Deep learning prediction of renal anomalies for prenatal ultrasound diagnosis.

Deep learning algorithms have demonstrated remarkable potential in clinical diagnostics, particularly in the field of medical imaging. In this study, we investigated the application of deep learning models in early detection of fetal kidney anomalies. To provide an enhanced interpretation of those models' predictions, we proposed an adapted two-class representation and developed a multi-class model interpretation approach for problems with more than two labels and variable hierarchical grouping of labels. Additionally, we employed the explainable AI (XAI) visualization tools Grad-CAM and HiResCAM, to gain insights into model predictions and identify reasons for misclassifications. The study dataset consisted of 969 ultrasound images from unique patients; 646 control images and 323 cases of kidney anomalies, including 259 cases of unilateral urinary tract dilation and 64 cases of unilateral multicystic dysplastic kidney. The best performing model achieved a cross-validated area under the ROC curve of 91.28% ± 0.52%, with an overall accuracy of 84.03% ± 0.76%, sensitivity of 77.39% ± 1.99%, and specificity of 87.35% ± 1.28%. Our findings emphasize the potential of deep learning models in predicting kidney anomalies from limited prenatal ultrasound imagery. The proposed adaptations in model representation and interpretation represent a novel solution to multi-class prediction problems.

Infant Infections Following Cesarean Delivery on Maternal Request: A Population-Based Cohort Study.

OBJECTIVES: Investigations about cesarean delivery (CD) on maternal request (CDMR) and infant infection risk frequently rely on administrative data with poorly defined indications for CD. We sought to determine the association between CDMR and infant infection using an intent-to-treat approach. METHODS: This was a population-based cohort study of low-risk singleton pregnancies with a term live birth in Ontario, Canada between April 2012 and March 2018. Subjects with prior CD were excluded. Outcomes included upper and lower respiratory tract infections, gastrointestinal infections, otitis media, and a composite of these 4. Relative risk and 95% CI were calculated for component and composite outcomes up to 1 year following planned CDMR versus planned vaginal deliveries (VDs). Subgroup and sensitivity analyses included age at infection (≤28 vs. >28 days), type of care (ambulatory vs. hospitalisation), restricting the cohort to nulliparous pregnancies, and including individuals with previous CD. Last, we re-examined outcome risk on an as-treated basis (actual CD vs. actual VD). RESULTS: Of 422 134 pregnancies, 0.4% (1827) resulted in a planned CDMR. After adjusting for covariates, planned CDMR was not associated with a risk of composite infant infections (adjusted relative risk 1.02; 95% CI 0.92-1.11). Findings for component infection outcomes, subgroup, and sensitivity analyses were similar. However, the as-treated analysis of the role of delivery mode on infant risk for infection demonstrated that actual CD (planned and unplanned) was associated with an increased risk for infant infections compared to actual VD. CONCLUSIONS: Planned CDMR is not associated with increased risk for neonatal or infant infections compared with planned VD. Study design must be carefully considered when investigating the impact of CDMR on infant infection outcomes.

The impact of isolated obesity compared with obesity and other risk factors on risk of stillbirth: a retrospective cohort study.

BACKGROUND: Maternal obesity is associated with stillbirth, but uncertainty persists around the effects of higher obesity classes. We sought to compare the risk of stillbirth associated with maternal obesity alone versus maternal obesity and additional or undiagnosed factors contributing to high-risk pregnancy. METHODS: We conducted a retrospective cohort study using the Better Outcomes Registry and Network (BORN) for singleton hospital births in Ontario between 2012 and 2018. We used multivariable Cox proportional hazard regression and logistic regression to evaluate the relationship between prepregnancy maternal body mass index (BMI) class and stillbirth (reference was normal BMI). We treated maternal characteristics and obstetrical complications as independent covariates. We performed mediator analyses to measure the direct and indirect effects of BMI on stillbirth through major common-pathway complications. We used fully adjusted and partially adjusted models, representing the impact of maternal obesity alone and maternal obesity with other risk factors on stillbirth, respectively. RESULTS: We analyzed data on 681 178 births between 2012 and 2018, of which 1956 were stillbirths. Class I obesity was associated with an increased incidence of stillbirth (adjusted hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.35-1.78). This association was stronger for class III obesity (adjusted HR 1.80, 95% CI 1.44-2.24), and strongest for class II obesity (adjusted HR 2.17, 95% CI 1.83-2.57). Plotting point estimates for odds ratios, stratified by gestational age, showed a marked increase in the relative odds for stillbirth beyond 37 weeks' gestation for those with obesity with and without other risk factors, compared with those with normal BMI. The impact of potential mediators was minimal. INTERPRETATION: Maternal obesity alone and obesity with other risk factors are associated with an increased risk of stillbirth. This risk increases with gestational age, especially at term.

Sensory nerve release of CGRP increases tumor growth in HNSCC by suppressing TILs.

BACKGROUND: Perineural invasion (PNI) and nerve density within the tumor microenvironment (TME) have long been associated with worse outcomes in head and neck squamous cell carcinoma (HNSCC). This prompted an investigation into how nerves within the tumor microenvironment affect the adaptive immune system and tumor growth. METHODS: We used RNA sequencing analysis of human tumor tissue from a recent HNSCC clinical trial, proteomics of human nerves from HNSCC patients, and syngeneic orthotopic murine models of HPV-unrelated HNSCC to investigate how sensory nerves modulate the adaptive immune system. FINDINGS: Calcitonin gene-related peptide (CGRP) directly inhibited CD8 T cell activity in vitro, and blocking sensory nerve function surgically, pharmacologically, or genetically increased CD8 and CD4 T cell activity in vivo. CONCLUSIONS: Our data support sensory nerves playing a role in accelerating tumor growth by directly acting on the adaptive immune system to decrease Th1 CD4 T cells and activated CD8 T cells in the TME. These data support further investigation into the role of sensory nerves in the TME of HNSCC and points toward the possible treatment efficacy of blocking sensory nerve function or specifically inhibiting CGRP release or activity within the TME to improve outcomes. FUNDING: 1R01DE028282-01, 1R01DE028529-01, 1P50CA261605-01 (to S.D.K.), 1R01CA284651-01 (to S.D.K.), and F31 DE029997 (to L.B.D.).

An optimized protocol for isolation of murine pancreatic single cells with high yield and purity.

Here, we present a protocol for rapidly isolating single cells from the mouse pancreas, minimizing damage caused by digestive enzymes in exocrine cells. We guide you through steps to optimize the dissection sequence, enzyme composition, and operational procedures, resulting in high yields of viable pancreatic single cells. This protocol can be applied across a wide range of research areas, including single-cell sequencing, gene expression profiling, primary cell culture, and even the development of spheroids or organoids. For complete details on the use and execution of this protocol, please refer to Jiang et al. (2023).1.

Screening for postpartum depression and risk of suicidality with obstetrical patients: a cross-sectional survey.

BACKGROUND: Pregnancy is a vulnerable time where the physical and social stress of the COVID-19 pandemic affects psychological health, including postpartum depression (PPD). This study is designed to estimate the prevalence and correlates of PPD and risk of suicidality among individuals who gave birth during the COVID-19 pandemic. METHODS: We surveyed individuals who gave birth at The Ottawa Hospital and were ≥ 20 days postpartum, between March 17 and June 16, 2020. A PPD screen consisted of a score ≥ 13 using the Edinburgh Postnatal Depression Scale. A score of 1, 2, or 3 on item 10 ("The thought of harming myself has occurred to me") indicates risk of suicidality. If a participant scores greater than ≥ 13 or ≥ 1 on item 10 they were flagged for PPD, the Principal Investigator (DEC) was notified within 24 h of survey completion for a chart review and to assure follow-up. Modified Poisson multivariable regression models were used to identify factors associated with PPD and risk of suicidality using adjusted risk ratios (aRR) and 95% confidence intervals (CI). RESULTS: Of the 216 respondents, 64 (30%) screened positive for PPD and 17 (8%) screened positive for risk of suicidality. The maternal median age of the total sample was 33 years (IQR: 30-36) and the infant median age at the time of the survey was 76 days (IQR: 66-90). Most participants reported some form of positive coping strategies during the pandemic (97%) (e.g. connecting with friends and family, exercising, getting professional help) and 139 (64%) reported negative coping patterns (e.g. over/under eating, sleep problems). In total, 47 (22%) had pre-pregnancy anxiety and/or depression. Negative coping (aRR:2.90, 95% CI: 1.56-5.37) and pre-existing anxiety/depression (aRR:2.03, 95% CI:1.32-3.11) were associated with PPD. Pre-existing anxiety/depression (aRR:3.16, 95% CI:1.28-7.81) was associated with risk of suicidality. CONCLUSIONS: Almost a third of participants in this study screened positive for PPD and 8% for risk of suicidality. Mental health screening and techniques to foster positive coping skills/strategies are important areas to optimize postpartum mental health.

Tff2 defines transit-amplifying pancreatic acinar progenitors that lack regenerative potential and are protective against Kras-driven carcinogenesis.

While adult pancreatic stem cells are thought not to exist, it is now appreciated that the acinar compartment harbors progenitors, including tissue-repairing facultative progenitors (FPs). Here, we study a pancreatic acinar population marked by trefoil factor 2 (Tff2) expression. Long-term lineage tracing and single-cell RNA sequencing (scRNA-seq) analysis of Tff2-DTR-CreERT2-targeted cells defines a transit-amplifying progenitor (TAP) population that contributes to normal homeostasis. Following acute and chronic injury, Tff2+ cells, distinct from FPs, undergo depopulation but are eventually replenished. At baseline, oncogenic KrasG12D-targeted Tff2+ cells are resistant to PDAC initiation. However, KrasG12D activation in Tff2+ cells leads to survival and clonal expansion following pancreatitis and a cancer stem/progenitor cell-like state. Selective ablation of Tff2+ cells prior to KrasG12D activation in Mist1+ acinar or Dclk1+ FP cells results in enhanced tumorigenesis, which can be partially rescued by adenoviral Tff2 treatment. Together, Tff2 defines a pancreatic TAP population that protects against Kras-driven carcinogenesis.

Persisting risk factors for preeclampsia among high-risk pregnancies already using prophylactic aspirin: a multi-country retrospective investigation.

BACKGROUND: Low-dose aspirin is recommended for pregnant individuals at high-risk of developing preeclampsia, but less is known about those that develop preeclampsia even while using prophylactic aspirin for preeclampsia prevention as the best course of treatment. OBJECTIVES: The objective of this study is to investigate the risk factors with the highest risk of developing preeclampsia among pregnant individuals already using aspirin from high-risk obstetrical centers across five countries. DESIGN: This is a secondary analysis of pregnant individuals from the Folic Acid Clinical Trial (FACT) who were using prophylactic aspirin before 16 weeks gestation. The FACT randomized control trial took place in 70 high risk obstetrical centers in Canada, United Kingdom, Australia, Jamaica, and Argentina between 2011-2015. Participants were included if they had any of the risk factors for preeclampsia: diabetes, chronic hypertension, twin pregnancy, history of preeclampsia, and/or obesity (Body Mass Index ≥35). The outcomes of interest were preeclampsia and preterm preeclampsia (<37 weeks). Log binomial regressions assessed factors significantly associated with any preeclampsia or preterm-preeclampsia (<37 weeks) using adjusted risk ratios (ARR) and 95% confidence intervals (CI). RESULTS: There were 2296 pregnant individuals with complete information on aspirin included in this study. At baseline, all patients were at high risk of preeclampsia and were eligible for aspirin prophylaxis, however, only 660 (28.7%) were taking aspirin. Among the 660 pregnant individuals taking aspirin, 132 (20%) developed preeclampsia and 60 (9.09%) preterm preeclampsia. Among pregnant individuals using aspirin, the risks of preeclampsia were highest for twins (ARR:2.62, 95% CI: 1.68-4.11), history of preeclampsia (ARR: 2.42, 95% CI: 1.74-3.38), and hypertension (ARR:1.92, 95% CI: 1.37-2.69). Similar trends were found for preterm-preeclampsia for twins (ARR:4.10, 95% CI:2.15-7.82), history of preeclampsia (ARR:2.75, 95% CI:1.62-4.67), and hypertension (ARR:2.18, 95% CI:1.28-3.72). No significant differences were found for obesity or diabetes. CONCLUSION: These findings suggest that individuals with twin pregnancies, a history of preeclampsia, or hypertension may not benefit from aspirin to the same extent as those with other complications such as obesity or diabetes. Careful clinical monitoring for these risks factors is recommended and future research into the effectiveness in these populations would increase our understanding of the current best practice of prophylactic aspirin use to prevent preeclampsia. TRIAL REGISTRATION: Current Controlled Trials ISRCTN23781770 and ClinicalTrials.gov NCT01355159.

Tumor Growth Rate Informs Treatment Efficacy in Metastatic Pancreatic Adenocarcinoma: Application of a Growth and Regression Model to Pivotal Trial and Real-World Data.

BACKGROUND: Methods for screening agents earlier in development and strategies for conducting smaller randomized controlled trials (RCTs) are needed. METHODS: We retrospectively applied a tumor growth model to estimate the rates of growth of pancreatic cancer using radiographic tumor measurements or serum CA 19-9 values from 3033 patients with stages III-IV PDAC who were enrolled in 8 clinical trials or were included in 2 large real-world data sets. RESULTS: g correlated inversely with OS and was consistently lower in the experimental arms than in the control arms of RCTs. At the individual patient level, g was significantly faster for lesions metastatic to the liver relative to those localized to the pancreas. Regardless of regimen, g increased toward the end of therapy, often by over 3-fold. CONCLUSIONS: Growth rates of PDAC can be determined using radiographic tumor measurement and CA 19-9 values. g is inversely associated with OS and can differentiate therapies within the same trial and across trials. g can also be used to characterize changes in the behavior of an individual's PDAC, such as differences in the growth rate of lesions based on metastatic site, and the emergence of chemoresistance. We provide examples of how g can be used to benchmark phase II and III clinical data to a virtual reference arm to inform go/no go decisions and consider novel trial designs to optimize and accelerate drug development.

Cannabis Use in Pregnancy and Downstream effects on maternal and infant health (CUPiD): a protocol for a birth cohort pilot study.

INTRODUCTION: Cannabis use in pregnancy and post partum is increasing. Accessibility to cannabis has expanded due to the legalisation of cannabis in Canada. Therefore, there is a critical need to monitor the impact of cannabis on pregnancy outcomes and infant neurodevelopment. This pilot study will assess the feasibility of modern recruitment and data collection strategies adapted to the current cannabis environment and inform the design of a multicentre prospective birth cohort. METHODS AND ANALYSIS: We will establish a pregnancy and birth cohort of 50 cannabis users and 50 non-users recruited before delivery. We will follow the participants at regular visits from recruitment to 12 weeks post partum. Participants will provide demographic and socioeconomic data, report their cannabis use patterns, and provide biological samples. Biological samples include maternal and infant urine and blood, breastmilk/chestmilk, cord blood, cord tissue, placenta and meconium. All samples will be processed and stored at -80°C until analysis by immunoassay or liquid chromatography-tandem mass spectrometry to determine the presence of cannabis metabolites. In addition, partners will be invited to provide additional socioeconomic and substance use data. ETHICS AND DISSEMINATION: Ethics was obtained from Ottawa Health Science Network Research Ethics Board through Clinical Trials Ontario (3791). Our findings will be published in peer-reviewed journals, presented at scientific conferences and shared broadly with patients, healthcare decision-makers, and project partners online and through social media. TRIAL REGISTRATION NUMBER: NCT05309226.Cite Now.

Worries, beliefs and factors influencing perinatal COVID-19 vaccination: a cross-sectional survey of preconception, pregnant and lactating individuals.

BACKGROUND: COVID-19 vaccines are recommended for pregnant and lactating individuals, and there is substantial evidence for their safety and effectiveness. As the pandemic continues, information on worries and beliefs surrounding perinatal COVID-19 vaccination remains important to inform efforts aimed at improving vaccine uptake. Our objectives were to assess factors associated with COVID-19 vaccination among perinatal individuals; and to explore motivational factors associated with willingness to be vaccinated among unvaccinated perinatal individuals. METHODS: This was a cross-sectional web-based survey of preconception, pregnant, and lactating individuals in Canada. The outcomes of interest were vaccination with at least one dose of any COVID-19 vaccine and willingness to be vaccinated among unvaccinated individuals. Sample characteristics were summarized using frequencies and percentages. The association between eight prespecified risk factors and two outcomes (vaccination status and willingness to be vaccinated) was assessed by logistic regression. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for the total sample, and across perinatal sub-groups. RESULTS: Among 3446 survey respondents, there were 447 (13.0%) preconception, 1832 (53.2%) pregnant, and 1167 (42.4%) lactating. There were 1460 (42.4%) and 1982 (57.5%) who were vaccinated and unvaccinated, respectively. Factors positively associated with COVID-19 vaccine status were speaking to a healthcare provider about vaccination during the perinatal period (aOR:2.35, 95% CI:1.97-2.80) and believing that the COVID-19 vaccine is effective (aOR:1.91, 95% CI:1.46-2.48). Factors negatively associated with vaccine status included worries about fetal growth and development (aOR:0.55, 95% CI:0.43-0.70) and future child behavioral/neurodevelopmental problems (aOR:0.59, 95% CI:0.46-0.75). Among unvaccinated individuals specifically, characteristics positively associated with willingness to vaccinate were speaking to a healthcare provider (aOR:1.67, 95% CI:1.32-2.12) and believing the COVID-19 vaccine is effective (aOR:3.56, 95% CI:2.70-4.69). Factors negatively associated with willingness were concerns over infertility (aOR:0.66, 95% CI:0.49-0.88), fetal growth and development (aOR:0.33, 95% CI:0.24-0.46), and future child behavioral/neurodevelopmental problems (aOR:0.64, 95% CI:0.48-0.84). CONCLUSIONS: In this Canadian perinatal population, approximately 42% reported COVID-19 vaccination. Among unvaccinated individuals, willingness to receive vaccination was high (73%). Factors enhancing vaccine willingness included discussions with healthcare providers and believing the vaccine was effective. Concerns regarding vaccine safety, particularly with respect to fetal/child development, were the greatest barriers to vaccine uptake.

Functional analysis of RYR1 variants in patients with confirmed susceptibility to malignant hyperthermia.

BACKGROUND: A major bottleneck to the introduction of noninvasive presymptomatic diagnostic tests for the pharmacogenetic disorder malignant hyperthermia is the lack of functional data for associated variants. METHODS: We screened 50 genes having a potential role in skeletal muscle calcium homeostasis using the HaloPlex™ (Agilent Technologies, Santa Clara, CA, USA) target enrichment system and next-generation sequencing. Twenty-one patients with a history of a clinical malignant hyperthermia reaction together with a positive in vitro contracture test were included. Eight variants in RYR1 were subsequently introduced into the cDNA for the human ryanodine receptor gene and tested in cultured human embryonic kidney (HEK293) cells for their effect on calcium release from intracellular stores in response to the ryanodine receptor-1 agonist 4-chloro-m-cresol using fura-2 as calcium indicator. Each variant was subjected to in silico curation using the European Malignant Hyperthermia Group scoring matrix and ClinGen RYR1 variant curation expert panel guidelines. RESULTS: Potentially causative RYR1 variants were identified in 15 patients. Of these, two families carried two RYR1 variants, five variants had been previously reported as 'pathogenic', two variants had been previously reported as 'likely benign', and eight were of 'uncertain significance'. Of these eight variants, four showed hypersensitivity to 4-chloro-m-cresol. Three variants were reclassified as either 'pathogenic' or 'likely pathogenic'. Two were classified as 'benign', whilst three remained of 'uncertain significance'. CONCLUSIONS: Three (p.Tyr1711Cys, p.Val2280Ile, and p.Arg4737Gln) additional variants can be added to the list of RYR1 disease-associated variants managed by the European Malignant Hyperthermia Group. These can therefore be used diagnostically in the future. Three variants (p.Glu2348Gly, p.Asn2634Lys, and p.Arg3629Trp) that remained classified as of uncertain significance require further family studies or a different functional test to determine clinical relevance in malignant hyperthermia.

Prevalence of SARS-CoV-2 infection among obstetric patients in Ottawa, Canada: a descriptive study.

BACKGROUND: There is limited information on the prevalence of SARS-CoV-2 infection in obstetric settings in Canada, beyond the first wave of the COVID-19 pandemic (February to June 2020). We sought to describe the prevalence of SARS-CoV-2 infection in pregnant people admitted to triage units at a tertiary care hospital in Ottawa, Canada. METHODS: We conducted a descriptive study of pregnant people admitted to obstetric triage assessment units at The Ottawa Hospital between Oct. 19 and Nov. 27, 2020 (second local wave of the COVID-19 pandemic). Participants underwent SARS-CoV-2 polymerase chain reaction (PCR) (via naso- or oropharyngeal swabs) and serology testing upon admission. We excluded individuals younger than 18 years, those who did not speak English or French, those who enrolled in conflicting studies, those admitted for pregnancy termination and those triaged between 11:31 pm and 7:29 am. Swab and serology samples were analyzed using digital droplet PCR and enzyme-linked immunosorbent assays, respectively. We defined SARS-CoV-2 seropositivity as a positive result for immunoglobulin (Ig) G, either alone or in combination with IgM or IgA. RESULTS: Of the 632 eligible patients, 363 (57.4%) consented to participation and 362 collectively provided 284 swab and 352 blood samples eligible for analysis. Common reasons for declining participation included feeling overwhelmed or anxious, being worried about repercussions of testing, pain or discomfort with testing or disinterest in research. Participants were mostly multiparous (53.9%) and in their third trimester upon admission (88.4%). In all, 18 (4.9%) participants had evidence of SARS-CoV-2 exposure; 2 (0.7%) of 284 were positive for SARS-CoV-2 by PCR and 16 (4.5%) of 352 were positive for IgG antibodies to SARS-CoV-2. INTERPRETATION: During the second local wave of the COVID-19 pandemic, the prevalence of active SARS-CoV-2 infection among obstetric patients in Ottawa was 0.7% and seroprevalence was 4.5%. Our low participation rate highlights the need for improvements in patient education and public health messaging on the benefits of SARS-CoV-2 testing programs.

Giving Birth in the Early Phases of the COVID-19 Pandemic: The Patient Experience.

OBJECTIVE: Obstetrical patients are at risk of complications from COVID-19 and face increased stress due to the pandemic and changes in hospital birth setting. The objective was to describe the perinatal care experiences of obstetrical patients who gave birth during the early phases of the COVID-19 pandemic. METHODS: A descriptive epidemiological survey was administered to consenting patients who gave birth at The Ottawa Hospital (TOH) between March 16th and June 16th, 2020. The participants reported on prenatal, in-hospital, and postpartum care experiences. COVID-19 pandemic related household stress factors were investigated. Frequencies and percentages are presented for categorical variables and median and interquartile range (IQR) for continuous variables. RESULTS: A total of 216 participants were included in the analyses. Median participants age was 33 years (IQR: 30-36). Collectively, 94 (43.5%) participants felt elevated stress for prenatal appointments and 105 (48.6%) for postpartum appointments because of COVID-19. There were 108 (50.0%) were scared to go to the hospital for delivery, 97 (44.9%) wore a mask during labour and 54 (25.0%) gave birth without a support person. During postpartum care, 125 (57.9%) had phone appointments (not offered prior to COVID-19), and 18 (8.3%) received no postpartum care at all. CONCLUSION: COVID-19 pandemic and public health protocols created a stressful healthcare environment for the obstetrical population where many were fearful of accessing services, experienced changes to standard care, or no care at all. As the pandemic continues, careful attention should be given to the perinatal population to reduce stress and improve continuity of care.

RéSUMé: OBJECTIF: Les patients obstétriques sont à risque de complications de la COVID-19 et font face à un stress accru en raison de la pandémie et des changements dans le cadre de l'accouchement en milieu hospitalier. L'objectif était de décrire les expériences de soins périnataux des patients obstétriques qui ont accouché au cours des premières phases de la pandémie de COVID-19. MéTHODES: Un sondage épidémiologique descriptif a été menée auprès de patients qui ont accouché à L'Hôpital d'Ottawa (TOH) entre le 16 mars et le 16 juin 2020. Les participants ont fait un compte rendu de leurs expériences en matière de soins prénataux, hospitaliers et post-partum. Les facteurs de stress domestique liés à la COVID-19 ont été étudiés. Les fréquences et les pourcentages sont présentés pour les variables catégorielles et la médiane et l'écart interquartile (IQR) sont présentés pour les variables continues. RéSULTATS: Au total, 261 participants ont répondu au sondage. L'âge maternel médian était de 33 ans (IQR: 30­36). Collectivement, 94 participants (43,5%) ressentaient un stress élevé en lien avec les rendez-vous prénataux et 105 (48,6%) pour les rendez-vous post-partum en raison de la COVID-19. Il y avait 108 patients (50,0%) qui avaient peur d'aller à l'hôpital pour accoucher, 97 (44,9%) qui portaient un masque pendant leur travail et 54 (25,0%) qui ont accouché sans personne de soutien. En lien avec les soins post-partum, 125 (57,9%) ont eu des rendez-vous téléphoniques (non offerts avant la pandémie COVID-19) et 18 (8,3%) n'ont reçu aucun soin post-partum. CONCLUSION: La pandémie de COVID-19 et les politiques de santé publique ont créé un environnement de soins de santé stressant pour la population obstétrique où beaucoup avaient peur d'accéder aux services de soins, ont connu des changements dans les soins de base ou n'ont pas eu de soins du tout. Alors que la pandémie se poursuit, une attention particulière doit être accordée à la population périnatale afin de réduire le stress et améliorer la continuité des soins.

The psychological impact of the COVID-19 pandemic and a SARS-CoV-2 testing programme on obstetric patients and healthcare workers.

OBJECTIVES: The aim of this study was to describe the psychological impact of the COVID-19 pandemic and the specific impact of a universal SARS-CoV-2 testing programme on obstetric patients and healthcare workers at The Ottawa Hospital. METHODS: This was a follow-up survey study of obstetric healthcare workers and then-pregnant patients who participated in a SARS-CoV-2 testing programme conducted in The Ottawa Hospital obstetrical triage units from 19 October to 17 November 2020. Surveys explored the effects of the COVID-19 pandemic and the testing programme on participants' psychological well-being. Responses were collected from April to September 2021. Descriptive summary statistics were calculated for both groups. RESULTS: During hospitalization for delivery, obstetric patients (n = 143) worried about giving COVID-19 to their new baby (88.11%), catching COVID-19 (83.22%), and giving COVID-19 to their partner (76.22%). Patients felt relief at being tested for COVID-19 during the universal testing programme (24.65%) and at getting their results (28.87%). Patients also believed that universal SARS-CoV-2 testing was a good way to slow COVID-19 spread (79.72%), reduce anxiety (75.52%), and increase relief (76.22%). In addition, patients felt good about participating in research that could help others (91.61%). Among obstetric healthcare workers (n = 94), job satisfaction decreased and job stress increased during the COVID-19 pandemic. The universal testing programme led to minor increases in healthcare worker job stress and burden, particularly among nurses, but the majority (85.23%) believed it was a valuable research initiative. CONCLUSION: The COVID-19 pandemic has had a negative psychological impact on obstetric patients and healthcare workers. Universal SARS-CoV-2 testing was generally viewed favourably and may serve as an effective strategy for estimating COVID-19 prevalence without adding undue stress onto patients and healthcare workers during the pandemic.

Using deep-learning in fetal ultrasound analysis for diagnosis of cystic hygroma in the first trimester.

OBJECTIVE: To develop and internally validate a deep-learning algorithm from fetal ultrasound images for the diagnosis of cystic hygromas in the first trimester. METHODS: All first trimester ultrasound scans with a diagnosis of a cystic hygroma between 11 and 14 weeks gestation at our tertiary care centre in Ontario, Canada were studied. Ultrasound scans with normal nuchal translucency were used as controls. The dataset was partitioned with 75% of images used for model training and 25% used for model validation. Images were analyzed using a DenseNet model and the accuracy of the trained model to correctly identify cases of cystic hygroma was assessed by calculating sensitivity, specificity, and the area under the receiver-operating characteristic (ROC) curve. Gradient class activation heat maps (Grad-CAM) were generated to assess model interpretability. RESULTS: The dataset included 289 sagittal fetal ultrasound images;129 cystic hygroma cases and 160 normal NT controls. Overall model accuracy was 93% (95% CI: 88-98%), sensitivity 92% (95% CI: 79-100%), specificity 94% (95% CI: 91-96%), and the area under the ROC curve 0.94 (95% CI: 0.89-1.0). Grad-CAM heat maps demonstrated that the model predictions were driven primarily by the fetal posterior cervical area. CONCLUSIONS: Our findings demonstrate that deep-learning algorithms can achieve high accuracy in diagnostic interpretation of cystic hygroma in the first trimester, validated against expert clinical assessment.

The influence of maternal and paternal education on birth outcomes: an analysis of the Ottawa and Kingston (OaK) birth cohort.

BACKGROUND: Education is considered one of the most robust determinants of health. However, it is unclear whether maternal education and paternal education have differential impacts on perinatal health outcomes. We assess maternal and paternal education differences and their association with adverse birth outcomes in a large birth cohort from Ontario, Canada. METHODS: The OaK Birth Cohort recruited patients from Ontario, Canada, between October 2002 and April 2009. We recruited mothers were recruited between 12 and 20 weeks' gestation and collected both mother and infant data. The final sample size of the cohort was 8,085 participants. We use logistic regression to model the probability of preterm birth (less than 34 and 37 weeks' gestation), small-for-gestational-age (SGA), or stillbirth as a function of maternal and paternal educational attainment. We adjust for household-level income, maternal and paternal race and ethnicity, and compare the strength of the association between maternal and paternal education on outcomes using Wald tests. RESULTS: 7,928 mother-father-offspring triads were available for the current analysis. 75% of mothers and fathers had college or university level education, and 8.7% of mothers experienced preterm delivery. Compared to mothers with college or university education, mothers with a high school education had an odds ratio of 1.37 (95% CI: 1.01-1.87) for SGA. Paternal education was not associated with infant outcomes. Comparing the odds ratios for maternal education and paternal education showed a stronger association than paternal education at the high school level for SGA birth (difference in odds ratio: 1.95, 95% CI: 1.13-3.36, p = .016) among women at least 25 years old. CONCLUSION: Maternal education was associated with SGA, and this effect was more robust than paternal education, but both associations were weaker than previously reported.

Folic Acid Supplementation in Early Pregnancy, Homocysteine Concentration, and Risk of Gestational Diabetes Mellitus.

We used a prospective cohort of pregnant women at 12 to 20 weeks gestation between 2002 and 2008 in Ottawa and Kingston to evaluate the impact of early pregnancy folic acid supplementation on the risk of gestational diabetes mellitus. Among 7552 eligible women, 84 (1.11%) were diagnosed of gestational diabetes mellitus. Non-significant associations were observed between gestational diabetes mellitus and folate supplementation, homocysteine levels, and methylenetetrahydrofolate reductase 677 TT genotype. Although we found no significant associations between folic acid supplementation and the risk of gestational diabetes mellitus, genetic associations were not confounded by lifestyle or socioeconomic factors, which may have biased previous studies.

Effect of high-dose folic acid supplementation on the prevention of preeclampsia in twin pregnancy.

OBJECTIVE: To determine the efficacy of high-dose folic acid for the prevention of preeclampsia in twin pregnancies. METHODS: Secondary analysis of a randomized controlled trial in 70 obstetrical sites in Argentina, Australia, Canada, Jamaica, and the UK between 2011 and 2015. Eligible women pregnant with twins who were aged 18 y or older and between 8 and 16 completed weeks' gestation were randomized between to receive daily high-dose folic acid (4.0-5.1 mg) or placebo. The primary outcome was preeclampsia, presenting as hypertension after 20 weeks' gestation with significant proteinuria. Secondary outcomes included severe preeclampsia, preterm birth, and adverse fetal and neonatal outcomes. RESULTS: Of 2464 participants randomized between 18 April 2011 and 14 December 2015, 462 (18.8%) had a confirmed twin pregnancy. Thirty-four of these participants withdrew consent or did not have primary outcome data available, and 428 women were analyzed. The rate of preeclampsia was significantly higher in the folic acid group compared to the placebo group in crude analyses (17.2 versus 9.9%; relative risk 1.75 [95% CI 1.06-2.88], p = .029). Multivariable analyses attenuated this effect, rendering it not statistically significant (RR 1.58 [95% CI 0.95-2.63], p = .079). CONCLUSION: High-dose folic acid supplementation was not significantly associated with preeclampsia in a subgroup of twin pregnancies. Although a suggested elevated risk cannot be confirmed, these results may help to gain novel insights in the etiology of preeclampsia, which continues to be poorly understood. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01355159.

Future directions in preclinical and translational cancer neuroscience research.

Recent advances in cancer neuroscience necessitate the systematic analysis of neural influences in cancer as potential therapeutic targets in oncology. Here, we outline recommendations for future preclinical and translational research in this field.