A prospective study of serum insulin-like growth factor I (IGF-I) and IGF-binding protein-3 in 942 healthy infants: associations with birth weight, gender, growth velocity, and breastfeeding.

CONTEXT: Many aspects of hormonal regulation and mechanisms of normal infancy growth are poorly understood. OBJECTIVE: The objective of this study was to establish the determinants of serum growth factor levels in infancy and their association with growth. DESIGN: A prospective, longitudinal, population-based birth cohort between 1997-2001 was studied. PARTICIPANTS: Study participants were 942 healthy appropriate weight for gestational age (AGA) infants (538 boys and 404 girls) and 49 small for gestational age (SGA) children (29 boys and 20 girls). INTERVENTIONS: INTERVENTIONS were anthropometrical measurements (0, 3, 18, and 36 months) and serum samples (3 months). MAIN OUTCOME MEASURES: Height, weight, and serum IGF-I and IGF-binding protein-3 (IGFBP-3) were the main outcome measures. RESULTS: IGF-I levels showed no gender difference [boys, 92 ng/ml (confidence interval, 49, 162); girls, 91 ng/ml (47, 149); P = 0.50]. IGFBP-3 levels were significantly higher in females [2174 ng/ml (1295, 3330)] than in males [2103 ng/ml (1266, 3143); P = 0.04]. Infants receiving breast milk had lower IGF-I levels [90 ng/ml (48, 154)] than infants receiving formula [n = 62; 97 ng/ml (58, 165)] or both [n = 123; 94 ng/ml (48, 169); P < 0.001]. IGF-I and IGFBP-3 levels were positively associated with weight gain and height gain from birth to 3 months of age in AGA, but not in SGA, children. SGA children had significantly lower IGF-I [88.0 ng/ml (28, 145); P = 0.05] and IGFBP-3 [1835 ng/ml (1180, 2793); P < 0.001] levels than AGA children. CONCLUSION: We found a significant, but weak, association between IGF-I and IGFBP-3 levels at 3 months and postnatal growth in AGA, but not SGA, children. Factors other than IGF-I must contribute to the regulation of normal postnatal growth, and these may differ between AGA and SGA children. IGFBP-3, but not IGF-I, showed a gender difference, which may reflect an influence of the postnatal activation of the pituitary-gonadal axis on binding protein levels.

Hypospadias in a cohort of 1072 Danish newborn boys: prevalence and relationship to placental weight, anthropometrical measurements at birth, and reproductive hormone levels at three months of age.

CONTEXT: Hypospadias is one of the most frequent male congenital malformations and may be part of the testicular dysgenesis syndrome. OBJECTIVE: The aim of the study was to investigate the prevalence of hypospadias in Denmark and evaluate the relationship to anthropometrical measurements at birth and reproductive hormone levels at 3 months of age. DESIGN: A prospective cohort study was conducted with 3-yr follow-up (1997-2004). SETTING: The population-based study was conducted at the University Hospital of Copenhagen. PARTICIPANTS: A total of 1072 Danish boys were consecutively recruited antenatally, with 74.4% completing the study. MAIN OUTCOME MEASURES: The study examined the position of the urethral meatus, anthropometrical measurements, placental weight, and reproductive hormone levels. RESULTS: The Danish birth prevalence of hypospadias was significantly higher than in a concomitant Finnish study (1.03 vs. 0.27%; P = 0.012). At 3 yr, the true prevalence was found to be 4.64% because additional mild cases were detected when physiological phimosis dissolved. Weight for gestational age (percentage deviation from expected mean) (-5.00 vs. -0.59%; P = 0.030) and placental weight (567 vs. 658 g; P = 0.023) were significantly lower, and FSH was significantly higher (1.48 vs. 1.15 IU/liter; P = 0.007) in boys with hypospadias, compared with healthy boys. CONCLUSIONS: We found a surprisingly high total rate of hypospadias of 4.6% in this large prospective cohort study. Seventy-two percent of the cases were apparent only after the prepuce could be retracted. Hypospadias were associated with elevated serum FSH levels at 3 months. We also confirmed an association between fetal growth impairment and hypospadias; however, it is yet unknown whether this indicates a causal relationship or a shared pathogenic factor.