Bronwyn K. Brew

Systematic review and meta‐analysis investigating breast feeding and childhood wheezing illness

There is conflicting evidence concerning the relationship between breast feeding and wheezing illness. The objective of this study was to investigate whether there is any association between breast feeding and wheezing in children aged over 5 years and to discover possible sources of heterogeneity. An electronic search of MEDLINE and EMBASE databases was conducted from January 2000 to June 2010. In addition, reference lists from relevant publications were searched. Birth cohort, cross-sectional and case-control studies were included if they measured any breast feeding or exclusive breast feeding for 3 or 4 months. Wheezing illness, including asthma, was identified based on symptoms, reported diagnosis or objective criteria. Thirty-one publications were identified for meta-analysis. There was no association found between any or exclusive breast feeding and wheezing illness, although there was a high level of heterogeneity between the studies. Subgroup analysis revealed that any breast feeding slightly lowers the odds of wheeze (pooled odds ratio 0.92 [0.86, 0.98]) but slightly increases the odds of asthma defined by specific criteria (pooled odds ratio 1.10 [1.00, 1.22]). This meta-analysis does not provide evidence that breast feeding is protective against wheezing illness in children aged 5 years and over. The difference in the effects of breast feeding according to the nature of the wheezing illness highlights the importance of the heterogeneity of illness phenotypes.

Transport characteristics of human proximal tubule cells in primary culture

Summary: In order to establish an in vitro model for studying human proximal tubule transport, primary culture of human proximal tubule cells (PTC) was carried out using an improved technique and the properties of these cells were characterised in detail. Using a combination of collagenase treatment, mechanical sieving and isopycnic ultracentrifugation, large numbers of highly purified populations of PTC were isolated and propagated from histologically normal regions of human nephrectomy specimens. Cultured human PTC demonstrated typical histologic and ultrastructural morphologies, well‐preserved brush border enzyme activities, and cyclic adenosine monophosphate (cAMP) production which was stimulated by parathyroid hormone (PTH) but not by vasopressin. Tight confluence, as evidenced by relative impermeability to the paracellular diffusion of inulin, was achieved on porous membrane inserts within 6–8 days. Confluent monolayers generated Na+, K+, Cl−, HCO3− and PO43‐ concentration gradients between apical and basolateral medium compartments, which correlated well with the reabsorption processes known to occur in human PTC in vivo. A number of polarised transport systems were demonstrated, including phlorizin‐inhibitable apical Na+‐glucose transport, PTH‐inhibitable apical Na+‐phosphate transport, probenecid‐inhibitable organic anion transport and quinine‐inhibitable organic cation transport. Using microspectrofluorimetric and 22Na+ uptake measurements, pharmacologically distinct apical and basolateral sodium‐hydrogen exchangers (NHE) were identified. Apical NHE was significantly inhibited by micromolar concentrations of phorbol esters, ethylisopropylamiloride (EIPA) and 3‐methylsulphonyl‐4‐piperidino‐benzoylguanidine methanesulphonate (HOE694). the mean resting intracellular pH of human PTC was 7.23 ± 0.04 and the mean intrinsic buffering capacity following a 20 mmol/L NH4Cl prepulse was 28.45 ± 0.96 mmol/L/unit pH. the results suggest that human PTC, prepared for culture as described herein, maintain morphological and physiological properties characteristic of the segment in vivo. the method therefore provides a useful model for the study of highly polarised transport processes in the human proximal tubule.

Breastfeeding, asthma, and allergy: a tale of two cities

To cite this article: Brew BK, Kull I, Garden F, Almqvist C, Bergström A, Lind T, Webb K, Wickman M, Marks GB. Breastfeeding, asthma, and allergy: a tale of two cities. Pediatric Allergy Immunology 2012: 23: 75–82.

Perinatal factors and respiratory health in children

There is conflicting evidence regarding the associations between anthropometric birth measures and asthma and lung function in children, particularly for apparently healthy infants born at term.

Using fathers as a negative control exposure to test the developmental origins of health and disease hypothesis : a case study on maternal distress and offspring asthma using Swedish register data

Background: Developmental Origins of Health and Disease Hypothesis (DOHaD) studies are often observational in nature and are therefore prone to biases from loss to follow-up and unmeasured confounding. Register-based studies can reduce these issues since they allow almost complete follow-up and provide information on fathers that can be used in a negative control analysis to assess the impact of unmeasured confounding. Aim: The aim of this study was to propose a causal model for testing DOHaD using paternal exposure as a negative control, and its application to maternal distress in pregnancy and offspring asthma. Methods: A causal diagram including shared and parent-specific measured and unmeasured confounders for maternal (fetal) and paternal exposures is proposed. The case study consisted of all children born in Sweden from July 2006 to December 2008 (n=254,150). Information about childhood asthma, parental distress and covariates was obtained from the Swedish national health registers. Associations between maternal and paternal distress during pregnancy and offspring asthma at age five years were assessed separately and with mutual adjustment for the other parent’s distress measure, as well as for shared confounders. Results: Maternal distress during pregnancy was associated with offspring asthma risk; mutually adjusted odds ratio (OR) (OR 1.32, 95% CI 1.23, 1.43). The mutually adjusted paternal distress−offspring asthma analysis (OR 1.05, 95% CI 0.97, 1.13) indicated no evidence for unmeasured confounding shared by the mother and father. Conclusions: Using paternal exposure in a negative control model to test the robustness of fetal programming hypotheses can be a relatively simple extension of conventional observational studies but limitations need to be considered.

Omega-3 supplementation during the first 5 years of life and later academic performance : a randomised controlled trial

Background/objectives:Consumption of oily fish more than once per week has been shown to improve cognitive outcomes in children. However, it is unknown whether similar benefits can be achieved by long-term omega-3 fatty acid supplementation. The objective was to investigate the effect of omega-3 fatty acid supplementation during the first 5 years of life on subsequent academic performance in children by conducting a secondary analysis of the CAPS (Childhood Asthma Prevention Study).Subjects/methods:A total of 616 infants with a family history of asthma were randomised to receive tuna fish oil (high in long-chain omega-3 fatty acids, active) or Sunola oil (low in omega-3 fatty acids, control) from the time breastfeeding ceased or at the age of 6 months until the age of 5 years. Academic performance was measured by a nationally standardised assessment of literacy and numeracy (National Assessment Program Literacy and Numeracy (NAPLAN)) in school years 3, 5, 7 and 9. Plasma omega-3 fatty acid levels were measured at regular intervals until 8 years of age. Between-group differences in test scores, adjusted for maternal age, birth weight and maternal education, were estimated using mixed-model regression.Results:Among 239 children, there were no significant differences in NAPLAN scores between active and control groups. However, at 8 years, the proportion of omega-3 fatty acid in plasma was positively associated with the NAPLAN score (0.13 s.d. unit increase in score per 1% absolute increase in plasma omega-3 fatty acid (95% CI 0.03, 0.23)).Conclusions:Our findings do not support the practice of supplementing omega-3 fatty acids in the diet of young children to improve academic outcomes. Further exploration is needed to understand the association between plasma omega-3 fatty acid levels at 8 years and academic performance.

Towards non-conventional methods of designing register-based epidemiological studies: An application to pediatric research

Aims: Various epidemiological designs have been applied to investigate the causes and consequences of fetal growth restriction in register-based observational studies. This review seeks to provide an overview of several conventional designs, including cohort, case-control and more recently applied non-conventional designs such as family-based designs. We also discuss some practical points regarding the application and interpretation of family-based designs. Methods: Definitions of each design, the study population, the exposure and the outcome measures are briefly summarised. Examples of study designs are taken from the field of low birth-weight research for illustrative purposes. Also examined are relative advantages and disadvantages of each design in terms of assumptions, potential selection and information bias, confounding and generalisability. Kinship data linkage, statistical models and result interpretation are discussed specific to family-based designs. Results: When all information is retrieved from registers, there is no evident preference of the case-control design over the cohort design to estimate odds ratios. All conventional designs included in the review are prone to bias, particularly due to residual confounding. Family-based designs are able to reduce such bias and strengthen causal inference. In the field of low birth-weight research, family-based designs have been able to confirm a negative association not confounded by genetic or shared environmental factors between low birth weight and the risk of asthma. Conclusions: We conclude that there is a broader need for family-based design in observational research as evidenced by the meaningful contributions to the understanding of the potential causal association between low birth weight and subsequent outcomes.

Breastfeeding and Snoring: A Birth Cohort Study

Objective To investigate the relationship between breastfeeding and snoring in childhood. Methods In a cohort of children with a family history of asthma who were recruited antenatally we prospectively recorded data on infant feeding practices throughout the first year of life. Snoring status and witnessed sleep apnea were measured at age 8 years by parent-completed questionnaire. Associations were estimated by logistic regression with, and without, adjustment for sets of confounders designed to exclude biasing effects. Results Habitual snoring was reported in 18.8% of the sample, and witnessed apnea in 2.7%. Any breastfeeding for longer than one month was associated with a reduced risk of habitual snoring at age 8 (adjusted OR 0.48, 95% CI 0.29 to 0.81) and duration of breastfeeding was inversely associated with the prevalence of habitual snoring (adjusted OR 0.79, 95% CI 0.62 to 1.00). Any breastfeeding for longer than 1 month was associated with a lower risk of witnessed sleep apnea (adjusted OR 0.17, 95% CI 0.04 to 0.71). The protective associations were not mediated by BMI, current asthma, atopy or rhinitis at age 8 years. Conclusions Breastfeeding for longer than one month decreases the risk of habitual snoring and witnessed apneas in this cohort of children with a family history of asthma. The underlying mechanism remains unclear but the finding would be consistent with a beneficial effect of the breast in the mouth on oropharyngeal development with consequent protection against upper airway dysfunction causing sleep-disordered breathing.

Longitudinal depression or anxiety in mothers and offspring asthma: a Swedish population-based study

Abstract Background Previous research has found that maternal stress during pregnancy increases the risk of offspring asthma. However, whether this association is consistent with a causal interpretation has never been tested. The objective is to determine whether there is a critical exposure period for maternal depression or anxiety on offspring asthma or whether cumulative exposure is most important, and to investigate evidence of confounding. Methods The study population included all children born in Sweden from July 2006 to December 2009 (n = 360 526). Information about childhood asthma, maternal depression or anxiety (diagnosis or medication) and covariates was obtained from the Swedish national health registers. The associations between exposure periods (pre-conception, pregnancy, postnatal or current) and childhood asthma were estimated using structured life course approach hypothesis testing. Paternal and cousin analyses were used to test for evidence of confounding from shared genes and environment. Results For childhood asthma, cumulative exposure best described the effect of exposure to maternal depression or anxiety up to a maximum of any two exposure periods [adjusted odds ratio 1.44, 95% confidence interval (CI) 1.38, 1.52]. The hypotheses of a critical period were not supported. The paternal and cousin analyses indicated minimal influence from familial confounding. Conclusions These findings support an association between cumulative exposure to maternal depression or anxiety and asthma development in offspring. This association is unique for maternal depression or anxiety and not due to familial confounding. The clinical implication is that effective psychological management of women with chronic distress may reduce offspring asthma risk.

Prenatal maternal psychosocial stress and offspring's asthma and allergic disease: a systematic review and meta-analysis

Prenatal maternal stress may influence offsprings atopic risk through sustained cortisol secretion resulting from activation of the hypothalamic‐pituitary axis (HPA), leading to Th2‐biased cell differentiation in the foetus. We undertook a systematic review and meta‐analysis investigating the relationship between prenatal maternal psychosocial stress and risk of asthma and allergy in the offspring.