Cancer related maternal mortality and delay in diagnosis and treatment: A case series on 26 cases

Background: Cancer during pregnancy is relatively rare but may lead to maternal mortality. We aimed to assess the incidence of cancer related maternal mortality and the neonatal outcome in these patients. Also, doctor- and patient-related delay in cancer diagnosis and therapy among patients with cancer related maternal mortality is assessed. Methods: Maternal mortality was defined as death during pregnancy or within 1 year after delivery. Data of the Dutch Maternal Mortality Committee was used to calculate the cancer related maternal mortality rate and to assess neonatal outcome in the Netherlands. Delay was scored by ten medical specialist based on case descriptions. Results: Cancer related maternal mortality rate was 1.23 per 100,000 live births. Delay in either diagnosis or treatment occurred in 65%. Delay in diagnosis was more frequent then delay in treatment, and was mainly caused by health care providers. Only 77% of pregnancies were ongoing, and 65% ended preterm of which 85% was induced. Conclusions: Avoiding delay in diagnosis and therapy in case of pregnancy related cancer could potentially improve maternal and neonatal outcome. It is therefore essential to increase awareness among health care providers about the occurrence and recurrence of cancer in pregnancy and the possibilities of diagnostic and therapeutic interventions in these women

Increased incidence of hypertensive disorders of pregnancy in women with a history of spontaneous preterm birth:A longitudinal linked national cohort study

Objective: Determine the risk of hypertensive disorders of pregnancy (HD) in women with a history of spontaneous preterm birth (SPTB). Study design: Longitudinal linked national cohort study within the Dutch Perinatal Registry (1999–2009) on linked data among 349,291 women with a first and second singleton pregnancy in the Netherlands. Main outcome measures: The incidence of HD, small for gestational age (SGA) and placental abruption in the second pregnancy. Results: Out of 349,291 women with a singleton first pregnancy, 19,991 (5.7%) had a SPTB. The incidence of HD in the second pregnancy was 8.1% in women with a previous SPTB, as compared to 5.6% in women with a previous term birth (aOR 1.49 (CI 1.41–1.57)). Also after excluding HD, SGA and/or placental abruption in the first pregnancy, women with a history of SPTB had a higher risk of HD in their second pregnancy compared to women with a previous term birth (4.6% versus 2.7%, aOR 1.77 (CI 1.64–191)). Similarly, the incidence of SGA and placental abruption was higher in the second pregnancy in women with a history of SPTB compared to term birth in the first pregnancy. Conclusions: Women with a history of SPTB are at elevated risk of HD in the subsequent pregnancy. These results support shared pathophysiology between SPTB and HD

Cardiovascular mortality in women in their forties after hypertensive disorders of pregnancy in the Netherlands : a national cohort study

Peer reviewedPublisher PD

Women with a Preterm Cesarean Have High Rates of Successful Trial of Labor in a Subsequent Term Pregnancy

Objective The rate of cesareans has increased worldwide. Therefore, an increasing number of women has to decide how to deliver in a subsequent pregnancy. Individualized information on risks and success chances is helpful. This study investigates the effect of a preterm cesarean on success of subsequent term trial of labor. Study Design Ten-year Dutch cohort (2000-2009) of women with one previous cesarean and a subsequent term trial of labor. Subgroups were made based on gestational age at first cesarean delivery (25-28, 28-30, 30-32 and 32-34 weeks) and stratified based the way in which second delivery started. Rates of vaginal deliveries, maternal, and neonatal outcomes were compared with women who had a first-term cesarean (37-43 weeks). Results Four thousand three-hundred forty-two women delivered by preterm cesarean in the first pregnancy. These women had high rates of successful trial of labor, both after spontaneous onset (86.2-96.2%) and induction (72.8-75.4%). Rates of adverse outcomes were low and similar compared with women with a previous term cesarean. Conclusion In this 10-year nationwide cohort, women with a preterm first cesarean who opted for trial of labor in a subsequent pregnancy had high rates of successful trial of labor

Induction of Labor for Maternal Indications at a Periviable Gestational Age; Survey on Management, Reporting and Auditing amongst Dutch Maternal-Feta Medicine Specialists and Neonatologists

Background In cases of life-threatening maternal conditions in the periviable period, professionals may consider immediate delivery with fetal demise as a consequence of the treatment. We sought the opinion of involved medical professionals on management, reporting, and auditing in these cases.Methods We performed an online survey amongst all registered maternal-fetal medicine (MFM) specialists and neonatologists in the Netherlands. The survey presented two hypothetical cases of severe early-onset pre-eclampsia at periviable gestational ages. Management consisted of immediate termination or expectant management directed towards newborn survival.Findings In the case managed by immediate termination, 62% percent answered that fetal demise resulting from induction of labor for maternal indications should be audited only within the medical profession. In the case of expectant management, 17% of the participants agreed with this management. Some answers revealed a significant difference in opinion between the medical specialists.Conclusion Perspective of MFM specialists and neonatologists differs with regard to counseling prospect parents in case of severe early onset pre-eclampsia. The majority of professionals is willing to report late termination (after 24 weeks' gestation) for severe maternal disease to medical experts for internal audits but not for legal auditing.</p

Angiogenic Factors in Women Ten Years after Severe Very Early Onset Preeclampsia

Background: Women with a history of mainly severe and early onset preeclampsia have an increased risk of future cardiovascular disease. During these complicated pregnancies increased levels of anti-angiogenic factors can be found. We hypothesize that women with a history of severe very early onset preeclampsia still have increased levels of these biomarkers years after this pregnancy, resulting in increased risk for cardiovascular disease. Methods: Twenty women with severe early onset preeclampsia before 24 weeks' gestation, who delivered between 1993-2003 in a tertiary referral centre and twenty matched controls with uncomplicated pregnancies and healthy term infants, were addressed for participation in the study. Venous plasma samples were analyzed for basic fibroblast growth factor (bFGF), placental growth factor (PLGF), soluble fms-like tyrosine kinase-1 (sFlt-1), vascular endothelial growth factor (VEGF), E- and P-selectin, soluble intercellular adhesion molecule-3 (sICAM-3) and thrombomodulin by ELISA. Results: Sixteen case subjects and 18 control subjects consented participation. The median time interval index pregnancy to study was 9.4 and 9.7 years for cases and controls, respectively. Median levels for cases-controls (p-value) were not different; bFGF: 17.43-11.11 pg/mL (0.33), sFlt-1: 102.98-101.92 pg/ml (0.84), PLGF: 3.57-4.20 pg/mL (0.38), VEGF: 64.05-45.72 pg/mL (0.73), E-selectin: 5.11-4.68 ng/mL (0.20), P-selectin: 85.35-71.69 ng/mL (0.69), sICAM-3: 0.42-0.63 ng/mL (0.41) and Thrombomodulin: 0.92-0.93 ng/mL (0.59). Conclusion: There were no differences in angiogenic biomarkers between women with a history of severe early onset preeclampsia versus uncomplicated pregnancy almost 10 years later, suggesting that these angiogenic factors will not contribute to the early detection of women at risk for future cardiovascular disease

Study protocol: differential effects of diet and physical activity based interventions in pregnancy on maternal and fetal outcomes--individual patient data (IPD) meta-analysis and health economic evaluation.

© 2014 Ruifrok et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.BACKGROUND: Pregnant women who gain excess weight are at risk of complications during pregnancy and in the long term. Interventions based on diet and physical activity minimise gestational weight gain with varied effect on clinical outcomes. The effect of interventions on varied groups of women based on body mass index, age, ethnicity, socioeconomic status, parity, and underlying medical conditions is not clear. Our individual patient data (IPD) meta-analysis of randomised trials will assess the differential effect of diet- and physical activity-based interventions on maternal weight gain and pregnancy outcomes in clinically relevant subgroups of women. METHODS/DESIGN: Randomised trials on diet and physical activity in pregnancy will be identified by searching the following databases: MEDLINE, EMBASE, BIOSIS, LILACS, Pascal, Science Citation Index, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and Health Technology Assessment Database. Primary researchers of the identified trials are invited to join the International Weight Management in Pregnancy Collaborative Network and share their individual patient data. We will reanalyse each study separately and confirm the findings with the original authors. Then, for each intervention type and outcome, we will perform as appropriate either a one-step or a two-step IPD meta-analysis to obtain summary estimates of effects and 95% confidence intervals, for all women combined and for each subgroup of interest. The primary outcomes are gestational weight gain and composite adverse maternal and fetal outcomes. The difference in effects between subgroups will be estimated and between-study heterogeneity suitably quantified and explored. The potential for publication bias and availability bias in the IPD obtained will be investigated. We will conduct a model-based economic evaluation to assess the cost effectiveness of the interventions to manage weight gain in pregnancy and undertake a value of information analysis to inform future research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2013: CRD42013003804.This study was funded by the National Institute for Health Research (NIHR) HTA (Health Technology Assessment) UK programme 12/01

Low dose aspirin in the prevention of recurrent spontaneous preterm labour - the APRIL study: A multicenter randomized placebo controlled trial

Background: Preterm birth (birth before 37 weeks of gestation) is a major problem in obstetrics and affects an estimated 15 million pregnancies worldwide annually. A history of previous preterm birth is the strongest risk factor for preterm birth, and recurrent spontaneous preterm birth affects more than 2.5 million pregnancies each year. A recent meta-analysis showed possible benefits of the use of low dose aspirin in the prevention of recurrent spontaneous preterm birth. We will assess the (cost-)effectiveness of low dose aspirin in comparison with placebo in the prevention of recurrent spontaneous preterm birth in a randomized clinical trial. Methods/design: Women with a singleton pregnancy and a history of spontaneous preterm birth in a singleton pregnancy (22-37 weeks of gestation) will be asked to participate in a multicenter, randomized, double blinded, placebo controlled trial. Women will be randomized to low dose aspirin (80 mg once daily) or placebo, initiated from 8 to 16 weeks up to maximal 36 weeks of gestation. The primary outcome measure will be preterm birth, defined as birth at a gestational age (GA) < 37 weeks. Secondary outcomes will be a composite of adverse neonatal outcome and maternal outcomes, including subgroups of prematurity, as well as intrauterine growth restriction (IUGR) and costs from a healthcare perspective. Preterm birth will be analyzed as a group, as well as separately for spontaneous or indicated onset. Analysis will be performed by intention to treat. In total, 406 pregnant women have to be randomized to show a reduction of 35% in preterm birth from 36 to 23%. If aspirin is effective in preventing preterm birth, we expect that there will be cost savings, because of the low costs of aspirin. To evaluate this, a cost-effectiveness analysis will be performed comparing preventive treatment with aspirin with placebo. Discussion: This trial will provide evidence as to whether or not low dose aspirin is (cost-) effective in reducing recurrence of spontaneous preterm birth. Trial registration: Clinical trial registration number of the Dutch Trial Register: NTR 5675. EudraCT-registration number: 2015-003220-31