Obstetric anal sphincter injury risk reduction: a retrospective observational analysis

Objective: To identify the risks of sustaining obstetric anal sphincter injury (OASI) during childbirth. Methods: Data were analysed from 12,612 vaginal deliveries recorded at Northwick Park District General Hospital, London, from 1 January 2006 to 30 November 2009. Results: A total of 85.6% were spontaneous deliveries and 14.2% were instrument deliveries. The majority (64.5%) sustained some form of perineal damage, 3.7% being OASI. Logistic regression analyses revealed the risk factors for OASI to be Asian ethnicity [odds ratio (OR) 4.798, 95% confidence interval (CI) 2.998–7.679], a maternal age of > 40 years (OR 2.722, 95% CI 1.315–5.636), higher foetal birth weight ( > 4500 g; OR 6.228, 95% CI 2.695–14.392),lower parity (para 0; OR 16.803, 95% CI 7.697–36.685), and instrumental delivery. Forceps delivery posed the greatest risk (OR 8.4, 95% CI 5.822–12.151). Not having an episiotomy increased the risk of OASI by five times compared with having one. Conclusions: Risk factors for OASI include maternal age > 40 years, higher foetal birth weight, lower parity, instrumental delivery, and Asian ethnicity. Mediolateral episiotomy appears to reduce the risk of OASI. Specific variables have been identified for incorporation into a risk-reduction strategy that could be introduced antenatally to evaluate and assess OASI risk

External validation of models and simple scoring systems to predict miscarriage in intrauterine pregnancies of uncertain viability

STUDY QUESTION: Does a logistic regression model and scoring system to predict viability of an intrauterine pregnancy of uncertain viability (PUV) perform as well in an independent patient group as the original patient group? SUMMARY ANSWER: The model and scoring system showed good performance on external validation confirming their value for the prediction of miscarriage/viability in PUV patients up to 11-14 weeks of gestation. WHAT IS KNOWN ALREADY: Several individual ultrasound and demographic factors have been described as predictors for miscarriage. A logistic regression model and simple scoring system using basic clinical and ultrasound features, such as maternal age, bleeding score, mean gestational sac diameter (MSD) and presence or absence of yolk sac, have been developed to allow patient-specific prediction of viability of PUV beyond the first trimester. STUDY DESIGN, SIZE, DURATION: Prospective observational external validation cohort study in two inner city early pregnancy assessment units over a period of 18 months. PARTICIPANTS/MATERIALS, SETTING, METHODS: All consecutive women with a PUV were recruited. Ultrasound (mean sac diameter and presence of yolk sac) and demographic variables (maternal age, bleeding score and gestational age) were noted. The outcome measure was first trimester (11-14 week) viability. Women with unknown first trimester outcome were excluded. Receiver operating characteristic (ROC) curves and calibration plots were constructed. Test performance was compared with the original development data set. A new model and scoring system, which did not include gestational age, was built and evaluated. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 575 women who were recruited, first trimester outcome was known for 89.2% (n = 513). The model could only be validated in 400 patients, due to missing values in model variables and outcome. The model predicted viability with an area under the ROC curve (AUC) of 0.845 [95% confidence interval (CI), 0.806-0.884] compared with 0.774 (95% CI, 0.701-0.848) in the original study. The AUC for the scoring system was 0.832 (95% CI, 0.792-0.872) compared with 0.771 (95% CI, 0.698-0.844) from the original study data set. The new model and the scoring system, excluding gestational age, could be evaluated on 503 patients and resulted in an AUC of 0.801 (95% CI, 0.765-0.841) for the model and 0.773 (95% CI, 0.733-0.812) for the scoring system. LIMITATIONS, REASONS FOR CAUTION: Approximately 22% of patients could not be validated due to missing variables and for 11% of patients the first trimester outcome was unknown. WIDER IMPLICATIONS OF THE FINDINGS: Both the model and the scoring system showed excellent performance on external validation confirming their generalizability and utility in prediction of viability beyond the first trimester in clinical practice. An advantage of the mathematical models original Mo and new Mn and scoring systems original SSo and new SSn is that they can provide women with an individualized probability of the viability of their pregnancy using only demographic information, symptoms and TVS findings. Furthermore, the risk of miscarriage can be given immediately following examination. STUDY FUNDING/COMPETING INTEREST(S): T.B. is supported by the Imperial Healthcare NHS Trust NIHR Biomedical Research Centre. This research is supported by Research Council KUL GOA MaNet, iMinds 2012, Belgian Federal Science Policy Office IUAP P719. VVB is a postdoctoral fellow of the Research Foundation - Flanders (FWO). There are no conflicts of interest.status: publishe

Defining safe criteria to diagnose miscarriage: prospective observational multicentre study

Objectives To validate recent guidance changes by establishing the performance of cut-off values for embryo crown-rump length and mean gestational sac diameter to diagnose miscarriage with high levels of certainty. Secondary aims were to examine the influence of gestational age on interpretation of mean gestational sac diameter and crown-rump length values, determine the optimal intervals between scans and findings on repeat scans that definitively diagnose pregnancy failure.) Design Prospective multicentre observational trial. Setting Seven hospital based early pregnancy assessment units in the United Kingdom. Participants 2845 women with intrauterine pregnancies of unknown viability included if transvaginal ultrasonography showed an intrauterine pregnancy of uncertain viability. In three hospitals this was initially defined as an empty gestational sac <20 mm mean diameter with or without a visible yolk sac but no embryo, or an embryo with crown-rump length <6 mm with no heartbeat. Following amended guidance in December 2011 this definition changed to a gestational sac size <25 mm or embryo crown-rump length <7 mm. At one unit the definition was extended throughout to include a mean gestational sac diameter <30 mm or embryo crown-rump length <8 mm. Main outcome measures Mean gestational sac diameter, crown-rump length, and presence or absence of embryo heart activity at initial and repeat transvaginal ultrasonography around 7-14 days later. The final outcome was pregnancy viability at 11-14 weeks’ gestation. Results The following indicated a miscarriage at initial scan: mean gestational sac diameter ≥25 mm with an empty sac (364/364 specificity: 100%, 95% confidence interval 99.0% to 100%), embryo with crown-rump length ≥7 mm without visible embryo heart activity (110/110 specificity: 100%, 96.7% to 100%), mean gestational sac diameter ≥18 mm for gestational sacs without an embryo presenting after 70 days’ gestation (907/907 specificity: 100%, 99.6% to 100%), embryo with crown-rump length ≥3 mm without visible heart activity presenting after 70 days’ gestation (87/87 specificity: 100%, 95.8% to 100%). The following were indicative of miscarriage at a repeat scan: initial scan and repeat scan after seven days or more showing an embryo without visible heart activity (103/103 specificity: 100%, 96.5% to 100%), pregnancies without an embryo and mean gestational sac diameter <12 mm where the mean diameter has not doubled after 14 days or more (478/478 specificity: 100%, 99.2% to 100%), pregnancies without an embryo and mean gestational sac diameter ≥12 mm showing no embryo heartbeat after seven days or more (150/150 specificity: 100%, 97.6% to 100%). Conclusions Recently changed cut-off values of gestational sac and embryo size defining miscarriage are appropriate and not too conservative but do not take into account gestational age. Guidance on timing between scans and expected findings on repeat scans are still too liberal. Protocols for miscarriage diagnosis should be reviewed to account for this evidence to avoid misdiagnosis and the risk of terminating viable pregnancies

Triaging women with pregnancy of unknown location using two-step protocol including M6 model: clinical implementation study

OBJECTIVE: The M6 risk-prediction model was published as part of a two-step protocol using an initial progesterone level of ≤ 2 nmol/L to identify probable failing pregnancies (Step 1) followed by the M6 model (Step 2). The M6 model has been shown to have good triage performance for stratifying women with a pregnancy of unknown location (PUL) as being at low or high risk of harboring an ectopic pregnancy (EP). This study validated the triage performance of the two-step protocol in clinical practice by evaluating the number of protocol-related adverse events and how effectively patients were triaged. METHODS: This was a prospective multicenter interventional study of 3272 women with a PUL, carried out between January 2015 and January 2017 in four district general hospitals and four university teaching hospitals in the UK. The final pregnancy outcome was defined as: a failed PUL (FPUL), an intrauterine pregnancy (IUP) or an EP (including persistent PUL (PPUL)). FPUL and IUP were grouped as low-risk and EP/PPUL as high-risk PUL. Serum progesterone and human chorionic gonadotropin (hCG) levels were measured at presentation in all patients. If the initial progesterone level was ≤ 2 nmol/L, patients were discharged and were asked to have a follow-up urine pregnancy test in 2 weeks to confirm a negative result. If the progesterone level was > 2 nmol/L or a measurement had not been taken, hCG level was measured again at 48 h and results were entered into the M6 model. Patients were managed according to the outcome predicted by the protocol. Those classified as 'low risk, probable FPUL' were advised to perform a urine pregnancy test in 2 weeks and those classified as 'low risk, probable IUP' were invited for a scan a week later. When a woman with a PUL was classified as high risk (i.e. risk of EP ≥ 5%) she was reviewed clinically within 48 h. One center used a progesterone cut-off of ≤ 10 nmol/L and its data were analyzed separately. If the recommended management protocol was not adhered to, this was recorded as a protocol deviation and classified as: unscheduled visit for clinician reason, unscheduled visit for patient reason or incorrect timing of blood test or ultrasound scan. The classifications outlined in the UK Good Clinical Practice (GCP) guidelines were used to evaluate the incidence of adverse events. Data were analyzed using descriptive statistics. RESULTS: Of the 3272 women with a PUL, 2625 were included in the final analysis (317 met the exclusion criteria or were lost to follow-up, while 330 were evaluated using a progesterone cut-off of ≤ 10 nmol/L). Initial progesterone results were available for 2392 (91.1%) patients. In Step 1, 407 (15.5%) patients were classified as low risk (progesterone ≤ 2 nmol/L), of whom seven (1.7%) were ultimately diagnosed with an EP. In 279 of the remaining 2218 women with a PUL, the M6 model was not applied owing to protocol deviation or because the outcome was already known (usually on the basis of an ultrasound scan) before a second hCG reading was taken; of these patients, 30 were diagnosed with an EP. In Step 2, 1038 women with a PUL were classified as low risk, of whom eight (0.8%) had a final outcome of EP. Of 901 women classified as high risk at Step 2, 275 (30.5%) had an EP. Therefore, 275/320 (85.9%) EPs were correctly classified as high risk. Overall, 1445/2625 PUL (55.0%) were classified as low risk, of which 15 (1.0%) were EP. None of these cases resulted in a ruptured EP or significant clinical harm. Sixty-two women participating in the study had an adverse event, but no woman had a serious adverse event as defined in the UK GCP guidelines. CONCLUSIONS: This study has shown that the two-step protocol incorporating the M6 model effectively triaged the majority of women with a PUL as being at low risk of an EP, minimizing the follow-up required for these patients after just two visits. There were few misclassified EPs and none of these women came to significant clinical harm or suffered a serious adverse clinical event. The two-step protocol incorporating the M6 model is an effective and clinically safe way of rationalizing the management of women with a PUL. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.status: publishe

External validation of models to predict the outcome of pregnancies of unknown location: a multicentre cohort study.

OBJECTIVE: To externally validate five approaches to predict ectopic pregnancy (EP) in pregnancies of unknown location (PUL): the M6P and M6NP risk models, the two-step triage strategy (2ST, which incorporates M6P), the M4 risk model, and beta human chorionic gonadotropin ratio cut-offs (BhCG-RC). DESIGN: Secondary analysis of a prospective cohort study. SETTING: Eight UK early pregnancy assessment units. POPULATION: Women presenting with a PUL and BhCG >25 IU/L. METHODS: Women were managed using the 2ST protocol: PUL were classified as low risk of EP if presenting progesterone ≤2 nmol/L; the remaining cases returned two days later for triage based on M6P. EP risk ≥5% was used to classify PUL as high risk. Missing values were imputed, and predictions for the five approaches were calculated post hoc. We meta-analysed centre-specific results. MAIN OUTCOME MEASURES: Discrimination, calibration and clinical utility (decision curve analysis) for predicting EP. RESULTS: Of 2899 eligible women, the primary analysis excluded 297 (1 0%) women who were lost to follow-up. The area under the ROC curve for EP was 0.89 (95% confidence interval 0.86-0.91) for M6P, 0.88 (0.86-0.90) for 2ST, 0.86 (0.83-0.88) for M6NP, and 0.82 (0.78-0.85) for M4. Sensitivities for EP were 96% (M6P), 94% (2ST), 92% (N6NP), 80% (M4), and 58% (BhCG-RC); false positive rates were 35%, 33%, 39%, 24%, and 13%. M6P and 2ST had the best clinical utility and good overall calibration, with modest variability between centres. CONCLUSIONS: 2ST and M6P performed best to predict and triage PUL

Abstracts of the 26th World Congress on Ultrasound in Obstetrics and Gynecology, Rome, Italy, 24-28 September 2016

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Evaluating cut-off levels for progesterone, beta human chorionic gonadotropin and beta human chorionic gonadotropin ratio to exclude pregnancy viability in women with a pregnancy of unknown location: A prospective multicenter cohort study

Introduction There is no global agreement on how to best determine pregnancy of unknown location viability and location using biomarkers. Measurements of progesterone and β human chorionic gonadotropin (βhCG) are still used in clinical practice to exclude the possibility of a viable intrauterine pregnancy (VIUP). We evaluate the predictive value of progesterone, βhCG, and βhCG ratio cut-off levels to exclude a VIUP in women with a pregnancy of unknown location. Material and methods This was a secondary analysis of prospective multicenter study data of consecutive women with a pregnancy of unknown location between January 2015 and 2017 collected from dedicated early pregnancy assessment units of eight hospitals. Single progesterone and serial βhCG measurements were taken. Women were followed up until final pregnancy outcome between 11 and 14 weeks of gestation was confirmed using transvaginal ultrasonography: (1) VIUP, (2) non-viable intrauterine pregnancy or failed pregnancy of unknown location, and (3) ectopic pregnancy or persisting pregnancy of unknown location. The predictive value of cut-off levels for ruling out VIUP were evaluated across a range of values likely to be encountered clinically for progesterone, βhCG, and βhCG ratio. Results Data from 2507 of 3272 (76.6%) women were suitable for analysis. All had data for βhCG levels, 2248 (89.7%) had progesterone levels, and 1809 (72.2%) had βhCG ratio. The likelihood of viability falls with the progesterone level. Although the median progesterone level associated with viability was 59 nmol/L, VIUP were identified with levels as low as 5 nmol/L. No single βhCG cut-off reliably ruled out the presence of viability with certainty, even when the level was more than 3000 IU/L, there were 39/358 (11%) women who had a VIUP. The probability of viability decreases with the βhCG ratio. Although the median βhCG ratio associated with viability was 2.26, VIUP were identified with ratios as low as 1.02. A progesterone level below 2 nmol/L and βhCG ratio below 0.87 were unlikely to be associated with viability but were not definitive when considering multiple imputation. Conclusions Cut-off levels for βhCG, βhCG ratio, and progesterone are not safe to be used clinically to exclude viability in early pregnancy. Although βhCG ratio and progesterone have slightly better performance in comparison, single βhCG used in this manner is highly unreliable

Triaging women with pregnancy of unknown location using two‐step protocol including M6 model: clinical implementation study

INTRODUCTION: The M6 risk prediction model has been shown to have good triage performance for stratifying women with a PUL as being at low or high-risk of harboring an ectopic pregnancy. There is evidence that M6 has better overall test performance than the hCG ratio (serum hCG at 48 hours/hCG at presentation) and older models such as the M4 model. M6 was published as part of a two-step protocol using an initial progesterone ≤2nmol/l to identify likely failing pregnancies (step 1), followed by M6 (step 2). This study validated the triage performance of this protocol in clinical practice by evaluating (1) the number of protocol-related adverse events and (2) how patients are effectively triaged. METHODS: This was a prospective multi-centre interventional study of 3272 women with a PUL carried out between January 2015 and January 2017 in four district general hospitals and four university teaching hospitals in the United Kingdom. We defined the final pregnancy outcome as: a failed PUL (FPUL), an intrauterine pregnancy (IUP) or an ectopic pregnancy (EP) (including persistent PUL (PPUL)). FPUL and IUP were grouped as low-risk and EP and PPUL as high-risk PUL. Patients had a serum progesterone and hCG level at 0 hours and repeat hCG at 48 hours. In seven centres, if the initial progesterone was ≤2nmol/l, patients were discharged with a follow-up urine pregnancy test in two weeks to confirm a negative result. If the progesterone was >2nmol/l or had not been taken, a 48 hour hCG level was taken and results entered into the M6 model. Patients were managed according to their predicted outcome: those classified with pregnancies likely to resolve (FPUL) were advised to perform a urine pregnancy test in two weeks and those with a likely IUP were invited for a scan a week later. When a women with a PUL was classified as high-risk (i.e. those with a risk of EP ≥ 5%) were reviewed clinically within 48 hours. One centre used a progesterone cut-off ≤10nmol/l and was analysed separately. If the recommended management protocol was not adhered to, this was recorded as an 'unscheduled visit (participant reason)', 'unscheduled visit (clinician reason)' or 'differences in timing (blood test/ultrasound)'. The classifications outlined in UK Good Clinical Practice guidelines were used to evaluate adverse events. Data were analysed with descriptive statistics. RESULTS: Data was available for main analysis in 2625/3272 women with PUL (317 met the exclusion criteria or were lost to follow-up, 330 were evaluated with a progesterone cut-off of ≤10nmol/l). Progesterone results were available for 2392 (91%). 407 (15.5%) patients were classified as low-risk at step 1 (progesterone ≤2nmol/l), of which 7 (1.7%) were ultimately diagnosed with an EP. For 279/2218 remaining women with a PUL, M6 was not used or the outcome was already known usually on the basis of an ultrasound scan before a second hCG level was taken (30 were EP). 1038 women with a PUL were classified as low-risk at step 2, of which 8 (0.8%) were EP. 901 women with a PUL were classified as high-risk at step 2, of which 275 (30.5%) were EP. 275/320 (85.9%) EP were correctly classified as high-risk. Overall, 1445/2625 PUL (55.0%) were classified as low-risk, of which 15 (1.0%) were EP. None of these 15 EP ruptured. CONCLUSIONS: This study has shown that the two-step protocol incorporating the M6 model effectively triaged a majority of women with a PUL as being at low-risk of an EP, minimizing the follow-up required for these patients after just two visits. There were few misclassified EP and none of these women came to significant clinical harm or suffered a serious adverse clinical event. The two-step protocol, incorporating the M6 model, is an effective and clinically safe way of rationalizing the management of women with a PUL