Methods of induction of labor in women with obesity: A secondary analysis of two multicenter randomized controlled trials.

INTRODUCTION: Obesity is an increasing public health concern worldwide and can lead to more complications in pregnancy and childbirth. Women with obesity more often require induction of labor for various indications. The aim of this study is to assess which method of induction of labor is safest and most effective in women with obesity. MATERIAL AND METHODS: This is a secondary analysis of two randomized controlled trials about induction of labor. Women with a term singleton pregnancy in cephalic presentation, an unfavorable cervix, intact membranes and without a previous cesarean section were randomly allocated to cervical priming with a Foley catheter or vaginal prostaglandin-E2-gel (PROBAAT-I) or a Foley catheter or oral misoprostol (PROBAAT-II). The inclusion and exclusion criteria for the studies were identical. Induction methods were compared in women with obesity (body mass index ≥30.0). Main outcomes were cesarean section and postpartum hemorrhage (blood loss >1000 mL). RESULTS: A total of 2664 women, were included in the trials, 517 of whom were obese: 254 women with obesity received a Foley catheter, 176 oral misoprostol and 87 prostaglandin E2 (PGE2). A cesarean section was performed in 29.1% of women allocated to Foley vs 22.2% in the misoprostol and 23.0% in the PGE2 groups. Comparisons between groups revealed no statistically significant differences: the relative risk [RR] was 1.31 (95% confidence interval [CI] 0.94-1.84) in the Foley vs misoprostol group and 1.27 (95% CI 0.83-1.95) in the Foley vs PGE2 group. The rates of postpartum hemorrhage were comparable (10.6%, 11.4% and 6.9%, respectively; P = 0.512). In women with obesity, more often a switch to another method occurred in the Foley group, (20.1% vs 6.3% in misoprostol vs 1.1% in the PGE2 group; P < 0.001). The risk of a failed Foley placement was higher in women with obesity than in women without obesity (8.3% vs 3.2%; adjusted odds ratio 3.12, 95% CI 1.65-5.90). CONCLUSIONS: In women with obesity we found a nonsignificant trend towards an increased rate of cesarean sections in the group induced with a Foley catheter compared to oral misoprostol; however, the study lacked power for this subgroup analysis. The finding of a higher risk of failed placement of a Foley catheter in women with obesity can be used in shared decision making.

Hypertensive disorders of pregnancy and cardiovascular disease risk: a Mendelian randomisation study.

OBJECTIVE: Observational studies show that hypertensive disorders of pregnancy (HDPs) are related to unfavourable maternal cardiovascular disease (CVD) risk profiles later in life. We investigated whether genetic liability to pre-eclampsia/eclampsia and gestational hypertension is associated with CVD risk factors and occurrence of CVD events. METHODS: We obtained genetic associations with HDPs from a genome-wide association study and used individual participant data from the UK Biobank to obtain genetic associations with CVD risk factors and CVD events (defined as myocardial infarction or stroke). In our primary analysis, we applied Mendelian randomisation using inverse-variance weighted regression analysis in ever pregnant women. In sensitivity analyses, we studied men and nulligravidae to investigate genetic liability to HDPs and CVD risk without the ability to experience the underlying phenotype. RESULTS: Our primary analysis included 221 155 ever pregnant women (mean age 56.8 (SD 7.9) years) with available genetic data. ORs for CVD were 1.20 (1.02 to 1.41) and 1.24 (1.12 to 1.38) per unit increase in the log odds of genetic liability to pre-eclampsia/eclampsia and gestational hypertension, respectively. Furthermore, genetic liability to HDPs was associated with higher levels of systolic and diastolic blood pressure and younger age at hypertension diagnosis. Sensitivity analyses revealed no statistically significant differences when comparing the findings with those of nulligravidae and men. CONCLUSIONS: Genetic liability to HDPs is associated with higher CVD risk, lower blood pressure levels and earlier hypertension diagnosis. Our study suggests similar findings in ever pregnant women, nulligravidae and men, implying biological mechanisms relating to HDPs are causally related to CVD risk.

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).

Variations across Europe in hospitalization and management of pregnant women with SARS-CoV-2 during the initial phase of the pandemic: Multi-national population-based cohort study using the International Network of Obstetric Survey Systems (INOSS).

INTRODUCTION: The majority of data on COVID-19 in pregnancy are not from sound population-based active surveillance systems. MATERIAL AND METHODS: We conducted a multi-national study of population-based national or regional prospective cohorts using standardized definitions within the International Network of Obstetric Survey systems (INOSS). From a source population of women giving birth between March 1 and August 31, 2020, we included pregnant women admitted to hospital with a positive SARS-CoV-2 PCR test ≤7 days prior to or during admission and up to 2 days after birth. The admissions were further categorized as COVID-19-related or non-COVID-19-related. The primary outcome of interest was incidence of COVID-19-related hospital admission. Secondary outcomes included severe maternal disease (ICU admission and mechanical ventilation) and COVID-19-directed medical treatment. RESULTS: In a source population of 816 628 maternities, a total of 2338 pregnant women were admitted with SARS-CoV-2; among them 940 (40%) were COVID-19-related admissions. The pooled incidence estimate for COVID-19-related admission was 0.59 (95% confidence interval 0.27-1.02) per 1000 maternities, with notable heterogeneity across countries (I2 = 97.3%, P = 0.00). In the COVID-19 admission group, between 8% and 17% of the women were admitted to intensive care, and 5%-13% needed mechanical ventilation. Thromboprophylaxis was the most frequent treatment given during COVID-19-related admission (range 14%-55%). Among 908 infants born to women in the COVID-19-related admission group, 5 (0.6%) stillbirths were reported. CONCLUSIONS: During the initial months of the pandemic, we found substantial variations in incidence of COVID-19-related admissions in nine European countries. Few pregnant women received COVID-19-directed medical treatment. Several barriers to rapid surveillance were identified. Investment in robust surveillance should be prioritized to prepare for future pandemics.

Spontaneous haemoperitoneum in pregnancy: Nationwide surveillance and Delphi audit system.

OBJECTIVE: To evaluate the incidence, diagnostic management strategies and clinical outcomes of women with spontaneous haemoperitoneum in pregnancy (SHiP) and reassess the definition of SHiP. DESIGN: A population-based cohort study using the Netherlands Obstetric Surveillance System (NethOSS). SETTING: Nationwide, the Netherlands. POPULATION: All pregnant women between April 2016 and April 2018. METHODS: This is a case study of SHiP using the monthly registry reports of NethOSS. Complete anonymised case files were obtained. A newly introduced online Delphi audit system (DAS) was used to evaluate each case, to make recommendations on improving the management of SHiP and to propose a new definition of SHiP. MAIN OUTCOME MEASURES: Incidence and outcomes, lessons learned about clinical management and the critical appraisal of the current definition of SHiP. RESULTS: In total, 24 cases were reported. After a Delphi procedure, 14 cases were classified as SHiP. The nationwide incidence was 4.9 per 100 000 births. Endometriosis and conceiving after artificial reproductive techniques were identified as risk factors. No maternal and three perinatal deaths occurred. Based on the DAS, adequate imaging of free intra-abdominal fluid, and identifying and treating women with signs of hypovolemic shock could improve the early detection and management of SHiP. A revised definition of SHiP was proposed, excluding the need for surgical or radiological intervention. CONCLUSIONS: SHiP is a rare and easily misdiagnosed condition that is associated with high perinatal mortality. To improve care, better awareness among healthcare workers is needed. The DAS is a sufficient tool to audit maternal morbidity and mortality.

Incidence, Indications, Risk Factors, and Outcomes of Emergency Peripartum Hysterectomy Worldwide: A Systematic Review and Meta-analysis.

OBJECTIVE: To describe the incidence, indications, risk factors, outcomes, and management of emergency peripartum hysterectomy globally and to compare outcomes among different income settings. DATA SOURCES: PubMed, MEDLINE, EMBASE, ClinicalTrials.gov, Cochrane Library, Web of Science, and Emcare databases up to December 10, 2021. METHODS OF STUDY SELECTION: Update of a systematic review and meta-analysis (2016). Studies were eligible if they reported the incidence of emergency peripartum hysterectomy, defined as surgical removal of the uterus for severe obstetric complications up to 6 weeks postpartum. Title and abstract screening and full-text review were performed using Endnote data-management software. Of 8,775 articles screened, 26 were included that were published after 2015, making the total number of included studies 154. A subanalysis was performed for the outcomes of interest per income setting. TABULATION, INTEGRATION, AND RESULTS: The meta-analysis included 154 studies: 14,409 emergency peripartum hysterectomies were performed in 17,127,499 births in 42 countries. Overall pooled incidence of hysterectomy was 1.1 per 1,000 births (95% CI 1.0-1.3). The highest incidence was observed in lower middle-income settings (3/1,000 births, 95% CI 2.5-3.5), and the lowest incidence was observed in high-income settings (0.7/1,000 births, 95% CI 0.5-0.8). The most common indications were placental pathology (38.0%, 95% CI 33.9-42.4), uterine atony (27.0%, 95% CI 24.6-29.5), and uterine rupture (21.2%, 95% CI 17.8-25.0). In lower middle-income countries, uterine rupture (44.5%, 95% CI 36.6-52.7) was the most common indication; placental pathology (48.4%, 95% CI 43.5-53.4) was most frequent in high-income settings. To prevent hysterectomy, uterotonic medication was used in 2,706 women (17%): 53.2% received oxytocin, 44.6% prostaglandins, and 17.3% ergometrine. Surgical measures to prevent hysterectomy were taken in 80.5% of women, the most common being compressive techniques performed in 62.6% (95% CI 38.3-81.9). The most common complications were febrile (29.7%, 95% CI 25.4-34.3) and hematologic (27.5%, 95% CI 20.4-35.9). The overall maternal case fatality rate was 3.2 per 100 emergency peripartum hysterectomies (95% CI 2.5-4.2) and was higher in lower middle-income settings (11.2/100 emergency peripartum hysterectomies 95% CI 8.9-14.1) and lower in high-income settings (1.0/100 emergency peripartum hysterectomies 95% CI 0.6-1.6). CONCLUSION: Substantial differences across income settings exist in the incidence of emergency peripartum hysterectomy. Women in lower-income settings have a higher risk of undergoing emergency peripartum hysterectomy and suffer more procedure-related morbidity and mortality. The frequency of emergency peripartum hysterectomy is likely to increase in light of increasing cesarean delivery rates.

The influence of various induction methods on adverse outcomes in small for gestational age neonates: A secondary analysis of the PROBAAT 1 and 2 trials.

OBJECTIVE: To evaluate the safety aspects of different induction methods in pregnancies with small-for-gestational-age neonates. STUDY DESIGN: This was a secondary analysis of two previously reported multicenter, randomized controlled trials conducted in the Netherlands. In the original trials, women were randomized to either a 30 cc Foley catheter, vaginal prostaglandin E2 (PROBAAT-1) or oral misoprostol (PROBAAT-2). A total of 425 patients with a term, singleton pregnancy in cephalic presentation with an indication for labor induction and a small-for-gestational-age neonate were included in this secondary analysis. Our primary outcome was a composed adverse neonatal outcome of Apgar score < 7 after 5 min and/or a pH in the umbilical artery < 7.05 and/or NICU admission. Secondary outcomes were mode of birth, operative birth for fetal distress and pH < 7.10 in the umbilical artery. For these outcome measures, multivariate as well as bivariate analyses were performed. RESULTS: An adverse neonatal outcome occurred in 4.7 % (10/214) induction with a Foley catheter, versus 12.8 % (19/149) after misoprostol (RR 0.36; 95 % CI 0.17-0.76) and 4.7 % (3/64) after Prostaglandin E2 (RR 0.98; 95 %CI 0.28-3.51). For individual components of the composed outcome of adverse events, a difference was found between a Foley catheter and misoprostol for Apgar score < 7 at 5 min (0.5 % versus 3.4; RR 0.14; 95 %CI 0.02-1.16) and NICU admission (1.9 % versus 6.1 %; RR 0.31; 0.10-0.97). No differences were found for mode of birth. CONCLUSIONS: For women who gave birth to a small-for-gestational-age neonate, a Foley catheter is probably a safer induction method compared to oral misoprostol.

COVID-19-related medicine utilization study in pregnancy: The COVI-PREG cohort.

AIM: The objective of this study was to describe the use of COVID-19-related medicines during pregnancy and their evolution between the early/late periods of the pandemic. METHODS: Pregnant women who tested positive for SARS-CoV-2 from March 2020 to July 2021 were included using the COVI-PREG registry. Exposure to the following COVID-19-related medicines was recorded: antibiotics, antivirals, hydroxychloroquine, corticosteroids, anti-interleukin-6 and immunoglobulins. We described the prevalence of medicines used, by trimester of pregnancy, maternal COVID-19 severity level and early/late period of the pandemic (before and after 1 July 2020). FINDINGS: We included 1964 pregnant patients who tested positive for SARS-CoV-2. Overall, 10.4% (205/1964) received at least one COVID-19-related medicine including antibiotics (8.6%; 169/1694), corticosteroids (3.2%; 62/1964), antivirals (2.0%; 39/1964), hydroxychloroquine (1.4%; 27/1964) and anti-interleukin-6 (0.3%; 5/1964). The use of at least one COVID-19-related medicine was 3.1% (12/381) in asymptomatic individuals, 4.2% (52/1233) in outpatients, 19.7% (46/233) in inpatients without oxygen, 72.1% (44/61) in those requiring standard oxygen, 95.7% (22/23) in those requiring high flow oxygen, 96.2% (25/26) in patients who required intubation and 57.1% (4/7) among patients who died. The proportion who received medicines to treat COVID-19 was higher before than after July 2020 (16.7% vs. 7.7%). Antibiotics, antivirals and hydroxychloroquine had lower rates of use during the late period. CONCLUSION: Medicine use in pregnancy increased with disease severity. The trend towards increased use of corticosteroids seems to be aligned with changing guidelines. Evidence is still needed regarding the effectiveness and safety of COVID-19-related medicines in pregnancy.

Balloon catheters versus vaginal prostaglandins for labour induction (CPI Collaborative): an individual participant data meta-analysis of randomised controlled trials.

BACKGROUND: Induction of labour is one of the most common obstetric interventions globally. Balloon catheters and vaginal prostaglandins are widely used to ripen the cervix in labour induction. We aimed to compare the effectiveness and safety profiles of these two induction methods. METHODS: We did an individual participant data meta-analysis comparing balloon catheters and vaginal prostaglandins for cervical ripening before labour induction. We systematically identified published and unpublished randomised controlled trials that completed data collection between March 19, 2019, and May 1, 2021, by searching the Cochrane Library, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and PubMed. Further trials done before March 19, 2019, were identified through a recent Cochrane review. Data relating to the combined use of the two methods were not included, only data from women with a viable, singleton pregnancy were analysed, and no exclusion was made based on parity or membrane status. We contacted authors of individuals trials and participant-level data were harmonised and recoded according to predefined definitions of variables. Risk of bias was assessed with the ROB2 tool. The primary outcomes were caesarean delivery, indication for caesarean delivery, a composite adverse perinatal outcome, and a composite adverse maternal outcome. We followed the intention-to-treat principle for the main analysis. The primary meta-analysis used two-stage random-effects models and the sensitivity analysis used one-stage mixed models. All models were adjusted for maternal age and parity. This meta-analysis is registered with PROSPERO (CRD42020179924). FINDINGS: Individual participant data were available from 12 studies with a total of 5460 participants. Balloon catheters, compared with vaginal prostaglandins, did not lead to a significantly different rate of caesarean delivery (12 trials, 5414 women; crude incidence 27·0%; adjusted OR [aOR] 1·09, 95% CI 0·95-1·24; I2=0%), caesarean delivery for failure to progress (11 trials, 4601 women; aOR 1·20, 95% CI 0·91-1·58; I2=39%), or caesarean delivery for fetal distress (10 trials, 4441 women; aOR 0·86, 95% CI 0·71-1·04; I2=0%). The composite adverse perinatal outcome was lower in women who were allocated to balloon catheters than in those allocated to vaginal prostaglandins (ten trials, 4452 neonates, crude incidence 13·6%; aOR 0·80, 95% CI 0·70-0·92; I2=0%). There was no significant difference in the composite adverse maternal outcome (ten trials, 4326 women, crude incidence 22·7%; aOR 1·02, 95% CI 0·89-1·18; I2=0%). INTERPRETATION: In induction of labour, balloon catheters and vaginal prostaglandins have comparable caesarean delivery rates and maternal safety profiles, but balloon catheters lead to fewer adverse perinatal events. FUNDING: Australian National Health and Medical Research Council and Monash Health Emerging Researcher Fellowship.

Increased microchimerism in peripheral blood of women with systemic lupus erythematosus: relation with pregnancy.

OBJECTIVES: We aimed to determine the presence, amount and origin of microchimerism in peripheral blood of pregnant and non-pregnant parous women with systemic lupus erythematosus (SLE) as compared to control subjects. METHODS: We performed a comparative study in which peripheral blood was drawn from eleven female non-pregnant SLE-patients and 22 control subjects, and from six pregnant SLE-patients and eleven control subjects during gestation and up to six months postpartum. Quantitative PCR for insertion-deletion polymorphisms and null alleles was used to detect microchimerism in peripheral blood mononuclear cells and granulocytes. RESULTS: Microchimerism was detected more often in non-pregnant SLE-patients than control subjects (54.4% vs. 13.6%, respectively; p=0.03). When present, the median total number of foetal chimeric cells was 5 gEq/106 in patients and 2.5gEq/106 in control subjects (p=0.048). Microchimerism was mostly foetal in origin; maternal microchimerism was detected in one patient and one control subject. In control subjects, microchimerism was always derived from only one source whereas in 50% of patients it originated from multiple sources. The pregnant patients had a significantly higher median number of foetal chimeric cells in the granulocyte fraction just after delivery than control subjects (7.5 gEq/106 vs. 0 gEq/106, respectively; p=0.02). CONCLUSIONS: Just after delivery, SLE-patients had more microchimerism than control subjects. Three months post-partum, microchimerism was no longer detectable, only to reappear many years after the last pregnancy, more often and at higher levels in SLE-patients than in control subjects. This suggests that these chimeric cells may originate from non-circulating foetal chimeric stem cells.

Pregnant women's willingness to participate in a randomized trial comparing induction of labor at 39 weeks versus expectant management: A survey in the Netherlands.

INTRODUCTION: A randomized controlled trial (RCT) in the United States, the ARRIVE trial, has indicated that induction of labor (IOL) in low-risk nulliparous women with a gestational age (GA) of 39 weeks compared to expectant management (EM) resulted in a significant lower rate of cesarean deliveries. The Dutch maternity care system is different compared to the United States with, among other factors, an overall significantly lower percentage of caesarean sections (CS). To investigate whether IOL has a favorable outcome in the Dutch maternity care system, a new trial is advised. In this questionnaire-based study we aim to evaluate whether Dutch low-risk pregnant women would be willing to participate in an RCT comparing IOL at 39 weeks to EM. MATERIALS AND METHODS: We conducted an online survey in 2020 in the Netherlands. Respondent recruitment took place both in outpatient clinics at hospitals and midwife practices and via social media. Inclusion criteria were pregnant women with singleton gestation, GA ≤ 39 weeks, age 18 years or older and residency in the Netherlands. Exclusion criteria were multiple gestation, a history of a CS, planned IOL or CS in current pregnancy and GA > 39 weeks. A subgroup was formed of low risk (receiving primary care) nulliparous women with a gestational age between 34 and 39 weeks, comparable with the ARRIVE trial. RESULTS: Three hundred eighty respondents participated. Of all respondents (nulli- and multiparous), 47 (12.4%) would be willing to participate in the hypothetical RCT and 70 (18.4%) might be willing to participate. Amongst the 70 women in the subgroup 11 women (15.7%) would be willing to participate and 17 (24.3%) might be willing to participate. DISCUSSION AND CONCLUSION: Calculating sample size in a country with a low CS rate, in relation to 69.2% of women are not willing to participate in an RCT comparing IOL at 39 weeks with EM, would require >18.000 women to be counselled for participation. We believe such a study is a challenge in the Netherlands.

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.

Analysing the protection from respiratory tract infections and allergic diseases early in life by human milk components: the PRIMA birth cohort.

BACKGROUND: Many studies support the protective effect of breastfeeding on respiratory tract infections. Although infant formulas have been developed to provide adequate nutritional solutions, many components in human milk contributing to the protection of newborns and aiding immune development still need to be identified. In this paper we present the methodology of the "Protecting against Respiratory tract lnfections through human Milk Analysis" (PRIMA) cohort, which is an observational, prospective and multi-centre birth cohort aiming to identify novel functions of components in human milk that are protective against respiratory tract infections and allergic diseases early in life. METHODS: For the PRIMA human milk cohort we aim to recruit 1000 mother-child pairs in the first month postpartum. At one week, one, three, and six months after birth, fresh human milk samples will be collected and processed. In order to identify protective components, the level of pathogen specific antibodies, T cell composition, Human milk oligosaccharides, as well as extracellular vesicles (EVs) will be analysed, in the milk samples in relation to clinical data which are collected using two-weekly parental questionnaires. The primary outcome of this study is the number of parent-reported medically attended respiratory infections. Secondary outcomes that will be measured are physician diagnosed (respiratory) infections and allergies during the first year of life. DISCUSSION: The PRIMA human milk cohort will be a large prospective healthy birth cohort in which we will use an integrated, multidisciplinary approach to identify the longitudinal effect human milk components that play a role in preventing (respiratory) infections and allergies during the first year of life. Ultimately, we believe that this study will provide novel insights into immunomodulatory components in human milk. This may allow for optimizing formula feeding for all non-breastfed infants.

Clinical value of early assessment of hyperfibrinolysis by rotational thromboelastometry during postpartum hemorrhage for the prediction of severity of bleeding: A multicenter prospective cohort study in the Netherlands.

INTRODUCTION: Coagulopathy may be the result of hyperfibrinolysis and could exacerbate bleeding following childbirth. Timely recognition of hyperfibrinolysis during the earliest stages of postpartum hemorrhage could identify women at risk of more severe blood loss who may benefit from targeted anti-fibrinolytic therapy. Rotational thromboelastometry (ROTEM® ) is a point-of-care test that could detect hyperfibrinolysis. The aim of this study was to evaluate whether early assessment of hyperfibrinolysis by ROTEM during postpartum hemorrhage could predict progression to severe postpartum hemorrhage. MATERIAL AND METHODS: During a prospective cohort study in the Netherlands among women with postpartum hemorrhage (total blood loss at least 1000 ml within 24 h after childbirth) ROTEM measurements were performed following 800-1500 ml of blood loss. Hyperfibrinolysis was defined as an enzymatic fibrinolysis index (ROTEM EXTEM maximum clot lysis [ML] minus the ROTEM APTEM ML) above 15%. Severe postpartum hemorrhage was defined as a composite end point of total blood loss greater than 2000 ml, transfusion of four or more units of packed cells, and/or need for an invasive intervention. The predictive value of hyperfibrinolysis for progression to severe postpartum hemorrhage was assessed by area under the receiver operating curve (AUC) and positive and negative predictive values. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02149472). RESULTS: Of 390 women included, 82 (21%) had severe postpartum hemorrhage. Four (1%) women had thromboelastometric evidence of hyperfibrinolysis, of whom two developed severe postpartum hemorrhage. The AUC for enzymatic fibrinolysis index more than 15% for progression to severe postpartum hemorrhage was 0.47 (95% CI 0.40-0.54). Positive and negative predictive values for this index were 50.0% (95% CI 6.8-93.2) and 79.3% (95% CI 74.9-83.2), respectively. CONCLUSIONS: Thromboelastometric evidence of hyperfibrinolysis was rare in women with postpartum hemorrhage when assessed between 800 and 1500 ml of blood loss. The clinical predictive value of viscoelastometric point-of-care testing for hyperfibrinolysis for progression to severe postpartum hemorrhage during early postpartum hemorrhage is limited.

Idiopathic multifocal choroiditis and punctate inner choroidopathy: an evaluation in pregnancy.

PURPOSE: To evaluate the clinical course of idiopathic multifocal choroiditis (MFC) and punctate inner choroidopathy (PIC) and the efficacy and safety of treatment options during pregnancy. METHODS: Patients with MFC or PIC and a pregnancy in 2011-2019 from two academic centres were enrolled. For the most recent pregnancy, data on best-corrected visual acuity (BCVA) before and after pregnancy, relapse rate in pregnancy and postpartum period and obstetric, maternal and neonatal outcomes were collected. Treatment regimens consisted of a wait-and-see regime and an immunosuppressive treatment regime with systemic corticosteroids and/or azathioprine, both combined with intravitreal antivascular endothelial growth factor injections when indicated. RESULTS: Sixteen women (26 affected eyes) were included. Median Snellen BCVA was 20/19 before pregnancy and 20/18 after delivery. In seven pregnancies a wait-and-see regime and in nine pregnancies an immunosuppressive treatment regime was carried out. Fourteen intravitreal anti-VEGF injections were given in six pregnancies. The relapse rate during pregnancy was 44% and in the postpartum period 31%. Maternal/obstetrical and fetal complications occurred in 31% and 13% of the pregnancies, respectively. Fifteen healthy children were born and one pregnancy ended in a stillbirth in a patient with a complicated obstetrical history. One patient treated with azathioprine developed intrahepatic cholestasis of pregnancy (ICP). CONCLUSIONS: Among women with MFC and PIC BCVA remained stable during pregnancy despite a relapse rate of 44% in pregnancy. No major maternal, obstetric and fetal complications occurred in pregnant patients treated with systemic corticosteroids, azathioprine or intravitreal anti-VEGF injections, though one patient developed ICP while treated with azathioprine.

Prevalence, burden and treatment effects of vaginal bleeding in women with (suspected) congenital platelet disorders throughout life: a cross-sectional study.

Congenital platelet disorders (CPDs) are rare bleeding disorders that are associated with mucocutaneous bleeds. However, data on vaginal bleeding in women with CPDs are scarce. A set of generic and bleeding-specific questionnaires were used to evaluate the prevalence of vaginal bleeding, its impact on quality of life (QoL) and sexual functioning and the consequences for pregnancy, miscarriage and delivery in a cohort of women who were referred for diagnostic evaluation for CPDs. A total of 78 women included in the study were either diagnosed with a CPD (n = 35) or were clinically suspected of a CPD (n = 43). Heavy menstrual bleeding (HMB) was reported by a large proportion of women, which mainly started at menarche. In all, 76% of women received any kind of HMB treatment, often leading to surgical prodecures. HMB was shown to have a high impact on QoL, which improved upon treatment. Even though women reported that vaginal bleeding affects sexuality, this topic is not frequently discussed with physicians. Heavy blood loss frequently occurred after miscarriage/delivery, often requiring treatment. Women with (suspected) CPDs frequently encounter HMB, negatively impacting daily life and sexual functioning. Together with peripartum bleeding, these data highlight the burden of vaginal bleeding in CPDs and importance of adequate treatment.

A qualitative study on the experiences of haemophilia carriers before, during and after pregnancy.

INTRODUCTION: Haemophilia carriers (HCs) face considerable haemostatic and psychological challenges during reproduction. AIM: To explore the perspectives of HCs on healthcare in the current standard of haemophilia treatment during all reproductive phases: preconception, pregnancy, childbirth and the postpartum period. In addition, we examined the psychological impact of haemophilia during these phases. MATERIAL AND METHODS: Focus group discussions (FGDs) and semi-structured interviews were conducted with HCs in January/February 2020 until data saturation was reached. All sessions were recorded, transcribed verbatim and analysed by two independent researchers through thematic content analysis using MAXQDA® software. The results were then discussed within the research team until consensus was reached. The constructed themes were shared with and reviewed by the HCs. RESULTS: Fifteen HCs were included in three FGDs and four interviews. Five central themes were constructed: (1) communication by healthcare professionals, (2) lack of knowledge, (3) feeling insecure, (4) autonomy and (5) family experiences with haemophilia. Desired improvements in care mainly concerned counselling during preconception and pregnancy. This included timely access to comprehensive information during each consecutive phase, acceptance of HCs' choices by healthcare providers and healthcare tailored to the HC's family experience with haemophilia. CONCLUSIONS: In recent years, haemophilia treatment has seen major advances, which could impact general and reproductive care for HCs. HCs indicated that reproductive care would benefit from a more personal and informative approach. Healthcare professionals could use these insights to adapt their consultations to meet the needs of these women when they are preparing for having children.

Changes in local protocols on inpatient cervical priming and introduction of outpatient priming: A nationwide survey in the Netherlands.

OBJECTIVE: The aims of this study are to assess (changes in) local procedures for inpatient cervical priming as part of induction of labor and to identify the implementation of outpatient cervical priming in the Netherlands. METHODS: This survey study was conducted from October 2019 until January 2020; obstetricians of all 72 hospitals with a maternity unit in the Netherlands received a questionnaire. The questionnaire consisted of three parts: basic hospital data, local protocol on methods of inpatient induction of labor (IPI), local protocol for outpatient induction of labor (OPI). RESULTS: A response was received from 66/72 hospitals, giving a response rate of 92%. For IPI the most preferred method was a Foley catheter (87.9%), 27.6% protocols switched to prostaglandins after day 1 if the cervix was not ripe yet. A prostaglandin gel or pessary was not the preferred method on day 1 but only used after 24 h in 5 hospitals (7.6%). OPI was offered in 53% (35/66 hospitals), all using a Foley catheter. CONCLUSION: In the Netherlands, local protocols for IPI have shifted towards the use of a Foley catheter. More than half of the hospitals offer OPI. As safety and efficacy data of OPI are lacking, research on this topic is urgently warranted.

From Passive Surveillance to Response: Suriname's Efforts to Implement Maternal Death Surveillance and Response.

Implementation of maternal death surveillance and response (MDSR) is crucial to reduce maternal deaths. In Suriname, MDSR was not implemented until 2015. We describe the process of MDSR implementation in Suriname and share the "lessons learned," as experienced by the health care providers, national maternal death review committee members, and public health experts. Before 2015, maternal deaths were identified using death certificates and by active surveillance in the hospitals. Based on the recommendations from a 2010-2014 Reproductive Age Mortality Survey in Suriname, a maternal death review committee has improved the identification of maternal deaths and has audited every death since 2015. Although this review committee initiated several actions to implement MDSR together with health care providers, the involvement of the Ministry of Health (MOH) was crucial. Therefore, the Maternal Health Steering Committee was recently installed as a direct working arm of MOH to guide MDSR implementation. One of the main barriers to implementing MDSR in Suriname has been the lack of action following recommendations. Delineating roles and responsibilities for action, establishing accountability mechanisms, and influencing stakeholders in a position to act are critical to ensure a response to the recommendations. To implement MDSR, the 5 Cs-commitment, "no blame, no shame" culture, coordination, collaboration, and communication-are crucial.