Change in cervical length after arrested preterm labor and risk of preterm birth.

OBJECTIVE: To assess the association between preterm birth and cervical length after arrested preterm labor in high-risk pregnant women. METHODS: In this post-hoc analysis of a randomized clinical trial, transvaginal cervical length was measured in women whose contractions had ceased 48 h after admission for threatened preterm labor. At admission, women were defined as having a high risk of preterm birth based on a cervical length of < 15 mm or a cervical length of 15-30 mm with a positive fetal fibronectin test. Logistic regression analysis was used to investigate the association of cervical length measured at least 48 h after admission and of the change in cervical length between admission and at least 48 h later, with preterm birth before 34 weeks' gestation and delivery within 7 days after admission. RESULTS: A total of 164 women were included in the analysis. Women whose cervical length increased between admission for threatened preterm labor and 48 h later (32%; n = 53) were found to have a lower risk of preterm birth before 34 weeks compared with women whose cervical length did not change (adjusted odds ratio (aOR), 0.24 (95% CI, 0.09-0.69)). The risk in women with a decrease in cervical length between the two timepoints was not different from that in women with no change in cervical length (aOR, 1.45 (95% CI, 0.62-3.41)). Moreover, greater absolute cervical length after 48 h was associated with a lower risk of preterm birth before 34 weeks (aOR, 0.90 (95% CI, 0.84-0.96)) and delivery within 7 days after admission (aOR, 0.91 (95% CI, 0.82-1.02)). Sensitivity analysis in women randomized to receive no intervention showed comparable results. CONCLUSION: Our study suggests that the risk of preterm birth before 34 weeks is lower in women whose cervical length increases between admission for threatened preterm labor and at least 48 h later when contractions had ceased compared with women in whom cervical length does not change or decreases. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Single- versus double-layer closure of the caesarean (uterine) scar in the prevention of gynaecological symptoms in relation to niche development - the 2Close study: a multicentre randomised controlled trial.

BACKGROUND: Double-layer compared to single-layer closure of the uterus after a caesarean section (CS) leads to a thicker myometrial layer at the site of the CS scar, also called residual myometrium thickness (RMT). It possibly decreases the development of a niche, which is an interruption of the myometrium at the site of the uterine scar. Thin RMT and a niche are associated with gynaecological symptoms, obstetric complications in a subsequent pregnancy and delivery and possibly with subfertility. METHODS: Women undergoing a first CS regardless of the gestational age will be asked to participate in this multicentre, double blinded randomised controlled trial (RCT). They will be randomised to single-layer closure or double-layer closure of the uterine incision. Single-layer closure (control group) is performed with a continuous running, unlocked suture, with or without endometrial saving technique. Double-layer closure (intervention group) is performed with the first layer in a continuous unlocked suture including the endometrial layer and the second layer is also continuous unlocked and imbricates the first. The primary outcome is the reported number of days with postmenstrual spotting during one menstrual cycle nine months after CS. Secondary outcomes include surgical data, ultrasound evaluation at three months, menstrual pattern, dysmenorrhea, quality of life, and sexual function at nine months. Structured transvaginal ultrasound (TVUS) evaluation is performed to assess the uterine scar and if necessary saline infusion sonohysterography (SIS) or gel instillation sonohysterography (GIS) will be added to the examination. Women and ultrasound examiners will be blinded for allocation. Reproductive outcomes at three years follow-up including fertility, mode of delivery and complications in subsequent deliveries will be studied as well. Analyses will be performed by intention to treat. 2290 women have to be randomised to show a reduction of 15% in the mean number of spotting days. Additionally, a cost-effectiveness analysis will be performed from a societal perspective. DISCUSSION: This RCT will provide insight in the outcomes of single- compared to double-layer closure technique after CS, including postmenstrual spotting and subfertility in relation to niche development measured by ultrasound. TRIAL REGISTRATION: Dutch Trial Register ( NTR5480 ). Registered 29 October 2015.

Cost-effectiveness of diagnostic testing strategies including cervical-length measurement and fibronectin testing in women with symptoms of preterm labor.

OBJECTIVE: To evaluate the cost-effectiveness of combining cervical-length (CL) measurement and fetal fibronectin (fFN) testing in women with symptoms of preterm labor between 24 and 34 weeks' gestation. METHODS: This was a model-based cost-effectiveness analysis evaluating seven test-treatment strategies based on CL measurement and/or fFN testing in women with symptoms of preterm labor from a societal perspective, in which neonatal outcomes and costs were weighted. Estimates of disease prevalence, test accuracy and costs were based on two recently performed nationwide cohort studies in The Netherlands. RESULTS: Strategies using fFN testing and CL measurement separately to predict preterm delivery are associated with higher costs and incidence of adverse neonatal outcomes compared with strategies that combine both tests. Additional fFN testing when CL is 15-30 mm was considered cost effective, leading to a cost saving of €3919 per woman when compared with a treat-all strategy, with a small deterioration in neonatal health outcomes, namely one additional perinatal death and 21 adverse outcomes per 10 000 women with signs of preterm labor (incremental cost-effectiveness ratios €39 million and €1.9 million, respectively). Implementing this strategy in The Netherlands, a country with about 180 000 deliveries annually, could lead to an annual cost saving of between €2.4 million and €7.6 million, with only a small deterioration in neonatal health outcomes. CONCLUSION: In women with symptoms of preterm labor at 24-34 weeks' gestation, performing additional fFN testing when CL is between 15 and 30 mm is a viable and cost-saving strategy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Longitudinal study of computerized cardiotocography in early fetal growth restriction.

OBJECTIVES: To explore whether, in early fetal growth restriction (FGR), the longitudinal pattern of fetal heart rate (FHR) short-term variation (STV) can be used to identify imminent fetal distress and whether abnormalities of FHR recordings are associated with 2-year infant outcome. METHODS: The original TRUFFLE study assessed whether, in early FGR, delivery based on ductus venosus (DV) Doppler pulsatility index (PI), in combination with safety-net criteria of very low STV on cardiotocography (CTG) and/or recurrent FHR decelerations, could improve 2-year infant survival without neurological impairment in comparison with delivery based on CTG monitoring only. This was a secondary analysis of women who delivered before 32 weeks and had consecutive STV data recorded > 3 days before delivery and known infant outcome at 2 years of age. Women who received corticosteroids within 3 days of delivery were excluded. Individual regression line algorithms of all STV values, except the last one before delivery, were calculated. Life tables and Cox regression analysis were used to calculate the daily risk for low STV or very low STV and/or FHR decelerations (below DV group safety-net criteria) and to assess which parameters were associated with this risk. Furthermore, it was assessed whether STV pattern, last STV value or recurrent FHR decelerations were associated with 2-year infant outcome. RESULTS: One hundred and forty-nine women from the original TRUFFLE study met the inclusion criteria. Using the individual STV regression lines, prediction of a last STV below the cut-off used by the CTG monitoring group had sensitivity of 42% and specificity of 91%. For each day after study inclusion, the median risk for low STV (CTG group cut-off) was 4% (interquartile range (IQR), 2-7%) and for very low STV and/or recurrent FHR decelerations (below DV group safety-net criteria) was 5% (IQR, 4-7%). Measures of STV pattern, fetal Doppler (arterial or venous), birth-weight multiples of the median and gestational age did not usefully improve daily risk prediction. There was no association of STV regression coefficients, a low last STV and/or recurrent FHR decelerations with short- or long-term infant outcomes. CONCLUSION: The TRUFFLE study showed that a strategy of DV monitoring with safety-net criteria of very low STV and/or recurrent FHR decelerations for delivery indication could increase 2-year infant survival without neurological impairment. This post-hoc analysis demonstrates that, in early FGR, the daily risk of abnormal CTG, as defined by the DV group safety-net criteria, is 5%, and that prediction is not possible. This supports the rationale for CTG monitoring more often than daily in these high-risk fetuses. Low STV and/or recurrent FHR decelerations were not associated with adverse infant outcome and it appears safe to delay intervention until such abnormalities occur, as long as DV-PI is within normal range. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

A multivariable model to guide the decision for pessary placement to prevent preterm birth in women with a multiple pregnancy: a secondary analysis of the ProTWIN trial.

OBJECTIVE: The ProTWIN Trial (NTR1858) showed that, in women with a multiple pregnancy and a cervical length < 25(th) percentile (38 mm), prophylactic use of a cervical pessary reduced the risk of adverse perinatal outcome. We investigated whether other maternal or pregnancy characteristics collected at baseline can improve identification of women most likely to benefit from pessary placement. METHODS: ProTWIN is a multicenter randomized trial in which 808 women with a multiple pregnancy were assigned to pessary or control. Using these data we developed a multivariable logistic model comprising treatment, cervical length, chorionicity, pregnancy history and number of fetuses, and the interaction of these variables with treatment as predictors of adverse perinatal outcome. RESULTS: Short cervix, monochorionicity and nulliparity were predictive factors for a benefit from pessary insertion. History of previous preterm birth and triplet pregnancy were predictive factors of possible harm from pessary. The model identified 35% of women as benefiting (95% CI, 32-39%), which is 10% more than using cervical length only (25%) for pessary decisions. The model had acceptable calibration. We estimated that using the model to guide the choice of pessary placement would reduce the risk of adverse perinatal outcome significantly from 13.5% when no pessary is inserted to 8.1% (absolute risk reduction, 5.4% (95% CI, 2.1-8.6%)). CONCLUSIONS: We developed and internally validated a multivariable treatment selection model, with cervical length, chorionicity, pregnancy history and number of fetuses. If externally validated, it could be used to identify women with a twin pregnancy who would benefit from a pessary, and lead to a reduction in adverse perinatal outcomes in these women. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Prediction of Time to Delivery Week-by-Week in Women with a Triplet Pregnancy.

Objective Some clinicians advise prophylactic administration of antenatal steroids for fetal lung maturation in women with a triplet pregnancy. However, the effect of corticosteroids is limited to 10 to 14 days after administration. The aim of this study was to assess the natural course of triplet pregnancies to allow a better anticipation for administration of corticosteroids. Study Design We collected data on all triplet pregnancies in the Netherlands from 1999 to 2007 from the Netherlands Perinatal Registration. We calculated time to delivery, the risk of delivery in 2-week intervals at different gestational ages, and the time frame between hospital admission and delivery of the first child. Results Median gestational age at delivery of 494 women with a triplet pregnancy was 33+4 weeks (interquartile range of 31-35+1 weeks). Twenty-one women (4.3%) delivered between 22 and 24 weeks and 146 women (29.6%) delivered before 32 weeks. At a gestational age of 24 weeks, the chance to deliver within the next week was 0.6%. For 26, 28, 30, 31, and 32 weeks, these risks were 2.4, 2.5, 8.1, 7, and 16.7%, respectively. Conclusion Before 32 weeks of gestation, prophylactic administration of steroids is not indicated as the risk to deliver within 7 days is < 10%.

Routine labour epidural analgesia versus labour analgesia on request: a randomised non-inferiority trial.

OBJECTIVE: To assess the effect on mode of delivery of the routine use of labour epidural analgesia (EA) compared with analgesia on request. DESIGN: Randomised non-inferiority trial. SETTING: One university and one non-university teaching hospital in The Netherlands. POPULATION: Women with a singleton pregnancy in cephalic presentation beyond 36 + 0 weeks' gestation. METHODS: Participants were randomly allocated to receive either routine EA or analgesia on request. Intention-to-treat (ITT) and per-protocol (PP) analyses were performed, with confidence intervals (CI) calculated for the differences in percentages or means. MAIN OUTCOME MEASURES: Rate of operative delivery (instrumental vaginal or caesarean), labour characteristics, and adverse labour and neonatal outcomes. RESULTS: A total of 488 women were randomly allocated to the routine EA (n = 233) or analgesia on request group (n = 255). In the routine EA group, 89.3% (208/233) received EA. According to ITT analysis, 34.8% (81/233) women in the routine EA group had an operative delivery, compared with 26.7% (68/255) in the analgesia on request group (difference 8.1%, 95% CI -0.1 to 16.3). The difference in rate of operative deliveries according to the PP analysis was statistically significant (difference 8.9%, 95% CI 0.4 to 17.4). Inferiority of EA could not be rejected, as in both analyses the upper bound of the confidence interval exceeded the pre-specified inferiority criterion of +10%. Women in the routine EA group had more adverse effects, including hypotension (difference 9.5%, 95% CI 4.2 to 14.9), and motor blockade (difference 6.8%, 95% CI 1.1 to 12.5). CONCLUSION: Non-inferiority of routine EA could not be demonstrated in this trial. Routine EA use is likely to lead to more operative deliveries and more maternal adverse effects. The results of our study do not justify routine use of EA.

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.

Vaginal birth after a caesarean section: the development of a Western European population-based prediction model for deliveries at term.

OBJECTIVE: To develop and internally validate a model that predicts the outcome of an intended vaginal birth after caesarean (VBAC) for a Western European population that can be used to personalise counselling for deliveries at term. DESIGN: Registration-based retrospective cohort study. SETTING: Five university teaching hospitals, seven non-university teaching hospitals, and five non-university non-teaching hospitals in the Netherlands. POPULATION: A cohort of 515 women with a history of one caesarean section and a viable singleton pregnancy, without a contraindication for intended VBAC, who delivered at term. METHODS: Potential predictors for a vaginal delivery after caesarean section were chosen based on literature and expert opinions. We internally validated the prediction model using bootstrapping techniques. MAIN OUTCOME MEASURES: Predictors for VBAC. For model validation, the area under the receiver operating characteristic curve (AUC) for discriminative capacity and calibration-per-risk-quantile for accuracy were calculated. RESULTS: A total of 371 out of 515 women had a VBAC (72%). Variables included in the model were: estimated fetal weight greater than the 90(th) percentile in the third trimester; previous non-progressive labour; previous vaginal delivery; induction of labour; pre-pregnancy body mass index; and ethnicity. The AUC was 71% (95% confidence interval, 95% CI = 69-73%), indicating a good discriminative ability. The calibration plot shows that the predicted probabilities are well calibrated, especially from 65% up, which accounts for 77% of the total study population. CONCLUSION: We developed an appropriate Western European population-based prediction model that is aimed to personalise counselling for term deliveries.

Involving women in personalised decision-making on mode of delivery after caesarean section: the development and pilot testing of a patient decision aid.

OBJECTIVE: To develop a patient decision aid (PtDA) for mode of delivery after caesarean section that integrates personalised prediction of vaginal birth after caesarean (VBAC) with the elicitation of patient preferences and evidence-based information. DESIGN: A PtDA was developed and pilot tested using the International Patients Decision Aid Standards (IPDAS) criteria. SETTING: Obstetric health care in the Netherlands. POPULATION: A multidisciplinary steering group, an expert panel, and 25 future users of the PtDA, i.e. women with a previous caesarean section. METHODS: The development consisted of a construction phase (definition of scope and purpose, and selection of content, framework, and format) and a pilot testing phase by interview. The process was supervised by a multidisciplinary steering group. MAIN OUTCOME MEASURES: Usability, clarity, and relevance. RESULTS: The construction phase resulted in a booklet including unbiased balanced information on mode of birth after caesarean section, a preference elicitation exercise, and tailored risk information, including a prediction model for successful VBAC. During pilot testing, visualisation of risks and clarity formed the main basis for revisions. Pilot testing showed the availability of tailored structured information to be the main factor involving women in decision-making. The PtDA meets 39 out of 50 IPDAS criteria (78%): 23 out of 23 criteria for content (100%) and 16 out of 20 criteria for the development process (80%). Criteria for effectiveness (n = 7) were not evaluated. CONCLUSIONS: An evidence-based PtDA was developed, with the probability of successful VBAC and the availability of structured information as key items. It is likely that the PtDA enhances the quality of decision-making on mode of birth after caesarean section.

Predicting successful intended vaginal delivery after previous caesarean section: external validation of two predictive models in a Dutch nationwide registration-based cohort with a high intended vaginal delivery rate.

OBJECTIVE: To externally validate two models from the USA (entry-to-care [ETC] and close-to-delivery [CTD]) that predict successful intended vaginal birth after caesarean (VBAC) for the Dutch population. DESIGN: A nationwide registration-based cohort study. SETTING: Seventeen hospitals in the Netherlands. POPULATION: Seven hundred and sixty-three pregnant women, each with one previous caesarean section and a viable singleton cephalic pregnancy without a contraindication for an intended VBAC. METHODS: The ETC model comprises the variables maternal age, prepregnancy body mass index (BMI), ethnicity, previous vaginal delivery, previous VBAC and previous nonprogressive labour. The CTD model replaces prepregnancy BMI with third-trimester BMI and adds estimated gestational age at delivery, hypertensive disease of pregnancy, cervical examination and induction of labour. We included consecutive medical records of eligible women who delivered in 2010. For validation, individual probabilities of women who had an intended VBAC were calculated. MAIN OUTCOME MEASURES: Discriminative performance was assessed with the area under the curve (AUC) of the receiver operating characteristic and predictive performance was assessed with calibration plots and the Hosmer-Lemeshow (H-L) statistic. RESULTS: Five hundred and fifteen (67%) of the 763 women had an intended VBAC; 72% of these (371) had an actual VBAC. The AUCs of the ETC and CTD models were 68% (95% CI 63-72%) and 72% (95% CI 67-76%), respectively. The H-L statistic showed a P-value of 0.167 for the ETC model and P = 0.356 for the CTD model, indicating no lack of fit. CONCLUSION: External validation of two predictive models developed in the USA revealed an adequate performance within the Dutch population.

Transfusion policy after severe postpartum haemorrhage: a randomised non-inferiority trial.

OBJECTIVE: To assess the effect of red blood cell (RBC) transfusion on quality of life in acutely anaemic women after postpartum haemorrhage. DESIGN: Randomised non-inferiority trial. SETTING: Thirty-seven Dutch university and general hospitals. POPULATION: Women with acute anaemia (haemoglobin 4.8-7.9 g/dl [3.0-4.9 mmol/l] 12-24 hours postpartum) without severe anaemic symptoms or severe comorbidities. METHODS: Women were allocated to RBC transfusion or non-intervention. MAIN OUTCOME MEASURES: Primary outcome was physical fatigue 3 days postpartum (Multidimensional Fatigue Inventory, scale 4-20; 20 represents maximal fatigue). Non-inferiority was demonstrated if the physical fatigue difference between study arms was maximal 1.3. Secondary outcomes were health-related quality of life and physical complications. Health-related quality of life questionnaires were completed at five time-points until 6 weeks postpartum. RESULTS: In all, 521 women were randomised to non-intervention (n = 262) or RBC transfusion (n = 259). Mean physical fatigue score at day 3 postpartum, adjusted for baseline and mode of delivery, was 0.8 lower in the RBC transfusion arm (95% confidence interval: 0.1-1.5, P = 0.02) and at 1 week postpartum was 1.06 lower (95% confidence interval: 0.3-1.8, P = 0.01). A median of two RBC units was transfused in the RBC transfusion arm. In the non-intervention arm, 33 women received RBC transfusion, mainly because of anaemic symptoms. Physical complications were comparable. CONCLUSIONS: Statistically, non-inferiority could not be demonstrated as the confidence interval crossed the non-inferiority boundary. Nevertheless, with only a small difference in physical fatigue and no differences in secondary outcomes, implementation of restrictive management seems clinically justified.

Willingness-to-use and preferences for model-informed antenatal doses: a cross-sectional study among European healthcare practitioners and pregnant women.

Background: Physiological changes in pregnancy may affect drug safety and efficacy, sometimes requiring dose adjustments. Pregnancy-adjusted doses, however, are missing for most medications. Increasingly, pharmacokinetic models can be used for antenatal dose finding. Given the novelty of this technique and questions regarding dose credibility, the acceptability of model-informed antenatal doses should be explored. Objective: We aimed to assess the willingness-to-use and preferred features for model-informed antenatal doses among healthcare practitioners (HCPs) and pregnant women in European countries. Methods: A cross-sectional, web-based study drawing on two open surveys was performed between 8 September and 30 November 2022. Each survey comprised statements drawn from prior focus groups, associated with Likert-scales. Themes included respondents' information needs, search behaviours along with their willingness-to-use and preferred features for model-informed antenatal doses. The surveys were disseminated through professional societies, pregnancy websites and social media. A descriptive analysis was performed. Results: In total, 608 HCPs from different specialties and 794 pregnant women across 15 countries participated, with 81% of respondents across both groups in the Netherlands or Belgium. Among pregnant women, 31% were medical professionals and 85% used medication during pregnancy. Eighty-three percent of HCPs found current antenatal pharmacotherapy suboptimal and 97% believed that model-informed antenatal doses would enhance the quality of antenatal care. Most HCPs (93%) and pregnant women (75%) would be willing to follow model-informed antenatal doses. Most HCPs desired access to the evidence (88%), including from pharmacokinetic modelling (62%). Most pregnant women (96%) wanted to understand antenatal dosing rationales and to be involved in dosing decisions (97%). Conclusion: The willingness-to-use model-informed antenatal doses is high among HCPs and pregnant women provided that certain information needs are met.

Cost-effectiveness of induction of labour at term with a Foley catheter compared to vaginal prostaglandin E2 gel (PROBAAT trial).

OBJECTIVE: To assess the economic consequences of labour induction with Foley catheter compared to prostaglandin E2 gel. DESIGN: Economic evaluation alongside a randomised controlled trial. SETTING: Obstetric departments of one university and 11 teaching hospitals in the Netherlands. POPULATION: Women scheduled for labour induction with a singleton pregnancy in cephalic presentation at term, intact membranes and an unfavourable cervix; and without previous caesarean section. METHODS: Cost-effectiveness analysis from a hospital perspective. MAIN OUTCOME MEASURES: We estimated direct medical costs associated with healthcare utilisation from randomisation to 6 weeks postpartum. For caesarean section rate, and maternal and neonatal morbidity we calculated the incremental cost-effectiveness ratios, which represent the costs to prevent one of these adverse outcomes. RESULTS: Mean costs per woman in the Foley catheter group (n = 411) and in the prostaglandin E2 gel group (n = 408), were €3297 versus €3075, respectively, with an average difference of €222 (95% confidence interval -€157 to €633). In the Foley catheter group we observed higher costs due to longer labour ward occupation and less cost related to induction material and neonatal admissions. Foley catheter induction showed a comparable caesarean section rate compared with prostaglandin induction, therefore the incremental cost-effectiveness ratio was not informative. Foley induction resulted in fewer neonatal admissions (incremental cost-effectiveness ratio €2708) and asphyxia/postpartum haemorrhage (incremental cost-effectiveness ratios €5257) compared with prostaglandin induction. CONCLUSIONS: Foley catheter and prostaglandin E2 labour induction generate comparable costs.

An economic analysis of induction of labour and expectant monitoring in women with gestational hypertension or pre-eclampsia at term (HYPITAT trial).

OBJECTIVE: To assess the economic consequences of labour induction compared with expectant monitoring in women with gestational hypertension or pre-eclampsia at term. DESIGN: An economic analysis alongside the Hypertension and Pre-eclampsia Intervention Trial At Term (HYPITAT). SETTING: Obstetric departments of six university and 32 teaching and district hospitals in the Netherlands. POPULATION: Women diagnosed with gestational hypertension or pre-eclampsia between 36(+0) and 41(+0) weeks of gestation, randomly allocated to either induction of labour or expectant monitoring. METHODS: A trial-based cost-effectiveness analysis was performed from a societal perspective during a 1-year time horizon. MAIN OUTCOME MEASURES: One-year costs were estimated and health outcomes were expressed as the prevalence of poor maternal outcome defined as either maternal complications or progression to severe disease. RESULTS: The average costs of induction of labour (n = 377) were €7077 versus €7908 for expectant monitoring (n = 379), with an average difference of -€831 (95% CI -€1561 to -€144). This 11% difference predominantly originated from the antepartum period: per woman costs were €1259 for induction versus €2700 for expectant monitoring. During delivery, more costs were generated following induction (€2190) compared with expectant monitoring (€1210). No substantial differences were found in the postpartum, follow-up and for non-medical costs. CONCLUSION: In women with gestational hypertension or mild pre-eclampsia at term, induction of labour is less costly than expectant monitoring because of differences in resource use in the antepartum period. As the trial already demonstrated that induction of labour results in less progression to severe disease without resulting in a higher caesarean section rate, both clinical and economic consequences are in favour of induction of labour in these women. TRIAL REGISTRATION: The trial has been registered in the clinical trial register as ISRCTN08132825.

Ketonuria is not associated with hyperemesis gravidarum disease severity.

OBJECTIVE: To assess the association between ketonuria and hyperemesis gravidarum (HG) disease severity. STUDY DESIGN: We included pregnant women hospitalised for HG who participated in the Maternal and Offspring outcomes after Treatment of HyperEmesis by Refeeding (MOTHER) trial and women who were eligible, chose not to be randomised and agreed to participate in the observational cohort. Between October 2013 and March 2016, in 19 hospitals in the Netherlands, women hospitalised for HG were approached for study participation. The presence of ketonuria was not required for study entry. Ketonuria was measured at hospital admission with a dipstick, which distinguishes 5 categories: negative and 1+ through 4 + . The outcome measures were multiple measures of HG disease severity at different time points: 1) At hospital admission (study entry): severity of nausea and vomiting, quality of life and weight change compared to pre-pregnancy weight, 2) One week after hospital admission: severity of nausea and vomiting, quality of life and weight change compared to admission, 3) Duration of index hospital admission and readmission for HG at any time point RESULTS: 215 women where included. Ketonuria was not associated with severity of nausea and vomiting, quality of life or weight loss at hospital admission, nor was the degree of ketonuria at admission associated with any of the outcomes 1 week after hospital admission. The degree of ketonuria was also not associated with the number of readmissions. However, women with a higher degree of ketonuria had a statistically significant longer duration of hospital stay (per 1+ ketonuria, difference: 0.27 days, 95 % CI: 0.05 to 0.48). CONCLUSIONS: There was no association between the degree of ketonuria at admission and severity of symptoms, quality of life, maternal weight loss, or number of readmissions, suggesting that ketonuria provides no information about disease severity or disease course. Despite this, women with a higher degree of ketonuria at admission were hospitalised for longer. This could suggest that health care professionals base length of hospital stay on the degree of ketonuria. Based on the lack of association between ketonuria and disease severity, we suggest it has no additional value in the clinical management of HG.

Effect of levothyroxine on live birth rate in euthyroid women with recurrent miscarriage and TPO antibodies (T4-LIFE study).

BACKGROUND: Thyroid peroxidase antibodies (TPO-Ab) in euthyroid women are associated with recurrent miscarriage (RM) and other pregnancy complications such as preterm birth. It is unclear if treatment with levothyroxine improves pregnancy outcome. AIM: The aim of this study is to determine the effect of levothyroxine administration on live birth rate in euthyroid TPO-Ab positive women with recurrent miscarriage. METHODS/DESIGN: We will perform a multicenter, placebo controlled randomized trial in euthyroid women with recurrent miscarriage and TPO-Ab. Recurrent miscarriage is defined as two or more miscarriages before the 20th week of gestation. The primary outcome is live birth, defined as the birth of a living fetus beyond 24weeks of gestation. Secondary outcomes are ongoing pregnancy at 12weeks, miscarriage, preterm birth, (serious) adverse events, time to pregnancy and survival at 28days of neonatal life. The analysis will be performed according to the intention to treat principle. We need to randomize 240 women (120 per group) to demonstrate an improvement in live birth rate from 55% in the placebo group to 75% in the levothyroxine treatment group. This trial is a registered trial (NTR 3364, March 2012). Here we discuss the rationale and design of the T4-LIFE study, an international multicenter randomized, double blind placebo controlled, clinical trial aimed to assess the effectiveness of levothyroxine in women with recurrent miscarriage and TPO-Ab.

Termination of pregnancy for maternal indications at the limits of fetal viability: a retrospective cohort study in the Dutch tertiary care centres.

OBJECTIVE: Maternal morbidity, either pregnancy related or pre-existent, can become life threatening and of such severity as to warrant termination of pregnancy (TOP). In this situation, chances of fetal survival are usually poor, either because of low gestational age and/or because of the fetal effects of the maternal condition. Examples include severe growth restriction in pre-eclampsia and intrauterine infection due to the very early preterm prelabour rupture of membranes. There are very few reports on the prevalence of TOP for maternal indication at the limits of fetal viability. We investigated the prevalence of and indications for TOP on maternal indication in the 10 tertiary care centres in the Netherlands during the past decade. STUDY DESIGN: We conducted a retrospective review of the medical records of all women who underwent TOP for maternal indications between 22 and 27 completed weeks of gestation in all 10 tertiary care centres from 2000 to 2009. RESULTS: During the study period, there were 1 929 470 deliveries; 163 052 (8.4%) of these took place in one of the 10 tertiary care centres and 177 pregnancies were terminated for severe maternal disease, 131 for hypertensive disorders, 29 for intrauterine infection and 17 for other reasons. The mean gestational age at TOP was 171 days (24(3/7))±10 days. No maternal deaths were recorded. The overall perinatal mortality was 99.4%. CONCLUSIONS: Over a 10-year period, TOP for maternal indications was performed in 1 in 1000 deliveries in the 10 Dutch tertiary care centres. Hypertensive disorders comprised three-quarters of the cases.