Mothers And Children's Environmental Health Research Articles

Infantile allergic diseases: a cohort study prenatal fish intake and mercury exposure context

BackgroundAllergic diseases (ADs) have been increasingly reported in infants and children over the last decade. Diet, especially the inclusion of fish intake, may help to lower the risk of ADs. However, fish also, can bioaccumulate environmental contaminants such as mercury. Hence, our study aims to determine what effects the type and frequency of fish intake have on ADs in six-month-old infants, independently and jointly with mercury exposure.MethodsThis study is part of the prospective birth cohort: Mothers and Children’s Environmental Health (MOCEH) study in South Korea. Data was collected on prenatal fish intake, prenatal mercury concentration and ADs for infants aged six months for 590 eligible mother-infant pairs. Logistic regression analysis was conducted to evaluate the risk of prenatal fish intake and mercury concentration on ADs in infants. Finally, interaction between fish intake and mercury concentration affecting ADs in infants was evaluated. Hazard ratios of prenatal fish intake on ADs in 6 month old infants were calculated by prenatal mercury exposure.ResultsLogistic regression analysis showed that white fish (OR: 0.53; 95% CI 0.30–0.94; P < 0.05) intake frequency, once a week significantly decreased the risk of ADs in infants. Stratification analysis showed that consuming white fish once a week significantly reduced the hazard of ADs (HR: 0.44; 95% CI 0.21–0.92; P < 0.05) in infants in the high-mercury (≥ 50th percentile) exposure group.ConclusionThe result indicates that prenatal white fish intake at least once a week reduces the risk of ADs in infants, especially in the group with high prenatal mercury exposure.

Association of postnatal exposure to mixture of bisphenol A, Di-n-butyl phthalate and Di-(2-ethylhexyl) phthalate with Children's IQ at 5 Years of age: Mothers and Children's environmental health (MOCEH) study

Early childhood is important for neurodevelopment, and exposure to endocrine disruptors such as bisphenol A (BPA) and phthalates in this period may cause neurodevelopmental disorders and delays. The present study examined the association between exposure to mixtures of BPA and three metabolites of phthalates in early childhood and IQ at 5 years of age. The Mother and Children's Environmental Health (MOCEH) study is a prospective birth cohort study conducted in Korea with 1751 pregnant women enrolled from 2006 to 2010. After excluding those without relevant data, 47 children were included in the final analysis. We measured children's urinary concentrations of metabolites of endocrine-disrupting chemicals (Bisphenol A, mono-(2-ethyl-5-oxohexyl) phthalate, mono-(2-ethyl-5-hydroxyhexyl) phthalate and mono-(2-ethyl-5-butyl) phthalate) at ages of 24 and 36 months. We evaluated the children's IQ with the Korean Wechsler Intelligence Test at the age of 5 years. After adjusting for potential confounders, a multiple linear regression was conducted to examine the associations between individual endocrine-disrupting chemicals and the IQ of the children. Weighted Quantile Sum (WQS) regression and quantile-based g-computation were used to assess the association between IQ at age 5 and exposure to mixtures of BPA and phthalates. In the single-chemical analyses, mono-(2-ethyl-5-butyl) phthalate exposure at 36 months was adversely associated with children's IQ (β = −4.93, 95% confidence interval (CI): -9.22, −0.64). In the WQS regression and quantile-based g-computation analyses, exposure to the mixture of BPA and phthalates was associated with lower IQ [β = −9.13 (P-value = 0.05) and β = −9.18 (P-value = 0.05), respectively]. The largest contributor to the overall association was exposure to mono-(2-ethyl-5-butyl) phthalate at 36 months. In the present study, postnatal exposure to mixtures of BPA and three metabolites of phthalates was associated with decreased IQ of children at age 5.

Association of maternal dietary patterns during pregnancy with small-for-gestational-age infants: Korean Mothers and Children’s Environmental Health (MOCEH) study

Nutrients that support the desired growth and development of the fetus (i.e., micronutrients like folate, iron, and zinc) have been associated with birth outcomes, such as gestational age at delivery and birth weight. We characterized the maternal dietary patterns that explain the maximum variation in folate, iron, and zinc intakes in pregnant Korean women using reduced-rank regression (RRR) and investigated the association of these patterns with small-for-gestational-age (SGA) risk. A total of 1158 pregnant Korean women at 12-28 weeks of gestation and their newborns were recruited for the Mothers and Children's Environmental Health (MOCEH) study between 2006 and 2010. A semiquantitative FFQ was collected from the women, and RRR was used to derive their dietary patterns. Log-transformed maternal intakes of folate, iron, and zinc were selected as the intermediate response variables to extract dietary patterns. Infant birth outcome measurements were obtained from hospital records. Associations were assessed by logistic regression with adjustment for confounding factors. Three dietary patterns were identified. Pattern 1, characterized by high intakes of grains, green/yellow and light-colored vegetables, kimchi, legumes, fruits, meat, eggs, fish, seaweeds, tofu/soymilk, yogurt, and nuts, was associated with a lower risk of SGA in the highest quartile than in the lowest quartile (OR: 0.36; 95% CI: 0.14, 0.94). Especially, maternal dietary pattern 1 was negatively related to high-sensitivity C-reactive protein in the blood and malondialdehyde concentrations in the urine. No association was observed between other dietary patterns and SGA. Among pregnant Korean women, adherence to a dietary pattern characterized by high intakes of grains, green/yellow and light-colored vegetables, kimchi, legumes, fruits, meat, eggs, fish, seaweeds, tofu/soymilk, yogurt, and nuts is associated with a lower risk of delivering SGA infants.

Prenatal Exposure to Heavy Metals Affects Gestational Age by Altering DNA Methylation Patterns.

Environmental exposure is known to have toxic effects. Maternal environmental exposure not only affects mothers but also their fetuses in utero, which may interrupt their early development. Preterm birth, one of the outcomes of prenatal exposure, is a significant factor in lifelong health risks. To understand the effects of prenatal exposome on preterm birth, we studied the association between maternal and prenatal heavy metal exposure and gestational age, using resources from the MOthers’ and Children’s Environmental Health (MOCEH) study in South Korea. Additionally, a methylation assay was performed to analyze epigenetic mediation using genomic DNA derived from the cord blood of 384 participants in the MOCEH study. The results suggest that maternal cadmium exposure is associated with a decrease in gestational age through an alteration in DNA methylation at a specific CpG site, cg21010642. The CpG site was annotated to a gene involved in early embryonic development. Therefore, irregular methylation patterns at this site may contribute to premature birth by mediating irregular biological mechanisms.

Mediation effect of air pollution and temperature on the association between greenness and infant’s neurodevelopment: to identify critical windows

BACKGROUND AND AIM: Green spaces can have a beneficial effect on health, but little is known about how they affect the neurodevelopment of infants. We investigated to identify mediation effect of TRAPs and temperature mixtures between greenness and infant’s neurodevelopment during windows of susceptibility. METHODS: 418 mother-infant pairs from the mothers and children environmental health (MOCEH) study were analyzed. Daily TRAPs concentrations including PM10 and NO2 were estimated by land-use regression and daily temperature levels obtained from the Korea Meteorological Administration were averaged over each period from pregnancy to 24 months of age. Infant’s neurodevelopment was evaluated based on mental development index (MDI) and physical development index (PDI) at 6 months, 12 months, and 24 months of age assessed by the Korean Bayley Scale of Infant Development II. Bayesian kernel machine regression was used to estimate the mixture index of TRAPs and temperature on infant’s MDI and PDI. Then, causal mediation approach was used to estimate the mediation effect of the mixture index on the association between greenness and infant’s MDI and PDI after adjusting for potential confounders. RESULTS:The total effect of greenness during the entire pregnancy and 6 months from birth on MDI at 6-month-old infants was 1.25 [95% confidence interval: 0.39, 2.39] and 1.09 (0.12, 2.09), respectively. And the indirect effect of the mixture index of TRAPs and temperature during the entire pregnancy and 6 months from birth was each 0.59 (0.19, 1.00) and 0.53(0.04, 1.09). Further, the total effect and the indirect effect of greenness during the entire pregnancy on PDI at 6-month-old infants was 1.45 (0.40, 2.72) and 0.47 (0.12, 0.99). No significant association was observed in other periods. CONCLUSIONS:Our finding suggested that the residential green space has a beneficial effect on infant’s neurodevelopment by reducing overall effect of TRAPs and temperature during pregnancy and early childhood. KEYWORDS: Neurodevelopmental outcomes, Green space, Multi-pollutant, Causal inference

Joint association of prenatal bisphenol-A and phthalates exposure with risk of atopic dermatitis in 6-month-old infants

BackgroundPrenatal exposure to bisphenol A (BPA) and phthalates could trigger immune response. Few studies have investigated the association between prenatal BPA and phthalate exposure and atopic dermatitis (AD) in infants. ObjectiveWe aimed to clarify the joint association of prenatal exposure to BPA and phthalate metabolites with AD incidence in 6-month-old infants. MethodsWe included 413 mother-child pairs from the Mothers and Children's Environmental Health (MOCEH) in a prospective birth cohort study. Maternal urinary BPA, mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP), and mono-n-butyl phthalate (MnBP) concentrations were measured during early and late pregnancy. We applied the Bayesian kernel machine regression (BKMR) with probit regression to estimate the association of BPA and phthalate metabolites with AD incidence after adjusting for potential confounders. Individual association was estimated by differences in predicted probabilities comparing each individual chemical concentration at 75th versus 25th percentiles, while other chemicals were set at their median. Overall joint effect was estimated by differences in predicted probabilities comparing all chemical concentrations at 75th versus 25th percentiles. ResultsIndividual effect of MEHHP in late pregnancy was strongly associated with incident AD [Difference: 0.244 (95% credible interval: −0.066, 0.554)] in the model including both early and late exposures. Furthermore, we confirmed overall joint association of urinary BPA and phthalate metabolites during pregnancy with a higher risk of AD [0.347 (0.168, 0.526) for late pregnancy exposure, and 0.307 (0.094, 0.521) for both early and late pregnancy]. Additionally, the joint association was more prominent among girls than that in boys. ConclusionsThe joint association of prenatal exposure to BPA and phthalates could be associated with the incident AD in 6-month-old infants. Further studies are needed to confirm the synergistic effect of BPA and phthalate exposures on AD in children.

Prenatal heavy metal exposures and atopic dermatitis with gender difference in 6-month-old infants using multipollutant analysis

Background: Prenatal exposure to heavy metals during critical developmental phases has been implicated in allergic phenotypes. However, few studies have been conducted on the gender-specific association of prenatal heavy metal exposure with atopic dermatitis (AD) in infants. Objective: To examine the gender-specific association of prenatal exposure to multiple heavy metals with AD incidence in 6-month-old infants using data from the Mothers and Children's Environmental Health (MOCEH). Methods: We evaluated 738 mother–child pairs from the MOCEH study, an ongoing prospective birth cohort. The concentrations of three heavy metals (lead, mercury and cadmium) in maternal blood samples were measured during early and late pregnancy. Each quartile of heavy metal concentration was used to consider the possible nonlinear association with AD. For assessing the multi-pollutant model, we constructed the multivariate regression model including all three heavy metals at both early and late pregnancy. Further, the group Lasso model was used to perform the variable selection with categorized exposures and assess the effect of multiple pollutants including their pairwise interactions. Results: A total of 200 incident cases of AD were diagnosed in 6-month-old infants. In the multivariate regression model of the boy group, adjusted odds ratios comparing the second, third and fourth quartile of lead exposure in boys with the first quartile were 1.83 (95% CI: 1.00, 3.38), 1.04 (0.91, 3.32) and 2.40 (1.18, 4.90), respectively. However, the only second quartile of lead exposure compared to first quartile was significantly associated with AD in girls. In addition, the results of the group Lasso model were similar with the results of multivariate regression model. Conclusion: The results suggest that lead exposure in late pregnancy increases risk of AD in 6-month-old boys although the strength of association is weak. Further studies are needed to confirm the susceptibility window and gender differences in lead-induced AD.

Association between prenatal polycyclic aromatic hydrocarbons and infantile allergic diseases modified by maternal glutathione S-transferase polymorphisms: results from the MOCEH birth cohort.

BackgroundPrenatal exposure to polycyclic aromatic hydrocarbons (PAH) has been linked to allergic disease onset. Variations in the glutathione S-transferase (GST) gene family can impact the progression of allergic diseases. We sought to examine the association between prenatal PAH exposure and infantile allergic diseases in 6-month-old infants, and how maternal glutathione S-transferase M1 (GSTM1) or T1 (GSTT1) polymorphism affects the association between prenatal PAH exposure and allergic diseases in the Mothers and Children's Environmental Health (MOCEH) study.MethodsThe study sample comprised 349 infants and their mothers from the MOCEH study, for whom 1-hydroxypyrene (1-OHP) and 2-naphthol were measured in both the early period of pregnancy and late period of pregnancy. An infant was deemed to be affected by an allergic disease if diagnosed with or if developed at least one of the allergic diseases. A logistic regression analysis was performed to study the association between urinary 1-OHP and 2-naphthol levels during pregnancy and allergic diseases in 6-month-old infants. Furthermore, analyses stratified by maternal GSTM1 or GSTT1 present/null polymorphisms were performed.ResultsThe risk of allergic diseases in 6-month-old infants was significantly increased in accordance with an increase in urinary 1-OHP during the early period of pregnancy (odds ratio [OR]: 1.84; 95% confidence interval [CI]: 1.05, 3.23; by one log-transformed unit of 1-OHP μg/g creatinine). The increased risk of infantile allergic diseases associated with urinary 1-OHP during the early period of pregnancy was limited to the maternal GSTT1 null type (OR: 2.69; 95% CI: 1.17, 6.21, by one log-transformed unit of 1-OHP μg/g creatinine); however, the Relative Excess Risk due to Interaction was not statistically significant.ConclusionsThe present study found that infantile allergic diseases could be affected by intrauterine PAH exposure, particularly in the early prenatal period and the risk was limited to the maternal GSTT1 null type.

Prenatal exposure to particulate matter and ADHD in children: a prospective cohort study

Background/Aim Environmental factors may play a role in the development of attention-deficit/hyperactivity disorder (ADHD) and some studies have shown that ambient air pollution is associated with the ADHD. This study was designed to investigate the impact of prenatal particulate matter (PM10) exposure on ADHD among children over 60 months of age in Korea by using MOCEH birth cohort study’s data.Methods This study is a part of the Mothers and Children's Environmental Health (MOCEH) study, a Korean multi-center prospective birth cohort study initiated in 2006. After the delivery, children were followed up at 60, 72, 84 and 96 months of age. The average exposure level of particulate matter (PM10) were estimated using the inverse distance weighting (IDW) method from the prenatal period. ADHD behaviour were assessed using the K-ARS, K-CBCL/1.5-5 and 6-18 at each follow-up period. Generalized Linear Models (GLM) were used to explore the association between PM10 and ADHD.Results The mean PM10 concentrations during total pregnancy was 54.1μg/m3 with a range from 24.2 to 85.7μg/m3. In the GLM model, exposure to PM10 at first trimester and during pregnancy showed significant positive association with 72 months K-ARS score (β=0.06, 95% CI: 0.01,0.11 for first trimester, β=0.10, 95% CI: 0.01,0.19 for total pregnancy exposure). Furthermore, exposure to PM10 at first trimester and during total pregnancy showed significant association with 60, 72, and 84 months K-CBCL score, especially with total problems, attention problems and aggressive behaviour (β=0.26, 95% CI: 0.07,0.44 between first trimester and total problem score at 60 months, β=0.10, 95% CI: 0.05,0.15 between first trimester and attention problems at 72 months).Conclusions In conclusions, our results have demonstrated that the prenatal PM10 concentration was significantly associated with ADHD behaviour in Korean children. Further studies regarding other air pollutants’ effects to the neurodevelopment in children are recommended.

Multi-pollutant effects of prenatal heavy metal exposure on atopic dermatitis in 6-month-old infants

Background: Prenatal exposures to endocrine-disrupting chemicals during critical developmental phases have been implicated in the development of the immune system and allergic phenotypes. However, there are few studies associating prenatal heavy metal exposure with atopic dermatitis (AD) in infants according to their sex. Objective: We aimed to examine prenatal exposure to multiple heavy metals with sex-specific AD incidence in 6-month-old infants using data from the Mothers and Children’s Environmental Health (MOCEH), a prospective birth cohort study. Methods: We evaluated 738 mother-child pairs from the MOCEH study. Concentrations of three heavy metals (mercury, lead, and cadmium) in maternal blood samples were measured at early and late pregnancy. Each quantile of heavy metal concentration was used for capturing nonlinear association with AD. To account for selection bias caused by loss to follow-up, we generated an inverse probability of censoring weight (IPCW). Furthermore, the group Lasso model with IPCW was used to perform variable selection with categorized exposures and assess the effect of multiple pollutants with selected exposures, and its optimal lambda was estimated by 5-fold cross-validation. 95% confidence intervals (CIs) were estimated by bootstrap method. Exposures in early and late pregnancy were simultaneously included in the model to identify the susceptible window. Results: A total of 200 incident cases of AD were diagnosed in 6-month-old infants. In late pregnancy model of the boy group, lead and mercury exposures were selected, and adjusted odds ratios (ORs) comparing the second, third and fourth quartiles of lead exposure with the first quartile group were 1.155 (95% CI: 0.965, 5.619), 1.097 (0.924, 5.715), and 1.191 (1.138, 8.390), respectively. However, no significant associations were observed in the girl group. Conclusion: Our findings suggest that lead exposure in late pregnancy may be independently associated with a higher risk of AD in 6-month-old boys.

Prenatal exposure to mixtures of heavy metals and neurodevelopment in infants at 6 months

BackgroundExposure to mixture of neurotoxic metals such as lead, mercury and cadmium occurs at a specific point of time. When exposed to metal mixtures, one metal may act as an agonist or antagonist to another metal. Thus, it is important to study the effects of exposure to a combination of metals on children's development using advance statistical methods. ObjectivesIn this study, we explored the effects of prenatal metal exposure including lead, mercury and cadmium in early pregnancy (12–20 weeks), late pregnancy (>28 weeks), and at birth on neurodevelopment of infants at 6 months of age. MethodsWe included 523 eligible mother-child pairs from the mothers and children environmental health (MOCEH) study, a prospective birth cohort study in Korea. We used linear regression, Bayesian kernel machine regression (BKMR) and generalized additive models (GAM), to evaluate the effects of exposure to metal mixtures on neurodevelopment of infants aged 6 months. The Korean version of Bayley scale of infant and toddler development-II was used to measure the child's neurodevelopment. ResultsLinear regression models showed a significant negative effect of lead exposure during late pregnancy on the mental development index (MDI) [β = -2.51 (−4.92, −0.10)] scores of infants aged 6 months following co-exposure to mercury. Further, linear regression analysis showed a significant interaction between late pregnancy lead and mercury concentrations. BKMR analysis showed similar results as those obtained in linear regression models. These results were also replicated in the GAM. Stratification analysis showed that greater than 50 percentile concentration of mercury in late pregnancy potentiated the adverse effects of lead in late pregnancy on MDI [β = −4.33 (−7.66, −1.00)] and psychomotor development index (PDI) [β = −5.30 (−9.13, −1.46)] at 6 months of age. Prenatal cadmium exposure did not show a significant association with MDI and PDI at 6 months in the linear regression or BKMR analysis. ConclusionBased on all the statistical methods used, we demonstrated the effect of combined exposure to metals on the neurodevelopment of infants aged 6 months, with significant interaction between lead and mercury.

Combined effects of multiple prenatal exposure to pollutants on birth weight: The Mothers and Children's Environmental Health (MOCEH) study

BackgroundIncreasing evidence shows that prenatal environmental exposures is a risk factor for restricted intrauterine growth. However, only a few studies have examined the effects of multiple environmental exposures on fetal growth. ObjectiveTo investigate the effects of prenatal exposure on multiple environmental pollutants (heavy metals, bisphenol, phthalates, and air pollutants) on birth weight. MethodsThe Mothers and Children's Environmental Health study is a prospective birth cohort comprising a total of 719 mother-child pairs, including 466 pairs undergoing early pregnancy exposure and 542 pairs of late pregnancy exposure. The concentrations of three heavy metals (mercury, lead, and cadmium) in the maternal blood samples were measured. The concentrations of three phthalate metabolites [mono(2-ethyl-5-hydroxyhexyl) phthalate, mono(2-ethyl-5-oxohexyl) phthalate, and mono-n-butyl phthalate] and bisphenol A in maternal urine samples were measured. Daily exposure to ambient particulate matter (PM10) and nitrogen dioxide (NO2) exposure was estimated based on residence and averaged by gestational age. To assess the combined effect of multiple pollutants, principal components analysis (PCA) and supervised principal components analysis (SCPA) were conducted. ResultsBased on PCA, the components representing PM10 and NO2 exposure during early pregnancy were significantly associated with birth weight of −32.68 g (95% CI: -64.45 g to −0.91 g) per unit increase of the corresponding component. In SCPA model, the components representing NO2 exposure during early pregnancy and the combined exposure to mercury and lead during late pregnancy were negatively associated with birth weight of −46.63 g (95% CI: -90.65 g to −2.62 g) and −55.32 g (95% CI: -99.01 g to −11.64 g), respectively, per unit increase of the corresponding component. ConclusionBased on our multi-pollutant model, PM10 and NO2 exposure in early pregnancy and the combined effect of Pb and Hg in late pregnancy were associated with reduced birth weight. Our results suggest that exposure to various pollutants during pregnancy has a significant cumulative effect on birth weight, even if each pollutant is at a level below the concentration required for direct effect.

Genomic Susceptibility Analysis for Atopy Disease Using Cord Blood DNA in a Small Cohort

Atopic disease is caused by a complex combination of environmental factors and genetic factors, and studies on influence of exposure to various environmental factors on atopic diseases are continuously reported. However, the exact cause of atopic dermatitis is not yet known. Our study was conducted to analyse the association of SNPs with the development of atopic disease in a small cohort. Samples were collected from the Mothers’ and Children’s Environmental Health (MOCEH) study and 192 cord blood DNA samples were used to identify incidence of atopy due to influence of exposure to environmental factors. Genetic elements were analysed using a precision medicine research (PMR) array designed with various SNPs for personalized medicine. Case-control analysis of atopy disease revealed 253 significant variants (p<0.0001) and SNPs on five genes (CARD11, ZNF365, KIF3A, DMRTA1, and SFMBT1) were variants identified in previous atopic studies. These results are important to confirm the genetic mutation that may lead to the onset of foetal atopy due to maternal exposure to harmful environmental factors. Our results also suggest that a small-scale genome-wide association analysis is beneficial to confirm specific variants as direct factors in the development of atopy.

Postnatal Exposure of PM10 and Autistic Behaviours among Children: The Mothers and Children's Environmental Health (MOCEH) Study

Background/AimEnvironmental factors may play a role in the development of neurodevelopment and some studies have shown that ambient air pollution is associated with the autistic behaviours. The study was designed to investigate the impact of outdoor air pollution on autistic behaviours among children at 4, 5 years of age in Korea by using MOCEH cohort study's data.MethodsThis study is a part of the Mothers and Children's Environmental Health (MOCEH) study, a Korean multi-center prospective birth cohort study initiated in 2006. After delivery, children were followed up at 48 and 60 months of age. Average exposure level of particulate matter (PM10) were estimated using the inverse distance weighting (IDW) method from prenatal period to postnatal period. A total of 322 mother-child pairs were included. Autistic behaviours were assessed using the Social Responsiveness Scale (SRS) at 4, 5 years of age. We also examined the result stratified by sex of the children.ResultsThe average levels of PM10 during pregnancy and 3 years of age were 54.07&amp;#956;g/m3 and 50.08&amp;#956;g/m3 each. In a multiple linear regression model, although we couldn&amp;#8217;t find significant positive relationship between exposure of PM10 in children, we found that PM10 at 3 years of age was associated with increased scores of SRS T-scores at 5 years of age in boys. (&amp;#946;&amp;#61;0.36, 95% confidence interval [CI]: 0.05,0.66) However, there was no significant positive association in girls.ConclusionsIn conclusions, postnatal exposure of PM10 is associated with the autistic behaviours, in boys at 4, 5 years of age. Further study on the other air pollutants effects to autistic behaviours in children is recommended.

Postnatal Exposure to Secondhand Smoke Measured with Urinary Cotinine and Neurodevelopment at 36 Months after Considering Outdoor Fine Particle (PM2.5)

Background/ObjectiveNeurodevelopment of infants have been associated with exposure to secondhand smoke (SHS) and air pollution (AP), respectively. There has been very few previous studies of combined effect of AP and SHS on early neurodevelopment. We aim to investigate the combined effect of postnatal AP and SHS exposure on neurodevelopment of infants at 36 months of age.MethodsThis study is a part of the Mothers and Children Environmental Health (MOCEH) study, a Korean multi-center prospective birth cohort study initiated in 2006. We measured infants&amp;#8217; urinary cotinine at 24 months and 36 months of age to represent postnatal SHS exposure. PM2.5 (particulate matter&amp;lt;2.5 in diameter) level from conception was modelled using the Community Multiscale Air Quality Modeling. The exposure estimations of PM2.5 of each subject were assigned in district level. Infant&amp;#8217;s mental developmental index (MDI) and psychomotor developmental index (PDI) were measured using the Bayley Scales of Infant Development at 36 months of age. General linear model was used to assess the relationship between combined exposure of PM2.5 and SHS and neurodevelopment.ResultsMDI score of 36 months aged infants was marginally associated with log-transformed urinary cotinine level at 24 months [&amp;#946;&amp;#61; -1.94, 95%confidence interval (CI): -3.92, 0.04] after adjusting for log-transformed urinary cotinine level at 36 months and PM2.5 level after birth. The association was statistically significant when the effect of PM2.5 level at early pregnancy was considered, &amp;#946;&amp;#61; -2.02 (95%CI: -4.01, -0.03). The effect was pronounced in the metropolitan city, &amp;#946;&amp;#61; -7.92 (95%CI: -13.15, -2.70). No association was found in PDI score.ConclusionsThese findings suggest that infants&amp;#8217; postnatal exposure to SHS combined with exposure to PM2.5 may result in delayed neurodevelopment in early childhood. Therefore, we should take care of both indoor and outdoor air pollution with regards to the neurodevelopment of infants.

Combined Effect of Air Pollution and Secondhand Smoke on Neurodevelopment at 24 Months

Background/Aim: Neurodevelopment of infants have been associated with exposure to secondhand smoke (SHS) and air pollution (AP), respectively. There has been very few previous studies of combined effect of AP and SHS on early neurodevelopment. We aim to investigate the combined effect of AP and SHS prenatal exposure on neurodevelopment of infants at 24 months of age. Methods: We analyzed 721 mothers and their offspring from Korean multicenter birth cohort study: Mothers and Children Environmental Health (MOCEH). We measured maternal urinary cotinine to represent SHS exposure during pregnancy. Average exposure levels to PM10 (particulate matter&lt;10in diameter) and nitrogen dioxide during the entire pregnancy were estimated using the inverse distance weighting method. Infant’s mental developmental index (MDI) and psychomotor developmental index (PDI) were measured using the Bayley Scales of Infant Development at 24 months of age. General linear model was used to assess the relationship between combined exposure of AP and SHS and neurodevelopment. Results: MDI score of 24 months aged infants was associated with cotinine [β= -2.56, 95%confidence interval (CI): -4.58, -0.53] in mothers with early pregnancy urinary cotinine levels &gt;1.90 ng/ml. The MDI score of infant was more decreased in mothers exposed to both PM10 &gt;50 mg/m3 during pregnancy and high exposure of SHS [β= -2.85, 95%CI: -5.17, -0.54]. The negative association was reduced when children received breast milk up to 6 months [β= 0.06, 95%CI: -3.13, 3.24]. However, the combined effect was more pronounced in mothers with both GSTM1/GSTT1 null type on MDI [β= -8.17, 95%CI: -12.27, -4.06] and PDI [β= -3.65, 95% CI: -7.38, 0.08]. Conclusions: These findings suggest that maternal combined exposure to PM10 and SHS during pregnancy may result in delayed neurodevelopment in early childhood and propose its combined effects. The effect might be modified by genetic polymorphism and breastfeeding.

Associations between prenatal lead exposure and birth outcomes: Modification by sex and GSTM1/GSTT1 polymorphism

Maternal lead exposure is associated with poor birth outcomes. However, modifying effects of polymorphism in glutathione S-transferases (GST) gene and infant sex remain unexplored. Our aim was to evaluate whether associations between prenatal lead and birth outcomes differed by maternal GST genes and infant sex. Prospective data of 782 mother-child pairs from Mothers and Children's Environmental Health (MOCEH) study were used. The genotyping of GST-mu 1 (GSTM1) and theta-1 (GSTT1) polymorphisms was carried out using polymerase chain reaction. Multivariable linear regression was used to examine whether the association between blood lead (BPb) level and birth outcomes (birthweight, length, and head circumference) varied by maternal GST genes and sex. We did not find a statistically significant association between prenatal BPb levels and birth outcomes; in stratified analyses, the association between higher BPb level during early pregnancy and lower birthweight (β=−224 per square root increase in BPb; 95% confidence interval (CI): −426, −21; false discovery rate p=0.036) was significant in males of mothers with GSTM1 null. Results were similar for head circumference model (β=−0.78 per square root increase in BPb; 95% CI: −1.69, 0.14, p=0.095), but the level of significance was borderline. Head circumference model showed a significant three-way interaction among BPb during early pregnancy, GSTM1, and sex (p=0.046). For combined analysis with GSTM1 and GSTT1, GSTM1 null and GSTT1 present group showed a significant inverse association of BPb with birthweight and head circumference in males. Our findings of the most evident effects of BPb on the reduced birthweight and head circumference in male born to the mother with GSTM1 null may suggest a biological interaction among lead, GST genes and sex in detoxification process during fetal development.

Prenatal mercury exposure, fish intake and neurocognitive development during first three years of life: Prospective cohort mothers and Children's environmental health (MOCEH) study

ObjectivesIn this prospective cohort study, the effects of prenatal Hg exposure on neurocognitive development during the first 3years of life were investigated. MethodsThe maternal blood levels of Hg were assessed during pregnancy and in cord blood. Maternal fish intake was assessed by interviewing the weekly frequency of fish intake during pregnancy. Maternal n-3 and n-6 fatty acid intake was estimated based on 24h recall food intake interview. The mental (MDI) and psychomotor (PDI) development index scores were assessed using the Bayley Scales of Infant Development at 6, 12, 24, 36months of age. ResultsThe geometric mean of the maternal blood Hg concentration was 3.3μg/L (10th percentile=1.81; 90th=5.91) during the early pregnancy, 3.0μg/L (10th=1.68; 90th=5.57) during late pregnancy, and 5.1μg/L (10th=2.94; 90th=8.93) in cord blood. After adjusting for weekly frequency of fish intake, the blood Hg concentrations during early pregnancy showed association with the adjusted MDI (β=−0.408, p=0.048) and PDI scores (β=−0.550, p=0.031) at 6months. After further adjusting for n-3 and n-6 fatty acids estimated based on 24h recall of food intake, the blood Hg concentrations during early pregnancy showed association with the MDI (β=−0.489, p=0.026) and PDI (β=−0.664, p=0.015) at 6months. ConclusionThese results show that prenatal Hg exposure during early pregnancy adversely associated with early neurodevelopment during infancy, after adjusting for fish and n-3, n-6 fatty acid intake. Consuming fish high in fatty acids and low in Hg during early pregnancy may be important to neurocognitive development at early infancy.

Stability of cognitive development during the first five years of life in relation to heavy metal concentrations in umbilical cord blood: Mothers' and Children's Environmental Health (MOCEH) birth cohort study

The objective of this study was to investigate stability of cognitive development during the first five years of life in relation to heavy metal concentrations in umbilical cord blood in Korean children. This research is part of the Mothers' and Children's Environmental Health (MOCEH) study, a multi-center prospective birth cohort study of pregnant women in Korea who were recruited from 2006 to 2010. We analyzed the complete follow-up data of children who were 5years-old in 2016. We measured lead, mercury, and cadmium levels in the umbilical cord blood of 251 children, and analyzed them, for whom neurodevelopmental data were available. We determined stability of cognitive development scores using three methods. First, we used partial correlation analyses to examine the stability of cognitive development at each measurement time. Second, we used Cramer's V to investigate the magnitude and direction of changes in cognitive development scores at each follow-up period among three groups (high, medium, and low scores). The results showed that cognitive development scores measured at the closest times had the strongest correlations, and the stability of cognitive development scores increased with age, from 6 to 60months. Groups at the extreme ends of cognitive development (high or low scores) had more stable scores, and this tendency was also stronger in infants >24months-old. The stability of cognitive development was unrelated to the umbilical cord level of heavy metals, based on analysis with Fisher's transformation. In conclusion, the present study showed that the cognitive development scores in a cohort of infants (6 to 60months-old) were stable.

Path analysis of prenatal mercury levels and birth weights in Korean and Taiwanese birth cohorts

Prospective cohort studies of the effect of mercury (Hg) exposure on birth weight have shown conflicting results. We combined data from Taiwanese and Korean birth cohorts, and assessed the effects of Hg exposure on birth weight. The first cohort was drawn from the Mothers and Children's Environmental Health (MOCEH) study performed in Korea from 2006 to 2010. The second cohort was enrolled from 2004 to 2005 and included singleton term births from the Taiwan Birth Panel Study (TBPS). In total, 1147 pregnant women were included in this study. A pooled analysis was performed to obtain combined estimates of the association between prenatal total Hg exposure and birth weight. A significant negative association between maternal and cord blood Hg and birth weight in the high-Hg group (Hg level>25th percentile) was detected (maternal blood: β=−0.056; 95% CI, −0.100 to −0.013, cord blood: β=−0.075; 95% CI, −0.121 to −0.028). Hg level showed a negative coefficient in the path analysis, indicating an adverse effect on birth weight (total effects: β=−0.177, P=0.01 in MOCEH, β=−0.204, P=0.03 in TBPS), but fish consumption exhibited a strong positive coefficient. In addition, fish consumption exerted a significant indirect effect on birth weight through exposure to cord blood Hg. Exposure to hazardous contaminants and beneficial nutrients may be highly correlated in those who frequently consume fish. Moreover, Hg in cord blood may adversely affect birth weight.