Eunsook Suh

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.

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.

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.

Exposure to lead and mercury through breastfeeding during the first month of life: A CHECK cohort study

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 Childrens 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.

Clinical characteristics of 2009 pandemic influenza A (H1N1) infection in children and the performance of rapid antigen test

Purpose In autumn 2009, the swine-origin influenza A (H1N1) virus spread throughout South Korea. The aims of this study were to determine the clinical characteristics of children infected by the 2009 H1N1 influenza A virus, and to compare the rapid antigen and real-time polymerase chain reaction (PCR) tests. Methods We conducted a retrospective review of patients ≥18 years of age who presented to Soonchunhyang University Hospital in Seoul with respiratory symptoms, including fever, between September 2009 and January 2010. A real-time PCR test was used to definitively diagnose 2009 H1N1 influenza A infection. Medical records of confirmed cases were reviewed for sex, age, and the time of infection. The decision to perform rapid antigen testing was not influenced by clinical conditions, but by individual factors such as economic conditions. Its sensitivity and specificity were evaluated compared to real-time PCR test results. Results In total, 934 patients tested positive for H1N1 by real-time PCR. The highest number of patients (48.9%) was diagnosed in November. Most patients (48.2%) were aged between 6 and 10 years. Compared with the H1N1 real-time PCR test results, the rapid antigen test showed 22% sensitivity and 83% specificity. Seventy-eight patients were hospitalized for H1N1 influenza A virus infection, and fever was the most common symptom (97.4%). Conclusion For diagnosis of 2009 H1N1 influenza A virus infection, the rapid antigen test was inferior to the real-time PCR test in both sensitivity and specificity. This outcome suggests that the rapid antigen test is inappropriate for screening.

Urinary phthalate metabolites over the first 15 months of life and risk assessment – CHECK cohort study

Phthalates are important group of endocrine disruptors. Infants and young children are susceptible to phthalate exposure. However, information on the phthalate exposure during the early stages of life is very limited. This study was conducted to understand the temporal trend of exposure to major phthalates among infants of Korea during the first 15months after birth, and to estimate associated risks. A total of 286 urine samples were collected from 171 children at 3, 9, 12, or 15months of age, with 77 children sampled for two or more times. Four phthalates, i.e., di(2-ethylhexyl) phthalate (DEHP), di-isobutyl phthalate (DiBP), di-n-butyl phthalate (DnBP), and diethyl phthalate (DEP) were chosen, and their major metabolites were analyzed in the urine. The DEHP metabolites were detected in 100% of the urine samples at relatively higher levels compared to those reported in other countries. The levels of mono-ethyl phthalate (MEP) were generally lower. Urinary concentrations of most phthalate metabolites, especially DEHP metabolites, increased as children grew older. Intra-class correlation coefficients (ICCs) calculated for DEHP metabolites over time were high (0.7-0.8), suggesting persistence of consistent exposure sources during this sensitive period of life. Hazard quotient (HQ) and hazard index (HI) were calculated from daily intake estimates divided by recommended toxicity thresholds. Among the study population, 4, 16, and 26% of the children showed HI >1 at 9, 12, and 15months of age, respectively. DEHP exposure explained most of the risk estimates. Considering vulnerability of young children to endocrine disruption, efforts to identify sources of exposure and to develop appropriate mitigation options are warranted.