Restrictive versus liberal fluid resuscitation strategy, influence on blood loss and hemostatic parameters in mild obstetric hemorrhage: An open-label randomized controlled trial. (REFILL study).

BACKGROUND: Evidence for optimal hemostatic resuscitation in postpartum hemorrhage (PPH) is lacking. Liberal fluid administration may result in acidosis, hypothermia and coagulopathy. OBJECTIVE: We hypothesize that in early PPH a restrictive fluid administration results in less progression to moderate PPH. STUDY DESIGN: In four Dutch hospitals we recruited women of 18 years and over, and more than 24 weeks pregnant. Exclusion criteria were: anticoagulant therapy, known coagulation disorders, pre-eclampsia, antenatal diagnosis of abnormally adhesive placenta, and a contraindication for liberal fluid therapy. We blindly randomized participants at 500 mL and ongoing blood loss in the third stage of labor between restrictive fluid administration (clear fluids 0.75-1.0 times the volume of blood lost) and liberal fluid administration (clear fluids 1.5-2.0 times the volume of blood lost). The primary outcome was progression to more than 1000 mL blood loss. Analyses were according to the intention-to-treat principle. RESULTS: From August 2014 till September 2019, 5190 women were informed of whom 1622 agreed to participate. A total of 252 women were randomized of which 130 were assigned to the restrictive group and 122 to the liberal group. In the restrictive management group 51 of the 130 patients (39.2%) progressed to more than 1000 mL blood loss versus 61 of the 119 patients (51.3%) in the liberal management group (difference, -12.0% [95%-CI -24.3% to 0.3%], p = 0.057). There was no difference in the need for blood transfusion, coagulation parameters, or in adverse events between the groups. CONCLUSIONS: Although a restrictive fluid resuscitation in women with mild PPH could not been proven to be superior, it does not increase the need for blood transfusion, alter coagulation parameters, or cause a rise in adverse events. It can be considered as an alternative treatment option to liberal fluid resuscitation. TRIAL REGISTRATION: NTR3789.

Lymphatic malformations adjacent to the airway in neonates: Risk factors for outcome.

PURPOSE: To evaluate imaging, treatment, and outcomes in neonates with a lymphatic malformation (LM) adjacent to the airway and to evaluate risk factors that can predict outcome. METHODS: A retrospective case series was conducted of ten patients treated between January 2011 and July 2019. The main outcome measures included airway compromise and clinical response to sclerotherapy ± surgery. Categorical data were compared using the Fisher's exact test. RESULTS: Ex-utero intrapartum therapy was performed in four cases, among whom one died due to sepsis. All patients underwent schlerotherapy, with surgical debulking in two. Four patients showed a good clinical response, and five started experimental systemic treatment. Patients with bilateral disease and patients with an LM with >180° tracheal surrounding were significantly at risk for airway compromise (bilateral: n = 6/6 versus n = 0/4, p = 0.005; >180°: n = 5/5 versus n = 1/5, p = 0.048). The need for LM treatment in the neonatal period was indicative of a poor clinical response ('non-responders' 5/6, 'responders' 0/4; p = 0.048). CONCLUSIONS: This study indicates that bilateral disease and >180° tracheal surrounding are risk factors for airway compromise in neonates with an LM adjacent to the airway. In addition, the need for early treatment seems to be indicative of a poor clinical response.

Neonatal developmental and behavioral outcomes of immediate delivery versus expectant monitoring in mild hypertensive disorders of pregnancy: 2-year outcomes of the HYPITAT-II trial.

BACKGROUND: Management of preterm hypertensive disorders remains a clinical dilemma. The maternal benefits of delivery need to be weighed against the adverse neonatal consequences of preterm birth. Long-term consequences of obstetric management in offspring of women with hypertensive disorders in preterm pregnancy are largely unknown. We report child neurodevelopmental and behavioral outcomes at 2 years after the Hypertension and Preeclampsia Intervention Trial at near Term (HYPITAT-II) trial, which compared immediate delivery versus expectant monitoring in mild late preterm hypertensive disorders of pregnancy. OBJECTIVE: To compare effects of immediate delivery vs expectant monitoring on neurodevelopmental and behavioral outcomes at 2 years of age in offspring of women with mild late preterm hypertensive disorders. MATERIALS AND METHODS: We studied children born in the HYPITAT-II trial, a study in which women (n = 704) with hypertensive disorders of pregnancy who were between 34 and 37 weeks' gestation were randomized to immediate delivery or expectant monitoring. Participating women were asked to complete the Ages and Stages Questionnaire for developmental outcome and the Child Behavior Checklist for behavioral problems when their toddlers were 2 years old. RESULTS: We approached 545 of 704 randomized women (77%); 330 of 545 (61%) returned the questionnaires. In the immediate delivery group, 45 of 162 infants (28%) had an abnormal Ages and Stages Questionnaire score compared to 27 of 148 (18%) in the expectant monitoring group (risk difference, 9.6%; 95% CI, 0.3-18.0%); P = .045. In the pregnancies (n = 94) that delivered before reaching 36 weeks, 27% (n = 25) had an abnormal Ages and Stages Questionnaire score compared to 22% (n = 47) when delivered after 36 weeks (odds ratio, 0.77; confidence interval, 0.44-1.34). An abnormal Child Behavior Checklist outcome was found in 31 of 175 (18%) in the delivery group vs 24 of 166 (15%) in the expectant monitoring group (risk difference, 3.2%; 95% CI, -4.6% to 11.0%). After correction for maternal education, management strategy remained an independent predictor of abnormal Ages and Stages Questionnaire score (odds ratio, 0.48; confidence interval, 0.24 to -0.96, P = .03). In multivariable analyses, low birth weight, low maternal education, and immediate delivery policy were all significantly associated with an abnormal Ages and Stages Questionnaire score. CONCLUSION: In this study, we found that early delivery in women with late preterm hypertensive disorders is associated with poorer neurodevelopmental outcomes in their children at 2 years of age. These findings indicate an increased risk of developmental delay after early delivery compared to expectant monitoring. This follow-up study underlines the conclusion of the original HYPITAT-II study that, until the clinical situation deteriorates, expectant monitoring remains the most appropriate management strategy in the light of short- and long-term neonatal outcomes in women with preterm hypertensive disorders.

Major obstetric hemorrhage: Patients' perspective on the quality of care.

OBJECTIVES: Major obstetric hemorrhage (MOH) is the leading cause of severe maternal morbidity and mortality, and can have a significant impact on a woman's life. This study aims to gain insight into the patients reported experiences (PREs) and outcomes (PROs) after a major obstetric hemorrhage, and to investigate which patients are most at risk for negative experiences. MATERIAL AND METHODS: A Consumer Assessment of Healthcare Providers and Systems (CAHPS) based questionnaire was developed covering items on the PREs and PROs, and send to all patients with blood loss exceeding 2500 ml in six hospitals over the period of 2008-2012. A regression analysis was performed to find determinants for negative experiences. RESULTS: In total 372 of the 570 questionnaires were returned. Women scored the overall care before, during and after the MOH with a mean of 7.67, 7.62 and 7.28, respectively. However, most PRE items individually were scored suboptimal, with items regarding information supply scoring the lowest. Our results on the PROs showed 81% of the women (362) sustaining extreme fatigue, whereas problems with concentration (53% of 373 women), memory (49% of 353), or reliving (49% of 356) and irritability (51% of 355) were also frequently endured. Negative long term effects were observed in 28% of the women (106 of 372). We found 'year of the MOH longer ago', 'a lower total blood loss' and 'a large location of birth' to be determinants for negative experiences. CONCLUSIONS: Women frequently reported negative experiences and outcomes following a MOH. Information supply after an MOH concerning both physical and psychological complaints is essential for the improvement of care.

Development of a tailored strategy to improve postpartum hemorrhage guideline adherence.

BACKGROUND: Despite the introduction of evidence based guidelines and practical courses, the incidence of postpartum hemorrhage shows an increasing trend in developed countries. Substandard care is often found, which implies an inadequate implementation in high resource countries. We aimed to reduce the gap between evidence-based guidelines and clinical application, by developing a strategy, tailored to current barriers for implementation. METHODS: The development of the implementation strategy consisted of three phases, supervised by a multidisciplinary expert panel. In the first phase a framework of the strategy was created, based on barriers to optimal adherence identified among professionals and patients together with evidence on effectiveness of strategies found in literature. In the second phase, the tools within the framework were developed, leading to a first draft. In the third phase the strategy was evaluated among professionals and patients. The professionals were asked to give written feedback on tool contents, clinical usability and inconsistencies with current evidence care. Patients evaluated the tools on content and usability. Based on the feedback of both professionals and patients the tools were adjusted. RESULTS: We developed a tailored strategy to improve guideline adherence, covering the trajectory of the third trimester of pregnancy till the end of the delivery. The strategy, directed at professionals, comprehending three stop moments includes a risk assessment checklist, care bundle and time-out procedure. As patient empowerment tools, a patient passport and a website with patient information was developed. The evaluation among the expert panel showed all professionals to be satisfied with the content and usability and no discrepancies or inconsistencies with current evidence was found. Patients' evaluation revealed that the information they received through the tools was incomplete. The tools were adjusted accordingly to the missing information. CONCLUSION: A usable, tailored strategy to implement PPH guidelines and practical courses was developed. The next step is the evaluation of the strategy in a feasibility trial. TRIAL REGISTRATION: Clinical trial registration: The Fluxim study, registration number: NCT00928863 .

Repeated cervical length measurements for the verification of short cervical length.

OBJECTIVE: To determine if the verification of short cervical length with a repeated measurement improved the identification of patients with short cervical length at increased risk of preterm delivery. METHODS: The present secondary analysis analyzed prospective cohort study data from patients with singleton pregnancies without a history of preterm delivery who presented for obstetric care in the Netherlands and delivered between November 18, 2009, and January 1, 2013. Cervical length was measured during standard anomaly scan and a second measurement was performed if the cervical length was 30 mm of shorter. Logistic regression and Cox proportional hazards modeling were used to evaluate associations between cervical length measurements and spontaneous preterm delivery before 37 weeks of pregnancy. RESULTS: Cervical length measurements from 12 358 patients were included; 221 (1.8%) had an initial cervical length measurement of 30 mm or shorter. A second cervical length measurement was performed for 167 (75.6%) patients; no differences were identified in the odds of spontaneous preterm delivery when evaluated using the first, second, or a mean of both measurements, regardless of whether cervical length was analyzed as a continuous or dichotomous variable. CONCLUSION: Among patients with singleton pregnancies, verification of short cervical length did not improve the identification of short cervical length.

Women's Experiences with and Preference for Induction of Labor with Oral Misoprostol or Foley Catheter at Term.

Objective We assessed experience and preferences among term women undergoing induction of labor with oral misoprostol or Foley catheter. Study Design In 18 of the 29 participating hospitals in the PROBAAT-II trial, women were asked to complete a questionnaire within 24 hours after delivery. We adapted a validated questionnaire about expectancy and experience of labor and asked women whether they would prefer the same method again in a future pregnancy. Results The questionnaire was completed by 502 (72%) of 695 eligible women; 273 (54%) had been randomly allocated to oral misoprostol and 229 (46%) to Foley catheter. Experience of the duration of labor, pain during labor, general satisfaction with labor, and feelings of control and fear related to their expectation were comparable between both the groups. In the oral misoprostol group, 6% of the women would prefer the other method if induction is necessary in future pregnancy, versus 12% in the Foley catheter group (risk ratio: 0.70; 95% confidence interval: 0.55-0.90; p = 0.02). Conclusion Women's experiences of labor after induction with oral misoprostol or Foley catheter are comparable. However, women in the Foley catheter group prefer more often to choose a different method for future inductions.

Prediction of progression to severe disease in women with late preterm hypertensive disorders of pregnancy.

INTRODUCTION: If hypertensive disorders of pregnancy are diagnosed before term, the benefits of immediate delivery need to be weighed against the neonatal consequences of preterm delivery. If we are able to predict which women are at high risk of progression to severe disease, they could be targeted for delivery and maternal complications might be reduced. In addition, this may prevent unnecessary preterm births in women at low risk. MATERIAL AND METHODS: We developed a prediction model using data from the HYPITAT-II trail, which evaluated immediate delivery vs. expectant monitoring in women with non-severe hypertensive disorders of pregnancy between 34 and 37 weeks of gestation. Univariate and multivariate logistic regression analysis were used to identify relevant variables from clinical and laboratory parameters. The performance of the resulting prediction model was assessed by receiver operating characteristic analysis, calibration and bootstrapping, using the average predicted probabilities. RESULTS: We included 519 women, 115 (22.2%) of whom developed severe hypertensive disorders of pregnancy. The prediction model included: maternal age (odds ratio 0.92 per year), gestational age (odds ratio 0.87 per week), systolic blood pressure (odds ratio 1.05 per mmHg), the presence of chronic hypertension (odds ratio 2.4), platelet count (odds ratio 0.996), creatinine (odds ratio 1.02) and lactate dehydrogenase (odds ratio 1.003). The model showed good fit (p = 0.64), fair discrimination (area under the curve 0.76, 95% confidence interval 0.73-0.81, p < 0.001) and could stratify women in three risk groups of average, intermediate and high risk (predicted probabilities <0.22, <0.44 and >0.45, respectively). CONCLUSION: In women with non-severe hypertension in pregnancy near term, progression to severe disease can be predicted. This model requires external validation before it can be applied in practice.

Which Factors Contribute to False-Positive, False-Negative, and Invalid Results in Fetal Fibronectin Testing in Women with Symptoms of Preterm Labor?

Objective We assessed the influence of external factors on false-positive, false-negative, and invalid fibronectin results in the prediction of spontaneous delivery within 7 days. Methods We studied symptomatic women between 24 and 34 weeks' gestational age. We performed uni- and multivariable logistic regression to estimate the effect of external factors (vaginal soap, digital examination, transvaginal sonography, sexual intercourse, vaginal bleeding) on the risk of false-positive, false-negative, and invalid results, using spontaneous delivery within 7 days as the outcome. Results Out of 708 women, 237 (33%) had a false-positive result; none of the factors showed a significant association. Vaginal bleeding increased the proportion of positive fetal fibronectin (fFN) results, but was significantly associated with a lower risk of false-positive test results (odds ratio [OR], 0.22; 95% confidence intervals [CI], 0.12-0.39). Ten women (1%) had a false-negative result. None of the investigated factors was significantly associated with a significantly higher risk of false-negative results. Twenty-one tests (3%) were invalid; only vaginal bleeding showed a significant association (OR, 4.5; 95% CI, 1.7-12). Conclusion The effect of external factors on the performance of qualitative fFN testing is limited, with vaginal bleeding as the only factor that reduces its validity.

Comparison of the Actim Partus test and the fetal fibronectin test in the prediction of spontaneous preterm birth in symptomatic women undergoing cervical length measurement.

OBJECTIVE: To compare the accuracy of the Actim Partus test and fetal fibronectin (fFN) test in the prediction of spontaneous preterm delivery within seven days in symptomatic women undergoing cervical length measurement. STUDY DESIGN: We performed a post-hoc analysis on frozen samples of a nationwide cohort study in all 10 perinatal centres in the Netherlands. We selected samples from women with signs of preterm labour between 24 and 34 weeks of gestational age and a cervical length below 30mm. Delivery within seven days after initial assessment was the primary endpoint. We calculated sensitivity, specificity, and positive and negative predictive values for the combination of both the Actim Partus test and fFN test with cervical length. A test was considered positive in case of a cervical length between 15 and 30mm with a positive Actim Partus or fFN test, and a cervical length below 15mm regardless the test result. RESULTS: In total, samples of 350 women were tested, of whom 69 (20%) delivered within seven days. Eighty-four women had a positive Actim Partus test and 162 women a positive fFN test, of whom 54 (64%) and 63 (39%) delivered within seven days, respectively. Ninety-seven women had a cervical length below 15mm, of whom 50 (52%) delivered within seven days. Sensitivity, specificity, positive and negative predictive values of combining cervical length with the Actim Partus test or the fFN test were 91%, 75%, 47% and 97%, and 96%, 58%, 36% and 98%, respectively. CONCLUSION: According to this post-hoc study, in combination with cervical length, the Actim Partus test could be used as an alternative for the fFN test to identify women who will not deliver within seven days after presentation. Further evidence should be collected in a prospective comparative study.

From Postpartum Haemorrhage Guideline to Local Protocol: A Study of Protocol Quality.

Objective Postpartum hemorrhage (PPH) has a continuously rising incidence worldwide, suggesting suboptimal care. An important step in optimizing care is the translation of evidence-based guidelines into comprehensive hospital protocols. However, knowledge about the quality of these protocols is lacking. The objective of this study was to evaluate the quality of PPH-protocols on structure and content in the Netherlands. Methods We performed an observational multicenter study. Eighteen PPH-protocols from 3 University Hospitals (UH), 8 Teaching Hospitals (TH) and 7 Non-Teaching hospitals (NTH) throughout the Netherlands were acquired. The structure of the PPH-protocols was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE-II) Instrument. The content was appraised using previously developed quality indicators, based on international guidelines and Advance-Trauma-Life-Support (ATLS)-based course instructions. Results The quality of the protocols for postpartum hemorrhage for both structure and content varied widely between different hospitals, but all of them showed room for improvement. The protocols scored mainly below average on the different items of the AGREE-II instrument (8 of the 10 items scored <4 on a 1-7 scale). Regarding the content, adoption of guideline recommendations in protocols was 46 %. In addition, a timely indication of 'when to perform' a recommendation was lacking in three-fourths of the items. Conclusion This study shows that the quality of the PPH-protocols for both structure and content in the Netherlands is suboptimal. This makes adherence to the guideline and ATLS-based course instructions difficult.

The impact of fetal gender and ethnicity on the risk of spontaneous preterm delivery in women with symptoms of preterm labor.

OBJECTIVE: The objective of this study is to evaluate the relation among fetal gender, ethnicity, and preterm labor (PTL) and preterm delivery (PTD). METHODS: A secondary analysis was performed of a prospective cohort study including women with symptoms of PTL between 24 and 34 weeks. The proportion of women carrying a male or female fetus at the onset of PTL was calculated. Gestational age at delivery and risk of PTD of both fetal genders was compared and interaction of fetal gender and maternal ethnicity on the risk of PTD was evaluated. RESULTS: Of the 594 included women, 327 (55%) carried a male fetus. Median gestational age at delivery in women pregnant with a male fetus was 37 5/7 (IQR 34 4/7-39 1/7) weeks compared with 38 1/7 (IQR 36 0/7-39 5/7) weeks in women pregnant with a female fetus (p = 0.032). The risk of PTD did not differ significantly. In Caucasians, we did find an increased risk of PTD before 37 weeks in women pregnant with a male fetus (OR 1.9 (95% CI 1.2-3.0)). CONCLUSIONS: The majority of women with PTL are pregnant with a male fetus and these women deliver slightly earlier. Race seems to affect this disparity.

Influencing factors for high quality care on postpartum haemorrhage in the Netherlands: patient and professional perspectives.

BACKGROUND: Postpartum haemorrhage (PPH) remains a major contributor to maternal morbidity even in high resource settings, despite the development and dissemination of evidence-based guidelines and Advance-Trauma-Life-Support (ATLS) based courses for optimal management of PPH. We aimed to assess current influencing factors (obstacles and facilitators) for the delivery of high quality PPH-care from both patient and professional perspective. METHODS: We qualitatively explored influencing factors for delivering high quality PPH-care, by having individual interviews with PPH-patients and focus group interviews with the different types of professionals working in the delivery room. For both perspectives, the theoretical frameworks of Grol and Cabana were used to classify the influencing factors for optimal PPH-care (factors of the guidelines, of professionals, of patients, of the social setting and of the organisation). In order to assess the importance of the influencing factors found among the professionals, we quantified these factors in a web-based questionnaire. RESULTS: A total of 12 patients and 41 professionals participated in the interviews, and 315 complete surveys were analyzed. The main obstacle for high quality PPH-care identified by patients was the lack of information given by the professionals to the patient and partner before, during and after the PPH event. An informative patient website, a patient leaflet and a follow-up consultation were mentioned as facilitators. The main obstacles according to the professionals were: lack of clarity of the guidelines, lack of knowledge and failing team-communication. Team training and checklists/ flowcharts were considered facilitators. CONCLUSIONS: Different obstacles to the delivery of high quality PPH-care were identified by both patients and professionals. These data can be used to develop a focused strategy to improve PPH-care. TRIAL REGISTRATION: NCT 00928863.

The capacity of mid-pregnancy cervical length to predict preterm birth in low-risk women: a national cohort study.

INTRODUCTION: We investigated the predictive capacity of mid-trimester cervical length (CL) measurement for spontaneous and iatrogenic preterm birth. MATERIAL AND METHODS: We performed a prospective observational cohort study in nulliparous women and low-risk multiparous women with a singleton pregnancy between 16(+0) and 21(+6) weeks of gestation. We assessed the prognostic capacity of transvaginally measured mid-trimester CL for spontaneous and iatrogenic preterm birth (<37 weeks) using likelihood ratios (LR) and receiver-operating-characteristic analysis. We calculated numbers needed to screen to prevent one preterm birth assuming different treatment effects. Main outcome measures were preterm birth <32, <34 and <37 weeks. RESULTS: We studied 11,943 women, of whom 666 (5.6%) delivered preterm: 464 (3.9%) spontaneous and 202 (1.7%) iatrogenic. Mean CL was 44.1 mm (SD 7.8 mm). In nulliparous women, the LRs for spontaneous preterm birth varied between 27 (95% CI 7.7-95) for a CL ≤ 20 mm, and 2.0 (95% CI 1.6-2.5) for a CL between 30 and 35 mm. For low-risk multiparous women, these LRs were 37 (95% CI 7.5-182) and 1.5 (95% CI 0.97-2.2), respectively. Using a cut-off for CL ≤ 30 mm, 28 (6.0%) of 464 women with spontaneous preterm birth were identified. The number needed to screen to prevent one case of preterm birth was 618 in nulliparous women and 1417 for low-risk multiparous women (40% treatment effect, cut-off 30 mm). CONCLUSION: In women at low risk of preterm birth, CL predicts spontaneous preterm birth. However, its isolated use as a screening tool has limited value due to low sensitivity.

Prescribing patterns of antenatal corticosteroids in women with threatened preterm labor.

OBJECTIVE: To assess the impact of cervical length (CL) measurement and fetal fibronectin testing (fFN) on the clinicians' decision to prescribe antenatal corticosteroids (ACS) to women with symptoms of preterm labor. STUDY DESIGN: This is a secondary analysis of a prospective cohort study including women with symptoms of preterm labor and intact membranes between 24 and 34 weeks' gestation. We compared the proportion prescribed and completed ACS courses, preterm delivery within seven days and median intervals from ACS to delivery in four groups: group 1 CL<10 mm, group 2 CL 10-30 mm and positive fFN, group 3 CL 10-30 mm and negative fFN, group 4 CL>30 mm. RESULTS: ACS were prescribed to 63/65 (97%) women in group 1, 176/192 (91%) in group 2, 111/172 women (65%) in group 3 and 55/242 (23%) in group 4. In group 1, 42 (65%) women delivered within seven days, compared to 34 (18%) in group 2, 6 (3%) in group 3 and 3 (1%) in group 4. Median intervals between ACS and delivery were 6 days (IQR 3-61 days), 44 days (IQR 17-69 days), 53 days (IQR 37-77 days) and 66 days (IQR 43-78 days) in group 1, 2, 3 and 4 respectively. CONCLUSION: ACS were prescribed frequently to women with a CL of 10-30 mm and a negative fFN test or a CL>30 mm. There is room for improvement in the prescription of ACS in these low risk women.

Guideline-based development of quality indicators for prevention and management of postpartum hemorrhage.

INTRODUCTION: To systematically develop a set of guideline-based quality indicators for postpartum hemorrhage (PPH) as a tool to measure guideline adherence in actual PPH care. MATERIAL AND METHODS: A Rand-modified Delphi procedure was used to systematically achieve consensus among a panel of 22 experts on PPH care on recommendations extracted from evidence-based guidelines, Managing-Obstetrics-Emergencies-Trauma (MOET) instructions and international literature. The selected recommendations were individually rated on health gain (prevention of maternal mortality and morbidity) and overall efficiency by the expert panel. Subsequently, consensus about the most important recommendations to measure quality of PPH care among the panel members was reached, followed by a final approval. Last, definition of the final set by critical appraisal of the recommendations regarding measurability took place. The main outcome measure was a set of valid quality indicators for prevention and management of PPH. RESULTS: From the 69 extracted recommendations, 50 were selected and translated into 22 quality indicators on professional performance (n = 17) and organization of PPH care (n = 5). The professional performance indicators covered all fields of PPH care, such as prevention (n = 2) and management of PPH, including communication and documentation (n = 4), monitoring and prevention of shock (n = 3), use of blood products (n = 3) and treatment of PPH (n = 5). Organizational indicators (n = 5) were clustered into protocols and agreements, audit, accessibility and documentation. CONCLUSIONS: This study describes a stepwise systematic development of 22 performance and organizational indicators to use for measuring the whole care process of prevention and management of PPH.

Immediate delivery versus expectant monitoring for hypertensive disorders of pregnancy between 34 and 37 weeks of gestation (HYPITAT-II): an open-label, randomised controlled trial.

BACKGROUND: There is little evidence to guide the management of women with hypertensive disorders in late preterm pregnancy. We investigated the effect of immediate delivery versus expectant monitoring on maternal and neonatal outcomes in such women. METHODS: We did an open-label, randomised controlled trial, in seven academic hospitals and 44 non-academic hospitals in the Netherlands. Women with non-severe hypertensive disorders of pregnancy between 34 and 37 weeks of gestation were randomly allocated to either induction of labour or caesarean section within 24 h (immediate delivery) or a strategy aimed at prolonging pregnancy until 37 weeks of gestation (expectant monitoring). The primary outcomes were a composite of adverse maternal outcomes (thromboembolic disease, pulmonary oedema, eclampsia, HELLP syndrome, placental abruption, or maternal death), and neonatal respiratory distress syndrome, both analysed by intention-to-treat. This study is registered with the Netherlands Trial Register (NTR1792). FINDINGS: Between March 1, 2009, and Feb 21, 2013, 897 women were invited to participate, of whom 703 were enrolled and randomly assigned to immediate delivery (n=352) or expectant monitoring (n=351). The composite adverse maternal outcome occurred in four (1·1%) of 352 women allocated to immediate delivery versus 11 (3·1%) of 351 women allocated to expectant monitoring (relative risk [RR] 0·36, 95% CI 0·12-1·11; p=0·069). Respiratory distress syndrome was diagnosed in 20 (5·7%) of 352 neonates in the immediate delivery group versus six (1·7%) of 351 neonates in the expectant monitoring group (RR 3·3, 95% CI 1·4-8·2; p=0·005). No maternal or perinatal deaths occurred. INTERPRETATION: For women with non-severe hypertensive disorders at 34-37 weeks of gestation, immediate delivery might reduce the already small risk of adverse maternal outcomes. However, it significantly increases the risk of neonatal respiratory distress syndrome, therefore, routine immediate delivery does not seem justified and a strategy of expectant monitoring until the clinical situation deteriorates can be considered. FUNDING: ZonMw.

Preventing Preterm Birth with Progesterone in Women with a Short Cervical Length from a Low-Risk Population: A Multicenter Double-Blind Placebo-Controlled Randomized Trial.

OBJECTIVE: The objective of this study was to evaluate the effectiveness of vaginal progesterone in reducing adverse neonatal outcome due to preterm birth (PTB) in low-risk pregnant women with a short cervical length (CL). STUDY DESIGN: Women with a singleton pregnancy without a history of PTB underwent CL measurement at 18 to 22 weeks. Women with a CL ≤ 30 mm received vaginal progesterone or placebo. Primary outcome was adverse neonatal outcome, defined as a composite of respiratory distress syndrome, bronchopulmonary dysplasia, intracerebral hemorrhage > grade II, necrotizing enterocolitis > stage 1, proven sepsis, or death before discharge. Secondary outcomes included time to delivery, PTB before 32, 34, and 37 weeks of gestation. Analysis was by intention to treat. RESULTS: Between 2009 and 2013, 20,234 women were screened. A CL of 30 mm or less was seen in 375 women (1.8%). In 151 women, a CL ≤ 30 mm was confirmed with a second measurement and 80 of these women agreed to participate in the trial. We randomly allocated 41 women to progesterone and 39 to placebo. Adverse neonatal outcomes occurred in two (5.0%) women in the progesterone and in four (11%) women in the control group (relative risk [RR], 0.47; 95% confidence interval [CI], 0.09-2.4). The use of progesterone resulted in a nonsignificant reduction of PTB < 32 weeks (2.0 vs. 8.0%; RR, 0.33; 95% CI, 0.04-3.0) and < 34 weeks (7.0 vs. 10%; RR, 0.73; 95% CI, 0.18-3.1) but not on PTB < 37 weeks (15 vs. 13%; RR, 1.2; 95% CI, 0.39-3.5). CONCLUSION: In women with a short cervix, who are otherwise low risk, we could not show a significant benefit of progesterone in reducing adverse neonatal outcome and PTB.

Patient controlled analgesia with remifentanil versus epidural analgesia in labour: randomised multicentre equivalence trial.

OBJECTIVE: To determine women's satisfaction with pain relief using patient controlled analgesia with remifentanil compared with epidural analgesia during labour. DESIGN: Multicentre randomised controlled equivalence trial. SETTING: 15 hospitals in the Netherlands. PARTICIPANTS: Women with an intermediate to high obstetric risk with an intention to deliver vaginally. To exclude a clinically relevant difference in satisfaction with pain relief of more than 10%, we needed to include 1136 women. Because of missing values for satisfaction this number was increased to 1400 before any analysis. We used multiple imputation to correct for missing data. INTERVENTION: Before the onset of active labour consenting women were randomised to a pain relief strategy with patient controlled remifentanil or epidural analgesia if they requested pain relief during labour. MAIN OUTCOME MEASURES: Primary outcome was satisfaction with pain relief, measured hourly on a visual analogue scale and expressed as area under the curve (AUC), thus providing a time weighted measure of total satisfaction with pain relief. A higher AUC represents higher satisfaction with pain relief. Secondary outcomes were pain intensity scores, mode of delivery, and maternal and neonatal outcomes. Analysis was done by intention to treat. The study was defined as an equivalence study for the primary outcome. RESULTS: 1414 women were randomised, of whom 709 were allocated to patient controlled remifentanil and 705 to epidural analgesia. Baseline characteristics were comparable. Pain relief was ultimately used in 65% (447/687) in the remifentanil group and 52% (347/671) in the epidural analgesia group (relative risk 1.32, 95% confidence interval 1.18 to 1.48). Cross over occurred in 7% (45/687) and 8% (51/671) of women, respectively. Of women primarily treated with remifentanil, 13% (53/402) converted to epidural analgesia, while in women primarily treated with epidural analgesia 1% (3/296) converted to remifentanil. The area under the curve for total satisfaction with pain relief was 30.9 in the remifentanil group versus 33.7 in the epidural analgesia group (mean difference -2.8, 95% confidence interval -6.9 to 1.3). For who actually received pain relief the area under the curve for satisfaction with pain relief after the start of pain relief was 25.6 in the remifentanil group versus 36.1 in the epidural analgesia group (mean difference -10.4, -13.9 to -7.0). The rate of caesarean section was 15% in both groups. Oxygen saturation was significantly lower (SpO2 <92%) in women who used remifentanil (relative risk 1.5, 1.4 to 1.7). Maternal and neonatal outcomes were comparable between both groups. CONCLUSION: In women in labour, patient controlled analgesia with remifentanil is not equivalent to epidural analgesia with respect to scores on satisfaction with pain relief. Satisfaction with pain relief was significantly higher in women who were allocated to and received epidural analgesia. TRIAL REGISTRATION: Netherlands Trial Register NTR2551.

Midtrimester preterm prelabour rupture of membranes (PPROM): expectant management or amnioinfusion for improving perinatal outcomes (PPROMEXIL - III trial).

BACKGROUND: Babies born after midtrimester preterm prelabour rupture of membranes (PPROM) are at risk to develop neonatal pulmonary hypoplasia. Perinatal mortality and morbidity after this complication is high. Oligohydramnios in the midtrimester following PPROM is considered to cause a delay in lung development. Repeated transabdominal amnioinfusion with the objective to alleviate oligohydramnios might prevent this complication and might improve neonatal outcome. METHODS/DESIGN: Women with PPROM and persisting oligohydramnios between 16 and 24 weeks gestational age will be asked to participate in a multi-centre randomised controlled trial. INTERVENTION: random allocation to (repeated) abdominal amnioinfusion (intervention) or expectant management (control). The primary outcome is perinatal mortality. Secondary outcomes are lethal pulmonary hypoplasia, non-lethal pulmonary hypoplasia, survival till discharge from NICU, neonatal mortality, chronic lung disease (CLD), number of days ventilatory support, necrotizing enterocolitis (NEC), periventricular leucomalacia (PVL) more than grade I, severe intraventricular hemorrhage (IVH) more than grade II, proven neonatal sepsis, gestational age at delivery, time to delivery, indication for delivery, successful amnioinfusion, placental abruption, cord prolapse, chorioamnionitis, fetal trauma due to puncture. The study will be evaluated according to intention to treat. To show a decrease in perinatal mortality from 70% to 35%, we need to randomise two groups of 28 women (two sided test, ß-error 0.2 and α-error 0.05). DISCUSSION: This study will answer the question if (repeated) abdominal amnioinfusion after midtrimester PPROM with associated oligohydramnios improves perinatal survival and prevents pulmonary hypoplasia and other neonatal morbidities. Moreover, it will assess the risks associated with this procedure. TRIAL REGISTRATION: NTR3492 Dutch Trial Register (http://www.trialregister.nl).