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Failure to Thrive: Who is at Risk, and How it is Treated

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Contact Hours: 3

This online independent study activity is credited for 3 contact hours at completion.

Course Purpose

The purpose of this course is to provide an overview of failure to thrive, the different categories, risk factors, diagnosis, and treatment options.

Contact Hour Designation

This online independent study activity is credited for 3 contact hours

Overview

Failure to thrive (FTT) is used to describe young children or infants whose current weight or rate of weight gain is below that expected of similar children of the same age, sex, and ethnicity.
In most cases, FTT is insidious and gradual, and parents may not notice the undernutrition until it is bought to their attention.2 Healthcare professionals who work closely with the family and community are in the best position to detect the problem. This course provides an overview of failure to thrive, the various categories, risk factors, how it is diagnosed, and options for treatment.

Objectives

Upon completion of the independent study, the learner will be able to:

  • Define failure to thrive
  • Describe the various categories of failure to thrive.
  • Recognize the risk factors for failure to thrive and how they can impact future development.
  • Understand how failure to thrive is diagnosed and weight parameters as recommended by the World Health Organization.
  • Understand dietary and pharmacological treatment options to improve weight gain.

Policy Statement

This activity has been planned and implemented in accordance with the policies of FastCEForLess.com.

Disclosures

Fast CE For Less, Inc and its authors have no disclosures. There is no commercial support.

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Definitions
Failure to ThriveA term used to describe young children or infants whose current weight or rate of weight gain is below that expected of similar children of the same age, sex, and ethnicity.  
Childhood MalnutritionDescribes children under the age of 2 years having weight below the 3rd or 5th percentile for their age on more than one occasion or children under the age of 2 years whose weight is less than 80% of the ideal weight for their age, or a child younger than 2 years whose weight crosses two major percentiles downward in a standardized growth grid using the 90th, 75th, 50th, 25th, 10th, and 5th percentiles as the major percentiles.  
Organic Failure to ThriveA medical condition that is responsible for the imbalance between caloric intake and body consumption requirements.  
Non-Organic Failure to ThriveA medical condition where psychological or family issues are responsible for low calorie intake.  
Mixed Failure to ThriveA medical condition where organic and nonorganic causes overlap.
Introduction

Failure to thrive (FTT) is a term that is often used in conjunction with growth faltering, weight faltering, or poor weight gain, describes a primary and secondary undernutrition condition that usually occurs in younger children or infants.1 In simple terms, failure to thrive is used to describe young children or infants whose current weight or rate of weight gain is below that expected of similar children of the same age, sex, and ethnicity.2 Failure to thrive is a common problem and can be present at any time in childhood.2

Childhood malnutrition is a major cause of morbidity and mortality, with 45% of mortality in children younger than 5 years linked to undernutrition.1 If we discuss FTT in routine clinical practice, it is defined as “children under the age of 2 years having weight below the 3rd or 5th percentile for their age on more than one occasion or children under the age of 2 years whose weight is less than 80% of the ideal weight for their age, or a child younger than 2 years whose weight crosses two major percentiles downward in a standardized growth grid using the 90th, 75th, 50th, 25th, 10th, and 5th percentiles as the major percentiles.”2

Faltering growth is usually detected in children using the parameters mentioned in the table below:

Table 1. Faltering growth: most commonly used anthropometric criteria.6

 BMI for age < 5th percentile
 Length-for-age < 5th percentile
 Weight-for-age < 5th percentile
 Weight < 75 % of median weight for age (Gomez’s criterion)
 Weight < 80 % of median weight for length (Waterlow criterion)
 Weight deceleration crossing two major percentile lines

Although weight according to the current age and sex is the most used parameter, length/height-for-age, and weight-for-length/height should also be considered.6 Moreover, children who falter in growth parameters sometimes display a normal variant of growth, such as catch-down growth in infants born large for gestational age. In such cases, conditional weight should be considered.6

In the United States, children with FTT account for 5-10% of primary care pediatric patients and 3-5% of pediatric hospital admissions.3 There are multiple problems associated with FTT, such as its effect on overall growth, head circumference, weight, and in severe cases, failing to achieve developmental milestones and affecting a child’s cognitive ability and immune system, with malnutrition and undernutrition being a predominant manifestation of FTT.4

In most cases, FTT is insidious and gradual, and parents may not notice the undernutrition until it is bought to their attention.2 Healthcare professionals who work closely with the family and community are in the best position to detect the problem.4 Often, healthcare professionals can document the type and amount of food the child consumes on a regular basis and observe subsequent consistent weight gain in 1–2 weeks. Hospitalization is rarely required, except in severe cases.4

Types of Failure to Thrive

According to the physiological factors, failure to thrive is categorized into 3 types; organic FTT, non-organic FTT, and mixed FTT.5

Organic Failure to Thrive

Organic Failure to Thrive is a medical condition that is responsible for the imbalance between caloric intake and body consumption requirements.5,6 It also interferes with absorption, metabolism, and excretion, and increases energy requirements.5

There are multiple causes of organic FTT, summarized in the table below.

Table 2: Causes of organic FTT5

MechanismDisorder 
Decreased nutrient intakeCleft lip or palate
Central nervous system (cerebral palsy)
Gastroesophageal reflux disease
Parasites
Pyloric stenosis
Rumination
 
 MalabsorptionCeliac disease
Cystic fibrosis
Short gut
Disaccharidase (lactase) deficiency
Inflammatory bowel disease
 MetabolismChromosomal abnormality (Down syndrome, Turner syndrome)
Galactose-1-phosphate uridyl transferase deficiency (classic galactosemia)
Inborn errors of metabolism
Fructose intolerance
 Increased excretionDiabetes mellitus
Proteinuria
 Increased energy requirementsInfection
Bronchopulmonary dysplasia
Cystic fibrosis
Heart failure
Hyperthyroidism

Non-Organic Failure to Thrive

Non-Organic FTT is a medical condition where psychological or family issues are responsible for low calorie intake.6 The mental stress in the child may cause increased levels of counter-regulatory hormones (corticosteroids, catecholamines), which oppose the effects of growth hormone, resulting in growth failure and accompanying poor weight gain.5

In a retrospective observational cross-sectional study on 729 children referred to a pediatric gastroenterology outpatient clinic, the most common cause of non-organic FTT was inadequate nutrition (61.4%), followed by psychiatric and behavioral disorders (17.2%).6

A common pattern followed in non-organic FTT includes growth in length and head circumference remaining normal for some time until they too become impacted by poor calorie intake.5

Up to 80% of children with growth failure do not have an apparent growth-inhibiting (organic) disorder.5 Rather, growth failure can also occur because of environmental neglect (such as lack of food), stimulus deprivation, or both.5 Several key nutrients have been described to play a unique role during the first 1000 days of life, including carotenoids, choline, folate, iodine, iron, omega-3 fatty acids, vitamin D, B vitamins, magnesium, and other trace minerals.6 Lack of access to these nutrients results in faltering growth and motor neuron diseases (MNDs).6

Many predisposing conditions also lead to faltering growth and MNDs, which are often overlooked, such as food allergies, vegan or vegetarian diets, lactose intolerance, food insecurity, or Avoidant/Restrictive Food Intake Disorder (ARFID).6

Non-organic FFT encompasses the complex child-caregiver interaction, where the unstimulated child can become depressed or apathetic if the caregiver is depressed or apathetic, has poor parenting skills, is anxious about or unfulfilled by the caregiver role, feels hostile toward the child, or is responding to real or perceived external stresses, such as financial crisis, loss of a loved one, etc.5

Despite this, not all non-organic FTT are a result of poor caregiving skills. Other causes include parent-child mismatches, a child’s temperament, and a difficult feeder.5

Mixed Failure to Thrive

Mixed FTT is a medical condition where organic and nonorganic causes overlap. For instance, children with organic disorders also have disturbed environments or dysfunctional parental/caregiver interactions. Likewise, children with severe undernutrition caused by nonorganic FTT can develop organic medical problems.5

Pathological Causes of Failure to Thrive

A combination of pathological, psychosocial, and environmental factors can also contribute to FTT.2 For instance:

  • In > 80% of cases, a clear underlying medical condition is never identified.2
  • Familial conditions and stress also contribute to FTT.2
  • In developing countries, poverty is the single most significant contributor to FTT.2
  • Inadequate food intake:2
  • Due to withholding of food
  • Poor parental-infant interactions
  • The type of available food is not appropriate
  • Chronic illness or psychosocial disorders lead to lack of appetite.
  • Excessive loss of nutrients due to vomiting, malabsorption, and diarrhea resulting from inflammatory bowel syndrome, colitis, metabolic disorders, gastro-intestinal obstructions, etc.2
  • Chronic illness, such as anemia, cardiac diseases, etc., leading to excessive utilization of energy.2
  • Anemia and other blood disorders.7
  • Brain and central nervous system disorders that result in feeding difficulties.7 It is an umbrella term that can be used to describe picky eating, food refusal, and not self-feeding appropriate for age.3
  • Pregnancy problems or low-birth weight.7
Risk Factors

As mentioned above, there are multiple factors, such as biological, psychosocial, developmental, and environmental factors, including deprivation, maternal educational level, family size, and a wide range of physical conditions that contribute to failure to thrive in infants and young children.2,3,4

Usually, a healthcare professional is in an optimal position to detect the signs and symptoms of FTT and provide care.4 The care involves documenting the type and amount of food the child consumes and observing subsequent consistent weight gain in 1–2 weeks, confirming the diagnosis of non-organic FTT.4

A child should only be suggested secondary care if the following risk factors are noted:4,7

  • Lack of emotional bond between parent and child
  • Poor parent-child interaction or extreme parental anxiety
  • Psychosocial factors in parents or environment that endangers the child
  • Poverty or lack of adequate nutrition
  • An underlying chronic disease or illness that suggests an associated disease
  • Poor eating habits and feeding difficulties
  • Exposure to toxins, parasites, and infections
Diagnosis

History taking and physical examination are essential to diagnose failure to thrive.2,5,6 Often, parents and caregivers do not recognize their child’s faltering growth and developmental delays because they see the children regularly, and do not recognize the slight changes in health,2 however a healthcare professional will be able to diagnose and treat the condition.2

Children with organic FTT may present at any age, depending on the underlying disorder. In contrast, children with nonorganic FTT manifest growth failure before age 1 and many by 6 months of age.5 To diagnose FTT, age should be graphed against weight, height, and head circumference as standards set by the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC).5When developmental delays and poor growth are noted; history evaluation, counseling, and constant weight monitoring are considered.5

Weight Monitoring

Weight is the most obvious indicator to check the nutritional status of a child or infant.5 Underweight children may be smaller and shorter than other children their age and may have symptoms like fussiness or crying, lethargy or sleepiness, and constipation.5 Furthermore, FTT is also associated with physical delays (sitting and walking), social delays (interacting and learning), and delayed puberty in older children.5

Failure to thrive may result from multiple causes. For instance, if FTT is caused by low-calorie intake, a child or infant’s weight may fall below the average percentile for weight at the child’s age. The reduction in weight is likely to occur and be noticed before a reduction in linear growth (height).5 Linear growth usually indicates severe, prolonged undernutrition. A reduction in linear growth in conjunction with being underweight suggests a primary growth disorder or a prolonged inflammatory state.5 When such conditions are observed, children are hospitalized, and a thorough patient history and diagnostic tests are conducted to identify the underlying illness or chronic disease associated with failure to thrive.5

Patient’s History

To diagnose and distinguish between organic and non-organic FTT, healthcare professionals should collect information regarding family, medical, and social history.2,5 The evaluation should be multidisciplinary and include an expert in child development.5

Table 3: Essentials of the patient’s history for failure to thrive.2,5,6

GrowthMeasures to determine growth trend (from birth to present age) Never base diagnosis on a single measurement unless undernutrition is obvious.
Family historyFamilial growth patterns in parents and siblings. Occurrence of diseases known to affect growth. Recent physical and psychiatric illness in parents affecting their ability to provide proper care to children. History of Intestinal Bowel Disease, Coeliac disease, or Cystic fibrosis. History of developmental delays or faltering growth Height and weight of parents Siblings’ growth pattern
Family backgroundFinancial status Living conditions Risk factors for neglect and abuse, such as a single parent, poverty, or postpartum depression. Parental-child interaction Parental coping skills
Diet historyFeeding schedules and techniques Formula preparation Volume consideration Who feeds the baby Position and placement of the infant for feeding, timing, and introduction of solids Strength of sucking Stool and vomiting patterns Calorie intake
Elimination patternsAbnormalities of urine or stool and frequent emesis should require an investigation to detect underlying renal disease, malabsorption syndrome, pyloric stenosis, or gastroesophageal reflux.
Medical historyHistory of recurrent infections Unusual, prolonged, or chronic infections Neurologic, cardiac, pulmonary, or renal disease History of illness and hospitalization Recurrent vomit or acid reflux Food intolerance
Social historyDesire for pregnancy Acceptance of child External stressors Family composition History of maternal depression
Eating habitsFood insecurity issues Suck-swallow problems Restricted diet such as vegan, vegetarian, junk Food routine Feeding difficulties
Pregnancy periodWas the child breastfed? Was the child born at term? Supplementation during pregnancy Was the child’s weight high or low during pregnancy?
Behavioral characteristicsSleeping and eating patterns Behavior that is moody, demanding, rejecting, or distractible

Other things that need to be observed during hospitalization include:2,5,6

  • Observe the infant while the caregiver or parent is feeding and playing.
  • Self-stimulatory behaviors, such as head banging.
  • Closely observe for signs of abuse.
  • Child’s interaction with the environment.
  • Child’s interaction with inanimate objects.

Physical Examination

If the causes and etiology of FTT are not determined after obtaining the history and evaluation, physical examination is considered.2,5,6 In physical examination, the focus is given to the patient’s weight, height, and head circumference based on standards set by the WHO for their age.2

  • Head circumference, weight, and height are proportionately reduced in infants and young children who have hereditary and congenital defects.2
  • Head circumference is normal, and weight is slightly reduced proportionately to height in children with constitutional growth delay, genetic dwarfism, or endocrinologic disorders.2
  • Head circumference is normal, and weight is reduced out of proportion to height in most infants with FTT, especially if malnutrition results from inadequate caloric intake, malabsorption, or altered metabolism.2

Table 4: The patient’s physical examination essentials for failure to thrive.2,6

AnthropometryWeight Length (<2 years) or height BMI Cranial Circumference
Developmental assessmentMotor impairment Milestones reached Learning or memory difficulties Social or emotional problems Behavioral problems Language skills
System reviewSigns of MNDs like skin abnormalities, dermatitis, pallor, edema, etc. Signs of dehydration Vital sign monitoring Signs of organic pathology
Signs of medical conditions causing FTTDevelopmental delay Dysmorphic feature Recurrent vomiting, diarrhea, or dehydration Severe or recurrent respiratory or urinary infection Unable to gain weight after sufficient calorie intake

Further physical examination includes physical signs of neglect or abuse, dysmorphic features, skin rashes, examination of the mouth for the presence of a cleft palate and quality of sucking movements, general appearance, body fat, and muscle wasting.2 These examinations are important to determine if the child should be hospitalized or not.2,6

Testing

Investigations should be made based on history, evaluation, and physical examination.2 For further investigation; laboratory testing is conducted.2 Laboratory testing is unlikely to lead to a specific organic diagnosis in a child whose failure to thrive is unexplained after careful history taking and physical examination.6 Consequently, routine laboratory testing is not recommended, as it has been shown to identify a definitive cause for faltering growth in <1% of children.6

Because of these reasons, screening tests are limited to:5

  • Blood lead level
  • Blood urea nitrogen and serum creatinine and electrolyte levels
  • Complete blood count with differential
  • Erythrocyte sedimentation rate
  • Stool for pH, reducing substances, odor, color, consistency, and fat content
  • Urinalysis (including the ability to concentrate and acidify) and culture

If growth in height is more severely affected than growth in weight or when height/length and weight fall off simultaneously, growth hormone assessment is conducted.5 Moreover, children with conditions predisposing to a high risk of MNDs should be tested for micronutrient plasma levels.6

Treatment Options

The treatment for failure to thrive focuses on replenishing nutritional value to increase weight in infants and young children, developing a care plan for the family, and guaranteeing adequate cognitive development.5,6,8 Interventional techniques focus on both nutritional and behavioral issues, and thus, a multidisciplinary team should be developed to tackle the challenge.6 Usually, healthcare professionals can treat FTT in an outpatient setting, but if usual treatment doesn’t work, secondary care professionals, like social workers, dietitians, lactation specialists, etc., are useful.8

Failure to thrive treatment combines pharmacological, behavioral, and nutritional changes. Let’s discuss each in detail. 5,6,8

Catch-Up Growth

Catch-up growth is characterized by height velocity above normal age limits for at least 1 year after a transient period of growth inhibition; it can be complete or incomplete.9 Simply put, catch-up growth occurs when an infant or child grows at 2 to 3x the average rate per age.8

Table 5: Normal Median Weight Gain in Children.8

Age (months)Median weight gain (grams per day)
 0 to 3 26 to 31
 3 to 6 17 to 18
 6 to 9 12 to 13
 9 to 12 9
 12 and older 7 to 9

Parents and caregivers should be informed and educated about high calorie, about 150% of the normal caloric requirement, recipes, and foods to help with catch-up growth, ideally provided in three meals and three snacks per day.5,6,8

For hospitalized children with non-organic FTT, the issues are more complex.5 Often, there is no differentiation between organic and non-organic FTT children gaining weight in a hospital setting. However, some non-organic FTT children lose weight in the hospital, even when given proper nutrition.5

In such cases, it is recommended to provide educational and emotional support to correct the parent-child relationship and bring in professional psychiatrists to identify the family’s needs, provide initial instruction and support, and institute appropriate referrals to community agencies.5 The parents should also be involved in the decision-making for tertiary care hospitals or local agencies and should consult with professional health care providers about the quality of care available.5

Table 6: Dietary Reference Intake for Young Children.8

AgeKcal per kg per day
0 to 6 months108
6 to 12 months98
1 to 3 years102

For breastfeeding infants, dietary and lactation adjustments need to be made to aid with catch-up growth.6,8 Parents and caregivers should be educated on breastfeeding attachment, formula preparation, and adequate calorie intake.6,8 Most infants can tolerate increasing formula concentration from 19 to 24 kcal per oz.8

Families with problems obtaining nutritious food should receive social work support or other community resources.6 Moreover, modular and complete oral nutritional supplements are also an option when caloric requirements are difficult to meet.6

When using the catch-up treatment, follow the below steps:

  • Provide age-appropriate nutritional counseling.6
  • Provide parenting skill training and psychological counseling.5
  • Provide follow-up visits ranging from weekly to every few months to document weight and adjust the plan as the child progresses.8
  • Ensure immunizations are up to date to support the child’s immune system.8
  • Weight change is better averaged over intervals of a few days to weeks until normal growth velocity is achieved.8
  • If weight is being checked in short intervals, ensure it happens on the same scale and the same time of the day as the previous weight check.8

Pharmacotherapy

The underlying disorder should be treated quickly in children with mixed or organic FTT.5 Pharmacotherapy, such as cyproheptadine or megestrol (Megace), has been studied and may be helpful for specific populations with significant underlying diseases, such as cystic fibrosis or chronic renal disease, or in patients undergoing cancer treatment. However, appetite stimulants are not recommended for most patients with FTT.8

Supplements

Diet habits are the cornerstone of FTT prevention and treatment, but both universal and individual supplementation can also play a key role.6 Not only is it necessary among high-risk groups and in emergencies, but it is also associated with a lower risk of deficiency even in well-nourished individuals.6

Supplementation treatment involves a multivitamin and mineral supplement and consuming a well-balanced diet that supplies the basic micronutrient requirements (e.g., RDA) for vitamins and minerals.6 Moreover, supplementation above the RDA is recommended for vitamins C and D, which promote optimal immune function and may help to control the impact of infections.6

Behavioral Intervention

  • Sleep disorders or underlying problems should be identified and addressed because poor sleep can contribute to poor activity and behavior and subsequently lead to poor nutrition.8
  • Parents and caregivers of children with FTT should be counseled on sick care management and the importance of encouraging a regular balanced diet.8
  • Behavioral interventions also involve meal regularization (eliminate grazing, scheduled meals, limited duration), an appropriate setting (e.g., highchair, adequate tools, limit distractions), and triggers elimination.6

Hospitalization is rarely required but should be considered for children who are at high risk.8 Following are some of the indications for hospitalization:8

Successful hospitalization requires careful integration of the child’s usual caretakers in the patient’s care and discharge planning.8 A predischarge planning conference should involve hospital-based personnel, representatives from the community agencies that will provide follow-up services, and the child’s primary physician.5 Parents should also be present in a summary session to meet with the health care providers, ask questions, and arrange follow-ups.5

Management And Long-Term Outlook

FTT still remains a widespread problem in pediatrics, but it is often overlooked, especially in the outpatient context.6 It also has serious implications if left untreated, especially in brain development.2 If malnutrition becomes severe and chronic during the first year of life, the child’s neurologic development may be permanently affected, making early recognition and prompt intervention critical.2

Thus, a multidisciplinary team approach is essential for management, involving healthcare clinicians, psychiatrists, social workers, nutritionists, physical and speech therapists, and behavioral and developmental specialists.2

Following are some management and prevention tips for children with FTT:

  • Nutritional counseling to the family.2
  • Routine health surveillance visits in early childhood to give primary care physicians opportunities to counsel and educate families on nutrition.8
  • Specific treatment of complications or deficiencies.2
  • Provision and diet of adequate calories, protein, and other nutrients.2
  • Supportive economic assistance.2
  • Long-term monitoring and follow-up.2
Conclusion

What we need to understand is that children referred with FTT have dynamic biopsychosocial characteristics that extend beyond “organic” and “nonorganic” characterization.3 Thus, a more comprehensive and multidisciplinary team approach to characterize children with FTT can be facilitated by assessing the medical, nutritional, feeding skills, and psychosocial domains.3

If FTT diagnosis is made and no underlying conditions are suggested after a thorough examination, age-based nutrition counseling should be conducted.2 Parents and caregivers should be guided on catch-up growth and what recipes and calorie intake they must maintain to see significant progress in their child.2

Nutritional supplements may be given until catch-up growth is achieved. During this period, parents are instructed to provide calorie-dense foods such as peanut butter, cheese, dried fruits, and cream sauces for older children or adolescents.2 Parents should follow the rule of 3’s – 3 meals, 3 snacks, and 3 choices.2

A systematic review shows that FTT during the first two years of life is not associated with a significant reduction in intelligence quotient, although some long-term reductions in weight and height are present. Although the possibility of long-term cognitive and behavioral sequelae is present and a child with a history of FTT is at increased risk of recurrent FTT; thus, their growth should be monitored closely.2 By taking a multidisciplinary approach, physicians can guarantee both a regular increase in size and overall adequate health status and development.6

References
  1. Tang MN, Adolphe S, Rogers SR, Frank DA. Failure to Thrive or Growth Faltering: Medical, Developmental/Behavioral, Nutritional, and Social Dimensions. Pediatrics In Review. 2021;42(11):590-603. doi:10.1542/pir.2020-001883
  2. Jeong SJ. Nutritional approach to failure to thrive. Korean Journal of Pediatrics. 2011;54(7):277. doi:10.3345/kjp.2011.54.7.277
  3. Mazze N, Cory E, Gardner J, et al. Biopsychosocial Factors in Children Referred With Failure to Thrive: Modern Characterization for Multidisciplinary Care. Global Pediatric Health. 2019;6:2333794X1985852. doi:10.1177/2333794×19858526
  4. Franceschi R, Rizzardi C, Maines E, Liguori A, Soffiati M, Tornese G. Failure to thrive in infant and toddlers: a practical flowchart-based approach in a hospital setting. Italian Journal of Pediatrics. 2021;47(1). doi:10.1186/s13052-021-01017-4
  5. Failure to Thrive (FTT) – Pediatrics. MSD Manual Professional Edition. Accessed August 24, 2022. https://www.msdmanuals.com/professional/pediatrics/miscellaneous-disorders-in-infants-and-children/failure-to-thrive-ftt#:~:text=Treatment%20of%20failure%20to%20thrive
  6. Lezo A, Baldini L, Asteggiano M. Failure to Thrive in the Outpatient Clinic: A New Insight. Nutrients. 2020;12(8):2202. doi:10.3390/nu12082202
  7. Failure to thrive: MedlinePlus Medical Encyclopedia. medlineplus.gov. https://medlineplus.gov/ency/article/000991.htm
  8. Homan GJ. Failure to Thrive: A Practical Guide. American Family Physician. 2016;94(4):295-299. https://www.aafp.org/pubs/afp/issues/2016/0815/p295.html
  9. Wit J. Catch-up growth: Definition, mechanism, and models. Journal of pediatric endocrinology & metabolism : JPEM. 2003;15 Suppl 5.
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