Predicting the risks and recognizing the signs: a two-year prospective population-based study on pregnant women with uterine rupture in The Netherlands.

OBJECTIVE: To estimate the incidence of uterine rupture in the Netherlands and evaluate risk indicators prelabour and during labor of women with adverse maternal and/or perinatal outcome. METHODS: This is a population-based nationwide study using the Netherlands Obstetrics Surveillance System (NethOSS). We performed a two-year registration of pregnant women with uterine rupture. The first year of registration included both women with complete uterine rupture and women with incomplete (peritoneum intact) uterine rupture. The second year of registration included women with uterine rupture with adverse maternal and/or perinatal outcome. We collected maternal and obstetric characteristics, clinical signs, and symptoms during labor and CTG abnormalities. The main outcome measures were incidence of complete uterine rupture and uterine rupture with adverse outcome and adverse outcome defined as major obstetric hemorrhage, hysterectomy, embolization, perinatal asphyxia and/or (neonatal) intensive care unit admission. RESULTS: We registered 41 women with a complete uterine rupture (incidence: 2.5 per 10,000 births) and 35 women with uterine rupture with adverse outcome (incidence: 0.9 per 10,000 births). No adverse outcomes were found among women with incomplete uterine rupture. Risk indicators for adverse outcome included previous cesarean section, higher maternal age, gestational age <37 weeks, augmentation of labor, migration background from Sub-Saharan Africa or Asia. Compared to women with uterine rupture without adverse outcomes, women with adverse outcome more often expressed warning symptoms during labor such as abdominal pain (OR 3.34, 95%CI 1.26-8.90) and CTG abnormalities (OR 9.94, 95%CI 2.17-45.65). These symptoms were present most often 20 to 60 min prior to birth. CONCLUSION: Uterine rupture is a rare condition for which several risk indicators were identified. Maternal symptoms and CTG abnormalities are associated with adverse outcomes and time dependent. Further analysis could provide guidance to expedite delivery.

[A pregnant woman with gastric cancer and placental involvement]. / Een zwangere vrouw met maagkanker en placentaire metastasen.

BACKGROUND: About 200 pregnant women in the Netherlands are yearly diagnosed with cancer. Pregnant women with cancer are often diagnosed later than non-pregnant women because symptoms of cancer are common during pregnancy and may elude suspicion. We report a patient with gastric carcinoma masquerading as hyperemesis gravidarum. CASE DESCRIPTION: A 39-year-old pregnant woman was admitted at 25 weeks' gestation for the evaluation of persistent nausea, vomiting and weight loss (29 kg) since the beginning of her pregnancy. A presumptive diagnosis of hyperemesis gravidarum was made. Endoscopic examination was not performed. At 28 weeks' gestation caesarean was performed due to fetal distress and revealed a gastric tumour with abnormalities of the omentum. Microscopic examination of the omentum and placental specimen demonstrated poorly differentiated adenocarcinoma cells. CONCLUSION: This case illustrates that endoscopic examination should be conducted in pregnant patients presenting with persistent gastrointestinal symptoms for the differential diagnosis of hyperemesis gravidarum.

SARS-CoV-2 infection in pregnancy during the first wave of COVID-19 in the Netherlands: a prospective nationwide population-based cohort study (NethOSS).

OBJECTIVE: To describe characteristics, risk factors and maternal, obstetric and neonatal outcomes of pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). DESIGN: Multi-centre prospective population-based cohort study. SETTING: Nationwide study in the Netherlands. POPULATION: Pregnant women with confirmed SARS-CoV-2 infection admitted to hospital or in home-isolation: 1 March 2020 to 31 August 2020. METHODS: Pregnant women with positive polymerase chain reaction or antibody tests were registered using the Netherlands Obstetrics Surveillance System (NethOSS). (Selective) testing occurred according to national guidelines. Data from the national birth registry (pregnant pre-coronavirus disease 2019 [COVID-19] cohort) and an age-matched cohort of COVID-19-positive women (National Institute for Public Health and the Environment; fertile age COVID-19 cohort) were used as reference. MAIN OUTCOME MEASURES: Incidence of SARS-CoV-2 infection in pregnant women. Maternal, obstetric and neonatal outcomes including hospital and intensive care admission. RESULTS: Of 376 registered pregnant women with confirmed SARS-CoV-2 infection, 20% (74/376) were admitted to hospital, of whom 84% (62/74) were due to SARS-CoV-2; 10% (6/62) were admitted to intensive care and 15% (9/62) to obstetric high-care units. Risk factors for admission were non-European country of origin (odds ratio [OR] 1.73, 95% CI 1.01-2.96) and being overweight/obese (OR 1.86, 95% CI 1.51-3.20). No maternal or perinatal deaths occurred. Caesarean section after labour-onset was increased (OR 1.58, 95% CI 1.09-2.28). Hospital and intensive care admission were higher compared with the fertile age COVID-19 cohort (OR 6.75, 95% CI 5.18-8.81 and OR 2.52, 95% CI 1.11-5.77, respectively). CONCLUSIONS: Non-European country of origin and being overweight/obese are risk factors for severe course of SARS-CoV-2 infection in pregnancy, risk of caesarean section and hospital and intensive care unit admission are increased. TWEETABLE ABSTRACT: Pregnant women with SARS-CoV-2 in the Netherlands show increased hospital/ICU admission and caesarean section.

Trends in direct oral anticoagulant (DOAC) use: health benefits and patient preference.

In 2012, the Dutch Health Council published a report addressing barriers for an early and broad introduction of direct oral anticoagulants (DOACs). The report raised concerns about the lack of an antidote, adherence, lack of monitoring in the case of overdose and the increased budget impact at DOAC introduction. In the past decade, international studies have shown that DOACs can provide healthcare benefits for a large number of patients. This has led to an increase in the prescription of DOACs, as they are an effective and user-friendly alternative to vitamin K antagonists (VKAs). Unlike VKAs, DOACs do not need monitoring of the international normalized ratio due to more predictable pharmacokinetics. However, the number of prescriptions of DOACs in the Netherlands is still lagging, compared to other European countries. This article highlights the potential health gains in the Netherlands if the use of DOACs were to increase, based on current international experience.

Effect of planned place of birth on obstetric interventions and maternal outcomes among low-risk women: a cohort study in the Netherlands.

BACKGROUND: The use of interventions in childbirth has increased the past decades. There is concern that some women might receive more interventions than they really need. For low-risk women, midwife-led birth settings may be of importance as a counterbalance towards the increasing rate of interventions. The effect of planned place of birth on interventions in the Netherlands is not yet clear. This study aims to give insight into differences in obstetric interventions and maternal outcomes for planned home versus planned hospital birth among women in midwife-led care. METHODS: Women from twenty practices across the Netherlands were included in 2009 and 2010. Of these, 3495 were low-risk and in midwife-led care at the onset of labour. Information about planned place of birth and outcomes, including instrumental birth (caesarean section, vacuum or forceps birth), labour augmentation, episiotomy, oxytocin in third stage, postpartum haemorrhage >1000 ml and perineal damage, came from the national midwife-led care perinatal database, and a postpartum questionnaire. RESULTS: Women who planned home birth more often had spontaneous birth (nulliparous women aOR 1.38, 95 % CI 1.08-1.76, parous women aOR 2.29, 95 % CI 1.21-4.36) and less often episiotomy (nulliparous women aOR 0.73, 0.58-0.91, parous women aOR 0.47, 0.33-0.68) and use of oxytocin in the third stage (nulliparous women aOR 0.58, 0.42-0.80, parous women aOR 0.47, 0.37-0.60) compared to women who planned hospital birth. Nulliparous women more often had anal sphincter damage (aOR 1.75, 1.01-3.03), but the difference was not statistically significant if women who had caesarean sections were excluded. Parous women less often had labour augmentation (aOR 0.55, 0.36-0.82) and more often an intact perineum (aOR 1.65, 1.34-2.03). There were no differences in rates of vacuum/forceps birth, unplanned caesarean section and postpartum haemorrhage >1000 ml. CONCLUSIONS: Women who planned home birth were more likely to give birth spontaneously and had fewer medical interventions.

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.

Eclampsia, a comparison within the International Network of Obstetric Survey Systems.

OBJECTIVE: To compare incidences, characteristics, management and outcome of eclampsia in the Netherlands and the UK. DESIGN: A comparative analysis of two population-based prospective cohort studies. SETTING: All hospitals with consultant-led maternity units. POPULATION: Women with eclampsia in the Netherlands (226) and the UK (264). METHODS: Comparison of individual level data from national studies in the Netherlands and the UK (LEMMoN 2004-06; UKOSS 2005/06). MAIN OUTCOME MEASURES: Incidence, maternal complications and differences in management strategies. RESULTS: Incidences of eclampsia differed significantly between both countries: the Netherlands 5.4/10,000 deliveries versus UK 2.7/10,000 (relative risk [RR] 1.94, 95% confidence intervals [95% CI] 1.6-2.4). The proportion of women with a preceding diagnosis of pre-eclampsia was comparable between both countries (the Netherlands 42%; UK 43%), as was the proportion who received magnesium sulphate prophylaxis. Women in the Netherlands had a significantly higher maximum diastolic blood pressure (111 mmHg versus 95 mmHg, P < 0.001); significantly fewer received anti-hypertensive medication (16% versus 71%; RR 0.2, 95% CI 0.1-0.3) and were treated less often with magnesium sulphate after their first fit (95% versus 99%; RR 0.96, 95% CI 0.92-0.99). Maternal death occurred in three cases in the Netherlands compared with zero in the UK. CONCLUSIONS: The incidence of eclampsia in the Netherlands was twice as high compared with the UK when using uniform definitions. Women with eclampsia in the Netherlands were not managed according to guidelines, particularly with respect to blood pressure management. Changes in management practice may reduce both incidence and poor outcomes.

The clinical benefit of blood transfusion: a hypothetical experiment based on a nationwide survey of severe maternal morbidity.

BACKGROUND: It is beyond doubt that blood transfusion services have added to the decline in maternal mortality in high-resource countries. To quantify the clinical benefit of red blood cell (RBC) transfusion in obstetric care, we performed a hypothetical experimental study using data from a prospective nationwide cohort of women giving birth in the Netherlands. STUDY DESIGN AND METHODS: Data were abstracted from a nationwide cohort study on severe maternal morbidity, including obstetric haemorrhage requiring 4 or more units of RBC, to obtain an observed and a hypothetical control group consisting of the same women. In the hypothetical control group, we simulated a situation where RBC transfusion was unavailable and estimated how many of these women would have died in that situation. A questionnaire survey asked experts in major (obstetric) haemorrhage to choose a critical minimal number of RBC transfusions at which a woman with obstetric haemorrhage would have died if RBC transfusion was not available. Maternal mortality rate per 100,000 maternities [maternal mortality ratios (MMR)] and relative risk were calculated for the observed and hypothetical group. RESULTS: The observed MMR was 13 per 100,000 maternities. According to 47 responding experts, the median number of RBC units without which a woman would have most probably died was nine, resulting in a hypothetical MMR of 87 per 100,000 maternities (relative risk 6·5; 95% confidence interval 4·2-10·0). CONCLUSIONS: It can be expected that unavailability of RBC transfusion in obstetric care increases the risk of maternal death 6.5-fold. Blood transfusion thus largely contributes to the decline of MMR and would also be an important pillar of improving quality of care in resource-poor settings.

Fatal meningitis during pregnancy in the Netherlands: a nationwide confidential enquiry.

OBJECTIVE: To determine the incidence of maternal deaths attributable to meningitis in the Netherlands, and to assess clinical features and risk factors. DESIGN: Confidential enquiry into the causes of maternal deaths. SETTING: Nationwide in the Netherlands. POPULATION: A total of 4 784 408 live births. METHODS: Analysis of all maternal deaths due to meningitis in pregnancy and puerperium from 1983 up to and including 2007 reported to the Maternal Mortality Committee of the Dutch Society of Obstetrics and Gynaecology. MAIN OUTCOME MEASURES: Incidence, clinical features and risk factors. RESULTS: Fifteen maternal deaths occurred due to meningitis, representing 4.4% of all maternal deaths. Twelve women (80%) presented with meningitis during pregnancy, 8 (66%) of them in the third trimester. Presenting symptoms were altered mental status (11; 73%), fever (9; 60%), nuchal rigidity (5; 33%) and headache (13; 87%). Nine women (60%) had otolaryngological infection at presentation or in the previous days or weeks. Twelve women (80%) underwent radiological examination, of which 5 (33%) showed distinct abnormalities. Cerebrospinal fluid (CSF) examination showed infected CSF in 8 (53%) women. In ten women (67%) Streptococcus pneumoniae was isolated. Substandard care was identified in 4 (27%) women. CONCLUSION: Pregnant or puerperal women presenting with classical symptoms of meningitis, particularly those with a history of otolaryngological infection or headache, should undergo thorough investigation and radiological and CSF examinations. Early diagnosis and immediate antibiotic treatment are imperative because of rapid deterioration in pregnant women. In case of doubt, the threshold for antibiotic treatment should be low and close monitoring is warranted.

Cardiac arrest in pregnancy: increasing use of perimortem caesarean section due to emergency skills training?

OBJECTIVE: Management of cardiac arrest in pregnancy is recommended to include perimortem caesarean section (PMCS) in the Managing Obstetric Emergencies and Trauma (MOET) course. In this study, we aimed to assess maternal and neonatal outcome of all cases of PMCS in the Netherlands performed in the last 15 years, and to test the hypothesis that PMCS was used more often since the introduction of the MOET-course in 2004. DESIGN: Retrospective cohort study. SETTING: Nationwide assessment of all cases of PMCS inside or outside hospitals. POPULATION: All known cases of PMCS in the Netherlands from 1993 to 2008. METHODS: Data collection through contacting all Dutch obstetricians and all MOET and Advanced Trauma Life Support instructors. All cases of cardiac arrest during pregnancy were collected by cross-checking with data from the Dutch Maternal Mortality Committee and a nationwide severe maternal morbidity study. MAIN OUTCOME MEASURES: Incidence and case fatality rate of PMCS. Incidence of PMCS before and after introduction of the MOET course. Maternal and neonatal outcome and the process of the PMCS were analysed. RESULTS: During the study period, 55 women had a cardiac arrest, 12 of whom underwent a PMCS. Before the introduction of the MOET course, four PMCSs were performed (0.36/year), compared with eight cases after its introduction (1.6/year, P = 0.01). No PMCS was performed within the recommended 5 minutes after starting resuscitation. Eight of the twelve women (67%) regained cardiac output after PMCS, with two maternal and five neonatal survivors. Maternal case fatality rate was 83%. Neonatal case fatality rate was 58%. CONCLUSIONS: Since the introduction of the MOET course, the use of PMCS has increased. Outcome, however, was still poor. An important factor to improve outcome is more timely application of this potentially life-saving procedure.

Introducing maternal morbidity audit in the Netherlands.

OBJECTIVE: To describe the panel audit process and to identify substandard care in selected women from a nationwide prospective cohort study into severe acute maternal morbidity (SAMM) in the Netherlands. DESIGN: Prospective audit of selected women with SAMM. SETTING: Eight audit meetings held throughout the Netherlands. POPULATION: All pregnant women in the Netherlands. METHODS: Before each meeting, SAMM details of selected women were sent to all panel members for individual assessment by completing an audit form. During a subsequent plenary meeting, findings were discussed and substandard care factors as judged by the majority of assessors were scored. MAIN OUTCOME MEASURES: Incidence of substandard care and recommendations for improving the quality of care. RESULTS: Substandard care was identified in 53 of 67 women (79%). Specific recommendations were formulated concerning the procedure of audit and concerning local as well as national management guidelines. CONCLUSION: Our findings reflect SAMM in the Netherlands and substandard care is present in four out of five women. Ongoing audit of women with SAMM is promoted both at local and national level.

Underreporting of major obstetric haemorrhage in the Netherlands.

Major obstetric haemorrhage (MOH) is the main cause of severe maternal morbidity, incidence being estimated at 4.5 per 1000 deliveries. Cases are not routinely registered in the Netherlands. The objective of this study is to quantify the degree of underreporting of MOH in a large nationwide survey of severe acute maternal morbidity in the Netherlands (LEMMoN) and to estimate the true incidence of MOH in the Netherlands. Retrospective cross-match of the LEMMoN-database with the databases of local blood transfusion laboratories in 65 of 98 hospitals in the Netherlands during a 20-month period, using the capture-recapture method was used. From 16 of 65 centres, the reported transfusion data could not be confirmed by a local obstetrician for logistical reasons. These centres were excluded leaving 49 hospitals available for final analysis. In both databases together, 1018 unique cases of MOH were identified. Underreporting to LEMMoN was 35%. Hence, the true incidence of MOH in the Netherlands is at least 6.1 instead of 4.5 per 1000 deliveries. The estimated underreporting of MOH of 35% is considerable. Underreporting is inherent to large observational multicentre studies and should be anticipated and quantified to facilitate fair comparison of epidemiologic data.

Uterine rupture in The Netherlands: a nationwide population-based cohort study.

OBJECTIVE: To assess incidence of uterine rupture in scarred and unscarred uteri and its maternal and fetal complications in a nationwide design. DESIGN: Population-based cohort study. SETTING: All 98 maternity units in The Netherlands. POPULATION: All women delivering in The Netherlands between August 2004 and August 2006 (n = 371,021). METHODS: Women with uterine rupture were prospectively collected using a web-based notification system. Data from all pregnant women in The Netherlands during the study period were obtained from Dutch population-based registers. Results were stratified by uterine scar. MAIN OUTCOME MEASURES: Population-based incidences, severe maternal and neonatal morbidity and mortality, relative and absolute risk estimates. RESULTS: There were 210 cases of uterine rupture (5.9 per 10,000 pregnancies). Of these women, 183 (87.1%) had a uterine scar, incidences being 5.1 and 0.8 per 10,000 in women with and without uterine scar. No maternal deaths and 18 cases of perinatal death (8.7%) occurred. The overall absolute risk of uterine rupture was 1 in 1709. In univariate analysis, women with a prior caesarean, epidural anaesthesia, induction of labour (irrespective of agents used), pre- or post-term pregnancy, overweight, non-Western ethnic background and advanced age had an elevated risk of uterine rupture. The overall relative risk of induction of labour was 3.6 (95% confidence interval 2.7-4.8). CONCLUSION: The population-based incidence of uterine rupture in The Netherlands is comparable with other Western countries. Although much attention is paid to scar rupture associated with uterotonic agents, 13% of ruptures occurred in unscarred uteri and 72% occurred during spontaneous labour.

Maternal mortality and serious maternal morbidity in Jehovah's witnesses in The Netherlands.

OBJECTIVE: To determine the risk of maternal mortality and serious maternal morbidity because of major obstetric haemorrhage in Jehovah's witnesses in The Netherlands. DESIGN: A retrospective study of case notes. SETTING: All tertiary care centres, general teaching hospitals and other general hospitals in The Netherlands. SAMPLE: All cases of maternal mortality in The Netherlands between 1983 and 2006 and all cases of serious maternal morbidity in The Netherlands between 2004 and 2006. METHODS: Study of case notes using two different nationwide enquiries over two different time periods. MAIN OUTCOME MEASURES: Maternal mortality ratio (MMR) and risk of serious maternal mortality. RESULTS: The MMR for Jehovah's witnesses was 68 per 100,000 live births. We found a risk of 14 per 1000 for Jehovah's witnesses to experience serious maternal morbidity because of obstetric haemorrhage while the risk for the total pregnant population was 4.5 per 1000. CONCLUSIONS: Women who are Jehovah's witnesses are at a six times increased risk for maternal death, at a 130 times increased risk for maternal death because of major obstetric haemorrhage and at a 3.1 times increased risk for serious maternal morbidity because of obstetric haemorrhage, compared to the general Dutch population.

Severe maternal morbidity during pregnancy, delivery and puerperium in the Netherlands: a nationwide population-based study of 371,000 pregnancies.

OBJECTIVE: To assess incidence, case fatality rate, risk factors and substandard care in severe maternal morbidity in the Netherlands. DESIGN: Prospective population-based cohort study. SETTING: All 98 maternity units in the Netherlands. POPULATION: All pregnant women in the Netherlands. METHODS: Cases of severe maternal morbidity were collected during a 2-year period. All pregnant women in the Netherlands in the same period acted as reference cohort (n = 371,021). As immigrant women are disproportionately represented in Dutch maternal mortality statistics, special attention was paid to the ethnic background. In a subset of 2.5% of women, substandard care was assessed through clinical audit. MAIN OUTCOME MEASURES: Incidence, case fatality rates, possible risk factors and substandard care. RESULTS: Severe maternal morbidity was reported in 2552 women, giving an overall incidence of 7.1 per 1000 deliveries. Intensive care unit admission was reported in 847 women (incidence 2.4 per 1000), uterine rupture in 218 women (incidence 6.1/10,000), eclampsia in 222 women (incidence 6.2/10,000) and major obstetric haemorrhage in 1606 women (incidence 4.5 per 1000). Non-Western immigrant women had a 1.3-fold increased risk of severe maternal morbidity (95% CI 1.2-1.5) when compared with Western women. Overall case fatality rate was 1 in 53. Substandard care was found in 39 of a subset of 63 women (62%) through clinical audit. CONCLUSIONS: Severe maternal morbidity complicates at least 0.71% of all pregnancies in the Netherlands, immigrant women experiencing an increased risk. Since substandard care was found in the majority of assessed cases, reduction of severe maternal morbidity seems a mandatory challenge.