scholarly journals DNA methylation of GFI1 as a mediator of the association between prenatal smoking exposure and ADHD symptoms at 6 years: the Hokkaido Study on Environment and Children’s Health

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Kunio Miyake ◽  
Chihiro Miyashita ◽  
Atsuko Ikeda-Araki ◽  
Ryu Miura ◽  
Sachiko Itoh ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Rating Scale ◽  
Children's Health ◽  
Children’S Health ◽  
Prenatal Smoking ◽  
Active Smoking ◽  
Adhd Symptoms ◽  
Smoking During Pregnancy ◽  
Smoking Exposure ◽  
Increased Risk

Abstract Background Prenatal smoking exposure has been associated with childhood attention-deficit/hyperactivity disorder (ADHD). However, the mechanism underlying this relationship remains unclear. We assessed whether DNA methylation differences may mediate the association between prenatal smoking exposure and ADHD symptoms at the age of 6 years. Results We selected 1150 mother–infant pairs from the Hokkaido Study on the Environment and Children’s Health. Mothers were categorized into three groups according to plasma cotinine levels at the third trimester: non-smokers (≤ 0.21 ng/mL), passive smokers (0.21–11.48 ng/mL), and active smokers (≥ 11.49 ng/mL). The children’s ADHD symptoms were determined by the ADHD-Rating Scale at the age of 6 years. Maternal active smoking during pregnancy was significantly associated with an increased risk of ADHD symptoms (odds ratio, 1.89; 95% confidence interval, 1.14–3.15) compared to non-smoking after adjusting for covariates. DNA methylation of the growth factor-independent 1 transcriptional repressor (GFI1) region, as determined by bisulfite next-generation sequencing of cord blood samples, mediated 48.4% of the total effect of the association between maternal active smoking during pregnancy and ADHD symptoms. DNA methylation patterns of other genes (aryl-hydrocarbon receptor repressor [AHRR], cytochrome P450 family 1 subfamily A member 1 [CYP1A1], estrogen receptor 1 [ESR1], and myosin IG [MYO1G]) regions did not exert a statistically significant mediation effect. Conclusions Our findings demonstrated that DNA methylation of GFI1 mediated the association between maternal active smoking during pregnancy and ADHD symptoms at the age of 6 years.

scholarly journals DNA methylation links prenatal smoking exposure to later life health outcomes in offspring

2018 ◽  
Author(s):  
Petri Wiklund ◽  
Ville Karhunen ◽  
Rebecca C Richmond ◽  
Alina Rodriguez ◽  
Maneka De Silva ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Health Outcomes ◽  
Maternal Smoking ◽  
Psychiatric Morbidity ◽  
Later Life ◽  
Prenatal Smoking ◽  
Smoking During Pregnancy ◽  
Mediation Analyses ◽  
Increased Risk ◽  
Prenatal Maternal Smoking

AbstractMaternal smoking during pregnancy is associated with adverse offspring health outcomes across their life course. We hypothesize that DNA methylation is a potential mediator of this relationship. To test this, we examined the association of prenatal maternal smoking with DNA methylation in 2,821 individuals (age 16 to 48 years) from five prospective birth cohort studies and perform Mendelian randomization and mediation analyses to assess, whether methylation markers have causal effects on disease outcomes in the offspring. We identify 69 differentially methylated CpGs in 36 genomic regions (P < 1×10−7), and show that DNA methylation may represent a biological mechanism through which maternal smoking is associated with increased risk of psychiatric morbidity in the exposed offspring.

scholarly journals Nicotine and Its Downstream Metabolites in Maternal and Cord Sera: Biomarkers of Prenatal Smoking Exposure Associated with Offspring DNA Methylation

2020 ◽  
Vol 17 (24) ◽  
pp. 9552
Author(s):  
Parnian Kheirkhah Rahimabad ◽  
Thilani M. Anthony ◽  
A. Daniel Jones ◽  
Shakiba Eslamimehr ◽  
Nandini Mukherjee ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Self Report ◽  
Major Constituent ◽  
Prenatal Smoking ◽  
Nicotine Exposure ◽  
Primary Metabolite ◽  
Prenatal Nicotine Exposure ◽  
Smoking Exposure ◽  
Prenatal Nicotine ◽  
In Pregnancy

Nicotine is a major constituent of cigarette smoke. Its primary metabolite in maternal and cord sera, cotinine, is considered a biomarker of prenatal smoking. Nicotine and cotinine half-lives are decreased in pregnancy due to their increased rate of metabolism and conversion to downstream metabolites such as norcotinine and 3-hydroxycotinine. Hence, downstream metabolites of nicotine may provide informative biomarkers of prenatal smoking. In this study of three generations (F0-mothers, F1-offspring who became mothers, and F2-offspring), we present a biochemical assessment of prenatal smoking exposure based on maternal and cord sera levels of nicotine, cotinine, norcotinine, and 3-hydroxycotinine. As potential markers of early effects of prenatal smoking, associations with differential DNA methylation (DNAm) in the F1- and F2-offspring were assessed. All metabolites in maternal and cord sera were associated with self-reported prenatal smoking, except for nicotine. We compared maternal self-report of smoking in pregnancy to biochemical evidence of prenatal smoking exposure. Self-report of F0-mothers of F1 in 1989–1990 had more accuracy identifying prenatal smoking related to maternal metabolites in maternal serum (sensitivity = 94.6%, specificity = 86.9%) compared to self-reports of F1-mothers of F2 (2010–2016) associated with cord serum markers (sensitivity = 66.7%, specificity = 78.8%). Nicotine levels in sera showed no significant association with any DNAm site previously linked to maternal smoking. Its downstream metabolites, however, were associated with DNAm sites located on the MYO1G, AHRR, and GFI1 genes. In conclusion, cotinine, norcotinine, and 3-hydroxycotinine in maternal and cord sera provide informative biomarkers and should be considered when assessing prenatal smoking. The observed association of offspring DNAm with metabolites, except for nicotine, may imply that the toxic effects of prenatal nicotine exposure are exerted by downstream metabolites, rather than nicotine. If differential DNA methylation on the MYO1G, AHRR, and GFI1 genes transmit adverse effects of prenatal nicotine exposure to the child, there is a need to investigate whether preventing changes in DNA methylation by reducing the metabolic rate of nicotine and conversion to harmful metabolites may protect exposed children.

scholarly journals DNA methylation links prenatal smoking exposure to later life health outcomes in offspring

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Petri Wiklund ◽  
Ville Karhunen ◽  
Rebecca C. Richmond ◽  
Priyanka Parmar ◽  
Alina Rodriguez ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Health Outcomes ◽  
Later Life ◽  
Prenatal Smoking ◽  
Smoking Exposure

scholarly journals Prenatal tobacco exposure and ADHD symptoms at pre-school age: the Hokkaido Study on Environment and Children’s Health

2019 ◽  
Vol 24 (1) ◽  
Author(s):  
Machiko Minatoya ◽  
Atsuko Araki ◽  
Sachiko Itoh ◽  
Keiko Yamazaki ◽  
Sumitaka Kobayashi ◽  
...  
Keyword(s):  
Passive Smoking ◽  
Maternal Plasma ◽  
School Age ◽  
Adhd Symptoms ◽  
Third Trimester ◽  
Smoking During Pregnancy ◽  
Passive Smoker ◽  
The Third ◽  
Increased Risk ◽  
Plasma Cotinine

Abstract Background There have been inconsistent findings reported on maternal passive smoking during pregnancy and child risk of ADHD. In this study, ADHD symptoms at pre-school age children in association with prenatal passive and active tobacco smoke exposure determined by maternal plasma cotinine levels in the third trimester were investigated. Methods This was a follow-up study of the birth cohort: the Hokkaido Study on Environment and Children’s Health. Children whose parents answered Strengths and Difficulties Questionnaire (SDQ) to identify child ADHD symptoms (hyperactivity/inattention and conduct problems) and total difficulties at age 5 years with available maternal plasma cotinine level at the third trimester were included (n = 3216). Cotinine levels were categorized into 4 groups; ≦ 0.21 ng/ml (non-smoker), 0.22–0.51 ng/ml (low-passive smoker), 0.52–11.48 ng/ml (high-passive smoker), and ≧ 11.49 ng/ml (active smoker). Results Maternal cotinine levels of active smokers were significantly associated with an increased risk of total difficulties (OR = 1.67) and maternal low- and high-passive smoking also increased the risk (OR = 1.11, 1.25, respectively) without statistical significance. Similarly, maternal cotinine levels of active smokers were associated with an increased risk of hyperactivity/inattention (OR = 1.49). Maternal low- and high-passive smoking and active smoking increased the risk of hyperactivity/inattention (OR = 1.45, 1.43, and OR = 1.59, respectively) only in boys. Conclusion Our findings suggested that maternal active smoking during pregnancy may contribute to the increased risk of child total difficulties and hyperactivity/inattention at pre-school age. Pregnant women should be encouraged to quit smoking and avoid exposure to tobacco smoke.

scholarly journals Invited Commentary: Is DNA Methylation an Actionable Mediator of Prenatal Exposure Effects on Child Health?

2019 ◽  
Vol 188 (11) ◽  
pp. 1887-1889 ◽  
Author(s):  
Christine Ladd-Acosta ◽  
M Daniele Fallin
Keyword(s):  
Dna Methylation ◽  
Birth Weight ◽  
Repeated Measures ◽  
Ethnically Diverse ◽  
Molecular Signature ◽  
Prenatal Smoking ◽  
Mediation Analyses ◽  
Adverse Health Outcomes ◽  
Smoking Exposure ◽  
The Impact

Abstract A substantial body of literature has shown robust associations between prenatal smoking exposure and DNA methylation levels. The pattern of DNA methylation can be used as a molecular signature of past prenatal smoking exposure and might also provide mechanistic insights into associations between prenatal smoking exposure and adverse health outcomes. In this issue of the Journal, Cardenas et al. (Am J Epidemiol. 2019;188(11):1878–1886) evaluated whether DNA methylation mediates the association between prenatal smoking and low birth weight in a tissue that is mechanistically relevant to birth weight—the placenta—using formal mediation analyses. They found that methylation levels, at 5 loci, mediated smoking exposure effects on birth weight but only among children whose mothers smoked during pregnancy. Given the use of formal mediation methods and measurement in a mechanistically relevant tissue, this work has the potential to inform novel directions for intervention. Replication of these findings in larger and more racially and ethnically diverse samples, repeated measures to better tease apart the timing of DNA methylation changes with respect to exposure and birth weight, and continued use of intervention-focused mediation methods are needed before the impact of these findings will be fully realized.

scholarly journals Global and gene‐specific DNA methylation across multiple tissues in early infancy: implications for children's health research

2014 ◽  
Vol 28 (5) ◽  
pp. 2088-2097 ◽  
Author(s):  
David A. Armstrong ◽  
Corina Lesseur ◽  
Elisabeth Conradt ◽  
Barry M. Lester ◽  
Carmen J. Marsit
Keyword(s):  
Dna Methylation ◽  
Health Research ◽  
Early Infancy ◽  
Children's Health ◽  
Children’S Health

scholarly journals Change in exposure of children to second-hand smoke with impact on children’s health and change in parental smoking habits after smoking ban in Bavaria – a multiple cross-sectional study.

2021 ◽  
Author(s):  
Mohammed El Sharkawy ◽  
Alisa Weinberger ◽  
Susanne Kutzora ◽  
Jonas Huß ◽  
Lana Hendrowarsito ◽  
...  
Keyword(s):  
Health Effects ◽  
Children's Health ◽  
Children’S Health ◽  
Second Hand Smoke ◽  
Smoking Ban ◽  
Active Smoking ◽  
Cross Sectional ◽  
Adverse Health Effects ◽  
Adverse Health ◽  
Children’S Exposure

Abstract Background: Concerns about smoking displacement from public places to private amenities aroused following smoking ban implementation in Bavaria in 2008. We analysed children’s exposure to second-hand smoke (SHS) before and after the ban, its effect on children’s health and prevalence of active smoking in adults. Methods: Six cross-sectional surveys (n=32,443) on pre-school children in Bavaria were analysed, two surveys before the smoking ban in years 2004 and 2005 (S1 and S2) and four after the ban in 2008, 2012, 2014 and 2016 (S4, S6, S7 and S8). Using multivariate logistic regression, we analysed change in children’s SHS exposure and its adverse health effects (Asthma, wheezing, bronchitis and neurodermatitis) as well as change in parental active smoking. Results: Odds of parents never smoking at home in presence of children increased significantly from before to after the ban with odds ratios (OR) 1.17 (CI 95% 1.01 – 1.35), 1.65 (CI 95% 1.39 – 1.95), 2.85 (CI 95% 2.32 – 3.51), 2.24 (CI 95% 1.84 – 2.72) and 3.66 (CI 95% 2.89 – 4.63) for S2, S4, S6, S7 and S8, respectively with S1 as reference. Compared to S4, odds of parents not actively smoking is significantly higher in S7 (OR= 1.13 (CI 95% 1.03 – 1.24)) and S8 (OR= 1.24 (CI 95% 1.13 – 1.36)). Adverse health effects related to children’s exposure to SHS are significantly less in S8 compared to S1. Conclusion: Smoking displacement to homes after the ban in Bavaria was disproved. Number of parents quitting smoking is increasing over time. Prevalence of health problems in children related to exposure to SHS is decreasing.

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