Background: A stepwise increment of the GH dose is an approach aimed at avoiding adverse events. We investigated GH sensitivity by studying IGF-I and IGFBP-3 concentrations during the initial phase of GH treatment. Methods: Our investigation was part of the regular follow-up of prepubertal children with GH deficiency (GHD) (n = 31) and small for gestational age (SGA) (n = 23). Dosage was increased in three steps: one-third at the start, two-thirds after 14 days, and the full dose after 28 days (full dose: GHD = 28 µg/kg body weight (BW)/day; SGA = 60 µg/kg BW/day). Blood samples were taken on days 0, 14 and 28, as well as in conjunction with anthropometrical examinations after 3, 6 and 12 months. IGF-I and IGFBP-3 were measured by means of published in-house RIAs and age-related references were used to calculate standard deviation scores (SDS). Height velocity (cm/year) and Δ HT SDS were taken as growth response parameters. Results:Before GH treatment (GHD vs. SGA; median and p values): age (years) (6.6 vs. 6.0; n.s.), HT SDS (–2.6 vs. –3.2; p < 0.05); GH amount after stepping up (µg/kg BW/day) (28 vs. 60; p < 0.01); BW SDS (–0.5 vs. –2.9; p < 0.01); max. GH stimulated (µg/l) (5.6 vs. 10.8; p < 0.01); IGF-I SDS (–3.5 vs. –1.8; p < 0.01); IGFBP-3 SDS (–2.0 vs. 0.8; p < 0.01). After 1 year of GH therapy: HT velocity (cm/year) (9.8 vs. 9.6; n.s.), Δ HT SDS (0.9 vs. 0.9; n.s.); WT velocity (kg/year) (3.3 vs. 3.5; n.s.). Our results show that changes in growth similar to GHD could be induced in SGA by a dosage that was twice as high as the replacement dose given in GHD. GH dose and HT velocity did not correlate in both groups. IGF-I and IGFBP-3 increased as follows in GHD and SGA during stepping up of the dosage (ng/ml, GHD vs. SGA): at start, 54 vs. 89; at day 14, 78 vs. 132; at day 28, 90 vs. 167; at 3 months, 118 vs. 218. There was the same relationship between dose levels and absolute IGF-I concentrations in both groups. In terms of IGF-I SDS, the dose-response curve in SGA showed a shift to the right in comparison to GHD, thus indicating lower sensitivity to GH. The dynamics of IGF-I and IGFBP-3 differed, as IGFBP-3 peaked earlier (on day 28). In GHD, IGF-I SDS at 3 months was –0.7 vs. +0.9 in SGA. Near-identical levels were found for Δ IGF-I SDS and IGFBP-3 SDS above basal levels for each time-point investigated. First year HT velocity in GHD correlated negatively with basal IGF-I SDS (R² = 0.33; p <0.001) and basal IGFBP-3 (R² = 0.17; p <0.05) but did not correlate with the IGF-I increment during the 0- to 3-month period. Conversely, first year HT velocity correlated (+) in SGA with the IGF SDS increment during the 0- to 3-month period (R² = 0.26; p = <0.05). Height velocity in SGA, however, correlated neither with basal IGF-I and IGFBP-3 nor with the 0- to 3-month increments of IGFBP-3 SDS. Conclusions: IGFs increase during initial GH therapy, thus raising questions about short-term IGF generation tests. (I) In terms of IGF generation, substantially lower sensitivity to GH was ...

Children born with very low birth weight (VLBW) are at risk of impaired growth. We aimed to study VLBW survivors (90.8%) born in 1998/1999 in the state of Baden-Württemberg (n ϭ 2103) for whom growth data were available up to age six. Classification as appropriate for gestational age (AGA) or small for gestational age (SGA) depended on size at birth. Models to predict height SDS at 5 y were developed using data for 1 yr (Model 1) and 2 yrs (Model 2). The data of 1320 (63%) children were available: SGA: n ϭ 730, AGA: n ϭ 590. At 6 yrs, 8.3% AGA and 13.4% SGA children were short (ϽϪ2.0 SDS). The following factors explained Ht SDS at 5 (and 6) yrs (order of importance): (a) Model 1 (n ϭ 1033; R 2 ϭ 0. A lthough the frequency of premature births has risen during the last decades, the number of surviving babies has risen due to improved perinatal care. This holds particularly true for children with very low birth weight (VLBW; BW Ͻ 1500 g), as their survival rate has reached about 90% (1). Several reports have shown more frequent impairments in growth development in this group in comparison to other prematurely born children with higher birth weights (2-9). After Barker and colleagues established that low birth weight was a major determinant of mortality and morbidity in adult life (10), overwhelming evidence became available from epidemiologic studies which show that impaired birth weight is associated with a higher prevalence of the metabolic syndrome. It has therefore been hypothesized that an impairment in prenatal growth influences the long-term "metabolic programme" of an individual. Several authors have reported that children born small for gestational age (SGA) showed impaired growth in contrast to children whose birth length was appropriate for gestational age (AGA). However the main group studied in these reports involved either children with birth weights higher than 1500 g (11-14) or VLBW children born earlier than 1990 (3,5,6,15,16). Our study of VLBW children was aimed at investigating growth development from birth until early school age and at identifying the factors to predict their height development during childhood. The two birth cohorts we studied derived from the state birth register in Baden-Württemberg in Germany for the years 1998 and 1999, respectively. METHODS Population.The state of Baden-Wuerttemberg represents about 10% of Germany's geographical area and approximately 13% of its population. According to the state birth register, there were 108,000 births in 1998 and 111,000 in 1999 (17). Of these, 2316 VLBW babies were born and 2103 (90.8%) of them survived (1). There are 30 neonatal intensive care units (NICU) in Baden-Wuerttemberg, including four university hospitals; and all excepting two small units participated in our study (see Acknowledgements).Data collection. In 2004, birth and follow-up data were available for 2040 (97%) surviving children born VLBW. Parents were sent a questionnaire and a description of the study by post. 1322 (62.9%) families returned the questionnai...

Preterm VLBW infants, whether AGA or SGA at birth, face the risk of being short at preschool age. Height outcome is probably influenced by postnatal factors. Our data also suggest that short stature is associated with developmental difficulties in this population.

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