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Objective To assess the cost-effectiveness of treatment with nifedipine compared with atosiban in women with threatened preterm birth. Design An economic analysis alongside a randomised clinical trial (the APOSTEL III study). Setting Obstetric departments of 12 tertiary hospitals and seven secondary hospitals in the Netherlands and Belgium. Population Women with threatened preterm birth between 25 and 34 weeks of gestation, randomised for tocolysis with either nifedipine or atosiban. Methods We performed an economic analysis from a societal perspective. We estimated costs from randomisation until discharge. Analyses for singleton and multiple pregnancies were performed separately. The robustness of our findings was evaluated in sensitivity analyses. Main outcome measures Mean costs and differences were calculated per woman treated with nifedipine or atosiban. Health outcomes were expressed as the prevalence of a composite of adverse perinatal outcomes. Results Mean costs per patients were significantly lower in the nifedipine group [singleton pregnancies: euro34,897 versus euro43,376, mean difference (MD) -euro8479 [95% confidence interval (CI) -euro14,327 to -euro2016)]; multiple pregnancies: euro90,248 versus euro102,292, MD -euro12,044 (95% CI -euro21,607 to euro -1671). There was a non-significantly higher death rate in the nifedipine group. The difference in costs was mainly driven by a lower neonatal intensive care unit admission (NICU) rate in the nifedipine group. Conclusion Treatment with nifedipine in women with threatened preterm birth results in lower costs when compared with treatment with atosiban. However, the safety of nifedipine warrants further investigation. Tweetable abstract In women with threatened preterm birth, tocolysis using nifedipine results in lower costs when compared with atosiban.

Objective To assess the effect of transabdominal amnioinfusion or no intervention on long‐term outcomes in children born after second‐trimester prelabour rupture of the membranes (PROM between 16+0/7–24+0/7 weeks) and oligohydramnios. Population Follow up of infants of women who participated in the randomised controlled trial: PPROMEXIL‐III (NTR3492). Methods Surviving infants were invited for neurodevelopmental assessment up to 5 years of corrected age using a Bayley Scales of Infant and Toddler Development or a Wechsler Preschool and Primary Scale of Intelligence. Parents were asked to complete several questionnaires. Main outcome measures Neurodevelopmental outcomes were measured. Mild delay was defined as −1 standard deviation (SD), severe delay as −2 SD. Healthy long‐term survival was defined as survival without neurodevelopmental delay or respiratory problems. Results In the amnioinfusion group, 18/28 children (64%) died versus 21/28 (75%) in the no intervention group (relative risk 0.86; 95% confidence interval [CI] 0.60–1.22). Follow‐up data were obtained from 14/17 (82%) children (10 amnioinfusion, 4 no intervention). In both groups, 2/28 (7.1%) had a mild neurodevelopmental delay. No severe delay was seen. Healthy long‐term survival occurred in 5/28 children (17.9%) after amnioinfusion versus 2/28 (7.1%) after no intervention (odds ratio 2.50; 95% CI 0.53–11.83). When analysing data for all assessed survivors, 10/14 (71.4%) survived without mild neurodevelopmental delay and 7/14 (50%) were classified healthy long‐term survivor. Conclusions In this small sample of women suffering second‐trimester PROM and oligohydramnios, amnioinfusion did not improve long‐term outcomes. Overall, 71% of survivors had no neurodevelopmental delay. Tweetable abstract Healthy long‐term survival was comparable for children born after second‐trimester PROM and treatment with amnioinfusion or no intervention., Tweetable abstract Healthy long‐term survival was comparable for children born after second‐trimester PROM and treatment with amnioinfusion or no intervention.

Background COVID-19 restrictions have significantly limited access to in-person educational and healthcare services for all, including individuals with intellectual and developmental disabilities (IDDs). The objectives of this online survey that included both national and international families were to capture changes in access to healthcare and educational services for individuals with IDDs that occurred shortly after restrictions were initiated and to survey families on resources that could improve services for these individuals. Methods This was an online survey for caregivers of individuals with (1) a genetic diagnosis and (2) a neurodevelopmental diagnosis, including developmental delay, intellectual disability, autism spectrum disorder or epilepsy. The survey assessed (1) demographics, (2) changes in access to educational and healthcare services and (3) available and preferred resources to help families navigate the changes in service allocation. Results Of the 818 responses (669 within the USA and 149 outside of the USA), most families reported a loss of at least some educational or healthcare services. Seventy-four per cent of parents reported that their child lost access to at least one therapy or education service, and 36% of respondents lost access to a healthcare provider. Only 56% reported that their child received at least some continued services through tele-education. Those that needed to access healthcare providers did so primarily through telemedicine. Telehealth (both tele-education and telemedicine) was reported to be helpful when available, and caregivers most often endorsed a need for an augmentation of these remote delivery services, such as 1:1 videoconference sessions, as well as increased access to 1:1 aides in the home. Conclusions COVID-19 restrictions have greatly affected access to services for individuals with syndromic IDDs. Telehealth may provide opportunities for delivery of care and education in a sustainable way, not only as restrictions endure but also after they have been lifted.

Objective: To evaluate whether in symptomatic women, the combination of quantitative fetal fibronectin (fFN) testing and cervical length (CL) improves the prediction of preterm delivery (PTD) within 7 days compared with qualitative fFN and CL. Design: Post hoc analysis of frozen fFN samples of a nationwide cohort study. Setting: Ten perinatal centres in the Netherlands. Population: Symptomatic women between 24 and 34 weeks of gestation. Methods: The risk of PTD 500 ng/ml). Multivariable logistic regression showed an increasing risk of PTD in 500 ng/ml: OR 39, 95% CI 9.4–164] and shortening of the CL (OR 0.86 per mm, 95% CI 0.82–0.90). Use of quantitative fFN instead of qualitative fFN resulted in reclassification of 18 (5%) women from high to low risk, of whom one (6%) woman delivered within 7 days. Conclusion: In symptomatic women, quantitative fFN testing does not improve the prediction of PTD within 7 days compared with qualitative fFN testing in combination with CL measurement in terms of reclassification from high to low (

Objective Some clinicians advise prophylactic administration of antenatal steroids for fetal lung maturation in women with a triplet pregnancy. However, the effect of corticosteroids is limited to 10 to 14 days after administration. The aim of this study was to assess the natural course of triplet pregnancies to allow a better anticipation for administration of corticosteroids.Study Design We collected data on all triplet pregnancies in the Netherlands from 1999 to 2007 from the Netherlands Perinatal Registration. We calculated time to delivery, the risk of delivery in 2-week intervals at different gestational ages, and the time frame between hospital admission and delivery of the first child.Results Median gestational age at delivery of 494 women with a triplet pregnancy was 33(+4) weeks (interquartile range of 31-35(+1) weeks). Twenty-one women (4.3%) delivered between 22 and 24 weeks and 146 women (29.6%) delivered before 32 weeks. At a gestational age of 24 weeks, the chance to deliver within the next week was 0.6%. For 26, 28, 30, 31, and 32 weeks, these risks were 2.4, 2.5, 8.1, 7, and 16.7%, respectively.Conclusion Before 32 weeks of gestation, prophylactic administration of steroids is not indicated as the risk to deliver within 7 days is

OBJECTIVE: To determine whether second-trimester cervical length (CL) in women with a twin pregnancy is associated with the risk of emergency Cesarean section. METHODS: This was a secondary analysis of two randomized trials conducted in 57 hospitals in The Netherlands. We assessed the univariable association between risk indicators, including second-trimester CL in quartiles, and emergency Cesarean delivery using a logistic regression model. For multivariable analysis, we assessed whether adjustment for other risk indicators altered the associations found in univariable (unadjusted) analysis. Separate analyses were performed for suspected fetal distress and failure to progress in labor as indications for Cesarean section. RESULTS: In total, 311 women with a twin pregnancy attempted vaginal delivery after 34 weeks' gestation. Emergency Cesarean delivery was performed in 111 (36%) women, of which 67 (60%) were performed owing to arrest of labor. There was no relationship between second-trimester CL and Cesarean delivery (adjusted odds ratio (aOR): 0.97 for CL 26(th) -50(th) percentiles; 0.71 for CL 51(st) - 75(th) percentiles; and 0.92 for CL > 75(th) percentile, using CL ≤ 25(th) percentile as reference). In multivariable analysis, the only variables associated with emergency Cesarean delivery were maternal age (aOR, 1.07 (95% CI, 1.00-1.13)), body mass index (BMI) (aOR, 3.99 (95% CI, 1.07-14.9) for BMI 20-23 kg/m(2) ; 5.04 (95% CI, 1.34-19.03) for BMI 24-28 kg/m(2) ; and 3.1 (95% CI, 0.65-14.78) for BMI > 28 kg/m(2) ) and induction of labor (aOR, 1.92 (95% CI, 1.05-3.5)). CONCLUSION: In nulliparous women with a twin pregnancy, second-trimester CL is not associated with risk of emergency Cesarean delivery. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Item does not contain fulltext OBJECTIVE: To assess the effect of red blood cell (RBC) transfusion on quality of life in acutely anaemic women after postpartum haemorrhage. DESIGN: Randomised non-inferiority trial. SETTING: Thirty-seven Dutch university and general hospitals. POPULATION: Women with acute anaemia (haemoglobin 4.8-7.9 g/dl [3.0-4.9 mmol/l] 12-24 hours postpartum) without severe anaemic symptoms or severe comorbidities. METHODS: Women were allocated to RBC transfusion or non-intervention. MAIN OUTCOME MEASURES: Primary outcome was physical fatigue 3 days postpartum (Multidimensional Fatigue Inventory, scale 4-20; 20 represents maximal fatigue). Non-inferiority was demonstrated if the physical fatigue difference between study arms was maximal 1.3. Secondary outcomes were health-related quality of life and physical complications. Health-related quality of life questionnaires were completed at five time-points until 6 weeks postpartum. RESULTS: In all, 521 women were randomised to non-intervention (n = 262) or RBC transfusion (n = 259). Mean physical fatigue score at day 3 postpartum, adjusted for baseline and mode of delivery, was 0.8 lower in the RBC transfusion arm (95% confidence interval: 0.1-1.5, P = 0.02) and at 1 week postpartum was 1.06 lower (95% confidence interval: 0.3-1.8, P = 0.01). A median of two RBC units was transfused in the RBC transfusion arm. In the non-intervention arm, 33 women received RBC transfusion, mainly because of anaemic symptoms. Physical complications were comparable. CONCLUSIONS: Statistically, non-inferiority could not be demonstrated as the confidence interval crossed the non-inferiority boundary. Nevertheless, with only a small difference in physical fatigue and no differences in secondary outcomes, implementation of restrictive management seems clinically justified.

Objective Perinatal hypoxia-induced free radical formation is an important cause of hypoxic-ischaemic encephalopathy and subsequent neurodevelopmental disabilities. Allopurinol reduces the formation of free radicals, which potentially limits hypoxia-induced brain damage. We investigated placental transfer and safety of allopurinol after maternal allopurinol treatment during labour to evaluate its potential role as a neuroprotective agent in suspected fetal hypoxia. Design We used data from a randomised, double-blind multicentre trial comparing maternal allopurinol versus placebo in case of imminent fetal hypoxia (NCT00189007). Patients We studied 58 women in labour at term, with suspected fetal hypoxia prompting immediate delivery, in the intervention arm of the study. Setting Delivery rooms of 11 Dutch hospitals. Intervention 500 mg allopurinol, intravenously to the mother, immediately prior to delivery. Main outcome measures Drug disposition (maternal plasma concentrations, cord blood concentrations) and drug safety (maternal and fetal adverse events). Results Within 5 min after the end of maternal allopurinol infusion, target plasma concentrations of allopurinol of ≥2 mg/L were present in cord blood. Of all analysed cord blood samples, 95% (52/55) had a target allopurinol plasma concentration at the moment of delivery. No adverse events were observed in the neonates. Two mothers had a red and/or painful arm during infusion. Conclusions A dose of 500 mg intravenous allopurinol rapidly crosses the placenta and provides target concentrations in 95% of the fetuses at the moment of delivery, which makes it potentially useful as a neuroprotective agent in perinatology with very little side effects. Trial registration The study is registered in the Dutch Trial Register (NTR1383) and the Clinical Trials protocol registration system (NCT00189007).

Objective To assess the economic consequences of labour induction with Foley catheter compared to prostaglandin E2 gel. Design Economic evaluation alongside a randomised controlled trial. Setting Obstetric departments of one university and 11 teaching hospitals in the Netherlands. Population Women scheduled for labour induction with a singleton pregnancy in cephalic presentation at term, intact membranes and an unfavourable cervix; and without previous caesarean section. Methods Cost-effectiveness analysis from a hospital perspective. Main outcome measures We estimated direct medical costs associated with healthcare utilisation from randomisation to 6 weeks postpartum. For caesarean section rate, and maternal and neonatal morbidity we calculated the incremental cost-effectiveness ratios, which represent the costs to prevent one of these adverse outcomes. Results Mean costs per woman in the Foley catheter group (n = 411) and in the prostaglandin E2 gel group (n = 408), were €3297 versus €3075, respectively, with an average difference of €222 (95% confidence interval −€157 to €633). In the Foley catheter group we observed higher costs due to longer labour ward occupation and less cost related to induction material and neonatal admissions. Foley catheter induction showed a comparable caesarean section rate compared with prostaglandin induction, therefore the incremental cost-effectiveness ratio was not informative. Foley induction resulted in fewer neonatal admissions (incremental cost-effectiveness ratio €2708) and asphyxia/postpartum haemorrhage (incremental cost-effectiveness ratios €5257) compared with prostaglandin induction. Conclusions Foley catheter and prostaglandin E2 labour induction generate comparable costs.

Please cite this paper as: Tajik P, van der Tuuk K, Koopmans C, Groen H, van Pampus M, van der Berg P, van der Post J, van Loon A, de Groot C, Kwee A, Huisjes A, van Beek E, Papatsonis D, Bloemenkamp K, van Unnik G, Porath M, Rijnders R, Stigter R, de Boer K, Scheepers H, Zwinderman A, Bossuyt P, Mol B. Should cervical favourability play a role in the decision for labour induction in gestational hypertension or mild pre-eclampsia at term? An exploratory analysis of the HYPITAT trial. BJOG 2012;119:11231130. Objective To examine whether cervical favourability (measured by cervical length and the Bishop score) should inform obstetricians decision regarding labour induction for women with gestational hypertension or mild pre-eclampsia at term. Design A post hoc analysis of the Hypertension and Pre-eclampsia Intervention Trial At Term (HYPITAT). Setting Obstetric departments of six university and 32 teaching and district hospitals in the Netherlands. Population A total of 756 women diagnosed with gestational hypertension or pre-eclampsia between 36 + 0 and 41 + 0 weeks of gestation randomly allocated to induction of labour or expectant management. Methods Data were analysed using logistic regression modelling. Main outcome measures The occurrence of a high-risk maternal situation defined as either maternal complications or progression to severe disease. Secondary outcomes were caesarean delivery and adverse neonatal outcomes. Results The superiority of labour induction in preventing high-risk situations in women with gestational hypertension or mild pre-eclampsia at term varied significantly according to cervical favourability. In women who were managed expectantly, the longer the cervix the higher the risk of developing maternal high-risk situations, whereas in women in whom labour was induced, cervical length was not associated with a higher probability of maternal high-risk situations (test of interaction P = 0.03). Similarly, the beneficial effect of labour induction on reducing the caesarean section rate was stronger in women with an unfavourable cervix. Conclusion Against widely held opinion, our exploratory analysis showed that women with gestational hypertension or mild pre-eclampsia at term who have an unfavourable cervix benefited more from labour induction than other women. Trial registration The trial has been registered in the clinical trial register as ISRCTN08132825.

Please cite this paper as: Becker J, van Rijswijk J, Versteijnen B, Evers A, van den Akker E, van Beek E, Bolte A, Rijnders R, Mol B, Moons K, Porath M, Drogtrop A, Schuitemaker N, Willekes C, Westerhuis M, Visser G, Kwee A. Is intrapartum fever associated with ST-waveform changes of the fetal electrocardiogram? A retrospective cohort study. BJOG 2012;119:1410–1416. Objective To investigate the association between maternal intrapartum fever and ST-waveform changes of the fetal electrocardiogram. Design Retrospective cohort study. Setting Three academic and six non-academic teaching hospitals in the Netherlands. Population Labouring women with a high-risk singleton pregnancy in cephalic position beyond 36 weeks of gestation. Methods We studied 142 women with fever (≥38.0°C) during labour and 141 women with normal temperature who had been included in two previous studies. In both groups, we counted the number and type of ST-events and classified them as significant (intervention needed) or not significant, based on STAN® clinical guidelines. Main outcome measures Number and type of ST-events. Results Both univariable and multivariable regression analysis showed no association between the presence of maternal intrapartum fever and the number or type of ST-events. Conclusions Maternal intrapartum fever is not associated with ST-segment changes of the fetal electrocardiogram. Interpretation of ST-changes in labouring women with fever should therefore not differ from other situations.

Aim: In 2001, we implemented the ‘surfactant without intubation’ (SWI) method to administer surfactant during spontaneous breathing with nasal continuous positive airway pressure in preterm infants. To determine whether application of the SWI method in infants born at ≤27 weeks gestational age influences early school age outcome. Methods: A historical control cohort was compared to an interventional cohort, when the SWI method had become part of primary respiratory support. According to the overall results of psychometric and neurological examinations, children were classified as showing no functional impairment, minor or major impairments. Results: Out of 79 surviving children, 54 (68%, two children not completely classifiable) were assessed at a median age of 6 5/12 years [25 (32%) lost to follow-up]. Thirteen of 31 (42%, interventional cohort) vs. 8 of 21 (38%, control cohort) children had no functional impairment, 16 (52%) vs. 9 (43%) showed minor, and 2 (7%) vs. 4 (19%) major impairments. Conclusion: There was no statistically significant difference regarding neurodevelopmental school age outcome in children treated after implementing the SWI procedure, even though surviving infants had been more immature and survival rates had increased.

Wir wollten herausfinden, welche Faktoren das Kurz- und Langzeitergebnis bei Diabetespatienten nach peripherer Bypass-Chirurgie beeinflussen. Retrospektive Analyse von 721 Patienten, die von 1/1996 bis 12/2005 mit einem Bypass fur ein einzelnes Unterschenkel- oder Fusgefas versorgt wurden. Das Gesamtkollektiv (GK) bestand aus folgenden Subgruppen: Diabetes mellitus (DM) 482 (68%), terminale Niereninsuffizienz (NI) 96 (14%), periphere arterielle Verschlusskrankheit (PAVK), Stadium III/IV, 644 (89%). 30-Tage-Ergebnisse: Bypass-Offenheit GK 85,4%/DM 87,3%, Majoramputation GK 7%/DM 6,5%, Tod GK 5%/DM 5,2%. Langzeitergebnisse aus den Kaplan-Meier-Uberlebenskurven: Sekundare Funfjahres-Bypass-Offenheit: DM 43,6%/Nicht-DM 44,4% (n.s.). Funfjahresbeinerhalt: DM 69,2%/Nicht-DM 70,6% (n.s.). Funfjahresuberleben: DM 47,7%/Nicht-DM 58,8% (p

Item does not contain fulltext OBJECTIVE: To evaluate whether tocolysis with nifedipine can be omitted in women with symptoms of preterm labor, a shortened cervix, and negative fetal fibronectin test. STUDY DESIGN: A randomized noninferiority trial was performed in all Dutch perinatal centers. Women with symptoms of preterm labor between 24 and 34 weeks, intact membranes, cervical length between 10 and 30 mm, and negative fibronectin test were randomly allocated to nifedipine (80 mg/day) or placebo. The primary outcome was delivery within 7 days. Secondary outcomes were severe neonatal morbidity and mortality. We also followed all eligible nonrandomized women. RESULTS: We allocated 37 women to nifedipine and 36 women to placebo. In the nifedipine group, three women (8.1%) delivered within 7 days, compared with one woman (2.8%) in the placebo group (difference -5.3%; one-sided 95% confidence limit 4.5%). Median gestational age at delivery were respectively 37 + 0 (interquartile range [IQR] 34 + 6 to 38 + 5) and 38 + 2 (IQR 37 + 0 to 39 + 6) weeks (p = 0.008). In the nifedipine group, three pregnancies (8.1%) had a poor outcome; there were no poor outcomes in the placebo group. We observed similar trends in eligible nonrandomized women. CONCLUSION: In symptomatic women with preterm labor, a shortened cervix, and negative fibronectin test, placebo treatment is not inferior to tocolysis with nifedipine.

Anencephaly is a lethal defect resulting from a disturbed closure of the neural tube. Prenatal diagnosis during first-trimester-scan is essential but implies pitfalls. Three findings of anencephaly at 20 weeks gestation are reported. Fetuses with anencephaly are correctly identified at 12 to 13 weeks gestation. Anencephaly occurs in absence of the cranial vault. Ultrasound findings can be normal until onset of ossification has definitely failed. A first trimester scan at 12 to 13 weeks allows reliable diagnosis and active management of anencephaly. At this gestational age fetal anatomy can be screened in detail by transvaginal ultrasound and nuchal translucency can be measured.

Item does not contain fulltext OBJECTIVE: To assess the economic consequences of immediate delivery compared with expectant monitoring in women with preterm non-severe hypertensive disorders of pregnancy. DESIGN: A cost-effectiveness analysis alongside a randomised controlled trial (HYPITAT-II). SETTING: Obstetric departments of seven academic hospitals and 44 non-academic hospitals in the Netherlands. POPULATION: Women diagnosed with non-severe hypertensive disorders of pregnancy between 340/7 and 370/7 weeks of gestation, randomly allocated to either immediate delivery or expectant monitoring. METHODS: A trial-based cost-effectiveness analysis was performed from a healthcare perspective until final maternal and neonatal discharge. MAIN OUTCOME MEASURES: Health outcomes were expressed as the prevalence of respiratory distress syndrome, defined as the need for supplemental oxygen for >24 hours combined with radiographic findings typical for respiratory distress syndrome. Costs were estimated from a healthcare perspective until maternal and neonatal discharge. RESULTS: The average costs of immediate delivery (n = 352) were euro10 245 versus euro9563 for expectant monitoring (n = 351), with an average difference of euro682 (95% confidence interval, 95% CI -euro618 to euro2126). This 7% difference predominantly originated from the neonatal admissions, which were euro5672 in the immediate delivery arm and euro3929 in the expectant monitoring arm. CONCLUSION: In women with mild hypertensive disorders between 340/7 and 370/7 weeks of gestation, immediate delivery is more costly than expectant monitoring as a result of differences in neonatal admissions. These findings support expectant monitoring, as the clinical outcomes of the trial demonstrated that expectant monitoring reduced respiratory distress syndrome for a slightly increased risk of maternal complications. TWEETABLE ABSTRACT: Expectant management in preterm hypertensive disorders is less costly compared with immediate delivery.

To determine whether second-trimester cervical length (CL) in women with a twin pregnancy is associated with the risk of emergency Cesarean section.This was a secondary analysis of two randomized trials conducted in 57 hospitals in The Netherlands. We assessed the univariable association between risk indicators, including second-trimester CL in quartiles, and emergency Cesarean delivery using a logistic regression model. For multivariable analysis, we assessed whether adjustment for other risk indicators altered the associations found in univariable (unadjusted) analysis. Separate analyses were performed for suspected fetal distress and failure to progress in labor as indications for Cesarean section.In total, 311 women with a twin pregnancy attempted vaginal delivery after 34 weeks' gestation. Emergency Cesarean delivery was performed in 111 (36%) women, of which 67 (60%) were performed owing to arrest of labor. There was no relationship between second-trimester CL and Cesarean delivery (adjusted odds ratio (aOR): 0.97 for CL 26(th) -50(th) percentiles; 0.71 for CL 51(st) - 75(th) percentiles; and 0.92 for CL75(th) percentile, using CL ≤ 25(th) percentile as reference). In multivariable analysis, the only variables associated with emergency Cesarean delivery were maternal age (aOR, 1.07 (95% CI, 1.00-1.13)), body mass index (BMI) (aOR, 3.99 (95% CI, 1.07-14.9) for BMI 20-23 kg/m(2) ; 5.04 (95% CI, 1.34-19.03) for BMI 24-28 kg/m(2) ; and 3.1 (95% CI, 0.65-14.78) for BMI28 kg/m(2) ) and induction of labor (aOR, 1.92 (95% CI, 1.05-3.5)).In nulliparous women with a twin pregnancy, second-trimester CL is not associated with risk of emergency Cesarean delivery.

Objective To investigate whether vaginal Group B Streptococcus (GBS) colonisation or other baseline characteristics of women with preterm premature rupture of membranes (PPROM) can help in identifying subgroups of women who would benefit from immediate delivery.Design Secondary analysis of the PPROMEXIL trials.Setting Sixty hospitals in the Netherlands.Population Women with PPROM between 34 and 37 weeks of gestation.Methods Random assignment of 723 women to immediate delivery or expectant management.Main outcome measures Early onset neonatal sepsis.Results Vaginal GBS colonisation status was the only marker which was significantly associated with the benefit of immediate delivery (P for interaction: 0.04). GBS colonisation was observed in 14% of women. The risk of early onset neonatal sepsis in GBS-positive women was high (15.2%) when they were managed expectantly but this risk was reduced to 1.8% with immediate delivery. The early onset neonatal sepsis risk was much lower in neonates of GBS-negative women: 2.6% after expectant management and 2.9% with immediate delivery. We estimated that by inducing labour only in GBS-positive women, there would be a 10.4% increase in term delivery rate, while keeping neonatal sepsis and caesarean delivery rates comparable to a strategy of labour induction for all.Conclusions Our post hoc findings suggest that women with PROM between 34 and 37 weeks might benefit from immediate delivery if they have GBS vaginal colonisation, while in GBS-negative women labour induction could be delayed until 37 weeks.

To assess the economic consequences of labour induction with Foley catheter compared to prostaglandin E2 gel.Economic evaluation alongside a randomised controlled trial.Obstetric departments of one university and 11 teaching hospitals in the Netherlands.Women scheduled for labour induction with a singleton pregnancy in cephalic presentation at term, intact membranes and an unfavourable cervix; and without previous caesarean section.Cost-effectiveness analysis from a hospital perspective.We estimated direct medical costs associated with healthcare utilisation from randomisation to 6 weeks postpartum. For caesarean section rate, and maternal and neonatal morbidity we calculated the incremental cost-effectiveness ratios, which represent the costs to prevent one of these adverse outcomes.Mean costs per woman in the Foley catheter group (n = 411) and in the prostaglandin E₂ gel group (n = 408), were €3297 versus €3075, respectively, with an average difference of €222 (95% confidence interval -€157 to €633). In the Foley catheter group we observed higher costs due to longer labour ward occupation and less cost related to induction material and neonatal admissions. Foley catheter induction showed a comparable caesarean section rate compared with prostaglandin induction, therefore the incremental cost-effectiveness ratio was not informative. Foley induction resulted in fewer neonatal admissions (incremental cost-effectiveness ratio €2708) and asphyxia/postpartum haemorrhage (incremental cost-effectiveness ratios €5257) compared with prostaglandin induction.Foley catheter and prostaglandin E2 labour induction generate comparable costs.

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.

To investigate the association between maternal intrapartum fever and ST-waveform changes of the fetal electrocardiogram.Retrospective cohort study.Three academic and six non-academic teaching hospitals in the Netherlands.Labouring women with a high-risk singleton pregnancy in cephalic position beyond 36 weeks of gestation.We studied 142 women with fever (≥38.0°C) during labour and 141 women with normal temperature who had been included in two previous studies. In both groups, we counted the number and type of ST-events and classified them as significant (intervention needed) or not significant, based on STAN(®) clinical guidelines.Number and type of ST-events.Both univariable and multivariable regression analysis showed no association between the presence of maternal intrapartum fever and the number or type of ST-events.Maternal intrapartum fever is not associated with ST-segment changes of the fetal electrocardiogram. Interpretation of ST-changes in labouring women with fever should therefore not differ from other situations.

Objectives Previous studies on singleton pregnancies have indicated that progestogens may reduce the rate of cervical shortening during pregnancy. The aim of this study was to investigate whether treatment with 17-alpha hydroxyprogesterone caproate (17-OHPC) has an effect on cervical shortening in twin pregnancies. Methods This was a secondary analysis of patients who had participated in a multicenter randomized clinical trial on the effectiveness of 17-OHPC in preventing preterm birth in multiple pregnancies (the AMPHIA-trial). We included all trial participants with a twin gestation who had undergone repeat cervical length measurements during pregnancy. We performed a separate analysis of women with repeat measurements in centers where this was standard protocol for multiple pregnancies. The rate of cervical shortening for both the 17-OHPC group and the placebo group was analyzed using a linear mixed model. Results Of the 671 patients who participated in the trial, 282 (42%) had a twin pregnancy and underwent two or more cervical length measurements. Of these women, 140 were monitored in centers where repeat measurements were standard protocol. We observed an overall reduction of cervical length from 44.3 mm at 14–18 weeks to 30.0 mm at 30–34 weeks' gestation. In the 17-OHPC group, cervical length decreased by 1.04 mm each gestational week, while this was 1.11 mm per week for the placebo group (P = 0.6). For the overall group, each 10% decrease in cervical length led to an increase in the risk of preterm birth (hazard ratio, 1.14; 95% CI, 1.08–1.21). Conclusion In women with a twin pregnancy, there is progressive shortening of the cervix during pregnancy, regardless of 17-OHPC use. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.

To evaluate the added value of the baseline T/QRS ratio to other known risk factors in predicting adverse outcome and interventions for suspected fetal distress.Prospective cohort study.Three academic and six non-academic teaching hospitals in the Netherlands.Laboring women with a high-risk cephalic singleton pregnancy beyond 36 weeks of gestation.We obtained STAN(®) recordings (ST-analysis, Neoventa, Sweden) from two previous studies. Three patient groups were defined: cases with adverse outcome, cases with emergency delivery because of suspected fetal distress without adverse outcome, and a reference group of uncomplicated cases. Baseline T/QRS ratios among the adverse outcome and intervention for suspected fetal distress cases were compared to those of the uncomplicated cases. The ability of baseline T/QRS to predict adverse outcome and suspected fetal distress was determined using a multivariable logistic model.The added value of the baseline T/QRS to other known risk factors in the prediction of adverse outcome and interventions for suspected fetal distress.From 3462 recordings, 2459 were available for analysis. Median baseline T/QRS for uncomplicated cases, adverse outcome and interventions for suspected fetal distress were 0.12 (range 0.00-0.52), 0.12 (0.00-0.42) and 0.13 (0.00-0.39), respectively. There was no statistical difference between these groups. Multivariable analysis showed no added value of baseline T/QRS in the prediction of either adverse outcome or interventions for suspected fetal distress.Baseline T/QRS has no added value in the prediction of adverse neonatal outcome or interventions for suspected fetal distress.

In 2001, we implemented the 'surfactant without intubation' (SWI) method to administer surfactant during spontaneous breathing with nasal continuous positive airway pressure in preterm infants. To determine whether application of the SWI method in infants born at ≤ 27 weeks gestational age influences early school age outcome.A historical control cohort was compared to an interventional cohort, when the SWI method had become part of primary respiratory support. According to the overall results of psychometric and neurological examinations, children were classified as showing no functional impairment, minor or major impairments.Out of 79 surviving children, 54 (68%, two children not completely classifiable) were assessed at a median age of 6 5/12 years [25 (32%) lost to follow-up]. Thirteen of 31 (42%, interventional cohort) vs. 8 of 21 (38%, control cohort) children had no functional impairment, 16 (52%) vs. 9 (43%) showed minor, and 2 (7%) vs. 4 (19%) major impairments.There was no statistically significant difference regarding neurodevelopmental school age outcome in children treated after implementing the SWI procedure, even though surviving infants had been more immature and survival rates had increased.

Two premature babies were admitted separately to the Neonatal Intensive Care Unit. One patient, a girl, presented with severe anaemia and thrombocytopaenia, the other, another girl, showed isolated thrombocytopaenia. During both pregnancies, ultrasound showed abnormalities of the placenta. The first patient also had intra-uterine growth restriction. A postpartum pathological examination showed abnormalities of both placentae consistent with placental mesenchymal dysplasia. Placental mesenchymal dysplasia is a rare condition which is associated with intra-uterine growth restriction, intra-uterine mortality, prematurity and Beckwith-Wiedemann syndrome. Thrombocytopaenia and anaemia are less commonly described in literature and are caused by micro-angiopathic haemolysis in the placenta. Both children had unrestricted growth and development patterns at one year and 6 months follow-up, respectively.

To determine the prognostic value of foetal fibronectin and cervical length for predicting imminent preterm labour among Dutch women, who in the Netherlands normally undergo a digital examination of the cervix prior to referral to a hospital or university medical centre.Prospective observational cohort study.Pregnant women with symptoms of preterm labour and a gestational age between 24 and 34 weeks were included. A fibronectin smear was taken from them and the cervical length was measured. Primary outcome was delivery within 7 days after inclusion. Sensitivity, specificity and a receiver-operating characteristics (ROC) curve were calculated.13 (12%) of the 108 included patients delivered spontaneously within 7 days after inclusion. The fibronectin test had a sensitivity of 92% and specificity of 60%. The positive and negative predictive values were 27% and 98% respectively. For women who had undergone a digital examination prior to testing, the predictive value was slightly less but the difference was not significant. Although measurement of the cervical length scarcely had a predictive value, none of the patients with a cervical length above 35 mm delivered within 7 days.In women with an imminent preterm labour, a negative fibronectin test virtually ruled out delivery within 7 days. The fibronectin test can therefore also be used in the Dutch situation. In women with a cervix length greater than 35 mm, the chance of a preterm labour within 7 days is very small and a fibronectin test does not need to be performed in their case.

Sir, We read with great interest the article by Ojala et al.1 The authors report that the incidence of metabolic acidosis after intrapartum monitoring by means of cardiotocography (CTG) supplemented by automatic ST analysis (STAN) of the fetal electrocardiogram is 1.7%, as compared with 0.7% after CTG alone. We wish to comment on the conclusion of the authors that CTG + STAN did not improve the neonatal outcome or decrease the caesarean section rate but that the need for fetal blood sampling (FBS) during labour was lower in the STAN group. In fact, although not statistically significant, there is a clinically relevant difference of 1% in the incidence of metabolic acidosis in favour of the CTG-alone group (metabolic acidosis being defined as a pH < 7.05 and base excess < –12 mmol/l). This is worrying because if confirmed in a larger study, such a difference could result in a poorer neonatal outcome. This finding contrasts with that of the previous study of AmerWahlin.2 Because of the importance of this outcome, we consider that the study was underpowered. Ojala et al. based their power calculation on the incidence of a neonatal umbilical artery pH < 7.10 rather than a pH < 7.05, which is more stringent and relevant to outcome. When using the lower cutoff level in pH, the incidence of neonatal acidaemia will be lower and the required sample size will therefore be higher. In general, the power of a study must be based on the primary endpoint, and this endpoint should be the same in both the power calculation and the final analysis. Second, although again not statistically significant, there is a 1.7% lower overall caesarean section rate in the CTG group. Little attention is paid to this important finding. No information is available about the rate of caesarean sections performed for failure to progress or a combination of failure to progress and fetal distress. It may be that the indications for caesarean section were significantly different in the two groups. In summary, we feel that the study of Ojala et al. raises concerns about fetal outcome when using STAN. In view of this concern, we have started a randomised clinical trial comparing CTG + STAN with CTG + FBS, with a larger sample size. j

Anencephaly is a lethal defect resulting from a disturbed closure of the neural tube. Prenatal diagnosis during first-trimester-scan is essential but implies pitfalls. Three findings of anencephaly at 20 weeks gestation are reported. Fetuses with anencephaly are correctly identified at 12 to 13 weeks gestation. Anencephaly occurs in absence of the cranial vault. Ultrasound findings can be normal until onset of ossification has definitely failed. A first trimester scan at 12 to 13 weeks allows reliable diagnosis and active management of anencephaly. At this gestational age fetal anatomy can be screened in detail by transvaginal ultrasound and nuchal translucency can be measured.

Background Hypoxic-ischemic encephalopathy due to perinatal hypoxia-induced free radical formation is an important cause of long-term neurodevelopmental disabilities. Allopurinol reduces the formation of free radicals, which potentially limits hypoxia-induced reperfusion damage. With this trial we aimed to assess whether maternal allopurinol treatment during fetal hypoxia would reduce the release of brain-tissue-specific biomarkers associated with neonatal brain damage. Methods We performed a randomized double blind placebo controlled multicenter trial (NCT00189007) studying laboring women at term with imminent fetal hypoxia. Fetal distress was suspected in case of an abnormal fetal heart rate trace, ST-wave abnormalities on fetal ECG or fetal scalp pH Results We randomized 222 women to allopurinol (n=111) or placebo (n=111). S100B was significantly lower in the allopurinol-group (median 43.4; IQR 20.2–71.5) compared to the placebo-group (median 54.9; IQR 26.8–94.7), RR 0.91 (95%CI 0.88–0.94). Neuroketal did not significantly differ between groups, geometric mean difference –7.57 (95%CI –15.6; 3.57). Post-hoc analysis showed a marked gender difference in treatment effect in favor of girls for S100B (RR 0.63 (95%CI 0.59–0.68)) and neuroketal (geometric mean difference –16.5 (95%CI –24.6; -1.83)). Conclusion Maternal treatment with allopurinol during fetal hypoxia reduces damage to neuronal cells as indicated by brain-tissue-specific chemical biomarkers.