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Confounding by ill health in the observed association between BMI and mortality: evidence from the HUNT Study using offspring BMI as an instrument.

ABSTRACT: BACKGROUND:The observational association between mortality and body mass index (BMI) is U-shaped, leading to highly publicized suggestions that moderate overweight is beneficial to health. However, it is unclear whether elevated mortality is caused by low BMI or if the association is confounded, for example by concurrent ill health. METHODS:Using HUNT, a Norwegian prospective study, 32 452 mother-offspring and 27 747 father-offspring pairs were followed up to 2009. Conventional hazard ratios for parental mortality per standard deviation of BMI were estimated using Cox regression adjusted for behavioural and socioeconomic factors. To estimate hazard ratios with reduced susceptibility to confounding, particularly from concurrent ill health, the BMI of parents' offspring was used as an instrumental variable for parents' own BMI. The shape of mortality-BMI associations was assessed using cubic splines. RESULTS:There were 18 365 parental deaths during follow-up. Conventional associations of mortality from all-causes, cardiovascular disease and cancer with parents' own BMI were substantially nonlinear, with elevated mortality at both extremes and minima at 21-25 kg m-2. Equivalent associations with offspring BMI were positive and there was no evidence of elevated parental mortality at low offspring BMI. The linear instrumental variable hazard ratio for all-cause mortality per standard deviation increase in BMI was 1.18 (95% confidence interval: 1.10, 1.26), compared with 1.05 (1.03, 1.06) in the conventional analysis. CONCLUSIONS:Elevated mortality rates at high BMI appear causal, whereas excess mortality at low BMI is likely exaggerated by confounding by factors including concurrent ill health. Conventional studies probably underestimate the adverse population health consequences of overweight.

SUBMITTER: Carslake D

PROVIDER: S-EPMC6005033 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Confounding by ill health in the observed association between BMI and mortality: evidence from the HUNT Study using offspring BMI as an instrument.

Carslake David D Davey Smith George G Gunnell David D Davies Neil N Nilsen Tom I L TIL Romundstad Pål P

International journal of epidemiology 20180601 3

<h4>Background</h4>The observational association between mortality and body mass index (BMI) is U-shaped, leading to highly publicized suggestions that moderate overweight is beneficial to health. However, it is unclear whether elevated mortality is caused by low BMI or if the association is confounded, for example by concurrent ill health.<h4>Methods</h4>Using HUNT, a Norwegian prospective study, 32 452 mother-offspring and 27 747 father-offspring pairs were followed up to 2009. Conventional ha ...[more]

PMID: 29206928

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Project description:BackgroundThis study used data from recent Demographic and Health Surveys (DHS) to examine the impact of high parity on under-five and neonatal mortality. The analyses used various techniques to attempt eliminating selection issues, including stratification of analyses by mothers' completed fertility.MethodsWe analyzed DHS datasets from 47 low- and middle-income countries. We only used data from women who were age 35 or older at the time of survey to have a measure of their completed fertility. We ran log-binominal regression by country to calculate relative risk between parity and both under-five and neonatal mortality, controlled for wealth quintile, maternal education, urban versus rural residence, maternal age at first birth, calendar year (to control for possible time trends), and birth interval. We then controlled for maternal background characteristics even further by using mothers' completed fertility as a proxy measure.ResultsWe found a statistically significant association between high parity and child mortality. However, this association is most likely not physiological, and can be largely attributed to the difference in background characteristics of mothers who complete reproduction with high fertility versus low fertility. Children of high completed fertility mothers have statistically significantly increased risk of death compared to children of low completed fertility mothers at every birth order, even after controlling for available confounders (i.e. among children of birth order 1, adjusted RR of under-five mortality 1.58, 95% CI: 1.42, 1.76). There appears to be residual confounders that put children of high completed fertility mothers at higher risk, regardless of birth order. When we examined the association between parity and under-five mortality among mothers with high completed fertility, it remained statistically significant, but negligible in magnitude (i.e. adjusted RR of under-five mortality 1.03, 95% CI: 1.02-1.05).ConclusionsOur analyses strongly suggest that the observed increased risk of mortality associated with high parity births is not driven by a physiological link between parity and mortality. We found that at each birth order, children born to women who have high fertility at the end of their reproductive period are at significantly higher mortality risk than children of mothers who have low fertility, even after adjusting for available confounders. With each unit increase in birth order, a larger proportion of births at the population level belongs to mothers with these adverse characteristics correlated with high fertility. Hence it appears as if mortality rates go up with increasing parity, but not for physiological reasons.

Project description:Evidence supports no link between maternal smoking in pregnancy and autism spectrum disorder (autism) overall. To address remaining questions about the unexplained heterogeneity between study results and the possibility of risk for specific autism sub-phenotypes, we conducted a whole-population cohort study in Denmark. We followed births 1991-2011 (1,294,906 persons, including 993,301 siblings in 728,271 families), from 1 year of age until an autism diagnosis (13,547), death, emigration, or December 31, 2012. Autism, with and without attention deficit hyperactivity disorder (ADHD) and with and without intellectual disability (ID) were based on ICD-8 and ICD-10 codes from Danish national health registers, including 3,319 autism + ADHD, 10,228 autism - no ADHD, 2,205 autism + ID, and 11,342 autism - no ID. We estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) between any maternal smoking (from birth records) and autism (or sub-phenotypes) using survival models with robust standard errors, stratifying by birth year and adjusting for child sex, parity, and parental age, education, income, and psychiatric history. To additionally address confounding using family designs, we constructed a maternal cluster model (adjusting for the smoking proportion within the family), and a stratified sibling model. Associations with maternal smoking and autism were elevated in conventional adjusted analyses (HR of 1.17 [1.13-1.22]) but attenuated in the maternal cluster (0.98 [0.88-1.09]) and sibling (0.86 [0.64-1.15]) models. Similarly, risks of autism sub-phenotypes with maternal smoking were attenuated in the family-based models. Together these results support that smoking in pregnancy is not linked with autism or select autism comorbid sub-phenotypes after accounting for familial confounding. Autism Res 2020, 13: 134-144. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Smoking during pregnancy has many harmful impacts, which may include harming the baby's developing brain. However, in a study of thousands of families in Denmark, it does not appear that smoking in pregnancy leads to autism or autism in combination with intellectual problems or attention deficits, once you account for the way smoking patterns and developmental disabilities run in families.

Dataset Information

Confounding by ill health in the observed association between BMI and mortality: evidence from the HUNT Study using offspring BMI as an instrument.

Publications

Confounding by ill health in the observed association between BMI and mortality: evidence from the HUNT Study using offspring BMI as an instrument.

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