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Hoey
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Growth in infancy and childhood
Professor Hilary Hoey
Growth in childhood and adolescence is the most sensitive indicator of well-being.
Normal growth only occurs if a child is healthy, adequately nourished and emotionally
secure.1, 2 A commonly used definition of short stature is where height is below the 3rd
centile for the community. Height below genetic potential for family height and height
falling to lower centiles may also warrant investigation.3 Early diagnosis of short stature is
important as final height in treatable conditions is related to age of treatment initiation.
Overweight and obesity is now a major worldwide problem.4, 5 A recent study, by Reilly
and Dorosty in the UK, showed that more than one third of 6 year olds are considered
overweight or obese and almost half of 15 year olds. 6 Obesity is a chronic, debilitating
disease associated with major morbidity and mortality including psychosocial problems,
cardiovascular risk and the metabolic syndrome.7, 8
A number of factors affect growth from birth to 2 years. These include: birth weight and
gestational age; nutrition; genetic background (family height, ethnicity etc); social
circumstances; seasonal factors; and the statistical phenomenon of ‘regression to the
mean’.9, 10, 11 Growth in those aged 2-18 years is affected by endocrine factors, the timing
of puberty, nutrition and well being.12, 13 The causes of short stature fall into 2 groups,
normal variant and pathological. The normal variant group includes constitutional growth
delay, familial short stature and intrauterine growth retardation. Of 100 consecutive
children referred to the National Children’s Hospital with short stature, 75% were normal
and underlying pathology was detected in 25% of cases. Pathological included: chronic
illness (5%); syndromal eg Turners, Prader Willi syndrome (6%); skeletal dysplasia (6%);
endocrinopathy (6%); and emotional deprivation (1%). A child growing with a normal
height velocity is generally normal whilst one growing with poor height velocity is
abnormal and requires evaluation.
Growth assessment requires accurate measurements with good regularly calibrated
equipment. Measurements must be made by a trained measurer and the measurements
should be accurately plotted on a centile chart. The appropriate centile chart for the
community must be used which enables comparison with the specific population growth
patterns. At all times interpretation should be made in clinical context.
A number of types of growth charts exist, these include: cross-sectional; longitudinal; and
longitudinal tempo-conditional.14 Cross-sectional charts involve the measurements of a
large number of children on one occasion. These charts enable global comparisons
between countries. They are also used for sub-population comparisons, e.g. comparing a
group of children with cystic fibrosis with the normal population. After the age of
approximately 9 years, growth is heavily influenced by the wide variation in timing of
puberty and these charts are unsuitable for growth monitoring of an individual child during
puberty. Longitudinal growth charts allow assessment of growth of individual children.
They are constructed using repeated measurements on the same group of children.
Longitudinal tempo-conditional growth charts are constructed from repeated measurements
and pubertal assessment on the same group of children. These charts enable the accurate
monitoring of growth of an individual child in association with the tempo of their pubertal
development, which has such a key influence on growth assessment.
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The clinical growth standards for Irish children aged 2-18 years provide tempo-conditional
longitudinal height reference data.15, 16 These growth standards were derived from data on
over 7,000 Irish children. Measurements were performed by a single trained measurer
using high quality standardised calibrated equipment. The methodology on which these
standards are based is extremely robust and exceeds that of many national standards which
include, self-reported data, multiple measurers, untrained measurers, varied equipment etc.
These charts are therefore the appropriate reference growth charts for Irish children. The
Irish clinical growth standards differ from the UK nine centile charts in that the Irish charts
are longitudinal whilst the UK charts are cross-sectional and less appropriate for
monitoring the growth of an individual child.17 The timing of the pubertal growth spurt
which has a significant effect of growth is earlier in UK children with menarche at 13.0
years versus 13.5 years in Irish girls.18 In addition the UK children are heavier, the Irish
97th centile for weight being approximately equivalent to the 91st for UK children. The
99.6th centile for UK children is approx 20Kg greater than the Irish top centile line which
is the 97th centile. This additional 20Kg which reflects a greater body weight amongst UK
children and if incorporated within the normal range for Irish children could encourage
obesity which is already a major problem in the Irish population. Assessment of childhood
obesity should be based on national Irish reference data.19 Children whose weight is 3 or
more centile lines greater than their height should be reassessed or referred.20 Irish
Growth standards are also available for skinfold thickness and head circumference.21, 22
Disease specific growth charts are available for many conditions including Down’s
Syndrome. It is important to be aware that these charts are based on measurements of
children and adolescents with this condition in the community who tend to be overweight
with a greater weight for height than the general population.23, 24
Growth assessment requires a comprehensive history, including birth weight and
gestational age, family history of height and puberty and psychological well-being of the
child. A complete physical examination should be performed and a careful search for
stigmata of chronic disease including hypothyroidism, coeliac disease, growth hormone
deficiency, renal disorders, Turner’s Syndrome and bone dysplasias. Auxology, bone age
assessment and measurement of height velocity are also essential..
In the investigation of a child with poor growth, auxological assessment should include
careful measurement of height, weight, sitting height and skinfold thickness.
Tests of growth hormone secretion are considered if there is short stature, poor height
velocity and when initial assessment and investigations fail to reveal a cause for the short
stature. When testing growth hormone function special precautions must be observed with
designated staff available for the duration of the test. Physiological and pharmacological
tests of growth hormone are used. Physiological tests include exercise and sleep. The
latter test involves serial growth hormone profiles which are both labour intensive and
expensive. This is, however, a vital test in certain circumstances but unsuitable for initial
screening.
A wide variety of pharmacological tests of growth hormone secretion are available, each
having its own merits and precautions.25 It is recommended that each unit develops
expertise with a limited number, generally 2–3 tests, that it will use on a regular basis for
patient assessment. Some of the most commonly used tests of growth hormone assessment
are: the insulin tolerance test; L-dopa propranolol; glucagon; clonidine; arginine; growth
hormone releasing hormone (GHRH or GRF test) and the IGF1 generation tests. An MRI
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of the pituitary can offer useful confirmatory evidence of growth hormone deficiency.
IGF1 and IGFBP3 are usually low but are not diagnostic in isolation of growth hormone
deficiency/insufficiency in childhood. Reliable assessment of growth hormone status
requires integrity of other endocrine pathways and consideration of pubertal status.
In addition, there are variations in growth hormone estimation between laboratories, each
unit should be aware of the method used and establish its own cut-off points for deficiency
and insufficiency. The sensitivity and specificity of growth hormone provocation tests are
approximately 80% and thus false positive and false negative results should be expected.
Interpretation must be in the overall clinical context. Most centres use two tests of growth
hormone function prior to diagnosing growth hormone deficiency/insufficiency. This is
the current recommendation from the National Institute of Clinical Excellence (NICE)
which was established in the UK to investigate the clinical efficiency of a wide variety of
therapies. Growth hormone therapy in children and adults has been the subject of their
recent consideration and is approved for the treatment of growth hormone deficiency,
Turner’s Syndrome, Prader Willi Syndrome, renal failure prior to transplantation and in
children born small for gestational age who fail to have a ‘catch up’ growth spurt.26 Early
identification of these conditions is important as treatment outcome is generally better in
those treated at a younger age.27
In the child who is considered growth hormone deficient and commenced on treatment,
monitoring of therapy includes: careful auxology with particular focus on height velocity;
monitoring for other pituitary deficiencies which may evolve or be unmasked during
therapy; monitoring of IGF1 and IGFBP3 levels during therapy to guide replacement and
avoid over treatment and the assessment of glucose intolerance particularly in the high risk
groups eg Turner and Prader Willi syndrome.
Growth is the most sensitive index of well being and early detection of growth
abnormalities is essential. Growth assessment requires good measuring equipment,
training in auxology and technique. Accurate interpretation of measurements is essential
with the use of appropriate growth charts together with clinical assessment. Action criteria
and follow up are necessary. Much research is needed in relation to growth surveillance,
including measuring technique, minimisation of measurement errors, and the choosing of
cut off points on growth charts. More information is required on the frequency of
measurements, criteria for action and also on the medical management and safety of
growth hormone treatment. Much can be done, particularly in relation to child health
surveillance and early detection of growth disorders to reduce long-term expensive
morbidity in adulthood. Our great challenge in the 21st century is to prevent the
development of adult diseases, which have their origin in childhood.
Irish growth charts are available from Castlemead Publications, Brickendonbury,
Brickendon Lane, Hertford SG13 8NP United Kingdom Tel:01992505692, Fax 01992
500076, www.castlemeadpublications.com
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References
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Hoey H. Early recognition of short stature. J Postgrad Med 1987; 424-432
Hoey H. Psycho-social aspects of short stature. J Pediatr Endocrinol 1993; 6: 291-294
Hindmarsh P. Monitoring children’s growth. BMJ 1996; 312: 122a
Roche E. Childhood Obesity. IMJ 2003; 96: 4, 100-102
Deckelbaum RJ, Williams CL. Childhood Obesity: The Health Issue. Obes Res 2001; 9: 239S-243S
Reilly JJ, Dorosty A. Epidemic of Obesity in UK Children. The Lancet 1999; 354(27): 1874-1875
Dietz WH. Health consequences of obesity in youth: childhood predictors of adult disease.
Paediatrics 1998; 108: 518-25
Vanhala M, Vanhala P, Kumpusalo E, et al. Relation between obesity from childhood to adulthood
and the metabolic syndrome: population based study. BMJ 1998; 317-319
Hall DMB, Elliman D. Health for all children, Oxford University Press; 4th Edition, 2003
Haschke F, van’t Hof M, Darvay S and the Euro-Growth Study Group, Ireland:
Freeman V, Hoey H, Gibney M. Euro-Growth References for Length, Weight and
Body Circumferences. J Pediatr Gastroenterol Nutr 2000; 31; Sup 1, 14-38
Eveleth P, Tanner J. World wide variation in human growth, London. Cambridge University Press
1976; 213-21
Hoey H. Short Stature, Pathways in Paediatrics, Ed. Loftus BG, London; Edward
Arnold, London. 1995; 245-254
Hoey H. Abnormal Puberty, Pathways in Paediatrics, Ed. Loftus BG, London;
Edward Arnold, 1995; 127-134
Hoey H. The design and use of growth standards. Growth Matters 1991; 7: 2-4
Hoey H. Auxology: The Irish Contribution: Essays on Auxology. Ed. Hauspie R,
Lingren G, Falkner F. U K; Castlemead Publications, 1995; 201-210
Hoey H, Tanner J, Cox L. Clinical Growth standards for Irish children. Acta Paed Scand
Supplement 1987; 388: 1-31
Freeman JV, Cole TJ, Chinn S, et al. Cross-sectional stature and weight reference
curves for the UK 1990. Arch Dis Child 1995; 73: 17-24
Hoey H, Cox L, Tanner J. The age of menarche in Irish girls. IMJ 1986; 79: 283-285
Reilly JJ. Assessment of childhood obesity: national reference data or international approach?
Obes Res 2000; 10(8):838-840
Hulse JA, Shilg S. Relation between height and weight centiles may be more useful. BMJ 1996;
312: 122
Hoey H, Cox LA. Irish standards for triceps and subscapular skin fold thickness. IMJ 1980, 11,
312-121
Hoey H, Cox LA. Head circumference standards for Irish children. Acta Paed Scand 1990; 79:
283-88
Parvin M, Roche E, Hoey H, et al. Treatment Outcome in Turner Syndrome IMJ 2004; 9:1,12-15
Styles ME, Cole TJ, Dennis J, Preece MA. New cross sectional stature, weight, and head
circumference references for Down’s syndrome in the UK and Republic of Ireland. Arch Dis Child
2001; 87 (2): 104 - 108
Mehta A, Hindmarsh P. The use of Somatropin (recombinant growth hormone) in
children of short stature. Paediatr Drugs 2002; 4 (1): 37-47
Guidance on the use of human growth hormone (Somatropin) in children with
growth failure. National Institute of Clinical Excellence (NICE). London, 2002
Harper J, Philip M, Murphy J, Hoey H. Growth in Irish children and adolescents
with Down Syndrome, from 3 months to 18 years. Ir J Med Sci 2000; 1: Sup 2, 64-65