, with a 61% reduction in the rate of respiratory distress syndrome in infants born to women receiving vaginal progesterone gel versus those receiving placebo. The safety profile of progesterone treatment in early pregnancy is well established, and studies of vaginal progesterone for prevention of preterm birth have identified no additional safety issues. Adverse events were comparable between women receiving progesterone and those receiving placebo. Recent guidelines issued by the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine recommend vaginal progesterone in women with no prior spontaneous preterm birth and cervical length of 20 mm or less at 24 weeks' gestation or earlier. Future studies will refine strategies for prevention of preterm birth to address other risk factors and determine the role of other interventions.