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Marleen MHJ van Gelder,1 Pim Beekers,1,2 Yrea RJ van Rijt-Weetink,3 Joris van Drongelen,4 Nel Roeleveld,1 Luc JM Smits5 1Department for Health Evidence, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands; 2National Health Care Institute, Diemen, the Netherlands; 3Netherlands Pharmacovigilance Centre Lareb,‘s-Hertogenbosch, the Netherlands; 4Department of Obstetrics & Gynecology, Radboud University Medical Center, Nijmegen, the Netherlands; 5Department of Epidemiology, CAPHRI Care and Public Health Research Institute, Maastricht University, Maastricht, the NetherlandsCorrespondence: Marleen MHJ van Gelder, Department for Health Evidence (HP 133), Radboud University Medical Center, P.O. Box 9101, Nijmegen, 6500 HB, the Netherlands, Tel +31 24 3615305, Fax +31 24 3613505, Email Marleen.vanGelder@radboudumc.nlPurpose: Preeclampsia is a leading cause of maternal morbidity and mortality. Calcium-based antacids and proton pump inhibitors (PPIs) are commonly used during pregnancy to treat symptoms of gastroesophageal reflux disease. Both have been hypothesized to reduce the risk of preeclampsia. We determined associations of calcium-based antacid and PPI use during pregnancy with late-onset preeclampsia (≥ 34 weeks of gestation), taking into account dosage and timing of use.Patients and Methods: We included 9058 pregnant women participating in the PRIDE Study (2012– 2019) or The Dutch Pregnancy Drug Register (2014– 2019), two prospective cohorts in The Netherlands. Data were collected through web-based questionnaires and obstetric records. We estimated risk ratios (RRs) for late-onset preeclampsia for any use and trajectories of calcium-based antacid and PPI use before gestational day 238, and hazard ratios (HRs) for time-varying exposures after gestational day 237.Results: Late-onset preeclampsia was diagnosed in 2.6% of pregnancies. Any use of calcium-based antacids (RR 1.2 [95% CI 0.9– 1.6]) or PPIs (RR 1.4 [95% CI 0.8– 2.4]) before gestational day 238 was not associated with late-onset preeclampsia. Use of low-dose calcium-based antacids in gestational weeks 0– 16 (< 1 g/day; RR 1.8 [95% CI 1.1– 2.9]) and any use of PPIs in gestational weeks 17– 33 (RR 1.6 [95% CI 1.0– 2.8]) seemed to increase risks of late-onset preeclampsia. We did not observe associations between late-onset preeclampsia and use of calcium-based antacids (HR 1.0 [95% CI 0.6– 1.5]) and PPIs (HR 1.4 [95% CI 0.7– 2.9]) after gestational day 237.Conclusion: In this prospective cohort study, use of calcium-based antacids and PPIs during pregnancy was not found to reduce the risk of late-onset preeclampsia.Keywords: extended Cox models, gestational hypertension, gastroesophageal reflux disease, longitudinal clustering methods, PRIDE study, The Dutch Pregnancy Drug Register

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. [ABSTRACT FROM AUTHOR]

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 90th 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. [ABSTRACT FROM AUTHOR]

Introduction: Nasopharyngeal cancer (NPC) is a relatively rare yet aggressive malignancy, primarily affecting regions of East and Southeast Asia. This study aims at providing an up-to-date quantification of the association between cigarette smoking and NPC risk, overall and by histological subsites., Methods: We conducted a systematic review and meta-analysis of case-control and cohort studies on the association between cigarette smoking and NPC risk published up to May 2023. The methodology used is original and efficient and includes both a comprehensive umbrella review and a traditional review. We estimated pooled relative risks (RR) of NPC according to smoking status, intensity, duration, and time since quitting., Results: Among 46 eligible articles, 40 original studies were included in this meta-analysis. Compared with never smokers, the pooled RR of NPC was 1.61 for current, 1.28 for former, and 1.62 for ever smokers. The RR for ever compared with never smokers was 2.37 for squamous cell NPC and 1.06 for undifferentiated NPC. NPC risk significantly increased linearly with smoking intensity and duration, and decreased linearly with increasing time since quitting., Conclusion: This meta-analysis confirms the link between tobacco smoking and NPC, highlighting the significant risk posed even by moderate cigarette consumption. Additionally, our findings underscore the differential risk between squamous cell and undifferentiated subtypes of NPC, shedding light on the distinct implications for NPC prevention strategies.

Most published prediction models for Coronavirus Disease 2019 (COVID-19) were poorly reported, at high risk of bias, and heterogeneous in model performance. To tackle methodological challenges faced in previous prediction studies, we investigated whether model updating and extending improves mortality prediction, using the Intensive Care Unit (ICU) as a proxy. All COVID-19 patients admitted to seven ICUs in the Euregio-Meuse Rhine during the first pandemic wave were included. The 4C Mortality and SEIMC scores were selected as promising prognostic models from an external validation study. Five predictors could be estimated based on cohort size. TRIPOD guidelines were followed and logistic regression analyses with the linear predictor, APACHE II score, and country were performed. Bootstrapping with backward selection was applied to select variables for the final model. Additionally, shrinkage was performed. Model discrimination was displayed as optimism-corrected areas under the ROC curve and calibration by calibration slopes and plots. The mortality rate of the 551 included patients was 36%. Discrimination of the 4C Mortality and SEIMC scores increased from 0.70 to 0.74 and 0.70 to 0.73 and calibration plots improved compared to the original models after updating and extending. Mortality prediction can be improved after updating and extending of promising models., (© 2024. The Author(s).)

Introduction: Tobacco-related diseases have a substantial economic impact in terms of medical expenses, loss of productivity, and premature death. Tobacco use is estimated to be responsible for more than 90000 deaths each year in Italy. We aimed to evaluate the annual direct economic impact on the National Health System of hospitalizations attributable to tobacco smoking in Italy., Methods: We analyzed data from all the hospitalizations of patients aged ≥30 years that occurred in Italy for 12 selected tobacco-related diseases, during 2018. These diseases included oropharyngeal cancer, esophageal cancer, gastric cancer, lung cancer, pancreatic cancer, bladder cancer, laryngeal cancer, ischemic heart disease, stroke, diseases of arteries, arterioles, and capillaries, pneumonia and influenza, and chronic obstructive pulmonary disease. We obtained information on 984322 hospital discharge records, including each hospitalization's direct costs. Using relative risk estimates from the scientific literature, we computed the population attributable fraction for various tobacco-related diseases to estimate the economic impact attributable to tobacco smoking., Results: One-third of all hospitalizations occurred in 2018 in Italy among people aged ≥30 years for 12 tobacco-related diseases were found to be attributable to smoking, accounting for a total cost of €1.64 billion. Among the diseases considered, those with the highest expenditures attributable to tobacco smoking were ischemic heart disease, cerebrovascular disease, and lung cancer, accounting for €556 million, €290 million, and €229 million, respectively., Conclusions: Tobacco has a substantial economic impact in Italy, accounting for around 6% of the total cost of hospitalizations in 2018. This figure is expected to be largely underestimated due to several conservative assumptions adopted in the statistical analyses. It is imperative to prioritize comprehensive tobacco control measures to counteract the huge healthcare costs due to tobacco smoking., Competing Interests: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none was reported., (© 2024 Possenti I. et al.)

Background: Continuous support during labor has many benefits including lower use of obstetrical interventions. However, implementation remains limited. Insights into birth outcomes and peripartum costs are essential to assess whether continuous care by a maternity care assistant is a potentially (cost) effective program to provide for all women., Objective: Continuous care during labor, provided by maternity care assistants, will reduce the use of epidural analgesia and peripartum costs owing to a reduction in interventions., Study Design: This was a randomized controlled trial comparing continuous support during labor (intervention group) with care-as-usual (control group) with prespecified intention-to-treat and per-protocol analyses. The primary outcome was epidural analgesia use. The secondary outcomes were use of other analgesia, referrals from midwife- to obstetrician-led care, modes of birth, hospital stay, sense of control (evaluated with the Labor Agentry Scale), maternal and neonatal adverse outcomes and peripartum costs. Data were collected using questionnaires. Anticipating incomplete adherence to providing continuous care, both intention-to-treat and per-protocol analyses were planned. Peripartum costs were estimated using a healthcare perspective. Mean costs per woman and cost differences between the intervention and control group were calculated., Results: The population consisted of 1076 women with 54 exclusions and 30 discontinuations, leaving 992 women to be analyzed (515 continuous care and 477 care-as-usual). Intention-to-treat analyses showed statistically nonsignificant differences between the intervention and control group for epidural use (relative risk, 0.88; 95% confidence interval, 0.74-1.04; P=.14) and peripartum costs (mean difference, € 185.83; 95% confidence interval, -€ 204.22 to € 624.54). Per-protocol analyses showed statistically significant decreases in epidural analgesia (relative risk, 0.64; 95% confidence interval, 0.48-0.84; P=.001), other analgesia (relative risk, 0.59; 95% confidence interval, 0.37-0.94; P=.02), cesarean deliveries (relative risk, 0.53; 95% confidence interval, 0.29-0.95; P=.03) and increase in spontaneous vaginal births (relative risk, 1.09; 95% confidence interval, 1.01-1.18; P=.001) in the intervention group, but difference in total peripartum costs remained statistically nonsignificant (mean difference, € 246.55; 95% confidence interval, -€ 539.14 to € 13.50)., Conclusion: If the provision of continuous care given by maternity care assistants during labor can be secured, continuous care leads to more vaginal births and less epidural use, pain medication, and cesarean deliveries while not leading to a difference in peripartum costs compared with care-as-usual., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Current obstetric guidelines for postpartum hemorrhage (PPH) vary in fluid resuscitation management. This study aimed to evaluate the effect of fluid management on coagulation parameters in early PPH., Methods: We performed a multicenter, randomized trial. Women who had 500 mL of blood loss in the third stage of labor were randomized to receive a restrictive fluid administration strategy or a liberal fluid administration strategy. A rotational thromboelastometry panel was performed in 72 patients. We evaluated within-group and between-group differences in the EXTEM clotting time (CT), EXTEM amplitude at 10 minutes (A10), INTEM CT, and FIBTEM A10. We also evaluated the mean fibrinogen concentration, activated partial thromboplastin time, and partial thromboplastin time in the total study population (n = 249)., Results: There were no significant differences in hemostatic parameters between the groups after correction for baseline values., Conclusions: In women with PPH <1500 mL, there is no clinically relevant effect of a restrictive or liberal fluid administration strategy on thromboelastometric hemostatic and regular coagulation parameters.

Background: Low-dose aspirin treatment reduces the risk of preeclampsia among high-risk pregnant women. Internationally, several first-trimester risk-calculation methods are applied., Objective: This study aimed to assess the costs and benefits of different first-trimester preeclampsia risk estimation algorithms: EXPECT (an algorithmic prediction model based on maternal characteristics), National Institute for Health and Care Excellence (a checklist of risk factors), and the Fetal Medicine Foundation (a prediction model using additional uterine artery Doppler measurement and laboratory testing) models, coupled with low-dose aspirin treatment, in comparison with no risk assessment., Study Design: We constructed a decision analytical model estimating the number of cases of preeclampsia with each strategy and the costs of risk assessment for preeclampsia and early aspirin treatment, expressed in euros (€) in a hypothetical population of 100,000 women. We performed 1-way sensitivity analyses to assess the impact of adherence rates on model outcomes., Results: Application of the EXPECT, National Institute for Health and Care Excellence, and Fetal Medicine Foundation models results in respectively 1.98%, 2.55%, and 1.90% of the women developing preeclampsia, as opposed to 3.00% of women in the case of no risk assessment. Overall, the net financial benefits of the EXPECT, National Institute for Health and Care Excellence, and Fetal Medicine Foundation models relative to no risk assessment are €144, €43, and €38 per patient, respectively. The respective percentages of women receiving aspirin treatment are 18.6%, 10.2%, and 6.0% for the 3 risk assessment methods., Conclusion: The EXPECT and Fetal Medicine Foundation model are comparable with regard to numbers of prevented preeclampsia cases, and both are superior to the National Institute for Health and Care Excellence model and to no risk assessment. EXPECT is less resource-demanding and results in the highest cost savings, but also requires the highest number of women to be treated with aspirin. When deciding which strategy is preferable, cost savings and easier use have to be weighed against the degree of overtreatment, although low-dose aspirin has no clear disadvantages during pregnancy., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: Many prediction models for coronavirus disease 2019 (COVID-19) have been developed. External validation is mandatory before implementation in the intensive care unit (ICU). We selected and validated prognostic models in the Euregio Intensive Care COVID (EICC) cohort., Study Design and Setting: In this multinational cohort study, routine data from COVID-19 patients admitted to ICUs within the Euregio Meuse-Rhine were collected from March to August 2020. COVID-19 models were selected based on model type, predictors, outcomes, and reporting. Furthermore, general ICU scores were assessed. Discrimination was assessed by area under the receiver operating characteristic curves (AUCs) and calibration by calibration-in-the-large and calibration plots. A random-effects meta-analysis was used to pool results., Results: 551 patients were admitted. Mean age was 65.4 ± 11.2 years, 29% were female, and ICU mortality was 36%. Nine out of 238 published models were externally validated. Pooled AUCs were between 0.53 and 0.70 and calibration-in-the-large between -9% and 6%. Calibration plots showed generally poor but, for the 4C Mortality score and Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) score, moderate calibration., Conclusion: Of the nine prognostic models that were externally validated in the EICC cohort, only two showed reasonable discrimination and moderate calibration. For future pandemics, better models based on routine data are needed to support admission decision-making., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate the effect of incorporating calcium advice into early pregnancy counseling on calcium intake during pregnancy in the Netherlands., Methods: A multicenter prospective before-after cohort study was conducted introducing risk-based care including calculating individual pre-eclampsia risk. Part of the intervention was to incorporate calcium advice into routine counseling. We calculated individual daily calcium intake and adequacy of calcium intake (≥1,000 mg/day) at 16, 24 and 34 weeks of pregnancy. We performed a multiple logistic regression adjusting for covariates to identify any differences in the risk of inadequate calcium intake between RC and CAC., Results: In regular care (RC, 2013-2015, n=2,477) 60% had inadequate calcium intake, compared to 49% during calcium advice care (CAC, 2017-2018, n=774) (aOR 0.75, 95% CI 0.64-0.88). Specific calcium supplements were used by 2% and 29% in RC and CAC, respectively (OR 25.1, 95% CI 17.8-36.0). Determinants of an inadequate calcium intake were lower age (aOR per additional year 0.96, 95% CI: 0.94-0.98), nulliparity (aOR 1.22, 95% CI: 1.03-1.45) and non-Caucasian origin (aOR 1.83, 95% CI 1.09-3.09). In CAC, risk of inadequate intake decreased with increasing predicted pre-eclampsia risk, which was a trend reversal compared to RC., Conclusions: Incorporating calcium advice into early pregnancy counseling was shown to lead to a decrease in the risk of inadequate calcium intake during pregnancy, but still inadequate intake in half of the women suggesting the need for further study on improving implementation. Awareness of individual increased PE risk had positive effect on calcium intake., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Satisfaction of pregnancy and childbirth is an important quality measure of maternity care. Satisfaction questionnaires generally result in high scores. However, it has been argued that dissatisfaction relies on a different construct. In response to a worldwide call for obstetric care that is more woman-centered, we identified and described the contributors to suboptimal satisfaction with pregnancy and childbirth., Methods: A prospective subcohort of 739 women from a larger cohort (Expect Study I, n  = 2614) received a pregnancy and childbirth satisfaction questionnaire. Scores were transformed to a binary outcome whereby a score <100 points corresponded with less satisfied women. We performed a multiple logistic regression analysis to define independent perinatal factors related to suboptimal satisfaction., Results: Decreased perceived personal well-being, antenatal anxiety, and obstetrician-led care during labor were all independently associated with suboptimal pregnancy and childbirth satisfaction. No difference in satisfaction was found between antenatal care led by a midwife or an obstetrician, but midwife-led antenatal care reduced the odds of suboptimal satisfaction compared to women who were transferred to an obstetrician in the antenatal period. Antenatal anxiety was experienced by 25% of all women and is associated with decreased satisfaction scores., Discussion: Screening and treatment of women suffering from anxiety might improve pregnancy and childbirth satisfaction, but further research is necessary. Women's birthing experience may improve by reducing unnecessary secondary obstetric care.

Rupture of a vulnerable carotid plaque is an important cause of ischemic stroke. Prediction models can support medical decision-making by estimating individual probabilities of future events, while magnetic resonance imaging (MRI) can provide detailed information on plaque vulnerability. In this review, prediction models for medium to long-term (>90 days) prediction of recurrent ischemic stroke among patients on best medical treatment for carotid stenosis are evaluated, and the emerging role of MRI of the carotid plaque for personalized ischemic stroke prediction is discussed. A systematic search identified two models; the European Carotid Surgery Trial (ECST) medical model, and the Symptomatic Carotid Atheroma Inflammation Lumen stenosis (SCAIL) score. We critically appraised these models by means of criteria derived from the CHARMS (CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modeling Studies) and PROBAST (Prediction model Risk Of Bias ASsessment Tool). We found both models to be at high risk of bias. The ECST model, the most widely used model, was derived from data of large but relatively old trials (1980s and 1990s), not reflecting lower risks of ischemic stroke resulting from improvements in drug treatment (e.g., statins and anti-platelet therapy). The SCAIL model, based on the degree of stenosis and positron emission tomography/computed tomography (PET/CT)-based plaque inflammation, was derived and externally validated in limited samples. Clinical implementation of the SCAIL model can be challenging due to high costs and low accessibility of PET/CT. MRI is a more readily available, lower-cost modality that has been extensively validated to visualize all the hallmarks of plaque vulnerability. The MRI methods to identify the different plaque features are described. Intraplaque hemorrhage (IPH), a lipid-rich necrotic core (LRNC), and a thin or ruptured fibrous cap (TRFC) on MRI have shown to strongly predict stroke in meta-analyses. To improve personalized risk prediction, carotid plaque features should be included in prediction models. Prediction of stroke in patients with carotid stenosis needs modernization, and carotid MRI has potential in providing strong predictors for that goal., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nies, Smits, Kassem, Nederkoorn, Oostenbrugge and Kooi.)

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., (© 2020 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

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., Competing Interests: The authors have declared that no competing interests exist.

Background: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk during pregnancy is required to plan management. Although there are many published prediction models for pre-eclampsia, few have been validated in external data. Our objective was to externally validate published prediction models for pre-eclampsia using individual participant data (IPD) from UK studies, to evaluate whether any of the models can accurately predict the condition when used within the UK healthcare setting., Methods: IPD from 11 UK cohort studies (217,415 pregnant women) within the International Prediction of Pregnancy Complications (IPPIC) pre-eclampsia network contributed to external validation of published prediction models, identified by systematic review. Cohorts that measured all predictor variables in at least one of the identified models and reported pre-eclampsia as an outcome were included for validation. We reported the model predictive performance as discrimination (C-statistic), calibration (calibration plots, calibration slope, calibration-in-the-large), and net benefit. Performance measures were estimated separately in each available study and then, where possible, combined across studies in a random-effects meta-analysis., Results: Of 131 published models, 67 provided the full model equation and 24 could be validated in 11 UK cohorts. Most of the models showed modest discrimination with summary C-statistics between 0.6 and 0.7. The calibration of the predicted compared to observed risk was generally poor for most models with observed calibration slopes less than 1, indicating that predictions were generally too extreme, although confidence intervals were wide. There was large between-study heterogeneity in each model's calibration-in-the-large, suggesting poor calibration of the predicted overall risk across populations. In a subset of models, the net benefit of using the models to inform clinical decisions appeared small and limited to probability thresholds between 5 and 7%., Conclusions: The evaluated models had modest predictive performance, with key limitations such as poor calibration (likely due to overfitting in the original development datasets), substantial heterogeneity, and small net benefit across settings. The evidence to support the use of these prediction models for pre-eclampsia in clinical decision-making is limited. Any models that we could not validate should be examined in terms of their predictive performance, net benefit, and heterogeneity across multiple UK settings before consideration for use in practice., Trial Registration: PROSPERO ID: CRD42015029349 .

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., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., (© 2020 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

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., (© 2020 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

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.

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.

Introduction: This study assessed the external validity of all published first trimester prediction models for the risk of preeclampsia (PE) based on routinely collected maternal predictors. Moreover, the potential utility of the best-performing models in clinical practice was evaluated., Material and Methods: Ten prediction models were systematically selected from the literature. We performed a multicenter prospective cohort study in the Netherlands between July 1, 2013, and December 31, 2015. Eligible pregnant women completed a web-based questionnaire before 16 weeks' gestation. The outcome PE was established using postpartum questionnaires and medical records. Predictive performance of each model was assessed by means of discrimination (c-statistic) and a calibration plot. Clinical usefulness was evaluated by means of decision curve analysis and by calculating the potential impact at different risk thresholds., Results: The validation cohort contained 2,614 women of whom 76 developed PE (2.9%). Five models showed moderate discriminative performance with c-statistics ranging from 0.73 to 0.77. Adequate calibration was obtained after refitting. The best models were clinically useful over a small range of predicted probabilities., Discussion: Five of the ten included first trimester prediction models for PE showed moderate predictive performance. The best models may provide more benefit compared to risk selection as used in current guidelines., (© 2018 The Author(s) Published by S. Karger AG, Basel.)

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 <35 pmol/L and MMA >0.45 μmol/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 < 0.001]. The OR (95% CI) of vitamin B-12 deficiency in the third compared with the first tertile of dairy-derived vitamin B-12 was 0.13 (0.04, 0.49), and the ORs for vitamin B-12 from meat and fish were 0.33 (0.11, 0.97) and 0.25 (0.08, 0.82), respectively. Egg-derived vitamin B-12 was only associated with holoTC. Additional analyses showed that self-defined vegetarians and FFQ-defined lacto-ovo-vegetarians had lower median total dietary vitamin B-12 intake and considerably worse vitamin B-12 biomarker status than omnivores and pescatarians., 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.

Study Question: Do embryo culture media used during an IVF/ICSI treatment have an effect on cognitive development of singleton IVF children at 9 years of age?, Summary Answer: Cognitive development of children born after culture in two different embryo culture media is comparable., What Is Known Already: Previously, we have shown that the culture medium used in an IVF/ICSI treatment affects birthweight and weight at 2 years of age after alternating assignment to embryo culture in either K-SCICM (Cook) or G1™ Version 3 (Vitrolife). Children with low birthweight are known to have an increased risk for learning disabilities. Data on cognitive development in general of children born after ART are still conflicting, and the only study reporting on the effects of culture medium on cognitive development shows significant differences in cognitive development between two culture medium groups., Study Design Size Duration: In this observational cohort follow-up study (MEDIUM-KIDS), parents of all singletons from our abovementioned study were approached after the ninth birthday of their child to participate in an additional follow-up study. Of the 294 eligible children included in the original study, 119 children (70 Vitrolife and 49 Cook) participated in the current study., Participants/materials Setting Methods: All follow-up measurements were performed between March 2014 and December 2016. CITO (Dutch Central Institute for Test Development) developed the Dutch pupil monitoring system, which involves nationwide independent, standardized, academic achievement score tests to monitor the child's school performance twice a year at fixed time points from third grade onward. The tests include language skills (vocabulary and orthography), mathematics and reading capability and comprehension. Results from the tests performed between third and sixth grades, expressed as ability scores, were obtained from the school. To investigate school performance development over the years, we used a mixed effects multilevel model. The least complex model with the best fit was selected to analyze whether culture medium affects cognitive development in our cohort. The study had enough power to detect a difference in ability score that reflects at least one performance category between the two groups., Main Results and the Role of Chance: No differences were seen in baseline characteristics between participants and non-participants (both parental and children characteristics). For all domains, the random intercept model was used. All analyses showed comparable results for the two culture medium groups. No significant differences were observed for any of the cognitive development domains, even after correction for potential confounders. Parental level of education was higher in the IVF group (45%) if compared to the national average level of education (35%), which most likely explains the higher CITO scores for the IVF children if compared to the National ability scores., Limitations Reasons for Caution: A limitation of the study was its pseudo-randomized design and the relatively low participation rate of 40.5%. This and the number of missing data prevent us from drawing robust causal conclusions. However, as this is the first and therewith oldest cohort of children where culture medium was allocated alternatingly and used in a blinded setting, in the same period, with all other conditions identical this study gives up until now the best available evidence., Wider Implications of the Findings: Our study analyzes the effects of culture medium on school performance of children born after IVF/ICSI in a prospective cohort study. Although further research on long-term academic skills and also on behavior is essential, our results are reassuring and should make parents of children born after IVF/ICSI feel comfortable with their children's cognitive development., Study Funding/competing Interests: The study was financially supported by the March of Dimes (Grant no. #6-FY13-153). The sponsor of the study had no role in study design, data collection, data analysis, data interpretation or writing of the report. The authors have no conflicts of interest to declare., Trial Registration Number: NTR4220.

Study Question: Is embryo culture media used during an IVF/ICSI treatment associated with differences in growth, body composition and cardiovascular development as determined in 9-year-old singleton IVF children?, Summary Answer: The choice of in vitro culture medium for human embryos is associated with differences in body weight, BMI, truncal adiposity, waist circumference and waist/hip ratio at the age of 9, while no significant differences were observed in cardiovascular development., What Is Known Already: Children born after IVF/ICSI have an increased risk of low birthweight, which is correlated with a higher risk of cardiovascular diseases. Some studies show that IVF children exhibit a significantly higher systolic and diastolic blood pressure and higher fasting glucose levels compared to naturally conceived children. After alternating assignment to G1™ Version 3 (Vitrolife) or K-SICM (Cook) embryo culture media, birthweight of the resulting children was significantly higher in the Vitrolife group and they remained heavier during the first 2 years of life., Study Design, Size, Duration: In this observational cohort study (MEDIUM-KIDS), parents of singletons from a previous study were approached for further follow-up after the ninth birthday of their child. The singletons were born after fresh embryo transfer of cleavage stage embryos resulting from an IVF/ICSI treatment performed between July 2003 and December 2006 in our clinic, when two different culture media were used alternately: either G1™ Version 3 (Vitrolife) or K-SICM (Cook). Follow-up measurements were performed between March 2014 and December 2016., Participant/materials, Settings, Methods: Parents were invited to attend our clinic with their child for a single visit lasting ~2.5 h. Two experienced clinicians performed all measurements as part of the MEDIUM-KIDS study in a standardized way. Height and weight of the child was measured using calibrated scales, 4-point skinfold thickness measurements were measured in triplicate and waist and hip circumference were measured using a tape measure. The following cardiovascular parameters were measured in a standardized way: blood pressure, heart rate and endothelial function by skin laser-Doppler with iontophoresis using vasodilatory drugs. Cortisol and cortisone concentrations in hair were measured. A blood sample was taken after an overnight fast for insulin, glucose, TSH and lipid analysis. Blood samples of the IVF children were compared with a non-IVF control group. Differences between culture medium groups were analysed by Student's t-test and effects of confounders were analysed using multivariable regression analysis., Main Results and the Role of Chance: Of the 294 eligible children (168 Vitrolife and 126 Cook), 136 children (75 Vitrolife and 61 Cook) participated in the study. Baseline characteristics of the participating children from the Vitrolife and Cook group were similar. Birthweight was higher in the Vitrolife group, in keeping with the full cohort. After correction for confounders, the difference in weight and BMI attributable to culture medium was 1.58 kg (95% CI: 0.01-3.14) and 0.84 kg/m2 (95% CI: 0.02-1.67), respectively, with the Vitrolife children being heavier. Height and height corrected for age and gender (SDS scores) were similar in both groups. Furthermore, waist circumference was significantly higher in the Vitrolife group with a corrected difference of 3.21 cm (95%CI: 0.60-5.81) leading to a 0.03 increase (95% CI: 0.01-0.05) in waist/hip ratio. Subscapular skinfolds combined with suprailiacal skinfolds (defined as truncal adiposity), was also significantly higher in Vitrolife children (adjusted difference 3.44 cm [95% CI: 0.27-6.62]). Both systolic (adj. beta 0.364 [95% CI: -2.129 to 2.856],) and diastolic (adj. beta 0.275 [95% CI: -2.105 to 2.654]) blood pressures (mmHg) were comparable for the two groups. After an overnight fast, cholesterol, glucose, insulin, low and high-density lipoprotein, triglycerides and TSH were normal and similar in the two groups. Endothelial function in the microcirculation was compared by using maximum perfusion units corrected for the baseline value as a measure for vasodilatory capacity. There were no significant differences between the two groups. Cortisol and cortisone concentration in hair samples were comparable., Limitations, Reasons for Caution: A limitation of the original study was its pseudo-randomized design. This and the dwindling enthusiasm of families for participation (47.7% after 9 years) prevent us from drawing robust causal conclusions from the observed association. Nevertheless, to date this is oldest cohort of IVF/ICSI children where culture medium was allocated alternatingly and used in a blinded setting, to be studied. We believe that our participants are representative for the full cohort. The current number of participants was sufficient to rule out differences as little as 3 mmHg in systolic and diastolic blood pressures., Wider Implications of the Findings: This study underlines the importance of structured follow-up of IVF/ICSI children to further elucidate possible long-term health effects. Health professionals and culture medium manufacturers should be aware that small changes in culture conditions and culture medium composition for the early embryo can have long-term health effects. The similar cardiovascular results for the two groups are reassuring but the children may still be too young to detect differences in cardiovascular development. Prolonged follow-up and structured investigations up until adulthood are necessary to gain more insight and reassurance in the cardiovascular development of IVF offspring, although long-term follow-up will become more complicated by confounding life-style and environmental factors possibly influencing development., Study Funding/competing Interest(s): The study was financially supported by the March of Dimes (Grant number #6-FY13-153). The sponsor of the study had no role in study design, data collection, data analysis, data interpretation or writing of the report. The authors have no conflicts of interest to declare., Trial Registration Number: NTR4220.

Introduction: Prediction models may contribute to personalized risk-based management of women at high risk of spontaneous preterm delivery. Although prediction models are published frequently, often with promising results, external validation generally is lacking. We performed a systematic review of prediction models for the risk of spontaneous preterm birth based on routine clinical parameters. Additionally, we externally validated and evaluated the clinical potential of the models., Material and Methods: Prediction models based on routinely collected maternal parameters obtainable during first 16 weeks of gestation were eligible for selection. Risk of bias was assessed according to the CHARMS guidelines. We validated the selected models in a Dutch multicenter prospective cohort study comprising 2614 unselected pregnant women. Information on predictors was obtained by a web-based questionnaire. Predictive performance of the models was quantified by the area under the receiver operating characteristic curve (AUC) and calibration plots for the outcomes spontaneous preterm birth <37 weeks and <34 weeks of gestation. Clinical value was evaluated by means of decision curve analysis and calculating classification accuracy for different risk thresholds., Results: Four studies describing five prediction models fulfilled the eligibility criteria. Risk of bias assessment revealed a moderate to high risk of bias in three studies. The AUC of the models ranged from 0.54 to 0.67 and from 0.56 to 0.70 for the outcomes spontaneous preterm birth <37 weeks and <34 weeks of gestation, respectively. A subanalysis showed that the models discriminated poorly (AUC 0.51-0.56) for nulliparous women. Although we recalibrated the models, two models retained evidence of overfitting. The decision curve analysis showed low clinical benefit for the best performing models., Conclusions: This review revealed several reporting and methodological shortcomings of published prediction models for spontaneous preterm birth. Our external validation study indicated that none of the models had the ability to predict spontaneous preterm birth adequately in our population. Further improvement of prediction models, using recent knowledge about both model development and potential risk factors, is necessary to provide an added value in personalized risk assessment of spontaneous preterm birth., (© 2018 The Authors Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

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 (1,000 mg/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 €4,621,465, €2,059,165, or €2,822,115 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., (© 2017 John Wiley & Sons Ltd.)

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 <3, concomitant CIN 1, and no more than 1 biopsy containing CIN 2 were predictive of disease regression. The AUC was 69.2% (95% confidence interval, 58.5%-79.9%), indicating a moderate discriminative ability of the model. The calibration plot indicated good calibration of the predicted probabilities. This prediction model for spontaneous regression of CIN 2 may aid physicians in the personalized management of these lesions., (Copyright © 2016 Elsevier Inc. All rights reserved.)