Study links prenatal stress to inflammation and mental health issues in offspring

An analysis of data from the Avon Longitudinal Study of Parents and Children (ALSPAC) found that children of mothers who experienced higher stress during pregnancy tended to have elevated levels of an inflammation marker, interleukin-6 (IL-6), at age 9. These children were also more likely to exhibit more severe symptoms of depression and anxiety during adolescence. The findings were published in Psychoneuroendocrinology.

Stress is the body’s natural response to challenges or demands, often referred to as the “fight-or-flight” reaction. It is triggered by real or perceived threats, activating the release of hormones like adrenaline and cortisol to prepare the body for action. While this response can enhance focus, energy, and performance in the short term, prolonged or chronic stress can disrupt bodily systems. This disruption can lead to physical, emotional, and mental health problems, such as high blood pressure, anxiety, or weakened immunity.

According to the developmental origins of health and disease hypothesis, exposure to stress during pregnancy can lead to physiological changes in the fetus. These stress-induced alterations may have long-lasting effects on the mental health and well-being of the child later in life. Several studies have demonstrated associations between maternal stressful life events and psychopathology during pregnancy and children’s mental health outcomes.

Study author Zahra M. Clayborne and her colleagues aimed to explore how maternal prenatal stress relates to inflammation processes and mental health outcomes in children. The researchers also examined whether these associations differed between sexes, given that symptoms of depression and anxiety often become more severe in girls than boys starting in middle childhood.

The study analyzed data from ALSPAC, a large dataset comprising women residing in Avon County, southwest England, who were pregnant between 1991 and 1992, and their children. The initial cohort included 14,541 pregnancies, which resulted in 14,062 live births. For this study, data from 3,723 mother-child pairs were used, as these participants provided the necessary information over nearly two decades.

The data used in the study included assessments of maternal stress during pregnancy (measured using a custom-designed index incorporating life stress, contextual stress, personal stress, and interpersonal stress), child inflammation at 9 years of age (measured by concentrations of IL-6 and C-reactive protein in blood serum), anxiety symptom severity at 16 years of age (assessed using the Development and Well-being Assessment), and depression symptom severity at 18 years of age (assessed using the Clinical Interview Schedule-Revised).

IL-6 is a type of protein called a cytokine. It plays a role in immune responses, inflammation, and the regulation of various biological processes, including metabolism. C-reactive protein (CRP) is a protein produced by the liver in response to inflammation. The concentrations of both proteins tend to rise during inflammatory conditions, making them valuable biomarkers for measuring the intensity of inflammation in the body.

The results showed that higher maternal prenatal stress was associated with elevated concentrations of IL-6 in children and more severe symptoms of depression and anxiety. Specifically, children of mothers who experienced more stress during pregnancy had higher levels of IL-6 at age 9 and exhibited more severe symptoms of anxiety and depression at ages 16 and 18, respectively. No significant differences were found between boys and girls in these associations, and no relationships were observed between inflammation markers at age 9 and later anxiety or depression symptoms.

“Our findings suggest that prenatal maternal stress is associated with IL-6 in childhood, and with depression and GAD [generalized anxiety disorder] in adolescence. Results highlight the importance of early-life strategies to minimize children’s risk towards mental disorders. The prenatal and postnatal periods may be sensitive windows to reduce the potential impacts of chronic stress on mothers and children given that pregnant individuals and new parents may experience more contacts with health care systems,” the study authors concluded.

The study provides valuable insights into the links between maternal prenatal stress and the health of their children. However, the study design does not allow for definitive cause-and-effect conclusions. Therefore, it remains unclear whether maternal stress directly caused the observed associations with inflammation and mental health symptoms or if other factors were responsible for both maternal stress and the children’s health outcomes.

The paper, “Associations between prenatal stress with offspring inflammation, depression and anxiety,” was authored by Zahra M. Clayborne, Stephen E. Gilman, Golam M. Khandaker, Ian Colman