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The aim of this study is to examine the association between transplacental exposure to dioxins/polychlorinated biphenyls (PCBs) and thyroid and growth hormones in newborns. We recruited 118 pregnant women, between 25 and 34 years of age, at the obstetric clinic. Personal data collected included reproductive and medical histories and physical factors. Clinicians gathered placental and umbilical cord serum upon delivery and carefully scored the 118 newborns, making both structural and functional assessments. We analyzed placentas for 17 polychlorinated dibenzo-p-dioxins and dibenzofurans and 12 dioxin-like PCB congeners with the World Health Organization–defined toxic equivalent factors, and six indicator PCBs by high-resolution gas chromatography and high-resolution mass spectrometry. We analyzed thyroid and growth hormones from cord serum using radioimmunoassay. Insulin-like growth factor (IGF)-1, IGF-binding globulin-3, and thyroxine × yroid-stimulating hormone (T4 × TSH) were significantly associated with increased placental weight and Quetelet index (in kilograms per square meter; correlation coefficient r = 0.2–0.3; p < 0.05). Multivariate analyses showed independently and significantly decreased free T4 (FT4) × TSH with increasing non-ortho PCBs (r = −0.2; p < 0.05). We suggest that significant FT4 feedback alterations to the hypothalamus result from in utero exposure to non-ortho PCBs. Considering the vast existence of bioaccumulated dioxins and PCBs and the resultant body burden in modern society, we suggest routine screening of both thyroid hormone levels and thyroid function in newborns.

Postnatal exposure to dioxins in breastfed infants occurs mainly during breast-feeding. The exposure to a substantial amount of endocrine disruptors in the early days of life may cause long-term health effects. Test subjects were healthy and primiparous mothers with a mean age of 28 (S.D. = 3.8) in 2001. The PCDD/F congeners were analyzed in the breast milk using gas chromatograph/high resolution mass spectrometry. The mean level of PCDD/Fs was 7.4 pg-WHO-TEQ/g lipid, which is significantly lower than the level found in individuals from other countries. The total PCDD WHO-TEQ levels in breast milk had a significant positive association with maternal age and a slightly negative association with perinatal BMI (body mass index of the period before and after the delivery). The estimated daily intake of 10.5 pg-WHO-TEQ/kg/day from individual breast milk was predicted for a breastfed infant at 6 months of age with proper assumption of 8 kg body weight, 854 g milk per day of consumption, 95% of dioxin absorption rate, and linear decline of dioxin during lactation. Based on the lower WHO-TEQ levels in the breast milk, breast-feeding should still be encouraged and continued in Taiwan.

We describe two siblings with generalized hypotonia, expressive language delay, developmental delay, mild facial dysmorphism, and accelerated growth. In addition, the male sibling had testis dysgenesis. Cytogenetic evaluation revealed an unbalanced maternally inherited translocation t(15;22)(q26;q13.3) resulting in partial monosomy 22q and trisomy 15q. The combination of deletion 22q and duplication 15q has not been described previously.

In Taiwan, the prevalence of obesity in children is increased 1.5 folds in the last decade. Exposure to endocrine disruptor, such as phthalates, could affect endocrine system and adipokine secretio...

Phthalate acid esters (PAEs) are widely used as plasticizers in many daily used products. Although some evidence of its reproductive effects has been shown, however; pubertal development effects fr...

Background: Few studies have examined the association between environmental phthalate exposure and children’s neurocognitive development, especially in birth cohort follow-up studies. Objectives: W...

In utero exposure to phthalates may adversely affect reproductive development in children due to the anti-androgenic properties of the pthalates. Accordingly, we aimed to determine the effects of in utero and environmental phthalate exposure on the reproductive development of eight-year-old children. We recruited 180 children in central Taiwan during November 2001 and followed them until August 2009 when all children became eight years old. Birth outcomes were collected. Bone age, hormone concentrations, and reproductive developmental stages were determined. Phthalate metabolite levels, including mono-2-ethylhexyl phthalate [MEHP], mono-n-butyl phthalate [MnBP], and mono-benzyl phthalate [MBzP], were assessed. No significant gender differences were found in in utero phthalate exposure. Maternal urinary levels of phthalate metabolites did not correlate significantly with birth outcomes, physical characteristics, and reproductive hormones of the eight-year-old children. Regarding the urinary phthalate metabolite levels of the eight-year-old children, MEHP correlated significantly with serum progesterone levels. MEHP levels in girls correlated significantly with serum progesterone levels. MnBP correlated significantly with serum FSH in all children. In girls, MnBP correlated with serum FSH, and MBzP correlated with serum progesterone and FSH levels. Urinary phthalate metabolite levels did not correlate with female developmental stages or the development of female reproductive organs. Phthalate metabolites did not correlate with the physical characteristics and reproductive hormones in boys. Therefore, environmental exposure to phthalates, as determined by urinary phthalate metabolite levels of eight-year-old children, may affect reproductive hormone levels in children, indicating that further studies on the environmental health effects of phthalates are warranted.

Phthalate esters are widely used plasticizers that are present in many daily used products. Although some of their reproductive effects have been reported, pubertal development effects from prenatal exposure to phthalates awaits further investigations. A population based birth cohort was established (N=437 at baseline) with maternal exposure to phthalates assessed in urine collected at the third trimester of pregnancy in 2001 and 2002. Their 133 children with prenatal phthalates exposure were followed up for the outcomes of pubertal development by sequential physical examinations at eight and 11 years old in 2009 and 2012. Urinary concentrations of major phthalate metabolites (i.e., mono-2-ethylhexyl phthalate [MEHP], mono-(2-ethyl-5-hydroxyhexyl) phthalate [MEHHP], mono-(2-ethyl-5-oxohexyl) phthalate [MEOHP], mono-butyl phthalate [MBP], mono-benzyl phthalate [MBzP], monomethyl phthalate [MMP], and mono-ethyl phthalate [MEP]) were determined using liquid chromatography linked to tandem mass spectrometry. The reproductive development measurements included bone age (for both genders), testicle size (for boys), uterus size, and ovarian volume (for girls). We reported results of 133 children with complete data by applying generalized estimating equations for the repeated continuous outcomes. After controlling for Tanner stage, we detected a significant association between reduced uterus size and increasing phthalate exposure in the 2(nd) tertile relative to the 1st tertile of creatinine-corrected MEHP (B=-0.40; 95% C.I.: -0.73, -0.07, relative to the 1st tertile) and total DEHP (B=-0.39, 95% C.I.:-0.66, -0.01 for the 2nd tertile and B=0.34, 95% C.I.: -0.67, -0.01 for the 3rd tertile, relative to the 1st tertile) with a linear trend among girls. MBzP was also found negatively associated with bone age/chronological age ratio (B=-0.07, 95% CI: -0.13, -0.01 for the 3rd tertile, relative to the 1st tertile) with a linear trend for girls. We found no evidence of an association between phthalate exposure and ovarian volume or testicle size. This analysis suggests phthalate exposure may affect specific pubertal development characteristics in human beings. Further studies with larger sample sizes and longer follow-up period are warranted.

Background: Few studies have shown an association between prenatal phthalate exposure and adverse effects on neurodevelopment and behavior in young children. Objectives: We aimed to assess the relationship between prenatal exposure to phthalate esters and behavior syndromes in children at 8 years of age. Methods: A total of 122 mother–child pairs from the general population in central Taiwan were studied from 2000 to 2009. Mono-methyl phthalate (MMP), mono-ethyl phthalate (MEP), mono-butyl phthalate (MBP), mono-benzyl phthalate (MBzP), and three di-(2-ethylhexyl) phthalate (DEHP) metabolites—mono-2-ethylhexyl, mono-2-ethyl-5-hydroxyhexyl, and mono-2-ethyl-5-oxohexyl phthalates (MEHP, MEHHP, and MEOHP)—were measured in maternal urine collected during the third trimester of pregnancy using liquid chromatography–electrospray ionization–tandem mass spectrometry. Behavioral syndromes of children at 8 years of age were evaluated using the Child Behavior Checklist (CBCL). Associations between log10-transformed creatinine-corrected phthalate concentrations and standardized scores of the CBCL were estimated using linear regression models or multinomial logistic regressions with adjustments for potential confounders. Results: Externalizing problem scores were significantly higher in association with a 1-unit increase in log10-transformed creatinine-corrected concentrations of maternal MBP (β = 4.29; 95% CI: 0.59, 7.99), MEOHP (β = 3.74; 95% CI: 1.33, 6.15), and MEHP (β = 4.28 ; 95% CI: 0.03, 8.26) after adjusting for the child’s sex, intelligence, and family income. Meanwhile, MBP and MEOHP were significantly associated with Delinquent Behavior and Aggressive Behavior scores. The same pattern was found for borderline and/or clinical ranges. Conclusions: Our findings suggest positive associations between maternal DEHP and dibutyl phthalate (DBP) exposure and externalizing domain behavior problems in 8-year-old children. Citation: Lien YJ, Ku HY, Su PH, Chen SJ, Chen HY, Liao PC, Chen WJ, Wang SL. 2015. Prenatal exposure to phthalate esters and behavioral syndromes in children at 8 years of age: Taiwan Maternal and Infant Cohort Study. Environ Health Perspect 123:95–100; http://dx.doi.org/10.1289/ehp.1307154

Taiwan is an emerging industrial country in subtropical Asia with a population of 23 million. There were around 200,000 newborns in 2011. Delayed first marriage, low birth rate, and rapid aging are major demographic issues. Genetic counseling services were established following the rapid introduction of genetic technology and enactment of relevant laws and regulations. Ultrasound was first used in 1968 to examine pregnant women. The first amniotic fluid laboratory was founded in 1981 to identify chromosomal abnormalities. In 1984, the Genetic Health Act was legislated for prevention and control of genetic disorders, and the metabolic disorder screen project was launched. National Health Insurance with overall coverage of prenatal examinations was established in 1995. A master-level genetic counseling program was launched in 2003 and by 2011 has graduated eighty students. Two professional societies have been formed to certify genetic counselors, and 66 professionals have been certified. In summary, genetic counseling services in Taiwan are continuously improving.

Background and Aims: Neonates are exposed to high levels of di-(2-ethylhexyl) phthalate (DEHP) through numerous medical procedures in the neonatal intensive care unit (NICU). Our aim is to assess t...

Background and Aims: Thyroid hormone is essential for development of pre-pubertal children. Toxicological evidence shows the probable thyroid-like function of some phthalates in vitro and in vivo, ...

Myotubular myopathy is a rare congenital disease characterized by hypotonia and respiratory compromise at birth in affected males. It causes high neonatal mortality. Most surviving newborns need prolonged ventilation and have significantly delayed motor development. Although all patients with congenital myotubular myopathy have respiratory problems such as atelectasis and recurrent lung infections, concurrent neonatal intrahepatic cholestasis is rare. We report a newborn with a myotubular myopathy, ventilator dependency, recurrent lung infections and pleural effusion, facial diplegia, ophthalmoplegia, and progressive intrahepatic cholestasis. A genetic study showed a novel mutation of the MTM1gene: c.1142 G>A (R381Q). We suggest that physicians consider probable concurrent disorders of other organs in neonates with congenital myotubular myopathy.

Mutations in the MID1 gene result in X-linked Opitz G/BBB syndrome (OS), a disorder that affects development of midline structures and comprises hypertelorism, cleft lip/palate, hypospadias, and laryngo-tracheo-esophageal abnormalities, and, at times, neurological, anal, and cardiac defects. MID1 gene abnormalities include missense, nonsense, and splicing mutations, small insertions, small deletions, and complex rearrangements. Here, we present a patient with Opitz G/BBB syndrome and a unique MID1 gene point mutation c.1703T

BACKGROUND Pentraxin 3 (PTX3) plays an important role in innate immune responses and in inflammation disease. The aim of this study was to investigate the diagnostic and prognostic potential of PTX3 in pelvic inflammatory disease (PID) and correlate it with the severity and outcome of PID. METHODS Blood specimens were collected from 64 patients with PID before and after treatment and 70 healthy controls and the plasma levels of PTX3 were measured using enzyme-linked immunosorbent assay (ELISA) kits. RESULTS It was found that the plasma level of PTX3 expression was elevated in PID patients compared with healthy controls and decreased significantly after they received treatment. When the cut-off level of plasma PTX3 was set at 2.87 ng/mL, PTX3 had higher sensitivity (84.38%) and lower false-negative rate (15.63%) than CRP (79.69% and 20.31%, respectively) in predicting PID. The level of PTX3 also exhibited a significant correlation with length of hospital stay (r=0.581, p

Backgrounds To detect the expression of plasma neutrophil gelatinase associated lipocalin (NGAL) and its complex with matrix metalloproteinase-9 (MMP-9) in patients with pelvic inflammatory disease (PID). Methods Enzyme-linked immunosorbent assay was used to measure the levels of plasma NGAL and NGAL/MMP-9 complex. Results The levels of plasma NGAL or NGAL/MMP-9 complex were increased in patients with PID compared with those in normal controls and decreased significantly after treatment. Pre-treatment plasma level of NGAL was significantly correlated with WBC and neutrophil counts. In patients with PID, plasma level of NGAL/MMP-9 complex was correlated with plasma level of NGAL or MMP-9 significantly. In predicting PID, the sensitivities of NGAL and NGAL/MMP-9 complex were 76.6% and 78.1%; the negative predictive values, 72.7% and 74.5%. Conclusions Plasma NGAL and NGAL/MMP-9 complex may act as diagnostic adjuvant biomarkers for PID. In patients with PID, about 80% have plasma levels of NGAL or NGAL/MMP-9 complex level > 10.04 ng/ml or 2.33 ng/ml, respectively.

Growth hormone deficiency (GHD) patients have lower weight, height, bone age, insulin-like growth factor 1 (IGF-1) levels, GH levels, fat metabolism and skeletal growth. The association of leptin with GHD characteristics and the effect of gene variants of leptin on GHD are unknown. Our aim was to examine the association of circulating leptin levels and common genetic variants in leptin (LEP) and leptin receptor (LEPR) genes with anthropometric measures, circulating hormone concentrations and GHD. A case control study of 125 GHD cases and 159 control subjects were characterized for bone age, body mass index (BMI), height, weight, leptin, IGF-1, GH and their genotype at the leptin promoter G-2548A, and LEPR variants, K109R and Q223R, at Chung Shan Medical University Hospital. Leptin levels were significantly associated with lower bone age, weight and BMI in GHD patients. Leptin levels were also significantly associated with reduced IGF-1 levels in girls but not boys in both groups. The frequency of LEPR223 [A/G or A/A] genotype was significantly higher than the LEPR223 G/G genotype in the GHD group. The LEPR223 [A/G or A/A] genotype was significantly associated with increased weight and BMI in the control group, but not in the GHD group. In conclusion, the GHD group carried a significantly higher frequency of the LEPR [G/A or A/A] genotype and of the A allele (LEPR223R). The LEPR223R polymorphism affected weight and BMI in control, but not in GHD patients, suggesting that the effect of LEPR223 [A/G or A/A] genotype was counteracted by other factor(s) in GHD patients.

Background Pleural effusion is rare and includes several disease entities in the neonatal period. The aim of this study was to investigate the etiology, management, and outcome of neonatal pleural effusions. Methods We retrospectively collected all neonates who were admitted to the neonatal intensive care unit of Chung Shan Medical University Hospital, Taichung, Taiwan, with discharge diagnosis of pleural effusion, chylothorax, hydrothorax, hemothorax, and empyema, from January 1999 to December 2009. The characteristics, etiology, management, and outcome were analyzed. Results There were 21 patients identified, 16 males (76%) and 5 females (24%). Eight patients (38%) had primary and 13 patients (62%) had secondary etiologies. The etiologies included four parapneumonic effusions or empyema (19%); nine chylothorax (42.8%) with four congenital and five iatrogenic after thoracic surgery; three percutaneously inserted central venous catheter extravasation (14%); one umbilical venous catheter extravasation (4.7%); three hydrops fetalis (14%); and one congestive heart failure (4.7%). Fifteen patients (71%) needed chest tube placement. Conservative management with complete cessation of enteral feedings and use of total parenteral nutrition followed with infant formula containing medium-chain triglyceride was successful in six of the patients (67%) with chylothorax. There were two patients (22%) with chylothorax who received somatostatin administration; one was successful and the other one failed. Thoracic duct ligation was performed uneventfully in two patients with acquired chylothorax. There were three mortalities (14.3%) in this study, which were related to causes other than pleural effusion. Conclusions Pleural effusions in the neonatal stage may result from chylothorax, hydrops fetalis, extravasation of percutaneously inserted central venous catheter, parapneumonic effusion, congestive heart failure, or other less frequently occurring conditions. Diagnostic chest tap is required for subsequent management. Good outcome is the rule except in hydrops fetalis, which carries high mortality rate.

Because placental polychlorinated dibenzo-p-dioxins,dibenzofurans (PCDD/Fs) levels are associated with decreased free thyroxine (FT(4)) and thyroid stimulating hormone (TSH) in neonates, we assessed development by gender and maternal PCDD/Fs exposure at years 2 and 5 in 92 mother and newborn pairs. RIA quantified thyroid, sex, and growth hormones. Of 200 subjects followed up from November 2000, 136 and 149 were observed at year 2 and year 5,respectively. PCDD/Fs exposure levels were low (n = 35) or high (n = 35) in 70 subjects at year 2, low (n = 21) or high (n = 20) in 41 at year 5. Height, weight, BMI, and head circumference were significantly higher in males, chest girth significantly higher in females at year 2. Significantly, more girls had higher bone age (BA) and chronological age (CA) at both times. Height, weight, FT(4) x TSH, and transthyretin(TTR) at year 2; and height, triiodothyronine, and IGF-1 at year 5 differed significantly by PCDD/Fs level. In females, height, weight, CA,BA, and thyroid hormones differed significantly at year 2. In males, FT(4) x TSH at year 2 and IGF-1 at year 5 were significantly higher in the high PCDD/Fs group. In utero exposure to PCDD/Fs differentially affects growth and hormone levels in male and female preschool children.

Most newborns with congenital unilateral facial palsy are expected to recover; however, when a patient has hearing loss, underlying developmental ear structure abnormalities should be investigated, particularly when the patient has internal auditory canal stenosis, which is rarely reported in newborns. All cases of internal auditory canal stenosis are accompanied by concomitant unilateral or bilateral hearing loss, but none with progressive hearing loss has been reported. We present the case of a newborn with rapidly declining hearing in the left ear within 1 month after birth. The hearing decline was associated with unilateral facial palsy. Using high-resolution computed tomography (CT) of the temporal bone, we diagnosed the patient with congenital internal auditory canal stenosis. This is the first case detected with progressive hearing loss after birth, which implies that prompt diagnosis and early habilitation are warranted, even when the hearing loss is initially mild.

Deletion of chromosome 18q (18q-) is a survivable autosomal abnormality, having an estimated incidence of one in 40,000 live births. Common features of affected individuals include developmental delay, growth retardation, hearing impairment, delayed myelination of the brain, and craniofacial dysmorphism. We describe herein a girl with psychomotor retardation and characteristic midface hypoplasia. The clinical, radioimaging, and cytogenetic findings as occur in 18q- are compared with a terminal deletion in the long arm of chromosome 18. We also monitored the effects of growth hormone treatment for changes in growth, and the patient's height velocity increased from 3.5 cm/yr to 7 cm/yr. Her nonverbal intelligence quotient (nIQ) increased from 30 to 48. Cognition of this patient is significantly improved. However, the brain MRI was not significantly improved after growth hormone treatments changes.

Kabuki make-up syndrome (Niikawa-Kuroki syndrome) is a rare congenital disorder of unknown etiology characterized by a dysmorphic face, postnatal growth retardation, skeletal abnormalities, mental retardation, and unusual dermatologic patterns. The latter include long palpebral fissures, broad eye brows sparse in the lateral half, prominent eyelashes, lower lateral palpebral ertropia, and depressed nasal tips. We describe a 13-year-old girl with short stature, delayed puberty, mental retardation, and typical face characteristics of Kabuki make-up syndrome. High-resolution banding chromosome analysis revealed a mos 45,X/46,X,r(X) karyotype. Fluorescence in situ hybridization detected a positive XIST gene signal. XIST expression was demonstrated by reverse transcription polymerase chain reaction using primers spanning exons 2, 3, 4, 5 in RNA prepared from lymphocytes. To our knowledge, this is the first description of Kabuki syndrome manifestation with r(X) and XIST expression in Taiwan.

Background The incidence of neonatal intraventricular hemorrhage (IVH) does not decrease even after using a surfactant and advanced intensive care. Posthemorrhagic hydrocephalus (PHH) is major complication after IVH. The roles of the ventriculoperitoneal (VP) shunt and the prognostic factors of neurodevelopmental outcomes in infants with PHH remain controversial. We compared the neurodevelopmental outcomes in newborns with and without VP shunts to delineate the clinical characteristics of patients with PHH and to determine the useful prognostic factors of short-term outcomes and neurodevelopmental results at a corrected age of more than 1 year old. Methods We retrospectively reviewed the records of 83 cases of neonatal IVH, grades 2-4. Thirty (36%) of the cases were complicated with PHH. We classified survivors into four groups by outcome—normal, mildly abnormal, moderately abnormal, and severely abnormal—to compare prognoses. Results Among the 30 PHH cases, 10 patients died during their first admission (early deaths), and four died after their first discharge (late deaths). We found no statistically significant differences in gestational age, birth weight, gender, the maximum number of red blood cells in cerebral ventricular fluid, the lowest glucose levels, or total protein. Patients with grade 3 IVH were more likely to have shunts than were patients with grade 2 IVH. Patients with shunts had more late deaths and fewer normal neurodevelopmental outcomes than those without shunts. Conclusion Patients who were shunt-dependent had worse neurodevelopmental outcomes and greater mortality than those without shunts. The results appeared to depend on how far the hydrocephalus had progressed and on the degree of IVH, but the necessity of VP shunts requires reevaluation before they are implanted.

We report on the clinical, cytogenetic, and imaging findings in a patient with a 7q terminal deletion. The 11-year-old girl had mental retardation, microcephaly, a distinctive face, relatively small hands and feet, and sacral dysgenesis. High resolution GTG banding (550-850 bands) showed a 7q terminal deletion. A detailed evaluation of associated malformations and the overall clinical picture should be taken into account when identifying the underlying diagnosis in cases of sacral dysgenesis with mental retardation.

Trisomy 18 syndrome is the second most common multiple malformation syndrome. The incidence is about 0.3 per 100 newborn babies. More than 130 different abnormalities have been noted in the literature on patients with the trisomy 18 syndrome. Trisomy 18 includes a broad spectrum of anomalies and malformations, among which we found Dandy-Walker malformation (DWM) rarely mentioned. DWM is estimated to occur in approximately 1 in 25,000 to 30,000 live births. The major components of DWM are the following: partial or complete absence of the cerebellar vermis, a posterior fossa cyst continuous with the fourth ventricle, and hydrocephalus. Although DWM has been associated with many chromosomal abnormalities and genetic syndromes in live birth, trisomy 18 with DWM is a rare condition. Here we present a female newborn with intrauterine growth retardation and multiple congenital abnormalities including: craniofacial anomaly, tracheoesophageal fistula, esophageal atresia, absent radius and thumb, short ulna, clenched hands, ventricular septal defect, coarctation of the aorta, patent ductus arteriosus, Meckel's diverticulum, ectopic pancreas in the ileum, and DWM. Her chromosome karyotype was 47,XX,+18. This is a case of Trisomy 18 with multiple rare malformations.

Background Premature thelarche in later childhood may progress to central precocious puberty (CPP), which does not spontaneously resolve. Thelarche variant (TV) is a slowly progressive variant of precocious puberty. Aim To determine and compare levels of insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3) and anthropomorphic measures in girls with TV and CPP. Subjects Prepubertal controls and girls with TV and CPP. Methods Chronological and bone age, weight, height, BMI, height velocity (HV), and serum IGF-I, IGFBP-3, leptin, follicle-stimulating hormone (FSH) and lutenizing hormone (LH) levels were assessed. Results Serum IGF-I levels, HV and IGF-I/ IGFBP-3 ratio were significantly higher in girls with CPP compared to both controls and girls with TV. IGFBP-3 values for bone age (IGFBP-3BA) were significantly higher in the TV group compared to both controls and girls with CPP. FSH and LH concentrations were significantly higher in the CPP group compared to TV. Conclusion HV, IGF-I, LH and FSH levels and IGF-I/IGFBP-3 ratio are elevated in girls with CPP compared to those with TV.

Oculo-auriculo-vertebral spectrum, the exact genetic predisposition of which has not yet been resolved, is characterized by varying degrees of the prevalently unilateral underdevelopment of craniofacial structures and spinal anomalies. Here, we analyzed four cases exhibiting multiple features of oculo-auriculo-vertebral spectrum and one case with Treacher-Collins syndrome. The cranium was analyzed using three-dimensional computed tomography, which reliably identifies craniofacial malformations. We detected one typical oculo-auriculo-vertebral spectrum patient who had a missense mutation in exon 9 of the TCOF1 gene complex and two silent mutations in exons 10 and 23, three partial oculo-auriculo-vertebral spectrum patients who had no detectable mutations in the TCOF1 gene complex, and one Treacher-Collins syndrome patient who had a nonsense mutation in exon 14. All five patients had eight previously reported polymorphic changes in the TCOF1 exons 10, 11, 12, 16, 21, 22, and 23, and four unreported polymorphisms in exons 9, 17, and 22 that were also detected in 51 Taiwanese control patients. These observations strongly suggest that the TCOF1 genetic changes observed in these five patients might be related to oculo-auriculo-vertebral spectrum symptoms.

Background Previous studies have reported an increased incidence of thyroid dysfunction in premature/low birth weight infants. The cord blood concentrations of transthyretin (TTR), a thyroid hormone binding protein, have also been found to be decreased in preterm infants. While thyroid hormone concentrations are decreased in sick infants, it is not known if physical condition influences TTR levels. Serial concentrations of TTR following birth have not previously been reported. Aims To measure serial serum concentrations of TTR in premature infants following birth, and determine whether TTR levels are related to physical condition. Methods A cohort of 65 premature very low birth weight (VLBW) and LBW infants were studied. Serum samples were obtained on the day of birth, and for 8 weeks following birth. Apgar scores at birth as well as the incidence of respiratory distress syndrome (RDS) were noted. Results Baseline serum T4 concentrations and Apgar scores were significantly lower in VLBW infants, while the severity of RDS was significantly higher in the VLBW group. Multivariate analyses revealed that T4 levels were negatively associated with RDS, while TSH concentrations were positively related to gestational age. TTR concentrations were not related to gestational age at birth, Apgar score, or RDS, and did not change markedly over 8 weeks. Conclusions These findings suggest that serum TTR concentrations are not related to birth weight/gestational age and are not associated with either clinical condition at birth (as assessed by Apgar score) or the occurrence of RDS. Reference values for TTR concentrations in VLBW and LBW infants are provided from birth to 8 weeks of age.

Chromosomal analysis is routinely considered in all girls--but not boys-of short stature to screen for Turner syndrome. We report three patients of short stature (body height3rd percentile) with 45,X/46,XY mosaicism karyotype. They were brought to our outpatient department at the ages of 10, 13, and 18 years, respectively. Two of them had some stigmata of Turner syndrome. Two were treated with growth hormone. In the first patient, body height increased by 20 cm in 3 years 7 months. The second case increased by 6.5 cm in 8 months. We suggest that boys with unexplained short stature should be screened with chromosomal analysis, and growth hormone treatment should be offered to boys of short stature and 45,X/46,XY mosaicism before the epiphyseal plates close.

Chromosome 21 is the smallest human chromosome; it contains 1.7% of the human genome, or about 54,000 kb. Multiple abnormalities have been observed in patients with a deletion of the long arm of chromosome 21. Phenotypic variability between cases involving different deletions of 21q have been described. We report four cases of deletion (21)(q11.2-q22.1). Three of the reported cases are familial, involving a mother and her two sons, and one is de novo. All cases had mild mental retardation, antimongolian slants, long philtrum, and protruding tongue as well as open mouth. Hypertonia was noted when each was young. Arachnoid cyst, cerebral dysfunction, thalassemia minor, and growth hormone deficiency were found in the de novo case. This is the first report of chromosomal deletion (21)(q11.2-q22.1) in the Taiwanese population.

Decreased fertility is one of the characteristics of Turner syndrome. Ovarian function in women with Turner syndrome is believed to be impaired because of an abnormal and very rapid maturation of oocytes and follicles. About 30% of mosaic Turner patients have partial ovarian function during puberty, but only 2-5% of them will ever become pregnant. We describe a woman with a mosaic form of Turner syndrome (45,X [6]/146,XX [94] karyotype from blood lymphocytes), who had a spontaneous puberty and normal fertility. After her second pregnancy, she gave birth to a set of monozygotic female twins; Twin B presented with a mild Turner syndrome phenotype and Twin A with a normal female phenotype. Karyotypic analysis performed on amniotic fluid and fetal blood samples demonstrated a normal 46,XX chromosome constitution in Twin A and a 45,X/46,XX mosaicism (27%:73% for amniotic fluid and 6%:94% for fetal blood) in Twin B. Postnatal cytogenetic investigation of blood lymphocytes showed the 45,X [7]/46,XX [93] mosaicism in Twin B. Further investigations of blood lymphocytes in both girls at the age of 4 years showed Twin A with a 46,XX karyotype and Twin B with a 45,X [4]/46,XX [96] mosaicism. The phenotype of twin A had a normal appearance, but webbing of the neck, low posterior hair line, shield chest, and mild psychomotor retardation were evident in Twin B.

Neonatal startle disease or stiff baby syndrome is a rare hereditary disease. It is often misdiagnosed as either neonatal seizure or cerebral palsy because of its characteristic exaggerated fits, which can be activated by external voice or touch. In fact, the exact diagnosis can be made easily according to the patient's family history and clinical examination at bedside. Glabellar tapping is a method to elicit the exaggerated responses, and the events can be relieved by forced knee-chest position. Herein, we report one case with hereditary startle disease accompanied with cyanosis and severe apneas, which could be relieved by forced knee-chest position and oral clonazepam. In conclusion, we suggest the diagnosis of the startle disease should be considered when newborns present the symptoms of neonatal seizure. Once the disease is noticed, we can pursue a simple method to confirm the diagnosis at bedside and unnecessary examination like magnetic resonance imaging can be avoided.

Goldenhar syndrome, also known as oculoauriculovertebral dysplasia, is an uncommon condition, characterized by a combination of anomalies: epibulbar dermoids or lipodermoids, preauricular appendices, malformation of the ears, hemifacial microsomia, vertebral anomalies, and others. The etiology of this disease has remained unclear; factors including chromosomal abnormalities, maternal diabetes mellitus or drug use, and influence of environment during pregnancy have been proposed. Here, we describe a case of Goldenhar syndrome in a 1-day-old female newborn, who presented with right external ear atresia, left preauricular appendices, cleft-like extension of the right oral angle, mandibular hypoplasia and relatively small hands. The literature on Goldenhar syndrome is briefly reviewed.

To examine the relationship between leptin serum levels and pubertal development in girls with progressive central precocious puberty. We longitudinally investigated the leptin levels of 37 girls with central precocious puberty before and during treatment with the gonadotropin-releasing hormone agonist depot (leuprorelin acetate). Leptin and other hormone levels were determined by radioimmunoassay. Girls with central precocious puberty before treatment showed no significant difference in leptin levels as compared to the puberty stage at diagnosis of disease. In addition, the changes in leptin concentrations of girls with central precocious puberty during treatment were not statistically significant. In the Spearman correlation analysis of leptin levels with body mass index, bone age, chronological age, clinical pubertal signs along with luteinizing, follicle-stimulating, and estradiol hormone levels, we found that body mass index, weight, and chronological age were significantly correlated with leptin levels (p0.05) at both 3 and 6 months of leuprorelin treatment. Leptin levels increased with body mass index; however, this trend did not reach statistical significance at all follow-up time points. These data demonstrated that treatment with depot gonadotropin-releasing hormone agonist does not influence leptin concentrations. Serum leptin levels in patients with central precocious puberty are associated with body weight and body mass index.

Klinefelter syndrome occurs in approximately 1 in 1000 males. A 4-year-old boy presented with precocious puberty and an anterior mediastinal mass. Serum alpha-fetoprotein and human chorionic gonadotropin levels were mildly increased. Computed tomography revealed a germ cell tumor (GCT) of the mediastinum. Complete resection of the tumor was performed. Histologic analysis revealed an immature teratoma. Males with Klinefelter syndrome develop GCTs at a rate 50 times higher than unaffected males. This case report calls attention to the need to rule out Klinefelter syndrome in boys who present with precocious puberty and a mediastinal GCT.

The deletion 9p with trisomy 19q syndrome is a rare disorder. We report 2 adults and 4 children with deletion 9p and trisomy 19q due to familial balanced 9p;19q translocation with clinical features suggestive of monosomy 9p. The children had dysmorphic features and psychomotor retardation while the adults were self-sufficient but worked in a sheltered environment. High-resolution chromosome analysis and fluorescence in situ hybridization confirmed that the 6 cases of unbalanced translocation, der(9)t(9;19)(p24.1;q13.4) were inherited from a balanced translocation carrier, t(9;19)(p24.1;q13.4). The dysmorphic features included trigonocephaly, small nose with stunted tip, and long philtrum. Associated anomalies included wide-set nipples, extra finger flexion creases, hernia, external genitalia hypoplasia, scoliosis, and hypopigmented skin patch. We suggest that genetic counseling is necessary for those who have family members with dysmorphic features and/or major anomalies and/or psychomotor retardation.

Enteroviral infections are more severe in neonates than in older children, and coxsackievirus B is most frequently associated with severe neonatal disease. We summarize the course and clinical data of four neonates with meningitis caused by coxsackievirus B5. Their clinical symptoms and signs were persistent fever, poor appetite, and decreased activity, with vomiting in two. Laboratory analysis of cerebrospinal fluid revealed the following: white blood count, 340-660/mm3; red blood count, 0-250/ mm3; glucose level, 47-59 mg/dl; and total protein level, 70-106 mg/dl. Echocardiography showed normal heart function. Final bacterial cultures of the cerebrospinal fluid showed no growth, whereas viral cultures showed coxsackievirus B5. All patients recovered without intravenous immunoglobulin. No complications occurred at 6-month follow-up.

Partial trisomy 3q syndrome is often the result of an unbalanced translocation or inversion. The duplicated segments are mostly from 3q25 to 3qter. We describe a karyotype of 46,XY,der(10)t(3;10)(q25.3;q26.1) in a 1-day-old male infant who presented with multiple congenital anomalies including synophrys, a long philtrum, thin lips with down-turned angles of the mouth, micrognathia, a high-arched and cleft palate, clenched hands, genital hypoplasia, cryptorchidism, a large ventricular septal defect, a subependymal cyst, and corpus callosum hypoplasia. The patient had cardiopulmonary distress resulting from multiple congenital anomalies. He died of heart failure at the age of 18 days. The chromosome aberration resulted from a maternal balanced translocation. The dup(3q) syndrome superficially resembles but can be distinguished from Brachmann-de Lange syndrome. Craniofacial features, cleft palate and urinary tract anomaly are more frequent in dup(3q) syndrome. Oligodactyly and phocomelia are more characteristic of Brachmann-de Lange syndrome.

The cutaneous lesions of incontinentia pigmenti classically evolve in stages, beginning with erythematous vesicular rash and bullae, followed by verrucose lesions, with an eventual macular pattern of splashed or whorled hyperpigmentation. We describe female twins presenting with the classic form of cutaneous expression. Ophthalmologic examination revealed abnormal vascular proliferations in the peripheral retinas in twin B. Several studies have confirmed linkage of familial incontinentia pigmenti to chromosome Xq28, with the factor VIII gene in Xq28 identified as the locus for incontinentia pigmenti. Two-hundred kilobases proximal to this locus, the gene for NEMO (NF-kappaB essential modulator)/IKKgamma (I kappaB kinase-gamma) has been mapped. We describe herein female twins with incontinentia pigmenti caused by a de novo mutation of this locus, as demonstrated by diagnostic polymerase chain reaction.

Deletion (14)(q11.2q13.1) is a rare cytogenetic abnormality associated with severe neurological deficit, microcephaly and psychomotor retardation. We report a case of de novo interstitial deletion of chromosome (14)(q11.2q13.1) in an 8-month-old girl, who presented with marked microcephaly, a nearly closed anterior fontanelle, dysmorphic facies, severe neurological deficits, and delayed developmental milestones. Three-dimensional computed tomography of the brain showed premature closure of the coronal suture and magnetic resonance imaging of the brain showed frontal atrophy and hypoplastic corpus callosum.

Background: Patent ductus arteriosus (PDA) is commonly found in very low-birthweight (VLBW) infants. The presence of respiratory distress syndrome (RDS) is also associated with increased frequency of significant PDA. Intravenous indomethacin has been used to treat and to prevent PDA in premature infants since 1976. However, concern remains regarding the safety of indomethacin, which affects renal, gastrointestinal and cerebral perfusion. Intravenous ibuprofen has recently been used to treat and to prevent PDA premature infants with PDA without reducing cerebral blood flow or affecting intestinal or renal hemodynamics. The aim of the present study is to compare intravenous ibuprofen and indomethacin with regard to efficacy and safety for the early treatment of PDA in preterm infants. Methods: A total of 63 preterm infants with RDS who had a birthweight of ≤1500 g and gestational age of ≤32 weeks, were enrolled in the present study. All patients were treated with nasal continuous positive airway pressure with additional oxygen supply in inspired air>30%, or with mechanical ventilation. The patients’ serum platelet counts were>100 000/uL, and serum creatinine values were

4p-syndrome, or Wolf-Hirschhorn syndrome, is associated with a deletion of chromosome 4p16.3 and involves multiple malformations that result in delayed growth and development and also facial dysmorphism. We report a case of Wolf-Hirschhorn syndrome in a female infant with a 4p deletion, for which the breakpoint was detected at p14. This patient had bilateral renal hypoplasia resulting from the oligohydramnios sequence (Potter syndrome), including characteristic facial abnormalities, deformed limbs, and pulmonary hypoplasia. Patent ductus arteriosus, ascites, and bilateral renal hypoplasia were noted. The patient had frequent pulmonary infections and died when she was 39 days old.

Aniridia is a rare condition occurring in 1 in 64,000 to 1 in 96,000 live births. Approximately one third of cases are sporadic and carry a 30% risk of Wilms' tumor developing before the age of 5. The remaining 66% are inherited in an autosomal dominant fashion. The aniridia candidate gene (PAX6) has a key role as a master regulator in the development of eye and central nervous tissues. The Wilms' tumor predisposing gene (WT1) plays an important role in the development of genitourinary tract diseases such as hypospadias, cryptorchism, horse-shoe kidney, and Wilms' tumor. The WT1 and PAX6 genes are about 700 kb apart, with the WT1 gene located centromeric to PAX6 in chromosome 11p13. We report a patient with incomplete aniridia, ptosis, hypospadias, and cryptorchism. Cytogenetic analysis revealed the presence of a de novo reciprocal translocation 46, XY, t (2; 11) (p25.1; p13) without microscopic deletion. We suggest that haploinsufficiency in PAX6 and WT1 genes resulted in aniridia and associated genitourinary abnormalities.

Leptin, a hormone that signals the brain about the status of body (fat) energy stores, has recently been shown to play a role in the regulation of several hypothalamic pituitary axes, including the growth hormone axis. To investigate a potential association of serum leptin concentrations and clinical condition in preterm, sick term and healthy term newborns, serum leptin concentrations were evaluated in 104 newborns. Twenty-eight of them were healthy term (18 males and 10 females; gestational age, 37-42 weeks), 21 were sick term (12 males and 9 females; gestational age, 37-42 weeks) and 55 were preterm neonates (35 males and 20 females; gestational age: 26-37 weeks). Leptin values correlate positively with birth weight, birth length, head circumference, waist circumference, hip circumference, body surface, weight/length ratio, and gestational age (r = 0.38, 0.42, 0.29, 0.21, 0.29, 0.40, 0.31 and 0.28), respectively. The concentrations of leptin are statistically significantly higher (p0.05) in term neonates (3.02 +/- 2.94 ng/ml) than preterm neonates (1.93 +/- 2.21 ng/ml). Female infants also have significantly higher (p0.05) serum leptin values than male infants in preterm and healthy term groups. We also found leptin present in venous blood after 26 weeks of gestation.

Congenital toxoplasmosis is a major cause of premature delivery and neonatal illness. Here we report a rare case of congenital toxoplasmosis with significant brain tissue loss to highlight the potential threat of congenital toxoplasmosis to neonates. A woman 27 years of age who was pregnant presented with fetal growth restriction at our obstetric clinic on October 12, 2009. Her blood sample was positive for Toxoplasma gondii-specific immunoglobin M (IgM). She gave birth to a boy at 37 weeks of gestation on February 1, 2010. The infant weighed 2050 g and had Apgar scores of 7 and 9 at birth and 5 minutes after birth, respectively. General examination did not show any morphologic abnormality. However, brain magnetic resonance imaging showed diffuse brain tissue loss with direct communication between the lateral ventricle and the adjacent cerebral surface, corpus callosum hypoplasia, porencephaly, encephalomalacia, intracerebral hemorrhage, and multiple calcifications (Fig. 1). Cerebrospinal fluid examination (CSF) showed an increased protein level (148.9 mg/dl); real-time polymerase chain reaction on the CSF sample showed a positive result for T gondii repeat element DNA. Serologic tests