Global Developmental Delay

Global developmental delay is a significant delay in two or more developmental domains (gross and fine motor, speech and language, cognition, social and personal, and daily living) in a child under 5 years of age. It indicates likely later intellectual disability, although some children catch up.

It affects about 1 to 3% of children. After age 5 years, when formal testing is possible, the term intellectual disability is used. Causes include genetic and chromosomal disorders (Down syndrome, fragile X, Rett syndrome, many single gene disorders), prenatal infections and toxins (including alcohol), hypoxic ischaemic encephalopathy, extreme prematurity, brain malformations, metabolic disease, hypothyroidism, severe iron deficiency, lead exposure, malnutrition, hearing or vision loss, meningitis, and psychosocial deprivation.

A cause is found in about 30 to 50% after full evaluation. Genetic testing has the highest diagnostic yield.

Pathophysiology.

Abnormal brain development or injury during the critical periods of synaptogenesis and myelination impairs cognitive and motor networks. The mechanisms depend on the cause: genetic dysregulation of synapse and neuronal function, toxic or hypoxic injury, nutritional deficiency or deprivation.

• Delayed motor milestones, late speech, poor social engagement, and slow learning, compared with age norms (corrected for prematurity).
• Associated: hypotonia or abnormal tone, microcephaly or macrocephaly, dysmorphic features, seizures, behaviour problems, sleep disorder, and feeding difficulty.
• Features pointing to a cause: neurocutaneous signs, hepatosplenomegaly, eye anomalies, hair or skin changes, congenital anomalies and growth failure.

Red flags.

• Regression or loss of skills (suggests a neurodegenerative, metabolic or epileptic disorder, Rett syndrome or autism).
• Seizures, microcephaly or rapidly increasing head size, focal neurological signs, abnormal eye movements or visual inattention.
• Dysmorphism, congenital anomalies, consanguinity, family history or metabolic features (vomiting, lethargy, hepatosplenomegaly).
• Absent babble by 12 months, no words by 18 months, or no social smile.

• Detailed history (pregnancy, birth, neonatal, development, family, social, regression) and examination (growth, head circumference, dysmorphism, skin, neurological and eye examination).
• Structured developmental assessment and formal hearing and vision testing.
• First line tests: chromosomal microarray (or exome or genome sequencing where available), fragile X testing, thyroid function, full blood count and ferritin, and lead level in at risk children. Creatine kinase in boys with motor delay, and MECP2 testing in girls with regression.
• Targeted second line tests: metabolic screen (glucose, lactate, ammonia, plasma amino acids, urine organic acids, acylcarnitines, urate, copper and caeruloplasmin, biotinidase, congenital disorders of glycosylation), EEG for seizures or regression, MRI brain when there are abnormal neurological signs, microcephaly, seizures, regression or abnormal tone.

Differential diagnosis. Isolated language delay, hearing impairment, autism spectrum disorder, cerebral palsy, neuromuscular disease, psychosocial deprivation, normal variants (late talker, late walker) and neurodegenerative disease.

• Treat the identified cause where possible (levothyroxine for hypothyroidism, iron for deficiency, dietary treatment for metabolic disease, antiseizure treatment for epilepsy).
• Early intervention: physiotherapy, occupational therapy, speech and language therapy, special educational support, and behaviour support. Correct hearing and vision deficits.
• Genetic counselling and recurrence risk where a diagnosis is made.
• Manage comorbidities (feeding, sleep, epilepsy, behaviour, constipation).
• Family support, social care and education planning.

Monitoring. Developmental reassessment every 6 to 12 months, review of the diagnostic evaluation as genetic testing improves, and formal cognitive testing at 5 to 6 years.

Referral and escalation. Refer to a developmental paediatrician or neurodevelopmental service for any child with delay in two or more domains, and urgently for regression.

Special groups. For preterm infants use corrected age until 2 years. Children with Down syndrome and cerebral palsy need syndrome specific surveillance.