Search

Introduction:Twin pregnancies have a high risk of extreme preterm birth (PTB) at less than 28 weeks of gestation, which is associated with increased risk of neonatal morbidity and mortality. Currently there is a lack of effective treatments for women with a twin pregnancy and a short cervix or cervical dilatation. A possible effective surgical method to reduce extreme PTB in twin pregnancies with an asymptomatic short cervix or dilatation at midpregnancy is the placement of a vaginal cerclage. Methods and analysis: We designed two multicentre randomised trials involving eight hospitals in the Netherlands (sites in other countries may be added at a later date). Women older than 16 years with a twin pregnancy at <24 weeks of gestation and an asymptomatic short cervix of ≤25 mm or cervical dilatation will be randomly allocated (1:1) to both trials on vaginal cerclage and standard treatment according to the current Dutch Society of Obstetrics and Gynaecology guideline (no cerclage). Permuted blocks sized 2 and 4 will be used to minimise the risk of disbalance. The primary outcome measure is PTB of <28 weeks. Analyses will be by intention to treat. The first trial is to demonstrate a risk reduction from 25% to 10% in the short cervix group, for which 194 patients need to be recruited. The second trial is to demonstrate a risk reduction from 80% to 35% in the dilatation group and will recruit 44 women. A cost-effectiveness analysis will be performed from a societal perspective. Ethics and dissemination: This study has been approved by the Research Ethics Committees in the Netherlands on 3/30/2023. Participants will be required to sign an informed consent form. The results will be presented at conferences and published in a peer-reviewed journal. Participants will be informed about the results.

Introduction: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. Methods and analysis: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (>= 4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. Ethics and dissemination: The Study Coordination Centre has obtained approval from Lon

Introduction: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. Methods and analysis: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (>= 4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. Ethics and dissemination: The Study Coordination Centre has obtained approval from Lon

Introduction: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. Methods and analysis: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (>= 4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. Ethics and dissemination: The Study Coordination Centre has obtained approval from Lon

Introduction: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. Methods and analysis: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (>= 4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. Ethics and dissemination: The Study Coordination Centre has obtained approval from Lon

Introduction: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. Methods and analysis: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (>= 4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. Ethics and dissemination: The Study Coordination Centre has obtained approval from Lon

1089-1095, In onze maatschappij wordt een zwangerschap sterk gemedicaliseerd ondanks dat het een fysiologisch gegeven is. Er worden geregeld onderzoeken aangevraagd en uitgevoerd zonder voldoende evidentie. Naar aanleiding hiervan deed het Federaal Kenniscentrum voor de Gezondheidszorg (KCE) onderzoek naar de minimale vereisten om een zo goed mogelijke basiszorg in een laagrisicozwangerschap te kunnen verzekeren en publiceerde in 2015 een aangepaste klinische richtlijn. Deze richtlijn werd gefundeerd op de huidige wetenschappelijke evidentie en omvat een aantal klinische aanbevelingen. Deze klinische aanbevelingen kwamen tot stand door een systematische review van de literatuur voor tien onderwerpen en het ADAPTE-proces op basis van de Australische richtlijn 2015 voor 24 specifieke klinische vragen. Het GRADE-systeem werd gebruikt om vervolgens de sterkte van elke aanbeveling te definiëren. De aanbevelingen behelzen zowel het klinisch onderzoek, technische onderzoeken zoals echografie, serologische testen en de specifieke screening naar klinische maternale en zwangerschapsgerelateerde problemen.

1347-1352, BACKGROUND: Several countries today struggle with suboptimal performances in many aspects of the fetal aneuploidy screening process and consider introducing non-invasive prenatal screening (NIPT) as a solution. In this study, costs and benefits of different scenarios for contingent NIPT screening in Belgium are evaluated with respect to partial redistribution of the national screening budget into quality improving measures for those screening activities that will be maintained when full NIPT screening is implemented. METHODS: Data from the Belgian National Institute for Health and Disability Insurance and the Study Centre for Perinatal Epidemiology were used in modeled calculations of medical and economic impact of NIPT after prior conventional screening (1) at thresholds 1:300 and 1:600, and (2) at current and improved screening sensitivity. RESULTS: Contingent NIPT screening under current screening conditions would maintain today's 7.9(0) /000 live birth prevalence of Down syndrome (LBPD) at an 11% reduction of overall short-term costs. Lowering the screening threshold to 1:600 or increasing sensitivity by 10% would reduce LBPD to 7(0) /000 at a maximum 3% increase of overall short-term costs. CONCLUSION: Today, in Belgium and in many other countries, full NIPT screening is considered too expensive for immediate introduction into the national fetal aneuploidy screening program. Contingent NIPT screening is both clinically and economically beneficial. A temporary contingent NIPT protocol allows for reinvesting economic savings into optimization of those screening aspects, which are to be maintained in parallel to full NIPT screening.

106 p., ill, SCIENTIFIC REPORT 8 -- 1 COST-EFFECTIVENESS OF NIPT 8 -- 1.1 RESEARCH QUESTIONS AND METHODS 8 -- 1.2 PRENATAL SCREENING FOR DOWN SYNDROME 9 -- 1.2.1 Down syndrome 9 -- 1.2.2 Current screening for Down syndrome 10 -- 1.2.3 Invasive tests for T21 diagnosis 11 -- 1.2.4 NIPT 13 -- 1.2.5 Decisions with regard to pregnancy termination after a T21 diagnosis 14 -- 1.3 LITERATURE SEARCH FOR ECONOMIC EVALUATIONS 14 -- 1.3.1 Search strategy 14 -- 1.3.2 Selection criteria 15 -- 1.4 OVERVIEW OF ECONOMIC EVALUATIONS 17 -- 1.4.1 General information 17 -- 1.4.2 Population 18 -- 1.4.3 Intervention and comparator 18 -- 1.4.4 Screening costs (and costs of Down syndrome) 18 -- 1.4.5 Test characteristics 19 -- 1.4.6 Other assumptions 19 -- 1.4.7 Quality of life 20 -- 1.4.8 Results and sensitivity analysis 20 -- 1.4.9 Authors’ conclusions 21 -- 1.5 DISCUSSION 22 -- 2 COST-EFFECTIVENESS OF NIPT: MODELING EXERCISE FOR BELGIUM 30 -- 2.1 METHODS 30 -- 2.1.1 Analytic technique 30 -- 2.1.2 Perspective 30 -- 2.1.3 Population 31 -- 2.1.4 Intervention and comparator 34 -- 2.1.5 Time horizon and discount rate 36 -- 2.1.6 Input variables 36 -- 2.1.7 Uncertainty 45 -- 2.1.8 Model development, calibration and validation 47 -- 2.2 RESULTS 48 -- 2.2.1 Base case analysis 48 -- 2.2.2 Sensitivity analysis 50 -- 3 DISCUSSION 57 -- 3.1 THE SCREENING PROCESS 57 -- 3.2 THE INVASIVE TEST FOR DIAGNOSIS 59 -- 3.3 DECISIONS WITH REGARD TO PREGNANCY TERMINATION 60 -- 3.4 THE DIFFICULT CHOICE OF THE TIME HORIZON 60 -- 3.5 NIPT 61 -- 3.6 NIPT FOR TRIAGE IN AT RISK WOMEN AFTER CURRENT SCREENING 62 -- 3.7 PRIMARY NIPT SCREENING USING CURRENT TESTING UPTAKE 63 -- 3.8 INCREASED NIPT UPTAKE OF 90% 63 -- 3.9 THE PRICE OF NIPT AND THRESHOLD ANALYSIS 64 -- 3.10 COST-CONSEQUENCES ANALYSIS OR (QA)LYS GAINED 65 -- 4 CONCLUSIONS 67

106 p., ill, SCIENTIFIC REPORT 8 -- 1 COST-EFFECTIVENESS OF NIPT 8 -- 1.1 RESEARCH QUESTIONS AND METHODS 8 -- 1.2 PRENATAL SCREENING FOR DOWN SYNDROME 9 -- 1.2.1 Down syndrome 9 -- 1.2.2 Current screening for Down syndrome 10 -- 1.2.3 Invasive tests for T21 diagnosis 11 -- 1.2.4 NIPT 13 -- 1.2.5 Decisions with regard to pregnancy termination after a T21 diagnosis 14 -- 1.3 LITERATURE SEARCH FOR ECONOMIC EVALUATIONS 14 -- 1.3.1 Search strategy 14 -- 1.3.2 Selection criteria 15 -- 1.4 OVERVIEW OF ECONOMIC EVALUATIONS 17 -- 1.4.1 General information 17 -- 1.4.2 Population 18 -- 1.4.3 Intervention and comparator 18 -- 1.4.4 Screening costs (and costs of Down syndrome) 18 -- 1.4.5 Test characteristics 19 -- 1.4.6 Other assumptions 19 -- 1.4.7 Quality of life 20 -- 1.4.8 Results and sensitivity analysis 20 -- 1.4.9 Authors’ conclusions 21 -- 1.5 DISCUSSION 22 -- 2 COST-EFFECTIVENESS OF NIPT: MODELING EXERCISE FOR BELGIUM 30 -- 2.1 METHODS 30 -- 2.1.1 Analytic technique 30 -- 2.1.2 Perspective 30 -- 2.1.3 Population 31 -- 2.1.4 Intervention and comparator 34 -- 2.1.5 Time horizon and discount rate 36 -- 2.1.6 Input variables 36 -- 2.1.7 Uncertainty 45 -- 2.1.8 Model development, calibration and validation 47 -- 2.2 RESULTS 48 -- 2.2.1 Base case analysis 48 -- 2.2.2 Sensitivity analysis 50 -- 3 DISCUSSION 57 -- 3.1 THE SCREENING PROCESS 57 -- 3.2 THE INVASIVE TEST FOR DIAGNOSIS 59 -- 3.3 DECISIONS WITH REGARD TO PREGNANCY TERMINATION 60 -- 3.4 THE DIFFICULT CHOICE OF THE TIME HORIZON 60 -- 3.5 NIPT 61 -- 3.6 NIPT FOR TRIAGE IN AT RISK WOMEN AFTER CURRENT SCREENING 62 -- 3.7 PRIMARY NIPT SCREENING USING CURRENT TESTING UPTAKE 63 -- 3.8 INCREASED NIPT UPTAKE OF 90% 63 -- 3.9 THE PRICE OF NIPT AND THRESHOLD ANALYSIS 64 -- 3.10 COST-CONSEQUENCES ANALYSIS OR (QA)LYS GAINED 65 -- 4 CONCLUSIONS 67

28 p., ill, En Belgique, chaque femme enceinte peut, si elle le souhaite, obtenir une estimation du risque que le fœtus soit porteur du syndrome de Down (trisomie 21 – T21). Actuellement, cette estimation est basée sur une biochimie sanguine et une échographie. Lorsque ce risque s'avère élevé, un test invasif (une biopsie de villosités choriales ou une amniocentèse) est alors pratiqué pour confirmer ou infirmer ce diagnostic. Toutefois, le nombre de fœtus porteurs d’une T21 non décelés par cette approche demeure important. A cela s’ajoute le fait que ces tests invasifs sont associés à un risque de fausse-couche de l’ordre de 1 %. Le test prénatal non invasif (NIPT) est un test génétique relativement récent effectué sur le sang de la mère, plus sensible et plus précis que le dépistage classique. Toutefois, il est toujours relativement onéreux. La ministre a demandé au Conseil Supérieur de la Santé (CSS) et au Centre Fédéral d'Expertise des Soins de Santé (KCE) d'effectuer une évaluation du NIPT. L'évaluation du KCE concernait surtout les aspects relatifs à l'économie de la santé. L'examen a porté sur deux façons dont le NIPT pourrait être introduit dans le cadre du dépistage prénatal du syndrome de Down : (1) Soit le NIPT est effectué en première ligne au lieu de la procédure de dépistage actuelle ; (2) Soit le NIPT est pratiqué en seconde ligne et uniquement lorsque les tests de dépistage actuels sur la base d'une analyse sanguine et d'une échographie indiquent un risque accru. Chacune de ces deux options permet d'aboutir à une estimation du risque nettement plus fiable que celle obtenue dans le cadre du dépistage actuel. Elles permettent en outre de réduire le nombre de tests invasifs pratiqués. Dès lors, elles représentent une amélioration par rapport au dépistage actuel. Au niveau purement technique, la préférence doit être accordée à l'option (1), dans laquelle le NIPT est proposé comme test de dépistage en première instance. En effet, grâce à celle-ci, non seulement le nom, PRÉFACE 1 -- SYNTHÈSE2 -- 1. INTRODUCTION .. 4 -- 1.1. DOWN SYNDROME 4 -- 1.2. NIPT 4 -- 1.3. SUJET D’ÉTUDE, QUESTIONS DE RECHERCHE ET MÉTHODOLOGIE 5 -- 2. REVUE DE LA LITTÉRATURE6 -- 3. MODÉLISATION SPÉCIFIQUE AU CONTEXTE BELGE 6 -- 3.1. GROSSESSES ET ENFANTS NÉS AVEC LE SYNDROME DE DOWN6 -- 3.2. LE DÉPISTAGE PRÉNATAL ACTUEL .. 7 -- 3.3. LES TESTS DIAGNOSTIQUES INVASIFS .. 11 -- 3.4. DÉCISIONS RELATIVES À L'INTERRUPTION DE LA GROSSESSE .. 12 -- 3.5. RÉSULTATS ET HORIZON TEMPOREL .. 12 -- 3.6. VARIABLES D'ENTRÉE DU MODÈLE 13 -- 4. RÉSULTAT DU MODÈLE .. 16 -- 4.1. NIPT POUR LE TRIAGE DES FEMMES À RISQUE APRÈS LE DÉPISTAGE ACTUEL16 -- 4.1.1. NIPT appliqué aux 5 % de cas positifs au dépistage à un seuil de risque de 1:30016 -- 4.1.2. NIPT appliqué aux 20 % de cas positifs au dépistage à un seuil de risque de 1:1700 16 -- 4.2. DÉPISTAGE PRIMAIRE PAR NIPT .. 17 -- 4.2.1. Dépistage primaire par NIPT sur base de la participation actuelle aux tests 17 -- 4.2.2. Participation accrue au NIPT de 90 % .. 17 -- 5. CONCLUSIONS20 -- 5.1. FORCES ET LIMITES DE L’ÉTUDE20 -- 5.2. DÉCISION ÉCLAIRÉE21 -- 5.3. UNE PLUS GRANDE SENSIBILITÉ21 -- 5.4. UNE PLUS GRANDE SPÉCIFICITÉ22 -- 5.5. OPTIONS POUR L’INTRODUCTION DU NIPT .. 23 -- RECOMMANDATIONS 24 -- RÉFÉRENCES 26

25 p., ill, FOREWORD 1 -- SYNTHESIS 2 -- 1. INTRODUCTION 4 -- 1.1. DOWN SYNDROME 4 -- 1.2. NIPT 4 -- 1.3. SCOPE, RESEARCH QUESTIONS AND METHODS 5 -- 2. LITERATURE REVIEW 6 -- 3. CONTEXT-SPECIFIC MODELLING 6 -- 3.1. PREGNANCIES AND CHILDREN BORN WITH DOWN SYNDROME 6 -- 3.2. CURRENT PRENATAL SCREENING 7 -- 3.3. THE INVASIVE DIAGNOSTIC TEST PROCEDURES 11 -- 3.4. DECISIONS WITH REGARD TO PREGNANCY TERMINATION 11 -- 3.5. OUTCOMES AND TIME HORIZON 12 -- 3.6. INPUT VARIABLES FOR THE MODEL 12 -- 4. RESULTS OF THE MODEL 15 -- 4.1. NIPT FOR TRIAGE IN AT RISK WOMEN AFTER CURRENT SCREENING 15 -- 4.1.1. NIPT in 5% screen positives at a 1:300 risk cut-off 15 -- 4.1.2. NIPT in 20% screen positives at a 1:1700 risk cut-off 15 -- 4.2. PRIMARY NIPT SCREENING 15 -- 4.2.1. Primary NIPT screening with current uptake 15 -- 4.2.2. Increased NIPT uptake of 90% 16 -- 5. CONCLUSIONS 18 -- 5.1. STRENGTHS AND LIMITATIONS OF THE STUDY 18 -- 5.2. INFORMED DECISION MAKING 18 -- 5.3. A HIGHER SENSITIVITY 19 -- 5.4. A HIGHER SPECIFICITY 20 -- 5.5. OPTIONS FOR INTRODUCING NIPT 20 -- RECOMMENDATIONS 21 -- REFERENCES 23

28 p., ill, Alle zwangere vrouwen in ons land die dit wensen kunnen vandaag het risico op het syndroom van Down (trisomie 21 - T21) laten vaststellen door een biochemische bloedtest en een echografie. Bij een verhoogd risico wordt vervolgens de diagnose bevestigd of weerlegd door een invasieve test (vlokkentest of vruchtwaterpunctie). Bij deze aanpak worden echter nog heel wat foetussen met T21 gemist, en bij de invasieve testen is er ook een risico van 1% op het onvrijwillig afbreken van de zwangerschap. De niet-invasieve prenatale test (NIPT) is een relatief nieuwe genetische bloedtest, die gevoeliger en nauwkeuriger is dan de klassieke testen, maar die nog erg duur is.De minister vroeg een evaluatie van de NIPT aan de Hoge Gezondheidsraad (HGR) en het Federaal Kenniscentrum voor de Gezondheidszorg (KCE). De evaluatie door het KCE ging vooral over de gezondheidseconomische aspecten. Twee mogelijke manieren om NIPT in te voeren werden onderzocht: (1) NIPT in de eerste lijn ter vervanging van de huidige screeningsprocedure, of (2) NIPT in de tweede lijn enkel nadat de huidige screeningtesten met bloed en echo een verhoogd risico aangeven. Beide opties geven een veel betere voorspelling dan de huidige screening, doen het aantal invasieve testen dalen en zijn een verbetering ten opzichte van de huidige screening. Optie (1), waarbij NIPT wordt aangeboden als screeningstest is puur technisch te verkiezen omdat niet alleen het aantal invasieve testen daalt maar ook minder foetussen die drager zijn van T21 gemist worden. Maaronder meer omdat de kost van de NIPT test vandaag relatief hoog is (460€) wordt op dit ogenblik echter aanbevolen NIPT te vergoeden in optie (2). Mits een substantiële daling van de prijs van de NIPT-test en voldoende kwaliteitsgaranties wordt de terugbetaling van NIPT in optie (1) aanbevolen. Voor beide opties is een systeem van registratie en evaluatie van de resultaten van NIPT aanbevolen., VOORWOORD 1 -- SYNTHESE 2 -- 1. INLEIDING 4 -- 1.1. DOWNSYNDROOM 4 -- 1.2. NIPT 4 -- 1.3. SCOPE, ONDERZOEKSVRAGEN EN -METHODES 5 -- 2. LITERATUUROVERZICHT. 6 -- 3. CONTEXT-SPECIFIEKE MODELLERING 6 -- 3.1. ZWANGERSCHAPPEN EN KINDEREN MET DOWNSYNDROOM 6 -- 3.2. DE HUIDIGE PRENATALE SCREENING 7 -- 3.3. DE INVASIEVE DIAGNOSTISCHE TEST PROCEDURES 11 -- 3.4. BESLISSINGEN MET BETREKKING TOT ZWANGERSCHAPSAFBREKING 12 -- 3.5. UITKOMSTMATEN EN TIJDSHORIZON 12 -- 3.6. INPUTVARIABELEN VOOR HET MODEL 13 -- 4. RESULTATEN VAN HET MODEL 16 -- 4.1. NIPT VOOR TRIAGE BIJ VROUWEN MET VERHOOGD RISICO NA DE HUIDIGE SCREENING 16 -- 4.1.1. NIPT in 5% screeningspositieven bij een 1:300 risico cut-off 16 -- 4.1.2. NIPT in 20% screeningspositieven bij een 1:1700 risico cut-off 16 -- 4.2. PRIMAIRE NIPT-SCREENING 17 -- 4.2.1. Primaire NIPT-screening met huidige deelname 17 -- 4.2.2. Verhoogde NIPT-deelname van 90% 17 -- 5. CONCLUSIES 20 -- 5.1. STERKSTES EN ZWAKTES VAN DE STUDIE 20 -- 5.2. HET NEMEN VAN EEN GEÏNFORMEERDE BESLISSING 21 -- 5.3. EEN HOGERE GEVOELIGHEID. 21 -- 5.4. EEN HOGERE SPECIFICITEIT 22 -- 5.5. OPTIES OM NIPT TE INTRODUCEREN 23 -- AANBEVELINGEN 24 -- REFERENTIES 26

We will present the fourth case in the English-language literature of a mid-gestational colonoscopy-assisted manual reposition of an incarcerated uterus. Despite the ready availability of ultrasound, a great number of incarcerations are not recognized before term. Since early diagnosis is the key to a successful treatment, it is important that providers acquire prompt knowledge of this obstetric disorder. Magnetic Resonance Imaging has an important additional value to ultrasound in the detailed scanning of this potentially perilous condition.

p. 1-10, The first- and second-trimester screening for trisomy 21 (T21) are reimbursed for all pregnant women in Belgium. Using a cut-off risk of 1:300 for T21, about 5% of all pregnant women are referred for definitive prenatal diagnosis using an invasive test, at a sensitivity of (only) 72.5%. The sensitivity and specificity of the non-invasive prenatal test (NIPT) are over 99% but come at a cost of €460 (£373) per test. The objective is to estimate the consequences of introducing NIPT for the detection of T21. METHODS: A cost-consequences analysis was performed presenting the impact on benefits, harms and costs. Context-specific real-world information was available to set up a model reflecting the current screening situation in Belgium. This model was used to construct the second and first line NIPT screening scenarios applying information from the literature on NIPT's test accuracy. RESULTS: Introducing NIPT in the first or second line reduces harm by decreasing the number of procedure-related miscarriages after invasive testing. In contrast with NIPT in the second line, offering NIPT in the first line additionally will miss fewer cases of T21 due to less false-negative test results. The introduction of NIPT in the second line results in cost savings, which is not true for NIPT at the current price in the first line. If NIPT is offered to all pregnant women, the price should be lowered to about €150 to keep the screening cost per T21 diagnosis constant. CONCLUSIONS: In Belgium, the introduction and reimbursement of NIPT as a second line triage test significantly reduces procedure-related miscarriages without increasing the short-term screening costs. Offering and reimbursing NIPT in the first line to all pregnant women is preferred in the long term, as it would, in addition, miss fewer cases of T21. However, taking into account the government's limited resources for universal reimbursement, the price of NIPT should first be lowered substantially before this can be realis

p. 21, Modelling of NIPT Figure 3 presents an overview of the current screening strategy in Belgium. In Figure 4, the current first trimester biochemistry screening and second trimester screening is replaced by NIPT at week 12. In the next part of this supplementary file, we present and explain the three models in detail (current screening, NIPT 2nd line and NIPT 1st line) with inclusion of the number of pregnant women and T21 pregnancies at different moments in the model.