In our study, except for infants with cerebral palsy, the number of abnormal primitive reflexes was significantly higher in infants with ASD aged 38 to 45 weeks corrected age and abnormal primitive reflexes in ASD were mainly weak (23/25).
While hyperactive or obligatory primitive reflexes in the neonatal period are considered indicators of risk for cerebral diseases, absent and hypoactive primitive reflexes are considered indicators of risk for hypotonic cerebral palsy, spinal cord injury or peripheral neuromuscular disease . But many studies reported the predictive power of primitive reflexes for cerebral palsy in infants aged 1 month was low [17, 18].
In contrast, the incidence rates of weak or incomplete primitive reflexes in full-term infants at around birth have been reported as about 36% in walking, 16% in standing, and 7% in placing, after excluding infants with asphyxia , 15% in Galant reflex after excluding infants with cerebral palsy and intellectual disability . And one study revealed some primitive reflexes (lower extremity placing reflex, Galant reflex, positive support, steeping reflex) could be weak or incomplete even at 40 weeks corrected age in pre-term infants and, although the main trend of the primitive reflexes became stronger and more complete with increasing corrected age. Those studies did not follow-up developmental prognosis.
Based on our research and previous reports mentioned above, we suspect abnormal primitive reflexes of full-term infants at around term or of preterm infants at around 40 weeks corrected age may indicate some developmental disorders including not only neuromuscular disorders as cerebral palsy but other developmental disorders as ASD.
Why did infants with than without ASD show more abnormalities in primitive reflexes? Primitive reflexes are considered to be mediated by the brainstem, and gait and movement develop thorough bidirectional connections among the cerebrum, cerebellum and midbrain [21, 22].
Although the pathogenesis of ASD is not fully understood, the general consensus is that ASD is caused by genetic factors that affect brain development, specifically neural connectivity. From the neuroanatomical view, candidates for causality of ASD seem to include the cerebellum, cerebrum (frontal and temporal lobe), amygdala, corpus callosum and brainstem. No one has demonstrated essential and consistent evidence of indicators for onset of ASD mainly due to heterogeneity of ASD diagnosis and the possibility of the developing trajectory of the brain and compensatory structural changes [23–25]. Some researchers have reported brainstem dysfunction in children with ASD by administrating auditory brainstem evoked responses or by the polyvagal theory [26–28].
Taking all of the above into account, abnormal primitive reflexes within the first 6 weeks corrected age in low birth weight infants with ASD might indicate some dysfunction in the cerebellum or brainstem which are strongly related to primitive reflexes and motor development in very early infancy. We believe two important points need to be addressed in our future research. One is to evaluate the precise hypoactive pattern of primitive reflexes and the trajectory of abnormal primitive reflexes in very low birth weight infants. The second determining is how to differentiate ASD from various neuromuscular or other developmental disorders by primitive reflexes with or without combinations of genetic, neuro-functional or movement assessment by increasing the number of study subjects.
This study has some limitations. One is potential selection bias stated in the METHOD section. Another is the small number of subjects. A third is the lack of the data on full term infants with or without ASD. And finally, these findings in very low birth weight infants may not generalize to other infants.