Growth hormone treatment in short children born prematurely--data from KIGS.

Children born prematurely with growth failure might benefit from GH treatment. The aim was to evaluate the first year growth response to GH treatment in short children born prematurely and to identify predictors of the growth response. A total of 3215 prepubertal children born prematurely who were on GH treatment were selected from KIGS (The Pfizer International Growth Database), a large observational database. They were classified according to gestational age as preterm (PT; 33 to no more than 37 wk) and very preterm (VPT; <33 wk), and according to birth weight as appropriate for gestational age [AGA; between -2 and +2 sd score (SDS)] and small for gestational age (SGA; -2 SDS or below). Four groups were identified: PT AGA (n = 1928), VPT AGA (n = 629), PT SGA (n = 519), and VPT SGA (n = 139). GH treatment was started at a median age of 7.5, 7.2, 6.7, and 6.0 yr, respectively. After the first year of GH treatment, all four groups presented a significant increase in weight gain and height velocity, with a median increase in height SDS higher than 0.6. Using multiple stepwise regression analysis, 27% of the variation in height velocity could be explained by the GH dose, GH peak during provocative test, weight and age at GH start, adjusted parental height, and birth weight SDS. The first year growth response of the children born PT and SGA could be estimated by the SGA model published previously. Short children born prematurely respond well to the first year of GH treatment. Long-term follow-up is needed.

Boguszewski MC ，Karlsson H ，Wollmann HA ，Wilton P ，Dahlgren J ... -  《-》

Short children born prematurely: data from KIGS.

Advances in neonatal care have enabled the survival of extremely preterm infants. Some of them have growth failure and remain short at later ages. As a consequence, children born prematurely may be candidates for growth hormone (GH) treatment. The goal of this study was to obtain information about children on GH therapy enrolled in the Pfizer International Growth Database (KIGS) who were born prematurely. The KIGS database was queried for data on prepubertal short children (height <-2 standard deviation score; SDS) born with gestational age below 37 weeks. Birth weight had to be available. In total, 3,215 patients were selected and classified according to gestational age and birth weight as preterm (<37 weeks' gestation), very preterm (VP; <33 weeks' gestation), appropriate for gestational age (AGA; birth weight between -2 and +2 SDS) or small for gestational age (SGA; birth weight <-2 SDS). Of these, 1,928 children were preterm AGA, 629 very preterm AGA, 519 preterm SGA, and 139 very preterm SGA. KIGS is a cumulative database and provides a unique opportunity to evaluate the growth response to GH therapy of premature children born with differences in gestational ages, size at birth, rate of postnatal growth, and GH secretion status.

Boguszewski MC ，Karlsson H ，Wilton P 《-》

Three-year growth response to growth hormone treatment in very young children born small for gestational age-data from KIGS.

Children born small for gestational age (SGA) with poor growth during the first years of life may remain short in stature during childhood and as adults. To evaluate the 3-year growth response to GH treatment in very young short children born SGA, and to test the existing predictions models for growth response developed for older SGA children. KIGS (The Pfizer International Growth Database). A total of 620 SGA children (birth length and/or weight below -2 SD score [SDS]) on GH treatment, 156 in the 2- to 4-year-old group (100 boys; median age, 3.3 y), and 464 in the 4- to 6-year-old group (284 boys; median age, 4.9 y). Median values and 10th-90th percentiles are presented. Both groups presented a significant increase in height velocity during GH treatment. Median height SDS increased from -3.9 (-5.4 to -2.9) at the start to -2.2 (-3.8 to -1.0) at 3 years in the 2- to 4-year-old group (P < .01) and from -3.4 (-4.5 to -2.6) to -2.0 (-3.3 to -0.9) in the 4- to 6-year-old group (P < .01). Median weight SDS increased from -3.8 (-5.9 to -2.4) to -2.1 (-4.1 to -0.5) in the 2- to 4-year-old group (P < .01). Respective values for the 4- to 6-year-old group were -3.1 (-4.8 to -1.8) to -1.6 (-3.1 to -0.1) SDS (P < .01). First- and second-year growth response could be estimated by the SGA model. Very young children born SGA without spontaneous catch-up growth presented a significant improvement in height and weight during the 3 years of GH treatment. Growth response could be estimated by the SGA model.

Boguszewski MC ，Lindberg A ，Wollmann HA 《-》

Near-Adult Height After Growth Hormone Treatment in Children Born Prematurely-Data From KIGS.

Children born prematurely have been treated with growth hormone (GH), and a significant improvement in height during the first years of treatment has been described. To evaluate the influence of prematurity on near-adult height (NAH) after GH treatment. KIGS (Pfizer International Growth Database) was queried for children born preterm treated with GH. KIGS database. A total of 586 children short in stature born preterm with various GH status and with available gestational age (GA), birth weight, and NAH, all treated with GH. GH treatment. NAH. Values were expressed as median. From the 586 children included, 482 born appropriate for GA (AGA; median age 8.26 years) and 104 born small for gestational age (SGA) (median age 8.54 years); 66.6% of preterm AGA had GH peak < 7 µg/L during a provocation test, whereas only 8.6% of preterm SGA. Change in height standard deviation scores (SDS) from GH start to NAH after 8.04 years of GH treatment was 1.82 in preterm AGA. Respective values were 7.08 years and 1.08 SDS for preterm SGA (P < 0.001); 57% of the variability of the growth response to NAH could be explained, and the distance to parental height was the strongest predictor. No significant changes in height SDS were observed from puberty start to NAH. No correlation was found with GA. GH treatment was well tolerated. GH treatment resulted in significant improvement in height in children born preterm, particularly during prepubertal years and for those with GH deficiency. The degree of prematurity did not influence the growth response.

Boguszewski MCS ，Carlsson M ，Lindberg A ，Dahlgren J ，Aydin F ，Camacho-Hübner C ，Hokken-Koelega ACS ... -  《-》

Height, muscle, fat and bone response to growth hormone in short children with very low birth weight born appropriate for gestational age and small for gestational age.

Growth hormone (GH) treatment is approved for short children born SGA but not for AGA. Our aim was to study the effect of GH in short VLBW SGA and AGA children. The study group comprised 44 prepubertal short children with a birth weight <1,500 g: 27 AGA (12 females) and 17 SGA (6 females). Mean values at GH start were (AGA, SGA): age 6.94, 7.14 years, height standard deviation score (SDS) -3.33, -3.33, and GH dose (mean ± SD) 54 ± 12, 51 ± 11 µg/kg/day. Arm and calf cross-sectional muscle area using peripheral quantitative computer tomography, body composition data using dual-energy X-ray absorptiometry and body impedance assessment, maximal isometric grip force and skin fold thickness, IGF-1 and IGFBP-3 were measured at the start and after 12 months of GH. At GH start, both groups had similar characteristics with low height, weight, height velocity, muscle mass, bone thickness and content. The first year of GH treatment led to changes in muscle area SDS (AGA, SGA) -2.23 to -0.73 (p = 0.0010), -3.18 to -1.17 (p = 0.060) (AGA vs. SGA p = 0.61), fat area SDS -1.06 to -1.83 (p = 0.054), -0.62 to -1.75 (p = 0.12) (AGA vs. SGA p = 0.65) and height velocity SDS -0.0015 to 4.2 (p < 0.0001), -0.18 to 3.3 (p < 0.0001) (AGA vs. SGA p = 0.36). Growth, muscle and fat mass are similarly impaired in short prepubertal AGA and SGA VLBW children. The children born AGA show a similar or better response to GH compared to those born SGA. These results reveal the arbitrary nature of using the criterion 'SGA' for eligibility to GH treatment in children born with a birth weight <1,500 g.

Berndt C ，Schweizer R ，Ranke MB ，Binder G ，Martin DD ... -  《-》