Gene-environment interactions related to maternal exposure to environmental and lifestyle-related chemicals during pregnancy and the resulting adverse fetal growth: a review

BACKGROUND@#There are only limited numbers of reviews on the association of maternal-child genetic polymorphisms and environmental and lifestyle-related chemical exposure during pregnancy with adverse fetal growth. Thus, this article aims to review: (1) the effect of associations between the above highlighted factors on adverse fetal growth and (2) recent birth cohort studies regarding environmental health risks.@*METHODS@#Based on a search of the PubMed database through August 2021, 68 epidemiological studies on gene-environment interactions, focusing on the association between environmental and lifestyle-related chemical exposure and adverse fetal growth was identified. Moreover, we also reviewed recent worldwide birth cohort studies regarding environmental health risks.@*RESULTS@#Thirty studies examined gene-smoking associations with adverse fetal growth. Sixteen maternal genes significantly modified the association between maternal smoking and adverse fetal growth. Two genes significantly related with this association were detected in infants. Moreover, the maternal genes that significantly interacted with maternal smoking during pregnancy were cytochrome P450 1A1 (CYP1A1), X-ray repair cross-complementing protein 3 (XRCC3), interleukin 6 (IL6), interleukin 1 beta (IL1B), human leukocyte antigen (HLA) DQ alpha 1 (HLA-DQA1), HLA DQ beta 1 (HLA-DQB1), and nicotinic acetylcholine receptor. Fetal genes that had significant interactions with maternal smoking during pregnancy were glutathione S-transferase theta 1 (GSTT1) and fat mass and obesity-associated protein (FTO). Thirty-eight studies examined the association between chemical exposures and adverse fetal growth. In 62 of the 68 epidemiological studies (91.2%), a significant association was found with adverse fetal growth. Across the studies, there was a wide variation in the analytical methods used, especially with respect to the genetic polymorphisms of interest, environmental and lifestyle-related chemicals examined, and the study design used to estimate the gene-environment interactions. It was also found that a consistently increasing number of European and worldwide large-scale birth cohort studies on environmental health risks have been conducted since approximately 1996.@*CONCLUSION@#There is some evidence to suggest the importance of gene-environment interactions on adverse fetal growth. The current knowledge on gene-environment interactions will help guide future studies on the combined effects of maternal-child genetic polymorphisms and exposure to environmental and lifestyle-related chemicals during pregnancy.

Hokkaido birth cohort study on environment and children's health: cohort profile 2021

BACKGROUND@#The Hokkaido Study on Environment and Children's Health is an ongoing study consisting of two birth cohorts of different population sizes: the Sapporo cohort and the Hokkaido cohort. Our primary objectives are to (1) examine the effects that low-level environmental chemical exposures have on birth outcomes, including birth defects and growth retardation; (2) follow the development of allergies, infectious diseases, and neurobehavioral developmental disorders, as well as perform a longitudinal observation of child development; (3) identify high-risk groups based on genetic susceptibility to environmental chemicals; and (4) identify the additive effects of various chemicals, including tobacco.@*METHODS@#The purpose of this report is to provide an update on the progress of the Hokkaido Study, summarize recent results, and suggest future directions. In particular, this report provides the latest details from questionnaire surveys, face-to-face examinations, and a collection of biological specimens from children and measurements of their chemical exposures.@*RESULTS@#The latest findings indicate different risk factors of parental characteristics on birth outcomes and the mediating effect between socioeconomic status and children that are small for the gestational age. Maternal serum folate was not associated with birth defects. Prenatal chemical exposure and smoking were associated with birth size and growth, as well as cord blood biomarkers, such as adiponectin, leptin, thyroid, and reproductive hormones. We also found significant associations between the chemical levels and neuro development, asthma, and allergies.@*CONCLUSIONS@#Chemical exposure to children can occur both before and after birth. Longer follow-up for children is crucial in birth cohort studies to reinforce the Developmental Origins of Health and Disease hypothesis. In contrast, considering shifts in the exposure levels due to regulation is also essential, which may also change the association to health outcomes. This study found that individual susceptibility to adverse health effects depends on the genotype. Epigenome modification of DNA methylation was also discovered, indicating the necessity of examining molecular biology perspectives. International collaborations can add a new dimension to the current knowledge and provide novel discoveries in the future.

Lifestyle behaviors and home and school environment in association with sick building syndrome among elementary school children: a cross-sectional study

BACKGROUND@#Sick building syndrome (SBS) refers to the combination of symptoms experienced by occupants of specific building characteristics. This study investigated the associations of children's lifestyle behaviors, allergies, home, and school environment with SBS symptoms.@*METHODS@#A total of 4408 elementary school children living in Sapporo City, Japan participated in this study. SBS was determined on parental answers to MM080 standardized school questionnaires on symptoms that were weekly experienced by these children, and if the symptom is attributed to their home or school environment. The Japanese version of the International Study of Asthma and Allergies in Childhood questionnaire was used to assess wheeze, rhino-conjunctivitis, and eczema. A logistic regression analysis was conducted to evaluate the associations between SBS symptoms and variables by controlling the potential confounders (gender, grade, school, and parental history of allergies). A stepwise backward elimination was conducted to assess independent variables related to SBS.@*RESULTS@#Participants revealed mucosal (6.9%), skin (2.0%), and general (0.8%) symptoms. The presence of one or more allergy was associated with increased mucosal and skin symptoms. Children who skipped breakfast, displayed faddiness (like/dislike of food), had constipation, have insufficient sleep, did not feel refreshed after sleep, and lacked deep sleep showed significantly high odds ratios with SBS symptoms. The stepwise analysis showed faddiness for mucosal symptoms and not feeling refreshed after sleep for mucosal and skin symptoms, whereas constipation and lacking deep sleep for general symptoms were independent variables in increasing the symptoms. We found no significant relationship between SBS in children and schools. Considering children's home, old building, no ventilation, wall-to-wall carpet, and heavy nearby traffic were associated with elevated mucosal symptom, while living in a multifamily home increased general symptoms. Home dampness was an independent variable in increasing all SBS symptoms.@*CONCLUSIONS@#Allergies and lifestyle behaviors were associated with increased SBS in children, including skipping breakfast, displaying faddiness, constipation, insufficient sleep, not feeling refreshed after sleep, and the lack of deep sleep. Further, dampness at home was associated with increase in all SBS symptoms. Lifestyle (e.g., eating and sleeping habits) and home (i.e., dampness) improvements might alleviate SBS symptoms in children.

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

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.

Prenatal exposure to bisphenol A and phthalates and behavioral problems in children at preschool age: the Hokkaido Study on Environment and Children's Health

BACKGROUND@#Studies reported adverse behavioral development including internalizing and externalizing problems in association with prenatal exposure to bisphenol A (BPA) and phthalates; however, findings were not sufficient due to using different assessment tools and child ages among studies. This study aimed to examine associations between maternal serum levels of BPA and phthalate metabolites and behavioral problems at preschool age.@*METHODS@#The Strengths and Difficulties Questionnaire (SDQ) was used to assess behavioral problems at 5 years of age. BPA and phthalate metabolite levels in the first trimester maternal serum was determined by LC-MS/MS for 458 children. Variables used for adjustment were parental ages, maternal cotinine levels, family income during pregnancy, child sex, birth order, and age at SDQ completed.@*RESULTS@#The median concentrations of BPA, MnBP, MiBP, MEHP, and MECPP, primary and secondary metabolites of phthalates, were 0.062, 26.0, 7.0, 1.40, and 0.20 ng/ml, respectively. MECPP level was associated with increase conduct problem risk (OR = 2.78, 95% CI 1.36-5.68) overall and the association remained after child sex stratification, and odds ratios were increased with wider confidence interval (OR = 2.85, 95% CI 1.07-7.57 for boys, OR = 4.04, 95% CI 1.31-12.5 for girls, respectively). BPA, ∑DBP (MnBP + MiBP), and ∑DEHP (MEHP+MECPP) levels were not associated with any of the child behavioral problems.@*CONCLUSIONS@#Our analyses found no significant association between BPA or summation of phthalate metabolite levels and any of the behavioral problems at 5 years of age but suggested possible association between MECPP levels and increased risk of conduct problems.

Inflammation as a cardiovascular risk factor and pulse wave velocity as a marker of early-stage atherosclerosis in the Japanese population

Inflammation and pulse wave velocity (PWV) are a potential risk factor and marker, respectively, for atherosclerosis in the primary prevention setting. Atherosclerosis is now generally accepted to be an inflammatory disorder of the arterial wall, and the high-sensitivity C-reactive protein (hs-CRP) level has been reported to be a strong predictor of cardiovascular events. High-sensitivity-CRP is associated with two factors related to inflammation: (1) the local production of CRP by atheromatous tissue or coronary artery smooth muscle cells and (2) adipose tissue as a potent source of inflammatory cytokines. Based on studies in North America and Europe, hs-CRP has been established as a cardiovascular risk factor and a cut-off value has been recommended. However, Japanese have lower hs-CRP values than their Western counterparts, partly because Japanese have a lower body mass index (BMI), which correlates positively to hs-CRP, and partly because lifestyle and genetic factors can affect hs-CRP values. Therefore, a cut-off value needs to be established by cohort studies for the Japanese population. Carotid-femoral PWV is most commonly measured by applanation tonometry, particularly in Europe, but this method is critically dependent upon the accurate placing of transducers over the arteries and is both time-consuming and complex. A novel device has been recently developed in Japan that measures brachial-ankle PWV (baPWV) using a volume-rendering method. Brachian-ankle PWV is a suitable screening method because of its technical simplicity and shorter measurement time. It is associated not only with conventional cardiovascular risk factors but also with new risk factors, such as inflammation, gamma-glutamyltransferase, chronic kidney disease, and psychosocial factors. However, a suitable cut-off value has yet to be established.

Indoor airborne mold spores in newly built dwellings

<p><b>OBJECTIVE</b>To investigate the relationships between sick building syndrome and mold in newly-built dwellings.</p><p><b>METHODS</b>Symptoms of 61 residents in 18 dwellings were surveyed by standardized questionnaires. Mold sampling was done by gravity sampling using an open Petri dish. Potato dextrose agar (PDA) and dichloran-18% glycerol agar (DG-18) were used as the culture medium.</p><p><b>RESULTS</b>There were 6 dwellings in which at least one inhabitant complained of one or more symptoms and 12 dwellings in which none of the inhabitants complained of symptoms. There was a tendency for the dwellings with inhabitants reporting symptoms to have larger colony forming units (CFU) on PDA than those without inhabitants reporting symptoms (p=0.1), but there was no difference in DG-18 result. There was a tendency for the dwellings with inhabitants reporting symptoms to have larger CFU ofCladosporium on PDA than those without (p=0.08), but there was no difference in DG-18 result. Significantly moreUlocladium sp. was detected in the dwellings with inhabitants reporting symptoms than in those without (p=0.03).Cladosporium cladosporioides was detected in all the dwellings with inhabitants reporting symptoms and 75% of the dwellings without.Cladosporium macrocarpum andCladosporium herbarum were detected in 33% of the dwellings with inhabitants reporting e symptoms and none of the dwellings without (p=0.1).</p><p><b>CONCLUSION</b>Cladosporium was dominant in the Japanese newly-built dwellings studied, andCladosporium andUlocladium were probably associated with the residents' symptoms in these newly-built dwellings.</p>

Indoor Airborne Mold Spores in Newly Built Dwellings

Objective: To investigate the relationships between sick building syndrome and mold in newly-built dwellings. Methods: Symptoms of 61 residents in 18 dwellings were surveyed by standardized questionnaires. Mold sampling was done by gravity sampling using an open Petri dish. Potato dextrose agar (PDA) and dichloran-18% glycerol agar (DG-18) were used as the culture medium. Results: There were 6 dwellings in which at least one inhabitant complained of one or more symptoms and 12 dwellings in which none of the inhabitants complained of symptoms. There was a tendency for the dwellings with inhabitants reporting symptoms to have larger colony forming units (CFU) on PDA than those without inhabitants reporting symptoms (p=0.1), but there was no difference in DG-18 result. There was a tendency for the dwellings with inhabitants reporting symptoms to have larger CFU of Cladosporium on PDA than those without (p=0.08), but there was no difference in DG-18 result. Significantly more Ulocladium sp. was detected in the dwellings with inhabitants reporting symptoms than in those without (p=0.03). Cladosporium cladosporioides was detected in all the dwellings with inhabitants reporting symptoms and 75% of the dwellings without. Cladosporium macrocarpum and Cladosporium herbarum were detected in 33% of the dwellings with inhabitants reporting e symptoms and none of the dwellings without (p=0.1). Conclusion: Cladosporium was dominant in the Japanese newly-built dwellings studied, and Cladosporium and Ulocladium were probably associated with the residents’ symptoms in these newly-built dwellings.

Relationship between Social Support and Network, and Health Status of the Elderly in Rural Areas. An Epidemiological Review of Recent Studies and Some Related Issues on Community Health-care, and Welfare Policies / 日本農村医学会雑誌

We reviewed recent concepts of social support networks and results of epidemiological studies on the relationship between the social relationships and health status of the elderly. Recent scientific researches have established strong empirical evidences for a causal impact of social relationship on the health status of the elderly. We showed our community-based longitudinal comparative epidemiological study data. From 1991, in Hokkaido prefecture, the health and the social relationship in the elderly living in three areas included a large city “Sapporo”, an ex-coal-mining town, and a rural area “Takasu”, were studied. Lumbar pain and arthritis were main symptoms that the elderly living in the rural town complained more frequently than in other areas. Number of persons with declined activities of daily living (ADL) or with dementia, who might need serious care and support from others, was not significantly different in three cohorts. However, availability of social supports and social participations of the elderly in the rural area was the best and highest among the three areas. From our prospective cohort data in men living in the rural area, Cox proportional hazard analysis showed emotional supports and social participations had protective effects to mortality after adjusting age, health behaviors and the subjective and objective health status. Such effects were not found in women. These findings suggests that the community care system in each town should pay attention to social relationship, especially participation of the elderly themselves. In addition, we discussed some future issues on the community health-care and welfare systems for the elderly and related policies in Japan.

Review of Pesticide Poisonings in U.S.A. and Regulatory Approaches / 日本農村医学会雑誌

Pesticide poisonings continue to be a national problem in U.S.A.. Recent epidemiological studies have suggested that approximately 3, 000 patients are hospitalized for pesticide poisonings each year. The problem of pesticide residues and issues of carcinogenesis are also causing grave concern.<BR>The aim of this paper is to review the pesticide poisonings in U.S.A. and introduce some regulatory approaches in recent years.