Association between miscarriage and cardiovascular disease in a Scottish cohort

Funding This work was supported by a grant from the ‘Merel Foundation’, the Netherlands. The AMND receives support from the University of Aberdeen.Peer reviewedPostprin

Pregnancy in Advanced Kidney Disease:Clinical Practice Considerations on a Challenging Combination

Background:Thanks to the advances in care, pregnancy is now attainable for the majority of young female CKD patients, although it is still a high-risk endeavor. Clinical decision-making in these cases is impacted by a myriad of factors, making (pre)pregnancy counseling a complex process. The complexities, further impacted by limited data and unknown risks regarding outcome, can cause discussions when deciding on the best care for a specific patient. Objectives:In this article, we provide an overview of the considerations and dilemmas we encounter in preconception counseling and offer our perspective on how to deal with them in daily clinical practice. Methods:The main topics we discuss in our counseling are (1) the high risk of pregnancy complications, (2) the risk of permanent CKD deterioration due to pregnancy and subsequent decreased life expectancy, (3) appropriate changes in renal medication, and (4) assisted reproduction, genetic testing, and prenatal or preimplantation genetic diagnostics. Results and Conclusions:In our clinic, we openly address moral dilemmas arising in clinical practice in pregnancy and CKD, both within the physician team and with the patient. We do this by ensuring an interpretive physician-patient interaction and shared decision-making, deliberating in a multidisciplinary setting and, if needed, with input from an expert committee

Public attitudes towards pricing policies to change health-related behaviours: a UK focus group study.

BACKGROUND: Evidence supports the use of pricing interventions in achieving healthier behaviour at population level. The public acceptability of this strategy continues to be debated throughout Europe, Australasia and USA. We examined public attitudes towards, and beliefs about the acceptability of pricing policies to change health-related behaviours in the UK. The study explores what underlies ideas of acceptability, and in particular those values and beliefs that potentially compete with the evidence presented by policy-makers. METHODS: Twelve focus group discussions were held in the London area using a common protocol with visual and textual stimuli. Over 300,000 words of verbatim transcript were inductively coded and analyzed, and themes extracted using a constant comparative method. RESULTS: Attitudes towards pricing policies to change three behaviours (smoking, and excessive consumption of alcohol and food) to improve health outcomes, were unfavourable and acceptability was low. Three sets of beliefs appeared to underpin these attitudes: (i) pricing makes no difference to behaviour; (ii) government raises prices to generate income, not to achieve healthier behaviour and (iii) government is not trustworthy. These beliefs were evident in discussions of all types of health-related behaviour. CONCLUSIONS: The low acceptability of pricing interventions to achieve healthier behaviours in populations was linked among these responders to a set of beliefs indicating low trust in government. Acceptability might be increased if evidence regarding effectiveness came from trusted sources seen as independent of government and was supported by public involvement and hypothecated taxation.The study was funded by the UK Department of Health Policy Research Programme (Policy Research Unit in Behaviour and Health [PR-UN-0409-10109]). The Department of Health had no role in the study design, data collection, analysis, or interpretation. The research was conducted independently of the funders, and the views expressed in this paper are those of the authors and not necessarily those of the Department of Health in England.This is the final version of the article. It was first available from Oxford University Press at http://dx.doi.org/10.1093/eurpub/ckv07

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

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

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

Classifying maternal deaths in Suriname using WHO ICD-MM: different interpretation by Physicians, National and International Maternal Death Review Committees

Plain English summary: The World Health Organization (WHO) provides a framework (ICD-MM) to classify pregnancy-related deaths systematically, which enables global comparison among countries. We compared the classification of pregnancy-related deaths in Suriname by the attending physician and by the national maternal death review (MDR) committee and among the MDR committees of Suriname, Jamaica and the Netherlands. There were 89 possible pregnancy-related deaths in Suriname between 2010 and 2014. Nearly half (47%) were classified differently by the Surinamese MDR committee as compared to the classification of the attending physicians. All three MDR committees agreed that 18% (n = 16/89) of the cases were no maternal deaths. Out of the remaining 73 cases, there was disagreement regarding whether 15% (n = 11) were maternal deaths. The Surinamese and Jamaican MDR committees achieved greater consensus in classification than the Surinamese and the Netherlands MDR committees. The Netherlands MDR committee classified more deaths as unspecified than Surinamese and the Jamaican MDR committees. Underlying causes that achieved a high level of agreement among the three committees were abortive outcomes and obstetric hemorrhage, while little agreement was reported for unspecified and other direct causes. The issues encountered during maternal death classification using the ICD-MM guidelines included classification of suicide during early pregnancy; when to assume pregnancy without objective evidence; how to count maternal deaths occurring outside the country of residence; the relevance of direct or indirect cause attribution; and how to select the underlying cause when direct and indirect conditions or multiple comorbidities co-occur. Addressing these classification barriers in future revisions of the ICD-MM guidelines could enhance the feasibility of maternal death classification and facilitate global comparison. Background: Insight into the underlying causes of pregnancy-related deaths is essential to develop policies to avert preventable deaths. The WHO International Classification of Diseases-Maternal Mortality (ICD-MM) guidelines provide a framework to standardize maternal death classifications and enable comparison in and among countries over time. However, despite the implementation of these guidelines, differences in classification remain. We evaluated consensus on maternal death classification using the ICD-MM guidelines. Methods: The classification of pregnancy-related deaths in Suriname during 2010–2014 was compared in the country (between the attending physician and the national maternal death review (MDR) committee), and among the MDR committees from Suriname, Jamaica and the Netherlands. All reviewers applied the ICD-MM guidelines. The inter-rater reliability (Fleiss kappa [κ]) was used to measure agreement. Results: Out of the 89 cases certified by attending physicians, 47% (n = 42) were classified differently by the Surinamese MDR committee. The three MDR committees agreed that 18% (n = 16/89) of these cases were no maternal deaths, and, therefore, excluded from further analyses. However, opinions differed whether 15% (n = 11) of the remaining 73 cases were maternal deaths. The MDR committees achieved moderate agreement classifying the deaths into type (direct, indirect and unspecified) (κ = 0.53) and underlying cause group (κ = 0.52). The Netherlands MDR committee classified more maternal deaths as unspecified (19%), than the Jamaican (7%) and Surinamese (4%) committees did. The mutual agreement between the Surinamese and Jamaican MDR committees (κ = 0.69 vs κ = 0.63) was better than between the Surinamese and the Netherlands MDR committees (κ = 0.48 vs κ = 0.49) for classification into type and underlying cause group, respectively. Agreement on the underlying cause category was excellent for abortive outcomes (κ = 0.85) and obstetric hemorrhage (κ = 0.74) and fair for unspecified (κ = 0.29) and other direct causes (κ = 0.32). Conclusions: Maternal death classification differs in Suriname and among MDR committees from different countries, despite using the ICD-MM guidelines on similar cases. Specific challenges in applying these guidelines included attribution of underlying cause when comorbidities occurred, the inclusion of deaths from suicides, and maternal deaths that occurred outside the country of residence

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

No funding was received for the original PROBAAT-I trial or this follow-up study. The original PROBAAT-II trial was funded by Fonds NutsOhra. MV received a doctoral grant for teachers from the Netherlands Organization for Scientific Research (023.011.051). BM is supported by a NHMRC Practitioner Fellowship (GNT1082548).Peer reviewe

Perinatal death in a term fetal growth restriction randomized controlled trial:the paradox of prior risk and consent

BACKGROUND: The disproportionate intrauterine growth intervention trial at term was an intention to treat analysis and compared labor induction with expectant monitoring in pregnancies complicated by fetal growth restriction at term and showed equivalence for neonatal outcomes. OBJECTIVE: To evaluate trial participation bias and to examine the generalizability of the results of an obstetrical randomized trial. STUDY DESIGN: We used data from participants and nonparticipants of a randomized controlled trial-the disproportionate intrauterine growth intervention trial at term (n=1116) -to perform a secondary analysis. This study compared induction of labor and expectant management in women with term growth restriction. Data were collected in the same manner for both groups. Baseline characteristics and neonatal and maternal outcomes were compared. The primary outcome was a composite measure of adverse neonatal outcome. Secondary outcomes were delivery by cesarean delivery and instrumental vaginal delivery; length of stay in the neonatal intensive care, neonatal ward, and the maternal hospital; and maternal morbidity. RESULTS: Nonparticipants were older, had a lower body mass index, had a higher level of education, smoked less, and preferred expectant management. The time between study inclusion and labor onset was shorter in participants than in nonparticipants. Notably, 4 perinatal deaths occurred among nonparticipants and none among participants. Among nonparticipants, there were more children born with a birthweight below the third centile. The nonparticipants who had expectant management were monitored less frequently than the participants in both the intervention and the expectant arm. CONCLUSION: We found less favorable outcomes and more perinatal deaths in nonparticipants. Protocol-driven management, differences between participants and nonparticipants, or the fact that nonparticipants had a preference for expectant management might explain the findings

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