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Background: On Apr. 1, 2008, a revision was made to the fee schedule for bone mineral density testing with dual-energy x-ray absorptiometry (DXA) in the province of Ontario, Canada, reducing the frequency of repeat screening in individuals at low risk of osteoporosis. We evaluated whether the change in physician reimbursement successfully promoted appropriate bone mineral density testing, with reduced use among women at low risk and increased use among women and men at higher risk of osteoporosis-related fracture. Methods: We analyzed data from administrative databases on physician billings, hospital discharges and emergency department visits. We included all physician claims for DXA in the province to assess patterns in bone mineral density testing from Apr. 1, 2002, to Mar. 31, 2011. People at risk of an osteoporosis-related fracture were defined as women and men aged 65 years or more and those who had a recent (< 6 mo) fracture after age 40 years. Joinpoint regression analysis was used to examine trends in DXA testing. Results: Before the policy change, the overall number of DXA tests increased from 433 419 in 2002/03 to 507 658 in 2007/08; after revision of the fee schedule, the number decreased to 422 915 by 2010/11. Most of this reduction was due to a decrease in the age-standardized rate of DXA testing among women deemed to be at low risk, from 5.7 per 100 population in 2008/09 to 1.8 per 100 in 2010/11. In the high-risk group of people aged 65 or more, the age-standardized rate of testing increased after the policy change among men but decreased among women. Among those at high risk because of a recent clinical fracture, the age-standardized rate of DXA testing increased for both sexes and then decreased after the policy change. Interpretation: A change in reimbursement designed to restrict access to bone mineral density testing among low-risk women was associated with an overall reduction in testing. Efforts to communicate guidelines for bone mineral density testing with greater clarity, particularly as they relate to high-risk individuals, need to be explored. [ABSTRACT FROM AUTHOR]

Background: There are gaps between what family practitioners do in clinical practice and the evidence-based ideal. The most commonly used strategy to narrow these gaps is the printed educational message (PEM); however, the attributes of successful printed educational messages and their overall effectiveness in changing physician practice are not clear. The current endeavor aims to determine whether such messages change prescribing quality in primary care practice, and whether these effects differ with the format of the message. Methods/design: The design is a large, simple, factorial, unblinded cluster-randomized controlled trial. PEMs will be distributed with informed, a quarterly evidence-based synopsis of current clinical information produced by the Institute for Clinical Evaluative Sciences, Toronto, Canada, and will be sent to all eligible general and family practitioners in Ontario. There will be three replicates of the trial, with three different educational messages, each aimed at narrowing a specific evidence-practice gap as follows: 1) angiotensin-converting enzyme inhibitors, hypertension treatment, and cholesterol lowering agents for diabetes; 2) retinal screening for diabetes; and 3) diuretics for hypertension. For each of the three replicates there will be three intervention groups. The first group will receive informed with an attached postcard-sized, short, directive "outsert." The second intervention group will receive informed with a two-page explanatory "insert" on the same topic. The third intervention group will receive informed, with both the above-mentioned outsert and insert. The control group will receive informed only, without either an outsert or insert. Routinely collected physician billing, prescription, and hospital data found in Ontario's administrative databases will be used to monitor pre-defined prescribing changes relevant and specific to each replicate, following delivery of the educational messages. Multi-level modeling will be used to study patterns in physician-prescribing quality over four quarters, before and after each of the three interventions. Subgroup analyses will be performed to assess the association between the characteristics of the physician's place of practice and target behaviours. A further analysis of the immediate and delayed impacts of the PEMs will be performed using time-series analysis and interventional, auto-regressive, integrated moving average modeling. [ABSTRACT FROM AUTHOR]

This article surveyed the processes and policies underlying the routine collection of clinical data in acute care hospitals in Ontario, Canada. Although there is evidence of a small shortfall in the availability of human resources, most health records departments employ experienced staff with health records certification. However, there is much more important variation in the documented and undocumented processes used to generate routinely collected clinical data. Current guidelines and coding schedules are helpful but insufficient to guide the production of good quality data. The variations in the processes used to produce clinical data have important implications for the management, reimbursement, and planning of healthcare. This is particularly critical at a time when hospitals and other stakeholders, such as governments, are relying more and more on accurate, reliable, and comparable data. [ABSTRACT FROM AUTHOR]

How models of health care financing and delivery affect patterns of procedure volumes, outcomes, and volume-outcome associations is not known. We compared volume-outcome studies done in Canada, which provides residents with universal, single-payer health care, with those done in the United States, to determine whether there was a difference in the likelihood of finding statistically significant volume-outcome associations. We analyzed 142 articles, most (90.1%) of which were from the United States. The articles described a total of 291 separate analyses. After adjusting for the clustering of multiple analyses in the same study, the likelihood of finding a statistically significant volume-outcome association was substantially lower in Canadian studies as compared with those from the United States (odds ratio 0.24, 95% confidence interval 0.08 to 0.74, p = 0.01). This result persisted after adjustment for the procedure/condition studied, and the number of study subjects. Canadian volume-outcome analyses are less likely to identify statistically significant volume-outcome associations than US studies, possibly because of the smaller size of some Canadian studies. It is also possible that different models of health care financing and delivery affect patterns of procedure volumes and volume-outcome associations. By promoting competition between hospitals and providers, market-based models may exacerbate existing variations in the quality of hospital care. [ABSTRACT FROM AUTHOR]

Background: Although single nucleotide polymorphisms may be potentially important pharmacogenetic determinants of cancer therapy, functional evidence regarding their relevance is currently lacking. The C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with changes in cellular composition of folates. We hypothesized that this polymorphism may modulate the cytotoxic effect of 5-fluorouracil (5FU) and methotrexate (MTX), two commonly used chemotherapeutic agents for colon and breast cancers, because the modes of action of 5FU and MTX are critically dependent on cellular composition of folates. Methods: Human HCT116 colon and MDA-MB-435 breast cancer cells were stably transfected with wild-type or mutant 677T human MTHFR cDNA. MTHFR enzyme activity and thermolability, intracellular folate composition, growth rate, and catalytic thymidylate synthase activity were determined. In vitro chemosensitivity to 5FU and MTX was determined using the sulforhodamine B assay. In vivo chemosensitivity of HCT116 cells to 5FU was determined in nude mice. Results: Compared with cells expressing the wildtype MTHFR, HCT116 and MDA-MB-435 cells expressing the mutant 677T MTHFR had decreased MTHFR activity, MTHFR thermolability, changed intracellular folate distribution, accelerated cellular growth rate, and increased thymidylate synthase activity. The MTHFR 677T mutation increased chemosensitivity of colon and breast cancers to 5FU, but decreased chemosensitivity of breast cancer cells to MTX. In nude mice, xenografts expressing the mutant 677T MTHFR grew faster, but were more sensitive to 5FU, than xenografts expressing the wild-type protein. Conclusions: Our data provide evidence that the MTHFR C677T polymorphism affects the concentration and intracellular distribution of folates and changes the growth and chemosensitivity of colon and breast cancer cells. The MTHFR C677T polymorphism may be a useful pharmacogenetic determinant for providing rational and effective tailored chemotherapy. [ABSTRACT FROM AUTHOR]

In recent years, cervical disc replacement (CDR) has gained popularity for cervical degenerative disorders. The rationale for CDR over anterior cervical discectomy and fusion (ACDF) is preservation of segmental motion and physiological spinal kinematics, which is hoped to delay development of adjacent segment disease and reoperation rates. Superiority of CDR over ACDF in rates of secondary surgeries has not been demonstrated in long-term follow-up. This study compares rate of reoperation in CDR and ACDF for treatment of cervical degenerative disc disease using population-based data for the province of Ontario. A population-based cohort study was conducted using health administrative databases including patients undergoing ACDF or CDR between October 2005 to March 2018. Patients receiving CDR vs ACDF were identified using physician service claims and hospital discharge abstracts. The primary outcome was revision surgery in the cervical spine defined as an operation more than 30 days after the index procedure. Secondary outcomes were immediate/acute complications within the first 30 days after the index operation, readmissions and length of hospital stay. METHODS: Cox proportional hazard models were used to identify predictors of time to revision surgery. Predictors of the binary outcome of an immediate complication within 30 days were estimated using logistic regression. A total of 5,207 patients were included. Mean follow-up was 2,728 days for CDR and 2,542 days for ACDF. Among 4,937 ACDF procedures, 7.5% underwent subsequent revision surgery and among 270 CDR procedures, 8.9% had revision surgery. While the study groups did not differ in their risk of revision surgery (adjusted HR 1.20, 95% CI 0.78-1.85), CDR was associated with a lower probability of an acute complication (adjusted OR 0.41, 95% CI 0.21-0.80). Among other factors, multi-level surgery was an independent predictor of acute complication [OR= 1.33 (95% CI 1.06 – 1.66)]. CDR patients experienced shorter mean (±SD) length of hospital stay [1.42 (±0.87) vs. 2.00 ± (3.08) d for ACDF]. This study does not demonstrate superiority of CDR over ACDF in revision surgery at the index and/or adjacent level of the cervical spine for single and multi-level procedures. CDR may have an advantage over ACDF in the acute postoperative phase, with a shorter length of hospital stay and lower probability of acute complication. This abstract does not discuss or include any applicable devices or drugs. [ABSTRACT FROM AUTHOR]

Preoperative opioid use has been shown to increase the risk for complications following total joint arthroplasty (TJA); however, these studies have not always accounted for differences in co-morbidities and socio-demographics between patients that use opioids and those that do not. They have also not accounted for the variation in degree of pre-operative use. The objective of this study was to determine if preoperative opioid use is associated with risk for surgical complications after TJA, and if this association varied by degree of use. Population-based retrospective cohort study. Older adult patients undergoing primary TJA of the hip, knee and shoulder for osteoarthritis between 2002 and 2015 in Ontario, Canada were identified. Using accepted definitions, patients were stratified into three groups according to their preoperative opioid use: no use, intermittent use and chronic use. The primary outcome was the occurrence of a composite surgical complication (surgical site infection, dislocation, revision arthroplasty) or death within a year of surgery. Intermittent and chronic users were matched separately to non-users in a 1:1 ratio, matching on TJA type plus a propensity score incorporating patient and provider factors. Overall, 108,067 patients were included in the study; 10% (N = 10,441) used opioids on a chronic basis before surgery and 35% (N = 37,668) used them intermittently. After matching, chronic pre-operative opioid use was associated with an increased risk for complications after TJA (HR 1.44, p = 0.001) relative to non-users. Overall, less than half of patients undergoing TJA used opioids in the year preceding surgery; the majority used them only intermittently. While chronic pre-operative opioid use is associated with an increased risk for complications after TJA, intermitted pre-operative use is not. [ABSTRACT FROM AUTHOR]

Background: Time at home before death is an emerging patient-centered metric of quality end-of-life care. It is unknown if immigrants who die from cancer in Ontario spend less time at home near the end of life. Objective: Compare the number of days at home (DAH) in the last six months of life for immigrants and long-term residents (LTRs) who die from cancer. Methods: Population-based cohort study (January 1, 2005 to December 31, 2013) using administrative databases. Participants were adults (≥18 years) who died from cancer in Ontario. Immigrants were defined as those who immigrated from 1985 onward. The outcome was DAH in the last six months of life. Analysis included univariate and multivariable regression, adjusting for patient and disease characteristics. Subgroup analyses assessed DAH by immigration class, time since immigration, and region of birth. Sensitivity analyses excluded patients with breast and prostate cancer to examine for sex differences. Results: Seventy-two thousand nine hundred eighty-eight individuals (3988 immigrants) were identified. Immigrants spent fewer DAH in the last six months (unadjusted 162 days vs. 164 days, p < 0.001). This remained statistically significant after adjusting (p = 0.0087). DAH varied by immigration class and region of birth. Sensitivity analyses suggest a sex difference in end-of-life time spent at home. Conclusions: Immigrants who die from cancer in Ontario spend fewer DAH before death than LTRs. This may be due to patient preferences, inequitable access to services, or availability of local relatives for support. Further research is needed to understand the causes of this association. [ABSTRACT FROM AUTHOR]

Background: For novel cancer treatments, effectiveness in clinical practice is not always aligned with clinical efficacy results. As such it is important to understand a treatment's real-world effectiveness. We examined real-world population-based comparative effectiveness of second-line ipilimumab versus non-ipilimumab treatments (chemotherapy or targeted treatments).Methods: We used a cohort of melanoma patients receiving systemic treatment for advanced disease since April 2005 from Ontario, Canada. Patients were identified from provincial drug databases and the Ontario Cancer Registry who received second-line ipilimumab from 2012 to 2015 (treated) or second-line non-ipilimumab treatment prior to 2012 (historical controls). Historical controls were chosen, to permit the most direct comparison to pivotal trial findings. The cohort was linked to administrative databases to identify baseline characteristics and outcomes. Kaplan-Meier curves and multivariable Cox regression models were used to assess overall survival (OS). Observed potential confounders were adjusted for using inverse probability of treatment weighting (IPTW).Results: We identified 329 patients with metastatic melanoma (MM) who had received second-line treatments (189 treated; 140 controls). Patients receiving second-line ipilimumab were older (61.7 years vs 55.2 years) compared to historical controls. Median OS were 6.9 (95% CI: 5.4-8.3) and 4.95 (4.3-6.0) months for ipilimumab and controls, respectively. The crude 1-year, 2-year, and 3-year OS probabilities were 34.3% (27-41%), 20.6% (15-27%), and 15.2% (9.6-21%) for ipilimumab and 17.1% (11-23%), 7.1% (2.9-11%), and 4.7% (1.2-8.2%) for controls. Ipilimumab was associated with improved OS (IPTW HR = 0.62; 95% CI: 0.49-0.78; p < 0.0001).Conclusions: This real-world analysis suggests second-line ipilimumab is associated with an improvement in OS for MM patients in routine practice. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What are the rates of serious cardiovascular events in those who undergo primary total joint arthroplasty (TJA) compared with those who do not within three years of initial assessment? SUMMARY ANSWER Undergoing elective primary TJA within three years of initial assessment was associated with a significant 12.4% absolute reduction in subsequent risk of serious cardiovascular events. WHAT IS KNOWN AND WHAT THIS PAPER ADDS Osteoarthritis is associated with increased mortality, particularly secondary to cardiovascular disease, with the risk for mortality proportional to the degree of disability secondary to the arthritis. This study suggests that management of hip or knee osteoarthritis with arthroplasty decreases the risk for subsequent serious cardiovascular events. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Is there a cut point in annual surgeon volume associated with increased risk for complications after primary elective total hip arthroplasty, and, if so, can we quantify this risk? SUMMARY ANSWER In a cohort of first time recipients of total hip arthroplasty, we found that patients operated on by surgeons who had performed 35 or fewer procedures in the year before the index arthroplasty were at increased risk for dislocation and early revision. WHAT IS KNOWN AND WHAT THIS PAPER ADDS Though there is a general consensus that increased surgeon volume is associated with a reduced risk of complications, there is a lack of consensus around what constitutes a “low” annual volume. This study showed that in patients undergoing total hip arthroplasty, the risks for dislocation and early revision increased by about 48% and 44%, respectively, when they were operated on by surgeons with annual volumes ≤35 procedures. [ABSTRACT FROM AUTHOR]

The article discusses research which examined the rates of cardiovascular events in those who undergo primary total joint arthroplasty (TJA). Topics discussed include the association of osteoarthritis with increased mortality and utilisation of baseline questionnaire data from the Ontario Hip/Knee Study and use of a propensity score matched landmark analysis. Findings revealed a lower chance of cardiovascular events in the TJA group.

Background: A small number of people with chronic obstructive pulmonary disease (COPD) receive pulmonary function testing around the time of diagnosis. Because omitting testing increases misdiagnosis, we sought to determine whether health outcomes differed between patients whose COPD was diagnosed with or without pulmonary function testing.Methods: We conducted a longitudinal population study of patients with physician-diagnosed COPD from 2005 to 2012 using health administrative data from Ontario, Canada. We assessed whether having pulmonary function testing around the time of diagnosis was associated with the composite outcome of admission to hospital for COPD or all-cause death, using adjusted survival analysis.Results: Chronic obstructive pulmonary disease was diagnosed in 68 898 patients during the study period; 41.2% of patients received peridiagnostic pulmonary function testing. In adjusted analysis, patients who underwent testing were less likely to die or be admitted to hospital for COPD (adjusted hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.89-0.94) and were more likely to be prescribed an inhaled long-acting bronchodilator than patients who did not undergo testing. Subgroup analysis suggested that the association of testing and outcomes was confined to patients with COPD diagnosed in the ambulatory care setting (adjusted HR 0.80, 95% CI 0.76-0.84).Interpretation: Confirmation of a COPD diagnosis using pulmonary function testing is associated with a decreased risk of death and admission to hospital for COPD. In ambulatory patients, this effect may be from increased use of appropriate COPD medications. The findings of this study validate current guideline recommendations that encourage pulmonary function testing for diagnosis in all patients with suspected COPD. [ABSTRACT FROM AUTHOR]

Background: Otitis media is the most common medical problem in young children. The usual surgical treatment is myringotomy with insertion of tympanostomy tubes. There is debate about the usefulness of concomitant adenoidectomy or adenotonsillectomy. We examined the effects of these adjuvant procedures on the rates of reinsertion of tympanostomy tubes and rehospitalization for conditions related to otitis media. Methods: Using hospital discharge records for the period 1995 through 1997, we examined the results of surgery for all 37,316 children (defined as persons 19 years of age or younger) in Ontario, Canada, who received tympanostomy tubes as their first surgical treatment for otitis media. We determined the time to the first readmission for conditions related to otitis media and the time to the first reinsertion of tympanostomy tubes. Results: As compared with treatment involving the insertion of tympanostomy tubes alone, adjuvant adenoidectomy was associated with a reduction in the likelihood of reinsertion of tympanostomy tubes (relative risk, 0.5; 95 percent confidence interval, 0.5 to 0.6; P<0.001) and the likelihood of readmission for conditions related to otitis media (relative risk, 0.5; 95 percent confidence interval, 0.5 to 0.6; P<0.001). The risk of these outcomes was further reduced if an adjuvant adenotonsillectomy was performed. The effect was age-related. Children as young as one year appeared to benefit from adjuvant adenotonsillectomy; the benefit of an adjuvant adenoidectomy was apparent in two-year-olds and was greatest for children three years of age or older. Conclusions: Performing adenoidectomy or adenotonsillectomy at the time of the initial insertion of tympanostomy tubes substantially reduces the likelihood of additional hospitalizations and operations related to otitis media among children two years of age or older. (N Engl J Med 2001;344:1188-95.) [ABSTRACT FROM AUTHOR]

Objectives: Local health leaders and the Director General of the World Health Organization alike have observed that COVID-19 "does not discriminate." Nevertheless, the disproportionate representation of people of low socioeconomic status among those infected resembles discrimination. This population-based retrospective cohort study examined COVID-19 case counts and publicly funded healthcare costs in Ontario, Canada, with a focus on marginalization.Methods: Individuals with their first positive severe acute respiratory syndrome coronavirus 2 test from January 1, 2020 to June 30, 2020, were linked to administrative databases and matched to negative/untested controls. Mean net (COVID-19-attributable) costs were estimated for 30 days before and after diagnosis, and differences among strata of age, sex, comorbidity, and measures of marginalization were assessed using analysis of variance tests.Results: We included 28 893 COVID-19 cases (mean age 54 years, 56% female). Most cases remained in the community (20 545, 71.1%) or in long-term care facilities (4478, 15.5%), whereas 944 (3.3%) and 2926 (10.1%) were hospitalized, with and without intensive care unit, respectively. Case counts were skewed across marginalization strata with 2 to 7 times more cases in neighborhoods with low income, high material deprivation, and highest ethnic concentration. Mean net costs after diagnosis were higher for males ($4752 vs $2520 for females) and for cases with higher comorbidity ($1394-$7751) (both P < .001) but were similar across levels of most marginalization dimensions (range $3232-$3737, all P ≥ .19).Conclusions: This study suggests that allocating resources unequally to marginalized individuals may improve equality in outcomes. It highlights the importance of reducing risk of COVID-19 infection among marginalized individuals to reduce overall costs and increase system capacity. [ABSTRACT FROM AUTHOR]

IMPORTANCE Chronic obstructive pulmonary disease (COPD), a manageable respiratory condition, is the third leading cause of death worldwide. Knowing which prescription medications are the most effective in improving health outcomes for people with COPD is essential to maximizing health outcomes. OBJECTIVE To estimate the long-term benefits of combination long-acting β-agonists (LABAs) and inhaled corticosteroids compared with LABAs alone in a real-world setting. DESIGN, SETTING, AND PATIENTS Population-based, longitudinal cohort study conducted in Ontario, Canada, from 2003 to 2011. All individuals aged 66 years or older who met a validated case definition of COPD on the basis of health administrative data were included. After propensity score matching, there were 8712 new users of LABA-inhaled corticosteroid combination therapy and 3160 new users of LABAs alone who were followed up for median times of 2.7 years and 2.5 years, respectively. EXPOSURES Newly prescribed combination LABAs and inhaled corticosteroids or LABAs alone. MAIN OUTCOMES AND MEASURES Composite outcome of death and COPD hospitalization. RESULTS The main outcome was observed among 5594 new users of LABAs and inhaled corticosteroids (3174 deaths [36.4%]; 2420 COPD hospitalizations [27.8%]) and 2129 new users of LABAs alone (1179 deaths [37.3%]; 950 COPD hospitalizations [30.1%]). New use of LABAs and inhaled corticosteroids was associated with a modestly reduced risk of death or COPD hospitalization compared with new use of LABAs alone (difference in composite outcome at 5 years, -3.7%; 95% CI, -5.7% to -1.7%; hazard ratio [HR], 0.92; 95% CI, 0.88-0.96). The greatest difference was among COPD patients with a codiagnosis of asthma (difference in composite at 5 years, -6.5%; 95% CI, -10.3% to -2.7%; HR, 0.84; 95% CI, 0.77-0.91) and those who were not receiving inhaled long-acting anticholinergic medication (difference in composite at 5 years, -8.4%; 95% CI, -11.9% to -4.9%; HR, 0.79; 95% CI, 0.73-0.86). CONCLUSIONS AND RELEVANCE Among older adults with COPD, particularly those with asthma and those not receiving a long-acting anticholinergic medication, newly prescribed LABA and inhaled corticosteroid combination therapy, compared with newly prescribed LABAs alone, was associated with a significantly lower risk of the composite outcome of death or COPD hospitalization. [ABSTRACT FROM AUTHOR]

In the context of mass incarceration and the opioid toxicity crisis in North America, there is a lack of data on the burden of opioid toxicity deaths in Black persons who experience incarceration. We aimed to describe absolute and relative opioid toxicity mortality for Black persons who experienced incarceration in Ontario, Canada between 2015 and 2020. We linked data for all persons incarcerated in provincial correctional facilities and all persons who died from opioid toxicity in Ontario between 2015 and 2020, and accessed public data on population sizes. We described the characteristics of Black persons who were incarcerated and died from opioid toxicity, and calculated absolute mortality rates, as well as age-standardized mortality rates compared with all persons in Ontario not incarcerated during this period. Between 2015 and 2020, 0.9% (n = 137) of 16,177 Black persons who experienced incarceration died from opioid toxicity in custody or post-release, for an opioid toxicity death rate of 0.207 per 100 person years. In the two weeks post-release, the opioid toxicity death rate was 1.34 per 100 person years. Standardized for age and compared with persons not incarcerated, the mortality ratio (SMR) was 17.8 (95%CI 16.4–23.1) for Black persons who experienced incarceration. We identified a large, inequitable burden of opioid toxicity death for Black persons who experience incarceration in Ontario, Canada. Work is needed to support access to culturally appropriate prevention and treatment in custody and post-release for persons who are Black, and to prevent incarceration and improve determinants of health. • We lack data on the opioid crisis in Black people in prison and post-release. • Black people in prison and post-release are at high risk of opioid toxicity death. • The opioid toxicity death burden is inequitably high for this population. • Risk of death from opioid toxicity is highest in the weeks post-release. [ABSTRACT FROM AUTHOR]

Dr. Yulia Lin and Dr. Matthew C Cheung contributed equally as co-senior authors to this study. We performed univariate and multivariable analyses using multilevel logistic regressions (adjusting for clustering within prescribing physician groups) to identify physician factors associated with inappropriate prescribing of vitamin B12. [Extracted from the article]

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] μ mol/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] μ mol/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. [ABSTRACT FROM AUTHOR]

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 CβS 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. [ABSTRACT FROM AUTHOR]

Background: Folate, vitamin B-6, vitamin B-12, and choline are involved in one-carbon metabolism and play critical roles in pregnancy including prevention of birth defects and promotion of neurodevelopment. However, excessive intakes may adversely affect disease susceptibility in offspring. Intakes of these nutrients during pregnancy are not well characterized. Objective: Our aim was to determine dietary and supplemental intakes and major dietary sources of one-carbon nutrients during pregnancy. Methods: In pregnant women (n = 368) at ≤16 wk postconception, supplement use >30 d before pregnancy was assessed by maternal recall and supplement and dietary intakes in early (0-16 wk) and late pregnancy (23-37 wk) were assessed by food-frequency questionnaire. Results: Preconception, 60.1 % (95% CI: 55.8, 64.3) of women used B vitamin-containing supplements. This increased to 92.8% (95% CI: 89.6, 95.2) in early and 89.0% (95% CI: 85.0, 92.3) in late pregnancy. Median supplemental folic acid, vitamin B-12, and vitamin B-6 were 1000 mg/d, 2.6 mg/d, and 1.9 mg/d, respectively. Forty-one percent and 50% of women had dietary intakes of folate and vitamin B-6 less than the estimated average requirement (520 mg/d dietary folate equivalents and 1.6 mg/d, respectively). Eight-seven percent of women had choline intakes less than the Adequate Intake (450 mg/d). Dietary intakes did not change appreciably during pregnancy. Fruits and vegetables and fortified foods contributed ~57% to total dietary folate intake. Fruits and vegetables contributed ~32% to total dietary vitamin B-6 intake and dairy and egg products contributed ~37% to total dietary vitamin B-12 intake. Conclusions: Vitamin supplements were an important source of one-carbon nutrients during pregnancy in our sample. Without supplements, many women would not have consumed quantities of folate and vitamin B-6 consistent with recommendations. Given the importance of choline in pregnancy, further research to consider inclusion in prenatal supplements is warranted. This trial was registered at clinicaltrials.gov as NCT02244684. [ABSTRACT FROM AUTHOR]