Stressful or traumatic events experienced during pregnancy can have long-lasting effects on the fetus, yet these effects may not become apparent until many years later, according to a study suggesting that girls born of such pregnancies may be at greater risk for developing a painful muscle condition called fibromyalgia as adults.

The study, presented at the 6th International Congress of Neuroendocrinology (ICN 2006), shows how vulnerable a fetus is to “prenatal programming.” Indeed, animal studies presented at ICN 2006 indicate that a synthetic hormone commonly given to pregnant women at risk for delivering early can permanently affect the newborn’s neuroendocrine system and may have even more profound effects on those born in the next generation. ICN 2006 is being held at the David L. Lawrence Convention Center in Pittsburgh June 19 – 22.

Summaries of these studies’ findings follow:

Stress during pregnancy may put baby girls at later risk for fibromyalgia

New research suggests girls who were born following pregnancies that were encumbered by stressful life events may be at greater risk for developing fibromyalgia later in life. While little is known about the causes of fibromyalgia, a condition affecting mostly women and characterized by extreme fatigue and widespread muscle pain, the studies led by Dirk Hellhammer, Ph.D., professor of psychobiology at the University of Trier, Germany, indicate “prenatal programming” likely plays a role. Stress experienced during pregnancy can affect the development of the fetus’s adrenal gland, permanently limiting its capacity for producing adequate amounts of the hormone cortisol, he reports.

Compared to 100 healthy female control subjects, significantly more patients among the 93 women diagnosed with fibromyalgia reported their mothers had experienced profound stress during pregnancy, such as the loss of a partner, physical or emotional trauma or lack of social support. Moreover, of these patients born of such pregnancies, only the women had “blunted” cortisol response in a standardized measure of psychological stress, an observation that supported findings in animal studies. Furthermore, low cortisol levels were only observed in patients with a history of prenatal stress. While more study is needed, results collected so far provide strong evidence that girls may be at added risk for developing fibromyalgia if, while in the womb, they were exposed to higher than normal levels of cortisol produced by their mothers in response to stress.

Effects of steroid drug during pregnancy can span generations

A synthetic hormone commonly given to pregnant women at risk for delivering early not only can result in permanent changes to the newborn’s neuroendocrine system, but may have even greater effects on those born in the next generation, indicate results from animal studies.

Approximately 7 percent of pregnant women are treated with synthetic glucocorticoid to help hasten lung development when pre-term birth seems likely. Both animal and human clinical studies have shown the treatment could have long-term effects on neuroendocrine function and behavior. Using a guinea pig model, Stephen G. Matthews, Ph.D., professor, physiology, obstetrics & gynecology and medicine, University of Toronto, Faculty of Medicine, has shown that late-pregnancy exposure affects neurotransmitter systems – the brain’s primary communications vehicle – and makes fundamental changes to stress response mechanisms. Moreover, exposure in the womb to these synthetic hormones, which also have potent anti-inflammatory and immunosuppressive properties, can have life-long consequences. According to Dr. Matthews’ research, exposure affects the hypothalamic-pituitary-adrenal axis (HPA), which controls how the body responds to stress and is involved in regulation of energy balance and the immune system as well. Now, in more recent studies, his group is finding such effects extend to second generation offspring, in whom changes to HPA function and behavior are even greater than in those directly exposed. For instance, animals whose grandmothers were treated with glucocorticoids exhibit reduced levels of stress hormones and modified activity.

The unexplained pain experienced by patients with fibromyalgia is the result of a mismatch between sensory and motor systems, new research suggests.

In a study published in the journal Rheumatology, researchers asked patients to look at a reflection of one arm whilst moving their other in a different direction which was hidden behind the mirror.

This created a mismatch between what the brain sees via sensory input and what it feels through the motor system that controls movement.

Of the 29 patients involved in the study, 26 reported feeling a transient increase in pain, temperature change or heaviness in their hidden limb – all symptoms of a ‘flare up’ of their condition.

This suggests that a mismatch between sensory and motor neurons could be at the root of the fibromyalgia – a condition affecting one in 100 people in the UK at some stage of their lives.

“The chronic pain experienced by people with fibromyalgia is hard to understand because there are no obvious clinical signs that pain should be experienced,” said Dr Candy McCabe, one of the researchers involved in the University of Bath and Royal National Hospital for Rheumatic Diseases study.

“We have shown that by confusing the motor and sensory systems we can exacerbate the symptoms felt by people diagnosed with the condition.

“This adds to a growing body of evidence that many of the symptoms of this common disorder may be perpetuated, or even triggered, by this sensory-motor conflict.

“We have had some success to date in using a similar technique to help alleviate the symptoms of this kind of chronic pain.

“This works by helping the brain to see a limb moving freely without pain – although in reality it is a reflection of their pain-free limb.”

Volunteers in the study were asked to perform a series of bilateral upper and lower limb movements with a mirror in front of them at a right-angle.

This meant that one limb was obscured from view behind the mirror whilst they could clearly see the other limb and its reflection.

They first carried out the same movements with both limbs, and then made different movements.

This enabled the researchers to see what effect confusing what the brain could see with what it could feel.

“Nearly all of the group reported an increase in the sensations connected with their condition in the hidden limb,” said Dr McCabe.

“This provides strong evidence that sensory-motor conflict is at the heart of this condition.

“Some clinicians do not recognise fibromyalgia as a diagnosis because of a lack of clinical reason for the pain.

“It is often considered to be a reflection of anxiety or attention seeking behaviour which, for people with the condition, can be very hard to deal with.

“Nevertheless, fibromyalgia is one of the most common conditions seen by rheumatologists.

“Hopefully we are beginning to understand more about the condition, and taking steps towards how it might be treated in the future.”

People with fibromyalgia complain of widespread pain, multiple tender points, stiffness, sleep disturbance and fatigue.

Around nine out of ten of those affected by fibromyalgia are women. In most cases it develops between the ages of 30 and 60, but it can develop in people of any age, including children and the elderly.

There are around 14,700 new cases in the UK each year.