Is there a link between prematurity and autism spectrum disorder (ASD)?

Prematurity and Autism Spectrum Disorder: Understanding the Link

Prematurity is a significant risk factor for autism spectrum disorder (ASD), with research showing a direct correlation between earlier gestational age at birth and increased ASD risk, particularly pronounced in females. 1 This relationship represents an important consideration for developmental surveillance and early intervention.

The Relationship Between Prematurity and ASD

Evidence for the Link

• Premature birth has been identified as a risk factor for ASD, with studies showing that the risk increases with the degree of prematurity 1
• Research indicates a significant correlation between birth week and ASD risk, with 22.6% of children born at 25 weeks receiving an ASD diagnosis, compared to 6% at 31 weeks 1
• The American Academy of Pediatrics recognizes that certain populations, including premature infants, require intensified developmental surveillance 2

Gender Differences in Risk

• The link between prematurity and ASD is more pronounced in females, with risk gradually decreasing as birth week progresses 1
• Males show an elevated risk throughout all premature birth weeks, even at near-term 1
• This gender difference suggests potentially different pathophysiological mechanisms in how prematurity affects neurodevelopment between sexes

Mechanisms and Contributing Factors

Several mechanisms may explain the association between prematurity and ASD:

• Brain development disruption: Premature birth interrupts critical periods of brain development that normally occur in the third trimester
• Inflammatory processes: Perinatal stress and inflammation may contribute to both premature birth and neurodevelopmental problems 3
• Shared risk factors: Several factors associated with ASD risk in premature infants include:
  • Male sex
  • Being small for gestational age
  • General cognitive impairment 4
• Blood-brain barrier development: Insufficient development of gut-blood-brain barriers in premature infants may permit exposure to potential neurotoxins 3

Diagnostic Challenges

Overlapping Clinical Presentations

• Premature infants and infants later diagnosed with ASD share many commonalities in clinical presentation 5
• These overlapping phenotypes can lead to misdiagnosis of ASD or missing an ASD diagnosis in preterm infants 5
• Careful developmental monitoring is essential to distinguish between prematurity-related developmental differences and ASD

Timing of Diagnosis

• ASD symptoms typically emerge in early childhood, with most cases being identifiable by 24 months of age 2
• The American Academy of Pediatrics recommends universal screening for ASD at 18 and 24 months 2
• For premature infants, developmental assessments should use corrected age (age from due date rather than birth date) until at least 2 years of age

Clinical Recommendations

Screening and Surveillance

• Enhanced developmental monitoring is recommended for all premature infants, with particular attention to social communication milestones
• ASD-specific screening should be included in the follow-up of all infants born prematurely, at all levels of prematurity 1
• Earlier and more frequent screening may be warranted for extremely premature infants (born before 28 weeks)

Early Intervention

• Evidence-based interventions designed for preterm toddlers or toddlers with ASD may benefit both populations 5
• Early intervention should target specific developmental domains affected in both premature infants and those with ASD:
  • Social communication
  • Language development
  • Sensory processing
  • Motor skills

Research Implications

The Pediatrics guideline highlights the need for research about early markers of ASD to include diverse high- and low-risk samples, specifically mentioning premature infants as an important cohort 6. These populations:

• May be easier to assemble in large sample sizes
• Have different genetic susceptibility factors than sibling cohorts
• Can help determine if early behavioral markers are specific to ASD or predict other developmental outcomes

This approach would improve our understanding of how prematurity and ASD interact and enhance early identification efforts.