Metabolomics analysis of maternal serum exposed to high air pollution during pregnancy and risk of autism spectrum disorder in offspring.

BACKGROUND: Previously, numerous epidemiologic studies reported an association between autism spectrum disorder (ASD) and exposure to air pollution during pregnancy. However, there have been no metabolomics studies investigating the impact of pregnancy pollution exposure to ASD risk in offspring. OBJECTIVES: To identify differences in maternal metabolism that may reflect a biological response to exposure to high air pollution in pregnancies of offspring who later did or did not develop ASD. METHODS: We obtained stored mid-pregnancy serum from 214 mothers who lived in California's Central Valley and experienced the highest levels of air pollution during early pregnancy. We estimated each woman's average traffic-related air pollution exposure (carbon monoxide, nitric oxides, and particulate matter <2.5 µm) during the first trimester using the California Line Source Dispersion Model, version 4 (CALINE4). By utilizing liquid chromatography-high resolution mass spectrometry, we identified the metabolic profiles of maternal serum for 116 mothers with offspring who later developed ASD and 98 control mothers. Partial least squares discriminant analysis (PLS-DA) was employed to select metabolic features associated with air pollution exposure or autism risk in offspring. We also conducted extensive pathway enrichment analysis to elucidate potential ASD-related changes in the metabolome of pregnant women. RESULTS: We extracted 4022 and 4945 metabolic features from maternal serum samples in hydrophilic interaction (HILIC) chromatography (positive ion mode) and C18 (negative ion mode) columns, respectively. After controlling for potential confounders, we identified 167 and 222 discriminative features (HILIC and C18, respectively). Pathway enrichment analysis to discriminate metabolic features associated with ASD risk indicated various metabolic pathway perturbations linked to the tricarboxylic acid (TCA) cycle and mitochondrial function, including carnitine shuttle, amino acid metabolism, bile acid metabolism, and vitamin A metabolism. CONCLUSION: Using high resolution metabolomics, we identified several metabolic pathways disturbed in mothers with ASD offspring among women experiencing high exposure to traffic-related air pollution during pregnancy that were associated with mitochondrial dysfunction. These findings provide us with a better understanding of metabolic disturbances involved in the development of ASD under adverse environmental conditions.

Association between sensitization and allergic diseases in 7-years-old Korean children.

BACKGROUND: Sensitization is associated with the exacerbation, severity, and prognosis of allergic diseases in children. OBJECTIVE: We characterized the association between sensitization patterns and allergic diseases. METHODS: A cohort of 548 children was enrolled from Panel Study of Korean Children (PSKC) study. Skin prick tests (SPTs) for 18 common allergens, blood tests, and methacholine bronchial challenge tests were performed at age 7. The Korean version of International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was used. RESULTS: The sensitization rate on SPTs was 46.4%. Sensitization to indoor allergens showed an association with symptoms of asthma (adjusted odds ratio [aOR], 2.39; 95% confidence intervals [95% CIs], 1.10-5.23), allergic rhinitis (AR, aOR 2.08, 95% CIs 1.42-3.06), and atopic dermatitis (AD, aOR 2.36, 95% CIs 1.24-4.50) in the preceding 12 months. In contrast, sensitization to outdoor allergens was associated with AR diagnosis only (aOR 2.40, 95% CIs 1.30-4.41). The number of sensitized allergens was associated with a lifetime diagnosis and symptoms in the preceding 12 months of AR and asthma, but not with AD or BHR. A higher degree of sensitization to indoor allergens was associated with symptoms in the preceding 12 months of asthma, AR, AD, and that for outdoor allergens was associated with symptoms in the prior 12 months of asthma and AR. CONCLUSIONS: The sensitization patterns including allergen type, number, and degree of sensitization are helpful for interpreting the association between sensitization and allergic diseases and identifying the pathophysiologies and diverse phenotypes of allergic diseases.

Vegetable dietary pattern may protect mild and persistent allergic rhinitis phenotype depending on genetic risk in school children.

BACKGROUND: The effect of diet on allergic rhinitis (AR), its severity in children, and whether it modifies AR depending on genetic susceptibility are unknown. We investigated the association between dietary patterns and AR in school children and the influence of diet on AR according to a genetic risk score (GRS). METHODS: Totally, 435 7-year-old school children were recruited from the Panel Study on Korean Children. We used dietary patterns (vegetable, sugar, and meat) and dietary inflammatory index (DII) as dietary parameters. AR and its severity were defined by questionnaires about treatment in the previous 12 months and the Allergic Rhinitis and its Impact on Asthma (ARIA) guideline, respectively. A GRS was calculated using 6 single nucleotide polymorphisms for allergic diseases. RESULTS: A vegetable diet containing a lot of anti-inflammatory nutrients and higher vitamin D level in blood were negatively correlated, while DII was positively correlated with triglyceride level and triglyceride/HDL cholesterol. Vegetable diet (aOR, 95% CI = 0.73, 0.58-0.94) and DII (1.13, 1.01-1.28) were associated with AR risk. In particular, a high-vegetable diet resulted in a lower risk of mild and persistent AR (aOR, 95% CI = 0.24, 0.10-0.56) while a high DII represented a higher risk (2.33, 1.06-5.10). The protective effect of vegetable diet on AR appeared only among children with a lower GRS (adjusted P = .018). CONCLUSIONS: A vegetable dietary pattern characterized by high intake of anti-inflammatory nutrients and higher vitamin D level in blood might be associated with a lower risk of mild and persistent AR. This beneficial effect is modified by a genetic factor.

High Maternal Blood Mercury Level Is Associated with Low Verbal IQ in Children.

The objective of the present study was to investigate the relationship of IQ in children with maternal blood mercury concentration during late pregnancy. The present study is a component of the Mothers and Children's Environmental Health (MOCEH) study, a multi-center birth cohort project in Korea that began in 2006. The study cohort consisted of 553 children whose mothers underwent testing for blood mercury during late pregnancy. The children were given the Korean language version of the Wechsler Preschool and Primary Scale of Intelligence, revised edition (WPPSI-R) at 60 months of age. Multivariate linear regression analysis, with adjustment for covariates, was used to assess the relationship between verbal, performance, and total IQ in children and blood mercury concentration of mothers during late pregnancy. The results of multivariate linear regression analysis indicated that a doubling of blood mercury was associated with the decrease in verbal and total IQ by 2.482 (95% confidence interval [CI], 0.749-4.214) and 2.402 (95% CI, 0.526-4.279), respectively, after adjustment. This inverse association remained after further adjustment for blood lead concentration. Fish intake is an effect modifier of child IQ. In conclusion, high maternal blood mercury level is associated with low verbal IQ in children.

Maternal Stress and Depressive Symptoms and Infant Development at Six Months: the Mothers and Children's Environmental Health (MOCEH) Prospective Study.

Our objective is to evaluate the relationships between prenatal maternal stress and depressive symptoms, respectively, and infant neurodevelopment at 6 months, adjusted for heavy metals and oxidative stress. This research is a part of a multi-center birth cohort study in South Korea. Information on stress and depressive symptoms was collected during the first trimester using Psychosocial Well-Being Index Short Form (PWI-SF) and Center for Epidemiological Studies Depression Scale (CES-D). The Korean Bayley Scales of Infant Development-II assessment (BSID-II), which includes the standardized mental development index (MDI) and psychomotor developmental index (PDI), and Korean Ages & Stages Questionnaires (K-ASQ) were applied to infants at six months of age. A higher index score indicates better development. Among 641 babies, 320 were female (50%). Maternal PWI ≥ 29 (vs. PWI ≤ 18) during early pregnancy was associated with a decrease in MDI scores of 5.37 points (P = 0.02) after adjusting for socioeconomic factors. Maternal CES-D ≥ 26 (vs. CES-D ≤ 10) during early pregnancy was associated with a decrease in MDI scores of 8.18 points (P = 0.01). The associations remained significant even after adjustment for lead, cadmium, and MDA levels (P < 0.05). However, no association was found between maternal PWI/CES-D and PDI score. No interaction was observed between stress and lead exposure. We found an inverse association between prenatal maternal stress and depressive symptoms, and MDI scores in 6-month-old infants after adjustment for prenatal lead exposure, which is known to affect cognitive function negatively.

Effect of Breastfeeding Duration on Cognitive Development in Infants: 3-Year Follow-up Study.

We investigated the association between breastfeeding and cognitive development in infants during their first 3 years. The present study was a part of the Mothers' and Children's Environmental Health (MOCEH) study, which was a multi-center birth cohort project in Korea that began in 2006. A total of 697 infants were tested at age 12, 24, and 36 months using the Korean version of the Bayley Scales of Infant Development II (K-BSID-II). The use and duration of breastfeeding and formula feeding were measured. The relationship between breastfeeding and the mental development index (MDI) score was analyzed by multiple linear regression analysis. The results indicated a positive correlation between breastfeeding duration and MDI score. After adjusting for covariates, infants who were breastfed for ≥ 9 months had significantly better cognitive development than those who had not been breastfed. These results suggest that the longer duration of breastfeeding improves cognitive development in infants.

Association between prenatal exposure to cadmium and atopic dermatitis in infancy.

Our objective was to evaluate the relationship between intrauterine exposure to cadmium and the presence of atopic dermatitis in infants 6 months of age, adjusted for covariates including exposure to other heavy metals. The present research is a component of the Mothers' and Children's Environmental Health (MOCEH) study, a multi-center birth cohort project conducted in Korea. Study subjects were restricted to pregnant women in whom cadmium and lead levels were measured at delivery and whose infants were assessed for the presence of atopic disease at 6 months of age. The odds ratio (OR) for the presence of atopic dermatitis in 6-month-old infants whose cord blood had elevated cadmium levels, after adjustment for other covariates, was 2.350 (95% CI, 1.126-4.906). The OR for the presence of atopic dermatitis in infants whose cord blood had elevated lead levels was not significant. In the present study, the cord blood cadmium level was significantly associated with the presence of atopic dermatitis in 6-month-old infants; this was not true of the cord blood lead level. To the best of our knowledge, this is the first prospective study to show a relationship between prenatal exposure to cadmium and atopic dermatitis in infancy.

Secondhand smoke exposure during pregnancy and infantile neurodevelopment.

During prenatal development, the nervous system may be more susceptible to environmental toxicants, such as secondhand smoke. The authors assessed the effects of prenatal and postnatal secondhand smoke exposure on the neurodevelopment of 6-month infants. The subjects were 414 mother and infant pairs with no medical problems, taken from the Mothers' and Children's Environmental Health study. Prenatal and postnatal exposures to secondhand smoke were determined using maternal self-reports. Examiners, unaware of exposure history, assessed the infants at 6 months of age using the Bayley Scales of Infant Development. Bayley scores were compared for secondhand smoke exposed and unexposed groups after adjusting for potential confounders. Multiple logistic regression analysis was carried out to estimate the risk of developmental delay posed by SHS exposure. The multivariate model included residential area, maternal age, pre-pregnancy body mass index, education, income, infant sex, parity, birth weight, and type of feeding. After adjusting for covariates, secondhand smoke exposure during pregnancy was found to be related to a decrease in mental developmental index score, but not to a decrease in psychomotor developmental index score. In addition, secondhand smoke exposure during pregnancy was found to increase the risk of developmental delay (mental developmental index score ≤85) at 6 months. This study suggests that the infants of non-smoking women exposed to secondhand smoke are at risk of neurodevelopmental delay.

Blood cadmium concentrations of male cigarette smokers are inversely associated with fruit consumption.

Decreased fruit and vegetable consumption, along with elevated blood cadmium concentrations, are frequently observed among cigarette smokers. Few studies have investigated whether the blood cadmium concentrations of cigarette smokers are associated with the consumption of antioxidative nutrients, as well as foods containing high concentrations of antioxidative nutrients and phytochemicals, such as fruits and vegetables. In this study, we aimed to determine where there is any relationship between blood cadmium concentration and the consumption of certain foods and nutrients in adult male smokers. Blood cadmium concentrations in whole blood samples from 546 adult men, whose pregnant wives were registered in the Mothers and Children's Environmental Health Study, were analyzed using the graphite furnace atomic absorption spectrophotometry method. Dietary intakes were assessed using a semiquantitative FFQ. Blood cadmium concentrations were higher in the smokers than in the nonsmokers (P < 0.001). Multiple regression analysis with covariates revealed that blood cadmium concentrations were negatively associated with intakes of fruit (P = 0.001), vitamin C (P = 0.035), and fiber (P = 0.049), but only in the smokers. These results warrant future studies to explore any mechanisms responsible for fruit's beneficial role against elevated blood cadmium concentrations in smokers.

Risk Factors and Comorbidities Associated With the Allergic Rhinitis Phenotype in Children According to the ARIA Classification.

PURPOSE: Data are lacking on the association between the allergic rhinitis (AR) phenotype and sensitization to specific allergens or bronchial hyperresponsiveness (BHR) in children. We here investigated risk factors and comorbidities, including sensitization to specific allergens and BHR, for the AR phenotype by AR and its Impact on Asthma (ARIA) classification in a general population-based birth cohort study. METHODS: We enrolled 606 children aged 7 years from the Panel Study of Korean Children. The AR phenotype was assigned in accordance with the ARIA classification in children. Skin prick tests and Provocholine provocation test were performed. Risk factors and comorbidities for AR phenotypes were then analyzed. RESULTS: The prevalence of mild and moderate to severe AR in our study cohort was 37.2% and 8.8%, respectively. Recent use of analgesics or antipyretics and current cat ownership were associated with the risk of mild persistent AR. Sensitizations to Dermatophagoides Pteronyssinus (Der p), Japanese hop and cat were associated with moderate to severe persistent AR. Children with moderate to severe AR had a higher risk of current asthma and BHR compared to mild AR cases (adjusted odds ratio [aOR], 5.26; 95% confidence interval [CI], 1.77-15.62). Moderate to severe AR with allergic sensitization was associated with the highest risk of BHR (aOR, 11.77; 95% CI, 3.40-40.74). CONCLUSIONS: Moderate to severe-persistent AR is more closely related to respiratory comorbidities and sensitizations than mild AR. Stratifying the AR phenotype by ARIA classification may assist in disease management.

The effect of rush immunotherapy with house dust mite in the production of IL-5 and IFN-gamma from the peripheral blood T cells of asthmatic children.

Although the mechanisms are unclear, rush immunotherapy (RIT) may be effective to treat allergic diseases. We investigated the long-term modifications of cellular immunity as a mechanism of RIT. The RIT group, included 15 house dust mite (HDM)-sensitized asthmatic children, received RIT only with Dermatophagoides farinae (Der f) and Dermatophagoides pteronyssinus (Der p), whereas the control group, consisted of 10 HDM-sensitized asthmatic children, did not receive RIT. The asthma symptom scores and the skin reactivities to Der f were measured. The cellular proliferative responses and intracellular interleukin (IL)-5 and interferon (IFN)-gamma productions from peripheral blood T cells were also measured before, 8 weeks and 1 yr after RIT. The symptom scores, skin reactivity to Der f and cellular proliferative responses to Der f were decreased significantly after 8 weeks and maintained until 1 yr of RIT. The IFN-gamma/IL-5 ratio of the CD3+ and CD4+ cells were increased significantly after 8 weeks and maintained until 1 yr of RIT, while there were no changes in the control group. These data indicate that the continuous functional modification from Th2 to Th1 phenotype of the CD4+ T cells are developed after RIT in the asthmatic children sensitized with HDM.

Clinical characteristics and etiologies of bronchiectasis in Korean children: A multicenter retrospective study.

BACKGROUND: Bronchiectasis is a chronic pulmonary disease characterized by progressive and irreversible bronchial dilatation. The aim of the present study was to investigate the etiologies and clinical features of bronchiectasis in Korean children. METHODS: We performed a retrospective review of the medical records for children diagnosed with bronchiectasis between 2000 and 2017 at 28 secondary or tertiary hospitals in South Korea. RESULTS: A total of 387 cases were enrolled. The mean age at diagnosis was 9.2 ±â€¯5.1 years and 53.5% of the patients were boys. The most common underlying cause of bronchiectasis was preexisting respiratory infection (55.3%), post-infectious bronchiolitis obliterans (14.3%), pulmonary tuberculosis (12.3%), and heart diseases (5.6%). Common initial presenting symptoms included chronic cough (68.0%), recurrent pneumonia (36.4%), fever (31.1%), and dyspnea (19.7%). The most predominantly involved lesions were left lower lobe (53.9%), right lower lobe (47.1%) and right middle lobe (40.2%). No significant difference was observed in the distribution of these involved lesions by etiology. The forced expiratory volume in 1 s (FEV1) levels were lowest in cases with interstitial lung disease-associated bronchiectasis, followed by those with recurrent aspiration and primary immunodeficiency. CONCLUSIONS: Bronchiectasis should be strongly considered in children with chronic cough and recurrent pneumonia. Long-term follow-up studies on pediatric bronchiectasis are needed to further clarify the prognosis and reduce the disease burden in these patients.

Prevalence, Risk Factors and Cutoff Values for Bronchial Hyperresponsiveness to Provocholine in 7-Year-Old Children.

BACKGROUND: A US Food and Drug Administration (FDA)-approved drug methacholine chloride (Provocholine®) was recently introduced to Korea where it is now widely used in clinical practice. We aimed to evaluate the prevalence, risk factors and cutoff value of bronchial hyperresponsiveness (BHR) to Provocholine in 7-year-old children. METHODS: Six hundred and thirty-three children from the Panel Study on Korean Children who visited 16 regional hospitals were evaluated. Skin prick tests, spirometry and bronchial provocation tests for Provocholine as well as a detailed history and physical examinations were performed. The bronchial provocation test was reliably performed on 559 of these children. RESULTS: The prevalence of ever-diagnosed asthma via medical records was 7.7%, and that of current asthma (wheezy episode in the last 12 months + diagnosed asthma by physicians) was 3.2%. The prevalence of BHR to Provocholine was 17.2% and 25.8%, respectively, for a PC20 < 8 and < 16 mg/mL. The risk factors for BHR (PC20 < 16 mg/mL) were atopic dermatitis diagnosis and current dog ownership, whereas those for current asthma were allergy rhinitis diagnosis, a history of bronchiolitis before the age of 3, recent use of analgesics/antipyretics and maternal history of asthma. The BHR prevalence trend showed an increase along with the increased immunoglobulin E (IgE) quartile. The cutoff value of PC20 for the diagnosis of current asthma in children at age 7 was 5.8 mg/mL (sensitivity: 47.1%, specificity: 87.4%). CONCLUSIONS: BHR to Provocholine (PC20 < 8 mg/mL) was observed in 17.2% of 7-year-olds children from the general population and the cutoff value of PC20 for the diagnosis of current asthma was 5.8 mg/mL in this age group. The risk factors for BHR and current asthma showed discrepancies suggesting different underlying mechanisms. Bronchial provocation testing with Provocholine will be a useful clinical tool in the future.

Blood heavy metal concentrations in pregnant Korean women and their children up to age 5years: Mothers' and Children's Environmental Health (MOCEH) birth cohort study.

The present study assessed the associations of heavy metal concentrations in pregnant women with the concentrations in their children during early childhood. This study is a part of the Mothers' and Children's Environmental Health (MOCEH) study, a Korean multi-center prospective birth cohort study of 1751 pregnant women who were recruited from 2006 to 2010. We completed the follow-up of children who were 5years-old in 2016. Lead, total mercury, and cadmium were measured in women during early and late pregnancy, in cord blood, and in children who were 2, 3, and 5years-old. Lead concentration was lowest in cord blood, highest in 24month-old children, and then decreased with child age. Total mercury concentration was highest in cord blood, and gradually decreased with child age. Cadmium concentration was lowest in cord blood, and increased with child age. After adjusting for child sex, maternal age, and maternal education level, we found strong correlations between the levels of lead and total mercury in women during late pregnancy with the levels in cord blood; however, there were weak correlations between the levels of these metals in women during late pregnancy and cord blood with the levels in their children. In conclusion, maternal lead and mercury concentrations correlated with the levels in cord blood and in children up to age 60months. This correlation may be due to high trans-placental transmission of these metals and shared living environment such as environmental exposure, food consumption, and lifestyle.

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.

Evidence that cognitive deficit in children is associated not only with iron deficiency, but also with blood lead concentration: a preliminary study.

OBJECTIVE: To investigate whether blood lead concentrations are elevated in iron-deficient children, and to examine the association between iron deficiency and/or elevated blood lead concentration and cognitive deficits in children. METHOD: The present study is a component of the Mothers' and Children's Environmental Health (MOCEH) study, a multi-center birth cohort project in Korea that began in 2006. The study cohort consisted of 194 children who underwent testing of blood lead and serum C-reactive proteins (CRPs) and ferritin concentrations, and the Korean version of the Wechsler Preschool and Primary Scale of Intelligence, revised edition (WPPSI-R), at 60 months of age. In addition, the mothers' blood lead concentrations during pregnancy were included in the analyses. Multivariate linear regression analysis was performed to analyze the correlation between high blood lead and low serum ferritin concentrations, after adjustment for covariates, in children, as well as to analyze the association of verbal IQ with serum ferritin and blood lead concentrations. RESULTS: Lead and ferritin concentrations were inversely and significantly associated in children after adjustment for covariates. Moreover, both concentrations were associated with verbal IQ, after adjustment for covariates, and each was associated with cognitive deficits after adjustment for the other. Sobel test statistics showed that blood lead concentration was a significant partial mediator for the relationship between iron deficiency and verbal IQ. CONCLUSION: Due to the results discussed in the present study, cognitive deficit in children seems to be associated not only with iron deficiency, but also with blood lead concentration.

Performance IQ in children is associated with blood cadmium concentration in early pregnancy.

OBJECTIVE: To investigate whether performance IQ in children is associated with maternal blood cadmium concentration in early pregnancy. METHOD: The present study is a component of the Mothers' and Children's Environmental Health (MOCEH) study, a multi-center birth cohort project in Korea that began in 2006. The study cohort consisted of 119 children whose mothers underwent testing of blood cadmium during early pregnancy. All children were evaluated using the Korean version of the Wechsler Preschool and Primary Scale of Intelligence, revised edition (WPPSI-R), at 60 months of age. Multivariate linear regression analysis was performed to analyze the correlation between IQ in children and maternal blood cadmium concentration in early pregnancy, after adjustment for covariates. RESULTS: Maternal blood cadmium concentration during early pregnancy was inversely associated with performance IQ, after adjustment for covariates such as sex, educational levels of both parents, family income, and maternal BMI. Maternal blood cadmium concentration, however, was not associated with cognitive IQ. CONCLUSION: Performance IQ in children is associated with maternal blood cadmium concentration in early pregnancy.

Relationship between prenatal and postnatal exposures to folate and risks of allergic and respiratory diseases in early childhood.

BACKGROUND: It is uncertain whether folate is risk or preventive factor for allergic and respiratory diseases. OBJECTIVE: To determine the relationship between maternal or offspring folate status and subsequent development of allergic and respiratory diseases in early childhood. METHODS: In total, 917 mother-child pairs from a prospective birth cohort in South Korea were studied. Data regarding the children's allergic and respiratory outcomes were obtained from standardized questionnaires completed by the mothers at postnatal months 6, 12, and 24. Serum folate levels were measured in the mothers at mid- and late-pregnancy, and in their children at 24 months of age. Atopic biomarkers were measured in the cord blood (CB) and at 24 months after birth. Biomarkers and clinical outcomes were analyzed and compared between the mother-child pairs divided into two groups according to median serum folate status at mid- and late-pregnancy. RESULTS: Serum folate levels during mid-pregnancy were inversely associated with CB eosinophil count (adjusted odds ratio [OR] 0.72, 95% confidence interval [CI], 0.54-0.96) and positively associated with CB interleukin-10 levels (1.47, 1.11-1.94). Maternal folate level above the median value (≥9.5 ng/ml) during mid-pregnancy was associated with a decreased risk for the child of lower respiratory tract infections (LRTIs) at 6 months of age (adjusted OR 0.50, 95% CI 0.28-0.91) and atopic dermatitis (AD) at 24 months (adjusted OR 0.52, 95% CI 0.31-0.88), but not with LRTIs and AD at other ages. CONCLUSIONS: A relatively high maternal serum folate level in mid-pregnancy was associated with a decreased risk of LRTIs and AD in early childhood.

Prenatal exposure to phthalates and infant development at 6 months: prospective Mothers and Children's Environmental Health (MOCEH) study.

BACKGROUND: There are increasing concerns over adverse effects of prenatal phthalate exposure on the neurodevelopment of infants. OBJECTIVES: Our goal was to explore the association between prenatal di(2-ethylhexyl) phthalate and dibutyl phthalate exposure and the Mental and Psychomotor Developmental Indices (MDI and PDI, respectively) of the Bayley Scales of Infant Development at 6 months, as part of the Mothers and Children's Environmental Health Study. METHODS: Between 2006 and 2009, 460 mother-infant pairs from Seoul, Cheonan, and Ulsan, Korea, participated. Prenatal mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-n-butyl phthalate (MBP) were measured in one urine sample acquired from each mother during the third trimester of pregnancy. Associations with log-transformed creatinine-corrected phthalate concentrations were estimated using linear regression models adjusted for potential confounders. RESULTS: MDI was inversely associated with the natural log concentrations (micrograms per gram creatinine) of MEHHP [ß = -0.97; confidence interval (CI), -1.85 to -0.08] and MEOHP (ß = -0.95; CI, -1.87 to -0.03), and PDI was inversely associated with MEHHP (ß = -1.20; CI, -2.33 to -0.08). In males, MDI was inversely associated with MEHHP (ß = -1.46; CI, -2.70 to -0.22), MEOHP (ß = -1.57; CI, -2.87 to -0.28), and MBP (ß = -0.93; CI, -1.82 to -0.05); PDI was inversely associated with MEHHP (ß = -2.36; CI, -3.94 to -0.79), MEOHP (ß = -2.05; CI, -3.71 to -0.39), and MBP (ß = -1.25; CI, -2.40 to -0.11). No significant linear associations were observed for females. CONCLUSIONS: The results suggest that prenatal exposure to phthalates may be inversely associated with the MDI and PDI of infants, particularly males, at 6 months.