Extreme prematurity and autism

Preterm birth is usually defined as the birth of a baby before 37 weeks of gestational age. Extreme prematurity refers to those babies born between 22 and 25 completed weeks of pregnancy. When followed longitudinally 1 out every 10 extreme premature babies screened with the Modified Checklist for Autism in Toddlers (M-CHAT) will test positive for autism. The figure excludes those babies with autistic behaviors who had cerebral palsy and other health problems.

One of the effects of prenatal care and specialized units in hospitals that address the health care needs of newborns has been the increased survival of extremely premature infants. Although care for the premature infants has significantly improved during the last few decades the prevalence of preterm birth has remained the same.  Improvement in survival during the last 30 years has risen 70 fold and correspondingly so have increased the problems peculiar to this patient population.

Fortunately the majority of premature infants who survive will be free of any major disability. However, 20 to 25% of them will have at least one major disability in the form of mental development, cerebral palsy, blindness or deafness. Subtle neurodevelopmental disabilities will be evident in half of the survivors. The risk of any and all complications grows as gestational age decreases.

An atypical behavioral profile in about 25% of extreme premature babies may suggest an autism spectrum disorder. Researchers have concluded that although extreme prematurity does not cause autism, it might be contributing factor. Advances in neuroimaging techniques offering both structural and functional measurements may provide insights as to how prematurity-related brain injuries become associated to an autism spectrum disorder. The idea being that ASD results from related abnormal brain development in this patient population.

The brunt of brain lesions in the extreme premature usually affect the germinal matrix.  This is the zone of proliferation in the developing brain for both neuronal and glial precursors. During the period of cellular proliferation the germinal zone requires a rich blood supply but the vessels are immature having large diameters and little in terms of supporting structures.

You have to think of the germinal matrix as granulation tissue. This is the connective tissue rich in tiny blood vessels that tries to repair and fill in the void within a wound. As you may know from personal experience this tissue is prone to bleeding with little provocation. Germinal tissue reacts the same way and hemorrhages inside the same (and into the ventricles) are often seen in extreme prematures within the first 6 postnatal days. In addition to hemorrhages the tortuous anatomy of veins in the white matter of the developing brain and their drainage into vessels within the germinal matrix predisposes susceptible individuals to slowing or stoppage of blood flow (leading to venous infarcts).

pat brain ivh 1micro

Figure: A coronal section through the brain of a premature infant of about 32 weeks gestation.  The central cavities of the brain are its ventricles and surrounding the same you can see the purple staining germinal cells.  The deep red blob on the left side is a hemmorhage.  The same has some mass effect and forces the germinal matrix to protrude into the ventricle.

Infarctions of the white matter and hemorrhages of the germinal matrix are both intimately related and occur frequently in extreme prematures. This is one in a series of blogs where I discuss different conditions manifesting autstic symptomatology of known origin or neuropathology (so-called syndromic autism). The first of these blogs was on tuberous sclerosis (http://bit.ly/17ExHYt ). The emphasis in all of these blogs is in the commonality of abnormalities in certain parts of the brain.  It is my belief that in autism there is a common lesion that interferes in some way with the division of germinal cells early during brain development. The end result is abnormalities in cell migration and malformed areas of the cerebral cortex and brainstem. You can find additional information about this process at:  http://bit.ly/1aM5KFu and http://bit.ly/136db0t In this blog I described a well known risk factor for autism and conclude that, like in all of the previously discussed cases of syndromic autism, the commonality is some type of lesion to the germinal matrix. In a future blog I will discuss one particular article about the type of lesion in extreme prematures as examined by ultrasound and ASD (Movsas et al., 2013).


Lorenz JM. The outcome of extreme prematurity. Semin Perinatol 25(5):348-59, 2001.

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