Prophylactic radiologic interventions to reduce postpartum hemorrhage in women with risk factors for placenta accreta spectrum disorder: a nationwide cohort study.

OBJECTIVE: To quantify the association between prophylactic radiologic interventions and perioperative blood loss in women with risk factors for placenta accreta spectrum disorder (PAS). METHODS: We conducted a retrospective nationwide cohort study of women with risk factors for placenta accreta spectrum disorder who underwent planned cesarean section in 69 Dutch hospitals between 2008 and 2013. All women had two risk factors for PAS: placenta previa/anterior low-lying placenta and a history of cesarean section(s). Women with and without ultrasonographic signs of PAS were studied as two separate groups. We compared the total blood loss of women with prophylactic radiologic interventions, defined as preoperative placement of balloon catheters or sheaths in the internal iliac or uterine arteries, with that of a control group consisting of women without prophylactic radiologic interventions using multivariable regression. We evaluated maternal morbidity by the number of red blood cell (RBC) units transfused within 24 h following childbirth (categories: 0, 1-3, >4), duration of hospital admission, and need for intensive care unit (ICU) admission. RESULTS: A total of 350 women with placenta previa/anterior low-lying placenta and history of cesarean section(s) were included: 289 with normal ultrasonography, of whom 21 received prophylactic radiologic intervention, and 61 had abnormal ultrasonography, of whom 22 received prophylactic intervention. Among women with normal ultrasonography without prophylactic intervention (n = 268), the median blood loss was 725 mL (interquartile range (IQR) 500-1500) vs. 1000 mL (IQR 550-1750) in women with intervention (n = 21); the adjusted difference in blood loss was 9 mL (95% confidence interval (CI) -315-513), p = .97). Among women with abnormal ultrasonography, those without prophylactic intervention (n = 39) had a median blood loss of 2500 mL (IQR 1200-5000) vs. 1750 mL (IQR 775-4000) in women with intervention (n = 22); the adjusted difference in blood loss was -1141 mL (95% CI -1694- -219, p = .02). Results of outcomes on maternal morbidity were comparable among women with and without prophylactic intervention. CONCLUSION: These findings suggest that prophylactic radiologic interventions prior to planned cesarean section may help to limit perioperative blood loss in women with clear signs of placenta accreta spectrum disorder on ultrasonography, but there was no evidence of a difference within the subgroup without such ultrasonographic signs. The use of these interventions should be discussed in a multidisciplinary shared decision-making process, including discussions of potential benefits and possible complications. TRIAL REGISTRATION: Netherlands Trial Registry, https://onderzoekmetmensen.nl/en/trial/28238, identifier NL4210 (NTR4363).

Confidential enquiry into maternal deaths in the Netherlands, 2006-2018.

INTRODUCTION: To calculate the maternal mortality ratio (MMR) for 2006-2018 in the Netherlands and compare this with 1993-2005, and to describe women's characteristics, causes of death and improvable factors. MATERIAL AND METHODS: We performed a nationwide, cohort study of all maternal deaths between January 1, 2006 and December 31, 2018 reported to the Audit Committee Maternal Mortality and Morbidity. Main outcome measures were the national MMR and causes of death. RESULTS: Overall MMR was 6.2 per 100 000 live births, a decrease from 12.1 in 1993-2005 (risk ratio [RR] 0.5). Women with a non-western ethnic background had an increased MMR compared with Dutch women (MMR 6.5 vs. 5.0, RR 1.3). The MMR was increased among women with a background from Surinam/Dutch Antilles (MMR 14.7, RR 2.9). Half of all women had an uncomplicated medical history (79/161, 49.1%). Of 171 pregnancy-related deaths within 1 year postpartum, 102 (60%) had a direct and 69 (40%) an indirect cause of death. Leading causes within 42 days postpartum were cardiac disease (n = 21, 14.9%), hypertensive disorders (n = 20, 14.2%) and thrombosis (n = 19, 13.5%). Up to 1 year postpartum, the most common cause of death was cardiac disease (n = 32, 18.7%). Improvable care factors were identified in 76 (47.5%) of all deaths. CONCLUSIONS: Maternal mortality halved in 2006-2018 compared with 1993-2005. Cardiac disease became the main cause. In almost half of all deaths, improvable factors were identified and women with a background from Surinam/Dutch Antilles had a threefold increased risk of death compared with Dutch women without a background of migration.

Nationwide confidential enquiries into maternal deaths because of obstetric hemorrhage in the Netherlands between 2006 and 2019.

INTRODUCTION: Obstetric hemorrhage-related deaths are rare in high income countries. Yet, with increasing incidences of obstetric hemorrhage in these countries, it is of utmost importance to learn lessons from each obstetric hemorrhage-related death to improve maternity care. Our objective was to calculate the obstetric hemorrhage-related maternal mortality ratio (MMR), assess causes of obstetric hemorrhage-related deaths, and identify lessons learned. MATERIAL AND METHODS: Nationwide mixed-methods prospective case-series with confidential enquiries into maternal deaths due to obstetric hemorrhage in the Netherlands from January 1, 2006 to December 31, 2019. RESULTS: The obstetric hemorrhage-related MMR in the Netherlands in 2006-2019 was 0.7 per 100 000 livebirths and was not statistically significantly different compared with the previous MMR of 1.0 per 100 000 livebirths in 1993-2005 (odds ratio 0.70, 95% confidence interval 0.38-1.30). Leading underlying cause of hemorrhage was retained placenta. Early recognition of persistent bleeding, prompt involvement of a senior clinician and timely management tailored to the cause of hemorrhage with attention to coagulopathy were prominent lessons learned. Also, timely recourse to surgical interventions, including hysterectomy, in case other management options fail to stop bleeding came up as an important lesson in several obstetric hemorrhage-related deaths. CONCLUSIONS: The obstetric hemorrhage-related MMR in the Netherlands in 2006-2019 has not substantially changed compared to the MMR of the previous enquiry in 1993-2005. Although obstetric hemorrhage is commonly encountered by maternity care professionals, it is important to remain vigilant for possible adverse maternal outcomes and act upon an ongoing bleeding following birth in a more timely and adequate manner. Our confidential enquiries still led to important lessons learned with clinical advice to professionals as how to improve maternity care and avoid maternal deaths. Drawing lessons from maternal deaths should remain a qualitative and moral imperative.

Evaluation of low-dose aspirin in the prevention of recurrent spontaneous preterm labour (the APRIL study): A multicentre, randomised, double-blinded, placebo-controlled trial.

BACKGROUND: Preterm birth is the leading cause of neonatal morbidity and mortality. The recurrence rate of spontaneous preterm birth is high, and additional preventive measures are required. Our objective was to assess the effectiveness of low-dose aspirin compared to placebo in the prevention of preterm birth in women with a previous spontaneous preterm birth. METHODS AND FINDINGS: We performed a parallel multicentre, randomised, double-blinded, placebo-controlled trial (the APRIL study). The study was performed in 8 tertiary and 26 secondary care hospitals in the Netherlands. We included women with a singleton pregnancy and a history of spontaneous preterm birth of a singleton between 22 and 37 weeks. Participants were randomly assigned to aspirin 80 mg daily or placebo initiated between 8 and 16 weeks of gestation and continued until 36 weeks or delivery. Randomisation was computer generated, with allocation concealment by using sequentially numbered medication containers. Participants, their healthcare providers, and researchers were blinded for treatment allocation. The primary outcome was preterm birth <37 weeks of gestation. Secondary outcomes included a composite of poor neonatal outcome (bronchopulmonary dysplasia, periventricular leukomalacia > grade 1, intraventricular hemorrhage > grade 2, necrotising enterocolitis > stage 1, retinopathy of prematurity, culture proven sepsis, or perinatal death). Analyses were performed by intention to treat. From May 31, 2016 to June 13, 2019, 406 women were randomised to aspirin (n = 204) or placebo (n = 202). A total of 387 women (81.1% of white ethnic origin, mean age 32.5 ± SD 3.8) were included in the final analysis: 194 women were allocated to aspirin and 193 to placebo. Preterm birth <37 weeks occurred in 41 (21.2%) women in the aspirin group and 49 (25.4%) in the placebo group (relative risk (RR) 0.83, 95% confidence interval (CI) 0.58 to 1.20, p = 0.32). In women with ≥80% medication adherence, preterm birth occurred in 24 (19.2%) versus 30 (24.8%) women (RR 0.77, 95% CI 0.48 to 1.25, p = 0.29). The rate of the composite of poor neonatal outcome was 4.6% (n = 9) versus 2.6% (n = 5) (RR 1.79, 95% CI 0.61 to 5.25, p = 0.29). Among all randomised women, serious adverse events occurred in 11 out of 204 (5.4%) women allocated to aspirin and 11 out of 202 (5.4%) women allocated to placebo. None of these serious adverse events was considered to be associated with treatment allocation. The main study limitation is the underpowered sample size due to the lower than expected preterm birth rates. CONCLUSIONS: In this study, we observed that low-dose aspirin did not significantly reduce the preterm birth rate in women with a previous spontaneous preterm birth. However, a modest reduction of preterm birth with aspirin cannot be ruled out. Further research is required to determine a possible beneficial effect of low-dose aspirin for women with a previous spontaneous preterm birth. TRIAL REGISTRATION: Dutch Trial Register (NL5553, NTR5675) https://www.trialregister.nl/trial/5553.

Association of Timing of Plasma Transfusion With Adverse Maternal Outcomes in Women With Persistent Postpartum Hemorrhage.

Importance: Early plasma transfusion for women with severe postpartum hemorrhage (PPH) is recommended to prevent coagulopathy. However, there is no comparative, quantitative evidence on the association of early plasma transfusion with maternal outcomes. Objective: To compare the incidence of adverse maternal outcomes among women who received plasma during the first 60 minutes of persistent PPH vs women who did not receive plasma for similarly severe persistent PPH. Design, Setting, and Participants: This multicenter cohort study used a consecutive sample of women with persistent PPH, defined as PPH refractory to first-line measures to control bleeding, between January 1, 2011, and January 1, 2013. Time-dependent propensity score matching was used to select women who received plasma during the first 60 minutes of persistent PPH and match each of them with a woman who had shown the same severity and received the same treatment of PPH but who had not received plasma at the moment of matching. Transfusions were not guided by coagulation tests. Statistical analysis was performed from June 2018 to June 2019. Exposures: Transfusion of plasma during the first 60 minutes of persistent PPH vs no or later plasma transfusion. Main Outcomes and Measures: Incidence of adverse maternal outcomes, defined as a composite of death, hysterectomy, or arterial embolization. Results: This study included 1216 women (mean [SD] age, 31.6 [5.0] years) with persistent PPH, of whom 932 (76.6%) delivered vaginally and 780 (64.1%) had PPH caused by uterine atony. Seven women (0.6%) died because of PPH, 62 women (5.1%) had a hysterectomy, and 159 women (13.1%) had arterial embolizations. Among women who received plasma during the first 60 minutes of persistent PPH, 114 women could be matched with a comparable woman who had not received plasma at the moment of matching. The incidence of adverse maternal outcomes was similar between the women, with adverse outcomes recorded in 24 women (21.2%) who received early plasma transfusion and 23 women (19.9%) who did not receive early plasma transfusion (odds ratio, 1.09; 95% CI, 0.57-2.09). Results of sensitivity analyses were comparable to the primary results. Conclusions and Relevance: In this cohort study, initiation of plasma transfusion during the first 60 minutes of persistent PPH was not associated with adverse maternal outcomes compared with no or later plasma transfusion, independent of severity of PPH.

Clinical characteristics of women captured by extending the definition of severe postpartum haemorrhage with 'refractoriness to treatment': a cohort study.

BACKGROUND: The absence of a uniform and clinically relevant definition of severe postpartum haemorrhage hampers comparative studies and optimization of clinical management. The concept of persistent postpartum haemorrhage, based on refractoriness to initial first-line treatment, was proposed as an alternative to common definitions that are either based on estimations of blood loss or transfused units of packed red blood cells (RBC). We compared characteristics and outcomes of women with severe postpartum haemorrhage captured by these three types of definitions. METHODS: In this large retrospective cohort study in 61 hospitals in the Netherlands we included 1391 consecutive women with postpartum haemorrhage who received either ≥4 units of RBC or a multicomponent transfusion. Clinical characteristics and outcomes of women with severe postpartum haemorrhage defined as persistent postpartum haemorrhage were compared to definitions based on estimated blood loss or transfused units of RBC within 24 h following birth. Adverse maternal outcome was a composite of maternal mortality, hysterectomy, arterial embolisation and intensive care unit admission. RESULTS: One thousand two hundred sixty out of 1391 women (90.6%) with postpartum haemorrhage fulfilled the definition of persistent postpartum haemorrhage. The majority, 820/1260 (65.1%), fulfilled this definition within 1 h following birth, compared to 819/1391 (58.7%) applying the definition of ≥1 L blood loss and 37/845 (4.4%) applying the definition of ≥4 units of RBC. The definition persistent postpartum haemorrhage captured 430/471 adverse maternal outcomes (91.3%), compared to 471/471 (100%) for ≥1 L blood loss and 383/471 (81.3%) for ≥4 units of RBC. Persistent postpartum haemorrhage did not capture all adverse outcomes because of missing data on timing of initial, first-line treatment. CONCLUSION: The definition persistent postpartum haemorrhage identified women with severe postpartum haemorrhage at an early stage of haemorrhage, unlike definitions based on blood transfusion. It also captured a large majority of adverse maternal outcomes, almost as large as the definition of ≥1 L blood loss, which is commonly applied as a definition of postpartum haemorrhage rather than severe haemorrhage.

SUGAR-DIP trial: oral medication strategy versus insulin for diabetes in pregnancy, study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial.

INTRODUCTION: In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. METHODS: The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NTR6134; Pre-results.

Maternal cardiac arrest in the Netherlands: A nationwide surveillance study.

BACKGROUND: Maternal cardiac arrest is a complex and demanding clinical situation requiring a well-attuned team effort of healthcare workers of multiple disciplines. A recent report on maternal cardiac arrest in the United Kingdom reported a rise in incidence over a span of 10 years, while maternal mortality increased in the United States between 2000 and 2014. However, reported causes of maternal cardiac arrest differed between both countries. OBJECTIVE(S): To determine the incidence, causes and management of maternal cardiac arrest in the Netherlands and compare incidence with previous estimates in the Netherlands and the United Kingdom. STUDY DESIGN: Using the Netherlands Obstetric Surveillance System, all Dutch cases of maternal cardiac arrest during a three-year period (2013-2016) were prospectively collected. Complete casefile copies were obtained for analysis. Main outcome measures were incidence of maternal cardiac arrest and cardiac arrest in pregnancy, use of perimortem caesarean section if appropriate and maternal death. RESULTS: The monthly card return rate was 97%; 18 women with cardiac arrest during pregnancy and 20 postpartum met the inclusion criteria. Incidence of maternal cardiac arrest was 7.6 per 100,000 pregnancies and 3.6 per 100,000 pregnancies excluding postpartum maternal cardiac arrest. Main causes were pulmonary embolism (n = 9), major obstetric hemorrhage (n = 7) and amniotic fluid embolism (n = 6). Aortocaval compression relief and perimortem caesarean section were performed in 9/14 (29%) and 11/14 (79%) respectively in pregnancies 20 weeks gestational age onwards. Twenty-two women died, representing a case fatality rate of 58% (95% CI 42-72%). CONCLUSION(S): There is a higher incidence of cardiac arrest in pregnancy compared to both previous estimates in the Netherlands and recently established figures in the United Kingdom. Main causes of maternal cardiac arrest are potentially preventable and/or treatable complications of pregnancy. Insufficient use of critical elements of obstetric resuscitation identifies the need for enhanced obstetric emergency training for obstetric and non-obstetric first responders.

External validation of prognostic models for preeclampsia in a Dutch multicenter prospective cohort.

OBJECTIVE: To perform an external validation of all published prognostic models for first-trimester prediction of the risk of developing preeclampsia (PE). METHODS: Women <14 weeks of pregnancy were recruited in the Netherlands. All systematically identified prognostic models for PE that contained predictors commonly available were eligible for external validation. RESULTS: 3,736 women were included; 87 (2.3%) developed PE. Calibration was poor due to overestimation. Discrimination of 9 models for LO-PE ranged from 0.58 to 0.71 and of 9 models for all PE from 0.55 to 0.75. CONCLUSION: Only a few easily applicable prognostic models for all PE showed discrimination above 0.70, which is considered an acceptable performance.

Fluid resuscitation during persistent postpartum haemorrhage and maternal outcome: A nationwide cohort study.

OBJECTIVE: To determine the association between increasing volumes of crystalloids and colloids administered before transfusion of packed red blood cells in women with persistent postpartum haemorrhage and adverse maternal outcomes. STUDY DESIGN: Retrospective cohort study in the Netherlands. Women with persistent postpartum haemorrhage and known clear fluids volume for resuscitation were included. Women who received ≤2 L of clear fluids were the reference group. We determined the effect of every additional litre of clear fluids on total blood loss, severe maternal morbidity and mortality. Results were adjusted for patient and bleeding characteristics. RESULTS: Of the 883 included women, 199 received ≤2 L of clear fluids. Median blood loss for the reference group was 2.9 L (interquartile range 2.2-3.4). Adjusted mean difference in blood loss compared with the reference group was 0.2 L (95% confidence interval -0.1 to 0.5) for women in the >2 to ≤3 L, 0.4 L (0.1-0.7) for the >3 to ≤4 L category, 0.6 L (0.5-0.7) for the >4 to ≤5 L category, and 1.9 L (1.5-2.3) for the >5 to ≤7 L category. Adjusted odds ratios for adverse maternal outcomes were 1.0 (0.7-1.6), 1.2 (0.8-1.9), 1.8 (1.1-3.1) and 4.4 (2.6-7.5) for women in the 2 to ≤3 L category, >3 to ≤4 L, >4 to ≤5 L, and >5 to ≤7 L volume categories respectively. Results were similar in strata of different severities of bleeding. CONCLUSION: Clear fluids volume >4 L was independently associated with adverse maternal outcome in women with persistent postpartum haemorrhage.

Women receiving massive transfusion due to postpartum hemorrhage: A comparison over time between two nationwide cohort studies.

INTRODUCTION: Incidence of massive transfusion after birth was high in the Netherlands between 2004 and 2006 compared with other high-income countries. This study investigated incidence, causes, management and outcome of women receiving massive transfusion due to postpartum hemorrhage in the Netherlands in more recent years. MATERIAL AND METHODS: Data for all pregnant women who received eight or more units of packed red blood cells from a gestational age of 20 weeks and within the first 24 hours after childbirth, during 2011 and 2012, were obtained from a nationwide retrospective cohort study, including 61 hospitals with a maternity unit in the Netherlands. RESULTS: Incidence of massive transfusion due to postpartum hemorrhage decreased to 65 per 100 000 births (95% CI 56-75) between 2011 and 2012, from 91 per 100 000 births (95% CI 81-101) between 2004 and 2006, while median blood loss increased from 4500 mL (interquartile range 3250-6000) to 6000 mL (interquartile range 4500-8000). Uterine atony remained the leading cause of hemorrhage. Thirty percent (53/176) underwent peripartum hysterectomy between 2011 and 2012, compared with 25% (83/327) between 2004 and 2006. Case fatality rate for women who received massive transfusion due to postpartum hemorrhage was 2.3% (4/176) between 2011 and 2012, compared with 0.9% (3/327) between 2004 and 2006. CONCLUSIONS: The incidence of postpartum hemorrhage with massive transfusion decreased in the Netherlands between both time frames, but remained an important cause of maternal mortality and morbidity, including peripartum hysterectomy. National surveillance of maternal morbidity and mortality due to postpartum hemorrhage through an improved and continuous registration with confidential enquiries may lead to the identification of clear improvements of maternal care.

A national surveillance approach to monitor incidence of eclampsia: The Netherlands Obstetric Surveillance System.

INTRODUCTION: There have been many efforts in the last decade to decrease the incidence of eclampsia and its related complications in the Netherlands, such as lowering thresholds for treatment of hypertension and mandatory professional training. To determine the impact of these policy changes on incidence and outcomes, we performed a nationwide registration of eclampsia, 10 years after the previous registration. MATERIAL AND METHODS: Cases of eclampsia were prospectively collected using the Netherlands Obstetric Surveillance System (NethOSS; 2013-2016) in all hospitals with a maternity unit in the Netherlands. Complete case file copies were obtained for comparative analysis of individual level data with the previous cohort (2004-2006). Primary outcome measure was incidence of eclampsia; main secondary outcomes were antihypertensive and magnesium sulfate use, and maternal and perinatal mortality. RESULTS: NethOSS identified 88 women with eclampsia. The incidence decreased from 6.2/10 000 in 2004-2006 to 1.8/10 000 births (relative risk [RR] 0.28, 95% confidence interval [CI] 0.22-0.36). Increases in the use of antihypertensive medication (61/82 vs 35/216; RR 18.4, 95% CI 9.74-34.70) and magnesium sulfate treatment (82/82 vs 201/216; RR 1.08, 95% CI 1.04-1.12) were observed. There was one intrauterine death following termination of pregnancy. No cases of neonatal mortality were reported in NethOSS compared with 11 in the LEMMoN. Maternal death occurred in one woman compared vs three in the previous registration. CONCLUSIONS: There has been a strong reduction of eclampsia and associated perinatal mortality in the Netherlands over the last decade. Management changes and increased awareness may have contributed to this reduction.

Coagulation parameters during the course of severe postpartum hemorrhage: a nationwide retrospective cohort study.

We describe the pattern of change in coagulation parameters during the course of severe postpartum hemorrhage in a retrospective cohort study among 1312 women experiencing severe postpartum hemorrhage necessitating blood transfusion. Levels of hemoglobin, hematocrit, platelet count, fibrinogen, activated partial thromboplastin time (aPTT) and prothrombin time (PT) per categorized volume of blood loss during severe postpartum hemorrhage were described and compared between women with and without the composite adverse outcome. Need for surgical intervention, severe acute maternal morbidity, and maternal mortality were jointly considered the composite adverse outcome. Of the 1312 women, 463 (35%) developed the composite adverse outcome. The incidence of a fibrinogen level <2 g/L was 26% (342 per 1312). Low fibrinogen and prolonged aPTT during the first 2 L of hemorrhage were associated with a subsequent composite adverse outcome; median fibrinogen and aPTT among women with and without the composite end point after 1.5 to 2 L of hemorrhage were 1.5 g/L (interquartile range [IQR], 1.0-1.9) vs 2.7 g/L (IQR, 1.9-3.4) and 39 s (IQR, 30-47) vs 32 s (IQR, 28-36), respectively. PT and platelet count as assessed during the first 2 L of hemorrhage were not associated with morbidity or mortality. Our results suggest that detection of low levels of fibrinogen and elevated aPTT levels during early postpartum hemorrhage can contribute to the identification of women that may benefit from targeted hemostatic treatment. Essential in this identification process is the moment of reaching a level of fibrinogen of <2 g/L during the course of postpartum hemorrhage.

Pregnancy outcomes in women with gestational diabetes mellitus diagnosed according to the WHO-2013 and WHO-1999 diagnostic criteria: a multicentre retrospective cohort study.

BACKGROUND: The World Health Organization (WHO) adopted more stringent diagnostic criteria for GDM in 2013, to improve pregnancy outcomes. However, there is no global consensus on these new diagnostic criteria, because of limited evidence. The objective of the study was to evaluate maternal characteristics and pregnancy outcomes in two cohorts in the Netherlands applying different diagnostic criteria for GDM i.e. WHO-2013 and WHO-1999. METHODS: A multicenter retrospective study involving singleton GDM pregnancies in two regions, between 2011 and 2016. Women were diagnosed according to the WHO-2013 criteria in the Deventer region (WHO-2013-cohort) and according to the WHO-1999 criteria in the Groningen region (WHO-1999-cohort). After GDM diagnosis, all women were treated equally based on the national guideline. Maternal characteristics and pregnancy outcomes were compared between the two groups. RESULTS: In total 1386 women with GDM were included in the study. Women in the WHO-2013-cohort were older and had a higher pre-gestational body mass index. They were diagnosed earlier (24.9 [IQR 23.3-29.0] versus 27.7 [IQR 25.9-30.7] weeks, p = < 0.001) and less women were treated with additional insulin therapy (15.6% versus 43.4%, p = < 0.001). Rate of spontaneous delivery was higher in the WHO-2013-cohort (73.1% versus 67.4%, p = 0.032). The percentage large-for-gestational-age (LGA) neonates (birth weight > 90th percentile, corrected for sex, ethnicity, parity, and gestational age) was lower in the WHO-2013- cohort, but not statistical significant (16.5% versus 18.5%, p = 0.379). There were no differences between the cohorts regarding stillbirth, birth trauma, low Apgar score, and preeclampsia. CONCLUSIONS: Using the new WHO-2013 criteria resulted in an earlier GDM diagnosis, less women needed insulin treatment and more spontaneous deliveries occurred when compared to the cohort diagnosed with WHO-1999 criteria. No differences were found in adverse pregnancy outcomes.

Laparotomy in women with severe acute maternal morbidity: secondary analysis of a nationwide cohort study.

BACKGROUND: Although pregnancy-related laparotomy is a major intervention, literature is limited to small case-control or single center studies. We aimed to identify national incidence rates for postpartum laparotomy related to severe acute maternal morbidity (SAMM) in a high-income country and test the hypothesis that risk of postpartum laparotomy differs by mode of birth. METHODS: In a population-based cohort study in all 98 hospitals with a maternity unit in the Netherlands, pregnant women with SAMM according to specified disease and management criteria were included from 01/08/2004 to 01/08/2006. We calculated the incidence of postpartum laparotomy after vaginal and cesarean births. Laparotomies were analyzed in relation to mode of birth using all births in the country as reference. Relative risks (RR) were calculated for laparotomy following emergency and planned cesarean section compared to vaginal birth, excluding laparotomies following births before 24 weeks' gestation and hysterectomies performed during cesarean section. RESULTS: The incidence of postpartum laparotomy in women with SAMM in the Netherlands was 6.0 per 10,000 births. Incidence was 30.1 and 1.8 per 10,000 following cesarean and vaginal birth respectively. Compared to vaginal birth, RR of laparotomy after cesarean birth was 16.7 (95% confidence interval [95% CI] 12.2-22.6). RR was 21.8 (95% CI 15.8-30.2) for emergency and 10.5 (95% CI 7.1-15.6) for planned cesarean section. CONCLUSIONS: Risk of laparotomy, although small, was considerably elevated in women who gave birth by cesarean section. This should be considered in counseling and clinical decision making.

The effect of tranexamic acid on blood loss and maternal outcome in the treatment of persistent postpartum hemorrhage: A nationwide retrospective cohort study.

BACKGROUND: Recent results show a protective effect of tranexamic acid on death due to bleeding in patients with postpartum hemorrhage in low- and middle-resource countries. We quantify the association between early administration of tranexamic acid compared to late or no administration and severe acute maternal morbidity and blood loss among women suffering from persistent severe postpartum hemorrhage in a high-income country. METHODS AND FINDINGS: We performed a nationwide retrospective cohort study in 61 hospitals in the Netherlands. The study population consisted of 1260 women with persistent postpartum hemorrhage who had received at least four units of red cells, or fresh frozen plasma or platelets in addition to red cells. A review of medical records was performed and cross-referenced with blood bank data. The composite endpoint comprised maternal morbidity (hysterectomy, ligation of the uterine arteries, emergency B-Lynch suture, arterial embolization or admission into an intensive care unit) and mortality. RESULTS: 247 women received early tranexamic acid treatment. After adjustment for confounding, odds ratio for the composite endpoint for early tranexamic acid (n = 247) versus no/late tranexamic acid (n = 984) was 0.92 (95% confidence interval (CI) 0.66 to 1.27). Propensity matched analysis confirmed the absence of a difference between women with and without tranexamic acid. Blood loss after administration of first line therapy did not differ significantly between the two groups (adjusted difference -177 mL, CI -509.4 to +155.0). CONCLUSIONS: Our findings suggest that in a high-resource country the effect of tranexamic acid on both blood loss and the combined endpoint of maternal mortality and morbidity may be disappointing.

Incidence, management and outcome of women requiring massive transfusion after childbirth in the Netherlands: secondary analysis of a nationwide cohort study between 2004 and 2006.

BACKGROUND: Postpartum hemorrhage remains the leading cause of maternal morbidity and mortality worldwide. Few population-based studies have examined the epidemiology of massive transfusion for postpartum hemorrhage. The aim of this study was to determine the incidence, management, and outcomes of women with postpartum hemorrhage who required massive transfusion in the Netherlands between 2004 and 2006. METHODS: Data for all women from a gestational age of 20 weeks onwards who had postpartum hemorrhage requiring eight or more red blood cell concentrates were obtained from a nationwide population-based cohort study including all 98 hospitals with a maternity unit in the Netherlands. RESULTS: Three hundred twenty-seven women who had postpartum hemorrhage requiring massive transfusion were identified (massive transfusion rate 91 per 100,000 deliveries (95% confidence interval: 81-101)). The median blood loss was 4500 mL (interquartile range 3250-6000 mL) and the median number of red blood cell concentrates transfused was 11 units (interquartile range 9-16 units). Among women receiving massive transfusion, the most common cause of hemorrhage was uterine atony. Eighty-three women (25%) underwent hysterectomy, 227 (69%) were admitted to an intensive care unit, and three women died (case fatality rate 0,9%). CONCLUSION: The number of women in the Netherlands who had postpartum hemorrhage treated with massive transfusion was relatively high compared to other comparable settings. Evidence-based uniform management guidelines are necessary.

External validation of prognostic models to predict risk of gestational diabetes mellitus in one Dutch cohort: prospective multicentre cohort study.

OBJECTIVE:  To perform an external validation and direct comparison of published prognostic models for early prediction of the risk of gestational diabetes mellitus, including predictors applicable in the first trimester of pregnancy. DESIGN:  External validation of all published prognostic models in large scale, prospective, multicentre cohort study. SETTING:  31 independent midwifery practices and six hospitals in the Netherlands. PARTICIPANTS:  Women recruited in their first trimester (<14 weeks) of pregnancy between December 2012 and January 2014, at their initial prenatal visit. Women with pre-existing diabetes mellitus of any type were excluded. MAIN OUTCOME MEASURES:  Discrimination of the prognostic models was assessed by the C statistic, and calibration assessed by calibration plots. RESULTS:  3723 women were included for analysis, of whom 181 (4.9%) developed gestational diabetes mellitus in pregnancy. 12 prognostic models for the disorder could be validated in the cohort. C statistics ranged from 0.67 to 0.78. Calibration plots showed that eight of the 12 models were well calibrated. The four models with the highest C statistics included almost all of the following predictors: maternal age, maternal body mass index, history of gestational diabetes mellitus, ethnicity, and family history of diabetes. Prognostic models had a similar performance in a subgroup of nulliparous women only. Decision curve analysis showed that the use of these four models always had a positive net benefit. CONCLUSIONS:  In this external validation study, most of the published prognostic models for gestational diabetes mellitus show acceptable discrimination and calibration. The four models with the highest discriminative abilities in this study cohort, which also perform well in a subgroup of nulliparous women, are easy models to apply in clinical practice and therefore deserve further evaluation regarding their clinical impact.

Severe acute maternal morbidity in multiple pregnancies: a nationwide cohort study.

BACKGROUND: Adverse neonatal outcomes in multiple pregnancies have been documented extensively, in particular those associated with the increased risk of preterm birth. Paradoxically, much less is known about adverse maternal events. The combined risk of severe acute maternal morbidity in multiple pregnancies has not been documented previously in any nationwide prospective study. OBJECTIVE: The objective of the study was to assess the risk of severe acute maternal morbidity in multiple pregnancies in a high-income European country and identify possible risk indicators. STUDY DESIGN: In a population-based cohort study including all 98 hospitals with a maternity unit in The Netherlands, pregnant women with severe acute maternal morbidity were included in the period Aug. 1, 2004, until Aug. 1, 2006. We calculated the incidence of severe acute maternal morbidity in multiple pregnancies in The Netherlands using The Netherlands Perinatal Registry. Relative risks (RR) of severe acute maternal morbidity in multiple pregnancies compared with singletons were calculated. To identify possible risk indicators, we also compared age, parity, method of conception, onset of labor, and mode of delivery for multiple pregnancies using The Netherlands Perinatal Registry as reference. RESULTS: A total of 2552 cases of severe acute maternal morbidity were reported during the 2 year study period. Among 202 multiple pregnancies (8.0%), there were 197 twins (7.8%) and 5 triplets (0.2%). The overall incidence of severe acute maternal morbidity was 7.0 per 1000 deliveries and 6.5 and 28.0 per 1000 for singletons and multiple pregnancies, respectively. The relative risk of severe acute maternal morbidity compared with singleton pregnancies was 4.3 (95% confidence interval [CI], 3.7-5.0) and increased to 6.2 (95% CI 2.5-15.3) in triplet pregnancies. Risk indicators for developing severe acute maternal morbidity in women with multiple pregnancies were age of ≥ 40 years, (RR, 2.5 95% CI, 1.4-4.3), nulliparity (RR, 1.8, 95% CI, 1.4-2.4), use of assisted reproductive techniques (RR, 1.9, 95% CI, 1.4-2.5), and nonspontaneous onset of delivery (RR, 1.6, 95% CI, 1.2-2.1). No significant difference was found between mono- and dichorionic twins (RR, 0.8, 95% CI, 0.6-1.2). CONCLUSION: Women with multiple pregnancies in The Netherlands have a more than 4 times elevated risk of sustaining severe acute maternal morbidity as compared with singletons.