Environmental and Genetic Risk Factors of Congenital Anomalies: an Umbrella Review of Systematic Reviews and Meta-Analyses.

BACKGROUND: The prevalence of congenital anomalies in newborns in South Korea was 272.9 per 100,000 in 2005, and 314.7 per 100,000 in 2006. In other studies, the prevalence of congenital anomalies in South Korea was equivalent to 286.9 per 10,000 livebirths in 2006, while it was estimated 446.3 per 10,000 births during the period from 2008 to 2014. Several systematic reviews and meta-analyses analyzing the factors contributing to congenital anomalies have been reported, but comprehensive umbrella reviews are lacking. METHODS: We searched PubMed, Google Scholar, Cochrane, and EMBASE databases up to July 1, 2019, for systematic reviews and meta-analyses that investigated the effects of environmental and genetic factors on any type of congenital anomalies. We categorized 8 subgroups of congenital anomalies classified according to the 10th revision of the International Statistical Classification of Diseases (ICD-10). Two researchers independently searched the literature, retrieved the data, and evaluated the quality of each study. RESULTS: We reviewed 66 systematic reviews and meta-analyses that investigated the association between non-genetic or genetic risk factors and congenital anomalies. Overall, 269 associations and 128 associations were considered for environmental and genetic risk factors, respectively. Congenital anomalies based on congenital heart diseases, cleft lip and palate, and others were associated with environmental risk factors based on maternal exposure to environmental exposures (air pollution, toxic chemicals), parental smoking, maternal history (infectious diseases during pregnancy, pregestational and gestational diabetes mellitus, and gestational diabetes mellitus), maternal obesity, maternal drug intake, pregnancy through artificial reproductive technologies, and socioeconomic factors. The association of maternal alcohol or coffee consumption with congenital anomalies was not significant, and maternal folic acid supplementation had a preventive effect on congenital heart defects. Genes or genetic loci associated with congenital anomalies included MTHFR, MTRR and MTR, GATA4, NKX2-5, SRD5A2, CFTR, and 1p22 and 20q12 anomalies. CONCLUSION: This study provides a wide perspective on the distribution of environmental and genetic risk factors of congenital anomalies, thus suggesting future studies and providing health policy implications.

Effects of an Online Imagery-Based Treatment Program in Patients with Workplace-Related Posttraumatic Stress Disorder: A Pilot Study.

OBJECTIVE: We developed easily accessible imagery-based treatment program for patients with post-traumatic stress disorder (PTSD) related to workplace accidents and investigated the effects of the program on various PTSD related symptoms. METHODS: The program was based on an online platform and consisted of eight 15-min sessions that included script-guided imagery and supportive music. Thirty-five patients with workplace-related PTSD participated in this program 4 days per week for 4 weeks. Its effects were examined using self-report questionnaires before and after the take-home online treatment sessions. RESULTS: After completing the 4-week treatment program, patients showed significant improvements in depressed mood (t=3.642, p=0.001) based on the Patient Health Questionnaire-9 (PHQ-9), anxiety (t=3.198, p=0.003) based on the Generalized Anxiety Disorder seven-item (GAD-7) scale, and PTSD symptoms (t=5.363, p<0.001) based on the Posttraumatic Stress Disorder Check List (PCL). In particular, patients with adverse childhood experiences exhibited a greater degree of relief related to anxiety and PTSD symptoms than those without adverse childhood experiences. CONCLUSION: The present. RESULTS: demonstrated that the relatively short online imagery-based treatment program developed for this study had beneficial effects for patients with workplace-related PTSD.

Associations of serum calcium levels and dietary calcium intake with incident type 2 diabetes over 10 years: the Korean Genome and Epidemiology Study (KoGES).

BACKGROUND: Previous evidence regarding the associations between serum calcium concentrations, dietary calcium intake, and type 2 diabetes (T2D) is limited. We investigated the longitudinal associations of serum calcium levels and dietary calcium intake with T2D development. METHODS: This study used data from the Ansung-Ansan cohort, a community-based, prospective cohort that was followed up for 10 years. Cox regression models adjusted for potential confounders were used to evaluate the associations of serum calcium levels (mean, 9.41 mg/dL) and dietary calcium intake (median, 389.59 mg/day) with T2D incidence. Association between dietary calcium intake and serum calcium levels was assessed using linear regression models. RESULTS: Albumin-adjusted serum calcium levels were not associated with T2D risk (hazard ratio [HR] = 1.07, 95% confidence interval [CI] 0.96, 1.19, p-value = 0.2333). A one-unit increase in log-transformed, energy-adjusted dietary calcium intake was associated with a decreased risk of T2D (HR = 0.88, 95% CI 0.77, 1.00, p-value = 0.0460) and lower albumin-adjusted serum calcium levels (ß = - 0.04, 95% CI - 0.07, - 0.02, p-value = 0.0014). The associations did not differ according to sex (all p-values for interaction > 0.10). CONCLUSIONS: Serum calcium levels were not associated with T2D risk, while higher dietary calcium intake was associated with a decreased risk of T2D development. These results have public health implications for predicting and preventing T2D development, as well as providing guidelines for diet and calcium supplementation.

The modifying effect of vitamin C on the association between perfluorinated compounds and insulin resistance in the Korean elderly: a double-blind, randomized, placebo-controlled crossover trial.

PURPOSE: There is limited evidence whether environmental exposure to perfluorinated compounds (PFCs) affects insulin resistance (IR) and whether vitamin C intake protects against the adverse effect of PFCs. This study was carried out to investigate the effect of PFCs on IR through oxidative stress, and the effects of a 4-week consumption of vitamin C supplement compared placebo on development of IR by PFCs. METHODS: For a double-blind, community-based, randomized, placebo-controlled crossover intervention of vitamin C, we assigned 141 elderly subjects to both vitamin C and placebo treatments for 4 weeks. We measured serum levels of PFCs to estimate PFC exposures and urinary levels of malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) for oxidative stress. We also measured levels of fasting glucose and insulin and derived the homeostatic model assessment (HOMA) index to assess IR. RESULTS: Perfluorooctane sulfonate (PFOS) and perfluorododecanoic acid (PFDoDA) levels were found to be positively associated with HOMA index at the baseline and after placebo treatment. Risks of IR for the top decile of PFOS and PFDoDA exposures were significantly elevated compared with those with lower PFOS and PFDoDA exposures (both, P < 0.0001). However, the effects of PFOS and PFDoDA on HOMA disappeared after vitamin C supplementation (both, P > 0.30). Furthermore, PFOS and PFDoDA levels were also significantly associated with MDA and 8-OHdG levels, and MDA levels were positively associated with HOMA index. CONCLUSION: PFOS and PFDoDA exposures were positively associated with IR and oxidative stress, and vitamin C supplementation protected against the adverse effects of PFOS and PFDoDA on IR.

Effect of hemoglobin adjustment on the precision of mercury concentrations in maternal and cord blood.

The cord-blood mercury concentration is usually considered the best biomarker in regard to developmental methylmercury neurotoxicity. However, the mercury concentration may be affected by the binding of methylmercury to hemoglobin and perhaps also selenium. As cord-blood mercury analyses appear to be less precise than suggested by laboratory quality data, we studied the interrelationships of mercury concentrations with hemoglobin in paired maternal and cord blood samples from a Faroese birth cohort (N=514) and the Mothers and Children's Environmental Health study in Korea (n=797). Linear regression and structural equation model (SEM) analyses were used to ascertain interrelationships between the exposure biomarkers and the possible impact of hemoglobin as well as selenium. Both methods showed a significant dependence of the cord-blood concentration on hemoglobin, also after adjustment for other exposure biomarkers. In the SEM, the cord blood measurement was a less imprecise indicator of the latent methylmercury exposure variable than other exposure biomarkers available, and the maternal hair concentration had the largest imprecision. Adjustment of mercury concentrations both in maternal and cord blood for hemoglobin improved their precision, while no significant effect of the selenium concentration in maternal blood was found. Adjustment of blood-mercury concentrations for hemoglobin is therefore recommended.

Maternal iron intake at mid-pregnancy is associated with reduced fetal growth: results from Mothers and Children's Environmental Health (MOCEH) study.

BACKGROUND: Iron supplementation is a common recommendation for pregnant women to prevent iron deficiency during pregnancy. There is an increasing concern about excessive iron consumption as a general iron prophylaxis by pregnant women without any due consideration about their dietary iron intake or iron status. Our present study investigated the association between total iron intake from diet and supplements and fetal growth in 337 pregnant women at mid-pregnancy in South Korea. METHODS: Iron intake from diet and supplements was examined by a 24-hour recall method. Subjects were divided into three groups based on tertiles of total iron intake levels. Fetal biometry was assessed by ultrasonography at mid-pregnancy. RESULTS: About 99% of the non-supplement users had iron intake below the recommended nutrient intake (RNI) for pregnant women (24 mg), whereas 64.9% of supplement users had iron intake above the upper level (UL) (45 mg). In the babies of mothers in the third tertile of iron intake (>17.04 mg), biparietal diameter, abdominal circumference, and femur length were lower by 0.41 cm (P =0.019), 0.41 cm (P = 0.027), and 0.07 cm (P = 0.051), respectively, than the babies of mothers in the second tertile of iron intake (11.49 ~ 17.04 mg). CONCLUSION: These results suggest that excessive maternal iron intake at mid-pregnancy is associated with reduced fetal growth. Iron supplementation for pregnant women should be individualized according to their iron status. Appropriate diet education is needed for pregnant women so that they can consume adequate amounts of iron from food and supplements.

Relationship between maternal sodium intake and blood lead concentration during pregnancy.

Pb is released from bone stores during pregnancy, which constitutes a period of increased bone resorption. A high Na intake has been found to be negatively associated with Ca and adversely associated with bone metabolism. It is possible that a high Na intake during pregnancy increases the blood Pb concentration; however, no previous study has reported on the relationship between Na intake and blood Pb concentration. We thus have investigated this relationship between Na intake and blood Pb concentrations, and examined whether this relationship differs with Ca intake in pregnant Korean women. Blood Pb concentrations were analysed in 1090 pregnant women at mid-pregnancy. Dietary intakes during mid-pregnancy were estimated by a 24 h recall method covering the use of dietary supplements. Blood Pb concentrations in whole-blood samples were analysed using graphite furnace atomic absorption spectrophotometry. Multiple regression analysis performed after adjustment for covariates revealed that maternal Na intake was positively associated with blood Pb concentration during pregnancy, but only when Ca intake was below the estimated average requirement for pregnant Korean women (P= 0·001). The findings of the present study suggest that blood Pb concentration during pregnancy could be minimised by dietary recommendations that include decreased Na and increased Ca intakes.

Birth weight of Korean infants is affected by the interaction of maternal iron intake and GSTM1 polymorphism.

Excessive iron consumption during pregnancy can lead to increased oxidative stress in the maternal body, which may result in adverse pregnancy outcomes. Glutathione S-transferases (GSTs) originate from a superfamily of detoxifying enzymes that play a role in reducing xenobiotic compounds and oxidative stress. The aim of this study was to determine the relationship among GST gene expression, maternal iron intake during pregnancy, and neonatal birth weight. The study participants were 1087 Korean gravidas and their newborns recruited for the Mothers and Children's Environmental Health study between 2006 and 2010. A 24-h dietary recall interview was conducted to estimate iron intake; additional intake through nutritional supplements was thoroughly investigated. Deletion polymorphisms of GSTM1 and GSTT1 were genotyped using PCR. Dietary iron consumption during pregnancy was positively associated with birth weight in pregnant women who were GSTM1-present after adjustment for the following covariates: maternal age, prepregnancy BMI, mother's education level, log-transformed urinary cotinine level, infant gender, gestational age at term, log-transformed energy intake, parity, and the use of folic acid supplements (P < 0.05). There were interactions between the GSTM1 genotype and iron intakes from animal foods (P < 0.05), diet (P < 0.05), and diet with supplements (P < 0.05). No relationship was found between maternal iron intake and birth weight for the GSTT1 polymorphism. This study demonstrates that increased iron consumption during pregnancy may improve infant birth weight for mothers who are GSTM1-present, but it might not be beneficial for mothers with the GSTM1-null genotype.

[Psychological health in residents participating in clean-up works of Hebei Spirit oil spill].

OBJECTIVES: Our objective was to examine and evaluate the psychological health of the residents of Taean during the cleanup of the Hebei Spirit (HS) oil spill and to review some factors associated with the results. METHODS: A community survey of 71 men and women was conducted 8 weeks after the HS oil spill. Questionnaires used were the PWI (Psychological Well-being Index) scale for psychosocial distress, the CES-D (Center for Epidemiologic Studies-Depression) scale for depressive symptoms, and a questionnaire created to assess suicidal impulses. RESULTS: The overall prevalence of high-risk psychosocial distress among the study group was 64.2%. The percentages of respondents with scores on the CES-D Scale above 16 and above 21 were 77.6% and 62.7%, respectively. The percentage of respondents categorized as having suicidal impulses was 18.3%. When compared with unexposed groups in the general population taken from various sources, the residents of Taean were 6.5 times as likely to have high stress and 9.4-9.7 times as likely to be depressed. No significant difference in the rate of suicidal impulse was found between the residents of Taean and the general population. Factors associated with high stress, depression, and suicidal impulses were age, a change in income, educational level, number of days working on the cleanup, and positive responses to questions about "affected daily activity" and "hospital visit due to work on cleanup." CONCLUSIONS: The results suggest that the HS oil spill had a significant impact on the psychological health of residents of Taean, but the comparability of the unexposed groups is a limitation of the study.

[The effects of wearing protective devices among residents and volunteers participating in the cleanup of the Hebei Spirit oil spill].

OBJECTIVES: To assess the protective effects of wearing protective devices among the residents and volunteers who participated in the cleanup of the Hebei Spirit oil spill. METHODS: A total of 288 residents and 724 volunteers were surveyed about symptoms, whether they were wearing protective devices and potential confounding variables. The questionnaires were administered from the second to the sixth week following the accident. Spot urine samples were collected and analyzed for metabolites of 4 volatile organic compounds (VOCs), 2 polycyclic aromatic hydrocarbons (PAHs), and 6 heavy metals. The association between the wearing of protective devices and various symptoms was assessed using a multiple logistic regression adjusted for confounding variables. A multiple generalized linear regression model adjusted for the covariates was used to test for a difference in least-square mean concentration of urinary biomarkers between residents who wore protective devices and those who did not. RESULTS: Thirty nine to 98% of the residents and 62-98% of volunteers wore protective devices. Levels of fatigue and fever were higher among residents not wearing masks than among those who did wear masks (odds ratio 4.5; 95% confidence interval 1.23-19.86). Urinary mercury levels were found to be significantly higher among residents not wearing work clothes or boots (p<0.05). CONCLUSIONS: Because the survey was not performed during the initial high-exposure period, no significant difference was found in metabolite levels between people who wore protective devices and those who did not, except for mercury, whose biological half-life is more than 6 weeks.

[BTEX exposure and its health effects in pregnant women following the Hebei Spirit oil spill].

OBJECTIVES: We evaluated the health effects of exposure to BTEX (Benzene, Toluene, Ethylbenzene, m,p-Xylene, o-Xylene) in the Taean area after the Hebei Spirit oil spill. METHODS: We used a questionnaire survey to look for health effects among 80 pregnant women 2 to 3 months following the Hebei Spirit oil spill. Their BTEX exposures were estimated using the CALPUFF method. We then used a multiple logistic regression analysis to evaluate the effects of BTEX exposure on the women's health effets. RESULTS: Pregnant women who lived near the accident site reported more symptoms of eye irritation and headache than those who lived farther from the site. There was a trend of decreasing symptoms with an increase in distance from the spill site. Pregnant women exposed to higher ambient cumulative levels of Xylene were significantly more likely to report symptoms of the skin (OR 8.01 95% CI=1.74-36.76) in the first day after the accident and significantly more likely to report abdominal pain (OR 3.86 95% CI=1.02-14.59 for Ethylbenzene, OR 6.70 95% CI=1.82-24.62 for Xylene) during the 1st through 4th days following the accident. CONCLUSIONS: This study suggests that exposure to BTEX from an oil spill is correlated with an increased risk of health effects among pregnant women. This implies the need to take proper measures, including the development of a national policy for environmental health emergencies and a plan for studying the short- and long-term chronic health effects associated with such spills.

Design issues in cross-sectional biomarkers studies: urinary biomarkers of PAH exposure and oxidative stress.

Cross-sectional biomarker studies can provide a snapshot of the frequency and characteristics of exposure/disease in a population at a particular point in time and, as a result, valuable insights for delineating the multi-step association between exposure and disease occurrence. Three major issues should be considered when designing biomarker studies: selection of appropriate biomarkers, the assay (laboratory validity), and the population validity of the selected biomarkers. Factors related to biomarker selection include biological relevance, specificity, sensitivity, biological half-life, stability, and so on. The assay attributes include limit of detection, reproducibility/reliability, inter-laboratory variation, specificity, time, and cost. Factors related to the population validity include the frequency or prevalence of markers, greater inter-individual variation than intra-individual variation, intra-class correlation coefficients (ICC), association with potential confounders, invasiveness of specimen collection, and subject selection. Three studies are selected to demonstrate different features of cross-sectional biomarker studies: (1) characterizing the determinants of the biomarkers (study I: urinary PAH metabolites and environmental particulate exposure), (2) relationship of multiple biomarkers of exposure and effect (study II: relationship between urinary PAH metabolites and oxidative stress), and (3) evaluating gene-environmental interaction (study III: effect of genetic polymorphisms of GSTM1 on the association of green tea consumption and urinary 1-OHPG levels in shipbuilding workers).