Garth Kendall

Association between breast feeding and asthma in 6 year old children: findings of a prospective birth cohort study

Abstract Objectives: To investigate the association between the duration of exclusive breast feeding and the development of asthma related outcomes in children at age 6 years. Design: Prospective cohort study. Setting: Western Australia. Subjects: 2187 children ascertained through antenatal clinics at the major tertiary obstetric hospital in Perth and followed to age 6 years. Main outcome measures: Unconditional logistic regression to model the association between duration of exclusive breast feeding and outcomes related to asthma or atopy at 6 years of age, allowing for several important confounders: sex, gestational age, smoking in the household, and early childcare. Results: After adjustment for confounders, the introduction of milk other than breast milk before 4 months of age was a significant risk factor for all asthma and atopy related outcomes in children aged 6 years: asthma diagnosed by a doctor (odds ratio 1.25, 95% confidence interval 1.02 to 1.52); wheeze three or more times since 1 year of age (1.41, 1.14 to 1.76); wheeze in the past year (1.31, 1.05 to 1.64); sleep disturbance due to wheeze within the past year (1.42, 1.07 to 1.89); age when doctor diagnosed asthma (hazard ratio 1.22, 1.03 to 1.43); age at first wheeze (1.36, 1.17 to 1.59); and positive skin prick test reaction to at least one common aeroallergen (1.30, 1.04 to 1.61). Conclusion: A significant reduction in the risk of childhood asthma at age 6 years occurs if exclusive breast feeding is continued for at least the 4 months after birth. These findings are important for our understanding of the cause of childhood asthma and suggest that public health interventions to optimise breast feeding may help to reduce the community burden of childhood asthma and its associated traits. Key messages Asthma is the leading cause of admission to hospital in Australian children and its prevalence is increasing Whether breast feeding protects against asthma or atopy, or both, is controversial Asthma is a complex disease, and the relative risks between breast feeding and asthma or atopy are unlikely to be large; this suggests the need for investigation in a large prospective birth cohort with timely assessment of atopic outcomes and all relevant exposures Exclusive breast feeding for at least 4 months is associated with a significant reduction in the risk of asthma and atopy at age 6 years and with a significant delay in the age at onset of wheezing and asthma being diagnosed by a doctor Public health interventions to promote an increased duration of exclusive breast feeding may help to reduce the morbidity and prevalence of childhood asthma and atop

Breast feeding and respiratory morbidity in infancy: a birth cohort study

Aim: To examine the relation between the duration of breast feeding and morbidity as a result of respiratory illness and infection in the first year of life. Methods: Prospective birth cohort study of 2602 live born children ascertained through antenatal clinics at the major tertiary obstetric hospital in Perth, Western Australia. Main outcome measures were hospital, doctor, or clinic visits, and hospital admissions for respiratory illness and infection in the first year of life. Main exposure measures were the duration of predominant breast feeding (defined as the age other milk was introduced) and partial (any) breast feeding (defined as the age breast feeding was stopped). Main confounders were gender, gestational age less than 37 weeks, smoking in pregnancy, older siblings, maternal education, and maternal age. Results: Hospital, doctor, or clinic visits for four or more upper respiratory tract infections were significantly greater if predominant breast feeding was stopped before 2 months or partial breast feeding was stopped before 6 months. Predominant breast feeding for less than six months was associated with an increased risk for two or more hospital, doctor, or clinic visits and hospital admission for wheezing lower respiratory illness. Breast feeding for less than eight months was associated with a significantly increased risk for two or more hospital, doctor, or clinic visits or hospital admissions because of wheezing lower respiratory illnesses. Conclusions: Predominant breast feeding for at least six months and partial breast feeding for up to one year may reduce the prevalence and subsequent morbidity of respiratory illness and infection in infancy.

Association of IL12B promoter polymorphism with severity of atopic and non-atopic asthma in children

BACKGROUND Severe asthma is a frequent cause of hospital admission, especially among children. The main environmental triggers of airway inflammation in asthma are viruses and aeroallergens. These agents elicit reciprocal immune responses, characterised by production of T helper 1 and T helper 2 cytokines, respectively. There is no genetic explanation for how hyper-responsiveness to these disparate environmental stimuli develops among individuals with asthma. Our aim was to assess relation between an IL12B promoter polymorphism and asthma. METHODS We did a cohort study in which we initially genotyped 411 6-year olds for the IL12B promoter polymorphism. We then assessed the relation between this polymorphism and asthma severity. A further 85 asthmatic children in an additional sample of 433 children from the same cohort were then assessed to confirm these findings. We also examined in-vitro interleukin-12 responses in a subgroup of individuals. FINDINGS Heterozygosity for the IL12B promoter polymorphism was observed in 76% (16) of atopic and non-atopic individuals with severe asthma in the initial sample. By comparison, heterozygotes comprised only 31% (17) of the moderate asthma group, and 48% (20) of individuals with mild asthma were heterozygous, as were unaffected controls. These findings were confirmed in the second sample (overall p<0.0001). Our data suggest that IL12B promoter heterozygosity contributes to asthma severity rather than susceptibility per se. The severity-predisposing genotype was associated with reduced interleukin 12 p40 gene transcription and decreased interleukin 12 p70 secretion. INTERPRETATION Interleukin 12 plays a key part in antagonism of T helper 2 differentiation, and in induction of antiviral host defense. Genetically determined attenuation of interleukin-12 response capacity would, therefore, provide a plausible common immunological pathway to disease severity for the two major forms of asthma.

Predictors of body mass index and associations with cardiovascular risk factors in Australian children: a prospective cohort study

OBJECTIVE:To examine predictors of body mass index (BMI) at the age of 8 y in a prospective study of Australian children.DESIGN:Longitudinal survey of a cohort of Australian children followed from the 16th week of gestation to 8 y.SUBJECTS:In total, 741 boys and 689 girls who attended the survey as 8 y olds.MEASUREMENTS:Weight and height, blood pressure measured by automated oscillometry, fasting blood lipids and glucose. Questionnaire assessment of activity and diet.RESULTS:Proportions of overweight including obesity in boys and girls were, respectively, 22 and 25% at 1 y, 14 and 14% at 3 y, 13 and 18% at 5 y and 15 and 20% at 8 y. At the age of 1, 3, 6 and 8 y, children with overweight including obesity showed significantly more adverse cardiovascular risk factors. Blood pressure (BP) was significantly higher by 2/3 mmHg (systolic/diastolic) at 1 y, 3/2 mmHg at 3 y, 4/2 mmHg at 5 y and 6/2 mmHg at 8 y; HDL was significantly lower (P=0.002) by 8% and triglycerides were significantly higher by 27% (P<0.001). In multivariate regression, BMI at the age of 8 y was significantly predicted positively by birth weight, mothers BMI and hours spent in watching television at the time of the survey of 6 y olds. Mothers being ex-smokers or non smokers and children being ‘slightly active’ and ‘active’ negatively predicted BMI in 8 y olds. In a subset of 298 children with information about fathers, paternal BMI was an additional independent predictor. Maternal or paternal overweight including obesity each independently increased risk of overweight including obesity at the age of 8 y three-fold. A food factor with consumption of cereals and breads as the major components derived from a Food Frequency Questionnaire in a subset of 340 children was also an independent negative predictor of BMI in multivariate models.CONCLUSION:The increasing rate of overweight including obesity, particularly in girls, is associated with an increase in cardiovascular risk factors very early in life. Improvement of health-related behaviours within the family and a focus on promotion of activity in children should be priorities in achieving weight control.

Regulation of T-helper cell responses to inhalant allergen during early childhood

Recent evidence suggests that preschool children manifest patterns of allergen‐specific skin prick test (SPT) reactivity and in vitro T‐cell cytokine production which are similar to that of either atopic or nonatopic adults. However, published studies on this age group involve small sample sizes and a restricted number of cytokines, usually in response to polyclonal stimuli.

Pre- and postnatal influences on preschool mental health: a large-scale cohort study.

BACKGROUND Methodological challenges such as confounding have made the study of the early determinants of mental health morbidity problematic. This study aims to address these challenges in investigating antenatal, perinatal and postnatal risk factors for the development of mental health problems in pre-school children in a cohort of Western Australian children. METHODS The Raine Study is a prospective cohort study of 2,868 live born children involving 2,979 pregnant women recruited at 18 weeks gestation. Children were followed up at age two and five years. The Child Behaviour Checklist (CBCL) was used to measure child mental health with clinical cut-points, including internalising (withdrawn/depressed) and externalising (aggressive/destructive) behaviours (n = 1707). RESULTS Multinomial logistic regression analysis showed that the significant risk factors for behaviour problems at age two were the maternal experience of multiple stress events in pregnancy (OR = 1.20, 95% CI = 1.06, 1.37), smoking during pregnancy (OR = 1.30, 95% CI = 1.06, 1.59) and maternal ethnicity (OR = 3.34, 95% CI = 1.61, 6.96). At age five the experience of multiple stress events (OR = 1.17, 95% CI = 1.08, 1.27), cigarette smoking (OR = 1.19, 95% CI = 1.03, 1.37), male gender (OR = 1.43, 95% CI = 1.02, 2.00), breastfeeding for a shorter time (OR = .97, 95% CI = .94, .99) and multiple baby blues symptoms (OR = 1.08, 95% CI = 1.02, 1.14) were significant predictors of mental health problems. CONCLUSIONS Early childhood mental health is significantly affected by prenatal events in addition to the childs later environment. Interventions targeting adverse prenatal, perinatal and postnatal influences can be expected to improve mental health outcomes for children in the early years.

The relation of breastfeeding and body mass index to asthma and atopy in children: A prospective cohort study to age 6 years

OBJECTIVES We investigated the relationship between breastfeeding, asthma and atopy, and child body mass index (BMI). METHODS From a prospective birth cohort (n = 2860) in Perth, Western Australia, 2195 children were followed up to age 6 years. Asthma was defined as doctor-diagnosed asthma and wheeze in the last year, and atopy was determined by skin prick test of 1596 children. Breastfeeding, BMI, asthma, and atopy were regressed allowing for confounders and the propensity score for overweight. RESULTS Using fractional polynomials, we found no association between breastfeeding and overweight. Less exclusive breastfeeding was associated with increased asthma and atopy, and BMI increased with asthma. CONCLUSIONS Less exclusive breastfeeding leads to increases in child asthma and atopy and a higher BMI is a risk factor for asthma.

Ratio of Omega-6 to Omega-3 Fatty Acids and Childhood Asthma

Asthma is a leading cause of morbidity for children and is a major public health problem in Australia. Ecological and temporal data suggest that dietary factors may have a role in recent increases in the prevalence of asthma. Aim: The aim of conducting this study was to investigate whether childhood asthma was associated with the ratio of omega 6 (n‐6) to omega 3 (n‐3) fatty acids in the diet (n‐6:n‐3). Method: The Western Australian Pregnancy Cohort Study is a prospective birth cohort of 2602 children. Using a nested case‐control cross‐sectional study design within this cohort, a group of children were identified as cases with current asthma at 6 or at 8 years of age or as controls with no asthma at 6 or at 8 years. Dietary details including n‐6 and n‐3 fatty acid intake data were collected by parent response to a questionnaire when the children were 8 years old. Logistical regression was used to compare quartiles of n‐6:n‐3 intake in cases and controls. Adjustment was made for covariates: gender, gestational age, breastfeeding, older siblings, maternal smoking during pregnancy, maternal age, maternal asthma, childs current age in months, body mass index, total energy intake, and antioxidant intake (vitamins A, C, E, and zinc). Results: A response rate of 83% was achieved by providing complete data from 335 children [49% cases with current asthma (n = 166), 51% controls (n = 169)]. Following adjustment for covariates the association between the ratio of n‐6:n‐3 fatty acids and risk for current asthma was statistically significant (p = 0.022). Conclusion: We found evidence for a modulatory effect of the dietary n‐6:n‐3 fatty acid ratio on the presence of asthma in children. Our results provide evidence that promotion of a diet with increased n‐3 fatty acids and reduced n‐6 fatty acids to protect children against symptoms of asthma is warranted.

The Long-Term Effects of Breastfeeding on Child and Adolescent Mental Health: A Pregnancy Cohort Study Followed for 14 Years

OBJECTIVES To determine whether there was an independent effect of breastfeeding on child and adolescent mental health. STUDY DESIGN The Western Australian Pregnancy Cohort (Raine) Study recruited 2900 pregnant women and followed the live births for 14 years. Mental health status was assessed by the Child Behaviour Checklist (CBCL) at 2, 6, 8, 10, and 14 years. Maternal pregnancy, postnatal, and infant factors were tested in multivariable random effects models and generalized estimating equations to examine the effects of breastfeeding duration on mental health morbidity. RESULTS Breastfeeding for less than 6 months compared with 6 months or longer was an independent predictor of mental health problems through childhood and into adolescence. This relationship was supported by the random effects models (increase in total CBCL score: 1.45; 95% confidence interval 0.59, 2.30) and generalized estimating equation models (odds ratio for CBCL morbidity: 1.33; 95% confidence interval 1.09, 1.62) showing increased behavioral problems with shorter breastfeeding duration. CONCLUSION A shorter duration of breastfeeding may be a predictor of adverse mental health outcomes throughout the developmental trajectory of childhood and early adolescence.

Perinatal and childhood origins of cardiovascular disease

Background:Features of the metabolic syndrome comprise a major risk for cardiovascular disease and will increase in prevalence with rising childhood obesity. We sought to identify early life influences on development of obesity, hypertension and dyslipidemia in children.Methods and results:Cluster analysis was used on a subset of a longitudinal Australian birth cohort who had blood samples at age 8 (n=406). A quarter of these 8-year-olds fell into a cluster with higher body mass index, blood pressure (BP), more adverse lipid profile and a trend to higher serum glucose resembling adult metabolic syndrome. There was a U-shaped relationship between percentage of expected birth weight (PEBW) and likelihood of being in the high-risk cluster. The high-risk cluster had elevated BP and weight as early as 1 and 3 years old. Increased likelihood of the high-risk cluster group occurred with greatest weight gain from 1 to 8 years old (odds ratio (OR)=1.4, 95% confidence interval (CI)=1.3–1.5/kg) and if mothers smoked during pregnancy (OR=1.82, CI=1.05–3.2). Risk was lower if children were breast fed for ⩾4 months (OR=0.6, 95% CI=0.37–0.97). Newborns in the upper two quintiles for PEBW born to mothers who smoked throughout pregnancy were at greatest risk (OR=14.0, 95% CI=3.8–51.1) compared to the nadir PEBW quintile of non-smokers.Conclusion:A U-shaped relationship between birth weight and several components of the metabolic syndrome was confirmed in a contemporary, well-nourished Western population of full-term newborns, but post-natal weight gain was the dominant factor associated with the high-risk cluster. There was a prominence of higher as well as lowest birth weights in those at risk. Future health programs should focus on both pre- and post-natal factors (reducing excess childhood weight gain and smoking during pregnancy), and possibly the greatest benefits may arise from targeting the heaviest, as well as lightest newborns, especially with a history of maternal smoking during pregnancy.