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. 2014 Apr 30;17(4):106. doi: 10.1136/eb-2014-101763

Neonatal factors associated with autism spectrum disorders in infants

Sara Jane Webb 1
PMCID: PMC4844341  NIHMSID: NIHMS605367  PMID: 24785736

What is already known on this topic?

Autism spectrum disorders (ASD) have a prevalence rate of 1 in 68 among children1; with genetic, familial (eg, maternal and paternal age), prenatal (eg, low birth weight and prematurity) and perinatal factors associated with an increased risk for later development of ASD.2 3

What does this paper add?

  • The likelihood of an ASD diagnosis increased with decreasing gestational age and decreasing birth weight. High-frequency ventilation and intraventricular cranial haemorrhages (ICH) were also related to increased risk.

  • ASD outcome was established through a combination of tools; results were stable regardless of diagnostic pathway.

Limitations

  • Not all potentially confounding variables were available on all infants; for example, only 76% of infants <34 weeks had an ultrasound to examine for ICH.

  • Premature children who developed ASD were more likely to have other developmental disabilities, reinforcing our understanding that this may be a particularly vulnerable group.

  • The findings do not address the causal pathway to ASD.

What next in research?

Sex (ie, being male) and familial history (ie, having an older sibling with ASD) represent the greatest known risks for development of ASD. A number of genetic mechanisms have also been found to be contributors to an ASD diagnosis. Incorporation of genetic findings with specific assessment of prenatal and neonatal factors will help to focus our understanding of the factors that contribute to ASD outcomes.2 3 Genetic vulnerabilities may be exacerbated by specific environments, resulting in an atypical cascade of neural development that is specific to ASD. Further understanding of the biological mechanisms that result in prematurity, as well as those that protect against it, will be important in relation to other ASD risk characteristics.

Could these results change your practices and why?

No. However, this study supports the emphasis on early monitoring of children born premature and with medical complications. As well, better implementation of integrated electronic medical records that include information about psychological and intellectual functioning will allow us to examine the sensitivity and specificity of developmental trajectories resulting in ASD.

These data suggest that infants affected by specific prenatal or neonatal events such as prematurity, small for gestational age, ICH and ventilation should be monitored so that early concerns can be quickly addressed through reference to specialised early evaluation and treatment programmes.

Footnotes

Competing interests: None.

References

  • 1.Autism and Developmental Disabilities Monitoring Network Surveillance Year 2010 Principal Investigators. Prevalence of autism spectrum disorders among children aged 8 years—autism and developmental disabilities monitoring network, 11 Sites, United States, 2010. MMWR Surveill Summ 2014;63:1–21. [PubMed] [Google Scholar]
  • 2.Krumm N, O'Roak BJ, Shendure J, et al. A de novo convergence of autism genetics and molecular neuroscience. Trends Neurosci 2014;37:95–105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Gardener H, Spiegelman D, Buka SL. Perinatal and neonatal risk factors for autism: a comprehensive meta-analysis. Pediatrics 2011;128:344–55. [DOI] [PMC free article] [PubMed] [Google Scholar]
Evid Based Ment Health. 2014 Apr 30;17(4):106.

Commentary

ABSTRACT FROM: Kuzniewicz MW, Wi S, Qian Y, et al. Prevalence and neonatal factors associated with autism spectrum disorders in preterm infants. J Pediatr 2014;164:20–5.

Participants In total 195 021 infants (≥24 weeks gestation) survived until discharge from hospital. Participants were representative of the general population (except for highest and lowest income earners). Children subsequently diagnosed with autism spectrum disorder (ASD) were identified from the KP Autism registry, which contains details of all children diagnosed with ASD. Children with symptoms indicating possible ASD but without formal evaluation were excluded.

Setting Kaiser Permanente Northern California hospitals; recruitment 1 January 2000 to 31 December 2007.

Exposure Gestational age from obstetrically assigned estimated date of confinement. For infants with a gestational age of <34 weeks, procedures performed (mechanical ventilation, transfusion, chest compressions) and diagnoses (intracranial haemorrhage, leukomalacia, bacteraemia or necrotising enterocolitis). Data were collected retrospectively.

Follow-up period Three years minimum.

OUTCOMES

Prevalence of ASD

Overall, 2457 children were diagnosed with ASD (1.26%). Prevalence of ASD was significantly higher among infants born at <37 weeks (1.78%) compared with infants born ≥37 weeks (1.22%; p<0.001).

Risk factors for ASD

Gestational age of 24–26 weeks significantly increased the risk of ASD compared with term (gestational age 37–41 weeks; HR=2.7, 95% CI 1.5 to 5.0; adjusted for covariates of maternal age and education, sex and being small for gestational age (SGA) and caesarean delivery). Infants born at 27–33 weeks were also at significantly increased risk of ASD compared with term infants (HR=1.4, 95% CI 1.1 to 1.8), as were infants born at 34–36 weeks (HR=1.3, 95% CI 1.1 to 1.4).

Independently of gestational age, SGA significantly increased risk of ASD (HR=1.5, 95% CI 1.1 to 1.9). Among infants born at <34 weeks, risk of ASD was also significantly increased with presence of intracranial haemorrhage and need for high-frequency ventilation (HR=2.2, 95% CI 1.1 to 4.6).

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