Is Stress a Teratogen?

In order to answer this question, we first need to define both stress and teratogen.

Stress 

Let’s begin with stress: What is it?  Stress in relation to health was first defined by a famous physiologist named Hans Selye as “the nonspecific response of the body to any demand made upon it” (Tan, 2018).  This sounds like an important adaptation that allows us to survive.  According to Dr. Sapolsky in his book, “Why Zebras Don’t Get Ulcers,” this state of hyperarousal, called “fight or flight,” causes the adrenal glands to release a flood of hormones, including adrenaline and cortisol.  These hormones, in turn, boost energy, increase heart rate and blood pressure, raise blood sugar levels, and increase lung capacity, while turning off some of the body’s reproductive and growth processes.  This comes in handy when we need to face a short-term demand, such as recovering from acute illness or surgery, completing a test at school, or a task at work for example.  The stress response is necessary for us to thrive in life and can have protective and beneficial effects.  However, we cannot remain in that state of hyperarousal.  Just as we need to sleep at night, it is equally important for the body to return to a state of relaxation in between stressors so the body can recover and resume growth and reproductive function.  

A famous psychologist named Richard Lazarus further defined stress as “any event in which environmental demands, internal demands, or both tax or exceed the adaptive resources of an individual” (Lazarus, 1984).  This sounds more like the chronic, “toxic” stress that is more prominent in our lives today.  Many of us find ourselves in a constant state of prolonged stress without much return to rest or relaxation in between – as soon as we overcome one demanding situation, we find ourselves in another.  Consider those in this country who are subject to the persistent and chronic stresses of direct exposure to negative attitudes based on race and systemic racism, for example.  While the stress response can be helpful in the short term, the impact of being in a continued state of stress is devastating to our health and well-being and can lead to a myriad of health and developmental problems.  According to research, toxic stress increases rates of heart disease, depression, digestive issues, sleep problems, anxiety, weight gain, sexual dysfunction, and memory loss, as well as reduced production of growth hormones and stunted physical development in children (Sapolsky, 1994).  

Teratogens

So, that is stress.  Now, how about our definition of teratogens?  According to the Embryo Project at Arizona State University, “Teratogens are substances that may produce physical or functional defects in the human embryo or fetus after the pregnant woman is exposed to the substance” (Teratogens, n.d.).  We are mostly familiar with actual substances that can cause birth defects, such as tobacco, alcohol, caffeine, other drugs, medications, environmental chemicals, and some maternal diseases like Rubella and varicella.  What about stress?  Well, let’s take a look at how stress impacts pregnancy and the developing fetus to see if we can define maternal stress as a teratogen.

Maternal Stress Effects

Intrauterine life has a key role in fetal development, birth outcomes, and subsequent child and adult psychological and physical health over several generations.  Stress before and during pregnancy has been associated with poor birth outcomes that can result in lasting and intergenerational behavioral, psychological, and immunological function disorders for children, according to a growing body of research.

Laplante et al. in 2004 took advantage of a natural disaster ice storm in Quebec, Canada, to study the effect of severe maternal stress on the general intellectual and language development of their children.  They found:

• “The more severe the level of prenatal stress exposure, the poorer the toddlers’ abilities.”
• “High levels of prenatal stress exposure, particularly early in the pregnancy, may negatively affect the brain development of the fetus, reflected in the lower general intellectual and language abilities in the toddlers.”

According to a study by Coussons-Read in 2013:

• Stress hormones can change the structure and development of the hippocampal system that is involved in memory and learning, leading to decreased cognitive function later in life.
• Elevated gestational stress can increase inflammation, alter glucocorticoid receptor function, and reduce immunity, which is associated with increased rates of allergy and asthma and reduced immunity at birth that persists into adulthood.

Another study by Douros et al., in 2017 reports:

• Maternal prenatal stress can modulate gene expression epigenetically in multiple complex pathways in fetuses to result in a range of long-term adverse events.  
• Genes interact with the environment dynamically and can be altered during critical stages of early gestation to produce profound consequences on the tissues’ structure and metabolic function.  These changes can be long-lasting and pass from one generation to the next.  
• On a cognitive level, this can manifest as behavioral problems, learning disorders, high anxiety, ADHD, autism, and schizophrenia.  
• On an immune and metabolic level, this can manifest as asthma, allergic disorders, cardiovascular disease, hypertension, hyperlipidemia, diabetes mellitus, and obesity.

Rakers et al., in 2017, elucidate the multiple synergistic ways in which maternal stress during vulnerable periods of gestation can lead to neuropsychiatric, cardiovascular, and metabolic disease later in life:

• Maternal stresses have programming influences that impact epigenetics and phenotypes.  
• Elevated cortisol impairs the development of the fetal hypothalamic-pituitary-adrenal axis (HPAA), which is associated with behavioral and cognitive alterations later in life.  
• Other mediators of stress from mother to child may include changes in catecholamines, cytokines, serotonin/tryptophan, reactive oxygen species, and the maternal microbiota.  
• The degree to which maternal stress will impact a child through development depends on the type and intensity of the stressor, the fetal sex, and the time of the stress experienced during critical stages of pregnancy.  For example, a certain stress introduced during early pregnancy can lead to more detrimental effects in the child than the same stress exposure later in gestation.  

So YES, chronic toxic stress IS INDEED a teratogen, in a big way!

What About Racial Stress?

Did you know that currently, in the US, African-American women face an increased risk of low birthweight and preterm delivery 2-3 times more than Non-Hispanic Whites?  These differences persist despite controlling for other possible risk factors such as genetics, education, socioeconomic status, and access to prenatal care.  

African-American women report a range of both direct and indirect experiences of unequal treatment based on race/ethnicity or skin color.  Direct experiences include negative reactions from others and constant vigilance in anticipation of future reactions.  Indirect experiences of racial stress include institutional inequalities established and perpetuated through many generations, as well as internalized negative stereotypes.  Chronic and severe stressors such as these may cause physiologic wear and tear, or “allostatic load,” that negatively impacts neuroendocrine, immune, and cardiovascular function and lead to premature aging. 

Cardiovascular reactivity to stress in pregnancy is associated with lower birth weight.  Reduced immunity is associated with a higher incidence of bacterial vaginosis, which is linked with preterm labor and delivery (Nuru-Jeter et al., 2008).  As we have seen from the studies above, poor birth outcomes lead to poor physical and cognitive development in children.  Therefore, racial and cultural stress is a serious teratogen for women of African American descent in our country, and this stress can be magnified across multiple generations.  

How to Reduce the Impact of General Stress as Teratogen?

How do you manage daily stress in your life?  Do you allow for periods of recovery in between?  

General stress can come from multiple sources, both externally and internally, some of which is necessary and some avoidable.  To mitigate the harmful effects of these stresses:

1. Eliminate or reduce unnecessary sources of stress:

• Learn to reduce commitments or activities that are beyond your limits.
• Limit time with people who tend to stress you out.
• Limit exposure to news and social media if that leads to stress, and choose more consciously what you are exposed to each day.
• Address any internal sources of stress due to health imbalances that are taxing your adrenals.  For example anemia, blood sugar dysregulation, gut inflammation, food intolerances, environmental toxins, and other nutrient deficiencies.  If you suspect any of these, it is best to see a skilled practitioner for evaluation and treatment. 

2. Incorporate stress management techniques for the necessary stress we cannot avoid

• Cultivate personal practices that support how stress impacts us – such as reframing perspective of situations, lowering standards, practicing acceptance, gratitude, empathy, and managing our time well.
• Exercise!  Physically, any activity that increases the heart rate helps to lower cortisol levels.  Find something you love to do for 30 minutes most days of the week.  Great options include walking, running, lifting weights, dancing, yoga, tai chi, choosing to take the stairs instead of the elevator, parking on the far side of the lot, etc.  
• Meditation, deep breathing, relaxation, and Mindfulness-Based Stress Reduction (MBSR).  There are multiple resources available to help with these approaches, here are a few:
  • Headspace App/Website – 10 free meditations, great for beginners. 
  • MBSR 8-week intensive training – in hospitals and medical centers around the world can be done online or via home study.   
  • Dartmouth College Relaxation Exercises – three breathing/guided relaxation recordings, also available on iTunes.  
  • Breathe2Relax (free) – deep breathing exercise.
• Social connection time – get together with your friends and loved ones, laugh, hug, talk, and play together.  Our social networks greatly support our physical and mental well-being.
• Acupuncture and Traditional Chinese Medicine have long been used as a treatment for stress-related disorders.  Research shows acupuncture treatment helps with stress on many levels:
  • Balances the sympathetic (activating) and parasympathetic (regenerating) parts of our nervous system (Hanley, 2018).
  • Improves symptoms of adrenal insufficiency and helps regulate and regenerate the sexual and adrenal glands (Chen & Liu, 2007). 
  • Activates the central autonomic network of the hypothalamus, periaqueductal grey, and medulla (Beissner, 2012).

What Can Be Done About Racial Stress as Teratogen?

In order to address the racial disparities in outcomes for pregnant African-American and their children, it is necessary to understand the causes for these differences.  These causes are multilevel, complex and deeply interwoven into our society.  Many organizations are working toward addressing both systemic and interpersonal oppression, some specifically with the aim to improve maternal outcomes.  

From 2015-2017, The Alliance for Innovation on Maternal Health reviewed scientific evidence and developed what is known as a care “bundle” – concrete action steps that clinicians and health systems can take during pregnancy to identify, measure, understand and begin to reduce maternal racial and ethnic disparities in perinatal health.  This organization trains professionals to use these evidence-informed recommendations in non-hospital settings such as outpatient and community-based clinical facilities, as well as other social and supportive services agencies that impact pregnancy and postpartum to improve maternal outcomes.   

Another grassroots organization called Holistic Resistance aims to undo racism, address both systemic and interpersonal oppression, and invite people to notice our own lenses through which we see the world.  They offer a trauma-healing approach that meets people where they are at with compassion while also inviting them to grow beyond the lenses they carry.  

According to this dedicated team, we need multiple approaches to dismantle our inherited and created conditions of racism in this country.  Racism cannot be undone without first deeply understanding our own internalized and systemic whiteness.  There is work to be done, and future generations of children who will benefit from it. 

Resources

Alliance For Innovation on Maternal Health-Community Care Initiative. (2023, June 1). Maternal Safety Bundles – Alliance for Innovation on Maternal Health Community Care Initiative. Alliance for Innovation on Maternal Health Community Care Initiative. 

Beissner F, Deichmann R, Henke C, Bar KJ. Acupuncture—deep pain with an autonomic dimension? Neuroimage. 2012;60(1):653–60. Epub 2012/01/10. 10.1016/j.neuroimage.2011.12.045 .

Chen J, Liu JH. [Acupuncture for treatment of kinetic insufficiency of kidney-qi and study on the mechanism]. Zhongguo Zhen Jiu. 2007;27(7):479–81. Epub 2007/08/29.

Coussons-Read, M. E. (2013). Effects of prenatal stress on pregnancy and human development: mechanisms and pathways. Obstetric Medicine, 6(2), 52–57. 

Douros, K., Moustaki, M., Tsabouri, S., Papadopoulou, A., Papadopoulos, M. C., & Priftis, K. N. (2017). Prenatal Maternal Stress and the Risk of Asthma in Children. Frontiers in Pediatrics, 5. 

Hanley KO, T. Der Weltärztekongress 2018. Deutsche Zeitung für Akupunktur. 2018;61(4):278–81.

Lazarus, R., & Folkman, S. (1984). Stress, Appraisal, and Coping. New York Springer. – References – Scientific Research Publishing. (n.d.). 

Laplante, D. P., Barr, R. D., Brunet, A., Du Fort, G. G., Meaney, M. J., Saucier, J., Zelazo, P. D., & King, S. (2004). Stress During Pregnancy Affects General Intellectual and Language Functioning in Human Toddlers. Pediatric Research, 56(3), 400–410. 

Nuru-Jeter, A., Dominguez, T. P., Hammond, W. P., Leu, J., Skaff, M. M., Egerter, S., Jones, C. P., & Braveman, P. (2008). “It’s The Skin You’re In”: African-American Women Talk About Their Experiences of Racism. An Exploratory Study to Develop Measures of Racism for Birth Outcome Studies. Maternal and Child Health Journal, 13(1), 29–39. 

Racial Justice Facilitation | Holistic Resistance | United States. (n.d.). Holistic Resistance. 

Rakers, F., Rupprecht, S., Dreiling, M., Bergmeier, C., Witte, O. W., & Schwab, M. (2017). Transfer of maternal psychosocial stress to the fetus. Neuroscience & Biobehavioral Reviews, 117, 185–197. 

Tan, S. Y., & Yip, A. M. (2018). Hans Selye (1907–1982): Founder of the stress theory. Singapore Medical Journal, 59(4), 170–171.

Teratogens | The Embryo Project Encyclopedia. (n.d.).

Sapolsky, R. M. (1994). Why zebras don’t get ulcers: A guide to stress, stress-related diseases, and coping. W.H. Freeman.