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Preeclampsia is often preceded by abnormal hemodynamic changes with heterogeneous patterns in the first half of pregnancy. We assessed the effect of timely tailored correction of nonphysiological hemodynamic changes on preventing preeclampsia in a high-risk population. Primiparous women with a history of preeclampsia were invited to participate in a longitudinal program in their next pregnancy, including repeated hemodynamic assessments at 12-, 16-, 20- and 30-week gestation additional to regular pregnancy checkups. When at least 2 of the hemodynamic variables were not within physiological reference values, the hemodynamic imbalance between cardiac output and peripheral vascular resistance was counteracted with either labetalol, methyldopa, or nifedipine using a simple treatment algorithm. Normogram-guided women (n=157) were matched to 157 women receiving care as usual (power, 80%; α=0.05). Risk of recurrent preeclampsia was analyzed with logistic regression adjusted for daily low-dose aspirin or calcium supplementation. Hemodynamic changes were considered nonphysiological in 90% of women in the normogram-guided group. Twelve percent of these women developed recurrent preeclampsia compared with 22% in the care-as-usual group (adjusted odds ratio, 0.47 [95% CI, 0.25–0.88]). There were no differences between groups in gestational age at delivery (38 1 and 38 2 weeks in the normogram-guided and care-as-usual groups, respectively) and neonatal birth weight (3148 and 3180 g in the normogram-guided and care-as-usual groups, respectively). Tailored circulatory normalization of nonphysiological hemodynamic changes during pregnancy halves the risk of recurrent preeclampsia, without disadvantageous effects on offspring outcome. This simple and innovative treatment strategy may also be beneficial to other women at increased risk for preeclampsia in pregnancy. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04216706.

Objectives Discussing the individual probability of a successful vaginal birth after caesarean (VBAC) can support decision making. The aim of this study is to externally validate a prediction model for the probability of a VBAC in a Dutch population. Methods In this prospective cohort study in 12 Dutch hospitals, 586 women intending VBAC were included. Inclusion criteria were singleton pregnancies with a cephalic foetal presentation, delivery after 37 weeks and one previous caesarean section (CS) and preference for intending VBAC. The studied prediction model included six predictors: pre-pregnancy body mass index, previous vaginal delivery, previous CS because of non-progressive labour, Caucasian ethnicity, induction of current labour, and estimated foetal weight ≥90th percentile. The discriminative and predictive performance of the model was assessed using receiver operating characteristic curve analysis and calibration plots. Results The area under the curve was 0.73 (CI 0.69–0.78). The average predicted probability of a VBAC according to the prediction model was 70.3% (range 33–92%). The actual VBAC rate was 71.7%. The calibration plot shows some overestimation for low probabilities of VBAC and an underestimation of high probabilities. Conclusions The prediction model showed good performance and was externally validated in a Dutch population. Hence it can be implemented as part of counselling for mode of delivery in women choosing between intended VBAC or planned CS after previous CS.

Purpose Adequate calcium intake during pregnancy is of major importance for the health of both mother and fetus. Up to date, evidence on the prevalence of inadequate calcium intake among pregnant women is sparse for Western countries, and it is unknown to what extent inadequate dietary calcium intake is adequately balanced by supplement use. The objective of this study was to estimate calcium intake from diet and supplement use during the early pregnancy in The Netherlands. Methods As part of the Expect cohort study, 2477 pregnant women (8-16 weeks of gestation) completed an online questionnaire including questions on baseline characteristics, the use of calcium containing supplements, and a short food-frequency questionnaire (FFQ). Intake data were used to calculate median calcium intakes from diet, from supplements, and combined, and to compare these values with currently accepted requirement levels. Results Forty-two percent of the pregnant women had a total calcium intake below the estimated average requirement of 800 mg/day. Median (interquartile range) calcium intake was 886 (611-1213) mg/day. Calcium or multivitamin supplements were used by 64.8% of the women at 8 weeks of gestation, with a median calcium content of 120.0 (60.0-200.0) mg/day. Prenatal vitamins were the most often used supplements (60.6%). Conclusions Forty-two percent of Dutch pregnant women have an inadequate calcium intake. Supplements are frequently used, but most do not contain sufficient amounts to correct this inadequate intake.

Contains fulltext : 229268.pdf (Publisher’s version ) (Open Access) INTRODUCTION: Low-dose aspirin (LDA) prophylaxis has been shown to reduce women's preeclampsia risk. Evidence regarding LDA adherence rates of pregnant women is based almost exclusively on clinical trials, giving a potentially biased picture. Moreover, these studies do not report on determinants of adherence. Since 2017, obstetric healthcare professionals in a Dutch region have assessed women's preeclampsia risk by means of a prediction tool and counseled those with an above-population average risk on LDA as a prophylactic measure. MATERIAL AND METHODS: From 2017 to 2018, 865 women were recruited in multiple centers and prospectively followed using web-based surveys (Expect Study II). Rates and determinants of LDA usage among women with an increased preeclampsia risk in daily practice were assessed. Results were compared with findings in a similar cohort from a care-as-usual setting lacking risk-based counseling (Expect Study I, n = 2614). Netherlands Trial Register NTR4143. RESULTS: In total, 306 women had a predicted increased preeclampsia risk. LDA usage was higher for women receiving risk-based care than care-as-usual (29.4% vs 1.5%, odds ratio 19.1, 95% confidence interval 11.2-32.5). Daily LDA usage was positively correlated with both predicted risk and women's concerns regarding preeclampsia. Most reported reasons for non- or incomplete use were unawareness of LDA as a preventive intervention, concerns about potential adverse effects and doubts regarding the benefits. CONCLUSIONS: Risk-based counseling was associated with a higher prevalence of LDA usage, but general usage rates were low. Future research regarding potential factors improving the usage of LDA during pregnancy is necessary.

BackgroundThe prenatal exposure to maternal n-6 and n-3 polyunsaturated fatty acids (PUFAs) might influence the development of social competence and internalizing and externalizing behaviours of the child, because of the numerous functions of PUFAs within the nervous system.MethodsTo analyse the association of selected maternal PUFAs (i.e., AA, EPA, DHA, total n-6, total n-3, and the n-6:n-3 ratio) measured during gestation with childhood social competence and problem behaviours, we examined 311 mother-child pairs from the Maastricht Essential Fatty Acid Birth (MEFAB) cohort. For each woman, PUFA-specific changes in relative concentrations were calculated by identifying the best-fitting curve of PUFA concentration by linear splines of gestational age. The associations of changes in maternal PUFAs in early and late pregnancy with childhood social competence, total problems, internalizing and externalizing behaviours, measured with the Child Behaviour Checklist 4/18 at age 7, were investigated with linear regression analyses adjusted for maternal and children's socio-demographic characteristics.ResultsIn late gestation (i.e., from gestational week 30), an increase in AA was associated with higher social competence, while a decrease in total n-6 was associated with lower externalizing behaviours. No other significant associations were found.DiscussionIn this prospective study, increasing maternal AA and decreasing total n-6 were associated with improved social competence and externalizing behaviours, respectively, in 7-year old children. Nonetheless, the clinical significance of the identified associations is modest and further investigations are warranted to clarify the relationship between maternal AA and total n-6 during pregnancy and childhood social and behavioural development.

Objectives Woman with a history of a previous cesarean section (CS) can choose between an elective repeat CS (ERCS) and a trial of labor (TOL), which can end in a vaginal birth after cesarean (VBAC) or an unplanned CS. Guidelines describe women’s rights to make an informed decision between an ERCS or a TOL. However, the rates of TOL and vaginal birth after CS varies greatly between and within countries. The objective of this study is to asses nation-wide implementation of counselling with a decision aid (DA) including a prediction model, on intended delivery compared to care as usual. We hypothesize that this may result in a reduction in practice variation without an increase in cesarean rates or complications. Methods In a multicenter controlled before and after cohort study we evaluate the effect of nation-wide implementation of a DA. Practice variation was defined as the standard deviation (SD) of TOL percentages. Results A total of 27 hospitals and 1,364 women were included. A significant decrease was found in practice variation (SD TOL rates: 0.17 control group vs. 0.10 intervention group following decision aid implementation, p=0.011). There was no significant difference in the ERCS rate or overall CS rates. A 21% reduction in the combined maternal and perinatal adverse outcomes was seen. Conclusions Nationwide implementation of the DA showed a significant reduction in practice variation without an increase in the rate of cesarean section or complications, suggesting an improvement in equality of care.

Objective The best screening strategy for gestational diabetes mellitus (GDM) remains a topic of debate. Several organizations made a statement in favor of universal screening, but the volume of oral glucose tolerance tests (OGTT) required may burden healthcare systems. As a result, many countries still rely on selective screening using a checklist of risk factors, but reported diagnostic characteristics vary. Moreover, women's discomfort due to an OGTT is often neglected. Since 2017, obstetric healthcare professionals in a Dutch region assessed women's GDM risk with a prediction model and counseled those with an increased risk regarding an OGTT. Methods From 2017 to 2018, 865 women were recruited in a multicenter prospective cohort. Results In total, 385 women (48%) had an increased predicted GDM risk. Of all women, 78% reported that their healthcare professional discussed their GDM risk. Predicted GDM risks were positively correlated with conducting an OGTT. Conclusion Implementation of a GDM prediction model resulted in moderate rates of OGTTs performed in general, but high rates in high‐risk women. As 25% of women experienced discomfort from the OGTT, a selective screening strategy based on a prediction model with a high detection rate may be an interesting alternative to universal screening. Study cohort registration Netherlands Trial Register: NTR4143; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4143., Synopsis Implementing a gestational diabetes mellitus prediction model resulted in a majority of high‐risk women receiving an oral glucose tolerance test within the recommended gestational window.

Background Evidence for optimal hemostatic resuscitation in postpartum hemorrhage (PPH) is lacking. Liberal fluid administration may result in acidosis, hypothermia and coagulopathy. Objective We hypothesize that in early PPH a restrictive fluid administration results in less progression to moderate PPH. Study design In four Dutch hospitals we recruited women of 18 years and over, and more than 24 weeks pregnant. Exclusion criteria were: anticoagulant therapy, known coagulation disorders, pre-eclampsia, antenatal diagnosis of abnormally adhesive placenta, and a contraindication for liberal fluid therapy. We blindly randomized participants at 500 mL and ongoing blood loss in the third stage of labor between restrictive fluid administration (clear fluids 0.75–1.0 times the volume of blood lost) and liberal fluid administration (clear fluids 1.5–2.0 times the volume of blood lost). The primary outcome was progression to more than 1000 mL blood loss. Analyses were according to the intention-to-treat principle. Results From August 2014 till September 2019, 5190 women were informed of whom 1622 agreed to participate. A total of 252 women were randomized of which 130 were assigned to the restrictive group and 122 to the liberal group. In the restrictive management group 51 of the 130 patients (39.2%) progressed to more than 1000 mL blood loss versus 61 of the 119 patients (51.3%) in the liberal management group (difference, -12.0% [95%-CI -24.3% to 0.3%], p = 0.057). There was no difference in the need for blood transfusion, coagulation parameters, or in adverse events between the groups. Conclusions Although a restrictive fluid resuscitation in women with mild PPH could not been proven to be superior, it does not increase the need for blood transfusion, alter coagulation parameters, or cause a rise in adverse events. It can be considered as an alternative treatment option to liberal fluid resuscitation. Trial registration NTR3789.

Background In contrast to severe gestational hypertension, it is questioned whether antihypertensive medication for mild to moderate gestational hypertension prevents adverse maternal and offspring outcomes. Hypertensive drugs halve the risk of severe hypertension, but do not seem to prevent progression to preeclampsia or reduce the risk of complications in offspring. In fact, beta-blockers, a first line therapy option, are suspected to impair foetal growth. Disappointing effects of antihypertensive medication can be anticipated when the pharmacological mode of action does not match the underlying haemodynamic imbalance. Hypertension may result from 1) high cardiac output, low vascular resistance state, in which beta blockade is expected to be most effective, or 2) low cardiac output, high vascular resistance state where dihydropyridine calcium channel blockers or central-acting alpha agonists might be the best corrective medication. In the latter, beta-blockade might be maternally ineffective and even contribute to impaired foetal growth by keeping cardiac output low. We propose a randomized controlled trial to determine whether correcting the haemodynamic imbalance in women with mild to moderate hypertension reduces the development of severe hypertension and/or preeclampsia more than non-pharmacological treatment does, without alleged negative effects on foetal growth. Methods Women diagnosed with mild to moderate hypertension without proteinuria or signs of other organ damage before 37 weeks of pregnancy are invited to participate in this randomized controlled trial. Women randomized to the intervention group will be prescribed tailored antihypertensive medication, using a simple diagnostic and treatment algorithm based on the mean arterial pressure/heart rate ratio, which serves as an easy-to-determine proxy for maternal circulatory state. Women randomized to the control group will receive non-pharmacological standard care according to national and international guidelines. In total, 208 women will be randomized in a 1:1 ratio. The primary outcome is progression to severe hypertension and preeclampsia and the secondary outcomes are adverse maternal and neonatal outcomes. Discussion This trial will provide evidence of whether tailoring treatment of mild to moderate gestational hypertension to the individual haemodynamic profile prevents maternal disease progression. Trial registration NCT02531490, registered on 24 August 2015.

Background Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk is needed to plan management. Objectives To assess the performance of existing pre-eclampsia prediction models and to develop and validate models for pre-eclampsia using individual participant data meta-analysis. We also estimated the prognostic value of individual markers. Design This was an individual participant data meta-analysis of cohort studies. Setting Source data from secondary and tertiary care. Predictors We identified predictors from systematic reviews, and prioritised for importance in an international survey. Primary outcomes Early-onset (delivery at Analysis We externally validated existing prediction models in UK cohorts and reported their performance in terms of discrimination and calibration. We developed and validated 12 new models based on clinical characteristics, clinical characteristics and biochemical markers, and clinical characteristics and ultrasound markers in the first and second trimesters. We summarised the data set-specific performance of each model using a random-effects meta-analysis. Discrimination was considered promising for C-statistics of ≥ 0.7, and calibration was considered good if the slope was near 1 and calibration-in-the-large was near 0. Heterogeneity was quantified using I 2 and τ2. A decision curve analysis was undertaken to determine the clinical utility (net benefit) of the models. We reported the unadjusted prognostic value of individual predictors for pre-eclampsia as odds ratios with 95% confidence and prediction intervals. Results The International Prediction of Pregnancy Complications network comprised 78 studies (3,570,993 singleton pregnancies) identified from systematic reviews of tests to predict pre-eclampsia. Twenty-four of the 131 published prediction models could be validated in 11 UK cohorts. Summary C-statistics were between 0.6 and 0.7 for most models, and calibration was generally poor owing to large between-study heterogeneity, suggesting model overfitting. The clinical utility of the models varied between showing net harm to showing minimal or no net benefit. The average discrimination for IPPIC models ranged between 0.68 and 0.83. This was highest for the second-trimester clinical characteristics and biochemical markers model to predict early-onset pre-eclampsia, and lowest for the first-trimester clinical characteristics models to predict any pre-eclampsia. Calibration performance was heterogeneous across studies. Net benefit was observed for International Prediction of Pregnancy Complications first and second-trimester clinical characteristics and clinical characteristics and biochemical markers models predicting any pre-eclampsia, when validated in singleton nulliparous women managed in the UK NHS. History of hypertension, parity, smoking, mode of conception, placental growth factor and uterine artery pulsatility index had the strongest unadjusted associations with pre-eclampsia. Limitations Variations in study population characteristics, type of predictors reported, too few events in some validation cohorts and the type of measurements contributed to heterogeneity in performance of the International Prediction of Pregnancy Complications models. Some published models were not validated because model predictors were unavailable in the individual participant data. Conclusion For models that could be validated, predictive performance was generally poor across data sets. Although the International Prediction of Pregnancy Complications models show good predictive performance on average, and in the singleton nulliparous population, heterogeneity in calibration performance is likely across settings. Future work Recalibration of model parameters within populations may improve calibration performance. Additional strong predictors need to be identified to improve model performance and consistency. Validation, including examination of calibration heterogeneity, is required for the models we could not validate. Study registration This study is registered as PROSPERO CRD42015029349. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 72. See the NIHR Journals Library website for further project information.

Contains fulltext : 229440.pdf (Publisher’s version ) (Open Access) BACKGROUND: Obstetric health care relies on an adequate antepartum risk selection. Most guidelines used for risk stratification, however, do not assess absolute risks. In 2017, a prediction tool was implemented in a Dutch region. This tool combines first trimester prediction models with obstetric care paths tailored to the individual risk profile, enabling risk-based care. OBJECTIVE: To assess impact and cost-effectiveness of risk-based care compared to care-as-usual in a general population. METHODS: A before-after study was conducted using 2 multicenter prospective cohorts. The first cohort (2013-2015) received care-as-usual; the second cohort (2017-2018) received risk-based care. Health outcomes were (1) a composite of adverse perinatal outcomes and (2) maternal quality-adjusted life-years. Costs were estimated using a health care perspective from conception to 6 weeks after the due date. Mean costs per woman, cost differences between the 2 groups, and incremental cost effectiveness ratios were calculated. Sensitivity analyses were performed to evaluate the robustness of the findings. RESULTS: In total 3425 women were included. In nulliparous women there was a significant reduction of perinatal adverse outcomes among the risk-based care group (adjusted odds ratio, 0.56; 95% confidence interval, 0.32-0.94), but not in multiparous women. Mean costs per pregnant woman were significantly lower for risk-based care (mean difference, -€2766; 95% confidence interval, -€3700 to -€1825). No differences in maternal quality of life, adjusted for baseline health, were observed. CONCLUSION: In the Netherlands, risk-based care in nulliparous women was associated with improved perinatal outcomes as compared to care-as-usual. Furthermore, risk-based care was cost-effective compared to care-as-usual and resulted in lower health care costs.

Background: The effect of vitamin B-12 from different animal foods on vitamin B-12 biomarker status has not previously been evaluated in pregnant women.Objective: We examined the association of vitamin B-12 intake from dairy, meat, fish (including shellfish), and eggs with circulating concentrations of vitamin B-12 biomarkers and with the presence of vitamin B-12 deficiency in 1266 pregnant women participating in the KOALA Birth Cohort Study.Methods: Blood samples were collected in weeks 34-36 of pregnancy, and vitamin B-12 intake from foods and supplements was estimated with a semiquantitative food-frequency questionnaire (FFQ). Total vitamin B-12, holotranscobalamin (holoTC), and methylmalonic acid (MMA) were determined in plasma. Vitamin B-12 deficiency was defined as holoTC 0.45 mu mol/L. Associations were evaluated with linear and logistic regression analyses, adjusting for potential confounders.Results: Significant dose-response relations were observed between vitamin B-12 intake from dairy, meat, and fish and plasma vitamin B-12, holoTC, and MMA [P-trend for (shell) fish with MMA = 0.002; P-trend for dairy, meat, and fish with all other markers Conclusions: In pregnant Dutch women, higher intakes of vitamin B-12 from dairy, meat, and fish were positively associated with vitamin B-12 status, suggesting that dairy, meat, and fish are good sources of bioactive vitamin B-12 in pregnancy. Nevertheless, for (lacto-) vegetarians, vitamin B-12 supplementation is recommended.

BACKGROUND: The effect of in vitro fertilisation (IVF) on breast cancer risk for BRCA1/2 mutation carriers is rarely examined. As carriers may increasingly undergo IVF as part of preimplantation genetic diagnosis (PGD), we examined the impact of ovarian stimulation for IVF on breast cancer risk in BRCA1/2 mutation carriers.METHODS: The study population consisted of 1550 BRCA1 and 964 BRCA2 mutation carriers, derived from the nationwide HEBON study and the nationwide PGD registry. Questionnaires, clinical records and linkages with the Netherlands Cancer Registry were used to collect data on IVF exposure, risk-reducing surgeries and cancer diagnosis, respectively. Time-dependent Cox regression analyses were conducted, stratified for birth cohort and adjusted for subfertility.RESULTS: Of the 2514 BRCA1/2 mutation carriers, 3% (n = 76) were exposed to ovarian stimulation for IVF. In total, 938 BRCA1/2 mutation carriers (37.3%) were diagnosed with breast cancer. IVF exposure was not associated with risk of breast cancer (HR: 0.79, 95% CI: 0.46-1.36). Similar results were found for the subgroups of subfertile women (n = 232; HR: 0.73, 95% CI: 0.39-1.37) and BRCA1 mutation carriers (HR: 1.12, 95% CI: 0.60-2.09). In addition, age at and recency of first IVF treatment were not associated with breast cancer risk.CONCLUSION: No evidence was found for an association between ovarian stimulation for IVF and breast cancer risk in BRCA1/2 mutation carriers.

Problem behaviors are of increasing public health concern. Twin studies have revealed substantial genetic and environmental influences on children's behavior, and examining birth-weight difference could allow the identification of the specific contribution of multiple non-shared prenatal environmental factors. The Twins and Multiple Births Association Heritability Study, a UK, volunteer-based study, recruited mothers of twins aged 18 months to 5 years; 960 twins (480 pairs) were included in the analysis. Twins’ mothers answered questions relative to their pregnancy and their twins’ characteristics, and completed the Child Behavior Checklist (CBCL) 1½–5. The association between the absolute birth-weight difference and each CBCL scale's score difference was analyzed by means of multiple linear regressions. Expected mean CBCL score differences were calculated. In monozygotic (MZ) twins, statistically and clinically significant associations were found between intrapair birth-weight difference and difference in total problems, internalizing problems, and emotional reactiveness. No significant results were observed neither in dizygotic (DZ) twins when analyzed as a separate group nor in MZ and DZ twins combined. The results of the present study suggest that with increasing the absolute birth-weight difference, the intrapair difference in total problems, internalizing behaviors and emotionality increases, with smaller twins being at major risk for later behavior problems. Moreover, these results suggest a causal association between birth weight and behavior development.

Objectives Maternal pre-pregnancy weight is known to affect foetal development. However, it has not yet been clarified if gestational weight gain is associated with childhood behavioural development. Methods We performed a pooled analysis of two prospective birth cohorts to investigate the association between gestational weight gain and childhood problem behaviours, and the effect modification of maternal pre-pregnancy BMI. In total, 378 mother–child pairs from the Maastricht Essential Fatty Acids Birth cohort (MEFAB) and 414 pairs from the Rhea Mother–Child cohort were followed up from early pregnancy to 6–7 years post-partum. At follow up, parents assessed their children’s behaviour, measured as total problems, internalizing and externalizing behaviours, with the Child Behaviour Checklist. We computed cohort- and subject-specific gestational weight gain trajectories using mixed-effect linear regression models. Fractional polynomial regressions, stratified by maternal pre-pregnancy BMI status, were then used to examine the association between gestational weight gain and childhood problem behaviours. Results In the pre-pregnancy overweight/obese group, greater gestational weight gain was associated with higher problem behaviours. On average, children of women with overweight/obesity who gained 0.5 kg/week scored 25 points higher (on a 0–100 scale) in total problems and internalizing behaviours, and about 18 points higher in externalizing behaviours than children whose mothers gained 0.2 kg/week. Inconsistent results were found in the pre-pregnancy normal weight group. Conclusions for Practice Excessive gestational weight gain in women with pre-pregnancy overweight/obesity might increase problem behaviours in school-age children. Particular attention should be granted to avoid excessive weight gain in women with a pre-pregnancy overweight or obesity.

Contains fulltext : 229441.pdf (Publisher’s version ) (Open Access) Background. Despite improved management, preeclampsia remains an important cause of maternal and neonatal mortality and morbidity. Low-dose aspirin (LDA) lowers the risk of preeclampsia. Although several guidelines recommend LDA prophylaxis in women at increased risk, they disagree about the definition of high risk. Recently, an externally validated prediction model for preeclampsia was implemented in a Dutch region combined with risk-based obstetric care paths. Objectives. To demonstrate the selection of a risk threshold and to evaluate the adherence of obstetric health care professionals to the prediction tool. Study Design. Using a survey (n = 136) and structured meetings among health care professionals, possible cutoff values at which LDA should be discussed were proposed. The prediction model, with chosen cutoff and corresponding risk-based care paths, was embedded in an online tool. Subsequently, a prospective multicenter cohort study (n = 850) was performed to analyze the adherence of health care professionals. Patient questionnaires, linked to the individual risk profiles calculated by the online tool, were used to evaluate adherence. Results. Health care professionals agreed upon employing a tool with a high detection rate (cutoff: 3.0%; sensitivity 75%, specificity 64%) followed by shared decision between patients and health care professionals on LDA prophylaxis. Of the 850 enrolled women, 364 women had an increased risk of preeclampsia. LDA was discussed with 273 of these women, resulting in an 81% adherence rate. Conclusion. Consensus regarding a suitable risk cutoff threshold was reached. The adherence to this recommendation was 81%, indicating adequate implementation.

Maternal pre-pregnancy weight has been related with young singletons’ cognitive and behavioral development, but it is not clear if it has an effect on temperament. We used a twin cohort to evaluate the association between maternal pre-pregnancy body mass index (BMI) and infants’ temperament. The mothers of 834 twins answered questions regarding their pre-pregnancy BMI and their 0- to 18-month-old children’s temperament using the Revised Infant Behavior Questionnaire. Three temperamental dimensions were examined: activity level, distress to limitation and duration of orienting. The relationship between maternal pre-pregnancy BMI and each temperamental component was investigated by means of multilevel mixed-effects linear regression analysis. We found no clear evidence of an association of maternal pre-pregnancy BMI with twins’ temperament. The development of temperament is influenced by a large number of factors, probably different from those influencing children’s emotional and behavioral development.

Introduction We performed an independent validation study of all published first trimester prediction models, containing non‐invasive predictors, for the risk of gestational diabetes mellitus. Furthermore, the clinical potential of the best performing models was evaluated. Material and methods Systemically selected prediction models from the literature were validated in a Dutch prospective cohort using data from Expect Study I and PRIDE Study. The predictive performance of the models was evaluated by discrimination and calibration. Clinical utility was assessed using decision curve analysis. Screening performance measures were calculated at different risk thresholds for the best model and compared with current selective screening strategies. Results The validation cohort included 5260 women. Gestational diabetes mellitus was diagnosed in 127 women (2.4%). The discriminative performance of the 12 included models ranged from 68% to 75%. Nearly all models overestimated the risk. After recalibration, agreement between the observed outcomes and predicted probabilities improved for most models. Conclusions The best performing prediction models showed acceptable performance measures and may enable more personalized medicine‐based antenatal care for women at risk of developing gestational diabetes mellitus compared with current applied strategies.

STUDY QUESTION To what extent are endometriosis and its related physical and mental symptoms associated with the perceived level of sexual functioning in women and their male partners? SUMMARY ANSWER Dyspareunia and depressive symptoms are associated with impaired sexual functioning in women with endometriosis, whereas sexual functioning in their male partners is not affected. WHAT IS KNOWN ALREADY Women with endometriosis suffer from more dyspareunia, lower sexual functioning, and lower quality of life. In qualitative studies, partners of women with endometriosis report that endometriosis affected their quality of life and produced relational distress. STUDY DESIGN SIZE, DURATION In this cross-sectional study, sexual functioning in women with endometriosis (n = 83) and their partners (n = 74) was compared with sexual functioning in a control group of women attending the outpatient department for issues related to contraception (n = 40), and their partners (n = 26). PARTICIPANTS/MATERIALS, SETTING, METHODS Women and partners were recruited in the Maastricht University Medical Centre (MUMC) and the VieCuri Medical Centre Venlo between June 2011 and December 2012. All participants were asked to complete a set of online questionnaires. MAIN RESULTS AND THE ROLE OF CHANCE Response rates were 59.3% (83/140) for women with endometriosis and 52.3% (74/140) for their partners. Response rates in the control group were respectively 43.2% and 27.4% (41/95 and 27/95), of whom 40 women and 26 partners could be included in the study. Women with endometriosis as compared with the control group, reported significantly more frequent pain during intercourse (53% versus 15%, P

Objective To assess the effect on mode of delivery of the routine use of labour epidural analgesia (EA) compared with analgesia on request. Design Randomised non-inferiority trial. Setting One university and one non-university teaching hospital in The Netherlands. Population Women with a singleton pregnancy in cephalic presentation beyond 36 + 0 weeks' gestation. Methods Participants were randomly allocated to receive either routine EA or analgesia on request. Intention-to-treat (ITT) and per-protocol (PP) analyses were performed, with confidence intervals (CI) calculated for the differences in percentages or means. Main outcome measures Rate of operative delivery (instrumental vaginal or caesarean), labour characteristics, and adverse labour and neonatal outcomes. Results A total of 488 women were randomly allocated to the routine EA (n = 233) or analgesia on request group (n = 255). In the routine EA group, 89.3% (208/233) received EA. According to ITT analysis, 34.8% (81/233) women in the routine EA group had an operative delivery, compared with 26.7% (68/255) in the analgesia on request group (difference 8.1%, 95% CI −0.1 to 16.3). The difference in rate of operative deliveries according to the PP analysis was statistically significant (difference 8.9%, 95% CI 0.4 to 17.4). Inferiority of EA could not be rejected, as in both analyses the upper bound of the confidence interval exceeded the pre-specified inferiority criterion of +10%. Women in the routine EA group had more adverse effects, including hypotension (difference 9.5%, 95% CI 4.2 to 14.9), and motor blockade (difference 6.8%, 95% CI 1.1 to 12.5). Conclusion Non-inferiority of routine EA could not be demonstrated in this trial. Routine EA use is likely to lead to more operative deliveries and more maternal adverse effects. The results of our study do not justify routine use of EA.

Purpose The aim of this study was to determine whether BRCA1/2 mutation carriers produce fewer mature oocytes after ovarian stimulation for in vitro fertilization (IVF) with preimplantation genetic diagnosis (PGD), in comparison to a PGD control group. Methods A retrospective, international, multicenter cohort study was performed on data of first PGD cycles performed between January 2006 and September 2015. Data were extracted from medical files. The study was performed in one PGD center and three affiliated IVF centers in the Netherlands and one PGD center in Belgium. Exposed couples underwent PGD because of a pathogenic BRCA1/2 mutation, controls for other monogenic conditions. Only couples treated in a long gonadotropin-releasing hormone (GnRH) agonist-suppressive protocol, stimulated with at least 150 IU follicle stimulating hormone (FSH), were included. Women suspected to have a diminished ovarian reserve status due to chemotherapy, auto-immune disorders, or genetic conditions (other than BRCA1/2 mutations) were excluded. A total of 106 BRCA1/2 mutation carriers underwent PGD in this period, of which 43 (20 BRCA1 and 23 BRCA2 mutation carriers) met the inclusion criteria. They were compared to 174 controls selected by frequency matching. Results Thirty-eight BRCA1/2 mutation carriers (18 BRCA1 and 20 BRCA2 mutation carriers) and 154 controls proceeded to oocyte pickup. The median number of mature oocytes was 7.0 (interquartile range (IQR) 4.0–9.0) in the BRCA group as a whole, 6.5 (IQR 4.0–8.0) in BRCA1 mutation carriers, 7.5 (IQR 5.5–9.0) in BRCA2 mutation carriers, and 8.0 (IQR 6.0–11.0) in controls. Multiple linear regression analysis with the number of mature oocytes as a dependent variable and adjustment for treatment center, female age, female body mass index (BMI), type of gonadotropin used, and the total dose of gonadotropins administered revealed a significantly lower yield of mature oocytes in the BRCA group as compared to controls (p = 0.04). This finding could be fully accounted for by the BRCA1 subgroup (BRCA1 mutation carriers versus controls p = 0.02, BRCA2 mutation carriers versus controls p = 0.50). Conclusions Ovarian response to stimulation, expressed as the number of mature oocytes, was reduced in BRCA1 but not in BRCA2 mutation carriers. Although oocyte yield was in correspondence to a normal response in all subgroups, this finding points to a possible negative influence of the BRCA1 gene on ovarian reserve. Electronic supplementary material The online version of this article (doi:10.1007/s10815-017-1014-3) contains supplementary material, which is available to authorized users.

Item does not contain fulltext BACKGROUND: Post-partum haemorrhage (PPH) causes rapidly developing deficiencies in clotting factors and contributes to substantial maternal morbidity and mortality. Rotational thromboelastometry (ROTEM((R))) is increasingly used as a point of care coagulation monitoring device in patients with massive haemorrhage; however, there are limited data on reference ranges in the peri-partum period. These are required due to the haemostatic changes in pregnancy. METHODS: In a Dutch multi-centre trial, 161 subjects were included; blood samples were obtained during labour (T1) and within 1 h of delivery (T2). Reference ranges of ROTEM((R)) INTEM, EXTEM, FIBTEM, and APTEM were set and correlation with laboratory results was investigated using the guidelines of the International Federation of Clinical Chemistry. RESULTS: Reference ranges were obtained for clotting time (CT), clot formation time (CFT), alpha-angle, clot firmness at 10 and 20 min (A10, A20), maximum clot firmness (MCF), and maximum lysis (ML). These were comparable from centre to centre, and between T1 and T2. Reference ranges T1: EXTEM: CT 31-63 s, CFT 41-120 s, and MCF 42-78 mm. INTEM: CT 109-225 s, CFT 40-103, and MCF 63-78 mm. FIBTEM: CT 31-79 s and MCF 13-45 mm. APTEM: CT 33-62 s, CFT 42-118, and MCF 61-79 mm. CONCLUSIONS: Reference values for ROTEM((R)) parameters are reported. The previously published correlation between FIBTEM parameters and plasma fibrinogen levels by the Clauss method is confirmed. Further research is needed to define threshold values for haemostatic therapy in the course of PPH. Clinical trial registration NTR 2515 (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2515).

Item does not contain fulltext OBJECTIVE: To develop and internally validate a model that predicts the outcome of an intended vaginal birth after caesarean (VBAC) for a Western European population that can be used to personalise counselling for deliveries at term. DESIGN: Registration-based retrospective cohort study. SETTING: Five university teaching hospitals, seven non-university teaching hospitals, and five non-university non-teaching hospitals in the Netherlands. POPULATION: A cohort of 515 women with a history of one caesarean section and a viable singleton pregnancy, without a contraindication for intended VBAC, who delivered at term. METHODS: Potential predictors for a vaginal delivery after caesarean section were chosen based on literature and expert opinions. We internally validated the prediction model using bootstrapping techniques. MAIN OUTCOME MEASURES: Predictors for VBAC. For model validation, the area under the receiver operating characteristic curve (AUC) for discriminative capacity and calibration-per-risk-quantile for accuracy were calculated. RESULTS: A total of 371 out of 515 women had a VBAC (72%). Variables included in the model were: estimated fetal weight greater than the 90(th) percentile in the third trimester; previous non-progressive labour; previous vaginal delivery; induction of labour; pre-pregnancy body mass index; and ethnicity. The AUC was 71% (95% confidence interval, 95% CI = 69-73%), indicating a good discriminative ability. The calibration plot shows that the predicted probabilities are well calibrated, especially from 65% up, which accounts for 77% of the total study population. CONCLUSION: We developed an appropriate Western European population-based prediction model that is aimed to personalise counselling for term deliveries.

Item does not contain fulltext OBJECTIVE: To externally validate two models from the USA (entry-to-care [ETC] and close-to-delivery [CTD]) that predict successful intended vaginal birth after caesarean (VBAC) for the Dutch population. DESIGN: A nationwide registration-based cohort study. SETTING: Seventeen hospitals in the Netherlands. POPULATION: Seven hundred and sixty-three pregnant women, each with one previous caesarean section and a viable singleton cephalic pregnancy without a contraindication for an intended VBAC. METHODS: The ETC model comprises the variables maternal age, prepregnancy body mass index (BMI), ethnicity, previous vaginal delivery, previous VBAC and previous nonprogressive labour. The CTD model replaces prepregnancy BMI with third-trimester BMI and adds estimated gestational age at delivery, hypertensive disease of pregnancy, cervical examination and induction of labour. We included consecutive medical records of eligible women who delivered in 2010. For validation, individual probabilities of women who had an intended VBAC were calculated. MAIN OUTCOME MEASURES: Discriminative performance was assessed with the area under the curve (AUC) of the receiver operating characteristic and predictive performance was assessed with calibration plots and the Hosmer-Lemeshow (H-L) statistic. RESULTS: Five hundred and fifteen (67%) of the 763 women had an intended VBAC; 72% of these (371) had an actual VBAC. The AUCs of the ETC and CTD models were 68% (95% CI 63-72%) and 72% (95% CI 67-76%), respectively. The H-L statistic showed a P-value of 0.167 for the ETC model and P = 0.356 for the CTD model, indicating no lack of fit. CONCLUSION: External validation of two predictive models developed in the USA revealed an adequate performance within the Dutch population.

Study question When does a difference in human intrauterine growth of singletons conceived after IVF and embryo culture in two different culture media appear? Summary answer Differences in fetal development after culture of embryos in one of two IVF media were apparent as early as the second trimester of pregnancy. What is known already Abnormal fetal growth patterns are a major risk factor for the development of chronic diseases in adult life. Previously, we have shown that the medium used for culturing embryos during the first few days after fertilization significantly affects the birthweight of the resulting human singletons. The exact onset of this growth difference was unknown. Study design, size and duration In this retrospective cohort study, all 294 singleton live births after fresh embryo transfer in the period July 2003 to December 2006 were included. These embryos originated from IVF treatments that were part of a previously described clinical trial. Embryos were allocated to culture in either Vitrolife or Cook commercially available sequential culture media. Participants/materials, setting, methods We analysed ultrasound examinations at 8 (n = 290), 12 (n = 83) and 20 weeks' (n = 206) gestation and used first-trimester serum markers [pregnancy-associated plasma protein-A (PAPP-A) and free β-hCG]. Differences between study groups were tested by the Student's t-test, χ(2) test or Fisher's exact test, and linear multivariable regression analysis to adjust for possible confounders (for example, parity, gestational age at the time of ultrasound and fetal gender). Main results and the role of chance A total of 294 singleton pregnancies (Vitrolife group nVL = 168, Cook group: nC = 126) from 294 couples were included. At 8 weeks' gestation, there was no difference between crown-rump length-based and ovum retrieval-based gestational age (ΔGA) (nVL = 163, nC = 122, adjusted mean difference, -0.04 days, P = 0.84). A total of 83 women underwent first-trimester screening at 12 weeks' gestation (nVL = 45, nC = 38). ΔGA, nuchal translucency (multiples of median, MoM) and PAPP-A (MoM) did not differ between the study groups. Free β-hCG (MoM) ± SEM differed significantly (1.55 ± 0.19 in Vitrolife versus 1.06 ± 0.10 in Cook; P = 0.031, Student's t-test). At 20 weeks' gestation, a more advanced GA, reflecting an increased fetal growth, was seen at ultrasound examination in the Vitrolife group (n = 115) when compared with the Cook group (n = 91). After adjustment for confounding factors, both the difference between GA based on three biparietal diameter dating formulas minus the actual (ovum retrieval based) GA (adjusted mean difference + 1.14 days (P = 0.04), +1.14 days (P = 0.04) and +1.36 days (P = 0.048)), as well as head circumference (HC) and trans-cerebellar diameter (TCD) were significantly higher in the Vitrolife group (HCvl 177.3 mm, HCc 175.9 mm, adjusted mean difference 1.8, P = 0.03; TCDvl 20.5 mm, TCDc 20.2 mm, adjusted mean difference 0.4, P = 0.008). Limitations, reasons for caution A first trimester (12 weeks) fetal screening was not yet offered routinely during the study period, therefore only 28% of women in our study participated in this elective screening programme. Although all sonographers were experienced and specially trained to perform these ultrasound examinations and were unaware of the randomization procedure, we cannot totally rule out possible intra- and inter-observer variability. Despite being indispensable in daily practice, sonographic weight formulas have a limited accuracy. Wider implications of the findings According to the fetal origins hypothesis, many adult diseases originate in utero owing to adaptations made by the fetus to the environment it encounters. This study indicates that the embryonic environment is already important for fetal development. Therefore, our study emphasizes the need to investigate fetal growth patterns after assisted reproduction technologies and long-term health outcomes of IVF children, especially in relation to the culture medium used during the first few days of preimplantation development. Trial registration number Not applicable.

Background: This study describes variables related to women's prelabour preference for epidural analgesia (PEA) in two neighbouring countries with a comparable socio-economic and cultural background. Methods: Dutch women in midwifery (n = 164) or obstetrical care (n = 162), and Belgian women (n = 188) of >= 36 weeks gestation with a singleton in cephalic presentation completed questionnaires on demographic factors, received labour analgesia information, perceived attitude of the caregiver towards epidural analgesia (EA), pain catastrophising and coping with labour pain. Multiple logistic regression analysis was performed with PEA as dependent variable. Results: PEA was 9.9% in Dutch midwifery care, 25.5% in Dutch obstetrical care and 38.3% in Belgian care (p value

Contains fulltext : 174756.pdf (Publisher’s version ) (Closed access) INTRODUCTION: Large practice variation exists in mode of delivery after cesarean section, suggesting variation in implementation of contemporary guidelines. We aim to evaluate this practice variation and to what extent this can be explained by risk factors at patient level. MATERIAL AND METHODS: This retrospective cohort study was performed among 17 Dutch hospitals in 2010. Women with one prior cesarean section without a contraindication for a trial of labor were included. We used multivariate logistic regression analysis to develop models for risk factor adjustments. One model was derived to adjust the elective repeat cesarean section rates; a second model to adjust vaginal birth after cesarean rates. Standardized rates of elective repeat cesarean section and vaginal birth after cesarean per hospital were compared. Pseudo-R2 measures were calculated to estimate the percentage of practice variation explained by the models. Secondary outcomes were differences in practice variation between hospital types and the correlation between standardized elective repeat cesarean section and vaginal birth after cesarean rates. RESULTS: In all, 1068 women had a history of cesarean section, of whom 71% were eligible for inclusion. A total of 515 women (67%) had a trial of labor, of whom 72% delivered vaginally. The elective repeat cesarean section rate at hospital level ranged from 6 to 54% (mean 29.8, standard deviation 11.8%). Vaginal birth after cesarean rates ranged from 50 to 90% (mean 71.8%, standard deviation 11.1%). More than 85% of this practice variation could not be explained by risk factors at patient level. CONCLUSION: A large practice variation exists in elective repeat cesarean section and vaginal birth after cesarean rates that can only partially be explained by risk factors at patient level. 8 p.

This study aims to develop a prediction model for spontaneous regression of cervical intraepithelial neoplasia grade 2 (CIN 2) lesions based on simple clinicopathological parameters. The study was conducted at Maastricht University Medical Center, the Netherlands. The prediction model was developed in a retrospective cohort of 129 women with a histologic diagnosis of CIN 2 who were managed by watchful waiting for 6 to 24months. Five potential predictors for spontaneous regression were selected based on the literature and expert opinion and were analyzed in a multivariable logistic regression model, followed by backward stepwise deletion based on the Wald test. The prediction model was internally validated by the bootstrapping method. Discriminative capacity and accuracy were tested by assessing the area under the receiver operating characteristic curve (AUC) and a calibration plot. Disease regression within 24months was seen in 91 (71%) of 129 patients. A prediction model was developed including the following variables: smoking, Papanicolaou test outcome before the CIN 2 diagnosis, concomitant CIN 1 diagnosis in the same biopsy, and more than 1 biopsy containing CIN 2. Not smoking, Papanicolaou class

OBJECTIVE To analyze the causes and underlying events in cases of perinatal mortality (PNM) in preterm children. SETTING Three regions within the Netherlands. STUDY DESIGN For this study, we combined data of a PNM audit over a 1-year (2003-2004) with the corresponding data of its source population (n=22,189). In the perinatal audit, all cases of perinatal death have been assessed by multi disciplinary teams of professionals in perinatal care in a consensus model for cause of death and the presence of substandard care factors (SSF). In this article, we restricted our analysis to children born between 22+0 and 37+0 weeks of pregnancy (≥154 and

Objective: To evaluate early-pregnancy changes in lipid profile in recurrent preeclampsia. Methods: In this retrospective observational study, blood samples were obtained from 41 normotensive women with a history of early-onset preeclampsia preconceptionally and at 12 and 16 weeks in the next pregnancy. We assessed triglycerides (TGs), total cholesterol (TC), and high-and low-density lipoprotein cholesterol (HDL-C and LDL-C, respectively). We analyzed differences in longitudinal patterns between normal and recurrent preeclamptic next pregnancy using mixed-design repeated measurements analysis of covariance (ANCOVA). Results: Eleven (28%) women developed recurrent preeclampsia. Eighteen (45%) women had a normal pregnancy. In normal pregnancy, LDL-C declines transiently in the first trimester (P

To investigate whether short interpregnancy interval (IPI) is associated with increased risk of low birth weight and preterm labour.The study was conducted in the labour ward of Khartoum hospital in Sudan during November 2007 through February 2008. Odds ratios (ORs) were adjusted for the confounding factors using multiple logistic regression models.Compared with IPI of 18-30 months, those women with intervals shorter than 18 months had an increased risk of low birth weight (OR = 1.9, 95% CI = 1.0-3.5, P = 0.04) and preterm labour (OR = 2.3, 95% CI = 1.1-4.7, P = 0.01).In this study, IPI shorter than 18 months are independently associated with increased risk of adverse perinatal outcomes.

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

Summary The aim of the study was to examine the association between stress and pregnancy outcome after adjustment for possible confounding and mediating variables. A prospective cohort study of 5511 pregnancies was conducted in 2001–03 in the Netherlands. A standardised questionnaire collecting demographics and mental health data was administered at 14 and 30 weeks of pregnancy. Medical data on the pregnancy and delivery were obtained from obstetricians and midwives. The results showed that a high level of perceived stress at 14 weeks of pregnancy increased the risk for delivery of an infant that was small-for-gestational-age (OR = 1.26 [95% CI 1.01, 1.56]), but the association was reduced after adjustment for the possible confounding effects of demographic variables (OR = 1.16 [95% CI 0.92, 1.47]). The results do not support a direct relationship between perceived stress and adverse pregnancy outcome. Demographic variables may explain the association between psychosocial stress and pregnancy outcome to a significant degree.

Background: Most studies on birth settings investigate the association between planned place of birth at the start of labor and birth outcomes and intervention rates. To optimize maternity care it also is important to pay attention to the entire process of pregnancy and childbirth. This study explores the association between the initial preferred place of birth and model of care, and the course of pregnancy and labor in low-risk nulliparous women in the Netherlands.Methods: As part of a Dutch prospective cohort study (2007-2011), we compared medical indications during pregnancy and birth outcomes of 576 women who initially preferred a home birth (n = 226), a midwife-led hospital birth (n = 168) or an obstetrician-led hospital birth (n = 182). Data were obtained by a questionnaire before 20 weeks of gestation and by medical records. Analyses were performed according to the initial preferred place of birth.Results: Low-risk nulliparous women who preferred a home birth with midwife-led care were less likely to be diagnosed with a medical indication during pregnancy compared to women who preferred a birth with obstetrician-led care (OR 0.41 95% CI 0.25-0.66). Preferring a birth with midwife-led care - both at home and in hospital - was associated with lower odds of induced labor (OR 0.51 95% CI 0.28-0.95 respectively OR 0.42 95% CI 0.21-0.85) and epidural analgesia (OR 0.32 95% CI 0.18-0.56 respectively OR 0.34 95% CI 0.19-0.62) compared to preferring a birth with obstetrician-led care. In addition, women who preferred a home birth were less likely to experience augmentation of labor (OR 0.54 95% CI 0.32-0.93) and narcotic analgesia (OR 0.41 95% CI 0.21-0.79) compared to women who preferred a birth with obstetrician-led care. We observed no significant association between preferred place of birth and mode of birth.Conclusions: Nulliparous women who initially preferred a home birth were less likely to be diagnosed with a medical indication during pregnancy. Women who initially preferred a birth with midwife-led care - both at home and in hospital - experienced lower rates of interventions during labor. Although some differences can be attributed to the model of care, we suggest that characteristics and attitudes of women themselves also play an important role.

A mathematical model that takes transmission by sexual contact and vertical transmission into account was employed to describe the transmission dynamics of hepatitis B virus (HBV) and vaccination against it. The model is an extension of a model by Williams et al. (Epidemiol Infect 1996; 116; 71–89) in that it takes immigration of hepatitis B carriers from countries with higher prevalence into account. Model parameters were estimated from data from The Netherlands where available. The main results were that, given the estimates for the parameters describing sexual behaviour in The Netherlands, the basic reproduction number R0 is smaller than 1 in the heterosexual population. As a consequence, the immigration of carriers into the population largely determines the prevalence of HBV carriage and therefore limits the possible success of universal vaccination. Taking into account the prevalence of hepatitis B carriage among immigrants and an age-dependent probability of becoming a carrier after infection, we estimate that a fraction of between 5 and 10% of carrier states could be prevented by universal vaccination.

Adequate calcium intake during pregnancy is important in the prevention of pre-eclampsia. A substantial proportion of pregnant women do not meet the recommended daily calcium intake, even in developed countries. Nonetheless, calcium supplementation is not routinely advised to pregnant women in most countries. We aimed to predict the impact of advising pregnant women to use calcium supplements (1,000mg/day) on the number of cases of pre-eclampsia prevented and related health care costs. By use of a decision-analytic model, we assessed the expected impact of advising calcium supplementation to either (1) all pregnant women, (2) women at high risk of developing pre-eclampsia, or (3) women with a low dietary calcium intake compared with current care. Calculations were performed for a hypothetical cohort of 100,000 pregnant women living in a high-income country, although input parameters of the model can be adjusted so as to fit other settings. The incidence of pre-eclampsia could be reduced by 25%, 8%, or 13% when advising calcium supplementation to all pregnant women, women at high risk of pre-eclampsia, or women with a low dietary calcium intake, respectively. Expected net financial benefits of the three scenarios were of Euro4,621,465, Euro2,059,165, or Euro2,822,115 per 100,000 pregnant women, respectively. Advising pregnant women to use calcium supplements can be expected to cause substantial reductions in the incidence of pre-eclampsia as well as related health care costs. It appears most efficient to advise calcium supplementation to all pregnant women, not subgroups only.

OBJECTIVE: To describe trends in the use of epidural analgesia (EA) and to evaluate the association of EA with operative deliveries. STUDY DESIGN: In this population-based, retrospective cohort study, women with an intention to deliver vaginally of a term, cephalic, singleton between 2000 and 2009 (n=1378458) were included. Main outcome measures were labor EA rates, unplanned caesarean section (CS), and instrumental vaginal delivery (IVD) including deliveries by either vacuum or forceps. Data were obtained from the Perinatal Registry of The Netherlands and logistic regression analyses were used. RESULTS: Among nulliparous, EA use almost tripled over the 10-year span (from 7.7% to 21.9%), while rates of CS and IVD did not change much (+2.8% and -3.3%, respectively). Among multiparous, EA use increased from 2.4% to 6.8%, while rates of CS and IVD changed slightly (+0.8% and -0.7%, respectively). Multivariable analysis showed a positive association of EA with CS, which weakened in ten years, from an adjusted OR of 2.35 (95% CI, 2.18 to 2.54) to 1.69 (95% CI, 1.60 to 1.79; p

The prevalence of the BLyS −817C>T polymorphic variant among women with either deep infiltrating endometriosis or adenomyosis compared with a group of gynecologic patients without symptomatic endometriosis and a group of healthy women was assessed in this study. Patients with deep infiltrating endometriosis had less often a BLyS −817C/T genotype as compared with the reference group, with an odds ratio of 0.50 (95% confidence interval 0.27–0.93 versus the C/C genotype).

Objective: To explore hospital costs by pregnant women with a history of early-onset preeclampsia or HELLP syndrome, managed according to customary, but non-standardized prenatal care, by relating maternal and child outcome to maternal health care expenditure. Study design: This was a cohort study, in women of 18 years or older who suffered from early-onset preeclampsia or HELLP syndrome in their previous pregnancy (n = 104). We retrieved data retrospectively from hospital information systems and medical records of patients who had received customary, non-standardized prenatal care between 1996 and 2012. Our analyses focused on the costs generated between the first antenatal visit at the outpatient clinic and postpartum hospital discharge. Outcome measures were hospital resource use, costs, maternal and child outcome (recurrence of preeclampsia or HELLP syndrome, incidence of eclampsia, gestational age at delivery, intrauterine fetal demise, small-for-gestational-age birth and low 5 min Apgar score). We used linear regression analyses to evaluate whether maternal and child outcome and baseline characteristics correlated with hospital costs. Results: Maternal hospital costs per patient averaged (sic) 8047. The main cost drivers were maternal admissions and outpatient visits, together accounting for 80% of total costs. Primary cost drivers were preterm birth and recurrent preeclampsia or HELLP syndrome. Conclusion: Hospital costs in the next pregnancy of formerly preeclamptic women varied widely with over 70% being medically unexplainable. The results of this study support the view that care standardization in these women can be expected to improve costs and efficacy of care without compromising outcome. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

Background The objective of this study was to evaluate the mediating role of maternal early pregnancy plasma levels of long chain polyunsaturated fatty acids (LCPUFAs) in the association of interpregnancy interval (IPI) with birth weight and smallness for gestational age (SGA) at birth. Methods We analysed a subsample of the Amsterdam Born Children and their Development (ABCD) cohort, comprising 1,659 parous pregnant women recruited between January 2003 and March 2004. We used linear and logistic regression to evaluate the associations between fatty acid status, interpregnancy interval and pregnancy outcome. Results Low plasma phospholipids concentrations of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and dihomo-gamma-linolenic acid (DGLA), and high concentrations of arachidonic acid (AA) during early pregnancy were associated with reduced birth weight and/or an increased risk of SGA. Short IPIs (< 6 months, with 18–23 months as a reference) were associated with a mean decrease of 207.6 g (SE: ± 73.1) in birth weight (p = 0.005) and a twofold increased risk of SGA (OR: 2.05; CI: 0.93–4.51; p = 0.074). Adjustment for maternal fatty acid concentrations did not affect these results to any meaningful extent. Conclusions Despite the observed association of maternal early pregnancy LCPUFA status with birth weight and SGA, our study provides no evidence for the existence of an important role of maternal EPA, DHA, DGLA or AA in the association of short interpregnancy intervals with birth weight and SGA.

background: We have previously shown that the medium used for culturing IVF embryos affects the birthweight of the resulting newborns. This observation with potentially far-reaching clinical consequences during later life, was made in singletons conceived during the first IVF treatment cycle after the transfer of fresh embryos. In the present study, we hypothesize that in vitro culture of embryos during the first few days of preimplantation development affects perinatal outcome, not only in singletons conceived in all rank order cycles but also in twins and in children born after transfer of frozen embryos. Furthermore, we investigated the effect of culture medium on gestational age (GA) at birth. methods: Oocytes and embryos from consecutive treatment cycles were alternately assigned to culture in either medium from Vitrolife or from Cook. Data on a cohort of 294 live born singletons conceived after fresh transfer during any of a patient’s IVF treatment cycles, as well as data of 67 singletons conceived after frozen embryo transfer (FET) and of 88 children of 44 twin pregnancies after fresh transfer were analysed by means of multiple linear regression. results: In vitro culture in medium from Cook resulted in singletons after fresh transfer with a lower mean birthweight (adjusted mean difference, 112 g, P ¼ 0.03), and in more singletons with low birthweight (LBW) ,2500 g (P ¼ 0.006) and LBW for GA ≥37 weeks (P ¼ 0.015), when compared with singletons born after culture in medium from Vitrolife AB. GA at birth was not related to the medium used (adjusted difference, 0.05 weeks, P ¼ 0.83). Among twins in the Cook group, higher inter-twin mean birthweight disparity and birthweight discordance were found. Z-scores after FET were 20.04 (+0.14) in the Cook group compared with 0.18 (+0.21) in the Vitrolife group (P . 0.05). conclusions: Our findings support our hypothesis that culture medium influences perinatal outcome of IVF singletons and twins. A similar trend is seen in case of singletons born after FET. GA was not affected by culture medium. These results indicate that in vitro culture might be an important factor explaining the poorer perinatal outcome after assisted reproduction technology (ART). Further research is needed to confirm this culture medium-induced effect in humans and to provide more insight into whether it is caused by epigenetic disturbance of imprinted genes in fetal or placental tissues. Moreover, embryo culture media and their effects need to be investigated thoroughly to select the best embryo culture medium in order to minimize or prevent short-term risks and maybe even long-term disease susceptibility.

ObjectiveThis study aimed to determine whether immunohistochemical markers in complex atypical endometrial hyperplasia could predict the presence of a concurrent endometrial carcinoma.MethodsEndometrial biopsies of 39 patients with complex atypical hyperplasia were selected retrospectively between 1999 and 2006. Only patients who underwent a hysterectomy were included. A coexisting endometrial carcinoma was present in 25 patients (64%). Immunohistochemical analysis was performed on formalin-fixed paraffin-embedded sections of the endometrial biopsies, using antibodies for MIB-1, β-catenin, E-cadherin, p53, PTEN, CD44, HER2-neu, survivin, COX-2, tenascin, and bcl-2. To evaluate the potential utility of these markers, a prediction model was constructed.ResultsIn the univariate analysis, expressions of both PTEN and HER2-neu were significantly different between the groups with and without a coexisting endometrial carcinoma (P< 0.05). Loss of PTEN staining was found in 13 (54%) and 1 (7%) of the patients with and without a coexistent carcinoma, respectively (odds ratio, 16.55; 95% confidence interval [CI], 1.87–146.65). HER2-neu expression was found in only 2 (8.6%) and 6 (43%) patients with and without a coexistent carcinoma, respectively, and was excluded from further analysis because of its low expression. A prediction model containing PTEN expression only showed an area under the curve of 73.4% (95% CI, 57.3%–89.6%). After adding MIB-1 and p53, discriminative power improved to 87.2% (95% CI, 75.1%–99.3%).ConclusionsThis study showed that PTEN expression in complex endometrial hyperplasia is a promising factor for the prediction of the presence of a coexisting endometrial carcinoma, and prediction may even better when MIB-1 and p53 expressions are considered simultaneously.

OBJECTIVE: The purpose of this study was to evaluate whether the association between short interpregnancy intervals and perinatal outcome varies with maternal age. STUDY DESIGN: We performed a retrospective cohort study among 263,142 Dutch women with second deliveries that occurred between 2000 and 2007. Outcome variables were preterm delivery (< 37 weeks of gestation), low birthweight in term deliveries (< 2500 g) and small-for-gestational age (< 10th percentile for gestational age on the basis of sex-and parity-specific Dutch standards). RESULTS: Short interpregnancy intervals (< 6 months) was associated positively with preterm delivery and low birthweight, but not with being small for gestational age. The association of short interpregnancy interval with the risk of preterm delivery was weaker among older than younger women. There was no clear interaction between short interpregnancy interval and maternal age in relation to low birthweight or small for gestational age. CONCLUSION: The results of this study indicate that the association of short interpregnancy interval with preterm delivery attenuates with increasing maternal age.

Background: Loss of a child has been associated with elevated mortality rates in parents. Studies that focus on the influence of the child's sex on parental mortality are sparse.Objective: The main objective of the present study was to reevaluate the combined impact of the parents' and child's sex within a larger sample and focus on adverse health effects as an objective measure of possible long-term effects of maladaptive grief reactions.Methods: For the time period between 1980 and 1996, all children in Denmark who died before 18 years of age were identified. Parents who had lost a child were identified as the bereaved (exposed) group. Mortality rates of parents within the same-sex parent-child dyad were compared with mortality rates of parents within the opposite-sex parent-child dyad. Separate analyses were performed for bereaved fathers and for bereaved mothers, and additional analyses were conducted to examine the sole effect of the child's sex, irrespective of parental gender. A Cox proportional hazards regression model was used to estimate the hazard ratios (HRs) with 95% CIs.Results: The study population consisted of 21,062 parents (mean age at entry, 32 years; 11,221 mothers, 9841 fathers). Bereaved parents who had lost a child of the same sex had similar overall mortality as bereaved parents who had lost a child of the opposite sex (HR = 1.02; 95% CI, 0.85-1.22). Similar findings were observed for mortality due to natural death (HR = 0.96; 95% CI, 0.78-1.18) or mortality due to unnatural death (HR = 1.22; 95% CI, 0.84-1.77). Bereaved fathers who had lost a son had similar mortality as those bereaved by the death of a daughter (HR = 1.10; 95% CI, 0.86-1.40). Bereaved mothers who had lost a daughter had similar mortality as those bereaved by the death of a son (HR = 0.93; 95% CI, 0.70-1.22). Bereaved parents who had lost a son had mortality rates similar to those who had lost a daughter (HR = 1.09; 95% CI, 0.91-1.31). The interactions between grouping variable and sex of parents were not significant, indicating that the differential effect of losing a child based on sex of the child was not greater for fathers than for mothers.Conclusions: The results of this study revealed no significant effect of sex of the deceased child on mortality in these bereaved parents. The results might differ if this study was replicated in a population with a different grief culture and, more importantly, different gender schemas. (Gend Med. 2010;7:39-46)

OBJECTIVE: To analyze avoidable perinatal mortality in small-for-gestational-age (SGA) children. METHODS: All SGA-children (< or =10(th) percentile) among 22,189 newborns delivered after 24 weeks' gestation (175 days), from three regions of the Netherlands during 2003-2004 were evaluated. Cases of perinatal mortality were identified and assessed in a consensus model by perinatal audit groups for cause of death and the presence of substandard care factors (SSF). We analyzed all singleton SGA-cases with and without SSF for avoidable perinatal mortality. RESULTS: Out of 20,927 singletons, 2396 newborns were SGA. Of those, 59 died perinatally (2.46%), and 55 of which were assessed by perinatal audit groups. SSF by caregivers were found in 22 cases (40%). In 16 of these cases (29%) the relation to the perinatal death was considered possible or (very) probable. Of the cases without SSF by caregivers, 15 cases (25%) could possibly have been avoided: in 13 cases an avoidable condition and in 2 cases avoidable death were identified. Failure in the correct and timely diagnosis of fetal growth restriction appears to be an important issue in all cases of perinatal mortality in SGA-children. Before referral growth restriction was suspected only in 22% of all SGA cases during the third trimester of pregnancy. CONCLUSIONS: More adequate action by caregivers could decrease perinatal mortality in nearly 1/3 among SGA-children. Adjustments in pregnancy monitoring, especially in low-risk pregnancies, such as routine ultrasound biometry examination, may improve the accuracy in detecting growth deviations and decreasing the number of possibly avoidable cases of perinatal mortality in this category.

Contains fulltext : 81541.pdf (Publisher’s version ) (Closed access) OBJECTIVE: We aimed to develop a simple clinically useful prediction rule for early-onset recurrent preeclampsia and/or HELLP syndrome. METHODS: Women with previous early-onset preeclampsia and/or HELLP, enrolled between 1996 and 2007, and a subsequent ongoing pregnancy were included. Prepregnant cardiovascular, metabolic, renal, and clotting parameters were evaluated as potential predictors for recurrent disease by logistic regression analysis. RESULTS: Early-onset preeclampsia and/or HELLP recurred in 16 (9%) of 186 next pregnancies. The prediction model included high-density lipoprotein (mmol/L) and 24-hour urinary total protein excretion (mg/mmol creatinine). The receiver operating characteristic area was 0.77 (95% confidence interval: 0.68-0.87). Predictive sensitivity and specificity were 94% (69%-99%) and 53% (45%-60%), respectively. Nearly 50% of the women could be classified as having

Serotonin transporter gene (SLC6A4) variations have been proposed as an explanation for interindividual differences in selective serotonin reuptake inhibitors (SSRIs) effects. Quantitative assessment of genetic influences is necessary to evaluate whether genetic testing before antidepressant prescription would lead to earlier treatment effects. This study evaluates the influence of two polymorphisms (5-HTTLPR and STin2) on SSRI treatment outcome in depression.We included 50 SSRI nonresponders (cases) and 164 referents meeting Diagnostic and Statistical Manual Of Mental Disorder-IV criteria for major depression and using an SSRI for at least 6 weeks. Blood samples or buccal swabs were gathered to determine 5-HTTLPR (N=48 for cases and 161 for referents) and STin2 (N=50 for cases and 162 for referents) genotypes. The association between genotype and SSRI response was assessed by use of logistic regression.Patients with the 5-HTTLPR s-allele had a nonsignificantly increased risk of SSRI nonresponse; odds ratio (OR) 1.60, 95% confidence interval (CI) 0.66-3.89. 5-HTTLPR effects were strongest in female patients (OR 3.54, 95% CI 1.05-11.92), and for male patients 5-HTTLPR seemed to have no effect (OR 0.29, 95% CI 0.04-2.34). An age-dependent effect of 5-HTTLPR was observed; patients under 44 years of age had an increased nonresponse risk (OR 9.34, 95% CI 1.41-61.98). STin2 genotype had no clear influence on treatment outcome.Our findings indicate that women with the 5-HTTLPR s-allele have a less favorable response to SSRI treatment. To our knowledge, this is the first time that a gender-dependent influence of 5-HTTLPR is reported. More research is needed, particularly in subgroups of patients, before implementation of genetic testing can be recommended.

This study was performed to evaluate mothers' views of their childbirth experience two years after term breech delivery.Two years after delivery mothers were asked to fill out a questionnaire concerning their breech birth experience and their view about the care provided to them while giving birth. Outcomes of the planned cesarean section (CS) group were compared with outcomes of the planned vaginal delivery (VD) group, whether or not a vaginal birth was realized or an emergency cesarean section was performed. Any differences were further analyzed by use of logistic regression, controlling for potential confounders.Significantly more women in the planned CS group were reassured about their baby's health (67.4% vs. 37.9%, p=0.0006) at the time of delivery, whereas more women in the planned VD group recalled having been worried about their baby's health at the time of delivery (45.0% vs. 25.6%, p=0.02). Also, more women in the planned VD group experienced more pain during labor and delivery than expected (46.9% vs. 18.5%, p=0.008). In the planned VD group fewer women indicated they had an active say in decision-making (59.1% vs. 85.3%, p=0.001).Evaluation of the mothers' views of their childbirth experience two years after term breech delivery showed that more women in the planned VD group recalled having been worried about their child's health at the time of delivery, experienced more pain than expected, and reported less involvement in decision-making.

During treatment with selective serotonin reuptake inhibitors, some patients experience adverse events whereas others do not. Assessment of predictors for selective serotonin reuptake inhibitors-induced adverse events would be useful for the identification of patients likely to develop these events. This study evaluates the association between adverse events during selective serotonin reuptake inhibitor treatment and two polymorphisms in the serotonin transporter (5-HTTLPR and STin2) gene. We included 214 patients meeting Diagnostic and statistical manual of mental disorder-IV criteria for major depression and using an selective serotonin reuptake inhibitor for at least 6 weeks. Blood samples or buccal swabs were taken to determine 5-HTTLPR and STin2 genotype. Information on adverse events was gathered through interviews and general practitioners' files. The association between serotonin transporter genotype and adverse events was assessed by use of logistic regression. Patients with the 5-HTTLPR s/s or s/l genotype appeared to have an increased risk of adverse events, especially general adverse events (dermatologic reactions, weight change and fatigue); odds ratio 1.77 (95% confidence interval 0.80-3.92) for the s/s genotype, odds ratio 2.37 (95% confidence interval 1.13-4.96) for the s/l genotype. For STin2, results were inconsistent and observed associations were weak and statistically nonsignificant. Our findings indicate that patients with the 5-HTTLPR s/s or s/l genotype have an increased risk of developing adverse events during selective serotonin reuptake inhibitor treatment.

In The Netherlands, in May 1999 an enhanced surveillance of hepatitis B was begun to collect detailed information of patients with acute hepatitis B virus (HBV) infection. The objective was to gain insight in transmission routes and source of infection of new HBV cases. Through public health services, patients were interviewed on risk factors. It appeared that the majority (59%) acquired the infection through sexual contact; 52% of these by homosexual and 48% by heterosexual contact. In 60% of the heterosexual cases, the source of infection was a partner originating from a hepatitis B-endemic region. Sexual transmission is the most common route of transmission of acute hepatitis B in The Netherlands and introduction of infections from abroad plays a key role in the current epidemiology of HBV. As well as prevention programmes targeted at sexual high-risk groups, prevention efforts should focus more on the heterosexual transmission from HBV carriers.