Original Article
Autism Spectrum Disorder Is Associated with Ventricular Enlargement in a Low Birth Weight Population

https://doi.org/10.1016/j.jpeds.2012.12.084Get rights and content

Objective

To determine the relation of neonatal cranial ultrasound abnormalities to autism spectrum disorders (ASD) in low birth weight (LBW) adult survivors, a population at increased ASD risk.

Study design

This is a secondary analysis of a prospectively-followed regional birth cohort of 1105 LBW infants systematically screened for perinatal brain injury with cranial ultrasound in the first week of life and later assessed for ASD using a two-stage process [screening at age 16 years (n = 623) followed by diagnostic assessment at age 21 years of a systematically selected subgroup of those screened (n = 189)]; 14 cases of ASD were identified. For this analysis, cranial ultrasound abnormalities were defined as ventricular enlargement (indicative of diffuse white matter injury), parenchymal lesions (indicative of focal white matter injury), and isolated germinal matrix/intraventricular hemorrhage.

Results

Compared with no cranial ultrasound abnormalities, any type of white matter injury (ventricular enlargement and/or parenchymal lesion) tripled the risk for screening positively for ASD [3.0 (2.2, 4.1)]. However, the risk of being diagnosed with ASD depended on type of white matter injury. With ventricular enlargement, the risk of ASD diagnosis was almost seven-fold that of no cranial ultrasound abnormality [6.7 (2.3, 19.7)], and no elevated risk was found for parenchymal lesion without ventricular enlargement [1.8 (0.2, 13.6)]. Isolated germinal matrix/intraventricular hemorrhage did not increase risk for a positive ASD screen or diagnosis.

Conclusion

In LBW neonates, cranial ultrasound evidence of ventricular enlargement is a strong and significant risk factor for subsequent development of rigorously-diagnosed ASD.

Section snippets

Methods

This secondary data analysis of longitudinal Neonatal Brain Hemorrhage Study data was approved by the Institutional Review Board of Michigan State University.

Enrollment in the Neonatal Brain Hemorrhage Study consisted of 1105 infants weighing between 500 and 2000 g who were born in or transferred into 3 central New Jersey study hospitals between 8/27/1984 and 6/30/1987. In the first year of the study, 598/687, (87%) of all babies <2000 g born in 1 of the 3 counties of central New Jersey

Characteristics of the Cohort

Table I compares characteristics of the study participants who were assessed for ASD at age 21 years (n = 189) by ASD status; Table I, includes many of the obstetric, birth, and postnatal factors that have been shown to be associated with higher incidence of ASD.19, 20 We found that a significantly higher percentage of study participants who screened positive for ASD had been born to mothers with maternal hypertension. We also found that the percentage of cerebral palsy and/or motor impairment

Discussion

In a prospective study of LBW infants assessed for ASD at 21 years of age with validated instruments, we found a strong and significant association between the presence of ventricular enlargement on cranial ultrasound in the newborn period and risk of ASD. The data did not allow a definite conclusion to be drawn regarding the relationship of parenchymal lesion to the diagnosis of ASD. However, both forms of white matter injury (parenchymal lesion and ventricular enlargement) were associated

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    T.M. was funded by the National Institutes of Health (T32 Perinatal Epidemiology Training Grant 2T32HD046377). The authors declare no conflicts of interest.

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