Perinatal morbidity among women with a previous caesarean delivery (PRISMA trial): a cluster-randomised trial.

BACKGROUND: Women with a previous caesarean delivery face a difficult choice in their next pregnancy: planning another caesarean or attempting vaginal delivery, both of which are associated with potential maternal and perinatal complications. This trial aimed to assess whether a multifaceted intervention, which promoted person-centred decision making and best practices, would reduce the risk of major perinatal morbidity among women with one previous caesarean delivery. METHODS: We conducted an open, multicentre, cluster-randomised, controlled trial of a multifaceted 2-year intervention in 40 hospitals in Quebec among women with one previous caesarean delivery, in which hospitals were the units of randomisation and women the units of analysis. Randomisation was stratified according to level of care, using blocked randomisation. Hospitals were randomly assigned (1:1) to the intervention group (implementation of best practices and provision of tools that aimed to support decision making about mode of delivery, including an estimation of the probability of vaginal delivery and an ultrasound estimation of the risk of uterine rupture), or the control group (no intervention). The primary outcome was a composite risk of major perinatal morbidity. This trial was registered with ISRCTN, ISRCTN15346559. FINDINGS: 21 281 eligible women delivered during the study period, from April 1, 2016 to Dec 13, 2019 (10 514 in the intervention group and 10 767 in the control group). None were lost to follow-up. There was a significant reduction in the rate of major perinatal morbidity from the baseline period to the intervention period in the intervention group as compared with the control group (adjusted odds ratio [OR] for incremental change over time, 0·72 [95% CI 0·52-0·99]; p=0·042; adjusted risk difference -1·2% [95% CI -2·0 to -0·1]). Major maternal morbidity was significantly reduced in the intervention group as compared with the control group (adjusted OR 0·54 [95% CI 0·33-0·89]; p=0·016). Minor perinatal and maternal morbidity, caesarean delivery, and uterine rupture rates did not differ significantly between groups. INTERPRETATION: A multifaceted intervention supporting women in their choice of mode of delivery and promoting best practices resulted in a significant reduction in rates of major perinatal and maternal morbidity, without an increase in the rate of caesarean or uterine rupture. FUNDING: Canadian Institutes of Health Research (CIHR, MOP-142448).

Bi-allelic variants in MYH3 cause recessively-inherited arthrogryposis.

Arthrogryposis is a clinical feature defined by congenital joint contractures in two or more different body areas which occurs in between 1/3000 and 1/5000 live births. Variants in multiple genes have been associated with distal arthrogryposis syndromes. Heterozygous variants in MYH3 have been identified to cause the dominantly-inherited distal arthrogryposis conditions, Freeman-Sheldon syndrome, Sheldon-Hall syndrome, and multiple pterygium syndrome. In contrast, MYH3 variants underlie both dominantly and recessively inherited Contractures, Pterygia, and Spondylocarpotarsal Fusion syndromes (CPSFS) which are characterized by extensive bony abnormalities in addition to congenital contractures. Here we report two affected sibs with distal arthrogryposis born to unaffected, distantly related parents. Sequencing revealed that both sibs were homozygous for two ultra-rare MYH3 variants, c.3445G>A (p.Glu1149Lys) and c.4760T>C (p.Leu1587Pro). Sequencing and deletion/duplication analysis of 169 other arthrogryposis genes yielded no other compelling candidate variants. This is the first report of biallelic variants in MYH3 being implicated in a distal arthrogryposis phenotype without the additional features of CPSFS. Thus, akin to CPSFS, both dominant and recessively inherited distal arthrogryposis can be caused by variants in MYH3.

First-trimester screening for Down syndrome using quadruple maternal biochemical markers.

OBJECTIVES: Placental growth factor (PlGF) is used for first-trimester preeclampsia screening and could be combined with other biochemical markers for Down syndrome screening. We aim to estimate the predictive value of the combination of pregnancy-associated plasma protein (PAPP-A), free ß-human chorionic gonadotropin (free ß-hCG), placental growth factor (PlGF) and α-fetoprotein (AFP) with and without nuchal translucency. METHODS: Singleton pregnancies recruited at 11-14 weeks and followed until delivery. The four maternal markers were measured using Kryptor (ThermoFisher-BRAHMS) and adjusted for gestational age and maternal characteristics. The risk of Down syndrome was calculated using the Fetal Medicine Foundation algorithm and multivariate linear regression analyses in all cases and in 2,200 controls. Receiver-operator characteristic (ROC) curves were used to calculate the detection and false-positive rates. RESULTS: Twenty-six (0.2%) cases of Down syndrome were diagnosed among 13,386 participants. The combination of the four biomarkers could have detected 88% (95% CI: 72-97%) of the cases at a false-positive rate of 13% (95% CI: 12-15%). The addition of nuchal translucency would have increased the detection rate to 96% (95% CI: 82-99%) at a false-positive rate of 4% (95% CI: 4-5%) using a 1:300 cut-off and to 100% (95% CI: 89-100%) at a false-positive rate of 6% (95% CI: 5-8%) using a 1:500 cut-off. CONCLUSIONS: First-trimester screening using biochemical markers allows the identification of approximately 88% of Down syndrome cases for a false-positive rate of 13%. The addition of nuchal translucency raises the detection rate above 95% with a false-positive rate below 5%.

Impact of Selective Fetal Growth Restriction on Laser Therapy Outcomes in Twin-Twin Transfusion Syndrome.

INTRODUCTION: The aim of this study was to determine if outcomes of fetoscopic laser photocoagulation in isolated twin-twin transfusion syndrome (TTTS) differ from TTTS with concomitant selective fetal growth restriction (sFGR). METHODS: This is a retrospective cohort study of all cases of TTTS treated at the CHU Sainte-Justine between February 2006 and January 2020. Data were collected from maternal, obstetrical, and neonatal chart review. RESULTS: A total of 149 patients were included in our study. Forty-seven patients (31.5%) had a pregnancy complicated by TTTS and sFGR. Mean gestational age at diagnosis and at treatment was 20+4 weeks and 20+6 weeks for TTTS alone, and 20+5 weeks and 21+2 weeks with concomitant sFGR. The presence of concomitant sFGR negatively impacted survival. Double survival in the TTTS + sFGR was 48.9% (23/47) versus 68.6% (70/102) in the TTTS-only group (p = 0.021). Fetal donor survival was 59.6% (28/47) in the TTTS + sFGR group and 84.3% (86/102) in the TTTS-only group (p = 0.001). However, the survival of at least one twin did not differ between the two groups: 93.6% (44/47) in the TTTS + sFGR group versus 92.2% (94/102) in the TTTS-only group (p = 0.751). The presence of type 2-3 sFGR (OR = 0.56; 95% CI 0.32-0.96, p = 0.033) and gestational age at laser therapy (OR = 1.17; 95% CI 1.01 = 1.36, p = 0.036) were independently associated with dual survival. CONCLUSION: sFGR is independently associated with decreased double survivorship at the expense of the donor in TTTS undergoing laser therapy. Type 2 or 3 sFGR and early gestational age at treatment are especially at risk. A larger cohort is needed to validate our results.

Risk factors for placental human papillomavirus infection.

OBJECTIVE: Human papillomavirus (HPV) has been associated with adverse pregnancy outcomes but placental HPV infection has been rarely studied. The objective was to determine the proportion of HPV-positive placentas and the associated risk factors among HPV-positive women during pregnancy. METHODS: We analysed data from pregnant women enrolled in HERITAGE cohort study between 2010 and 2016 with positive vaginal HPV infection during the first trimester of pregnancy (n=354). Placental swabs and biopsies were collected. HPV genotyping was performed using Linear Array. The predictors of placental HPV detection were identified by generalised estimating equations models. RESULTS: HPV was detected in 78 placentas (22.0%) (one among 96 caesarean sections and 77 among 258 vaginal deliveries). Overall, 91% of HPV-positive placentas were positive for a genotype that was detected in vaginal samples during pregnancy. Among women who delivered vaginally, abnormal cytology (adjusted OR (aOR) 1.78 (95% CI 1.02 to 3.10)), other genitourinary infection (aOR 2.41 (95% CI 1.31 to 4.44)), presence of multiple HPV genotypes in the first trimester (aOR 2.69 (95% CI 1.76 to 4.12)) and persistence of high-risk HPV infections during pregnancy (HPV-16/18: aOR 3.94 (95% CI 2.06 to 7.55) and other than HPV-16/18: aOR 2.06 (95% CI 1.05 to 4.02)) were independently associated with placental HPV. CONCLUSIONS: HPV was frequently detected in the placenta of women who delivered vaginally and may be associated with host immune response characteristics.

Optimal Gestational Weight Gain for Women With Obesity.

OBJECTIVE: To determine the optimal gestational weight gain interval for women with obesity in order to minimize neonatal and maternal adverse events. METHODS: Secondary analysis of the QUARISMA trial, including women with obesity who delivered a full-term singleton in cephalic presentation from 2008 to 2011 in Québec. The primary outcome was a composite risk of major neonatal morbidity. Secondary outcomes were composite risks of major maternal morbidity, minor neonatal and maternal morbidity, and cesarean delivery. Various ranges of weight gain were compared with the current recommendations (reference group) using logistic regression to identify an optimal gestational weight gain interval. In a secondary analysis, women with obesity were stratified by obesity class (I-III). RESULTS: Among 16 808 eligible women with obesity, 3270 gained less weight than recommended, 4355 gained weight as recommended (5-9.09 kg), and 9183 gained more weight than recommended. Optimal gestational weight change for all women with obesity was -1 to +4 kg and was associated with reduced risk of major neonatal morbidity (aOR 0.49; 95%CI 0.33-0.73, P < 0.001) compared with the reference group. Analysis by class of obesity showed a reduced risk of major neonatal morbidity with a weight change of -1 to +4 kg for class I, -2 to +2 for class II), and -2 to +3 kg for class III. CONCLUSION: Compared with the current guidelines, a gestational weight change of -1 to +4 kg is associated with reduced risk of adverse perinatal outcomes. While similar findings were seen among women with class I obesity, women with class II or III obesity could benefit from a lower weight gain.

Impact of Gestational Weight Gain Recommendations for Obese Women on Neonatal Morbidity.

INTRODUCTION: In 2013, the American College of Obstetricians and Gynecologists (ACOGs) developed gestational weight gain guidelines to minimize the risks associated with obesity during pregnancy. However, a growing body of evidence suggests that current recommendations should be revised for obese women. OBJECTIVES: The objective of this study is to assess the impact of gestational weight gain recommendations for obese women (body mass index ≥ 30 kg/m2) on neonatal and maternal outcomes in Quebec. STUDY DESIGN: Secondary analysis of the QUARISMA trial was performed including obese women who delivered a full-term singleton in cephalic presentation from 2008 to 2011 in Quebec. Outcomes assessed were composite risks of major neonatal and maternal complications, minor neonatal and maternal complications, as well as obstetrical interventions. Outcomes were compared between weight gain recommendations (reference group) and three weight gain/loss categories using logistic regressions. In second analysis, obese women were stratified by obesity class. RESULTS: Among the 16,808 eligible obese women, 605 lost weight during pregnancy, 2,665 gained between 0 and 4.9 kg, 4,355 gained weight within the recommendations (5-9.09 kg), and 9,183 gained at least 9.1 kg. Results showed a significant reduction in major neonatal morbidity (adjusted odds ratio [aOR] = 0.69, 95% confidence interval [CI] = 0.51-0.94), minor maternal morbidity (aOR = 0.79, 95%CI = 0.67-0.93), and assisted vaginal delivery (aOR = 0.82, 95%CI = 0.68-0.99) among women who gained 0 to 4.9 kg compared with the reference group. Cesarean delivery and preeclampsia/eclampsia were significantly reduced with weight loss (aOR = 0.76, 95%CI = 0.64-0.89 and 0.58, 95%CI = 0.42-0.78) compared with the reference group. Weight gain above recommendations was associated with an increased risk of minor neonatal morbidity, major and minor maternal morbidity, as well as cesarean delivery. CONCLUSIONS: Compared with a weight gain within the recommendations, a gestational weight gain/loss of less than 5 kg in obese women is associated with a reduced risk of major neonatal morbidity, minor maternal morbidity, preeclampsia/eclampsia, cesarean delivery, and assisted vaginal delivery. Guidelines on gestational weight gain for obese women should be updated. KEY POINTS: · Gestational weight gain/loss of less than 5 kg reduces the risk of perinatal complications.. · As suggested by ACOG recommendations, guidelines for obese women should be updated.. · Recommendations stratified by obesity class should be included in revised guidelines..

External validation of prognostic models predicting pre-eclampsia: individual participant data meta-analysis.

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 .

Left Superior Vena Cava in the Fetus: A Rarely Isolated Anomaly.

The frequency of chromosomal anomalies among fetuses with isolated persistent left superior vena cava (PLSVC) is still debated. The objective of the present study was to assess the prevalence of genetic and morphological anomalies identified in fetuses with PLSVC. We conducted a single-center retrospective study including all fetuses diagnosed with a PLSVC between 2010 and 2017. PLSVC was categorized as isolated or associated according to antenatal diagnosis of associated congenital heart defects, hypoplastic aortic isthmus, abnormal venous/arterial connections, and extracardiac anomalies. Among 229 fetuses diagnosed with PLSVC, 39 cases (17%) were strictly isolated and no syndromic/genetic anomaly or aortic coarctation was diagnosed. Seventy-two fetuses had a cardiovascular defect with a rate of genetic anomalies of 22%, 29 had an extracardiac malformation, and 89 had both an extracardiac and a cardiovascular defect. Among fetuses with abnormal development of the arterial/venous system as the only associated anomaly such as aberrant right subclavian artery or absent ductus venosus, 22% had a genetic anomaly. Overall, sixty-five fetuses or infants had a genetic concern, including 23 aneuploidies, 15 pathogenic micro-deletions/duplications, and 5 variants of unknown significance; 12 patients had VACTERL association, and 12 heterotaxy syndrome. Seven infants had an aortic coarctation diagnosed at birth.In conclusion, a thorough prenatal ultrasound examination is paramount, and the identification of variants of the venous/arterial system in addition to PLSVC should raise suspicion for genetic or morphologic abnormalities. Invasive prenatal diagnosis with array-CGH should be offered when PLSVC is non-isolated, after a detailed ultrasound evaluation in a tertiary center.

A cluster-randomized trial to reduce cesarean delivery rates in Quebec.

BACKGROUND: In Canada, cesarean delivery rates have increased substantially over the past decade. Effective, safe strategies are needed to reduce these rates. METHODS: We conducted a cluster-randomized, controlled trial of a multifaceted 1.5-year intervention at 32 hospitals in Quebec. The intervention involved audits of indications for cesarean delivery, provision of feedback to health professionals, and implementation of best practices. The primary outcome was the cesarean delivery rate in the 1-year postintervention period. RESULTS: Among the 184,952 participants, 53,086 women delivered in the year before the intervention and 52,265 women delivered in the year following the intervention. There was a significant but small reduction in the rate of cesarean delivery from the preintervention period to the postintervention period in the intervention group as compared with the control group (change, 22.5% to 21.8% in the intervention group and 23.2% to 23.5% in the control group; odds ratio for incremental change over time, adjusted for hospital and patient characteristics, 0.90; 95% confidence interval [CI], 0.80 to 0.99; P=0.04; adjusted risk difference, -1.8%; 95% CI, -3.8 to -0.2). The cesarean delivery rate was significantly reduced among women with low-risk pregnancies (adjusted risk difference, -1.7%; 95% CI, -3.0 to -0.3; P=0.03) but not among those with high-risk pregnancies (P=0.35; P = 0.03 for interaction). The intervention group also had a reduction in major neonatal morbidity as compared with the control group (adjusted risk difference, -0.7%; 95% CI, -1.3 to -0.1; P=0.03) and a smaller increase in minor neonatal morbidity (adjusted risk difference, -1.7%; 95% CI, -2.6 to -0.9; P<0.001). Changes in minor and major maternal morbidity did not differ significantly between the groups. CONCLUSIONS: Audits of indications for cesarean delivery, feedback for health professionals, and implementation of best practices, as compared with usual care, resulted in a significant but small reduction in the rate of cesarean delivery, without adverse effects on maternal or neonatal outcomes. The benefit was driven by the effect of the intervention in low-risk pregnancies. (Funded by the Canadian Institutes of Health Research; QUARISMA Current Controlled Trials number, ISRCTN95086407.).

Genomic study of severe fetal anomalies and discovery of GREB1L mutations in renal agenesis.

PURPOSE: Fetal anomalies represent a poorly studied group of developmental disorders. Our objective was to assess the impact of whole-exome sequencing (WES) on the investigation of these anomalies. METHODS: We performed WES in 101 fetuses or stillborns who presented prenatally with severe anomalies, including renal a/dysgenesis, VACTERL association (vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb abnormalities), brain anomalies, suspected ciliopathies, multiple major malformations, and akinesia. RESULTS: A molecular diagnosis was obtained in 19 cases (19%). In 13 of these cases, the diagnosis was not initially suspected by the clinicians because the phenotype was nonspecific or atypical, corresponding in some cases to the severe end of the spectrum of a known disease (e.g., MNX1-, RYR1-, or TUBB-related disorders). In addition, we identified likely pathogenic variants in genes (DSTYK, ACTB, and HIVEP2) previously associated with phenotypes that were substantially different from those found in our cases. Finally, we identified variants in novel candidate genes that were associated with perinatal lethality, including de novo mutations in GREB1L in two cases with bilateral renal agenesis, which represents a significant enrichment of such mutations in our cohort. CONCLUSION: Our study opens a window on the distinctive genetic landscape associated with fetal anomalies and highlights the power-but also the challenges-of WES in prenatal diagnosis.

Prenatal vitamin D status and offspring's growth, adiposity and metabolic health: a systematic review and meta-analysis.

In this systematic review and meta-analysis of observational studies, we aimed to estimate the associations between prenatal vitamin D status and offspring growth, adiposity and metabolic health. We searched the literature in human studies on prenatal vitamin D status and offspring growth in PubMed, up to July 2017. Studies were selected according to their methodological quality and outcomes of interest (anthropometry, fat mass and diabetes in offspring). The inverse variance method was used to calculate the pooled mean difference (MD) with 95 % CI for continuous outcomes, and the Mantel-Haenszel method was used to calculate the pooled OR with 95 % CI for dichotomous outcomes. In all, thirty observational studies involving 35 032 mother-offspring pairs were included. Vitamin D status was evaluated by circulating 25-hydroxyvitamin D (25(OH)D) level. Low vitamin D status was based on each study's cut-off for low 25(OH)D levels. Low prenatal vitamin D levels were associated with lower birth weight (g) (MD -100·69; 95 % CI -162·25, -39·13), increased risk of small-for-gestational-age (OR 1·55; 95 % CI 1·16, 2·07) and an elevated weight (g) in infant at the age of 9 months (g) (MD 119·75; 95 % CI 32·97, 206·52). No associations were observed between prenatal vitamin D status and other growth parameters at birth, age 1 year, 4-6 years or 9 years, nor with diabetes type 1. Prenatal vitamin D may play a role in infant adiposity and accelerated postnatal growth. The effects of prenatal vitamin D on long-term metabolic health outcomes in children warrant future studies.

Factors associated to early intrauterine fetal demise after laser for TTTS by preoperative fetal heart and Doppler ultrasound.

OBJECTIVE: To determine the prognostic value of fetal Doppler and echocardiographic parameters for intrauterine fetal demise (IUFD) within 24 hours and within 1 week after laser coagulation in monochorionic pregnancies complicated by twin-twin transfusion syndrome. METHOD: This retrospective study correlated the preoperative hemodynamic and echocardiography parameters to the outcome in fetuses with twin-twin transfusion syndrome undergoing laser therapy. RESULTS: One hundred and twelve laser coagulations were performed between February 2006 and June 2015. The total (single and double) IUFD rate was 27.7%. Further, 59% of IUFD occurred within 24 hours and 74.4% occurred within 1 week after laser. The following were associated to IUFD within 24 hours: the middle cerebral arterial pulsatility index in the donor, abnormal umbilical artery (UA) end diastolic flow, increased middle cerebral artery peak systolic velocity, and right ventricular myocardial performance index (RV-MPI) z-score in the recipient. For IUFD within 1 week were the pulsatility index in the donor UA and the recipient abnormalities in UA, ductus venosus, middle cerebral artery-peak systolic velocity, and RV-MPI z-score. CONCLUSION: Following laser was early IUFD that was associated with Doppler findings suggesting donor cerebroplacental redistribution, and recipient overload cardiomyopathy, such as abnormal ductus venosus and UA Dopplers as well as an increase of RV-MPI.

No. 363-Investigation and Management of Non-immune Fetal Hydrops.

OBJECTIVE: To describe the current investigation and management of non-immune fetal hydrops with a focus on treatable or recurring etiologies. OUTCOMES: To provide better counselling and management in cases of prenatally diagnosed non-immune hydrops. EVIDENCE: Published literature was retrieved through searches of PubMed or MEDLINE, CINAHL, and The Cochrane Library in 2017 using key words (non-immune hydrops fetalis, fetal hydrops, fetal therapy, fetal metabolism). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, observational studies, and significant case reports. Additional publications were identified from the bibliographies of these articles. There were no date or language restrictions. Searches were updated on a regular basis and incorporated in the guideline to September 2017. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinicalpractice guideline collections, clinical trial registries, and national and international medical specialty societies. BENEFITS, HARMS, AND COSTS: These guidelines educate readers about the causes of non-immune fetal hydrops and its prenatal counselling and management. It also provides a standardized approach to non-immune fetal hydrops, emphasizing the search for prenatally treatable conditions and recurrent genetic etiologies. VALUES: The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care.

N° 363 - Évaluation et prise en charge de l'anasarque fœtoplacentaire non immune.

OBJECTIF: Décrire les méthodes actuelles d'évaluation et de prise en charge de l'anasarque fœtoplacentaire non immune en mettant l'accent sur les étiologies traitables ou récurrentes. RéSULTATS: Offrir de meilleurs services de conseil et de prise en charge en cas d'anasarque fœtoplacentaire non immune diagnostiquée en période prénatale. DONNéES: La littérature publiée a été récupérée au moyen de recherches menées dans PubMed, MEDLINE, CINAHL, et la Bibliothèque Cochrane en 2017 à l'aide de mots-clés (« non-immune hydrops fetalis ¼, « fetal hydrops ¼, « fetal therapy ¼, « fetal metabolism ¼). Les articles retenus portaient sur des revues systématiques, des essais cliniques contrôlés, randomisés ou non, des études observationnelles et des études de cas importantes. D'autres publications ont été repérées dans les bibliographies de ces articles. Aucune restriction de date ou de langue n'a été employée. Les recherches ont été mis à jour régulièrement, et les résultats ont été incorporés à la directive clinique jusqu'en septembre 2017. Nous avons également tenu compte de la littérature grise (non publiée) trouvée sur les sites Web d'organismes d'évaluation des technologies de la santé et d'autres organismes liés aux technologies de la santé, dans des collections de directives cliniques et des registres d'essais cliniques, et obtenue auprès d'associations nationales et internationales de médecins spécialistes. AVANTAGES, INCONVéNIENTS ET COûTS: La présente directive clinique renseigne les lecteurs sur les causes de l'anasarque fœtoplacentaire non immune ainsi que sur son évaluation et sa prise en charge. Elle propose également une approche standardisée d'évaluation et de prise en charge, et met l'accent sur la recherche des conditions traitables en période prénatale et des étiologies génétiques récurrentes. VALEURS: La qualité des données probantes a été évaluée en fonction des critères décrits dans le rapport du Groupe d'étude canadien sur les soins de santé préventifs. RECOMMANDATIONS.

Cell-Free DNA-Based Non-invasive Prenatal Screening for Common Aneuploidies in a Canadian Province: A Cost-Effectiveness Analysis.

OBJECTIVE: Yearly, 450 000 pregnant Canadians are eligible for voluntary prenatal screening for trisomy 21. Different screening strategies select approximately 4% of women for invasive fetal chromosome testing. Non-invasive prenatal testing (NIPT) using maternal blood cell-free DNA could reduce those invasive procedures but is expensive. This study evaluated the cost-effectiveness of NIPT strategies compared with conventional strategies. METHODS: This study used a decision analytic model to estimate the cost-effectiveness of 13 prenatal screening strategies for fetal aneuploidies: six frequently used strategies, universal NIPT, and six strategies incorporating NIPT as a second-tier test. The study considered a virtual cohort of pregnant women of similar size and age as women in Quebec. Model data were obtained from published sources and government databases. The study predicted the number of chromosomal anomalies detected (trisomies 21, 13, and 18), invasive procedures and euploid fetal losses, direct costs, and incremental cost-effectiveness ratios. RESULTS: Of the 13 strategies compared, eight identified fewer cases at a higher cost than at least one of the remaining five strategies. Integrated serum screening with conditional NIPT had the lowest cost, and the cost per case detected was $63 139, with a 90% reduction of invasive procedures. The number of cases identified was improved with four other screening strategies, but with increasing of incremental costs per case (from $61 623 to $1 553 615). Results remained robust, except when NIPT costs and risk cut-offs varied. CONCLUSION: NIPT as a second-tier test for high-risk women is likely to be cost-effective as compared with screening algorithms not involving NIPT.

Aortic Isthmus Flow Recording Predicts the Outcome of the Recipient Twin after Laser Coagulation in Twin-Twin Transfusion Syndrome.

INTRODUCTION: The objective was to assess the prognostic value of the systolic flow through the aortic isthmus in monochorionic pregnancies complicated by twin-twin transfusion syndrome (TTTS) treated by placental laser ablation. MATERIAL AND METHODS: Fetal echocardiography and outcome data of 105 cases of TTTS treated by laser photocoagulation of placental anastomoses were reviewed. Hemodynamic parameters were collected before and after treatment. The isthmic systolic index (ISI) was calculated as the peak systolic velocity/systolic nadir ratio. RESULTS: A total of 105 laser coagulations were studied. Fetal echocardiography pre- and post-laser were available in 68 cases, including 55 with data on aortic isthmic Doppler. Survival rates were 17, 22, and 61% for 0, 1, or 2 twins, respectively. At least 1 twin was delivered alive in 83% of the pregnancies. The mean gestational age at surgery was 21 weeks (range 16-26). Median ISI values were similar for donor and recipient twins, before and after laser ablation (all p > 0.05). A lower recipient ISI before laser was related to early recipient demise within 24 h (p = 0.04). DISCUSSION: A lower ISI before placental laser ablation for TTTS is associated with postoperative demise of the recipient twin.

Comparison of first-tier cell-free DNA screening for common aneuploidies with conventional publically funded screening.

OBJECTIVE: This study evaluates the impact of offering cell-free DNA (cfDNA) screening as a first-tier test for trisomies 21 and 18. METHODS: This is a prospective study of pregnant women undergoing conventional prenatal screening who were offered cfDNA screening in the first trimester with clinical outcomes obtained on all pregnancies. RESULTS: A total of 1198 pregnant women were recruited. The detection rate of trisomy 21 with standard screening was 83% with a false positive rate (FPR) of 5.5% compared with 100% detection and 0% FPR for cfDNA screening. The FPR of cfDNA screening for trisomies 18 and 13 was 0.09% for each. Two percent of women underwent an invasive diagnostic procedure based on screening or ultrasound findings; without the cfDNA screening, it could have been as high as 6.8%. Amongst the 640 women with negative cfDNA results and a nuchal translucency (NT) ultrasound, only 3 had an NT greater or equal to 3.5 mm: one had a normal outcome and two lost their pregnancy before 20 weeks. CONCLUSIONS: cfDNA screening has the potential to be a highly effective first-tier screening approach leading to a significant reduction of invasive diagnostic procedures. For women with a negative cfDNA screening result, NT measurement has limited clinical utility.

No. 262-Prenatal Screening for and Diagnosis of Aneuploidy in Twin Pregnancies.

OBJECTIVE: To provide a Canadian consensus document with recommendations on prenatal screening for and diagnosis of fetal aneuploidy (e.g., Down syndrome and trisomy 18) in twin pregnancies. OPTIONS: The process of prenatal screening and diagnosis in twin pregnancies is complex. This document reviews the options available to pregnant women and the challenges specific to screening and diagnosis in a twin pregnancy. OUTCOMES: Clinicians will be better informed about the accuracy of different screening options in twin pregnancies and about techniques of invasive prenatal diagnosis in twins. EVIDENCE: PubMed and Cochrane Database were searched for relevant English and French language articles published between 1985 and 2010, using appropriate controlled vocabulary and key words (aneuploidy, Down syndrome, trisomy, prenatal screening, genetic health risk, genetic health surveillance, prenatal diagnosis, twin gestation). Results were restricted to systematic reviews, randomized controlled trials, and relevant observational studies. Searches were updated on a regular basis and incorporated in the guideline to August 2010. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The previous Society of Obstetricians and Gynaecologists of Canada guidelines regarding prenatal screening were also reviewed in developing this clinical practice guideline. VALUES: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). BENEFITS, HARMS, AND COSTS: There is a need for specific guidelines for prenatal screening and diagnosis in twins. These guidelines should assist health care providers in the approach to this aspect of prenatal care of women with twin pregnancies. SUMMARY STATEMENTS: RECOMMENDATIONS.

No. 348-Joint SOGC-CCMG Guideline: Update on Prenatal Screening for Fetal Aneuploidy, Fetal Anomalies, and Adverse Pregnancy Outcomes.

OBJECTIVE: To review the available prenatal screening options in light of the recent technical advances and to provide an update of previous guidelines in the field of prenatal screening. INTENDED USERS: Health care providers involved in prenatal screening, including general practitioners, obstetricians, midwives, maternal fetal medicine specialists, geneticists, and radiologists. TARGET POPULATION: All pregnant women receiving counselling and providing informed consent for prenatal screening. EVIDENCE: Published literature was retrieved through searches of Medline, PubMed, and the Cochrane Library in and prior to March 2016 using an appropriate controlled vocabulary (prenatal diagnosis, amniocentesis, chorionic villi sampling, non-invasive prenatal screening) and key words (prenatal screening, prenatal genetic counselling). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies written in English and published from January 1985 to May 2016. Searches were updated on a regular basis and incorporated in the guideline. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical speciality societies. GUIDELINE UPDATE: Evidence will be reviewed 5 years after publication to determine whether all or part of the guideline should be updated. However, if important new evidence is published prior to the 5-year cycle, the review process may be accelerated for a more rapid update of some recommendations.