Associations among IGF-1, IGF2, IGF-1R, IGF-2R, IGFBP-3, insulin genetic polymorphisms and central precocious puberty in girls.

BACKGROUND: Insulin and insulin-like growth factor (IGF)-1 coupled with growth hormone helps control timing of sexual maturation. Mutations and variants in multiple genes are associated with development or reduced risk of central precocious puberty (CPP). METHODS: We assessed single nucleotide polymorphisms (SNPs) in the IGF-1, IGF-2, IGF-3, IGF-1 receptor (IGF1R), IGF-2 receptor (IGF2R), and IGF -binding protein 3 (IGFBP-3) genes, and their association with demographics and metabolic proteins in girls with CPP. Z-scores of height, weight, and body mass index (BMI) were calculated with the WHO reference growth standards for children. RESULTS: IGF-1 serum levels of CPP group exhibited a higher correlation with bone age, z-scores of height and weight, and luteinizing hormone (LH) than those of control group, regardless of BMI adjustment. In the CPP group, height was associated with IGF-2(3580), an adenine to guanine (A/G) SNP at position + 3580. BMI in the CPP group was associated with IGF-2(3580), IGF1R, and the combinations of [IGF-2(3580) + IGF2R], and [IGF-2(3580) + IGFBP-3]. Body weight in the CPP group was associated with the combination of [IGF-2(3580) + IGFBP-3] (p = 0.024). Weight and BMI were significantly associated with the combination of [IGF-2(3580) + IGF2R + IGFBP-3] in the CPP group. These associations were not significantly associated with z-scores of weight, height, or BMI. The distribution of these genotypes, haplotypes, and allele frequencies were similar between control and CPP groups. CONCLUSIONS: These known SNPs of these IGF-1 axis genes appear to play minor roles in the risk for development of CPP.

Factors Associated with Post-Traumatic Symptoms in Mothers of Preterm Infants.

OBJECTIVES: Symptoms of post-traumatic distress in mothers of preterm infants have been a subject of mental health research. The aim of this study was to assess the prevalence of and risk factors associated with such symptoms in mothers of preterm infants in Taiwan. METHODS: This was a cross-sectional study performed between January 1, 2010 and June 30, 2011. One hundred and two mothers of preterm infants born at less than 37 weeks gestation and with a subsequent neonatal intensive care unit (NICU) stay between 2005 and 2009 were recruited. Participants completed a demographic questionnaire, the Impact of Event Scale-Revised (IES-R), the Center for Epidemiologic Studies Depression Scale (CES-D) and the neuroticism subscale of the Maudsley Personality Inventory (MPI). The preterm infants' data were taken from medical records. RESULTS: The prevalence of symptoms of distress was 25.5% (26/102) in the participants. These symptoms were associated with previous miscarriages, preterm premature rupture of membranes, neurotic personality and depression. CONCLUSIONS: The experience of preterm birth and NICU hospitalization can be traumatic to mothers. Early support for mothers during the preterm infants' NICU stay and transition to home care are recommended.

Sociodemographic and meteorological correlates of sudden infant death in Taiwan.

BACKGROUND: This study was designed, using three national datasets including the Taiwan Death Registry, Taiwan Birth Registry, and National Meteorological Dataset, to examine the sociodemographic, geographic and meteorological correlates of sudden infant death syndrome (SIDS). METHODS: One thousand, six hundred and seventy-one cases of SIDS occurring between 1994 and 2003, and 8355 matched controls were included in this nested case-control study. RESULTS: Over the study period, the annual rate of SIDS declined only slightly, with an average annual rate of 57.9/10(5) . Male infants (adjusted odds ratio [AOR], 1.19; 95% confidence interval [CI]: 1.06-1.33), preterm births (AOR, 1.69; 95%CI: 1.33-2.13), low birthweight (AOR, 2.87; 95%CI: 2.30-3.59), and birth order ≥3 (AOR, 1.62; 95%CI: 1.37-1.92) were the demographic risk factors for SIDS. Additionally, paternal age <25 years (AOR, 1.37; 95%CI: 1.09-1.71), urbanization (AOR, 1.46; 95%CI: 1.20-1.78), lower paternal education (elementary and less; AOR, 1.28; 95%CI: 1.01-1.64), and parental age difference >10 years (AOR, 1.72; 95%CI: 1.24-2.39) were also associated with increased risk of SIDS. It was also noted that daily average temperature ranging from 9.2°C to 14.2°C (AOR, 2.10; 95%CI: 1.67-2.64) was associated with the most increased risk, while temperature ≥26.4°C (AOR 0.60, 0.61) was significantly associated with the most reduced risk. CONCLUSION: Sociodemographic, geographic and meteorological data can be used to identify families in greater need of early guidance and to promote various prevention measures to avoid the occurrence of SIDS.

Phthalates exposure and pubertal development in a 15-year follow-up birth cohort study in Taiwan.

Purpose: Phthalates are ubiquitous endocrine disruptors that can affect pubertal development in children. The association of fetal and childhood levels of phthalates with pubertal development were explored. Methods: We conduct a population-based birth cohort study to investigate the association between prenatal and childhood exposure to phthalates and pubertal development. Initially, a total of 445 children were recruited from 2000 to 2001, of which 90 children were followed for 15 years which measurements of urine and development assessed at 2, 5, 8, 11, and 14 years. We defined higher Tanner stage as the 14-year-old Tanner stage ≥ 4 and 5 for boys and girls, respectively. A logistic regression analysis was conducted to estimate the crude and adjusted odds ratio of a higher Tanner stage at 14 years old. The Pearson correlation coefficient and multiple linear regression were used to estimate the association of testicular volume, uterine volume, ovarian volume, and blood hormones at 14 years of age with the log-transformed concentration of phthalates at 2, 5, 8, 11, and 14 years. Results: In boys, a significantly different geometric mean of mono-benzyl phthalate (MBzP) was observed in 11-year-olds; 6.82 and 2.96 in the lower Tanner stage group and higher Tanner stage group. In girls, a significant difference in the geometric mean of mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) in 11-year-olds and mono-ethyl phthalate (MEP) in 2-year-olds was observed; MEHHP was 32.97 and 18.13 in the lower Tanner stage group and higher Tanner stage group, and MEP was 26.54 and 65.74 in the lower Tanner stage group and higher Tanner stage group, respectively. Uterine volume at 14 years old was negatively associated with several phthalate metabolites (MEHP at 8 years old, MnBP at 8 years old, MBzP at 14 years old, MMP prenatally, MMP at 8 years old, and MEP at 8 years old) after adjusting for covariates. However, no significant correlations were found between phthalate metabolites and ovarian or testicular volume. Conclusion: Phthalate exposure at certain time points may influence the reproductive development of children during puberty; however, further studies should be conducted to determine the causal nature of this association.

Exposure to di(2-ethylhexyl) phthalate in premature neonates in a neonatal intensive care unit in Taiwan.

OBJECTIVE: Neonates are exposed to high levels of di(2ethylhexyl) phthalate through numerous medical procedures in the neonatal intensive care unit. Our aim was to assess the contribution of specific medical devices to the di(2-ethylhexyl) phthalate exposure of neonates. DESIGN: Prospective. SETTING: University hospital. PATIENTS: We recruited 32 premature neonates, 20 with very low birth weight (<1500 g) and 12 with low birth weight (<2500 g), and 31 controls at a neonatal intensive care unit from a medical center in central Taiwan. INTERVENTIONS: Interventions were based on a clinical need and used standard materials and devices, including endotracheal tubes, continuous positive airway pressure, oxygen hood, intravenous injection, intralipid injection, blood transfusion, orogastric tubes, nasogastric tubes, umbilical venous catheterization, umbilical arterial catheterization, chest tube, and isolate. MEASUREMENTS AND MAIN RESULTS: We recorded the medical procedures of each subject, collected their urine samples, and determined the urinary concentration of three metabolites of di(2-ethylhexyl) phthalate using reversed-phase high-performance liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry. Median levels of di(2-ethylhexyl) phthalate metabolites in premature neonates treated with an endotracheal tube and orogastric tube or nasogastric tube were significantly higher than those not treated with an endotracheal tube, orogastric tube, or nasogastric tube. Median levels of di(2-ethylhexyl) phthalate metabolites in premature neonates treated with intravenous injection were ≥ 2-fold higher than those of healthy controls who received intravenous injections (p = .01). Median levels of three di(2-ethylhexyl) phthalate metabolites were similar in very-low-birth-weight and low-birth-weight neonates. CONCLUSIONS: These data suggest that polyvinyl chloride-containing devices are the major defining factor in di(2-ethylhexyl) phthalate exposure levels in neonates in the neonatal intensive care unit. We urge the use of polyvinyl chloride-free or alternative materials in medical devices, especially for endotracheal tubes, orogastric tubes, nasogastric tubes, and intravenous tubing in the neonatal intensive care unit. The health effects of high di(2-ethylhexyl) phthalate exposure on premature neonates in the neonatal intensive care unit is worthy of further investigation.

The Age Distribution among Children Seeking Medical Treatment for Precocious Puberty in Taiwan.

OBJECTIVE: Children with precocious puberty (PP) may have increased physiological and psychological problems. In this study, we aimed to explore the trend of parents seeking medical care for their children with precocious puberty. METHODS: The Taiwan National Health Insurance Research Dataset (NHIRD) was used to estimate the prevalence (2000-2013) and incidence (2002-2013) of PP (ICD-9 code: 259.1) among boys aged 0-11 years and girls aged 0-10 years. The proportions of PP management within 1 year from the date of first diagnosis were also compared between two periods (2002-2007 and 2008-2012). The trends of PP prevalence or incidence were determined by join-point regression. RESULTS: In 2000, 309 boys and 2706 girls had at least one visit for PP, the crude prevalence rates (per 10,000 persons) were 0.99 (95% confidence interval, 95% CI 0.87-1.14) and 13.56 (95% CI 13.01-14.13) in boys and girls, respectively. In 2013, the crude prevalence rates increased to 7.01 (95% CI 6.56-7.84) and 110.95 (95% CI 108.97-112.96) in boys and girls, respectively. A total of 2584 girls and 207 boys with incident PP cases were identified in 2002, and 7498 girls and 739 boys were identified in 2013. For girls, the incidence rates (per 10,000 person-years) were 16.17 (95% CI 15.55-16.80) and 70.23 (95% CI 68.65-71.83) in 2002 and 2013, respectively. For boys, the incidence rates were 1.09 (95% CI 0.95-1.24) and 5.72 (95% CI 5.32-6.15) in 2002 and 2013, respectively. The sex ratio (F:M) of the incidence of PP cases was 14.89 in 2002 and 12.28 in 2013. CONCLUSION: In this study, from 2000 to 2013, the frequency of visiting pediatric endocrinology outpatient clinics for precocious puberty increased in both genders. We advocate that it is important to pay increased attention to children's health, environmental hormones, and diet. Researchers should consider how to survey precocious puberty and offer parents more education to avoid the waste of medical resources or delays in seeking medical care.

Transthyretin levels are not related to Apgar score in low birth weight and very low birth weight infants.

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.

Prenatal cytogenetic diagnosis in Taiwan: a nationwide population-based study.

PURPOSE: The goal of this study was to gain a better understanding of the status of advanced maternal age among criteria for provision of amniocentesis in pregnant women in Taiwan. MATERIALS AND METHOD: Data of 315 670 second-trimester amniocenteses from 28 national certified cytogenetics laboratories were retrospectively analyzed from the Prenatal Genetic Diagnosis Declaring and Database System of the Health Promotion Administration, Ministry of Health and Welfare in Taiwan between 2006 and 2013. RESULTS: The number of pregnant women undergoing amniocentesis in Taiwan between 2006 and 2013 increased, and the most common three indications for amniocentesis were advance maternal age (75.11%), abnormal second trimester maternal serum screening (13.22%) and abnormal sonographic finding (8.00%). Down syndrome was the most common autosomal abnormality identified (25.74%); Turner syndrome was the most common sex chromosome abnormality (7.04%). Of structural rearrangements, 26.93% were balanced translocations and 17.10% were unbalanced translocations. The greatest proportion of fetal chromosomal abnormalities was found in cases where parents were also affected (38.02%). CONCLUSIONS: Clinical workers should provide detailed genetic diagnostic information to pregnant women, especially those with the common amniocentesis indications, which will enable them to determine a birth plan.

Factors affecting adequate prenatal care and the prenatal care visits of immigrant women to Taiwan.

This paper investigates prenatal care utilization, identifies factors affecting the adequacy of prenatal care, and explores the effect of adequate initial timing of prenatal care on total prenatal care visits among Taiwan new immigrant females. Data was obtained from the 2008 Prenatal Care Utilization among Taiwan New Immigrant Females Survey on women who either had at least one preschool-aged child or had delivered their infants but were still hospitalized (N = 476). The Adequacy of Prenatal Care Utilization Index was applied to rate the prenatal care adequacy. The logistic regression model was used to investigate factors associated with the adequacy of prenatal care utilization, and the linear regression model was estimated to identify the impact of influential factors on the prenatal care usage. Females' nationality, employment, and transportation convenience increased the likelihood of receiving adequate prenatal care. Having adequate initial timing of prenatal care was found to be positively related to the frequency of prenatal care visits. Prenatal care utilization can be affected by factors within the health care system and by characteristics of the population; therefore, a measure of prenatal care utilization cannot distinguish these factors but reflects the result of all of them in varying combinations.

Prevalence and factors associated with depressive symptoms in mothers with infants or toddlers.

BACKGROUND: The objective of this study is to explore the prevalence of and factors associated with depressive symptoms in mothers with young children. METHODS: This is a cross-sectional face-to-face study performed between January 1, 2010 and June 30, 2011. Mothers of premature infants with a gestational age of less than 37 weeks were recruited. Premature infants with any congenital anomaly or severe congenital heart disease were excluded. Controls were mothers of full-term infants with birth weight over 2500 g and without admission to a neonatal intensive care unit. Outcome measures included the Center for Epidemiologic Studies Depression Scale for maternal depressive symptoms, the Family Apgar Index for family support, and the Chinese Maudsley Personality Inventory for personality traits. RESULTS: A total of 102 mothers of preterm infants and 111 mothers of full-term infants were recruited. The prevalence of depressive symptoms was 27.7% (59/213) in all mothers of this study, 29.4% (30/102) in mothers of preterm infants, and 26.1% (29/111) in mothers of full-term infants. Predictors of maternal depressive symptoms included the following: extended family structure, lack of postpartum confinement, low family support, and a personality characterized by neuroticism. CONCLUSION: Depressive symptoms were common among mothers of young children. Family function and neurotic personality were highly correlated with depressive symptoms in mothers caring for young children. Pediatric health care providers are suggested to screen for maternal depressive symptoms and provide family-oriented support in Taiwan.

Efficacy of intermediate-dose oral erythromycin on very low birth weight infants with feeding intolerance.

BACKGROUND: Erythromycin is generally used as a prokinetic agent for the treatment of feeding intolerance in preterm infants; however, results from previous studies significantly vary due to different medication dosages, routes of administration, and therapy durations. The effectiveness and safety of intermediate-dose oral erythromycin in very low birth weight (VLBW) infants with feeding intolerance was examined in this study. METHODS: Between November 2007 and August 2009, 45 VLBW infants with feeding intolerance, who were all at least 14 days old, were randomly allocated to a treatment group and administered 5mg/kg oral erythromycin every 6hours for 14 days (n=19). Another set of randomly selected infants was allocated to the control group, which was not administered erythromycin (n=26). RESULTS: The number of days required to achieve full enteral feeding (36.5±7.4 vs. 54.7±23.3 days, respectively; p=0.01), the duration of parenteral nutrition (p<0.05), and the time required to achieve a body weight ≥2500g (p<0.05) were significantly shorter in the erythromycin group compared with the control group. The incidence of parenteral nutrition-associated cholestasis (PNAC) and necrotizing enterocolitis (NEC) ≥ stage II after 14 days of treatment were significantly lower (p<0.05) in the erythromycin group. No significant differences were observed in terms of the incidences of sepsis, bronchopulmonary dysplasia, or retinopathy of prematurity. No adverse effects were associated with erythromycin treatment. CONCLUSIONS: Intermediate-dose oral erythromycin is effective and safe for the treatment of feeding intolerance in VLBW infants. The incidences of PNAC and ≥ stage II NEC were significant lower in the erythromycin group.

Common etiologies of neonatal pleural effusion.

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.