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      Impact of prenatal tobacco smoking on infant telomere length trajectory and ADHD symptoms at 18 months: a longitudinal cohort study

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          Abstract

          Background

          Prenatal maternal tobacco smoking is a predictor of child attention-deficit/hyperactivity disorder (ADHD) and is associated with offspring telomere length (TL). In this study, we examine the relationship between maternal prenatal smoking, infant TL, and maternal report of early childhood symptoms of ADHD.

          Methods

          One-hundred and eighty-one mother-infant dyads were followed prospectively for the infant’s first 18 months of life. Prenatal smoking was assessed from maternal report and medical records. TL was measured from infant buccal swab DNA obtained across the first 18 months of life. ADHD symptoms were obtained from maternal report on the Child Behavior Check List. Multiple regression models tested the relation between prenatal smoking and both ADHD symptoms and infant TL. Additional analyses tested whether the change in infant TL influenced the relation between prenatal smoking and ADHD symptoms.

          Results

          Sixteen percent of mothers reported prenatal smoking. Infant TL at 4, 12, and 18 months of age were correlated. Consistent with previous cross-sectional studies linking shorter offspring TL to maternal prenatal smoking, maternal prenatal smoking predicted greater telomere shortening from four to 18 months of infant age ( β = − 5.797, 95% CI [-10.207, -1.386]; p = 0.010). Maternal depression was positively associated with both prenatal smoking (odds ratio (OR): 4.614, 95% CI [1.733, 12.282]; p = 0.002) and child ADHD symptoms ( β = 4.713, 95% CI [2.073, 7.354]; p = 0.0006). To prevent confounding, analyses examined the relation between TL, ADHD symptoms, and prenatal smoking only in non-depressed mothers. In non-depressed mothers, infant TL attrition across the first 18 months moderated the relation between smoking and child ADHD.

          Conclusions

          The findings extend previous studies linking prenatal smoking to shorter infant TL by providing data demonstrating the effect on TL trajectory. The relation between prenatal smoking and early infant ADHD symptoms was moderated by the change in TL. The findings provide novel initial evidence suggesting that TL dynamics are one mechanistic pathway influencing the relation between maternal prenatal smoking and ADHD.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12916-022-02340-1.

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          Most cited references35

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          Missing data analysis: making it work in the real world.

          This review presents a practical summary of the missing data literature, including a sketch of missing data theory and descriptions of normal-model multiple imputation (MI) and maximum likelihood methods. Practical missing data analysis issues are discussed, most notably the inclusion of auxiliary variables for improving power and reducing bias. Solutions are given for missing data challenges such as handling longitudinal, categorical, and clustered data with normal-model MI; including interactions in the missing data model; and handling large numbers of variables. The discussion of attrition and nonignorable missingness emphasizes the need for longitudinal diagnostics and for reducing the uncertainty about the missing data mechanism under attrition. Strategies suggested for reducing attrition bias include using auxiliary variables, collecting follow-up data on a sample of those initially missing, and collecting data on intent to drop out. Suggestions are given for moving forward with research on missing data and attrition.
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            Cellular senescence in ageing: from mechanisms to therapeutic opportunities

            Cellular senescence, first described in vitro in 1961, has become a focus for biotech companies that target it to ameliorate a variety of human conditions. Eminently characterized by a permanent proliferation arrest, cellular senescence occurs in response to endogenous and exogenous stresses, including telomere dysfunction, oncogene activation and persistent DNA damage. Cellular senescence can also be a controlled programme occurring in diverse biological processes, including embryonic development. Senescent cell extrinsic activities, broadly related to the activation of a senescence-associated secretory phenotype, amplify the impact of cell-intrinsic proliferative arrest and contribute to impaired tissue regeneration, chronic age-associated diseases and organismal ageing. This Review discusses the mechanisms and modulators of cellular senescence establishment and induction of a senescence-associated secretory phenotype, and provides an overview of cellular senescence as an emerging opportunity to intervene through senolytic and senomorphic therapies in ageing and ageing-associated diseases.
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              Obesity, cigarette smoking, and telomere length in women.

              Obesity and smoking are important risk factors for many age-related diseases. Both are states of heightened oxidative stress, which increases the rate of telomere erosion per replication, and inflammation, which enhances white blood cell turnover. Together, these processes might accelerate telomere erosion with age. We therefore tested the hypothesis that increased body mass and smoking are associated with shortened telomere length in white blood cells. We investigated 1122 white women aged 18-76 years and found that telomere length decreased steadily with age at a mean rate of 27 bp per year. Telomeres of obese women were 240 bp shorter than those of lean women (p=0.026). A dose-dependent relation with smoking was recorded (p=0.017), and each pack-year smoked was equivalent to an additional 5 bp of telomere length lost (18%) compared with the rate in the overall cohort. Our results emphasise the pro-ageing effects of obesity and cigarette smoking.
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                Author and article information

                Contributors
                sdrury@tulane.edu
                Journal
                BMC Med
                BMC Med
                BMC Medicine
                BioMed Central (London )
                1741-7015
                28 April 2022
                28 April 2022
                2022
                : 20
                : 153
                Affiliations
                [1 ]GRID grid.265219.b, ISNI 0000 0001 2217 8588, Department of Pediatrics, , Tulane University School of Medicine, ; 1430 Tulane Avenue, #8526, New Orleans, Louisiana 70112 USA
                [2 ]GRID grid.25879.31, ISNI 0000 0004 1936 8972, Department of Psychiatry, Perelman School of Medicine, , University of Pennsylvania, ; Philadelphia, PA USA
                [3 ]GRID grid.67033.31, ISNI 0000 0000 8934 4045, Tufts University School of Medicine, ; Boston, MA USA
                [4 ]GRID grid.265219.b, ISNI 0000 0001 2217 8588, Department of Psychiatry and Behavioral Science, , Tulane University School of Medicine, ; 1430 Tulane Avenue, #8526, New Orleans, Louisiana 70112 USA
                [5 ]GRID grid.265219.b, ISNI 0000 0001 2217 8588, Department of Orthopedic Surgery, , Tulane University School of Medicine, ; 1430 Tulane Avenue, #8526, New Orleans, Louisiana 70112 USA
                [6 ]GRID grid.265219.b, ISNI 0000 0001 2217 8588, Department of Epidemiology, , Tulane University School of Public Health and Tropical Medicine, ; New Orleans, LA USA
                [7 ]GRID grid.265219.b, ISNI 0000 0001 2217 8588, Global Community Health and Behavioral Sciences, Tulane University School of Public Health and Tropical Medicine, ; 1430 Tulane Avenue, #8526, New Orleans, Louisiana 70112 USA
                [8 ]GRID grid.265219.b, ISNI 0000 0001 2217 8588, Clinical Neuroscience Research Center, , Tulane University School of Medicine, ; 1430 Tulane Avenue, #8526, New Orleans, Louisiana 70112 USA
                Article
                2340
                10.1186/s12916-022-02340-1
                9047258
                35477473
                5cf14452-1c1d-49b3-8adc-b45ea777cf2c
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 20 July 2021
                : 14 March 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, national institutes of health;
                Award ID: R01 MH101533
                Award ID: 5T32HL007713
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2022

                Medicine
                smoking,tobacco,prenatal,telomere length,telomere attrition,maternal depression,attention deficit/hyperactivity disorder

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