Search

Background Partners of women are increasingly present during childbirth and may be exposed to a traumatic experience. Since parents’ mental health issues (i.e. posttraumatic stress disorder) have been shown to increase the risk of problems in the child’s development, it is important to identify these risk factors. Partners often describe severe postpartum haemorrhage as traumatic. Aim Whether witnessing severe postpartum haemorrhage is a risk factor for developing posttraumatic stress disorder in partners. Methods In this prospective cohort study, we compared partners of women with severe postpartum haemorrhage (≥2000 mL) and partners of women with ≤500 mL of blood loss (controls). Four weeks after birth partners were screened for posttraumatic stress disorder symptoms with a self-report questionnaire. Scores ≥11 were followed by a gold standard clinical interview to diagnose posttraumatic stress disorder. Findings We included 123 severe postpartum haemorrhage partners and 62 control partners. Partners of women with severe postpartum haemorrhage reported higher scores than control partners (median 3.0 (0.0–7.0) vs 2.0 (0.0–4.0), p = 0.04) on symptoms of posttraumatic stress, but no significant difference in probable posttraumatic stress disorder diagnosis according to the self-report questionnaire was found. According to the clinical interview no partners were diagnosed with posttraumatic stress disorder. Severe postpartum haemorrhage was experienced as traumatic by the partners who felt excluded. Conclusion None of the partners developed posttraumatic stress disorder, revealing the resilience of young fathers. Because some partners reported severe postpartum haemorrhage as traumatic, we recommend sufficient information and support is provided during childbirth.

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.

Objective: To study the impact of fetal gender on the risk of spontaneous preterm birth in various ethnicities. Study design: National cohort study in which all singleton live births from 25+0 weeks onwards without congenital anomalies were included of African, Asian, and Mediterranean women (1999–2010). Our primary outcome measure was preterm birth before 37 weeks. Per ethnic group, male and female neonates were compared. Result: In each ethnic group, male fetuses were at increased risk of preterm birth (adjusted odds ratio (aOR) 1.63 for African, aOR 1.71 for Asian, and aOR 1.84 for Mediterranean males). The population-attributable risk of male gender on spontaneous preterm birth is lower in African women (3.9%) than in Asian (10.3%) and Mediterranean women (9.0%). Conclusion: Male fetal gender is associated with spontaneous preterm birth in African, Asian, and Mediterranean women, but the total impact of ethnicity on spontaneous preterm birth rate is different.

Background and Objectives: Therapeutic interventions targeting molecular factors involved in the transition from uterine quiescence to overt labour are not substantially reducing the rate of spontaneous preterm labour. The identification of novel rational therapeutic targets are essential to prevent the most common cause of neonatal mortality. Based on our previous work showing that Tbx2 (T-Box transcription factor 2) is a putative upstream regulator preceding progesterone withdrawal in mouse myometrium, we now investigate the role of TBX2 in human myometrium. Materials and Methods: RNA microarray analysis of (A) preterm human myometrium samples and (B) myometrial cells overexpressing TBX2 in vitro, combined with subsequent analysis of the two publicly available datasets of (C) Chan et al. and (D) Sharp et al. The effect of TBX2 overexpression on cytokines/chemokines secreted to the myometrium cell culture medium were determined by Luminex assay. Results: Analysis shows that overexpression of TBX2 in myometrial cells results in downregulation of TNFα- and interferon signalling. This downregulation is consistent with the decreased expression of cytokines and chemokines of which a subset has been previously associated with the inflammatory pathways relevant for human labour. In contrast, CXCL5 (C-X-C motif chemokine ligand 5), CCL21 and IL-6 (Interleukin 6), previously reported in relation to parturition, do not seem to be under TBX2 control. The combined bioinformatical analysis of the four mRNA datasets identifies a subset of upstream regulators common to both preterm and term labour under control of TBX2. Surprisingly, TBX2 mRNA levels are increased in preterm contractile myometrium. Conclusions: We identified a subset of upstream regulators common to both preterm and term labour that are activated in labour and repressed by TBX2. The increased TBX2 mRNA expression in myometrium collected during a preterm caesarean section while in spontaneous preterm labour compared to tissue harvested during iatrogenic preterm delivery does not fit the bioinformatical model. We can only explain this by speculating that the in vivo activity of TBX2 in human myometrium depends not only on the TBX2 expression levels but also on levels of the accessory proteins necessary for TBX2 activity.

Purpose: To evaluate whether severe postpartum hemorrhage (PPH) is a risk factor for posttraumatic stress disorder (PTSD). Severe PPH can be experienced as a traumatic event. PTSD leads to negative mental health effects. Knowing risk factors for PTSD during childbirth offers opportunities for early interventions, which may prevent the development of PTSD.Materials and methods: In this prospective study, we compared two groups of participants; women with ≥2000 mL of blood loss (severe PPH, patients) and women with ≤500 mL of blood loss (controls). Participants were screened for PTSD using the PCL-5 four to six weeks after delivery. Positive screening was followed by the CAPS-5 to diagnose PTSD.Results: We included 187 PPH patients and 121 controls. Median PCL-5 scores were higher for PPH patients (5.0) than controls (4.0, p = 0.005). Thirteen PPH patients (7.0%) and two controls (1.7%) scored ≥32 on the PCL-5, indicative of probable PTSD (OR 4.45, 95% CI 0.99-20.06, p = 0.035). Significant more PPH patients than controls met criteria for a clinical diagnosis of PTSD on the CAPS-5 (n = 10, 5.6% vs n = 0, 0.0%; p = 0.007).Conclusions: There is a significant and clinically relevant increased risk for developing PTSD after severe PPH. Gynecologists and midwives are advised to screen for PTSD at postpartum follow-up visits to prevent long-term negative mental health effects. Clinical Trial Registration: NL50273.100.14.

Contains fulltext : 238937.pdf (Publisher’s version ) (Open Access) INTRODUCTION: Little is known about the pathophysiology of hyperemesis gravidarum (HG). Proposed underlying causes are multifactorial and thyroid function is hypothesized to be causally involved. In this study, we aimed to assess the utility of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) as a marker and predictor for the severity and clinical course of HG. MATERIAL AND METHODS: We conducted a prospective cohort study including women admitted for HG between 5 and 20 weeks of gestation in 19 hospitals in the Netherlands. Women with a medical history of thyroid disease were excluded. TSH and FT4 were measured at study entry. To adjust for gestational age, we calculated TSH multiples of the median (MoM). We assessed HG severity at study entry as severity of nausea and vomiting (by the Pregnancy Unique Quantification of Emesis and nausea score), weight change compared with prepregnancy weight, and quality of life. We assessed the clinical course of HG as severity of nausea and vomiting and quality of life 1 week after inclusion, duration of hospital admissions, and readmissions. We performed multivariable regression analysis with absolute TSH, TSH MoMs, and FT4. RESULTS: Between 2013 and 2016, 215 women participated in the cohort. TSH, TSH MoM, and FT4 were available for, respectively, 150, 126, and 106 of these women. Multivariable linear regression analysis showed that lower TSH MoM was significantly associated with increased weight loss or lower weight gain at study entry (ΔKg; β = 2.00, 95% CI 0.47-3.53), whereas absolute TSH and FT4 were not. Lower TSH, not lower TSH MoM or FT4, was significantly associated with lower nausea and vomiting scores 1 week after inclusion (β = 1.74, 95% CI 0.36-3.11). TSH and FT4 showed no association with any of the other markers of the severity or clinical course of HG. Twenty-one out of 215 (9.8%) women had gestational transient thyrotoxicosis. Women with gestational transient thyrotoxicosis had a lower quality of life 1 week after inclusion than women with no gestational transient thyrotoxicosis (p = 0.03). CONCLUSIONS: Our findings show an inconsistent role for TSH, TSH MoM, or FT4 at time of admission and provide little guidance on the severity and clinical course of HG.

Introduction: The associations of epidural analgesia and low Apgar score found in the Swedish Registry might be a result of confounding by indication. The objective of this study was to assess the possible effect of intrapartum epidural analgesia on low Apgar score and neonatal intensive care unit (NICU) admission in term born singletons with propensity score matching. Material and methods: This was a propensity score matched study (n = 257 872) conducted in a national cohort of 715 449 term live born singletons without congenital anomalies in the Netherlands. Mothers with prelabor cesarean section were excluded. Main outcome measures were 5-minute Apgar score

Background In the Netherlands, several initiatives started after the publication of the PERISTAT findings that showed the perinatal mortality risk was higher than in other European countries. The objective of this study is 1) to report recent trends in perinatal mortality and in intermediate risk groups (preterm birth, congenital anomalies and small for gestational age (SGA)), 2) describing perinatal mortality risk among children born preterm, with congenital anomalies or SGA, and born in maternal high risk groups (parity, age, ethnicity and socio-economic status (SES)). Methods A nationwide cohort study in the Netherlands among 996,423 singleton births in 2010–2015 with a gestational age between 24.0 and 42.6 weeks. Trend tests, univariate and multivariable logistic regression analyses were used. We did separate analyses for gestational age subgroups and line of care. Results The perinatal mortality rate was 5.0 per 1000 and it decreased significantly from 5.6 in 2010 to 4.6 per 1000 in 2015. Preterm birth significantly declined (6.1% in 2010 to 5.6% in 2015). Analysis by gestational age groups showed that the largest decline in perinatal mortality of 32% was seen at 24–27 weeks of gestation where the risk declined from 497 to 339 per 1000. At term, the decline was 23% from 2.2 to 1.7 per 1000. The smallest decline was 3% between 32 and 36 weeks. In children with preterm birth, congenital anomalies or SGA, the perinatal mortality risk significantly declined. Main risk factors for perinatal mortality were African ethnicity (adjusted odds ratio (aOR) 2.1 95%CI [1.9–2.4]), maternal age ≥ 40 years (aOR1.9 95%CI [1.7–2.2]) and parity 2+ (aOR 1.4 95%CI [1.3–1.5]). Among the (post)term born neonates, there was no significant decline in perinatal mortality in women with low age, low or high SES, non-Western ethnicity and among women who started or delivered under primary care. Conclusions There is a decline in preterm birth and in perinatal mortality between 2010 and 2015. The decline in perinatal mortality is both in stillbirths and in neonatal mortality, most prominently among 24–27 weeks and among (post)term births. A possible future target could be deliveries among 32–36 weeks, women with high maternal age or non-Western ethnicity.

Contains fulltext : 220481.pdf (Publisher’s version ) (Open Access) INTRODUCTION: The examination of the fetal heart in mid-pregnancy is by ultrasound examination. The quality of the examination is highly dependent on the skill of the sonographer, fetal position and maternal body mass index. An additional tool that is less dependent on human experience and interpretation is desirable. The fetal electrocardiogram (ECG) could fulfill this purpose. We aimed to show the feasibility of recording a standardized fetal ECG in mid-pregnancy and explored its possibility to detect congenital heart disease (CHD). MATERIALS AND METHODS: Women older than 18 years of age with an uneventful pregnancy, carrying a healthy singleton fetus with a gestational age between 18 and 24 weeks were included. A fetal ECG was performed via electrodes on the maternal abdomen. After removal of interferences, a vectorcardiogram was constructed. Based on the ultrasound assessment of the fetal orientation, the vectorcardiogram was rotated to standardize for fetal orientation and converted into a 12-lead ECG. Median ECG waveforms for each lead were calculated. RESULTS: 328 fetal ECGs were recorded. 281 were available for analysis. The calculated median ECG waveform showed the electrical heart axis oriented to the right and inferiorly i.e. a negative QRS deflection in lead I and a positive deflection in lead aVF. The two CHD cases show ECG abnormalities when compared to the mean ECG of the healthy cohort. DISCUSSION: We have presented a method for estimating a standardized 12-lead fetal ECG. In mid-pregnancy, the median electrical heart axis is right inferiorly oriented in healthy fetuses. Future research should focus on fetuses with congenital heart disease.

Contains fulltext : 196297.pdf (Publisher’s version ) (Closed access) BACKGROUND: Postterm pregnancy is associated with increased perinatal risk. The WHO defines postterm pregnancy as a pregnancy at or beyond 42 weeks+0 days, though currently labour is induced at 41 weeks in many settings. Guidelines on timing of labour induction are frequently based on the Cochrane systematic review 'Induction of labour for improving birth outcomes for women at or beyond term' in which is concluded that a policy of induction of labour is associated with fewer adverse perinatal outcome and fewer Caesarean sections. However, the included trials differed regarding the timing of induction, ranging from 39 to beyond 42 weeks while the upper limit of expectant management exceeded a gestational age of 42 weeks in most studies. OBJECTIVE: to evaluate perinatal mortality, meconium aspiration syndrome and Caesarean section rate of trials comparing a policy of elective induction of labour and expectant management according to timeframes of comparison with a focus on studies within the 41-42 weeks' timeframe. DESIGN: Review. METHODS: The systematic review of Cochrane was used as a starting point for assessing relevant trials and a search was performed for additional recent trials. We evaluated incidence and causes of perinatal mortality, incidence of meconium aspiration syndrome and Caesarean section according to three time frames of comparison. We pooled estimates and heterogeneity was tested. The quality of the included trials was assessed using the Quality Assessment Tool for Quantative Studies (EPHPP). FINDINGS: In total 22 trials were included which had all different timeframes of comparison. Only one trial compared induction of labour at 41 weeks+0-2 days with induction at 42 weeks+0 days, three other trials compared induction of labour at 41 weeks+0-6 days with induction at 42 weeks+0-6 days. In 18 trials the comparison was outside the 41-42 weeks' timeframe: in six trials induction was planned

Objective: To determine whether women delivering preterm have unfavorable cardiovascular profiles as compared with women who deliver at term. Methods: A prospective observational cohort study enrolled 165 women with spontaneous preterm delivery (sPTD) at 24 +0 and 36 +6 gestational weeks in three perinatal care centers in The Netherlands between August 2012 and August 2014. Total cholesterol, triglycerides, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, apolipoprotein, glucose, and homocysteine were measured within 24 hours after delivery. Lipids and cardiovascular biochemical risk factors were compared between women with sPTD and an external comparison group of 30 women with term delivery via analysis of covariance. Results: Mean gestational age at delivery was 30.7 ± 3.6 weeks in the sPTD group and 40.3 ± 1.3 weeks in the reference group. Data were adjusted for body mass index, age, and center. As compared with the reference group, total cholesterol and LDL-cholesterol levels were lower and glucose levels were higher among women with sPTD. Conclusion: An association between sPTD and unfavorable lipids and cardiovascular biochemical risk factors was not established. The higher levels of glucose in the sPTD group might be due to increased insulin resistance, which is associated with a higher risk of sPTD.

Context Small for gestational age (SGA) can be the result of fetal growth restriction, which is associated with perinatal morbidity and mortality. Mechanisms that control prenatal growth are poorly understood. Objective The aim of the current study was to gain more insight into prenatal growth failure and determine an effective diagnostic approach in SGA newborns. We hypothesized that one or more copy number variations (CNVs) and disturbed methylation and sequence variants may be present in genes associated with fetal growth. Design A prospective cohort study of subjects with a low birth weight for gestational age. Setting The study was conducted at an academic pediatric research institute. Patients A total of 21 SGA newborns with a mean birth weight below the first centile and a control cohort of 24 appropriate-for-gestational-age newborns were studied. Interventions Array comparative genomic hybridization, genome-wide methylation studies, and exome sequencing were performed. Main Outcome Measures The numbers of CNVs, methylation disturbances, and sequence variants. Results The genetic analyses demonstrated three CNVs, one systematically disturbed methylation pattern, and one sequence variant explaining SGA. Additional methylation disturbances and sequence variants were present in 20 patients. In 19 patients, multiple abnormalities were found. Conclusion Our results confirm the influence of a large number of mechanisms explaining dysregulation of fetal growth. We concluded that CNVs, methylation disturbances, and sequence variants all contribute to prenatal growth failure. These genetic workups can be an effective diagnostic approach in SGA newborns.

Introduction and hypothesis Overt postpartum urinary retention (PUR) is the inability to void after delivery and affects up to 7% of patients. Clean intermittent catheterization (CIC) and transurethral indwelling catheterization (TIC) are both standard treatments, but have not previously been compared. Clinical guidelines on postpartum bladder management are lacking. Methods A total of 85 patients were randomised for TIC (n=45) and CIC (n=40). In total 68 patients (34 patients with TIC and 34 patients with CIC) completed the UDI-6 questionnaire 3 months after delivery.. Patients allocated to TIC received an indwelling catheter for 24 h and if necessary, another catheter for 48 h. Patients with CIC were intermittently catheterized or taught to self-catheterize until adequate voiding with a postvoid residual volume (PVRV) of

Purpose & para;& para;To investigate the association between learning climate and adverse perinatal and maternal outcomes in obstetrics-gynecology departments.& para;& para;Method & para;& para;The authors analyzed 23,629 births and 103 learning climate evaluations from 16 nontertiary obstetrics-gynecology departments in the Netherlands in 2013. Multilevel logistic regressions were used to calculate the odds of adverse perinatal and maternal outcomes, by learning climate score tertile, adjusting for maternal and department characteristics. Adverse perinatal outcomes included fetal or early neonatal mortality, five-minute Apgar score

Introduction and hypothesis Covert (asymptomatic) postpartum urinary retention (PUR) is defined as post-void residual volume (PVRV) ≥150 mL. Although often supposed to be a common and harmless phenomenon, no data are available on the potential long-term micturition problems of increased PVRV after vaginal delivery. Methods After the first spontaneous void post-vaginal delivery, PVRV was measured using a portable scanning device. Micturition symptoms were compared using validated questionnaires between women with PVRV

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.

IntroductionPreterm birth complicates >15 million pregnancies annually worldwide. In many countries, women who present with signs of preterm labour are treated with tocolytics for 48 hours. Although this delays birth, it has never been shown to improve neonatal outcome. In 2015, the WHO stated that the use of tocolytics should be reconsidered and that large placebo-controlled studies to evaluate the effectiveness of tocolytics are urgently needed.Methods and analysisWe designed an international, multicentre, randomised, double-blinded, placebo-controlled clinical trial. Women with threatened preterm birth (gestational age 30–34 weeks), defined as uterine contractions with (1) a cervical length of < 15 mm or (2) a cervical length of 15–30 mm and a positive fibronectin test or (3) in centres where cervical length measurement is not part of the local protocol: a positive fibronectin test or insulin-like growth factor binding protein-1 (Actim-Partus test) or (4) ruptured membranes, will be randomly allocated to treatment with atosiban or placebo for 48 hours. The primary outcome is a composite of perinatal mortality and severe neonatal morbidity. Analysis will be by intention to treat. A sample size of 760 participants (380 per group) will detect a reduction in adverse neonatal outcome from 11.95% to 6% (alpha error 0.05, beta error 0.2). A cost-effectiveness analysis will be performed from a societal perspective.Ethics and disseminationThis study has been approved by the Research Ethics Committee (REC) of the Amsterdam University Medical Centres, location AMC, as well as the REC’s in Dublin and the UK. The results will be presented at conferences and published in a peer-reviewed journal. Participants will be informed about the results.Trial registration numberNederlands Trial Register (Trial NL6469).

Objective: The aim of this study was to study growth patterns of children born after suspected fetal growth restriction (FGR) at term and to compare the effect of induction of labor (IoL) and expectant management (EM), also in relation to neurodevelopmental and behavioral outcome at age 2. Methods: We performed a 2 years' follow-up of growth of children included in the Disproportionate Intrauterine Growth Restriction Trial at Term (DIGITAT) study, a Randomized Controlled Trial (RCT) comparing IoL with EM in pregnancies with suspected FGR at term. We collected data on child growth until the age of 2 years. Standard deviation scores (SDSs) for height and weight were calculated at different ages. We assessed the effects of IoL compared with EM and the effects of a birth weight below or above the 3rd or 10th centile on catch-up growth. Target height SDSs were calculated using the height of both parents. Results: We found a significant increase in SDS in the first 2 years. Children born after EM showed more catch-up growth in the first month [height: mean difference -0.7 (95% CI: 0.2; 1.3)] and weight [mean difference -0.5 (95% CI: 0.3; 0.7)]. Children born with a birth weight below the 3rd and 10th centiles showed more catch-up growth after 1 year [mean difference -0.8 SDS (95% CI: -1.1; -0.5)] and after 2 years [mean difference -0.7 SDS (95% CI: -1.2; -0.2)] as compared to children with a birth weight above the 3rd and 10th centiles. SDS at birth had the strongest effect on adverse neurodevelopmental outcome at 2 years of age. Conclusion: After FGR at term, postnatal catch-up growth is generally present and associated with the degree of FGR. Obstetric management in FGR influences postnatal growth. Longer-term follow-up is therefore needed and should be directed at growth and physical health. Clinical Trial Registration: www.ClinicalTrials.gov, identifier SRCTN10363217.

Introduction: Midwife-led models of care have been the subject of debate for many years. We conducted a study to compare intrapartum and neonatal mortality rates in midwife-led (primary) vs obstetrician-led (secondary) care at the onset of labor in low-risk term women. Material and methods: We performed an unmatched and a propensity score matched cohort study using data from the national perinatal audit registry (PAN) and from the national perinatal registry (PERINED) of the Netherlands. We included women with singleton pregnancies (without congenital anomalies or antepartum fetal death) who gave birth at term between 2010 and 2012. We excluded the following major risk factors: non-vertex position of the fetus, previous cesarean birth, hypertension, diabetes mellitus, prolonged rupture of membranes (≥24 hours), vaginal bleeding in the second half of pregnancy, nonspontaneous start of labor and post-term pregnancy (≥42 weeks). The primary outcome was intrapartum or neonatal mortality up to 28 days after birth. Secondary outcome measures were mode of delivery and a 5-minute Apgar score

Objective To compare induction of labour at 41 weeks with expectant management until 42 weeks in low risk women. Design Open label, randomised controlled non-inferiority trial. Setting 123 primary care midwifery practices and 45 hospitals (secondary care) in the Netherlands, 2012-16. Participants 1801 low risk women with an uncomplicated singleton pregnancy: randomised to induction (n=900) or to expectant management until 42 weeks (n=901). Interventions Induction at 41 weeks or expectant management until 42 weeks with induction if necessary. Primary outcome measures Primary outcome was a composite of perinatal mortality and neonatal morbidity (Apgar score Results Median gestational age at delivery was 41 weeks+0 days (interquartile range 41 weeks+0 days-41 weeks+1 day) for the induction group and 41 weeks+2 days (41 weeks+0 days-41 weeks+5 days) for the expectant management group. The primary outcome was analysed for both the intention-to-treat population and the per protocol population. In the induction group, 15/900 (1.7%) women had an adverse perinatal outcome versus 28/901 (3.1%) in the expectant management group (absolute risk difference −1.4%, 95% confidence interval −2.9% to 0.0%, P=0.22 for non-inferiority). 11 (1.2%) infants in the induction group and 23 (2.6%) in the expectant management group had an Apgar score v expectant management n=102 (11.3%)) or in caesarean section rate (both groups n=97 (10.8%)). Conclusions This study could not show non-inferiority of expectant management compared with induction of labour in women with uncomplicated pregnancies at 41 weeks; instead a significant difference of 1.4% was found for risk of adverse perinatal outcomes in favour of induction, although the chances of a good perinatal outcome were high with both strategies and the incidence of perinatal mortality, Apgar score Trial registration Netherlands Trial Register NTR3431.

Background Seizures are the main cause of maternal death in women with epilepsy, but there are no tools for predicting seizures in pregnancy. We set out to develop and validate a prognostic model, using information collected during the antenatal booking visit, to predict seizure risk at any time in pregnancy and until 6 weeks postpartum in women with epilepsy on antiepileptic drugs. Methods and findings We used datasets of a prospective cohort study (EMPiRE) of 527 pregnant women with epilepsy on medication recruited from 50 hospitals in the UK (4 November 2011–17 August 2014). The model development cohort comprised 399 women whose antiepileptic drug doses were adjusted based on clinical features only; the validation cohort comprised 128 women whose drug dose adjustments were informed by serum drug levels. The outcome was epileptic (non-eclamptic) seizure captured using diary records. We fitted the model using LASSO (least absolute shrinkage and selection operator) regression, and reported the performance using C-statistic (scale 0–1, values > 0.5 show discrimination) and calibration slope (scale 0–1, values near 1 show accuracy) with 95% confidence intervals (CIs). We determined the net benefit (a weighted sum of true positive and false positive classifications) of using the model, with various probability thresholds, to aid clinicians in making individualised decisions regarding, for example, referral to tertiary care, frequency and intensity of monitoring, and changes in antiepileptic medication. Seizures occurred in 183 women (46%, 183/399) in the model development cohort and in 57 women (45%, 57/128) in the validation cohort. The model included age at first seizure, baseline seizure classification, history of mental health disorder or learning difficulty, occurrence of tonic-clonic and non-tonic-clonic seizures in the 3 months before pregnancy, previous admission to hospital for seizures during pregnancy, and baseline dose of lamotrigine and levetiracetam. The C-statistic was 0.79 (95% CI 0.75, 0.84). On external validation, the model showed good performance (C-statistic 0.76, 95% CI 0.66, 0.85; calibration slope 0.93, 95% CI 0.44, 1.41) but with imprecise estimates. The EMPiRE model showed the highest net proportional benefit for predicted probability thresholds between 12% and 99%. Limitations of this study include the varied gestational ages of women at recruitment, retrospective patient recall of seizure history, potential variations in seizure classification, the small number of events in the validation cohort, and the clinical utility restricted to decision-making thresholds above 12%. The model findings may not be generalisable to low- and middle-income countries, or when information on all predictors is not available. Conclusions The EMPiRE model showed good performance in predicting the risk of seizures in pregnant women with epilepsy who are prescribed antiepileptic drugs. Integration of the tool within the antenatal booking visit, deployed as a simple nomogram, can help to optimise care in women with epilepsy., John Allotey and colleagues describe their model for predicting seizures in pregnant women with epilepsy., Author summary Why was this study done? Pregnant women with epilepsy are at increased risk of death and complications from seizures; their high-risk status during pregnancy and after childbirth is often not recognised. Knowledge of an individual’s risk of seizures could help healthcare professionals and pregnant women make decisions regarding management. To our knowledge, there are currently no models to predict risk of seizures in pregnant women with epilepsy on medication. What did the researchers do and find? We developed the EMPiRE model to predict the risk of seizures in pregnancy and up to 6 weeks after delivery in women with epilepsy on medication whose drug doses were managed based on clinical findings; we validated the model in a separate group of women whose dose management was based on drug levels in the blood. The model discriminated well between those with and without seizures, with good agreement between predicted and observed risks across both low- and high-risk women. The model is clinically useful for decision-making where the threshold of choice for seizure risk is between 12% and 99%. The model showed promising transportability to the validation cohort. What do these findings mean? The EMPiRE prediction model can be used by healthcare professionals to identify pregnant women at high risk of seizures and to plan early referral for specialist input; determine the need for close monitoring in pregnancy, labour, and after childbirth; and assess antiepileptic drug management. The performance of the model is unlikely to vary with the antiepileptic drug dose management strategy.

Background Oxytocin is an effective drug for induction of labour, but is associated with serious adverse effects of which uterine tachysystole, fetal distress and the need of immediate delivery are the most common. Discontinuation of oxytocin once the active phase of labour is established could reduce the adverse effects. The objective is to investigate how the caesarean section rate is affected when oxytocin stimulation is discontinued in the active phase of labour compared to labours where oxytocin is continued. Methods CONDISOX is a double-blind multicentre randomised controlled trial conducted at Danish and Dutch Departments of Obstetrics and Gynaecology. The first participant was recruited on April 8 2016. Based on a clinically relevant relative reduction in caesarean section rate of 7%, an alpha of 0.05, a beta of 80%, we aim for 1200 participating women (600 in each arm). The CONDISOX trial includes women at a gestational age of 37–42 complete weeks of pregnancy, who have uterine activity stimulated with oxytocin infusion for the induction of labour. Women are randomised when the active phase of labour becomes established, to study medication containing either oxytocin (continuous group) or placebo (discontinued group) infusion. Women are stratified by birth site, indication for oxytocin stimulation (induction of labour, prelabour rupture of membranes) and parity (nulliparous, parous +/− previous caesarean section). We will compare the primary outcome, caesarean section rate, in the two groups using a chi-square test with a p-value of 0.05. If superiority is not demonstrated, we have a pre-defined post hoc non-inferiority boundary (margin, delta) at 1.09. Secondary outcomes include duration of the active phase of labour, incidence of uterine tachysystole, postpartum haemorrhage, admission to the neonatal intensive care unit, Apgar score, umbilical arterial blood pH, and birth experience. Discussion The high frequency of oxytocin use and the potential risks of both maternal and fetal adverse effects of oxytocin emphasise the need to determine the optimal oxytocin regime for induction of labour. Trial registration NCT02553226 (registered September 17, 2015). Eudra-CT number: 2015–002942-30. Electronic supplementary material The online version of this article (10.1186/s12884-019-2461-x) contains supplementary material, which is available to authorized users.

Contains fulltext : 171740.pdf (Publisher’s version ) (Closed access) OBJECTIVE: The objective of this study is to evaluate the relation among fetal gender, ethnicity, and preterm labor (PTL) and preterm delivery (PTD). METHODS: A secondary analysis was performed of a prospective cohort study including women with symptoms of PTL between 24 and 34 weeks. The proportion of women carrying a male or female fetus at the onset of PTL was calculated. Gestational age at delivery and risk of PTD of both fetal genders was compared and interaction of fetal gender and maternal ethnicity on the risk of PTD was evaluated. RESULTS: Of the 594 included women, 327 (55%) carried a male fetus. Median gestational age at delivery in women pregnant with a male fetus was 37 5/7 (IQR 34 4/7-39 1/7) weeks compared with 38 1/7 (IQR 36 0/7-39 5/7) weeks in women pregnant with a female fetus (p = 0.032). The risk of PTD did not differ significantly. In Caucasians, we did find an increased risk of PTD before 37 weeks in women pregnant with a male fetus (OR 1.9 (95% CI 1.2-3.0)). CONCLUSIONS: The majority of women with PTL are pregnant with a male fetus and these women deliver slightly earlier. Race seems to affect this disparity.

Item does not contain fulltext BACKGROUND: In women with threatened preterm birth, delay of delivery by 48 h allows antenatal corticosteroids to improve neonatal outcomes. For this reason, tocolytics are often administered for 48 h; however, there is no consensus about which drug results in the best maternal and neonatal outcomes. In the APOSTEL III trial we aimed to compare the effectiveness and safety of the calcium-channel blocker nifedipine and the oxytocin inhibitor atosiban in women with threatened preterm birth. METHODS: We did this multicentre, randomised controlled trial in ten tertiary and nine teaching hospitals in the Netherlands and Belgium. Women with threatened preterm birth (gestational age 25-34 weeks) were randomly assigned (1:1) to either oral nifedipine or intravenous atosiban for 48 h. An independent data manager used a web-based computerised programme to randomly assign women in permuted block sizes of four, with groups stratified by centre. Clinicians, outcome assessors, and women were not masked to treatment group. The primary outcome was a composite of adverse perinatal outcomes, which included perinatal mortality, bronchopulmonary dysplasia, sepsis, intraventricular haemorrhage, periventricular leukomalacia, and necrotising enterocolitis. Analysis was done in all women and babies with follow-up data. The study is registered at the Dutch Clinical Trial Registry, number NTR2947. FINDINGS: Between July 6, 2011, and July 7, 2014, we randomly assigned 254 women to nifedipine and 256 to atosiban. Primary outcome data were available for 248 women and 297 babies in the nifedipine group and 255 women and 294 babies in the atosiban group. The primary outcome occurred in 42 babies (14%) in the nifedipine group and in 45 (15%) in the atosiban group (relative risk [RR] 0.91, 95% CI 0.61-1.37). 16 (5%) babies died in the nifedipine group and seven (2%) died in the atosiban group (RR 2.20, 95% CI 0.91-5.33); all deaths were deemed unlikely to be related to the study drug. Maternal adverse events did not differ between groups. INTERPRETATION: In women with threatened preterm birth, 48 h of tocolysis with nifedipine or atosiban results in similar perinatal outcomes. Future clinical research should focus on large placebo-controlled trials, powered for perinatal outcomes. FUNDING: ZonMw (the Netherlands Organisation for Health Research and Development).

Objective To compare intrapartum and neonatal mortality in low-risk term women starting labour in midwife-led versus obstetrician-led care. Study design We performed a propensity score matched study using data from our national perinatal register, completed with data from medical files. We studied women without major risk factors with singleton pregnancies who gave birth at term between 2005 and 2008 in the Amsterdam region of the Netherlands. Major risk factors comprised non-vertex position of the fetus, previous Caesarean birth, hypertension, (gestational) diabetes mellitus, post-term pregnancy (≥42 weeks), prolonged rupture of membranes (>24 hours), vaginal bleeding in the second half of pregnancy or induced labour. Groups were devided by midwife-led versus obstetrician-led care at the onset of labour. The primary outcome was intrapartum and neonatal (24 hours. Results We studied 57 396 women. Perinatal mortality occurred in 30 of 46 764 (0.64‰) women in midwife-led care and in 2 of 10 632 (0.19‰) women in obstetrician-led care (OR 3.4, 95% CI 0.82 to 14.3). A propensity score matched analysis in a 1:1 ratio with 10 632 women per group revealed an OR for perinatal mortality of 4.0 (95% CI 0.85 to 18.9). Conclusion Among low-risk women, midwife-led care at the onset of labour was associated with a statistically non-significant higher mortality rate.

Background: The aim of this study was to present the validation and optimization process for a new innovative medical device to create a standardized episiotomy. Design: We performed a preclinical validation study. Setting: This study was performed at the University hospital. Sample: Animal, cadaver. Methods: Together with technical engineers, we designed a new medical device that involves a knife and cuts back from buttock toward introitus, in contrast to the conventional episiotomy. We optimized the design and its performance in consecutive animal and cadaver studies. Main Outcome Measures: Ability to perform a standardized incision, ease of use. Results: After multiple adjustments, based on the results of multiple animal and cadaver studies, a medical device was developed to perform a standardized clean-cut episiotomy of 4-6 cm length. Conclusion: We have shown that optimizing the technical performance and safety of an innovative device in animals, prior to opposing patients to its potential hazards, is feasible. Our design optimizing study can be used as a model for the pre-clinical validation of future innovative medical devices.

Item does not contain fulltext OBJECTIVE: To stratify the risk of spontaneous preterm delivery using cervical length (CL) and fetal fibronectin (fFN) in women with threatened preterm labor who remained pregnant after 7 days. DESIGN: Prospective observational study. SETTING: Nationwide cohort of women with threatened preterm labor from the Netherlands. POPULATION: Women with threatened preterm labor between 24 and 34 weeks with a valid CL and fFN measurement and remaining pregnant 7 days after admission. METHODS: Kaplan-Meier and Cox proportional hazards models were used to estimate cumulative percentages and hazard ratios (HR) for spontaneous delivery. MAIN OUTCOME MEASURES: Spontaneous delivery between 7 and 14 days after initial presentation and spontaneous preterm delivery before 34 weeks. RESULTS: The risk of delivery between 7 and 14 days was significantly increased for women with a CL < 15 mm or a CL >/=15 to /=30 mm: HR 22.3 [95% confidence interval (CI) 2.6-191] and 14 (95% CI 1.8-118), respectively. For spontaneous preterm delivery before 34 weeks the risk was increased for women with a CL < 15 mm [HR 6.3 (95% CI 2.6-15)] or with a CL >/=15 to /= 30 mm. CONCLUSIONS: In women remaining pregnant 7 days after threatened preterm labor, CL and fFN results can be used in risk stratification for spontaneous delivery.

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.

Intrahepatic cholestasis of pregnancy (ICP) is defined by pruritus, elevated total fasting serum bile salts (TBS) and transaminases, and an increased risk of adverse fetal outcome. An accurate diagnostic marker is needed. Increased serum autotaxin correlates with cholestasis-associated pruritus. We aimed at unraveling the diagnostic accuracy of autotaxin in ICP. Serum samples and placental tissue were collected from 44 women with uncomplicated pregnancies and 105 with pruritus and/or elevated serum transaminases. Autotaxin serum levels were quantified enzymatically and by Western blotting, autotaxin gene expression by quantitative PCR. Serum autotaxin was increased in ICP (mean ± SD: 43.5 ± 18.2 nmol ml(-1)min(-1), n=55, p

The effects of artificial reproductive techniques and subfertility on cardiovascular and metabolic profiles of children aged 5-6 years were investigated using data from the Amsterdam Born Children and their Development study. Of the 2577 children, 34 were conceived through ovulation induction, 51 through artificial insemination and 28 through IVF or intracytoplasmic sperm injection (ICSI). Two hundred and twenty children were born to couples who conceived after more than 12 months and 2244 were born to couples who conceived within 12 months of unprotected intercourse ('subfertile' and 'fertile', respectively). At the age of 5-6 years, fasting glucose levels were higher among children conceived through ovulation induction and IVF-ICSI compared with those of children of fertile couples (adjusted difference: ovulation induction: 0.4 mmol/l, 95% CI 0.2 to 0.6; IVF-ICSI: 0.2 mmol/l, 95% CI 0.0 to 0.5). Blood pressure was higher in children of subfertile couples compared with that of children of fertile couples (adjusted difference systolic blood pressure: 0.8 mmHg, 95% CI -0.2 to 1.8; diastolic blood pressure: 1.4 mmHg, 95% CI 0.6 to 2.3). Subfertility and conception through ovulation induction and IVF-ICSI each contributed to aspects of an adverse cardiovascular and metabolic profile in childhood.

To provide an overview of existing prediction models for successful ECV, and to assess their quality, development and performance. We searched MEDLINE, EMBASE and the Cochrane Library to identify all articles reporting on prediction models for successful ECV published from inception to January 2015. We extracted information on study design, sample size, model-building strategies and validation. We evaluated the phases of model development and summarized their performance in terms of discrimination, calibration and clinical usefulness. We collected different predictor variables together with their defined significance, in order to identify important predictor variables for successful ECV. We identified eight articles reporting on seven prediction models. All models were subjected to internal validation. Only one model was also validated in an external cohort. Two prediction models had a low overall risk of bias, of which only one showed promising predictive performance at internal validation. This model also completed the phase of external validation. For none of the models their impact on clinical practice was evaluated. The most important predictor variables for successful ECV described in the selected articles were parity, placental location, breech engagement and the fetal head being palpable. One model was assessed using discrimination and calibration using internal (AUC 0.71) and external validation (AUC 0.64), while two other models were assessed with discrimination and calibration, respectively. We found one prediction model for breech presentation that was validated in an external cohort and had acceptable predictive performance. This model should be used to council women considering ECV.

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.

Objective To study the association of the intended mode of delivery and perinatal morbidity and mortality among breech fetuses who are delivered preterm. Methods We conducted a nationwide cohort study of women with a singleton pregnancy in breech presentation who delivered preterm (26 0/7-36 6/7 weeks of gestation) in the years 2000-2011. We compared perinatal outcomes according to the intended and actual mode of delivery using multivariate logistic regression analysis. We performed subgroup analyses of gestational age and parity. Results We studied 8,356 women with a preterm singleton breech delivery. Intended cesarean delivery (n=1,935) was not associated with a significant reduction in perinatal mortality compared with intended vaginal delivery (n=6,421) (1.3% compared with 1.5%; adjusted odds ratio [OR] 0.97, 95% confidence interval [CI] 0.60-1.57). However, the composite of perinatal mortality and morbidity was significantly reduced in the intended cesarean delivery group (8.7% compared with 10.4%; adjusted OR 0.77, 95% CI 0.63-0.93). In the subgroup of women delivering at 28-32 weeks of gestation, intended cesarean delivery was associated with a 1.7% risk of perinatal mortality compared with 4.1% with intended vaginal delivery (adjusted OR 0.27, 95% CI 0.10-0.77) and significantly reduced composite mortality and severe morbidity, 5.9% compared with 10.1% (adjusted OR 0.37, 95% CI 0.20-0.68). Conclusion In women delivering a preterm breech fetus, cesarean delivery is associated with reduced perinatal mortality and morbidity. Level of evidence II.

Contains fulltext : 177805.pdf (Publisher’s version ) (Open Access) 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.

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.

Contains fulltext : 170521.pdf (Publisher’s version ) (Closed access) Objective We assessed the influence of external factors on false-positive, false-negative, and invalid fibronectin results in the prediction of spontaneous delivery within 7 days. Methods We studied symptomatic women between 24 and 34 weeks' gestational age. We performed uni- and multivariable logistic regression to estimate the effect of external factors (vaginal soap, digital examination, transvaginal sonography, sexual intercourse, vaginal bleeding) on the risk of false-positive, false-negative, and invalid results, using spontaneous delivery within 7 days as the outcome. Results Out of 708 women, 237 (33%) had a false-positive result; none of the factors showed a significant association. Vaginal bleeding increased the proportion of positive fetal fibronectin (fFN) results, but was significantly associated with a lower risk of false-positive test results (odds ratio [OR], 0.22; 95% confidence intervals [CI], 0.12-0.39). Ten women (1%) had a false-negative result. None of the investigated factors was significantly associated with a significantly higher risk of false-negative results. Twenty-one tests (3%) were invalid; only vaginal bleeding showed a significant association (OR, 4.5; 95% CI, 1.7-12). Conclusion The effect of external factors on the performance of qualitative fFN testing is limited, with vaginal bleeding as the only factor that reduces its validity.

Adverse intrauterine conditions can program hypertension. Because one of the underlying mechanisms is thought to be cardiac autonomic balance, we investigated the association between prepregnancy body mass index (BMI) and blood pressure and indicators of the autonomic balance in the child at age 5 to 6 years. Also investigated was whether these associations were mediated by standardized birth weight and child BMI. Pregnant women (n=3074) participating in the Amsterdam Born Children and their Development study completed a questionnaire at gestational week 14. At age 5 to 6 years, offspring's sympathetic drive (pre-ejection period), parasympathetic drive (respiratory sinus arrhythmia), and heart rate were measured by electrocardiography and impedance cardiography at rest. Blood pressure was assessed simultaneously. After adjusting for possible maternal/offspring confounders, prepregnancy BMI was positively linearly associated with diastolic blood pressure (β=0.11 mm Hg; 95% confidence interval, 0.05-0.17), systolic blood pressure (β=0.14 mm Hg; 95% confidence interval, 0.07-0.21), but not with heart rate, sympathetic or parasympathetic drive. After adding birth weight and child BMI to the model, the independent effect size of prepregnancy body mass index on systolic blood pressure (β=0.07 mm Hg; 95% confidence interval, 0.00-0.14) and diastolic blood pressure (β=0.07 mm Hg; 95% confidence interval, 0.01-0.13) decreased by ≈50%. Birth weight did not mediate these relationships, but was independently and negatively associated with blood pressure. Child BMI was positively associated with blood pressure and partly mediated the association between prepregnancy BMI and blood pressure. In conclusion, higher prepregnancy BMI is associated with higher blood pressure in the child (aged 5-6 years) but does not seem to be attributable to early alterations in resting cardiac autonomic balance. Child BMI, but not birth weight, mediated the association between prepregnancy BMI and blood pressure. © 2013 American Heart Association, Inc.

Objective Preterm prelabor rupture of membranes (PPROM) before 27 weeks’ gestation is associated with severe perinatal complications, but quantitative estimates are lacking. The aim of this study was to report and predict outcomes of pregnancies complicated by early PPROM and to study antepartum risk factors that might predict perinatal death in future patients. Study design We performed a retrospective cohort study of women with PPROM between 13 +0 weeks and 27 +0 weeks’ gestation between 1994 and 2009 in three perinatal centers. Main outcome measures Perinatal mortality, composite neonatal morbidity and premature delivery. A model to predict these outcomes was developed from antepartum variables. Results We identified 314 women with PPROM before 27 weeks, including 28 multiple pregnancies. Six pregnancies (2%) were terminated before 24 weeks’ gestation, and three were lost to follow up, leaving 305 pregnancies for analysis. Overall, there were 166 perinatal deaths (49%). The perinatal mortality rate decreased with increasing gestational age at PPROM (from 70% in the group PPROM 13–20 weeks to 27% in the group PPROM 24–27 weeks). Of the 170 surviving neonates, 70 suffered from serious morbidity (41%). Early gestational age at PPROM, long interval between PPROM and birth and positive vaginal culture (any bacteria) were associated with perinatal mortality. Conclusion Perinatal mortality in PPROM before 27 weeks occurred in half of the cases and among those who survive approximately 40% suffered serious morbidity. Antenatal parameters can be helpful to predict perinatal mortality.

External cephalic version (ECV) is a relatively simple and safe maneuver that reduces the cesarean section (CS) rate for breech presentation. There is professional consensus that ECV should be offered to all women, but only up to 70% of patients opt for this treatment. To improve counseling, we investigated the value patients place on various aspects of ECV. We studied patient preferences by means of a vignette study. Varying levels of treatment characteristics were investigated in 16 scenarios, all including the "opt out" alternative of an elective CS. The probability that women preferred ECV was estimated using a logistic regression approach. Forty seven women participated in the study. Pain was the most important factor negatively influencing the willingness to opt for ECV (OR 0.11 (95% confidence interval (CI) 0.05-0.23) for a pain score of 8-10 compared to 1-2 on a visual analog scale of 0-10). Higher success rates of vaginal delivery after successful ECV increased women's willingness (OR 3.42 (95% CI 2.04-5.74), if chance of vaginal delivery after successful ECV increased from 24% to 52%). The risk of an emergency CS during ECV did not influence the willingness to opt for ECV (OR 0.83 (95% CI 0.59-1.18) of chance increased from 0% to 1%). We conclude that expected pain during treatment and the success rate are the most important factors influencing the willingness to undergo ECV. Taking this information into account when counseling for ECV and reassuring women that unbearable pain is always a reason to stop ECV, and that the vast majority of women reported that the experienced pain is bearable, might improve the uptake of ECV and decrease the number of CS due to breech presentation

Objective It is not known whether automated devices for measuring blood pressure perform better than conventional sphygmomanometry in predicting preeclampsia. This study compares two different automated devices with conventional sphygmomanometry for their association with development of preeclampsia or gestational hypertension. Design Prospective observational cohort study. Setting University hospital, Amsterdam, the Netherlands. Population 289 healthy normotensive women of whom 235 were nulliparous and 44 parous with preeclampsia in a previous pregnancy. Methods At 8–11 weeks of pregnancy, blood pressure was measured with two different automated devices (continuous finger arterial pressure waveform registration and ambulatory blood pressure monitoring) and with conventional sphygmomanometry. Main outcome measures Preeclampsia and gestational hypertension. Results Blood pressure in the first trimester, as measured with all three methods, was significantly higher in women who developed preeclampsia or gestational hypertension. After adjustment for previous preeclampsia, the point estimate of the odds ratios for association with later preeclampsia for both automated devices were comparable and higher than for conventional sphygmomanometry; however, differences were not statistically significant. The odds ratio (95% confidence intervals) for every 1 mmHg pressure increase of mean arterial pressure was 1.08 (1.02–1.15) for sphygmomanometry, 1.17 (1.09–1.27) for finger arterial pressure waveform registration, and 1.17 (1.07–1.27) for ambulatory blood pressure monitoring. Results were comparable if preeclampsia and gestational hypertension were analyzed together. Conclusion Blood pressure in the first trimester was associated with the development of hypertensive disorders of pregnancy. No significant differences were found between measurements by automatic devices compared with conventional sphygmomanometry.

Contains fulltext : 172184.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To compare the accuracy of the Actim Partus test and fetal fibronectin (fFN) test in the prediction of spontaneous preterm delivery within seven days in symptomatic women undergoing cervical length measurement. STUDY DESIGN: We performed a post-hoc analysis on frozen samples of a nationwide cohort study in all 10 perinatal centres in the Netherlands. We selected samples from women with signs of preterm labour between 24 and 34 weeks of gestational age and a cervical length below 30mm. Delivery within seven days after initial assessment was the primary endpoint. We calculated sensitivity, specificity, and positive and negative predictive values for the combination of both the Actim Partus test and fFN test with cervical length. A test was considered positive in case of a cervical length between 15 and 30mm with a positive Actim Partus or fFN test, and a cervical length below 15mm regardless the test result. RESULTS: In total, samples of 350 women were tested, of whom 69 (20%) delivered within seven days. Eighty-four women had a positive Actim Partus test and 162 women a positive fFN test, of whom 54 (64%) and 63 (39%) delivered within seven days, respectively. Ninety-seven women had a cervical length below 15mm, of whom 50 (52%) delivered within seven days. Sensitivity, specificity, positive and negative predictive values of combining cervical length with the Actim Partus test or the fFN test were 91%, 75%, 47% and 97%, and 96%, 58%, 36% and 98%, respectively. CONCLUSION: According to this post-hoc study, in combination with cervical length, the Actim Partus test could be used as an alternative for the fFN test to identify women who will not deliver within seven days after presentation. Further evidence should be collected in a prospective comparative study.

Preterm birth is estimated to affect between 5% and 13% of all pregnancies and is the reason for more than 50% of neonatal morbidity and 50% and 75% of neonatal mortality cases worldwide. It causes long-term physical and developmental impairment, thus having a substantial burden on families and health care costs. A delay of delivery by 48 hours in cases with threatened preterm birth allows for the administration of antenatal corticosteroids, which improves neonatal outcomes. Therefore, treatment with tocolytics for 48 hours may prolong pregnancy long enough to optimize the beneficial effects of steroid administration. However, there is no consensus about which drug is most effective at improving neonatal outcomes while minimizing maternal risks. The aim of this study was to compare the effectiveness and safety of the calcium-channel blocker nifedipine and the oxytocin inhibitor atosiban in women with threatened preterm birth. The APOSTEL III, multicenter randomized controlled trial was conducted in 10 tertiary and 9 teaching hospitals in the Netherlands and Belgium. Participants included women with threatened preterm birth (gestational age, 25–34 weeks). In this study, 254 women, from 2011 to 2014, were randomly assigned (1:1) to oral nifedipine and 256 to intravenous atosiban for 48 hours. The primary outcome included a composite of adverse perinatal outcomes, which included perinatal mortality, bronchopulmonary dysplasia, sepsis, intraventricular hemorrhage, periventricular leukomalacia, and necrotizing enterocolitis. Data were analyzed in all women and babies, including during follow-up. The study revealed that the primary outcome occurred in 42 babies (14%) in the nifedipine group and in 45 (15%) in the atosiban group (relative risk, 0.91; 95% confidence interval, 0.61–1.37). A total of 16 babies (5%) died in the nifedipine group and 7 babies (2%) died in the atosiban group (relative risk, 2.20; 95% confidence interval, 0.91–5.33); all deaths were deemed unlikely to be related to the study drug. It is to be noted that maternal adverse events did not differ between the groups. The study concluded that in women with threatened preterm birth, 48 hours of tocolysis with nifedipine or atosiban results in similar perinatal outcomes. It proposed that future clinical research must focus on large placebo-controlled trials powered for perinatal outcomes.

Circulating blood cells, trophoblast cells and endothelial cells release microparticles (MP) into the maternal blood by membrane shedding. This process occurs upon activation or apoptosis of these cells. Evidence is accumulating that MP play a role in the development of thrombotic diseases. In recent years, the importance of changes in circulating MP numbers and in composition in preeclampsia has been recognized and research is now directed to discover the functional consequences of these changes. In this review we will discuss the structure and function of MP, with special emphasis on the changes in MP numbers, composition and function in pregnancy and preeclampsia. © 2010 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

BACKGROUND: Microparticles (MP) are pro-coagulant vesicles derived from various cells. Evidence is accumulating that MP are of pathophysiological relevance in autoimmune, cardiovascular, and thromboembolic diseases and inflammatory disorders. Therefore, their role in the development of preeclampsia was investigated and MP from preeclamptic patients influenced endothelial-dependent vasodilatation. Knowledge about changes in circulating MP numbers during pregnancy and preeclampsia is lacking. We determined this longitudinally and investigated whether these numbers related to the severity of preeclampsia. METHODS: Samples were obtained from pregnant women and preeclamptic patients during pregnancy and postpartum. MP were isolated and studied by flow cytometry. RESULTS: During pregnancy, MP were decreased at 12 weeks gestation and then returned to postpartum values. In patients with preeclampsia, MP numbers were reduced at 28 and 36 weeks (both p = 0.04). Monocyte-derived MP were elevated in preeclampsia at 28 (p = 0.007), 32 (p = 0.02), and 36 weeks (p = 0.01), as were erythrocyte-derived MP at 28 weeks (p = 0.04). Placenta-derived MP increased in pregnancy and preeclampsia. During pregnancy, a correlation was present between placenta-derived MP and systolic blood pressure (r = 0.33, p = 0.015). No other correlations were found. CONCLUSIONS: During pregnancy, numbers of MP initially decrease and subsequently normalize. Placenta-derived MP increase, possibly because of placental growth. In preeclampsia, reduced numbers of PMP are due to decreased platelet counts. Increased numbers of monocyte-derived MP reflect monocyte activation, which may be an expression of the systemic inflammation in preeclampsia. Lack of correlation between numbers of MP and severity of preeclampsia suggests that MP numbers alone do not explain the reported vascular effects of MP.

Objective: To assess the effect of maintenance tocolysis in women who are at high or low risk for preterm delivery according to fetal fibronectin (fFN) status and cervical length (CL). Study design: We compared the risk of preterm delivery in fFN pos and fFN neg women and in women with a CL