Peer-reviewed article
Effectiveness and Safety of Early Growth Hormone Treatment in Children Born Small for Gestational Age: Long-Term Data From NordiNet® International Outcome Study (IOS) and ANSWER Program
Juul A, Pietropoli A, Kelepouris N, Geffner M ·
Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001This study evaluated the long-term safety and effectiveness of growth hormone treatment in children born small for gestational age (SGA), comparing those who started treatment before age 4, between ages 4-6, and at age 6 or older. Children who started treatment earlier showed greater height gains, particularly after 4 and 8 years of therapy. The treatment was safe across all age groups, with similar rates of adverse events regardless of when treatment began.
Key points
- Children starting GH before age 4 showed mean height gain of 2.5 SDS after 8 years, compared with 2.2 SDS (ages 4-6) and 1.7 SDS (ages 6+)
- Early treatment group (age <4) had lower height standard deviation scores at baseline (−3.3) compared with older groups (−3.1 and −2.8)
- Near-adult heights were similar across groups (around −1.8 to −1.9 SDS), though few children in early groups reached final height measurement
- Safety profile was consistent across all age groups; most common adverse events were headache and joint pain, which were rare
- Study included 3,351 children in effectiveness analysis and 5,643 in safety analysis from two complementary international registries
Limitations
Very few children in the younger age groups (n=3 and n=10) reached near-adult height measurement, making final height comparisons unreliable for early treatment groups. The study is observational and non-randomized, so differences between groups reflect clinical practice patterns rather than controlled comparison, and results cannot demonstrate causation.
Abstract
Abstract Background: Growth hormone (GH) is indicated for the treatment of short stature in children born small for gestational age (SGA) who fail to show catch-up growth. In pilot studies, early initiation of GH has been associated with favorable growth responses in short SGA children. However, few studies have examined the short- and long-term effects of initiating GH in children born SGA who are <4 years (yr) of age, compared with those starting later. This analysis therefore investigated the effect of age at GH initiation on long-term effectiveness and safety in children born SGA. Methods: The NordiNet IOS (NCT00960128) and ANSWER (NCT01009905) programs are complementary, non-interventional, multicenter studies that evaluated the long-term effectiveness and safety of Norditropin (somatropin; Novo Nordisk A/S, Denmark) as prescribed in real-life clinical practice. In this analysis, children born SGA who were prepubertal at GH initiation were grouped according to age at GH start: <4 yr, 4-6 yr, and ≥6 yr. Patient characteristics at birth and at GH start, auxological measurements, and adverse events were evaluated in each group. Results: Overall, 3351 SGA patients were included in the effectiveness set (age at GH start: <4 yr [n=389, 54.8% male]; 4-6 yr [n=1048, 57.6% male]; and ≥6 yr [n=1914, 56.6% male]). The proportion of patients born pre-term (<37-week gestation) was 38.6% in the <4 yr group, 36.1% in the 4-6 yr group, and 28.2% in the ≥6 yr group. Mean (SD) birth length standard deviation score (SDS) and birth weight SDS were: −2.9 (1.6) and −2.3 (1.2) in the <4 yr group, −2.8 (1.3) and −2.2 (1.1) in the 4-6 yr group, and −2.5 (1.4) and −2.0 (1.2) in the ≥6 yr group. Mean (SD) age at GH start was 3.1 (0.7), 4.9 (0.6), and 9.3 (2.2) years in the <4 yr, 4-6 yr, and ≥6 yr groups, respectively. Mean (SD) GH duration and daily GH dose in the study were: 3.5 (3.1) yr and 0.044 (0.016) mg/kg in the <4 yr group, 4.1 (3.1) yr and 0.039 (0.012) mg/kg in the 4-6 yr group, and 3.5 (2.5) yr and 0.042 (0.012) mg/kg in the ≥6 yr group. Mean (SD) height SDS (HSDS) at GH start was −3.3 (1.2) in the <4 yr group, −3.1 (0.9) in the 4-6 yr group, and −2.8 (0.8) in the ≥6 yr group. After 4 and 8 yr of GH, mean (SD) ΔHSDS from baseline was 1.7 (0.7) and 2.5 (0.6) in the <4 yr group, 1.6 (0.7) and 2.2 (0.8) in the 4-6 yr group and 1.3 (0.7), and 1.7 (0.6) in the ≥6 yr group. Among patients who reached near-adult height in the study, mean (SD) HSDS was −1.9 (0.6) in the <4 yr group (n=3), −1.9 (0.8) in the 4-6 yr group (n=10), and −1.8 (1.0) in the ≥6 yr group (n=220). In the safety set (n=5643), the most commonly reported non-serious adverse reactions (AR) were headache (n=20) and arthralgia (n=5). The most common serious ARs were headache (n=3) and epiphysiolysis (n=4). ARs and serious ARs were distributed equally among groups. Conclusions: This analysis of real-world data confirms the effectiveness and safety of GH in children born SGA, irrespective of patient age at treatment initiation.