Consequences of cervical pessary for subsequent pregnancy: follow-up of randomized clinical trial (ProTWIN).

OBJECTIVE: To evaluate the effect of cervical pessary, as a strategy to prevent preterm birth (PTB), on the outcome of subsequent pregnancy and maternal quality of life 4 years after the index twin pregnancy. METHODS: Between 2009 and 2012, the ProTWIN trial randomized women with a multiple pregnancy to pessary use vs standard care for the prevention of PTB. The trial showed no benefit in unselected women with a twin pregnancy, but showed a 60% reduction in poor perinatal outcomes in favor of the pessary group in the subgroup of women with a mid-trimester short cervix (cervical length < 38 mm). All women were invited to participate in a follow-up study 4 years after their participation in the ProTWIN trial. In this follow-up study, maternal quality of life was assessed using the EQ-5D-3L questionnaire and women were asked separate questions about subsequent pregnancies. Results were compared between women who were randomized to the pessary vs the control group in the ProTWIN trial by calculating relative risk (RR) and 95% CI. Subgroup analysis was performed for women with a mid-trimester short cervix (cervical length < 38 mm). RESULTS: Of the 813 women included in the ProTWIN trial, 408 (50.2%) participated in this follow-up study, comprising 228 randomized to the pessary group and 180 to the control group in the original trial. The median interval between participation in the ProTWIN trial and participation in this follow-up study was 4.1 (interquartile range (IQR), 3.9-7.1) years. Ninety-eight (24.0%) participants tried to conceive after their participation in the ProTWIN trial. Of those, 22 (22.4%) women did not have a subsequent pregnancy (no difference between pessary and control groups), seven (7.1%) women had at least one miscarriage but no live birth, and 67 (68.4%) women had at least one live birth (35 in the pessary vs 32 in the control group; RR, 0.93 (95% CI, 0.8-1.07)). In two women, the pregnancy outcome was unknown. Preterm delivery (< 37 weeks of gestation) of the first live birth occurred in three women in the pessary vs one woman in the control group (all singleton; RR, 2.57 (95% CI, 0.28-23.44)). No differences were found between the pessary and control groups in the subgroup of women with mid-trimester short cervix, but the numbers analyzed were small. The median health state index score was 0.95 (IQR, 0.82-0.95), with no difference between the pessary and control groups. CONCLUSION: Our findings suggest that there are no long-term effects of pessary use on the outcome of subsequent pregnancies and maternal quality of life. Data on obstetric outcome were limited due to the small numbers. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Association between COVID-19 lockdown measures and the incidence of iatrogenic versus spontaneous very preterm births in the Netherlands: a retrospective study.

BACKGROUND: The COVID-19 pandemic led to regional or nationwide lockdowns as part of risk mitigation measurements in many countries worldwide. Recent studies suggest an unexpected and unprecedented decrease in preterm births during the initial COVID-19 lockdowns in the first half of 2020. The objective of the current study was to assess the effects of the two months of the initial national COVID-19 lockdown period on the incidence of very and extremely preterm birth in the Netherlands, stratified by either spontaneous or iatrogenic onset of delivery, in both singleton and multiple pregnancies. METHODS: Retrospective cohort study using data from all 10 perinatal centers in the Netherlands on very and extremely preterm births during the initial COVID-19 lockdown from March 15 to May 15, 2020. Incidences of very and extremely preterm birth were calculated using an estimate of the total number of births in the Netherlands in this period. As reference, we used data from the corresponding calendar period in 2015-2018 from the national perinatal registry (Perined). We differentiated between spontaneous versus iatrogenic onset of delivery and between singleton versus multiple pregnancies. RESULTS: The incidence of total preterm birth < 32 weeks in singleton pregnancies was 6.1‰ in the study period in 2020 versus 6.5‰ in the corresponding period in 2015-2018. The decrease in preterm births in singletons was solely due to a significant decrease in iatrogenic preterm births, both < 32 weeks (OR 0.71; 95%CI 0.53 to 0.95) and < 28 weeks (OR 0.53; 95%CI 0.29 to 0.97). For multiple pregnancies, an increase in preterm births < 28 weeks was observed (OR 2.43; 95%CI 1.35 to 4.39). CONCLUSION: This study shows a decrease in iatrogenic preterm births during the initial COVID-19-related lockdown in the Netherlands in singletons. Future studies should focus on the mechanism of action of lockdown measures and reduction of preterm birth and the effects of perinatal outcome.

Induction of labor with Foley catheter and risk of subsequent preterm birth: follow-up study of two randomized controlled trials (PROBAAT-1 and -2).

OBJECTIVE: To evaluate the rate of preterm birth (PTB) in a subsequent pregnancy in women who had undergone term induction using a Foley catheter compared with prostaglandins. METHODS: This was a follow-up study of two large randomized controlled trials (PROBAAT-1 and PROBAAT-2). In the original trials, women with a term singleton pregnancy with the fetus in cephalic presentation and with an indication for labor induction were randomized to receive either a 30-mL Foley catheter or prostaglandins (vaginal prostaglandin E2 in PROBAAT-1 and oral misoprostol in PROBAAT-2). Data on subsequent ongoing pregnancies > 16 weeks' gestation were collected from hospital charts from clinics participating in this follow-up study. The main outcome measure was preterm birth < 37 weeks' gestation in a subsequent pregnancy. RESULTS: Fourteen hospitals agreed to participate in this follow-up study. Of the 1142 eligible women, 572 had been allocated to induction of labor using a Foley catheter and 570 to induction of labor using prostaglandins. Of these, 162 (14%) were lost to follow-up. In total, 251 and 258 women had a known subsequent pregnancy > 16 weeks' gestation in the Foley catheter and prostaglandin groups, respectively. There were no differences in baseline characteristics between the groups. The overall rate of PTB in a subsequent pregnancy was 9/251 (3.6%) in the Foley catheter group vs 10/258 (3.9%) in the prostaglandin group (relative risk (RR), 0.93; 95% CI, 0.38-2.24), and the rate of spontaneous PTB was 5/251 (2.0%) vs 5/258 (1.9%) (RR, 1.03; 95% CI, 0.30-3.51). CONCLUSION: In women with term singleton pregnancy, induction of labor using a 30-mL Foley catheter is not associated with an increased risk of PTB in a subsequent pregnancy, as compared to induction of labor using prostaglandins. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The long-term effect of prenatal progesterone treatment on child development, behaviour and health: a systematic review.

BACKGROUND: Progesterone is widely used in prenatal care. However, long-term effects of prenatal progesterone treatment on child development are unclear. OBJECTIVES: To evaluate long-term outcomes in children after prenatal progesterone treatment. SEARCH STRATEGY: MEDLINE, Embase and Cochrane Central Register of Controlled Trials from inception to 24 May 2020. SELECTION CRITERIA: Randomised controlled trials (RCTs) reporting outcomes in children born to women who received progesterone treatment (compared with placebo or another intervention) during any trimester in pregnancy. DATA COLLECTION AND ANALYSIS: Two authors independently selected and extracted data. We used the Cochrane Risk of Bias tool for randomised trials and Quality In Prognosis Studies. MAIN RESULTS: Of 388 papers, we included seven articles based on five RCTs, comprising 4222 measurements of children aged 6 months to 8 years. All studies compared progesterone to placebo in second and/or third trimester for the prevention of preterm birth. Meta-analysis (two studies, n = 890 children) showed no difference in neurodevelopment as assessed by the Bayley-III Cognitive Composite score at 2 years between children exposed to progesterone versus placebo (Standardised Mean Difference -0.04, 95% Confidence Interval -0.26 to 0.19), I2  = 22%. Heterogeneity prohibited additional meta-analyses. Other long-term outcomes showed no differences. CONCLUSIONS: Our systematic review comprising a multitude of developmental measurements with a broad age range did not find evidence of benefit or harm in offspring prenatally exposed to progesterone treatment for the prevention of preterm birth. We identified an urgent need for follow-up studies of prenatal progesterone administration in early pregnancy and effects in offspring beyond early childhood. TWEETABLE ABSTRACT: Progesterone to prevent preterm birth: no effect on child development. Outcomes after first trimester progesterone are unclear.

Tocolysis compared with no tocolysis in women with threatened preterm birth and ruptured membranes: A propensity score analysis.

INTRODUCTION: In women with preterm ruptured membranes and contractions, the administration of tocolysis is controversial. This study compares tocolysis with no tocolysis in women with threatened preterm birth and ruptured membranes. OBJECTIVE: To compare tocolysis with no tocolysis in women with threatened preterm birth and ruptured membranes. STUDY DESIGN: Data from the APOSTEL III RCT was combined with data from the National Maternity Hospital, Dublin. In the APOSTEL III trial, women with threatened preterm birth were randomized to atosiban or nifedipine. Patient data from Ireland were obtained from a cohort of women with threatened preterm birth with ruptured membranes. The Irish women received no tocolytic treatment. Only women with ruptured membranes and contractions were selected. We studied women with singleton or twin pregnancies and a gestational age between 25+0 and 33+6 weeks. Propensity score matching was performed to create comparable groups. Primary outcome was a composite adverse neonatal outcome. Secondary outcomes were individual components of the primary outcome, as well as neonatal intensive care unit (NICU) admission, gestational age at delivery, prolongation of pregnancy and mode of delivery. RESULTS: 153 women from the Apostel III trial were compared with 51 eligible women of the Irish cohort. We could match 46 women who received tocolysis and 46 women who received no tocolysis. All women had ruptured membranes. Maternal age, BMI, parity and gestational age at study entry were comparable between the groups after matching. There were no statistically significant differences in neonatal composite outcome (9.6 % in the tocolysis group versus 18 % in the control group, OR 0.46, 95 % CI 0.13-1.63). We found a lower incidence of NICU admission in the tocolysis group (63 %) than in the control group (94 %; OR 0.11, 95 % CI 0.03-0.41), which could be explained by differences in national admission policies. There were no statistically significant differences between tocolysis and no tocolysis in any of the other outcomes including sepsis, gestational age at delivery and time to delivery. CONCLUSION: In this propensity score analysis of women with threatened preterm birth and ruptured membranes, tocolytic therapy did not alter composite adverse neonatal outcome or time to delivery.

Effects of tocolysis with nifedipine or atosiban on child outcome: follow-up of the APOSTEL III trial.

OBJECTIVE: To compare the long-term effects of tocolysis with nifedipine or atosiban on child outcome at age 2.5-5.5 years. DESIGN: The APOSTEL III trial was a multicentre randomised controlled trial that compared tocolysis with nifedipine or atosiban in 503 women with threatened preterm birth. Neonatal outcomes did not differ between both treatment arms, except for a higher incidence of intubation in the atosiban group. METHODS: Parents were asked to complete four questionnaires regarding neurodevelopment, executive function, behaviour problems and general health. MAIN OUTCOME MEASURES: The main long-term outcome measure was a composite of abnormal development at the age of 2.5-5.5 years. RESULTS: Of the 426 women eligible for follow-up, 196 (46%) parents returned the questionnaires for 115 children in the nifedipine group and 110 children in the atosiban group. Abnormal development occurred in 32 children (30%) in the nifedipine group and in 38 children (38%) in the atosiban group (OR 0.74, 95% CI 0.41-1.34). The separate outcomes for neurodevelopment, executive function, behaviour, and general health showed no significant differences between the groups. Sensitivity analysis for all children of the APOSTEL III trial, including a comparison of deceased children, resulted in a higher rate of healthy survival in the nifedipine group (64 versus 54%), but there was no significant difference in the overall mortality rate (5.4 versus 2.7%). There were no significant subgroup effects. CONCLUSION: Outcomes on broad child neurodevelopment, executive function, behaviour and general health were comparable in both groups. Neither nifedipine nor atosiban can be considered as the preferred treatment for women with threatened preterm birth. TWEETABLE ABSTRACT: Nifedipine- and atosiban-exposed children had comparable long-term outcomes, including neurodevelopment, executive function and behaviour.

Risk of preterm birth after prior term cesarean.

OBJECTIVE: To determine the risk of overall preterm birth (PTB) and spontaneous PTB in a pregnancy after a caesarean section (CS) at term. DESIGN: Longitudinal linked national cohort study. SETTING: The Dutch Perinatal Registry (1999-2009). POPULATION: 268 495 women with two subsequent singleton pregnancies were identified. METHODS: A cohort study based on linked registered data from two subsequent pregnancies in the Netherlands. MAIN OUTCOME MEASURES: The incidence of overall PTB and spontaneous PTB with subgroup analysis on gestational age at first delivery and type of CS (planned or unplanned). RESULTS: Of 268 495 women with a singleton first pregnancy who delivered at term, 15.76% (n = 42 328) had a CS. The incidence of PTB in the second pregnancy was 2.79% (n = 1182) in women with a previous CS versus 2.46% (n = 5570) in women with a previous vaginal delivery (adjusted odds ratio [aOR] 1.14, 95% confidence interval [CI] 1.07-1.21). This increased risk is mainly driven by an increased risk of spontaneous PTB after previous CS at term (aOR 1.50, 95% CI 1.38-1.70). Analysis for type of CS compared with vaginal delivery showed an aOR on spontaneous PTB of 1.86 (95% CI 1.58-2.18) for planned CS and an aOR of 1.40 (95% CI 1.24-1.58) for unplanned CS. CONCLUSIONS: CS at term is associated with a marginally increased risk of spontaneous PTB in a subsequent pregnancy. TWEETABLE ABSTRACT: Caesarean section at term is associated with a marginally increased risk of spontaneous PTB in a subsequent pregnancy.

Cost effectiveness of nifedipine compared with atosiban in the treatment of threatened preterm birth (APOSTEL III trial).

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: €34,897 versus €43,376, mean difference (MD) -€8479 [95% confidence interval (CI) -€14,327 to -€2016)]; multiple pregnancies: €90,248 versus €102,292, MD -€12,044 (95% CI -€21,607 to € -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.

Maternal right ventricular function, uteroplacental circulation in first trimester and pregnancy outcome in women with congenital heart disease.

OBJECTIVE: Pregnant women with congenital heart disease (CHD) have an increased risk of abnormal uteroplacental flow, measured from the second trimester onwards, which is associated with pregnancy complications affecting the mother and the fetus. Maternal right ventricular (RV) dysfunction has been suggested as a predisposing factor for impaired uteroplacental flow in these women. The aim of this study was to investigate the association of first-trimester uteroplacental flow measurements with prepregnancy maternal cardiac function and pregnancy complications in women with CHD, with particular focus on the potential role of RV (dys)function. METHODS: This study included 138 pregnant women with CHD from the prospective ZAHARA III study (Zwangerschap bij Aangeboren HARtAfwijkingen; Pregnancy and CHD). Prepregnancy clinical and echocardiographic data were collected. Clinical evaluation, echocardiography (focused on RV function, as assessed by tricuspid annular plane systolic excursion (TAPSE)) and uterine artery (UtA) pulsatility index (PI) measurements were performed at 12, 20 and 32 weeks of gestation. Univariable and multivariable regression analyses were performed to assess the association between prepregnancy variables and UtA-PI during pregnancy. The association between UtA-PI at 12 weeks and cardiovascular, obstetric and neonatal complications was also assessed. RESULTS: On multivariable regression analysis, prepregnancy TAPSE was associated negatively with UtA-PI at 12 weeks of gestation (ß = -0.026; P = 0.036). Women with lower prepregnancy TAPSE (≤ 20 mm vs > 20 mm) had higher UtA-PI at 12 weeks (1.5 ± 0.5 vs 1.2 ± 0.6; P = 0.047). Increased UtA-PI at 12 weeks was associated with obstetric complications (P = 0.003), particularly hypertensive disorders (pregnancy-induced hypertension and pre-eclampsia, P = 0.019 and P = 0.026, respectively). CONCLUSIONS: In women with CHD, RV dysfunction before pregnancy seems to impact placentation, resulting in increased resistance in UtA flow, which is detectable as early as in the first trimester. This, in turn, is associated with pregnancy complications. Early monitoring of uteroplacental flow might be of value in women with CHD with pre-existing subclinical RV dysfunction to identify pregnancies that would benefit from close obstetric surveillance. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

[Fibronectin test in threatened preterm labour: cost-saving but not yet widely implemented in the Netherlands]. / Fibronectinetest bij dreigende vroeggeboorte.

OBJECTIVE: Analysis of national implementation of the foetal fibronectin test in the diagnostics of threatened preterm labour in the Netherlands, and indication of the possible obstacles and consequences of implementation or no implementation. DESIGN: National questionnaire, retrospective cohort study and cost-effectiveness calculation. METHODS: We approached all hospitals in the Netherlands (n = 86) with a questionnaire on use of the fibronectin test. We also collected data on women who were referred to the Academic Medical Center (AMC), a tertiary care centre in Amsterdam, with symptoms of threatened preterm labour. We investigated whether the referred patients gave birth within 7 days, and whether unnecessary transfer to a centre with a neonatal intensive care unit (NICU) could have been avoided by implementation of the fibronectin test in the referring hospital. RESULTS: The fibronectin test was used in 34% of the hospitals and an additional 17% were in the process of implementation. The most important reasons not to use the fibronectin test were of a financial nature (50%). The cohort study included 96 women who were referred from secondary care. In our cohort, 36% of all transfers could have been avoided by implementation of the fibronectin test in secondary care. CONCLUSION: The fibronectin test can greatly reduce overtreatment and unnecessary transfer in threatened preterm labour, but implementation remains limited. Costs of the test are an obstacle for the referring hospitals, while implementation prevents unnecessary transport, admission and treatment of pregnant women, giving a potential saving of at least EUR 1,027,930 per year. Inclusion in the Netherlands Society for Obstetrics and Gynaecology (Nederlandse Vereniging voor Obstetrie en Gynaecologie, NVOG) guidelines would be a first step towards wider implementation. Slow implementation exemplifies a more widespread problem: the current reimbursement system does not stimulate such cost-saving innovations.

Effect of nifedipine and atosiban on perinatal brain injury: secondary analysis of the APOSTEL-III trial.

OBJECTIVE: Brain injury in neonates born prematurely is associated strongly with poor neurodevelopmental outcome. The aim of this study was to evaluate whether tocolysis with nifedipine or atosiban in women with threatened preterm birth can reduce the incidence of overall brain injury in neonates born prematurely. METHODS: This was a secondary analysis of the APOSTEL-III trial (Dutch Clinical Trial Registry, no. NTR2947), a randomized clinical trial in which women with threatened preterm labor between 25 and 34 weeks of gestation were allocated to treatment with nifedipine or atosiban. In this secondary analysis, women delivered at ≤ 32 weeks of gestational age in the two main contributing centers were included. Primary outcome was the presence of neonatal brain injury, which was defined as presence of abnormalities on ultrasound investigation and classified into mild and severe. To evaluate type and severity of brain injury, all neonatal ultrasounds performed during neonatal intensive and medium care admission were analyzed. To test the robustness of our results, a sensitivity analysis was performed assessing differences in baseline or known risk factors for brain injury. RESULTS: A total of 117 neonates (from 102 women) were studied, of which 51 had been exposed to nifedipine and 66 to atosiban. Brain injury was observed in 22 (43.1%) neonates in the nifedipine group compared with 37 (56.1%) in the atosiban group (OR, 0.60; 95% CI, 0.29-1.24). Presence of mild brain injury was comparable between the nifedipine (33.3%) and atosiban (48.5%) groups (OR, 0.53; 95% CI, 0.25-1.13). Severe brain injury was also comparable between the groups, observed in 9.8% of neonates in the nifedipine vs 7.6% of those in the atosiban group (OR, 1.33; 95% CI, 0.36-4.85). Intraventricular hemorrhage (≥ Grade I) was the most frequently seen ultrasound abnormality, observed in 18 (35.3%) neonates in the nifedipine group vs 25 (37.9%) in the atosiban group (OR, 0.90; 95% CI, 0.42-1.91). The sensitivity analysis, with adjustment for maternal age and gestational age at randomization, showed no statistical difference between the groups for presence of brain injury (OR, 0.58; 95% CI, 0.27-1.27). CONCLUSION: In children born before 32 weeks of gestation after the use of tocolytics, the prevalence of brain injury was high. No significant differences were found with respect to overall brain injury between neonates exposed to nifedipine and those exposed to atosiban. However, as this study was a secondary analysis of the APOSTEL III trial, it was underpowered for brain injury. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Cost-effectiveness of diagnostic testing strategies including cervical-length measurement and fibronectin testing in women with symptoms of preterm labor.

OBJECTIVE: To evaluate the cost-effectiveness of combining cervical-length (CL) measurement and fetal fibronectin (fFN) testing in women with symptoms of preterm labor between 24 and 34 weeks' gestation. METHODS: This was a model-based cost-effectiveness analysis evaluating seven test-treatment strategies based on CL measurement and/or fFN testing in women with symptoms of preterm labor from a societal perspective, in which neonatal outcomes and costs were weighted. Estimates of disease prevalence, test accuracy and costs were based on two recently performed nationwide cohort studies in The Netherlands. RESULTS: Strategies using fFN testing and CL measurement separately to predict preterm delivery are associated with higher costs and incidence of adverse neonatal outcomes compared with strategies that combine both tests. Additional fFN testing when CL is 15-30 mm was considered cost effective, leading to a cost saving of €3919 per woman when compared with a treat-all strategy, with a small deterioration in neonatal health outcomes, namely one additional perinatal death and 21 adverse outcomes per 10 000 women with signs of preterm labor (incremental cost-effectiveness ratios €39 million and €1.9 million, respectively). Implementing this strategy in The Netherlands, a country with about 180 000 deliveries annually, could lead to an annual cost saving of between €2.4 million and €7.6 million, with only a small deterioration in neonatal health outcomes. CONCLUSION: In women with symptoms of preterm labor at 24-34 weeks' gestation, performing additional fFN testing when CL is between 15 and 30 mm is a viable and cost-saving strategy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

An economic analysis of immediate delivery and expectant monitoring in women with hypertensive disorders of pregnancy, between 34 and 37 weeks of gestation (HYPITAT-II).

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 €10 245 versus €9563 for expectant monitoring (n = 351), with an average difference of €682 (95% confidence interval, 95% CI -€618 to €2126). This 7% difference predominantly originated from the neonatal admissions, which were €5672 in the immediate delivery arm and €3929 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.

Uteroplacental Doppler flow and pregnancy outcome in women with tetralogy of Fallot.

OBJECTIVE: Pregnancy in women with surgically corrected tetralogy of Fallot (ToF) is associated with cardiac, obstetric and neonatal complications. We compared uteroplacental Doppler flow (UDF) measurements and pregnancy outcome in women with ToF and in healthy women and aimed to assess whether a relationship exists between cardiac function and UDF in women with ToF. METHODS: We evaluated prospectively pregnant women with ToF and healthy pregnant women from the ZAHARA studies. Clinical evaluation, standardized echocardiography and UDF measurements were performed at 20 and 32 weeks' gestation. RESULTS: We included 62 women with ToF and 69 healthy controls. Cardiac complications, mostly arrhythmia, occurred in 8.1% of women with ToF. There was a higher incidence of small-for-gestational age (21.0% vs 4.4%, P = 0.004) and low birth weight (16.1% vs 2.9%, P = 0.009) in the group of women with ToF than in healthy controls. In women with ToF, early diastolic notching of uterine artery waveform at 20 and 32 weeks occurred more frequently (9.8% vs 1.5%, P = 0.034 and 7.0% vs 0%, P = 0.025, respectively) and the umbilical artery pulsatility index at 32 weeks was higher (1.02 ± 0.20 vs 0.94 ± 0.17, P = 0.015) than in healthy controls. Right ventricular function parameters prepregnancy and at 20 weeks' gestation were significantly associated with abnormal UDF. UDF parameters were associated with adverse neonatal outcome. CONCLUSION: The majority of women with surgically corrected ToF tolerate pregnancy well. However, UDF indices are more frequently abnormal in these women, suggesting impaired placentation. The association of impaired right ventricular function parameters with abnormal UDF suggests that cardiac dysfunction contributes to defective placentation or placental perfusion mismatch and may explain the increased incidence of obstetric and neonatal complications. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Nifedipine maintenance tocolysis and perinatal outcome: an individual participant data meta-analysis.

BACKGROUND: Preterm birth is the leading cause of neonatal mortality and morbidity in developed countries. Whether continued tocolysis after 48 hours of rescue tocolysis improves neonatal outcome is unproven. OBJECTIVES: To evaluate the effectiveness of maintenance tocolytic therapy with oral nifedipine on the reduction of adverse neonatal outcomes and the prolongation of pregnancy by performing an individual patient data meta-analysis (IPDMA). SEARCH STRATEGY: We searched PubMed, Embase, and Cochrane databases for randomised controlled trials of maintenance tocolysis therapy with nifedipine in preterm labour. SELECTION CRITERIA: We selected trials including pregnant women between 24 and 36(6/7)  weeks of gestation (gestational age, GA) with imminent preterm labour who had not delivered after 48 hours of initial tocolysis, and compared maintenance nifedipine tocolysis with placebo/no treatment. DATA COLLECTION AND ANALYSIS: The primary outcome was perinatal mortality. Secondary outcome measures were intraventricular haemorrhage (IVH), necrotising enterocolitis (NEC), infant respiratory distress syndrome (IRDS), prolongation of pregnancy, GA at delivery, birthweight, neonatal intensive care unit admission, and number of days on ventilation support. Pre-specified subgroup analyses were performed. MAIN RESULTS: Six randomised controlled trials were included in this IPDMA, encompassing data from 787 patients (n = 390 for nifedipine; n = 397 for placebo/no treatment). There was no difference between the groups for the incidence of perinatal death (risk ratio, RR 1.36; 95% confidence interval, 95% CI 0.35-5.33), intraventricular haemorrhage (IVH) ≥ grade II (RR 0.65; 95% CI 0.16-2.67), necrotising enterocolitis (NEC) (RR 1.15; 95% CI 0.50-2.65), infant respiratory distress syndrome (IRDS) (RR 0.98; 95% CI 0.51-1.85), and prolongation of pregnancy (hazard ratio, HR 0.74; 95% CI 0.55-1.01). CONCLUSION: Maintenance tocolysis is not associated with improved perinatal outcome and is therefore not recommended for routine practice. TWEETABLE ABSTRACT: Nifedipine maintenance tocolysis is not associated with improved perinatal outcome or pregnancy prolongation.

Prediction of Time to Delivery Week-by-Week in Women with a Triplet Pregnancy.

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 < 10%.

Cardiac adaption during pregnancy in women with congenital heart disease and healthy women.

OBJECTIVE: Pregnancy in women with congenital heart disease (CHD) is associated with deterioration in cardiac function. However, longitudinal data are scarce. This study describes serial changes in cardiac dimensions and function during pregnancy in women with CHD and compares these with healthy pregnant women (controls). METHODS: Eight tertiary centres prospectively enrolled 125 pregnant women with CHD (pregnancy duration <20 weeks). Controls (N=49) were recruited from low-risk midwife practices. Standardised echocardiography at 20 and 32 weeks gestation and 1 year postpartum was performed. RESULTS: Age and parity were comparable between both groups (p>0.1). Left ventricular ejection fraction (LVEF) <45% was present in 3.2% of women with CHD and 14.4% had tricuspid annular plane systolic excursion (TAPSE) <16 mm. Absolute values of ventricular function parameters and diameters were less favourable in women with CHD. No permanent changes occurred in right and left ventricular function parameters and dimensions in women with CHD. The patterns of change in cardiac function and dimensions were comparable between women with CHD and controls, except for LVEF (p=0.026). In women with right-sided CHD the pattern of TAPSE over time differed from controls (p=0.043) (no decrease in TAPSE postpregnancy in CHD). In women with left-sided CHD left ventricular end-diastolic diameter (LVEDD) tended to increase compared with controls (p=0.045). CONCLUSIONS: Absolute levels of ventricular function parameters and diameters differ between CHD and controls, but changes during and after pregnancy are generally comparable. However, different patterns over time seen for TAPSE and LVEDD in women with right-sided and left-sided CHD, respectively, compared with controls indicate the importance of echocardiographic follow-up during pregnancy in women with CHD.

Multicenter impact analysis of a model for predicting recurrent early-onset preeclampsia: A before-after study.

OBJECTIVE: This study aims to determine the impact of using a prediction model for recurrent preeclampsia to customize antenatal care in subsequent pregnancies. METHODS: We compared care consumption, pregnancy outcomes, and self-reported health state of two risk-based subgroups, and compared these to a reference group receiving standard care. RESULTS: We included a total of 311 women from 12 hospitals. Compared to standard care, recurrence-risk guided care did not lead to different outcomes or self-perceived health. CONCLUSION: Our study exemplifies that recurrence-risk-based stratification of antenatal care in former preeclampsia patients is feasible; it does not lead to worse pregnancy outcomes.

Risk assessment and management to prevent preterm birth.

Preterm birth is the most important cause of neonatal mortality and morbidity worldwide. In this review, we review potential risk factors associated with preterm birth and the subsequent management to prevent preterm birth in low and high risk women with a singleton or multiple pregnancy. A history of preterm birth is considered the most important risk factor for preterm birth in subsequent pregnancy. General risk factors with a much lower impact include ethnicity, low socio-economic status, maternal weight, smoking, and periodontal status. Pregnancy-related characteristics, including bacterial vaginosis and asymptomatic bacteriuria, appear to be of limited value in the prediction of preterm birth. By contrast, a mid-pregnancy cervical length measurement is independently associated with preterm birth and could be used to identify women at risk of a premature delivery. A fetal fibronectin test may be of additional value in the prediction of preterm birth. The most effective methods to prevent preterm birth depend on the obstetric history, which makes the identification of women at risk of preterm birth an important task for clinical care providers.