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LETTERS
William H. James, PhD
University College London
London, UK
1. James WH. The difficulties in establishing a birth order or maternal
age effect in ankylosing spondylitis: comment on the article by
Baudoin et al [letter]. Arthritis Rheum 2002;46:563–4.
2. Baudoin P, van der Horst-Bruinsma IE, Dekker-Saeys AJ, Weinreich S, Bezemer PD, Dijkmans BAC. Increased risk of developing
ankylosing spondylitis among first-born children. Arthritis Rheum
2000;43:2818–22.
3. Said-Nahal R, Miceli-Richard C, Dougados M, Breban M. Increased risk of ankylosing spondylitis among first-born children:
comment on the article by Baudoin et al [letter]. Arthritis Rheum
2001;44:1964–5.
4. Brophy S, Taylor G, Calin A. Birth order and ankylosing spondylitis: no increased risk of developing ankylosing spondylitis among
first-born children. J Rheumatol 2002;29:527–9.
DOI 10.1002/art.10702
Reply
To the Editor:
Recently, Dr. James discussed the statistical method
used in our study (1). The point of discussion now concentrates
on the issue of whether an individual with AS has an equal
probability of being first-, second-, or later-born. Dr. James is
correct that our method is based on the assumption that, in the
absence of a relationship between AS and birth order, the
probability of being first-, second-, . . . nth-born would be equal
within each family size. He states that this assumption is almost
certainly invalid for our study population, because family size
distribution is not constant over time. This reasoning would
correctly apply to a cross-sectional, random sample (especially
of the elderly) but is not applicable to our study population.
Our AS patients were followed up at our outpatient clinic
shortly after diagnosis (at relatively young ages) during a long
period of many years. If Dr. James’ reasoning would still apply
to our study population, the arguments for a relationship
between AS and birth order would be even stronger, because
we observed relatively higher numbers of patients who were
first-born (for review, see ref. 1, Tables 2 and 4). Moreover, we
already observed this relationship within families with 2 children.
We agree that use of a control sample, providing more
direct evidence, would be fine, but use of a control sample is
not necessary to reach the conclusion presented in our article.
The fact that our data on the birth order effect were not
confirmed by Brophy et al (2) is, however, disappointing. The
lower mean maternal age at first delivery of (healthy) mothers
of AS patients compared with mothers of healthy controls that
was observed in our study was not taken into account by
Brophy et al. This relationship cannot be explained by the
observations of other investigators (3), i.e., that mothers with
early symptoms of AS are more likely to pass on the disease to
their children, because all of the mothers in our study were
healthy. Therefore, we still believe that there is an effect of
both lower maternal age at first delivery, as was observed in
animal models, as well as birth order (being first-born) that
increases the risk of AS.
Irene E. van der Horst-Bruinsma, MD, PhD
P. Dick Bezemer, PhD
Ben A. C. Dijkmans, MD, PhD
Vrije Universiteit Medical Centre
Amsterdam, The Netherlands
1. Baudoin P, van der Horst-Bruinsma IE, Dekker-Saeys AJ, Weinreich S, Bezemer PD, Dijkmans BAD. Increased risk of developing
ankylosing spondylitis among first-born children. Arthritis Rheum
2000;43:2818–22.
2. Brophy S, Taylor G, Calin A. Birth order and ankylosing spondylitis: no increased risk of developing ankylosing spondylitis among
first-born children. J Rheumatol 2002;29:527–9.
3. Calin A, Brophy S, Blake D. Impact of sex on inheritance of
ankylosing spondylitis: a cohort study. Lancet 1999;354:1687–90.
DOI 10.1002/art.539
Erratum
In the article by Delgado Alves et al published in the October 2002 issue of Arthritis & Rheumatism (pp
2686–2694), the name of the fifth author was spelled incorrectly. The correct spelling is J. Nourooz-Zadeh.
We regret the error.