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.
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•Not enough data on tissue distribution of BPA in mother‑neonate (or fetus) pair•The order of BPA concentrations in examined tissue or bio-samples are urine in mother and neonates>cord serum>maternal serum>breast milk>placenta.•BPA in cord serum, significantly associated with in maternal serum and urine but not in others.•The variations of BPA ratio show individual differences in the amounts of BPA delivered from mother to fetus.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
•PFOS, PFOA, PFUnDA, and PFNA were the predominant compounds in breast milk.•Concentrations of PFASs were significantly correlated with maternal age, BMI, and parity.•Increased levels of PFASs were ...found in breast milk after the first month of nursing.•Snack consumption and frequency of eating-out were significantly associated with increased PFAS levels.•The infant exposure levels of PFOS and PFOA via breast milk were lower than the TDI.
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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).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Exposure to persistent organic pollutants (POPs) during pregnancy is associated with a disruption in thyroid hormone balance. The placenta serves as an important environment for fetal development and ...also regulates thyroid hormone supply to the fetus. However, epigenetic changes of thyroid regulating genes in placenta have rarely been studied. This study was conducted to evaluate the association between several POP concentrations in maternal serum and DNA methylation of thyroid hormone-related genes in the placenta. The placenta samples were collected from 106 Korean mother at delivery, and the promoter methylation of the placental genes was measured by a bisulfite pyrosequencing. The deiodinase type 3 (DIO3), monocarboxylate transporter 8 (MCT8), and transthyretin (TTR) genes were selected as the target genes as they play an important role in the regulation of fetal thyroid balance. Because people are exposed to multiple chemicals at the same time, a multiple-POP model using principal component analysis (PCA) was applied to evaluate the association between the multiple POPs exposure and the epigenetic change in placenta. In addition, a single-POP model which includes one chemical each in the statistical model for association was conducted.
Based on the single-POP models, serum concentrations of p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE) and brominated diphenyl ether-47 (BDE-47) were significantly associated with an increase in placental DIO3 methylation, but only among female infants. Among male infants, a positive association between serum p,p′-DDT and MCT8 methylation level was found. According to the multiple-POP models, serum DDTs were positively associated with DIO3 methylation in the placenta of female infants, while a positive association with MCT8 methylation was observed in those of the male infants. Our observation showed that in utero exposure to DDTs may influence the DNA methylation of DIO3 and MCT8 genes in the placenta, in a sexually dimorphic manner. These alterations in placental epigenetic regulation may in part explain the thyroid hormone disruption observed among the newborns or infants followed by in utero exposure to POPs.
•Promoter DNA methylation of placental genes related to thyroid hormone was measured.•Some maternal serum POPs were associated with methylation of these placental genes.•DNA methylation of DIO3 and MCT8 genes by maternal POP was differed by infant sex.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Chronic kidney disease (CKD) is a global health threat of growing concern. Recently, exposure to endocrine disrupting compounds (EDCs) such as phthalates and bisphenol A has been suggested as a risk ...factor for CKD. However, most epidemiological studies have focused on a limited number of urinary chemicals. This study aimed to identify chemical determinants of the urinary albumin-to-creatinine ratio (ACR), which is a kidney function marker, among multiple major EDCs including phthalate metabolites, bisphenols, and benzophenones in a Korean female population (20–45 years old, n = 441). First, the creatinine-adjusted urinary concentration of each urinary chemical was associated with ACR in a linear regression model (single-pollutant model). Then, compounds with a significant association with ACR in the single-pollutant model were added in a multi-pollutant model and evaluated for their association with ACR. Moreover, to prevent potential reverse causality due to impaired kidney function, quartile analyses were performed for the subjects with healthy renal function (ACR < 9.71 mg/g). In addition to creatinine adjustment, the statistical analysis was also conducted with specific gravity-adjusted concentrations of urinary chemicals, and the results were compared. Several compounds measured in the urine showed a significant association with ACR in the single-pollutant model. In the multi-pollutant model, however, only monobutyl phthalate and benzophenone-1, which are metabolites of dibutyl phthalate and benzophenone-3, respectively, showed significant positive associations. The association of these chemicals remained significant in a couple of the sensitivity analyses with a different adjustment of urine dilution and in a subpopulation with normal ACR. In conclusion, among dozens of urinary chemicals, monobutyl phthalate and benzophenone-1 consistently showed a strong association with urinary ACR. Confirmation of our observation in other human populations and experimental studies is warranted.
•Multiple urinary compounds were associated with ACR among healthy adult female.•For the first time, association of benzophenones with kidney function was observed.•MBP, a metabolite of DBP, also consistently showed strong association with ACR.•Association of bisphenol A and DEHP with ACR was not obvious.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Current knowledge on adverse endocrine disruption effects of persistent organic pollutants (POPs) among newborn infants is limited and often controversial. To investigate the associations between ...prenatal exposure to major POPs and thyroid hormone levels among newborn infants, both cord serum or maternal serum concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides (OCPs) were compared with five thyroid hormones in cord serum of newborn infants as well as TSH in bloodspot collected at 2 day after birth (n=104). Since cord serum thyroid hormones could be affected by those of mothers, thyroid hormone concentrations of the matching mothers at delivery were adjusted. In cord serum, BDE-47, -99, and Σchlordane (CHD) showed significant positive associations with cord or bloodspot TSH. At the same time, p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) and hexachlorbenzene (HCB) showed negative associations with total T3 and total T4 in cord serum, respectively. Maternal exposure to β-hexachlorhexane (β-HCH), ΣCHD, ΣDDT, or p,p'-DDE were also associated with neonatal thyroid hormones. Although the sample size is small and the thyroid hormone levels of the subjects were within the reference range, our observation supports thyroid disrupting potential of several POPs among newborn infants, at the levels occurring in the general population. Considering the importance of thyroid hormones during gestation and early life stages, health implication of thyroid hormone effects by low level POPs exposure deserves further follow up investigations.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
•Associations between POPs and thyroid hormone levels were examined in pregnant women.•Several PCBs and OCPs are significantly associated with T3 or T4 levels.•PBDEs showed thyroid disrupting potential, but the directions were inconsistent.•Implications of POPs exposure on fetus during gestation deserve further investigation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Mercury and lead are naturally occurring toxicants and are responsible for various health issues including neurobehavioral and developmental disorders. Because of crucial synchronized developmental ...processes occurring at the early stage of life, infancy and childhood are considered as among the most susceptible windows to the exposure to these metals. Breastmilk is often the only source of nutrition during the first months of life. As breastmilk can be contaminated with these metals, breastfeeding may serve as a significant route of heavy metal exposure among infants. In order to understand current levels of exposure to mercury and lead through breastfeeding, and their associated risks, a total of 157 lactating mothers were recruited from Children's Health and Environmental Chemicals of Korea (CHECK) cohort, and breastmilk samples were collected at 15 and 30days after delivery (n=207). Mercury was detected from 100% of breastmilk with a median concentration of 0.59μg/L, and lead was detected in 77% of the samples with a median at 4.71μg/L. Higher concentrations of lead were found in the 30- day breastmilk than in the 15-day. Up to 45% of the breastmilk samples exceeded the normal range of the breastmilk lead suggested by WHO. Based on Monte Carlo simulation, about 71% of 15days old infants and 56% of 30days old infants were estimated at risk due to lead exposure through breastfeeding. Considering vulnerability of infants and well-known neurological toxicity of these metals, further studies to identify major exposure sources that contribute the lead concentration in breastmilk and health implication of early life stage exposure to lead among the breastfed infants are warranted.
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•We analyzed mercury and lead in 207 breastmilk collected at 15 and 30days after delivery.•Mercury was detected from 100% of breastmilk with the median of 0. 59μg/L.•Lead was detected in 77 % of breastmilk with the median of 4.71μg/L.•The hazard quotient of lead exceeded 1.0 for 71% of 15days and for 56% for 30days old infants from breastfeeding.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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.
•The highest levels of HHCB and AHTN worldwide were found in breast milk from Korea.•No significant changes in SMCs and BUVSs were found within a month of lactation.•Accumulation features of SMCs and BUVSs were dependent on the consumption patterns of these contaminants.•Estimated daily intakes of SMCs via breast milk were lower than the PTDI.•This study is the first to examine the occurrence of BUVSs in breast milk.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Prenatal exposure to heavy metals is known to be associated with adverse birth outcomes and oxidative stress biomarkers. In this study, we examined whether maternal free cortisol or ...8-Hydroxy-2-Deoxyguanosine (8-OHdG) could mediate associations between maternal heavy metal exposure and birth outcomes. A total of 182 healthy pregnant women were recruited. Heavy metals (including Pb, Hg, and Cd), free-cortisol, and 8-OHdG were analyzed in urine at delivery. Birth outcomes including birth weight, length, Ponderal index, and head circumference were measured. To examine associations of maternal urinary heavy metals with biomarkers and birth outcomes, generalized linear models were employed. Birth length was positively associated with Pb (β = 0.78, 95% CI: 0.09−1.46) and Hg (β = 0.84, 95% CI: 0.23−1.45) (both p < 0.05). The Ponderal index, a measure of a newborn’s leanness, was negatively associated with maternal urinary Pb (β = −0.23, 95% CI: −0.46−−0.07) and Hg (β = −0.26, 95% CI: −0.44−−0.08) (both p < 0.05). No association between maternal Cd and birth outcomes was observed. Most heavy metals showed positive associations with free cortisol and 8-OHdG. Free cortisol was identified as a mediator underlying the observed relationship between Hg and birth length or Ponderal index. This study observed adverse birth outcomes from maternal exposures to Pb and Hg. Increased free cortisol related to Hg exposure was suggested as a possible causal pathway from Hg exposure to birth outcomes such as the Ponderal index.
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.
•No significant changes were found in the PBDE concentrations within a month of lactation after delivery.•Predominance of BDE 153 rather than BDE 47 was found in the most samples.•Corn, seafood and nut correlated significantly with PBDE levels in breast milk.•Estimated daily intake of PBDEs for breast-feeding infants was lower than the guideline proposed by the US EPA.•This is the first comprehensive study to assess infant exposure to PBDEs via breast milk in Korea.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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