Benefits of GH treatment in children born small for gestational age
Growth hormone therapy for short stature: Importance of first-year response
Children born small for gestational age (SGA) who do not show spontaneous catch-up growth by 2 years of age generally remain short for life. Although the majority of them are not growth hormone (GH)-deficient, GH treatment has been shown to improve growth in this population. In a recent interview, Dr Pik-Shun Cheng, Specialist in Paediatrics in private practice in Hong Kong, discussed the role and benefits of recombinant GH ( Saizen, Merck) supplementation, and shared her clinical experience in the management of short stature in children.
The risk of having a short final height(<-2 standard deviation scored [SDS]) is five times higher for children with a low birth weight and seven times higher for those with a low birth length compared with children with a normal birth size. [Horm Res 1998;49(suppl 2):7-13]
GH has been shown to increase final height to within the normal range in children born SGA and in other disorders, such as GH deficiency, idiopathic short stature, Turner syndrome, chronic renal insufficiency, and Prader-Will syndrome.
GH treatment in children born SGA
“ The mechanism of action of GH in children born SGA is unclear, but it is assumed that some of them have hypersecretion of GH during the initial catch-up growth period in the first 6 months of life. For those 10to 15 percent who do not catch up, we need to consider GH to induce catch-up growth,” suggested Cheng.
Diagnosis and therapy initiation
According to Cheng, roughly 2.3 to 3.0 percent of Hong Kong’s population are born SGA, indicating it is not uncommon. “The statistical definition of SGA is based on a birth length or a birth weight of <-2 SDS,” she explained. “A survey by the Chinese University of Hong Kong showed that the average birth weight of local babies was 3.11 kg and average birth length was 50 cm. Therefore, if the baby’s weight is <2.5 kg and / or birth length is <45 cm, it is considered SGA.”
[http://www.healthyhk.gov.hk/phisweb/plain/en/health_info/vit_stat/birth_weight/]
GH has been licensed for the treatment of children born SGA who have not exhibited catch-up growth by 2 years of age (in the US) or by 4 years of age(in Europe). “ There are no local guidelines in Hong Kong on how to manage children born SGA, but we monitor their growth routinely. In my practice, I usually consider GH from 4 years of age onward,” she said.
In the past, low awareness among Hong Kong parents regarding the issue of short stature might have caused delays in treatment initiation. “For example, teens with short stature would come to my clinic, and we would discover from their history that they were born SGA,” she said. “Nowadays, with more education and awareness, parents seek treatment earlier, probably when the children are around 3 or 4 years of age.”
Dosage, treatment duration and managing “catch-down” growth
GH is administered by daily subcutaneous injection, preferably in the evening. The dosage is individually determined based on the patient’s body surface area or body weight. “Based on the literature, we prescribe 40 to 60 μg/kg/day,” said Cheng.
The majority of patients are using the GH autoinjector, a convenient and easy-to-use device. “ The autoinjector is preprogrammed with the correct dose. You just insert the cartridge and press, and the dose is released automatically,” said Cheng. “Importantly, the autoinjector has memory, so we can monitor compliance, which is particularly important for adolescents who inject themselves. You hook it up to a computer and download all the data, so monitoring any missed doses is easy, increasing treatment reliability and compliance.”
“Long-term continuous GH therapy can significantly increase final height to within the normal range”
GH treatment duration is usually given from the time of diagnosis until puberty, where a spontaneous boost in height takes place. “One problem usually encountered with GH therapy is something we call ‘ catch-down’ growth, which happens after ceasing treatment with GH. The reason behind this phenomenon is still unclear. The strategy we employ to diminish this is by continuous long-term GH treatment, while keeping the off-treatment periods to a minimum,” suggested Cheng. [J clin Endocrinol Metab2004;89:1234-1239]
Efficacy and safety
Studies have demonstrated that treatment with GH can induce sustained catch-up growth in young children born SGA, and long-term continuous GH therapy can significantly increase final height to within the normal range. (Table) [ Acta Paediatr 1998;87:511-517; Adv Ther 2008; 25:951-978]
“Most studies have demonstrated an increase in final height. In general, the earlier the children are started on GH and the longer the treatment period, the better the effect. Successful GH treatment relies on regular and continued injection,” Cheng pointed out.
In all reported studies, GH was well tolerated, even at high doses. Two large observational studies of patients treated with GH for different indications have raised no unexpected safety concerns for SGA patient. [J Clin Endocrinol Metab 1996;81:1704-1710; Horm Res 2007;68(suppl 5):41-47]
In Cheng’s experience, the most common side effect reported by GH-treated children is growing pain. “ This may occur in any child during growth spurts. Usually they tolerate it quite well and it will resolve spontaneously,” she said. “Some patients have fluid retention at the beginning of treatment , but it’s rare in my experience.”
Another rare but serious adverse event is slipped capital femoral epiphysis(SCFE), which may also occur in growing children without GH therapy. “ It’s a growth- related problem. Clinical suspicion is advised in children complaining of unilateral pain in the hips or knees, and treatment is either bed rest or surgical, depending on the severity,” said Cheng.
Other GH-related adverse events include increased intracranial pressure, disturbance in glucose metabolism, and hypertension. “ We need to monitor and watch out for those problems, although they are quite rare,” she suggested. “Studies looking at cancer risk found no increase risk in GH-treated patients.”
Clinical Considerations
Physicians who encounter paediatric patient with short stature(<-2 SDS) are advised to review their medical history for SGA. Children born SGA should be referred at an early age to consider GH treatment, as studies have shown that long-term, continuous GH therapy unit puberty might improve their chances of achieving final height within the normal range.
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