May 2022

The editors and current author would like to thank and acknowledge the significant contribution of the previous author of this chapter from the 2004 first edition and 2013 second edition, Dr. Vince K. Yamashiroya. This current third edition chapter is a revision and update of the original author’s work.

*A 4-month-old female comes to your office for her scheduled well baby checkup. She was born at 39 weeks gestation by normal spontaneous vaginal delivery without any complications. At birth, her weight was 3856 g, length 53 cm, and head circumference 34 cm. She was discharged from the nursery by 48 hours of life. She has been breast-fed since birth, although her mother started to also use formula between one to two months of age. She is now being breast-fed once a day, given pumped breast milk in a bottle two to three times a day, and formula the rest of the time (about 16 oz or 480 ml per day). She has 2 to 3 bowel movements a day with many wet diapers. Her past medical history is otherwise significant for a vibratory heart murmur heard from the second week of life, which was thought to be innocent. Parents have no concerns.
*

* Exam: VS are normal. Weight 7.4 kg (95%tile), length 64 cm (90%tile), and head circumference 43 cm (90%tile). She is a robust, active, and healthy appearing infant. Her heart murmur has resolved, and the rest of her examination is otherwise normal.
*

Monitoring a child's growth is one of the most important jobs of a pediatrician. It is not only essential for the general pediatrician, but for other subspecialties as well. An aberration in growth pattern is often the first clue that there is something wrong with the child. Often, the growth of the child is used in conjunction with other signs and symptoms to help the physician determine what the problem might be. For example, an older child who is not gaining weight could be the first clue to inflammatory bowel disease. A girl who is short in stature might have Turner syndrome. A baby with an abnormally increasing head size might have hydrocephalus.

The most important tool for assessing and monitoring a child's growth is the growth chart, which plots height (length), weight, and head circumference. There are different growth charts for boys and girls and two age-group specific growth charts. A source of confusion is that there are two commonly used growth charts for healthy children; the World Health Organization (WHO) growth *standard* and the Centers for Disease Control (CDC) growth* reference.* The CDC recommends that the WHO growth standard be used for children from 0 to 2 years of age, while the CDC growth reference be used in children from 2 years of age and older (1) for the following reasons. The WHO growth standard is used for children less than 2 years of age since the WHO establishes breastfeeding as the biological norm and thus the breastfed infant is the standard for growth. For children over the age of 2 years, the CDC growth reference is used up to 20 years of age (whereas the WHO growth standard only goes up to 5 years of age) (2). The WHO growth standard is based on the Multicentre Growth Reference Study (1997–2003) which followed the growth of healthy children under optimal environmental conditions across different ethnic populations and cultural settings from six participating countries. Thus, these growth standards can be applied to all children everywhere regardless of ethnicity and socioeconomic status. In contrast, the CDC growth chart is based on the growth of children living in the United States from 1963 to 1994 through five national health examination surveys prepared by the National Center for Health Statistics (NCHS). Therefore, there will be differences in percentiles when a child transitions from the WHO growth chart to the CDC growth chart at age 2 (3). Both the WHO and CDC growth charts can be found on the CDC website at http://www.cdc.gov/growthcharts/ (1).

It should be emphasized that these growth charts are only reflective of the population who are healthy and born at term. There are several growth charts available for premature infants that use a corrected age based on gestational rather than chronological age, beginning at 26 weeks of gestation (4). A premature infant’s corrected age is equal to the infant’s chronologic age minus the number of weeks of prematurity (using 40 weeks as full-term gestation) and should be used up to 3 years, or until the infant catches up. If the WHO or CDC growth charts are used; however, the child's growth parameters (weight, height, head circumference) should be adjusted for prematurity (i.e., use the corrected age) until 24 months of age or up to three years for infants born at less than 1500 grams. Very low birth weight (VLBW, <1,500 g) infants may continue to show catch-up growth through early school age (5).

There are also other growth charts available for children with various conditions including Down syndrome, Prader-Willi syndrome, Williams syndrome, Cornelia de Lange syndrome, Turner syndrome, and Marfan syndrome. While condition-specific growth charts can show families how a specific condition can alter growth potential, unfortunately, these charts are based on relatively small, possibly non-representative samples (4). Therefore, WHO or CDC growth charts are still recommended in all cases due to limited reference data for condition-specific growth charts.

It is essential to look at the trajectory of the child's growth curve. Typically, infants and children stay within one or two growth percentile channels, which is due to the control that genetics exert over body size. A growth channel is the area between the percentile lines. A normal exception occurs during the first two years of life. For full term infants, size at birth reflects the influence of the uterine environment. Term infants typically lose 5% to 10% of their birth weight but regain the weight within 2 weeks. Size at age 2 years correlates with mean parental height, reflecting the influence of genetics. Therefore, from birth through 18 months, small infants will often shift percentiles upward toward their parents' mean percentile, and large infants will shift downwards (4). Tanner's height prediction formula can be used to calculate the estimated adult height by taking the mid-parental height (mother's height + father's height, divided by 2), and adding 6.5 cm for males, and subtracting 6.5 cm for females, with a range of 2 standard deviations (one standard deviation is about 5 cm) (6). Another way of estimating adult height is to double the height at 24 months of age for boys and double the height at 18 months of age for girls. Growth is influenced by many factors (nutrition, chronic disease, etc.). Therefore, this formula is based purely on genetic potential.

In adolescents, normal variations in the timing of the growth spurt can lead to a misdiagnosis of growth abnormalities. In primary care, it is important to know the relationship between sexual maturity and growth, which is discussed in other chapters. However, a few general rules can be kept in mind. Before the onset of puberty, the average height velocity is about 5 to 6 cm per year. In females, peak height velocity occurs about 2 years after the growth spurt begins and averages about 9 cm per year. This is also around the time when the nipple and areola have developed but before any other significant breast development (7), and about 6 to 12 months prior to menarche. After menarche, females will usually not grow more than 5 cm, with epiphyseal closure occurring about 2 years later. In males, peak height velocity occurs after girls and averages about 10 cm per year. This is about the time that the male's genitalia are fully developed. Males are taller because of this greater velocity of height in addition to having about 2 more years of prepubescent growth over females (8).

The growth curve is not linear but rather sigmoidal. Growth normally starts to slow down at about 12 to 15 months of age, which is reflected in the growth chart. The periods of rapid growth occur during the first 12 months of age, and from puberty until adulthood. The growth chart is an essential tool to diagnose growth failure or undernutrition, previously called failure to thrive (FTT). Although there are no universal criteria for growth failure, most pediatricians consider the diagnosis if the child's weight is below the 2nd percentile and drops two or more major percentile lines, considering that the child does not have any genetic abnormalities. However, children who are below the 2nd percentile and have a normal weight gain velocity do not have growth failure (9).

Calculation of weight gain in grams per day also allows more precise estimation of growth rate as can be seen in the table below. Neonates should gain weight at a rate of 15 g/kg/day (10). Another way of estimating what weight should be is that birth weight doubles at 6 months and triples at 1 year of age.

When curves are outside the percentile ranges of the chart, it is useful to mention the age at which the growth parameter is at its median value (50th percentile). For example, if a 10-year-old female weighs 18 kg, this weight is below the 5th percentile for a 10-year-old but is at the 50th percentile for a 5-year-old. One could state that her weight age is 5 years, which is a better quantitative description of the growth abnormality.

Lastly, the CDC growth curves identify obesity by measuring the body mass index (BMI), which is calculated by the weight in kilograms divided by the square of the height in meters (or weight in pounds divided by the square of the height in inches multiplied by 703). In adults, a BMI value greater than 25 units is widely accepted as being overweight and a value larger than 30 units is accepted as obesity. However, since the cutoff values for children differ with age and sex, they must be based on percentiles (also known as Z scores), with the 85th percentile being suggested as the cutoff point for being overweight and the 95th percentile as the cutoff for being obese for children over the age of 2. These percentiles are also justified by studies showing that the risk of large BMI values in adulthood and the prevalence of cardiovascular and other diseases increase dramatically for children ages 8 years and older who are over the 85th percentile for BMI.

BMI values decrease from 2 years to 5 years of age, after which there is an increase to 20 years of age. The changes with age in BMI reference values reflect normal alterations in total body fat and fat-free mass. Fat-free mass increases with age in both sexes, but increases are more rapid in boys than in girls after age 13. Likewise, total body fat increases from 8 to 18 years in girls but decreases after age 14 in boys. Another interesting point is the time of rebound, or the point when the BMI values change from decreasing to increasing. It has been observed that individuals who rebound earlier than 5 years of age have higher BMI compared to those who rebound later after 5 years of age. This helps in predicting those individuals who are at risk for obesity later in life. One needs to keep in mind that BMI is limited in that it does not provide an accurate index of adiposity since it does not differentiate between lean tissue and bone from fat. When BMI is used to identify obese children, there are many false negatives (obese children not identified) but few false positives (non-obese children classified as obese). However, BMI values correlate with total body fat, fat as a percentage of body weight (percent body fat), and the mass of all lean tissues (fat-free mass). Although percent body fat is the best measure of obesity, its measurement requires complex laboratory procedures. In assessing patients, it is important to not only evaluate age- and sex-appropriate growth charts and BMI, but to also conduct a thorough history regarding diet and activity, family history, review of systems, and physical exam.

Common student and board examination questions include the growth chart patterns for various diseases and conditions such as constitutional growth delay, familial short stature, nutritional insufficiency, and congenital pathologic short stature. The following list describes the characteristics of each (6):

1. **Congenital pathologic short stature:** These infants are born small, and growth gradually tapers off throughout infancy. These babies are born with intrauterine growth retardation (IUGR) and are small for gestational age (SGA). Examples are chromosomal abnormalities, congenital TORCH (toxoplasmosis, other-syphilis, rubella, cytomegalovirus, herpes) infections, teratogens, extreme prematurity, maternal smoking, etc.

2. **Constitutional growth delay:** In this type of delay, these patients enter puberty later; therefore, their growth spurt occurs later in adolescence. The growth curve has the following appearance: weight and height drop in their percentiles near the end of infancy, parallel the norm through middle childhood, and accelerate toward the end of adolescence. Adult size is normal or often taller than average because their duration of growth is longer than others. Frequently, one or both parents may have a history of short stature during childhood, delayed puberty, and eventual normal adult height. Delayed puberty can be identified by asking about age of menarche in mother and age at which father first started shaving. Tanner staging (sexual maturity rating) is also useful in evaluating these patients because of their delayed puberty.

3. **Familial short stature:** Infant and parents are small. Growth runs parallel to and just below the normal curves.

4. **Nutritional insufficiency:** In this condition, weight declines before length. Body mass index is also low.

Questions

1. What is the formula for calculating BMI?

2. At what age does the uterine environment play a role in the growth of a child versus the influence on growth by the genetic makeup?

3. What are the two ways that failure to thrive is recognized in a growth chart?

4. What percentile of BMI is considered the cutoff point for being overweight?

5. What is the approximate weight gain in grams per day for a healthy term infant from birth to 3 months of age?

6. At what age does rebound occur in BMI? If a child rebounds early, what is this predictive of?

7. What is a weakness of using BMI to identify obesity?

8. What do the growth curves for congenital pathologic short stature, constitutional growth delay, and familial short stature look like?

9. What is the formula used to estimate a child's adult height (Tanner's height prediction formula)?

References

1. National Center For Health Statistics, Centers for Disease Control and Prevention. Growth Charts. https://www.cdc.gov/growthcharts/. Accessed May 6, 2022.

2. National Center For Health Statistics, Centers for Disease Control and Prevention. WHO Growth Charts. From Centers for Disease Control and Prevention. https://www.cdc.gov/growthcharts/who_charts.htm. Accessed May 6, 2022.

3. Nichols J. Normal growth patterns in infants and prepubertal children: Treatment. In: Duryea TK (ed). UpToDate. 2022. https://www.uptodate.com/contents/normal-growth-patterns-in-infants-and-prepubertal-children. Wolters Kluwer, Amsterdam. Accessed May 10, 2022.

4. Charite JL. Nutrition and Growth. In: Kleinman K, McDaniel L, Molloy M (eds). The Harriet Lane Handbook, 22nd edition. 2021, Missouri: Mosby, Inc., pp. 523-545.e3.

5. Landau-Crangle E, Rochow N, Fenton TR, et al. In: Individualized Postnatal Growth Trajectories for Preterm Infants. J Parenter Enteral Nutr. 2018;42(6):1084-1092.

6. Atteih S, Ratner J. Endocrinology. In: Kleinman K, McDaniel L, Molloy M (eds). The Harriet Lane Handbook, 22nd edition. 2021, Missouri: Mosby, Inc., pp: 228-260.e3.

7. Garibarldi LR, Chemaitilly W. Chapter 577. Physiology of Puberty. In: Kliegman R, Bonita S, St. Geme JW, et al (eds). Nelson Textbook of Pediatrics, 21st edition. 2020. W.B. Saunders Company, Philadelphia. pp: 2898-2899.e1.

8. Neinstein LS, Kaufman FR. Normal physical growth and development. In: Neinstein LS (ed). Adolescent Health Care: A Practical Guide, 6th ed. 2016. Williams & Wilkins, Baltimore. pp: 3-39.

9. Kirkland RT, Motil KJ. Poor weight gain in children younger than two years in resource-abundant countries: Etiology and evaluation. In: Drutz JE, Jensen C, Augustyn M (eds). UpToDate. 2021. https://www.uptodate.com/contents/poor-weight-gain-in-children-younger-than-two-years-in-resource-abundant-countries-etiology-and-evaluation. Wolters Kluwer, Amsterdam. Accessed May 6, 2022.

10. Onigbanjo MT, Feigelman S. Chapter 22. The First Year. In: Kliegman R, Bonita S, St. Geme JW, et al (eds). Nelson Textbook of Pediatrics, 21st edition. 2020, W.B. Saunders Company, Philadelphia. pp. 131-137.e1.

Answers to questions

1. BMI = weight in kilograms divided by the square of the height in meters. (Or pounds divided by height in inches squared x 703.)

2. First 2 years of life.

3. a) If the child's weight is below the 2nd percentile, and b) if weight drops more than two major percentile lines.

4. 85th percentile.

5. 30 grams (1 ounce) per day.

6. At 5 years of age. Those who rebound before 5 years have a higher risk of obesity in childhood and adulthood.

7. It does not provide an accurate index of adiposity since it does not differentiate between lean tissue and bone from fat.

8. Congenital pathologic short stature: infant born small, and growth gradually tapers off throughout infancy. Constitutional growth delay: weight and height drop in their percentiles near the end of infancy, parallel the norm through middle childhood, and accelerate toward the end of delayed adolescence. Adult size is normal. Familial short stature: Infant and parents are small. Growth runs parallel to and just below the normal curves.

9. Predicted adult height = (mother's height + father's height) divided by 2, and adding 6.5 cm for males, and subtracting 6.5 cm for females, with a range of 2 standard deviations (one standard deviation is about 5 cm).