Sooran Choi

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 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.

Perfluoroalkyl substances (PFASs) in breast milk from Korea: Time-course trends, influencing factors, and infant exposure

Breastfeeding is an important exposure pathway to perfluoroalkyl substances (PFASs) for newborn infants. Nevertheless, reports are limited on the occurrence and time-course of PFASs in breast milk, and most studies have focused on the analysis of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). In this study, 16 PFASs were analyzed in breast milk samples (n=293) collected from 128 mothers in Korea during various lactation periods to assess maternal exposure levels, contamination profiles, time-course variations, and infant health risks. The total concentrations of PFASs (ΣPFAS) ranged from 31.7 to 1004 (median: 188) ng/L, which was within the ranges recently reported for Asian and European populations. After a month of nursing, the concentrations of PFOS, PFOA, perfluorononanoic acid (PFNA), and ΣPFAS significantly increased. This could be due to changes in the dietary and behavior patterns of the mothers after the first month of lactation. The concentrations of PFOS and PFOA were significantly correlated with maternal age, body mass index, and parity. Certain types of diet (e.g. consuming snacks and milk) and eating-out frequency were significantly associated with increasing levels of PFAS. Significant correlations and similar time-course trends were found between PFASs and PCBs/DDTs, implying similar exposure sources and biokinetics for these contaminants. The estimated daily intakes of PFOS and PFOA via the consumption of breast milk were below the tolerable daily intakes for infants suggested by the European Food Safety Authority (EFSA).

Infant exposure to polybrominated diphenyl ethers (PBDEs) via consumption of homemade baby food in Korea.

Limited data are available on the residue levels of polybrominated diphenyl ethers (PBDEs) in baby food. In this study, 24 PBDE congeners were determined in 147 homemade baby food samples collected from 97 households for 6-, 9-, 12-, 15-, and from 24 to 27-month-old infant groups during the period of 2012-2013. The concentrations of total PBDEs (ΣPBDE) ranged from 24.5 to 6000 (mean: 263) pg/g fresh weight, higher than those found in commercial formulae from the United States. The predominant congeners were BDEs 209 and 47, accounting for 92% of the ΣPBDE concentrations, reflected by high deca-BDE consumption in Korea. The residue levels and detection rates of BDE 47 in the baby food samples showed a gradual increasing trend with an increase in infant ages, due to changes in the food ingredients from hypoallergenic to greasy. The daily intakes of BDEs 47 and 209 via baby food consumption ranged from 0.04 to 0.58, 0.80 to 20.3, and 1.06 to 22.3 ng/kg body weight/day for 6-, 9-, 12-, 15-, and 24-27-month-old infant groups, respectively; these intakes were lower than the oral reference doses proposed by the US EPA. Together with three exposure sources, baby food, breast milk and dust ingestion for 6-month-old infants, the daily intake of ΣPBDE was 25.5 ng/kg body weight/day, which was similar to the intake via baby food consumption only for over 24-month-old infants in our study. This indicates that baby food is an important exposure pathway of PBDEs for over 24-month-old infants. This is the first study regarding the occurrence and exposure assessment of PBDEs via homemade baby food.

Association between maternal exposure to major phthalates, heavy metals, and persistent organic pollutants, and the neurodevelopmental performances of their children at 1 to 2 years of age- CHECK cohort study

Exposure of the developing fetus and infants to toxic substances can cause serious lifelong health consequences. Several chemicals have been associated with adverse neurodevelopmental disorders in the early life stages of humans. However, most epidemiological studies have focused on a limited number of chemicals, and hence may exclude important chemicals from consideration or result in conclusions built on associations by chance. In the present study, we investigated the chemical exposure profile of the women, and associated these with the early neurodevelopmental performance of their offspring at 13-24months of age. The chemicals assessed include four phthalates, bisphenol A, three heavy metals, 19 polychlorinated biphenyls (PCBs), 19 organochlorine pesticides, and 19 polybrominated diphenyl ethers, which were measured from urine, whole blood, serum, and/or breastmilk of the pregnant or lactating women. For neurodevelopmental performance, the Bayley Scales of Infant Development-II (BSID-II), Social Maturity Scale (SMS), and Child Behavior Checklist (CBCL) were measured from a total of 140 toddlers. Among the measured chemicals, monoethyl phthalate (MEP) in maternal urine was significantly associated with early mental, psychomotor, and social development. In addition, breast milk di-ethylhexyl phthalate (DEHP) metabolite and blood lead concentrations were inversely associated with mental and psychomotor development indices, respectively. Maternal blood PCB153, heavy metals, and urinary MEP levels were also higher among the children with behavioral problems, as indicated by the CBCL range. Taken together, maternal exposure to several EDCs such as PCBs and DEHP was associated with adverse neurodevelopmental performances among the children aged 1-2years. Confirmation of these association in larger populations, as well as longer-term consequences of such exposure warrant further investigation.

Bisphenol A distribution in serum, urine, placenta, breast milk, and umbilical cord serum in a birth panel of mother-neonate pairs

Bisphenol A (BPA) exposure during the perinatal and postnatal periods increases the susceptibility to disease over the life cycle. However, information on the BPA delivered to fetuses or infants via the placenta and breastfeeding is limited. We determined the BPA exposure levels in various bodily fluids and tissues of pregnant women and described fetus and infant exposures to BPA based on associations and BPA ratios in mother-neonate paired samples. Maternal serum, urine, placenta, breast milk, cord serum, and neonatal urine samples were collected from 318 mother-neonate pairs at six university hospitals in Korea. BPA levels were detected using liquid chromatography tandem mass spectrometry. The ratios of the BPA levels in the other sample types to the levels in maternal serum were calculated. BPA was detected in 79.5-100% of the maternal and fetal samples. The median BPA concentration in the samples decreased in the order of neonatal urine (4.75ng/mL), maternal urine (2.86ng/mL), cord serum (1.71ng/mL), maternal serum (1.56ng/mL), breast milk (0.74ng/mL), and the placenta (0.53ng/g). We estimated the ratios of BPA levels in the other sample types to those in maternal serum. The median (95th percentile) cord serum-to-maternal serum ratio was 1.12 (15.2) for 160 mother-fetal pairs, in which BPA was detected in both samples. The placenta-, maternal urine-, neonatal urine-, and breast milk-to-maternal serum ratios were 0.28 (5.31), 1.79 (29.9), 1.98 (28.2), and 0.51 (10.5), respectively. In addition, the median (95th percentile) cord serum-to-placenta ratio was 4.03 (45.8), and the neonatal urine-to-cord serum ratio was 1.95 (25.6). The 95th percentile values were 14-20-fold greater than the medians. Urine contained the highest BPA concentrations, followed by serum, breast milk, and the placenta. The variations of BPA ratio show individual differences in the amounts of BPA delivered from mother to fetus.