Impact of maternal pre-pregnancy overweight on infant overweight at 1 year of age: associations and sex-specific differences.

BACKGROUND: Maternal overweight or obesity (OWOB) is linked to gestational diabetes, fetal macrosomia and higher rates of caesarean delivery. OBJECTIVES: The study aims to assess whether maternal pre-pregnancy OWOB is associated with infant overweight in a sex-dependent manner, independent of microbiota-altering variables. METHODS: Weight and length measurements of 955 mother-infant pairs were obtained from the Canadian Healthy Infant Longitudinal Development cohort. Maternal pre-pregnancy weight was defined as follows: normal, overweight (25 ≤ body mass index < 30) and obese (body mass index ≥ 30). Age and sex-adjusted weight-for-length z-scores >97th percentile were classified as infant overweight at age 1 year. Associations between pre-pregnancy and infant overweight were determined by linear and logistic regression, adjusting for covariates. RESULTS: Maternal pre-pregnancy OWOB were associated with infant weight-for-length and overweight risk at 1 year. Except for pre-pregnancy obesity, these associations were not attenuated appreciably after adjustment for birth mode, exclusivity of breastfeeding, exposure to antibiotics and infant sex. Yet only boys born to mothers with obesity were three times more likely to become overweight at age 1 independent of microbiota-altering variables. Pre-pregnancy obesity was associated with weight-for-length in male and female infants. CONCLUSIONS: Maternal pre-pregnancy OWOB increases the risk of infant overweight, and this association is more evident in male infants.

Gut microbial metabolism defines host metabolism: an emerging perspective in obesity and allergic inflammation.

The presence of >100 trillion microorganisms (collectively called gut microbiota) in our large intestine is essential for the maintenance of health. The gut microbiota starts to develop before birth and matures within first three years of life. The Western diet and lifestyle have been implicated in causing an imbalance of gut microbial communities and their metabolites that consequence in disease states, such as obesity and asthma. With more than 13% of the world population currently living with obesity and one out of 10 children diagnosed with asthma, we explore here the recent developments in the biosynthesis and mode of action of the key metabolites in relation to these two chronic inflammatory conditions.

Associations between postpartum depressive symptoms and childhood asthma diminish with child age.

BACKGROUND: Affecting 19% of women, postpartum depression is a major concern to the immediate health of mothers and infants. In the long-term, it has been linked to the development of early-onset asthma at school entry, but only if the depression persists beyond the postnatal period. No studies have tested whether associations with postpartum depressive symptoms and early-onset asthma phenotypes persist into later school age. OBJECTIVE: To determine associations between maternal postpartum depressive symptoms and childhood asthma between the ages of 5-10 by using a nested longitudinal design. METHODS: Data were drawn from the 1994-2004 administrations of the Canadian National Longitudinal Survey of Children and Youth, which tracks the health of a nationally representative sample of children in Canada. Child asthma was diagnosed by a health professional, and maternal depressive symptoms were assessed by the Centre for Epidemiological Studies Depression scale. Analyses were conducted by using a multilevel modelling approach, in which longitudinal assessments of asthma in 1696 children were nested within the exposure of postpartum depression. RESULTS: Postpartum depressive symptoms had a 1.5-fold significant association with childhood asthma between the ages 6-8. This was independent of male sex, maternal asthma, non-immigrant status, low household socioeconomic status, being firstborn, low birthweight, low family functioning and urban-rural residence, of which the first 4 covariates elevated the risk of asthma. Statistical significance was lost at age 8 when maternal prenatal smoking replaced urban-rural residence as a covariate. At ages 9-10, an association was no longer evident. CONCLUSIONS AND CLINICAL RELEVANCE: Women affected by postpartum depressive symptoms are concerned about long-term health effects of their illness on their infants. Although postpartum depressive symptoms were associated with school-age asthma at ages 6 and 7, this association diminished later. Both home and school life stress should be considered in future studies on asthma development later in childhood.

Impact of maternal intrapartum antibiotics, method of birth and breastfeeding on gut microbiota during the first year of life: a prospective cohort study.

OBJECTIVE: Dysbiosis of the infant gut microbiota may have long-term health consequences. This study aimed to determine the impact of maternal intrapartum antibiotic prophylaxis (IAP) on infant gut microbiota, and to explore whether breastfeeding modifies these effects. DESIGN: Prospective pregnancy cohort of Canadian infants born in 2010-2012: the Canadian Healthy Infant Longitudinal Development (CHILD) Study. SETTING: General community. SAMPLE: Representative sub-sample of 198 healthy term infants from the CHILD Study. METHODS: Maternal IAP exposures and birth method were documented from hospital records and breastfeeding was reported by mothers. Infant gut microbiota was characterised by Illumina 16S rRNA sequencing of faecal samples at 3 and 12 months. MAIN OUTCOME MEASURES: Infant gut microbiota profiles. RESULTS: In this cohort, 21% of mothers received IAP for Group B Streptococcus prophylaxis or pre-labour rupture of membranes; another 23% received IAP for elective or emergency caesarean section (CS). Infant gut microbiota community structures at 3 months differed significantly with all IAP exposures, and differences persisted to 12 months for infants delivered by emergency CS. Taxon-specific composition also differed, with the genera Bacteroides and Parabacteroides under-represented, and Enterococcus and Clostridium over-represented at 3 months following maternal IAP. Microbiota differences were especially evident following IAP with emergency CS, with some changes (increased Clostridiales and decreased Bacteroidaceae) persisting to 12 months, particularly among non-breastfed infants. CONCLUSIONS: Intrapartum antibiotics in caesarean and vaginal delivery are associated with infant gut microbiota dysbiosis, and breastfeeding modifies some of these effects. Further research is warranted to explore the health consequences of these associations. TWEETABLE ABSTRACT: Maternal #antibiotics during childbirth alter the infant gut #microbiome.

Infant gut immunity: a preliminary study of IgA associations with breastfeeding.

Secretory immunoglobulin A (IgA) plays a critical role in gut mucosal immune defense. Initially provided by breastmilk, IgA production by the infant gut is gradually stimulated by developing gut microbiota. This study reports associations between infant fecal IgA concentrations 4 months after birth, breastfeeding status and other pre/postnatal exposures in 47 infants in the Canadian Healthy Infant Longitudinal Development cohort. Breastfed infants and first-born infants had higher median fecal IgA concentrations (23.11 v. 9.34 µg/g protein, P<0.01 and 22.19 v. 8.23 µg/g protein, P=0.04). IgA levels increased successively with exclusivity of breastfeeding (ß-coefficient, 0.37, P<0.05). This statistical association was independent of maternal parity and household pets. In the absence of breastfeeding, female sex and pet exposure elevated fecal IgA to levels found in breastfed infants. In addition to breastfeeding, infant fecal IgA associations with pre/postnatal exposures may affect gut immunity and risk of allergic disease.

Fetal programming of overweight through the microbiome: boys are disproportionately affected.

Maternal and childhood obesity in pregnancy are worrisome public health issues facing our world today. New gene sequencing methods have advanced our knowledge of the disruptive effect of birth interventions and postnatal exposures on the maturation of gut microbiota and immunity during infancy. Yet, little is known about the impact of maternal pregnancy overweight on gut microbes and related processes, and how this may affect overweight risk in offspring. To address this gap in knowledge, we surveyed human studies for evidence in children, infants and pregnant women to piece together the limited literature and generate hypotheses for future investigation. From this literature, we learned that higher Lactobacillus yet lower Bacteroides spp. colonization of gut microbiota within 3 months of birth predicted risk for infant and child overweight. The abundance of bifidobacteria and staphylococci also appeared to play a role in the association with overweight, as did infant fecal immunoglobulin A levels, glycoproteins of the gut immune system that are acquired from breast milk and produced by the infant. We proposed that pregnancy overweight influences the compositional structure of gut microbiota in infants through vertical transfer of microbiota and/or their metabolites during pregnancy, delivery and breastfeeding. Finally, we brought forward emerging evidence on sex dimorphism, as well as ethnic and geographic variation, in reported associations between maternal overweight-induced gut microbiota dysbiosis and overweight risk.

Infant gut microbiota and food sensitization: associations in the first year of life.

BACKGROUND: The gut microbiota is established during infancy and plays a fundamental role in shaping host immunity. Colonization patterns may influence the development of atopic disease, but existing evidence is limited and conflicting. OBJECTIVE: To explore associations of infant gut microbiota and food sensitization. METHODS: Food sensitization at 1 year was determined by skin prick testing in 166 infants from the population-based Canadian Healthy Infant Longitudinal Development (CHILD) study. Faecal samples were collected at 3 and 12 months, and microbiota was characterized by Illumina 16S rRNA sequencing. RESULTS: Twelve infants (7.2%) were sensitized to ≥ 1 common food allergen at 1 year. Enterobacteriaceae were overrepresented and Bacteroidaceae were underrepresented in the gut microbiota of food-sensitized infants at 3 months and 1 year, whereas lower microbiota richness was evident only at 3 months. Each quartile increase in richness at 3 months was associated with a 55% reduction in risk for food sensitization by 1 year (adjusted odds ratio 0.45, 95% confidence interval 0.23-0.87). Independently, each quartile increase in Enterobacteriaceae/Bacteroidaceae ratio was associated with a twofold increase in risk (2.02, 1.07-3.80). These associations were upheld in a sensitivity analysis among infants who were vaginally delivered, exclusively breastfed and unexposed to antibiotics. At 1 year, the Enterobacteriaceae/Bacteroidaceae ratio remained elevated among sensitized infants, who also tended to have decreased abundance of Ruminococcaceae. CONCLUSIONS AND CLINICAL RELEVANCE: Low gut microbiota richness and an elevated Enterobacteriaceae/Bacteroidaceae ratio in early infancy are associated with subsequent food sensitization, suggesting that early gut colonization may contribute to the development of atopic disease, including food allergy.

Infant antibiotic exposure and the development of childhood overweight and central adiposity.

BACKGROUND: Obesity has been associated with disruption of the gut microbiota, which is established during infancy and vulnerable to disruption by antibiotics. OBJECTIVES: To investigate the association between early-life antibiotic exposure and subsequent development of overweight and central adiposity. METHODS: Provincial health-care records were linked to clinical and survey data from a Canadian longitudinal birth cohort study. Antibiotic exposure during the first year of life was documented from prescription records. Overweight and central adiposity were determined from anthropometric measurements at ages 9 (n=616) and 12 (n=431). Associations were determined by multiple logistic regression. RESULTS: Infants receiving antibiotics in the first year of life were more likely to be overweight later in childhood compared with those who were unexposed (32.4 versus 18.2% at age 12, P=0.002). Following adjustment for birth weight, breastfeeding, maternal overweight and other potential confounders, this association persisted in boys (aOR 5.35, 95% confidence interval (CI) 1.94-14.72) but not in girls (aOR 1.13, CI 0.46-2.81). Similar gender-specific associations were found for overweight at age 9 (aOR 2.19, CI 1.06-4.54 for boys; aOR 1.20, CI 0.53-2.70 for girls) and for high central adiposity at age 12 (aOR 2.85, CI 1.24-6.51 for boys; aOR 1.59, CI 0.68-3.68 for girls). CONCLUSIONS: Among boys, antibiotic exposure during the first year of life was associated with an increased risk of overweight and central adiposity in preadolescence, indicating that antibiotic stewardship is particularly important during infancy. Given the current epidemic of childhood obesity and the high prevalence of infant antibiotic exposure, further studies are necessary to determine the mechanisms underlying this association, to identify the long-term health consequences, and to develop strategies for mitigating these effects when antibiotic exposure cannot be avoided.

Associations between bacterial communities of house dust and infant gut.

The human gut is host to a diverse and abundant community of bacteria that influence health and disease susceptibility. This community develops in infancy, and its composition is strongly influenced by environmental factors, notably perinatal anthropogenic exposures such as delivery mode (Cesarean vs. vaginal) and feeding method (breast vs. formula); however, the built environment as a possible source of exposure has not been considered. Here we report on a preliminary investigation of the associations between bacteria in house dust and the nascent fecal microbiota from 20 subjects from the Canadian Healthy Infant Longitudinal Development (CHILD) Study using high-throughput sequence analysis of portions of the 16S rRNA gene. Despite significant differences between the dust and fecal microbiota revealed by Nonmetric Multidimensional Scaling (NMDS) analysis, permutation analysis confirmed that 14 bacterial OTUs representing the classes Actinobacteria (3), Bacilli (3), Clostridia (6) and Gammaproteobacteria (2) co-occurred at a significantly higher frequency in matched dust-stool pairs than in randomly permuted pairs, indicating an association between these dust and stool communities. These associations could indicate a role for the indoor environment in shaping the nascent gut microbiota, but future studies will be needed to confirm that our findings do not solely reflect a reverse pathway. Although pet ownership was strongly associated with the presence of certain genera in the dust for dogs (Agrococcus, Carnobacterium, Exiguobacterium, Herbaspirillum, Leifsonia and Neisseria) and cats (Escherichia), no clear patterns were observed in the NMDS-resolved stool community profiles as a function of pet ownership.

Genome-wide association study of body mass index in 23 000 individuals with and without asthma.

BACKGROUND: Both asthma and obesity are complex disorders that are influenced by environmental and genetic factors. Shared genetic factors between asthma and obesity have been proposed to partly explain epidemiological findings of co-morbidity between these conditions. OBJECTIVE: To identify genetic variants that are associated with body mass index (BMI) in asthmatic children and adults, and to evaluate if there are differences between the genetics of BMI in asthmatics and healthy individuals. METHODS: In total, 19 studies contributed with genome-wide analysis study (GWAS) data from more than 23 000 individuals with predominantly European descent, of whom 8165 are asthmatics. RESULTS: We report associations between several DENND1B variants (P = 2.2 × 10(-7) for rs4915551) on chromosome 1q31 and BMI from a meta-analysis of GWAS data using 2691 asthmatic children (screening data). The top DENND1B single nucleotide polymorphisms(SNPs) were next evaluated in seven independent replication data sets comprising 2014 asthmatics, and rs4915551 was nominally replicated (P < 0.05) in two of the seven studies and of borderline significance in one (P = 0.059). However, strong evidence of effect heterogeneity was observed and overall, the association between rs4915551 and BMI was not significant in the total replication data set, P = 0.71. Using a random effects model, BMI was overall estimated to increase by 0.30 kg/m(2) (P = 0.01 for combined screening and replication data sets, N = 4705) per additional G allele of this DENND1BSNP. FTO was confirmed as an important gene for adult and childhood BMI regardless of asthma status. CONCLUSIONS AND CLINICAL RELEVANCE: DENND1B was recently identified as an asthma susceptibility gene in a GWAS on children, and here, we find evidence that DENND1B variants may also be associated with BMI in asthmatic children. However, the association was overall not replicated in the independent data sets and the heterogeneous effect of DENND1B points to complex associations with the studied diseases that deserve further study.

Street drug use during pregnancy: potential programming effects on preschool wheeze.

Street drug use during pregnancy is detrimental to fetal development. Although the prevalence of wheeze is high in offspring of substance-abusing mothers, nothing is known about the role of street drug use during pregnancy in its development. We investigated the impact of maternal street drug use and distress during pregnancy on the development of wheeze and allergy in preschool children. Questionnaire data were accessed from the Community Perinatal Care trial of 791 mother-child pairs in Calgary, Alberta. Using logistic regression, the association between maternal substance use and distress during pregnancy, and wheeze and allergy at age 3 years was determined in boys and girls. After adjusting for alcohol use during pregnancy, pre- and postnatal tobacco use, preterm birth, duration of exclusive breastfeeding, daycare attendance and maternal socioeconomic status, maternal street drug use during pregnancy [odds ratio (OR): 5.02, 95% confidence interval (CI): 1.30-19.4] and severe maternal distress during pregnancy (OR: 5.79, 95% CI: 1.25-26.8) were associated with wheeze in girls. In boys, an independent association was found between severe distress during pregnancy (OR: 3.85, 95% CI: 1.11-13.3) and allergies, but there was no association with maternal street drug use. In conclusion, we found an association between maternal street drug use and wheeze in preschool girls that could not be accounted for by maternal distress, smoking or alcohol use during pregnancy. Prenatal programming effects of street drugs may explain this association.

Maternal distress in early life predicts the waist-to-hip ratio in schoolchildren.

We report on life course stress determinants of overweight in children, using data from the longitudinal follow-up of the nested case-control arm of the SAGE (study of asthma genes and the environment) birth cohort in Manitoba, Canada. Waist and hip measurements were obtained during a clinic visit at age 9-11 years. Multiple linear regression was conducted to determine the relationship between the waist-to-hip ratio and maternal smoking during pregnancy, postpartum maternal distress and stress reactivity in children (cortisol, cortisol-DHEA [dihydroepiandrostrenone] ratio quartiles) following a clinic stressor at age 8-10 years. We found waist-to-hip risk at age 9-11 years to be elevated among boys and girls whose mothers had experienced distress in the postnatal period. This association varied by gender and asthma status. In healthy girls, postpartum distress increased waist-to-hip ratio by a factor of 0.034 (P < 0.01), independent of the child's stage of puberty and adrenarche, cortisol-DHEA ratio and duration of exclusive breastfeeding. Among girls with asthma, maternal smoking during pregnancy was associated with an increased waist-to-hip ratio, if the mother also experienced distress in the postpartum period (0.072, P = 0.038). Among asthmatic boys, an association between maternal distress and waist-to-hip ratio was evident at the highest cortisol-DHEA ratios. Stress-induced changes to leptin and infant over-eating pathways were proposed to explain the postnatal maternal distress effects. Drawing on the theories of evolutionary biology, our findings underscore the significance of postnatal stress in disrupting hypothalamic-pituitary-adrenal axis function in infants and increasing risk for child overweight.

Frequent nocturnal awakening in early life is associated with nonatopic asthma in children.

Sleep deprivation has become a common phenomenon of the Western world and is associated with a variety of medical problems in children. This retrospective longitudinal analysis of a community-based birth cohort was undertaken to determine whether frequent nocturnal awakening during early life was associated with the development of childhood asthma. 2,398 children born to mothers recruited from the antenatal clinics of a single hospital in Perth, Australia during 1989-1991 were followed up at years 1, 2, 3, 6, 8, 10 and 14. Parent-completed questionnaires were analysed. The odds ratio for asthma at age 6 and 14 yrs in children with frequent nocturnal awakening during the first 3 yrs after birth was determined from multiple logistic regression. Following adjustment for asthma risk factors, co-sleeping and family stress, persistent nocturnal awakening was associated with nonatopic asthma at age 6 and 14 yrs (at age 14 yrs: OR 2.18, 95% CI 1.15-4.13) but not with atopic asthma. We found an increased risk of nonatopic asthma in children following frequent nocturnal awakening during the first 3 yrs of life. These hypothesis-generating data suggest the need for further systematic study of the effects of disordered sleep in early life on the development of asthma.

A novel study design to investigate the early-life origins of asthma in children (SAGE study).

This is a description of the Study of Asthma, Genes and the Environment (SAGE), a novel birth cohort created from provincial healthcare administrative records. It is a general population-based cohort, composed of children at high and low risk for asthma, living in urban and rural environments in Manitoba, Canada. The SAGE study captures the complete longitudinal healthcare records of children born in 1995 and contains detailed information on early-life exposures, such as antibiotic utilization and immunization, in relationship to the development of asthma. Nested within the birth cohort is a case-control study, which was created to collect information on home environmental exposures from detailed surveys and home dust sampling, to confirm asthma status in children and use this data to validate healthcare database measures of asthma, to determine differences in immune system responsiveness to innate and adaptive immune stimuli in asthma, to genotype children for genes likely associated with the development of asthma and to study the epigenetic regulation of pre-established protective vs allergic immune responses. The SAGE study is a multidisciplinary collaboration of researchers from pediatric allergy, population health, immunology, and genetic and environmental epidemiology. As such, it serves as a fertile, interdisciplinary training ground for graduate students, and postdoctoral and clinician fellows.

Fast food consumption counters the protective effect of breastfeeding on asthma in children?

BACKGROUND: Fast food consumption and childhood asthma have rapidly increased in recent decades. During the same period there has been an increased rate of prolonged breastfeeding. OBJECTIVE: To evaluate if fast food consumption was associated with asthma in children, and if the proposed protective effect of breastfeeding on asthma was altered by fast food consumption. METHODS: This case-control study included 246 children with allergist-diagnosed asthma and 477 non-asthmatic controls at age 8-10 years. Information on fast food consumption and exclusive breastfeeding was obtained from questionnaire data. The association between asthma and fast food consumption was evaluated. Asthma in relation to exclusive breastfeeding was also evaluated, taking into account fast food consumption as a modifying factor. RESULTS: Children with asthma were more likely to consume fast food than children without asthma [crude odds ratio (OR) 1.70, 95% confidence interval (CI) 1.23-2.34]. In comparison to prolonged exclusive breastfeeding (> or =12 weeks), asthma was positively associated with short-term exclusive breastfeeding (<12 weeks) in children who never or occasionally consumed fast food (crude OR 1.84, 95% CI 1.09-3.11), but not in children who frequently consumed fast food (crude OR 1.07, 95% CI 0.72-1.61). The P-value for this interaction (0.109) was borderline. Children with high fast food consumption who were exclusively breastfed <12 weeks as infants, had greater than a twofold risk of asthma compared with infants who had been exclusively breastfed for a longer time period and who did not become high consumers of fast food in later childhood. These findings were not affected after final adjustment of confounders and covariates. CONCLUSION: Fast food consumption is associated with asthma in children and potentially counteracts the protective effect of prolonged breastfeeding on asthma. This may explain the paradoxical phenomenon of parallel increased rates of prolonged breastfeeding and asthma in children. 556-561.

Infrequent milk consumption plus being overweight may have great risk for asthma in girls.

BACKGROUND: Inadequate milk consumption and being overweight are each associated with asthma symptoms in children. Milk consumption has been inversely related to childhood overweight. Thus, being overweight may be a pathway or a confounder in milk-asthma relationship. A combination of both factors may be associated with greater risk of asthma than one factor alone. METHODS: This study included 246 children with allergist-diagnosed asthma and 477 nonasthmatic controls at the age of 8-10 years. Information on milk consumption during the last 12 months was obtained from questionnaires. Being overweight was defined as body mass index > or =85th percentile. Being overweight as a possible pathway or confounder was formally tested. The odds ratio (OR) for combined infrequent milk consumption and being overweight in asthmatic vs nonasthmatic children was determined in multivariate logistic regression analyses. RESULTS: There was a significant interaction between milk consumption and sex of the child in relation to asthma. Asthma was significantly associated with infrequent milk consumption in girls (crude OR 2.11, 95% CI 1.05-4.24) but not in boys. The asthma-milk relation in girls was neither mediated by being overweight (p(mediation tests) = 0.27) nor was the relationship confounded by being overweight (a 9% change in coefficient). Asthmatic girls had 3.6 times increased odds of having combination of infrequent milk consumption and being overweight than nonasthmatic girls (adjusted OR 3.64, 95% CI 1.18-11.24). Asthma was not associated with either factor or with absence of the other in girls. CONCLUSION: Infrequent milk consumption plus being overweight may have great risk for asthma in girls.

Socioeconomic status, drug insurance benefits, and new prescriptions for inhaled corticosteroids in schoolchildren with asthma.

BACKGROUND: Low-income children with asthma are less likely to receive inhaled corticosteroid prescriptions that can prevent asthma morbidity. OBJECTIVE: To determine whether the receipt of inhaled corticosteroids in children with asthma is related to household socioeconomic status and type of drug insurance. DESIGN: Using population-based prescription and health care data from Manitoba, a cohort study of the determinants of receiving new prescriptions for inhaled corticosteroids was conducted in children treated with asthma drugs. PARTICIPANTS: School-aged children (n = 12 481) receiving asthma prescriptions from January 1995 to March 1996 but no inhaled corticosteroid prescriptions in the initial 6-month period. MAIN OUTCOME MEASURES: Household socioeconomic and drug insurance predictors of the probability of receiving a new inhaled corticosteroid prescription from July 1995 to March 1998, following adjustment for disease and health care utilization factors. RESULTS: In comparison with higher-income children insured through a provincial cost-sharing drug plan, the adjusted likelihood ratio for a new inhaled corticosteroid prescription was 0.88 (95% confidence interval, 0.80-0.97) in low-income children insured through the same drug plan and 0.82 (95% confidence interval, 0.76-0.88) in children receiving prescriptions at no charge through provincial income assistance or First Nations benefits programs (Winnipeg, Manitoba). CONCLUSION: Independent of asthma severity, type of drug insurance, or health care utilization patterns, low-income children with asthma are significantly less likely to receive inhaled corticosteroid prescriptions.

Income-based drug benefit policy: impact on receipt of inhaled corticosteroid prescriptions by Manitoba children with asthma.

BACKGROUND: Drug benefit policies are an important determinant of a population's use of prescription drugs. This study was undertaken to determine whether a change in a provincial drug benefit policy, from a fixed deductible and copayment system to an income-based deductible system, resulted in changes in receipt of prescriptions for inhaled corticosteroids by Manitoba children with asthma. METHODS: Using Manitoba's health care administrative databases, we identified a population-based cohort of 10,703 school-aged children who met our case definition for asthma treatment before and after the province's drug benefit policy was changed in April 1996. The effects of the program change on the probability of receiving a prescription for an inhaled corticosteroid and on the mean number of inhaled corticosteroid doses dispensed were compared between a group of children insured under other drug programs (the comparison group) and 2 groups of children insured under the deductible program: those living in low-income neighbourhoods and those living in higher-income neighbourhoods. All analyses were adjusted for a measure of asthma severity. RESULTS: For higher-income children with severe asthma who were covered by the deductible program, the probability of receiving an inhaled corticosteroid prescription and the mean annual number of inhaled corticosteroid doses declined after the change to the drug policy. A trend toward a decrease in receipt of prescriptions was also observed for low-income children, but receipt of prescriptions was unaltered in the comparison group. Before the policy change, among children with severe asthma, the mean annual number of inhaled corticosteroid doses was lowest for low-income children, and this pattern persisted after the change. Among children with mild to moderate asthma, those covered by the deductible program (both low income and higher income) were less likely to receive prescriptions for inhaled corticosteroids than those in the comparison group, and this difference was statistically significant for the higher-income children. INTERPRETATION: The change to an income-based drug benefit policy was associated with a decrease in the use of inhaled corticosteroids by higher-income children with severe asthma and did not improve use of these drugs by low-income children.

Short course antibiotics for acute otitis media.

BACKGROUND: Otitis media is a common pediatric problem, for which antibiotics are frequently prescribed. OBJECTIVES: To determine the effectiveness of a short course of antibiotics (less than seven days) in comparison to a longer course (seven days or greater) for the treatment of acute otitis media in children. SEARCH STRATEGY: The medical literature was searched for randomized controlled studies of the treatment of ear infections in children with antibiotics published from January 1966 to July 1997. Search last updated March 1998. SELECTION CRITERIA: Studies were included if they met the following criteria: subjects one month to 18 years of age, clinical diagnosis of ear infection, no previous antimicrobial therapy and randomization to treatment with less than seven days versus seven days or more of antibiotics. DATA COLLECTION AND ANALYSIS: Data on treatment outcomes were extracted from individual studies, and combined in the form of a summary odds ratio. A summary odds ratio (OR) equivalent to one indicated that the treatment failure rate following less than seven days of antibiotic treatment was similar to the failure rate following seven days or more of antibiotic. MAIN RESULTS: The summary OR for treatment outcomes at eight to 19 days in 1,524 children treated with short-acting antibiotics for five days versus eight to 10 days was 1.52, 95% CI: 1.17-1.98, but by 20 to 30 days outcomes between treatment groups (n=2,115) were comparable (OR=1.22, 95% CI:0.98-1.54). The absolute difference in treatment failure (Random effects model RD=2.9%, 95%CI:-0.3% to 6.1%) at 20 to 30 days suggests that at minimum 17 children would need to be treated with the long course of short-acting antibiotics to avoid one treatment failure. Similarity in outcomes was observed for up to three months following therapy (OR=1.16,95% CI=0.9-1.5). Comparable outcomes were shown between treatment with ceftriaxone or azithromycin, and more than seven days of other antibiotics. REVIEWER'S CONCLUSIONS: This review suggests that five days of short-acting antibiotic is effective treatment for uncomplicated ear infections in children.