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The risk for neonatal sepsis in the GBS subgroup was significantly higher after EM (1.8% after IoL vs. 15.2% after EM, OR 0.10, 95% CI 0.01-0.84); therefore, in the PPROMEXIL-trials IoL was strongly advised (Tajik et al. 2014 I BJOG i ;121:1263-72). A number of randomised trials have evaluated induction of labour (IoL) versus expectant management (EM) for late preterm prelabour rupture of membranes (PPROM) occurring between 34 and 37 weeks of gestation, including the PPROMEXIL-trials (van der Ham et al. 2012 I PLoS Med i ;9:e1001208; van der Ham et al. I Am J Obstet Gynecol i 2012;207:276.e1-10) and the PPROMT trial (Morris et al. I Lancet i 2016;387:444-52). Therefore, given the morbidity of neonatal sepsis and the data showing increased neonatal sepsis rates in patients testing positive for GBS, immediate delivery should be considered. [Extracted from the article]

Objective: To validate previously computed correction factors for free β-human chorionic gonadotrophin (fβ-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) pregnancies with hormone treatment and to determine the effect on false-positive rate (FPR). Methods: Retrospective study on 249 IVF and 250 ICSI cases and 20,190 controls. Correction factors 1.42 (PAPP-A), 1.17 (fβ-hCG) in IVF; 1.56 (PAPP-A) in ICSI were applied on the absolute serum concentrations. Analysis was done on log10-transformed multiples of medians (MoMs). Results: In the controls, mean PAPP-A and fβ-hCG MoM were 1.004 and 1.062. Before correction, mean PAPP-A MoM was significantly lower in IVF (0.757; p < 0.001) and in ICSI (0.671; p < 0.001) and after correction comparable (1.071; p = 0.053 in IVF; 1.048; p = 0.178 in ICSI). Before correction, mean fβ-hCG MoM was comparable (1.054; p = 0.59 in IVF and 1.051; p = 0.56 in ICSI) and after correction significantly higher in IVF (1.241; p < 0.001). After correction the likelihood for receiving a false-positive result was 1.03 in IVF pregnancies (95% CI 0.98-1.09; p = 0.248) and 1.02 in ICSI pregnancies (95% CI 0.97-1.07; p = 0.448). Conclusions: After correction the FPR in IVF and ICSI pregnancies with hormone treatment reduces to the observed FPR in the controls. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

We also realise that a low-lying placenta can prevent descent of the presenting part through the pelvis, and therefore a vaginal delivery will not be possible for all women; however, the chance of a normal vaginal delivery is still more than 1 in 2. Of course, this trial of labour should be in a clinical setting and women should be aware of the risk of a secondary caesarean delivery as a consequence of haemorrhage. Consequently, when counselling women about the risks of vaginal delivery in low-lying placenta, we should not omit counselling women about the possible consequences of a caesarean section in a future pregnancy. [Extracted from the article]

Most published data on the detection of fetal anomalies at 11-14 weeks are from specialized centres with considerable experience in fetal anomaly scanning. However, there is still limited information on the feasibility and limitations of the screening of these anomalies compared with the now classical mid-gestation screening. This review indicates that overall, the detection rate of fetal anomalies at 11-14 weeks is 44% compared with 74% by the mid-pregnancy scan. Major abnormalities of the fetal head, abdominal wall and urinary tract, and of the umbilical cord and placenta, can be reliably detected at 10-11 weeks of gestation. Detection of other anomalies such as spina bifida, diaphragmatic hernia or heart defects is limited before 13 weeks of gestation. So far it cannot be stated that routine first trimester screening can be used on a large scale to evaluate the fetal spine and heart in the general population. In particular, in screening for congenital heart defects, the ability to perform a full cardiac examination increases from 20% at 11 weeks to 92% at 13 weeks. The early prenatal diagnosis of these anomalies may be improved by screening at 13-14 weeks rather than during the first trimester. [ABSTRACT FROM AUTHOR]

Introduction Material and Methods Results Conclusions The decision to terminate a pregnancy due to fetal anomalies can have a significant emotional impact, especially in second‐trimester terminations. Previous studies on the psychological consequences of pregnancy termination have had limitations, and little is known about the outcomes for partners and the impact of fetal donation. Therefore, we aimed to investigate the psychological effects of second‐trimester pregnancy termination and identify factors associated with outcomes in both women and men, including donation of fetal remains to science.A longitudinal cohort study was conducted at the Amsterdam UMC in the Netherlands, involving women and partners who underwent termination at or before 23 weeks and 6 days of gestation. Questionnaires were administered at termination, 6 weeks, and 4 months after. We utilized validated questionnaires to assess psychological morbidity (grief, post‐traumatic stress and postnatal depression and quality of life [QoL]), and factors that could potentially influence outcomes.Of 241 participants, women displayed more pronounced psychological distress than men, though both groups improved over time. Four months after termination, 27.4% of women and 9.1% of men showed signs of pathological grief. Scores indicative for postnatal depression occurred in 19.8% women and 4.1% of men. A prior psychiatric history was a consistent predictor of poorer outcomes. Fetal donation to the Dutch Fetal Biobank was associated with reduced likelihood of symptoms of complicated grief four months after termination.Second‐trimester termination of pregnancy for fetal anomalies can lead to psychological morbidity, particularly in women. However, there is a notable improvement over time for both groups. Individuals with prior psychiatric history appear more vulnerable post‐termination. Also, fetal donation to science did not have a negative impact on psychological well‐being. [ABSTRACT FROM AUTHOR]

Introduction: The prenatal detection rate of a right aortic arch (RAA) has increased with the implementation of the three-vessel view (3VV) to the second-trimester anomaly scan formed by the pulmonary artery (PA), aorta (Ao), and superior vena cava (SVC). We examined the value of measuring the distance between PA and Ao in the 3VV in cases with an RAA. Methods: We conducted a case-control study in which fetuses with an isolated RAA were matched to 3 healthy controls. Using 3VV images, the distances between PA, Ao, and SVC were measured and the ratio between PA to Ao (PAAo) distance and Ao to SVC (AoSVC) distance was calculated. Results: Fifty-four RAA cases and 162 matched controls were included. The mean absolute distance PAAo was 3.1 mm in cases and 1.8 mm in controls (p < 0.001), and the mean PAAo/AoSVC ratio was 2.9 and 1.4, respectively (p < 0.001). The ROC curve of PAAo/AoSVC ratio showed a cut-off point of 1.9 with sensitivity and specificity over 87% for the diagnosis of RAA. Conclusions: The pulmonary-aortic interspace and the PAAo/AoSVC ratio were significantly larger for RAA cases as compared to controls. If an increased pulmonary-aortic interspace is observed, a PAAo/AoSVC of ≥1.9 can be helpful in the diagnosis of an RAA. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion The optimal management of placenta accreta spectrum (PAS) requires the participation of multidisciplinary teams that are often not locally available in low‐resource settings. Telehealth has been increasingly used to manage complex obstetric conditions. Few studies have explored the use of telehealth for PAS management, and we aimed evaluate the usage of telehealth in the management of PAS patients in low‐resource settings.Between March and April 2023, an observational, survey‐based study was conducted, and obstetricians‐gynecologists with expertise in PAS management in low‐ and middle‐income countries were contacted to share their opinion on the potential use of telehealth for the diagnosis and management of patients at high‐risk of PAS at birth. Participants were identified based on their authorship of at least one published clinical study on PAS in the last 5 years and contacted by email. This is a secondary analysis of the results of that survey.From 158 authors contacted we obtained 65 responses from participants in 27 middle‐income countries. A third of the participants reported the use of telehealth during the management obstetric emergencies (38.5%, n = 25) and PAS (36.9%, n = 24). Over 70% of those surveyed indicated that they had used “informal” telemedicine (phone call, email, or text message) during PAS management. Fifty‐nine participants (90.8%) reported that recommendations given remotely by expert colleagues were useful for management of patients with PAS in their setting.Telehealth has been successfully used for the management of PAS in middle‐income countries, and our survey indicates that it could support the development of specialist care in other low resource settings. [ABSTRACT FROM AUTHOR]

Recent studies of human embryos and fetuses have advanced our understanding not only of basic biology but also of health and disease, through a combination of detailed three-dimensional (3D) morphology and processes such as gene expression, cellular decision-making and differentiation, and epigenetics during the various phases of human development and growth. Large-scale research initiatives focusing on these topics have been initiated during the last decade, all of which depend on biobanks that provide high-quality images of human embryonic and fetal morphology, as well as on high-quality collections of tissue samples that are obtained and stored appropriately. In this perspective, we describe our experience in establishing the Dutch Fetal Biobank to present the framework and workflow of the biobank, provide a brief discussion of the main legal and ethical aspects involved in establishing a pre-natal tissue bank, and present the preliminary data on the first 329 donated specimens. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective Urinary tract infections are among the most common infections during pregnancy. The association between symptomatic lower urinary tract infections during pregnancy and fetal and maternal complications such as preterm birth and low birthweight remains unclear. The aim of this research is to evaluate the association between urinary tract infections during pregnancy and maternal and neonatal outcomes, especially preterm birth. Study Design This study is a secondary analysis of a multicenter prospective cohort study, which included patients between October 2011 and June 2013. The population consists of women with low risk singleton pregnancies. We divided the cohort into women with and without a symptomatic lower urinary tract infection after 20 weeks of gestation. Baseline characteristics and maternal and neonatal outcomes were compared between the two groups. Multivariable logistic regression analysis was used to correct for confounders. The main outcome was spontaneous preterm birth at <37 weeks. Results We identified 4,918 pregnant women eligible for enrollment, of whom 9.4% had a symptomatic lower urinary tract infection during their pregnancy. Women with symptomatic lower urinary tract infections were at increased risk for both preterm birth in general (12 vs. 5.1%, adjusted OR 2.5; 95% CI 1.7–3.5) as well as a spontaneous preterm birth at <37 weeks (8.2 vs. 3.7%, adjusted OR 2.3; 95% CI 1.5–3.5). This association was also present for early preterm birth at <34 weeks. Women with symptomatic lower urinary tract infections during pregnancy are also at increased risk of endometritis (8.9 vs. 1.8%, adjusted OR 5.3; 95% CI 1.4–20) and mastitis (7.8 vs. 1.8%, adjusted OR 4.0; 95% CI 1.6–10) postpartum. Conclusion Low risk women with symptomatic lower urinary tract infections during pregnancy are at increased risk of spontaneous preterm birth. In addition, an increased risk for endometritis and mastitis postpartum was found in women with symptomatic lower urinary tract infection during pregnancy. Key Points UTIs increase the risk of preterm birth. UTIs increase the risk of endometritis postpartum. UTIs increase the risk of mastitis postpartum. [ABSTRACT FROM AUTHOR]

Background: Evidence for progestogen maintenance therapy after an episode of preterm labour (PTL) is contradictory. Objectives: To assess effectiveness of progestogen maintenance therapy after an episode of PTL. Search Strategy: An electronic search in Central Cochrane, Ovid Embase, Ovid Medline and clinical trial databases was performed. Selection Criteria: Randomised controlled trials (RCT) investigating women between 16+0 and 37+0 weeks of gestation with an episode of PTL who were treated with progestogen maintenance therapy compared with a control group. Data Collection and Analysis: Systematic review and meta‐analysis were conducted. The primary outcome was latency time in days. Secondary neonatal and maternal outcomes are consistent with the core outcome set for preterm birth studies. Studies were extensively assessed for data trustworthiness (integrity) and risk of bias. Main Results: Thirteen RCT (1722 women) were included. Progestogen maintenance therapy demonstrated a longer latency time of 4.32 days compared with controls (mean difference [MD] 4.32, 95% CI 0.40–8.24) and neonates were born with a higher birthweight (MD 124.25 g, 95% CI 8.99–239.51). No differences were found for other perinatal outcomes. However, when analysing studies with low risk of bias only (five RCT, 591 women), a significantly longer latency time could not be shown (MD 2.44 days; 95% CI −4.55 to 9.42). Conclusions: Progestogen maintenance therapy after PTL might have a modest effect on prolongation of latency time. When analysing low risk of bias studies only, this effect was not demonstrated. Validation through further research, preferably by an individual patient data meta‐analysis is highly recommended. [ABSTRACT FROM AUTHOR]

Background: Gestational age is positively associated with cognitive development, but socio‐demographic factors also influence school performance. Previous studies suggested possible interaction, putting children with low socio‐economic status (SES) at increased risk of the negative effects of prematurity. Objectives: To investigate the association between gestational age in weeks, socio‐demographic characteristics, and school performance at the age of 12 years among children in regular primary education. Methods: Population‐based cohort study among liveborn singletons (N = 860,332) born in the Netherlands in 1999–2006 at 25–42 weeks' gestation, with school performance from 2011 to 2019. Regression analyses were conducted investigating the association of gestational age and sociodemographic factors with school performance and possible interaction. Results: School performance increased with gestational age up to 40 weeks. This pattern was evident across socio‐demographic strata. Children born at 25 weeks had −0.57 SD (95% confidence interval −0.79, −0.35) lower school performance z‐scores and lower secondary school level compared to 40 weeks. Low maternal education, low maternal age, and non‐European origin were strongly associated with lower school performance. Being born third or later and low socioeconomic status (SES) were also associated with lower school performance, but differences were smaller than among other factors. When born preterm, children from mothers with low education level, low or high age, low SES or children born third or later were at higher risk for lower school performance compared to children of mothers with intermediate education level, aged 25–29 years, with intermediate SES or first borns (evidence of interaction). Conclusions: Higher gestational age is associated with better school performance at the age of 12 years along the entire spectrum of gestational age, beyond the cut‐off of preterm birth and across socio‐demographic differences. Children in socially or economically disadvantaged situations might be more vulnerable to the negative impact of preterm birth. Other important factors in school performance are maternal education, maternal age, ethnicity, birth order and SES. Results should be interpreted with caution due to differential loss to follow‐up. [ABSTRACT FROM AUTHOR]

• With an own financial contribution, there is no equal access to fetal aneuploidy screening. • To overcome this inequality, the own contribution of the NIPT should be abandoned. • Since the majority of the parents makes an informed choice, the fear of routinization is redundant. First trimester non-invasive prenatal testing (NIPT) provides pregnant women with a reliable, non-invasive method to screen for fetal aneuploidies. In the Netherlands, there is a nationwide prenatal screening program in which pregnant women and their partners are counseled about their options around 10 weeks of pregnancy. The first trimester and second trimester scan are fully reimbursed but the NIPT has an own financial contribution of €175 per participant, irrespective of type of insurance. The arguments for this own contribution are fear of uncritical use of NIPT or routinization. NIPT has a relatively stable uptake of 51%, against over 95% for second trimester anomaly scan. We aimed to explore the effect of this financial contribution on the decision to opt out of NIPT. We performed a survey among 350 pregnant women undergoing a second trimester anomaly scan in our center, Amsterdam UMC, between January 2021 and April 2022. All pregnant women who declined NIPT in the first trimester, were asked to participate and answered 11–13 questions about the decision-making process, the reasons to opt out and the financial contribution. Information about NIPT was desired in 92% of women and 96% felt sufficiently informed. Most women took the decision not to perform NIPT with their partner and did not experience difficulties in taking this decision. The most important reason to decline NIPT was: "Every child is welcome" (69%). "The test was too expensive" was answered in 12% and was significantly correlated with lower maternal age. Additionally, one in five women (19%) said they would have done NIPT if it had been for free, which was significantly higher in younger women. The own financial contribution plays a role in the decision-making to decline NIPT and partly explains the low uptake in the Netherlands. This suggests that there is no equal access to fetal aneuploidy screening. To overcome this inequality, this own contribution should be abandoned. We speculate that this will have a positive effect on the uptake, which will increase to at least 70% and potentially 94%. [ABSTRACT FROM AUTHOR]

A response from the author of the article "Prenatal detection of congenital heart disease-results of a national screening programme" that was published in the previous issue, is presented.

• Significant decrease in perinatal mortality due to improvement of quality of care combined with centralization of care. • Declining trend is stronger in Amsterdam compared to the Netherlands. • Preterm birth remains the biggest risk factor for perinatal mortality. • Prevention on preterm birth remains a major challenge. • Increasing trend in asphyxia and postpartum hemorrhage is of concern. To assess differences in adverse maternal and neonatal outcomes before and after closure of a secondary obstetric care unit of a community hospital in an urban district. Retrospective cohort study using aggregated data from National Perinatal Registry of the Netherlands (PERINED) in the very urban region of Amsterdam, consisting of data of five secondary and two tertiary hospitals. We assessed maternal and neonatal outcomes in singleton hospital births between 24+0 weeks of gestational age (GA) up to 42+6 weeks. Data of 78.613 births were stratified in two groups: before closure (years 2012–2015) and after closure (2016–2019). Perinatal mortality decreased significantly from 0.84 % to 0.63 % (p = 0.0009). The adjusted odds ratio (aOR) of the closure on perinatal mortality was 0.73 (95 % CI 0.62–0.87). Both antepartum death (0.46 % vs 0.36 %, p = 0.02) and early neonatal death (0.38 % vs 0.28 %, p = 0.015) declined after closure of the hospital. The number of preterm births decreased significantly (8.7 % vs 8.1 %, p=<0.007) as well as number of neonates with congenital abnormalities (3.2 % vs2.2 %, p=<0.0001). APGAR < 7 after 5 min increased (2.3 % vs 2.5 %, p = 0.04). There was no significant difference in SGA or NICU admission. Postpartum hemorrhage increased significantly from 7.7 % to 8.2 % (p=<0.003). Perinatal mortality from 32 weeks onwards was not significantly different after closure 0.29 % to 0.27 %. After closure of an obstetric unit in a community hospital in Amsterdam, there was a significant decrease in perinatal, intrapartum and early neonatal mortality in neonates born from 24+0 onwards. The mortality decrease coincides with a reduction of preterm deliveries. The increasing trend in asphyxia and postpartum hemorrhage is of concern.. Centralization of care and increasing birth volume per hospital may lead to improvement of quality of care. A broad integrated, multidisciplinary maternity healthcare system linked with the social domain can achieve health gains in maternity care for all women. [ABSTRACT FROM AUTHOR]

Background: Since the introduction of non-invasive prenatal testing (NIPT) in 2011, mainly by commercial companies, a growing demand for NIPT from the public and healthcare professionals has been putting pressure on the healthcare systems of various countries. This study identifies the challenges of establishing a responsible implementation of NIPT for aneuploidy in prenatal healthcare, by looking at the Netherlands.Methods: A mixed methods approach involving 13 stakeholder interviews, document analysis and (participatory) observations of the Dutch NIPT Consortium meetings were used. The Diffusion of Innovation Theory and a Network of Actors model were used to interpret the findings.Results: Implementation of NIPT was facilitated by several factors. The set-up of a national NIPT Consortium enabled discussion and collaboration between stakeholders. Moreover, it led to the plan to offer NIPT through a nationwide research setting (TRIDENT studies), which created a learning phase for careful implementation. The Dutch legal context was perceived as a delaying factor, but eventually gave room for the parties involved to organise themselves and their practices.Conclusions: This study shows that implementing advanced technologies with profound effects on prenatal care benefit from a learning phase that allows time to carefully evaluate the technical performance and women's experiences and to enable public debate. Such a coordinated learning phase, involving all stakeholders, will stimulate the process of responsible and sustainable implementation. [ABSTRACT FROM AUTHOR]

Introduction: Early detection of isolated severe congenital heart defects (CHDs) allows extra time for chromosomal analysis and informed decision making, resulting in improved perinatal management and patient satisfaction. Therefore, the aim of this study was to assess the value of an additional first-trimester screening scan compared to only a second-trimester scan in fetuses diagnosed with isolated severe CHDs. Prenatal detection rate, time of prenatal diagnosis, and pregnancy outcome were evaluated in the Netherlands after implementation of a national screening program. Materials and Methods: We performed a retrospective geographical cohort study and included 264 pre- and postnatally diagnosed isolated severe CHD cases between January 1, 2007, and December 31, 2015, in the Amsterdam region. Severe CHD was defined as potentially life threatening if intervention within the first year of life was required. Two groups were defined: those with a first- and second-trimester anomaly scan (group 1) and those with a second-trimester anomaly scan only (group 2). A first-trimester scan was defined as a scan between 11 + 0 and 13 + 6 weeks of gestation. Results: Overall, the prenatal detection rate for isolated severe CHDs was 65%; 63% were detected before 24 weeks of gestation (97% of all prenatally detected CHDs). Prenatal detection rate was 70.2% in the group with a first- and second-trimester scan (group 1) and 58% in the group with a second-trimester scan only (group 2) (p < 0.05). Median gestational age at detection was 19 + 6 (interquartile range [IQR] 15 + 4 – 20 + 5) in group 1 versus 20 + 3 (IQR: 20 + 0 – 21 + 1) in group 2 (p < 0.001). In group 1, 22% were diagnosed before 18 weeks of gestation. Termination of pregnancy rate in group 1 and group 2 were 48% and 27%, respectively (p < 0.01). Median gestational age at termination did not differ between the two groups. Conclusion: Prenatal detection rate of isolated severe CHDs and termination of pregnancy rate was higher in the group with both a first- and second-trimester scan. We found no differences between timing of terminations. The additional time after diagnosis allows for additional genetic testing and optimal counseling of expectant parents regarding prognosis and perinatal management, so that well-informed decisions can be made. [ABSTRACT FROM AUTHOR]

Introduction: The incidence of induction of labor, for both medical reasons and as an elective procedure, has been rising and a further increase in induction of labor following the ARRIVE trial may be expected. The effects of induction of labor at term on childhood neurodevelopment, however, are not well studied. We aimed to study the influence of elective induction of labor for each week of gestation separately from 37 to 42 weeks on offspring school performance at 12 years of age after uncomplicated pregnancies. Material and methods: We performed a population‐based study among 226 684 liveborn children from uncomplicated singleton pregnancies, born from 37+0 to 42+0 weeks of gestation in cephalic presentation in 2003–2008 (no hypertensive disorders, diabetes or birthweight ≤p5) in the Netherlands. Children with congenital anomalies, of non‐white mothers and born after planned cesarean section were excluded. Birth records were linked with national data on school achievement. We compared, using a fetus‐at‐risk approach and per week of gestation, school performance score and secondary school level at age 12 in those born after induction of labor to those born after non‐intervention, ie spontaneous onset of labor in the same week plus all those born at later gestations. Education scores were standardized to a mean of 0 and a standard deviation of 1 and adjusted in the regression analyses. Results: For each gestational age up to 41 weeks, induction of labor was associated with decreased school performance scores compared with non‐intervention (at 37 weeks −0.05 SD, 95% confidence interval [CI] −0.10 to −0.01 SD; adjusted for confounding factors). After induction of labor, fewer children reached higher secondary school level (at 38 weeks 48% vs 54%; adjusted odds ratio [aOR] 0.88, 95% CI 0.82–0.94). Conclusions: In women with uncomplicated pregnancies at term, consistently, at every week of gestation from 37 to 41 weeks, induction of labor is associated with lower offspring school performance at age 12 and lower secondary school level compared with non‐intervention, although residual confounding may remain. These long‐term effects of induction of labor should be incorporated in counseling and decision making. [ABSTRACT FROM AUTHOR]

Women of Black and other non-Western ethnicity and women who live in deprived neighborhoods are at increased risk for preterm birth (PTB). These women may live clustered in certain urban areas. If ethnicity reflects a biological rather than a socioeconomic risk factor, women should have a PTB risk independent of the urban area where they live. In this study we explored the association between urban living and the risk of PTB, combined with knowledge on ethnicity and neighborhood deprivation in these specific urban areas in the Netherlands. National cohort study of 935,381 women (2014–2019) with a singleton pregnancy resulting in live birth between 24.0 and 42.6 weeks. Antepartum death and severe congenital anomalies were excluded. We performed logistic regression analysis and analyzed the impact of living in one of the four main urban areas on PTB. We adjusted for maternal age, parity and fetal gender. We tested for interaction between ethnicity, neighborhood deprivation index (NDI) and urban living. Mean PTB rate among singleton pregnancies in The Netherlands is 5.1%. There was a strong ethnic difference in PTB risk, with the highest prevalence among South Asian women (7.9%) and African women (6.6%). In the most deprived neighborhoods the PTB risk was 5.7%. We found a significant interaction between ethnicity and urban living, and between NDI and urban living. South Asian and African women living in urban areas had the greatest risk of PTB, between 7.0% and 8.8%. Ethnicity remains a fixed biological risk for PTB that cannot be fully explained by socioeconomic status or neighborhood deprivation. Independent of ethnicity and neighborhood deprivation, urban living has a great influence on the risk of preterm birth. Future studies and policies should focus on population-based interventions in those urban areas where South Asian and African ethnic groups live and where the preterm birth risk is the highest. [ABSTRACT FROM AUTHOR]

To systematically review the literature on hypertensive disorders of pregnancy (HDP) after multifetal pregnancy reduction (MFPR). A comprehensive search in PubMed, Embase, Web of Science, and Scopus was performed. Prospective or retrospective studies reporting on MFPR from triplet or higher-order to twin compared to ongoing (i.e., non-reduced) triplets and/or twins were included. A meta-analysis of the primary outcome HDP was carried out using a random-effects model. Subgroup analyses of gestational hypertension (GH) and preeclampsia (PE) were performed. Risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scale. Thirty studies with a total of 9,811 women were included. MFPR from triplet to twin was associated with a lower risk for HDP compared to ongoing triplets (OR 0.55, 95% CI, 0.37–0.83; p = 0.004). In a subgroup analysis, the decreased risk of HDP was driven by GH, and PE was no longer significant (OR 0.34, 95% CI, 0.17–0.70; p = 0.004 and OR 0.64, 95% CI, 0.38–1.09; p = 0.10, respectively). HDP was also significantly lower after MFPR from all higher-order (including triplets) to twin compared to ongoing triplets (OR 0.55, 95% CI, 0.38–0.79; p = 0.001). In a subgroup analysis, the decreased risk of HDP was driven by PE, and GH was no longer significant (OR 0.55, 95% CI 0.32–0.92; p = 0.02 and OR 0.55, 95% CI 0.28–1.06; p = 0.08, respectively). No significant differences in HDP were found in MFPR from triplet or higher-order to twin versus ongoing twins. MFPR in women with triplet and higher-order multifetal pregnancies decreases the risk of HDP. Twelve women should undergo MFPR to prevent one event of HDP. These data can be used in the decision-making process of MFPR, in which the individual risk factors of HDP can be taken into account. [ABSTRACT FROM AUTHOR]

Objective We assessed, in women with a previous spontaneous preterm birth, the effect of interpregnancy interval on the subsequent preterm birth rate. Design Retrospective cohort study. Setting A nationwide longitudinal dataset of the the Netherlands Perinatal Registry. Population Women with three sequential singleton pregnancies between 1999 and 2009 and a spontaneous preterm birth <37 weeks in the first pregnancy. Methods We evaluated the impact of interpregnancy interval on the course of the next pregnancies. Antenatal death and/or congenital abnormalities were excluded. Conventional and conditional logistic regression analysis were applied. We adjusted for maternal age, ethnicity, socioeconomic status, artificial reproductive techniques, and year of birth. Main Outcome Measures Outcomes studied were preterm birth <37 weeks, <32 weeks, low birth weight <2500 g, and small for gestational age <10th percentile. Results Among 2,361 women with preterm birth in the first pregnancy, logistic regression analysis indicated a significant effect of a short interpregnancy interval (0-5 mo) on recurrent preterm birth <37 weeks (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.62-3.05), <32 weeks (OR, 2.90; 95% CI, 1.43-5.87), and low birth weight (OR, 2.69; 95% CI, 1.79-4.03). In addition, a long interval (≥60 mo) had a significant effect on preterm birth <37 weeks (OR, 2.19; 95% CI, 1.29-3.74). Conditional logistic regression analysis confirmed the effect of a short interval on the recurrence of preterm birth rate <37 weeks and low birth weight. Conclusion In women with a previous spontaneous preterm birth, a short interpregnancy interval has a strong impact on the risk of preterm birth before 37 weeks and low birth weight in the next pregnancy, irrespective of the type of analysis performed. [ABSTRACT FROM AUTHOR]

Introduction: As the prenatal detection rates of congenital heart defects (CHDs) increase, obstetricians are more frequently faced with pregnancies complicated by a fetal CHD. Congenital anomalies in general are associated with preterm birth and fetal demise. The aim of this study was to gain insight into the prevalence of preterm birth and fetal demise in singleton pregnancies with fetuses with isolated CHDs.Material and Methods: A geographical cohort study was performed in a large region in the Netherlands. Fetuses and infants from singleton pregnancies diagnosed with severe isolated CHD, born between 1 January 2002 and 1 January 2012, were included. All cases in the CHD cohort were assessed for preterm birth or fetal demise. The proportions of preterm birth and fetal demise were compared with those in a control group and odds ratios were calculated.Results: The proportion of preterm births in the CHD cohort (n = 1013) was 9.1% (95% CI 7.3-10.9) compared with 5.6% (95% CI 5.4-5.8) in the control group, with an odds ratio of 1.7 (95% CI 1.4-2.1). The preterm birth started spontaneously in 49.5% and 38.4% were induced. In 15 cases fetal demise occurred (1.5%; 95% CI 0.8-2.2), compared with 0.7% (95% CI 0.6-0.8) in the control group, odds ratio 2.0 (95% CI 1.2-3.4).Conclusions: Higher rates of preterm birth and fetal demise occur in fetuses with isolated CHD compared with the general population. Prenatal specialists should be vigilant for signs of heart failure, premature closure of the foramen ovale or fetal distress in fetuses with isolated CHDs. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Increased nuchal translucency as a marker for fetal chromosomal defects," by P. Taipale, V. Hiilesmaa and colleagues in the December 4, 1997 issue.

Background: Worldwide, nifedipine and atosiban are the two most commonly used tocolytic agents for the treatment of threatened preterm birth. The aim of this study was to evaluate the effectiveness of nifedipine and atosiban in an individual participant data meta-analysis (IPDMA).Methods: We investigated the occurrence of adverse neonatal outcomes in women with threatened preterm birth by performing an IPDMA, and sought to identify possible subgroups in which one treatment may be preferred. We searched PubMed, Embase, and Cochrane for trials comparing nifedipine and atosiban for treatment of threatened preterm birth between 240/7 and 340/7 weeks' gestational age. Primary outcome was a composite of perinatal mortality and neonatal morbidities including respiratory distress syndrome, intraventricular haemorrhage, periventricular leucomalacia, necrotising enterocolitis, and sepsis. Secondary outcomes included NICU admission, prolongation of pregnancy and GA at delivery. For studies that did not have the original databases available, metadata was used. This led to a two-stage meta-analysis that combined individual participant data with aggregate metadata.Results: We detected four studies (N = 791 women), of which two provided individual participant data (N = 650 women). The composite neonatal outcome occurred in 58/364 (16%) after nifedipine versus 69/359 (19%) after atosiban (OR 0.76, 95%CI 0.47-1.23). Perinatal death occurred in 14/392 (3.6%) after nifedipine versus 7/380 (1.8%) after atosiban (OR 2.0, 95%CI 0.80-5.1). Nifedipine results in longer prolongation of pregnancy, with a 18 days to delivery compared with 10 days for atosiban (HR 0.83 (96% CI 0.69-0.99)). NICU admission occurred less often after nifedipine (46%) than after atosiban (59%), (OR 0.32, 95%CI 0.14-0.75). The sensitivity analysis revealed no difference in prolongation of pregnancy for 48 hours (OR 1.0, 95% CI 0.73-1.4) or 7 days (OR 1.3, 95% CI 0.85-5.8) between nifedipine and atosiban. There was a non-significant higher neonatal mortality in the nifedipine-exposed group (OR 1.4, 95% CI 0.60-3.4).Conclusions: In this IPDMA, we found no differences in composite outcome between nifedipine and atosiban in the treatment of threatened preterm birth. However, the non-significant higher mortality after administering nifedipine warrants further investigation of the use of nifedipine as a tocolytic drug.Study Registration: We conducted this study according to a prospectively prepared protocol, registered with PROSPERO (the International Prospective Register of Systematic Reviews) under CRD42016024244. [ABSTRACT FROM AUTHOR]

Introduction: Midtrimester prelabor rupture of membranes (PROM) between 16 and 24 weeks of gestational age is a major obstetric complication with high rates of perinatal morbidity and mortality. Amnioinfusion has been proposed in women with midtrimester PROM to target oligohydramnios and subsequently enhance pulmonary development and perinatal outcomes. Material and Methods: The purpose of this study was to perform a systematic review and meta-analysis including all randomized clinical trials investigating amnioinfusion versus no intervention in women with PROM between 16+0 and 24+0 weeks of gestational age. Databases Central, Embase, Medline, ClinicalTrials.gov and references of identified articles were searched from inception of database to December 2021. The primary outcome was perinatal mortality. Secondary outcomes included neonatal, maternal, and long-term developmental outcomes as defined in the core outcome set for preterm birth studies. Summary measures were reported as pooled relative risk (RR) or mean difference with corresponding 95% confidence interval (CI). Results: Two studies (112 patients, 56 in the amnioinfusion group and 56 in the no intervention group) were included in this review. Pooled perinatal mortality was 66.1% (37/56) in the amnioinfusion group compared with 71.4% (40/56) in no intervention group (RR 0.92, 95% CI: 0.72–1.19). Other neonatal and maternal core outcomes were similar in both groups, although due to the relatively small number of events and wide CIs, there is a possibility that amnioinfusion can be associated with clinically important benefits and harms. Long-term healthy survival was seen in 35.7% (10/28) of children assessed for follow-up and treated with amnioinfusion versus 28.6% (8/28) after no intervention (RR 1.30, 95% CI: 0.47–3.60, "best case scenario"). Conclusions: Based on these findings, the benefits of amnioinfusion for midtrimester PROM <24 weeks of gestational age are unproven, and the potential harms remain undetermined. [ABSTRACT FROM AUTHOR]

Objective: To identify neonatal risk for severe adverse perinatal outcomes across birth weight centiles in two Dutch and one international birth weight chart.Background: Growth restricted newborns have not reached their intrinsic growth potential in utero and are at risk of perinatal morbidity and mortality. There is no golden standard for the confirmation of the diagnosis of fetal growth restriction after birth. Estimated fetal weight and birth weight below the 10th percentile are generally used as proxy for growth restriction. The choice of birth weight chart influences the specific cut-off by which birth weight is defined as abnormal, thereby triggering clinical management. Ideally, this cut-off should discriminate appropriately between newborns at low and at high risk of severe adverse perinatal outcomes and consequently correctly inform clinical management.Methods: This is a secondary analysis of the IUGR Risk Selection (IRIS) study. Newborns (n = 12 953) of women with a low-risk status at the start of pregnancy and that received primary antenatal care in the Netherlands were included. We examined the distribution of severe adverse perinatal outcomes across birth weight centiles for three birth weight charts (Visser, Hoftiezer and INTERGROWTH) by categorizing birth weight centile groups and comparing the prognostic performance for severe adverse perinatal outcomes. Severe adverse perinatal outcomes were defined as a composite of one or more of the following: perinatal death, Apgar score < 4 at 5 min, impaired consciousness, asphyxia, seizures, assisted ventilation, septicemia, meningitis, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, or necrotizing enterocolitis.Results: We found the highest rates of severe adverse perinatal outcomes among the smallest newborns (< 3rd percentile) (6.2% for the Visser reference curve, 8.6% for the Hoftiezer chart and 12.0% for the INTERGROWTH chart). Discriminative abilities of the three birth weight charts across the entire range of birth weight centiles were poor with areas under the curve ranging from 0.57 to 0.61. Sensitivity rates of the various cut-offs were also low.Conclusions: The clinical utility of all three charts in identifying high risk of severe adverse perinatal outcomes is poor. There is no single cut-off that discriminates clearly between newborns at low or high risk.Trial Registration: Netherlands Trial Register NTR4367 . Registration date March 20th, 2014. [ABSTRACT FROM AUTHOR]

Introduction: Cervical length is an important predictor of spontaneous preterm birth. So far, the best way to measure cervical length has not been established. We aimed to compare the incidence of short cervical length between three methods of cervical length measurement with and without the inclusion of cervico-isthmic complex (CIC) (six methods in total) and to determine the positive predictive value for spontaneous preterm birth. Material and Methods: We performed a prospective single-center cohort study in women with a singleton pregnancy between August 2014 and December 2018. During the routine fetal anomaly scan (18–22 weeks), women were offered transvaginal ultrasound for cervical length measurement to screen for the risk of spontaneous preterm birth. Each cervix was measured in six different ways: single-line, two-line, and tracing method between the internal and external os of the cervix with and without CIC. We evaluated the predictive value of the different measurements for spontaneous delivery before 37 weeks using positive predictive values. Results: Our final study population comprised 1,691 women. The overall rate of preterm birth <37 weeks was 8.0% (4.6% spontaneous, 3.4% iatrogenic preterm birth). The mean gestational age at cervical length measurement was 19+6 weeks. The different measuring techniques resulted in significant different cervical lengths, showing a maximum difference of >8 mm between the techniques (41.04 mm [SD 7.1] with one-line without CIC and 49.18 [SD 9.05] mm with trace with CIC) with an incidence of short cervical length below <25 mm ranging from 0.4% to 1.1% (p = 0.18). The positive predictive values for spontaneous preterm birth <37 weeks ranged from 42.9% to 20.0%. Conclusion: Different measurement methods for cervical length resulted in statistically significant differences in measured cervical length. Depending on the chosen cut-off this translates to different incidences of short cervical length and influences the number of women designated as high risk for preterm birth and receiving treatment. For interpretation and comparability between (inter-) national studies, it is important to adequately report on the employed technique. Future research should focus on determining the optimal measuring technique and a universal method of measurement. [ABSTRACT FROM AUTHOR]

Summary: Fetal neonatal alloimmune thrombocytopenia (FNAIT) is caused by maternal alloantibodies directed against the human platelet antigens (mostly HPA‐1a or HPA‐5b) of the (unborn) child and can lead to severe bleeding. Anti‐HPA‐1a‐mediated FNAIT shows a severe clinical outcome more often than anti‐HPA‐5b‐mediated FNAIT. Given the relatively high prevalence of anti‐HPA‐5b in pregnant women, the detection of anti‐HPA‐5b in FNAIT‐suspected cases may in some cases be an incidental finding. Therefore we investigated the frequency of anti‐HPA‐5b‐associated severe bleeding in FNAIT. We performed a retrospective nationwide cohort study in cases with clinical suspicion of FNAIT. HPA antibody screening was performed using monoclonal antibody‐specific immobilisation of platelet antigens. Parents and neonates were typed for the cognate antigen. Clinical data were collected by a structured questionnaire. In 1 864 suspected FNAIT cases, 161 cases (8·6%) had anti‐HPA‐1a and 60 (3·2%) had anti‐HPA‐5b. The proportion of cases with severe bleeding did not differ between the cases with anti‐HPA‐1a (14/129; 11%) and anti‐HPA‐5b (4/40; 10%). In multigravida pregnant women with a FNAIT‐suspected child, 100% (81/81) of anti‐HPA‐1a cases and 79% (38/48) of anti‐HPA‐5b cases were HPA‐incompatible, whereas 86% and 52% respectively were expected, based on the HPA allele distribution. We conclude that anti‐HPA‐5b can be associated with severe neonatal bleeding symptoms. A prospective study is needed for true assessment of the natural history of anti‐HPA‐5b mediated FNAIT. [ABSTRACT FROM AUTHOR]

Objective: Perinatal mortality after previable prelabor rupture of membranes (previable PROM) might be underestimated as most studies exclude patients with poor prognosis, or solely include patients in tertiary-care centers. We aimed to report perinatal, neonatal and long-term outcomes in a consecutive series of women with pregnancies complicated by previable PROM.Study Design: We conducted a prospective cohort study including women with singleton pregnancies and previable PROM ≤ 23+6 weeks gestational age (GA) from one tertiary hospital and eight affiliated secondary hospitals in the region of Amsterdam, the Netherlands (June 2012 until January 2016, PPROMEXIL-III cohort). Exclusion criteria were signs of active labor before onset of PROM or fetal structural anomalies visible at ultrasound. We assessed perinatal mortality. Furthermore, outcomes were maternal, perinatal, neonatal and long-term child characteristics.Results: We included 98 pregnancies with previable PROM. Twelve women (12.2%) opted for termination of pregnancy, resulting in 86 pregnancies included in further analyses. Median GA at PROM was 20+2 weeks (interquartile range (IQR) 17+6-22+0). Median GA at delivery was 22+6 weeks (IQR 20+1-26+4). Delivery within 1 week occurred in 38.4% of women and 60.4% delivered before 24 weeks GA (viability). Perinatal mortality occurred in 73.3% of pregnancies. 23/33 (69.7%) live-born neonates survived to discharge, representing 26.7% of total. None of the children died after discharge. Developmental data at two and/or five years of age was available for 13/23 children (i.e. all children born before 32 weeks of gestation), with 69.2% of children reporting a normal neurodevelopment. However, more than half of children reported respiratory problems.Conclusion: In women with previable PROM perinatal mortality was 73.3%, with a normal neurodevelopment in 69.2% of surviving children with follow-up data. Due to broad inclusion criteria, this cohort represents a population more generalizable to daily practice as compared to previous studies. [ABSTRACT FROM AUTHOR]

Background: Cervical cerclage is a recognised treatment to prevent late miscarriage and pre-term birth (PTB). Emergency cervical cerclage (ECC) for cervical dilatation with exposed unruptured membranes is less common and the potential benefits of cerclage are less certain. A randomised control trial is needed to accurately assess the effectiveness of ECC in preventing pregnancy loss compared to an expectant approach.Methods: C-STICH2 is a multicentre randomised controlled trial in which women presenting with cervical dilatation and unruptured exposed membranes at 16 + 0 to 27 + 6 weeks gestation are randomised to ECC or expectant management. Trial design includes 18 month internal pilot with embedded qualitative process evaluation, minimal data set and a within-trial health economic analysis. Inclusion criteria are ≥16 years, singleton pregnancy, exposed membranes at the external os, gestation 16 + 0-27 + 6 weeks, and informed consent. Exclusion criteria are contraindication to cerclage, cerclage in situ or previous cerclage in this pregnancy. Randomisation occurs via an online service in a 1:1 ratio, using a minimisation algorithm to reduce chance imbalances in key prognostic variables (site, gestation and dilatation). Primary outcome is pregnancy loss; a composite including miscarriage, termination of pregnancy and perinatal mortality defined as stillbirth and neonatal death in the first week of life. Secondary outcomes include all core outcomes for PTB. Two-year development outcomes will be assessed using general health and Parent Report of Children's Abilities-Revised (PARCA-R) questionnaires. Intended sample size is 260 participants (130 each arm) based on 60% rate of pregnancy loss in the expectant management arm and 40% in the ECC arm, with 90% power and alpha 0.05. Analysis will be by intention-to-treat.Discussion: To date there has been one small trial of ECC in 23 participants which included twin and singleton pregnancies. This small trial along with the largest observational study (n = 161) found ECC to prolong pregnancy duration and reduce deliveries before 34 weeks gestation. It is important to generate high quality evidence on the effectiveness of ECC in preventing pregnancy loss, and improve understanding of the prevalence of the condition and frequency of complications associated with ECC. An adequately powered RCT will provide the highest quality evidence regarding optimum care for these women and their babies.Trial Registration: ISRCTN Registry ISRCTN12981869 . Registered on 13th June 2018. [ABSTRACT FROM AUTHOR]

The aim of this study is to determine the influence of withdrawal of reimbursement on the uptake of the first-trimester combined test. Until January 2007 the combined test was offered to all pregnant women in a designated geographical area as a pilot study before the introduction of the national screening program in the Netherlands, to test the logistic procedures. In January 2007 the insurance companies suddenly stopped paying for the combined test with respect to women aged ≤35 years by decision of the government. In 2006 the combined test was performed in 4616 women compared with 3459 who had the combined test in 2007, a reduction of 25% (95% CI 23.8-26.3%, p < 0.001). A decline was observed in the uptake of the combined test in women aged ≤35 years ( p < 0.001) as opposed to an increase in uptake in women aged ≥36 years ( p < 0.001). The financial impact on the uptake of the first-trimester combined test should not be underestimated. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether double‐layer uterine closure after a first caesarean section (CS) is superior compared with single‐layer uterine closure in terms of postmenstrual spotting and niche development in the uterine caesarean scar. Design: Multicentre, double‐blind, randomised controlled superiority trial. Setting: Thirty‐two hospitals in the Netherlands. Population: A total of 2292 women aged ≥18 years undergoing a first CS were randomly assigned to each procedure (1:1): 1144 women were assigned to single‐layer uterine closure and 1148 women were assigned to double‐layer uterine closure. Methods: Single‐layer unlocked closure and double‐layer unlocked closure, with the second layer imbricating the first. Main outcome measures: Number of days with postmenstrual spotting during one menstrual cycle 9 months after CS. Secondary outcomes: perioperative and menstrual characteristics; transvaginal ultrasound measurements. Results: A total of 774 (67.7%) women from the single‐layer group and 770 (67.1%) women from the double‐layer group were evaluable for the primary outcome, as a result of drop‐out and amenorrhoea. The mean number of postmenstrual spotting days was 1.33 (bootstrapped 95% CI 1.12–1.54) after single‐layer closure and 1.26 (bootstrapped 95% CI 1.07–1.45) after double‐layer closure (adjusted mean difference −0.07, 95% CI −0.37 to 0.22, P = 0.810). The operative time was 3.9 minutes longer (95% CI 3.0–4.9 minutes, P < 0.001) and niche prevalence was 4.7% higher (95% CI 0.7–8.7%, P = 0.022) after double‐layer closure. Conclusions: The superiority of double‐layer closure compared with single‐layer closure in terms of postmenstrual spotting after a first CS was not shown. Long‐term obstetric follow‐up of our trial is needed to assess whether uterine caesarean closure guidelines should be adapted. Double‐layer uterine closure is not superior for postmenstrual spotting after a first caesarean; single‐layer closure performs slightly better on other outcomes. Double‐layer uterine closure is not superior for postmenstrual spotting after a first caesarean; single‐layer closure performs slightly better on other outcomes. [ABSTRACT FROM AUTHOR]

Using genome-wide transcriptome analysis by RNA sequencing of first trimester plasma RNA, we tested whether the identification of pregnancies at risk of developing pre-eclampsia with or without preterm birth or growth restriction is possible between weeks 9–14, prior to the appearance of clinical symptoms. We implemented a metaheuristic approach in the self-learning SVM algorithm for differential gene expression analysis of normal pregnancies (n = 108), affected pregnancies (n = 34) and non-pregnant controls (n = 19). Presymptomatic candidate markers for affected pregnancies were validated by RT-qPCR in first trimester samples (n = 34) from an independent cohort. PRKG1 was significantly downregulated in a subset of pregnancies with birth weights below the 10thpercentile as shared symptom. The NRIP1/ZEB2 ratio was found to be upregulated in pregnancies with pre-eclampsia or trisomy 21. Complementary quantitative analysis of both the linear and circular forms of NRIP1 permitted discrimination between pre-eclampsia and trisomy 21. Pre-eclamptic pregnancies showed an increase in linear NRIP1 compared to circular NRIP1, while trisomy 21 pregnancies did not. [ABSTRACT FROM AUTHOR]

Objective: The far majority of women with a placenta previa in the second trimester will no longer have a placenta that overlies the internal os in the third trimester. Women with a placenta previa in the third trimester are at risk for complication such as preterm birth and blood loss. Four counselling purposes we aim to identify which women with a second trimester placenta previa have a low-risk and a high-risk for persistence of the placenta previa.Study Design: A prospective cohort study of women with a placenta previa in the second trimester between 2014 and 2019. The odds for having a placenta previa in the third trimester were calculated for different baseline characteristics. Multilevel likelihood ratios for ranges of the placenta overlying the internal os in the second trimester and the corresponding ROC curve were calculated to identify the optimal cut-off values.Results: We included 313 women with a placenta previa in the second trimester. The placenta was more frequently located on the posterior wall (62 %) than on the anterior wall (38 %). At evaluation in the third trimester, 37 women (14 %) still had a placenta previa. Women with a larger distance of the placenta overlying the internal os, women having a previous cesarean delivery and women after a conception with assisted reproductive technique had a significant higher risk of placenta previa persistence (p-values <0.001). Women with a placenta overlying less than 14 mm can be considered as low-risk, indicated by a likelihood ratio of 0. Women with a placenta with more than 55 mm overlap can be considered as high-risk, indicated a the likelihood ratio of ∞.Conclusion: The majority of the second trimester placenta previa will no longer overly the internal os in the third trimester. Placenta previa persistence is associated with the distance overlying the internal os, a previous cesarean delivery and assisted reproductive techniques. In the second trimester, women can be identified as low-risk and high-risk for persistence of placenta previa. This can be used for risk stratification, counselling and individualized care for women with a second trimester placenta previa. [ABSTRACT FROM AUTHOR]

Low-lying placentas, placenta previa and abnormally invasive placentas are the most frequently occurring placental abnormalities in location and anatomy. These conditions can have serious consequences for mother and fetus mainly due to excessive blood loss before, during or after delivery. The incidence of such abnormalities is increasing, but treatment options and preventive strategies are limited. Therefore, it is crucial to understand the etiology of placental abnormalities in location and anatomy. Placental formation already starts at implantation and therefore disorders during implantation may cause these abnormalities. Understanding of the normal placental structure and development is essential to comprehend the etiology of placental abnormalities in location and anatomy, to diagnose the affected women and to guide future research for treatment and preventive strategies. We reviewed the literature on the structure and development of the normal placenta and the placental development resulting in low-lying placentas, placenta previa and abnormally invasive placentas. [ABSTRACT FROM AUTHOR]

Objective: To assess the association between asymptomatic bacteriuria (ASB) and short cervical length (CL), since they are both associated with preterm delivery.Study Design: In two prospective multicentre cohort studies, pregnant women were screened for the presence of ASB and short CL (≤25 mm). We compared CL in women with and without ASB. Both studies had a small randomised clinical trial embedded.Results: Our study population comprised 1 610 women, of whom 114 were ASB positive. Median cervical length was similar in women with and without ASB (44.0 vs 44.0 mm, P = 0.60). More women in the ASB positive group had a short CL compared to the ASB negative group (1.8 % versus 0.4 %, P = 0.047)). The gestational age at delivery did not differ between the groups (ranging from 38 + 3 in women with ASB and short CL to 39 + 5 in women without ASB with a short CL P = 0.52). No preterm births occurred in women with a short cervical length (regardless of ASB status). In the women without ASB and no short CL 4.8 % had a preterm birth, in the women with ASB but not a short CL 4.1 % had a preterm birth.Conclusion: While ASB status did not influence median cervical length, we found a significant relationship between a short CL and ASB positive women. We found no statistical significant difference on the preterm birth rate and mean gestational age. [ABSTRACT FROM AUTHOR]

Background: Preterm birth is the leading cause of perinatal mortality and neonatal morbidity worldwide. Many factors have been associated with preterm birth, including parity. The aim of the present study was to investigate associations between parity and risk of spontaneous preterm birth.Methods: We conducted a retrospective study including live singleton births (≥22 weeks) of women with a first, second, third, fourth or fifth pregnancy in The Netherlands from 2010 through 2014. Our primary outcome was risk of spontaneous preterm birth < 37 weeks. Secondary outcomes were spontaneous preterm birth < 32 and < 28 weeks.Results: We studied 802,119 pregnancies, including 30,237 pregnancies that ended spontaneously < 37 weeks. We identified an increased risk for spontaneous preterm birth < 37 weeks in nulliparous women (OR 1.95, 95% CI 1.89-2.00) and women in their fifth pregnancy (OR 1.26, 95% CI 1.13-1.41) compared to women in their second pregnancy. Similar results were seen for spontaneous preterm birth < 32 and < 28 weeks.Conclusion: Our data show an independent association between nulliparity and spontaneous preterm birth < 37, < 32 and < 28 weeks. Furthermore, we observed an increased risk for spontaneous preterm birth in women in their fifth pregnancy, with highest risk for preterm birth at early gestational age. [ABSTRACT FROM AUTHOR]

Objective: Preterm birth is the most important cause of perinatal morbidity and mortality. Over the past years several preventive measures have been studied and implemented. Preterm birth percentage in 2015 in the Netherlands was 6.9 %, according to data from the European Peristat project, reporting on perinatal health in Europe. Various preventive measures might have influenced the incidence and outcome of preterm birth. Our aim was to give an overview of the trends in preterm births for both singleton and multiple gestations in the Netherlands in order to guide future research.Study Design: We studied a nationwide cohort including both singleton and multiple gestations without congenital anomalies between 2008 and 2015. Outcomes were total preterm birth (defined as birth before 37 weeks of gestation), spontaneous and iatrogenic preterm birth < 37 weeks, spontaneous and iatrogenic preterm birth percentages between 34-36 weeks, 32-34 weeks, 28-31 weeks and ≤ 27 weeks using a moving average technique. Trend analysis was performed using the Cochran Armitage test. Singleton and multiple gestations were analyzed separately.Results: Our final study population comprised 1,303.786 women with a singleton and 44,951 women with a multiple pregnancy. Preterm birth < 37 weeks in singletons decreased from 5.6 % in 2008 to 5.3 % in 2015 (P < 0.0001), in both spontaneous and iatrogenic preterm birth. Preterm birth ≤ 27 weeks increased from 0.40 % to 0.45 % (P for trend <0.0001). The number of multiple gestations decreased over the years, as well as the percentage of multiples conceived through IVF/ICSI. There was an increase in total and iatrogenic preterm birth < 37 weeks from 36.7-38.2% (P < 0.0001) in multiples. The number of multiples <32 decreased, in both the spontaneous and iatrogenic group.Conclusion: In the Netherlands preterm birth risk in singletons decreased between 2008 and 2015 but an increase was noted in preterm birth ≤ 27 weeks. In multiples the total preterm birth risk increased, due to an increase in indicated preterm birth. [ABSTRACT FROM AUTHOR]

Introduction: Mid-trimester uterine artery resistance measured with Doppler sonography is predictive for iatrogenic preterm birth. In view of the emerging association between hypertensive disease in pregnancy and spontaneous preterm birth, we hypothesized that uterine artery resistance could also predict spontaneous preterm birth.Material and Methods: We performed a cohort study of women with singleton pregnancies. Uterine artery resistance was routinely measured at the 18-22 weeks anomaly scan. Pregnancies complicated by congenital anomalies or intrauterine fetal death were excluded. We analyzed if the waveform of the uterine artery (no notch, unilateral notch or bilateral notch) was predictive for spontaneous and iatrogenic preterm birth, defined as delivery before 37 weeks of gestation. Furthermore, we assessed whether the uterine artery pulsatility index was associated with the risk of preterm birth.Results: Between January 2009 and December 2016 we collected uterine Doppler indices and relevant outcome data in 4521 women. Mean gestational age at measurement was 19+6  weeks. There were 137 (3.0%) women with a bilateral and 213 (4.7%) with a unilateral notch. Mean gestational age at birth was 38+6  weeks. Spontaneous and iatrogenic preterm birth rates were 5.7% and 4.9%, respectively. Mean uterine artery resistance was 1.12 in the spontaneous preterm birth group compared with 1.04 in the term group (P = 0.004) The risk of preterm birth was increased with high uterine artery resistance (OR 2.9 per unit; 95% CI 2.4-3.9). Prevalence of spontaneous preterm birth increased from 5.5% in women without a notch in the uterine arteries to 8.0% in women with a unilateral notch and 8.0% in women with a bilateral notch. For iatrogenic preterm birth, these rates were 3.9%, 13.6% and 23.4%, respectively. Likelihood ratios for the prediction of spontaneous preterm birth were 1.6 (95% CI 1.0-2.6) and 1.9 (95% CI 1.0-3.5) for unilateral and bilateral notches, respectively, and for iatrogenic preterm birth they were 3.6 (95% CI 2.5-5.2) and 6.8 (95% CI 4.7-9.9) for unilateral and bilateral notches, respectively. Of all women with bilateral notching, 31.4% delivered preterm.Conclusions: Mid-trimester uterine artery resistance measured at 18-22 weeks of gestation is a weak predictor of spontaneous preterm birth. [ABSTRACT FROM AUTHOR]

Introduction: The objective was to evaluate the association between fetal sex and adverse pregnancy outcome, while correcting for fetal growth and gestational age at delivery.Material and Methods: Data from the Netherlands Perinatal Registry (1999-2010) were used. The study population comprised all white European women with a singleton delivery between 25+0 and 42+6  weeks of gestation. Fetuses with structural or chromosomal abnormalities were excluded. Outcomes were antepartum death, intrapartum/neonatal death (from onset of labor until 28 days after birth), perinatal death (antepartum death or intrapartum/neonatal death), a composite of neonatal morbidity (including infant respiratory distress syndrome, sepsis, necrotizing enterocolitis, meconium aspiration, persistent pulmonary hypertension of the newborn, periventricular leukomalacia, Apgar score <7 at 5 minutes, and intracranial hemorrhage) and a composite adverse neonatal outcome (perinatal death or neonatal morbidity). Outcomes were expressed stratified by birthweight percentile (p90 [large for gestation]) and gestational age at delivery (25+0 -27+6 , 28+0 -31+6 , 32+0 -36+6 , 37+0 -42+6  weeks). The association between fetal sex and outcome was assessed using the fetus at risk approach.Results: We studied 1 742 831 pregnant women. We found no increased risk of antepartum, intrapartum/neonatal and perinatal death in normal weight and large-for-gestation males born after 28+0  weeks compared with females. We found an increased risk of antepartum death among small-for-gestation males born after 28+0  weeks (relative risk [RR] 1.16-1.40). All males born after 32+0  weeks of gestation suffered more neonatal morbidity than females regardless of birthweight percentile (RR 1.07-1.34). Infant respiratory distress syndrome, sepsis, persistent pulmonary hypertension of the newborn, Apgar score <7 at 5 minutes, and intracranial hemorrhage all occurred more often in males than in females.Conclusions: Small-for-gestation males have an increased risk of antepartum death and all males born after 32+0  weeks of gestation have an increased risk of neonatal morbidity compared with females. In contrast to findings in previous studies we found no increased risk of antepartum, intrapartum/neonatal or perinatal death in normal weight and large-for-gestation males born after 28+0  weeks. [ABSTRACT FROM AUTHOR]

Low-positioned placentas which are located in the lower uterine segment (LUS), either a low-lying placenta or a placenta previa, are associated with increased obstetric risks. However, most second trimester low-positioned placentas resolve during pregnancy and have a higher position in the third trimester, without posing any risks. We performed a systematic review and meta-analysis to evaluate the proportion of second trimester low-positioned placentas that have a position towards the fundus in the third trimester. Our aim was to find a cut-off value that included all women in whom the placenta will remain low in the third trimester, thus who are at increased risk of obstetric complications. Subsequently, we assessed whether an anterior or posterior placental location influenced this proportion. We searched MEDLINE and EMBASE and clinicaltrials.gov up to April 2019 for studies on the sonographic follow-up of second trimester low-positioned placentas, with a distance between the placenta and the internal os of the cervix of 20 mm or less at a gestational age of above 15 week and a follow up after 28 weeks. Studies were scored on methodological quality using the Newcastle-Ottowa Scale (NOS). A meta-analysis was conducted to summarize the proportion of second trimester low-positioned placentas with a position towards the fundus in the third trimester. We calculated the proportion at different cut-off values of the distance from the placental edge to the internal os of the cervix (0 mm, 10 mm and 20 mm). Also, anteriorly and posteriorly located placentas and women with and without a prior cesarean delivery were compared. We included 11 eligible studies which reported on 3586 women with a low-positioned placenta in the second trimester. Proportions of placentas with a position towards the fundus in the third trimester ranged between 0.63 and 1.0. Pooled proportions were 0.90 (95% CI 0.87-0.93) for IOD <10 mm and 0.80 (95% CI 0.74-0.85) for IOD < 0 mm. Due to heterogeneity between studies, the subgroup of <20 mm could not be pooled. Overall, anteriorly located placentas more often had a position towards the fundus in the third trimester, but studies did report conflicting results. Prior cesarean section had no influence except for an IOD of <0 mm, in which women without a prior cesarean delivery more often had a placenta towards the fundus. The majority of second trimester low-positioned placentas will be located towards the fundus at the time of follow-up. However, we could not determine a cut-off value for anterior and posterior placentas that included all women at high risk. The cut-off value, placental side and prior cesarean section should be assessed in a large prospective observational study. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response on article on the risk factors of a pregnancy complication vasa praevia (VP).

Objective: We studied the incidence of postpartum hemorrhage and manual removal of the placenta and their recurrence rate in a subsequent pregnancy. We hypothesized that the risk of recurrence was dependent on the gestational age at first birth and whether or not a manual removal of the placenta was necessary. Knowledge on this subject can potentially improve counselling, prevention and management in obstetric care for women at risk for PPH or identify women at low risk for recurrence.Study Design: This was a retrospective national cohort study consisting of women with two consecutive singleton deliveries between 1999 and 2009 in the Netherlands. A longitudinal linked national cohort with information on subsequent singleton deliveries in the Netherlands was used. Main outcome measures were: postpartum hemorrhage (defined as ≥1000 mL after vaginal delivery or Caesarean section) and manual removal of the placenta. We calculated incidence and recurrence rates of postpartum hemorrhage and manual removal of the placenta for all women and stratified by gestational age.Results: After application of in- and exclusion criteria 359 737 women were studied. A total of 5.4% women experienced postpartum hemorrhage in the first pregnancy and 2.7% of women had a manual removal of the placenta. The risk of postpartum hemorrhage in a subsequent pregnancy was significantly higher in women with a history of postpartum hemorrhage compared to women without a previous postpartum hemorrhage (18% vs 3.9%, adjusted odds ratio 4.5; 95% confidence interval 4.3-4.7). The risk of manual removal of the placenta in the second pregnancy was only 1.4% in women without a previous manual removal compared to 17% of women with a previous manual removal of the placenta. Women with a manual removal of the placenta in the first pregnancy between 32 and 37 weeks were most at risk for recurrence (adjusted odds ratio 8.9; 95% confidence interval 7.2-11).Conclusion: Women with a previous delivery complicated by postpartum hemorrhage or manual removal of the placenta are at increased risk for recurrence. The magnitude of this risk is highest in women with deliveries beyond 32 weeks in the first pregnancy. [ABSTRACT FROM AUTHOR]

Objective: To investigate the best criteria for discriminating fetuses with isolated posterior urethral valves from those theoretically not eligible for fetal treatment because of complex megacystis, high chance of spontaneous resolution, and urethral atresia.Methods: A retrospective national study was conducted in fetuses with megacystis detected before 17 weeks' gestation (early megacystis).Results: In total, 142 cases with fetal megacystis were included in the study: 52 with lower urinary tract obstruction, 29 with normal micturition at birth, and 61 with miscellaneous syndromal associations, chromosomal and multiple structural abnormalities (complex megacystis). Only a nuchal translucency > 95th centile, and not a longitudinal bladder diameter ≤15 mm (p = 0.24), significantly increased the risk of complex megacystis (p < 0.01). Cases with a high chance of spontaneous resolution were identified by using the cut-off of 12 mm, as demonstrated in a previous study, and the finding of an associated umbilical cord cyst carried a high-risk of urethral atresia (odds ratio: 15; p = 0.026), an unfavorable condition for antenatal treatment. An algorithm encompassing these three criteria demonstrated good accuracy in selecting fetuses theoretically eligible for fetal treatment (specificity 73%; sensitivity 92%).Conclusions: Cases theoretically eligible for early fetal therapy are those with normal nuchal translucency, a longitudinal bladder diameter > 12 mm, and without ultrasound evidence of umbilical cord cysts. [ABSTRACT FROM AUTHOR]

Objective: To assess the effectiveness of amnioinfusion in women with second-trimester preterm prelabor rupture of membranes.Methods: We performed a nationwide, multicenter, open-label, randomized controlled trial, the PPROM: Expectant Management versus Induction of Labor-III (PPROMEXIL-III) trial, in women with singleton pregnancies and preterm prelabor rupture of membranes at 16 0/7 to 24 0/7 weeks of gestation with oligohydramnios (single deepest pocket less than 20 mm). Participants were allocated to transabdominal amnioinfusion or no intervention in a one-to-one ratio by a web-based system. If the single deepest pocket was less than 20 mm on follow-up visits, amnioinfusion was repeated weekly until 28 0/7 weeks of gestation. The primary outcome was perinatal mortality. We needed 56 women to show a reduction in perinatal mortality from 70% to 35% (β error 0.20, two-sided α error 0.05).Results: Between June 15, 2012, and January 13, 2016, we randomized 28 women to amnioinfusion and 28 to no intervention. One woman was enrolled before the trial registration date (June 19, 2012). Perinatal mortality rates were 18 of 28 (64%) in the amnioinfusion group vs 21 of 28 (75%) in the no intervention group (relative risk 0.86, 95% CI 0.60-1.22, P=.39).Conclusion: In women with second-trimester preterm prelabor rupture of membranes and oligohydramnios, we found no reduction in perinatal mortality after amnioinfusion.Clinical Trial Registration: NTR Dutch Trial Register, NTR3492. [ABSTRACT FROM AUTHOR]

Objective: To assess the effectiveness of cervical pessary in reducing the rate of preterm birth in women at high risk for preterm birth who did not deliver after an episode of threatened preterm labor.Methods: In a multicenter open-label randomized controlled trial, a cervical pessary was compared with no intervention (control group) (one-to-one ratio). Women between 24 and 34 weeks of gestation at high risk for preterm birth based on a short cervical length (less than 15 mm) or an intermediate cervical length (between 15 and 30 mm) with a positive fetal fibronectin test who did not deliver after an episode of threatened preterm labor were eligible. The primary outcome was birth before 37 weeks of gestation. Secondary outcomes were a composite adverse neonatal outcome, preterm birth before 34 and 32 weeks of gestation, and side effects. A total sample size of 200 women carrying singletons was planned so as to have adequate statistical power to detect a reduction in the rate of preterm birth from 40% to 20%. Women with twin gestations were also enrolled but were considered only in secondary analyses. After a planned interim analysis, the trial was stopped for futility.Results: From November 2013 through September 2016, 130 women with a singleton pregnancy (65 pessary, 65 no treatment) were recruited. The groups had comparable baseline characteristics. In the cervical pessary group, 31 (48%) women delivered before 37 weeks of gestation compared with 25 (39%) in the no-treatment group (relative risk 1.2, 95% CI 0.83-1.8). Nine (15%) children in the cervical pessary group had the composite adverse perinatal outcome compared with eight (13%) in the control group (relative risk 1.2, 95% CI 0.49-2.9).Conclusion: In women at high risk for preterm birth who did not deliver after an episode of threatened preterm labor, treatment with a cervical pessary is not effective.Clinical Trial Registration: Netherlands Trial Register, NTR4210. [ABSTRACT FROM AUTHOR]

Background: In this study we determined the outcome of subsequent pregnancies after termination of pregnancy for preeclampsia, with the purpose of presenting data useful for counselling these women on future pregnancies. Study design: The cohort consisted of 131 women with a history of termination of pregnancy for preeclampsia. Results: Data of 79 pregnancies were available for analysis, including 13 women with chronic hypertension and 16 women with thrombophilia. There were seven miscarriages (8.8%) and 72 ongoing pregnancies. Low‐dose aspirin was prescribed for 64 women (89%). The mean gestational age at delivery was 356/7 ± 4 weeks with a mean birth weight of 2571 ± 938 g. Overall recurrence rate for preeclampsia was 29% at a mean gestational age of 32 weeks. Thirty‐eight women had an uncomplicated pregnancy (53%). The women with chronic hypertension had the highest recurrence rate of 38%. Neonatal mortality was 4%. Conclusion: The course of subsequent pregnancies after mid‐trimester termination for preeclampsia is uncomplicated in 53% with a recurrence rate for preeclampsia of 29%. The mean gestational age at delivery was 11 weeks later and birth weight 2000 g higher than in the index pregnancy. [ABSTRACT FROM AUTHOR]

Objective: To compare the effects of immediate delivery an expectant management among women whose pregnancies were complicated by preterm prelabor rupture of membranes (PROM) in the late preterm period (from 34 0/7 weeks until 36 6/7 weeks of gestation).Data Sources: PubMed, Scopus, ClinicalTrials.gov, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from inception until December 2016.Methods Of Study Selection: We included all randomized controlled trials with individual participant data reporting on late preterm PROM with randomization to immediate delivery or expectant management. The primary outcome was a composite of adverse neonatal outcomes: probable or definitive neonatal sepsis, necrotizing enterocolitis, respiratory distress syndrome, stillbirth, or neonatal death.Tabulation, Integration and Results: Of eight eligible trials (total n=3,203 mothers), three (2,563 mothers, 2,572 neonates) had individual participant data available. The composite adverse neonatal outcome occurred in 9.6% of neonates in the immediate delivery group and 8.3% in the expectant management group (relative risk [RR] 1.20, 95% CI 0.94-1.55). Neonatal sepsis rates were 2.6% and 3.5%, respectively (RR 0.74, 95% CI 0.47-1.15). Neonates in the immediate delivery group were more likely to be diagnosed with respiratory distress syndrome (RR 1.47, 95% CI 1.10-1.97), and to be admitted to the neonatal intensive care unit or special care nursery (RR 1.17, 95% CI 1.11-1.23) and had longer admissions. Mothers randomized to immediate delivery were less likely to have an antepartum hemorrhage (RR 0.57, 95% CI 0.34-0.95) or chorioamnionitis (RR 0.21, 95% CI 0.13-0.35), but more likely to undergo cesarean delivery (RR 1.26, 95% CI 1.08-1.47).Conclusion: In women with late preterm PROM, immediate delivery and expectant management resulted in comparable rates of the composite of adverse neonatal outcomes. Effects on individual secondary maternal and neonatal outcomes were mixed.Systematic Review Registration: PROSPERO, 42016032972. [ABSTRACT FROM AUTHOR]

Objective: To determine if the verification of short cervical length with a repeated measurement improved the identification of patients with short cervical length at increased risk of preterm delivery.Methods: The present secondary analysis analyzed prospective cohort study data from patients with singleton pregnancies without a history of preterm delivery who presented for obstetric care in the Netherlands and delivered between November 18, 2009, and January 1, 2013. Cervical length was measured during standard anomaly scan and a second measurement was performed if the cervical length was 30 mm of shorter. Logistic regression and Cox proportional hazards modeling were used to evaluate associations between cervical length measurements and spontaneous preterm delivery before 37 weeks of pregnancy.Results: Cervical length measurements from 12 358 patients were included; 221 (1.8%) had an initial cervical length measurement of 30 mm or shorter. A second cervical length measurement was performed for 167 (75.6%) patients; no differences were identified in the odds of spontaneous preterm delivery when evaluated using the first, second, or a mean of both measurements, regardless of whether cervical length was analyzed as a continuous or dichotomous variable.Conclusion: Among patients with singleton pregnancies, verification of short cervical length did not improve the identification of short cervical length. [ABSTRACT FROM AUTHOR]

Background: Preterm birth is in quantity and in severity the most important topic in obstetric care in the developed world. Progestogens and cervical pessaries have been studied as potential preventive treatments with conflicting results. So far, no study has compared both treatments.Methods/design: The Quadruple P study aims to compare the efficacy of vaginal progesterone and cervical pessary in the prevention of adverse perinatal outcome associated with preterm birth in asymptomatic women with a short cervix, in singleton and multiple pregnancies separately. It is a nationwide open-label multicentre randomized clinical trial (RCT) with a superiority design and will be accompanied by an economic analysis. Pregnant women undergoing the routine anomaly scan will be offered cervical length measurement between 18 and 22 weeks in a singleton and at 16-22 weeks in a multiple pregnancy. Women with a short cervix, defined as less than, or equal to 35 mm in a singleton and less than 38 mm in a multiple pregnancy, will be invited to participate in the study. Eligible women will be randomly allocated to receive either progesterone or a cervical pessary. Following randomization, the silicone cervical pessary will be placed during vaginal examination or 200 mg progesterone capsules will be daily self-administered vaginally. Both interventions will be continued until 36 weeks gestation or until delivery, whichever comes first. Primary outcome will be composite adverse perinatal outcome of perinatal mortality and perinatal morbidity including bronchopulmonary dysplasia, intraventricular haemorrhage grade III and IV, periventricular leukomalacia higher than grade I, necrotizing enterocolitis higher than stage I, Retinopathy of prematurity (ROP) or culture proven sepsis. These outcomes will be measured up until 10 weeks after the expected due date. Secondary outcomes will be, among others, time to delivery, preterm birth rate before 28, 32, 34 and 37 weeks, admission to neonatal intensive care unit, maternal morbidity, maternal admission days for threatened preterm labour and costs.Discussion: This trial will provide evidence on whether vaginal progesterone or a cervical pessary is more effective in decreasing adverse perinatal outcome in both singletons and multiples.Trial Registration: Trial registration number: NTR 4414 . Date of registration January 29th 2014. [ABSTRACT FROM AUTHOR]