Timing of Co-occurring Chronic Conditions in Children With Neurologic Impairment

This is a retrospective longitudinal analysis of the IBM Watson Medicaid MarketScan Database, 2009–2015, which contains Medicaid health care claims across the care continuum for Medicaid enrollees from 12 US states. Children born in 2009 with an NI diagnosis in the first 3 years of life were included if they were continuously enrolled in Medicaid through the study period (ie, 11 of 12 months yearly through age 6).

NI was defined as “a neurological diagnosis reasonably expected to last longer than 12 months and result in substantial functional impairments that require subspecialty medical care.”⁷  The diagnosis of NI was identified with an established set of International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes used in previous studies.^7,21,22  NI subtypes included genetic and/or metabolic (eg, trisomy 21), progressive (eg, metachromatic leukodystrophy), peripheral (eg, muscular dystrophy), anatomic (eg, myelodysplasia), stroke and/or hemorrhage, and static (eg, cerebral palsy). Because children may have multiple NI diagnoses, a hierarchy was established by the study team through group consensus to assign each child to 1 primary NI subtype to allow for us to examine differences across subtypes. The hierarchy prioritized categorization of children to specific NI diagnoses on the basis of the likelihood of primary etiology (eg, a child with cerebral palsy due to an intracranial hemorrhage was categorized in the stroke and/or hemorrhage subtype). The final hierarchy used in this study was genetic and/or metabolic, progressive, peripheral, anatomic, stroke and/or hemorrhage, and static.

The main outcome measures of interest were the prevalence and onset timing of co-occurring chronic conditions. Those conditions were assessed with the Agency for Healthcare Research and Quality open-source, publicly available diagnosis classification schemes, the Chronic Condition Indicator and the Clinical Classification System (CCS),²³  adapted for use in pediatric patients.²⁴  The Chronic Condition Indicator classifies ∼14 000 ICD-9 codes as chronic or not chronic. The CCS is a clinically comprehensive map that assigns every ICD-9 code to exactly 1 common chronic condition category.^23,25  The CCS also assigns each chronic condition code to 1 of 25 mutually exclusive categories organized by organ system.^23,25  For example, constipation, dysphagia, and gastroesophageal reflux disease were grouped as digestive system conditions. NI diagnoses used to define the study cohort were not included in the neurologic system condition category. Diagnostic codes from all encounters were examined.

The onset timing of co-occurring chronic conditions was assessed by age in months. Onset was defined for each Medicaid enrollee as the first occurrence of the diagnostic code listed within any health care claim across the continuum (eg, outpatient primary or specialty care visit, hospitalization, emergency department visit, etc), including the birth hospitalization.

Patient demographic characteristics assessed included age, sex, race and/or ethnicity, Medicaid enrollment criteria (disability versus other), and Medicaid plan type (fee for service versus managed care).

The total number of co-occurring chronic conditions accumulated by age 6 years and the onset timing of individual co-occurring chronic conditions were compared across NI subtypes by using Wilcoxon rank tests. The mean cumulative function (MCF) was used to assess trends in the total number of co-occurring chronic conditions with increasing age (through age 6 years). The MCF is a nonparametric staircase analysis used to estimate (with 95% confidence bounds) the accrued number of occurrences of a recurrent event, such as the accumulation of the number of co-occurring chronic conditions over time. The MCF of the total number of co-occurring chronic conditions was estimated for the study population overall as well as for each NI subtype. SAS version 9.4 (SAS Institute, Inc, Cary, NC) was used, and the statistical significance threshold was P < .05 for all analyses.

Of the 6229 children with NI included for analysis, 54.3% were male and 45.6% were non-Hispanic white (Table 1). Most children were enrolled in Medicaid through the disability pathway (83.4%) and were in Medicaid managed care (67.0%). The median age at the first NI diagnosis was 4.1 months (interquartile range [IQR] 0.2–11.1 months).

The most common NI subtypes were static (41.4%), anatomic (21.7%), genetic and/or metabolic (22.8%), and stroke and/or hemorrhage (11.2%). Across all NI subtypes, cerebral palsy (10.0%), microcephaly (8.0%), and hydrocephalus (6.0%) were the most common diagnoses. The median age at first NI diagnosis varied significantly by NI subtype (P < .001). The stroke and/or hemorrhage NI subtype had the earliest age at first diagnosis (median 0 months [IQR 0–2.5 months]). The static NI subtype had the latest age at first diagnosis (median 7.3 months [IQR 2.5–14.9 months]). All NI subtypes had a median age at onset of ≤12 months.

Neurologic co-occurring conditions (ie, neurologic diagnoses other than those used to define the study cohort) were commonly diagnosed by age 6 (39.8%) (Fig 1). More than 1 in 10 children (11.1%) had epilepsy. By age 6 years, 36.0% had received a diagnosis of vision defects and 26.3% had hearing loss identified. A communication disorder was diagnosed in 32.9%, and a learning disorder was diagnosed in 29.3%. The majority (61.0%) of children with NI also had a mental and/or behavioral health diagnosis, with the most common being attention-deficit/hyperactivity disorder (ADHD) (9.8%), conduct disorder (8.8%), and anxiety (8.4%). The prevalence of other notable mental health problems was 6.6% for pervasive developmental disorder and 4.7% for depression.

By age 6, co-occurring chronic conditions affecting nonneurologic organ systems were also commonly identified. Respiratory (86.5%) and digestive (49.4%) co-occurring chronic conditions had the highest prevalence. Across all organ systems, the most common co-occurring chronic conditions diagnosed were asthma (56.5%), gastroesophageal reflux (40.8%), and chronic respiratory insufficiency (25.5%). Enterostomy (ie, enteral feeding tubes) and tracheostomy were present in 8.3% and 1.7% of children, respectively, by age 6 years.

The prevalence of common co-occurring chronic conditions varied by NI subtype, as illustrated in Supplemental Fig 5.

The co-occurring chronic conditions began accruing early in life (Fig 2). For example, the percentages of children with NI who had at least 1 co-occurring chronic condition identified at age 0 months, 1 year, and 6 years were 50.7%, 90.1%, and 99.0%, respectively.

The timing of diagnosis of co-occurring chronic conditions varied across the conditions. For example, the timing was earlier for digestive co-occurring chronic conditions than for mental and/or behavioral health problems. The median ages at first diagnosis of gastroesophageal reflux disease, enterostomy, and dysphagia in children with NI were 0.2 years (IQR 0.1–0.5 years), 0.7 years (IQR 0.3–1.5 years), and 1.0 years (IQR 0.5–1.9 years), respectively. In contrast, the median ages at first diagnosis of conduct disorder, anxiety, and ADHD were 3.9 years (IQR 2.9–4.7 years), 4.0 years (IQR 3.1–4.8 years), and 4.6 years (IQR 3.8–5.1 years), respectively.

The timing of common co-occurring chronic conditions varied by NI subtype, as illustrated in Supplemental Fig 5.

There was early development of multiple co-occurring chronic conditions among children with NI (Fig 3). By ages 2, 4, and 6 years, the mean numbers of co-occurring chronic conditions of children with NI were 3.7 (95% confidence interval [CI] 3.7–3.8), 4.6 (95% CI 4.5–4.7), and 5.1 (95% CI 5.1–5.2), respectively (Fig 4, Supplemental Fig 6). Among all children with NI, the most common multimorbidity combination at age 6 was respiratory, mental health, digestive, and vision problems, affecting 17.8% of all children in the cohort. Among children with NI with 2 to 4 co-occurring chronic conditions, respiratory and skin problems was the most common combination. Among children with NI with 5 to 8 co-occurring chronic conditions, digestive, mental health, musculoskeletal, respiratory, and vision problems was the most common combination.

A small percentage of children with NI had ≥9 co-occurring chronic conditions, with an increasing prevalence as they aged: 5.3% by 2 years, 10.0% by 4 years, and 12.8% by 6 years (Fig 3, Supplemental Fig 6). Cardiac (78.0%), endocrine (45.8%), and skin (41.9%) problems emerged as prevalent in those children compared with children who had fewer co-occurring chronic conditions earlier in their lives (Fig 3). Children with anatomic and stroke and/or hemorrhage NI diagnoses accumulated co-occurring chronic conditions faster and in greater number overall than children with genetic and static NI diagnoses (Fig 4).

In this cohort of children with NI enrolled in Medicaid, co-occurring chronic conditions were prevalent by age 6 years, with the extent of multimorbidity increasing through early childhood years. Digestive, respiratory, and mental health problems were particularly paramount. These chronic problems layered with time; digestive problems presented early in infancy, whereas respiratory and mental health problems were diagnosed in early toddler and school-aged years, respectively. One of every 8 children with NI experienced ≥9 chronic conditions co-occurring by age 6 years, with cardiac, endocrine, and skin problems most prevalent in those children. There was variability in both the extent and timing of multimorbidity across NI subtypes.

Multimorbidity has been recognized as “rather the rule than the exception”²⁶  for aging adults, affecting 3 in 4 individuals aged 65 years and older.²⁷  Although multimorbidity is much lower in the population-level studies of children,^28,29  there has been growing focus on multimorbidity experienced by children with medical complexity.^24,30,31  The extensive multimorbidity of young children with NI in the current study complements previous literature. For example, authors of cross-sectional studies in children of all ages with cerebral palsy enrolled in Medicaid report a high rate of multimorbidity (eg, median of 6 co-occurring chronic conditions).⁶  The current study revealed that multimorbidity emerges quickly in the early childhood years across a broad array of NI subtypes.

Clinical practice guidelines for care maintenance in children with specific NI diagnoses (eg, cerebral palsy, trisomy 21) prompt clinicians to recognize co-occurring chronic conditions.^32–34  However, children with NI are most often purposefully excluded from research studies and the development of evidence-based and consensus-driven recommendations to guide care.^35–37  Furthermore, such recommendations and guidelines do not offer direction on how to manage and treat multiple co-occurring chronic conditions that affect different organ systems.^38,39 

More attention to the diagnosis and management of specific coexisting conditions in children with NI is warranted. For example, our data reveal a high prevalence of respiratory co-occurring chronic conditions in children with NI; nearly 9 of 10 children with NI had a co-occurring respiratory chronic condition by age 6 years. The children’s prevalence of asthma, in particular, was nearly 7 times higher than the 8.3% that has been reported in the general pediatric population.⁴⁰  Although the commonality of chronic respiratory problems in children with NI is well known, authors of previous studies of children with cerebral palsy and other NI diagnoses have not reported a high prevalence of asthma.⁴¹  Etiologies of bronchospasm in children with NI include aspiration of oropharyngeal sections, gastroesophageal reflux, and impaired clearance and/or bronchial plugging of respiratory mucous.⁴²  Children with NI are not known to have a higher risk of bronchospasm from atopy or environmental exposures. Characteristic reactive airway disease in children with NI may be particularly challenging to accurately diagnose, especially because of the children’s limitations in performance with pulmonary function testing.⁴³  It is possible that the diagnosis of asthma may have been applied liberally to some children with NI in the current study. Nonetheless, further investigation is needed on the diagnosis and treatment of chronic respiratory comorbidities in children with NI, including the effectiveness of inhaled corticosteroids and β-agonists in the setting of NI-related bronchospasm etiologies.

Additionally, the high prevalence of mental and behavioral health problems in children with NI is important to highlight. Authors of previous studies in children with cerebral palsy also report a higher prevalence of these problems, especially ADHD and anxiety^44,45 ; although, the early emergence of these diagnoses in this study raises questions as to the possibility of misclassification or bias in diagnosis. Existing mental and behavioral health screening tools and methods have been largely validated in otherwise healthy children.⁴⁶  Little is known about how those tools and methods perform in children with NI.⁴⁷  Moreover, the efficacy of pharmacologic and behavioral interventions for mental and behavioral problems in children with NI has been understudied.^48,49  In general, better integration of mental and physical health care for all patients has been a long-standing goal of the US pediatric health system.⁵⁰  Young children with NI who have mental and behavioral health problems, in particular, deserve that care integration, with sufficient attention to opportunities for positive parenting and resiliency as well as for improvements in quality of care with mental health screening, specialty comanagement, and treatment.⁴⁷ 

Emerging literature highlights care concerns for individuals with multimorbidity, including care that is disease centered rather than patient centered.^26,27,51,52  Disease-centered care lacks sufficient attention to the interactions between co-occurring conditions and is often fragmented across numerous health care providers, resulting in limited care coordination and planning.⁵³  Additionally, disease-centered care has been associated with higher, yet often ineffective, use of health care services and increased health care costs as well as suboptimal treatment of chronic disease, increased risk of adverse events, and decreased health-related quality of life in adults with multimorbidity.^26,52,54,55  Although not measured in the current study, there is a critical need to assess whether these experiences and outcomes relate to infants and toddlers with NI as they rapidly acquire multiple co-occurring chronic conditions.

The current study has several limitations. Co-occurring chronic conditions were distinguished with diagnosis codes from administrative claims of health care encounters. It is likely that the conditions had an earlier onset, with symptoms emerging before the encounters, and thus we likely underestimate the true degree of multimorbidity experienced by these children at any given time. Given the limited number of diagnosis codes available to submit with a health care claim (eg, in some cases, 2 codes), undercoding, and therefore underdiagnosis, for some of the conditions may have occurred. Alternatively, there may have been misclassification for some co-occurring chronic conditions, especially those that are difficult to diagnose in children with NI (eg, asthma). Furthermore, our count variable of multimorbidity misses nuances of severity and longevity of the co-occurring chronic conditions. Some comorbid chronic conditions may be mild in symptomatology or improve over time, whereas others may greatly impact overall lifelong health and function for the child. Finally, the findings from this study may generalize best to children with NI continuously enrolled in Medicaid. Further investigation is needed to assess whether the attributes and severity of NI are similar for children who are not continuously enrolled in Medicaid and for those using private insurance. In future studies, researchers should also assess the evolvement of multimorbidity and the trajectories of co-occurring chronic conditions experienced by children with NI through adolescence and beyond.⁵⁶ 

Despite these limitations, the findings describing the extent of multimorbidity and the types of co-occurring chronic conditions experienced by young children with NI in the current study may be helpful in informing approaches to care, both for individual patients and for the health care system at large. For example, findings on prevalence and timing of multimorbidity may inform approaches to anticipatory guidance for infants and toddlers with NI. Additionally, incorporating data regarding the likelihood of experiencing co-occurring chronic conditions into prognostic discussions may shape families’ awareness of and preparedness for future multimorbidity. Future work focused on identifying trajectories of chronic comorbidities would enable clinicians to anticipate the future health care problems and needs of children with NI and tailor care delivery. Existing multidisciplinary care models for children with NI could be redesigned to better encompass health care professionals, services, and therapies that match the children’s coexisting chronic condition patterns. Such efforts may better prepare the health system to anticipate and address concomitant increases in health services use (eg, emergency department visits and hospitalizations) associated with increasing multimorbidity in children.^6,57–59 

In addition, the prevalence and extent of disease beyond neurologic manifestations of NI highlights the importance of education on multimorbidity.^60,61  Most, if not all, pediatric trainees will care for this growing pediatric population in the future, regardless of their area of practice.

Increased emphasis on the clinical and physiologic interactions of common co-occurring chronic conditions in children with NI (eg, impact of obesity on obstructive sleep apnea or impact of reflux on asthma), as well as the interprofessional skills to work across clinical disciplines and specialties to manage multimorbidity, is necessary.⁶² 

Diagnosis of multiple co-occurring chronic conditions was nearly universal by age 6 in this cohort of children with NI enrolled in Medicaid. Given the challenges inherent in the care of individuals with multimorbidity, this study highlights the need for research, education, and reevaluation of health infrastructure to meet the needs of this fragile population of children.

ADHD

attention-deficit/hyperactivity disorder

CCS

Clinical Classification System

CI

confidence interval

ICD-9

International Classification of Diseases, Ninth Revision

IQR

interquartile range

MCF

mean cumulative function

NI

neurologic impairment