eMedicine Specialties > Pediatrics: General Medicine > Endocrinology

Growth Failure

Author: Stephen Kemp, MD, PhD, Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas and Arkansas Children's Hospital
Coauthor(s): Neslihan Gungor, MD, Instructor, Department of Pediatrics, Section of Endocrinology, Children's Hospital of Pittsburgh and University of Pittsburgh
Contributor Information and Disclosures

Updated: Sep 15, 2009

Introduction

Background

Short stature may be the normal expression of genetic potential, in which case the growth rate is normal, or it may be the result of a condition that causes growth failure with a lower-than-normal growth rate.¹ Growth failure is the term that describes a growth rate below the appropriate growth velocity for age.

A child is considered short if he or she has a height that is below the fifth percentile; alternatively, some define short stature as height less than 2 standard deviations below the mean, which is near the third percentile. Thus, 3-5% of all children are considered short. Many of these children actually have normal growth velocity. These short children include those with familial short stature or constitutional delay in growth and maturation. In order to maintain the same height percentile on the growth chart, growth velocity must be at least at the 25th percentile. When considering all children with short stature, only a few actually have a specific treatable diagnosis. Most of these are children with a slow growth velocity.

Pathophysiology

The most rapid phase of human growth is intrauterine. Following birth, a gradual decline in growth rate occurs over the first several years of life. The average length of an infant at birth is about 20 inches, the length at age 1 year is approximately 30 inches, the length at age 2 years is approximately 35 inches, and the length at age 3 years is approximately 38 inches. After age 3 years, linear growth proceeds at the relatively constant rate of 2 inches per year (5 cm/y) until puberty.

Normal growth is the result of the proper interaction of genetic, nutritional, metabolic, and endocrine factors. To a large extent, growth potential is determined by polygenic inheritance, which is reflected in the heights of parents and relatives. Secretion of growth hormone (GH) by the pituitary is stimulated by growth hormone–releasing hormone (GHRH) from the hypothalamus. Another signal, which is stimulated by certain growth hormone–releasing peptides (GHRPs), may be present; the receptor for the GHRPs has been identified, and a possible natural ligand for these receptors has been determined. Somatostatin secreted by the hypothalamus inhibits growth hormone secretion.

When growth hormone pulses are secreted into the systemic circulation, insulinlike growth factor (IGF)–1 is released, either locally or at the site of the growing bone. Growth hormone circulates bound to a specific binding protein (GHBP), which is the extracellular portion of the growth hormone receptor. IGF-1 circulates bound to one of several binding proteins (IGFBPs). The IGFBP that most depends on growth hormone is IGFBP-3.

A peptide hormone that stimulates growth hormone release, named ghrelin (from the word ghre, a root word in proto-Indo-European languages meaning grow), has been described. This hormone is unique in that it is a small polypeptide modified at the third amino acid (serine) by esterification of n-octanoic acid. Ghrelin appears to be made in the stomach and stimulates growth hormone secretion by binding with its own receptor, which had previously been known to bind synthetic GHRPs. Ghrelin may play a role in regulation of growth hormone at the hypothalamic level, permitting an adequate energy supply for maintenance, growth, and repair.

Frequency

United States

In 1994, Lindsay et al studied 114,881 school children in Utah.² After 1 year, 79,495 of the original group were available for evaluation. Of these, 555 (0.7%) had heights that were below the third percentile and a growth rate that was less than 5 cm/y. When examined further, causes for short stature within this group of children included familial short stature (37%), constitutional delay (27%), a combination of familial short stature and constitutional delay (17%), other medical causes (10%), idiopathic short stature (5%), growth hormone deficiency (3%), Turner syndrome (3% of girls), and hypothyroidism (0.5%).

International

Several studies have been conducted to determine the frequency of various causes of short stature. In 1974, Lacey and Parkin evaluated children in Newcastle upon Tyne in England.³ They studied 2256 children, 111 of whom were below the third percentile in stature. Of the 98 children that they were able to examine, only 16 had evidence of organic disease causing their short stature. Diagnoses included Down syndrome, cystic fibrosis, chronic renal insufficiency, growth hormone deficiency, juvenile rheumatoid arthritis (treated with glucocorticoid), and Hurler syndrome.

Mortality/Morbidity

Short stature has been thought to have far-reaching effects on psychological well-being, including poor academic achievement (despite normal intelligence, healthy family dynamics, and high socioeconomic status) and behavioral problems (eg, anxiety, attention-seeking actions, poor social skills).

Morbidity related to the underlying cause of the growth failure may also be observed. Some studies involving children who have not been seen in a clinic that treats short stature (and, therefore, may represent a different patient population) have challenged the notion that short stature has psychological implications. At the present time, this issue is not completely resolved.

Mortality rates in children with growth failure relate to the underlying cause of the growth failure. Mortality is not related to growth failure itself; rather, it is related only to the cause of the growth failure.

Sex

The sex distribution of children treated with growth hormone is about 3 boys for every girl. Recent work in this area suggests that this is mostly due to a referral bias, either from parents themselves or from the referring physician.

Clinical

History

History of those with growth failure should focus on the following areas:

• Birth weight and birth length: One of the issues in the differential diagnosis is intrauterine growth retardation, which should be apparent from the birth history.
• Parents' heights: In order to evaluate a child's genetic potential, calculation of the sex-adjusted midparental height (ie, target height) is helpful. The sex-adjusted midparental height is calculated by adding 2.5 inches to (for boys) or subtracting 2.5 inches from (for girls) the mean of the parents' heights; it represents the most statistically probable adult height for the child, based on parental contribution. By calculating the percentile for this midparental target height, one can determine the percentile at which a child's height is expected to track.
• Timing of puberty in parents: Constitutional delay in growth and maturation may have a family history. Most mothers can remember their age at menarche (average age, 12-12.5 y). Eliciting pubertal history from a father is more difficult because no specific landmark is recognized. Evidence of delayed puberty may include continuing to grow after high school or not shaving until age 20 years or older.
• Previous growth points
  • The most useful part of a workup for growth failure is observing the growth pattern. Previous growth data may be obtained from physicians' offices, schools, or marks that have been kept on a door or wall at home.
  • If the growth rate is normal (approximately 2 inches/y [5 cm/y] from age 3 y to puberty), the cause of the child's short stature is likely one of the normal variants, and the child does not actually have growth failure.
  • If the growth rate is low, growth failure is present, and a pathological cause for the growth failure is more likely.
  • Children with constitutional delay in growth and maturation often appear to be growing slowly just before the pubertal growth spurt; they may be confused with children who have actual growth failure.
• The child's general health: Ruling out a chronic disease or poor nutrition as a cause of growth failure is important. Worldwide, malnutrition is probably the most likely cause of growth failure.

Physical

The following items in the physical examination are targeted toward assessing growth failure:

• Height (or length) and weight: A determination of weight is not difficult; height (standing) or length (lying down) should be measured with care. Using a single steady stadiometer and obtaining more than one measurement provides accurate values.
  • Taking accurate measurements of length requires attention to the following:
    • An accurate measuring device should be used. For infants, the device should consist of a board with a yardstick attached (or embedded), a stationary head plate, and a movable footplate.
    • Gently stretch the child. The heels, buttocks, shoulders, and the back of the head should touch the base of the device, and the soles of the feet should be perpendicular to the base of the device.
    • Repeating the measurement 2-3 times (and taking an average of these measurements) improves the accuracy of the measurement.
  • When taking height measurements, the following should be addressed:
    • Always have the child barefoot or in stocking feet. The heels, buttocks, and shoulders should be in contact with the wall or the measuring device.
    • The child should be standing with heels together, feet slightly spread.
    • The child should look straight ahead. This is called having the head in the Frankfurt horizontal plane, which is a plane represented in the profile by a line between the lowest point on the margin of the orbit and the highest point on the margin of the auditory meatus.
    • At the time of the measurement, have the child hold a deep breath.
    • Use proper equipment. The ideal device for height measurement is a stadiometer, which may be mounted on the wall, with an arm that moves vertically. The arm is placed on the head, and the height can be read from a counter or from a ruler on the wall. If a stadiometer is not available, good height measurements may be obtained from a yardstick (or meter stick) attached to the wall and a device that makes a right angle with the wall and the child's head. The floppy arm devices mounted on weight scales are inherently variable and frequently yield inaccurate measurements. A height measurement can be determined using this device, but even more attention is required.
    • For precise height determinations, measure the child 2-3 times and take the mean. If the first 2 measurements agree, they should be considered accurate.
    • In order to minimize diurnal variation in height, always measure the child at the same time of day.
• Proportionality: Inspect the child for proportionality of limbs and trunk. If disproportion is suspected, the following measurements may be taken:
  • Arm span: Measure outstretched arms from fingertip to fingertip. In children of European origin, the arm span should approximate the height. In comparisons of people of Asian, European, and African heritage, Asians had proportionally shorter arms, Europeans had intermediate-length arms, and Africans had significantly longer arms.
  • Lower segment (LS): Measure from the symphysis pubis to the floor.
  • Upper segment (US): Subtract the LS from the height.
  • The US/LS ratio is calculated by dividing the US by the LS. In children of European origin, this ratio is about 1.7 at birth and decreases to 1 at about age 10, where it remains throughout adulthood. In comparisons of people of Asian, European, and African heritage, Asians had proportionally shorter legs (therefore, larger US/LS ratios), Europeans had intermediate length legs, and Africans had significantly longer legs.
• Pubertal status: Puberty should be staged using the Tanner staging system. In constitutional delay as well as many pathological causes of short stature (including growth hormone [GH] deficiency), puberty is delayed.
• Look for signs of specific syndromes: Numerous specific syndromes include short stature and slow growth velocity.
  • For Turner syndrome, look for webbing of the neck (pterygium colli), a wide carrying angle (cubitus valgus), a low hairline, a high-arched palate, short fourth metacarpals, and multiple nevi.
  • Noonan syndrome and Russell-Silver syndrome, among others, should be considered.
  • Examine for disproportion of limbs to trunk when considering the possibility of skeletal dysplasias.
  • Other syndromes may be present as well.

Causes

The following are possible causes of growth failure (slow growth velocity):

• Familial short stature: Children with familial short stature have a history of parents with short stature. They have a normal growth velocity (thus, they do not exhibit true growth failure). Bone age is not delayed. These children have puberty at a normal time and most often finish their growth with a short adult height.
• Constitutional delay in growth and maturation: This entity is sometimes called delayed puberty. Children with constitutional delay have a normal birth weight, and during the first year of life, their growth slows. For most of the period of linear growth (approximately age 3 y to puberty), they maintain an adequate growth velocity. Bone age is usually delayed, and puberty is late, giving a longer time for prepubertal growth, which usually results in a normal adult height. Children with constitutional delay may have a family history of the same. Usually, these children do not exhibit growth failure (a slow growth velocity); however, a period of slow growth velocity usually occurs during the first year of life, and, just before the onset of puberty, growth velocity is again slow (especially when compared with peers who are in the midst of their pubertal growth spurt).
• Malnutrition: Worldwide, malnutrition is probably the most common cause of growth failure and is usually poverty related. In developed countries, nutritional deficiencies are more often the result of self-restricted nutrient intake. Often, poor weight gain is more striking than short stature.
• Chronic disease, systemic disorders
  • Nervous system: Microcephaly may be a feature.
  • Circulatory system: Cyanotic heart disease may be present.
  • Gastrointestinal system: Gluten enteropathy, ulcerative colitis, or regional enteritis (Crohn disease) may be present. In inflammatory bowel disease (in particular, Crohn disease), the growth failure may be apparent before other symptoms appear.
  • Liver, chronic renal failure: People with renal tubular acidosis may present with growth failure without any other features.
  • Lungs: Cystic fibrosis may be present.
  • Connective tissue: Dermatomyositis may be present.
• Psychosocial dwarfism
• Chromosomal abnormalities: In particular, Turner syndrome (45,X) and Down syndrome (trisomy 21) have growth failure as a part of the syndromes. Growth charts specific for these syndromes are available.
• Other syndromes (nonchromosomal): Syndromes that have growth failure as a feature include Noonan syndrome, Russell-Silver syndrome, and Prader-Willi syndrome.
• Target tissue defects
  • Intrauterine growth retardation: The category of intrauterine growth retardation describes children who have birth weights less than 5.5 lb at full term or who are small for gestational age (SGA) if born preterm. Numerous etiologies for this condition are contained in this category, including fetal alcohol syndrome and placental insufficiency syndromes. In some of these conditions, spontaneous "catch-up" growth occurs, while in others, growth rate remains slow. Overall, 10% of children who are SGA have not caught up in growth by age 2 years.
  • Bone and cartilage disorders: The most common disorder of bone and cartilage is achondroplasia, which is recognizable by frontal bossing, lumbar lordosis, and short limbs. Other skeletal disorders are less easily recognized, such as hypochondroplasia, which may be diagnosed radiologically. Patients with hypochondroplasia also have short limbs, but the disproportion is subtle and may be apparent only with careful measurements of arm span and US and LS. Both of these disorders are due to mutations of the fibroblast growth factor receptor 3.
• Endocrine causes
  • Thyroid hormone deficiency (hypothyroidism): Thyroid hormone is absolutely necessary for normal growth. With hypothyroidism, the growth rate is extremely slow, and with replacement of thyroid hormone, catch-up growth is rapid. Although hypothyroidism is often suspected based on history and physical examination findings, cases have also been reported in which the signs and symptoms are subtle. Because of the possibility of subtle signs, evaluation of thyroid hormone levels in all children with slow growth is advised.
  • Growth hormone deficiency: Children who are growth hormone deficient have normal proportions but may appear younger than their age. They have delayed skeletal maturation. Although Growth hormone deficiency may be suspected because of damage or malformation of the pituitary gland, in most children diagnosed with growth hormone deficiency, the etiology is idiopathic.
  • Growth hormone insensitivity (primary IGF-1 deficiency): Sometimes called Laron dwarfism, this disorder appears to be similar to growth hormone deficiency, except that large amounts of growth hormone are produced but levels of IGF-1 are low. This is a rare condition, except in populations where the gene is present with a greater frequency (eg, in Ecuador).
  • Glucocorticoid excess (Cushing syndrome, Cushing disease): Children with glucocorticoid excess almost always have growth failure as part of the presentation.
  • Androgen excess: When prepubertal children are exposed to excessive amounts of androgen, the growth velocity increases in the short term, but epiphyseal fusion occurs early, resulting in premature slowing of growth velocity, usually resulting in a short adult height. Causes of androgen excess include exposure to exogenous androgen, precocious puberty, and congenital adrenal hyperplasia.

• Search for CME/CE on This Topic »

• Child Abuse & Neglect (Pediatrics: Developmental and Behavioral)
• Failure to Thrive (Pediatrics: General Medicine)
• Child Abuse & Neglect (Pediatrics: Developmental and Behavioral)
• Acrodermatitis Enteropathica (Ophthalmology)

• Growth Failure in Children Causes
• Growth Hormone Deficiency Center
• Growth Failure in Children Overview
• Symptoms of Children Growth Failure
• Growth Failure in Children Treatment
• Growth Hormone Deficiency Overview
• Growth Hormone Deficiency FAQs
• Understanding Growth Hormone Deficiency Medications

• Does Preterm Birth Influence the Response to Growth Hormone Treatment in Short, Small for Gestational Age Children?
• IGF System in Children With Congenital Disorders of Glycosylation
• Cases in Pediatric Gastroenterology From The Children's Hospital of Philadelphia: A 2-Year-Old Boy With Diarrhea, Failure to Thrive, and Hepatomegaly