New Biomarker Measures Infant Stress and Development Risks

Summary: Researchers discovered a biomarker that can predict the impact of early toxic stress on infant cognitive development and health. The study used F2-isoprostane, a marker for oxidative stress, to assess the effects of adversity on mothers and infants.

This biomarker, previously used in adults, showed a strong correlation with cognitive development in infants as young as one year old. This breakthrough provides a critical tool for early intervention in at-risk infants, potentially altering life trajectories.

Key Facts:

  1. F2-isoprostane levels in mothers and infants can indicate the impact of toxic stress from early adversity on infant development.
  2. High levels of this biomarker in infants correlate with lower cognitive development scores at one year old.
  3. This discovery enables early detection and intervention for infants exposed to high levels of toxic stress, offering new insights into child development.

Source: Children’s Hospital of Los Angeles

While multiple studies have shown a relationship between adversity in early childhood and negative lifelong health effects on groups of people, no reliable measures exist to measure the impact of early adversity on the risk of individual children.

A joint exploratory study conducted by researchers at Children’s Hospital Los Angeles and Boston Children’s Hospital found that a standard biomarker could predict the risk of early toxic stress on the cognitive development and overall health of individual infants.

Their findings are published in PLOS Global Public Health.

This shows a baby.
An overload of toxic stress can disrupt and damage cell function. Credit: Neuroscience News

Toxic stress is a prolonged, repeated and harmful overactivation of the body’s stress response. It literally can imprint itself on the body. An overload of toxic stress can disrupt and damage cell function. That can be caused by several factors, including adversity.

The groundbreaking Adverse Childhood Experiences (ACEs) study as well as several subsequent studies connected adversity— (psychological, physical or sexual abuse, parental violence, exposure to substance abuse, mentally ill or imprisoned household members) occurring in childhood as recalled by the adult—that is associated on average, with adult health-risk behaviors, chronic illness and shorter life span in a large population group.

More recent studies showed that high ACE scores in individuals did not necessarily predict worse disease risk later in life, as some may be more resilient and others more susceptible.

In children, studies have shown that early exposure to adversity-caused stressors can disrupt cognitive development, hormones and the immune system. But these studies also showed that the impacts of early adversity can be prevented by reducing the sources of stress, as well as buffered by building supportive relationships between children and their caregivers along with learning life and coping skills.

Measuring the toll of toxic stress

In this study, the researchers investigated if a standard biomarker could measure the effects of toxic stress stemming from adversity on mothers and their infants. The researchers measured levels of F2-isoprostane, a sensitive chemical biomarker that indicates cell disruption and damage from oxidative stress, in samples of blood from mothers and urine from infants.

Oxidative stress occurs when cells cannot properly process their waste products, known as free radicals, produced as the body processes food or reacts to environmental factors.

The researchers wanted to know if F2-isoprostane—which has been previously used to reliably measure the effects of oxidative stress in adults—could be used to measure the impact of stressors from adversity and connect these effects to the early development and neurocognitive outcomes of infants.

“In this exploratory study, we aimed to evaluate the individual effects from adversity experienced around the time of birth,” says Kameelah Gateau, MD, MS, neonatologist at Children’s Hospital Los Angeles and lead study author.

“We found a measure of the biological signature of toxic stress on infant brain development, something that no previous study has yet managed to accomplish. We believe that this sensitive and objective biomarker shows great promise in detecting how toxic stress affects the bodies and brains of children.”

Statistical analysis found that cumulative risk scores were correlated with higher F2-isoprostane levels in mothers and infants after six months in the study. The infants who had higher levels of this biomarker of damage from toxic stress at their two-month study visit were more likely to have lower scores on a standard test of child cognitive development when they were a year old.

The team also found that higher cumulative risk scores predicted a higher average level of the toxic-stress biomarker in the bodies of mothers during the one-year study.

The researchers suggested that the relationship between cumulative risk scores around the time of birth and higher maternal and infant stress biomarker levels at six months may reflect oxidative stress levels. The researchers also believe that this initial six-month window of development could be an optimal window of time that can reveal the physical impacts of early adversity in the body and brain.

Stress affects small bodies

The study, conducted at Children’s Hospital Los Angeles and Boston Children’s Hospital, followed 116 pairs of mothers and their infants under two months old and born after 36 weeks of gestation.

The mothers were assessed using a risk score composed of maternal mental health and demographic information including education, marital status and income. The researchers checked infant development at six and 12 months, measuring the levels of oxidative stress biomarker in samples of blood from mothers and urine from babies.

About 80% of the children in the study in Los Angeles identified as White or Latino, and in the Boston group about half identified as Black.

“The infants who had higher measures of biological stress when measured with this biomarker did worse on this learning test,” says Pat Levitt, Ph.D., Chief Scientific Officer at CHLA and study senior author.

“This could mean that the infants who had higher stress levels do worse on learning and retention. These effects are already appearing in 2-month-old infants but are even more apparent at the six-month mark.”

About this stress and neurodevelopment research news

Author: Pat Levitt
Source: Children’s Hospital of Los Angeles
Contact: Pat Levitt – Children’s Hospital of Los Angeles
Image: The image is credited to Neuroscience News

Original Research: Open access.
Exploratory study evaluating the relationships between perinatal adversity, oxidative stress, and infant neurodevelopment across the first year of life” by Kameelah Gateau et al. PLOS Global Public Health


Exploratory study evaluating the relationships between perinatal adversity, oxidative stress, and infant neurodevelopment across the first year of life

Early childhood adversity increases risk for negative lifelong impacts on health and wellbeing. Identifying the risk factors and the associated biological adaptations early in life is critical to develop scalable early screening tools and interventions. Currently, there are limited, reliable early childhood adversity measures that can be deployed prospectively, at scale, to assess risk in pediatric settings.

The goal of this two-site longitudinal study was to determine if the gold standard measure of oxidative stress, F2-Isoprostanes, is potentially a reliable measure of a physiological response to adversity of the infant and mother.

The study evaluated the independent relationships between F2-Isoprostanes, perinatal adversity and infant neurocognitive development. The study included mother-infant dyads born >36 weeks’ gestation.

Maternal demographic information and mental health assessments were utilized to generate a perinatal cumulative risk score. Infants’ development was assessed at 6 and 12 months and both mothers and infants were assayed for F2-isoprostane levels in blood and urine, respectively.

Statistical analysis revealed that cumulative risk scores correlated with higher maternal (p = 0.01) and infant (p = 0.05) F2-isoprostane levels at 6 months. Infant F2-isoprostane measures at 2 months were negatively associated with Mullen Scales of Early Learning Composite scores at 12 months (p = 0.04). Lastly, higher cumulative risk scores predicted higher average maternal F2-isoprostane levels across the 1-year study time period (p = 0.04).

The relationship between perinatal cumulative risk scores and higher maternal and infant F2-isoprostanes at 6 months may reflect an oxidative stress status that informs a sensitive period in which a biomarker can be utilized prospectively to reveal the physiological impact of early adversity.

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