Approach to Pediatric Neurology Signs and Symptoms: Developmental Delay

Kyaw Linn

Developmental delay is among the most frequent concerns in pediatric neurology practice. It represents a heterogeneous group of conditions with varied etiologies, ranging from benign familial variants to serious neurogenetic or metabolic disorders. The challenge in pediatrics is that the presentation is age- and domain-dependent, influenced by caregiver reporting, and can be complicated by comorbidities such as seizures, feeding difficulties, or behavioral disorders.

Applying a structured clinical framework is essential to avoid both under-investigation and unnecessary testing. In this article, I apply the CELE approach (Confirmation, Emergency, Localization, Etiology) to developmental delay in children, but first, it is important to understand about child development and the role of developmental surveillance and screening in early detection.

Definition and Phenomenology

• Developmental delay: Failure to achieve developmental milestones within the expected timeframe.
• Global developmental delay (GDD): Significant delay in two or more domains – gross motor, fine motor/adaptive, speech/language, or social/personal interaction.
• Isolated delay: Limited to a single domain (e.g., isolated motor delay, isolated speech delay).

Delay is distinct from regression, in which a child loses previously acquired skills, often pointing to neurodegenerative or metabolic disease.

Developmental Surveillance and Screening

Beyond clinical recognition, a critical aspect of pediatric neurology practice is the systematic use of developmental surveillance and screening. These strategies aim to detect delays or disabilities early, before they manifest as obvious clinical concerns.

• Developmental surveillance is the ongoing process at every preventive or well-child visit, incorporating parental concerns, developmental history, risk and protective factors, direct observation, and collaboration with other providers.
• Developmental screening uses standardized, validated tools to identify children at risk. A positive screen always requires formal developmental-behavioral evaluation.
• Developmental-behavioral evaluation is a comprehensive assessment (history, observation, testing) that leads to a clear diagnosis and management plan.

Benefits and Risks

The integration of systematic developmental surveillance and screening into pediatric care offers substantial benefits. Evidence suggests that surveillance combined with structured screening significantly increases the rate of referrals for early intervention services, with approximately 6–8% of children referred compared to only 2–3% when surveillance alone is used. Early identification and intervention are associated with better long-term outcomes, including improved school readiness, enhanced family support, and stronger social integration, while also helping to reduce disparities in access to services.

Despite these advantages, there are also potential risks. False positives may lead to unnecessary evaluations, increased caregiver anxiety, and strain on healthcare systems, while false negatives risk delayed diagnosis and missed opportunities for timely intervention. However, these limitations can be mitigated by the use of validated, age-appropriate screening tools with adequate psychometric performance, generally defined as at least 70% sensitivity and specificity. In this way, the benefits of screening can be maximized while minimizing its potential harms.

Age-Specific Screening Recommendations

Screening should occur at any age if caregivers or clinicians have concerns, in addition to scheduled assessments.

Children <4 years

• 9 months
  • • Focus: motor, vision, hearing, communication.
    • Purpose: early detection and caregiver education on monitoring language/communication.
• 18 months
  • • General developmental screening: fine/gross motor, language.
    • Autism Spectrum Disorder (ASD)-specific screening recommended.
• 24 months
  • • Repeat autism-specific screening (captures children missed at 18 months).
    • General developmental screening if likelihood of missing 30-month visit.
• 30 months
  • • General developmental screening: motor, language, cognitive delays.

Tools commonly used:

• Ages & Stages Questionnaire (ASQ-II) for broad developmental screening.
• Modified Checklist for Autism in Toddlers (M-CHAT) for autism-specific screening.

Children ≥4 years

• 4 years
  • Focus: school readiness and social-emotional well-being (“5 Rs”: reading, rhyming, routines, rewards, relationships).
  • Motor skills assessment.

• ≥5 years
  • Annual behavioral/mental health screening using validated tools.
  • Indications: poor school performance, recurrent somatic complaints, family disruption, behavioral concerns, or involvement with social/justice services.

Choice of screening test

• No single mandated tool; must be validated, age-appropriate, sensitive and specific (≥70%).
• Broadband tests (general developmental/behavioral) are preferred for routine screening.
• Domain-specific tools are used if targeted concerns (e.g., speech/language, ASD).
• Examples for ≥5 years: Pediatric Symptom Checklist (PSC), Strengths and Difficulties Questionnaire (SDQ).

Follow-Up

• Positive screen → comprehensive evaluation (medical + developmental) and referral:
  • <3 yrs → Early Intervention programs (IDEA Part C).
  • ≥3 yrs → School system for special education (IEP).
• Negative screen → reassurance and continued surveillance, unless concerns persist.

Epidemiology

Developmental and behavioral disorders are relatively common in childhood, with early life carrying a particularly high burden. Global estimates suggest that around 8% of all children under 5 years have some form of developmental deficit, with disability-adjusted life years (DALYs) reflecting significant neurodevelopmental impact. According to Global Burden of Disease data, neurodevelopmental conditions affect approximately 4.1% of children under 5, with cerebral palsy accounting for about 1.6% of these cases. In low- and middle-income countries, the pooled prevalence of developmental delay under age 5 is even higher around 18.8%, with particularly elevated rates (up to 26.7%) reported in African populations.

Beyond early childhood, the burden of mental health disorders becomes increasingly evident: 20–25% of youth will meet criteria for a mental health disorder during their lifetime. Average ages of onset vary: anxiety disorders around age 6, behavioral disorders around age 11, mood disorders by about age 13, and substance use disorders in early adolescence.

Importantly, the prevalence of certain conditions, particularly autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), has risen over recent decades. This reflects both heightened awareness and demographic trends such as improved survival of preterm infants, increasing parental age, and higher rates of multiple births.

In Myanmar, disability remains a significant public health concern. A 2019 Inter-Censal Survey documented a 12.8% prevalence of disability across the population. In 2020, estimates suggested that approximately 6.7% of Myanmar’s population, or about 3.6 million people, live with some form of disability. Certain regions, including Chin, Rakhine, Ayeyarwady, and Magway, report even higher rates, up to 21% in Chin and 17% in Rakhine and Ayeyarwady. These figures underscore the disproportionate burden of developmental and neurological disorders in Myanmar and highlight the urgency of strengthening early detection and intervention systems.

CELE Framework for Approach to a Child with Developmental Delay

C – Confirmation of Signs and Symptoms

The first and most crucial step in evaluating a child with suspected developmental delay is to confirm whether a true delay is present. Caregivers often raise concerns about late milestones, but not all such observations indicate a pathological problem. Some children may simply fall within the normal variation of developmental timing, while in other cases cultural expectations, environmental factors, or inaccurate comparisons with siblings and peers may lead parents to believe their child is delayed when they are not. Careful assessment therefore prevents mislabeling and avoids unnecessary anxiety, investigations, and referrals.

Confirmation also requires determining the type of delay. Distinguishing between isolated developmental delay (affecting a single domain such as speech or motor function) and global developmental delay (involving two or more domains) has major implications for differential diagnosis, prognosis, and management planning. Equally important is differentiating between a child who shows a static delay, progressing slowly but consistently and one who demonstrates regression, losing skills previously acquired. Regression is a red flag for underlying neurodegenerative, metabolic, or epileptic encephalopathic disorders and mandates urgent evaluation.

The process of confirmation relies heavily on detailed history and physical examination, with systematic documentation of milestones across gross motor, fine motor/adaptive, speech/language, and social-personal domains. Clinicians must also be mindful of the broad normal ranges for milestone acquisition; for example, independent walking may be normal anytime between 9 and 18 months. In addition, environmental influences such as inadequate stimulation, multilingual households, or differing cultural expectations can alter the apparent pace of development.

Finally, careful clinical observation can provide important diagnostic clues that point toward specific underlying disorders. Dysmorphic features may suggest a chromosomal syndrome such as Down or Fragile X. Microcephaly or macrocephaly may indicate structural or metabolic brain disease. The presence of regression, abnormal tone, or neurological signs can help distinguish between central nervous system causes (such as cerebral palsy or genetic syndromes) and neuromuscular disorders (such as muscular dystrophies or spinal muscular atrophy). These characteristic features, when integrated with the history, allow the clinician to move beyond merely confirming delay and toward an early “spot diagnosis,” ensuring that further investigations are rational and targeted.

To anchor clinical judgment in age-expected norms, the key developmental skills are summarized below across gross motor, fine motor/adaptive, language/communication, and social–personal domains. The milestones are adapted from the CDC “Learn the Signs. Act Early.”

Table 1. Normal Developmental Milestones by Domain (adapted from CDC milestone checklists)

Note: CDC milestones reflect skills achieved by ≥75% of children at the specified ages; absence of a single milestone does not, by itself, confirm delay. Apply clinical context (e.g., bilingual environments, opportunity for practice, health conditions) when interpreting timing.

E – Emergency Considerations

Developmental red flags are not always life-threatening emergencies in the conventional sense, but they must be regarded as urgent because of their lifelong consequences. Early recognition allows timely intervention, which may prevent irreversible disability and optimize developmental potential. Although many children with developmental delay present with chronic and slowly evolving patterns, certain features demand immediate evaluation and referral.

One of the most critical is developmental regression, where a child loses previously acquired skills. This is always pathological and often reflects neurodegenerative conditions, inborn errors of metabolism, epileptic encephalopathies, or acquired brain injury. Prompt recognition is essential, since early intervention, such as metabolic correction, seizure control, or immune therapy, may halt or even reverse progression.

Another urgent presentation is severe hypotonia with feeding or respiratory compromise, commonly associated with neuromuscular disorders such as spinal muscular atrophy or congenital myopathies. Early diagnosis is critical, as disease-modifying therapies are now available and outcomes depend heavily on timing of initiation.

Children with developmental delay accompanied by seizures, encephalopathy, or acute neurological decline may be experiencing epileptic encephalopathy, infectious or inflammatory brain disease, or metabolic crises. These conditions require urgent stabilization and targeted therapy to prevent further neurological injury. Similarly, signs of raised intracranial pressure, such as persistent morning vomiting, papilledema, or abnormal ocular movements, may reflect hydrocephalus or posterior fossa tumors, which constitute true neurosurgical emergencies.

Systemic and metabolic red flags are also crucial to recognize. Congenital hypothyroidism, if untreated in infancy, leads to severe intellectual disability, but early detection through newborn screening and timely thyroxine replacement ensures near-normal development. Similarly, lead poisoning can present subtly with developmental delay, irritability, or anemia, but once neuronal injury occurs it is largely irreversible. Early identification through targeted screening and removal of exposure is essential to preserve cognitive outcomes.

It is also important to acknowledge that not all urgent developmental concerns are linked to curable diseases. Conditions such as autism spectrum disorder, intellectual disability, or certain genetic syndromes are not reversible, but early diagnosis enables early intervention, including behavioral therapy, speech and language support, occupational therapy, and structured educational planning, which can significantly improve adaptive functioning, school readiness, and long-term independence. Thus, the principle of “early diagnosis, early intervention” applies universally, regardless of whether a condition is curable.

In practice, clinicians should be familiar with age-specific developmental red flags, which serve as practical triggers for urgent referral and investigation.

Table 2. Red flag developmental signs requiring urgent consultation (adapted from CDC “Learn the Signs. Act Early.” checklists)

Clinical Pearl: Any regression of milestones at any age should be treated as an emergency, as it frequently reflects progressive neurological disease, epileptic encephalopathy, or metabolic decompensation, many of which are treatable if identified promptly.

L – Localization of the Lesion

Once developmental delay has been confirmed and urgent conditions excluded, the next step is to consider localization of the primary dysfunction. This process helps determine whether the delay arises from the nervous system or from other systemic, sensory, or environmental causes. Careful localization not only directs clinicians toward the most likely etiology but also prevents unnecessary neurological investigations when the cause lies outside the nervous system.

Neurological causes

Motor delay is frequently encountered. Clinical examination allows differentiation between upper motor neuron (UMN) lesions, as seen in cerebral palsy or other central nervous system insults, and lower motor neuron (LMN) lesions, such as muscular dystrophies and spinal muscular atrophy (SMA). UMN pathology is suggested by spasticity, hyperreflexia, and persistent primitive reflexes, often with accompanying global impairment. In contrast, LMN disorders typically present with hypotonia, proximal muscle weakness, absent reflexes, and at times fasciculations, while cognition and social development are usually preserved.

Speech and language delay may be neurological or extra-neurological. Hearing impairment is a common and reversible contributor and must be formally excluded. Autism spectrum disorder and social communication disorders represent central causes where speech delay coexists with impaired interaction, play, or non-verbal communication. In contrast, environmental deprivation, poverty, or psychosocial adversity may contribute to speech delay without primary neurological disease.

Global developmental delay is usually central in origin, resulting from perinatal hypoxic-ischemic injury, malformations of brain development, chromosomal syndromes, or inborn errors of metabolism. These children often show delay across multiple domains, sometimes accompanied by seizures, abnormal tone, microcephaly or macrocephaly, or dysmorphic features.

A broad clinical distinction is therefore between central and peripheral causes. Central causes are characterized by global involvement, seizures, abnormal tone, and cognitive impairment. Peripheral causes are suggested when motor skills are disproportionately affected but social and cognitive development are relatively preserved, for example, in Duchenne muscular dystrophy.

Non-neurological causes

Not all developmental delay is due to primary neurological disease. Systemic, nutritional, and metabolic disorders can impair development either directly or through their impact on the developing brain :

• Nutritional deficiencies: Iron-deficiency anemia, vitamin B12 deficiency, and chronic undernutrition can impair attention, language, and psychomotor development.
• Endocrine/metabolic disorders: Congenital hypothyroidism is a classical cause of preventable intellectual disability, underscoring the importance of newborn screening and early treatment. Other examples include untreated congenital adrenal hyperplasia or rickets affecting motor function.
• Chronic systemic illnesses: Congenital heart disease, chronic renal failure, and chronic liver disease may compromise growth and development due to hypoxia, metabolic derangements, or hospital-related psychosocial deprivation.
• Environmental and psychosocial deprivation: Neglect, poverty, or lack of stimulation can mimic or exacerbate developmental delay, particularly in speech and social-emotional domains.
• Toxic exposures: Lead poisoning and prenatal alcohol exposure are well-recognized non-neurological causes of developmental impairment.

Thus, systematic localization requires clinicians to first determine whether developmental delay is neurological or non-neurological in origin. Within neurology, distinguishing central from peripheral involvement helps focus the differential diagnosis. Considering non-neurological causes is equally important, as many, such as nutritional deficiencies, congenital hypothyroidism, and lead poisoning, are preventable or treatable if identified early. This localization step transforms the non-specific presentation of “delay” into a focused diagnostic pathway that guides rational investigations and management.

Table 3. Neurological vs non-neurological causes of developmental delay

Clinical Pearl: Localization should not stop at “neurological versus non-neurological.” Many systemic, nutritional, and environmental causes are preventable or treatable, making their recognition as urgent as identifying neurological pathology.

E – Evaluation for Etiology

The final step in the CELE framework is to determine the underlying etiology of developmental delay. This step builds on the preceding phases: once the delay has been confirmed, emergencies have been excluded, and preliminary localization has been achieved, the clinician can move toward a targeted diagnostic strategy.

Stepwise approach

1. Identify an obvious clinical cause

In many cases, careful history and physical examination reveal a likely etiology, reducing the need for extensive investigations. Examples include :

• Perinatal insults: hypoxic-ischemic encephalopathy, severe neonatal jaundice, CNS infections.
• Syndromic dysmorphism: recognizable patterns such as Down syndrome, Fragile X, or other chromosomal anomalies.
• Neuromuscular features: Gower’s sign and calf hypertrophy in Duchenne muscular dystrophy, tongue fasciculations in spinal muscular atrophy.
• Known epilepsy syndromes: such as West syndrome or Lennox–Gastaut syndrome, diagnosed on clinical and electroencephalographic grounds.

2. Consider the type of delay (affected domain)

The underlying cause often correlates with the developmental domain most affected :

• Isolated motor delay→ frequently neurological (e.g., cerebral palsy, neuromuscular disorders) but may also reflect nutritional rickets or hypothyroidism.
• Isolated speech and language delay→ commonly due to hearing impairment, autism spectrum disorder, or psychosocial/environmental deprivation.
• Isolated social delay→ strongly suggestive of autism spectrum disorder or social communication disorder.
• Global developmental delay→ typically central in origin, caused by genetic syndromes, chromosomal anomalies, perinatal brain injury, malformations, or metabolic disorders.

3. Utilize localization findings

The localization step helps refine the differential :

• Central nervous system involvement(seizures, tone abnormalities, global delay) suggests etiologies such as cerebral malformations, metabolic disorders, or genetic syndromes.
• Peripheral nervous system involvement(isolated motor delay with preserved cognition) directs attention to neuromuscular disorders such as dystrophies, SMA, or congenital myopathies.
• Non-neurological/systemic causes(growth faltering, anemia, chronic organ disease, endocrine disorders) should also be considered when neurological findings are absent.

4. Assess associated features

Additional features provide important diagnostic clues :

• Microcephaly or macrocephaly→ malformations, metabolic or storage disorders.
• Organomegaly→ lysosomal storage disease, metabolic hepatopathy.
• Recurrent vomiting, lethargy, episodic encephalopathy→ inborn errors of metabolism.
• Hearing or vision impairment→ sensory causes of speech or global delay.
• Regression→ degenerative or metabolic disease.

5. Perform targeted examination and investigations

When the above steps do not reveal a clear diagnosis, structured baseline investigations are indicated :

• First-line screening: hearing and vision testing; thyroid function test; creatinine kinase (CK) if muscular etiology suspected, blood lead level if risk factors are present.
• Neuroimaging: MRI brain is preferred if neurological features are present or no etiology is clinically evident.
• Metabolic evaluation: blood lactate, ammonia, plasma amino acids, urine organic acids, and acylcarnitine profile, particularly when regression, episodic symptoms, or systemic features are present.
• Genetic testing: chromosomal microarray analysis (CMA) as a first-tier test; Fragile X testing in boys; targeted gene panels when a specific neuromuscular or syndromic suspicion exists; whole exome sequencing (WES) if initial testing is inconclusive and resources allow.

A rational evaluation for etiology follows a stepwise pathway : 

1. Identify obvious clinical causes.
2. Consider which developmental domain(s) are affected, as the pattern of delay provides critical diagnostic direction.
3. Refine differential through localization.
4. Incorporate associated systemic and neurological features.
5. Proceed to targeted investigations when the cause is not clinically evident.

This approach avoids unnecessary, indiscriminate testing while ensuring that important, treatable conditions, such as congenital hypothyroidism, iron deficiency anemia, lead poisoning, or metabolic disorders, are not missed.

Summary

Developmental delay, defined as failure to achieve age-appropriate milestones, is common in pediatrics. Global developmental delay (GDD) involves two or more domains, while regression is always pathological.

Surveillance and screening are vital: the CDC/AAP recommend screening at 9, 18, 24, and 30 months, with autism-specific tools (e.g., M-CHAT), school readiness checks at 4 years, and annual behavioral screening from 5 years. Tools like ASQ-II, M-CHAT, PSC, and SDQ improve early detection and referrals.

The CELE framework provides a structured approach :

• C – Confirmation: Confirm true delay vs normal variation; determine isolated/global; identify regression. Look for clinical clues (dysmorphism, head size, abnormal tone).
• E – Emergency: Red flags (regression, severe hypotonia, seizures/encephalopathy, raised ICP, systemic/metabolic features). Though not always life-threatening, they require urgent referral as early intervention can change outcomes.
• L – Localization: Distinguish neurological (central vs peripheral) from non-neurological causes. Central causes involve global delay, seizures, tone abnormalities; peripheral causes show isolated motor delay with preserved cognition. Non-neuro causes include nutritional deficiencies, hypothyroidism, chronic illness, psychosocial deprivation, and lead toxicity.
• E – Etiology: Stepwise evaluation—look for obvious clinical causes, consider type of delay (motor, speech, social, global), refine with localization and associated features, then proceed to targeted investigations (hearing/vision, thyroid, lead, MRI, metabolic and genetic testing).

Conclusion : Developmental delay is a symptom, not a diagnosis. A structured CELE approach ensures treatable causes are identified early, interventions are initiated promptly, and long-term outcomes optimized, even in non-curable conditions such as autism or intellectual disability.

Algorithmic Approach to Developmental Delay in Children: The CELE Framework

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Author Information

Kyaw Linn
Professor, Paediatric Neurology
Senior Consultant Paediatrician