AUTHOR INFORMATION	Section 1 of 9
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Author: Reda W Bassali, MBChB, Associate Professor, Departments of General Pediatrics and Adolescent Medicine, Medical College of Georgia Coauthor(s): John Benjamin, MD, Chief, General Section of Pediatrics and Adolescent Medicine, Vice Chair for Clinical Activities, Professor, Department of General Pediatrics, Medical College of Georgia

Reda W Bassali, MBChB, is a member of the following medical societies: Ambulatory Pediatric Association, and American Academy of Pediatrics

Editor(s): Maria Rebello Mascarenhas, MBBS, Associate Professor of Pediatrics, University of Pennsylvania School of Medicine; Section Chief, Division of Gastroenterology and Nutrition, Director, Nutrition Support Service, Children's Hospital of Philadelphia; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Jatinder Bhatia, MD, Professor of Pediatrics, Chief, Section of Neonatology, Vice Chairman for Clinical Research, Department of Pediatrics, Medical College of Georgia; Merrily P M Poth, MD, Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences; and Steven M Altschuler, MD, President and CEO, Children's Hospital Foundation, Children's Hospital of Philadelphia

Disclosure

	INTRODUCTION	Section 2 of 9
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Background: Growth failure, or failure to thrive (FTT), is a descriptive term and not a specific diagnosis. Although definitions vary, most authors use this term only when growth has been noted to be low or to have decreased over time. For instance, some authors define FTT as height or weight less than the third to fifth percentiles for age on more than one occasion. Other authors cite height or weight measurements falling 2 major percentile lines using the standard growth charts of the National Center for Health Statistics (NCHS). Still others state that true malnutrition (weight <80% of ideal body weight for age) should be present to state a child is failing to thrive. All authorities agree that only by comparing height and weight on a growth chart over time can FTT be assessed accurately. Although measurements of head circumference are important in the evaluation of infants and toddlers, failure of the head to grow by itself is not part of the FTT entity.

Normal growth and growth charts of term and premature infants, as well as the etiology, evaluation, management, and outcome of FTT are discussed in this article.

Pathophysiology:

Normal growth in term infants

To recognize abnormal growth, one needs to understand normal growth. The average birth weight for a term infant is 3.3 kg. Weight drops as much as 10% in the first few days of life, probably as a result of loss of excess fluid; however, birth weight should be regained within 2 weeks after birth. Breastfed infants tend to regain birth weight a little later than bottle-fed infants.

The median increase in weight per day in children is summarized in Table 1. On average, infants gain 1 kg/mo for the first 3 months, 0.5 kg/mo from age 3-6 months, 0.33 kg/mo from age 6-9 months, and 0.25 kg/mo from age 9-12 months. Term infants double their birth weight by age 4 months and triple their weight by age 12 months.

Table 1. Median Daily Weight

Age	Median Daily Weight Gain, grams
0-3 mo	26-31 g
3-6 mo	17-18 g
6-9 mo	12-13 g
9-12 mo	9 g
1-3 y	7-9 g
4-6 y	6 g

Term infants grow 25 cm in length during the first year, 12.5 cm in the second year, and then slow down to approximately 5-6 cm between age 4 years and the onset of puberty, at which time growth can increase up to 12 cm per year.

The average head circumference is 35 cm at birth and increases rapidly to 47 cm by age 1 year; the rate of growth then slows, reaching an average of 55 cm by age 6 years.

Also, the upper-to-lower body segment ratio changes with growth. Normally, the ratio at birth is 1.7, the ratio at age 3 years is 1.3, and the ratio by age 7 years becomes 1.0. The lower body segment is the measurement of the symphysis pubis to the floor.

Normal growth in premature infants

When plotting growth charts for premature babies, a "corrected age" should be used. This corrected age can be calculated by subtracting the number of weeks of prematurity from the postnatal age. Special growth charts based on gestational age rather than chronological age have been developed for infants, beginning at 26 weeks' gestational age; however, because these charts represent a compilation of a relatively small number of infants, they may not be completely reliable. Whichever technique is used for premature babies (eg, adjustment of age, using specific premature growth charts), consistency of methodology is essential. Once a method for plotting growth is chosen, that technique should be followed each time plotting occurs.

After catch-up growth is attained, at approximately age 18 months for head circumference, age 24 months for weight, and age 40 months for height, normal growth charts can be used. In some premature babies with very low birth-weight, catch-up growth does not occur until early school age.

Growth charts

Growth charts were developed by the National Center for Health Statistics based on data collected through the Third National Health and Nutrition Examination Survey III. The growth charts, which have been used since 1977, are available for males and females aged 0-36 months and aged 2-18 years. The growth charts for boys and girls aged 0-36 months include weight and height for age and head circumference; growth charts for both age groups include weight for stature.

These charts have recently been revised and are available from the Centers for Disease Control and Prevention (2000 CDC Growth Charts: United States). The new charts are applicable to infants, children, and adolescents from birth to age 20 years and have 7 percentile curves (fifth, tenth, twenty-fifth, fiftieth, seventy-fifth, ninetieth, ninety-fifth). Charts are available for use in subspecialty patients (eg, endocrine, gastroenterology) with additional third and ninety-seventh percentile curves.

Body mass index (BMI) charts, which are available for individuals aged 2-20 years, have replaced the weight-for-stature charts. BMI is calculated by dividing weight in kilograms by height in meters squared.

Accurate measurements are essential to the interpretation of growth charts. Scales need to be calibrated regularly; length should be measured carefully, and head circumference should be measured using standardized techniques.

Alternate growth charts are available for children with Down syndrome, Turner syndrome, meningomyelocele, low birth weight, and very low birth weight. No matter which growth chart is used, the most valuable information is obtained by careful measuring and plotting on the same chart over time. Infants and children remain within 1-2 percentile curves over time.

Frequency:

• In the US: In reports from 1980-1989, FTT accounted for 1-5% of tertiary hospital admissions for infants younger than 1 year. An estimated 10% of children in primary care settings show signs of FTT.

• Internationally: In underdeveloped countries, malnutrition manifesting as FTT is more common.

Mortality/Morbidity: Ultimate physical growth may be decreased in children with FTT. Cognitive development is affected in children younger than 5 years who have FTT. With improvement of nutritional status, these deficits may not be completely reversed. Traditionally, it has been thought that nonorganic causes of FTT resulted in more cognitive deficits than are observed with organic causes. In developing countries, malnutrition is a significant cause of mortality, whether directly or secondary to complications (eg, infection).

Race: FTT can occur in all socioeconomic strata, although it is more frequent in families living in poverty. Studies indicate increased incidence in children receiving Medicaid, children living in rural areas, and children who are homeless.

Sex: Nonorganic FTT is reported more commonly in females than in males.

	CLINICAL	Section 3 of 9
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History: The most important part of the evaluation of children with FTT may be obtaining a careful detailed history. Once FTT is identified in a particular child, an attempt then should be made to determine from the history whether nonorganic FTT, organic FTT, or a combination of the 2 is present. Prenatal history is extremely important and information regarding the following should be obtained:

• Smoking

• Alcohol consumption

• Use of medications

• Any illness during the pregnancy

Similarly, a history of any problems in the nursery should be obtained. Dietary history provides very important information. A simple formula for bottle-feeding infants to determine the proper number of ounces they should consume in 24 hours is to multiply the weight in kilograms by 5. (Calculation is reached by assuming that children need 100 kcal/kg and that each ounce of standard formula contains 20 kcal/oz; thus, for each kilogram of a child's weight, 5 [ie, 100 divided by 20] ounces are needed for proper growth and weight gain. For example, a child who weighs 4 kg needs 20 oz of standard formula per day [4 kg X 100/20 = 20]).

A history of how formula is prepared for infants is very important. Improperly prepared formula can result in FTT and serious electrolyte imbalances. If solid foods are being consumed, a careful history of the type of food, meal frequency, and volume per feeding all may be helpful in determining whether a child is receiving enough energy intake. If history is difficult to obtain, a food diary of up to 3 days may be requested from the parents. Although nutritionists are helpful in calculating the exact number of calories consumed by each child, pediatricians may obtain an accurate view of the child's intake by using diaries.

In breastfed infants and formula-fed infants, the frequency of feeds, number of wet diapers and stools each day, and a history of sequential weights allow the physician the ability to gauge if the child is receiving adequate amounts of fluid and calories and is gaining weight appropriately.

In addition to obtaining specific history about method and efficacy of feeding, gathering any information about the bowel habits of a child being evaluated for FTT is important. Babies with chronic diarrhea may fail to grow properly.

Parents also should be asked about any illnesses that occurred since the neonatal period. Particularly serious infections, such as meningitis, may have deleterious effects on the growth potential of children. Also, any history of signs of chronic conditions, such as cerebral palsy (CP), spasticity, seizures, and delayed development, may be important clues when evaluating a child for FTT.

Family and social history should include other siblings, living conditions, stressors, and data on parents' growth history.

Physical: The first thing that pediatricians should do in all health assessments is to plot the head circumference, height, and weight on a growth chart. Insisting on careful measurements during each examination is important. Every effort should be made to obtain as many previous growth parameters as possible to detect trends in growth rather than to rely on measurements at one particular visit.

Growth charts should be evaluated for the pattern of FTT. If weight, height, and head circumference are all less than what is expected for age, this may result from in utero insults or genetic or chromosomal factors (see Image 1). If weight and height growth are delayed with a normal head circumference, endocrinopathies (Images 2-3) or constitutional delay (Image 4) should be suspected. This pattern also can occur in long-standing FTT. Ultimately head circumference is delayed, emphasizing the importance of following these growth parameters over time. When only weight gain is delayed, this usually reflects recent energy (caloric) deprivation (see Image 5).

Vital signs usually are within the reference range, but documenting the following vital signs is important:

• Blood pressure

• Respiration

• Pulse rate

• Oxygen saturation in certain clinical situations

The physical examination of children with FTT may show the following:

• Edema

• Wasting

• Hepatomegaly

• Rash or skin changes

• Hair color and texture changes

• Mental status changes

• Signs of vitamin deficiency

Marasmus (caused by insufficient caloric intake) must be distinguished from dehydration, which is characterized by the following signs:

• Decreased skin turgor

• Depressed sensorium

• Sunken anterior fontanelle

• Dry mucous membranes

• Absence of tears

• Acutely ill appearance

Causes: Different classification systems have been developed to identify the reasons for FTT in children. Three categories into which all FTT can be classified are nonorganic FTT, organic FTT, and a combination of nonorganic and organic FTT.

• Nonorganic FTT (see Nonorganic causes of FTT ): Nonorganic FTT usually results from various environmental and psychosocial factors. It often is associated with abnormal interactions between the caregiver and the infant or child. This can result in an inadequate provision of food and/or inadequate intake of food. Nonorganic FTT can begin prenatally or occur postnatally.

• Prenatal causes of nonorganic FTT: Mothers who are malnourished often have babies who are malnourished and small. Some evidence exists that, if mothers do not bond with their unborn babies, those babies undergo FTT in utero as well. Lower birth weights also are associated with teen pregnancies, lower socioeconomic level, and multiple gestations. Maternal eating disorders (eg, anorexia, bulimia) certainly can affect the growth of fetuses as well.

• Postnatal causes of nonorganic FTT
  • Traditionally, it was thought that nonorganic postnatal causes of FTT were due to maternal rejection or neglect. In 1985, Skuse suggested that clinicians inquire about more than just the nutrition offered to children. He found behavior at meals and psychosocial issues to be important variables affecting whether children obtain sufficient energy. Poor parenting and family dysfunction can negatively affect a child's energy intake. Families characterized by less adaptive relationships, higher levels of family conflict, and less emotional support for the mother have an increased percentage of children with FTT. The term psychosocial deprivation was created for these types of situations.

  • Other nonorganic reasons for FTT in younger children may be a failure to signal hunger, a poor suck, difficulty in weaning, or a refusal to eat; in older children, eating disorders, including anorexia and bulimia, may lead to severe growth disturbances.

• Nonorganic causes of FTT are summarized as follows:
  • Poor feeding or feeding-skills disorder

  • Dysfunctional family interactions

  • Difficult parent-child interactions

  • Lack of support (eg, no friends, no extended family)

  • Lack of preparation for parenting

  • Family dysfunction (eg, divorce, spouse abuse, chaotic family style)

  • Difficult child

  • Child neglect

  • Emotional deprivation syndrome

  • Feeding disorders (eg, anorexia, bulimia)

• Organic FTT: Similar to the nonorganic reasons for FTT, organic reasons also may exist prenatally or postnatally.

• Prenatal onset of FTT (See Table 2.)
  • Prenatal causes of FTT often are associated with complications of prematurity. Premature babies have increased incidences of almost all medical conditions, including renal disease, heart disease, lung disease, and CNS disorders. All these disorders can lead to intrauterine FTT.

  • When babies are born prematurely and have associated intrauterine growth retardation (IUGR), they are more likely to have FTT and decreased growth potential. Most premature babies catch up to the growth of term babies by the time they are aged 2-4 years. However, some premature babies, particularly those with concomitant IUGR, never catch up in their growth.

  • Whether babies are small because of prematurity or whether they have decreased growth potential and fall into the FTT category sometimes is unclear. A clue to this diagnostic dilemma is that, if infants double their birth weight by age 4 months and triple their birth weight by age 1 year, full catch-up growth can be anticipated.

  • Other causes of the prenatal onset of FTT include exposure to toxins, environmental influences, maternal factors, intrauterine infection, and placental or chromosomal abnormalities.

  • Examples of toxins affecting growth are tobacco use in pregnancy, which is known to produce placental insufficiency, and alcohol ingestion during pregnancy. Prenatal ingestion of drugs of abuse, such as cocaine and amphetamines, also can play a role in the prenatal onset of FTT. Because these drugs often are taken together, separating the effects of each drug may be difficult. Also, maternal exposure to medications, such as hydantoin and phenobarbital, can lead to in utero FTT. In addition, maternal illness, such as hypertension, preeclampsia, heart disease, anemia, and advanced diabetes mellitus, can lead to uteroplacental insufficiency and, therefore, result in smaller babies. Another example of prenatal FTT is demonstrated by children affected by chromosomal abnormalities.

  • Genetic short stature and constitutional delay of growth are 2 conditions associated with decreased growth that need to be distinguished from FTT. From birth to about age 2 years, a baby's weight changes to follow the genetic predisposition of the parents' height and weight. During this time of transition, children with genetic short stature may cross percentiles downward and still be considered normal. However, most children in this category find their true growth curve by age 3 years. Although children with genetic short stature often are below the third percentile on the growth chart, they have normal weight-to-height ratios and bone ages equal to their chronological ages.

  • The other condition associated with short stature that must be distinguished from FTT is constitutional delay of growth, another variation of normal growth. Children with short stature resulting from constitutional delay often have a family history of delayed growth and puberty. They have a deceleration of growth in the first 2 years that can be confused with FTT, but then grow parallel to but below the third percentile. Puberty is delayed, but ultimate height may be normal. A distinguishing point from genetic short stature is that bone age is delayed.

• Postnatal causes of organic FTT (See Table 2.)
  • Although differential diagnosis of the category of postnatal causes of organic FTT is vast, it can be subclassified into the following 3 general areas: inadequate energy intake, poor absorption and/or the inability to use absorbed nutrients, and increased metabolic demands.

  • Causes of inadequate energy intake can result from mechanical problems, craniofacial abnormalities, lack of appetite, breathing difficulties, metabolic problems, and excessive vomiting. Mechanical problems result from a poor suck or swallow secondary to hypotonia or Prader-Willi syndrome or from a neuromuscular or CNS system disease leading to incoordination of this process. Craniofacial abnormalities also are commonly associated with inadequate energy intake and, therefore, cause FTT. For instance, severe micrognathia makes eating difficult, as does cleft lip and cleft palate.

  • Some children simply have unexplained poor appetites that are unrelated to mechanical problems or structural abnormalities. An example of a cause of inadequate intake is the breathing difficulties that can result from congestive heart failure (CHF) or chronic lung disease (eg, bronchopulmonary dysplasia [BPD]); any difficulty in breathing makes eating more difficult and can result in FTT. Inadequate intake also can result from metabolic abnormalities, excessive vomiting caused by CNS disease, GI tract obstruction, or renal causes. Also, pathological gastroesophageal reflux causing esophagitis may lead to regurgitation of formula or refusal of feeding.

  • Even when energy intake is adequate, FTT can occur because of poor absorption of food, inability of the body to use absorbed nutrients, or increased loss of nutrients. For example, children with cystic fibrosis (CF) lack pancreatic enzymes that are required for absorption of nutrients. Unless supplemented with exogenous enzymes, children with this condition have FTT from the inadequate use of ingested food. Another example of the inability to use absorbed nutrients is observed in children with celiac disease who have decreased nutrient absorption caused by villous atrophy.

  • Illnesses that increase metabolic demands, such as hyperthyroidism, also can cause FTT. Some illnesses are characterized by both inadequate intake and increased metabolic demands. For instance, children who have congenital heart disease with CHF and children with BPD have both decreased intake of nutrients and increased metabolic demands. Other medical conditions, such as hyperthyroidism, are associated with FTT based primarily on increased metabolic demands.

  • Examples of increased loss of nutrients occur with milk protein allergy or other conditions that can be associated with protein-losing enteropathies. Celiac disease has been more recognized in recent years with the introduction of noninvasive tests and should be considered in children with failure to thrive. The prevalence of celiac disease is 1:100 in some studies.

  • Whether FTT occurs for any of the above reasons alone or a combination of reasons, an important part of the evaluation of all children is observation of the infant while feeding. Observing infants while they are feeding sheds light on maternal-infant interactions, the infant's ability to suck and swallow, and on the fatigability of the child.

  Table 2. Organic Causes of FTT
  
  
  

  Prenatal causes

  Prematurity with complications Maternal malnutrition Toxic exposure in utero Alcohol, smoking, medications, infections IUGR Chromosomal abnormalities

  Postnatal causes

  Inadequate intake Lack of appetite (eg, iron deficiency anemia, CNS pathology, chronic infection) Inability to suck or swallow: CNS or muscular Vomiting (eg, CNS, metabolic, obstruction, renal) Gastroesophageal reflux and esophagitis Poor absorption and/or use of nutrients GI disorder (eg, CF, celiac disease, Schwachman-Diamond syndrome, chronic diarrhea) Renal: renal failure, renal tubular acidosis Endocrine: hypothyroidism, diabetes mellitus, growth hormone deficiency Inborn error of metabolism Chronic infection (eg, HIV, tuberculosis, parasites) Increased metabolic demand Hyperthyroidism Chronic disease (eg, heart failure, BPD) Chronic inflammatory conditions (eg, inflammatory bowel disease, lupus erythematosus) Renal failure Malignancy

  
  
  

• Combined organic and nonorganic FTT

• FTT in a patient can result from the combination of both organic and nonorganic reasons. In one study, half of the cases with organic etiology had a psychosocial factor contributing to the FTT. This is caused by a number of reasons. It is clear that illnesses in children, particularly chronic illnesses, can take their toll on families. Stresses from coping with chronic illnesses may lead to parental dysfunction, such as depression, alcohol or drug abuse, divorce, or chaotic home environments. Parental dysfunction and the resultant negative atmosphere in which children are reared affect their food intake. In addition, children may undergo personality changes when they have chronic diseases. Medications (eg, steroids) are well known to cause behavioral changes, but the mere presence of a chronic illness also can result in resistance or noncompliance in many aspects of a child's life, including consumption of proper energy intake.

• Many examples of children having both organic and nonorganic causes of FTT exist. For example, children with CF, asthma, heart disease, and CP all have organic reasons for FTT. In addition, the social pressures that children with these conditions experience can cause behavioral changes that result in decreased energy intake and, therefore, FTT.

	DIFFERENTIALS	Section 4 of 9
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Child Abuse & Neglect: Failure to Thrive
Constitutional Growth Delay
Eating Disorder: Anorexia
Eating Disorder: Bulimia
Fetal Alcohol Syndrome

Other Problems to be Considered:

Isolated growth hormone deficiency
Other causes for IUGR
Other chromosomal/genetic causes of delayed growth