Bacterial vaginosis in a subfertile population undergoing fertility treatments: a prospective cohort study.

PURPOSE: This study investigates the role of bacterial vaginosis (BV) on pregnancy rates during various fertility treatments. BV is known to influence several obstetric outcomes, such as preterm delivery and endometritis. Only few studies investigated the effect of BV in subfertile women, and studies found a negative effect on fecundity especially in the in vitro fertilisation population. METHODS: Observational prospective study, 76 couples attending a fertility clinic in the Netherlands between July 2019 and June 2022, undergoing a total of 133 attempts of intra uterine insemination, in vitro fertilization or intra cytoplasmatic sperm injection. Vaginal samples taken at oocyte retrieval or insemination were analysed on qPCR BV and 16S rRNA gene microbiota analysis of V1-V2 region. Logistic regression with a Generalized Estimated Equations analysis was used to account for multiple observations per couples. RESULTS: A total of 26% of the 133 samples tested positive for BV. No significant differences were observed in ongoing pregnancy or live birth rates based on BV status (OR 0.50 (0.16-1.59), aOR 0.32 (0.09-1.23)) or microbiome community state type. There was a tendency of more miscarriages based on positive BV status (OR 4.22 (1.10-16.21), aOR 4.28 (0.65-28.11)) or community state type group III and IV. On baseline qPCR positive participants had significantly higher body mass index and smoked more often. Odds ratios were adjusted for smoking status, body mass index, and socioeconomic status. CONCLUSION: Bacterial vaginosis does not significantly impact ongoing pregnancy rates but could affect miscarriage rates.

CenteringPregnancy in the Netherlands: Who engages, who doesn't, and why.

BACKGROUND: CenteringPregnancy (CP), a model of group antenatal care, was implemented in 2012 in the Netherlands to improve perinatal health; CP is associated with improved pregnancy outcomes. However, motivating women to participate in CP can be difficult. As such, we explored the characteristics associated with CP uptake and attendance and then investigated whether participation differs between health care facilities. In addition, we examined the reasons why women may decline participation and the reasons for higher or lower attendance rates. METHODS: Data from a stepped-wedge cluster randomized controlled trial were used. Univariate and multivariate logistic regression models were used to determine associations among women's health behavior, sociodemographic and psychosocial characteristics, health care facilities, and participation and attendance in CP. RESULTS: A total of 2562 women were included in the study, and the average participation rate was 31.6% per health care facility (range of 10%-53%). Nulliparous women, women <26 years old or >30 years old, and women reporting average or high levels of stress were more likely to participate in CP. Participation was less likely for women who had stopped smoking before prenatal intake, or who scored below average on lifestyle/pregnancy knowledge. For those participating in CP, 87% attended seven or more out of the 10 sessions, and no significant differences were found in women's characteristics when compared for higher or lower attendance rates. After the initial uptake, group attendance rates remained high. CONCLUSION: A more comprehensive understanding of the variation in participation rate between health care facilities is required, in order to develop effective strategies to improve the recruitment of women, especially those with less knowledge and understanding of health issues and smoking habits.

Clinical value of early viscoelastometric point-of-care testing during postpartum hemorrhage for the prediction of severity of bleeding: A multicenter prospective cohort study in the Netherlands.

INTRODUCTION: To evaluate rotational fibrin-based thromboelastometry (ROTEM® FIBTEM) with amplitude of clot firmness at 5 min (A5) as an early point-of-care parameter for predicting progression to severe postpartum hemorrhage, and compare its predictive value with that of fibrinogen. MATERIAL AND METHODS: Prospective cohort study in the Netherlands including women with 800-1500 ml of blood loss within 24 h following birth. Blood loss was quantitatively measured by weighing blood-soaked items and using a fluid collector bag in the operating room. Both FIBTEM A5 values and fibrinogen concentrations (Clauss method) were measured between 800 and 1500  ml of blood loss. Predictive accuracy of both biomarkers for the progression to severe postpartum hemorrhage was measured by area under the receiver operating curves (AUC). Severe postpartum hemorrhage was defined as a composite endpoint of (1) total blood loss >2000 ml, (2) transfusion of ≥4 packed cells, and/or (3) need for an invasive intervention to cease bleeding. RESULTS: Of the 391 women included, 72 (18%) developed severe postpartum hemorrhage. Median (IQR) volume of blood loss at blood sampling was 1100 ml (1000-1300) with a median (interquartile range [IQR]) fibrinogen concentration of 3.9 g/L (3.4-4.6) and FIBTEM A5 value of 17 mm (13-20). The AUC for progression to severe postpartum hemorrhage was 0.53 (95% confidence interval [CI] 0.46-0.61) for FIBTEM A5 and 0.58 (95% CI 0.50-0.65) for fibrinogen. Positive predictive values for progression to severe postpartum hemorrhage for FIBTEM A5 ≤12 mm was 22.5% (95% CI 14-33) and 50% (95% CI 25-75) for fibrinogen ≤2 g/L. CONCLUSIONS: The predictive value of FIBTEM A5 compared to fibrinogen concentrations measured between 800 and 1500 ml of blood loss following childbirth was poor to discriminate between women with and without progression towards severe postpartum hemorrhage.

Assessment of human fetal cardiac autonomic nervous system development using color tissue Doppler imaging.

OBJECTIVES: Functional development of the fetal cardiac autonomic nervous system (cANS) plays a key role in fetal maturation and can be assessed through fetal heart rate variability (fHRV)-analysis, with each HRV parameter representing different aspects of cANS activity. Current available techniques, however, are unable to assess the fHRV parameters accurately throughout the whole pregnancy. This study aims to test the feasibility of color tissue Doppler imaging (cTDI) as a new ultrasound technique for HRV analysis. Secondly, we explored time trends of fHRV parameters using this technique. METHODS: 18 healthy singleton fetuses were examined sequentially every 8 weeks from 10 weeks GA onwards. From each examination, 3 cTDI recordings of the four-chamber view of 10 seconds were retrieved to determine accurate beat-to-beat intervals. The fHRV parameters SDNN, RMSSD, SDNN/RMSSD, and pNN10, each representing different functional aspects of the cANS, were measured, and time trends during pregnancy were explored using spline functions within a linear mixed-effects model. RESULTS: In total, 77% (95% Cl 66-87%) of examinations were feasible for fHRV analysis from the first trimester onwards, which is a great improvement compared to other techniques. The technique is able to determine different maturation rates of the fHRV parameters, showing that cANS function, presumably parasympathetic activity, establishes around 20 weeks GA and matures rapidly until 30 weeks GA. CONCLUSIONS: This is the first study able to assess cANS function through fHRV analysis from the first trimester onwards. The use of cTDI to determine beat-to-beat intervals seems feasible in just 3 clips of 10 seconds, which holds promise for future clinical use in assessing fetal well-being.

The prevalence of genetic diagnoses in fetuses with severe congenital heart defects.

PURPOSE: Congenital heart defects (CHD) are associated with genetic syndromes. Rapid aneuploidy testing and chromosome microarray analysis (CMA) are standard care in fetal CHD. Many genetic syndromes remain undetected with these tests. This cohort study aims to estimate the frequency of causal genetic variants, in particular structural chromosome abnormalities and sequence variants, in fetuses with severe CHD at mid-gestation, to aid prenatal counselling. METHODS: Fetuses with severe CHD were extracted from the PRECOR registry (2012-2016). We evaluated pre- and postnatal genetic testing results retrospectively to estimate the frequency of genetic diagnoses in general, as well as for specific CHDs. RESULTS: 919 fetuses with severe CHD were identified. After exclusion of 211 cases with aneuploidy, a genetic diagnosis was found in 15.7% (111/708). These comprised copy number variants in 9.9% (70/708). In 4.5% (41/708) sequence variants were found that would have remained undetected with CMA. Interrupted aortic arch, pulmonary atresia with ventricular septal defect and atrioventricular septal defect were most commonly associated with a genetic diagnosis. CONCLUSION: In case of normal CMA results, parents should be offered exome sequencing sequentially, if time allows for it, especially if the CHD is accompanied by other structural malformations due to the large variety in genetic syndromes.

Is fear of childbirth related to the woman's preferred location for giving birth? A Dutch low-risk cohort study.

BACKGROUND: In The Netherlands, women with low-risk pregnancy are routinely given the option of home birth, providing a unique opportunity to study the relationship between fear of childbirth (FOC) and preference for childbirth location, and whether women experience higher FOC when the actual location differs from their preference. METHODS: In this prospective cohort study, 331 nulliparous and parous women completed a questionnaire at gestational week 30 (T1) and two months postpartum (T2). FOC was assessed using versions A (T1) and B (T2) of the Wijma Delivery Expectancy/Experience Questionnaire (W-DEQ). RESULTS: At T1, women who preferred home birth had significantly lower FOC compared with women who preferred a hospital birth (mean ± SD W-DEQ scores: 55 ± 19.8 and 64 ± 18.3, respectively, P < .01). About 28% of women who responded at T2 gave birth at home. Congruence between the preferred and actual childbirth location was not predictive of FOC assessed at T2 when adjusted for obstetric and psychological variables. In an extended analysis, we found that except for prepartum FOC, the following variables also correlated with postpartum FOC: being referred because of complications and poor neonatal condition. CONCLUSIONS: Compared to women who prefer hospital birth, women who prefer home birth have lower prepartum and postpartum FOC. Giving birth at a location other than the preferred location does not appear to affect postpartum FOC. Whether giving birth at home or in the hospital, caregivers should pay extra attention to women with high FOC because they are vulnerable to postpartum FOC, especially after a complicated birth and referral.

Women receiving massive transfusion due to postpartum hemorrhage: A comparison over time between two nationwide cohort studies.

INTRODUCTION: Incidence of massive transfusion after birth was high in the Netherlands between 2004 and 2006 compared with other high-income countries. This study investigated incidence, causes, management and outcome of women receiving massive transfusion due to postpartum hemorrhage in the Netherlands in more recent years. MATERIAL AND METHODS: Data for all pregnant women who received eight or more units of packed red blood cells from a gestational age of 20 weeks and within the first 24 hours after childbirth, during 2011 and 2012, were obtained from a nationwide retrospective cohort study, including 61 hospitals with a maternity unit in the Netherlands. RESULTS: Incidence of massive transfusion due to postpartum hemorrhage decreased to 65 per 100 000 births (95% CI 56-75) between 2011 and 2012, from 91 per 100 000 births (95% CI 81-101) between 2004 and 2006, while median blood loss increased from 4500 mL (interquartile range 3250-6000) to 6000 mL (interquartile range 4500-8000). Uterine atony remained the leading cause of hemorrhage. Thirty percent (53/176) underwent peripartum hysterectomy between 2011 and 2012, compared with 25% (83/327) between 2004 and 2006. Case fatality rate for women who received massive transfusion due to postpartum hemorrhage was 2.3% (4/176) between 2011 and 2012, compared with 0.9% (3/327) between 2004 and 2006. CONCLUSIONS: The incidence of postpartum hemorrhage with massive transfusion decreased in the Netherlands between both time frames, but remained an important cause of maternal mortality and morbidity, including peripartum hysterectomy. National surveillance of maternal morbidity and mortality due to postpartum hemorrhage through an improved and continuous registration with confidential enquiries may lead to the identification of clear improvements of maternal care.

Cortical development in fetuses with congenital heart defects using an automated brain-age prediction algorithm.

INTRODUCTION: Congenital heart defects are associated with neurodevelopmental delay. It is hypothesized that fetuses affected by congenital heart defect have altered cerebral oxygen perfusion and are therefore prone to delay in cortical maturation. The aim of this study was to determine the difference in fetal brain age between consecutive congenital heart defect cases and controls in the second and third trimester using ultrasound. MATERIAL AND METHODS: Since 2014, we have included 90 isolated severe congenital heart defect cases in the Heart And Neurodevelopment (HAND)-study. Every 4 weeks, detailed neurosonography was performed in these fetuses, including the recording of a 3D volume of the fetal brain, from 20 weeks onwards. In all, 75 healthy fetuses underwent the same protocol to serve as a control group. The volumes were analyzed by automated age prediction software which determines gestational age by the assessment of cortical maturation. RESULTS: In total, 477 volumes were analyzed using the age prediction software (199 volumes of 90 congenital heart defect cases; 278 volumes of 75 controls). Of these, 16 (3.2%) volume recordings were excluded because of imaging quality. The age distribution was 19-33 weeks. Mixed model analysis showed that the age predicted by brain maturation was 3 days delayed compared with the control group (P = .002). CONCLUSIONS: This study shows that fetuses with isolated cases of congenital heart defects show some delay in cortical maturation as compared with healthy control cases. The clinical relevance of this small difference is debatable. This finding was consistent throughout pregnancy and did not progress during the third trimester.

Comparison of outcome between intrauterine balloon tamponade and uterine artery embolization in the management of persistent postpartum hemorrhage: A propensity score-matched cohort study.

INTRODUCTION: The aim of this study was to compare the outcomes of women who were initially managed by intrauterine balloon tamponade or uterine artery embolization because of persistent postpartum hemorrhage demanding an immediate intervention to control bleeding. MATERIAL AND METHODS: Propensity score-matched cohort study including women who had intrauterine balloon tamponade or uterine artery embolization as initial management strategy to control persistent postpartum hemorrhage, that is, refractory to first-line therapy combined with at least one uterotonic agent. The primary outcome measure was a composite of peripartum hysterectomy and/or maternal mortality. Secondary outcomes measures were total volume of blood loss and total number of packed red blood cells transfused. RESULTS: Our 1:1 propensity score-matched cohort comprised of 50 women who had intrauterine balloon tamponade and 50 women who underwent uterine artery embolization at a blood loss between 1000 and 7000 mL. There was no statistically significant difference in the hysterectomy risk between the two groups (n = 6 in each group, odds ratio [OR] 1.00, 95% confidence interval [CI] .30-3.34), in total volume of blood loss (median 4500 mL, interquartile range [IQR] 3600-5400) for balloon vs 4000 mL (IQR 3250-5000) for embolization, P = 0.382) or in total units of packed red blood cells transfused (median 7 (IQR 5-10) for balloon vs 6 [IQR 4-9] for embolization, P = 0.319). Fifteen women (30%) who were initially managed by an intrauterine balloon still underwent uterine artery embolization, of whom one had an embolization-related thrombo-embolic event. Maternal mortality occurred in neither of the intervention groups. CONCLUSIONS: No difference in the risk of peripartum hysterectomy and/or maternal death was observed between women who had intrauterine balloon tamponade and women who underwent uterine artery embolization as an initial management for persistent postpartum hemorrhage. Although this study was underpowered to demonstrate equivalence, our study design provides a framework for future research in which intrauterine balloon tamponade may prove to be a suitable intervention of first choice in the management of persistent postpartum hemorrhage.

Pregnancy before recurrent pregnancy loss more often complicated by post-term birth and perinatal death.

INTRODUCTION: The cause of recurrent pregnancy loss often remains unknown. Possibly, pathophysiological pathways are shared with other pregnancy complications. MATERIAL AND METHODS: All women with secondary recurrent pregnancy loss (SRPL) visiting Leiden University Medical Center (January 2000-2015) were included in this retrospective cohort to assess whether women with SRPL have a more complicated first pregnancy compared with control women. SRPL was defined as three or more consecutive pregnancy losses before 22 weeks of gestation, with a previous birth. The control group consisted of all Dutch nullipara delivering a singleton (January 2000-2015). Information was obtained from the Dutch Perinatal Registry. Outcomes were preeclampsia, preterm birth, post-term birth, intrauterine growth restriction, breach position, induction of labor, cesarean section, congenital abnormalities, perinatal death and severe hemorrhage in the first ongoing pregnancy. Subgroup analyses were performed for women with idiopathic SRPL and for women ≤35 years. RESULTS: In all, 172 women with SRPL and 1 196 178 control women were included. Women with SRPL were older and had a higher body mass index; 29.7 years vs. 28.8 years and 25.1 kg/m2 vs. 24.1 kg/m2 , respectively. Women with SRPL more often had a post-term birth (OR 1.86, 95% CI 1.10-3.17) and more perinatal deaths occurred in women with SRPL compared with the control group (OR 5.03, 95% CI 2.48-10.2). Similar results were found in both subgroup analyses. CONCLUSIONS: The first ongoing pregnancy of women with (idiopathic) SRPL is more often complicated by post-term birth and perinatal death. Revealing possible links between SRPL and these pregnancy complications might lead to a better understanding of underlying pathophysiology.

Increased cardiovascular disease risk in women with a history of recurrent miscarriage.

INTRODUCTION: Cardiovascular disease is the leading cause of death in women. Observational studies suggest that women with a history of recurrent miscarriage have an increased risk of cardiovascular disease. MATERIAL AND METHODS: Women who visited the recurrent miscarriage clinic at Leiden University Medical Center between 2000 and 2010 and who had their third consecutive miscarriage before the age of 31 years, were invited to participate in this follow-up study (between 2012 and 2014). The reference group consisted of women with at least one uncomplicated pregnancy and no miscarriage, matched by zip code, age, and date of pregnancy. All women were invited for risk factor screening, including physical examination and blood collection. Main outcome measures were the (extrapolated) 10- and 30-year cardiovascular risk scores using the Framingham risk score. A subanalysis was performed for women with idiopathic recurrent miscarriage. RESULTS: Thirty-six women were included in both groups. Mean follow up was 7.5 years. Women with recurrent miscarriage had a significantly higher extrapolated 10-year cardiovascular risk score (mean 6.24%, SD 5.44) compared with women with no miscarriage (mean 3.56%, SD 1.82, P = .007) and a significantly higher 30-year cardiovascular risk score (mean 9.86%, SD 9.10) compared with women with no miscarriage (mean 6.39%, SD 4.20, P = .04). Similar results were found in women with idiopathic recurrent miscarriage (n = 28). CONCLUSIONS: Women with a history of recurrent miscarriage differ in cardiovascular risk profile at a young age compared with women with no miscarriage. The findings support an opportunity to identify women at risk of cardiovascular disease later in life and a possible moment for intervention.

Encouraging residents' professional development and career planning: the role of a development-oriented performance assessment.

BACKGROUND: Current postgraduate medical training programmes fall short regarding residents' development of generic competencies (communication, collaboration, leadership, professionalism) and reflective and deliberate practice. Paying attention to these non-technical skills in a structural manner during postgraduate training could result in a workforce better prepared for practice. A development-oriented performance assessment (PA), which assists residents with assessment of performance and deliberately planned learning activities, could potentially contribute to filling this gap. This study aims to explore residents experiences with the PA. METHODS: We conducted a qualitative interview study with 16 residents from four different medical specialties who participated in the PA, scheduled halfway postgraduate training. The PA was conducted by an external facilitator, a psychologist, and focused specifically on professional development and career planning. Residents were interviewed 6 months after the PA. Data were analysed using the framework method for qualitative analysis. RESULTS: Residents found the PA to be of additional value for their training. The overarching merit was the opportunity to evaluate competencies not usually addressed in workplace-based assessments and progress conversations. In addition, the PA proved a valuable tool for assisting residents with reflecting upon their work and formulating their learning objectives and activities. Residents reported increased awareness of capacity, self-confidence and enhanced feelings of career-ownership. An important factor contributing to these outcomes was the relationship of trust with the facilitator and programme director. CONCLUSION: The PA is a promising tool in fostering the development of generic competencies and reflective and deliberate practice. The participating residents, facilitator and programme directors were able to contribute to a safe learning environment away from the busy workplace. The facilitator plays an important role by providing credible and informative feedback. Commitment of the programme director is important for the implementation of developmental plans and learning activities.

Fetal brain imaging in isolated congenital heart defects - a systematic review and meta-analysis.

Congenital heart defects (CHDs) are associated with neurodevelopmental (ND) delay. This study aims to assess evidence for impaired prenatal brain development, in fetuses with CHD. A systematical search was performed, and 34 studies evaluating the fetal brain [magnetic resonance imaging (MRI) or ultrasound] in isolated CHD were included (1990-2015). Data regarding cerebral abnormalities, head circumference growth and middle cerebral artery flow were extracted. Prenatal MRI was studied in ten articles (445 fetuses), resulting in a pooled prevalence of 18% (95%CI -6%; 42%) for combined structural and acquired cerebral abnormalities. Prenatal head circumference was studied in 13 articles (753 fetuses), resulting in a pooled z-score of -0.51 (95%CI -0.84; -0.18). Doppler was studied in 21 articles (1412 fetuses), resulting in a lower middle cerebral artery pulsatility index (z-score -0.70 95%CI -0.99; -0.41) in left-sided CHD only. We conclude that prenatal MRI and ultrasound demonstrate brain abnormalities, delay in head growth and brainsparing in subgroups of CHD. However, large MRI studies are scarce, and ultrasound data are biased towards severe and left-sided CHD. Long-term follow-up studies correlating prenatal findings with postnatal ND outcome are limited, and data are lacking to support counseling families regarding ND outcome based on prenatal findings suggestive of altered brain development. © 2016 John Wiley & Sons, Ltd.

Group based prenatal care in a low-and high risk population in the Netherlands: a study protocol for a stepped wedge cluster randomized controlled trial.

BACKGROUND: CenteringPregnancy (CP) is a multifaceted group based care-model integrated in routine prenatal care, combining health assessment, education, and support. CP has shown some positive results on perinatal outcomes. However, the effects are less obvious when limited to the results of randomized controlled trials: as there are few trials and there is a variation in reported outcomes. Furthermore, former research was mostly conducted in the United States of America and in specific (often high risk) populations. Our study aims to evaluate the effects of CP in the Netherlands in a general population of pregnant women (low and high risk). Furthermore we aim to explore the mechanisms leading to the eventual effects by measuring potential mediating factors. DESIGN: We will perform a stepped wedge cluster randomized controlled trial, in a Western region in the Netherlands. Inclusion criteria are <24 weeks of gestation and able to communicate in Dutch (with assistance). Women in the control period will receive individual care, women in the intervention period (starting at the randomized time-point) will be offered the choice between individual care or CP. Primary outcomes are maternal and neonatal morbidity, retrieved from a national routine database. Secondary outcomes are health behavior, psychosocial outcomes, satisfaction, health care utilization and process outcomes, collected through self-administered questionnaires, group-evaluations and individual interviews. We will conduct intention-to-treat analyses. Also a per protocol analysis will be performed comparing the three subgroups: control group, CP-participants and non-CP-participants, using multilevel techniques to account for clustering effects. DISCUSSION: This study contributes to the evidence regarding the effect of CP and gives a first indication of the effect and implementation of CP in both low and high-risk pregnancies in a high-income Western society other than the USA. Also, measuring factors that are hypothesized to mediate the effect of CP will enable to explain the mechanisms that lead to effects on maternal and neonatal outcomes. TRIAL REGISTRATION: Dutch Trial Register, NTR4178 , registered September 17th 2013.

Current controversies in prenatal diagnosis 1: NIPT for chromosome abnormalities should be offered to women with low a priori risk.

In its successful annual cycle of controversies and debates, the International Society of Prenatal Diagnosis and Therapy once again addressed non-invasive prenatal testing (NIPT) by following up on the 2013 controversy, 'Should non-invasive DNA testing be the standard screening test for Down syndrome in all pregnant women'? with the proposition, 'NIPT for chromosomel abnormalities should be offered to women with low a priori risk'.

Prenatal screening: current practice, new developments, ethical challenges.

Prenatal screening pathways, as nowadays offered in most Western countries consist of similar tests. First, a risk-assessment test for major aneuploides is offered to pregnant women. In case of an increased risk, invasive diagnostic tests, entailing a miscarriage risk, are offered. For decades, only conventional karyotyping was used for final diagnosis. Moreover, several foetal ultrasound scans are offered to detect major congenital anomalies, but the same scans also provide relevant information for optimal support of the pregnancy and the delivery. Recent developments in prenatal screening include the application of microarrays that allow for identifying a much broader range of abnomalities than karyotyping, and non-invasive prenatal testing (NIPT) that enables reducing the number of invasive tests for aneuploidies considerably. In the future, broad NIPT may become possible and affordable. This article will briefly address the ethical issues raised by these technological developments. First, a safe NIPT may lead to routinisation and as such challenge the central issue of informed consent and the aim of prenatal screening: to offer opportunity for autonomous reproductive choice. Widening the scope of prenatal screening also raises the question to what extent 'reproductive autonomy' is meant to expand. Finally, if the same test is used for two different aims, namely detection of foetal anomalies and pregnancy-related problems, non-directive counselling can no longer be taken as a standard. Our broad outline of the ethical issues is meant as an introduction into the more detailed ethical discussions about prenatal screening in the other articles of this special issue.

Microarrays as a diagnostic tool in prenatal screening strategies: ethical reflection.

Genomic microarray analysis is increasingly being applied as a prenatal diagnostic tool. Microarrays enable searching the genome at a higher resolution and with higher sensitivity than conventional karyotyping for identifying clinically significant chromosomal abnormalities. As yet, no clear guidelines exist on whether microarrays should be applied prenatally for all indications or only in selected cases such as ultrasound abnormalities, whether a targeted or genome-wide array should be used, and what these should include exactly. In this paper, we present some ethical considerations on the prenatal use of microarrays. There is a strong consensus, at least in Western countries, that the aim of prenatal screening for foetal abnormalities should be understood as facilitating autonomous reproductive choice for prospective parents. The tests offered should be valid and useful to reach that purpose. Against this background, we address several ethical issues raised by the prenatal application of microarrays. First, we argue that the general distinction between a targeted and a genome-wide microarray needs to be scrutinised. Then we examine whether microarrays are 'suitable tests' to serve either a screening or a diagnostic purpose. Given the wide range of findings possibly generated by microarrays, the question arises whether microarrays actually promote or interfere with autonomous reproductive decision-making. Moreover, if variants of unknown clinical significance are identified, this adds to the burden and complexity of reproductive decision-making. We suggest a qualified use of microarrays in the prenatal context.

Prophylactic radiologic interventions to reduce postpartum hemorrhage in women with risk factors for placenta accreta spectrum disorder: a nationwide cohort study.

OBJECTIVE: To quantify the association between prophylactic radiologic interventions and perioperative blood loss in women with risk factors for placenta accreta spectrum disorder (PAS). METHODS: We conducted a retrospective nationwide cohort study of women with risk factors for placenta accreta spectrum disorder who underwent planned cesarean section in 69 Dutch hospitals between 2008 and 2013. All women had two risk factors for PAS: placenta previa/anterior low-lying placenta and a history of cesarean section(s). Women with and without ultrasonographic signs of PAS were studied as two separate groups. We compared the total blood loss of women with prophylactic radiologic interventions, defined as preoperative placement of balloon catheters or sheaths in the internal iliac or uterine arteries, with that of a control group consisting of women without prophylactic radiologic interventions using multivariable regression. We evaluated maternal morbidity by the number of red blood cell (RBC) units transfused within 24 h following childbirth (categories: 0, 1-3, >4), duration of hospital admission, and need for intensive care unit (ICU) admission. RESULTS: A total of 350 women with placenta previa/anterior low-lying placenta and history of cesarean section(s) were included: 289 with normal ultrasonography, of whom 21 received prophylactic radiologic intervention, and 61 had abnormal ultrasonography, of whom 22 received prophylactic intervention. Among women with normal ultrasonography without prophylactic intervention (n = 268), the median blood loss was 725 mL (interquartile range (IQR) 500-1500) vs. 1000 mL (IQR 550-1750) in women with intervention (n = 21); the adjusted difference in blood loss was 9 mL (95% confidence interval (CI) -315-513), p = .97). Among women with abnormal ultrasonography, those without prophylactic intervention (n = 39) had a median blood loss of 2500 mL (IQR 1200-5000) vs. 1750 mL (IQR 775-4000) in women with intervention (n = 22); the adjusted difference in blood loss was -1141 mL (95% CI -1694- -219, p = .02). Results of outcomes on maternal morbidity were comparable among women with and without prophylactic intervention. CONCLUSION: These findings suggest that prophylactic radiologic interventions prior to planned cesarean section may help to limit perioperative blood loss in women with clear signs of placenta accreta spectrum disorder on ultrasonography, but there was no evidence of a difference within the subgroup without such ultrasonographic signs. The use of these interventions should be discussed in a multidisciplinary shared decision-making process, including discussions of potential benefits and possible complications. TRIAL REGISTRATION: Netherlands Trial Registry, https://onderzoekmetmensen.nl/en/trial/28238, identifier NL4210 (NTR4363).

Single molecule sequencing of free DNA from maternal plasma for noninvasive trisomy 21 detection.

BACKGROUND: Noninvasive fetal aneuploidy detection by use of free DNA from maternal plasma has recently been shown to be achievable by whole genome shotgun sequencing. The high-throughput next-generation sequencing platforms previously tested use a PCR step during sample preparation, which results in amplification bias in GC-rich areas of the human genome. To eliminate this bias, and thereby experimental noise, we have used single molecule sequencing as an alternative method. METHODS: For noninvasive trisomy 21 detection, we performed single molecule sequencing on the Helicos platform using free DNA isolated from maternal plasma from 9 weeks of gestation onwards. Relative sequence tag density ratios were calculated and results were directly compared to the previously described Illumina GAII platform. RESULTS: Sequence data generated without an amplification step show no GC bias. Therefore, with the use of single molecule sequencing all trisomy 21 fetuses could be distinguished more clearly from euploid fetuses. CONCLUSIONS: This study shows for the first time that single molecule sequencing is an attractive and easy to use alternative for reliable noninvasive fetal aneuploidy detection in diagnostics. With this approach, previously described experimental noise associated with PCR amplification, such as GC bias, can be overcome.

Neonatal morbidity after induction vs expectant monitoring in intrauterine growth restriction at term: a subanalysis of the DIGITAT RCT.

OBJECTIVE: The Disproportionate Intrauterine Growth Intervention Trial at Term (DIGITAT) compared induction of labor and expectant management in suspected intrauterine growth restriction (IUGR) at term. In this subanalysis, we report neonatal morbidity between the policies based on the Morbidity Assessment Index for Newborns (MAIN). STUDY DESIGN: We used data from the DIGITAT. For each neonate, we calculated the MAIN score, a validated outcome scale. RESULTS: There were no differences in mean MAIN scores or in MAIN morbidity categories. We found that neonatal admissions are lower after 38 weeks' gestational age compared with 36 and 37 weeks in both groups. CONCLUSION: The incidence of neonatal morbidity in IUGR at term is comparable and relatively mild either after induction or after an expectant policy. However, neonatal admissions are lower after 38 weeks of pregnancy, so if induction to preempt possible stillbirth is considered, it is reasonable to delay until 38 weeks, provided watchful monitoring.