Study: Prenatal choline deficiency linked to mental illness, stress, and preterm birth

By Danielle Masterson

- Last updated on GMT

Getty Images /  damircudic
Getty Images / damircudic

Related tags Choline Prenatal

Researchers say supplementation may be more realistic than trying to achieve enough choline through diet.

There may be a potential link between choline deficiency in Black pregnant women in the United States and increased risk of developmental and behavioral issues for their children, which can then evolve into mental illness later on in life. 

The findings come from two articles published in Schizophrenia Bulletin​. The first article, published last year, is "Black American Maternal Prenatal Choline, Offspring Gestational Age at Birth, and Developmental Predisposition to Mental Illness”​ and the second, published in May, "Targeting Treatments to Health Disparities,"​ is a follow-up article delving more deeply into known healthcare disparities highlighted by the study results.

The studies are the result of more than 20 years of research by the group, which includes Sharon Hunter, PhD, an associate professor in the University of Colorado School of Medicine Department of Psychiatry, and M. Camille Hoffman, MD, MSc, an associate professor in the University of Colorado School of Medicine Department of Obstetrics and Gynecology, along with their research team. 

Tom Druke, director of marketing at VitaCholine, told NutraIngredients-USA​ that the University of Colorado has long been a leader in the field of choline and prenatal neurodevelopment, first under the late Dr. Randal Ross, and now with Dr. Robert Freedman and Dr. Camille Hoffman. 

“Their pioneering work began as an investigation into the roots of mental illness and has explored the link between choline and neurodevelopmental outcomes. Several of their papers have shown that higher maternal choline levels may play a neuroprotective role during pregnancy by mitigating the effects of certain impairments to infant cognitive development,”​ said Druke.

Mental illness and prenatal neurodevelopment

According to the authors, their research began with wanting to better understand the in utero risk factors of schizophrenia.

"At that time, there was a lot of discussion around the idea that mental illnesses like schizophrenia were tied to prenatal neurodevelopment,"​ noted Hunter. 

Choline, an essential nutrient, is vital for fetal neurodevelopment, including the development of inhibitory neurocircuits in the brain. According to previous studies, these neurocircuits were found to be abnormal in those with schizophrenia and many of their family members.

Initial research 

The researchers launched their first clinical trial in 2004. During the trial, they supplemented pregnant women with a specific form of choline, phosphatidylcholine, then monitored their children until the age of four. Phosphatidylcholine is less likely to cause side effects, such as stomach upset, associated with pure choline. The results found that the inhibitory neurocircuits were functioning properly in more children from supplemented mothers when compared to children whose mothers didn't receive the choline supplement.

"It showed that mothers who had lower choline levels during the second trimester of pregnancy gave birth to babies who were more likely to have worse neurodevelopmental scores, which can be a marker for later mental illness or behavioral problems,​" said Hoffman. 

Druke noted that this research, along with other studies, suggests that increased choline during pregnancy may have a meaningful positive impact on both individual and societal maternal outcomes. 


The authors noted that the ultimate goal of the study was to find out whether supplementing with choline could reduce the risk of developing schizophrenia—however, the condition isn't typically diagnosed until an individual is in their 20s. So instead, the group monitored for early indicators of the condition.

"We couldn't follow these children for 20 years, but we could test them as children to see if they had problems with attention or withdrawal or aggression, which can be indicators not just of schizophrenia but of other mental issues as well,"​ explained Hunter. 

Racial health care disparities 

After the first choline trial, the group conducted a follow-up study in which they measured choline levels in 183 pregnant women. Although the women were told about choline and the researchers suggested that they try to get more choline in their diets, they did not administer any choline supplements to the participants. It was during this study that the group noticed a demographic disparity: overall, choline levels were notably lower in Black women when compared to the other groups. 

"When we found these differences in choline levels, we started to wonder whether this also translated to differences in outcomes," ​Hunter said. "And preliminary data suggests that it does."

Lightbulb moment 

This disparity in choline levels prompted the researchers to reexamine their previous results from the first clinical trial. Upon reflection, they found that the gestational age at delivery in Black mothers who had been supplemented with choline was extended by an average of three weeks compared to Black mothers who didn't receive choline supplementation.

"As an Ob/Gyn, preterm birth is one of the main adverse pregnancy outcomes that we're always working towards preventing," ​said Hoffman. "And there are known disparities in both birth weight and risk of preterm birth between Black women and their children and almost every other group."

The results of the clinical trial and the subsequent observational study suggest two potential benefits of choline supplementation for pregnant women, especially Black women: enhanced prenatal development of inhibitory neuro-circuits in the brain and older gestational age at delivery.


Next, the researchers compared the choline levels of the Black pregnant women in the American study to blood samples from a cohort of pregnant women in Uganda and found that the choline levels of the Ugandan women were much higher than their American counterparts.

"Of course, we know that not all Black women in America are African American or of African heritage,” ​said Hunter. "But still, it seemed like there was something else going on that might account for the racial differences we were seeing."

The research team hypothesized that the more stressed a mother is, the more her liver may seize choline for itself, potentially resulting in the fetus not receiving enough choline for neurodevelopment and a higher risk for preterm birth.

The team collected measures of maternal stress in the observational study participants. And while the Black women didn't report feeling more stress, their hair cortisol levels, a biomarker of stress exposure, were higher than those of participants of other races.

"Even though they don't report it, their bodies looked more stressed," ​Hunter said. "Our question now is whether there are stressors that Black women experience but that our questionnaires do not capture, or are cortisol levels reflecting accumulated exposure to low-level, background stressors, perhaps stemming from decades or lifetimes or even generations of institutional racism in this country. We don't have the data to answer those questions yet, but we wanted to get this study out there to say, 'this is something we should be paying attention to.'"

“Equal access to high quality prenatal care is of paramount importance and this research demonstrates the disparities that often exist among minority groups,” ​said Druke. “In January of this year, the 2020 Dietary Guidelines for Americans highlighted the significance of choline intake during pregnancy and lactation, going so far as to note that many current prenatal supplements contain inadequate levels of choline.”

The FDA currently recommends that pregnant women get 550 milligrams of choline a day, but Hunter pointed out that about 90% of pregnant women don't meet that amount. 

"If we're telling women that they need 550 milligrams of choline per day, but some other factor limits how much choline can get to the fetus, that level of intake may not adequately meet the needs of the developing fetus. We need to understand this,"​ said Hunter. 

Hoffman likened the choline challenge to the early days of folic acid research, where the risk was significantly reduced when folate was included in a supplement rather than trying to achieve it via dietary intake. 

Down the road, the researchers hope to do another clinical trial where they supplement one cohort of Black women at the FDA-recommended choline level, plus another group at about two to three times the recommended amount to see if there is any additional benefit to supplementing at a higher level.


Source: Schizophrenia Bulletin

03 May 2021

“Targeting Treatments to Health Disparities”

Authors: S. Hunter et al.


Source: Schizophrenia Bulletin

13 November 2020

“Black American Maternal Prenatal Choline, Offspring Gestational Age at Birth, and Developmental Predisposition to Mental Illness”

Authors: S. Hunter et al.

Related topics Research Maternal & infant health

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