Growth hormone treatment of short children born small for gestational age: metanalysis of four independent, randomized, controlled, multicentre studies

Abstract

A minority of children born small for gestational age (SGA) fail to achieve sufficient catch-up growth during infancy and remain short throughout childhood, apparently without being growth hormone (GH) deficient. The effect of GH administration was evaluated over 2 years in short prepubertal children born SGA. The children (n = 244), who were taking part in four independent multicentre studies, had been randomly allocated to groups receiving either no treatment or GH treatment at a daily dose of 0.1, 0.2 or 0.3 IU/kg (0.033, 0.067 or 0.1 mg/kg) s.c. At birth, their mean length SD score (SDS) was -3.6 and their mean weight SDS -2.6; at the start of the study, mean age was 5.2 years, bone age 3.8 years, height SDS -3.3, height SDS adjusted for parental height -2.4, weight SDS -4.7 and body mass index (BMI) SDS -1.4. The untreated children had a low-normal growth velocity and poor weight gain. Although bone maturation progressed more slowly than chronological age, final height prognosis tended to decrease, according to height SDS for bone age, GH treatment induced a dose-dependent effect on growth, up to a near doubling of height velocity and weight gain; BMI SDS was not altered. Bone maturation was also accelerated differentially; however, final height prognosis increased in all GH treatment groups. The more pronounced growth responses were observed in younger children with a lower height and weight SDS. In conclusion, GH administration is a promising therapy for normalizing short stature and low weight after insufficient catch-up growth in children born SGA. Long-term strategies incorporating GH therapy now remain to be established.