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Birth Weight, Early Childhood Growth and Lung Function In Respiratory epidemiology ORIGINAL ARTICLE Thorax: first published as 10.1136/thoraxjnl-2014-206457 on 16 July 2015. Downloaded from Birth weight, early childhood growth and lung function in middle to early old age: 1946 British birth cohort Yutong Cai,1 Seif O Shaheen,2 Rebecca Hardy,3 Diana Kuh,3 Anna L Hansell1,4 ▸ Additional material is ABSTRACT published online only. To view Background Findings from previous studies Key messages please visit the journal online (http://dx.doi.org/10.1136/ investigating the relationship between birth weight and thoraxjnl-2014-206457). adult lung function have been inconsistent, and data on birth weight and adult lung function decline are lacking. 1Department of Epidemiology What is the key question? and Biostatistics, MRC-PHE Few studies have investigated the relation between early ▸ Do associations between birth weight, early Centre for Environment and childhood growth and adult lung function. childhood growth and lung function change Health, School of Public Methods FEV1 and FVC were measured at ages 43 during midlife to early old age? Health, Imperial College years, 53 years and 60–64 years in the 1946 British London, London, UK 2 birth cohort study. Multiple linear regression models What is the bottom line? Centre for Primary Care and ▸ Early childhood growth and birth weight were Public Health, Barts and The were fitted to study associations with birth weight and London School of Medicine weight gain at age 0–2 years. Multilevel models associated with lung function in middle age, and Dentistry, Queen Mary particularly in women, but the effect size assessed how associations changed with age, with FEV1 University of London, London, and FVC as repeated outcomes. decreased with age and no associations were UK seen in either sex in early old age. 3MRC Unit for Lifelong Health Results 3276 and 3249 participants were included in and Ageing at UCL, Institute of FEV1 and FVC analyses, respectively. In women, there Why read on? Epidemiology and Health Care, was a decreasing association between birth weight and ▸ This is the first study reporting on whether University College London, FVC with age. From the multilevel model, for every 1 kg London, UK associations between birth weight and lung 4 higher birth weight, FVC was higher on average by Directorate of Public Health function vary with age within the same and Primary Care, Imperial 66.3 mL (95% CI 0.5 to 132) at 43 years, but fi – individuals with repeated lung function College Healthcare NHS Trust, signi cance was lost at 53 years and 60 64 years. measurements over a 20-year period. London, UK Similar associations were seen with FEV1, but linear change (decline) from age 43 years lost statistical Correspondence to fi http://thorax.bmj.com/ Dr Anna Hansell, Department signi cance after full adjustment. In men, associations of Epidemiology and with birth weight were null in multilevel models. Higher Biostatistics, MRC-PHE Centre early life weight gain was associated with higher FEV at – – – 1 association,6 14 and others not.51518 Six891114 for Environment and Health, age 43 years in men and women combined but not in studies adjusted for potential confounding factors School of Public Health, each sex. Imperial College London, throughout the life course, while four5151618 ’ Conclusions Birth weight is positively associated with St Mary s Campus, Norfolk only accounted for a limited set of potential con- Place, London W2 1PG, UK; adult lung function in middle age, particularly in women, [email protected] founders. All published studies were based on lung but the association diminishes with age, potentially due on September 24, 2021 by guest. Protected copyright. function measurement at a single time point and to accumulating environmental influences over the life Received 16 October 2014 conducted in different populations at different course. Revised 15 June 2015 ages. No studies to date have investigated whether Accepted 25 June 2015 the relation between birth weight and adult lung Published Online First 16 July 2015 function changes longitudinally with age. Similarly, there is a paucity of data on associations between INTRODUCTION growth in early childhood and adult lung function, Impaired lung function is an important parameter although two studies have reported positive associa- of health and has been found to predict future mor- tions with weight gain in the first 3 years of life13 bidity and mortality from COPD and coronary and in infancy,10 and higher infant weight was asso- heart disease,12independent of other major risk ciated with lower mortality from COPD in men in factors.3 It has been postulated that adverse ‘pro- a historical cohort study.6 gramming’, as a consequence of impaired growth The Medical Research Council National Survey during critical periods in utero and early child- of Health and Development (NSHD) (1946 British hood, has a lasting effect on lung function and birth cohort) is one of the longest running birth health more generally in adulthood.4 cohorts worldwide with over 20 follow-ups, includ- Birth weight is often used as an indicator of fetal ing spirometric lung function measurements at ages growth. A meta-analysis of eight studies by Lawlor 43 years, 53 years and 60–64 years.19 We tested et al5 in 2005 reported that for every 1 kg increase whether the effect of birth weight on adult lung To cite: Cai Y, Shaheen SO, in birth weight, FEV1 increased by 48 mL (95% CI function changes as participants age, controlling Hardy R, et al. Thorax 26 to 70). Findings across studies are inconsistent, for potential confounders operating through the – 2016;71:916 922. however, with some studies reporting an life course. 916 Cai Y, et al. Thorax 2016;71:916–922. doi:10.1136/thoraxjnl-2014-206457 Respiratory epidemiology METHODS lower respiratory tract infections under 2 years was obtained by Thorax: first published as 10.1136/thoraxjnl-2014-206457 on 16 July 2015. Downloaded from Study population interviewing the child’s mother in 1948 and coded as a binary The NSHD originally recruited 16 695 babies who were born in variable (yes vs no). Childhood social class at 4 years was defined the one week of March 1946 in England, Scotland and Wales.19 by father’s occupation (manual vs non-manual). All singletons born to married mothers in a non-manual or agri- cultural occupational social class and 25% of babies born to a Adult variables manual social class were selected as the study sample (N=5362), Education qualification by age 26 years was categorised as consisting of 2547 women and 2815 men. Cohort members were A-level or equivalent (advanced secondary qualifications interviewed and assessed in their own homes by trained research achieved at 18 years) and above, up to O-level or equivalent nurses at ages 43 years and 53 years, and at clinical research facil- (secondary qualifications achieved at 16 years) and less than ities (or in their homes) at 60–64 years. At the follow-up in 1989 O-level or no qualifications. Adult standing heights at 43 years, – (aged 43 years), the 1st year in which FEV1 and FVC were mea- 53 years and 60 64 years were measured to the nearest 0.1 cm sured, 3839 of the original 5362 individuals were eligible for by using a portable stadiometer. Current asthma status (yes vs study (365 deaths, 540 refusals, 618 emigrations), 3262 indivi- no) was obtained at every age. Smoking status was obtained at duals (85%) were contacted and provided data11 (figure 1). The each interview and expressed as a categorical variable (never, most recent follow-up took place during 2006–2010, in which ex-smoker, current smoker) and in ever-smokers, pack-years 2856 individuals of the original sample were invited to a clinic were also calculated for each age. visit and 2229 (78%) participants were interviewed by a research nurse at the clinic or in their homes.20 Statistical analysis 3276 and 3249 participants met the inclusion criteria and were Spirometry measurements included in the FEV1 and FVC analyses, respectively. Mean (SD) More information about the spirometry protocol in NSHD is lung function for categories of birth weight and current available in the online supplementary material (S1). In brief, at smoking status at every age was calculated. To assess the rela- each follow-up, prebronchodilator (but not postbronchodilator) tionships between birth weight and measurements of FEV1 and spirometry was carried out (standing, without nose clips) and FVC at every age, multiple linear regression models were fitted, supervised by a trained nurse using a Micro Medical Micro Plus with models specified a priori. Sex by birth weight interactions turbine spirometer. The quality of spirometry was assessed by was investigated and analyses were conducted for both sexes the nurse and formally recorded at the 1999 and 2006–2010 and for men and women separately. A sequence of nested follow-ups. Three manoeuvres were recorded in 1989, and two models was fitted: M0—unadjusted model; M1—adjusted for in 1999 and 2006–2010, but otherwise the protocol was the current adult height; M2—further adjusted for current adult same, which was developed before current ATS/ERS guidelines covariates including education level, smoking status, smoking were published.21 As with a previous study,22 participants were pack years and asthma status; M3—additionally adjusted for excluded from the analysis if the difference between the two early life covariates including weight gain at 2 years, lower largest values was greater than 0.3 L23 and if values were more respiratory tract infection under 2 years and childhood social than 3 SD from the mean value (adjusted for sex and height).11 class (fully adjusted model). http://thorax.bmj.com/ Social class of head of household at every age was added to Early life variables the fully adjusted model as a sensitivity analysis to address Birth weight to the nearest quarter of a pound was extracted from potential residual confounding by socioeconomic status.
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