Prenatal Inflammation May Affect Brain Development


A normal pregnancy usually lasts around 40 weeks, but births that occur before 37 weeks are defined as being premature. Premature births are associated with a wide range of problems in infant children, and generally, the shorter the term of a pregnancy, the greater the health problems there will be for the infant. In fact, individuals that are born extremely premature (at less than 28 weeks of pregnancy) have the highest risk for many health issues, such as anemia, chronic lung disease, and serious infections.  Currently, premature births are the leading cause of infant disease and infant death in the United States. One such important health implication of premature births is related to brain development, with approximately 1 million preterm individuals every year affected by negatively altered brain development.

The exact causes of premature births are not yet known by scientists. However, it is known that there are many factors (environmental, genetic, and behavioural), that can increase the risk of a premature birth. These factors, such as smoking cigarettes, poor nutrition, stressful life events, and even chronic conditions such as high blood pressure and diabetes, all ultimately work to influence an early induction of the normal birthing process. What medical scientists and physicians do understand is that many of these identified risk factors have the potential to promote intrauterine (within the uterus) inflammatory processes during pregnancy. In fact, indicators of intrauterine inflammation are present in as many as 70% of premature births, versus only 1% – 13% in full term births. This supports a hypothesis that the risk of premature birth is increased by such factors that promote inflammation, inducing an early delivery.

Recently, researchers at the University of North Carolina, Boston University, and Tufts University set out to understand whether changes in gene expression (the activity level of genes) occurred along with this pre-birth intrauterine inflammation. If so, these scientists wanted to determine whether these genomic changes could also predict cognitive function in these prematurely born individuals later in their lives. To do this, the scientists explored data which was already collected from a group of infants born between 23 and 28 weeks of pregnancy in 2004 in the United States.

From these infants, isolated total RNA from umbilical cord tissue was collected. Recall from your high school science class that RNA’s main function is to transfer the genetic code for the creation of proteins from the DNA, which makes it a good measure of the activity of genes. Next, when these individuals were 10 years of age, their general cognitive ability (or IQ) was assessed with various ability and reasoning scales. These researchers used a range of statistical methods to test whether the activity of genes that were associated with pre-birth inflammation could predict later cognitive ability.

The researchers discovered that there were 445 genes that showed altered levels of activity in association with intrauterine inflammation, with 334 of the genes (75.1%) showing increased gene expression, and the remaining 111 (24.9%) showing decreased expression. Of significance was the fact that many of the 111 genes that showed decreased expression are related to neurological development. Further, of these 445 genes, the expression of 6 genes were predictive of neurocognitive impairment at 10 years of age: increased levels of two genes (GPX3 and C10orf54), and decreased levels of 4 genes (PNMAL1, CRISPLD1, OLFML1, ECM2), predicted more severe neurocognitive impairments at 10 years of age. Two of these genes, ECM2 and CRISPLD1 have actually been previously indicated in being involved in neurodevelopmental processes.

This demonstration that genes that are active in brain development will change or reduce their activity in conjunction with pre-birth inflammation supports a growing body of evidence that there is an association between intrauterine inflammation and cognitive impairment in later childhood. What is significant for physicians and clinicians is that the identification of these genes could allow for earlier intervention for children who are at risk. Early intervention services such as family education and counseling, parent support groups, speech pathology, and physical therapy are shown to be an effective treatment method for children with intellectual disabilities. Still, there is much work to be done, and future research could better understand  the underlying mechanisms for this altered gene expression, leading to strategies to better reduce the risk for cognitive impairment in prematurely born children.

Research Institutes:

Gillings School of Global Public Health, University of North Carolina; Boston University School of Medicine; Tufts University School of Medicine; University of North Carolina

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