Adverse Babyhood Experiences and Rheumatoid Disease / Arthritis (ABEs & RA)

In her memoir “Sonata” about living with rheumatoid arthritis, piano virtuoso Andrea Avery wonders whether being born cesarean or not being breastfed affected her risk of getting a debilitating, life-altering disease.

Readers on Kelly Young’s Rheumatoid Arthritis Warrior blog also share possible links between adverse babyhood experiences and rheumatoid disease / arthritis in some of their onset stories:

• Kate had polio in her first year of life.
• Julie was so sick after she was born that her doctors didn’t think she’d live through the night.
• Brenda was born with a birth defect that left her deaf and with neck and back problems.
• Reader URandomnessK was born 3 1/2 weeks premature and has a form of autoimmune arthritis called ankylosing spondylitis.

These stories raise an important question. Are adverse events during pregnancy, birth and infancy risk factors for rheumatoid arthritis / disease?

Get the Free PDF of this Post

The form will appear momentarily.

Most doctors have never heard of such risk factors. The research, however, explains that there is indeed a link between what I refer to as adverse babyhood experiences and rheumatoid disease / rheumatoid arthritis (RA/RD) and other autoimmune and chronic diseases.

What we’re learning is pretty big news. It also explains why it’s not your fault, not your mother’s fault, and what you can do about it.

In today’s post I start with a little background on RA/RD. I then give you a foundation for how to begin to make sense of the stories I’ve mentioned above.

I share research showing how early life events increase risk for many if not most chronic diseases.

Afterwards, I describe the early research showing similar risk factors in RA/RD.

I then describe some of the mechanisms now being discovered that explain how this process happens.

This includes how life experiences affect the developing brain and influence gene function.

I introduced this topic on adverse babyhood experiences (ABEs) in the discovery series where I first summarized the evidence found in type 1 diabetes. I also summarize ABEs in a detailed overview with a free 90 page downloadable pdf or kindle ebook in this post.

These studies explain that chronic illnesses arise from an intelligent process gone awry rather than from random problems or mistakes.

I end the post by coming back to the stories shared by Andrea, Kate, Julie, Brenda and URandomnessK and highlighting how their ABEs may very well have been important early risk factors for the development of RA/RD.

If you have a chronic illness other than RA/RD this post may also be relevant for you because similar events contribute to risk for all kinds of autoimmune diseases and other chronic illnesses ⁽¹⁾Meda, F., et al. (2011). “The epigenetics of autoimmunity.” Cell Mol Immunol 8(3): 226-236, p. 234.

I. Facts About Rheumatoid Disease

Rheumatoid arthritis is an autoimmune disease most well-known for causing pain, inflammation and deformity in joints. It is now increasingly understood to also be a system-wide disease that affects many organs including the lungs, heart, eyes and other tissues. Joints are not always involved and are just one of many potential systems affected. As such, RA /RD is increasingly referred to as rheumatoid disease.

Very loosely, there are two general types of autoimmune rheumatoid arthritis.

Juvenile Idiopathic Arthritis (JIA)

Juvenile idiopathic arthritis (JIA) was formerly referred to as juvenile rheumatoid arthritis (JRA) in the U.S. and juvenile chronic arthritis (JCA) in Europe. JIA begins in childhood, often in the first 1 to 3 years of life. Age of onset varies depending on the kind and is diagnosed before the age of 16. It has many symptoms in common with adult onset RA/RD but comes in multiple different forms instead of one, can affect growth and development, and may remit with time. Antibodies are less common in JIA than in RA/RD ⁽²⁾Huang, J. L. (2012). “New advances in juvenile idiopathic arthritis.” Chang Gung Med J 35(1): 1-14.

Rheumatoid Arthritis

Onset of RA/RD can begin around puberty although highest rates of onset are in the 40s ad 50s in women and slightly later in men (wiki). There may be a family history of RA/RD and it is much more common than JIA. Women are affected more than men in RA/RD and in most types of JIA as well. Not everyone with RA/RD tests positive for the antibodies we are currently aware of.

II. Environment & Genes: What Causes Rheumatoid Arthritis (RA/RD)?

As with other autoimmune diseases including type 1 diabetes, causes of rheumatoid arthritis remain unclear.

Research has cast a wide net beyond genetics, looking for potential risk factors such as lifestyle, diet, exercise, parental income, vitamin D, and infections. Smoking is the one well recognized risk factor in whites (wiki) although it appears to require 20 years or more of accumulated exposure to influence onset of the disease ⁽³⁾Klareskog, L., et al. (2004). “What precedes development of rheumatoid arthritis?” Ann Rheum Dis 63 Suppl 2: ii28-ii31, full text.

The reason such risk factors are being studied is because genes play only a partial or small role in RA/RD. Even having susceptibility genes does not mean a person will get the disease.

This emphasizes the fact that non-genetic events affect risk for rheumatoid arthritis.

Risk for Rheumatoid Arthritis is < 50% Genetic

Although risk for RA/RD is 3 to 5 times higher when a first degree relative (parent or sibling) has the disease ⁽⁴⁾Holers, V. M. (2014). “Insights from populations at risk for the future development of classified rheumatoid arthritis.” Rheum Dis Clin North Am 40(4): 605-620, genes account for less than half of the risk of developing RA/RD:

• If one identical twin develops RA/RD, for example, the co-twin – who has the same genetic make-up – will develop the disease 15%-20% of the time (wiki).
• In some studies, none of the co-twins developed RA/RD, suggesting that genes actually play a very minor role in risk ⁽⁵⁾Svendsen, A. J., et al. (2002). “Relative importance of genetic effects in rheumatoid arthritis: historical cohort study of Danish nationwide twin population.” BMJ 324(7332): 264-266 .

The fact that genes are responsible for less than half of the “cause” of rheumatoid arthritis means that other risk factors exist. These other factors are not genetic. They are environmental.

Non-genetic factors are critical to understand because, unlike genes, they may help identify risk factors that are preventable, treatable or even reversible.

These are events that we, as people with a chronic disease, may have control over.

It also means that even when there is a family history or a genetic risk for the development of RA/RD, it is far from predetermined that a person will ever develop the disease.

Typical environmental factors include elements mentioned earlier such as diet, exercise or other lifestyle habits such as smoking. They also include infections, vaccines, vitamins, hormones, and medications. These have been the main focus of non-genetic RA/RD research.

But an entirely different set of risk factors for RA/RD has been mostly overlooked by the research community as well as by doctors and medical professionals.

An emerging understanding of how genes function is pointing in the direction of adverse life experiences as risk factors for RA/RD and other autoimmune diseases and chronic illnesses.

Some researchers have been wondering specifically whether any links exist between adverse babyhood experiences and rheumatoid disease / arthritis.

A major block to unraveling the role of environmental factors in RA / RD may be that we are looking too late.

Is it biologically plausible that events during  neonatal life  & childhood could have lifelong effects?

There is now a large body of evidence suggesting that early life events can lead to disease in later life ⁽⁶⁾Edwards, 2010, p. 1

The rest of this blog post introduces the research about adverse babyhood experiences and rheumatoid disease / arthritis.

I describe studies showing how antibodies have lead researchers to consider early risk factors.

After, I explain how ABEs increase risk for chronic diseases in general and then present similar findings in RA/RD. Later, I describe some of the mechanisms being identified about how events from the distant past can affect health so many years or decades later, and why it’s not psychological.

III. Antibody Patterns in RA/RD Indicate That Risk Occurs in Early Life

Although not everyone who develops rheumatoid disease tests positive for antibodies, studies of people who DO have antibodies offer important new insights:

• antibodies typically precede onset of RA/RD symptoms by 3 to 5 years ⁽⁷⁾Holers, V. M. (2014). “Insights from populations at risk for the future development of classified rheumatoid arthritis.” Rheum Dis Clin North Am 40(4): 605-620 and sometimes by 10 years or more ⁽⁸⁾Edwards, C. J. and C. Cooper (2006). “Early environmental factors and rheumatoid arthritis.” Clin Exp Immunol 143(1): 1-5. This is often referred to as a latency period.
• antibody levels fluctuate in the early stages and can increase, decrease or even resolve completely
• almost 50% of first degree relatives in one study were found to have one RA/RD related antibody even though they did not have the disease; the only family member to develop RA/RD had more types of antibodies (four).
• greater risk for RA/RD is associated with having more types of antibodies (risk was greater with 5 types of antibodies on average, in contrast to 1 type in family members without RA/RD) ⁽⁹⁾Barra, L., et al. (2013). “Anti-citrullinated protein antibodies in unaffected first-degree relatives of rheumatoid arthritis patients.” Arthritis Rheum 65(6): 1439-1447.
• Similar antibody patterns have been seen in type 1 diabetes

Because RA/RD is influenced by non-genetic factors and because antibody levels can fluctuate and appear long before the onset of symptoms, researchers have begun to look for risk factors early in life ⁽¹⁰⁾Carlens, C., et al. (2009). “Perinatal characteristics, early life infections and later risk of rheumatoid arthritis and juvenile idiopathic arthritis.” Ann Rheum Dis 68(7): 1159-1164, ⁽¹¹⁾Colebatch, A. N. and C. J. Edwards (2011). “The influence of early life factors on the risk of developing rheumatoid arthritis.” Clin Exp Immunol 163(1): 11-16, ⁽¹²⁾Edwards, C. J. (2010). “Can the Events of Early Life Influence the Development of Rheumatoid Arthritis?” J Rheumatol 37(1): 1-2.

It has become clear that immunological and inflammatory changes begin many years before the onset of joint pain and swelling. The autoantibodies rheumatoid factor (RF) and anti-cyclic citrullinated peptides (anti-CCP) and a raised C-reactive protein (CRP) are all detectable in serum years before symptoms begin.

There is now a large body of evidence suggesting that early life events can lead to disease in later life ⁽¹³⁾Edwards, C. J. (2010). “Can the Events of Early Life Influence the Development of Rheumatoid Arthritis?” J Rheumatol 37(1): 1-2.

IV. Adverse Babyhood Experiences (ABEs) Increase Risk for Disease

FOAD: The Fetal Origins of Disease Studies

One well respected set of studies known as the Fetal Origins of Adult Disease or “FOAD” has discovered that prenatal adversity affects risk for chronic illness in adults.

Dr. David Barker, the initial investigator in the FOAD studies, followed a group of women who were pregnant during the Dutch Hunger Winter in WWII. The studies showed that the stress of war conditions and famine increased the risk that their children would develop chronic illnesses later in life. Other studies of less intense types of prenatal stress have also shown increased risk for chronic disease later in life.

Diseases associated with prenatal stress include:

• high blood pressure
• heart disease
• obesity
• type 2 diabetes
• asthma
• cancer
• depression, anxiety, bipolar disorder, schizophrenia
• kidney Failure – glomerulosclerosis
• liver Failure – cholestasis, steatosis
• immune dysfunction
• reduced bone mass (osteoporosis)
• Alzheimer’s disease
• and other health conditions

The FOAD research also found that prenatal stress increases risk of premature birth and that birth weight can be a reflection of the womb environment and a response to stress.

Like type 1 diabetes researcher Dr. Gisela Dahlquist ⁽¹⁴⁾Dahlquist, G. and B. Kallen (1992). “Maternal-child blood group incompatability and other perinatal events increase the risk for early-onset type 1 (insulin-dependent) diabetes mellitus.” Diabetologia 35(7): 671-675, Dr. Lisa Mandl  has wondered whether the prenatal environment affects risk for RA/RD. She did a study looking at birth weight and risk for RA/RD ⁽¹⁵⁾Mandl, L. A., et al. (2009). “Is birthweight associated with risk of rheumatoid arthritis? Data from a large cohort study.” Ann Rheum Dis 68(4): 514-518.

We examine[d] whether the fetal environment, as reflected by birthweight, could modulate an individual’s future risk of rheumatoid arthritis (RA).

Birthweight >4.54 kg [10 lb] was associated with a two-fold increased risk of adult onset RA, compared with those of average birthweight. Further study of this observation may provide insight into the pathogenesis of RA.

Some other studies have also found that people who develop rheumatoid arthritis tended to be larger babies than their counterparts at birth ⁽¹⁶⁾Colebatch, A. N. and C. J. Edwards (2011). “The influence of early life factors on the risk of developing rheumatoid arthritis.” Clin Exp Immunol 163(1): 11-16, ⁽¹⁷⁾Edwards, C. J. (2010). “Can the Events of Early Life Influence the Development of Rheumatoid Arthritis?” J Rheumatol 37(1): 1-2, ⁽¹⁸⁾Jacobsson, L. T., et al. (2003). “Perinatal characteristics and risk of rheumatoid arthritis.” BMJ 326(7398): 1068-1069.

Higher birth weights are also linked to higher risk for other autoimmune diseases such as type 1 diabetes, lupus, and Sjogren’s in some studies.

Mother-Infant Separation Increases Risk for Disease

The following section is based on research I presenting in more detail about the role of early life events in affecting risk for disease [see Part 1 insights from type 1 diabetes. Part 2 insights from asthma, Part 3 (epigenetics and other mechanisms)].

Human babies, like other mammals, need the close proximity of their adult caregivers for safety and care. Research studies have also found that babies need adult caregivers in order to regulate their immature emotional states as well as their young bodies and physiologies. This is why the practice of skin-to-skin contact between parents and babies is increasingly used in hospitals after birth and especially for babies who are born prematurely. Kangaroo care, as it is also known, helps babies better regulate body temperature, heart rate, breathing rates and to gain weight more easily.

Studies have also found that the ability of parents to care for their newborns is affected by how they bond with their infants.

Holding one’s baby in the first hours after birth actually fosters and strengthens the parent-baby bond, and this ability to bond is a natural, innate state that exists in all of us.

When parents are more bonded, they hold, gaze, caress and talk to their babies more.

Mothers who get more skin-to-skin time with their babies in the first 2 hours after birth are more likely to bond and to have more ease and success with breastfeeding. They are more likely to breastfeed for longer and to find it harder to leave their babies in the care of others.

Babies whose mothers hold them in the first 2 hours after birth are calmer, more interactive, less stressed. In childhood, these babies have higher IQs.

In a study of kids with asthma, psychologist Dr. Tony Madrid discovered that mothers of asthmatic kids had experienced more stressful events in their pregnancies, during birth and in their infancies. His findings replicated previous studies showing that stressful events could interfere with the degree to which mothers were able to bond with their babies.

Risk factors identified in Dr. Madrid’s study included emotional stressors such as loss of a loved one, lack of support, trauma such as domestic violence, or financial stress; and physical separation, such as from events like surgery for cesareans, incubator care for the baby, or hospitalization of mom or baby in the first year or two of life, and more. These stressors contributed to experiences of emotional or physical separation and interfered with mothers’ abilities to bond and feel the natural built-in love we are designed to feel for our kids.

It also turned out that mothers of children with asthma had experienced more adversities than moms of healthy kids in the study.

When Dr. Madrid treated moms and helped them heal from the adverse events they’d experienced, they felt a shift and a stronger love for their children. In his studies, treating mothers helped children’s asthma improve or, most often, resolve completely ⁽¹⁹⁾Klaus, M. H. and J. H. Kennell (1976). Maternal-infant bonding. St. Louis, Mosby, ⁽²⁰⁾Madrid, A., et al. (2012). “The Mother and Child Reunion Bonding Therapy: The Four Part Repair.” Journal of Prenatal and Perinatal Psychology and Health 26(3) .

Swedish researcher Dr. Gisela Dahlquist discovered that events such as prematurity, infections, cesarean birth, jaundice, incubator care and other adverse events in early life were risk factors for type 1 diabetes. Like Dr. Madrid, she believed a common feature between these different risk factors was that they were stressful and caused separation between mother and baby. A follow-up study in diabetes-prone mice supported her suspicion that separation was the factor that increased risk of developing the disease.

These types of studies show that different kinds of adverse experiences affect the ability of mothers to bond and influence how they feel about their babies. Bonding disruptions, in turn, affect risk for depression and can change maternal behaviors. They also affect the ease and success of breastfeeding.

These studies demonstrate that risk factors for later disease can be numerous, that adverse events can interact and influence one another, such as how physical or emotional separation affects bonding, which in turn can interfere with breastfeeding, holding and gazing and caressing a baby as well as other forms of connection between mothers and their babies.

Each of these factors affects a baby’s physiology and his or her ability to regulate basic bodily functions.

They also increases risk for disease later in life.

Using this kind of lens helps explain some of the potential links between adverse babyhood experiences and rheumatoid disease / arthritis.

V. Adverse Babyhood Experiences and Rheumatoid Disease

Prenatal Stress

A mother’s previous miscarriage or loss of a baby is a risk factor for RA/RD ⁽²¹⁾Bell, S. W., et al. (2017). “Juvenile idiopathic arthritis in relation to perinatal and maternal characteristics: a case control study.” Pediatric Rheumatology Online Journal 15(1): 36. This could be due to many reasons, one of which is that loss and grief increase risk for bonding disruptions and difficulties in feeling connected to a new baby.

Another study noted that risk for RA/RD grew with an increasing number of adverse events such as socioeconomics status and food insecurity ⁽²²⁾Parks, C. G., et al. (2013). “Childhood socioeconomic factors and perinatal characteristics influence development of rheumatoid arthritis in adulthood.” Annals of the Rheumatic Diseases 72(3): 350-356.

Hospitalization in First Year of Life

The single factor most clearly identified with increased risk for JIA as well as RA in one study in Sweden is that of being hospitalized for infection during the first year of life ⁽²³⁾Carlens, C., et al. (2009). “Perinatal characteristics, early life infections and later risk of rheumatoid arthritis and juvenile idiopathic arthritis.” Ann Rheum Dis 68(7): 1159-1164. While infections may be a risk factor in and of themselves, research in the cell danger response and in mother-infant separation both suggest that the isolation and separation are risk factors in and of themselves.

Breast Feeding

Some studies find that people with RA/RD were not breastfed as much or for as long ⁽²⁴⁾Colebatch, A. N. and C. J. Edwards (2011). “The influence of early life factors on the risk of developing rheumatoid arthritis.” Clin Exp Immunol 163(1): 11-16, ⁽²⁵⁾Jacobsson, L. T., et al. (2003). “Perinatal characteristics and risk of rheumatoid arthritis.” BMJ 326(7398): 1068-1069 and why breastfeeding may be protective in kids with JIA ⁽²⁶⁾Mason, T., et al. (1995). “Breast feeding and the development of juvenile rheumatoid arthritis.” J Rheumatol 22(6): 1166-1170. The subtlety of influences on breastfeeding may also help explain why other studies show no link between breastfeeding and RA or JIA ⁽²⁷⁾Carlens, C., et al. (2009). “Perinatal characteristics, early life infections and later risk of rheumatoid arthritis and juvenile idiopathic arthritis.” Ann Rheum Dis 68(7): 1159-1164, ⁽²⁸⁾Simard, J. F., et al. (2010). “Early life factors and adult-onset rheumatoid arthritis.” J Rheumatol 37(1): 32-37.

Another possible clue for the differences in study findings was suggested by Young et al ⁽²⁹⁾Young, K. A., et al. (2007). “Perinatal and early childhood risk factors associated with rheumatoid factor positivity in a healthy paediatric population.” Ann Rheum Dis 66(2): 179-183, noting that breastfeeding reduces JIA in children who were at higher risk because they were already antibody positive for rheumatoid factor and carried a particular gene.

Breastfeeding can be protective for babies because of the nutrients in breast milk. It also involves close mother-baby contact and supports regulation of a baby’s physiology. As mentioned above, difficulty or shorter duration of breastfeeding can reflect interruptions in mother-baby bonding and exposure to ABEs or can simply be an indication of a choice a mother has made.

Timing of Birth (premature vs late)

Premature birth is a risk factor for some diseases and one study has found it to be a risk factor for one type of arthritis in which inflammation occurs at the sites where tendons or ligaments insert into the bone. It is also a risk factor for rheumatoid factor positive polyarticular (multi-joint) juvenile idiopathic arthritis (JIA) ⁽³⁰⁾Bell, S. W., et al. (2017). “Juvenile idiopathic arthritis in relation to perinatal and maternal characteristics: a case control study.” Pediatric Rheumatology Online Journal 15(1): 36.

Another study found no increased risk with premature birth ⁽³¹⁾Colebatch, A. N. and C. J. Edwards (2011). “The influence of early life factors on the risk of developing rheumatoid arthritis.” Clin Exp Immunol 163(1): 11-16, ⁽³²⁾Simard, J. F., et al. (2010). “Early life factors and adult-onset rheumatoid arthritis.” J Rheumatol 37(1): 32-37.

Being born 2 weeks after one’s due date may also increase risk ⁽³³⁾Carlens, C., et al. (2009). “Perinatal characteristics, early life infections and later risk of rheumatoid arthritis and juvenile idiopathic arthritis.” Ann Rheum Dis 68(7): 1159-1164.

These may not be contradictory findings as much as indicators of potential stressors in early life that affect the timing of birth.

Cesareans and Risk for RA/RD in Babies

Very few studies have looked at the role of birth complications in trying to understand risk factors for rheumatoid disease / arthritis. January 2021 update: A 40 year study of cesareans looking at effects on the entire 2.5 million inhabitants of Denmark was published in January 2020 finding that cesareans increase risk for RA/RD and other autoimmune diseases. The study began in 1973 and concluded in 2016. Cesarean rates overall were 15%. The 4 diseases studies were more commonly seen in adulthood but there was also onset for some in childhood ⁽³⁴⁾Andersen V, Möller S, Jensen PB, Møller FT, A. G. Caesarean Delivery and Risk of Chronic Inflammatory Diseases (Inflammatory Bowel Disease, Rheumatoid Arthritis, Coeliac Disease, and Diabetes Mellitus): A Population Based Registry Study of 2,699,479 Births in Denmark During 1973–2016 Clin Epidemiol. 2020;12(287-293.

These findings are consistent with one other study that found a borderline increase in risk for RA/RD with cesarean birth ⁽³⁵⁾Carlens, C., et al. (2009). “Perinatal characteristics, early life infections and later risk of rheumatoid arthritis and juvenile idiopathic arthritis.” Ann Rheum Dis 68(7): 1159-1164.

The Carlens et al study compared a group of individuals with RA/RD with controls who ranged in age from 16 to 29. Both groups had birth data in a Swedish registry that tracks events and other information during pregnancy and birth. We’ll learn more one way or another as the groups get older, given that RA most commonly begins later in life ⁽³⁶⁾Carlens, C., et al. (2009). “Perinatal characteristics, early life infections and later risk of rheumatoid arthritis and juvenile idiopathic arthritis.” Ann Rheum Dis 68(7): 1159-1164.

Cesarean sections are done for reasons ranging from life-saving and highly stressful, to avoidance of risk due to past events such as previous emergency c-sections and other issues. A cesarean can be an intensely scary or even traumatic experience for women ⁽³⁷⁾Clement, S. (2001). “Psychological aspects of caesarean section.” Best Pract Res Clin Obstet Gynaecol 15(1): 109-126, ⁽³⁸⁾Fenwick, J., et al. (2003). “Women’s experiences of caesarean section and vaginal birth after caesarian: a Birthrites initiative.” Int J Nurs Pract 9(1): 10-17, ⁽³⁹⁾Ryding, E. L., et al. (1997). “Posttraumatic stress reactions after emergency cesarean section.” Acta Obstet Gynecol Scand 76: 856-861 as well as for their babies (think life-threatening situations).

Risk from cesareans may vary as a result of a number of factors that are not usually measured or evaluated.

For example, cesareans:

• typically lead to longer periods of mother-infant separation
• can be stressful in and of themselves
• can increase parental stress and risk for bonding disruptions
• influence a baby’s gut flora and microbiome
• increase risk for respiratory infections
• are associated with lower rates of breastfeeding ⁽⁴⁰⁾Clement, S. (2001). “Psychological aspects of caesarean section.” Best Pract Res Clin Obstet Gynaecol 15(1): 109-126, ⁽⁴¹⁾Isik, Y., et al. (2016). “Early postpartum lactation effects of cesarean and vaginal birth.” Ginekol Pol 87(6): 426-430, Abstract. These may be factors that influence risk for RA/RD.

VI. Mechanisms of ABEs

The Womb Environment Influences Nervous System Development

RA//RD researchers are interested in the fact that the nervous system, immune system and other organ systems are influenced by prenatal stress and other life experiences during early development in the womb.

Mandl and her colleagues who looked at whether birth weight was associated with risk for RA/RD are among those wondering about links between adverse babyhood experiences and rheumatoid arthritis:

Patients with RA are known to have dysregulation of the hyopthalamic-pituitary-adrenal (HPA) axis. This axis may be modulated in utero.

The “fetal origins of adult disease” hypothesis posits that an increased risk of adult onset chronic disease can be a function of fetal environment. … Changes in fetal nutrition or gene-environment interactions could be responsible for determining a fetus’ susceptibility to disease later in life ⁽⁴²⁾Mandl, L. A., et al. (2009). “Is birthweight associated with risk of rheumatoid arthritis? Data from a large cohort study.” Ann Rheum Dis 68(4): 514-518, p. 2.

Epigenetics: Early Life Events Affect Gene Function

McGill University researcher Michael Meaney and colleagues examined whether a mother’s behaviors had an impact on her baby’s genes, nervous system and stress responses.

Their study looked for differences in two groups of rat pups. One group was raised by nurturing dams that licked and groomed more often and arched their backs to make it easier for pups to nurse. The pups in the control group were raised by mothers who licked, groomed and arched less.

They found that these kinds of maternal behaviors turned certain genes on and off in rat pups.

These maternal behaviors affected the pups’ ability to regulate cortisol and influenced how sensitive they were to stress.

Rat pups sensitivity to stress reflected patterns of regulation in the hypothalamic-pituitary-adrenal (HPA) axis. They also discovered that these changes lasted throughout the lives of the rat pups. They occurred because chemicals attached to genes to affect how they functioned.

This study helps explain why bonding disruptions and mother-baby separation can have an effect not only on a mother’s behaviors with her baby, but also on her baby’s health. It’s not psychological – it’s because stress and adverse life experiences influence genes, the nervous system and ultimately, our health.

Life experiences affect health by telling our genes what to do through the process of epigenetics.

Epigenetics refers to the way our bodies prepare for our unique environments by attaching chemicals to our DNA to guide how our genes will function in our circumstances. These epigenetic changes do not alter our actual genetic code. Instead, they simply attach to the surface of our genes (“epi”) to tell them what to do and how to do it – make proteins and enzymes or not; do it fast or slow, go full-bore or not at all, etc.

Meaney and his colleagues have since found that gene function in humans, like in rat pups, is similarly affected by adverse early life experiences.  In other words, maternal bonding in humans has an impact on genes just as it does in in rat pups.

Adverse experiences during pregnancy are also associated with epigenetic changes in cord blood ⁽⁴³⁾Turecki, G. and M. J. Meaney (2016). “Effects of the Social Environment and Stress on Glucocorticoid Receptor Gene Methylation: A Systematic Review.” Biol Psychiatry 79(2): 87-96. Abstract.

Prenatal stress alters genes in babies and epigenetic changes are found in cord blood.

The effects of prenatal stress can influence very specific cell and tissue types as well as the HPA based stress response (Turecki, 2016).

What this means is that life experiences can have a very specific impact on particular tissues or cells.

This helps explain why one person who experiences difficult events early in life develops RA/RD, while another develops ankylosing spondylitis and a third gets type 1 diabetes or multiple sclerosis. Or, in my case, chronic fatigue syndrome (ME/CFS) and asthma.

Researchers have also found that epigenetic changes add up. Changes are influenced by the amount of exposures to adverse events that happen over time, including in prenatal life, during birth, and in childhood.

VII. Epigenetics, Autoimmune Disease & Rheumatoid Disease

Epigenetic changes have been identified in a number of autoimmune diseases, including rheumatoid arthritis / rheumatoid disease (RA/RD). These changes are slightly different in each disease and are being identified in type 1 diabetes, lupus, inflammatory bowel disease, and other diseases ⁽⁴⁴⁾Meda, F., et al. (2011). “The epigenetics of autoimmunity.” Cell Mol Immunol 8(3): 226-236, ⁽⁴⁵⁾Wang, L., et al. (2015). “Human autoimmune diseases: a comprehensive update.” J Intern Med 278(4): 369-395.

Epigenetic Changes in RA/RD

One example of epigenetic change in RA/RD is seen in cells called “fibroblast-like synoviocytes (FLS). FLS represent a type of cell type involved in RA/RD. They are located inside joints in the synovium and function to make joints move more freely and easily. They also provide nutrients to cartilage in the joint areas and play a crucial role in chronic inflammatory diseases such as rheumatoid disease (more on wiki).

These FLS cells can be distinguished from FLS cells in people who have osteoarthritis (a common form of arthritis symptoms associated with “wear and tear” rather than an autoimmune process) and from people who are healthy.

Another study found that as many as 1,859 loci that were relevant to cell movement and other cell functions (“adhesion and trafficking”), were epigenetically altered in RA/RD compared with osteoarthritis ⁽⁴⁶⁾Viatte, S., et al. (2013). “Genetics and epigenetics of rheumatoid arthritis.” Nat Rev Rheumatol 9(3): 141-153, p. 149.

This speaks to a large number of changes influencing gene function in RA/RD.

For the purpose of today’s post this little glimpse tells us that there is evidence of effects of environmental risk factors in RA/RD ⁽⁴⁷⁾Holers, V. M. (2014). “Insights from populations at risk for the future development of classified rheumatoid arthritis.” Rheum Dis Clin North Am 40(4): 605-620, p6) and it will have many implications for treatment.

VIII. How Do We Interpret Early Risk Factors for RA/RD?

So what does one do on learning about the potentially important relationship between adverse babyhood experiences and rheumatoid disease / arthritis?

What if you have RA/RD but were born small or preterm, for example? How do you make sense of “borderline” risk for anything, such as being born cesarean? What about the fact that some studies show risk while others do not?

We’re discovering that risk factors for chronic illnesses like rheumatoid disease, type 1 diabetes, and other autoimmune and chronic diseases such as asthma are not purely mechanical, biological or genetic.

Our health is influenced by interactions with our environments. And this includes what we and our mothers experienced during conception and pregnancy, birth and infancy.

What we’re seeing is that there are complex interactions between risk factors. Some of these are understood. Few are recognized in medical practice.

IX. Making Sense of Andrea and RAW Readers’ Onset Stories

https://i0.wp.com/chronicillnesstraumastudies.com/wp-content/uploads/2014/11/trees-and-gray-background-to-thistles.jpg?resize=300%2C185&ssl=1 300w" sizes="(max-width: 630px) 100vw, 630px" />

Understanding the role of early risk factors may help explain events that happened to Andrea and readers of Kelly’s rheumatoid arthritis blog.

Andrea’s cesarean and lack of breastfeeding. As described above, cesarean sections affect a baby’s gut flora, increase risk for respiratory infections and perhaps most importantly, increase mother-baby separation and chances of bonding disruptions. They are also associated with decreased rates of breastfeeding, which may reflect exposures to stress.

Kate’s polio. Polio is a potentially life-threatening disease that can be associated with long periods of treatment, stress, and the likelihood of hospitalization and separation.

Julie’s illness. A life-threatening illness at birth can contribute to bonding interruptions through both emotional and physical separation. Illness in early life can may reflect other risk factors such as a prenatal stress, complicated birth, hospitalization(s) etc.

URandomnessK was born prematurely and has ankylosing spondylitis. They describe multiple challenging events related to their birth:

I was born … three and a half weeks premature. I was the first child to be carried “to term” and born to my parents. My mother had experienced ten years of fertility challenges including more miscarriages than she could ever count.  She begged and pleaded with G-d for ten years before being blessed with a child.  I was born with no complications but soon after … was diagnosed with asthma.

As discussed above, prenatal stress is a risk factor for premature birth and a decade long experience of miscarriages is a profound exposure to loss. Even with the blessing of finally having a child, there are many important risk factors for emotional and physical separation, bonding disruptions and other adversities in URandomnessK’s story. Their experience of asthma may be another indicator of stress, as described earlier and in greater detail in this blog post (Part 2).

Brenda’s birth defect(s). When the nervous and immune system and other organs undergo the process of growth in prenatal and early life, they are especially sensitive to their environments and are influenced by them. The timing of exposure has an effect on organs that are at particularly vulnerable stages of development. As a result, exposures to adverse babyhood experiences can influence the developing body, physiology and more to affect later health. Birth defects may also reflect prenatal exposure to toxins, medications and other factors.

X. Why It Helps to Understand the Role of Adversity in Early Life

https://i0.wp.com/chronicillnesstraumastudies.com/wp-content/uploads/2017/02/P1150438-Version-4.jpg?resize=300%2C183&ssl=1 300w, https://i0.wp.com/chronicillnesstraumastudies.com/wp-content/uploads/2017/02/P1150438-Version-4.jpg?resize=282%2C173&ssl=1 282w" sizes="(max-width: 640px) 100vw, 640px" />

If you have RA/RD or some other chronic disease illness, the research shows that it is not your fault, and not because you are lazy, weak or flawed.

The science also explains that illness arises when our exposure to adversity is larger or more intense than our experiences of support, nurturing and safety.

This means that disease may be much more reversible, treatable and manageable than our current model of health currently understands. The science of epigenetics supports this too because epigenetic changes are potentially reversible.

The science also shows us that we are actually remarkably resilient. In other words, it tends to take a lot of events to lead to illness and to changes in brain structure ((Wadhwa, P. D., et al. (2009). “Developmental origins of health and disease: brief history of the approach and current focus on epigenetic mechanisms.” Semin Reprod Med 27(5): 358-368.

This science suggests there is potential for reversibility of RA/RD. We see this already in the way that RA/RD sometimes resolves in childhood or regresses when caught early (Holers). And that some adults recover from RA/RD.

Stories of recovery from RA/RD and of improvement and cures of asthma in children provide new tools that can support the possibility of working with, decreasing or even healing symptoms.

Understanding the effects of adversity can also help make sense of and work with, decrease or even prevent flare-ups.

These 10 tools will give you resources and a context for approaching health and healing from the nervous system and epigenetic perspectives presented here.

Here’s a list of therapies for working with difficult events in early life – whether you are an adult with RA/RD, the parent of a child with JIA or planning a pregnancy.

XI. Summary of ABEs and Rheumatoid Disease

Here’s a summary of the research links between adverse babyhood experiences and rheumatoid disease / arthritis and the major points made in this article.

Autoimmune Diseases

• Autoimmune diseases require environmental events to trigger autoimmunity
• Environmental events interact with genes through the process of epigenetic changes
• Epigenetic changes have been found in many autoimmune diseases
• Epigenetic changes are potentially reversible
• Chronic disease may be reversible too
• Environmental events capable of altering genes include life experiences

Rheumatoid Disease

1. Antibodies for RA/RD arise years before onset, suggesting risk in early life
2. Early risk factors for RA/RD include emotional and physical stress and separation
3. Risk factors for RA/RD may reflect bonding interruptions and prenatal stress
4. Bonding interruptions and prenatal stress alter epigenetics in babies
5. Epigenetic changes have been found in RA/RD and other autoimmune diseases
6. Indicators of adverse babyhood experiences may include small or large birth size, cesarean birth, breastfeeding rates, hospitalization in first year, premature or late birth, a mother’s history of loss and adversity, and other events

Related Posts:

Adverse Babyhood Experiences and Chronic Illness (Free ABE Fact Sheets & Checklist)

Adverse Childhood Experiences (ACEs) and RA/RD

Adverse Childhood Experiences (ACEs) and Risk for Chronic Illness

Part 1: What Causes Chronic Illness? Early Risk for Type 1 Diabetes

Part 2: Early Risk Factors for Asthma and Keys to Healing

Part 3: Epigenetics in Early Life and Risk for Chronic Disease