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BackgroundPerinatal depression and anxiety are associated with unfavourable child outcomes.AimsTo assess among women with antenatal depression or anxiety the effectiveness of prenatally initiated cognitive–behavioural therapy (CBT) on mother and child compared with care as usual (CAU). Trial registration: Netherlands Trial Register number NTR2242.MethodPregnant women (n= 282) who screened positive for symptoms of depression and/or anxiety were randomised to either CBT (n= 140) or CAU (n= 142). The primary outcome was child behavioural and emotional problems at age 18 months, assessed using the Child Behavior Checklist (CBCL). Secondary outcomes were maternal symptoms during and up to 18 months after pregnancy, neonatal outcomes, mother–infant bonding and child cognitive and motor development at age 18 months.ResultsIn total, 94 (67%) women in the CBT group and 98 (69%) in the CAU group completed the study. The mean CBCL Total Problems score was non-significantly higher in the CBT group than in the CAU group (mean difference: 1.38 (95% CI −1.82 to 4.57);t= 0.85,P= 0.399). No effects on secondary outcomes were observed except for depression and anxiety, which were higher in the CBT group than in the CAU group at mid-pregnancy. Apost hocanalysis of the 98 women with anxiety disorders showed lower infant gestational age at delivery in the CBT than in the CAU group.ConclusionsPrenatally initiated CBT did not improve maternal symptoms or child outcomes among non-help-seeking women with antenatal depression or anxiety. Our findings are not in line with present recommendations for universal screening and treatment for antenatal depression or anxiety, and future work may include the relevance of baseline help-seeking.

Objective: We aimed to identify determinants that predict hyperemesis gravidarum (HG) disease course and severity.Study design: For this study, we combined data of the Maternal and Offspring outcomes after Treatment of HyperEmesis by Refeeding (MOTHER) randomized controlled trial (RCT) and its associated observational cohort with non-randomised patients. Between October 2013 and March 2016, in 19 hospitals in the Netherlands, women hospitalised for HG were approached for study participation. In total, 215 pregnant women provided consent for participation. We excluded women enrolled during a readmission (n = 24). Determinants were defined as patient characteristics and clinical features, available to clinicians at first hospital admission. Patient characteristics included i.e. age, ethnicity, socio-economic status, history of mental health disease and HG and gravidity. Clinical features included weight loss compared to pre-pregnancy weight and symptom severity measured with Pregnancy Unique Quantification of Emesis (PUQE-24) questionnaire and the Nausea and Vomiting in Pregnancy specific Quality of Life questionnaire (NVPQoL). Outcome measures were measures of HG disease severity present at 1 week after hospital admission, including weight change, PUQE-24 and NVPQoL scores. Total days of admission hospital admission and readmission were also considered outcome measures.Results: We found that high PUQE-24 and NVPQoL scores at hospital admission were associated with those 1 week after hospital admission (difference (beta) 0.36, 95 %CI 0.16 to 0.57 and 0.70,95 %CI 0.45-1.1). PUQE-24 and NVPQoL scores were not associated with other outcome measures. None of the patient characteristics were associated with any of the outcome measures.Conclusion: Our findings suggest that the PUQE-24 and NVPQoL questionnaires can identify women that maintain high symptom scores a week after admission, but that patient characteristics cannot be used as determinants of HG disease course and severity. (C) 2020 Elsevier B.V. All rights reserved.

AbstractPre-eclampsia (PE) affects 2–8% of pregnancies and is responsible for significant morbidity and mortality. The maternal clinical syndrome (defined by hypertension, proteinuria, and organ dysfunction) is the result of endothelial dysfunction. The endothelial response to increased levels of soluble FMS-like Tyrosine Kinase 1 (sFLT1) is thought to play a central role. sFLT1 is released from multiple tissues and binds VEGF with high affinity and antagonizes VEGF. Expression of soluble variants of sFLT1 is a result of alternative splicing; however, the mechanism is incompletely understood. We hypothesize that neuro-oncological ventral antigen 2 (NOVA2) contributes to this. NOVA2 was inhibited in human umbilical vein endothelial cells (HUVECs) and multiple cellular functions were assessed. NOVA2 and FLT1 expression in the placenta of PE, pregnancy-induced hypertension, and normotensive controls was measured by RT-qPCR. Loss of NOVA2 in HUVECs resulted in significantly increased levels of sFLT1, but did not affect expression of membrane-bound FLT1. NOVA2 protein was shown to directly interact with FLT1 mRNA. Loss of NOVA2 was also accompanied by impaired endothelial functions such as sprouting. We were able to restore sprouting capacity by exogenous VEGF. We did not observe statistically significant regulation of NOVA2 or sFLT1 in the placenta. However, we observed a negative correlation between sFLT1 and NOVA2 expression levels. In conclusion, NOVA2 was found to regulate FLT1 splicing in the endothelium. Loss of NOVA2 resulted in impaired endothelial function, at least partially dependent on VEGF. In PE patients, we observed a negative correlation between NOVA2 and sFLT1.

Background. Up to 43% of women perceive giving birth as traumatic which may result in the development of posttraumatic stress disorder (PTSD) or related symptoms. Negative and traumatic childbirth experiences can also lead to fear of childbirth, avoiding or negatively influencing a subsequent pregnancy, mother-infant bonding problems, problems with breastfeeding, depression and reduced quality of life. For PTSD in general, eye movement desensitization and reprocessing (EMDR) therapy has proven to be effective. However, little is known about the preventive effects of early intervention EMDR therapy in women after a traumatic birth experience. The purpose of this study is to determine the effectiveness of early intervention EMDR therapy in preventing PTSD and reducing PTSD symptoms in women with a traumatic birth experience. Methods. The PERCEIVE-study is a randomized controlled trial. Women suffering from the consequences of a traumatic birth experience will be randomly allocated at maximum 14 days postpartum to either EMDR therapy or “care-as-usual”. Patients in the EMDR condition receive two sessions of therapy between fourteen (T0) and thirty-five days postpartum. All participants will be assessed at T0, and at nine weeks postpartum (T1). At T1 all participants will undergo a CAPS-interview about the presence and severity of PTSD symptoms. The primary outcome measure is severity of PTSD symptoms, whereas the secondary outcomes pertain to fear of childbirth, mother-infant bonding, breastfeeding, depression and quality of life. The study will be conducted at a large city hospital and at several midwifery practices in Amsterdam, the Netherlands. Discussion. It is to be expected that the results of this study will provide more insight about the safety and effectiveness of early intervention EMDR therapy in the prevention and reduction of PTSD (symptoms) in women with a traumatic birth experience. Trial registration. Trial register. NL73231.000.20. Registered on August 21, 2020. https://www.trialregister.nl/trial/8843

The field of obstetrics and gynecology requires complex decision-making and skills because of unexpected high-risk situations. These skills are influenced by alertness, reaction time, and concentration. Night shifts result in sleep deprivation, which might impair these functions, although it is still unclear to what extent.This study aimed to investigate whether a night shift routinely impairs the obstetrics and gynecology consultants' and residents' fitness to perform and whether this reaches a critical limit compared with relevant frames of reference.Residents (n=33) and consultants (n=46) in obstetrics and gynecology conducted multiple measurements (n=415) at precall, postcall, and noncall moments with the fitness to perform self-test. The self-test consists of an adaptive pursuit tracking task that is able to objectively measure alertness, reaction time, concentration, and hand-eye coordination and Visual Analog Scale tests to subjectively score alertness. The test is validated with a sociolegal reference of a 0.06% ethanol blood concentration (the peak level after 2 units of alcohol, the legal driving limit). This equals -1.37% on the objective score and -8.17 points on subjective alertness. Linear mixed models were used to analyze the difference within subjects over a night shift, integrating repeated measures over time.The overnight objective difference between postcall and precall measurements was -0.62 (P.05) for residents and 0.28 (P=NS) for consultants, both not exceeding the sociolegal reference as a group. Objective impairment exceeded the reference for 31% of the residents and 28% of the consultants. Subjective alertness decreased in residents (-18.26; P.001) and consultants (-10.85; P.001), both exceeding the reference. No residents had to continue work postcall versus 7.8% of the consultants. None of the consultants that had to continue work were in an objective critically impaired state.This study provides insight and awareness of individual performance after night shifts with clear frames of reference. The performance of residents is negatively and significantly affected by night shifts; therefore, a scheduled day off after a night shift is justified. Consultants showed no overall impairment; however, a quarter did exceed the alcohol limit reference after their night shift. If not logistically feasible to schedule a protected day off after a night shift, our group recommends safe shift scheduling, including options to transfer care after a demanding night shift to prevent working in a compromised state.

Background: PTSD in pregnant women is associated with adverse outcomes for mothers and their children. It is unknown whether pregnant women with PTSD, or symptoms of\ud PTSD, can receive targeted treatment that is safe and effective. \ud \ud Objective: The purpose of the present paper was to assess the effectiveness and safety of treatment for (symptoms of) PTSD in pregnant women. \ud \ud Method: A systematic review was conducted in accordance with the PRISMA guidelines in Pubmed, Embase, PsychINFO, and Cochrane. In addition, a case is presented of a pregnant woman with PTSD who received eye-movement desensitization and reprocessing (EMDR) therapy aimed at processing the memories of a previous distressing childbirth. \ud \ud Results: In total, 13 studies were included, involving eight types of interventions (i.e. trauma-focused cognitive behavioural therapy, exposure therapy, EMDR therapy, interpersonal psychotherapy, explorative therapy, self-hypnosis and relaxation, Survivor Moms\ud Companion, and Seeking Safety Intervention). In three studies, the traumatic event pertained to a previous childbirth. Five studies reported obstetrical outcomes. After requesting additional information, authors of five studies indicated an absence of serious adverse\ud events. PTSD symptoms improved in 10 studies. However, most studies carried a high risk of bias. In our case study, a pregnant woman with a PTSD diagnosis based on DSM-5 no longer fulfilled the criteria of PTSD after three sessions of EMDR therapy. She had an uncomplicated pregnancy and delivery. \ud \ud Conclusion: Despite the fact that case studies as the one presented here report no adverse events, and treatment is likely safe, due to the poor methodological quality of most studies it is impossible to allow inferences on the effects of any particular treatment of PTSD (symptoms) during pregnancy. Yet, given the elevated maternal stress and cortisol levels in pregnant women with PTSD, and the fact that so far no adverse effects on the unborn child have been reported associated with the application of trauma-focused therapy, treatment of PTSD during pregnancy is most likely safe.

Background After a traumatic childbirth experience, women are often afraid of future pregnancies, and may be at risk for also experiencing their subsequent childbirth as traumatic. Aims Two questions were investigated regarding women's experience of their subsequent childbirth after a previous traumatic birth: (1) which factors in the previous traumatic birth are associated with the subsequent childbirth experience, and (2) fear of childbirth and coping behaviour during the subsequent pregnancy associated with the subsequent birth experience. Methods A total 474 Dutch women (mean age during traumatic childbirth=28.9 years; SD=3.9) answered an online survey about their previous traumatic and subsequent birth experience. Findings Making a birth plan, choosing a home birth in a high-risk pregnancy, and having a planned caesarean section emerged as statistically significant correlates of positive subsequent birth experience. Conclusion Experiencing control over the subsequent birth might underlie practices associated with more positive subsequent childbirth experience among women with a traumatic childbirth history.

Introduction: Between 9 and 44% of women experience giving birth as traumatic, and 3% of women develop a post-traumatic stress disorder following childbirth. Knowledge on risk factors is abundant, but studies on treatment are limited. This study aimed to present an overview of means to prevent traumatic birth experiences and childbirth-related post-traumatic stress disorder. Material and methods: Major databases [Cochrane; Embase; PsycINFO; PubMed (Medline)] were searched using combinations of the key words and their synonyms. Results: After screening titles and abstracts and reading 135 full-text articles, 13 studies were included. All evaluated secondary prevention, and none primary prevention. Interventions included debriefing, structured psychological interventions, expressive writing interventions, encouraging skin-to-skin contact with healthy newborns immediately postpartum and holding or seeing the newborn after stillbirth. The large heterogeneity of study characteristics precluded pooling of data. The writing interventions to express feelings appeared to be effective in prevention. A psychological intervention including elements of exposure and psycho-education seemed to lead to fewer post-traumatic stress disorder symptoms in women who delivered via emergency cesarean section. Conclusions: No research has been done on primary prevention of traumatic childbirth. Research on secondary prevention of traumatic childbirth and post-traumatic stress disorder following delivery provides insufficient evidence that the described interventions are effective in unselected groups of women. In certain subgroups, results are inhomogeneous.

In some cases childbirth leads to negative psychological responses such as posttraumatic stress disorder (PTSD). Postpartum hemorrhage (PPH) is a common and major complication of childbirth, which occasionally requires emergency hysterectomy in severe cases. Patients often describe these complications as a traumatic experience. It is unknown whether PPH is a risk factor for developing PTSD. In this systematic review we summarize the current knowledge about the association between PPH with or without emergency hysterectomy and posttraumatic stress symptoms or PTSD. If PPH is a risk factor for PTSD, this will allow adequate preventive measures with the aim to reduce the long-term effects and socioeconomic problems associated with PTSD. To conduct this review MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials, Cochrane Library and PsycINFO databases were searched for publications between January 1986 and October 2017. Manuscripts evaluating the association between PPH and peripartum emergency hysterectomy and PTSD or posttraumatic stress symptoms were included. Fifty-two articles met the criteria for full-text review. Seven articles were included in this review. Five studies focused on the association between PPH and PTSD and two studies evaluated the association between emergency hysterectomy and PTSD. Three studies found no association between PPH and PTSD. Two studies reported a higher risk of developing PTSD or posttraumatic stress symptoms after PPH. Two studies reported a higher risk of developing PTSD after emergency hysterectomy. Meta-analysis was not possible due to the heterogeneity of these studies. Based on the results of these studies there may be an association between PPH and PTSD. Secondly, it seems likely that an association exists between emergency postpartum hysterectomy and PTSD, but the strength of this conclusion is limited by the small amount of studies included.

Background: Hyperemesis gravidarum (HG) leads to dehydration, poor nutritional intake, and weight loss. HG has been associated with adverse pregnancy outcomes such as low birth weight. Information about the potential effectiveness of treatments for HG is limited.Objective: We hypothesized that in women with HG, early enteral tube feeding in addition to standard care improves birth weight.Design: We performed a multicenter, open-label randomized controlled trial [Maternal and Offspring outcomes after Treatment of HyperEmesis by Refeeding (MOTHER)] in 19 hospitals in the Netherlands. A total of 116 women hospitalized for HG between 5 and 20 wk of gestation were randomly allocated to enteral tube feeding for >= 7 d in addition to standard care with intravenous rehydration and antiemetic treatment or to standard care alone. Women were encouraged to continue tube feeding at home. On the basis of our power calculation, a sample size of 120 women was anticipated. Analyses were performed according to the intention-to-treat principle.Results: Between October 2014 and March 2016 we randomly allocated 59 women to enteral tube feeding and 57 women to standard care. The mean 6 SD birth weight was 3160 +/- 770 g in the enteral tube feeding group compared with 3200 +/- 680 g in the standard care group (mean difference: -40 g, 95% CI: -230, 310 g). Secondary outcomes, including maternal weight gain, duration of hospital stay, readmission rate, nausea and vomiting symptoms, decrease in quality of life, psychological distress, prematurity, and small-for-gestationalage, also were comparable. Of the women allocated to enteral tube feeding, 28 (47%) were treated according to protocol. Enteral tube feeding was discontinued within 7 d of placement in the remaining women, primarily because of its adverse effects (34%).Conclusions: In women with HG, early enteral tube feeding does not improve birth weight or secondary outcomes. Many women discontinued tube feeding because of discomfort, suggesting that it is poorly tolerated as an early routine treatment of HG. This trial was registered at www.trialregister.nl as NTR4197.

Introduction: Postpartum symptoms of anxiety and depression are known to have a negative impact on mother and child, and major life events constitute a major risk factor for these symptoms. We aimed to investigate to what extent specific life events during pregnancy, delivery complications, unfavorable obstetric outcomes, and antenatal levels of anxiety or depression symptoms were independently associated with postpartum levels of anxiety and depression symptoms. Methods: Within a prospective population-based cohort study (n = 3842) in The Netherlands, antenatal symptoms of anxiety or depression were measured at the end of the first trimester and at five months postpartum. Antenatal life events were assessed during the third trimester, and information on delivery and obstetric outcomes was obtained from midwives and gynecologists. Linear regression analyses were performed to quantify the associations. Results: Antenatal levels of both anxiety and depression symptoms were associated with postpartum levels of anxiety and depression symptoms. Life events related to health and sickness of self or loved ones, to the relation with the partner or conflicts with loved ones, or to work, finance, or housing problems were significantly associated with higher postpartum levels of anxiety symptoms (p &lt, 0.001) and depression symptoms (p &lt, 0.001) adjusted for antenatal levels. No statistically significant results were observed for pregnancy-related events, delivery complications, or unfavorable obstetric outcomes. Conclusions: Women with increased antenatal levels of anxiety or depression symptoms are at increased risk of elevated levels of both postpartum depression and anxiety symptoms. Experiencing life events during pregnancy that were not related to the pregnancy was associated with higher levels of anxiety and depression in the postpartum period, as opposed to pregnancy-related events, delivery complications, or unfavorable obstetric outcomes. These results suggest that events during pregnancy but not related to the pregnancy and birth are a highly important predictor for postpartum mental health.

Contains fulltext : 205398.pdf (Publisher’s version ) (Open Access) INTRODUCTION: When women with a previous cesarean section and an unfavorable cervix have an indication for delivery, the choice is to induce labor or to perform a cesarean section. This study aims to assess the effectiveness and safety of a balloon catheter as a method of induction of labor in women with one previous cesarean section and an unfavorable cervix compared with an elective repeat cesarean section. MATERIAL AND METHODS: We performed a prospective cohort study in 51 hospitals in the Netherlands on term women with one previous cesarean section, a live singleton fetus in cephalic position, an unfavorable cervix and an indication for delivery. We recorded obstetric, maternal and neonatal characteristics. We compared the outcome of women who were induced with a balloon catheter with the outcome of women who delivered by elective repeat cesarean section. Main outcomes were maternal and neonatal morbidity. Mode of delivery was a secondary outcome for women who were induced. Adjusted odds ratios (aOR) were calculated using logistic regression, adjusted for potential confounders. RESULTS: Analysis was performed on 993 women who were induced and 321 women who had a repeat cesarean section (August 2011 until September 2012). Among the women who were induced, 560 (56.4%) delivered vaginally and 11 (1.1%) sustained a uterine rupture. Composite adverse maternal outcome (uterine rupture, severe postpartum hemorrhage or postpartum infection) occurred in 73 (7.4%) in the balloon and 14 (4.5%) women in the repeat cesarean section group (aOR 1.58, 95% confidence interval [CI] 0.85-2.96). Composite adverse neonatal outcome (Apgar score

Problem: Low socioeconomic status and prior negative life events are documented risk factors for antenatal anxiety and depression, preterm birth and birth weight. We aimed to asses whether the adverse effects of prior negative life events increase with lower socioeconomic status and which aspects of socioeconomic status are most relevant.Methods: We performed a population-based cohort study in the Netherlands including 5398 women in their first trimester of pregnancy. We assessed the number of negative life events prior to pregnancy, aspects of paternal and maternal socio-economic position and symptoms of anxiety and depression. Associations of the number of prior negative life events with anxiety, depression, low birth weight and gestational age were quantified.Findings: The number of prior negative life events, particularly when they had occurred in the two years before pregnancy and maternal aspects of low socioeconomic status (educational level, unemployment and income) were associated with antenatal anxiety and depression. Furthermore, low socioeconomic status increased the adverse effects of prior negative life events. Obstetric outcomes showed similar trends, although mostly not statistically significant.Discussion: Low socioeconomic status and prior negative life events both have an adverse effect on antenatal anxiety and depression. Furthermore, low socioeconomic status increases the adverse impact of prior negative life events on anxiety and depressive symptoms in pregnancy.Conclusion: Interventions for anxiety and depression during pregnancy should be targeted particularly to unemployed, less-educated or low-income women who recently experienced negative life events. (c) 2018 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

Lymphangioleiomyomatosis (LAM) is a progressive cystic lung disease which mostly affects premenopausal women and could be exacerbated by pregnancy. Therefore, it is thought that oestrogen plays an important role in LAM pathogenesis. Here, a case of LAM is described in which the first presentation of symptoms occurred during the third trimester of pregnancy. Symptoms included acute onset dyspnoea and chest pain at gestational age of 39 weeks and 2 days. A CT was performed which showed multiple thin-walled cysts and a small pneumothorax. Serum levels of vascular endothelial growth factor-D (VEGF-D) was 1200 pg/mL. The typical cystic lung changes on chest CT in combination with elevated VEGF-D is diagnostic for LAM. Given the risk of respiratory complications, the decision was made to deliver the baby at a gestational age of 39 weeks and 6 days by a planned caesarean section. Both mother and child were discharged home in good condition.

When pregnancy complications pose a threat to the mother or fetus or both, induction of labor is often required. Induction of labor is accomplished through a variety of methods; in pregnant women having an unfavourable cervix, cervical ripening of the cervix is accomplished through various mechanical and pharmacological means. Oral misoprostol and Foley catheter are believed to be equally effective in women with an unfavorable cervix in accomplishing vaginal birth. The current open-label randomized noninferiority trial was conducted in pregnant women with a singleton gestation in 29 hospitals in the Netherlands (2012 to 2013) to directly compare oral misoprostol with Foley catheter. Women with a viable singleton pregnancy in cephalic presentation, intact membranes, gestational age of 37 weeks or more, and an unfavorable cervix were included in the trial. The women were then randomly allocated (1:1) to oral misoprostol (n = 932) or Foley catheter (n = 927). Oral misoprostol dosage given was 50 µg orally once every 4 hours with a maximum of 3 times a day. Placement of a 30-mL Foley catheter in the cervix was done either digitally or using a vaginal speculum. The results of the study showed that the primary outcome (asphyxia or postpartum hemorrhage) occurred in 12.2% women in the misoprostol group and in 11.5% women in the Foley catheter group (adjusted relative risk [RR], 1.06; 90% confidence interval [CI], 0.86–1.31). Cesarean delivery resulted in 16.8% of labors in the misoprostol group and in 20.1% of the time in the Foley catheter group (no significant difference between groups [RR, 0.84; 95% CI, 0.69–1.01]). When the indication for cesarean delivery was examined, fewer cesarean deliveries for failure to progress in the first stage occurred after induction in the misoprostol group than in the Foley catheter group (6.2% vs 10.6%; RR, 0.58; 95% CI, 0.42–0.79). In addition, operative vaginal delivery occurred more frequently in the misoprostol group. Among the misoprostol group spontaneous membrane rupture was more common and labor augmentation with oxytocin was less likely. The study leads to a conclusion that in terms of safety and effectiveness, induction of labour using oral misoprostol is as safe as mechanical induction using Foley catheter.

Contains fulltext : 152606.pdf (Publisher’s version ) (Open Access) Objective The aim of this study was to assess which characteristics and results of vaginal examination are predictive for delivery within 7 days, in women with threatened preterm labor after initial treatment. Study Design A secondary analysis of a randomized controlled trial on maintenance nifedipine includes women who remained undelivered after threatened preterm labor for 48 hours. We developed one model for women with premature prelabor rupture of membranes (PPROM) and one without PPROM. The predictors were identified by backward selection. We assessed calibration and discrimination and used bootstrapping techniques to correct for potential overfitting. Results For women with PPROM (model 1), nulliparity, history of preterm birth, and vaginal bleeding were included in the multivariable analysis. For women without PPROM (model 2), maternal age, vaginal bleeding, cervical length, and fetal fibronectin (fFN) status were in the multivariable analysis. Discriminative capability was moderate to good (c-statistic 0.68; 95% confidence interval [CI] 0.60-0.77 for model 1 and 0.89; 95% CI, 0.84-0.93 for model 2). Conclusion PPROM and vaginal bleeding in the current pregnancy are relevant predictive factors in all women, as are maternal age, cervical length, and fFN in women without PPROM and nulliparity, history of preterm birth in women with PPROM.

Item does not contain fulltext OBJECTIVE: The pharmacokinetics of nifedipine as a tocolytic agent has not been studied in great detail in pregnant women and has instead focused on immediate release tablets and gastrointestinal therapeutic system (GITS) tablets. The aim of this study was to determine nifedipine slowrelease half-life and distribution volume in pregnant women and to compare these with pharmacokinetic parameters of nifedipine in non-pregnant subjects described in the literature. MATERIALS: This is a study parallel to a trial studying women with threatened preterm labor between 26 + 0 and 32 + 2 weeks after initial tocolysis and a completed course of corticosteroids, who were randomly allocated to maintenance nifedipine (slow-release tablets 20 mg 4 times daily) or placebo. Exclusion criteria for the pharmacokinetic study were contra-indications for nifedipine, impaired liver function, and concomitant intake of inhibitors or inducers of the cytochrome P450 3A4 isoenzyme. Blood samples for measuring nifedipine plasma concentrations were drawn at t = 0, t = 12 hours, t = 24 hours, t = 48 hours, t = 72 hours, t = 7 days, and t = 9 days. METHODS: Pharmacokinetic parameters were estimated using iterative two-stage Bayesian population pharmacokinetic analysis by MWPharm(c) software. The study was designed to establish a correlation between body weight and nifedipine plasma level. RESULTS: The pharmacokinetic parameters of nifedipine slow-release tablets were determined from the data of 8 pregnant women. Nifedipine slow-release had a half-life of 2 - 5 hours, a mean distribution volume of 6.2 +/- 1.9 L/kg (calculated while using a fixed biological availability of 0.45 taken from the literature due to lack of intravenous data in this population) compared to a half-life of 6 - 11 hours, and a distribution volume of 1.2 - 1.3 L/kg described in non-pregnant subjects in the literature. None of the women delivered during study medication. Study medication was continued for the duration of the pharmacokinetic study (9 days) in all women. A correlation between nifedipine plasma levels and maternal body weight was not demonstrated. This may have been caused by lack of power. CONCLUSION: Pregnant subjects in this study, using nifedipine slow-release tablets, showed a larger volume of distribution and a shorter elimination half-life than for non-pregnant subjects as published in the literature.

Objectives: To describe the incidence and predictive factors for massive haemorrhage during a caesarean delivery in women with placenta praevia. Methods: We performed a retrospective cohort study among consecutive women with a placenta praevia planned for a caesarean delivery between 2001-2011 in one academic centre and two teaching hospitals in the Netherlands. Massive haemorrhage was defined as ≥1000 mL blood loss during caesarean section. We used logistic regression analysis to assess which maternal and pregnancy characteristics were predictors for massive haemorrhage during caesarean delivery. Results: Of 54,794 deliveries, we identified 215 (0.39%) women with placenta praevia who underwent a Caesarean delivery, of whom 94 (44%) had massive haemorrhage at or after surgery. After univariable preselection, multivariable logistic regression indicated that higher maternal age (OR 2.09; 95% CI 1.17 - 3.74), no Caucasian ethnicity (OR 1.73; 95% CI 0.92 - 3.27), multiple pregnancy (OR 3.92; 95% CI 0.72 - 21.28), lower systolic blood pressure during pregnancy (OR 1.03; 95% CI 1.00 - 1.07) and the placenta located at the anterior wall (OR 2.21; 95% CI 1.20 - 4.04) were independent predictors for massive haemorrhage during a caesarean delivery in women with placenta praevia. Predicted probabilities varied between 22% and 71%. The model has a reasonable discriminative ability and acceptable calibration. Conclusions: Women with placenta praevia are at high risk for massive haemorrhage during caesarean delivery. The risk profile can be used to identify extreme high-risk women in whom extensive preventive measures are justified.

Objective: To determine the influence of socio-demographic, clinical parameters and obstetric complications on postpartum health-related quality of life (HRQoL).Study design: We used data of three randomized controlled trials to investigate HRQoL determinants in women after an obstetric complication. The DIGITAT and HYPITAT trials compared induction of labor and expectant management in women with intra-uterine growth restriction (IUGR) and hypertensive disorders. The WOMB trial randomized anemic women after postpartum hemorrhage to red blood cell transfusion or expectant management. The HRQoL-measure Short-Form36 was completed at six weeks postpartum. Multivariable analyses were used to identify which parameters affected the Short-Form36 physical component score (PCS) and mental component score (MCS).Results: HRQoL analyses included 1391 women (60%) of the 2310 trial participants. HYPITAT and DIGITAT participants had significantly lower MCS than WOMB participants. In multivariable analysis, PCS after elective and emergency cesarean section was 5-6 points lower than after vaginal delivery. Gestational hypertension, neonatal admission and delivery in an academic hospital had a small negative effect on PCS. No effect was found for randomization status, maternal age, BMI, country of birth, education, parity, induction of labor, analgesics, birth weight, perineal laceration, delivery of placenta, postpartum hemorrhage, congenital anomaly, urinary tract infection, thromboembolic event or endometritis. MCS was influenced only mildly by these parameters.Conclusions: IUGR and hypertensive disorders lead to lower HRQoL scores postpartum than PPH. In a heterogeneous obstetric population, only mode of delivery by cesarean section has a profound, negative impact, on physical HRQoL (PCS). No profound impacts on MCS were detected. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

Objective To compare the effectiveness of the oxytocin receptor antagonist atosiban with the beta mimetic fenoterol as uterine relaxants in women undergoing external cephalic version (ECV) for breech presentation. Design Multicentre, open label, randomised controlled trial. Setting Eight hospitals in the Netherlands, August 2009 to May 2014. Participants 830 women with a singleton fetus in breech presentation and a gestational age of more than 34 weeks were randomly allocated in a 1:1 ratio to either 6.75 mg atosiban (n=416) or 40 μg fenoterol (n=414) intravenously for uterine relaxation before ECV. Main outcome measures The primary outcome measures were a fetus in cephalic position 30 minutes after the procedure and cephalic presentation at delivery. Secondary outcome measures were mode of delivery, incidence of fetal and maternal complications, and drug related adverse events. All analyses were done on an intention-to-treat basis. Results Cephalic position 30 minutes after ECV occurred significantly less in the atosiban group than in the fenoterol group (34% v 40%, relative risk 0.73, 95% confidence interval 0.55 to 0.93). Presentation at birth was cephalic in 35% (n=139) of the atosiban group and 40% (n=166) of the fenoterol group (0.86, 0.72 to 1.03), and caesarean delivery was performed in 60% (n=240) of women in the atosiban group and 55% (n=218) in the fenoterol group (1.09, 0.96 to 1.20). No significant differences were found in neonatal outcomes or drug related adverse events. Conclusions In women undergoing ECV for breech presentation, uterine relaxation with fenoterol increases the rate of cephalic presentation 30 minutes after the procedure. No statistically significant difference was found for cephalic presentation at delivery. Trial registration Dutch Trial Register, NTR 1877.

Objective The objective of this study was to identify the predictors of emergency delivery in women with placenta previa. Methods This is a retrospective study of pregnancies complicated by placenta previa, scheduled for a cesarean delivery between 2001 and 2011. Using univariable and multivariable regression predictors for emergency delivery in these women were determined. Predictive performance was assessed using receiver operating characteristic analysis and calibration plot. Internal validation was performed by bootstrap analysis. Results Of 214 women with singleton pregnancies, 93 (43%) had an emergency cesarean delivery, and 43 (20%) were preterm. Independent predictors for emergency delivery were history of cesarean section (odds ratio [OR], 4.7; 95% confidence interval [CI], 1.2-12), antepartum bleeding with one (OR, 7.5; 95% CI, 2.5-23), two (OR, 14; 95% CI, 4.3-47), and three or more episodes (OR, 27; 95% CI, 8.3-90) as well as need for blood transfusion (OR, 6.4; 95% CI, 1.7-23). For emergency preterm delivery, covariates were comparable. The area under the curve was 0.832 on the original data and 0.821 on the bootstrap samples. Conclusion Predictors for emergency delivery in women with placenta previa can be used for individualized antenatal care concerning timing of delivery and corticosteroid cover. Potentially, careful selection in women with placenta previa can result in more conservative treatment in an outpatient setting and reduction of iatrogenic preterm delivery.

Introduction During preeclampsia, the leading cause of maternal death in developed countries, the levels of proinflammatory cytokines, like TNF-α and IFN-γ, are increased. These proinflammatory cytokines have the potential to induce the secretion of Guanylate-Binding Protein-1 (GBP-1), a factor regulating angiogenesis, by endothelial cells. We hypothesized that the plasma levels of GBP-1 would be increased during pregnancy and even further during preeclampsia (PE). Objective The objective of this study was te measure GBP-1 in pregnancy and preeclampsia. Methods GBP-1 was measured in peripheral plasma samples by ELISA. These plasma samples were collected from 6 severe late-onset PE and 48 severe early-onset PE pregnancies, 42 gestational age matched healthy pregnant women (25 for the early-onset and 17 for the late-onset PE) and 22 non-pregnant women. The levels of GBP-1 mRNA were determined in biopsies of the chorionic villi from 13 healthy pregnancies, 9 severe early-onset PE and 6 severe late-onset PE pregnancies using qPCR. Results The GBP-1 concentration of severe early-onset PE pregnancies (median 31 pg/ml; 95%CI 12 – 72 pg/ml) and those with severe late-onset PE (median 50 pg/ml; 42 – 68 pg/ml) were comparable (Mann Whitney, p = 0.518), but both were significantly decreased as compared to their gestational matched healthy pregnancies (respective medians 94 pg/ml (95%CI 77 – 160 pg/ml) and 117 pg/ml (95%CI 103 – 234 pg/ml) and Mann Whitney respectively p Conclusions In line with our hypothesis, GBP-1 plasma levels were increased during pregnancy. In contrast to our hypothesis we observed decreased GBP-1 plasma levels during PE as compared to healthy pregnancy. Although the placenta may be the source of increased GBP-1 during pregnancy, the reason why GBP-1 is decreased in preeclampsia remains to be established. More research is needed to get insight into the GBP-1 production during pregnancy and preeclampsia.

Introduction We recently showed that a cervical pessary prevents preterm birth and reduces poor neonatal outcomes in women with a twin pregnancy and a short cervix (

There is ample evidence from observational prospective studies that maternal depression or anxiety during pregnancy is a risk factor for adverse psychosocial outcomes in the offspring. However, to date no previous study has demonstrated that treatment of depressive or anxious symptoms in pregnancy actually could prevent psychosocial problems in children. Preventing psychosocial problems in children will eventually bring down the huge public health burden of mental disease. The main objective of this study is to assess the effects of cognitive behavioural therapy in pregnant women with symptoms of anxiety or depression on the child's development as well as behavioural and emotional problems. In addition, we aim to study its effects on the child's development, maternal mental health, and neonatal outcomes, as well as the cost-effectiveness of cognitive behavioural therapy relative to usual care.We will include 300 women with at least moderate levels of anxiety or depression at the end of the first trimester of pregnancy. By including 300 women, we will be able to demonstrate effect sizes of 0.35 or more on the total problems scale of the Child Behaviour Checklist 1.5-5 with alpha 5 % and power (1-beta) 80 %.Women in the intervention arm are offered 10-14 individual cognitive behavioural therapy sessions, 6-10 sessions during pregnancy and 4-8 sessions after delivery (once a week). Women in the control group receive care as usual.Primary outcome is behavioural/emotional problems at 1.5 years of age as assessed by the total problems scale of the Child Behaviour Checklist 1.5-5 years.Secondary outcomes are mental, psychomotor and behavioural development of the child at age 18 months according to the Bayley scales; maternal anxiety and depression during pregnancy and postpartum; and neonatal outcomes such as birth weight, gestational age and Apgar score, health-care consumption and general health status (economic evaluation).NTR2242.

Women with multiple gestations often deliver at less than 37 weeks, increasing the risks of perinatal morbidity and mortality. Treatment with a pessary might prevent preterm birth by changing the inclination of the cervical canal and preventing premature dilatation of the cervix, rupture of the membranes, and deterioration or loss of the cervical mucous plug. This multicenter, open-label, randomized controlled trial at 40 hospitals was performed to determine whether a cervical pessary could prevent poor perinatal outcomes in parturients with a multiple pregnancy. At 12 to 20 weeks' gestation, patients were assigned to the pessary or control group; cervical length was measured at 16 to 22 weeks. Women in the study group received an Arabin pessary at 16 to 20 weeks, which was removed in week 36 or in case of preterm premature rupture of the membranes, active vaginal bleeding, other signs of preterm labor, or patient discomfort. Obstetric care was otherwise similar in the 2 groups. The primary outcome was a composite of poor perinatal outcomes, including stillbirth, preventricular leukomalacia, severe respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, sepsis, and neonatal death within 6 weeks after the anticipated term date. Secondary outcomes were time to delivery, preterm birth at less than 32 and less than 37 weeks, days in the neonatal intensive care unit, days of maternal admission for preterm labor, and maternal morbidity. A total of 401 of 403 women in the pessary group and 407 of 410 in the control group completed the study. Five women in the pessary group had a surgical cerclage; 1 patient died, and the others delivered at 21.6 to 36.7 weeks, with 3 having poor perinatal outcomes. No patients in the control group had a cerclage. Vaginal discharge occurred in 104 women (26%) in the pessary group and in none of the controls. The pessary was removed from 57 women (14%) at less than 28 weeks and from 22 women (5%) at 28 to 32 weeks; 7 and 13, respectively, delivered within 48 hours of removal. At 32 to 36 weeks, the pessary was removed from 107 women; 70 delivered within 48 hours. The most common reasons for pessary removal in these women were preterm premature rupture of the membranes, vaginal bleeding, contractions, and induction of labor. The composite poor perinatal outcome occurred in 53 women (13%) and 55 women (14%) in the pessary and control groups, respectively (relative risk (RR), 0.98; 95% confidence interval, 0.69-1.39). Ten stillbirths (2%) occurred in each group. The other conditions within the composite outcome did not differ between the 2 groups. In the pessary and control groups, 16 and 18 infants, respectively, died before discharge. The groups were similar in median gestational age at delivery; frequencies of delivery at less than 28, less than 32, and less than 37 weeks; and frequency and length of neonatal intensive care unit admission. In the women with a cervical length of less than 25th percentile (

Objective: To explore hospital costs by pregnant women with a history of early-onset preeclampsia or HELLP syndrome, managed according to customary, but non-standardized prenatal care, by relating maternal and child outcome to maternal health care expenditure. Study design: This was a cohort study, in women of 18 years or older who suffered from early-onset preeclampsia or HELLP syndrome in their previous pregnancy (n = 104). We retrieved data retrospectively from hospital information systems and medical records of patients who had received customary, non-standardized prenatal care between 1996 and 2012. Our analyses focused on the costs generated between the first antenatal visit at the outpatient clinic and postpartum hospital discharge. Outcome measures were hospital resource use, costs, maternal and child outcome (recurrence of preeclampsia or HELLP syndrome, incidence of eclampsia, gestational age at delivery, intrauterine fetal demise, small-for-gestational-age birth and low 5 min Apgar score). We used linear regression analyses to evaluate whether maternal and child outcome and baseline characteristics correlated with hospital costs. Results: Maternal hospital costs per patient averaged (sic) 8047. The main cost drivers were maternal admissions and outpatient visits, together accounting for 80% of total costs. Primary cost drivers were preterm birth and recurrent preeclampsia or HELLP syndrome. Conclusion: Hospital costs in the next pregnancy of formerly preeclamptic women varied widely with over 70% being medically unexplainable. The results of this study support the view that care standardization in these women can be expected to improve costs and efficacy of care without compromising outcome. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

A 32-year-old primigravida presented at our emergency room at 6 weeks of gestation with acute severe right upper quadrant abdominal pain, radiating to the right flank. Vital signs were stable. Abdominal ultrasound showed a round inhomogeneous mass of 10 cm diameter behind the right kidney, suspected for adrenal haemorrhage. The patient was admitted for observation. An MRI showed some right-sided pleural effusion and a round mass in the adrenal region with no recognisable adrenal gland, therefore most likely originating from the right adrenal. After 10 days the patient was discharged with no change in size of the haematoma. MRI was carried out every 2 months which showed a decrease in size of the haematoma, with no other abnormalities. Based on stable MRI and the patient’s preference, a vaginal delivery mode was chosen. At 37 weeks of gestation labour was induced, followed by an uncomplicated delivery.

Contains fulltext : 118346.pdf (Publisher’s version ) (Open Access) IMPORTANCE: In threatened preterm labor, maintenance tocolysis with nifedipine, after an initial course of tocolysis and corticosteroids for 48 hours, may improve perinatal outcome. OBJECTIVE: To determine whether maintenance tocolysis with nifedipine will reduce adverse perinatal outcomes due to premature birth. DESIGN, SETTING, AND PARTICIPANTS: APOSTEL-II (Assessment of Perinatal Outcome with Sustained Tocolysis in Early Labor) is a double-blind, placebo-controlled trial performed in 11 perinatal units including all tertiary centers in The Netherlands. From June 2008 to February 2010, women with threatened preterm labor between 26 weeks (plus 0 days) and 32 weeks (plus 2 days) gestation, who had not delivered after 48 hours of tocolysis and a completed course of corticosteroids, were enrolled. Surviving infants were followed up until 6 months after birth (ended August 2010). INTERVENTION: Randomization assigned 406 women to maintenance tocolysis with nifedipine orally (80 mg/d; n = 201) or placebo (n = 205) for 12 days. Assigned treatment was masked from investigators, participants, clinicians, and research nurses. MAIN OUTCOME MEASURES: Primary outcome was a composite of adverse perinatal outcomes (perinatal death, chronic lung disease, neonatal sepsis, intraventricular hemorrhage >grade 2, periventricular leukomalacia >grade 1, or necrotizing enterocolitis). Analyses were completed on an intention-to-treat basis. RESULTS: Mean (SD) gestational age at randomization was 29.2 (1.7) weeks for both groups. Adverse perinatal outcome was not significantly different between groups: 11.9% (24/201; 95% CI, 7.5%-16.4%) for nifedipine vs 13.7% (28/205; 95% CI, 9.0%-18.4%) for placebo (relative risk, 0.87; 95% CI, 0.53-1.45). CONCLUSIONS AND RELEVANCE: In patients with threatened preterm labor, nifedipine-maintained tocolysis did not result in a statistically significant reduction in adverse perinatal outcomes when compared with placebo. Although the lower than anticipated rate of adverse perinatal outcomes in the control group indicates that a benefit of nifedipine cannot completely be excluded, its use for maintenance tocolysis does not appear beneficial at this time. TRIAL REGISTRATION: trialregister.nl Identifier: NTR1336.

Contains fulltext : 172293.PDF (Publisher’s version ) (Open Access) BACKGROUND: There is an ongoing discussion on the rising CS rate worldwide. Suboptimal guideline adherence may be an important contributor to this rise. Before improvement of care can be established, optimal CS care in different settings has to be defined. This study aimed to develop and measure quality indicators to determine guideline adherence and identify target groups for improvement of care with direct effect on caesarean section (CS) rates. METHOD: Eighteen obstetricians and midwives participated in an expert panel for systematic CS quality indicator development according to the RAND-modified Delphi method. A multi-center study was performed and medical charts of 1024 women with a CS and a stratified and weighted randomly selected group of 1036 women with a vaginal delivery were analysed. Quality indicator frequency and adherence were scored in 2060 women with a CS or vaginal delivery. RESULTS: The expert panel developed 16 indicators on planned CS and 11 indicators on unplanned CS. Indicator adherence was calculated, defined as the number of women in a specific obstetrical situation in which care was performed as recommended in both planned and unplanned CS settings. The most frequently occurring obstetrical situations with low indicator adherence were: 1) suspected fetal distress (frequency 17%, adherence 46%), 2) non-progressive labour (frequency 12%, CS performed too early in over 75%), 3) continuous support during labour (frequency 88%, adherence 37%) and 4) previous CS (frequency 12%), with adequate counselling in 15%. CONCLUSIONS: We identified four concrete target groups for improvement of obstetrical care, which can be used as a starting point to reduce CS rates worldwide.

Contains fulltext : 108337.pdf (Publisher’s version ) (Open Access) BACKGROUND: At present, there is insufficient evidence to guide appropriate management of women with preterm prelabor rupture of membranes (PPROM) near term. METHODS AND FINDINGS: We conducted an open-label randomized controlled trial in 60 hospitals in The Netherlands, which included non-laboring women with >24 h of PPROM between 34(+0) and 37(+0) wk of gestation. Participants were randomly allocated in a 1:1 ratio to induction of labor (IoL) or expectant management (EM) using block randomization. The main outcome was neonatal sepsis. Secondary outcomes included mode of delivery, respiratory distress syndrome (RDS), and chorioamnionitis. Patients and caregivers were not blinded to randomization status. We updated a prior meta-analysis on the effect of both interventions on neonatal sepsis, RDS, and cesarean section rate. From 1 January 2007 to 9 September 2009, 776 patients in 60 hospitals were eligible for the study, of which 536 patients were randomized. Four patients were excluded after randomization. We allocated 266 women (268 neonates) to IoL and 266 women (270 neonates) to EM. Neonatal sepsis occurred in seven (2.6%) newborns of women in the IoL group and in 11 (4.1%) neonates in the EM group (relative risk [RR] 0.64; 95% confidence interval [CI] 0.25 to 1.6). RDS was seen in 21 (7.8%, IoL) versus 17 neonates (6.3%, EM) (RR 1.3; 95% CI 0.67 to 2.3), and a cesarean section was performed in 36 (13%, IoL) versus 37 (14%, EM) women (RR 0.98; 95% CI 0.64 to 1.50). The risk for chorioamnionitis was reduced in the IoL group. No serious adverse events were reported. Updating an existing meta-analysis with our trial results (the only eligible trial for the update) indicated RRs of 1.06 (95% CI 0.64 to 1.76) for neonatal sepsis (eight trials, 1,230 neonates) and 1.27 (95% CI 0.98 to 1.65) for cesarean section (eight trials, 1,222 women) for IoL compared with EM. CONCLUSIONS: In women whose pregnancy is complicated by late PPROM, neither our trial nor the updated meta-analysis indicates that IoL substantially improves pregnancy outcomes compared with EM. TRIAL REGISTRATION: Current Controlled Trials ISRCTN29313500

Contains fulltext : 96560.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To estimate whether administration of 17alpha-hydroxyprogesterone caproate can prevent neonatal morbidity in multiple pregnancies by reducing the preterm birth rate. METHODS: We conducted a multicenter, double-blind, placebo-controlled randomized trial in 55 obstetric clinics in the Netherlands. Women with a multiple pregnancy were randomized to weekly injections of either 250 mg 17alpha-hydroxyprogesterone caproate or placebo, starting between 16 and 20 weeks of gestation and continuing until 36 weeks of gestation. The main outcome measure was adverse neonatal outcome. Secondary outcome measures were gestational age at delivery and delivery before 28, 32, and 37 weeks of gestation. RESULTS: We randomized 671 women. A composite measure of adverse neonatal outcome was present in 110 children (16%) born to mothers in the 17alpha-hydroxyprogesterone caproate group, and in 80 children (12%) of mothers in the placebo group (relative risk [RR] 1.34; 95% confidence interval [CI] 0.95-1.89). The mean gestational age at delivery was 35.4 weeks for the 17alpha-hydroxyprogesterone caproate group and 35.7 weeks for the placebo group (P=.32). Treatment with 17alpha-hydroxyprogesterone caproate did not reduce the delivery rate before 28 weeks (6% in the 17alpha-hydroxyprogesterone caproate group compared with 5% in the placebo group, RR 1.04; 95% CI 0.56-1.94), 32 weeks (14% compared with 10%, RR 1.37; 95% CI 0.91-2.05), or 37 weeks of gestation (55% compared with 50%, RR 1.11; 95% CI 0.97-1.28). CONCLUSION: 17alpha-hydroxyprogesterone caproate does not prevent neonatal morbidity or preterm birth in multiple pregnancies. CLINICAL TRIAL REGISTRATION: ISRCTN Register, www.isrctn.org, ISRCTN40512715.

Background Preeclampsia and HELLP syndrome may have serious consequences for both mother and fetus. Women who have suffered from preeclampsia or the HELLP syndrome, have an increased risk of developing preeclampsia in a subsequent pregnancy. However, most women will develop no or only minor complications. In this study, we intend to determine cost-effectiveness of recurrence risk guided care versus care as usual in pregnant women with a history of early-onset preeclampsia. Methods/design We developed a prediction model to estimate the individual risk of recurrence of early-onset preeclampsia and the HELLP syndrome. In a before-after study, pregnant women with preeclampsia or HELLP syndrome in their previous pregnancy receiving care as usual (before introduction of the prediction model) will be compared with women receiving recurrence risk guided care (after introduction of the prediction model). Eligible and pregnant women will be recruited at six university hospitals and seven large non-university tertiary referral hospitals in the Netherlands. The primary outcome measure is the recurrence of early-onset preeclampsia or HELLP syndrome in women allocated to the regular monitoring group. For the economic evaluation, a modelling approach will be used. Costs and effects of recurrence risk guided care with those of care as usual will be compared by means of a decision model. Two incremental cost-effectiveness ratios will be calculated: 1) cost per Quality Adjusted Life Year (mother unit of analysis) and 2) cost per live born child (child unit of analysis). Discussion This is, to our knowledge, the first study that evaluates prospectively the efficacy of a multivariable prediction rule for recurrent hypertensive disease in pregnancy. Results of this study could either be integrated into the current guideline on Hypertensive Disorders in Pregnancy, or be used to develop a new guideline.

Background Preterm labour is the main cause of perinatal morbidity and mortality in the Western world. At present, there is evidence that tocolysis for 48 hours is useful in women with threatened preterm labour at least before 32 weeks. This allows transfer of the patient to a perinatal centre, and maximizes the effect of corticosteroids for improved neonatal survival. It is questionable whether treatment with tocolytics should be maintained after 48 hours. Methods/Design The APOSTEL II trial is a multicentre placebo-controlled study. Pregnant women admitted for threatened preterm labour who have been treated with 48 hours corticosteroids and tocolysis will be eligible to participate in the trial between 26+0 and 32+2 weeks gestational age. They will be randomly allocated to nifedipine (intervention) or placebo (control) for twelve days or until delivery, whatever comes first. Primary outcome is a composite of perinatal death, and severe neonatal morbidity up to evaluation at 6 months after birth. Secondary outcomes are gestational age at delivery, number of days in neonatal intensive care and total days of the first 6 months out of hospital. In addition a cost-effectiveness analysis will be performed. Analysis will be by intention to treat. The power calculation is based on an expected 11% difference in adverse neonatal outcome. This implies that 406 women have to be randomised (two sided test, β 0.2 at alpha 0.05). Discussion This trial will provide evidence as to whether maintenance tocolysis reduces severe perinatal morbidity and mortality in women with threatened preterm labour before 32 weeks. Trial Registration Clinical trial registration: http://www.trialregister.nl, NTR 1336, date of registration: June 3rd 2008.

Objective: Plasma hemopexin activity, associated with increased vascular permeability, was evaluated in healthy pregnant and non-pregnant women and in pre-eclamptic women. Methods: Hemopexin activity and the hemopexin inhibitor, extracellular ATP, were assayed in plasma from pregnant (n=10), preeclamptic (n=9), and non-pregnant women (n=10) using standard methods. Abdominal fascia tissue fragments from preeclamptic and pregnant women were immunohistochemically stained for vascular ectoapyrase or ecto-5'nucleotidase. Results: The data show significantly enhanced Hx activity exclusively in plasma from pregnant women and significantly enhanced plasma ATP in pre-eclamptic women compared with the other groups. Dephosphorylation of preeclamptic plasma resulted in reactivation of Hx activity. Fascia tissue-samples from preeclamptic women showed reduced ecto-apyrase activity and enhanced ecto-5'nucleotidase activity compared to pregnant women. Conclusion: Enhanced hemopexin activity may be associated with normal pregnancy, but not with preeclampsia. Decreased hemopexin in pre-eclamptic patients may be due to enhanced plasma ATP, which is possibly promoted by diminished activity of vascular ecto-apyrase.

Introduction Depression is among the leading causes of disability adjusted life years. For women in their fertile ages the occurrence of depression is of great impact for their selves and families. We analyzed the association between term hypertensive pregnancy disorders and depression scores. Methods Two to six years after pregnancy, women with a history of term preeclampsia or gestational hypertension were included in the hypertensive pregnancy cohort (HTP cohort) (n = 257). Controls were women who had an uncomplicated pregnancy (n = 83) (NTP cohort).The Edinburgh Postnatal Depression Scale (EPDS score) (Cox et al., 1987) was used to determine individual depression scores. Depression was defined as an EPDS score >12 or the use of antidepressants. Potential differences between groups were compared using the Student’s T test, the Chi-squared test ( X 2 test), or the Mann–Whitney U test when appropriate. We used logistic regression analyses to adjust for potential confounders. Results Women in the HTP cohort had higher depression scores than women in the NTP cohort (Table 1) and were more often depressed (OR 5.8 (1.4–24.6)). After correction for parity (adjusted OR 1.3 (0.8–2.0), BMI (adjusted OR 1.2 (1.1–1.2) and antihypertensive medication use (adjusted OR 1.1 (0.3–3.8), no significant differences were found in depression rates with an adjusted OR 4.2 (0.9–18.8). Conclusion More than three years postpartum women with a history of term hypertensive pregnancy disorders are more often depressed compared to women with a history of a normotensive pregnancy. Download : Download full-size image

In fertile women, the laparoscopic Roux-en-Y gastric bypass (LRYGB) is being increasingly performed. Pregnancy and LRYGB both give an increased risk of intussusception, which can lead to bowel necrosis, sepsis and preterm labour. We describe two pregnant women with a history of LRYGB who presented to the emergency department with non-specific abdominal pain. Both were diagnosed with intussusception. These cases illustrate that intussusception should be considered in pregnant women with a history of LRYGB who present with non-specific abdominal pain. Only MRI, CT scan or diagnostic laparoscopy is sufficient for diagnosis. Early diagnosis may prevent serious complications.

ESM-1 plays a role in the regulation of angiogenesis and is released by activated endothelial cells.To test the hypothesized that ESM-1 is increased in preeclampsia (PE).Plasma samples from high risk pregnancies divided in 23 healthy (CON), 11 severe early-onset PE (SE) and 7 severe late-onset PE (SL) pregnancies were collected at regular intervals between week 12 and birth. ESM-1 was measured by ELISA.(see figure) Between GA week 24 and birth, ESM-1 concentrations were significantly increased in both early and late preeclampsia compared to controls (Mann Whitney, p0.05). Surprisingly, the concentration of ESM-1 also differed between the three groups at weeks 12 and 16. The ESM-1 concentration of healthy pregnancies (mean±SEM:1857±861pg/ml) and those that developed severe late-onset PE (1298±371pg/ml) are comparable, but in those pregnancies that develop severe early-onset PE, the concentration (410±355pg/ml) is significantly lower as compared with healthy pregnancies.ESM-1 concentrations are increased during early and late severe preeclampsia, which may be due to endothelial cell activation in these conditions. Interestingly, since ESM-1 is decreased at 12-16 weeks in patients that later on develop early onset severe PE, it might be a prognostic marker which can determine the risk of women to develop severe early-onset PE already as early as 12 to 16 weeks of gestation.