Autism spectrum disorder (ASD) is a complex developmental condition characterized by challenges with social skills, speech and nonverbal communication, and restricted/repetitive behaviors. Recent research has explored potential connections between being born prematurely and developing ASD later in life. While no direct causal relationship has been proven, studies suggest preterm birth may increase the risk for autism spectrum disorder. In this article, we’ll explore the current evidence on links between prematurity and ASD and what factors may explain this association.
Key Questions
Here are some key questions we’ll address on the relationship between preterm birth and autism:
What is the connection between preterm birth and autism risk?
Multiple studies show a higher prevalence of autism diagnoses in children born prematurely compared to full-term peers. The increased risk appears to be most significant in very preterm infants born before 32 weeks gestation. The exact mechanisms behind this relationship are still being investigated.
Are there other factors that could explain the association?
Research points to several possible explanations beyond solely prematurity that could underlie the association between preterm birth and increased autism risk:
- Genetic vulnerability – Inherited genes may jointly predispose a child to preterm birth and ASD.
- Pregnancy complications – Complications like preeclampsia or infection can necessitate early delivery and may also affect fetal neurodevelopment.
- Neonatal factors – The stressful extrauterine environment, intensive care interventions, abnormal brain development in the NICU may contribute to atypical neural wiring.
Disentangling the contributions of these different perinatal and postnatal variables is an active area of research.
Does gestational age at birth impact autism risk?
Yes, studies find the risk of autism is higher the earlier a baby is born, especially prior to 32 weeks. The immature brains of very preterm infants are especially vulnerable during critical periods of development in the NICU. However, even late preterm infants (34-36 weeks) show a slightly elevated autism risk.
What role might the NICU environment play?
The neonatal intensive care unit exposes preterm infants to numerous stressors including infection, inflammation, medication, pain, disruption of sleep cycles, and interference with maternal-infant bonding. This atypical early environment occurring during sensitive neurodevelopmental windows could plausibly increase risk of neural connectivity differences underlying ASD.
Are all preterm children at equal risk?
No, individual factors also influence susceptibility. Preterm infants with very low birth weight and evidence of specific newborn medical complications appear to have the highest risk of later autism. Male sex, genetic predisposition, and certain pregnancy/obstetric factors can also amplify risk. However, the majority of preterm infants will not go on to develop autism.
The Evidence Linking Preterm Birth and Autism
Many studies over the past decade have found evidence for increased autism spectrum disorder risk following preterm birth compared to babies born full term. Here is a summary of key research findings:
Population Data
- A 2020 meta-analysis of over 25 million children found a significantly higher risk of autism diagnoses in those born preterm compared to full-term peers across multiple countries. Very preterm birth before 32 weeks conferred the greatest risk.
- A Swedish population study found children born extremely preterm at 22-26 weeks were over 3 times more likely to be diagnosed with autism compared to those born full term. Those born at 27-33 weeks had double the risk.
- A U.S. study found preterm infants had a 36% higher chance of developing autism compared to term infants. The risk was greatest for those also exhibiting intrauterine growth restriction.
Neuroimaging Studies
- MRI scans reveal atypical development of brain structures linked to social-cognitive processing in preterm infants who later developed autism symptoms compared to preterm infants without autism.
- Altered neural connectivity patterns seen on MRIs of some preterm infants mirror connectivity differences observed in studies of adolescents with autism.
Brain Biomarkers
- Elevated levels of specific proteins in the blood of newborns born very preterm have been associated with increased autism risk at age 2.
- Placental abnormalities and certain newborn blood biomarkers found more often in preterm infants have also been linked to later autism diagnosis.
Overall, these findings consistently indicate preterm delivery, especially at very early gestations, confers an increased likelihood of autism spectrum disorder in childhood. Ongoing research aims to clarify the mechanisms.
Possible Biological Mechanisms
Exactly how preterm birth could increase susceptibility to autism is still under investigation. Current theories center around how prematurity disrupts normal brain development:
Altered Brain Connectivity
The preterm brain exhibits reduced structural connectivity between key regions. Disrupted wiring during critical developmental windows could impact emerging social, communication, and cognitive skills—the hallmark challenges of ASD.
Inflammation
Preterm infants experience higher inflammation from infections, treatments, and other NICU exposures. Increased inflammatory cytokines in the brain inhibit normal synaptic pruning processes during key periods of neural development.
Epigenetic Dysregulation
Evidence suggests preterm birth could alter epigenetic programming of gene expression in the brain, disrupting typical developmental trajectories. Dysregulated genes may jointly increase risk for both preterm birth and ASD.
Hormonal Surges
Premature transition from the intrauterine to extrauterine environment induces hormonal surges which can impair brain development. For example, abnormally high cortisol has been linked to abnormal neural connectivity and behavior changes reminiscent of autism.
Loss of Neuroprotection
Preterm birth removes the infant from the protective, nourishing environment of the placenta and amniotic fluid prematurely during critical windows of neural development and connectivity formation.
Non-Biological Factors That May Contribute
While the preterm brain appears especially vulnerable, other pregnancy, neonatal, and sociodemographic variables likely interplay and compound autism risk:
Prenatal Factors
Pregnancy complications increasing preterm risk include infection/inflammation, preeclampsia, placental insufficiency, gestational diabetes, immune activation, and certain pharmaceutical exposures—all of which could independently impact fetal neurodevelopment.
Neonatal Factors
Medical complications common in preemies, like neonatal sepsis, pneumonia, meningitis, and broncho-pulmonary dysplasia, as well as interventions like oxygen support, steroids, analgesia, and anesthesia may affect short- and long-term neurologic function.
Psychosocial Factors
The stress of the NICU environment coupled with disrupted parent-child bonding during critical periods could plausibly contribute to altered infant neurobehavioral development.
Sociodemographic Factors
Confounding social variables associated with preterm birth—low income, maternal education, access to care—may also impart increased autism risk above and beyond prematurity alone. However, studies control for these factors.
Disentangling the relative contributions of this complex web of pre-, peri- and postnatal risk variables remains challenging but important work.
Modifying Factors That May Increase or Reduce Risk
While research reveals an association between preterm birth and increased autism risk, some factors can modify an individual’s susceptibility:
Increased Risk
- Very early gestational age (under 28 weeks)
- Extremely low birth weight (ELBW)
- Intrauterine growth restriction (IUGR)
- Perinatal brain injury
- Male sex
- Genetic risk factors
Preterm infants with certain newborn complications are more likely to exhibit autism-associated behaviors as toddlers. Genetic vulnerabilities can also amplify risk.
Decreased Risk
- Late preterm (34-36 weeks)
- Higher birth weight
- Female sex
- Absence of neonatal health complications
- High-quality NICU care
- Strong parent attachment
Less extreme prematurity, healthier neonatal course, evidence-based NICU practices, and a nurturing early environment may impart some degree of neuroprotection for preterm infants.
Long-Term Outcomes
While preterm infants as a group appear to have elevated autism risk, most will not develop ASD. However, prematurity remains associated with higher likelihood of certain developmental challenges:
- Language delays
- Learning disabilities
- Cognitive impairment
- Behavior disorders
- Motor deficits
- Lower IQ
- ADHD symptoms
Preterm infants require close developmental monitoring to identify emerging concerns early. Early intervention can improve outcomes.
With supportive therapies tailored to their needs, many preemies catch up developmentally and live happy, healthy lives. But understanding autism risk remains important as we seek to enhance outcomes for this special population of infants.
Conclusion
In summary, a consistent body of evidence demonstrates preterm birth, especially at very low gestations (
