Maternal Immune Activation in Pregnancy Affects Fetal Nervous System Development

Activation of the maternal immune system, especially during the third trimester might affect the developing fetal brain, according to a team of scientists led by Bradley Peterson, MD, director of the Institute for the Developing Mind in the Department of Pediatrics at Children's Hospital Los Angeles. The study appears in the Journal of Neuroscience. The immune system responds to several stimuli such as infections, stress, illness, and allergies. Upon activation by various stimuli, proteins are released as part of this immune/ inflammatory response. Studies in animals have shown that certain proteins released during this response can affect offspring, but little is known about the effect on humans.

The current study was designed to find whether and how immune/inflammatory response during pregnancy could impact the developing brain of infants.

The study enrolled young women in the second trimester of pregnancy with the following tests:

• Blood test and fetal heart monitoring in the third trimester,
• Brain scans of the newborns, and
• Mental and motor development assessment of the infants at 14 months of age

In this novel prospective study, Peterson and his colleagues regularly monitored babies from a critical point in fetal brain development in utero, then at birth, and all the way into their second year. The aim was to determine the existence of a possible link between fetal brain development and maternal immune system activation during pregnancy, especially the third trimester.

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Methods and Results of Study

• During their third trimester maternal blood was obtained and tested for levels of IL-6 (interleukin-6) and CRP (C reactive protein) - two acute phase proteins that are elevated during activation of the inflammatory response
• The team also monitored fetal heart rate as a measure of nervous system development

Interestingly, the team found that CRP levels did correlate with variations of the fetal heart rate, which is in turn dependent on the nervous system, suggesting that maternal inflammation during pregnancy may begin to impact fetal brain development.

• When the babies were born, they underwent MRI scans in their first few weeks of life, enabling the team to view the babies nervous system development and possible influence of prenatal factors

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MRI Imaging Finding of Newborn - Disturbance in Salience Network

A significant alteration in the connections between specific brain regions termed salience network was noted to correlate with elevated maternal IL-6 and CRP levels. The function of this network is to filter stimuli coming into the brain and prioritize them on the basis of those which need immediate attention.

"Our brain is constantly receiving information from our bodies and the external world," explains Peterson, who is also the director of the Division of Child and Adolescent Psychiatry and Professor of Pediatrics in the Keck School of Medicine at USC. "The salience network sifts through that information and decides what is important and warrants action."

Disturbances in the normal function of the salience network have been shown to be associated with the development of autism spectrum disorders and psychiatric illnesses, such as schizophrenia

This is the first study to study about a possible association between the effect of maternal inflammation directly in the disruption of the salience network in infants.

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Assessment of Mental Development of the Babies at 14 Months

At 14 months of age, the babies were assessed for motor skills, language development, and behavior following the guidelines of Bayley Scales of Infant and Toddler Development-Third Edition.

Peterson found marked variations in the scores of toddlers whose mothers had elevated IL-6 and CRP levels during pregnancy.

This study suggests a possible association between maternal immune response and fetal brain development and disorders such as autism spectrum disorders. Nevertheless, more work needs to be done to validate these findings and gain more insight.

To conclude in the words of Dr Petersen, "This finding fills in a missing piece. Although studies in animals have suggested it, this study indicates that markers of inflammation in a mom's blood can be associated with short- and long-term changes in their child's brain, which will now allow us to identify ways to prevent those effects and ensure children develop in the healthiest possible way beginning in the womb and continuing through later childhood and beyond."

References:

1. Immune System Activation Pregnant Women can Shape Brain Development their Babies - (https://www.chla.org/research/immune-system-activation-pregnant-women-can-shape-brain-development-their-babies)

Source-Medindia