BACKGROUND AND OBJECTIVES

Growth faltering (GF) (previously failure to thrive) is a common reason for hospital admission, but there is little data on whether diagnoses made during initial admission remain accurate in follow-up. We sought to characterize infants admitted for isolated GF and identify diagnoses at discharge and ultimate diagnoses determined over 2 years of follow-up, to determine how diagnoses changed. We also sought to identify patient factors on admission associated with ultimate diagnosis.

METHODS

We conducted a retrospective study of children aged 2 weeks to 2 years with index admissions for GF from 2013 to 2017. We reviewed clinical data and documentation to determine discharge and ultimate diagnosis, and identify factors associated with ultimate diagnosis.

RESULTS

Of 497 patients, 292 (59%) had insufficient intake, 103 (20%) had organic disease including 36 genetic disorders, 52 (11%) had mechanical feeding difficulties, and 50 (10%) had mixed or unknown diagnoses 2 years after admission. Over 90% of cases of insufficient intake were diagnosed during admission. Sixty-five percent of organic diseases, and only 39% of genetic disorders, were diagnosed during admission. Patient factors associated with genetic disorders included previous NICU stay, low birth weight, dysphagia, hypotonia, and dysmorphisms.

CONCLUSIONS

Insufficient intake remains the most common diagnosis, and this diagnosis was accurately made during admission. Organic disease, especially genetic disease, was often not diagnosed during admission. Better tools are needed to identify patients with organic disease. We identified patient factors on admission associated with ultimate diagnosis, which could be used to prioritize evaluation and expedite follow-up.

Growth faltering (GF) (previously called failure to thrive) is a descriptive diagnosis that encompasses many causes of poor weight gain, from simple inadequate caloric intake to more complex medical conditions requiring long-term management.1  Although GF can be successfully managed in the outpatient setting, it is still a common cause of hospital admission, and concern for underlying serious medical conditions often prompts extensive inpatient evaluation.2  Previous work exploring the etiology of GF in children reports that the most common cause of GF is insufficient intake. The data on other etiologies, however, are more limited. Small retrospective studies of hospitalized children from the 1970s to 1980s found rates of organic disease of 18% to 30%, but the definition of organic disease varied among studies, and these studies often focused exclusively on identifying organic versus inorganic diagnoses rather than the broader view of categories favored now.35  Two more recent studies found similar rates of organic pathology (19% and 31%), but definitions again varied and 1 study included patients with previous diagnoses, complicating the interpretation.2,6  All of these studies, whether retrospective or prospective, define the ultimate diagnosis of these patients as that given at the time of hospital discharge. However, many complex conditions cannot be elucidated in a short hospitalization and it is likely that some of these discharge diagnoses were inaccurate. To improve care of children with GF, we need to know whether discharge diagnoses are accurate and if any factors present during admission could improve diagnostic accuracy.

In this study, we characterized patients admitted for GF, identified their diagnosis at discharge, and reviewed documentation for 2 years postdischarge to determine ultimate diagnosis. We then determined how frequently certain diagnoses were not identified during admission. Finally, we were able to identify components of the history and physical exam that were associated with these diagnoses, which could allow for earlier identification of such patients and closer follow-up in the future.

This is a retrospective study of children 2 weeks to 2 years of age admitted to a tertiary-care children’s hospital with a diagnosis of GF. Encounters from January 1, 2013, to December 31, 2017, were identified from the electronic medical record by International Classification of Diseases, Ninth and 10th Editions, codes: failure to thrive in the newborn (779.34/P92.6), failure to thrive in a child >28 days (783.41/R62.51), and abnormal weight loss (783.21/R63.4). Any diagnosis entered during evaluation was used to identify all patients with a primary complaint of GF. Our institution does not have specific admission criteria for GF. Most often, patients are referred to the emergency department (ED) after having failed outpatient management or are referred to a gastroenterology (GI) clinic for subspecialty consultation and directly admitted from the clinic. Rarely, patients presented to the ED for evaluation of other concerns and were found to have GF and were admitted for evaluation, or they were admitted after referral by child protective services because of concern for neglect.

Only index (first) admissions for GF were included. Only patients admitted to pediatric hospital medicine or GI were included.

Because the goal of this study was to evaluate the etiology of isolated GF, patients with known significant medical conditions were excluded (Supplemental Table 5), as were infants born at <35 weeks’ gestation. Significant medical conditions were defined using criteria described by Feudtner et al to describe complex chronic conditions.7  Milk protein intolerance (MPI), reflux, and unspecified developmental delay were not criteria for exclusion. Encounters were also excluded if documentation indicated an absence of GF or if there was no follow-up in the 2 years after admission. Follow-up was defined as any visits to outpatient clinics, EDs, or urgent cares, and any subsequent hospital admissions. We had access to records from all pediatric subspecialists, all pediatric ED visits, all admissions to our children’s hospital, and to most other regional hospitals that admit children. We were also able to see outpatient follow-up visits within the 2 largest outpatient pediatric practice groups in our area through our electronic medical record (Cerner) and via Epic Care Everywhere.

Data were extracted from the chart by 1 of 5 reviewers and training was done on a sample data set before starting chart review. Fleiss κ calculated for interrater reliability on final diagnosis in a random sample of 20 charts was 0.818 among all 5 reviewers. Diagnoses of organic disease, mechanical feeding difficulty, and neglect were reviewed by at least 2 reviewers. Documentation was reviewed to identify components of the history and physical exam and to determine diagnosis. Data up to 2 years from admission were reviewed to determine final diagnosis, but components of the history and physical were only evaluated from the index hospitalization. Data were collected, deidentified, and stored using Research Electronic Data Capture.

Diagnoses were grouped into 5 categories, with subcategories, defined below. These categories were developed iteratively during initial analysis of 100 charts and agreed upon by all reviewers.

  • Insufficient Intake: includes breastfeeding failure, inadequate formula feeding, improper formula mixing, inappropriate diet, and neglect. These patients were able to gain weight once offered adequate calories, without significant feeding interventions, and continued to gain weight appropriately after discharge. No further diagnoses were made in follow-up. Neglect was defined as documented concern for neglect in primary service documentation with associated child advocacy and/or social work consult that also documented concern for neglect.

  • Organic disease

    • ∘ Genetic disorder: any chromosomal anomaly or single gene defect contributing to poor growth. Variants of unknown significance or disorders with no effect on growth or development are not included.

    • ∘ Malabsorption: includes MPI, protein losing enteropathy, celiac disease, chronic diarrhea, and allergic colitis. These patients frequently required formula changes and even total parenteral nutrition during acute hospitalization.

    • ∘ Reflux: patients were unable to take adequate calories because of severe fussiness or emesis and required medication and/or thickened feeds to gain weight. Other etiologies, including MPI, were considered and ruled out.

    • ∘ Other: diseases not included in the above categories but noted to be causative of poor weight gain.

  • Mechanical feeding difficulty: these patients were unable to safely take adequate calories without feeding interventions including thickening of feeds, chin and cheek support, feeding tube placement, or ear, nose, and throat procedures. Patients were able to gain weight after these interventions and were not subsequently found to have other diagnoses. Specific diagnoses include oropharyngeal dysphagia, aspiration, laryngomalacia, and oral aversion.

  • Mixed etiology: documentation of >1 class of etiology leading to poor weight gain.

  • Unknown: No definitive diagnosis was given in documentation. Often, these patients continued to follow up with subspecialty providers, especially genetics, but no definitive diagnosis was made within the 2-year study window.

Statistical analysis was performed in IBM SPSS Statistics. Descriptive statistics were summarized as frequencies for categorical data or as mean (SD) or median (interquartile range) for normally distributed or non-normally distributed continuous data, respectively. Analysis of variance was used to examine associations between demographic or clinical factors and diagnosis. If analysis of variance was statistically significant, post-hoc pairwise comparisons were performed using Pearson’s χ2 or Fisher’s exact test for categorical variables and Mann-Whitney U test for continuous variables. Variables that were associated with specific diagnoses with P < .05 were then included in multivariable modeling using logistic regression. When individual variables were strongly correlated with each other, these were combined into a single variable for multivariate analysis, wherein the presence of either individual variable was scored as presence of the combined variable. Past medical history of eczema and rash on physical exam were combined into “eczema/rash,” history of NICU admission and low birth weight (LBW) were combined into “neonatal history,” hypotonia and dysmorphic features were combined as “hypotonia/dysmorphism,” coughing with feeds and prolonged feeds were combined as “dysphagia”, and fussiness with feeds and feeding refusal were combined as “aversion”. Adequacy of daily weight gain was evaluated as a subgroup analysis because this could only be assessed for patients with length of stay (LOS) >24 hours and age <12 months.

A total of 1387 unique encounters were identified, of which 562 met inclusion/exclusion criteria (Fig 1). A total of 65 patients were lost to follow-up and could not be analyzed at 2 years postadmission, leaving 497 cases for complete analysis. See Supplemental Table 6 for demographic and clinical characteristics of included patients.

FIGURE 1

Inclusion and exclusion diagram for children admitted for GF included in this study.

FIGURE 1

Inclusion and exclusion diagram for children admitted for GF included in this study.

Close modal

We identified 5 classes of diagnoses: insufficient intake (traditionally nonorganic), organic disease, mechanical feeding difficulty (MFD), mixed diagnoses, and those whose diagnosis remained unknown at 2 years (Table 1).

TABLE 1

Classification of Ultimate Diagnosis

DiagnosisN% of Type% of Total
Insufficient intake 292 — 58.8 
 Neglect 47 16.1 9.5 
Organic 103 — 20.3 
 Malabsorption 45 43.7 9.1 
 Genetic disorders 36 35.0 7.2 
 Reflux 13 12.6 2.6 
 Other 8.7 1.8 
MFDa 52 — 10.5 
Mixed 11 — 2.2 
Unknownb 39 — 7.8 
DiagnosisN% of Type% of Total
Insufficient intake 292 — 58.8 
 Neglect 47 16.1 9.5 
Organic 103 — 20.3 
 Malabsorption 45 43.7 9.1 
 Genetic disorders 36 35.0 7.2 
 Reflux 13 12.6 2.6 
 Other 8.7 1.8 
MFDa 52 — 10.5 
Mixed 11 — 2.2 
Unknownb 39 — 7.8 

—, not applicable.

a

One patient diagnosed with dysphagia was diagnosed with Potocki-Lupski syndrome >2 years after admission.

b

Three patients were diagnosed with genetic disorders >2 years from admission (17q12 deletion, SMACC2 mutation, and cerebral creatine transporter deficiency). One patient was diagnosed with neuropathic-like small bowel dysmotility >2 years after admission. Five patients also had variants of unknown significance identified on chromosomal microarray or exome sequencing.

The majority of patients (59%) had GF because of insufficient intake. Twenty percent of patients had an organic disease including malabsorption (9%), genetic disorders (7%), reflux (2.6%), or other organic etiologies (1.8%) (Supplemental Table 7). Ten percent of patients had MFD, 2% of patients had mixed etiologies, and 8% of patients had diagnoses that remained unknown.

Among patients lost to follow-up, 75% were diagnosed with insufficient intake at the time of discharge (Supplemental Table 6). Seventeen percent had organic disease, most often MPI or reflux, and 5% had MFD.

Among patients with a single definitive diagnosis (excluding mixed and unknown etiologies), 86.6% were diagnosed during initial admission (Table 2). Insufficient intake and MFD were most often diagnosed during admission (93.5% and 90%). Of note, a diagnosis of neglect (a subtype of insufficient intake) was made less frequently (66% of the time) and was often diagnosed only after returning to care with continued GF or other signs of maltreatment.

TABLE 2

Timing of Diagnoses

DiagnosisTotalDiagnosed During Admission, N (%)Suspected During Admission, N (%)Not Suspected, N (%)Time to Diagnosis, Median (Range)
All 447 387 (86.6) 16 (3.6) 44 (9.8) — 
Insufficient intake 292 273 (93.5) 2 (0.7) 17 (5.8) — 
 Neglect 47 31 (66) — 16 (34) 2.0 (0.0–136.0) 
Organic 103 67 (65.0) 13 (12.7) 23 (22.3) 4.0 (1–672) 
 Malabsorption 45 35 (78) 2 (4) 8 (18) 2.0 (1–135) 
 Genetic disorders 36 14 (39)** 9 (25) 13 (36) 77.5 (1–672)* 
 Reflux 13 12 (93) — 1 (7) 2.0 (1.0–9.0) 
 Other 6 (67) 2 (22) 1 (11) 5.0 (1.0–232.0) 
MFD 52 47 (90) 1 (2) 4 (8) — 
DiagnosisTotalDiagnosed During Admission, N (%)Suspected During Admission, N (%)Not Suspected, N (%)Time to Diagnosis, Median (Range)
All 447 387 (86.6) 16 (3.6) 44 (9.8) — 
Insufficient intake 292 273 (93.5) 2 (0.7) 17 (5.8) — 
 Neglect 47 31 (66) — 16 (34) 2.0 (0.0–136.0) 
Organic 103 67 (65.0) 13 (12.7) 23 (22.3) 4.0 (1–672) 
 Malabsorption 45 35 (78) 2 (4) 8 (18) 2.0 (1–135) 
 Genetic disorders 36 14 (39)** 9 (25) 13 (36) 77.5 (1–672)* 
 Reflux 13 12 (93) — 1 (7) 2.0 (1.0–9.0) 
 Other 6 (67) 2 (22) 1 (11) 5.0 (1.0–232.0) 
MFD 52 47 (90) 1 (2) 4 (8) — 

Time to diagnosis is given in days from admission. For laboratory diagnoses (genetic disorders, diagnosis made on imaging), date of diagnosis is defined by the date the diagnostic test was sent. For clinical diagnoses (MPI, dysphagia), date of diagnosis is defined by the documentation of the diagnosis in physician or therapist documentation. Genetic disorders were less often diagnosed during admission (

**

P < .001) and had a longer time to diagnosis (

*

P < .05). —, not applicable.

Organic diagnoses were less frequently identified during admission. Sixty-five percent of diagnoses were made definitively during admission; 22% were neither diagnosed nor suspected (Table 2). Genetic disorders were most often undiagnosed during initial admission. Thirty-eight percent of these patients were diagnosed by testing sent during admission. An additional 25% of patients were suspected of having an underlying genetic disorder during admission, but diagnostic testing was inconclusive or deferred. Thirty-six percent of patients ultimately diagnosed with genetic disorders were not suspected during admission. At discharge, these patients were most often diagnosed with MFD (58%) or insufficient intake (33%).

Univariate analysis was used to identify demographic features and components of the history and physical exam associated with ultimate diagnosis (Table 3). Patients with insufficient intake were more likely to have public insurance, whereas organic diagnoses and MFD were all associated with private insurance.

TABLE 3

Univariate Analysis of Demographics, Components of the History and Physical Exam, and Features of the Hospital Stay

Patient CharacteristicsInsufficient Intake, n = 292Malabsorption, n = 45Genetic Disease, n = 36MFD, n = 52Unknown, n = 39P
Male sex, n (%) 147 (50.3)* 31 (68.9)* 16 (44.4) 22 (42.3) 26 (66.7) <.001 
Public insurance, n (%) 208 (71.2)** 18 (40.0)** 15 (41.7)* 26 (50.0)* 28 (71.8) <.001 
Age, median (range) 75 (14–698) 84 (15–529) 87 (15–633) 61 (15–506)* 125 (18–605)* .003 
Weight z score, mean ± SD −3.01 ± 1.25* −1.88 ± 1.31** −3.26 ± 1.19 −2.69 ± 1.29 −3.36 ± 1.26 <.001 
Breastfeeding, n (%) 120 (41.1)* 22 (48.9) 10 (27.8) 15 (29.4) 9 (23.1) .007 
Past medical history, n (%)       
 None 140 (47.9)** 14 (31.1) 7 (19.4) 14 (26.9) 14 (35.9) .005 
 NICU stay 38 (13.0) 2 (4.4) 11 (30.6)* 12 (23.1) 9 (23.1) .004 
 LBW (<2.5 kg) 26 (8.9) — 10 (27.8)* 7 (13.5) 10 (25.6)* <.001 
 Reflux 71 (24.3) 15 (33.3) 8 (22.2) 25 (48.1)** 12 (30.8) .035 
 Eczema 12 (4.1) 7 (15.6)** — 2 (3.8) 2 (5.1) .011 
Symptoms, n (%)       
 Vomiting 100 (34.2) 29 (64.4)** 9 (25.0) 15 (28.8) 11 (28.2) <.001 
 Diarrhea 25 (8.6) 18 (40.0)** 2 (5.6) — 6 (15.4) <.001 
 Prolonged feeds 34 (11.6) 1 (2.2) 11 (30.6)* 12 (23.1)* 10 (25.6)* <.001 
 Coughing/gagging with feeds 20 (6.8) 6 (13.3) 8 (22.2) 18 (34.6)** 6 (15.4) <.001 
 Fussiness with feeds 16 (5.5) 7 (15.6) 6 (16.7) 12 (23.1)** 4 (10.3) <.001 
 Feeding refusal 14 (4.8) 8 (17.8) 4 (11.1) 14 (26.9)** 5 (1.3) <.001 
Physical exam findings, n (%)       
 No abnormality 174 (59.6)** 22 (48.9) 5 (13.9) 23 (44.2) 8 (20.5) <.001 
 Rash 31 (10.6) 14 (31.1)** 2 (5.6) 6 (11.5) 9 (23.1) .005 
 Hypotonia 13 (4.5) 2 (4.4) 13 (36.1)** — 5 (12.8) <.001 
 Dysmorphic features 4 (1.4) — 11 (30.6)** 1 (1.9) 6 (15.4)* <.001 
 Stridor 4 (1.4) — 2 (5.6) 10 (19.2)** 2 (5.1) <.001 
LOS, median (range) 2.5 (0.1–41.8)** 2.7 (0.5–19.8) 4.8 (0.4–13.5)** 3.7 (0.9–17.7)** 3.0 (0.8–19.7) <.001 
Adequate weight gain (n = 424) 195 (81.3)** 23 (63.4) 13 (43.3)** 31 (63.3) 18 (54.5)* <.001 
Patient CharacteristicsInsufficient Intake, n = 292Malabsorption, n = 45Genetic Disease, n = 36MFD, n = 52Unknown, n = 39P
Male sex, n (%) 147 (50.3)* 31 (68.9)* 16 (44.4) 22 (42.3) 26 (66.7) <.001 
Public insurance, n (%) 208 (71.2)** 18 (40.0)** 15 (41.7)* 26 (50.0)* 28 (71.8) <.001 
Age, median (range) 75 (14–698) 84 (15–529) 87 (15–633) 61 (15–506)* 125 (18–605)* .003 
Weight z score, mean ± SD −3.01 ± 1.25* −1.88 ± 1.31** −3.26 ± 1.19 −2.69 ± 1.29 −3.36 ± 1.26 <.001 
Breastfeeding, n (%) 120 (41.1)* 22 (48.9) 10 (27.8) 15 (29.4) 9 (23.1) .007 
Past medical history, n (%)       
 None 140 (47.9)** 14 (31.1) 7 (19.4) 14 (26.9) 14 (35.9) .005 
 NICU stay 38 (13.0) 2 (4.4) 11 (30.6)* 12 (23.1) 9 (23.1) .004 
 LBW (<2.5 kg) 26 (8.9) — 10 (27.8)* 7 (13.5) 10 (25.6)* <.001 
 Reflux 71 (24.3) 15 (33.3) 8 (22.2) 25 (48.1)** 12 (30.8) .035 
 Eczema 12 (4.1) 7 (15.6)** — 2 (3.8) 2 (5.1) .011 
Symptoms, n (%)       
 Vomiting 100 (34.2) 29 (64.4)** 9 (25.0) 15 (28.8) 11 (28.2) <.001 
 Diarrhea 25 (8.6) 18 (40.0)** 2 (5.6) — 6 (15.4) <.001 
 Prolonged feeds 34 (11.6) 1 (2.2) 11 (30.6)* 12 (23.1)* 10 (25.6)* <.001 
 Coughing/gagging with feeds 20 (6.8) 6 (13.3) 8 (22.2) 18 (34.6)** 6 (15.4) <.001 
 Fussiness with feeds 16 (5.5) 7 (15.6) 6 (16.7) 12 (23.1)** 4 (10.3) <.001 
 Feeding refusal 14 (4.8) 8 (17.8) 4 (11.1) 14 (26.9)** 5 (1.3) <.001 
Physical exam findings, n (%)       
 No abnormality 174 (59.6)** 22 (48.9) 5 (13.9) 23 (44.2) 8 (20.5) <.001 
 Rash 31 (10.6) 14 (31.1)** 2 (5.6) 6 (11.5) 9 (23.1) .005 
 Hypotonia 13 (4.5) 2 (4.4) 13 (36.1)** — 5 (12.8) <.001 
 Dysmorphic features 4 (1.4) — 11 (30.6)** 1 (1.9) 6 (15.4)* <.001 
 Stridor 4 (1.4) — 2 (5.6) 10 (19.2)** 2 (5.1) <.001 
LOS, median (range) 2.5 (0.1–41.8)** 2.7 (0.5–19.8) 4.8 (0.4–13.5)** 3.7 (0.9–17.7)** 3.0 (0.8–19.7) <.001 
Adequate weight gain (n = 424) 195 (81.3)** 23 (63.4) 13 (43.3)** 31 (63.3) 18 (54.5)* <.001 

Group P values obtained via analysis of variance or χ2. Individual associations (

*

P < .05;

**

P < .001) were determined by Mann-Whitney U test (continuous variables) or Pearson’s χ2 or Fisher’s exact test (categorical variables).

Multivariable regression modeling was performed on components of the history and physical associated with ultimate diagnosis (Table 4). Insufficient intake was associated with more severe GF on presentation (lower z score for weight), unremarkable past medical history, and unremarkable physical exam. Malabsorption was positively associated with less severe GF (higher z score for weight), history of eczema or rash on presentation, and symptoms of vomiting or diarrhea. Genetic disease was associated with a history of NICU admission, LBW, dysphagia, and hypotonia and dysmorphic features on exam. MFD was associated with a history of reflux, dysphagia, aversion, and stridor on exam.

TABLE 4

Components of the History and Physical Exam and Features of the Hospital Stay Are Associated With Ultimate Diagnosis

Patient CharacteristicsInsufficient IntakeMalabsorptionGenetic DiseaseMFD
Z score, weight for age 0.71 (0.61–0.83) 1.92 (1.42–2.59) — — 
Past medical history     
 None 1.81 (1.22–2.70) — — — 
 Reflux — — — 2.33 (1.22–4.44) 
 Neonatal history — — 2.50 (1.16–5.42) — 
Symptoms     
 Vomiting — 2.73 (1.33–5.63) — — 
 Diarrhea — 6.75 (3.11–14.66) — — 
 Dysphagia — — 2.28 (1.06–4.93) 2.63 (1.37–5.06) 
 Aversion — — — 3.19 (1.62–6.29) 
Physical exam findings     
 No abnormality 2.94 (1.98–4.39) — — — 
 Eczema/rash — 3.31 (1.45–7.55) — — 
 Stridor — — — 7.11 (2.48–20.43) 
 Hypotonia/dysmorphism — — 12.19 (5.63–26.39) — 
LOS 0.76 (0.68–0.84) — — — 
Adequate weight gaina 2.57 (1.55–4.26) — 0.41 (0.17–0.99) — 
Patient CharacteristicsInsufficient IntakeMalabsorptionGenetic DiseaseMFD
Z score, weight for age 0.71 (0.61–0.83) 1.92 (1.42–2.59) — — 
Past medical history     
 None 1.81 (1.22–2.70) — — — 
 Reflux — — — 2.33 (1.22–4.44) 
 Neonatal history — — 2.50 (1.16–5.42) — 
Symptoms     
 Vomiting — 2.73 (1.33–5.63) — — 
 Diarrhea — 6.75 (3.11–14.66) — — 
 Dysphagia — — 2.28 (1.06–4.93) 2.63 (1.37–5.06) 
 Aversion — — — 3.19 (1.62–6.29) 
Physical exam findings     
 No abnormality 2.94 (1.98–4.39) — — — 
 Eczema/rash — 3.31 (1.45–7.55) — — 
 Stridor — — — 7.11 (2.48–20.43) 
 Hypotonia/dysmorphism — — 12.19 (5.63–26.39) — 
LOS 0.76 (0.68–0.84) — — — 
Adequate weight gaina 2.57 (1.55–4.26) — 0.41 (0.17–0.99) — 

Adjusted odds ratios (95% confidence interval) obtained via multivariable logistic regression for each diagnosis. When individual variables were strongly correlated with each other, these were combined into a single variable, wherein the presence of either individual variable was scored as presence of the combined variable. Past medical history of eczema and rash on physical exam were combined into eczema/rash, history of NICU admission and LBW were combined into neonatal history, hypotonia and dysmorphic features were combined as hypotonia/dysmorphism, coughing with feeds and prolonged feeds were combined as dysphagia, and fussiness with feeds and feeding refusal were combined as aversion. —, not applicable.

a

Adequacy of daily weight gain was evaluated as a subgroup analysis, because this could only be assessed for patients with LOS >24 hours and age <12 months.

Initial hospital outcomes were also associated with ultimate diagnosis (Table 4). Patients with insufficient intake had shorter LOS, whereas patients with genetic disease and MFD had longer LOS, though only the association with insufficient intake remained significant in multivariable analysis. Patients with insufficient intake were also more likely to have adequate weight gain for age during hospitalization (81%), whereas patients with genetic disease were less likely to have adequate weight gain (43%). Association remained significant in subgroup regression modeling.

This is the largest study to date of patients admitted for GF, and the first to review data after admission to determine ultimate diagnosis. Previous studies have evaluated the diagnosis at hospital discharge, but many complex medical conditions cannot be diagnosed in a short hospital admission, so determining the long-term outcome of patients provides valuable information. Our results confirm that GF is most often because of insufficient caloric intake, as shown in previous studies, and this diagnosis is accurately made during hospital admission.2,3,5,8,9  However, we also found that 20% of otherwise-healthy infants and toddlers admitted for GF have an underlying organic diagnosis, consistent with previous studies showing 5% to 50% of patients having organic disease.2,3,812  Interestingly, 7% of our patients were ultimately diagnosed with a genetic disorder, a higher rate than previously reported, though data are limited.2,8  This higher rate is likely because of the long-term follow-up in this study. The true rate of genetic disorders may be even greater; of the 39 patients with unknown diagnoses at 2 years postadmission, 3 were later diagnosed with genetic disorders and 5 had variants of unknown significance on chromosome microarray or exome sequencing without definitive diagnosis.

Previous studies found that organic diagnosis were almost always suspected on admission.2,5,11  However, in this study, 22% of organic diseases were not suspected during admission and over one-third of patients with genetic disorders were not suspected of having a genetic disorder at the time of discharge. This suggests that our diagnostic accuracy for organic disease is not as high as previously reported.

However, this finding does not mean that more aggressive testing is indicated in admissions for GF, or that inpatient genetic testing should be the norm. Diagnosis of most of the genetic disorders identified in this study would not have changed acute inpatient management. Furthermore, many diagnoses could only be made with specific testing sent on the basis of symptoms that developed after discharge, and indiscriminate testing would not have identified these disorders.

Rather than indicating a need for more low-value testing, these results reinforce the importance of close outpatient follow-up for GF and the need for better predictive tools to determine which patients are likely to have significant underlying disease.

Some previous studies have attempted to identify patients most likely to have insufficient intake, but these focused on evaluating parenting and attachment, parental attitudes toward feeding, and even typologies of family structure.3,1315  Such evaluations are subjective and prone to bias. Many review articles suggest that patients with “asymmetric” GF (decrease in weight without corresponding decrease in length and/or head circumference) are more likely to have insufficient intake, but this has not been validated, and in this study, the relationship between z scores for length or head circumference and z score for weight did not correlate with ultimate diagnosis.8,13,16  Weight gain during admission has also been used to identify patients with insufficient intake; however, a recent study found that greater than average weight gain during admission was not specific for a diagnosis of inadequate intake.6  Here, we identified components of the history and physical exam that were positively associated with ultimate diagnosis.

Patients with genetic disorders were more likely to have a history of NICU stay and/or LBW, dysphagia, and hypotonia or dysmorphic features on initial physical exam. Thirty-one of 36 patients (86%) with a genetic disorder had at least 1 of these features, but of these, only 62% were suspected of having a genetic disorder during their admission, delaying appropriate referrals at discharge. Patients with genetic disorders were also less likely to have adequate weight gain for age during admission. These features should prompt suspicion for genetic disease and consideration of genetics consultation or close follow-up with medical genetics for continued evaluation after discharge.

Similarly, a diagnosis of malabsorption was associated with less severe GF, symptoms of vomiting and/or diarrhea, and a history of eczema or rash on physical exam. Patients with these findings might benefit from a trial of elemental formula and/or outpatient follow-up with GI.

The retrospective nature of this study introduces several limitations, especially reliance on diagnosis codes for patient identification. The codes used were stringently reviewed and multiple codes considered. Also, all diagnosis codes input at any point in hospitalization were included, which should mitigate bias in final coding. However, because of the variable and subjective nature of the diagnosis of GF, it is possible that patients were included in this study who do not meet all definitions of GF. Also, because our institution has no standardized criteria for admission for GF, this study population is heterogeneous and may differ from patient populations at centers with standardized admission parameters.

Sixty-five patients were also lost to follow-up and could not be analyzed at 2 years postadmission. These patients were more likely to have been diagnosed with insufficient intake and they may have been lost to follow-up because they gained adequate weight and did not require reevaluation. This could lead to an undercount of this diagnosis and subsequent overrepresentation of other etiologies in our study. Given that we were able to see outpatient records for the vast majority of patients and all subspecialist records, the likelihood that patients with significant medical diagnoses were missed is low.

Although this study is the largest of its kind, given the rarity of individual organic diagnoses, we were not able to analyze many possible associations between history and physical exam findings and ultimate diagnosis. The heterogeneity of diagnostic groupings also made identifying associated variables difficult. Factors that were associated with genetic disease included signs of poor muscle tone (hypotonia and feeding difficulty) and dysmorphic features, which are classically associated with chromosomal anomalies. It is unlikely that these features are truly predictive of a genetic disorder such as Schwachman-Diamond syndrome, although this diagnosis is included in the same category.

Ultimately, although the broad outlines of this work are consistent with previously published literature, we have shown that organic disease, especially genetic disorders, are not as accurately suspected in admission as previously thought. With this large sample size, evaluated over a long period of time, we have detected more complex, difficult-to-diagnose disorders that were likely missed in previous studies. We have also identified features correlated with ultimate diagnosis that were present at initial admission, even if the diagnosis was not suspected at the time. Thus, the history and physical remain the most powerful diagnostic tools in the evaluation of GF.

This information can be used to better risk-stratify patients admitted for GF and tailor both inpatient evaluation and outpatient referrals. Ultimately, this data, if validated and expanded, could be used to generate diagnostic algorithms or practice guidelines to better standardize inpatient care of GF and reduce unnecessary testing.

FUNDING: No external funding.

CONFLICT OF INTEREST DISCLOSURES: The authors have indicated they have no conflicts of interest relevant to this article to disclose.

Dr Lu designed the study, identified included charts, designed the data capture tool, completed chart review, performed data analysis, and wrote the manuscript; Dr Bowen completed chart review, performed data analysis, and reviewed the manuscript; Drs Foglia and Ribar helped develop the data capture tool, completed chart review, and reviewed the manuscript; Drs Mack and Sondhi completed chart review and reviewed the manuscript; Dr Hickey assisted in initial study design, reviewed data collection and analysis, and reviewed and edited the manuscript; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

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Supplementary data