Cost Evaluation of the Ontario Virtual Urgent Care Pilot Program: Population-Based, Matched Cohort Study.

BACKGROUND: In 2020, the Ministry of Health (MoH) in Ontario, Canada, introduced a virtual urgent care (VUC) pilot program to provide alternative access to urgent care services and reduce the need for in-person emergency department (ED) visits for patients with low acuity health concerns. OBJECTIVE: This study aims to compare the 30-day costs associated with VUC and in-person ED encounters from an MoH perspective. METHODS: Using administrative data from Ontario (the most populous province of Canada), a population-based, matched cohort study of Ontarians who used VUC services from December 2020 to September 2021 was conducted. As it was expected that VUC and in-person ED users would be different, two cohorts of VUC users were defined: (1) those who were promptly referred to an ED by a VUC provider and subsequently presented to an ED within 72 hours (these patients were matched to in-person ED users with any discharge disposition) and (2) those seen by a VUC provider with no referral to an in-person ED (these patients were matched to patients who presented in-person to the ED and were discharged home by the ED physician). Bootstrap techniques were used to compare the 30-day mean costs of VUC (operational costs to set up the VUC program plus health care expenditures) versus in-person ED care (health care expenditures) from an MoH perspective. All costs are expressed in Canadian dollars (a currency exchange rate of CAD $1=US $0.76 is applicable). RESULTS: We matched 2129 patients who presented to an ED within 72 hours of VUC referral and 14,179 patients seen by a VUC provider without a referral to an ED. Our matched populations represented 99% (2129/2150) of eligible VUC patients referred to the ED by their VUC provider and 98% (14,179/14,498) of eligible VUC patients not referred to the ED by their VUC provider. Compared to matched in-person ED patients, 30-day costs per patient were significantly higher for the cohort of VUC patients who presented to an ED within 72 hours of VUC referral ($2805 vs $2299; difference of $506, 95% CI $139-$885) and significantly lower for the VUC cohort of patients who did not require ED referral ($907 vs $1270; difference of $362, 95% CI 284-$446). Overall, the absolute 30-day costs associated with the 2 VUC cohorts were $18.9 million (ie, $6.0 million + $12.9 million) versus $22.9 million ($4.9 million + $18.0 million) for the 2 in-person ED cohorts. CONCLUSIONS: This costing evaluation supports the use of VUC as most complaints were addressed without referral to ED. Future research should evaluate targeted applications of VUC (eg, VUC models led by nurse practitioners or physician assistants with support from ED physicians) to inform future resource allocation and policy decisions.

Health care utilization and outcomes of patients seen by virtual urgent care versus in-person emergency department care.

BACKGROUND: Virtual urgent care (VUC) is intended to support diversion of patients with low-acuity complaints and reduce the need for in-person emergency department visits. We aimed to describe subsequent health care utilization and outcomes of patients who used VUC compared with similar patients who had an in-person emergency department visit. METHODS: We used patient-level encounter data that were prospectively collected for patients using VUC services provided by 14 pilot programs in Ontario, Canada. We linked the data to provincial administrative databases to identify subsequent 30-day health care utilization and outcomes. We defined 2 subgroups of VUC users; those with a documented prompt referral to an emergency department by a VUC provider, and those without. We matched patients in each cohort to an equal number of patients presenting to an emergency department in person, based on encounter date, medical concern and the logit of a propensity score. For the subgroup of patients not promptly referred to an emergency department, we matched patients to those who were seen in an emergency department and then discharged home. RESULTS: Of the 19 595 patient VUC visits linked to administrative data, we matched 2129 patients promptly referred to the emergency department by a VUC provider to patients presenting to the emergency department in person. Index visit hospital admissions (9.4% v. 8.7%), 30-day emergency department visits (17.0% v. 17.5%), and hospital admissions (12.9% v. 11.0%) were similar between the groups. We matched 14 179 patients who were seen by a VUC provider with no documented referral to the emergency department. Patients seen by VUC were more likely to have a subsequent in-person emergency department visit within 72 hours (13.7% v. 7.0%), 7 days (16.5% v. 10.3%) and 30 days (21.9% v. 17.9%), but hospital admissions were similar within 72 hours (1.1% v. 1.3%), and higher within 30 days for patients who were discharged home from the emergency department (2.6% v. 3.4%). INTERPRETATION: The impact of the provincial VUC pilot program on subsequent health care utilization was limited. There is a need to better understand the inherent limitations of virtual care and ensure future virtual providers have timely access to in-person outpatient resources, to prevent subsequent emergency department visits.

Sex differences among children, adolescents and young adults for mental health service use within inpatient and outpatient settings, before and during the COVID-19 pandemic: a population-based study in Ontario, Canada.

OBJECTIVES: The pandemic and public health response to contain the virus had impacts on many aspects of young people's lives including disruptions to daily routines, opportunities for social, academic, recreational engagement and early employment. Consequently, children, adolescents and young adults may have experienced mental health challenges that required use of mental health services. This study compared rates of use for inpatient and outpatient mental health services during the pandemic to pre-pandemic rates. DESIGN: Population-based repeated cross-sectional study. SETTING: Publicly delivered mental healthcare in primary and secondary settings within the province of Ontario, Canada. PARTICIPANTS: All children 6-12 years of age (n=2 043 977), adolescents 13-17 years (n=1 708 754) and young adults 18-24 years (n=2 286 544), living in Ontario and eligible for provincial health insurance between March 2016 and November 2021. PRIMARY OUTCOME MEASURES: Outpatient mental health visits to family physicians and psychiatrists for: mood and anxiety disorders, alcohol and substance abuse disorders, other non-psychotic mental health disorders and social problems. Inpatient mental health visits to emergency departments and hospitalisations for: substance-related and addictive disorders, anxiety disorders, assault-related injuries, deliberate self-harm and eating disorders. All outcomes were analysed by cohort and sex. RESULTS: During the pandemic, observed outpatient visit rates were higher among young adults by 19.01% (95% CI: 15.56% to 22.37%; 209 vs 175 per 1000) and adolescent women 24.17% (95% CI: 18.93% to 29.15%; 131 vs 105 per 1000) for mood and anxiety disorders and remained higher than expected. Female adolescents had higher than expected usage of inpatient care for deliberate self-harm, eating disorders and assault-related injuries. CONCLUSIONS: Study results raise concerns over prolonged high rates of mental health use during the pandemic, particularly in female adolescents and young women, and highlights the need to better monitor and identify mental health outcomes associated with COVID-19 containment measures and to develop policies to address these concerns.

Utilization of physician mental health services by birthing parents with young children during the COVID-19 pandemic: a population-based, repeated cross-sectional study.

BACKGROUND: The COVID-19 pandemic and nonpharmaceutical interventions that reduced the spread of infection had impacts on social interaction, schooling and employment. Concerns have been raised about the impact of these disruptions on the mental health of high-risk groups, including birthing parents of young children. METHODS: This population-based, repeated cross-sectional study used health administrative databases in Ontario, Canada, to link children to birth parents and to measure subsequent mental health visits of birthing parents of younger (age 0-5 yr) and school-aged (6-12 yr) children. We used a repeated cross-sectional study design to estimate expected rates for visits to physicians for mental health diagnoses, based on prepandemic trends (March 2016-February 2020), and to compare those to observed visit rates during the March 2020-November 2021 period of the pandemic. RESULTS: We identified 2 cohorts: 986 870 birthing parents of younger children and 1 012 997 birthing parents of school-aged children. In both cohorts, observed visit rates were higher than expected in the June 2020-August 2020 quarter (incidence rate ratio [IRR] 1.13, 95% confidence interval [CI] 1.10-1.16; and IRR 1.10, 95% CI 1.07-1.13, respectively), peaked in December 2020-February 2021 (IRR 1.24, 95% CI 1.20-1.27; and IRR 1.20, 95% CI 1.16-1.23) and remained higher than expected in September 2021-November 2021 (IRR 1.12, 95% CI 1.08-1.16; and IRR 1.09, 95% CI 1.06-1.13). The increases were driven mostly by visits for mood and anxiety disorders, and trends in increases were similar across physician type, birthing-parent age and deprivation quintile. INTERPRETATION: The COVID-19 pandemic was associated with increased mental health visits for parents of young children. This raises concerns about mental health impacts and highlights the need to address these concerns.

Clinical and economic impact of a community-based, hybrid model of in-person and virtual care in a Canadian rural setting: a cross-sectional population-based comparative study.

OBJECTIVES: To determine the clinical and economic impact of a community-based, hybrid model of in-person and virtual care by comparing health-system performance of the rural jurisdiction where this model was implemented with neighbouring jurisdictions without such a model and the broader regional health system. DESIGN: A cross-sectional comparative study. SETTING: Ontario, Canada, with a focus on three largely rural public health units from 1 April 2018 until 31 March 2021. PARTICIPANTS: All residents of Ontario, Canada under the age of 105 eligible for the Ontario Health Insurance Plan during the study period. INTERVENTIONS: An innovative, community-based, hybrid model of in-person and virtual care, the Virtual Triage and Assessment Centre (VTAC), was implemented in Renfrew County, Ontario on 27 March 2020. MAIN OUTCOME MEASURES: Primary outcome was a change in emergency department (ED) visits anywhere in Ontario, secondary outcomes included changes in hospitalisations and health-system costs, using per cent changes in mean monthly values of linked health-system administrative data for 2 years preimplementation and 1 year postimplementation. RESULTS: Renfrew County saw larger declines in ED visits (-34.4%, 95% CI -41.9% to -26.0%) and hospitalisations (-11.1%, 95% CI -19.7% to -1.5%) and slower growth in health-system costs than other rural regions studied. VTAC patients' low-acuity ED visits decreased by -32.9%, high-acuity visits increased by 8.2%, and hospitalisations increased by 30.0%. CONCLUSION: After implementing VTAC, Renfrew County saw reduced ED visits and hospitalisations and slower health-system cost growth compared with neighbouring rural jurisdictions. VTAC patients experienced reduced unnecessary ED visits and increased appropriate care. Community-based, hybrid models of in-person and virtual care may reduce the burden on emergency and hospital services in rural, remote and underserved regions. Further study is required to evaluate potential for scale and spread.

Prevalence and predictors for being unscreened for diabetic retinopathy: a population-based study over a decade.

OBJECTIVE: To determine the population-level predictors for being unscreened for diabetic retinopathy (DR) among individuals with diabetes in a developed country. DESIGN: A retrospective population-based repeated-cross-sectional study. PARTICIPANTS: All individuals with diabetes (types 1 and 2) aged ≥20 years in the universal health care system in Ontario were identified in the 2011-2013 and 2017-2019 time periods. METHODS: The Mantel-Haenszel test was used for the relative risk (RR) comparison of subcategories stratified by the 2 cross-sectional time periods. RESULTS: A total of 1 145 645 and 1 346 578 individuals with diabetes were identified in 2011-2013 and 2017-2019, respectively. The proportion of patients unscreened for DR declined very slightly from 35% (n = 405 967) in 2011-2013 to 34% (n = 455 027) in 2017-2019 of the population with diabetes (RR = 0.967; 95% CI, 0.964-0.9693; p < 0.0001). Young adults aged 20-39 years of age had the highest proportion of unscreened patients (62% and 58% in 2011-2013 and 2017-2019, respectively). Additionally, those who had a lower income quintile (RR = 1.039; 95% CI, 1.036-1.044; p < 0.0001), were recent immigrants (RR = 1.286; 95% CI, 1.280-1.293; p < 0.0001), lived in urban areas (RR = 1.149; 95% CI, 1.145-1.154; p < 0.0001), had a mental health history (RR = 1.117; 95% CI, 1.112-1.122; p < 0.0001), or lacked a connection to a primary care provider (RR = 1.656; 95% CI, 1.644-1.668; p < 0.0001) had a higher risk of being unscreened. CONCLUSIONS: This population-based study suggests that over 1 decade, 33% of individuals with diabetes are unscreened for DR, and young age, low income, immigration, residing in a large city, mental health illness, and no primary care access are the main predictors.

Impact of the COVID-19 Pandemic on Diabetes Care for Adults With Type 2 Diabetes in Ontario, Canada.

OBJECTIVES: The COVID-19 pandemic and related public health prevention measures have led to a disruption of the delivery of routine care and may have had an impact on the quality of diabetes care. Our aim in this study was to evaluate the extent to which structure, process and outcome quality measures in diabetes care changed in the first 6 months of the pandemic compared with previous periods. METHODS: A before-and-after observational study of all community-living Ontario residents >20 years of age and living with diabetes. The patients were divided into 3 cohorts: a pandemic cohort, alive March to September 2020 (n=1,393,404); reference cohort 1, alive March to September 2019 (n=1,415,490); and reference cohort 2, alive September 2019 to February 2020 (n=1,444,000). Outcome measures were in-person/virtual visits to general practitioners and specialists, eye examinations, glycated hemoglobin (A1C) and low-density lipoprotein (LDL) testing, filled prescriptions, and admissions to emergency departments (EDs) and hospitals for acute and chronic diabetes complications. RESULTS: The probability of an in-person visit to a GP decreasing by 47% (95% confidence interval [CI], 47% to 47%) in the pandemic period compared with both previous periods. The probability of having an eye exam was lower by 43% (95% CI, 44% to 43%), an A1C test by 28% (95% CI, 29% to 28%) and an LDL test by 31% (95% CI, 31% to 31%) in the pandemic period compared with the same 6-month period the year before. There were very small decreases in drug prescriptions and decreases of 18% and 16% in ED and hospital visits for complications. CONCLUSIONS: We observed disruptions to both structure and processes measures of diabetes care in Ontario during the first wave of the pandemic.

COVID-19 positivity rates, hospitalizations and mortality of adults with and without intellectual and developmental disabilities in Ontario, Canada.

BACKGROUND: Across and within countries there is a need to understand how the COVID-19 pandemic has impacted populations of individuals with intellectual and developmental disabilities (IDD). OBJECTIVE: Rates of COVID-19 positivity for adults with IDD, including Down syndrome, relative to adults without IDD in Ontario, Canada were compared. Health profiles and case-based rates of hospitalizations, intensive care unit admissions, and mortality within 30 days of testing positively were compared for those with IDD, including Down syndrome, versus those without IDD. METHODS: This retrospective cohort study linked health administrative databases using unique encoded identifiers to describe population-level COVID-19 positivity, related hospital use and mortality from January 15, 2020 to January 10, 2021. Incidence rate ratios (RR) and 95% confidence intervals were calculated. RESULTS: Relative to adults without IDD, COVID-19 positivity rates were 1.28 times higher for adults with IDD and 1.42 times higher for adults with Down syndrome. Compared to adults without IDD, adults with IDD were more than twice as likely to be hospitalized following COVID-19 (RR:2.21 (95%CI: 1.93,2.54)) and to die (RR:2.23 (95%CI: 1.86,2.67). These RRs were greater for adults under 65. For adults with Down syndrome, mortality rates were 6.59 (95%CI: 4.51,9.62) times higher than those without IDD. DISCUSSION: In Ontario, Canada, hospitalization and mortality rates associated with COVID-19 are higher for adults with IDD than other adults. These findings should inform vaccination strategies that often prioritize older adults in the general population resulting in people with IDD, who are often in younger age groups, being overlooked.

Supporting policy and practice in Ontario through ICES' Applied Health Research Question (AHRQ) program.

ICES upholds a strong reputation for generating high-quality evidence to inform policy and practice through its collaborations with a broad range of health system stakeholders including government policymakers and healthcare providers including clinicians. Supported by the Ontario Ministry of Health and Ministry of Long-Term Care, the ICES Applied Health Research Question (AHRQ) Program leverages the data holdings and, scientific and clinical expertise to generate evidence tailored to the information needs of requestors. This paper outlines the approach, process, strengths, challenges and the resulting influence and impact to the healthcare landscape in Ontario.

Health care utilization in medically complex people living with HIV before and after admission to an HIV-specific community facility: a pre-post comparison study.

BACKGROUND: People living with HIV and multiple comorbidities have high rates of health service use. This study evaluates system usage before and after admission to a community facility focused on HIV care. METHODS: We used Ontario administrative health databases to conduct a pre-post comparison of rates and costs of hospital admissions, emergency department visits, and family physician and home care visits among medically complex people with HIV in the year before and after admission to Casey House, an HIV-specific hospital in Toronto, for all individuals admitted between April 2009 and March 2015. Negative binomial regression was used to compare rates of health care utilization. We used Wilcoxon rank sum tests to compare associated health care costs, standardized to 2015 Canadian dollars. To contextualize our findings, we present rates and costs of health service use among Ontario residents living with HIV. RESULTS: During the study period, 268 people living with HIV were admitted to Casey House. Emergency department use declined from 4.6 to 2.5 visits per person-year (p = 0.02) after discharge from Casey House, and hospitalization rates declined from 1.4 to 1.1 admissions per person-year (p = 0.05). Conversely, home care visits increased from 24.3 to 35.6 visits per person-year (p = 0.01) and family physician visits increased from 18.3 to 22.6 visits per person-year (p < 0.001) in the year after discharge. These changes were associated with reduced overall costs to the health care system. The reduction in overall costs was not significant (p = 0.2); however, costs of emergency department visits (p < 0.001) and physician visits (p < 0.001) were significantly less. INTERPRETATION: Health care utilization by people with HIV was significantly different before and after admission to a community hospital focused on HIV care. This has implications for health care in other complex patient populations.

Acute Care Visits for Assault and Maltreatment Before vs During the COVID-19 Pandemic in Ontario, Canada.

This cross-sectional study compares rates of emergency department visits and hospitalizations for assault and maltreatment by age category and sex in Ontario, Canada, before vs during the COVID-10 pandemic.

Comprehensive assessment of the morbidity of renal mass biopsy: A population-based assessment of biopsy-related complications.

INTRODUCTION: We sought to assess seven-day and 30-day complications following renal mass biopsy (RMB), including mortality, hospitalizations, emergency department (ED) visits, and operative and non-operative complications and compare these to rates in population-matched controls. METHODS: We performed a population-based, matched, retrospective cohort study of patients undergoing RMB following consultation with a urologist and axial imaging from 2003-2015 in Ontario, Canada. Data on seven-day and 30-day rates of mortality, as well as operative and non operative complications after RMB were reported. The seven-day and 30-day rates of mortality, operative and non-operative interventions, hospitalizations, and ED visits were compared to matched controls using multivariable logistic regression. RESULTS: Among 6840 patients who underwent RMB in the study period, 24 (0.4%) and 159 (2.3%) died within seven and 30 days of their biopsy, respectively. Seven- and 30-day operative intervention rates were 79 (1.2%) and 236 (3.4%), respectively. Seven- and 30-day non-operative intervention rates were 227 (3.3%) and 529 (7.7%), respectively. Thirty-day mortality (odds ratio [OR] 8.1, 95% confidence interval [CI] 5.1-13.0), hospitalizations (OR 12.6, 95% CI 10.6-15.2), and ED visits (OR 3.8, 95% CI 3.4-4.3) were more common among patients who underwent RMB than the matched controls (p<0.001 for each). CONCLUSIONS: Patients undergoing RMB may have a small but non-negligible increased risk of mortality, hospital readmission, and ED visits compared to matched controls. However, limitations in the granularity of the dataset limits the strength of these conclusions. Further studies are needed to confirm our results. These risks should be discussed with patients for shared decision-making and considered in the risk/benefit tradeoff for the management of small renal masses.

Maternal and Cord Blood Folate Concentrations Are Inversely Associated with Fetal DNA Hydroxymethylation, but Not DNA Methylation, in a Cohort of Pregnant Canadian Women.

BACKGROUND: Aberrancies in fetal DNA methylation programming may modify disease susceptibility of the offspring. Maternal folate status has potential to alter fetal DNA methylation. OBJECTIVES: We examined the association of maternal and cord blood concentrations of folate and unmetabolized folic acid (UMFA), vitamin B-12, vitamin B-6, and choline with fetal DNA methylation and hydroxymethylation and assessed potential modifying effects of 38 fetal genetic variants in 22 genes. METHODS: Nutrient blood concentrations were measured in 368 pregnant women in early pregnancy (12-16 wk of gestation) and at delivery (37-42 wk of gestation) and in cord blood. DNA methylation and hydroxymethylation in cord blood mononuclear cells were quantified by LC-MS/MS. Pearson partial correlations were used to determine the association between individual nutrients and DNA methylation and hydroxymethylation. RESULTS: Serum and RBC folate and plasma UMFA concentrations (primary outcomes) in early pregnancy, at delivery, and in cord blood were not significantly associated with fetal DNA methylation. In contrast, maternal RBC folate in early pregnancy (r = -0.16, P = 0.04) and cord plasma UMFA (r = -0.23, P = 0.004) were inversely correlated with fetal DNA hydroxymethylation. Neither maternal and cord blood concentrations of other nutrients nor fetal genotypes (secondary outcomes) were significantly associated with fetal DNA methylation or hydroxymethylation. Infants born to mothers with RBC folate concentrations in the highest quartile and serum vitamin B-12 concentrations in the lowest quartile in early pregnancy had significantly lower fetal DNA methylation and higher birth weight compared with those born to mothers with lower RBC folate and higher serum vitamin B-12 concentrations (P = 0.01). CONCLUSIONS: Maternal and cord blood folate concentrations are associated with fetal DNA hydroxymethylation, but not DNA methylation, in a cohort of pregnant Canadian women. The observation that high folate and low vitamin B-12 maternal status in early pregnancy may be associated with decreased fetal DNA methylation and higher birth weight warrants further investigation. This trial was registered at clinicaltrials.gov as NCT02244684.

Formate concentrations in maternal plasma during pregnancy and in cord blood in a cohort of pregnant Canadian women: relations to genetic polymorphisms and plasma metabolites.

BACKGROUND: One-carbon metabolism, responsible for purine and thymidylate synthesis and transmethylation reactions, plays a critical role in embryonic and fetal development. Formate is a key player in one-carbon metabolism. In contrast to other one-carbon metabolites, it is not linked to tetrahydrofolate, is present in plasma at appreciable concentrations, and may therefore be distributed to different tissues. OBJECTIVE: The study was designed to determine the concentration of formate in cord blood in comparison with maternal blood taken earlier in pregnancy and at delivery and to relate formate concentrations to potential precursors and key fetal genotypes. METHODS: Formate and amino acids were measured in plasma during early pregnancy (12-16 wk), at delivery (37-42 wk), and in cord blood samples from 215 mothers, of a prospective cohort study. Three fetal genetic variants in one-carbon metabolism were assessed for their association with cord plasma concentrations of formate. RESULTS: The formate concentration was ∼60% higher in the cord blood samples than in mothers' plasma. The maternal formate concentrations did not differ between the early pregnancy samples and those taken at delivery. Plasma concentrations of 4 formate precursors (serine, glycine, tryptophan, and methionine) were increased in cord blood compared with the maternal samples. Cord blood formate was influenced by fetal genotype, being ∼12% higher in infants harboring the MTHFR A1298C (rs1801131) AC or CC genotypes and 10% lower in infants harboring the MTHFD1 G1958A (rs2236225) GA or AA genotypes. CONCLUSIONS: The increased formate concentrations in cord blood may support the increased activity of one-carbon metabolism in infants. As such, it would support increased rates of purine and thymidylate synthesis and the provision of methionine for methylation reactions.

Antiretroviral Prescription Pick-up and Physician Follow-up After Hospital Discharge Among Medically Complex People With HIV.

In this study, only 22 of 206 (10.7%) socially marginalized individuals living with HIV and multiple comorbid conditions filled a prescription for antiretroviral therapy within 7 days of discharge from an HIV specialty hospital, despite comprehensive discharge planning. Additional interventions facilitating postdischarge continuity of care are required for this population.

Fetal one-carbon nutrient concentrations may be affected by gestational diabetes.

Both insufficiency and excess of one-carbon nutrients (folate, choline, vitamins B6 and B12) during pregnancy have been associated with gestational diabetes mellitus (GDM). However, the precise nature of this association has not been clearly established. We hypothesized that GDM may affect one-carbon nutrients concentrations in the fetus, thus possibly participating in epigenetic programing of the offspring. Maternal blood was collected at recruitment (12-16 weeks). At delivery (28-42 weeks), both maternal and cord blood were collected. Blood concentrations of one-carbon nutrients and their metabolites were compared between the two groups. A total of 368 women were included in the study, of whom 19 (5.6%) were later diagnosed with GDM. No significant differences were found in maternal blood concentrations of one-carbon nutrients and their metabolites between the GDM and control groups at recruitment or at delivery. In cord blood, however, serum folate (87.7 [IQR 70.4-103.9] vs 66.6 [IQR 45.5-80.3] nmol/L, P = .025) and plasma TMAO (2.82 [IQR 1.3-3.2] vs 1.35 [IQR 1.0-2.0] µmol/L, P = .017) concentrations were higher, while plasma betaine concentrations were lower (17.5 [IQR 16.3-19.4] vs 21.1 [IQR 18.0-24.1] µmol/L, P = .019) in infants born to mothers with GDM compared with control. Our data suggest that while maternal blood concentrations of one-carbon nutrients and their metabolites may not affect the risk of GDM, GDM may alter concentrations of serum folate, plasma betaine and TMAO in cord blood. These alterations in one-carbon nutrient concentrations in fetal circulation may impact epigenetic programing, thereby contributing to physiologic changes and disease susceptibility in adulthood associated with GDM offspring.

Suboptimal maternal and cord plasma pyridoxal 5' phosphate concentrations are uncommon in a cohort of Canadian pregnant women and newborn infants.

Vitamin B6 is important in fetal development, but little is known of the vitamin B6 status of pregnant women and newborns in North America and potential modifying factors. This prospective study determined maternal and cord plasma concentrations of pyridoxal 5' phosphate (PLP; an indicator of vitamin B6 status) in a convenience sample of 368 Canadian pregnant women and their newborns. The association of maternal intake of vitamin B6 and fetal genetic variants with cord plasma PLP and homocysteine concentrations was also examined. Dietary and supplemental intakes of vitamin B6 were assessed in early and mid to late pregnancy. PLP concentrations were measured in maternal plasma in early pregnancy and at delivery, and in cord plasma. Six fetal variants of the MTHFR and CßS genes were assessed for their association with cord plasma PLP and homocysteine concentrations. Geometric mean (95% CI) PLP concentrations were 107 (98, 116) nmol/L in early pregnancy and 58 (53, 62) nmol/L at delivery, respectively, and 296 (275, 319) nmol/L in cord blood (p < .0001). During early pregnancy and at delivery, 3.6% and 5.5% of women had plasma PLP concentrations <20 nmol/L, respectively. Ninety eight percent of the women with supplemental B6 intake of at least the recommended dietary allowance had PLP concentrations >20 nmol/L. Fetal genetic variants were not associated with cord PLP and homocysteine concentrations. Vitamin B6 deficiency is uncommon in a cohort of Canadian pregnant women due largely to prevalent vitamin B6 supplement use.

Severe Obesity, Obesity, and Cardiometabolic Risk in Children 0 to 6 Years of Age.

BACKGROUND: The prevalence of obesity in children has been shown to be plateauing or decreasing in some countries. However, the burden of severe obesity is often not assessed. Children with severe obesity may be at an increased risk for cardiovascular disease and diabetes. The objective is to determine the prevalence of severe obesity in young children and to examine the association with cardiometabolic risk factors. METHODS: A longitudinal study was conducted through The Applied Research Group for Kids! (TARGet Kids!), a practice-based research network in Toronto, Canada. Healthy children from birth to 6 years of age were recruited and followed through middle childhood. The main outcomes of the study were as follows: total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and non-HDL cholesterol, triglycerides, glucose, systolic blood pressure (SBP), and diastolic blood pressure (DBP). BMI was age and sex standardized based on the WHO growth standards. A BMI z-score >3 was used to define obesity for children <5 years of age, and severe obesity for children ≥5 years of age. RESULTS: Among 5738 children <5 years, 0.8% had a zBMI >3. In 626 children who were 5 and 6 years old, 2.1% had a zBMI >3. In the multivariable analysis adjusted for age, sex, maternal ethnicity, and family history, using repeated measures, children with a zBMI >3 had significantly higher odds of having abnormal SBP [odds ratio (OR) 6.4, 95% confidence interval (CI) 1.5-27.9; p = 0.01] and DBP (OR, 3.6 95% CI 1.2-10.6; p = 0.02), respectively, as compared with healthy-weight children. Trends demonstrating an association between a zBMI >3 and abnormal lipid levels were also identified. CONCLUSION: Young children with a zBMI >3 have significantly higher blood pressure measures and trends toward worse lipid profiles than children at lower zBMIs.

Longitudinal Analysis of Sleep Duration and Cardiometabolic Risk in Young Children.

BACKGROUND: The aim of this study is to determine if sleep duration in early childhood is associated with cardiometabolic risk (CMR) in later childhood as assessed by a CMR cluster score [sum of age- and sex-standardized z-scores of waist circumference (WC), systolic blood pressure, triglycerides, glucose, and (inverse) high-density lipoprotein (HDL)]. Secondary objectives included examining sleep duration and the individual CMR factors and BMI z-score. PATIENTS AND METHODS: A prospective cohort study was conducted using data from the TARGet Kids! practice-based research network in Toronto, Canada. Children (n = 597) with parent-reported 24-hour sleep duration in early childhood (12-36 months) and a follow-up visit (36-96 months) with all five CMR factors were included in the analysis. Multivariable linear regression was used to assess the relationship between early childhood sleep duration and later childhood CMR, adjusting for relevant covariates. RESULTS: Average 24-hour sleep duration in early childhood [mean age: 28.1 (6.6) months] was 11.8 (1.4) hours, with 87% meeting or exceeding total sleep recommendations for their age. Sleep duration in early childhood was not associated with the CMR cluster score in later childhood. Shorter sleep duration was associated with higher HDL concentrations [adjusted ß = -0.028 (95% confidence interval: -0.049 to -0.007), p = 0.009]. CONCLUSIONS: Further research is needed to determine if early childhood sleep duration is associated with HDL in later childhood. Future studies, which investigate sleep quality in addition to sleep duration, may be helpful.

Low Serum Vitamin B-12 Concentrations Are Prevalent in a Cohort of Pregnant Canadian Women.

BACKGROUND: Among Canadian women of reproductive age, 5% and 20% have serum vitamin B-12 concentrations indicative of deficiency (<148 pmol/L) and marginal status (148-220 pmol/L), respectively. Given the association between suboptimal vitamin B-12 and adverse pregnancy outcomes, an understanding of vitamin B-12 status during pregnancy, and factors that influence it, is required. OBJECTIVE: This prospective analysis from the PREFORM (PREnatal FOlic acid exposuRe on DNA Methylation in the newborn infant) study investigated 1) vitamin B-12 status in a cohort of Canadian pregnant women and their newborns, 2) the association of maternal dietary vitamin B-12 intake with maternal and cord blood concentrations of vitamin B-12 and its biomarkers, and 3) the association of fetal genetic polymorphisms with cord blood concentrations of vitamin B-12 and its biomarkers. METHODS: In pregnant Canadian women (n = 368; mean ± SD age: 32 ± 5 y), vitamin B-12 intakes were assessed in early (0-16 wk) and mid- to late (23-37 wk) pregnancy. Serum vitamin B-12 and plasma total homocysteine (tHcy) and methylmalonic acid (MMA) in maternal blood at 12-16 wk of pregnancy and at delivery (28-42 wk) and in cord blood were measured and compared by using regression analyses. The associations of 28 fetal genetic variants in vitamin B-12 metabolism and cord blood vitamin B-12, tHcy, and MMA concentrations were assessed by using regression analysis, with adjustment for multiple testing. RESULTS: A total of 17% and 38% of women had deficient and 35% and 43% had marginal serum vitamin B-12 concentrations at 12-16 wk of pregnancy and at delivery, respectively. Only 1.9-5.3% had elevated MMA (>271 nmol/L), and no women had elevated tHcy (>13 µmol/L). Maternal dietary vitamin B-12 intake during pregnancy was either weakly associated or not associated with maternal and cord blood vitamin B-12 (r(2) = 0.17-0.24, P < 0.0008), tHcy (P = NS) and MMA (r(2) = 0.05-0.11, P < 0.001). Fetal genetic polymorphisms were not associated with cord blood concentrations of vitamin B-12 and its biomarkers. CONCLUSIONS: Deficient and marginal serum vitamin B-12 concentrations are prevalent in Canadian pregnant women with the use of traditional cutoffs, despite supplement use. Given the growing interest among women to adhere to a vegetarian diet that may be lower in vitamin B-12, and vitamin B-12's importance in pregnancy, the functional ramifications of these observations need to be elucidated. This trial was registered at clinicaltrials.gov as NCT02244684.