Arthritis risk and birthweight

“Women are more likely to develop rheumatoid arthritis later in life if they were heavy at birth,” reported The Guardian . The newspaper reported that a major study of the condition, which affects 400,000 people in the UK, found that those who weigh more than 10lb (4.54kg) at birth are twice as likely to develop it than those of an average birth weight.

The report was based on a study in a population of nurses from 1976 to 2002. This particular publication investigated the effect of birth weight on the risk of developing rheumatoid arthritis. Rheumatoid arthritis is a complex autoimmune condition where the sufferer’s immune system targets tissue in the joints.

This study may have identified a birth weight above which the risk of the condition increases. However, the causes of rheumatoid arthritis are not certain. Genetics have a strong association, and other environmental and hormonal factors have also been implicated. Therefore, the cause is unlikely to be a single factor such as birth weight. More research is now needed to confirm the findings and further quantify the possible role that birth weight and other factors have in the development of this condition.

Where did the story come from?

Dr LA Mandl and colleagues from Weill Cornell Medical College in New York, Brigham and Women’s Hospital and Harvard Medical School carried out the research. The study was funded by the National Institute of Health. The investigators were supported by various awards, including an award from the American College of Rheumatology, and the National and New York State Arthritis Foundations. The study was published in the peer-reviewed medical journal Annals of Rheumatic Diseases .

What kind of scientific study was this?

In this prospective cohort study, the researchers investigated the relationship between birth weight and rheumatoid arthritis. This study used data from 87,077 women who were followed as part of a larger study called the Nurses’ Health Study. The women were aged between 30 and 55 years of age when they  enrolled in 1976. At the beginning of the study they completed a questionnaire asking about their health status, age, smoking history, weight, height, father’s occupation when the nurse was 16 years old, and reproductive history. From this point on, they completed follow-up questionnaires every two years about their lifestyle, health, and family medical history. In 1992, the questionnaire also asked about birth weight, and only those who responded to this were included in later analyses.

The researchers contacted all women who had at any point between 1976 and 2002 reported rheumatoid arthritis (RA) or another connective tissue disease (CTD) - inflammatory conditions, usually autoimmune, which affect the collagen and elastin in the body. The researchers also asked permission to review the womens’ medical records to confirm these diagnoses. This confirmed 683 new cases of rheumatoid arthritis (out of 13,639 women who reported RA or CTD at baseline or during follow up). Women who had reported cancer at any point, or those who reported having a CTD at the beginning of the study, were not included in this analysis. Those who had reported having rheumatoid arthritis, but for whom it was not possible to confirm their diagnosis, were also excluded. Of these 683 women, 619 of them had responded to the question about birth weight and these were included in the final analysis.

The researchers analysed the relationship between self-reported birth weight and new cases of rheumatoid arthritis. As the women had been contacted regularly throughout the follow-up period, the researchers were able to take into account other factors that can affect birth weight or incidence of RA, e.g. BMI, smoking, use of oral contraceptives, age, age at menarche (first menstruation), father’s occupation at age 16 (as a measure of socioeconomic status), birth location, breastfeeding, maternal size, and maternal diabetes.

What were the results of the study?

Women who reported a birthweight greater than 4.54kg were twice as likely to have new onset rheumatoid arthritis than those with normal birthweight (3.2 to 3.85kg) during the study follow-up period. There was no significant relationship between the participants’ fathers’ occupation or mothers’ diabetes and rheumatoid arthritis, or between other birth weight categories and risk (compared to normal birth weight).

What interpretations did the researchers draw from these results?

The researchers concluded that their study has confirmed a statistically significant association between high birth weight and risk of rheumatoid arthritis.They said that foetal growth is “profoundly influenced by foetal nutrition and foetal environment, independent of genetics”, and that if nutrition has an impact on rheumatoid arthritis, it is a potentially modifiable factor.

What does the NHS Knowledge Service make of this study?

The researchers highlight several potential weaknesses with their study that should affect how the results are interpreted:

• The women self-reported their birth weight, and if they had given the wrong weight this would have affected the results. However, the researchers say that the use of self-report for birth weight has been validated in a separate study.
• Birth weight information was not available for a large number of women in this study who were excluded as a result. In answer to this, the researchers suggest that these women were not demographically different from those who responded, and so neither was their incidence of RA.
• The effects of several factors could have been measured more fully and some were not assessed at all. These include the following: socioeconomic status was only assessed by one question at age 16; body length at birth and childhood weight were not collected; gestational age was not determined; maternal diabetes data may have been inaccurate; genetic effects; nutrition. All of these factors could have played a part in increasing the risk of rheumatoid arthritis in some of the nurses.
• A baby’s weight at birth is due to both environmental and genetic factors. It is unclear what contribution each has on birth weight.

This study may have identified a birth weight above which the risk of rheumatoid arthritis increases. To confirm this, further studies that make a more comprehensive assessment of other factors linked to birth weight or disease need to repeat these findings.

Sir Muir Gray adds...

The fact that two phenomena are statistically related does not mean that the earlier causes the later.