19.1 Growth and variations of growth
Growth is a multifactorial process influenced by genetic, nutritional, hormonal, psychosocial and other factors, including the general health of a child. As such, growth mirrors the psychosocial and physical wellbeing of a child and adolescent.
Physiological and pathological processes exert effects on growth and development at different stages of life. The three major determinants of growth are:
Genetic factors
The genetic background of individuals is the major determinant of growth potential: tall parents generally have tall children, whereas short parents have short children. Although children’s heights at maturity resemble those of their parents, little is known about the exact location of the individual height controlling genes, how many genes are involved or how they direct cellular growth. Major genetic disturbances such as chromosomal abnormalities are often reflected in poor growth patterns. For example, with loss of a sex chromosome in 45,XO Turner syndrome, as shown in Figure 19.1.1 (see also Chapter 10.3), adult stature is severely compromised. Other less severe chromosomal abnormalities also may result in abnormalities in stature.
Many inherited genetic conditions can also result in growth disturbance. The most striking of these are the skeletal dysplasias, which often follow an autosomal dominant mode of inheritance. The classical example of a skeletal dysplasia is achondroplasia, described in Chapter 10.3. Chromosomes may also influence tall stature, as seen in the case of an individual with an extra sex chromosome, for example Klinefelter syndrome XXY, which frequently leads to an adult height above that anticipated from the family pattern.
Nutritional factors
Nutrition is the second most important factor determining normal growth in childhood and adolescence. Malnutrition is the world’s primary cause of poor growth. In developed countries, both undernutrition and overnutrition may have long-lasting effects on growth patterns. Undernutrition, particularly intrauterine or at significant postnatal periods, may affect both the weight and height growth patterns and also the development of body organs. For example, children who are born small for gestational age and who experience significant catch-up growth in the first few months of life have been shown to have an increased risk of cardiovascular morbidity and mortality as well as type 2 diabetes later in life.
Many situations throughout childhood can cause poor nutrition and affect the growth of the child. Undernutrition due to poor quality and low quantity of food may lead to poor growth, particularly if prolonged. In addition, chronic disease may also lead to poor nutrition. Finally, emotional deprivation also has a profound influence on growth. On the other hand, overnutrition may lead to obesity with advanced linear growth and early pubertal maturation.
Hormonal factors
Those of significance in growth are:
Growth hormone–insulin-like growth factor I axis
The major hormonal influence involved in growth regulation at all ages is the growth hormone–insulin-like growth factor I axis (GH–IGF-I). GH is secreted by the anterior pituitary gland in a pulsatile pattern. Major peaks of secretion occur particularly at night. GH is bound to a specific growth hormone-binding protein and subsequently acts on a broad range of tissues via cell surface receptors, resulting in a range of metabolic and growth-related effects. Many of these effects are mediated via IGF-I, which is produced by the liver and many other tissues. The secreted IGF-I then acts either locally on adjacent tissues (paracrine action) or via endocrine mechanisms (i.e. via the circulation). IGF-I levels are age-dependent, being low in the fetus, rising through infancy and childhood, peaking during puberty and then falling to adult levels. IGF-I is very sensitive to nutritional status and its measurement is of limited diagnostic value in the assessment of short stature. It circulates bound to one of its major binding proteins (IGFBPs).
Thyroid hormone
Thyroxine is very important for postnatal growth. Children with untreated hypothyroidism may show both intellectual impairment and profound growth retardation, with delayed bony maturation (see Chapter 19.2).
Testosterone and adrenal androgens
These hormones are anabolic and growth promoting. In males, testosterone and GH act synergistically to promote the adolescent growth spurt. Excess androgens in childhood may be produced as a consequence of adrenal enzyme disorders (congenital adrenal hyperplasia), precocious puberty and tumours, or may come from exogenous treatment. Some androgens are aromatized to oestrogens and will rapidly cause bone age advancement and may limit the potential for final height.
Phases of growth
There are three main phases of growth: fetal growth, childhood growth and the pubertal growth spurt.
Fetal growth
Fetal growth is the most rapid phase of growth. Initial embryonal/fetal growth is characterized by rapid differentiation of body organs, whereas late fetal growth involves continued rapid enlargement in tissues and organs, and growth in length. The most rapid linear growth velocity of all ages occurs in the weeks before birth. Factors controlling fetal growth include placental supply of nutrients and oxygen, and a range of local growth factors including insulin-like growth factors (IGFs). Pituitary GH probably plays a relatively small part in this phase of growth, whereas thyroxine is involved in brain and bone growth in the fetus. Pituitary gonadotrophins (luteinizing hormone (LH) and follicle-stimulating hormone (FSH)) regulate testicular testosterone synthesis in the male fetus, which is essential for normal growth of the male phallus. Thus a male infant with hypopituitarism may have a micropenis at birth.
Childhood growth
During the first years of life, linear growth velocity is still very rapid (on average 8–12 cm/year) but plateaus through childhood to an average of approximately 5–6 cm/year. The growth velocity immediately before the pubertal growth spurt may be lower than this and represents a transient phase of poor growth. If the onset of the pubertal growth spurt is delayed, this phase of poor growth may be prolonged. During the childhood growth phase the limbs grow faster than the trunk, so the ratio of upper to lower body segments (divided at the pubic symphysis) diminishes from approximately 1.7 : 1 during infancy to 1 : 1 by age 10. It may fall to around 0.8 by mid-puberty. The arm span : height ratio increases during childhood and reaches 1 : 1 during puberty.
Factors controlling this phase of growth include genetic determinants, nutrition, absence of chronic disease and normal secretion of hormones, the most important of which are GH and thyroxine.
Pubertal growth spurt
Puberty is associated with the onset of sex hormone production in boys and girls under the influence of pulsatile release of gonadotrophins (FSH/LH) from the pituitary gland. In girls, ovarian oestrogen secretion leads to the earliest pubertal sign of breast development at an average age of 10–11 years, followed by pubic and axillary hair growth in response to adrenal and ovarian androgens. The earliest sign of puberty in boys, at an average age of 11 years, is testicular enlargement (volume ≥ 4 mL measured with an orchidometer). Penile and scrotal growth follow, with development of pubic and axillary hair in response to testosterone synthesis. In boys testosterone also leads to muscle growth, whereas in girls oestrogens cause pelvic broadening and fat redistribution, leading to a female body shape. In both sexes, the onset of puberty is followed by a peak linear growth velocity, at an average age of 11.5 years in girls and 13.5 years in boys.
The hormonal changes of puberty include an increase in the amplitude of GH pulses, probably due to sex hormone effects. IGF-I levels rise during puberty in association with the high GH levels. Oestrogens have direct effects at the skeletal growth plate, ultimately leading to fusion of the bony epiphyses and cessation of growth at an average age of 15 years in girls and 17 years in boys. The pubertal growth spurt may be influenced by genetic factors and may also be affected adversely by poor nutrition or chronic disease, both of which can cause pubertal delay.
Puberty
• The earliest sign of puberty in females is breast budding, at an average age of 10–11 years.
• The earliest sign of puberty in males is testicular enlargement, at an average age of 11 years.
• Pubic and axillary hair development usually follow the onset of breast development in girls and of testicular enlargement and genital development in boys.
• The pubertal growth spurt occurs at an average age of 11.5 years in females and 13.5 years in males.
• The growth spurt in puberty is the most rapid phase of postnatal growth.
Assessment of growth
Percentile charts
Any health professional who deals with children must have a working knowledge of normal variations in growth and development, and must be able to use a percentile chart. Childhood and pubertal growth patterns can be appreciated by examining growth charts, including linear height and weight charts (Fig. 19.1.2) as well as height velocity charts, indicating annual rate of growth (Fig. 19.1.3).
Fig. 19.1.2 Male height centile chart. A similar chart is available for females. CDC, Centers for Disease Control.
(Reproduced with permission from Pfizer.)
Fig. 19.1.3 Male height velocity chart. A similar chart is available for females.
(Reproduced with permission from Pfizer.)
These charts demonstrate the range of normal growth, expressed either as percentiles or as standard deviations (sd) from the mean for age. The percentile curves are derived from the normal distribution (bell-shaped curve) of the data. The median is the 50th percentile and indicates that 50% of the measurements of a normal group of children are above and 50% are below that point. The 50th centile ‘final’ height value for males is 176 cm and for females is 163 cm. Children whose height or weight are 2 sd above or below the mean fall approximately between the 3 rd and 97th percentiles (Fig. 19.1.2). There will be three normal children in every 100 who will be at or below the 3 rd centile and three in every 100 who will be at or above the 97th centile.
Assessment of growth velocity (Fig. 19.1.3) is of far greater clinical significance than single measurements of height, and should be based on sequential measurements taken at 3-monthly intervals during a period of 6–12 months. When measured over this time period, a normal child will tend to follow the same height percentile (Fig. 19.1.2). A child with an organic or endocrine disease will tend to deviate from the percentile and may move across percentile lines. Thus serial measurement of children is the key to the assessment of their growth status.
Bone age
Bone age is an index of physiological maturity, indicating the state of bony epiphyseal maturation. A bone age is obtained by performing an X-ray of the left wrist and hand, and is interpreted according to an atlas of age- and sex-specific standards. The bone age indicates the average age of children at a similar stage of bony maturation and is a guide to the remaining growth potential of the child. In normal children, the bone age will be within 1.5–2 years of the chronological age.
Short stature
The management of a child with short stature requires consideration of a number of issues. It is important to realize that the majority of short children will have no pathology but will either be following a familial pattern or have a variant of normal growth. The main causes of short stature in order of frequency of diagnosis are summarized in Box 19.1.1. As can be seen, endocrine causes of short stature are the least common.
Variations from normal
Familial (genetic) short stature
Important features of familial short stature are as follows:
• Height will track parallel to and below the 3rd centile.
• The growth rate (growth velocity) is usually normal.
• The adult height percentiles of both parents should be plotted on the child’s growth chart to assess whether the child’s height is appropriate for the heights of the parents.
• Pubertal development usually occurs at the appropriate time.
• Markers of physical maturation such as bone age tend to be consistent with chronological age.
Constitutional delay in growth and puberty
Constitutional delay in growth and puberty is a very common variation of growth and leads to short stature during childhood with an adult height prognosis consistent with the mid-parental height expectation. Important features are:
• affects boys more commonly than girls, and boys are more likely to present to medical attention
• often there is a family history of a parent being short as a child, with delayed puberty and eventual catch-up with peers
• these children are the so-called ‘slow growers and late bloomers’
• markers of physical maturation such as bone age are delayed
• the delay in puberty and associated delay in fusion of bony epiphyses means that both the pubertal growth spurt and the completion of growth will be delayed
• these children (most often boys) tend to grow into their late teenage years or early twenties.
Pathological causes
Small for gestational age
Babies may be born small for gestational age (SGA) as a result of a number of fetal, maternal and environmental factors (see Chapter 11.2). Some SGA children fail to demonstrate catch-up growth in the first 2 years of life and remain small.
Chronic disease
Chronic disease is a major cause of growth failure:
• Usually the growth failure is associated with a similar fall off in weight velocity.
• An endocrine problem is unlikely to be the cause of poor growth if both the weight and height are affected.
• Nutritional insufficiency may contribute to the growth failure of chronic disease as a result of inadequate or inappropriate intake, poor absorption or impaired or excessive tissue utilization.
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