Poor Weight Gain

Poor weight gain is a common presenting problem in pediatrics. We review literature supporting the notion that extensive workup is generally not needed, particularly in younger children and discuss a management approach depending on a patient’s age. Understanding normal growth, particularly in infancy, is important. Breastfed and formula-fed infants as well as older children have different etiologies for poor growth. Diagnostic workup and hospitalization are rarely indicated or useful. An attempt to increase energy intake is often the appropriate first step in management. Poor weight gain can affect children of all ages. Understanding expected growth, common etiologies by age, and how to assess nutritional status can help with appropriate diagnostic workup and management.


Introduction
Poor weight gain is a common problem in childhood and frequently leads to outpatient clinic visits and inpatient hospitalizations for workup and management. In the USA, failure to thrive occurs in up to 10% of children in the primary care setting and in up to 5% of pediatric hospitalizations [1••, 2]. Recent literature demonstrates long-lasting adverse effects of early growth problems [3], making poor growth a potentially significant problem with long-term sequelae. Infants with poor growth have a higher prevalence of feeding problems, and failure to thrive in infancy has been associated with worse intellectual outcomes later in life [3]. Weight and height differences may persist beyond infancy, as well [4•]. Malnutrition can potentially lead to immune dysfunction, developmental delay, and poor wound healing [5••]. From an economic standpoint, diagnostic investigations and hospitalizations for poor weight gain may be unhelpful and simultaneously lead to increased health care costs [6]. Finally, poor growth requiring medical attention may be a source of ongoing stress for children and parents [7,8].

Definitions
Various terminologies are used interchangeably when discussing poor weight gain including poor weight gain itself, weight loss, decreased growth velocity from expected, failure to thrive, malnutrition, undernutrition, and faltering weight/growth. Of note, these are clinical findings rather than diagnoses [1••, 9].
Historically, the term "failure to thrive" (FTT) has been used to describe a state where energy intake is insufficient to maintain growth. However, this term can be potentially pejorative, critical, or alarming for parents and caretakers [1••]. Qualitatively, FTT is described as a condition where a child has suboptimal weight velocity in which improvement would better the child's outcome [1••]. There are several quantitative definitions for FTT [10]. However, a consensus definition is lacking.
The American Society for Parenteral and Enteral Nutrition (ASPEN) defines malnutrition (undernutrition) as "an imbalance between nutrition requirement and intake which results in cumulative deficits of energy, protein, or micronutrients that may negatively affect growth, development, and other outcomes" [11••]. The World Health Organization (WHO) classifies malnutrition as moderate or severe based on various parameters including presence of symmetrical edema, mid-upper arm circumference, weight-for-age z-score, and height-for-age z-score [12].
While the ASPEN malnutrition criteria have attempted to quantify poor weight gain based upon WHO weight gain velocity, due to the dynamism of growth in the first 2 years of life, these criteria either do not identify all children with poor weight gain or also include children with normal growth. Hence, weight gain should be assessed using subjective measures using some of the nuances of expected growth. Also, weight loss that is inexplicable and/ or persistent is always likely to be abnormal in children [13].

Expected Growth
Understanding expected growth is critical to recognizing normal patterns versus abnormal variations (Table 1). Children born small for gestational age (SGA) show "catch-up" growth, while children who are born large for gestational age (LGA) show "catch-down" growth to reach their appropriate growth curve [14]. Mei et al. analyzed longitudinal growth data in 10,844 children and found shifts in growth rates to be most common from birth to 6 months, and somewhat less common between 6 and 24 months of age [15•]. Roughly 25% of normal infants experience shifts to a lower growth percentile in the first 2 years of life then continue on that percentile [16]. In general, children born at or above the 75th percentile for weight are much more likely to cross percentiles downwards. In addition, children born LGA typically gain weight more slowly than expected such that their weight is between a z-score of 0 and 1 (50-85th percentile at age 2 months). While children born LGA are more likely to be overweight later in life, children who catch down are less likely to be overweight [14,17]. On the contrary, 85% of children born SGA will catch up with regard to weight. When children are born after 30-32 weeks gestation and are SGA, it is debatable as to whether they should be made to catch up by increasing energy intake. Premature infants born SGA derive significant neurodevelopmental benefits from catching up but like in all SGA infants, catch-up growth is associated with a higher risk of metabolic syndrome later in life [18][19][20].
There are also other normal variants of growth that may accompany poor weight gain in older children, including genetic short stature and constitutional delay. Patients with genetic short stature have parents with relatively short height. These patients track along low growth percentiles but do not cross percentiles. Patients with constitutional delay often have a family history of similar growth patterns. These patients have an initial drop in percentile points, then follow their own curve. These cases highlight the importance of obtaining and trending serial measurements over time.

Etiology: Breastfed Infant
Human milk is universally recommended as the optimal source of nutrition for infants due to numerous health benefits. Human milk contains variable amounts of carbohydrate, protein, and fat and changes in composition as an infant grows [21]. Both the WHO and the American Academy of Pediatrics (AAP) recommend exclusive breastfeeding for the first 6 months of life and continued periods of breastfeeding until ages 1-2 while complementary foods are introduced and advanced [22]. Knowing the differences in growth patterns between breastfed and formula-fed infants helps one understand what is normal, expected growth depending on nutritional intake. Of note, poor weight gain is more common in infancy as compared to later stages in life due to high growth rates and nutritional needs during this time. Breastfeeding is associated with lower rates of weight and length gain after 2 months of age and may be due to human milk macronutrient composition or lower total energy intake [23]. After initial increases in weight and length in the first 2 to 3 months of life, these infants have a slower velocity up to 12 months when compared to formula-fed infants [24]. Bell et al. assessed 276 infants from birth to age 7 months, obtaining anthropometric data and dual-energy X-ray absorptiometry to assess body composition at 1, 4, and 7 months. They found that formula-fed infants had lower birth-weight z-scores than breastfed infants but gained more in weight and body mass index (BMI) through 7 months of age [25].

Problems with Supply
Secretory activation and copious milk production occur within 48 to 72 h after birth and are related to a rapid decline in maternal progesterone levels [26••]. Delayed secretory activation beyond 72 h has been associated with suboptimal lactation outcomes such as lower milk production and reduced duration of breastfeeding. Delayed secretory activation has been associated with long labor, cesarean section, stressful deliveries, poorly controlled diabetes, and obesity [27]. Early intervention to assist with maternal lactation needs is critical, as failure to remove colostrum has been associated poor prognosis of successful lactation [27]. After birth, frequent and effective milk removal is critical to establishment and maintenance of milk production. A minimum of 5 expressions per 24-h period is needed to maintain milk production, though more frequent expressions may be warranted in those who have not yet established their supply [28]. Perceived insufficient milk supply is a common problem and a frequent reason women seek lactation counseling [28]. Milk production is established in the first 1 to 2 weeks. Milk production has been shown to be similar over the first 6 months of lactation in exclusively breastfeeding women [28], suggesting breastfed infants take in similar volumes of milk during this period while formula-fed infants have increasing milk and energy intake.

Problems with Infant Feeding
Healthy infants should feed effectively and without distress within 20 to 30 min [29]. Variation from this, in addition to poor weight gain, may suggest a feeding problem. Feeding disorders have been classified in various ways, including structural abnormalities, neurological conditions, behavioral, cardiorespiratory problems, metabolic dysfunction, and mixed [30]. Anatomic abnormalities which can affect feeding include ankyloglossia and cleft/lip palate [31]. Infants may also have difficulty creating an effective vacuum due to ineffective latch or various medical conditions including low tone, prematurity, and Down syndrome.

Etiology: Formula-Fed Infant
Infant formulas attempt to mimic the nutritional composition of human milk and are generally based on cow's milk protein. There are limited indications for use of soy protein formulas, including patients with disorders of carbohydrate metabolism such as galactosemia or hereditary primary lactase deficiency or when a strict vegetarian diet is preferred [32]. Compared to breastfed infants, formula-fed infants appear to have more rapid gains in weight-for-length and higher absolute weights in the first year of life [33]. However, poor weight gain may occur in the formula-fed patient population for some of the reasons listed below.

Proper Mixing
Infant formulas are available "ready to feed" or in powder form, requiring mixing with water prior to use. When infants have poor growth, it is important to ensure caregivers are properly mixing powered infant formula. Formula that is mixed incorrectly can lead to formula dilution. This can lead to either hypocaloric or hyper-concentrated formula and electrolyte imbalances. Traditionally, formula is mixed to a 1 scoop to 2 oz of water ratio to yield a 20 kcal/oz formula, with the powder being added to water that has already been measured out. However, exceptions to this rule exist, and pediatricians should be cognizant of the exceptions or read individual labels.

Infant Feeding Problems
Infant feeding problems among formula-fed infants are similar to those of breastfed infants, as mentioned above.

Beyond Newborn up to age 2 years
Current guidelines recommend using the 2006 WHO growth charts to assess growth and nutrition for children up to 2 years of age. These growth charts included data from 6 countries, Brazil, Ghana, India, Norway, Oman, and the USA. Specialized growth charts should be used for infants born prematurely. The Fenton growth charts and the intergrowth charts for premature infants both segue into the WHO growth charts and are preferred.
When approaching a patient with poor growth, it can be helpful to think about a framework of inadequate energy intake, inadequate nutrient absorption, and increased energy expenditure. Detailed history taking and a thorough physical exam can help determine etiology and guide further workup and management.

Insufficient Energy Intake
In most cases (greater than 90%), poor weight gain is due to inadequate energy intake. Decreased energy intake can lead to insufficient energy available for adequate growth. This could be due to insufficient energy intake whose causes range from food insecurity to improper formula mixing. Children may also have difficulty with inadequate food intake due to developmental delay, poor oral neuromotor coordination, gastroesophageal reflux, eating disorder, or craniofacial abnormalities such as cleft lip or palate.

Increased Energy Losses (Malabsorption)
Another category of poor weight gain is inadequate nutrient absorption. Clinically, this may present with poor weight gain and diarrhea, with or without emesis. These etiologies may include gastrointestinal (GI) conditions such as pancreatic insufficiency, celiac disease, inflammatory bowel disease, milk protein allergy, and eosinophilic esophagitis. Two important etiologies where the losses may be covert include pancreatic insufficiency and celiac disease; these may present with constipation and without emesis.

Increased Energy Expenditure
Diseases associated with poor weight gain may include those leading to increased energy expenditure and metabolism. These include congenital heart disease, pulmonary disease (cystic fibrosis), renal disease (rental tubular acidosis, Bartter's syndrome, renal failure), inflammatory diseases (asthma, inflammatory bowel disease), immunodeficiency, and thyroid disease (hyperthyroidism). When a child fails to gain weight due to cardiopulmonary disease, the child usually has significant symptomatology (i.e., it is not the child with a murmur that does not gain weight but the child who has cardiorespiratory difficulties during feeding and struggles to finish feeds).

Older Child
For children and adolescents aged 2 to 20 years, the Center for Disease Control (CDC) 2000 growth charts are recommended. These growth charts are intended for children in the USA, as they were based on national survey data and incorporated an estimation for size-for-age. Condition-specific growth charts can be used for children with specific diagnoses such as Down syndrome. While specialty growth charts provide useful growth references, most do not include BMI charts and in those cases, the CDC BMI charts should be used. In general, specialized growth charts are not encouraged due to concerns about their limitations such as small sample sizes, lack of heterogeneity, and unresolved questions of whether altered growth is due to genetic potential or external conditions.

Eating Disorders
Eating disorders such as anorexia nervosa and bulimia are particularly common in adolescent females. They are being increasingly recognized in younger children and in boys. Anorexia nervosa is characterized by an intense fear of weight gain, a disturbed body image, or both which leads to dietary restriction or weight loss behaviors such as excessive physical activity or purging [31]. Bulimia nervosa is characterized by recurrent episodes of binge eating with compensatory measures such as self-induced vomiting, fasting, inappropriate use of medication, and extreme physical activity to prevent weight gain. It may occur in patients with normal weight or elevated BMI [31].

Avoidant/Restrictive Food Intake Disorder
The DSM-V classification of avoidant/restrictive food intake disorder (ARFID) characterizes this condition by avoidant or restrictive eating behavior that may be linked to various underlying features such as low interest in food or eating, avoidance linked to sensory issues, and fear-related avoidance.

Stimulant Medication
When considering poor weight gain in the older child, it is important to consider medications that could lead to decreased appetite. Attention-deficit hyperactivity disorder is common in pediatrics and treated with stimulant medications such as methylphenidate and dexamphetamine. Poulton and Cowell retrospectively reviewed growth data from the first 6 months on stimulant medication in 51 children [32]. Weight loss was noted in 76% of children, and weight standard deviation scores showed a decline that was significant after 6 and 18 months. Faraone et al. assessed the effects of stimulant medication on height and weight in a quantitative analysis of longitudinal studies [33]. They found that treatment with stimulant medication led to statistically significant delays in height and weight, although there was evidence of attenuation over time. They also found that growth deficits did not seem to differ between methylphenidate and amphetamine, growth deficits seemed to be dose dependent, and treatment cessation led to normalization of growth.

Assessment of Nutrition Status
Assessment of the child with poor weight gain should take into account age, gender, birth weight, parental size, medical history, nutrient intake, socioeconomic background, and medications. The current preferred method for determining poor growth is via anthropometric z-scores [5••]. Serial measurements of weight and height should be accurately obtained and charted on an appropriate growth chart. It should be noted that ongoing severe malnutrition first affects weight, followed by length, and then head circumference.
Physical exam tools such as measurement of mid-upper arm circumference from children greater than 2 months and triceps skinfold measurement in children 3 months and older can also be helpful as a screening and diagnostic tool for poor weight gain and malnutrition. These measurements can be particularly useful in children with disease states that can elevate weight measurement through fluid retention, such as ascites or organomegaly.
Various subjective assessment exist which can help identify pediatric patients at risk for poor growth and malnutrition. The Subjective Global Nutritional Assessment (SGNA) is validated in for hospitalized pediatric patients [34•]. The Semi-Objective Failure to Thrive (SOFTT) diagnosis tool was shown to correlate with anthropometric measurements in children with poor weight gain [35].

When to get Labs
Although frequently obtained, laboratory, radiologic, and endoscopic workup rarely yield diagnostic clarity in the diagnosis of children with poor growth [36•]. Sills et al. retrospectively reviewed charts of 185 patients hospitalized for evaluation of FTT and found 18% had proven organic etiologies. However, only 1.4% of laboratory studies performed were diagnostically helpful [37]. A more recent study assessed patients presenting with FTT in a tertiary pediatric gastroenterology clinic and confirmed that laboratory testing is not helpful in young children (most children in this study were under 2 years of age) [38].
No standard set of laboratory tests is recommended in the workup of poor growth but instead should be obtained in a focused manner depending on history obtained. In general, younger children should get labs only if they do not respond to standard nutritional intervention. It is reasonable for older children (likely older than ages 2 or 3) to get screening labs at the first or second visit to the general pediatrician or subspecialist (Table 2).

Management
Early identification and management addressing poor weight gain are vital. Treatment of poor weight gain due to an underlying disease state should address the underlying etiology. In cases of poor weight gain without an identified underlying etiology, management should focus on behavioral intervention and increasing energy intake. In both cases, nutritional assessment and co-management with a dietitian can be very helpful. Multidisciplinary care with social workers and occupational therapists should be considered if needed based on the patient's history. With most patients, an appropriate weight velocity can be attained with outpatient management including nutritional counseling and support.

Newborn
In the newborn child, increasing energy intake may consist of increasing the volume or frequency of breastmilk or formula feeds. Breastfed infants may require formula supplementation if maternal breast milk supply is inadequate. In some formula-fed infants, particularly in infants who were born prematurely and require catch up growth, gradual formula fortification up to 24 kcal/oz or even 27 kcal/oz may be required.

Beyond newborn up to age 2 years
Some interventions that can be taken to increase daily energy intake are decreasing or eliminating juice intake and adding or increasing infant formula fortification. High-energy beverages such as high-energy milk drinks or powders that can be added to whole milk can be used beyond the first year of life. Regular, scheduled mealtime and snacks can also be helpful, including (1) offering a meal or snack every 3 h, (2) limiting meals to 20 min, and (3) allowing only water outside of mealtime. High-energy foods can be added such as avocados, butter, cream, cheese, and oil. Children may need up to 150% of their recommended daily energy intake based on their expected weight for catch up growth [39].

Older Child
In older children, similar methods of increasing energy intake as younger children can be utilized. However, it may be easiest to institute high-energy beverages in these children as it is not easy to manipulate the diets of children attending school. The use of high-energy beverages also makes it easier to measure compliance to the regimen. When using these beverages, it is important that they either be given towards the end of a meal (4-8 oz), or they can be used as a snack (typically 4 oz). Children should not drink them in small amounts during the day as that can curb appetite for food. Also, they can be given as a bedtime beverage (usually 8 oz) as this routine is not likely to interfere with other meals. If these interventions do not help, cyproheptadine can be added as an appetite stimulant. Cyproheptadine is a histamine H1 antagonist which promotes gastric accommodation. The main side effect is drowsiness, and so parents should be counseled accordingly and may be advised to administer it at nighttime. Cyproheptadine is FDA approved for children 2 years and greater. Sant'Anna et al. retrospectively assessed 82 pediatric patients (age 7-80 months) who received cyproheptadine in combination with multidisciplinary programmatic intervention for poor weight gain. They noted a significant improvement in weight z-score after starting cyproheptadine [40].
In the older child, the clinician should utilize a multidisciplinary approach with social worker or psychology colleagues in the case that there is a challenging social situation or underlying psychological concern.

Long-term Outcomes of Poor Growth
Several studies have investigated the long-term physical and cognitive outcomes of FTT. Most studies demonstrate long-lasting decreased height, weight, and BMI years after FTT in infancy, but results are conflicting regarding cognitive outcomes later in life [3, 4•, 41, 42]. A systematic review by Rudolf and Logan found minimal IQ difference (3 IQ points) with a greater difference in weight and height [4•]. Black et al. assessed the impact of a randomized, controlled trial of home visiting in infants with FTT. At age 8 years, they found children with previous FTT had worse short stature, poorer arithmetic performance, and poor work habits, although these findings were attenuated by the home visits [43]. Corbett and Drewett performed a meta-analysis assessing long-term cognitive outcomes of FTT in infancy and showed adverse intellectual outcomes later in life and noted the effect size was smaller when children were older. It is important to note that these studies are relatively dated, and updated studies would be beneficial [3]. Finally, given that overall IQ is not affected by cocaine exposure during pregnancy [44,45] and that breastfeeding causes a change in only 2-3 IQ points [44], it is unclear whether IQ is the optimal method to study outcomes of early life interventions.

Conclusion
Poor weight gain is common in pediatric patients. This is usually due to insufficient energy intake and improves with behavioral and nutritional intervention. Thorough history taking and an understanding of common etiologies by age is helpful. Subjective elements should be involved in the assessment of nutritional status. Children presenting with poor weight gain often do not need a diagnostic workup and management should start with a trial of increased energy intake.

Conflict of Interest
Tanyaporn K. Kaenkumchorn and Praveen S. Goday each declare no potential conflicts of interest.

Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.