Central congenital hypothyroidism caused by maternal thyrotoxicosis.

Central congenital hypothyroidism (CCH) is a rare and underdiagnosed disease that sometimes is caused by maternal Graves' disease. We report a case of CCH caused by undiagnosed, initially antibody-negative maternal thyrotoxicosis with possible disruption of fetal hypothalamic-pituitary-thyroid axis maturation. In CCH, maternal thyroid disease should be considered.

How to stent the ureter after kidney transplantation in children?-A comparison of two methods of urinary drainage.

Ureteral stenting after pediatric renal transplantation serves to prevent obstruction and urinary leakage, but can also cause complications. This study compares the complication rates of both methods. Data were retrospectively collected at Erasmus MC, Rotterdam, the Netherlands (splint group, n = 61) and Hospital for Sick Children, Toronto, Canada (JJ catheter group, n = 50). Outcome measures included urological interventions and incidence of UTIs during the first 3 months post-transplantation. The splint was removed after a median of 9 (IQR 8-12), the JJ catheter after 42 (IQR 36-50) days. Seven (11.5%) children in the splint group needed at least one urological re-intervention versus two in the JJ catheter group (P-value .20). UTIs developed in 19 children (31.1%) in the splint group and in twenty-five (50.0%) children in the JJ catheter group (P-value .04), with a total number of 27 vs. 57 UTIs (P-value .02). Nine (33.3%) vs. 35 (61.4%) of these, respectively, occurred during the presence of the splint (P-value <.001). Children with a JJ catheter developed more UTIs than children with a splint; the latter, however, tended to require more re-interventions. Modification of either method is needed to find the best way to stent the ureter.

Health profile of young adults born preterm: negative effects of rapid weight gain in early life.

INTRODUCTION: Early postnatal weight gain is associated with determinants of cardiovascular disease (CVD) and type 2 diabetes mellitus (DM2) in adults born term. We aimed to investigate the association of weight gain during different periods, and weight trajectories in early life after preterm birth, with determinants of CVD and DM2 in early adulthood. METHODS: Associations of first-year growth and tempo of weight gain with determinants of CVD and DM2 in 162 young adults (18-24 yr) born preterm (gestational age <36 wk) were determined and compared with data of young adults born term (n = 217). RESULTS: Gain in weight for length in the period from preterm birth up to term age, and in the first 3 months after term age, was positively associated with body fat percentage and waist circumference at 21 yr. Gain in weight for length in the first 3 months after term age was also positively associated with total cholesterol and low-density lipoprotein cholesterol levels in early adulthood. Subjects with the highest gain in weight from birth to term age (highest quartile) had significantly higher body fat percentage, waist circumference, acute insulin response, and disposition index in early adulthood than the subgroups with moderate and low gain in weight. Rapid catch-up in weight during the first 3 months after term age resulted in a higher fat percentage, waist circumference, and serum triglycerides level than slower catch-up in weight. CONCLUSION: Accelerated neonatal gain in weight relative to length after preterm birth (immediately after birth and during the first 3 months after term age) is associated with determinants of CVD in early adulthood and should therefore be avoided.

Early origins of the metabolic syndrome: role of small size at birth, early postnatal weight gain, and adult IGF-I.

BACKGROUND: The relationship between low birth weight and increased risk for metabolic syndrome (MetS) in later life has been frequently described, but mechanisms underlying this association remain unknown. METHODS: In 280 young adults of the PROGRAM study, aged 18-24 yr, we investigated associations of birth weight, gain in weight for length during early life, and adult IGF-I sd score (SDS), with number of MetS components (ordinal regression analyses), prevalence of MetS components and MetS (logistic regression analyses), and other metabolic parameters (linear regression analyses). Revised criteria of the National Cholesterol Educational Program (Adult Treatment Panel III) were used to determine components of MetS. The other metabolic parameters were C-reactive protein, insulin sensitivity, trunk fat mass, total cholesterol, and low-density lipoprotein cholesterol. RESULTS: More gain in weight for length SDS in the first 3 months of life was significantly associated with an increased number of MetS components [odds ratio (OR) = 1.34], prevalence of low high-density lipoprotein cholesterol (OR = 1.49), prevalence of MetS (OR = 2.51), increased C-reactive protein levels, and lower insulin sensitivity (P = 0.007) at the age of 21 yr. Low birth weight SDS was associated with lower insulin sensitivity (P = 0.036), but low birth weight SDS and adult IGF-I SDS were not significantly associated with any of the MetS components or MetS prevalence at 21 yr. CONCLUSION: Our study demonstrates that higher gain in weight for length in the first 3 months of life is associated with a higher prevalence of MetS at 21 yr, whereas low birth weight and low adult IGF-I are not.

Does preterm birth influence cardiovascular risk in early adulthood?

OBJECTIVE: To investigate the effect of preterm birth on risk factors for cardiovascular disease (CVD), independent of birth size. STUDY DESIGN: Observational study using data of 406 healthy participants aged 18-24 years, from the PROgramming factors for Growth And Metabolism and Prematurity and Small for Gestational Age studies. Associations between gestational age (GA), systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), blood pressure variability, heart rate (HR), pulse wave velocity, and carotid intima media thickness (cIMT) were studied. To study the differential effects of preterm birth and small birth size for gestational age, these parameters were also analyzed in subgroups born either preterm or term: young adults born small for gestational age with short or normal adult stature, and young adults born appropriate for gestational age with normal adult stature. RESULTS: Subjects born preterm (GA <36 weeks) had higher unadjusted SBP, PP, SBP and DBP variability, and HR, but a lower DBP than subjects born term. GA was inversely associated with SBP, PP, blood pressure variability, and HR, and positively associated with DBP, also after adjustment for confounders. There was no effect of GA on pulse wave velocity and cIMT, a marker of atherosclerosis. Of all the CVD risk factors measured, higher PP affected cIMT the most. CONCLUSIONS: Young adults born preterm might have a higher risk for CVD than those born term.

Preterm birth does not affect bone mineral density in young adults.

OBJECTIVE: Previous studies showed conflicting data on the effect of prematurity on bone mineral density (BMD) in infants and children. Only a few studies investigated the long-term effects of prematurity on BMD in early adulthood. The objective of our study was to assess the long-term effects of preterm birth on BMD of the total body (BMD(TB)), lumbar spine (BMD(LS)) and bone mineral apparent density of the LS (BMAD(LS)). DESIGN: Cross-sectional study. METHODS: It consists of two hundred and seventy-six healthy subjects without serious postnatal complications, aged 18-24 years. The contribution of gestational age to the variance in BMD in young adulthood and the differences in BMD between 151 subjects born preterm (median gestational age 32.2 weeks (interquartile range (IQR) 30.3-34.0)) and 125 subjects born at term (median gestational age 40.0 weeks (IQR 39.0-40.0)) were investigated. BMD was determined by dual-energy X-ray absorptiometry. RESULTS: There were no significant linear correlations between gestational age and BMD(TB) (r=0.063, P=0.30), BMD(LS) (r=0.062, P=0.31) and BMAD(LS) (r=0.069, P=0.26). Also after adjustment for possible confounders, gestational age was no significant contributor to the variance in BMD(TB) (P=0.27), BMD(LS) (P=0.91) and BMAD(LS) (P=0.87). No significant differences were found between preterm and term subjects with regard to BMD(TB), BMD(LS) and BMAD(LS). CONCLUSION: In our cohort of 276 young adults, aged 18-24 years, gestational age was not a significant determinant in the variance of BMD. Preterm birth without serious postnatal complications is not associated with a lower BMD in young adulthood.

Pathways leading to atherosclerosis: a structural equation modeling approach in young adults.

Several risk factors of cardiovascular diseases have been studied using direct association measures. Because the incidence of obesity and cardiovascular diseases is rising, it is important to correctly model these risk factors involved in development of cardiovascular diseases. Until now, statistical methods lacked to achieve this goal because of complex interrelationships involved. Structural Equation Modeling (SEM) is an advanced statistical technique that enables solving this issue. The aims of this study were to investigate whether SEM could unravel pathways involved in cardiovascular diseases and to visualize these pathways in a model. In 322 healthy participants of the PROGRAM (PROgramming factors for GRowth And Metabolism) study, 18 to 24 years of age, we explored pathways leading to atherosclerosis measured by carotid intima-media thickness. Using SEM, we were able to model these pathways for males and females using body fat percentage, serum lipid levels, and blood pressure. We are the first to present a model of complex direct and indirect effects of fat mass leading to atherosclerosis using SEM. Both male and female path-model had an excellent fit. Fat mass had a significant effect on carotid intima-media thickness through various pathways, with the largest effect size on carotid intima-media thickness via blood pressure. SEM showed that the pathways differed between males and females, with a larger effect of serum lipids on carotid intima-media thickness in males. In conclusion, SEM is suitable in identifying models to unravel potential causal pathways in complex origins of diseases. We present a model involving several pathways, showing that fat mass has an influence on risk factors for atherosclerosis, already at 21 years of age.

Cardiovascular and metabolic risk profile and acylation-stimulating protein levels in children with Prader-Willi syndrome and effects of growth hormone treatment.

CONTEXT: Reports on the cardiovascular and metabolic risk profile in children with Prader-Willi syndrome (PWS) and the effects of GH treatment are scarce. Acylation-stimulating protein (ASP) stimulates glucose uptake and triglyceride storage in adipose tissue. OBJECTIVES: The aim was to study the metabolic and cardiovascular risk profile and ASP levels and to investigate the effects of GH treatment. DESIGN: We conducted a randomized controlled GH trial. Infants and prepubertal children were assigned to receive GH (1 mg/m(2) . d) or to serve as controls for 12 and 24 months, respectively. PATIENTS: Eighty-five children with PWS (mean +/- sd age of 4.9 +/- 3.0 yr) participated in the study. MAIN OUTCOME MEASURES: We measured fat percentage (fat%) with dual-energy x-ray absorptiometry, blood pressure, fasting insulin and glucose levels, serum lipids, and ASP levels. RESULTS: Mean +/- SD fat% was 28.4 +/- 6.2 in infants and 36.9 +/- 8.5 in prepubertal children. Fat% sd score (SDS) was above 2 SDS in 95% of prepubertal children. In addition, 63% of infants and 73% of prepubertal children demonstrated at least one cardiovascular risk factor, defined as hypertension or dyslipidemia. The metabolic syndrome was demonstrated in 5% of all children. Mean +/- sd baseline ASP was 107 +/- 45 nmol/liter (normal < 58 nmol/liter) and correlated with fat mass and TG levels. GH improved fat%SDS and the HDLc/LDLc ratio (P < 0.0001 and P = 0.04). GH had no effect on mean ASP levels in this population. CONCLUSIONS: Many children with PWS had dyslipidemia and high ASP levels. GH improved fat% and high-density lipoprotein cholesterol/low-density lipoprotein cholesterol, but not ASP. High ASP levels may prevent complete normalization of fat%SDS during GH treatment but may contribute in keeping glucose and insulin levels within normal range.

Serum insulin-like growth factor-binding protein-2 levels and metabolic and cardiovascular risk factors in young adults and children born small for gestational age.

BACKGROUND: IGF binding protein (IGFBP)-2 might protect against cardiovascular disease. Small for gestational age (SGA) birth could be associated with a higher risk for type 2 diabetes mellitus and cardiovascular disease in later life. No data are available on the relationship between serum IGFBP-2 levels and cardiovascular risk factors in young adults and children born SGA. OBJECTIVE: The aim of the study was to determine circulating IGFBP-2 levels in subjects born SGA and to investigate the association with cardiovascular risk factors. METHODS: IGFBP-2 levels were measured in sera from 151 young adults born SGA and 147 short SGA children. Age- and gender-adjusted sd scores (SDS) were calculated. We determined blood pressure, serum lipids, body composition by dual-energy x-ray absorptiometry, and glucose homeostasis by homeostasis model of assessment for insulin resistance or frequently sampled iv glucose tolerance test. RESULTS: Serum IGFBP-2 SDS was significantly reduced in SGA young adults (with normal or short stature). Fat mass SDS was relatively high in SGA young adults and was reduced in short SGA children. Serum IGFBP-2 SDS in SGA young adults correlated positively with insulin sensitivity and negatively with fat mass SDS, insulin secretion (acute insulin response), fasting insulin, homeostasis model of assessment for insulin resistance, total cholesterol, triglycerides, and blood pressure SDS. The association between serum IGFBP-2 SDS and insulin sensitivity, blood pressure, total cholesterol, and triglyceride levels persisted after adjustment for known covariates including fat mass SDS. In short SGA children, IGFBP-2 SDS did not correlate with any of the cardiovascular risk factors. CONCLUSION: In young adults who were born SGA, serum IGFBP-2 levels associate with cardiovascular risk markers.

Influence of preterm birth and birth size on gonadal function in young men.

BACKGROUND/OBJECTIVES: Preterm birth has been associated with reduced reproduction rates and being born small for gestational age (SGA) with reduced gonadal function. We hypothesized that alterations concerning gonadal function in young men are not due to preterm birth or being born SGA, but are due to other (environmental) factors. METHODS: In 207 young men of the PROGRAM/PREMS cohort study, aged 18-24 yr, the influence of preterm birth, birth length, and birth weight on serum levels of anti-Mullerian hormone, inhibin B, testosterone, SHBG, non-SHBG-bound testosterone, LH, and FSH was analyzed with multiple regression modeling. In addition, markers of male gonadal function were analyzed in four subgroups: men born SGA with either short stature or catch-up growth, or men born appropriate for gestational age with idiopathic short stature or with normal stature (control). RESULTS: Preterm birth and SGA did not affect gonadal function. After adjustment for age, birth size, adult height, fat mass, and socioeconomic status (SES), preterm birth even showed a positive relation with inhibin B. Higher SES was associated with higher inhibin B levels. Higher fat mass was associated with decreased testosterone and SHBG levels and maternal smoking with increased LH and non-SHBG-bound testosterone levels. After adjustment for confounders, there were no significant differences in gonadal function between the subgroups. CONCLUSION: Preterm birth and SGA did not affect gonadal function in young men. Factors that affected gonadal function were: lower SES, a higher fat mass, and maternal smoking during pregnancy.

Timing and tempo of first-year rapid growth in relation to cardiovascular and metabolic risk profile in early adulthood.

CONTEXT: Growth during infancy appears to be an important determinant of cardiovascular disease and type 2 diabetes later in life. OBJECTIVES: To specify which period in the first year of life is related to determinants of cardiovascular disease and type 2 diabetes in early adulthood and to investigate the association between tempo of first-year weight gain (>0.67 SDs) and these determinants. DESIGN, SETTING, AND PARTICIPANTS: Observational study using longitudinal data collected in the Programming Factors for Growth and Metabolism (PROGRAM) study of 217 healthy participants, aged 18 to 24 years, including a relatively large sample of participants born small for gestational age and participants with short stature, performed at a medical center in The Netherlands between August 2004 and September 2007. The association of cardiovascular disease and type 2 diabetes with tempo of weight gain was assessed in a subgroup of 87 participants. MAIN OUTCOME MEASURES: Associations between periods of first-year growth and tempo of weight gain and determinants of cardiovascular disease and type 2 diabetes in early adulthood. RESULTS: Weight gain in the first 3 months of life was inversely associated with insulin sensitivity (beta, -0.223; 95% confidence interval [CI], -0.386 to -0.060) and serum high-density lipoprotein cholesterol level (beta, -0.053; 95% CI, -0.090 to -0.016) and positively associated with waist circumference (beta, 1.437; 95% CI, 0.066 to 2.808), acute insulin response (beta, 0.210; 95% CI, 0.024 to 0.395), ratio of total cholesterol to high-density lipoprotein cholesterol (beta, 0.052; 95% CI, 0.010 to 0.094), and level of triglycerides (beta, 0.066; 95% CI, 0.003 to 0.129) in early adulthood. Rapid weight gain during the first 3 months of life resulted in a higher percentage of body fat, more central adiposity, and reduced insulin sensitivity in early adulthood than when slower weight gain occurred during the entire first year. CONCLUSION: Rapid weight gain in the first 3 months of life is associated with several determinants of cardiovascular disease and type 2 diabetes in early adulthood.

Prematurity is not associated with reduced insulin sensitivity in adulthood.

BACKGROUND: In 2005, 12.7% of all babies were born preterm, and the incidence is rising. Nowadays, due to improved survival, an increasing number of children born preterm reach young adulthood. A recent report suggested lower insulin sensitivity in children born preterm, which may put them at risk for the development of type 2 diabetes. It is, however, still unknown whether this reduced insulin sensitivity persists into adulthood. METHODS: We determined insulin sensitivity and beta-cell function with frequently sampled iv glucose tolerance tests in 305 young adults (aged 18-24 yr; 169 preterm and 136 term). Adult body composition was measured by dual energy x-ray absorptiometry. We investigated the effect of gestational age, size at birth, and adult body composition on insulin sensitivity. RESULTS: In contrast to previous reports, we found no evidence that preterm birth has a deleterious effect on insulin sensitivity in young adulthood. Adult trunk fat and the use of oral contraceptives in women were the most important determinants of insulin insensitivity, independently of size at birth and duration of pregnancy. CONCLUSION: Contrary to our hypothesis, preterm birth was not associated with reduced insulin sensitivity in young adulthood.