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DNA modifications found in cord blood relate to maternal mood effects on infant brain development
February 21, 2022

Babies’ brains are very malleable and dynamic, which is critical for their development. At early stages, a baby’s brain development is heavily influenced by genetic and environmental factors that shape their brain structure and function. This lays the foundation for cognition, behavior and well-being.

A recent study done at the Center for Healthy Minds and Waisman Center, University of Wisconsin-Madison and published in Scientific Reports found that the impact of prenatal maternal depression and anxiety on early postnatal brain development is associated with DNA modifications in blood obtained from the umbilical cord. These results reveal a potential way through which maternal behavior influences a baby’s brain development.

Maternal depression and anxiety symptoms during pregnancy have an effect on infants’ brain development at one month old after birth. In particular, it can affect white matter tracts, or fibers in the brain that carry signals between different brain regions. The investigators set out to understand this link.

They evaluated the mothers’ depression and anxiety symptoms during their third trimester of pregnancy and acquired blood samples from the umbilical cord upon childbirth. Cord blood, says Pamela Kling, professor of pediatrics and one of the principal investigators of the study, is easily obtained, has markers such as stress indicators “and it really does reflect what's happened in the last part of your pregnancy,” says Kling.

At one month old, babies were brought back to obtain images of their brains through magnetic resonance imaging (MRI). “Environmental factors can greatly influence brain and child development in significant ways,” says Doug Dean, assistant professor of pediatrics and medical physics and lead author of the study. “By getting at a very early time point, just [one month] after birth, there's not as much time to let the postnatal environment impact [brain development]. We're really looking at their prenatal environment.”

To find the link between maternal behavior and changes in the infant’s brain they used cord blood to look at DNA modifications called epigenetics (outside of the gene) which alter the expression of genes. In particular, methylation is a type of epigenetic change commonly involved in turning off gene expression. It is heritable, but also alterable. “Lots of different things relate to brain development and one those things is DNA methylation. Your genes are transcribing how your brain develops,” says Elizabeth Planalp, scientist at the Waisman Center and co-author of the study.

They found that DNA methylation levels were associated with white matter pathways altered by maternal behavior during pregnancy. The majority of the genes had higher DNA methylation levels, which suggests they could be being suppressed during development. This can have

different effects depending on the roles of each gene. The specific genes found to be affected by changes in methylation levels are ones involved in roles that are important for brain development such as cell fate and specialization, neuronal growth and patterning of white matter microstructure. In other words, maternal depression and anxiety symptoms alter the expression of genes that result in changes in fetal brain development.

The researchers also found that exposure to prenatal maternal depression and anxiety symptoms affected white matter microstructure and epigenetic changes differently in males versus females. Although the research explaining such differences is currently limited, Dean and Planalp think these sex-based differences could be due to different sensitivities to prenatal environmental factors, or different rates at which children’s white matter develops.

All mothers that participated in the study presented subclinical, rather than severe, levels of depression and anxiety symptoms. “I think it’s important to understand how a mother's small behavioral changes can really impact child development. It's not just in extreme cases, but it's in the subclinical or sub-threshold level cases that we're seeing how maternal depression and anxiety can impact children, which is important to understand,” says Planalp.

This information obtained from cord blood, says Reid Alisch, professor of neurological surgery and co-author of the study, can give insight into what’s happening during brain development. “We’ve just started to scratch the surface for identifying markers in cord blood that are connected to the development of the white matter microstructure,” says Alisch. “So now if we take that information into a population that's higher risk, it could actually guide us into novel treatments for these individuals at much earlier stages.”

In depression, anxiety or other neurodevelopmental disorders, the earlier information is obtained to help guide the care for individuals, the better the outcomes, says Alisch. Using cord blood, which is highly accessible, they can gain insights into how the brain is developing at very early stages.

By: Charlene N. Rivera-Bonet