Correlation between neonatal outcomes of twins depends on the outcome: secondary analysis of twelve randomised controlled trials.

OBJECTIVE: To estimate the magnitude of the correlation between neonatal outcomes of twins and demonstrate how this information can be used in the design of randomised controlled trials (RCTs) in women with twin pregnancies. DESIGN: Secondary analysis of data from 12 RCTs. SETTING: Obstetric care in multiple countries, 2004-2012. POPULATION OR SAMPLE: 4504 twin pairs born to women who participated in RCTs to assess treatments given during pregnancy. METHODS: Intraclass correlation coefficients (ICCs) were estimated using log-binomial and linear models. MAIN OUTCOME MEASURES: Perinatal death, respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular haemorrhage, necrotising enterocolitis, sepsis, neonatal intensive care unit admission, birthweight, low birthweight and two composite measures of adverse neonatal outcome. RESULTS: ICCs for the composite measures of adverse neonatal outcome were all above 0.5, indicating moderate to strong correlation between adverse outcomes of twins. For individual neonatal outcomes, median ICCs across trials ranged from 0.13 to 0.79 depending on the outcome. An example illustrates how ICCs can be used in sample size calculations for RCTs in women with twin pregnancies. CONCLUSIONS: The correlation between neonatal outcomes of twins varies considerably between outcomes and may be lower than expected. Our ICC estimates can be used for designing and analysing RCTs that recruit women with twin pregnancies and for performing meta-analyses that include such RCTs. Researchers are encouraged to report ICCs for neonatal outcomes in twins in their own RCTs. TWEETABLE ABSTRACT: Correlation between neonatal outcomes of twins depends on the outcome and may be lower than expected.

Brain size evolution in pipefishes and seahorses: the role of feeding ecology, life history and sexual selection.

Brain size varies greatly at all taxonomic levels. Feeding ecology, life history and sexual selection have been proposed as key components in generating contemporary diversity in brain size across vertebrates. Analyses of brain size evolution have, however, been limited to lineages where males predominantly compete for mating and females choose mates. Here, we present the first original data set of brain sizes in pipefishes and seahorses (Syngnathidae) a group in which intense female mating competition occurs in many species. After controlling for the effect of shared ancestry and overall body size, brain size was positively correlated with relative snout length. Moreover, we found that females, on average, had 4.3% heavier brains than males and that polyandrous species demonstrated more pronounced (11.7%) female-biased brain size dimorphism. Our results suggest that adaptations for feeding on mobile prey items and sexual selection in females are important factors in brain size evolution of pipefishes and seahorses. Most importantly, our study supports the idea that sexual selection plays a major role in brain size evolution, regardless of on which sex sexual selection acts stronger.

17-Hydroxyprogesterone caproate in triplet pregnancy: an individual patient data meta-analysis.

BACKGROUND: Preterm birth complicates almost all triplet pregnancies and no preventive strategy has proven effective. OBJECTIVE: To determine, using individual patient data (IPD) meta-analysis, whether the outcome of triplet pregnancy is affected by prophylactic administration of 17-hydroxyprogesterone caproate (17OHPc). SEARCH STRATEGY: We searched literature databases, trial registries and references in published articles. SELECTION CRITERIA: Randomised controlled trials (RCTs) of progestogens versus control that included women with triplet pregnancies. DATA COLLECTION AND ANALYSIS: Investigators from identified RCTs collaborated on the protocol and contributed their IPD. The primary outcome was a composite measure of adverse perinatal outcome. The secondary outcome was the rate of birth before 32 weeks of gestation. Other pre-specified outcomes included randomisation-to-delivery interval and rates of birth at <24, <28 and <34 weeks of gestation. MAIN RESULTS: Three RCTs of 17OHPc versus placebo included 232 mothers with triplet pregnancies and their 696 offspring. Risk-of-bias scores and between-study heterogeneity were low. Baseline characteristics were comparable between 17OHPc and placebo groups. The rate of the composite adverse perinatal outcome was similar among those treated with 17OHPc and those treated with placebo (34 and 35%, respectively; risk ratio [RR] 0.98, 95% confidence interval [95% CI] 0.79-1.2). The rate of birth at <32 weeks was also similar in the two groups (35 and 38%, respectively; RR 0.92, 95% CI 0.55-1.56). There were no significant between-group differences in perinatal mortality rate, randomisation-to-delivery interval, or other specified outcomes. CONCLUSION: Prophylactic 17OHPc given to mothers with triplet pregnancies had no significant impact on perinatal outcome or pregnancy duration. TWEETABLE ABSTRACT: 17-Hydroxyprogesterone caproate had no significant impact on the outcome or duration of triplet pregnancy.

The effect of gestational age and cervical length measurements in the prediction of spontaneous preterm birth in twin pregnancies: an individual patient level meta-analysis.

OBJECTIVE: To assess the effect of gestational age (GA) and cervical length (CL) measurements at transvaginal ultrasound (TVUS) in the prediction of preterm birth in twin pregnancy. DESIGN: Individual patient data (IPD) meta-analysis. SETTING: International multicentre study. POPULATION: Asymptomatic twin pregnancy. METHODS: MEDLINE and EMBASE searches were performed and IPD obtained from authors of relevant studies. Multinomial logistic regression analysis determined probabilities for birth at ≤28(+0) , 28(+1) to 32(+0) , 32(+1) to 36(+0) , and ≥36(+1) weeks as a function of GA at screening and CL measurements. MAIN OUTCOME MEASURES: Predicted probabilities for preterm birth at ≤28(+0) , 28(+1) to 32(+0) , and 32(+1) to 36(+0) . RESULTS: A total of 6188 CL measurements were performed on 4409 twin pregnancies in 12 studies. Both GA at screening and CL had a significant and non-linear effect on GA at birth. The best prediction of birth at ≤28(+0) weeks was provided by screening at ≤18(+0) weeks (P < 0.001), whereas the best prediction of birth between 28(+1) and 36(+0) weeks was provided by screening at ≥24(+0) weeks (P < 0.001). Negative prediction value of 100% for birth at ≤28(+0) weeks is achieved at CL 65 mm and 43 mm at ultrasound GA at ≤18(+0) weeks and at 22(+1) to 24(+0) weeks, respectively. CONCLUSION: In twin pregnancies, prediction of preterm birth depends on both CL and the GA at screening. When CL is <30 mm, screening at ≤18(+0) weeks is most predictive for birth at ≤28(+0) weeks. Later screening at >22(+0) weeks is most predictive of delivery at 28(+1) to 36(+0) weeks. In twins, we recommend CL screening in twins to commence from ≤18(+0) weeks. TWEETABLE ABSTRACT: An individual patient meta-analysis assessing gestation and CL in the prediction of preterm birth in twins.

Effectiveness of progestogens to improve perinatal outcome in twin pregnancies: an individual participant data meta-analysis.

BACKGROUND: In twin pregnancies, the rates of adverse perinatal outcome and subsequent long-term morbidity are substantial, and mainly result from preterm birth (PTB). OBJECTIVES: To assess the effectiveness of progestogen treatment in the prevention of neonatal morbidity or PTB in twin pregnancies using individual participant data meta-analysis (IPDMA). SEARCH STRATEGY: We searched international scientific databases, trial registration websites, and references of identified articles. SELECTION CRITERIA: Randomised clinical trials (RCTs) of 17-hydroxyprogesterone caproate (17Pc) or vaginally administered natural progesterone, compared with placebo or no treatment. DATA COLLECTION AND ANALYSIS: Investigators of identified RCTs were asked to share their IPD. The primary outcome was a composite of perinatal mortality and severe neonatal morbidity. Prespecified subgroup analyses were performed for chorionicity, cervical length, and prior spontaneous PTB. MAIN RESULTS: Thirteen trials included 3768 women and their 7536 babies. Neither 17Pc nor vaginal progesterone reduced the incidence of adverse perinatal outcome (17Pc relative risk, RR 1.1; 95% confidence interval, 95% CI 0.97-1.4, vaginal progesterone RR 0.97; 95% CI 0.77-1.2). In a subgroup of women with a cervical length of ≤25 mm, vaginal progesterone reduced adverse perinatal outcome when cervical length was measured at randomisation (15/56 versus 22/60; RR 0.57; 95% CI 0.47-0.70) or before 24 weeks of gestation (14/52 versus 21/56; RR 0.56; 95% CI 0.42-0.75). AUTHOR'S CONCLUSIONS: In unselected women with an uncomplicated twin gestation, treatment with progestogens (intramuscular 17Pc or vaginal natural progesterone) does not improve perinatal outcome. Vaginal progesterone may be effective in the reduction of adverse perinatal outcome in women with a cervical length of ≤25 mm; however, further research is warranted to confirm this finding.

Second-trimester cervical length as risk indicator for Cesarean delivery in women with twin pregnancy.

OBJECTIVE: To determine whether second-trimester cervical length (CL) in women with a twin pregnancy is associated with the risk of emergency Cesarean section. METHODS: This was a secondary analysis of two randomized trials conducted in 57 hospitals in The Netherlands. We assessed the univariable association between risk indicators, including second-trimester CL in quartiles, and emergency Cesarean delivery using a logistic regression model. For multivariable analysis, we assessed whether adjustment for other risk indicators altered the associations found in univariable (unadjusted) analysis. Separate analyses were performed for suspected fetal distress and failure to progress in labor as indications for Cesarean section. RESULTS: In total, 311 women with a twin pregnancy attempted vaginal delivery after 34 weeks' gestation. Emergency Cesarean delivery was performed in 111 (36%) women, of which 67 (60%) were performed owing to arrest of labor. There was no relationship between second-trimester CL and Cesarean delivery (adjusted odds ratio (aOR): 0.97 for CL 26(th) -50(th) percentiles; 0.71 for CL 51(st) - 75(th) percentiles; and 0.92 for CL > 75(th) percentile, using CL ≤ 25(th) percentile as reference). In multivariable analysis, the only variables associated with emergency Cesarean delivery were maternal age (aOR, 1.07 (95% CI, 1.00-1.13)), body mass index (BMI) (aOR, 3.99 (95% CI, 1.07-14.9) for BMI 20-23 kg/m(2) ; 5.04 (95% CI, 1.34-19.03) for BMI 24-28 kg/m(2) ; and 3.1 (95% CI, 0.65-14.78) for BMI > 28 kg/m(2) ) and induction of labor (aOR, 1.92 (95% CI, 1.05-3.5)). CONCLUSION: In nulliparous women with a twin pregnancy, second-trimester CL is not associated with risk of emergency Cesarean delivery.

Sound production in the tiger-tail seahorse Hippocampus comes: Insights into the sound producing mechanisms.

Acoustic signals of the tiger-tail seahorse (Hippocampus comes) during feeding were studied using wavelet transform analysis. The seahorse "click" appears to be a compounded sound, comprising three acoustic components that likely come from two sound producing mechanisms. The click sound begins with a low-frequency precursor signal, followed by a sudden high-frequency spike that decays quickly, and a final, low-frequency sinusoidal component. The first two components can, respectively, be traced to the sliding movement and forceful knock between the supraorbital bone and coronet bone of the cranium, while the third one (purr) although appearing to be initiated here is produced elsewhere. The seahorse also produces a growling sound when under duress. Growling is accompanied by the highest recorded vibration at the cheek indicating another sound producing mechanism here. The purr has the same low frequency as the growl; both are likely produced by the same structural mechanism. However, growl and purr are triggered and produced under different conditions, suggesting that such "vocalization" may have significance in communication between seahorses.

Novel life-history data for threatened seahorses provide insight into fishery effects.

Life-history variables for three incidentally captured species of seahorse (Kellogg's seahorse Hippocampus kelloggi, the hedgehog seahorse Hippocampus spinosissimus and the three-spot seahorse Hippocampus trimaculatus) were established using specimens obtained from 33 fisheries landing sites in Peninsular Malaysia. When samples were pooled by species across the peninsula, sex ratios were not significantly different from unity, and height and mass relationships were significant for all species. For two of these species, height at physical maturity (HM ) was smaller than the height at which reproductive activity (HR ) commenced: H. spinosissimus (HM = 99·6 mm, HR = 123·2 mm) and H. trimaculatus (HM = 90·5 mm, HR = 121·8 mm). For H. kelloggi, HM could not be estimated as all individuals were physically mature, while HR = 167·4 mm. It appears that all three Hippocampus spp. were, on average, caught before reproducing; height at 50% capture (HC ) was ≥HM but ≤HR . The results from this study probe the effectiveness of assessment techniques for data-poor fisheries that rely heavily on estimates of length at maturity, especially if maturity is poorly defined. Findings also question the sustainability of H. trimaculatus catches in the south-west region of Peninsular Malaysia, where landed specimens had a notably smaller mean height (86·2 mm) and markedly skewed sex ratio (6% males) compared with samples from the south-east and north-west of the peninsula.

Does 17-α-hydroxyprogesterone caproate affect fetal biometry and birth weight in twin pregnancy?

OBJECTIVE: Increasingly, maternal administration of 17-α-hydroxyprogesterone caproate (17-OHPC) is utilized to prevent preterm birth, but the fetal safety of 17-OHPC is still a matter of concern. This study aimed to assess whether exposure to 17-OHPC during the second and third trimesters of pregnancy affects fetal biometry in twin gestations. METHODS: This study included a subset of women with a twin pregnancy who had been previously included in a randomized clinical trial comparing the effectiveness of 17-OHPC and placebo on neonatal outcomes and preterm birth rates in multiple pregnancy. In the present study, the individual growth patterns of femur length, head circumference and abdominal circumference were compared between fetuses of women who had been randomized to receive weekly injections of either 17-OHPC (n = 52) or placebo (n = 58) at between 16-20 and 36 weeks' gestation. RESULTS: The three biometric variables assessed developed similarly in fetuses in both the group exposed to 17-OHPC and the placebo group during the second half of pregnancy. Birth weight adjusted for parity and fetal sex was also comparable between groups. CONCLUSION: The use of 17-OHPC has no adverse effects on fetal biometry and birth weight in twins.

Effect of 17-alpha hydroxyprogesterone caproate on cervical length in twin pregnancies.

OBJECTIVES: Previous studies on singleton pregnancies have indicated that progestogens may reduce the rate of cervical shortening during pregnancy. The aim of this study was to investigate whether treatment with 17-alpha hydroxyprogesterone caproate (17-OHPC) has an effect on cervical shortening in twin pregnancies. METHODS: This was a secondary analysis of patients who had participated in a multicenter randomized clinical trial on the effectiveness of 17-OHPC in preventing preterm birth in multiple pregnancies (the AMPHIA-trial). We included all trial participants with a twin gestation who had undergone repeat cervical length measurements during pregnancy. We performed a separate analysis of women with repeat measurements in centers where this was standard protocol for multiple pregnancies. The rate of cervical shortening for both the 17-OHPC group and the placebo group was analyzed using a linear mixed model. RESULTS: Of the 671 patients who participated in the trial, 282 (42%) had a twin pregnancy and underwent two or more cervical length measurements. Of these women, 140 were monitored in centers where repeat measurements were standard protocol. We observed an overall reduction of cervical length from 44.3 mm at 14-18 weeks to 30.0 mm at 30-34 weeks' gestation. In the 17-OHPC group, cervical length decreased by 1.04 mm each gestational week, while this was 1.11 mm per week for the placebo group (P = 0.6). For the overall group, each 10% decrease in cervical length led to an increase in the risk of preterm birth (hazard ratio, 1.14; 95% CI, 1.08-1.21). CONCLUSION: In women with a twin pregnancy, there is progressive shortening of the cervix during pregnancy, regardless of 17-OHPC use.

Patient-specific affect-abdominal pain interactions in endometriosis: an experience sampling method (ESM) study.

OBJECTIVES: Cross-sectional studies show that endometriosis-related pain is associated with affect. Measuring these symptoms in real-time in a longitudinal perspective yields the ability to analyze the temporal relationship between variables. The aim was to evaluate the association between affect and abdominal pain, using the Experience Sampling Method (ESM) as a real-time, randomly repeated assessment. METHODS: Thirty-four endometriosis patients and 31 healthy subjects completed up to 10 real-time self-assessments concerning abdominal pain and affective symptoms during seven consecutive days. RESULTS: Endometriosis patients experienced more abdominal pain and negative affective symptoms, and scored lower on positive affect compared to healthy controls. A significant association was found between abdominal pain and both positive and negative affect in endometriosis patients. For healthy controls, less strong or non-significant associations were found. When looking at abdominal pain as a predictor for affect and vice versa, we found that only in endometriosis patients, pain was subsequently accompanied by negative affect, and positive affect may alleviate pain in these patients. CONCLUSIONS: This study confirms a concurrent and temporal relationship between affect and abdominal pain in endometriosis patients and supports the use of real-time symptom assessment to interpret potential influencers of abdominal complaints in patients with endometriosis.

Cervical length measurement for the prediction of preterm birth in multiple pregnancies: a systematic review and bivariate meta-analysis.

OBJECTIVES: To review the literature on cervical length as a predictor of preterm birth in asymptomatic women with a multiple pregnancy. METHODS: We searched MEDLINE, Embase and reference lists of included articles to identify all studies that reported on the accuracy of cervical length for predicting preterm birth in asymptomatic women with a multiple pregnancy. We scored study characteristics and study quality, and extracted data in order to construct two-by-two tables cross-classifying cervical length and preterm delivery. Meta-analysis using a bivariate model was performed. Summary receiver-operating characteristics (ROC) curves were generated for various test characteristics and outcome definitions. RESULTS: We found 21 studies reporting on 2757 women. There was a large variation in gestational age at measurement, cut-off point for cervical length and definition of preterm birth. The summary ROC curve indicated a good predictive capacity of short cervical length for preterm birth. Summary estimates of sensitivity and specificity for preterm birth before 34 weeks' gestation were 78% and 66%, respectively, for 35 mm, 41% and 87% for 30 mm, 36% and 94% for 25 mm and 30% and 94% for 20 mm. CONCLUSIONS: In women with a multiple pregnancy, second-trimester cervical length is a strong predictor of preterm birth. In the absence of effective preventive strategies, there is currently no place in clinical practice for cervical length measurement in this population. However, future studies should evaluate preventive interventions in women with multiple pregnancies and a short cervix, and cervical length should be measured in any trial studying preventive strategies in multiple pregnancies.

A role for Tlg1p in the transport of proteins within the Golgi apparatus of Saccharomyces cerevisiae.

Members of the syntaxin protein family participate in the docking-fusion step of several intracellular vesicular transport events. Tlg1p has been identified as a nonessential protein required for efficient endocytosis as well as the maintenance of normal levels of trans-Golgi network proteins. In this study we independently describe Tlg1p as an essential protein required for cell viability. Depletion of Tlg1p in vivo causes a defect in the transport of the vacuolar protein carboxypeptidase Y through the early Golgi. Temperature-sensitive (ts) mutants of Tlg1p also accumulate the endoplasmic reticulum/cis-Golgi form of carboxypeptidase Y at the nonpermissive temperature (38 degrees C) and exhibit underglycosylation of secreted invertase. Overexpression of Tlg1p complements the growth defect of vti1-11 at the nonpermissive temperature, whereas incomplete complementation was observed with vti1-1, further suggesting a role for Tlg1p in the Golgi apparatus. Overexpression of Sed5p decreases the viability of tlg1 ts mutants compared with wild-type cells, suggesting that tlg1 ts mutants are more susceptible to elevated levels of Sed5p. Tlg1p is able to bind His6-tagged Sec17p (yeast alpha-SNAP) in a dose-dependent manner and enters into a SNARE complex with Vti1p, Tlg2p, and Vps45p. Morphological analyses by electron microscopy reveal that cells depleted of Tlg1p or tlg1 ts mutants incubated at the restrictive temperature accumulate 40- to 50-nm vesicles and experience fragmentation of the vacuole.

Hybridization cross-reactivity within homologous gene families on glass cDNA microarrays.

Glass cDNA microarrays can be used to profile the expression of thousands of gene targets in a single experiment. However, the potential for hybridization cross-reactivity needs to be considered when interpreting the results. Here, we describe hybridization experiments with a model array representing four distinct functional classes (families): chemokines, cytochrome P-450 isozymes, G proteins, and proteases. The cDNA clones selected for this array exhibited pairwise sequence identities ranging from 55% to 100%, as determined by a homology scoring algorithm (LALIGN). Targets for microarraying were amplified by PCR and spotted in 4-fold replication for signal averaging. One designated target from each family was further amplified by PCR to incorporate a T7 promoter sequence for the production of synthetic RNA transcripts. These transcripts were used to generate fluorescent hybridization probes by reverse transcription at varying input concentrations. As expected, hybridization signals were highest at the matching target elements. Targets containing less than 80% sequence identity relative to the hybridization probe sequences showed cross-reactivities ranging from 0.6% to 12%. Targets containing greater than 80% identity showed higher cross-reactivities (26%-57%). These cross-reactive signals were analyzed for statistical correlation with the length of sequence overlap, percent sequence identity, and homology score determined by LALIGN. Overall, percent sequence identity was the best predictor of hybridization cross-reactivity. These results provide useful guidelines for interpreting glass cDNA microarray data.

Detrusor hyperreflexia in strokes.

Urodynamic evaluation via water cystometry was undertaken in 27 patients from 12 to 120 days after cerebrovascular accidents. Seven patients had urinary symptoms--five with urge incontinence, one with frequency and one with sensation of incomplete bladder emptying. The remaining 20 were asymptomatic. Cystometry revealed normal bladder function in 15 patients (55.6%), detrusor areflexia in one patient (3.7%) and detrusor hyperreflexia in 11 patients (40.7%). Of the 11 patients with detrusor hyperreflexia, six (54.5%) were asymptomatic and the remaining five (45.5%) had urge incontinence. The former group had a statistically significant higher first sensation and functional cystometric capacity than the latter. Urge incontinence was also found to be an accurate predictor of detrusor hyperreflexia.

Progress in Australian teledermatology.

Because of their remoteness, the majority of rural towns in Australia are disadvantaged in terms of access to dermatological services. Telemedicine offers one solution. Since the mid-1990s, Australian dermatologists have experimented with telemedicine as an adjunct to clinical practice. The technical viability of teledermatology was first demonstrated in 1997. In 1999, the accuracy and reliability of teledermatology were demonstrated in a real-life urban setting. In 2001, Broken Hill (in western New South Wales), a location remote from dermatology services, served as a trial site for the institution of teledermatology as the primary method of accessing dermatological services. High patient and general practitioner acceptability and positive medical outcomes were demonstrated, but the study also revealed unexpected barriers and pitfalls in the effective operation of rural teledermatology.

A case of mistaken identity. A rare presentation of gonadal dysgenesis.

BACKGROUND: The incidence of gonadal dysgenesis (hermaphroditism) is recognised to be low. Rarer still is an initial late presentation in the general practice setting. OBJECTIVE: To present a case study of a 35 year old man diagnosed as a hermaphrodite after routine investigations in general practice for lower abdominal pain. He has normal male external genitalia, a fully formed uterus and vagina, with no identifiable gonads. DISCUSSION: This incidental finding in general practice is supported by a 46,X,i(Yp)/45,X karyotype and mosaicism for an isochromosome of the short arm of the Y. It is not unusual that with normal male genitalia, such patients are likely to survive undiagnosed or incorrectly diagnosed into adulthood.

Cervical length measurement for the prediction of preterm birth in symptomatic women with a twin pregnancy: a systematic review and meta-analysis.

Objective. The aim of this study was to assess whether cervical length measurement (CL) could predict preterm birth (PTB) in symptomatic women with a twin pregnancy. Methods. We searched MEDLINE and EMBASE to identify studies investigating the accuracy of CL measurement in predicting PTB in symptomatic women with a twin pregnancy. We extracted data to construct two-by-two tables and used bivariate meta-analysis to generate point estimates of sensitivity and specificity. Results. Five studies (N = 226) were included. Variation in definition of PTB and cut-off points for CL was strong. One study investigated delivery within seven days, demonstrating a sensitivity of 1.0 (95% CI: 0.83-1.0) and a specificity of 0.31 (95% CI 0.2-0.43) for a CL cutoff at 25 mm. Three studies reported on predicting PTB < 37 weeks at a CL cutoff of 30 mm, with sROC point estimates of 0.76 (95% CI: 0.66 to 0.84) and 0.37 (95% CI: 0.21 to 0.56) for sensitivity and specificity, respectively. For preterm birth <34 weeks, no pooled estimates could be estimated since only 2 studies with large heterogeneity were identified. Conclusions. There is limited evidence on the accuracy of cervical length measurement testing the prediction of preterm birth in symptomatic women with a twin pregnancy, especially on the most important outcome, that is, delivery within 7 days.

Risk factors for uterine rupture during a vaginal birth after one previous caesarean section: a case-control study.

OBJECTIVE: To study risk factors for uterine rupture (UR) in women with one previous caesarean section (CS) undergoing a vaginal birth after CS (VBAC). STUDY DESIGN: A nested case-control study was conducted. Baseline characteristics, general obstetric history, details of the previous CS, current delivery and maternal and neonatal outcome were analysed for 41 cases with a UR and 157 controls (no rupture). Data were extracted from 21 Dutch hospitals. RESULTS: Labour induction was more common in cases than in controls (51% vs. 25% respectively, P=0.001), and in case of induction therapy especially the use of prostaglandins (PGE2) was more frequent in the case group (86% vs. 46%, P=0.014 for cases and controls respectively). Patients with UR had a significantly lower Bishop score (median: 2.0 vs. 4.0, P=0.005) and received more augmentation of labour compared to controls (36% vs. 18%, P=0.010). In the multivariate analysis induction with PGE2 and oxytocin, induction with PGE2 alone, and augmentation of labour were independent variables affecting the occurrence of UR (respectively OR 13.0, CI 2.3-74.2; OR 4.6, CI 1.9-11.3 and OR 2.7, CI 1.2-6.3). Forty-four percent of the ruptures can be explained by induction of labour with prostaglandins+/-oxytocin. CONCLUSION: Having studied baseline characteristics, general obstetric history, details of the previous CS and of the current delivery, we show that no factors other than the use of PGE2 (+/-oxytocin) in response to a low Bishop score, and augmentation of labour with oxytocin are associated with an increased risk for UR in women undergoing VBAC after one previous CS.