In this review article, the definition, aetiology, evaluation, differential diagnoses, management, prevention and prognosis of failure to thrive are discussed.

Failure to thrive (FTT) is a common problem in paediatric practice, affecting 5-10% of under-fives in developed countries with a higher incidence in developing countries. Majority of cases of FTT are due to a combination of nutritional and environmental deprivation secondary to parental poverty and/or ignorance. Many infants with FTT are not identified. The key to diagnosing FTT is finding the time in busy clinical practice to accurately measure and plot a child’s weight, height and head circumference, and then assess the trend. In the evaluation of the child who has failed to thrive, three initial steps required to develop an economical treatment-centred approach are: (i) A thorough history including itemized psychosocial review, (ii) Careful physical examination and (iii) Direct observation of the child’s behaviour and of parent-child interaction. Laboratory evaluation should be guided by history and physical examination findings only. Once FTT is identified in a particular child, the management should begin with a careful search for its aetiology. Two principles that hold true irrespective of aetiology are that all children with FTT need a high-calorie diet for catch-up growth (typically 150 percent of their caloric requirement for their expected, not actual weight) and all children with FTT need a careful follow up. Social issues of the family must also be addressed. A multidisplinary approach is recommended when FTT persists despite intervention or when it is severe. Overall, only a third of children with FTT are ultimately judged to be normal.

Keywords: Failure to thrive, growth deficiency, undernutrition.

INTRODUCTION

Although the term failure to thrive (FTT) has been in use in the medical parlance for quite some time now, its precise definition has remained debatable1. consequently, other terms such as “undernutrition”1 and “growth deficiency”2 have been proposed as preferable. FTT is a descriptive term applied to young children physical growth is less than that of his or her peers.3 The growth failure may begin either in the neonatal period or after a period of normal physical development.4 The term FTT is not, in itself, a disease but a symptom or sign common to a wide variety of disorders which may have little in common except for their negative effect on growth.5 In this regard, a cause must always be sought.

Often, the evaluation of children who fail to thrive pose a difficult diagnostic problem. Some of the difficulties result from the numerous differential diagnoses, the definition used or misdirected tendency to search aggressively for underlying organic diseases while neglecting aetiologies based on environmental deprivation.6 In addition, early accusations and alienation of the child’s parents by the health-care provider will make the evaluation and management of the child who has failed to thrive more difficult.7

In general, factors that influence a child’s growth include: (i) A child’s nutritional status; (ii) A child’s health; (iii) Family issues; and (iv) The parent-child interactions.3,8,9 All these factors must be considered in evaluation and management of child who has failed to thrive. This paper presents a simplified but detailed approach to the evaluation and management of the child with FTT.

DEFINITION

The best definition for FTT is the one that refers to it as inadequate physical growth diagnosed by observation of growth over time using a standard growth chart, such as the National Center for Health Statistics (NCHS) growth chart.10 All authorities agree that only by comparing height and weight on a growth chart over time can FTT be assessed accurately.11 So far, no consensus has been reached concerning the specific anthropometric criteria to define FTT.11 Consequently, where serial anthropometric records is not available, FTT has been variously defined statistically. For instance, some authors defined FTT as weight below the third percentile for age on the growth chart or more than two standard deviations below the mean for children of the same age and sex1-3 or a weight-for-age (weight-for-hieght) Z-score less than minus two.1 Others cite a downward change in growth that has crossed two major growth percentiles in a short time.3 Still others, for diagnostic purposes, defined FTT as a disproportionate failure to gain weight in comparison to height without an apparent aetiology.6 Brayden et al.,2 suggested that FTT should be considered if a child less than 6 months old has not grown for two consecutive months or a child older than 6 months has not grown for three consecutive months. Recent research has validated that the weight-for-age approach is the simplest and most reasonable marker of FTT.12

Pitfalls of these definitions:

One limitation of using the third percentile for defining FTT is that some children whose weight fall below this arbitrary statistical standard of normal are not failing to thrive but represent the three percent of normal population whose weight is less than the third percentile.5,6 In the first 2 years of life, the child’s weight changes to follow the genetic predisposition of the parent’s height and weight.13,14 During this time of transition, children with familial short stature may cross percentiles downward and still be considered normal.14 Most children in this category find their true curve by the age of 3 years.6,14 When the percentile drop is great, it is helpful to compare the child’s weight percentile to height and head circumference percentiles. These should be consistent with the position of height and head circumference percentiles of the patient.5 Another limitation of the third percentile as a criterion to define FTT is that infants can be failing to thrive with marked deceleration of weight gain, but they remain undiagnosed and therefore, untreated until they have fallen below the arbitrary third percentile.6 These normal small children do not demonstrate the disproportionate failure to gain weight that children with FTT do.6 This approach attempts not only to prevent normal small children from being incorrectly labeled as failing to thrive, but also excludes children with pathologic proportionate short stature.14 Having excluded these easily distinguishable disorders from the differential diagnosis of FTT, simplifies the approach to evaluation of the child who has failed to thrive.6

A more encompassing definition of FTT includes any child whose weight has fallen more than two standard deviations from a previous growth curve.3,15,16 Normal shifts in growth curves in the first 2 years of life will result in less severe decline (i.e, less than 2 SD).13

Some authors have even limited the definition of FTT to only children less than 3 years old17,18 A precise age limitation is arbitrary. However, most children with FTT are under 3 years of age.6,8

EPIDEMIOLOGY

In young children, FTT which does not reach the severe classical syndrome of marasmus is common in all societies.19 However, the true incidence of FTT is not known as many infants with FTT are not identified, even in developed countries.20-22 It is estimated to affect 5 – 10% of young children and approximately 3 – 5% of children admitted into teaching hospitals.3,5,23 Mitchell et al,24 using multiple criteria found that nearly 10% of under-fives attending primary health care centre in the United States showed FTT. About 5% of paediatric admissions in United Kingdom are for FTT.4 The prevalence is even higher in developing countries with wide-spread poverty and high rates of malnutrition and/or HIV infections.3,19 Children born to single teenage mothers and working mothers who work for long hours are at increased risk.22 The same is true of children in institutions such as orphanage homes and homes for the mentally retarded5,22 with an estimated incidence of 15% as a group.5 Under-feeding is the single commonest cause of FTT and results from parental poverty and/or ignorance.19,22,24 Ninety five percent of cases of FTT are due to not enough food being offered or taken.25 The peak incidence of FTT occurs in children between the age of 9 – 24 months with no significant sex difference.22 Majority of children who fail to thrive are less than 18 months old.3 The syndrome of FTT is uncommon after the age of 5 years.3,22

AETIOLOGY

Traditionally, causes of FTT have been classified as non-organic and organic. However, some authors have stated that this terminology is misleading.27 They based their opinion on the fact that all cases of FTT are produced by inadequate food or undernutrition and in that context, is organically determined. In addition, the distinction based on organic and non-organic causes is no longer favoured because many cases of FTT are of mixed aetiologies.3

Based on pathophysiology (the preferred classification), FTT may be classified into those due to: (i) Inadequate caloric intake; (ii) Inadequate absorption; (iii) Increased caloric requirement; and (iv) Defective utilization of calories. This classification leads to a logical organization of the many conditions that cause or contribute to FTT.10

Non – organic (psychosocial) failure to thrive

In non-organic failure to thrive (NFTT), there is no known medical condition causing the poor growth. It is due to poverty, psychosocial problems in the family, maternal deprivation, lack of knowledge and skill in infant nutrition among the care-givers5,11. Other risk factors include substance abuse by parents, single parenthood, general immaturity of one or both parents, economic stress and strain, temporary stresses such as family tragedies (accidents, illnesses, deaths) and marital disharmony.6,8,22 Weston et al,28 reported that 66% of mothers whose infants failed to thrive has a positive history of having been abused as children themselves, compared to 26% of controls from similar socioeconomic background. NFTT accounts for over 70% of cases of FTT.6 Of this number, approximately one-third is due to care-giver’s ignorance such as incorrect feeding technique, improper preparation of formula or misconception of the infant’s nutritional needs,29 all of which are easily corrected. A close look at these risk factors for NFTT suggest that infants with growth failure may represent a flag for serious social and psychological problems in the family. For example, a depressed mother may not feed her infant adequately. The infant may, in turn, become withdrawn in response to mother’s depression and feed less well.10 Extreme parental attention, either neglect or hypervigilance, can lead to FTT.10

Organic failure to thrive

It occurs when there is a known underlying medical cause. Organic disorders causing FTT are most commonly infections (e.g HIV infection, tuberculosis, intestinal parasitosis), gastrointestinal (e.g., chronic diarrhoea, gastroesophageal reflux, pyloric stenosis) or neurologic (e.g., cerebral palsy, mental retardation) disorders.6,19,22 Others include genitourinary disorders (e.g., posterior urethral valve, renal tubular acidosis, chronic renal failure, UTI), congenital heart disease, and chromosomal anomalies.6,7 Together neurologic and gastrointestinal disorders account for 60 – 80% of all organic causes of under nutrition in developed countries.30 An important medical risk factor for under nutrition in childhood is premature birth.1 Among preterm infants, those who are small for gestational age are particularly vulnerable since prenatal factors have already exerted deleterious effect on somatic growth.1 In societies where lead poisoning is common, it is a recognized risk factor for poor growth.5,31 Organic FTT virtually never presents with isolated growth failure, other signs and symptoms are generally evident with a detailed history and physical examination.32 Organic disorders accounts for less than 20% of cases of FTT.6

Mixed failure to thrive

In mixed FTT, organic and non organic causes coexist. Those with organic disorders may also suffer from environmental deprivation. Likewise, those with severe undernutrition from non-organic FTT can develop organic medical problems.

FTT with no specific aetiology

Review of the literature on FTT indicate that in 12 – 32% of cases of children who have failed to thrive, no specific aetiology could be established.23,33-34

Causes of failure to thrive

A. Prenatal cases: (i) Prematurity with its complication (ii) Toxic exposure in utero such as alcohol, smoking, medications, infections (eg rubella, CMV) (iii) Intrauterine growth restriction from any cause (iv) Chromosomal abnormalities (eg Down syndrome, Turner syndrome) (v) Dysmorphogenic syndromes.

B. Postnatal causes based on pathophysiology:

A. Inadequate caloric intake which may result from:

i. Under feeding

Incorrect preparation of formula (e.g. too dilute, too concentrated).

Behaviour problems affecting eating (e.g., child’s temperament).

Unsuitable feeding habits (e.g., uncooperative child)

Poverty leading to food shortages.

Child abuse and neglect.

Mechanical feeding difficulties e.g., congenital anomalies (cleft lip/palate), oromotor dysfunction.

Prolonged dyspnoea of any cause

B. Inadequate absorption which may be associated with:

Malabsorption syndromes e.g. Celiac disease, cystic fibrosis, cow’s milk protein allergy, giardiasis, food sensitivity/intolerance

Vitamins and mineral deficiencies e.g., zinc, vitamins A and C deficiencies.

Hepatobiliary diseases e.g., biliary atresia.

Necrotizing enterocolitis

Short gut syndrome.

C. Increased Caloric requirement due to

Hyperthyroidism

Chronic/recurrent infections e.g., UTI, respiratory tract infection, tuberculosis, HIV infection

Chronic anaemias

D. Defective Utilization of Calories

Inborn errors of metabolism e.g., galactosaemia, aminoacidopathies, organic acidurias and storage diseases.

Diabetes inspidus/mellitus

Renal tubular acidosis

Chronic hypoxaemia

Clinical manifestations of FTT3,22

Commonly the parents/care-givers may complain that the child is “not growing well” or “losing weight” or “not feeding well” or “not doing well” or “not like his other siblings/age mates”. Usually FTT is discovered and diagnosed by the infant’s physician using the birthweight and health clinic anthropometric records of the child.

The infant looks small for age. The child may exhibit loss of subcutaneous fat, reduced muscle mass, thin extremities, a narrow face, prominent ribs, and wasted buttocks, Evidence of neglected hygiene such as diaper rash, unwashed skin, overgrown and dirty fingernails or unwashed clothing. Other findings may include avoidance of eye contact, lack of facial expression, absence of cuddling response, hypotonia and assumption of infantile posture with clenched fists. There may be marked preoccupation with thumb sucking.

EVALUATION

A. Initial evaluation

It has been proposed that only three initial investigations are required to develop an economical, treatment-centred approach to the child who presents with FTT and this include:35 (i) A thorough history including an itemized psychosocial review; (ii) Careful physical examination including determination of the auxological parameters; and (iii) Direct observation of the child’s behaviour and of parent-child interactions.

The Psychosocial Review: The psychosocial history should be as thorough and systematic as a classic physical examination Goldbloom35 suggested that the interviewers should ask themselves three questions about every family: (i) How do they look; (ii) What do they say; and (iii) What do they do?

a. HISTORY

(1) Nutritional history

Nutritional history should include:

Details of breast feeding to get an idea of number of feeds, time for each feeding, whether both breasts are given or one breast, whether the feeding is continued at night or not and how is the child’s behaviour before, after and in between the feeds. It would give an idea of the adequacy or inadequacy of mothers milk. If the infant is on formula feeding: Is the formula prepared correctly? Dilute milk feed will be poor in calorie with excess water. Too concentrated milk feed may be unpalatable leading to refusal to drink. It is also essential to know the total quantity of the formula consumed. Is it given by bottle or cup and spoon? Also assess the feeling of the mother e.g., ask “how do you feel when the baby does not feed well?” Time of introduction of complementary feeds and any difficulty should be noted.

Vitamin and mineral supplement; when started, type, amount, duration.

Solid food; when started, types, how taken.

Appetite; whether the appetite is temporarily or persistently impaired (if necessary calculate the caloric intake).

For older children enquire about food likes and dislikes, allergies or idiosyncracies. Is the child fed forcibly? It is desirable to know the feeding routine from the time the child wakes up in the morning till he sleeps at night, so that one can get an idea of the total caloric intake and the calories supplied from protein, fat and carbohydrate as well as adequacy of vitamins and minerals intake.

(2) Past and current medical history

The history of prenatal care, maternal illness during pregnancy, identified fetal growth problems, prematurity and birth weight. Indicators of medical diseases such as vomiting, diarrhoea, fever, respiratory symptoms and fatigue should be noted. Past hospitalization, injuries, accidents to evaluate for child abuse and neglect. Stool pattern, frequency, consistency, presence of blood or mucus to exclude malabsorption syndromes, infection and allergy.

(3) Family and social history

Family and social history should include the number, ages and sex of siblings. Ascertain age of parents (Down syndrome and Klinerfelter syndrome in children of elderly mothers) and the child’s place in the family (pyloric stenosis). Family history should include growth parameters of siblings. Are there other siblings with FTT (e.g., genetic causes of FTT), family members with short stature (e.g. familial short stature). Social history should determine occupation of parents, income of the family, identify those caring for the child. Child factors (e.g., temperament, development), parental factors (e.g., depression, domestic violence, social isolation, mental retardation, substance abuse) and environmental and societal factors (e.g., poverty, unemployment, illiteracy) all may contribute to growth failure.5 Historical evaluation of the child with FTT is summarized in Table 1.

(b) PHYSICAL EXAMINATION

The four main goals of physical examination include (i) identification of dysmorphic features suggestive of a genetic disorder impeding growth; (ii) detection of under lying disease that may impair growth; (iii) assessment for signs of possible child abuse; and (iv) assessment of the severity and possible effects of malnutrition.36,37

The basic growth parameters such as weight, height / length, head circumference and mid-upper-arm circumference must be measured carefully. Recumbent length is measured in children below 2 years of age because standing measurements can be as much as 2cm shorter.36,37 Other anthropometric data such as upper-segment-to-lower-segment ratio, sitting height and arm span should also be noted. The anthropometric index used for FTT should be weight-for-length or height. Mid-parental height (MPH) should be determined using the formula.40

For boys, the formula is:

MPH = [FH + (MH – 13)]

2

For girls, the formula is:

MPH = [(FH – 13) + MH]

2

In both equations, FH is father’s height in centimetres and MH is mother’s height in centimetres. The target range is calculated as the MPH ± 8.5cm, representing the two standard deviation (2SD) confidence limits.14

Assessment of degree FTT

The degree of FTT is usually measured by calculating each growth parameter (weight, height and weight/height ratio) as a percentage of the median value for age based on appropriate growth charts3 (See Table 3)

Table 3: Assessment of degree of failure to thrive (FTT)

Growth parameter

Degree of Failure to Thrive

Mild

Moderate

Severe

Weight

75-90%

60 -74%

<60%

Height

90 -95%

85 – 89%

<85%

Weight/height ratio

81-90%

70 -80%

<70%

Adapted from Baucher H.3

It should be noted that appropriate growth charts are often not available for children with specific medical problems, therefore serial measurements are especially important for these children.3 For premature infants, correction must be made for the extent of prematurity. Corrected age, rather than chronologic age, should be used in calculations of their growth percentiles until 1-2 years of corrected age.3

Table 2: Physical examination of infants and children with growth failure.

Abnormality

Diagnostic Consideration

Vital signs

Hypotension

Hypertension

Tachypnoea/Tachycardia

Adrenal or thyroid insufficiency

Renal diseases

Increased metabolic demand

Skin

Pallor

Poor hygiene

Ecchymoses

Candidiasis

Eczema

Erythema nodosum

Anaema

Neglect

Abuse

Immunodeficiency, HIV infection

Allergic disease

Ulcerative colitis, vasculitis

HEENT

Hair loss

Chronic otitis media

Cataracts

Aphthous stomatitis

Thyroid enlargement

Stress

Immunodeficiency, structural oro- facial defect

Congenital rubella syndrome, galactosaemia

Crohn’s disease

Hypothyroidism

Chest

Wheezes

Cystic fibrosis, asthma

Cardiovascular

Murmur

Congenital heart disease(CHD)

Abdomen

Distension hyperactive Bowel sound Hepatosplenomegaly

Malabsorption

Liver disease, glycogen storage disease

Genitourinary

Diaper rashes

Diarrhoea, neglect

Rectum

Empty ampulla

Hirschsprung’s disease

Extremities

Oedema

Loss of muscle mass Clubbing

Hypoalbuminaemia

Chronic malnutrition

Chronic lung disease, Cyanotic CHD

Nervous system

Abnormal deep tendon Reflexes

Developmental delay

Cranial nerve palsy

Cerebral palsy

Altered caloric intake or requirements

Dysphagia

Behaviour and temperament

Uncooperative

Difficult to feed.

Adapted from Collins et al 41

Growth charts should be evaluated for pattern of FTT. If weight, height and head circumference are all less than what is expected for age, this may suggest an insult during intrauterine life or genetic/chromosomal factors.2 If weight and height are delayed with a normal head circumference, endocrinopathies or constitutional growth should be suspected.2 When only weight gain is delayed, this usually reflects recent energy (caloric) deprivation.2 Physical examination in infants and children with FTT is summarized in Table 2.

Failure to thrive due to environmental deprivation

Children with environmental deprivation primarily demonstrate signs of failure to gain weight: loss of fat, prominence of ribs and muscles wasting, especially in large muscle groups such as the gluteals.6

Developmental assessment

It is important to determine the child’s developmental status at the time of diagnosis because children with FTT have a higher incidence of developmental delays than the general population.36 With environmental deprivation, all milestones are usually delayed once the infant reaches 4 months of age.42 Areas dependent on environmental interactions such as language development and social adaptation are often disproportionately delayed. Specific behavioural evaluations (e.g., recording responses to approach and withdrawal), have been developed to help differentiate underlying environmental deprivation from organic disease.43 Assess the infant’s developmental status with a full Denver Developmental Standardized test.44

Parent-child interaction:

Evaluate interaction of the parents and the child during the examination. In environmental deprivation, the parent often readily walks away from the examination table, appearing to easily abandon the child to the nurse or physician.6 There is little eye contact between child and parent and the infant is held distantly with little moulding to the parent’s body.6 Often the infant will not reach out for the parent and little affectionate touching is noted.6 There is little parental display of pleasure towards the infant.6

Observation of feeding is an integral part of the examination, but it is ideally done when the parents are least aware that they are being observed. Breast-fed infants should be weighed before and after several feedings over a 24-hour period since volume of milk consumed may vary with each meal. In environmental deprivation, the parents often miss the infants cues and may distract him during feeding; the infant may also turn away from food and appear distressed.6 Unnecessary force may be used during feeding. Developing a portrait of the child-parent relationship is a key to guiding intervention.11

LABORATORY EVALUATION

The role of laboratory studies in the evaluation of FTT is to investigate for possible organic diagnoses suggested by the history and physical examination.33,34 If an organic aetiology is suggested, appropriate studies should be undertaken. If history and physical examination do not suggest an organic aetiology, extensive laboratory test is not indicated.6 However, on admission full blood count, ESR, urinalysis, urine culture, urea and electrolyte (including calcium and phosphorus) levels should be carried out. Screen for infections such as HIV infection, tuberculosis and intestinal parasitosis. Skeletal survey is indicated if physical abuse is strongly suspected. In addition to being unproductive, blind laboratory fishing expeditions should be avoided for the following reason:5,6 (i) they are expensive; (ii) they impair the child’s ability to gain weight in a new environment both by frightening him/her with venepuncture, barium studies and other stressful procedures and the no oral feeds associated with some investigations prevent him/her from getting enough calories; (iii) they can be misleading since a number of laboratory abnormalities are associated with psychosocial deprivation (e.g., increased serum transaminases , transient abnormalities of glucose tolerance, decreased growth hormone and iron deficiency);21 and (iv) they divert attention and resources from the more productive search for evidence of psychosocial deprivation. In one study, a total of 2,607 laboratory studies were performed, with an average of 14 tests per patient. With all tests considered, only 10(0.4%) served to establish a diagnosis and an additional 1% were able to support a diagnosis.34

Further Evaluation

(1) Hospitalization: Although some authors state that most children with failure to thrive can be treated as outpatients,4,5,11,45 I think it is best to hospitalize the infant with FTT for 10 – 14 days. Hospitalization has both diagnostic and therapeutic benefits. Diagnostic benefits of admission may include observation for feeding, parental-child interaction, and consultation of sub-specialists. Therapeutic benefits include administration of intravenous fluids for dehydration, systemic antibiotic for infection, blood transfusion for anaemia and possibly, parenteral nutrition, all of which are often in-hospital procedures. In addition, if an organic aetiology is discovered for the FTT, specific therapy can be initiated during hospitalization. In psychosocial FTT, hospitalization provides opportunity to educate parents about appropriate foods and feeding styles for infants. Hospitalization is necessary when the safety of the child is a concern. In most situations in our set up, there is no viable alternative to hospitalization.

(2) Quantitative assessment of intake: A prospective 3-day diet record should be a standard part of the evaluation. This is useful in assessing under nutrition even when organic disease is present. A 24-hour food recall is also desirable. Having parents write down the types of food and amounts a child eats over a three-day is one way of quantifying caloric intake. In some instances, it can make parents aware of how much the child is or is not eating.11

Table 4: Summary of risk factors for the development of failure to thrive

Infant characteristics

Any chronic medical condition resulting in:

– Inadequate intake (e.g, swallowing dysfunction, central nervous system

depression, or any condition resulting in anorexia)

– Increased metabolic rate (e.g, bronchopulmonary dysplasia, congenital heart

disease, fevers)

– Maldigestion or malabsorption (e.g, AIDS, cystic fibrosis, short gut,

inflammatory bowel disease, celiac disease).

– Infections (e.g., HIV, TB, Giardiasis)

Premature birth (especially with intrauterine growth restriction)

Developmental delay

Congenital anomalies

Intrauterine toxin exposure (e.g. alcohol)

Plumbism and/or anaemia

Family characteristics

Poverty

Unusual health and nutrition beliefs

Social isolation

Disordered feeding techniques

Substance abuse or other psychopathology (include Muschausen syndrome by proxy)

Violence or abuse

Adapted from Kleinman RE.1

Table 1: Summary of historical evaluation of infants and children with growth failure

Prenatal

General obstetrical history

Recurrent miscarriages

Was the pregnancy planned?

Use of medications, drugs, or cigarettes

Labour, delivery, and neonatal events

Neonatal asphyxia or Apgar scores

Prematurity

Small for gestational age

Birth weight and length

Congenital malformations or infections

Maternal bonding at birth

Length of hospitalization

Breastfeeding support

Feeding difficulties during neonatal period

Medical history of child

Regular physician

Immunizations

Development

Medical or surgical illnesses

Frequent infections

Growth history

Plot previous points

Nutrition history

Feeding behavior and environment

Perceived sensitivities or allergies to foods

Quantitative assessment of intake (3-day diet record, 24-hour food recall)

Social history

Age and occupation of parents

Who feeds the child?

Life stresses (loss of job, divorce, death in family)

Availability of social and economic support (Special Supplemental Nutrition Program for

Women, Infants and Children; Aid for Families with Dependent Chi