Andrea Sherriff

Early life risk factors for obesity in childhood: cohort study

Abstract Objective To identify risk factors in early life (up to 3 years of age) for obesity in children in the United Kingdom. Design Prospective cohort study. Setting Avon longitudinal study of parents and children, United Kingdom. Participants 8234 children in cohort aged 7 years and a subsample of 909 children (children in focus) with data on additional early growth related risk factors for obesity. Main outcome measures Obesity at age 7 years, defined as a body mass index 3 95th centile relative to reference data for the UK population in 1990. Results Eight of 25 putative risk factors were associated with a risk of obesity in the final models: parental obesity (both parents: adjusted odds ratio, 10.44, 95% confidence interval 5.11 to 21.32), very early (by 43 months) body mass index or adiposity rebound (15.00, 5.32 to 42.30), more than eight hours spent watching television per week at age 3 years (1.55, 1.13 to 2.12), catch-up growth (2.60, 1.09 to 6.16), standard deviation score for weight at age 8 months (3.13, 1.43 to 6.85) and 18 months (2.65, 1.25 to 5.59); weight gain in first year (1.06, 1.02 to 1.10 per 100 g increase); birth weight, per 100 g (1.05, 1.03 to 1.07); and short (< 10.5 hours) sleep duration at age 3 years (1.45, 1.10 to 1.89). Conclusion Eight factors in early life are associated with an increased risk of obesity in childhood.

Associations of wheezing phenotypes in the first 6 years of life with atopy, lung function and airway responsiveness in mid-childhood

Background: Patterns of wheezing during early childhood may indicate differences in aetiology and prognosis of respiratory illnesses. Improved characterisation of wheezing phenotypes could lead to the identification of environmental influences on the development of asthma and airway diseases in predisposed individuals. Methods: Data collected on wheezing at seven time points from birth to 7 years from 6265 children in a longitudinal birth cohort (the ALSPAC study) were analysed. Latent class analysis was used to assign phenotypes based on patterns of wheezing. Measures of atopy, airway function (forced expiratory volume in 1 s (FEV1), mid forced expiratory flow (FEF25-75)) and bronchial responsiveness were made at 7–9 years of age. Results: Six phenotypes were identified. The strongest associations with atopy and airway responsiveness were found for intermediate onset (18 months) wheezing (OR for atopy 8.36, 95% CI 5.2 to 13.4; mean difference in dose response to methacholine 1.76, 95% CI 1.41 to 2.12 %FEV1 per μmol, compared with infrequent/never wheeze phenotype). Late onset wheezing (after 42 months) was also associated with atopy (OR 6.6, 95% CI 4.7 to 9.4) and airway responsiveness (mean difference 1.61, 95% CI 1.37 to 1.85 %FEV1 per μmol). Transient and prolonged early wheeze were not associated with atopy but were weakly associated with increased airway responsiveness and persistent wheeze had intermediate associations with these outcomes. Conclusions: The wheezing phenotypes most strongly associated with atopy and airway responsiveness were characterised by onset after age 18 months. This has potential implications for the timing of environmental influences on the initiation of atopic wheezing in early childhood.

Hospitalization for RSV bronchiolitis before 12 months of age and subsequent asthma, atopy and wheeze: A longitudinal birth cohort study

Several epidemiological studies have reported recurrent wheezing and asthma in children after respiratory syncytial virus (RSV) bronchiolitis in infancy. The relationship with allergic sensitization is less clear and recent evidence suggests an interaction between atopy and RSV infection in the development of asthma. Data from a large, population‐based, birth‐cohort (Avon Longitudinal Study of Parents and Children) were used to compare outcomes of children according to whether or not they had been admitted to hospital in the first 12 months with RSV‐proven bronchiolitis. Outcomes considered were 12‐month prevalence of wheeze at two ages (between 30–42 and 69–81 months), cumulative prevalence of doctor‐diagnosed asthma at 91 months and skin prick test defined atopy at 7 yr. Multivariable logistic regression models were used to calculate odds ratios for outcomes adjusted for potential confounders. A total of 150 infants (1.1% of the cohort) were admitted to hospital within 12 months of birth with RSV bronchiolitis. The prevalence of wheezing was 28.1% in the RSV group and 13.1% in controls at 30–42 months and 22.6% vs. 9.6% at 69–81 months. The cumulative prevalence of asthma was 38.4% in the RSV group and 20.1% in controls at 91 months. Atopy was found in 14.6% of the RSV group and in 20.7% of controls at 7 yr. RSV bronchiolitis was associated with subsequent wheezing between 30–42 (Odds ratio [95% CI] 2.3 [1.3, 3.9]) and 69–81 months (OR 3.5 [1.8, 6.6]) and with the cumulative prevalence of asthma at 91 months (OR 2.5 [1.4, 4.3]) but not with atopy (OR 0.7 [0.2, 1.7]). In a population‐based birth cohort, RSV bronchiolitis was associated with subsequent wheezing and asthma but not with the development of atopy by age 7 yr.

Paracetamol use in pregnancy and wheezing in early childhood

Background: We recently reported links between frequent paracetamol (acetaminophen) use and wheezing and asthma in adults and children, but data are lacking on possible effects of prenatal exposure on wheezing in early childhood. Methods: In the population based Avon Longitudinal Study of Parents and Children (ALSPAC) women were asked twice during pregnancy (at 18–20 weeks and 32 weeks) about their usage of paracetamol and aspirin. Six months after birth, and at yearly intervals thereafter, mothers were asked about wheezing and eczema symptoms in their child. The effects of paracetamol and aspirin use in pregnancy on the risk in the offspring of wheezing at 30–42 months (n=9400) and eczema at 18–30 months (n=10 216) and on their risk of different wheezing patterns (defined by presence or absence of wheezing at <6 months and at 30–42 months) were examined. Results: Paracetamol was taken frequently (most days/daily) by only 1% of women. After controlling for potential confounders, frequent paracetamol use in late pregnancy (20–32 weeks), but not in early pregnancy (<18–20 weeks), was associated with an increased risk of wheezing in the offspring at 30–42 months (adjusted odds ratio (OR) compared with no use 2.10 (95% CI 1.30 to 3.41); p=0.003), particularly if wheezing started before 6 months (OR 2.34 (95% CI 1.24 to 4.40); p=0.008). Assuming a causal relation, only about 1% of wheezing at 30–42 months was attributable to this exposure. Frequent paracetamol use in pregnancy was not associated with an increased risk of eczema. Frequent aspirin use in pregnancy was associated with an increased risk of wheezing only at <6 months. Conclusions: Frequent use of paracetamol in late pregnancy may increase the risk of wheezing in the offspring, although such an effect could explain only about 1% of the population prevalence of wheezing in early childhood.

Frequent use of chemical household products is associated with persistent wheezing in pre-school age children

Background: In the UK and other developed countries the prevalence of asthma symptoms has increased in recent years. This is likely to be the result of increased exposure to environmental factors. A study was undertaken to investigate the association between maternal use of chemical based products in the prenatal period and patterns of wheeze in early childhood. Methods: In the population based Avon Longitudinal Study of Parents and Children (ALSPAC), the frequency of use of 11 chemical based domestic products was determined from questionnaires completed by women during pregnancy and a total chemical burden (TCB) score was derived. Four mutually exclusive wheezing patterns were defined for the period from birth to 42 months based on parental questionnaire responses (never wheezed, transient early wheeze, persistent wheeze, and late onset wheeze). Multinomial logistic regression models were used to assess the relationship between these wheezing outcomes and TCB exposure while accounting for numerous potential confounding variables. Complete data for analysis was available for 7019 of 13 971 (50%) children. Results: The mean (SD) TCB score was 9.4 (4.1), range 0–30. Increased use of domestic chemical based products was associated with persistent wheezing during early childhood (adjusted odds ratio (OR) per unit increase of TCB 1.06 (95% confidence interval (CI) 1.03 to 1.09)) but not with transient early wheeze or late onset wheeze. Children whose mothers had high TCB scores (>90th centile) were more than twice as likely to wheeze persistently throughout early childhood than children whose mothers had a low TCB score (<10th centile) (adjusted OR 2.3 (95% CI 1.2 to 4.4)). Conclusion: These findings suggest that frequent use of chemical based products in the prenatal period is associated with persistent wheezing in young children. Follow up of this cohort is underway to determine whether TCB is associated with wheezing, asthma, and atopy at later stages in childhood.

Umbilical cord trace elements and minerals and risk of early childhood wheezing and eczema

It has been suggested that foetal nutrition might influence the inception of wheezing and atopic disorders in childhood but specific nutrients have not been implicated. In the Avon Longitudinal Study of Parents and Children umbilical cord samples were assayed for trace elements and minerals, and mothers were asked about wheezing and eczema in their children. Associations of cord concentrations of selenium, zinc, copper, manganese, magnesium, iron, lead and mercury with wheezing at 30–42 months, with wheezing patterns defined by the presence or absence of transient infant, later onset or persistent wheezing at 0–6 months and 30–42 months, respectively (n=2,044), and with eczema at 18–30 months (n=2,173), were analysed. Cord selenium was negatively associated with persistent wheeze (adjusted odds ratio (OR) per doubling concentration: 0.67). Cord iron was negatively associated with later onset wheeze (OR: 0.86) and with eczema (OR: 0.90). Children with high cord concentrations of selenium and iron were less likely than those with low concentrations to wheeze transiently in infancy. The level of foetal exposure to selenium and iron may possibly influence the risk of wheezing and eczema in early childhood although, in view of the multiple analyses carried out, it is possible that the main findings occurred by chance.

Mode of delivery is not associated with asthma or atopy in childhood

Background Caesarean‐section delivery has been associated with the subsequent development of atopy and wheezing in childhood.

Haemoglobin and ferritin concentrations in children aged 12 and 18 months

AIMS To define the normal ranges and investigate associated factors for haemoglobin and ferritin in British children at 12 and 18 months of age, and to estimate correlations between both haemoglobin and ferritin concentrations at 8, 12, and 18 months of age. SUBJECTS AND METHODS Subjects were part of the “children in focus” sample, randomly selected from the Avon longitudinal study of pregnancy and childhood. Capillary blood samples were taken from 940 children at 12 months and 827 children at 18 months of age. RESULTS Haemoglobin was distributed normally and ferritin was distributed log normally at 12 and 18 months of age. Ninety five per cent reference ranges were established from empirical centiles of haemoglobin and ferritin. Haemoglobin concentrations at 18 months were associated with sex and maternal education. Concentrations of ferritin at 12 and 18 months of age were associated with birth weight and current weight. Girls at 12 months, but not at 18 months, had 8% higher ferritin concentrations than boys. Haemoglobin and ferritin concentrations were significantly correlated over time (8–12 months:r Hb = 0.26,r Fer = 0.46; 12–18 months:r Hb = 0.37,r Fer = 0.34; 8–18 months:r Hb = 0.22,r Fer = 0.24). CONCLUSION Iron stores are depleted by rapid growth in infancy. A definition of anaemia based on the fifth centile gives cut off points at 12 and 18 months of age of haemoglobin < 100 g/l, and for iron deficiency of ferritin < 16 μg/l and < 12 μg/l, respectively. Because children below the fifth centile at one time point differ from those six months later, it is unclear whether screening would be effective.

Hygiene levels in a contemporary population cohort are associated with wheezing and atopic eczema in preschool infants

Background: The hygiene hypothesis states that insufficient exposure to certain infectious agents during childhood increases the risk of developing asthma and atopic diseases. Improvements in hygiene levels may be partly responsible for this decline in exposure. Aims: To assess whether hygiene levels in infancy are associated with wheeze and/or atopic eczema, independent of a number of possible confounding factors. Methods: Data were gathered from the Avon Longitudinal Study of Parents and Children (ALSPAC). Parental self completion questionnaires provided symptom data on infant wheeze and atopic eczema at 0–6 months and 30–42 months, respectively. A simple hygiene score was derived using questionnaire responses at 15 months, which ranged from least hygienic to most hygienic. Multivariable logistic regression models analysed the effect of hygiene scores on health outcomes, while adjusting for a number of important confounding variables. Results: Increasing hygiene scores were independently associated with wheezing (OR = 1.04; 95% CI: 1.00 to 1.08) and atopic eczema (OR = 1.04; 95% CI: 1.01 to 1.07) between 30 and 42 months, but not in the first six months. The odds ratio was higher for atopic eczema if the rash was reported to have become sore and oozy (OR = 1.09; 95% CI: 1.02 to 1.16). Conclusions: High levels of hygiene at 15 months of age were independently associated with wheeze and atopic eczema reported between 30 and 42 months, and there was an increased risk for children with more severe eczema during this period. The importance of hygiene in public health should not be dismissed; however, the creation of a sterile environment through excessive cleanliness may potentially be harmful to the immune system.

Should infants be screened for anaemia? A prospective study investigating the relation between haemoglobin at 8, 12, and 18 months and development at 18 months

AIMS To investigate the relation between haemoglobin in children followed longitudinally from 8 to 18 months, and developmental outcome at 18 months. METHODS The Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC) is a longitudinal survey of a geographically defined population of children born in 1991–92. In a randomly selected subsample, blood samples were assayed for Hb at 8, 12, and 18 months; a developmental assessment was carried out at 18 months on 1141 children using the Griffiths Scales of Mental Development. RESULTS There was a strong quadratic association between Hb at 8 months and performance on the locomotor subscale at 18 months. Average scores increased with increasing Hb up to 95 g/l; there was little additional developmental benefit in Hb levels beyond 95 g/l. Infants with Hb <95 g/l at 8 months of age scored on average 6 points lower on the locomotor subscale than infants with Hb ⩾ 95 g/l; infants with Hb <90 g/l at 8 months scored 12 points lower on the locomotor subscale than children with Hb ⩾ 90 g/l. CONCLUSIONS Low Hb concentrations (⩽ 95 g/l) in 8 month old children are associated with impaired motor development at 18 months. This cut off point corresponds to the 5th centile of Hb at 8 months. The results indicate that if there is an adverse effect of low Hb on developmental outcome, screening may be more effective at 8 months or earlier, rather than after this age. We propose to examine the importance of infant anaemia in relation to more accurate and detailed long term outcomes as the children get older.