Gyuyeon Choi

Urinary paraben concentrations among pregnant women and their matching newborn infants of Korea, and the association with oxidative stress biomarkers.

Parabens have been used in multiple products including personal care products, pharmaceuticals, and foods for more than 50 years but increasing numbers of studies have raised concerns on their safety. The present study was designed to determine urinary paraben levels among pregnant women and their matching newborn infants (<48 h after delivery), and the association between paraben levels and stress markers. Pregnant women (n=46) and their matching newborn infants were recruited from four university hospitals located in Seoul, Ansan and Jeju of Korea, 2011. Parabens including methyl paraben (MP), ethyl paraben (EP), n-propyl paraben (PP), and n-butyl paraben (BP) were measured in the urine using an automatic, high throughput online SPE-LC-MS/MS method. Urinary concentrations were normalized with specific gravity (SG). Free cortisol, malondealdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) were measured in the urine as stress marker. Urinary MP was detected as the highest, and BP was detected as the lowest paraben in the urine samples of both pregnant women and their infants. Significant correlations between paraben concentrations of maternal and their newborn infants urine were observed. The levels of urinary parabens among Korean pregnant women are comparable to those reported elsewhere, except for EP which were 4-9 folds higher than pregnant women of other countries. The ratios of infant to maternal urinary paraben concentrations varied between 0.5 and 0.6 for MP and PP, but approximately 10 fold lower for EP. Urinary MP or EP levels were associated with several oxidative stress related biomarkers such as urinary 8-OHdG and MDA, even after the adjustment of relevant covariates such as maternal age, mode of delivery, pre-pregnancy BMI, gestational age and parity. This is the first study that reported the levels of major parabens in the first urine of newborn infants. Further studies are warranted to understand the implications of paraben exposure among biologically susceptible human populations.

Association between several persistent organic pollutants and thyroid hormone levels in serum among the pregnant women of Korea

Persistent organic pollutants such as polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides (OCPs) are of global concern because of their widespread contamination and adverse health effects. Potential endocrine disruption, especially of thyroid status by PCBs has been repeatedly suggested in both experimental and epidemiological studies. However the associations with PBDEs or OCPs have been arguable especially in human populations. We investigated the associations between major groups of POPs and thyroid hormone balances among pregnant women. One hundred five pregnant women at delivery were recruited from four cities of Korea in 2011 and were investigated. Blood samples were collected within a day before delivery. Serum was then analyzed for 19 PCBs, 19 PBDEs, and 19 OCPs, along with five thyroid hormones (free and total T3 and T4, and TSH). Several PCBs such as PCB28, 52, and 118 showed negative associations with T3 or T4. BDE47 and total PBDEs showed significant associations with T3 or T4. For OCPs, dichlorodiphenyltrichloroethanes (DDTs) and hexachlorobenzene (HCB) were generally associated with reduction of T3 or T4. The thyroid hormone levels of all subjects were within the reference range, however exposure to several target POPs were clearly related with potential for disrupting thyroid hormone balance among pregnant women, at the current level of exposure. Although subtle, the changes in thyroid hormones should be seen with caution because even minor changes within pregnant women may have significant consequences especially on sensitive population like fetus.

Concentrations of phthalate metabolites in breast milk in Korea: Estimating exposure to phthalates and potential risks among breast-fed infants

Phthalates have been associated with endocrine disruption and developmental effects in many experimental and epidemiological studies. Developing infants are among the most susceptible populations to endocrine disruption. However, limited information is available on phthalate exposure and its associated risks among breast-fed newborn infants. In the present study, breast milk samples were collected from 62 lactating mothers at 1 month post-partum from four cities of Korea in 2012 and were evaluated for six phthalate metabolites (mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), mono(2-ethyl-hexyl) phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and monoethyl phthalate (MEP)). MEP was detected in all breast milk samples, with a median concentration of 0.37 μg/L, and MiBP, MnBP and MEHP were detected in 79-89% of samples, with median concentrations of 1.10, 1.70, and 2.08 μg/L, respectively. However, MEHHP and MEOHP, the oxidized forms of di-ethyl-hexyl phthalate (DEHP), were detected in only one sample. For exposure assessment, the levels of phthalate diesters were estimated based on the parent:metabolite ratios in the breast milk that are reported elsewhere. For risk assessment, the endocrine-related toxicity of the monoester was assumed to be the same as that of its diester form. Median daily intake estimates of phthalates, including both monoester and diester forms, through breast milk consumption ranged between 0.91 and 6.52 μg/kg body weight (bw) for DEHP and between 0.38 and 1.43 μg/kg bw for di-n-butyl phthalate (DnBP). Based on the estimated daily intake, up to 8% of infants exceeded the reference dose of anti-androgenicity (RfD AA) for DEHP, and 6% of infants exceeded the tolerable daily intake (TDI) for DnBP. Breast milk MiBP and MnBP concentrations showed significant positive associations with maternal consumption of whipped cream or purified water. Considering vulnerability of young infants, efforts to mitigate phthalate exposure among lactating women are warranted.

Occurrences of major polybrominated diphenyl ethers (PBDEs) in maternal and fetal cord blood sera in Korea

Polybrominated diphenyl ethers (PBDEs) are of growing public health concern because of their potential toxicities which range from endocrine disruption to neurodevelopment. However, information on their exposure among sensitive human populations is limited. The objectives of this study were to determine the levels of major PBDEs in blood sera of pregnant women and their matching newborn infants. For this purpose, a total of 198 maternal blood samples and 118 matching umbilical cord blood samples were collected from four regions of South Korea in 2011, and were determined for 19 PBDE congeners. Various demographic, dietary, and behavioral characteristics were asked in a questionnaire survey. Average concentration of total PBDEs in maternal blood serum was 3.34 ± 8.42 ng/g lipid weight (lw) at delivery and 3.14 ± 7.46 ng/g lw at 6 months of pregnancy, respectively. In cord blood serum, an average of 9.37 ± 12.60 ng/g lw was detected. Among the measured PBDE congeners, BDE-47, BDE-99 and BDE-153 were most dominant in both maternal and cord blood sera. Relatively higher levels of BDE-99 were detected in cord blood serum. Strong positive correlations were detected between maternal and cord blood serum samples, indicating the importance of maternal transfer. Health consequences of transplacental exposure to PBDEs among fetuses and newborn infants warrant further investigation.

Association of diethylhexyl phthalate with obesity-related markers and body mass change from birth to 3 months of age

Background Several studies have suggested potential links of phthalates to obesity in children and adults. Limited evidence, however, has been available for the relations between diethylhexyl phthalate (DEHP) and obesity-related markers or body mass change in early life. Methods 128 healthy pregnant women were recruited and, after delivery, their newborns’ first urine and umbilical cord blood samples were collected. We measured urinary levels of two DEHP metabolites, mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP). We also measured the levels of leptin, total cholesterol and triglyceride (TG) in cord serum, and used them along with weight, length, head circumference and ponderal index (PI, 100 g/cm3) at birth, as obesity-related markers, and estimated the relations between DEHP metabolites and obesity-related markers using generalised linear models. For the evaluation of body mass increase by early life DEHP exposure, body mass index (BMI) z-score change during 3 months after birth by DEHP metabolites in the first urine samples of the newborns were evaluated using logistic regression. Results DEHP exposure was associated with decrease of PI and increase of TG (PI, β=−0.11, p=0.070 and TG, β=0.14, p=0.027), especially for boys (PI, β=−0.13, p=0.021; and TG, β=0.19, p=0.025). Moreover, DEHP exposure was positively associated with body mass increase during 3 months after birth (change of BMI z-scores, OR=4.35, p=0.025). Conclusions Our findings suggest that DEHP exposure may affect body mass change in early life through changes of obesity-related markers.

Polybrominated diphenyl ethers (PBDEs) in breast milk of Korea in 2011: Current contamination, time course variation, influencing factors and health risks

Breast milk is a valuable biological specimen to assess maternal and infant exposure to polybrominated diphenyl ethers (PBDEs). In this study, 208 breast milk samples were collected from 89 participants during lactation period, at <7, 15, 30, and 90 days postpartum, in four cities in Korea, and were determined for 19 PBDE congeners. The total PBDE concentrations (ΣPBDE) ranged from 0.23 to 68.4 (mean: 2.73) ng/g lipid weight, and were within the ranges reported for European and Asian countries. Within a month of lactation after delivery, no significant changes were found in the PBDE concentrations. The predominance of BDE 153 rather than BDE 47 was found in the most samples that BDE 153 was detected, and was likely to be associated with stepwise debromination of BDE 209. No associations were found between PBDE concentrations in breast milk and demographic parameters, except for ΣPBDE with maternal age and delivery mode. Certain types of diet such as corn, seafood and nut correlated significantly with PBDE levels in breast milk. The estimated daily intakes of ΣPBDE for breast-feeding infants were lower than the guidelines proposed by the US EPA, indicating limited health risk from PBDEs through breast feeding.

Contamination of polychlorinated biphenyls and organochlorine pesticides in breast milk in Korea: time-course variation, influencing factors, and exposure assessment.

Breast milk is a noninvasive specimen to assess maternal and infant exposure to polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs). In this study, 206 breast milk samples were collected from 87 participants during lactation, at <7, 15, 30, or 90 days postpartum in four cities in Korea. The total concentrations of PCBs (ΣPCB) and OCPs (ΣOCP) ranged from <LOQ to 84.0 (median: 12.1) ng g(-1) lipid weight and from <LOQ to 559 (median: 144) ng g(-1) lipid weight, respectively. The residue levels of these contaminants measured in our study were relatively lower than those reported for European, African and Asian populations. Within a month postpartum typically after day seven the levels of ΣPCB and ΣOCP significantly increased. Some OCP compounds were correlated with maternal age, BMI, parity, and delivery mode. Certain types of dietary habits such as seafood and noodle consumption were significantly associated with ΣPCB and ΣOCP. The estimated daily intakes (EDIs) of ΣPCB and ΣOCP were 45.2-127 ng kg(-1) bw day(-1) and 625-1259 ng kg(-1) bw day(-1) during lactation, respectively, which are lower than the threshold values proposed by the US EPA and Health Canada. The exposure of Korean infants to chlordanes via breast milk had a potential health risk which deserves further investigation.

Polybrominated Diphenyl Ethers in Maternal Serum, Breast Milk, Umbilical Cord Serum, and House Dust in a South Korean Birth Panel of Mother-Neonate Pairs

Polybrominated diphenyl ethers (PBDEs) have been used as flame retardants. Although many reports have indicated an association between exposure to PBDEs and developmental neurotoxicity, the relative contributions of different sources of dust PBDE congeners to the levels in various tissues of mother–baby pairs is not well understood. The aims of this study were thus to measure the quantitative relationship between the level of PBDEs in house dust and tissues of mother-neonate pairs, and to investigate the chemical sources of the PBDEs. Forty-one mother-neonate pairs were recruited and provided samples of maternal serum (n = 29), umbilical cord serum (n = 25), breast milk (n = 50), and house dust (n = 41), where PBDEs were determined with high-resolution gas chromatography coupled with high-resolution mass spectrometry. While deca- (e.g., BDE 209, detected 100%), nona- (BDE 206/207, 95.1%), octa- (BDE 183, 100%), penta- (BDE 99/153, 100%, 98%) and tetra-BDEs (BDE 47, 100%) were detected abundantly in dust, penta- (BDE 99, 76%, 92%) and tetra-BDEs (BDE 47, 84%, 98%) were detected abundantly in umbilical cord serum and breast milk, respectively; tetra-BDEs (BDE 47, 86%) were detected more often relative to other congeners in maternal serum. Spearman’s pairwise comparison showed that the levels of BDE 47 (ρ = 0.52, p < 0.001) and −99 (ρ = 0.64, p < 0.01) in umbilical cord serum were associated with BDE 209 levels in dust; BDE 47 in maternal serum also showed correlation with BDE 99 in cord serum (ρ = 0.48, p < 0.01) but there was no significant correlation between maternal BDE 47 and dust BDE 209. On the other hand, a comparison of the distribution among congeners suggested probable associations of BDE 47 in maternal serum, breast milk, and umbilical cord serum with BDE 209 in dust; and of BDE 99 in maternal and umbilical cord serum, breast milk, and dust with BDE 209 in dust. Although further studies are needed, a radar chart-based distributional comparison among congeners supported associations between BDE 47 or −99 in human tissues and BDE 209 in dust.

Synthetic musk compounds and benzotriazole ultraviolet stabilizers in breast milk: Occurrence, time-course variation and infant health risk

Synthetic musk compounds (SMCs) and benzotriazole ultraviolet stabilizers (BUVSs) are used as additives in many consumer products. Limited data are available on the accumulation of SMCs in human fluids, and no data are available on BUVSs. In this study, 208 human breast milk samples were collected from 87 participants during the lactation period at <7, 15, 30, and 90 days after delivery in Korea. The total concentrations of SMCs and BUVSs ranged from <LOQ to 1593 (median: 286) ng/g lipid weight and from <LOQ to 2172 (median: 64.7) ng/g lipid weight, respectively. The residue levels of HHCB and AHTN in our samples were the highest, compared to those reported in the US, Europe, and China. The predominant compounds were HHCB and AHTN for SMCs and UV-328 for BUVSs, consistent with consumption patterns of these contaminants. Over the lactation period, no significant changes were found in concentrations of SMCs and BUVSs for both parity groups. Maternal age, body mass index, and parity were not associated with the concentrations of SMCs and BUVSs, while gestational age and delivery mode were associated with these contaminants. The estimated daily intakes of HHCB and AHTN were lower than the provisional tolerable daily intake values, suggesting a limited health risk to Korean infants. This study is the first to comprehensively investigate the current levels, accumulation features, contributing factors of BUVSs associated with breast milk consumption in Korea.

Association of food consumption during pregnancy with mercury and lead levels in cord blood.

In utero exposure to mercury and lead has been linked to various adverse health effects related to growth and development. However, there was no evidence on the relationship between food consumption during pregnancy and mercury or lead level in cord blood. Therefore we measured mercury and lead levels in bloods, urines, and cord bloods obtained from 302 pregnant women and estimated relationships between food consumption during pregnancy and mercury or lead level in cord blood to identify perinatal mercury and lead exposures originated from foods during pregnancy. Relationship between food consumption and mercury or lead level was estimated using a generalized linear model after adjustment for body mass index (BMI), delivery experience, income, recruitment year, and other dietary factors for mercury and age, BMI, cesarean section, delivery experience, recruitment year, and other dietary factors for lead. Fish consumption was positively associated with mercury level in cord blood (p=0.0135), while cereal and vegetable consumptions were positively associated with lead level in cord blood (p=0.0517 for cereal and p=0.0504 for vegetable). Furthermore, tea consumption restrained increase of lead level in cord blood (p=0.0014). Our findings support that mercury or lead exposure in Korean pregnant women may come from frequent fish and cereal or vegetable consumption while tea consumption may decrease lead exposure in pregnant women. Therefore, careful intervention through food consumption should be considered.