A 14-month-old term boy with no significant medical history presents with 2 days of fever, vomiting, and diarrhea and 1 month of weight loss and poor appetite. On further history, his mother reported a 5 lb weight loss over 1 month, change in eating, and loss of developmental milestones. He was previously eating some solid foods but started refusing to eat or drink anything but breast milk. He also had loss of gross motor (he could no longer sit unsupported, crawl, or pull to stand), language (no longer speaking, previously said ∼5 words), and social (no longer exhibiting social reciprocity) milestones. He was last seen by a pediatrician at 6 months of age because of the family moving cross country and changing insurances. On physical examination, he was cachectic (BMI less than third percentile), had decreased muscle bulk and tone, and was mildly hyperreflexic with 3+ patellar reflexes bilaterally. He also had dry mucous membranes and tachycardia.

He underwent fluid resuscitation and workup for his acute symptoms of fever, vomiting, and diarrhea and his chronic issues of poor feeding, weight loss, and loss of developmental milestones. Initial differential diagnosis included inadequate caloric intake, metabolic disorders, gastroesophageal reflux, malrotation, volvulus, intracranial process, and nonaccidental trauma.

Initial laboratory workup was significant for metabolic alkalosis, hypocalcemia, and mildly elevated C-reactive protein. His infectious workup was notable for a positive Clostridium difficile assay. He was treated with a course of Flagyl. Imaging obtained on admission included chest radiograph, abdominal ultrasound and radiograph, echocardiogram, and skeletal survey for nonaccidental trauma, all of which were normal, and brain MRI, which showed significant diffuse white matter loss.

Given his presentation, MRI findings, and the broad differential, neurology, medical genetics, and ophthalmology were consulted. He was also evaluated by speech and dysphagia specialists and found to have significant oral aversion. He was further evaluated by physical and occupational therapists who noted that he made poor eye contact, had little interest in play therapy, and was sensitive to noises.

After developing rapport with family and different care team members reviewing the patient’s developmental history, it was discovered that the family had been withholding information, most notably that there was a strong family history of autism spectrum disorder (ASD), and the patient had been experiencing delays in developmental milestones for longer than the initial reported month. The mother had been concerned about ASD but had never sought evaluation. Over the course of the hospitalization, the parents revealed significant social stressors: both parents were young and unemployed in a new city, and the mother was pregnant. They also felt overwhelmed by the hospitalization, having multiple providers, and lack of clarity in his care plan. The patient underwent a metabolic workup that was ultimately negative, and he was diagnosed with ASD resulting in global developmental delay, regression, and sensory aversion. He required nasogastric tube feeds, with eventual gastrostomy tube placement for his failure to thrive (FTT) secondary to oral aversion. The patient was discharged and referred to our general pediatric clinic and has been doing well with outpatient follow-up and behavioral, occupational, and physical therapies. His overall hospital course was a month in duration, and the total cost of the hospitalization was >$15 000 (Table 1).

TABLE 1

Costs of Diagnostic Workups

Diagnostic TestHospital Cost (US Dollars)aCost for Private InsuranceaCost for Public Insurancea
Imaging    
 MRI brain with and without contrast 3422 578 654 
 Skeletal survey 375 42 41 
 Radiograph abdomen (×3) 375 42 41 
 Ultrasound abdomen 1106 170 169 
 Echocardiogram 4361 317 291 
Laboratory tests    
 CBC with differential (×3) 51 11 11 
 CHEM20 (×14) 179 15 15 
 TFT 108 24 23 
Diagnostic TestHospital Cost (US Dollars)aCost for Private InsuranceaCost for Public Insurancea
Imaging    
 MRI brain with and without contrast 3422 578 654 
 Skeletal survey 375 42 41 
 Radiograph abdomen (×3) 375 42 41 
 Ultrasound abdomen 1106 170 169 
 Echocardiogram 4361 317 291 
Laboratory tests    
 CBC with differential (×3) 51 11 11 
 CHEM20 (×14) 179 15 15 
 TFT 108 24 23 

Source: Belk D. True Cost of Health Care: Diagnostic Tests. Available at: https://truecostofhealthcare.org/diagnostic-tests/2017. Accessed November 12, 2019. CBC, complete blood cell; CHEM20, chemistry 20 panel; TFT, thyroid function tests.

a

Per individual test.

Ideally, the care we provide starts with thorough histories and physicals, which, combined with sound clinical reasoning and evidence-based medicine, leads to quality care. However, variations at any one of these ventures could lead to a different path toward diagnosis and treatment. In the case of our patient, we were missing key pieces of developmental and social history, which impacted our workup. This was likely multifactorial: he was admitted overnight, and he was ill-appearing with acute symptoms, leading focus of care toward stabilization and potentially away from seeking clarification of developmental history. Additionally, the family had not felt comfortable sharing their concerns regarding ASD, possible developmental delays, and their social situation with providers. With better rapport with the family and further focus on history, these missing pieces of history would have further supported a diagnosis of oral aversion secondary to autism early on.

Given this patient’s initial history and presentation, it was reasonable to pursue a more thorough workup of FTT, particularly to rule out more serious causes. However, many researchers have evaluated the need for extensive inpatient work ups for FTT and have shown that the most common cause of FTT is disruption to oral–motor and oral–sensory processes (ie oral aversion).1  Furthermore, researchers in one study have identified that feeding difficulties may occur in ∼80% of children with developmental delays compared with ∼30% in children without developmental delays, stressing the importance of obtaining social and developmental history and staging.2  Autism and other neurodevelopmental disorders have a significant correlation with oral aversion, FTT, and low BMI, especially in male children.36  Researchers in one study have postulated that there may be overlapping etiologies and a central regulatory mechanism that influences both appetite regulation and personality features.7 

One key factor in the decision-making for this patient’s workup was his abnormal MRI. The decision was made to obtain neuroimaging because of concerns of FTT, vomiting, and loss of developmental milestones. Although the clinical picture likely warranted imaging because of the concerning history, in our patient’s case, the abnormal MRI led to a cascade effect of further extensive and expensive consultation and workup. Consulting neurology as a first step would likely have been reasonable, but consultation of all the services at once further contributed to the cascade effect and likely was unnecessary.

Another example of the cascade effect lies within the C difficile testing. Although it is possible that he had a symptomatic infection, given this patient’s age, neither testing nor treatment of C difficile were indicated per current guidelines.810  Children age <2 can be colonized with C difficile, and there is little value in treating the infection, and the effects of antibiotics is not negligible. However, the patient’s gastrostomy tube placement was delayed out of concern for an active infection.

The cascade effect first described by Mold and Stein in 1986 is characterized by an initiating factor followed by a series of events with increasing momentum so that the further events progress, the more difficult they are to stop.11  These events often include unnecessary tests and procedures and risks for patients and families. In a recent survey of physicians, it was also noted that cascade effects from incidental findings also have negative repercussions for physicians, including wasted time and effort, frustration, and anxiety.12 

Despite initial concerns, our patient’s MRI findings of diffuse white matter loss were decided to be nonspecific, which can be seen in both significant nutritional deficiency13  and in neurodevelopmental pathologies (such as attention-deficit/hyperactivity disorder and autism).1416  Autism has been found to be associated with a variety of other abnormal findings on neuroimaging; as such, current guidelines do not recommend any neuroimaging for newly diagnosed autism.15,1719 

This case serves as an important reminder that a thorough, focused history can act as an important diagnostic tool, particularly with red flag symptoms. An extensive developmental and social history may not always be possible on initial admission, but using screening questions and establishing a plan to obtain a more thorough history at a later time is key. It also highlights the need to develop rapport and trust with families through timely communication and a family-centered approach. Although it is important to rule out dangerous and uncommon diagnoses, it is also crucial to remember the key tenet of do no harm. Although autism and other neurodevelopmental diagnoses are associated with their own psychological stressors (including higher rates of anxiety and depression in caregivers),20  the uncertainty of diagnosis, extensive workup, and emotional burden of the cascade effect was more stressful to this family.

Additionally, physicians need to be mindful of cascade effects with nonspecific findings and remain vigilant to avoid anchoring and pursuing unnecessary workups. The effect of these decisions can not only burden patients and families but also impact physicians and the medical system as a whole. When thinking about heading down the path of extensive workups, it is important to remember that sometimes less is more.

FUNDING: No external funding.

Dr Khan conceptualized and designed the study, drafted the initial manuscript; Dr Barqadle reviewed and revised the manuscript; and both authors approved the final manuscript as submitted

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Competing Interests

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

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.