Researchers from McGill University in Canada, Children’s Hospital in Boston, Harvard Medical School and Brigham and Women’s Hospital* published an article in Pediatrics this month that reports, for the first time, a high prevalence of positive initial screening for autism spectrum behaviors in survivors of extreme prematurity. They found that several factors are associated with a positive screening, including lower birth weight and gestational age, male gender, prenatal infection, more severe illness at birth and abnormal MRI scans.

Major advances in neonatal intensive care have decreased the mortality of preterm infants, but have not led to a comparable decrease in long-term neurodevelopmental conditions such as cerebral palsy. This trend underlies the ever increasing population of very low birth weight (VLBW) children with significant and costly developmental disabilities. In addition, it has been reported that there is a high prevalence of atypical psychosocial development in VLBW children with symptoms such as difficulty with social integration, excessive shyness, attentional difficulties and hyperactivity. These symptoms are similar to those typically seen in children with autism spectrum disorder; however, the prevalence of autism spectrum disorder has never been explored in the VLBW population. These researchers sought to use validated screening tools for detection of early autistic features in a cohort of children with a history of VLBW as well as to identify clinical predictors of positive autism screening results.

Using the Modified Checklist for Autism in Toddlers (M-CHAT), the researchers screened 91 infants with a history of VLBW, aged 18 to 24 months. In addition, they used the Child Behavior Checklist (CBCL) questionnaire for caregivers that assess the frequency of behavioral and emotional problems in young children as well as the Vineland Adaptive Behavior Scale (VABS) that measures functional status in communication, daily living, socialization and motor skills in children 0 to 18 years of age. Finally, demographic, maternal, prenatal, delivery, post-delivery and short-term outcome data was collected on all of the infants in the study. This included such clinical data as gestational age, weight, maternal age, prenatal infection, fetal heart rate, Apgar scores, placental pathology reports, postnatal blood gases and MRI results.

Results indicated a population of infants with a gestational age of 23 to 30 weeks and a birth weight of 460 to 1490 grams. Sixty-five percent were delivered by cesarean section, 88% required ventilatory resuscitation at birth and there was evidence of intrauterine infection in 31% of these infants. Screening of these infants with the M-CHAT indicated that 25% had positive results for early signs of autism. Twenty-nine percent of the infants had functional delays in motor abilities, 23% had communication deficits and 29% experienced socialization difficulties as assessed by the VABS. Behavioral outcomes as assessed by the CBCL indicated that 29% experienced internalizing behavior problems and 13% experienced external behavioral problems such as attention problems and aggression. Those who screened positive for early signs of autism also showed internalizing behavior problems such as being withdrawn and emotionally reactive as indicated by the CBCL. These children also showed difficulties in socialization and communication skills but did not show delays in functional mobility as assessed by the VABS. The MRI studies indicated that 67% had normal results and 33% had abnormal results such as diffuse periventricular leukomalacia (PVL), periventricular hemorrhagic infarction (PVHI), cerebellar hemorrhagic injury and ventriculomegaly.

Statistical analyses of the clinical data found that lower birth weight and gestational age, male gender, more severe illness at birth, intrauterine infection and acute intrapartum hemorrhage were associated with a positive screen for autism. In addition, long term complications and abnormal MRI were also associated with a positive screen. More specifically, the preterm infants with cerebellar hemorrhagic injury and combined supratentorial and infratentorial parenchymal lesions were more likely to have a positive screen for early autistic features than those with PVL or PVHI.

Discussion

This study suggests that there is a high prevalence of early autistic behaviors in very low birth weight infants, a previously unrecognized feature of this population. Larger studies with longer follow-up are needed to corroborate these findings. The clinical and testing data presented here seem to suggest, however, that although the risk factors for autism and other neurodevelopmental conditions such as epilepsy and cerebral palsy may have commonality, the etiologic pathways are different. Nonetheless, these conditions can co-occur in children as it has been reported that 1 in 9 children with cerebral palsy have features of autism and 1 in 4 children with cerebral palsy also have epilepsy. Furthermore, many of the common risk factors for autism and cerebral palsy (50% of children with cerebral palsy are born prematurely) are ones that can be addressed through research to prevent prematurity and improve maternal health.

Positive Screening for Autism in Ex-preterm Infants: Prevalence and Risk Factors
Catherine Limperopoulus, Haim Bassan, Nancy R. Sullivan, Janet S. Soul, Richard L. Robertson, Jr, Marianne Moore, Steven A. Ringer, Joseph J. Volpe, and Andre J. du Plessis. Pediatrics 2008;121;758-765