U of M team leading ‘largest study of early childhood brain development’

The National Institutes of Health is funding one of the largest studies into child brain development ever conducted.

It aims to understand how the opioid epidemic affects infants and children by following a family from pregnancy through the child’s 10th birthday. The study will also investigate how factors including stress, nutrition, poverty and others influence development.

“Something like this really hasn’t been done before,” said Dr. Anna Zilverstand, an assistant professor of psychiatry and behavioral sciences at the University of Minnesota.

She is co-leading the study alongside Dr. Sylia Wilson, who is an assistant professor at the University of Minnesota’s Institute of Child Development.

“This is an incredible opportunity,” said Wilson. “It will certainly be the largest study of early childhood brain development that has yet been conducted in the United States or the world to my knowledge.”

The ambitious study will involve 25 sites across the country, including the University of Minnesota. Other locations will be in Arkansas, Massachusetts, California, Pennsylvania, Ohio, Georgia, Maryland, New York, Illinois, Oklahoma, Oregon, Rhode Island, Alabama, Florida, Minnesota, New Mexico, North Carolina, Vermont, Wisconsin, Tennessee, Missouri, South Dakota, Washington D.C. and Nebraska.

The University of Minnesota received two grants amounting to $26 million for this research.

“It’s very important that Minnesota be part of it because Minnesota has a very unique population. For example, there is a big Native American community in Minnesota and also there is a big rural population in Minnesota,” said Zilverstand. “They tried to find 25 states that sort of fit together to then be representative of the United States as a whole so Minnesota is an important piece for those two populations.”

The study aims to enroll about 7,500 pregnant people, including 300 people in Minnesota. The research teams are primarily focused on recruiting patients in their second trimester.

They will track the children through the next 10 years of life.

“The amount of brain development that happens during the first couple of years of life is just tremendous so it’s really critical that we understand what’s happening during that period,” said Wilson. “Partly because it’s growing and changing so quickly, things that happen during that period can have a real impact, a real effect and then that real effect can compound over the next period of life into childhood, adolescence and adulthood.”

They explained they will record data in a number of ways, including brain scans, interviews and questionnaires. The team will analyze them at the U of M’s Masonic Institute of the Developing Brain, which will act as the data coordinating center for the entire study.

“We will have these very different aspects of the data that we can then put together and hopefully learn what are the most important factors to have a child grow up as a healthy individual,” said Zilverstand. “The goals are to look at how adversity — so for example poverty, or stress, or substance use during pregnancy or early childhood — influences the children and the goal is really to understand how we could develop interventions so we can prevent negative consequences for the children.”

About 20-30% of participants in Minnesota will be from rural areas, according to Zilverstand. Those struggling with substance use disorder — whether due to opioids, alcohol or other drugs — are expected to make up about 25% of the participants in Minnesota.

“We are never going to be able to understand how to help them if we can’t understand what’s driving their addiction,” said Zilverstand. “I went around and talked to a bunch of researchers and there wasn’t any research being done on this at all in Minnesota because of the laws so this is the first time anybody is actually looking at this in a local context.”

State law previously required health care professionals to report a patient’s drug or alcohol use during pregnancy, with limited exceptions. The statute allowed those using “tetrahydrocannabinol or alcoholic beverages during pregnancy” an exemption “if the professional is providing the woman with prenatal care or other health care services.”

Republican State Sen. Michelle Benson and DFL Rep. Kelly Morrison sponsored legislation in 2021 to change the reporting requirement to allow that exception for all controlled substances “if the professional is providing or collaborating with other professionals to provide the woman with prenatal care, postpartum care, or other health care services, including care of the woman’s infant.”

Benson also added an amendment that said if a woman doesn’t continue to receive that routine care and cannot be reached, the healthcare worker is required to report the patient.

“I wanted to make sure the woman does continue to receive appropriate care and participate in that care because our goal is health moms, healthy babies,” said Benson during a Feb. 2021 hearing on the bill.

Zilverstand testified in support of the legislation during that hearing.

She said, “Minnesota is the only state among the 25 study sites that are participating, which has mandated reporting for substance use during pregnancy by researchers or educators making it nearly impossible for us to conduct our research without adding legal risk for these women.”

Lawmakers approved the language change and included it in the omnibus Health and Human Services budget bill.

“That has been so critical,” said Dr. Quyen Ngo, the executive director of the Butler Center for Research at the Hazelden Betty Ford Foundation. “We want evidence-based treatment. We want to have evidence and treatments and interventions that we know work. And in order to be able to do that, we have to conduct good research.”

The Hazelden Betty Ford Foundation provides inpatient and outpatient addiction treatment services. It’s one of about two dozen clinics helping recruit patients for the study in Minnesota.

“This study will really help to elucidate or help us pinpoint some of the things that can help us treat infants who have that prenatal exposure to alcohol and drugs,” said Ngo. “There’s a lot of interest and emphasis right now on personalized medicine on individualized medicine, and this is really about getting individualized medicine and personalized medicine for these babies who really need support in their early days.”

According to the University of Minnesota, instances of Neonatal Abstinence Syndrome (NAS) have increased 10-fold in Minnesota in the last decade. NAS occurs when an infant is exposed to drugs in utero and undergoes withdrawal after birth. Cases of NAS statewide increased from 1 in 1,000 births in 2009 to 1 in 100 births in 2019, especially affecting rural communities.

Ngo said pregnant patients that seek treatment through their facilities will be informed of the option to participate in the University’s study.

“The most important thing for me in this research is really raising awareness about how we talk about and think about pregnancy and addiction,” said Ngo. “This is a really monumental study because we hear a lot about the research on prenatal exposure to alcohol and drugs.

"Most people have heard of all of the behavioral things that can happen and the health consequences that can happen both for mothers and their babies," Ngo said. "This is really the first major study where we’re really looking closely at the brain development of infants who are exposed to alcohol and drugs before they’re born, compared to infants who don’t have the same exposure. It really gives us a window into what exactly the impact of that prenatal exposure will be on these developing baby’s brains.”