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The previous story
It is surprising that although clear reports were given in the pilot work of Ferguson and colleagues,1 Farthing and colleagues,2 and others about 20 years ago, coeliac disease (CD) has not yet gained popularity among obstetricians. In the subsequent two decades, many epidemiological studies clearly showed that it is a very common disease, that it affects women more than men, and that it has to be considered in relation to reproductive function.
The actual story
In the past few years several groups have shown that untreated CD is an important cause of abortion, poor outcome of pregnancy, and intrauterine growth retardation.3 4 Most authors agree that malnutrition could not have explained the reproductive difficulties of many, now most, coeliac women. Martinelli and colleagues5 recently found that 1 in every 70 pregnant women admitted to a major city hospital suffered from untreated CD: 70% had a poor outcome of pregnancy, and 8/9 women had a second healthy baby after one year on a gluten free diet.
But the paper of Ludvigsson and Ludvigsson in this issue ofGut 6 raises new questions on a well described story: an unfavourable neonatal outcome was not only associated with maternal CD but also with paternal CD, which is a new finding (see page 169). Infants of coeliac mothers weighed 222 g less than the population average, and infants of coeliac fathers weighed 266 g less than the population average. The risk of a low birth weight baby to coeliac fathers was five times higher than that in the general population (11% v 2.5%).
Ludvigsson and Ludvigsson6 report on a large (10 597 births) population based study with the drawback that it was limited to pregnant women who delivered a live baby: the results, although impressive, tend to underestimate the actual prevalence of untreated CD and the damage induced by undiagnosed disease. There is little doubt that more women who did not become pregnant, had an abortion, or who did not deliver a live baby need to be identified and inclusion of these women would change the results. Similarly, men who could not father a child need to be identified.
The other debatable point is the assumption that mothers with CD were all “treated”, which means free from gluten. Unfavourable neonatal outcome would then have not been corrected, or completely corrected, by the gluten free regimen. I agree that awareness of CD is increasing all over Europe and it may be that most diagnosed cases are “treated”, but all those involved in the care of CD patients are well aware of the complexity of adhering to a gluten free diet.
The main message of the paper is reinforced by the interesting comparison with diabetes and other autoimmune diseases. It is impressive to see that such symptomatic and severe diseases do not affect pregnancy outcome as much as CD! Diabetic fathers did not generate as many low birth weight babies as coeliac fathers (odds ratio between the two group 13.3). Curiously, the two infants born to both coeliac parents were healthy with a good birth weight: suspicion of a good or very good gluten free kitchen?
Finally, there was a constant significant correlation between the birth weight of infants born to mothers with CD and that of infants born to fathers with CD, but also with the birth weight of infants who had a sibling or other relative with CD. Thus it appears that there may be “coeliac families”.
A special genetic environment?
Autoimmunity is a reasonable candidate to explain the unfavourable outcome of pregnancy7 but it is hard to attribute this hypothesis to coeliac fathers. HLA, as declared by the authors, is unlikely to explain more than a small percentage of this “genetic pattern”. CD does not appear to be associated with major genetic defects but it may be caused by a pattern of several genetic “features” in term of genes involved in the immune response as well as those involved in cytokine action and signalling. Coeliac patients are a unique entity, not single individuals, with their own characteristics and features in terms of regulation of cytokines, specificity of immune responses, processing of food antigens, and so on. We still need the artist to paint a clearer portrait of the coeliac patient: many of us scribble on the paper in the attempt.
See article on page 169
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