Genetic Variations of the KISS1R Gene in Korean Girls with Central Precocious Puberty

The timing of puberty onset varies greatly among individuals, and much of this variation is modulated by genetic factors. This study aimed to identify the kisspeptin receptor (KISS1R) gene variations and to investigate the associations between these variations and central precocious puberty (CPP). Korean girls with CPP (n = 194) and their healthy controls (n = 99) were included in this study. The entire coding region and the exon-intron boundaries (exon 1 through 5) of the KISS1R gene were directly sequenced. Seven polymorphisms were identified in the KISS1R gene. A missense change c.1091T>A, and an intron variant c.738+64G>T showed significantly higher allele frequencies in CPP patients than in controls (c.1091T>A: 30.7% vs. 22.2%, P = 0.031; c.738+64G>T: 45.6% vs. 35.9%, P = 0.023). The missense variant (c.1091T>A) was a nonsynonymous polymorphism that induces amino acid substitution of p.Leu364His. The haplotype CAGTGTC was detected more frequently in the CPP group (P = 0.042). The sequence variants of the KISS1R gene can be inducible factors in the development of CPP. The association between sequence variants and CPP should be validated by further evidence obtained from larger samples of children with CPP.

The different effects of gonadotropin-releasing hormone agonist therapy on body mass index and growth between normal-weight and overweight girls with central precocious puberty

PURPOSE: The effects of gonadotropin-releasing hormone agonist (GnRHa) treatment on body mass index (BMI) are controversial in girls with central precocious puberty (CPP). We therefore evaluated auxological parameters during GnRHa therapy in patients with CPP, specifically focusing on changes in BMI. METHODS: Seventy-seven girls with idiopathic CPP who underwent GnRHa therapy were retrospectively recruited. We investigated BMI changes during the treatment period after stratifying them according to baseline BMI status as follows: normal (BMI percentile of <85th) and overweight groups (BMI percentile of ≥85th). RESULTS: The incidence of overweight/obesity (40.3%/23.4%) was very high in the girls with CPP. In the overall study population, no significant BMI change was observed during the GnRHa treatment period. However, when stratified according to baseline BMI status, the normal-weight group showed a significant increase in BMI-standard deviation score (SDS), whereas the overweight group showed no change in BMI-SDS. Baseline BMI-SDS was an independent predictor of changes in BMI during the GnRHa treatment period. Changes in weight-SDS were similar, but changes in height-SDS were significantly greater in the overweight group than in the normal-weight group, which explains the observed difference in BMI-SDS. CONCLUSION: Our results demonstrate that the difference in the pattern of BMI changes among our CPP patients suggests that delayed puberty induced by GnRHa treatment may have different effects on linear growth according to baseline body composition. This study underscores the importance of individualized lifestyle intervention in CPP children.

Neonatal Outcomes of Premature Infants Who Were Delivered from Mother with Hypertensive Disorders of Pregnancy and Effects of Antihypertensive Drugs and MgSO4 / 대한주산의학회잡지

PURPOSE: Hypertensive disorders of pregnancy increase morbidity and mortality of fetus and neonates. Recently some studies revealed that antihypertensive agents affected the neonatal outcomes. The aim of this study was to investigate the prognosis of preterm infants delivered from the mothers with hypertensive disorders who were treated with antihypertensive agents and magnesium sulfate. METHODS: This retrospective study was conducted on preterm infants who were delivered from normotensive mother (control, n=436) and antihypertensive drugs +/- magnesium sulfate treated mother (study, n=150) between January 2009 and December 2013. Study group were divided into two groups based on whether they received antihypertensive drugs only (n=110) and additional magnesium sulfate (n=40). We compared the characteristics of mothers and neonatal outcomes. RESULTS: Study group had shorter gestational age (32.2+/-3.5 weeks vs. 33.7+/-3.0 weeks, P=0.000) and lower birth weight (1,810.5 +/- 689.2 g, 2,212.1 +/- 604.9 g, P=0.000), and higher rate of small for gestational age infants (22% vs 11%, P=0.000). One minute and 5 minutes Apgar score were lower, but duration of hospital days, oxygen supplement and mechanical ventilation were longer in study group. Respiratory distress syndrome, bronchopulmonary dysplasia, patent ductus arteriosus, retinopathy of prematurity, intraventricular hemorrhage occurred more in study group than control. The group treated with magnesium sulfate together with antihypertensive agent had lower 1 minute and 5 minutes Apgar score than the group taken antihypertensive agent only. CONCLUSIONS: Mothers with hypertensive disorders have increased the risk of preterm delivery, low birth weight, and high neonatal morbidity rate. Therefore it is important to predict and manage possible complication. Moreover, if magnesium sulfate is taken, careful neonatal monitoring is needed because of possible low Apgar score.

Risk factors of allergic sensitization in preschool children with chronic cough

PURPOSE: Chronic cough is one of the major symptoms of asthma and allergic sensitization and may appear prior to the onset of asthma. The object of this study was to investigate the risk of allergic sensitization in preschool children with chronic cough. METHODS: We reviewed the medical records of 99 preschool children presenting with chronic cough but not with allergic rhinitis, atopic dermatitis, recurrent wheezing, or lower respiratory tract infection between November 2011 and July 2013. RESULTS: Fifty-four children (55%) were sensitized at least one of the following inhalant allergens: Dermatophagoides pteronyssinus, Dermatophagoides farinae, cockroach, Alternaria alternata, dog dander, and cat epithelium. Children with allergic sensitization had a higher blood total IgE levels transformed by common logarithm (1.9+/-0.6 IU/mL vs. 1.3+/-0.5 IU/mL, P<0.001) and eosinophils (3.7%+/-2.5% vs. 2.7%+/-2.0%, P=0.043), more frequent parental history of allergy (68% vs. 48%, P=0.044) and less frequent history of breast milk feeding (68% vs. 86%, P=0.041) than those without. CONCLUSION: These results suggest that the ratio of allergic sensitization may be 50% or more in preschool children with chronic cough and that parental history of allergy and formula milk feeding may be associated with allergic sensitization.

Influence of Bottle-Feeding on Serum Bisphenol A Levels in Infants

Exposure to endocrine disrupting chemicals (EDCs), particularly during developmental periods, gives rise to a variety of adverse health outcomes. Bisphenol A (BPA) is a well-known EDC commonly found in plastic products including food and water containers, baby bottles, and metal can linings. This study investigates infant exposure to BPA and the effect of bottle-feeding on serum BPA levels in infants. Serum BPA levels in normal healthy infants 6 to 15 months of age (n=60) were evaluated by a competitive ELISA. BPA was detected in every study sample. Serum BPA levels of bottle-fed infants (n=30) were significantly higher than those of breast-fed infants (n=30) (96.58+/-102.36 vs 45.53+/-34.05 pg/mL, P=0.014). There were no significant differences in serum BPA levels between boys (n=31) and girls (n=29). No significant correlations were found between serum BPA levels and age, body weight, birth weight, and gestational age. Bottle-feeding seems to increase the risk of infant exposure to BPA. Establishment of health policies to reduce or prevent BPA exposure in infants is necessary.

Clinical and radiological findings of incidental Rathke's cleft cysts in children and adolescents

PURPOSE: In the pediatric population, Rathke's cleft cysts (RCCs) are known to be an infrequent cause of headaches, visual disturbances, and pituitary dysfunction. We investigated the clinical characteristics of children in whom RCCs were incidentally discovered and evaluated whether RCCs influence the treatment response of patients with proven endocrinopathy. METHODS: A retrospective analysis was conducted in 34 patients with RCCs who were diagnosed between 2006 and 2013 at Hallym University Medical Center. Their clinical, hormonal, and imaging findings were reviewed. We evaluated the clinical outcomes of the patients with concomitant RCCs and endocrinopathy compared to matched controls. RESULTS: Twenty-six of 34 patients with radiologically proven RCCs had endocrine disorders. They were 9 boys and 17 girls, with ages ranging from 4.8 to 17.4 years at the time of the diagnosis. Of these, 7 (27%) had idiopathic short stature, 7 (27%) had growth hormone deficiency (GHD), and 12 (46%) had central precocious puberty (CPP). Nineteen of 26 patients (73.1%) showed low signal intensities on T1-weighted images (T1WI) and high signal intensities on T2-weighted images. The incidence of hypointensity on T1WI was higher in the patients with RCCs accompanied by endocrinopathy than in those without endocrinopathy (P=0.033). The treatment outcomes of the patients with CPP and GHD with and without RCCs were similar. CONCLUSION: CPP and GHD patients with a small RCC (less than 20 mm) expressing cystic magnetic resonance intensity can be managed with medical treatment, although the RCCs need to be closely monitored in radiological studies to observe their growth.

Age of menarche and near adult height after long-term gonadotropin-releasing hormone agonist treatment in girls with central precocious puberty

PURPOSE: Gonadotropin-releasing hormone agonist (GnRHa) is known for improving final adult height in patients with central precocious puberty (CPP). This study aimed to investigate the age of menarche and near adult height in girls with CPP who had been treated with GnRHa. METHODS: In this retrospective study, we reviewed the medical records of 71 Korean girls with CPP who had started menarche or reached over 13 years of bone age after long-term GnRHa treatment. We estimated near adult height using the Bayley-Pinneau method and identified the age of menarche in girls with CPP. RESULTS: Mean chronological and bone age at menarche were 11.9+/-0.7 and 12.8+/-0.4 years, respectively. The period between menarche and the end of treatment was 14.0+/-5.6 months. Posttreatment near adult height was 163.8+/-4.7 cm, which was significantly greater than pretreatment predicted adult height (158.7+/-4.1 cm). CONCLUSION: GnRHa treatment in girls with CPP could improve final adult height and made the age of menarche close to that of the general population.

Prevalence of Voiding Dysfunction and Constipation in Children with Attention Deficit Hyperactivity Disorder

PURPOSE: Attention deficit hyperactivity disorder (ADHD) has been associated with impairments in frontal inhibitory function and the catecholaminergic system. ADHD is diagnosed in 3-5% of children. Children with ADHD seem develop various forms of urinary problems such as nocturnal enuresis, dysfunctional voiding, and diurnal incontinence. However, no data exist to confirm the presence of these problems in Korean children with ADHD. We investigated the clinical findings of voiding dysfunction in children with ADHD. METHODS: Between October 2009 and March 2011, a total of 63 children (33 with ADHD, 30 with an upper respiratory infection, as a control group) were enrolled. ADHD was diagnosed using the diagnostic and statistical manual of mental disorders (DSM)-IV criteria. A comprehensive survey of voiding and defecation was administered. RESULTS: The patient group included 28 boys and 5 girls; the control group comprised 20 boys and 10 girls. The mean age was 9.09+/-2.8 years in the ADHD group and 8.58+/-3.1 years in the control group. Children with ADHD had a statistically significantly higher incidence of urgency (P=0.017), urge incontinence (P=0.033), and constipation (P=0.045). There was no significant difference in the incidence of straining, intermittency, holding maneuvers, or nocturnal enuresis. CONCLUSION: Children with ADHD in Korea have significantly higher rates of urgency, urge incontinence, and constipation than those without ADHD.

A Case of Herpes Simplex Virus Type 2 Encephalitis of a Newborn Delivered by a Mother without Prenatal Screening / 대한주산의학회잡지

Neonatal herpes simplex virus (HSV) encephalitis is a rare disease nowadays because of prenatal screening test and management. It shows progressive central nervous system manifestations affecting predominantly temporal and frontal lobes. Early diagnosis of HSV encephalitis is important since even with the early initiation of high-dose intravenous acyclovir therapy, it results in serious morbidity among survivors. A 14-day-old neonate with fever and poor oral intake was admitted via emergency department. The next day she had seizures and the brain was damaged with permanent sequelae despite of early administration of intravenous acyclovir on day 2 of admission. We report a serious case of HSV encephalitis diagnosed as type 2 HSV by polymerase chain reaction and culture of a newborn without proper prenatal screening test.

The Comparison of Clinical Factors according to Growth Velocity during Gonadotropin-Releasing Hormone Agonist Treatment in Central Precocious Puberty Girls

BACKGROUND: The aim of this study was to investigate the favorable factors for gonadotropin-releasing hormone (GnRH) agonist treatment with regard to the growth velocity and the predicted adult height (PAH) in central precocious puberty (CPP) girls. METHODS: We reviewed the clinical and auxological parameters in 46 CPP girls who were treated with GnRH agonist at the pediatric endocrinology clinic of Korea University Hospital from January 2001 to August 2007. We divided the two groups according to the growth velocity of 5 cm/yr and we assessed the related factors associated with growth velocity. We also assessed the changes in PAH for two years. RESULTS: The pretreatment chronological age and bone age were significantly younger in the high growth velocity group (> 5 cm/yr) compared to that of the low growth velocity group (7.8 +/- 0.9 year vs. 8.4 +/- 0.5 year, 9.4 +/- 1.2 year vs. 10.1 +/- 0.9 year, respectively) (P 5 cm/yr)(P < 0.05). Growth velocity during treatment had negative correlation with the pretreatment chronological age and positive correlation with the PAH after one and two years of treatment (r = -0.45, P < 0.05 and r = 0.51, P < 0.01). PAH had positive correlation with the treatment duration (r = 0.31, P < 0.05). CONCLUSION: In our study, the growth velocity during GnRH agonist treatment was negatively related to age at the initiation of treatment. Therefore, earlier treatment is important to improve the outcomes and to maintain appropriate growth velocity in CPP girls.

A study of adolescent smoking and drinking in Korea / 소아과

PURPOSE: Adolescence is a period of growth and development in body structure and physiologic, psychologic, and social functioning. Smoking and drinking in this period are very harmful and may lead to other forms of substance abuse. We surveyed the actual aspects of smoking and drinking among Korean adolescents and analyzed associated factors. METHODS: A survey was performed among adolescents using a questionnaire about smoking and drinking. Data were collected from students who visited pediatric clinics for routine school examinations from July to November 2007. RESULTS: A total of 2,546 adolescents (smoking 1,512; drinking 1,034) participated in the study. The overall smoking and drinking rates were 29.2% and 48.2%, respectively, and the mean age at the first instance of smoking and drinking was 13.8 and 14.1 years, respectively. Among drinking adolescents, 30.1% were offered a drink by their parents, although most adolescents were encouraged to smoke or drink by their friends. Dissatisfaction with family and school life, economic status, and school performance was associated with a higher smoking and drinking rate (P<0.001). Broken families were associated with a high rate of smoking, but peer satisfaction was not related to smoking or drinking. The frequency and amount of smoking and drinking in adolescents were as high as those in adults. Social sanctions seemed insufficient to keep adolescents from smoking and drinking. CONCLUSION: Adolescent smoking and drinking are highly influenced by family and school environments, so more active social sanctions are required, including parental involvement and legislation preventing adolescents from smoking and drinking.

Bone Mineral Density and Correlation Factors in Normal Children and Adolescence / 대한소아내분비학회지

PURPOSE:The mean height of Korean children has been increased recently, and new version of growth chart was made in 2007. Nevertheless, the reference value on bone mineral density (BMD) of normal children has not been established yet. The aims of this study were to obtain mean values of BMD in normal children and to investigate correlation between BMD and their relating factors. METHODS:One hundred thirty five normal children from 6 to 14 years old were included, who were 69 boys and 66 girls. Bone density was measured at the lumbar spine and the proximal femur by dual energy x-ray absorptiometry (Discovery A, Hologic, 2004). We assessed bone age, body mass index, bone alkaline phosphatase, insulin-like growth factor I (IGF-I), sex steroid level and analyzed their correlation with BMD. Results:The result showed a trend of an increase in BMD according to the age in both boys and girls. The mean value of BMD showed the greatest increase during age of 10 to 11 in girls and 12 to 13 in boys. A sudden increase of BMD in both boys and girls occurred during the overt puberty. Bone age and IGF-I level indicated the most significant relating factors of BMD of lumbar spine. The mean values of BMD of this study were similar to the previous studies about BMD of Korean children. CONCLUSION:The results could be utilized as fundamental data for normal BMD value of Korean children and larger population study is needed.

Comparison of predicted adult heights measured by Bayley-Pinneau and Tanner-Whitehouse 3 methods in normal children, those with precocious puberty and with constitutional growth delay / 소아과

PURPOSE: This study compared bone ages measured by the Greulich-Pyle (GP) and Tanner-Whitehouse 3 (TW3 ) methods and investigated the differences in predicted adult heights measured by Bayley-Pinneau (BP) and TW3 methods. METHODS: Bone ages were assessed from left-wrist radiographs by two investigators, one for each GP and TW3 methods in 85 normal children, 30 precocious puberty girls, and 30 constitutional growth delay boys. The differences between the measured predicted adult heights using the BP and TW3 methods were compared in each group. RESULTS: The bone age measured by the TW3 method was less than that by the GP method in normal children. The predicted adult heights measured by the two methods showed no significant difference in normal boys, while the predicted adult height measured by the TW3 method was higher than that by the BP method for normal girls (156.4+/-4.7 cm vs. 158.9+/-3.8 cm, P<0.01) and for precocious puberty girls (156.3+/-4.0 cm vs. 159.3+/-4.2 cm, P<0.01). In contrast, the predicted adult height was higher from the BP method than from the TW3 method in constitutional growth delay boys (173.3+/-4.4 cm vs. 169.7+/-3.2 cm, P<0.01). CONCLUSION: There were significant differences in predicted adult heights between the BP and TW3 method in normal girls, precocious puberty girls, or constitutional growth delay boys. In precocious puberty and constitutional growth delay, the BP method might be preferred to predict adult height, but further studies on final adult height are needed.

Effects of inhaled corticosteroids on bone mineral density and bone metabolism in children with asthma / 소아과

PURPOSE: Inhaled corticosteroids (ICS) are used as first-line agents for the treatment of persistent asthma; however, their use is accompanied by apprehension of potential systemic adverse effects. This study aimed to assess the effects of ICS on bone mineral density (BMD) and bone metabolism in children with asthma. METHODS: From February 2008 to September 2008, 26 asthmatic children treated with ICS (ICS group), 15 asthmatic children treated with leukotriene receptor antagonist (LTRA) (LTRA group), and 30 healthy children (Control group) were selected from the Korea University Anam Hospital. BMD and serum bone-specific alkaline phosphatase (BALP) levels were measured. The asthmatic children underwent spirometry and methacholine bronchial challenge test. RESULTS: There were no significant differences in BMD in the lumbar spine (P=0.254) and proximal femur (P=0.297) among the 3 groups. The serum BALP levels were significantly higher in both the ICS (P=0.017) and LTRA (P=0.025) groups than in the Control group. None of the parameters pertaining to ICS use, such as the mean daily dose during the last 6 months, the total cumulative dose, duration of use, and age of commencement of use, showed significant correlations with BMD (P>0.05 for all parameters). CONCLUSIONS: We demonstrated that a low dose of ICS does not exert any significant adverse effect on bone metabolism in asthmatic children. These findings support the current recommendations with regard to the use of ICS for asthmatic children.

Comparison of the Greulich-Pyle and Tanner Whitehouse (TW3) Methods in Bone Age Assessment / 대한소아내분비학회지

PURPOSE: The determination of skeletal age is important for the analysis of growth and growth disorders in children. The aim of this study is to investigate the difference of bone age comparing Greulich-Pyle (GP) and Tanner Whitehouse (TW3) methods. We also evaluated the reproducibility of results of each method by different observers (interobserver variation) and by same observer (intraobserver variation). METHODS: Bone ages were assessed from left hand-wrist radiographs of 200 children (108 males and 92 females) aged 7 to 15 years by GP and TW3 methods. To evaluate the reproducibility of each method, 102 radiographs were assessed independently by three observers and 100 radiographs were reassessed by one same observer using both methods. RESULTS: The average bone age by GP and TW3 were 10.65+/-2.24 years and 10.48+/-2.18 years, respectively (P<0.01). There is significant correlation between GP and TW3 methods (R(2)=0.94, P<0.01). The interobserver variation of GP and TW3 was not different significantly (0.51+/-0.44 years by GP vs 0.54+/-0.42 years by TW3). The intraobserver variation also was not different significantly (0.48+/-0.44 years by GP vs 0.45+/-0.37 years by TW3). CONCLUSION: Our data indicate that bone age by TW3 method was slightly younger than that by GP method but similar, and the reproducibility of both methods were not different. Therefore, both GP and TW3 methods are useful for estimation of bone age in Korea children.

Increased vascular endothelial growth factor in children with acute Mycoplasma pneumoniae pneumonia and wheezing / 소아과

Purpose: Although Mycoplasma pneumoniae (M. pneumoniae) infection can cause wheezing in non-asthmatic children, the mechanisms of this symptom remain unclear. Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis and vascular permeability, and is also known to be elevated in cases of chronic pulmonary disease such as asthma. We hypothesized that VEGF may increase in children with acute M. pneumoniae pneumonia and wheezing. Methods: Nine patients with clinical and laboratory evidence of acute M. pneumoniae pneumonia were enlisted from children admitted to Korea University Hospital. They had had more than one episode of wheezing during the illness, which was confirmed by a physician; they comprised the wheezer group. The individuals with M. pneumoniae pneumonia without wheezing were 63 in number, and they comprised the non-wheezer group. Patients with a history of asthma or who had received asthma medications were excluded. Serum concentrations of VEGF, total IgE, eosinophil cationic protein (ECP), and peripheral blood eosinophil counts were measured. Results: The serum VEGF concentrations were higher in the wheezer group (mean+/-SD; 650.2+/-417.9 pg/mL) than in the non-wheezer group (376.5+/-356.2 pg/mL, P=0.049). M. pneumoniae antibody (1:1,380 vs. 1:596, P=0.048) and serum total IgE (591.8 IU/mL vs. 162.2 IU/mL, P=0.032) were higher in the wheezer group than in the non-wheezer group. There were no differences between the two groups in terms of serum ECP concentration or blood eosinophil count. Conclusion: In the presence of wheezing, serum VEGF concentrations were higher in the children with M. pneumoniae pneumonia. This finding suggests that VEGF may associate with wheeze-related symptoms in children with acute M. pneumoniae pneumonia.