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MarjaOjaniemi

Normal and Abnormal Growth in Childhood

Essentials

An assessment of a child's growth should always be based on long-term observation and plotting of growth charts, which must be updated and consulted regularly.
The growth of the child should be assessed at every scheduled routine check-up visit at a child health clinic or at school health care and, if needed, at a medical consultation.
The growth charts and screening rules presented in this article are based on the principles and data that have been in use in Finland for a considerable length of time. New charts have been defined in 2010-2011 and integrated into several electronic growth chart applications.
Normal growth of a child is characterised by consistency.
The follow-up of the growth aims at diagnosing in good time all conditions and diseases that affect growth.
Possible psychosocial consequences of growth disturbances should also be anticipated and treated accordingly. In some cases, growth may be accelerated even in the absence of a specific treatable cause.
Consult also national and local guidelines regarding the management of children's growth disturbances and obesity. A specialist should be consulted early whenever a child's growth is abnormal and requires assessment and further management.
See also article Overweight and obesity in children Overweight and Obesity in Children.

Definitions

Current and expected length/height-for-age

Length/height-for-age (L/A) removes age and gender differences. A current L/A expresses deviation from the average in standard deviation (SD) units, and a score of 0 represents an average height for age and gender.
Growth is consistent when the L/A score remains almost unchanged.
An expected L/A score corresponds to a family-specific average height (mid-parental target height).
The expected L/A score is shown in the electronic growth charts. It can also be calculated with the formula [(average of parents' height in cm)-171)]/10.
- E.g. if the father's height is 185 cm and the mother's 165 cm the expected L/A score of the child is [(185+165)/2-171)]/10 = 4/10 = +0.4 SD.

Weight-for-height, BMI-for-age and ISO-BMI

E.g. in the Finnish growth charts, the weight of children less than 2 years of age is assessed in relation to the child's height (weight-for-height), because there is only little experience on the use of body mass index (BMI) in this age group.
Weight-for-height is expressed as a percentage deviation from the median weight of children of the same gender and with the same height.
In children over 2 years of age, weight can be assessed either by weight-for-height or by age- and gender-specific BMI (BMI = weight in kilograms divided by the square of height in metres; unit kg/m² ). Changes in BMI are evaluated in relation to the normal values (expressed in SDS units).
BMI in a child can be transformed to the corresponding adult ISO-BMI that reflects the child's BMI as an adult. In interpreting the ISO-BMI values, the adult cut-off points for overweight (25 kg/m² ) and obesity (30 kg/m² ) are used (ISO-BMI calculator Body Mass Index (Iso-Bmi) Calculator for Children).

Tempo of growth, growth reserve, skeletal maturation and bone age

The concept ”tempo of growth” refers to the duration of the various stages of growth and development. The developmental years in girls last on average two years less than in boys.
Growth reserve denotes an individual's genetic remaining growth potential under favourable conditions.
Skeletal maturation is determined most objectively by measuring the bone age, i.e. a gender-adjusted median age that corresponds to the child's bone maturity stage.
The bone age denotes skeletal maturity in comparison with chronological age. Its interpretation requires experience.

Body proportions and sitting height

Fetal growth mainly involves the growth of the head and trunk.
Growth in childhood principally affects the limbs, and the pubertal growth spurt again involves truncal growth.
Sitting height (picture F1) describes the ratio between the lower limbs and the trunk. It is determined when investigating the aetiology of abnormal growth. Sitting height is expressed as a percentage of the total height T1.

Normal percentage of sitting height (95% confidence interval) vs. total height

Age (years)	Boys and girls	Age (years)	Boys	Girls
0.25	60.0-72.5	9.0	50.5-55.5	50.7-55.8
0.50	60.7-71.4	10.0	49.9-54.9	50.2-55.5
1.0	60.3-68.2	11.0	49.5-54.6	50.0-55.3
1.5	59.3-66.1	12.0	49.1-54.1	49.9-55.1
2.0	58.3-64.2	13.0	48.8-53.8	50.1-55.0
2.5	57.2-62.5	14.0	48.8-53.7	50.5-55.0
3.0	56.1-61.3	15.0	48.9-53.7	51.1-55.1
4.0	54.5-59.5	Adult	51.1-55.9	51.6-56.4
5.0	53.4-58.3
6.0	52.5-57.3
7.0	51.8-56.6
8.0	51.2-56.1

Phases of growth

A child's growth after birth may be divided into three phases which overlap to some extent: infancy, childhood and puberty. Each phase has its own regulatory mechanisms and disorders.
In the infancy phase the growth velocity is high and continues with sharp deceleration up to the age of about 2-3 years.
- The most important requisite for the normal progress of the infancy phase is an adequate amount of high-quality nutrition.
- In the infancy, the child's height growth settles into a growth channel which is then consistently followed during the childhood.
- If the child's L/A score at birth markedly differs from the score corresponding to the final height there may be significant shifts in the growth channel.
The childhood phase begins around the age of 6 months, i.e. whilst the infancy phase is still continuing, and continues with slowly decelerating velocity throughout the entire growing years.
- In the childhood phase, the child's growth is consistent with no marked changes in the L/A score.
- Many children show a mild transitory acceleration of growth velocity between 6 and 8 years of age. This is known as the mid-childhood growth spurt.
- Growth velocity is at its slowest immediately prior to the pubertal growth spurt.
- In practice, a child should grow annually from 4 to 7 cm.
The puberty phase has three stages: slow growth in early puberty, a growth spurt lasting for approximately two years which is followed by final deceleration and cessation of growth.
- Early puberty will bring the growth spurt forward, and the growth chart will show an upward deviation.
- If puberty appears late, the child will continue to grow with the decelerating velocity of childhood growth, and the growth chart will show a downward deviation.

Length/height measurements and growth charts

Appropriate equipment and the correct measuring technique are the cornerstones of height monitoring.
It is important to complete the section, provided in the growth charts, for personal and family history (e.g. measurements at birth, height of the parents, parents' developmental pattern).
Ethnic background should be taken into account when assessing growth. In immigrants, growth should primarily be assessed using the growth charts of the country of origin. For practical reasons, it is often the charts of the current country of living that have to be used, and the ethnic background is taken into account when interpreting the findings.
It is advisable to use condition- or disease-specific charts if available (e.g. in Down's syndrome Down's Syndrome).

Interpretation of the charts

If the measurement suggests a deviation from the child's growth pattern, the correctness of the actual measurement and of the chart entry should be initially checked.
If a deviation from the growth pattern is confirmed with repeated measurements, the reason for the growth disturbance should be sought. The child's overall health status should also be checked.
A concurrent change both in the height and weight is often suggestive of an illness, particularly when a discrepancy is observed: weight increases while growth slows down, or vice versa.
If the growth deviation is associated with signs and symptoms of an illness, medical intervention is needed urgently.
If several measurements confirm that the screening thresholds for height are broken, specialist intervention is warranted, even if routine investigations were within the normal range.
To be noted in the interpretation:
- The growth of an infant less than 1 year of age should be interpreted with care. Final settling into one's own growth channel may in a healthy child cause a significant shift on the growth chart. Weight may fluctuate particularly according to bladder and bowel functioning. Repeated infections will also quickly affect an infant's weight. A single measurement on its own is usually without any value; long-term monitoring of growth is already of importance at this early age.
- Usual screening rules do not apply for adolescents, and growth must be related to the pubertal development and overall status of the adolescent.

Length/height and weight screening

Growth screening aims at identifying children who require further investigations in relation to growth.
The screening rules based on the new growth charts applied in Finland are mathematically complex and can only be used in electronic applications. The rules described below can be applied if such an electronic application is not available.

Length/height screening

Screening threshold for length/height is broken if the deviation from expected L/A score is ± 2.3 SD, or ± 2.7 SD from the age-adjusted average length/height if the expected L/A score is not known. The screening threshold is also broken if the deviation of the L/A score during a set period of time exceeds the limits for acceptable deviation (tables T2 and T3).

Acceptable deviation of the L/A score (SD) in children less than 2 years of age

Age, years	During the preceding 0.25 years	During the preceding 0.5 years	During the preceding 1.0 years
0.25	1.7
0.5	1.1	2.1
0.75	0.9	1.6
1.0	0.9	1.5	2.3
1.25	0.8	1.4	1.9
1.5	0.7	1.3	1.7
1.75	0.6	1.2	1.6
2.0	0.6	1.0	1.5

Acceptable deviation of the L/A score (decrease and increase) during the various time periods, as indicated by the column headings, preceding the age stated for a row.

Acceptable deviation of the L/A score (SD) in children 2-12 years of age

Age, years	During the preceding 1 year	During the preceding 3 years	During the preceding 5 years
2	1.5
3	1.4
4	1.2	1.8
5	0.9	1.5
6	0.9	1.2	1.9
7	0.9	1.1	1.7
8	0.7	0.9	1.4
9	0.6	0.9	1.3
10	0.6	0.9	1.3
11	0.7	1.0	1.3
12	0.7	1.1	1.3

Acceptable deviation of the L/A score (decrease and increase) during the various time periods, as indicated by the column headings, preceding the age stated for a row.

Weight screen

Screening threshold for weight is broken if there is an unacceptable deviation of weight-for-height from the median weight (table T4) or if the deviation of the weight-for-height score exceeds the acceptable limits (table T5).

Acceptable thresholds for weight-for-height (% of median)

Height, cm	50-120	130-150	160-170
-	15	20	25
+	20	25	30

Acceptable deviation of the weight-for-height score (% of median)

Length, cm	During the preceding growth of 5 cm	During the preceding growth of 5 cm	During the preceding growth of 20 cm	During the preceding growth of 20 cm
55	- 16	+ 18
60	- 14	+ 16
65	- 12	+ 14
70	- 12	+ 14	- 26	+ 28
75	- 12	+ 14	- 26	+ 28
80	- 10	+ 12	- 26	+ 26
90	- 10	+ 12	- 22	+ 22
100	- 10	+ 12	- 18	+ 20
110	- 10	+ 12	- 16	+ 18
120	- 12	+ 14	- 16	+ 18
130	- 14	+ 16	- 18	+ 20
140	- 14	+ 16	- 20	+ 22
150	- 14	+ 16	- 20	+ 22

The columns with a minus sign denote the limit of an acceptable decrease and the columns with a plus sign the limit of an acceptable increase during the growth period (5 or 20 cm) preceding the length stated for a row.

Short stature

Causes of short stature

The most common factor behind short stature is variation to normal. Children with normal-variant short stature (familial short stature) have inherited a short adult stature. Their birth size is small, but their growth pattern is consistent and bone age is within the normal range.
Children with normal-variant delayed growth (constitutional growth delay, CGD, or constitutional delay of growth and puberty, CDGP) have inherited a slow pace of growth and maturing. The condition is more common among boys and leads to a delayed pubertal growth spurt. There are usually close family members with the same condition. In such cases growth may be hastened by accelerating puberty by pharmacotherapy. Such treatment should be considered if the delay in puberty and growth causes significant social or psychological harm to a boy. Differential diagnosis must exclude the possibility of chronic illnesses.
Children with double minus variants have inherited both a short adult height and a delayed growth pattern.
Worldwide, malnutrition is the most common cause of disturbed growth. In industrialised countries, malnutrition may be caused by, for example, eating disorders, depression or by chronic illnesses.
Different forms of rickets Rickets may also retard growth.
Psychosocial growth retardation (psychosocial dwarfism) is caused by emotional deprivation and lack of care for the child. The child's growth slows down or, in extreme cases, stops altogether. In addition, the child characteristically suffers from emotional and behavioural disturbances.
Chronic illnesses, such as heart and lung diseases,severe renal disease Renal Disease in Children (Nephrotic and Nephritic Syndrome), coeliac disease Coeliac Disease, inflammatory bowel diseases Inflammatory Bowel Diseases in Children, often retard growth and development.
Glucocorticoid excess, associated either with the treatment of a disease or seldom with endogenous oversecretion, retards growth. For example in children with asthma, an increase in weight-for-height and simultaneous slowing down of growth suggest overtreatment. In such a situation the harms and benefits of glucocorticoid therapy must be carefully reconsidered.
Hypothyroidism is always associated with retarded growth. As the child's growth shows a downward shift his/her weight-for-height will show an upward shift (a cross-deviation). Skeletal maturing will show marked delay.
Growth hormone deficiency may be associated with various developmental anomalies of the brain (e.g. septo-optic dysplasia) or perinatal disturbances (intrauterine hypoxia, perinatal asphyxia). The deficiency may develop as a result of e.g. a brain tumour (e.g. craniopharyngioma) or its treatment (radiation therapy). The deficiency may be either complete or partial and vary in severity from mild to severe. Growth hormone deficiency may be associated with deficiencies of other pituitary hormones.
- The growth of a patient with growth hormone deficiency is always slow, and the L/A score shows a progressive decrease.
- Children with growth hormone deficiency look younger than other children of the same age. However, their physical appearance is quite normal.
Conditions affecting the skeletal system (osteochondrodysplasias) typically cause growth disorders with disproportionate body proportions. Proportionately short limbs are the most common manifestation: the measuring of sitting height is important. Diagnostics is based on clinical and radiological findings as well as genetic analysis. E.g. in Finland, the three most common conditions causing short-limb dwarfism which reduce adult height by 40-50 cm are:
- cartilage-hair hypoplasia (autosomal recessive); in addition to the growth failure other principal clinical features include hypoplastic hair, increased ligamentous laxity, limited elbow extension, pronounced lumbar lordosis and bow legs http://www.orpha.net/consor4.01/www/cgi-bin/OC_Exp.php?lng=EN&Expert=175
- diastrophic dysplasia (autosomal recessive) which is often associated with marked physical disability due to skeletal deformation http://www.orpha.net/consor4.01/www/cgi-bin/Disease_Search.php?lng=EN&data_id=209
- achondroplasia (autosomal dominant) which is characterised by a large skull with a narrow base and a depressed nasal ridge http://www.orpha.net/consor4.01/www/cgi-bin/Disease_Search.php?lng=EN&data_id=148.
Syndromes that include growth disorders can be recognized by the characteristic features of the patient's appearance. They often lead to growth disturbance already at the prenatal phase. The most common autosomal aberration is Down's syndrome Down's Syndrome and the most common sex chromosome aberration is Turner's syndrome http://www.orpha.net/consor4.01/www/cgi-bin/Disease_Search.php?lng=EN&data_id=44.
- Typical clinical findings for Turner's syndrome (45,X or its mosaic forms) include small birth size, lymphoedema of the neonate's hands and feet, broad chest, widely spaced nipples and hypoplastic nipples, high arched palate, low hairline, webbed neck and cubitus valgus. The number of naevi is also often higher than normal. The appearance of the girl may also be totally normal with the short stature being the only obvious feature http://www.orpha.net/consor4.01/www/cgi-bin/Disease_Search.php?lng=EN&data_id=44.
- Mulibrey nanism (mu-li-br-ey = muscle, liver, brain, eyes) is one of the conditions of the Finnish disease heritage http://www.orpha.net/consor4.01/www/cgi-bin/Disease_Search.php?lng=EN&data_id=2376. It is an autosomal recessive syndrome which causes shortness of stature. Clinical manifestations include triangular facial features, prominent forehead as well as slender limbs and body.
- Clinical characteristics of Silver-Russell syndrome include small triangular face, asymmetrical body proportions, slender physique and clinodactyly of the fifth finger http://www.orpha.net/consor4.01/www/cgi-bin/Disease_Search.php?lng=EN&data_id=584.
Other prenatal growth disturbances may be caused by infections, placental dysfunction, medicines, genetic causes, a disease in the mother or by maternal alcohol or other substance abuse.

Investigations of short stature

The height and pubertal timing of close relatives, growth pattern of siblings, the social environment of the child and possible symptoms of a disease should be taken into account when taking the medical history.
In addition to the general clinical status, possible structural abnormalities, features suggestive of a known syndrome, body proportions (sitting height) and the stage of pubertal development should be assessed.
Any data relating to the child's growth should be analysed carefully (check the original readings and measurement dates). It is essential obtain answers to the following questions (picture F2):
- Is the child genuinely short? (< -2.5 SD)
- Is the child growing slowly?
- Does the growth failure date back to the prenatal period or has it developed later?
- Are there any other clinical features?
- Has growth followed a consistent pattern or is there a downward shift?
Growth in height follows a consistent pattern.
- If the physical appearance of the child is normal the short stature is likely to represent a normal variant, unless the shortness of stature is very marked.
- If the child's physical appearance is suggestive of a congenital syndrome, investigations should be undertaken in order to confirm whether the appearance is consistent with some known syndrome.
- If the limbs are short (high relative sitting height), the child may have a skeletal developmental disorder, i.e. osteochondrodysplasia.
Growth with a downward shift
- Concurrent decrease in weight-for-height scores is suggestive of malnutrition, a chronic illness (intestinal, kidneys, heart, lung) or emotional deprivation.
- Concurrent increase in weight-for-height scores is suggestive of hypothyroidism, hyperglucocorticoidism (usually iatrogenic) or pituitary failure (growth hormone deficiency).
- Determination of the secretion of growth hormone is considered in a specialist unit only after hypothyroidism, coeliac disease, rickets and other chronic diseases as well as psychosocial growth retardation have been ruled out.
Laboratory investigations to exclude chronic illnesses:
- basic blood count with platelet count, ESR
- serum free thyroxine (T4) and TSH
- screening tests for coeliac disease
- plasma calcium, inorganic phosphate, alkaline phosphatase
- plasma creatinine
- ALT.

Indications for referral to specialist care and information to be included

If repeated measurements confirm that the screening thresholds for height are broken, specialist intervention is warranted, even if routine investigations were within the normal range.
Note! The growth of an infant should be interpreted with caution: at this age, fluctuation due to search for one's individual growth channel is the most common cause of breaking the screening thresholds. Usual screening rules do not apply in puberty.
The referral must always include the history of the child's growth pattern as well as the adult height and developmental pattern of the child's parents.

Treatment of short stature Recombinant Growth Hormone in Children and Adolescents with Turner Syndrome, Effect of Zinc Supplementation on Children's Growth, Growth Hormone for Children with Chronic Renal Failure

Short stature may have psychosocial consequences and cause problems with self-esteem.
- A child is often treated according to his/her height rather than his/her age.
- Problems become more pronounced in puberty when the need for support is at its highest.
The aim of treatment is to address the attitudes of others and to promote the child's self-esteem as well as to enhance growth.
Treatment of the underlying disease (e.g. hypothyroidism or coeliac disease) usually corrects the growth in next few months.
The initiation of growth hormone therapy requires thorough investigations and consideration. The treatment is expensive and of long duration and not easy to execute (the subcutaneous injections are given once daily by using a special pen).
- The indications for treatment vary from country to country, but usually in order to be eligible for treatment the child must have proven growth hormone deficiency or a recognised growth failure syndrome.
- The treatment should only be prescribed by appropriate specialist physicians.

Tall stature

Causes and investigations of tall stature

Hereditary normal variant is the most likely cause of tall stature.
- The child's genetic inheritance is of the utmost importance when making a diagnosis.
- In a normal variant, the pattern of growth is consistent.
- Normal body proportions (sitting height and arm span) and bone age as well as lack of atypical features in the appearance will exclude pathological conditions.
Normal obesity Overweight and Obesity in Children leads to a slight acceleration of height growth and skeletal maturation.
Precocious pubertyPubertal Development and its Disturbances causes a clear acceleration in growth, and early skeletal maturation, as well as other signs of androgen or oestrogen effects.
In congenital adrenal hyperplasia http://www.orpha.net/consor4.01/www/cgi-bin/Disease_Search.php?lng=EN&data_id=648, androgen excess icauses accelerated growth. The possibility of this condition should be considered particularly in boys who present with accelerated growth.
In hyperthyroidism accelerated growth in height and skeletal maturation may precede the diagnosis by several years. Weight-for-height usually shows a simultaneous decrease.
Tall stature syndromes are often associated with atypical features in the appearance.
- The most common tall stature syndromes which are associated with excessive growth of the limbs (reduced relative sitting height) include Marfan's syndrome http://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=109&Disease_Disease_Search_diseaseGroup=marfan&Disease_Disease_Search_diseaseType=Pat&Disease(s) concerned=Marfan-syndrome&title=Marfan-syndrome&search=Disease_Search_Simple and Klinefelter's syndrome (47,XXY and variants) Male Hypogonadism and Hormone Replacement.
- E.g. Sotos' syndrome http://www.orpha.net/consor4.01/www/cgi-bin/Disease_Search.php?lng=EN&data_id=588 or Beckwith-Wiedemann syndrome http://www.orpha.net/consor4.01/www/cgi-bin/Disease_Search.php?lng=EN&data_id=260 may be found behind normally proportioned tall stature. Anomalies and atypical features may suggest the aetiology.

Diagnosis of tall stature and prevention of excessively tall stature

Closer investigations and calculations of predicted adult height should be centralised into specialised units.
Any interference with normal growth should only be undertaken after careful consideration.
Treatment forms are still experimental and eligibility should only be considered under strict criteria.

References

Saari A, Sankilampi U, Hannila ML et al. New Finnish growth references for children and adolescents aged 0 to 20 years: Length/height-for-age, weight-for-length/height, and body mass index-for-age. Ann Med 2011;43(3):235-48. [PubMed]

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