Effect of human papillomavirus (HPV) vaccination on clinical indicators of sexual behaviour among adolescent girls: the Ontario Grade 8 HPV Vaccine Cohort Study

Background:

Suboptimal human papillomavirus (HPV) vaccine coverage in some jurisdictions is partly attributed to fears that vaccination may increase risky sexual behaviour. We assessed the effect of HPV vaccination on clinical indicators of sexual behaviour among adolescent girls in Ontario.

Methods:

Using Ontario’s administrative health databases, we identified a population-based cohort of girls in grade 8 in the 2 years before (2005/06 and 2006/07) and after (2007/08 and 2008/09) implementation of Ontario’s grade 8 HPV vaccination program. For each girl, we then obtained data on vaccine receipt in grades 8 and 9 and data on indicators of sexual behaviour (pregnancy and non–HPV-related sexually transmitted infections) in grades 10–12. Using a quasi-experimental method known as regression discontinuity, we estimated, for each outcome, the risk difference (RD) and relative risk (RR) attributable to vaccination and to program eligibility.

Results:

The cohort comprised 260 493 girls, of whom 131 781 were ineligible for the program and 128 712 were eligible. We identified 15 441 (5.9%) cases of pregnancy and sexually transmitted infection and found no evidence that vaccination increased the risk of this composite outcome: RD per 1000 girls −0.61 (95% confidence interval [CI] −10.71 to 9.49) and RR 0.96 (95% CI 0.81 to 1.14). Similarly, we found no discernible effect of program eligibility: RD per 1000 girls −0.25 (95% CI −4.35 to 3.85) and RR 0.99 (95% CI 0.93 to 1.06). The findings were similar when outcomes were assessed separately.

Interpretation:

We present strong evidence that HPV vaccination does not have any significant effect on clinical indicators of sexual behaviour among adolescent girls. These results suggest that concerns over increased promiscuity following HPV vaccination are unwarranted and should not deter from vaccinating at a young age.Infection with the human papillomavirus (HPV) is the most commonly diagnosed sexually transmitted infection in Canada and around the world.¹ Although most of these infections are transient and self-resolving, others persist and can cause important health outcomes, including cervical cancer and anogenital warts.In 2006, Canada was among 49 countries to license Gardasil (Merck, Whitehouse Station, New Jersey), a quadrivalent HPV vaccine designed to protect against 4 types of HPV (6, 11, 16, 18) that cause 70% of cases of cervical cancer and most cases of anogenital warts.^2–4 As one of the first cancer-preventing vaccines, this vaccine received expedited approval in several countries and was the subject of intensive marketing, lobbying and public health campaigns around the world.⁵ By 2012, it had been approved in almost 100 countries, many of which also implemented nationwide HPV vaccination programs aimed primarily at immunizing young girls before the onset of sexual activity.⁶Despite the popularity of large-scale immunization programs, HPV vaccination has faced a great deal of controversy regarding unanswered questions about the real-world effects of this vaccine.^7,8 A major topic of public debate has been the possibility that HPV vaccination might lead to sexual disinhibition,⁹ that is, that receipt of the vaccine might give women and girls a false sense of protection against all sexually transmitted infections and that this false sense of protection might lead them to engage in more risky sexual behaviours than they would otherwise (e.g., be more promiscuous or neglect to use condoms). Increases in these risky behaviours could have important clinical consequences, including increased risk of pregnancy and sexually transmitted infections. Although there is little empirical support for the notion that sexual health interventions promote risky sexual behaviours,^10,11 this possible unintended effect of the HPV vaccine would undermine its value for reducing the burden of sexual health–related diseases. Moreover, parental fears of increased promiscuity following HPV vaccination have been reported as a major determinant of vaccine refusal,¹² which may help to explain suboptimal HPV vaccine coverage in some jurisdictions.^6,13 Evidently, both actual and perceived sexual disinhibition can have a negative effect on the potential health benefits of HPV vaccination. Therefore, we conducted a population-based, retrospective cohort study to assess the effect of HPV vaccination on clinical indicators of sexual behaviour among adolescent girls in Ontario.     

Effects of prenatal multimicronutrient supplementation on pregnancy outcomes: a meta-analysis

Background

Reduced intake of micronutrients during pregnancy exposes women to nutritional deficiencies and may affect fetal growth. We conducted a systematic review to examine the efficacy of prenatal supplementation with multimicronutrients on pregnancy outcomes.

Methods

We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library for relevant articles published in English up to December 2008. We also searched the bibliographies of selected articles as well as clinical trial registries. The primary outcome was low birth weight; secondary outcomes were preterm birth, small-for-gestational-age infants, birth weight and gestational age.

Results

We observed a significant reduction in the risk of low birth weight among infants born to women who received multimicronutrients during pregnancy compared with placebo (relative risk [RR] 0.81, 95% confidence interval [CI] 0.73–0.91) or iron–folic acid supplementation (RR 0.83, 95% CI 0.74–0.93). Birth weight was significantly higher among infants whose mothers were in the multimicronutrient group than among those whose mothers received iron–folic acid supplementation (weighted mean difference 54 g, 95% CI 36 g–72 g). There was no significant differences in the risk of preterm birth or small-for-gestational-age infants between the 3 study groups.

Interpretation

Prenatal multimicronutrient supplementation was associated with a significantly reduced risk of low birth weight and with improved birth weight when compared with iron–folic acid supplementation. There was no significant effect of multimicronutrient supplementation on the risk of preterm birth or small-for-gestational-age infants.Nutrition plays an important role in the growth and development of the fetus. Studies of the nutritional status of pregnant women during the Dutch famine revealed increased risks of infertility, abortion, fetal intrauterine growth restriction and perinatal mortality among malnourished women.¹ In many parts of the world, a similar situation exists for many pregnant women with respect to nutrition. Overall, the diet of pregnant women has been reported to be deficient in calories and micronutrients.² Both macro- and micronutrients are important for a woman to sustain pregnancy and for appropriate growth of the fetus.The exact mechanisms of how supplementation with micronutrients can affect pregnancy outcomes are not completely understood. Possible mechanisms for beneficial effects include a generalized improvement in the immune function of women, with a reduced incidence of infections and subsequent reduced incidence of preterm birth;³ improved energy metabolism and anabolic processes in the mother, with a reduced incidence of fetal intrauterine growth restriction;³ improved ability to respond to stress;³ expansion of plasma volume secondary to fluid retention, with subsequent improvements in fetal growth;⁴ improved hemoglobin levels;⁵ and increased absorption of iron related to intake of vitamin C and riboflavin, with subsequent improvement in hemoglobin levels.⁵Potential disadvantages include adverse interactions of micronutrients when supplied in combination;⁶ enhanced or reduced absorption of one nutrient by other nutrients (e.g., interaction between iron and vitamin C, and iron and zinc);⁷ deleterious effects on the fetus and the mother from overdose of any one component (e.g., vitamin A overdose);⁶ and cost.⁶Potential barriers include the lack of well-defined government policies on maternal health and nutrition.⁶ A multicomponent approach has been criticized from the standpoint that some micronutrients may be necessary, some may not be needed and some may even be harmful.² Generalized or mass supplementation with multimicronutrients may have different effects on pregnancy outcomes depending on the underlying nutritional status of the women.On the basis of a systematic review performed in 2005, the World Health Organization currently recommends iron–folic acid supplementation for all pregnant women.^8,9 The review reported that multimicronutrient supplementation during pregnancy were more efficacious than 2 or fewer micronutrients in reducing the rates of low birth weight and small-for-gestational-age births. However, when multimicronutrients were compared with iron–folic acid supplementation, no evidence of a difference was noted.⁷ Further research in this area was encouraged because information was derived from a few reports. Since then, several randomized controlled trials have evaluated the efficacy of multimicronutrients and have reported varied results. With advancement in our knowledge from recently reported trials,¹⁰ we conducted a systematic review and meta-analysis of the efficacy of supplementation with multimicronutrients during pregnancy in reducing the rates of low birth weight, preterm birth and small-for-gestational-age births compared with placebo or iron–folic acid supplementation.     

Effectiveness of training family physicians to deliver a brief intervention to address excessive substance use among young patients: a cluster randomized controlled trial

Background:

Brief interventions delivered by family physicians to address excessive alcohol use among adult patients are effective. We conducted a study to determine whether such an intervention would be similarly effective in reducing binge drinking and excessive cannabis use among young people.

Methods:

We conducted a cluster randomized controlled trial involving 33 family physicians in Switzerland. Physicians in the intervention group received training in delivering a brief intervention to young people during the consultation in addition to usual care. Physicians in the control group delivered usual care only. Consecutive patients aged 15–24 years were recruited from each practice and, before the consultation, completed a confidential questionnaire about their general health and substance use. Patients were followed up at 3, 6 and 12 months after the consultation. The primary outcome measure was self-reported excessive substance use (≥ 1 episode of binge drinking, or ≥ 1 joint of cannabis per week, or both) in the past 30 days.

Results:

Of the 33 participating physicians, 17 were randomly allocated to the intervention group and 16 to the control group. Of the 594 participating patients, 279 (47.0%) identified themselves as binge drinkers or excessive cannabis users, or both, at baseline. Excessive substance use did not differ significantly between patients whose physicians were in the intervention group and those whose physicians were in the control group at any of the follow-up points (odds ratio [OR] and 95% confidence interval [CI] at 3 months: 0.9 [0.6–1.4]; at 6 mo: 1.0 [0.6–1.6]; and at 12 mo: 1.1 [0.7–1.8]). The differences between groups were also nonsignificant after we re stricted the analysis to patients who reported excessive substance use at baseline (OR 1.6, 95% CI 0.9–2.8, at 3 mo; OR 1.7, 95% CI 0.9–3.2, at 6 mo; and OR 1.9, 95% CI 0.9–4.0, at 12 mo).

Interpretation:

Training family physicians to use a brief intervention to address excessive substance use among young people was not effective in reducing binge drinking and excessive cannabis use in this patient population. Trial registration: Australian New Zealand Clinical Trials Registry, no. ACTRN12608000432314.Most health-compromising behaviours begin in adolescence.¹ Interventions to address these behaviours early are likely to bring long-lasting benefits.² Harmful use of alcohol is a leading factor associated with premature death and disability worldwide, with a disproportionally high impact on young people (aged 10–24 yr).^3,4 Similarly, early cannabis use can have adverse consequences that extend into adulthood.^5–8In adolescence and early adulthood, binge drinking on at least a monthly basis is associated with an increased risk of adverse outcomes later in life.^9–12 Although any cannabis use is potentially harmful, weekly use represents a threshold in adolescence related to an increased risk of cannabis (and tobacco) dependence in adulthood.¹³ Binge drinking affects 30%–50% and excessive cannabis use about 10% of the adolescent and young adult population in Europe and the United States.^10,14,15Reducing substance-related harm involves multisectoral approaches, including promotion of healthy child and adolescent development, regulatory policies and early treatment interventions.¹⁶ Family physicians can add to the public health messages by personalizing their content within brief interventions.^17,18 There is evidence that brief interventions can encourage young people to reduce substance use, yet most studies have been conducted in community settings (mainly educational), emergency services or specialized addiction clinics.^1,16 Studies aimed at adult populations have shown favourable effects of brief alcohol interventions, and to some extent brief cannabis interventions, in primary care.^19–22 These interventions have been recommended for adolescent populations.^4,5,16 Yet young people have different modes of substance use and communication styles that may limit the extent to which evidence from adult studies can apply to them.Recently, a systematic review of brief interventions to reduce alcohol use in adolescents identified only 1 randomized controlled trial in primary care.²³ The tested intervention, not provided by family physicians but involving audio self-assessment, was ineffective in reducing alcohol use in exposed adolescents.²⁴ Sanci and colleagues showed that training family physicians to address health-risk behaviours among adolescents was effective in improving provider performance, but the extent to which this translates into improved outcomes remains unknown.^25,26 Two nonrandomized studies suggested screening for substance use and brief advice by family physicians could favour reduced alcohol and cannabis use among adolescents,^27,28 but evidence from randomized trials is lacking.²⁹We conducted the PRISM-Ado (Primary care Intervention Addressing Substance Misuse in Adolescents) trial, a cluster randomized controlled trial of the effectiveness of training family physicians to deliver a brief intervention to address binge drinking and excessive cannabis use among young people.     

Effect of ambient air pollution on the incidence of appendicitis

Background

The pathogenesis of appendicitis is unclear. We evaluated whether exposure to air pollution was associated with an increased incidence of appendicitis.

Methods

We identified 5191 adults who had been admitted to hospital with appendicitis between Apr. 1, 1999, and Dec. 31, 2006. The air pollutants studied were ozone, nitrogen dioxide, sulfur dioxide, carbon monoxide, and suspended particulate matter of less than 10 μ and less than 2.5 μ in diameter. We estimated the odds of appendicitis relative to short-term increases in concentrations of selected pollutants, alone and in combination, after controlling for temperature and relative humidity as well as the effects of age, sex and season.

Results

An increase in the interquartile range of the 5-day average of ozone was associated with appendicitis (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.03–1.25). In summer (July–August), the effects were most pronounced for ozone (OR 1.32, 95% CI 1.10–1.57), sulfur dioxide (OR 1.30, 95% CI 1.03–1.63), nitrogen dioxide (OR 1.76, 95% CI 1.20–2.58), carbon monoxide (OR 1.35, 95% CI 1.01–1.80) and particulate matter less than 10 μ in diameter (OR 1.20, 95% CI 1.05–1.38). We observed a significant effect of the air pollutants in the summer months among men but not among women (e.g., OR for increase in the 5-day average of nitrogen dioxide 2.05, 95% CI 1.21–3.47, among men and 1.48, 95% CI 0.85–2.59, among women). The double-pollutant model of exposure to ozone and nitrogen dioxide in the summer months was associated with attenuation of the effects of ozone (OR 1.22, 95% CI 1.01–1.48) and nitrogen dioxide (OR 1.48, 95% CI 0.97–2.24).

Interpretation

Our findings suggest that some cases of appendicitis may be triggered by short-term exposure to air pollution. If these findings are confirmed, measures to improve air quality may help to decrease rates of appendicitis.Appendicitis was introduced into the medical vernacular in 1886.¹ Since then, the prevailing theory of its pathogenesis implicated an obstruction of the appendiceal orifice by a fecalith or lymphoid hyperplasia.² However, this notion does not completely account for variations in incidence observed by age,^3,4 sex,^3,4 ethnic background,^3,4 family history,⁵ temporal–spatial clustering⁶ and seasonality,^3,4 nor does it completely explain the trends in incidence of appendicitis in developed and developing nations.^3,7,8The incidence of appendicitis increased dramatically in industrialized nations in the 19th century and in the early part of the 20th century.¹ Without explanation, it decreased in the middle and latter part of the 20th century.³ The decrease coincided with legislation to improve air quality. For example, after the United States Clean Air Act was passed in 1970,⁹ the incidence of appendicitis decreased by 14.6% from 1970 to 1984.³ Likewise, a 36% drop in incidence was reported in the United Kingdom between 1975 and 1994¹⁰ after legislation was passed in 1956 and 1968 to improve air quality and in the 1970s to control industrial sources of air pollution. Furthermore, appendicitis is less common in developing nations; however, as these countries become more industrialized, the incidence of appendicitis has been increasing.⁷Air pollution is known to be a risk factor for multiple conditions, to exacerbate disease states and to increase all-cause mortality.¹¹ It has a direct effect on pulmonary diseases such as asthma¹¹ and on nonpulmonary diseases including myocardial infarction, stroke and cancer.^11–13 Inflammation induced by exposure to air pollution contributes to some adverse health effects.^14–17 Similar to the effects of air pollution, a proinflammatory response has been associated with appendicitis.^18–20We conducted a case–crossover study involving a population-based cohort of patients admitted to hospital with appendicitis to determine whether short-term increases in concentrations of selected air pollutants were associated with hospital admission because of appendicitis.     

Association of macrosomia with perinatal and postneonatal mortality among First Nations people in Quebec

Background

High prevalence of infant macrosomia (up to 36%, the highest in the world) has been reported in some First Nations communities in the Canadian province of Quebec and the eastern area of the province of Ontario. We aimed to assess whether infant macrosomia was associated with elevated risks of perinatal and postneonatal mortality among First Nations people in Quebec.

Methods

We calculated risk ratios (RRs) of perinatal and postneonatal mortality by birthweight for gestational age, comparing births to First Nations women (n = 5193) versus women whose mother tongue is French (n = 653 424, the majority reference group) in Quebec 1991–2000.

Results

The prevalence of infant macrosomia (birthweight for gestational age > 90th percentile) was 27.5% among births to First Nations women, which was 3.3 times (confidence interval [CI] 3.2–3.5) higher than the prevalence (8.3%) among births to women whose mother tongue is French. Risk ratios for perinatal mortality among births to First Nations women were 1.8 (95% CI 1.3–2.5) for births with weight appropriate for gestational age, 4.1 (95% CI 2.4–7.0) for small-for-gestational-age (< 10th percentile) births and < 1 (not significant) for macrosomic births compared to births among women whose mother tongue is French. The RRs for postneonatal mortality were 4.3 (95% CI 2.7–6.7) for infants with appropriate-for-gestational-age birthweight and 8.3 (95% CI 4.0–17.0) for infants with macrosomia.

Interpretation

Macrosomia was associated with a generally protective effect against perinatal death, but substantially greater risks of postneonatal death among births to First Nations women in Quebec versus women whose mother tongue is French.A trend toward higher birthweights has emerged in recent decades.^1–3 Reflected in this trend is a rise in the prevalence of infant macrosomia, commonly defined as either a birthweight greater than 4000 g or a birthweight for gestational age greater than the 90th percentile relative to a fetal growth standard.^4–8 Maternal obesity, impaired glucose tolerance and gestational diabetes mellitus are important risk factors for infant macrosomia^9,10 and are known to afflict a much higher proportion of people in Aboriginal populations than in the general population.^11–14 This is true especially for Aboriginal populations in which a traditional lifestyle has changed to a less physically active, modern lifestyle in recent decades. A high prevalence of infant macrosomia (up to 36%, which, to the best of our knowledge, is the highest in the world) has been reported in some First Nations communities of Quebec and eastern Ontario in Canada.^15–17 However, little is known about the implications of this high prevalence for perinatal and infant health of First Nations people in these regions. We examined whether infant macrosomia was associated with increased risk for perinatal and postneonatal death among First Nations infants in Quebec.     

Risk of vascular events in patients with polymyalgia rheumatica

Background:

Polymyalgia rheumatica is one of the most common inflammatory rheumatologic conditions in older adults. Other inflammatory rheumatologic disorders are associated with an excess risk of vascular disease. We investigated whether polymyalgia rheumatica is associated with an increased risk of vascular events.

Methods:

We used the General Practice Research Database to identify patients with a diagnosis of incident polymyalgia rheumatica between Jan. 1, 1987, and Dec. 31, 1999. Patients were matched by age, sex and practice with up to 5 patients without polymyalgia rheumatica. Patients were followed until their first vascular event (cardiovascular, cerebrovascular, peripheral vascular) or the end of available records (May 2011). All participants were free of vascular disease before the diagnosis of polymyalgia rheumatica (or matched date). We used Cox regression models to compare time to first vascular event in patients with and without polymyalgia rheumatica.

Results:

A total of 3249 patients with polymyalgia rheumatica and 12 735 patients without were included in the final sample. Over a median follow-up period of 7.8 (interquartile range 3.3–12.4) years, the rate of vascular events was higher among patients with polymyalgia rheumatica than among those without (36.1 v. 12.2 per 1000 person-years; adjusted hazard ratio 2.6, 95% confidence interval 2.4–2.9). The increased risk of a vascular event was similar for each vascular disease end point. The magnitude of risk was higher in early disease and in patients younger than 60 years at diagnosis.

Interpretation:

Patients with polymyalgia rheumatica have an increased risk of vascular events. This risk is greatest in the youngest age groups. As with other forms of inflammatory arthritis, patients with polymyalgia rheumatica should have their vascular risk factors identified and actively managed to reduce this excess risk.Inflammatory rheumatologic disorders such as rheumatoid arthritis,^1,2 systemic lupus erythematosus,^2,3 gout,⁴ psoriatic arthritis^2,5 and ankylosing spondylitis^2,6 are associated with an increased risk of vascular disease, especially cardiovascular disease, leading to substantial morbidity and premature death.^2–6 Recognition of this excess vascular risk has led to management guidelines advocating screening for and management of vascular risk factors.^7–9Polymyalgia rheumatica is one of the most common inflammatory rheumatologic conditions in older adults,¹⁰ with a lifetime risk of 2.4% for women and 1.7% for men.¹¹ To date, evidence regarding the risk of vascular disease in patients with polymyalgia rheumatica is unclear. There are a number of biologically plausible mechanisms between polymyalgia rheumatica and vascular disease. These include the inflammatory burden of the disease,^12,13 the association of the disease with giant cell arteritis (causing an inflammatory vasculopathy, which may lead to subclinical arteritis, stenosis or aneurysms),¹⁴ and the adverse effects of long-term corticosteroid treatment (e.g., diabetes, hypertension and dyslipidemia).^15,16 Paradoxically, however, use of corticosteroids in patients with polymyalgia rheumatica may actually decrease vascular risk by controlling inflammation.¹⁷ A recent systematic review concluded that although some evidence exists to support an association between vascular disease and polymyalgia rheumatica,¹⁸ the existing literature presents conflicting results, with some studies reporting an excess risk of vascular disease^19,20 and vascular death,^21,22 and others reporting no association.^23–26 Most current studies are limited by poor methodologic quality and small samples, and are based on secondary care cohorts, who may have more severe disease, yet most patients with polymyalgia rheumatica receive treatment exclusively in primary care.²⁷The General Practice Research Database (GPRD), based in the United Kingdom, is a large electronic system for primary care records. It has been used as a data source for previous studies,²⁸ including studies on the association of inflammatory conditions with vascular disease²⁹ and on the epidemiology of polymyalgia rheumatica in the UK.³⁰ The aim of the current study was to examine the association between polymyalgia rheumatica and vascular disease in a primary care population.     

Relation between fractures and mortality: results from the Canadian Multicentre Osteoporosis Study

Background

Fractures have largely been assessed by their impact on quality of life or health care costs. We conducted this study to evaluate the relation between fractures and mortality.

Methods

A total of 7753 randomly selected people (2187 men and 5566 women) aged 50 years and older from across Canada participated in a 5-year observational cohort study. Incident fractures were identified on the basis of validated self-report and were classified by type (vertebral, pelvic, forearm or wrist, rib, hip and “other”). We subdivided fracture groups by the year in which the fracture occurred during follow-up; those occurring in the fourth and fifth years were grouped together. We examined the relation between the time of the incident fracture and death.

Results

Compared with participants who had no fracture during follow-up, those who had a vertebral fracture in the second year were at increased risk of death (adjusted hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.1–6.6); also at risk were those who had a hip fracture during the first year (adjusted HR 3.2, 95% CI 1.4–7.4). Among women, the risk of death was increased for those with a vertebral fracture during the first year (adjusted HR 3.7, 95% CI 1.1–12.8) or the second year of follow-up (adjusted HR 3.2, 95% CI 1.2–8.1). The risk of death was also increased among women with hip fracture during the first year of follow-up (adjusted HR 3.0, 95% CI 1.0–8.7).

Interpretation

Vertebral and hip fractures are associated with an increased risk of death. Interventions that reduce the incidence of these fractures need to be implemented to improve survival.Osteoporosis-related fractures are a major health concern, affecting a growing number of individuals worldwide. The burden of fracture has largely been assessed by the impact on health-related quality of life and health care costs.^1,2 Fractures can also be associated with death. However, trials that have examined the relation between fractures and mortality have had limitations that may influence their results and the generalizability of the studies, including small samples,^3,4 the examination of only 1 type of fracture,^4–10 the inclusion of only women,^8,11 the enrolment of participants from specific areas (i.e., hospitals or certain geographic regions),^{3,4,7,8,10,12} the nonrandom selection of participants^3–11 and the lack of statistical adjustment for confounding factors that may influence mortality.^3,5–7,12We evaluated the relation between incident fractures and mortality over a 5-year period in a cohort of men and women 50 years of age and older. In addition, we examined whether other characteristics of participants were risk factors for death.     

Comparison of black–white disparities in preterm birth between Canada and the United States

Background:

A higher risk of preterm birth among black women than among white women is well established in the United States. We compared differences in preterm birth between non-Hispanic black and white women in Canada and the US, hypothesizing that disparities would be less extreme in Canada given the different historical experiences of black populations and Canada’s universal health care system.

Methods:

Using data on singleton live births in Canada and the US for 2004–2006, we estimated crude and adjusted risk ratios and risk differences in preterm birth (< 37 wk) and very preterm birth (< 32 wk) among non-Hispanic black versus non-Hispanic white women in each country. Adjusted models for the US were standardized to the covariate distribution of the Canadian cohort.

Results:

In Canada, 8.9% and 5.9% of infants born to black and white mothers, respectively, were preterm; the corresponding figures in the US were 12.7% and 8.0%. Crude risk ratios for preterm birth among black women relative to white women were 1.49 (95% confidence interval [CI] 1.32 to 1.66) in Canada and 1.57 (95% CI 1.56 to 1.58) in the US (p value for heterogeneity [p_H] = 0.3). The crude risk differences for preterm birth were 2.94 (95% CI 1.91 to 3.96) in Canada and 4.63 (95% CI 4.56 to 4.70) in the US (p_H = 0.003). Adjusted risk ratios for preterm birth (p_H = 0.1) were slightly higher in Canada than in the US, whereas adjusted risk differences were similar in both countries. Similar patterns were observed for racial disparities in very preterm birth.

Interpretation:

Relative disparities in preterm birth and very preterm birth between non-Hispanic black and white women were similar in magnitude in Canada and the US. Absolute disparities were smaller in Canada, which reflects a lower overall risk of preterm birth in Canada than in the US in both black and white populations.In the United States, a higher risk of preterm birth among black women than among white women is well established.^1–3 This racial disparity is of great concern because preterm birth is a leading cause of perinatal mortality and is predictive of developmental problems and adverse health outcomes later in life.⁴ The underlying causes of the racial disparity in preterm birth in the US are not well understood, although research has suggested contributing roles for a wide range of factors, including socioeconomic disadvantage,⁵ poor neighbourhood conditions (e.g., poverty, crime),^5,6 lack of access to health care,⁷ psychosocial stress,⁸ racial discrimination⁹ and adverse health behaviours.¹⁰Rates of preterm birth have consistently been lower in Canada than in the US.^11,12 However, in contrast to the US, little is known about differences in rates by race or ethnicity in Canada. There is evidence that African-born and Caribbean-born women in the provinces of Quebec and Ontario have higher rates of preterm birth than Canadian-born women.^13–15 Although the magnitude of these differences is smaller than the disparity in preterm births between black and white women in the US,¹⁶ foreign-born black women in the US have been found to be at lower risk of preterm birth than US-born black women.^17,18In both Canada and the US, socioeconomic conditions at both individual and neighbourhood levels are important predictors of preterm birth.^19–21 Although the income gap between black and white people is markedly smaller in Canada than in the US,²² black populations in both countries have lower education levels, higher unemployment rates and a greater likelihood of living in low-quality neighbourhoods compared with white populations.²³ Canada and the US share similar social and economic influences, yet the historical experiences of black populations and the social welfare systems (e.g., universal health care) are quite different in the 2 countries. Black people constitute about 13% of the total US population, but only about 3% of the Canadian population.^24,25 The overwhelming majority of Canada’s black population are immigrants who entered the country after 1960 and their descendants, whereas more than 85% of black Americans can trace their ancestry 3 or more generations in the US, with most being descendants of slaves.²²The objectives of our study are twofold. First, using data from a new cohort linking birth registrations with information from the 2006 Canadian long-form census, we present Canada-wide estimates of differences in preterm birth rates between black and white populations. Second, we use comparable methodology to compare racial differences in preterm birth rates between Canada and the US. Given different historical experiences of black populations in the 2 countries, as well as Canada’s commitment to universal health care and its general perception as a more egalitarian society than the US,²² we hypothesized that we would observe smaller racial disparities in the rates in Canada than in the US.     

Prevalence of and risk factors for persistent postoperative nonanginal pain after cardiac surgery: a 2-year prospective multicentre study

Background:

Persistent postoperative pain continues to be an underrecognized complication. We examined the prevalence of and risk factors for this type of pain after cardiac surgery.

Methods:

We enrolled patients scheduled for coronary artery bypass grafting or valve replacement, or both, from Feb. 8, 2005, to Sept. 1, 2009. Validated measures were used to assess (a) preoperative anxiety and depression, tendency to catastrophize in the face of pain, health-related quality of life and presence of persistent pain; (b) pain intensity and interference in the first postoperative week; and (c) presence and intensity of persistent postoperative pain at 3, 6, 12 and 24 months after surgery. The primary outcome was the presence of persistent postoperative pain during 24 months of follow-up.

Results:

A total of 1247 patients completed the preoperative assessment. Follow-up retention rates at 3 and 24 months were 84% and 78%, respectively. The prevalence of persistent postoperative pain decreased significantly over time, from 40.1% at 3 months to 22.1% at 6 months, 16.5% at 12 months and 9.5% at 24 months; the pain was rated as moderate to severe in 3.6% at 24 months. Acute postoperative pain predicted both the presence and severity of persistent postoperative pain. The more intense the pain during the first week after surgery and the more it interfered with functioning, the more likely the patients were to report persistent postoperative pain. Pre-existing persistent pain and increased preoperative anxiety also predicted the presence of persistent postoperative pain.

Interpretation:

Persistent postoperative pain of nonanginal origin after cardiac surgery affected a substantial proportion of the study population. Future research is needed to determine whether interventions to modify certain risk factors, such as preoperative anxiety and the severity of pain before and immediately after surgery, may help to minimize or prevent persistent postoperative pain.Postoperative pain that persists beyond the normal time for tissue healing (> 3 mo) is increasingly recognized as an important complication after various types of surgery and can have serious consequences on patients’ daily living.^1–3 Cardiac surgeries, such as coronary artery bypass grafting (CABG) and valve replacement, rank among the most frequently performed interventions worldwide.⁴ They aim to improve survival and quality of life by reducing symptoms, including anginal pain. However, persistent postoperative pain of nonanginal origin has been reported in 7% to 60% of patients following these surgeries.^5–23 Such variability is common in other types of major surgery and is due mainly to differences in the definition of persistent postoperative pain, study design, data collection methods and duration of follow-up.^1–3,24Few prospective cohort studies have examined the exact time course of persistent postoperative pain after cardiac surgery, and follow-up has always been limited to a year or less.^9,14,25 Factors that put patients at risk of this type of problem are poorly understood.²⁶ Studies have reported inconsistent results regarding the contribution of age, sex, body mass index, preoperative angina, surgical technique, grafting site, postoperative complications or level of opioid consumption after surgery.^{5–7,9,13,14,16–19,21–23,25,27} Only 1 study investigated the role of chronic nonanginal pain before surgery as a contributing factor;²¹ 5 others prospectively assessed the association between persistent postoperative pain and acute pain intensity in the first postoperative week but reported conflicting results.^{13,14,21,22,25} All of the above studies were carried out in a single hospital and included relatively small samples. None of the studies examined the contribution of psychological factors such as levels of anxiety and depression before cardiac surgery, although these factors have been shown to influence acute or persistent postoperative pain in other types of surgery.^1,24,28,29We conducted a prospective multicentre cohort study (the CARD-PAIN study) to determine the prevalence of persistent postoperative pain of nonanginal origin up to 24 months after cardiac surgery and to identify risk factors for the presence and severity of the condition.     

Improving the quality of care for infants: a cluster randomized controlled trial

Background

We developed and tested a new method, called the Evidence-based Practice for Improving Quality method, for continuous quality improvement.

Methods

We used cluster randomization to assign 6 neonatal intensive care units (ICUs) to reduce nosocomial infection (infection group) and 6 ICUs to reduce bronchopulmonary dysplasia (pulmonary group). We included all infants born at 32 or fewer weeks gestation. We collected baseline data for 1 year. Practice change interventions were implemented using rapid-change cycles for 2 years.

Results

The difference in incidence trends (slopes of trend lines) between the ICUs in the infection and pulmonary groups was − 0.0020 (95% confidence interval [CI] − 0.0007 to 0.0004) for nosocomial infection and − 0.0006 (95% CI − 0.0011 to − 0.0001) for bronchopulmonary dysplasia.

Interpretation

The results suggest that the Evidence-based Practice for Improving Quality method reduced bronchopulmonary dysplasia in the neonatal ICU and that it may reduce nosocomial infection.Although methods for continuous quality improvement have been used to improve outcomes,^1–3 some, such as the National Institutes of Child Health and Human Development Quality Collaborative,⁴ have reported little or no effect in neonatal intensive care units (ICUs). These methods have been criticized for being based on intuition and anecdotes rather than on evidence.⁵ To address these concerns, researchers have developed methods aimed at improving the use of evidence in quality improvement. Tarnow-Mordi and colleagues,⁶ Sankaran and colleagues⁷ and others^8–10 have used benchmarking instruments^6,8,11 to show risk-adjusted variations in outcomes in neonatal ICUs. Synnes and colleagues¹² reported that variations in the rates of intraventricular hemorrhage could be attributed to practice differences. MacNab and colleagues¹³ showed how multilevel modelling methods can be used to identify practice differences associated with variations in outcomes for targeted interventions and to quantify their attributable risks.Building on these results, we developed the Evidence-based Practice for Improving Quality method for continuous quality improvement. This method is based on 3 pillars: the use of evidence from published literature; the use of data from participating hospitals to identify hospital-specific practices for targeted intervention; and the use of a national network to share expertise. By selectively targeting hospital-specific practices for intervention, this method reduces the reliance on intuition and anecdotes that are associated with existing quality-improvement methods.Our objective was to evaluate the efficacy of the Evidence-based Practice for Improving Quality method by conducting a prospective cluster randomized controlled trial to reduce nosocomial infection and bronchopulmonary dysplasia among infants born at 32 or fewer weeks’ gestation and admitted to 12 Canadian Neonatal Network hospitals¹⁴ over a 36-month period. We hypothesized that the incidence of nosocomial infection would be reduced among infants in ICUs randomized to reduce infection but not among those in ICUs randomized to reduce bronchopulmonary dysplasia. We also hypothesized that the incidence of bronchopulmonary dysplasia would be reduced among infants in the ICUs randomized to reduce this outcome but not among those in ICUs randomized to reduce infections.     

Effectiveness of interventions designed to reduce the use of imaging for low-back pain: a systematic review

Background:Rates of imaging for low-back pain are high and are associated with increased health care costs and radiation exposure as well as potentially poorer patient outcomes. We conducted a systematic review to investigate the effectiveness of interventions aimed at reducing the use of imaging for low-back pain.Methods:We searched MEDLINE, Embase, CINAHL and the Cochrane Central Register of Controlled Trials from the earliest records to June 23, 2014. We included randomized controlled trials, controlled clinical trials and interrupted time series studies that assessed interventions designed to reduce the use of imaging in any clinical setting, including primary, emergency and specialist care. Two independent reviewers extracted data and assessed risk of bias. We used raw data on imaging rates to calculate summary statistics. Study heterogeneity prevented meta-analysis.Results:A total of 8500 records were identified through the literature search. Of the 54 potentially eligible studies reviewed in full, 7 were included in our review. Clinical decision support involving a modified referral form in a hospital setting reduced imaging by 36.8% (95% confidence interval [CI] 33.2% to 40.5%). Targeted reminders to primary care physicians of appropriate indications for imaging reduced referrals for imaging by 22.5% (95% CI 8.4% to 36.8%). Interventions that used practitioner audits and feedback, practitioner education or guideline dissemination did not significantly reduce imaging rates. Lack of power within some of the included studies resulted in lack of statistical significance despite potentially clinically important effects.Interpretation:Clinical decision support in a hospital setting and targeted reminders to primary care doctors were effective interventions in reducing the use of imaging for low-back pain. These are potentially low-cost interventions that would substantially decrease medical expenditures associated with the management of low-back pain.Current evidence-based clinical practice guidelines recommend against the routine use of imaging in patients presenting with low-back pain.^1–3 Despite this, imaging rates remain high,^4,5 which indicates poor concordance with these guidelines.^6,7Unnecessary imaging for low-back pain has been associated with poorer patient outcomes, increased radiation exposure and higher health care costs.⁸ No short- or long-term clinical benefits have been shown with routine imaging of the low back, and the diagnostic value of incidental imaging findings remains uncertain.^9–12 A 2008 systematic review found that imaging accounted for 7% of direct costs associated with low-back pain, which in 1998 translated to more than US$6 billion in the United States and £114 million in the United Kingdom.¹³ Current costs are likely to be substantially higher, with an estimated 65% increase in spine-related expenditures between 1997 and 2005.¹⁴Various interventions have been tried for reducing imaging rates among people with low-back pain. These include strategies targeted at the practitioner such as guideline dissemination,^15–17 education workshops,^18,19 audit and feedback of imaging use,^7,20,21 ongoing reminders⁷ and clinical decision support.^22–24 It is unclear which, if any, of these strategies are effective.²⁵ We conducted a systematic review to investigate the effectiveness of interventions designed to reduce imaging rates for the management of low-back pain.     

Utility of prior screening for methicillin-resistant Staphylococcus aureus in predicting resistance of S. aureus infections

Background:

Screening for methicillin-resistant Staphylococcus aureus (MRSA) is intended to reduce nosocomial spread by identifying patients colonized by MRSA. Given the widespread use of this screening, we evaluated its potential clinical utility in predicting the resistance of clinical isolates of S. aureus.

Methods:

We conducted a 2-year retrospective cohort study that included patients with documented clinical infection with S. aureus and prior screening for MRSA. We determined test characteristics, including sensitivity and specificity, of screening for predicting the resistance of subsequent S. aureus isolates.

Results:

Of 510 patients included in the study, 53 (10%) had positive results from MRSA screening, and 79 (15%) of infecting isolates were resistant to methicillin. Screening for MRSA predicted methicillin resistance of the infecting isolate with 99% (95% confidence interval [CI] 98%–100%) specificity and 63% (95% CI 52%–74%) sensitivity. When screening swabs were obtained within 48 hours before isolate collection, sensitivity increased to 91% (95% CI 71%–99%) and specificity was 100% (95% CI 97%–100%), yielding a negative likelihood ratio of 0.09 (95% CI 0.01–0.3) and a negative predictive value of 98% (95% CI 95%–100%). The time between swab and isolate collection was a significant predictor of concordance of methicillin resistance in swabs and isolates (odds ratio 6.6, 95% CI 1.6–28.2).

Interpretation:

A positive result from MRSA screening predicted methicillin resistance in a culture-positive clinical infection with S. aureus. Negative results on MRSA screening were most useful for excluding methicillin resistance of a subsequent infection with S. aureus when the screening swab was obtained within 48 hours before collection of the clinical isolate.Antimicrobial resistance is a global problem. The prevalence of resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), has reached high levels in many countries.^1–3 Methicillin resistance in S. aureus is associated with excess mortality, hospital stays and health care costs,^3,4 possibly owing to increased virulence or less effective treatments for MRSA compared with methicillin-sensitive S. aureus (MSSA).⁵The initial selection of appropriate empirical antibiotic treatment affects mortality, morbidity and potential health care expenditures.^6–8 The optimal choice of antibiotics in S. aureus infections is important for 3 major reasons: β-lactam antibiotics have shown improved efficacy over vancomycin and are the ideal treatment for susceptible strains of S. aureus;⁶ β-lactam antibiotics are ineffective against MRSA, and so vancomycin or other newer agents must be used empirically when MRSA is suspected; and unnecessary use of broad-spectrum antibiotics (e.g., vancomycin) can lead to the development of further antimicrobial resistance.⁹ It is therefore necessary to make informed decisions regarding selection of empirical antibiotics.^10–13 Consideration of a patient’s previous colonization status is important, because colonization predates most hospital and community-acquired infections.^10,14Universal or targeted surveillance for MRSA has been implemented widely as a means of limiting transmission of this antibiotic-resistant pathogen.^15,16 Although results of MRSA screening are not intended to guide empirical treatment, they may offer an additional benefit among patients in whom clinical infection with S. aureus develops.Studies that examined the effects of MRSA carriage on the subsequent likelihood of infection allude to the potential diagnostic benefit of prior screening for MRSA.^17,18 Colonization by MRSA at the time of hospital admission is associated with a 13-fold increased risk of subsequent MRSA infection.^17,18 Moreover, studies that examined nasal carriage of S. aureus after documented S. aureus bacteremia have shown remarkable concordance between the genotypes of paired colonizing and invasive strains (82%–94%).^19,20 The purpose of our study was to identify the usefulness of prior screening for MRSA for predicting methicillin resistance in culture-positive S. aureus infections.     

Development of guidelines for recently arrived immigrants and refugees to Canada: Delphi consensus on selecting preventable and treatable conditions

Background:

Setting priorities is critical to ensure guidelines are relevant and acceptable to users, and that time, resources and expertise are used cost-effectively in their development. Stakeholder engagement and the use of an explicit procedure for developing recommendations are critical components in this process.

Methods:

We used a modified Delphi consensus process to select 20 high-priority conditions for guideline development. Canadian primary care practitioners who care for immigrants and refugees used criteria that emphasize inequities in health to identify clinical care gaps.

Results:

Nine infectious diseases were selected, as well as four mental health conditions, three maternal and child health issues, caries and periodontal disease, iron-deficiency anemia, diabetes and vision screening.

Interpretation:

Immigrant and refugee medicine covers the full spectrum of primary care, and although infectious disease continues to be an important area of concern, we are now seeing mental health and chronic diseases as key considerations for recently arriving immigrants and refugees.Canada consistently receives more than 239 000 immigrants yearly, up to 35 000 of whom are refugees.¹ Many arrive with similar or better self-reported health than the general Canadian population reports, a phenomenon described as the “healthy immigrant effect.”^2–6 However, subgroups of immigrants, for example refugees, face health disparities and often a greater burden of infectious diseases.^7,8 These health issues sometimes differ from the general population because of differing disease exposures, vulnerabilities, social determinants of health and access to health services before, during and after migration. Cultural and linguistic differences combined with lack of evidence-based guidelines can contribute to poor delivery of services.^9,10Community-based primary health care practitioners see most of the immigrants and refugees who arrive in Canada. This is not only because Canada’s health system centres on primary care practice, but also because people with lower socioeconomic status, language barriers and less familiarity with the system are much less likely to receive specialist care.¹¹Guideline development can be costly in terms of time, resources and expertise.¹² Setting priorities is critical, particularly when dealing with complex situations and limited resources.¹³ There is no standard algorithm on who should and how they should determine top priorities for guidelines, although burden of illness, feasibility and economic considerations are all important.¹⁴ Stakeholder engagement to ensure relevance and acceptability, and the use of an explicit procedure for developing recommendations are critical in guideline development.^15–17 We chose primary care practitioners, particularly those who care for immigrants and refugees, to help the guideline committee select conditions for clinical preventive guidelines for immigrants and refugees with a focus on the first five years of settlement.     

Likelihood of coronary angiography among First Nations patients with acute myocardial infarction

Background:

Morbidity due to cardiovascular disease is high among First Nations people. The extent to which this may be related to the likelihood of coronary angiography is unclear. We examined the likelihood of coronary angiography after acute myocardial infarction (MI) among First Nations and non–First Nations patients.

Methods:

Our study included adults with incident acute MI between 1997 and 2008 in Alberta. We determined the likelihood of angiography among First Nations and non–First Nations patients, adjusted for important confounders, using the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) database.

Results:

Of the 46 764 people with acute MI, 1043 (2.2%) were First Nations. First Nations patients were less likely to receive angiography within 1 day after acute MI (adjusted odds ratio [OR] 0.73, 95% confidence interval [CI] 0.62–0.87). Among First Nations and non–First Nations patients who underwent angiography (64.9%), there was no difference in the likelihood of percutaneous coronary intervention (PCI) (adjusted hazard ratio [HR] 0.92, 95% CI 0.83–1.02) or coronary artery bypass grafting (CABG) (adjusted HR 1.03, 95% CI 0.85–1.25). First Nations people had worse survival if they received medical management alone (adjusted HR 1.38, 95% CI 1.07–1.77) or if they underwent PCI (adjusted HR 1.38, 95% CI 1.06–1.80), whereas survival was similar among First Nations and non–First Nations patients who received CABG.

Interpretation:

First Nations people were less likely to undergo angiography after acute MI and experienced worse long-term survival compared with non–First Nations people. Efforts to improve access to angiography for First Nations people may improve outcomes.Although cardiovascular disease has been decreasing in Canada,¹ First Nations people have a disproportionate burden of the disease. First Nations people in Canada have a 2.5-fold higher prevalence of cardiovascular disease than non–First Nations people,² with hospital admissions for cardiovascular-related events also increasing.³The prevalence of cardiovascular disease in First Nations populations is presumed to be reflective of the prevalence of cardiovascular risk factors.^4–7 However, the disproportionate increase in rates of hospital admission suggests that suboptimal management of cardiovascular disease or its risk factors may also influence patient outcomes.^2,3 Racial disparities in the quality of cardiovascular care resulting in adverse outcomes have been documented, although most studies have focused on African-American, Hispanic and Asian populations.^8,9 As a result, it is unclear whether suboptimal delivery of guideline-recommended treatment contributes to increased cardiovascular morbidity and mortality among First Nations people.^10–12We undertook a population-based study involving adults with incident acute myocardial infarction (MI) to examine the receipt of guideline-recommended coronary angiography among First Nations and non–First Nations patients.^10–12 Among patients who underwent angiography, we sought to determine whether there were differences between First Nations and non–First Nations patients in the likelihood of revascularization and long-term survival.     

Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months

Background:

The gut microbiota is essential to human health throughout life, yet the acquisition and development of this microbial community during infancy remains poorly understood. Meanwhile, there is increasing concern over rising rates of cesarean delivery and insufficient exclusive breastfeeding of infants in developed countries. In this article, we characterize the gut microbiota of healthy Canadian infants and describe the influence of cesarean delivery and formula feeding.

Methods:

We included a subset of 24 term infants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Mode of delivery was obtained from medical records, and mothers were asked to report on infant diet and medication use. Fecal samples were collected at 4 months of age, and we characterized the microbiota composition using high-throughput DNA sequencing.

Results:

We observed high variability in the profiles of fecal microbiota among the infants. The profiles were generally dominated by Actinobacteria (mainly the genus Bifidobacterium) and Firmicutes (with diverse representation from numerous genera). Compared with breastfed infants, formula-fed infants had increased richness of species, with overrepresentation of Clostridium difficile. Escherichia–Shigella and Bacteroides species were underrepresented in infants born by cesarean delivery. Infants born by elective cesarean delivery had particularly low bacterial richness and diversity.

Interpretation:

These findings advance our understanding of the gut microbiota in healthy infants. They also provide new evidence for the effects of delivery mode and infant diet as determinants of this essential microbial community in early life.The human body harbours trillions of microbes, known collectively as the “human microbiome.” By far the highest density of commensal bacteria is found in the digestive tract, where resident microbes outnumber host cells by at least 10 to 1. Gut bacteria play a fundamental role in human health by promoting intestinal homeostasis, stimulating development of the immune system, providing protection against pathogens, and contributing to the processing of nutrients and harvesting of energy.^1,2 The disruption of the gut microbiota has been linked to an increasing number of diseases, including inflammatory bowel disease, necrotizing enterocolitis, diabetes, obesity, cancer, allergies and asthma.¹ Despite this evidence and a growing appreciation for the integral role of the gut microbiota in lifelong health, relatively little is known about the acquisition and development of this complex microbial community during infancy.³Two of the best-studied determinants of the gut microbiota during infancy are mode of delivery and exposure to breast milk.^4,5 Cesarean delivery perturbs normal colonization of the infant gut by preventing exposure to maternal microbes, whereas breastfeeding promotes a “healthy” gut microbiota by providing selective metabolic substrates for beneficial bacteria.^3,5 Despite recommendations from the World Health Organization,⁶ the rate of cesarean delivery has continued to rise in developed countries and rates of breastfeeding decrease substantially within the first few months of life.^7,8 In Canada, more than 1 in 4 newborns are born by cesarean delivery, and less than 15% of infants are exclusively breastfed for the recommended duration of 6 months.^9,10 In some parts of the world, elective cesarean deliveries are performed by maternal request, often because of apprehension about pain during childbirth, and sometimes for patient–physician convenience.¹¹The potential long-term consequences of decisions regarding mode of delivery and infant diet are not to be underestimated. Infants born by cesarean delivery are at increased risk of asthma, obesity and type 1 diabetes,¹² whereas breastfeeding is variably protective against these and other disorders.¹³ These long-term health consequences may be partially attributable to disruption of the gut microbiota.^12,14Historically, the gut microbiota has been studied with the use of culture-based methodologies to examine individual organisms. However, up to 80% of intestinal microbes cannot be grown in culture.^3,15 New technology using culture-independent DNA sequencing enables comprehensive detection of intestinal microbes and permits simultaneous characterization of entire microbial communities. Multinational consortia have been established to characterize the “normal” adult microbiome using these exciting new methods;¹⁶ however, these methods have been underused in infant studies. Because early colonization may have long-lasting effects on health, infant studies are vital.^3,4 Among the few studies of infant gut microbiota using DNA sequencing, most were conducted in restricted populations, such as infants delivered vaginally,¹⁷ infants born by cesarean delivery who were formula-fed¹⁸ or preterm infants with necrotizing enterocolitis.¹⁹Thus, the gut microbiota is essential to human health, yet the acquisition and development of this microbial community during infancy remains poorly understood.³ In the current study, we address this gap in knowledge using new sequencing technology and detailed exposure assessments²⁰ of healthy Canadian infants selected from a national birth cohort to provide representative, comprehensive profiles of gut microbiota according to mode of delivery and infant diet.