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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.

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 β-human chorionic gonadotropin (free β-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%.

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

ObjectivesTo determine the efficacy and safety of sildenafil citrate to improve outcomes in pregnancies complicated by early-onset, dismal prognosis, fetal growth restriction (FGR). Eligibility: women ≥18 years, singleton, 18 +0–27 +6 weeks’ gestation, estimated fetal weight ResultsBetween May 2017 and June 2018, 21 (90 planned) women were randomised (10 sildenafil; 11 placebo [1 withdrawal]). Baseline characteristics, PlGF levels, maternal and perinatal outcomes, and adverse events did not differ. Delivery GA: 30 +1 weeks (sildenafil) vs 28 +6 weeks (placebo); p=0.555. Early trial termination precluded statistical power; however, there were signals of neither benefit nor harm. Data will contribute to an individual participant data meta-analysis.

Hypertension Canada's 2020 guidelines for the prevention, diagnosis, risk assessment, and treatment of hypertension in adults and children provide comprehensive, evidence-based guidance for health care professionals and patients. Hypertension Canada develops the guidelines using rigourous methodology, carefully mitigating the risk of bias in our process. All draft recommendations undergo critical review by expert methodologists without conflict to ensure quality. Our guideline panel is diverse, including multiple health professional groups (nurses, pharmacy, academics, and physicians), and worked in concert with experts in primary care and implementation to ensure optimal usability. The 2020 guidelines include new guidance on the management of resistant hypertension and the management of hypertension in women planning pregnancy.

Key Points Question Is human papillomavirus (HPV) infection during pregnancy associated with preterm delivery? Findings In this multicenter cohort study of 899 pregnant women, persistent HPV-16/18 infection during pregnancy was significantly associated with preterm birth. Meaning If the identified association between HPV infection during pregnancy and preterm delivery is causal, HPV vaccination may reduce preterm birth and the associated burden., Importance Preterm birth remains a leading cause of perinatal mortality and lifelong morbidity worldwide. The cause of most preterm births is unknown, although several infectious processes have been implicated. Objective To assess whether human papillomavirus (HPV) infection, a frequent infection among women of childbearing age, is associated with preterm birth. Design, Setting, and Participants The prospective HERITAGE cohort study was conducted at 3 academic hospitals in Montreal, Québec, Canada, among 899 pregnant women recruited between November 8, 2010, and October 16, 2016. Follow-up was completed on June 15, 2017. Statistical analysis was conducted from February 6, 2020, to January 21, 2021. Exposures Vaginal HPV DNA detection in the first and third trimesters of pregnancy and placental HPV infection. Main Outcomes and Measures The main outcome was preterm birth (defined as a live birth or stillbirth between 20 weeks and 0 days and 36 weeks and 6 days of gestation). The association between HPV DNA detection and preterm birth was measured using logistic regression. Odds ratios (ORs) and 95% CIs were adjusted by inverse probability of treatment weights of the propensity score. Results The study included 899 women (mean [SD] age, 31.3 [4.6] years [range, 19-47 years]) with singleton pregnancies. A total of 378 women (42.0%) had HPV DNA detected in vaginal samples collected during the first trimester, and it was detected in 91 of 819 placentas (11.1%) at delivery. Fifty-five participants experienced preterm birth (38 spontaneous and 17 medically indicated). Persistent vaginal HPV-16/18 detection was significantly associated with all preterm births (adjusted OR [aOR], 3.72; 95% CI, 1.47-9.39) and spontaneous preterm births (aOR, 3.32; 95% CI, 1.13-9.80), as was placental HPV infection (all preterm births: aOR, 2.53; 95% CI, 1.06-6.03; spontaneous preterm births: aOR, 2.92; 95% CI, 1.09-7.81). Results were similar when restricting the analysis to participants without a history of cervical intraepithelial neoplasia treatment. Conclusions and Relevance The study’s results suggest that persistent HPV-16/18 infection is associated with an increased risk of preterm birth, independent of cervical treatment. Future studies should investigate the association of HPV vaccination and vaccination programs with the risk of preterm birth., This cohort study assesses whether human papillomavirus infection, a frequent infection among women of childbearing age, is associated with preterm birth.

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

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. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Objective To examine the associations between risk of pre-eclampsia and pregnancy levels of maternal 25-hydroxyvitamin D (25[OH]D) and oxidative stress biomarkers. Methods A nested case-control study (n = 99; 34 cases; 65 controls) within a prospective pregnancy cohort. Maternal 25(OH)D and oxidative stress markers (six isomers of F2 -isoprostanes; F2 -isoPs) were measured in plasma at 12-18 and 24-26 gestational weeks. Vitamin D deficiency was defined as 25[OH]D less than 50 nmol/L. Results Maternal vitamin D deficiency was associated with increased 8-iso-PGF2α (P = 0.037), 15(R)-PGF2α (P = 0.004), (±)5-iPF2α -VI (P = 0.026) at 12-18 weeks. Vitamin D deficiency was inversely associated with 8-iso-PGF2α (P = 0.019) and (±)5-iPF2α -VI isomer (P = 0.010) at 24-26 weeks. Both maternal vitamin D deficiency (adjusted odds ratio [aOR], 4.79; 95% confidence interval [CI], 1.67-13.75) and increased (±)5-iPF2α -VI (aOR, 2.46; 95% CI, 1.16-5.22) at 24-26 weeks were associated with risk of pre-eclampsia. However, the interaction test between 25(OH)D and (±)5-iPF2α -VI was not significant (P = 0.143). Conclusion Plasma 25(OH)D below 50 nmol/L was associated with increased oxidative stress levels during pregnancy as measured by two F2 -isoP isomers, including the well-studied marker 8-iso-PGF2α . Whether vitamin D-induced oxidative stress mediates the risk of pre-eclampsia warrants future study.

Objective Examine the levels of plasma antioxidant vitamins before and during a treatment with placebo or vitamin E + C supplement to prevent preeclampsia (PE). Study design Per-protocol analysis of a subset group of pregnant women (n = 295) from the International Trial of Antioxidants for the Prevention of PE (INTAPP) randomized case-control study. Normotensive receiving placebo or vitamins (n = 115 and 87 respectively) were compared to gestational hypertension (GH) without proteinuria (n = 30 and 27) and PE (n = 21 and 15). Vitamin quantification was performed at 12–18, 24–26 and 32–34 weeks of gestation. Main outcome measures Coenzyme (Co) Q10, β-carotene and vitamins E (α and γ forms) plasma levels. Results Vitamin E + C supplementation was found to increase the α-tocopherol levels by 40% but was associated with a 57% decrease in the γ-tocopherol isoform for all study groups (p Conclusions A more personalized approach that target the suboptimal levels of specific antioxidants without disturbing the α/γ-tocopherol ratio could be a more successful approach to counteract oxidative stress in PE.

Resume Objectif Decrire les moyens actuels de proceder a l'exploration et a la prise en charge de l'anasarque fœtoplacentaire non immune, en mettant l'accent sur les etiologies traitables ou recurrentes. issues Offrir de meilleurs services de counseling et de prise en charge en presence de cas d'anasarque non immune identifies par diagnostic prenatal. Resultats La litterature publiee a ete recuperee par l'intermediaire de recherches menees dans PubMed, CINAHL et The Cochrane Library en 2011 au moyen de mots cles (« non-immune hydrops fetalis », « fetal hydrops », « fetal therapy », « fetal metabolism »). Les resultats ont ete restreints aux analyses systematiques, aux essais comparatifs randomises / essais cliniques comparatifs, aux etudes observationnelles et aux exposes de cas significatifs. D'autres publications ont ete reperees a partir des bibliographies de ces articles. Aucune restriction n'a ete appliquee en matiere de date ou de langue. Les recherches ont ete mises a jour de facon reguliere et integrees a la directive clinique jusqu'en mai 2012. La litterature grise (non publiee) a ete identifiee par l'intermediaire de recherches menees dans les sites Web d'organismes s'interessant a l'evaluation des technologies dans le domaine de la sante et d'organismes connexes, dans des collections de directives cliniques, dans des registres d'essais cliniques et aupres de societes de specialite medicale nationales et internationales. Avantages, desavantages et couts La presente directive clinique sensibilise les lecteurs aux causes de l'anasarque fœtoplacentaire non immune, ainsi qu'au diagnostic prenatal et a la prise en charge de celle-ci. Elle offre egalement une approche standardisee envers l'anasarque fœtoplacentaire non immune, en mettant l'accent sur la recherche de troubles pouvant etre pris en charge pendant la periode prenatale et d'etiologies genetiques recurrentes. valeurs La qualite des resultats est evaluee au moyen des criteres decrits dans le rapport du Groupe d'etude canadien sur les soins de sante preventifs (Tableau 1). Recommandations 1.Toutes les patientes qui presentent une anasarque fœtoplacentaire devraient etre orientees sans delai vers un centre de soins tertiaires a des fins d'evaluation. Certains troubles pouvant faire l'objet d'un traitement prenatal constituent une urgence therapeutique apres 18 semaines. (II-2A) 2.L'analyse chromosomique fœtale et le depistage moleculaire sur microreseau d'ADN devraient etre offerts (la ou cela s'avere possible) dans tous les cas d'anasarque fœtoplacentaire non immune. (II-2A) 3.Les etudes d'imagerie devraient comprendre une echographie obstetricale exhaustive (dont des etudes Doppler arterielles et veineuses fœtales) et une echocardiographie fœtale. (II-2A) 4.Chez les femmes exposees a des risques en raison de leur origine ethnique, des explorations visant des infections fœto-maternelles et l'alpha-thalassemie devraient etre menees dans tous les cas d'anasarque fœtoplacentaire inexpliquee. (II-2A) 5.Pour evaluer le risque d'anemie fœtale, la mesure du pic de vitesse systolique de l'artere cerebrale moyenne par etude Doppler devrait etre menee chez tous les fœtus hydropiques apres 16 semaines de gestation. Lorsque l'on soupconne la presence d'une anemie fœtale, le prelevement de sang fœtal et la transfusion intra-uterine devraient etre offerts rapidement. (II-2A) 6.Tous les cas d'anasarque fœtoplacentaire inexpliquee devraient etre orientes vers des services de genetique medicale, lorsque de tels services sont disponibles. Une evaluation postnatale detaillee devrait etre menee par un geneticien medical pour tous les nouveau-nes presentant une anasarque non immune inexpliquee. (II-2A) 7.La tenue d'une autopsie devrait etre recommandee dans tous les cas d'interruption de grossesse ou de deces fœtal ou neonatal. (II-2A) Du liquide amniotique et/ou des cellules fœtales devraient etre conserves aux fins de la tenue d'un futur depistage genetique. (II-2B)

Background Diabetes and pregnancy are both associated with oxidative stress, characterized by an increase of F2-isoprostanes from the non-enzymatic oxidation of arachidonic acid, a n − 6 polyunsaturated fatty acid (PUFA). We hypothesized that pregnant women with pre-existing diabetes will be characterized by elevated levels of specific F2-isoPs isomers and altered PUFA composition in plasma early pregnancy when compared to normoglycemic controls. Methods Plasma samples from 23 women with uncomplicated pregnancies and 11 women with pre-existing diabetes in pregnancy were collected between 12 and 18 weeks of pregnancy (MIROS cohort). Six F2-isoprostanes isomers were measured by high-performance liquid chromatography coupled to tandem mass spectrometry. Fatty acids concentrations in plasmatic phospholipids were measured by gas chromatography coupled to a flame ionization detector. Results F2-isoprostanes, specifically the 8-iso-15(R)-PGF2α levels, were 67% higher in diabetic than normoglycemic pregnancies (p = 0.026). The total n − 6 PUFA and arachidonic acid level did not differ between study groups. In contrast, total n − 3 level was 32% lower in diabetic pregnancies than in controls (p = 0.002); EPA(20:5) and DHA(22:6) being specifically reduced (p = 0.035 and p = 0.003 respectively). Delta-6-desaturase (D6D) activity index, calculated using fatty acid ratios, was 9% lower in pre-existing diabetes than in controls (p = 0.042). Conclusions Pre-existing diabetes in early pregnancy displays a distinctive F2-isoprostanes profile when compared to other pathologies of pregnancy, such as preeclampsia, as previously assessed in the same cohort.

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. Recommendations 1.All patients with fetal hydrops should be referred promptly to a tertiary care centre for evaluation. Some conditions amenable to prenatal treatment represent a therapeutic emergency after 18 weeks, allowing prolongation of pregnancy with improved fetal/neonatal outcomes (II-2A). 2.Fetal chromosome analysis through array comparative genomic hybridization (microarray) molecular testing should be offered where available in all cases of non-immune fetal hydrops (II-2A). 3.Imaging studies should include comprehensive obstetrical ultrasound (including arterial and venous fetal Doppler) and fetal echocardiography (II-2A). 4.Investigation for maternal–fetal infections and alpha-thalassemia in women at risk because of their ethnicity should be performed in all cases of unexplained fetal hydrops (II-2A). 5.To evaluate the risk of fetal anemia, Doppler measurement of the middle cerebral artery peak systolic velocity should be performed in all hydropic fetuses after 16 weeks of gestation. In case of suspected fetal anemia, fetal blood sampling and intrauterine transfusion should be offered rapidly (II-2A). 6.All cases of unexplained fetal hydrops should be referred to a medical genetics service where available. Detailed postnatal evaluation by a medical geneticist should be performed on all cases of newborns with unexplained non-immune hydrops (II-2A). 7.Autopsy is strongly recommended for all cases of fetal or neonatal death for which no diagnosis is reached prenatally (II-2A).

Background: There is a paucity of data on the dynamics of human papillomavirus (HPV) antibodies in children. We aimed to describe the vertical transmission and clearance of antibodies against HPV6, 11, 16 and 18 in children.Methods: We used data from pregnant women recruited into the HERITAGE cohort study between 2009 and 2012 who were positive for HPV-DNA at baseline. Dried blood spots were collected during the first trimester in pregnant participants, and at birth, 6, 12, and 24 months of age in children. The level of total immunoglobulin G (IgG) against HPV6, 11, 16 and 18 were measured using Luminex immunoassays. Spearman's coefficients were used to correlate HPV antibody levels between newborns and mothers. Panel and Kaplan-Meier graphics described antibody dynamics in the first 24 months of life.Findings: Antibodies from newborns and mothers (n = 58 pairs) were moderately to highly correlated with coefficients of 0·81 (95% confidence intervals (CI):0·70–0·88), 0·68 (95% CI:0·5–0·80), 0·90 (95% CI:0·83–0·94) and 0·85 (95% CI:0·76–0·91) against HPV6, 11, 16 and 18, respectively. In newborns seropositive at birth, anti-HPV antibodies were cleared by 80% and 100% at 12 and 24 months, respectively. Only two children presented detectable HPV antibodies at 24 months. The first child had no detectable antibodies at birth and the second presented increasing levels after two undetected measures.Interpretation: Correlation between mother and newborn IgG antibodies against HPV suggests vertical transfer. Most children cleared anti-HPV antibodies within six to 12 months.Funding: The Canadian Institutes of Health Research (CIHR) Keywords: Human papillomavirus, Serology, Mother-newborn correlation, Vertically acquired immunity, Antibody clearance, Antibody dynamics

OBJECTIVE To determine whether pre-eclampsia is associated with polymorphisms in superoxide dismutase (SOD) genes among mother-father-infant triads. METHODS We did this follow-up cohort study at 17 urban hospitals in Canada between October 1, 2008, and September 30, 2010. We recruited Canadian participants who had participated in the International Trial of Antioxidant Supplementation for the Prevention of Pre-eclampsia. Saliva specimens were collected for DNA extraction. The SOD1 +35A/C (rs2234694) and SOD2 Ala16Val C/T (rs4880) single-nucleotide polymorphisms (SNPs) were genotyped. RESULTS Dual presence of the SOD2 Ala16Val TT variant among mother-father pairs (n=657) was associated with an increased risk of pre-eclampsia when compared with the absence of the TT variant among the mother-father pairs (7/48 [14.6%] vs 11/339 [3.2%]; adjusted odds ratio 6.80, 95% confidence interval 2.32-19.95; P

We present Hypertension Canada's inaugural evidence-based Canadian recommendations for the management of hypertension in pregnancy. Hypertension in pregnancy is common, affecting approximately 7% of pregnancies in Canada, and requires effective management in order to reduce maternal, fetal and newborn complications. Given this importance, these guidelines were developed in partnership with the Society of Obstetricians and Gynaecologists of Canada with the main common objective of improving the management of women with hypertension in pregnancy. Guidelines for the diagnosis, assessment, prevention and treatment of hypertension in adults and children are published separately. In this first Hypertension Canada Guidelines for hypertension in pregnancy, seven recommendations for the management of non-severe and severe hypertension in pregnancy are presented. For non-severe hypertension in pregnancy (systolic blood pressure 140-159 mm Hg and/or diastolic blood pressure 80-109 mm Hg), we provide guidance for the threshold for initiation of antihypertensive therapy, blood pressure targets, as well as first- and second-line antihypertensive medications. Severe hypertension (systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥110 mm Hg) requires urgent antihypertensive therapy to reduce maternal, fetal and newborn adverse outcomes. The specific evidence and rationale underlying each of these guidelines are discussed.

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.

Resume Objectif Elaborer un document de consensus canadien formulant des recommandations quant au depistage et au diagnostic prenatals de l'aneuploidie foetale (p. ex, syndrome de Down et trisomie 18) en ce qui concerne les grossesses gemellaires. Options Le processus mis en oeuvre pour le depistage et le diagnostic prenatals dans les cas de grossesse gemellaire est complexe. Le present document analyse les options offertes aux femmes enceintes et les defis propres au depistage et au diagnostic dans le cadre d'une grossesse gemellaire. Issues Les cliniciens seront mieux renseignes au sujet de la precision des differentes options de depistage en ce qui concerne les grossesses gemellaires, ainsi qu'au sujet des techniques de diagnostic prenatal effractif a utiliser dans les cas de grossesse gemellaire. Resultats Des recherches ont ete menees dans PubMed et la base de donnees Cochrane afin d'en tirer les articles pertinents publies en anglais et en francais entre 1985 et 2010, au moyen d'un vocabulaire controle et de mots cles appropries (« aneuploidy », « Down syndrome », « trisomy », « prenatal screening », « genetic health risk », « genetic health surveillance », « prenatal diagnosis », « twin gestation »). Les resultats ont ete restreints aux analyses systematiques, aux essais comparatifs randomises / essais cliniques comparatifs et aux etudes observationnelles pertinentes. Les recherches ont ete mises a jour de facon reguliere et integrees a la directive clinique jusqu'en aout 2010. La litterature grise (non publiee) a ete identifiee par l'intermediaire de recherches menees dans les sites Web d'organismes s'interessant a l'evaluation des technologies dans le domaine de la sante et d'organismes connexes, dans des collections de directives cliniques, dans des registres d'essais cliniques et aupres de societes de specialite medicale nationales et internationales. Les directives cliniques precedemment publiees par la Societe des obstetriciens et gynecologues du Canada au sujet du depistage prenatal ont egalement ete analysees dans le cadre de l'elaboration de la presente directive clinique. Valeurs La qualite des resultats a ete evaluee au moyen des criteres decrits dans le rapport du Groupe d'etude canadien sur les soins de sante preventifs (Tableau 1). Avantages, desavantages et couts La formulation d'une directive clinique traitant particulierement du depistage et du diagnostic prenatals dans les cas de grossesse gemellaire s'avere requise. La presente directive clinique devrait aider les fournisseurs desoins de sante a aborder cet aspect des soins prenatals a offrir aux femmes connaissant une grossesse gemellaire. Declarations sommaires 1.L'utilisation concomitante de la clarte nucale foetale et de l'âge maternel constitue un test de depistage acceptable des aneuploidies au cours du premier trimestre, dans les cas de grossesse gemellaire. (II-2) 2.L'utilisation concomitante des marqueurs seriques et de la clarte nucale dans le cadre du depistage mene au cours du premier trimestre pourrait etre envisagee pour ce qui est des grossesses gemellaires. Elle offre une certaine amelioration en matiere de rendement, par comparaison avec l'utilisation de la clarte nucale et de l'âge maternel, en occasionnant une baisse du taux de faux positif. (II-3) 3.Le depistage integre (clarte nucale, conjointement avec le depistage serique mene au cours du premier et du deuxieme trimestres) constitue une option pour ce qui est des grossesses gemellaires. La tenue d'autres etudes prospectives s'avere requise dans ce domaine, puisque ce type de depistage n'a pas ete valide dans le cadre d'etudes prospectives portant sur des grossesses gemellaires. (III) 4.L'offre d'un counseling non directif s'avere essentielle lorsque l'on envisage le recours au depistage effractif. (III) 5.Lorsque l'on procede au prelevement des villosites choriales dans le cadre de grossesses multiples non monochorioniques, le recours a une approche combinee transabdominale et transcervicale ou a une approche seulement transabdominale semble fournir les meilleurs resultats pour ce qui est de la minimisation de la probabilite d'erreurs de prelevement. (II-2) Recommandations 1.Toutes les Canadiennes enceintes, sans egard a l'âge, devraient se voir offrir, par l'intermediaire d'un processus de counseling eclaire, l'option de subir un test de depistage prenatal visant les aneuploidies foetales significatives sur le plan clinique les plus courantes, en plus d'une echographie au deuxieme trimestre a des fins de datation, d'evaluation de l'anatomie foetale et de depistage des grossesses multiples. (I-A) 2.Les services de counseling doivent etre de nature non directive et doivent respecter le choix de la patiente d'accepter ou de refuser toute option ou tout depistage offert, et ce, a n'importe quel moment au cours du processus. (III-A) 3.Lorsqu'il s'avere possible de proceder a un depistage prenatal non effractif de l'aneuploidie, l'âge maternel seul ne devrait pas constituer une indication pour la mise en oeuvre d'un diagnostic prenatal effractif dans le cadre d'une grossesse gemellaire. (II-2A) Lorsque la mise en oeuvre d'un depistage prenatal non effractif ne s'avere pas possible, un diagnostic prenatal effractif devrait etre offert aux femmes de 35 ans ou plus qui connaissent une grossesse gemellaire. (II-2B) 4.La chorionicite exerce un effet important sur le processus de depistage prenatal et devrait etre determinee par echographie au cours du premier trimestre de toute grossesse gemellaire. (II-2A) 5.Lorsque le depistage est effectue au moyen de la clarte nucale et de l'âge maternel, et en presence de jumeaux monochorioniques, un risque propre a la grossesse devrait etre calcule. En presence de jumeaux dichorioniques, un risque propre au foetus devrait etre calcule. (II-3C) 6.Pour ce qui est des grossesses gemellaires monochorioniques, les deux poches amniotiques devraient faire l'objet d'un prelevement pendant l'amniocentese, sauf lorsque la monochorionicite a ete confirmee avant 14 semaines et que les foetus semblent presenter une concordance en matiere de croissance et d'anatomie. (II-2B) 7.Avant que le medecin ne procede a un depistage effractif ou lorsque des jumeaux presentent une discordance en ce qui concerne une anomalie, la reduction selective devrait faire l'objet de discussions et etre offerte aux patientes qui en font la demandeapres avoir recu des services de counseling adequats. (III-B) 8.La mise en oeuvre d'une surveillance visant la coagulation intravasculaire disseminee ne s'avere pas indiquee en ce qui concerne les grossesses gemellaires dichorioniques qui subissent une reduction selective. (II-2B)

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.

Resume Objectif Mettre a jour et passer en revue les techniques et les indications du diagnostic genetique preimplantatoire et du depistage genetique preimplantatoire. Options Discussion au sujet des aspects techniques et genetiques des techniques genesiques preimplantatoires, particulierement en ce qui concerne celles qui font appel aux nouvelles technologies cytogenetiques et a la biopsie au stade de l'embryon. Issues Les issues cliniques obtenues par les techniques genesiques a la suite du recours au diagnostic genetique preimplantatoire et au depistage genetique preimplantatoire sont incluses. La presente mise a jour ne traite pas en detail des issues indesirables qui ont ete signalees en association avec les technologies de procreation assistee. Resultats La litterature publiee a ete recuperee par l'intermediaire de recherches menees dans Medline et The Cochrane Library en avril 2014 au moyen d'un vocabulaire controle (« aneuploidy », « blastocyst/physiology », « genetic diseases », « preimplantation diagnosis/methods », « fertilization in vitro ») et de mots cles (p. ex. « preimplantation genetic diagnosis », « preimplantation genetic screening », « comprehensive chromosome screening », « aCGH », « SNP microarray », « qPCR » et « embryo selection ») appropries. Les resultats ont ete restreints aux analyses systematiques, aux etudes observationnelles et aux essais comparatifs randomises / essais cliniques comparatifs publies en anglais entre 1990 et avril 2014. Aucune restriction n'a ete imposee en matiere de langue. Les recherches ont ete mises a jour de facon reguliere et integrees a la directive clinique jusqu'en janvier 2015. Des publications additionnelles ont ete identifiees a partir des bibliographies des articles recuperes. La litterature grise (non publiee) a ete identifiee par l'intermediaire de recherches menees dans les sites Web d'organismes s'interessant a l'evaluation des technologies dans le domaine de la sante et d'organismes connexes, dans des collections de directives cliniques, dans des registres d'essais cliniques et aupres de societes de specialite medicale nationales et internationales. Valeurs La qualite des resultats a ete evaluee au moyen des criteres decrits dans le rapport du Groupe d'etude canadien sur les soins de sante preventifs (Tableau 1). Avantages, desavantages et couts La presente mise a jour permettra aux lecteurs d'en apprendre davantage au sujet des nouveautes en ce qui concerne les concepts, les orientations et les technologies genetiques preimplantatoires. Les principaux couts et desavantages identifies sont ceux qui sont associes aux technologies de procreation assistee. Sommaire Le diagnostic genetique preimplantatoire constitue une solution de rechange au diagnostic prenatal pour la detection des troubles genetiques chez les couples exposes a des risques de transmettre une pathologie genetique a leur progeniture. On avance que le depistage genetique preimplantatoire est en mesure d'ameliorer l'efficacite de la fecondation in vitro en permettant le depistage de l'aneuploidie embryonnaire. Bien que l'on ait constate que le depistage genetique preimplantatoire fonde sur la FISH donne lieu a des effets indesirables en ce qui concerne la reussite de la FIV, des donnees probantes issues de nouvelles etudes ayant fait appel au depistage chromosomique exhaustif semblent prometteuses. Recommandations 1.Avant la tenue d'un diagnostic genetique preimplantatoire, les patients doivent beneficier de services de counseling genetique offerts par un conseiller genetique agree, de facon a pouvoir bien comprendre le risque d'obtenir un enfant affecte, les effets de la maladie sur l'enfant affecte, ainsi que les avantages et les limites de toutes les options disponibles en matiere de diagnostic preimplantatoire et prenatal. (III-A) 2.Les couples devraient etre avises de la capacite du diagnostic genetique preimplantatoire a reduire le risque de concevoir un enfant presentant une anomalie genetique portee par l'un des parents ou les deux, lorsque l'anomalie en question peut etre identifiee au moyen de tests menes sur une seule cellule ou sur de multiples cellules trophectodermiques. (II-2B) 3.Le recours a des modalites effractives de depistage prenatal ou postnatal en vue de confirmer les resultats du diagnostic genetique preimplantatoire est favorise, puisque la possibilite de donner lieu a de faux resultats figure parmi les limites techniques de ce dernier. (II-2B) 4.La biopsie de cellules trophectodermiques n'exerce aucun effet mesurable sur le developpement de l'embryon, contrairement a la biopsie de blastomeres. Ainsi, dans la mesure du possible, la biopsie de cellules trophectodermiques devrait constituer la methode a privilegier pour la biopsie de l'embryon et devrait etre menee par des professionnels experimentes. (I-B) 5.Le diagnostic genetique preimplantatoire des maladies monogeniques devrait idealement etre effectue au moyen d'une amplification en chaine par polymerase multiplex, conjointement avec une biopsie de cellules trophectodermiques (lorsque cela s'avere possible). (II-2B) 6.Chez les couples porteurs de translocations chromosomiques, l'utilisation concomitante d'une technologie de depistage chromosomique exhaustif et d'une biopsie de cellules trophectodermiques est recommandee dans le cadre du diagnostic genetique preimplantatoire, car elle est associee a des issues cliniques favorables. (II-2B) 7.Avant la tenue d'un depistage genetique preimplantatoire, des renseignements et des services de counseling exhaustifs doivent etre offerts pour s'assurer que les patientes comprennent bien les limites de la technique, le risque d'erreur et le debat toujours en cours quant a la question de savoir si la tenue d'un tel depistage est necessaire pour l'amelioration des taux de naissance vivante dans le cadre de la fecondation in vitro. (III-A) 8.La mise en œuvre d'un depistage genetique preimplantatoire faisant appel a l'hybridation in situ en fluorescence appliquee a un embryon biopsie au jour 3 est associee a une baisse des taux de naissance vivante; un tel depistage ne devrait donc pas etre mene dans le cadre de la fecondation in vitro. (I-E) 9.La mise en œuvre d'un depistage genetique preimplantatoire faisant appel au depistage chromosomique exhaustif applique a un blastocyste biopsie entraine une hausse des taux d'implantation et une amelioration de la selection des embryons dans le cadre des cycles de FIV menes chez des patientes presentant un bon pronostic. (I-B)

Resume Objectif Fournir, aux professionnels de la sante des domaines de l'obstetrique et de la genetique, des lignes directrices et des recommandations en ce qui a trait au depistage / diagnostic prenatal et a la prise en charge obstetricale du dysraphisme spinal ouvert / ferme (DSOF) chez le fœtus. Options La presente analyse englobe les techniques de depistage / diagnostic prenatal qui sont actuellement utilisees aux fins de la detection du DSOF, y compris le depistage des concentrations seriques en alphafoetoproteines chez la mere, l'echographie, l'imagerie par resonance magnetique visant le fœtus et l'amniocentese. Issues Ameliorer le depistage / diagnostic prenatal et la prise en charge obstetricale du DSOF, tout en prenant en consideration les soins offerts a la patiente, l'efficacite, les couts et les interventions de soins. Resultats La litterature publiee a ete recuperee par l'intermediaire de recherches menees dans PubMed ou MEDLINE, CINAHL et The Cochrane Library en novembre 2013 au moyen d'un vocabulaire controle et de mots cles appropries (p. ex. « prenatal screening », « congenital anomalies », « neural tube defects », « alpha-fetoprotein », « ultrasound scan », « magnetic resonance imaging »). Les resultats ont ete restreints aux analyses systematiques, aux essais comparatifs randomises / essais cliniques comparatifs et aux etudes observationnelles publies en anglais entre 1977 et 2012. Les recherches ont ete mises a jour de facon reguliere et ont ete integrees a la directive clinique jusqu'au 30 novembre 2013. La litterature grise (non publiee) a ete identifiee par l'intermediaire de recherches menees dans les sites Web d'organismes s'interessant a l'evaluation des technologies dans le domaine de la sante et d'organismes connexes, dans des collections de directives cliniques, dans des registres d'essais cliniques et aupres de societes de specialite medicale nationales et internationales. Une enquete en ligne menee aupres des praticiens de la sante a egalement fait l'objet d'une analyse. Valeurs La qualite des resultats est evaluee au moyen des criteres decrits dans le rapport du Groupe d'etude canadien sur les soins de sante preventifs (Tableau). Avantages, desavantages et couts La presente analyse permettra aux professionnels de la sante de mieux comprendre les methodes de depistage prenatal du DSOF dont nous disposons a l'heure actuelle, ainsi que les avantages et les risques qui sont associes a chacune de ces methodes, pour assurer la prise de decisions factuelles en ce qui concerne le depistage, le diagnostic et la prise en charge obstetricale du DSOF.

Objectives To determine the prognostic value of fetal Doppler and echocardiographic parameters for neonatal survival up to 30 days after laser coagulation in monochorionic pregnancies complicated by twin-twin transfusion syndrome (TTTS). Methods Fetal echocardiography and outcome data of consecutive cases of TTTS treated by laser were retrospectively reviewed. Hemodynamic and cardiac function parameters were collected before and after laser. Results Between February 2006 and January 2015, 106 fetoscopic laser were performed. The final analysis was limited to cases with ultrasound within 2 days before laser (n = 77) and 4 weeks after laser (n = 86). Overall neonatal survival rate was 64.9% (135/208) and 77.9% of pregnancies (81/104) had at least one baby alive. For the recipient twin, the preoperative predictors of neonatal survival were umbilical artery (UA) pulsatility index (PI), cerebro-placental PI ratio, UA end diastolic flow (EDF), ductus venosus a-wave, right ventricular myocardial performance index (RV-MPI) and CHOP score. The postoperative predictors of donor survival were donor RV-MPI and recipient UA EDF, umbilical vein pulsations, tricuspid regurgitation, cardiac hypertrophy and CHOP score. Conclusion The hemodynamic predictors of postnatal survival after laser were preoperative signs of recipient cardiomyopathy and postoperative signs of cardiac overload in both twins.

Perinatal route of transmission of human papillomavirus (HPV) has been demonstrated in several small studies. We designed a large prospective cohort study (HERITAGE) to better understand perinatal HPV. The objective of this article is to present the study design and preliminary data. In the first phase of the study, we recruited 167 women in Montreal, Canada, during the first trimester of pregnancy. An additional 850 are currently being recruited in the ongoing phase. Cervicovaginal samples were obtained from mothers in the first trimester and tested for HPV DNA from 36 mucosal genotypes (and repeated in the third trimester for HPV-positive mothers). Placental samples were also taken for HPV DNA testing. Conjunctival, oral, pharyngeal and genital samples were collected for HPV DNA testing in children of HPV-positive mothers at every 3–6 months from birth until 2 years of age. Blood samples were collected in mother and children for HPV serology testing. We found a high prevalence of HPV in pregnant women (45%[95%CI:37–53%]) and in placentas (14%[8–21%]). The proportion of HPV positivity (any site) among children at birth/3-months was 11%[5–22%]. HPV was detected in children in multiple sites including the conjunctiva (5%[10–14%]). The ongoing HERITAGE cohort will help provide a better understanding of perinatal HPV. Keywords: Human papillomavirus (HPV), Perinatal transmission, Pregnancy, Placenta, Children, Persistence

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.

OBJECTIVE Describe renal function of preterm infants

Background The 3D Cohort Study (Design, Develop, Discover) was established to help bridge knowledge gaps about the links between various adverse exposures during pregnancy with birth outcomes and later health outcomes in children. Methods Pregnant women and their partners were recruited during the first trimester from nine sites in Quebec and followed along with their children through to 2 years of age. Questionnaires were administered during pregnancy and post‐delivery to collect information on demographics, mental health and life style, medical history, psychosocial measures, diet, infant growth, and neurodevelopment. Information on the delivery and newborn outcomes were abstracted from medical charts. Biological specimens were collected from mothers during each trimester, fathers (once during the pregnancy), and infants (at delivery and 2 years of age) for storage in a biological specimen bank. Results Of the 9864 women screened, 6348 met the eligibility criteria and 2366 women participated in the study (37% of eligible women). Among women in the 3D cohort, 1721 of their partners (1704 biological fathers) agreed to participate (73%). Two thousand two hundred and nineteen participants had a live singleton birth (94%). Prenatal blood and urine samples as well as vaginal secretions were collected for ≥98% of participants, cord blood for 81% of livebirths, and placental tissue for 89% of livebirths. Conclusions The 3D Cohort Study combines a rich bank of multiple biological specimens with extensive clinical, life style, and psychosocial data. This data set is a valuable resource for studying the developmental etiology of birth and early childhood neurodevelopmental outcomes.

It is unclear whether objectively measured maternal sleep-disordered breathing (SDB) leads to poor fetal outcomes. In this study, we prospectively assessed whether polysomnography-based diagnosis of SDB in the third trimester is associated with the delivery of small for gestational age (SGA) infants.Participants were recruited from a multicentre pregnancy cohort study. Eligible participants were evaluated for SDB based on symptoms (snoring and/or witnessed apnoeas assessed using the Pittsburgh Sleep Quality Index questionnaire) and in-home complete polysomnography in the third trimester. SGA was defined as10th centile using customised birthweight centiles adjusted for maternal parity, prepregnancy body mass index (BMI), ethnicity, gestational age and infant sex.Of the 234 pregnant participants who completed a sleep study, 82% were Caucasian, with mean (SD) age of 31 (4.3) years and a prepregnancy BMI of 23 (4) kg/m(2). The delivery of SGA infants occurred in 27 (12%) of the study participants. The symptoms of SDB had poor overall sensitivity and specificity for diagnosing SDB identified by polysomnography. Symptoms of SDB in the third trimester demonstrated a potential association with delivering an SGA infant, however this did not reach statistical significance (OR 2.36 (95% CI 0.85 to 6.54, p=0.10)). However, the odds of delivering an SGA infant were significantly increased with polysomnography-based diagnosis of maternal SDB (using apnoea-hypopnoea index cut-off of 10, OR 2.65 (95% CI 1.15 to 6.10, p=0.02)).Objectively measured SDB in the third trimester is significantly associated with the delivery of SGA infants.

ContextFetal overgrowth is associated with increased risk for type 2 diabetes in adulthood. It is unclear whether there are alterations in insulin sensitivity and β-cell function in early life.ObjectiveTo determine whether large-for-gestational-age (LGA) (birth weight > 90th percentile), an indicator of fetal overgrowth, is associated with altered fetal insulin sensitivity and β-cell function.Study Design, Population, and OutcomesIn the Design, Development, and Discover birth cohort in Canada, we studied 106 pairs of LGA and optimal-for-gestational-age (OGA; birth weight, 25th to 75th percentiles) infants matched by maternal ethnicity, smoking status, and gestational age. Cord plasma glucose-to-insulin ratio was used as an indicator of fetal insulin sensitivity, and proinsulin-to-insulin ratio was used as an indicator of β-cell function. Cord plasma leptin and high-molecular-weight (HMW) adiponectin concentrations were measured.ResultsComparisons of infants who were born LGA vs OGA, adjusted for maternal and newborn characteristics, showed that cord blood insulin, proinsulin, and leptin concentrations were significantly higher, whereas HWM adiponectin concentrations were similar. Glucose-to-insulin ratios were significantly lower (15.4 ± 28.1 vs 22.0 ± 24.9; P = 0.004), and proinsulin-to-insulin ratios significantly higher (0.73 ± 0.82 vs 0.60 ± 0.78; P = 0.005) in LGA vs OGA newborns, indicating lower insulin sensitivity and β-cell function in LGA newborns. These significant differences were almost unchanged after further adjustment for cord blood adiponectin levels but disappeared upon additional adjustment for cord blood leptin levels.ConclusionsThis study demonstrates that LGA may be associated with decreases in both fetal insulin sensitivity and β-cell function. The alterations appear to be linked to elevated leptin levels.

Diabetes and pregnancy are both associated with oxidative stress, characterized by an increase of FPlasma samples from 23 women with uncomplicated pregnancies and 11 women with pre-existing diabetes in pregnancy were collected between 12 and 18 weeks of pregnancy (MIROS cohort). Six FFPre-existing diabetes in early pregnancy displays a distinctive F

To compare short-term and long-term outcomes of preterm infants born at

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.