Familial chylomicronemia syndrome: case reports of siblings with deletions of the GPIHBP1 gene.

BACKGROUND: Familial chylomicronemia syndrome (FCS) is a rare monogenic form of severe hypertriglyceridemia, caused by mutations in genes involved in triglyceride metabolism. Herein, we report the case of a Korean family with familial chylomicronemia syndrome caused by compound heterozygous deletions of glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1). CASE PRESENTATION: A 4-year-old boy was referred for the evaluation of severe hypertriglyceridemia (3734 mg/dL) that was incidentally detected 4 months prior. His elder brother also demonstrated an elevated triglyceride level of 2133 mg/dL at the age of 9. Lipoprotein electrophoresis revealed the presence of chylomicrons, an increase in the proportion of pre-beta lipoproteins, and low serum lipoprotein lipase levels. The patient's parents and first elder brother had stable lipid profiles. For suspected FCS, genetic testing was performed using the next-generation sequencing-based analysis of 31 lipid metabolism-associated genes, which revealed no pathogenic variants. However, copy number variant screening using sequencing depth information suggested large heterozygous deletion encompassing all the coding exons of GPIHBP1. A real-time quantitative polymerase chain reaction was performed to validate the deletion site. The results showed that the siblings had two heterozygous copy number variants consisting of the whole gene and an exon 4 deletion, each inherited from their parents. During the follow-up period of 17 months, the patient did not develop pancreatitis, following dietary intervention. CONCLUSION: These siblings' case of familial chylomicronemia syndrome caused by rare GPIHBP1 deletions highlight the implementation of copy number variants-beyond next-generation sequencing-as an important consideration in diagnosis. Accurate genetic diagnosis is necessary to establish the etiology of severe hypertriglyceridemia, which increases the risk of pancreatitis.

High intakes of iodine among women during pregnancy and the postpartum period has no adverse effect on thyroid function.

PURPOSE: Given the high consumption of seaweed soup by pregnant and lactating Korean women, concerns have been raised about excessive iodine intake. We evaluated the effects of maternal iodine intake on maternal thyroid function and birth outcomes. We also evaluated iodine intake via seaweed soup during late pregnancy and the early postpartum period. METHODS: A total of 349 pregnant women of the Ideal Breast Milk cohort were recruited in late pregnancy, of whom 302 revisited after delivery. Three-day dietary records were assessed at each visit. Blood was collected for thyroid function test. Obstetrical and birth outcomes were obtained. RESULTS: The median dietary iodine intake was 459 µg/day (interquartile range [IQR] 326.5-647.4 µg/day) during pregnancy. Dietary iodine intake by quartile was not significantly associated with maternal thyroid status, or obstetrical or neonatal outcomes. However, the dietary iodine intake in the early postpartum period was 1759 µg/day (IQR 1026.7-2491.1 µg/day) because of a marked increase in seaweed soup consumption. Of all women, 25.8% consumed seaweed soup more than once over the 3 days of dietary records when pregnant, but the figure rose to 93.4% postpartum. Of postpartum women who consumed seaweed soup daily, the median dietary iodine intakes were 1355, 2394, and 3063 µg/day (soup at one, two, and three-or-four meals). CONCLUSIONS: In these iodine-replete pregnant women, dietary iodine intake during pregnancy showed no effect on maternal thyroid function or birth outcomes. However, iodine intake in the early postpartum period was markedly increased by the frequency of seaweed soup consumption.

Relationship Between the Serum FGF21 Level and Growth in Children of Short Stature.

BACKGROUND: This study investigated the relationship between fibroblast growth factor 21 (FGF21) levels and growth in children with growth hormone deficiency (GHD) and idiopathic short stature (ISS), and the effects of the FGF21 level on response to growth hormone (GH) treatment. METHODS: We included 171 pre-pubertal children with a GHD (n = 54), ISS (n = 46), and normal height (n = 71). Fasting FGF21 levels were measured at baseline and every 6 months during GH treatment. Factors associated with growth velocity (GV) after GH therapy were investigated. RESULTS: The FGF21 level was higher in short children than in the controls without significant difference between the GHD and ISS groups. In the GHD group, the FGF21 level was inversely associated with the free fatty acid (FFA) level at baseline (r = -0.28, P = 0.039), however, was positively correlated with the FFA level at 12 months (r = 0.62, P = 0.016). The GV over 12 months of GH therapy was positively associated with the delta insulin-like growth factor 1 level (ß = 0.003, P = 0.020). The baseline log-transformed FGF21 level was inversely associated with GV with marginal significance (ß = -0.64, P = 0.070). CONCLUSION: The FGF21 level was higher in children of short stature, both those with GHD and the ISS, than in children with normal growth. The pretreatment FGF21 level negatively affected the GV of children with GH-treated GHD. These results suggest the existence of a GH/FFA/FGF21 axis in children.

Investigating factors influencing post-operative growth in pre-pubertal children after adenotonsillectomy.

PURPOSE: To check the change in growth-for-age after adenotonsillectomy in pre-pubertal children and investigate the affecting factors. METHODS: Two hundred and six pediatric patients who underwent adenotonsillectomy by a single surgeon between January 2011 and December 2014 were included for the retrospective cohort study. The z-scores of height-, weight-, and body mass index (BMI)-for-age were measured before adenotonsillectomy and 1 year after the operation. The Korean version of the obstructive sleep apnea-18 questionnaire (OSA-18), symptom questionnaire, physical examinations, demographic data, and pre-operative z-scores were used to analyze the factors affecting z-score change. RESULTS: Among 206 pediatric patients, 167 patients were normal growth; 19 were undergrowth; and 20 were obese. After the operation, height, weight, and BMI z-scores all increased both in 167 normal-growth patients and 19 undergrowth patients (p value < 0.05). However, in 20 obese patients, only height z-score significantly increased (p value = 0.028). The multiple regression test showed that the sleep disturbance domain of OSA-18 was positively correlated with height z-score change (p value = 0.041), and age was negatively correlated with weight z-score change (p value = 0.016). Pre-operative BMI z-score was negatively correlated (p value = 0.019) and adenoid grade was positively correlated (p value = 0.023) with BMI z-score change. CONCLUSIONS: These findings suggest that adenotonsillectomy may positively affect growth in pre-pubertal children, without undesirable weight gain. Additionally, the sleep disturbance domain of OSA-18 may play a role in predicting post-operative height increase in pre-pubertal children.

Dietary patterns are associated with attention-deficit hyperactivity disorder (ADHD) symptoms among preschoolers in South Korea: a prospective cohort study.

OBJECTIVES: Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurobehavioral disorder in children. There are limited studies for diet or dietary supplement effects on ADHD in preschool children in Asia. This study aimed to determine the association between dietary patterns in 4-year-old children and ADHD symptoms in 6-year-old children. METHODS: We estimated dietary intake in 4-year-old children using a food frequency questionnaire. Using 33 food groups, major dietary patterns were identified in relation to the consumption of sweets, vegetables, meats, and carbohydrates. Parents of 6-year-old children used the Korean version of the ADHD Rating Scale for ADHD symptom assessment. RESULTS: A sweet dietary pattern was associated with a higher risk of attention deficit (AD) (relative risk [RR], 1.34; confidence interval [CI], 1.17-1.55), hyperactivity (RR, 1.40; CI, 1.19-1.64), and ADHD symptoms (RR, 1.37; CI, 1.23-1.52). A vegetable dietary pattern was associated with a lower risk of ADHD symptoms (RR, 0.81; CI, 0.72-0.90). Food item analysis of the sweet dietary pattern showed that intake scores for chocolate, chips, and fruit jams positively correlated with AD, hyperactivity, and ADHD symptoms. DISCUSSION: These findings can be useful to further understand the roles of dietary factors in ADHD.

Association Between Sleep Duration and Intelligence Quotient in 6-Year-Old Children.

BACKGROUND: Sufficient sleep during childhood is important for cognitive functions such as learning and successful school performance. This study aimed to investigate the effects of sleep duration on the intelligence quotient (IQ) of 6-year-old children and aimed to analyze whether these effects differed by sex. METHODS: The IQ of 538 6-year-old Korean participants from the cohort study, "The Environment and Development of Children," was measured during follow-up using the Korean Educational Developmental Institute's Wechsler Intelligence Scale for Children. The total, verbal, and performance IQ scores were evaluated. The relationship between sleep duration and IQ scores after adjusting for maternal age, maternal educational level, maternal occupation, maternal IQ, exposure to secondhand smoking, gestational age, and monthly age and birth season was also assessed. RESULTS: Longer sleep duration was significantly associated with improved verbal IQ measures (ß 0.55; p value 0.030). After stratifying participants by sex, a significant association was observed between sleep duration and total, verbal, and performance IQ scores in boys (total IQ 2.49, p value 0.012; verbal IQ 0.75, p value: 0.037; performance IQ 0.73, p value 0.048), but not in girls. CONCLUSIONS: The results indicated that only boys show a significant association between IQ scores and sleep duration. These findings support the hypothesis that sleep duration is associated with IQ, in a sex dependent manner. Future studies are needed for a thorough evaluation of the connection between sleep duration and health outcome in young children.

Thyroid nodules in childhood-onset Hashimoto's thyroiditis: Frequency, risk factors, follow-up course and genetic alterations of thyroid cancer.

OBJECTIVE: We evaluated the frequency, risk factors and the follow-up outcomes of thyroid nodules, and genetic alterations in thyroid cancer, in youth with childhood-onset Hashimoto thyroiditis (HT) residing in an iodine-sufficient country. DESIGN: A retrospective cohort study. PATIENTS AND MEASUREMENTS: A total of 213 patients (194 females, mean age 10.6 years at the time of HT diagnosis) were ultrasonographically evaluated. Thyroid nodules were categorized using the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) and the American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TI-RADS). RESULTS: Thyroid nodules were detected in 40 (18.8%) patients over a median follow-up period of 3.4 years, usually after the onset of puberty. A family history of thyroid disease (hazard ratio 2.1, p = .031) was predictive of thyroid nodule detection. Papillary thyroid carcinoma (PTC) was diagnosed in 9 (4.2% of all and 22.5% of nodule-positive patients). The malignant nodules had a higher K-TIRADS or ACR-TI-RADS risk level compared with benign nodules (p < .01 for both). Genetic alterations were revealed in 7 (BRAFV600E in 6 and RET-ERC1 fusion in 1) of the eight available tumour tissue samples. None showed evidence of disease over a median follow-up period of 3.4 years. CONCLUSIONS: The nodule detection rate was 18.8%, with a 22.5% risk of malignancy among the detected nodules in childhood-onset HT patients, showing increased risk in those with a family history. Additional large-scale studies are required to evaluate the usefulness of K-TIRADS or ACR-TI-RADS risk level for the differentiation of paediatric thyroid nodules.

Recombinant growth hormone therapy in children with Turner Syndrome in Korea: a phase III Randomized Trial.

BACKGROUND: Short stature is the most consistent characteristic feature of Turner syndrome (TS). To improve final heights of children with TS effectively, it is important to provide them with early and appropriate treatment using growth hormone (GH). The objective of this study was to assess the efficacy and safety of a new recombinant human GH, Growtropin®-II (DA-3002, Dong-A ST Co., Ltd) versus a comparator (Genotropin®, Pfizer Inc.) for Korean children with TS. METHODS: This open-label, active-controlled, parallel-group, randomized controlled phase III trial was conducted at 11 hospitals in Korea. Eligible patients (n = 58) were randomized to two groups: 1) DA-3002 group (administrated with DA-3002 at 0.14 IU [0.0450-0.050 mg] /kg/day); and 2) comparator group (administrated with the comparator at 0.14 IU [0.0450-0.050 mg] /kg/day). RESULTS: The change from baseline in annualized height velocity (HV) after a 52-week treatment period was 4.15 ± 0.30 cm/year in the DA-3002 group and 4.34 ± 0.29 cm/year in the comparator group. The lower bound of 95% two-sided confidence interval for group difference in the change of annualized HV (- 1.02) satisfied the non-inferiority margin (- 1.5). The change in height standard deviation score (HtSDS) at 52-week was 0.70 ± 0.23 for the DA-3002 group and 0.66 ± 0.39 for the comparator group, showing no significant (p = 0.685) difference between the two groups. The change of skeletal maturity defined as change in bone age/change in chronological age between the two groups was not significantly different (1.25 ± 0.58 for the DA-3002 group and 1.47 ± 0.45 for the comparator group, p = 0.134). Changes from baseline in serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) after 52 weeks of treatment did not differ significantly between the two groups (p = 0.565 and p = 0.388, respectively) either. The occurrence of adverse events was not statistically different between groups. CONCLUSIONS: This study demonstrates that the efficacy and safety of GH treatment with DA-3002 in children with TS are comparable with those of the comparator. It is expected to analysis the long-term effect of DA-3002 on the increase of final adult height in children with TS and possible late-onset complications in the future. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov. ClinicalTrials.gov identifier: NCT01813630 (19/03/2013).

Impact of very preterm birth and post-discharge growth on cardiometabolic outcomes at school age: a retrospective cohort study.

BACKGROUND: Adverse metabolic outcomes later in life have been reported among children or young adults who were born as preterm infants. This study was conducted to examine the impact of very preterm/very low birth weight (VP/VLBW) birth and subsequent growth after hospital discharge on cardiometabolic outcomes such as insulin resistance, fasting glucose, and systolic and diastolic blood pressure (BP) among children at 6-8 years of age. METHODS: This retrospective cohort study included children aged 6-8 years and compared those who were born at < 32 weeks of gestation or weighing < 1,500 g at birth (n = 60) with those born at term (n = 110). Body size, fat mass, BP, glucose, insulin, leptin, adiponectin, and lipid profiles were measured. Weight-for-age z-score changes between discharge and early school-age period were also calculated, and factors associated with BP, fasting glucose, and insulin resistance were analyzed. RESULTS: Children who were born VP/VLBW had significantly lower fat masses, higher systolic BP and diastolic BP, and significantly higher values of fasting glucose, insulin, and homeostatic model assessment of insulin resistance (HOMA-IR), compared to children born at term. VP/VLBW was correlated with HOMA-IR and BPs after adjusting for various factors, including fat mass index and weight-for-age z-score changes. Weight-for-age z-score changes were associated with HOMA-IR, but not with BPs. CONCLUSIONS: Although children aged 6-8 years who were born VP/VLBW showed significantly lower weight and fat mass, they had significantly higher BPs, fasting glucose, HOMA-IR, and leptin levels. The associations of VP/VLBW with cardiometabolic factors were independent of fat mass and weight gain velocity.

Autonomic Dysfunction is Associated with Increased Cardiometabolic Risk in Patients with Childhood-Onset Craniopharyngioma.

Patients with craniopharyngioma are susceptible to autonomic dysfunction as a result of hypothalamic damage. We evaluated indices of heart rate variability (HRV) in patients with childhood-onset craniopharyngioma to investigate autonomic function and its relationship with components of the metabolic syndrome (MetS). This cross-sectional, case-only study included 53 patients (10-30 years of age). We measured the standard deviation of all normal R-R intervals (SDNN) and total power indicating overall HRV, the root-mean square of the difference of successive R-R intervals (RMSSD) and high frequency indicating parasympathetic modulation, and low frequency. These indices were compared according to the presence of the MetS. During the mean 10.8 years of follow-up, 25% of patients were diagnosed with the MetS. Patients with the MetS showed significantly lower levels of SDNN (29.0 vs. 40.6 ms), total power (416.1 vs. 1129.6 ms2), RMSSD (20.1 vs. 34.5 ms), high frequency (94.7 vs. 338.5 ms2), and low frequency (94.5 vs. 289.4 ms2) than those without (p <0.05, for all). Individual components of the MetS including insulin resistance, serum triglycerides levels, and systolic blood pressure were inversely associated with SDNN, total power, RMSSD and high frequency. Higher overall variability and parasympathetic modulation were related to decreased odds ratios for having the MetS (OR 0.91, p=0.029 for SDNN; OR 0.91, p=0.032 for total power). In conclusion, autonomic dysfunction, as evidenced by reduced HRV indices, is associated with increased cardiometabolic risk in patients with childhood-onset craniopharyngioma.

Prenatal exposure to di-(2-ethylhexyl) phthalate and decreased skeletal muscle mass in 6-year-old children: A prospective birth cohort study.

BACKGROUND/AIM: Phthalate is a well-known endocrine-disrupting chemical that has anti-androgenic effects. Although there are several studies on the relationship between body composition and phthalate, studies that investigated the effects of phthalate on skeletal muscle during childhood are lacking. METHODS: We analyzed data from 481 mother-and-child pairs enrolled in the Environment and Development of Children cohort in South Korea. We examined the association between phthalate metabolites (mono [2-ethyl-5-hydroxyhexyl] phthalate [MEHHP], mono [2-ethyl-5-oxohexyl] phthalate [MEOHP], molar sum of MEHHP and MEOHP [Σ DEHP], and mono-n-butyl phthalate [MnBP]) in prenatal maternal urine and children's urine at the age of 6, and body composition indices (body mass index [BMI] z-score, percentage of fat mass, fat mass index, percentage of skeletal muscle, and the skeletal muscle index [SMI]) measured when the child was 6 years using a bioelectrical impedance analyzer. RESULTS: A 2-fold increase in Σ DEHP and MnBP in the prenatal maternal urine was significantly associated with a -0.07 unit (95% CI: -0.11, -0.03) and -0.09 unit (95% CI: -0.14, -0.03) change in SMI, respectively, in 6-year old girls alone. BMI z-score was also negatively associated with a 2-fold increase in MEHHP and MnBP in prenatal maternal urine as -0.11 unit (95% CI: -0.22, -0.01) and -0.15 unit (95% CI: -0.28, -0.02) change, respectively, only among girls. Among boys, phthalate metabolites in the prenatal and children's urine were not significantly associated with any body composition indices. CONCLUSIONS: Our longitudinal study shows that high levels of prenatal exposure to phthalates are significantly associated with decreased SMI among girls. We can postulate that anti-androgenic effects of phthalates during pregnancy may affect girl offspring's muscle growth.

Residential pyrethroid insecticide use, urinary 3-phenoxybenzoic acid levels, and attention-deficit/hyperactivity disorder-like symptoms in preschool-age children: The Environment and Development of Children study.

Previous animal studies have reported that pyrethroids can cause dopamine system abnormalities and attention-deficit/hyperactivity disorder (ADHD) phenotypes. However, epidemiological studies investigating the associations between pyrethroid exposure and ADHD are limited. We aimed to investigate the association between pyrethroid exposure and ADHD-like symptoms among preschool-age children. We used data from 385 children at 4 years of age participating in the Environment and Development of Children (EDC) study. We evaluated pyrethroid exposure through questionnaires and urinary 3-phenoxybenzoic acid (3-PBA) concentrations. We assessed ADHD-like symptoms using the Korean ADHD rating scale (K-ARS). We conducted negative binomial regressions to evaluate the associations between pyrethroid exposure and ADHD-like symptoms. Residential use of insecticide adhesive (ß = 0.42, 95% CI: 0.11, 0.74) and insecticide spray (ß = 0.33, 95% CI: 0.08, 0.59) was associated with an increase in log-transformed creatinine-adjusted urinary 3-PBA concentrations. Residential insecticide adhesive use was associated with a 51.6% increase in K-ARS scores (95% confidence interval [CI]: 6.3, 116.1) among boys, when compared with non-users. When compared with creatinine-adjusted 3-PBA levels <0.50 µg/g creatinine, creatinine-adjusted 3-PBA levels ≥3.80 µg/g creatinine were associated with a 58% increase in K-ARS scores (95% CI: 0.1, 150.5) among boys. We found associations of residential pyrethroid insecticide use and urinary 3-PBA concentrations with K-ARS scores among preschool-age boys. Since the present study explored cross-sectional associations in preschool-age children, the possibility of reverse causality cannot be dismissed. Further studies implementing a cohort study design are warranted.

A Case of Consumptive Hypothyroidism in a 1-Month-Old Boy with Diffuse Infantile Hepatic Hemangiomas.

Consumptive hypothyroidism is a rare paraneoplastic syndrome characterized by excessive inactivation of the thyroid hormones due to increased type 3 iodothyronine deiodinase activity of tumors. We report the case of severe consumptive hypothyroidism in a 1-month-old boy with infantile hepatic hemangiomas who presented with cardiac failure and cholestasis. Diffuse infiltration of hepatic hemangiomas was detected on abdominal imaging studies, and thyroid function screening test revealed severe hypothyroidism, which necessitated the administration of higher-than-usual doses of levothyroxine for the normalization of thyroid function. The patient was successfully treated with propranolol, prednisolone, and levothyroxine, and he showed normal thyroid function at 3 months of age and normal neurodevelopment at 9 months of age. This case highlights the importance of early recognition and prompt management of consumptive hypothyroidism in patients with infantile hepatic hemangiomas.

A 9-year-old Korean girl with Fontaine progeroid syndrome: a case report with further phenotypical delineation and description of clinical course during long-term follow-up.

BACKGROUND: Gorlin-Chaudhry-Moss syndrome (GCMS) and Fontaine-Farriaux syndrome (FFS) are extremely rare genetic disorders that share similar clinical manifestations. Because a de novo missense mutation of the solute carrier family 25 member 24 (SLC25A24) gene was suggested to be the common genetic basis of both syndromes, it has been proposed recently that they be integrated into a single disorder under the name of Fontaine progeroid syndrome (FPS). CASE PRESENTATION: A 9-year-old Korean girl presented with typical clinical features of FPS. She had generalized loose skin with decreased subcutaneous fat, skin wrinkling on the forehead and limbs, skull deformities and a peculiar facial appearance with microphthalmia and midface hypoplasia, anomalies of the digits and nails, a large umbilical hernia and a nearly normal developmental outcome. She exhibited prenatal and postnatal growth retardation together with short stature, and records showed that her height and weight were invariably under - 2.0 SD from birth to the age of 10 years. SLC25A24 analysis revealed a heterozygous mutation reported previously, NM_013386:c.650G > A, p.[Arg217His]. After screening her family for the identified mutation, she was confirmed as being a de novo case of FPS caused by an SLC25A24 mutation. CONCLUSION: We describe a Korean girl with typical clinical findings of FPS and a de novo mutation in SLC25A24, as well as 10 years of clinical follow-up, including growth and developmental achievements.

Relationship between systolic hypertension assessed by 24-hour ambulatory blood pressure monitoring and aortic diameters in young women with Turner syndrome.

OBJECTIVE: Patients with Turner syndrome (TS) are at high risk for cardiovascular morbidity and mortality due to aortic dilation. We evaluated the prevalence of hypertension and its risk factors and investigated the relationship between systolic hypertension and aortic diameter in young patients with TS. DESIGN: Observational, cross-sectional study. PATIENTS AND MEASUREMENTS: Forty-two patients with TS (15-35 years) who had achieved final adult heights underwent 24-h ambulatory blood pressure monitoring (ABPM). Fasting glucose, insulin and lipid profiles were measured. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Echocardiography was performed to evaluate aortic diameters (aortic annulus, aortic root at the sinuses of Valsalva, sinotubular junction and ascending aorta), which were converted into Turner-specific z-scores. RESULTS: Systolic and/or diastolic hypertension was identified in 71.4% (n = 30) of patients, as assessed by 24-hour ABPM. Twenty-eight patients (66.7%) were nondippers. Patients with systolic hypertension (n = 8, 19.0%) had a higher weight, waist circumference and HOMA-IR levels than those without hypertension (P < 0.05 for all). After adjusting for covariates, HOMA-IR was independently associated with systolic hypertension (odds ratio 10.1, P = 0.043). After adjusting for age and bicuspid aortic valve, systolic hypertension was independently related to increased aortic diameter at the aortic annulus (ß = 1.064, P = 0.009) and sinotubular junction (ß = 1.124, P = 0.016). CONCLUSIONS: Hypertension is highly prevalent and independently associated with IR in young patients with TS. The significant relationship between systolic hypertension and aortic diameters underscores the importance of BP and IR control.

The relationship of urinary 3-phenoxybenzoic acid concentrations in utero and during childhood with adiposity in 4-year-old children.

BACKGROUND: Pyrethroid pesticides are reported to be the most commonly used residential insecticides worldwide. We aimed to investigate the relationship between prenatal and postnatal 3-phenoxybenzoic acid (3-PBA) concentrations, and growth and adiposity parameters in 4-year-old children. METHOD: We obtained data from 578 children who participated in the prospective Environment and Development of Children (EDC) study at around 4 years of age (45-55 months) between August 2008 and July 2011. Anthropometric measurements were obtained at age 4 years. Prenatal and postnatal urinary 3-PBA concentration was measured in maternal urine samples at around 20 weeks of gestation, and in the 4-year-old children, respectively. RESULT: The detection frequency of urinary 3-PBA (geometric mean concentration) was 98-99% (0.98 µg/g Cr) in maternal urine, and almost 99-100% (1.34 µg/g Cr) in 4-year-old children. Prenatal urinary3-PBA concentration was not associated with height, weight, or body mass index (BMI) z-scores at 4 years of age, regardless of sex. Postnatal urinary3-PBA concentration was not related to height z-scores, but was positively associated with weight z-scores with marginal significance among only girls (p = 0.058). Analyzed by sex, there was a significant relationship between postnatal urinary 3-PBA concentration and BMI z-scores (p = 0.015) among girls, after adjusting for covariates. CONCLUSION: Childhood urinary 3-PBA concentration measured at 4 years of age was positively associated with BMI z-scores in 4-year-old girls, but prenatal urinary 3-PBA concentration at midterm pregnancy exhibited no association.

The effects of maternal and children phthalate exposure on the neurocognitive function of 6-year-old children.

The primary purpose of this study was to investigate the effects of phthalate exposure on the intelligence and attentional performance of 6-year old children when adjusting each other as covariates. We also investigated the differential effects of phthalate exposure on the intelligence and attention according to exposure period (maternal or children). Urine concentrations of mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-n-butyl phthalate (MBP) were analyzed. Multivariable linear regression models were used to investigate the relationship between exposure to various phthalates with IQ scores and continuous performance test (CPT) variables. There were robust associations between child MEHHP and MEOHP levels with full scale IQ (FSIQ) even after adjusting for demographic variables and CPT scores (MEHHP -9.27, 95% CI: -17.25, -1.29; MEOHP -9.83, 95% CI: -17.44, -2.21). Child MEHHP and MEHOP levels negatively affected omission errors (MEHHP -20.36, 95% CI: -34.17, -6.55; MEOHP -18.93, 95% CI: -32.58, -5.28) and the response time variability (MEHHP -21.07, 95% CI: -39.04, -3.10; MEOHP -20.41, 95% CI -38.14, -2.69) of the CPT after adjusting for demographic variables and IQ. Maternal phthalate exposure had no effects on IQ or CPT variables. These results suggest that children phthalate exposure, but not maternal exposure, has an adverse effect on IQ and attentional performance, and these associations were found to be independent of each other.

Prenatal and postnatal bisphenol A exposure and social impairment in 4-year-old children.

BACKGROUND: Prenatal and postnatal exposure to bisphenol A (BPA) may affect early brain development. Rodent studies suggest that prenatal and postnatal neurodevelopmental toxicity from BPA exposure may manifest as social deficits in offspring. We investigated the association between prenatal and postnatal exposure to BPA and social impairments in a sample of 4-year-old children. METHODS: We recruited second-trimester pregnant women between 2008 and 2011, and measured their creatinine-adjusted prenatal urine BPA levels. In 2014-2015, a subset of 4-year-old children born to these women underwent neurobehavioral assessment and physical examination. We collected urine and blood from the children and assessed social impairments, including deficits in social interaction, social communication, and other behavior patterns using the Korean version of the Social Communication Questionnaire (K-SCQ) (n = 304). We examined social impairments associated with prenatal exposure at mid-term pregnancy and postnatal exposure to BPA at 4 years of age, using linear and piecewise linear regression models. RESULTS: The relationship between prenatal BPA exposure and social communication was non-linear and statistically significant at or above the flexion point for BPA levels of 3.0 µg/g creatinine in girls (58.4%, 95% confidence interval [CI], 6.5% to 135.8%). Each 2-fold increase in postnatal BPA exposure was significantly associated with an 11.8% (95% CI, 0.6% to 24.3%) increase in impairment in social communication in 4-year old girls, as indicated by the linear regression model. CONCLUSION: Prenatal and postnatal BPA exposure is associated with social impairment at 4 years of age, particularly in girls.

Contributions of CAG repeat length in the androgen receptor gene and androgen profiles to premature pubarche in Korean girls.

The CAG repeat length of the androgen receptor (AR) gene, which exhibits an inverse relationship to AR sensitivity, might influence the development of the pubarche along with hyperandrogenemia. There are ethnic differences in the AR CAG repeat length, however, no Asian studies on premature pubarche (PP) have been reported, including Korea. Our objectives were to examine the hormone levels and AR CAG repeat length, and to assess their contributions to PP in Korean girls. Subjects with PP (n=16) and normal pubarche (NP, n=16), and normal controls (NC, n=16) were enrolled. The levels of dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEAS), 17-hydroxyprogesterone (17-OHP), and free testosterone (FT) were checked. The methylation-weighted (MW) average CAG repeat lengths were analyzed. The median ages at pubarche were 7.4 and 8.9 years in the PP and NP groups, respectively, and the levels of 17-OHP, DHEAS, and FT were similar in both groups. The PP group exhibited a higher DHEAS:DHEA ratio than the NP group (P=0.014). The medians of the MW average CAG repeat length of the AR gene were 22.4 for all subjects and did not differ among the PP (22.3), NP (22.4), and NC (22.2) groups. The AR CAG repeat lengths in the PP and NP groups did not correlate with DHEAS or FT levels. These results suggest that the AR CAG repeat length was not involved in the development of PP in Korean girls. However, excessive adrenal androgen levels, particularly those caused by increased sulfotransferase activity, might be important in the pathogenesis of PP.