Marielle van Pampus

Plasma hemopexin activity in pregnancy and preeclampsia.

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 ecto-apyrase 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.

Induction of labour at term with oral misoprostol versus a Foley catheter (PROBAAT-II): a multicentre randomised controlled non-inferiority trial

BACKGROUND Labour is induced in 20-30% of all pregnancies. In women with an unfavourable cervix, both oral misoprostol and Foley catheter are equally effective compared with dinoprostone in establishing vaginal birth, but each has a better safety profile. We did a trial to directly compare oral misoprostol with Foley catheter alone. METHODS We did an open-label randomised non-inferiority trial in 29 hospitals in the Netherlands. Women with a term singleton pregnancy in cephalic presentation, an unfavourable cervix, intact membranes, and without a previous caesarean section who were scheduled for induction of labour were randomly allocated to cervical ripening with 50 μg oral misoprostol once every 4 h or to a 30 mL transcervical Foley catheter. The primary outcome was a composite of asphyxia (pH ≤7·05 or 5-min Apgar score <7) or post-partum haemorrhage (≥1000 mL). The non-inferiority margin was 5%. The trial is registered with the Netherlands Trial Register, NTR3466. FINDINGS Between July, 2012, and October, 2013, we randomly assigned 932 women to oral misoprostol and 927 women to Foley catheter. The composite primary outcome occurred in 113 (12·2%) of 924 participants in the misoprostol group versus 106 (11·5%) of 921 in the Foley catheter group (adjusted relative risk 1·06, 90% CI 0·86-1·31). Caesarean section occurred in 155 (16·8%) women versus 185 (20·1%; relative risk 0·84, 95% CI 0·69-1·02, p=0·067). 27 adverse events were reported in the misoprostol group versus 25 in the Foley catheter group. None were directly related to the study procedure. INTERPRETATION In women with an unfavourable cervix at term, induction of labour with oral misoprostol and Foley catheter has similar safety and effectiveness. FUNDING FondsNutsOhra.

Cervical pessaries to prevent preterm birth in women with a multiple pregnancy : A per-protocol analysis of a randomized clinical trial

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 (<38 mm). The objective of this study was to evaluate the full potential treatment effect of the pessary in the whole group and in women with a short cervix.

Preventing post‐traumatic stress disorder following childbirth and traumatic birth experiences: a systematic review

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.

Atosiban versus fenoterol as a uterine relaxant for external cephalic version: randomised controlled trial

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.

Early enteral tube feeding in optimizing treatment of hyperemesis gravidarum : the Maternal and Offspring outcomes after Treatment of HyperEmesis by Refeeding (MOTHER) randomized controlled trial

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 ± 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-gestational-age, 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.

Posttraumatic stress disorder related to postpartum haemorrhage: A systematic review

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.

Induction of labour at term with oral misoprostol versus a foley catheter (PROBAAT-II) : A multicentre randomised controlled non-inferiority trial

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.

PP077. New prognostic marker for the risk to develop early-onset preeclampsia.

INTRODUCTION ESM-1 plays a role in the regulation of angiogenesis and is released by activated endothelial cells. OBJECTIVE To test the hypothesized that ESM-1 is increased in preeclampsia (PE). METHODS 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. RESULTS (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, p<0.05). 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. CONCLUSIONS 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.