Small for Gestational Age (SGA ) and Genotropin (somatropin, rbe)

Genotropin (somatropin, rbe) is indicated for the treatment of growth disturbance in short children born small for gestational age (SGA), with a birth weight and/or length below - 2 SD, who failed to show catch-up growth by 4 years of age or later.

Children classified as born small for gestational age may have concurrent diagnoses such as familial short stature, Turner syndrome, or growth hormone deficiency. Approximately 10% of children born small for gestational age do not reach the normal height range. Those whose growth has not caught up by 4 years of age are candidates for treatment with growth hormone.

Efficacy of Growth Hormone in Achieving Catch Up Growth

Genotropin has proven efficacy in children born small for gestational age, who fail to manifest catch-up growth.

Genotropin helps to:

  • Achieve catch up growth
  • Normalise the stature of short SGA children

Study results: effect of growth hormone (GH) on SGA children treated until final height

Achieving catch-up growth and normalising final height 1

Increase in height following initiation of treatment with growth hormone (GH) (0.033mg/kg/day) 1

Mean attained height graph

 

Δ GH treated >2 year before puberty
▽ GH treated <2 years before puberty
O Untreated group

Study findings

GH normalised final height in short children born SGA, allowing most patients to reach their target final height. 1

Study methods

Observational study of 77 pre-pubertal short children born SGA (-2SD birth weight or length; mean age 10.7 years) in which patients received 0.033 mg/kg/day GH treatment until final height (1 year after height velocity <1 cm/year). During puberty, 24 children were randomised to 66 µg/kg/day GH. Children were subdivided according to the duration of GH treatment before puberty (>2 years [n=36] and < 2 years [n=41]). Growth response was compared with a comparison group of 34 untreated short pre-pubertal SGA children. Values are means ± standard error (SE). MPH SDS mid-parental height SD score.

Adapted from Dahlgren et al, 2005 1

Defining small for gestational age 3

Various thresholds for height and weight at birth are used to define 'small for gestational age', the three most commonly used being:

  • a height at birth that is 2 standard deviations or more below the population average, or
  • a weight at birth that is 2 standard deviations or more below the population average, or
  • a weight at birth below the 10th percentile.


The international consensus definition of 'small for gestational age' is a length or weight at birth that is 2 standard deviations below ( −2 SD) the population average for birth or weight.

In addition to accurate measurements of a newborn's weight, length and head circumference, the diagnosis of small for gestational age requires accurate assessment of gestational age and valid data from a reference population.

Dosage recommendations for treatment of growth disturbance in short children born small for gestational age.2

A dose of 0.035 mg/kg body weight per day (1 mg/m2 body surface area per day) is usually recommended until final height is reached (see section 5.1). Treatment should be discontinued after the first year of treatment if the height velocity SDS is below + 1. Treatment should be discontinued if height velocity is < 2 cm/year and, if confirmation is required, bone age is > 14 years (girls) or > 16 years (boys), corresponding to closure of the epiphyseal growth plates.

Adverse events in SGA children treated long term with somatropin.2

Long-term Treatment of Children with Growth Disturbance due to Born Small for Gestational Age

System Organ Class

Very Common

≥1/10

Common

≥1/100 to <1/10

Uncommon

≥1/1,000 to <1/100

Rare

≥1/10,000 to <1/1,000

Very Rare

<1/10,000

Not Known (cannot be estimated from available data)

Neoplasms Benign, Malignant and Unspecified (including cysts and polyps)

 

 

 

 

 

Leukaemia†

Metabolism and Nutrition Disorders

 

 

 

 

 

Type 2 diabetes mellitus

Nervous System Disorders

 

 

 

 

 

Paraesthesia*

Benign intracranial hypertension

Musculoskeletal, Connective Tissue and Bone Disorders

 

 

Arthralgia*

 

 

Myalgia*

Musculoskeletal stiffness*

General Disorders and Administration Site Conditions

 

Injection site reaction$

 

 

 

Oedema peripheral*

Investigations

 

 

 

 

 

Blood cortisol decreased

 

*In general, these adverse effects are mild to moderate, arise within the first months of treatment, and subside spontaneously or with dose-reduction. The incidence of these adverse effects is related to the administered dose, the age of the patients, and possibly inversely related to the age of the patients at the onset of growth hormone deficiency.

$ Transient injection site reactions in children have been reported.

‡ Clinical significance is unknown

† Reported in growth hormone deficient children treated with somatropin, but the incidence appears to be similar to that in children without growth hormone deficiency.

References

  1. Dahlgren J et al. Pediatr Res 2005; 57(2): 216–222.
  2. Genotropin Summary of Product Characteristics
  3. NICE Guidance [TA188]. Human growth hormone (somatropin) for the treatment of growth failure in children. Accessed March 2018

Abbreviations: SGA, small for gestational age; GH, growth hormone; MPH, mid-parental height; SE, standard error.

 

PP-GEN-GBR-0470. July 2018