NEW YORK—June 30, 2008
People who have a birth weight over 10 pounds are twice as likely to develop rheumatoid arthritis when they are adults compared to individuals born with an average birth weight, according to a study published by researchers from Hospital for Special Surgery online in advance of print in the Annals of the Rheumatic Diseases. While the mechanism for this association is unclear, the study identifies a potentially modifiable risk factor and highlights a potential way to decrease the incidence of the disease.
“There may be a relationship between being born over 10 pounds and getting rheumatoid arthritis later in life,” said Lisa Mandl, M.D., MPH, who led the study and is an attending rheumatologist at Hospital for Special Surgery (HSS) in New York City. “If there was some way that you could prevent someone from getting rheumatoid arthritis by making sure their birth weight wasn’t over 10 pounds, this is a risk factor that could be modifiable. You can’t change someone’s age. You can’t change someone’s gender, but potentially, you could change someone’s birth weight. This is, however, only speculative at this point.”
Previously, investigators have demonstrated that an increased risk of adult onset chronic disease can be a function of the fetal environment. Strong associations between low birth weight and an increased risk of type 2 diabetes mellitus, coronary heart disease and hypertension have been documented in a number of different populations. Published in 2003, a case-control study of roughly 400 individuals in Sweden identified an association between high birth weight and rheumatoid arthritis.
To see if this association played out in a larger population, Dr. Mandl and colleagues turned to a study of 87,077 women in the Nurses’ Health Study. In 1976, nurses were invited to participate in this study, which involved a baseline survey and then a biennial questionnaire regarding health status, lifestyle, family medical history and health practices. The investigators excluded women who had cancer or any type of connective tissue disease at baseline or follow-up because these can cause joint swelling, symptoms that can be confused with rheumatoid arthritis. Also excluded were women who reported having rheumatoid arthritis or connective tissue disease during follow-up, but in whom the diagnosis could not be confirmed by review of their medical record. The study population included only women who answered a 1992 survey that collected information about birth weight. After these exclusions, 87,077 individuals were included in the study and 619 of them developed rheumatoid arthritis.
Through statistical analysis, the investigators discovered that a birth weight of greater than 4.54 kg doubled the risk that a person would develop rheumatoid arthritis as an adult compared with individuals who had an average birth weight.
“In utero, the fetus will react appropriately to different stressors. However, this may preprogram the fetus so that when it gets out into the world, this preprogramming is not helpful out in the ‘real world’,” said Dr. Mandl. In other words, the fetal environment may be preprogramming people’s brains or endocrine systems to be maladapted in later life.
“There have now been two different groups, in different countries with different patients born at different times, that both suggest a similar relationship between birth weight and rheumatoid arthritis,” said Dr. Mandl. “I hope that other people will think about looking for this association in other populations.”
Dr. Mandl said that patients with rheumatoid arthritis are known to have a dysregulated hypothalamic-pituitary-adrenal (HPA) axis, and this axis may be affected in utero. The HPA axis is the body’s neuroendocrine system that involves the hypothalamus, pituitary and adrenal glands; this system is responsible for handling stress by regulating the production of cortisol, neurotransmitters and key hormones.
“If you look at this as a theoretic biologic underpinning for why this might be true, it might give basic scientists interesting ideas to think about regarding what causes rheumatoid arthritis, and provide support for a new hypothesis,” Dr. Mandl said.
According to the National Institute of Arthritis and Musculoskeletal and Skin Diseases, about 2.1 million people, or between 0.5 and 1 percent of the U.S. adult population, have rheumatoid arthritis, an autoimmune disease that causes chronic inflammation of the joints. The disease is more common in women and has no cure, but can be managed in a way that allows individuals to live productive lives.
In addition to researchers from Hospital for Special Surgery and Weill Cornell Medical College, investigators from the Brigham and Women’s Hospital, Harvard Medical School contributed to the study. This research was supported by grants from the National Institutes of Health.
About HSS | Hospital for Special Surgery
HSS is the world’s leading academic medical center focused on musculoskeletal health. At its core is Hospital for Special Surgery, nationally ranked No. 1 in orthopedics (for the eighth consecutive year) and No. 3 in rheumatology by U.S. News & World Report (2017-2018). Founded in 1863, the Hospital has one of the lowest infection rates in the country and was the first in New York State to receive Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center four consecutive times. The global standard total knee replacement was developed at HSS in 1969. An affiliate of Weill Cornell Medical College, HSS has a main campus in New York City and facilities in New Jersey, Connecticut and in the Long Island and Westchester County regions of New York State. In 2017 HSS provided care to 135,000 patients and performed more than 32,000 surgical procedures. People from all 50 U.S. states and 80 countries travelled to receive care at HSS. In addition to patient care, HSS leads the field in research, innovation and education. The HSS Research Institute comprises 20 laboratories and 300 staff members focused on leading the advancement of musculoskeletal health through prevention of degeneration, tissue repair and tissue regeneration. The HSS Global Innovation Institute was formed in 2016 to realize the potential of new drugs, therapeutics and devices. The culture of innovation is accelerating at HSS as 130 new idea submissions were made to the Global Innovation Institute in 2017 (almost 3x the submissions in 2015). The HSS Education Institute is the world’s leading provider of education on the topic on musculoskeletal health, with its online learning platform offering more than 600 courses to more than 21,000 medical professional members worldwide. Through HSS Global Ventures, the institution is collaborating with medical centers and other organizations to advance the quality and value of musculoskeletal care and to make world-class HSS care more widely accessible nationally and internationally.