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Early life exposures and risk of adult respiratory disease during 50 years of follow-up.

ABSTRACT: Adult health is influenced by factors during fetal life affecting organ development and birth weight. We aimed to study such factors in relation to adult respiratory disease (ARD) risk. The Helsingborg Birth Cohort, Sweden, contributed baseline data collected by medical staff through clinical examination and questionnaires on maternal and birth characteristics 1964-1967. Register linkages were performed with completions of data on ARD by ICD 8-10 classifications (1969-2016), and/or ARD-related drug usage (2005-2016) enabling a 50-year follow-up time. Cox proportional hazard regression analyses were made to adjust for potential confounders, adjusted hazard ratio (aHR). A total of 3675 mothers and their offspring were included. Female offspring showed higher frequency of ARD than males, aHR 1.5 (95% CI 1.3-1.8). Maternal use of sedatives during second trimester, aHR 2.2 (95% CI 1.4-3.4), and maternal smoking during most of pregnancy, aHR 1.2 (95% CI 1.0-1.4), were associated with offspring ARD. Stratified by sex, large-for-gestational-age, aHR 1.4 (95% CI 1.0-1.9), was significantly associated with ARD in female offspring along with maternal sedative use during second trimester and maternal smoking during most of pregnancy. Maternal sedative use during second trimester or all trimesters were the only significant risk factors for male offspring. In conclusion, maternal sedative use in second trimester was independently associated with subsequent respiratory disease in adult offspring irrespective of sex.

SUBMITTER: Johansson CJ

PROVIDER: S-EPMC7762746 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Early life exposures and risk of adult respiratory disease during 50 years of follow-up.

Johansson Carl J CJ Nilsson Peter M PM Ignell Claes C

European journal of epidemiology 20200408 12

Adult health is influenced by factors during fetal life affecting organ development and birth weight. We aimed to study such factors in relation to adult respiratory disease (ARD) risk. The Helsingborg Birth Cohort, Sweden, contributed baseline data collected by medical staff through clinical examination and questionnaires on maternal and birth characteristics 1964-1967. Register linkages were performed with completions of data on ARD by ICD 8-10 classifications (1969-2016), and/or ARD-related d ...[more]

PMID: 32270394

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Project description:Genetic influences on body mass index (BMI) appear to markedly differ across life, yet existing research is equivocal and limited by a paucity of life course data. We thus used a birth cohort study to investigate differences in association and explained variance in polygenic risk for high BMI across infancy to old age (2-69 years). A secondary aim was to investigate how the association between BMI and a key purported environmental determinant (childhood socioeconomic position) differed across life, and whether this operated independently and/or multiplicatively of genetic influences. Data were from up to 2677 participants in the MRC National Survey of Health and Development, with measured BMI at 12 timepoints from 2-69 years. We used multiple polygenic indices from GWAS of adult and childhood BMI, and investigated their associations with BMI at each age. For polygenic liability to higher adult BMI, the trajectories of effect size (β) and explained variance (R2) diverged: explained variance peaked in early adulthood and plateaued thereafter, while absolute effect sizes increased throughout adulthood. For polygenic liability to higher childhood BMI, explained variance was largest in adolescence and early adulthood; effect sizes were marginally smaller in absolute terms from adolescence to adulthood. All polygenic indices were related to higher variation in BMI; quantile regression analyses showed that effect sizes were sizably larger at the upper end of the BMI distribution. Socioeconomic and polygenic risk for higher BMI across life appear to operate additively; we found little evidence of interaction. Our findings highlight the likely independent influences of polygenic and socioeconomic factors on BMI across life. Despite sizable associations, the BMI variance explained by each plateaued or declined across adulthood while BMI variance itself increased. This is suggestive of the increasing importance of chance ('non-shared') environmental influences on BMI across life.

Project description:ImportanceEarly-life exposures, such as prenatal maternal lifestyle, illnesses, nutritional deficiencies, toxin levels, and adverse birth events, have long been considered potential risk factors for neurodevelopmental disorders in offspring. However, maternal genetic factors could be confounding the association between early-life exposures and neurodevelopmental outcomes in offspring, which makes inferring a causal relationship problematic.ObjectiveTo test whether maternal polygenic risk scores (PRSs) for neurodevelopmental disorders were associated with early-life exposures previously linked to the disorders.Design, setting, and participantsIn this UK population-based cohort study, 7921 mothers with genotype data from the Avon Longitudinal Study of Parents and Children (ALSPAC) underwent testing for association of maternal PRS for attention-deficit/hyperactivity disorder (ADHD PRS), autism spectrum disorder (ASD PRS), and schizophrenia (SCZ PRS) with 32 early-life exposures. ALSPAC data collection began September 6, 1990, and is ongoing. Data were analyzed for the current study from April 1 to September 1, 2018.ExposuresMaternal ADHD PRS, ASD PRS, and SCZ PRS were calculated using discovery effect size estimates from the largest available genome-wide association study and a significance threshold of P < .05.Main outcomes and measuresOutcomes measured included questionnaire data on maternal lifestyle and behavior (eg, smoking, alcohol consumption, body mass index, and maternal age), maternal use of nutritional supplements and medications in pregnancy (eg, acetaminophen, iron, zinc, folic acid, and vitamins), maternal illnesses (eg, diabetes, hypertension, rheumatism, psoriasis, and depression), and perinatal factors (eg, birth weight, preterm birth, and cesarean delivery).ResultsMaternal PRSs were available from 7921 mothers (mean [SD] age, 28.5 [4.8] years). The ADHD PRS was associated with multiple prenatal factors, including infections (odds ratio [OR], 1.11; 95% CI, 1.04-1.18), use of acetaminophen during late pregnancy (OR, 1.11; 95% CI, 1.04-1.18), lower blood levels of mercury (β coefficient, -0.06; 95% CI, -0.11 to -0.02), and higher blood levels of cadmium (β coefficient, 0.07; 95% CI, 0.05-0.09). Little evidence of associations between ASD PRS or SCZ PRS and prenatal factors or of association between any of the PRSs and adverse birth events was found. Sensitivity analyses revealed consistent results.Conclusions and relevanceThese findings suggest that maternal risk alleles for neurodevelopmental disorders, primarily ADHD, are associated with some pregnancy-related exposures. These findings highlight the need to carefully account for potential genetic confounding and triangulate evidence from different approaches when assessing the effects of prenatal exposures on neurodevelopmental disorders in offspring.

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Early life exposures and risk of adult respiratory disease during 50 years of follow-up.

Publications

Early life exposures and risk of adult respiratory disease during 50 years of follow-up.

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