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Coeliac disease and birth defects in offspring
  1. Pediatric Department
  2. National Research Institute of Mother and Child
  3. ul.Kasprzaka 17a, 01-211 Warsaw, Poland
  4. khozyasz{at}
  1. L GRECO
  1. Pediatra all'Ateneo Federico II di Napoli
  2. Via Pansini 5 80131, Napoli, Italy
  3. ydongre{at}

Statistics from

Editor,—I read with interest the paper by Martinelli et al (Gut 2000;46:332–335) and letter by Unsworthet al (Gut 2000;47:598) which stress the high prevalence of coeliac disease in anaemic pregnant women. Untreated coeliac disease can adversely affect the reproductive system and result in infertility, multiple abortions, low birth weight babies, and short breast feeding periods.1 2 A low plasma level of folic acid is a common finding in newly diagnosed patients3: there are good theoretical reasons for hypothesising that coeliac disease could also be a maternal risk factor for birth defects.4 5 The seven coeliac women identified in the study of Martinelli et al had a further pregnancy and reached term. One of them had a boy with a major cardiac malformation; she was the only one on a gluten containing diet.

I examined sera from 40 mothers of children with non-syndromic spina bifida, 37 mothers of children with non-syndromic cleft lip with or without cleft palate, and 24 mothers of children with isolated cleft palate.6 I found that 1/40 and 1/37 women were positive for IgA class antiendomysium antibody (AEA). Jejunal biopsy of the mother of a child with cleft lip and palate showed normal villous height/crypt depth ratio and increased number of intraepithelial lymphocytes; jejunal biopsy of the mother of a child with spina bifida was normal. Both AEA positive women were two of the four smallest (<155 cm) among all investigated mothers (n=101). Coeliac patients have acquired the reputation of being short in stature but tall patients do exist.3

Frequent reports of increased reproduction problems in women with untreated coeliac disease emphasise the importance of early and correct diagnosis followed by adherence to a gluten free diet. Health care professionals need to recognise the manifestations of the disease in women of reproductive age and be prepared to use serological screening tests more frequently to identify patients who could benefit from dietetic treatment.

I suggest that coeliac disease should be considered as a cause of birth defects associated with folic acid deficiency (for example, spina bifida,7 orofacial clefts,8 heart defects9) in offspring of women of short stature.



Editor,—Women affected by untreated coeliac disease have indeed a considerable risk of having low birth weight babies and unfavourable outcome of pregnancy. Very recently in Sweden it was suggested that offspring of coeliac fathersare also at risk of low birth weight.1-1 1-2 The mean birth weight of offspring of mother and fathers with untreated CD is 2–300 g less than the offspring of mothers or fathers affected by other autoimmune diseases. The authors of the large population based Swedish study suggest that there are “coeliac” families in which the risk of unfavourable outcome of pregnancy is considerable.

Folate deficiency is one of the suggested explanations but it is unlikely to explain the large series of problems in women with no gastrointestinal signs of the disease, and mostly no signs of malabsorption.

Now Hozyasz reports that 1/40 mothers of spina bifida children and 1/37 mothers of children with cleft lip were found to have untreated coeliac disease at endomysium antibody screening, one of whom was confirmed at biopsy. Both of these women were very short in stature but unfortunately no data on their folate status were reported.

How much do these isolated numbers of women indicate a special risk of untreated coeliac women? Not very much: if we had to compare the data of Hozyasz with the expected prevalence rate among a cohort of women (with or without an unfavourable outcome of pregnancy), their values would be well within the 95% confidence interval of a rate of 1%. We reported a rate of 1:70 among a general population of pregnant women1-3 which would be compatible with the number reported by Hozyasz. The increasing sensitivity of the screening tests now available for coeliac disease (antiendomysium and antitransglutaminase) is likely to gradually change the estimate of the population prevalence of the disease,1-4but also, repetition of screening over time increases considerably the rate of identification of previously negative cases.1-5

I personally feel that we have little evidence that coeliac disease should be considered “ a cause of birth defects associated with folic acid deficiency...” but I do agree that doctors and obstetricians should widely screen for coeliac disease as they do (often overdo) for many quite rare diseases.


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