North European Small for Gestational Age Study (NESGAS)

NESGAS is being organised in the UK by the British Society for Paediatric Endocrinology (BSPED) in collaboration with Paediatric Endocrinologists in Denmark, Ireland and Sweden.

Background

Children born small for gestational age (SGA) have an increased risk of short adult stature.

Several studies have shown that both children and adults born SGA have reduced insulin sensitivity. Adults born SGA have an increased risk of insulin resistance and type 2 diabetes.

Growth hormone treatment improves both short and long-term height gain.  However it has also been shown to further reduce insulin sensitivity and the long term outcome of this remains unclear with one study demonstrating recovery of insulin sensitivity once growth hormone therapy was completed and another not.  Careful monitoring during and after treatment is therefore required.

Suggested doses of growth hormone doses for children born SGA without catch-up growth vary from 35 to 67 µg/kg/day across Europe.

Aim of Study

To evaluate in short children born SGA:

• Different growth hormone doses (low vs. high vs. IGF-1 titrated dose) on short-term height velocity, final height and insulin sensitivity
• Auxological, biochemical and genetic predictors of growth response and effects on insulin resistance following growth hormone therapy
• Long-term effects and safety of childhood growth hormone therapy evaluated in adulthood (5 and 10 years after attaining final height)

Objectives

The primary objective is to evaluate changes in insulin sensitivity and secretion and incidence of impaired glucose tolerance in short children born SGA. This will be assessed by annual oral glucose tolerance tests (OGTT) alternating with intravenous glucose tolerance tests (IVGTT). Insulin sensitivity will be assessed by HOMA and first phase insulin secretion will be assessed during long term growth hormone treatment.

UK Study Population:

100 short children born SGA

Inclusion Criteria

• Small for gestational age (BW < -2 SD according to country specific references)
• Gestational age at birth more than 28 weeks
• Short at 4 years of age (Height SDS < -2.5 according to country specific references)
• Short for parental height (HSDS > 1 SD below parental adjusted HSDS (=mid parental height SDS)
• Age 4-8.99 years (girls) and 4-9.99 years (boys)
• Prepubertal at start of treatment (largest testis volume < 4 ml, breast stage 1)
• Height records must be available for 6 months prior to inclusion into the study
• Height velocity SDS < 0 during last 6 months (according to country specific references)
• Subjects must be naïve to growth hormone therapy

Exclusion criteria

• Known or suspected allergy to growth hormone
• Previous participation in growth hormone trial
• Severe mental retardation as judged by the investigator
• Previous or active malignancy
• Benign intracranial hypertension (present or past)
• Diabetes
• Growth retardation due to chronic diseases, syndromes (like FAS) and chromosomal anomalies (except for Silver Russell syndrome).
• Psychological problems likely to lead to significant non-compliance

NESGAS Extension

Ethical approval has been given to invite NESGAS patients who have completed 3 years of growth hormone treatment within NESGAS to join the NESGAS Extension. Patients who consent to take part in the NESGAS Extension will continue to receive 35 µg/kg/day growth hormone until they reach final height. The purpose of the extension is to evaluate the long term safety of growth hormone treatment.

Contact for further information

Further information is available from the BSPED website