Explaining Poor Pregnancy Outcomes in Women with Celiac Disease
Abstract & Commentary
By Sarah L. Berga, MD, James Robert McCord Professor and Chair, Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, is Associate Editor for OB/GYN Clinical Alert.
Dr. Berga is a consultant to Promedica Communications, Upsher-Smith Laboratories, Inc., Dannemiller Memorial Education Foundation, The Endocrine Society, QuatRx Pharm Company, Wyeth Pharmaceuticals, and Pfizer, and is on the speakers bureaus of Ascend Therapeutics, Inc., Novogyne Pharmaceuticals, and Merck Serono.
Synopsis: The poor pregnancy outcomes observed in women with celiac disease (gluten enteropathy), including a 9-fold increase in intrauterine growth restriction, may be explained in part by autoantibodies that bind to placental tissue transglutaminase and interfere with placental function, particularly nutrient import.
Source: Anjum N, et al. Maternal celiac disease autoantibodies bind directly to syncytiotrophoblast and inhibit placental tissue transglutaminase activity. Reprod Biol Endocrinol 2009;7:16.
Celiac disease is associated with poor reproductive outcomes, particularly fetal growth restriction, but the mechanisms mediating this association are not understood. In this study, the investigators sought to determine if autoantibodies obtained from women with celiac disease that are directed against enteric tissue transglutaminase cross-react with placental tissue transglutaminase and, if so, where the autoantibodies localized within the placenta.
To test the hypothesis, the investigators used autoantibodies recovered from women with celiac disease that were directed against enteric tissue transglutaminase (anti-tTG) and exposed the villous placenta. Monoclonal anti-tTG strongly stained the syncytial microvillus membrane as well as the cytotrophoblast and stromal and vascular elements. They noted that the microvillus membrane is critical to nutrient transport and that tTG plays a fundamental role in regulating placental viability in that it has GTPase activity and is a kinase involved in apoptosis.
Commentary
Celiac disease occurs in as many as 1 in 80 pregnant women. It is essentially an autoimmune disease caused by hyperimmunity/hypersensitivity to a class of proteins, called gliadins, which are found in the outer husk of common grains such as wheat, barley, rye, and oats. Once elicited, these autoantibodies react against mucosal proteins in gut, particularly tissue transglutaminase and endomysium, and provoke inflammatory damage to the small intestine, malabsorption, and nutritional deficiencies. Unrecognized and poorly managed celiac disease is associated with reproductive compromise, including anovulation, infertility, recurrent miscarriage, stillbirth, and intrauterine growth restriction. The mechanisms linking celiac disease and reproductive compromise are not clear, although nutritional deficiency has been implicated. Adherence to a gluten-free diet reduces both circulating autoantibodies and the risk of fetal growth restriction.1
In reproductive age women, celiac disease is as common as diabetes and thyroid disease. Most individuals have either a clinically silent form or only a minor enteropathy and most physicians do not screen for this condition in women contemplating conception or in those who are pregnant. Screening for celiac disease/gluten enteropathy can be readily accomplished by assaying serum for anti-endomysial and anti-tissue transglutaminase antibodies. Screening for both antibodies yields a higher detection rate than either antibody alone. If positive, further evaluation may be necessary.
Women with celiac disease are at risk for nutritional deficiencies, particularly of folic acid, iron, and vitamin D, all of which are critical during pregnancy. Women with celiac disease may develop or have other autoimmune conditions, including eczema, dermatitis herpetiformis, cutaneous vasculitis, connective tissue diseases, Hashimoto's thyroiditis, and Graves' disease. Celiac disease is thought to be primarily genetic in origin, although overexposure to gluten, which is commonly used as a stabilizer in processed foods, may increase the risk. In one study, the concordance in monozygotic twins was 83% and 17% in dizygotic twins.2
In summary, women who are pregnant or contemplating pregnancy who have even minor gastrointestinal complaints may wish to be screened for celiac disease, especially if there is a personal or family history of autoimmune thyroiditis, insulin-dependent diabetes mellitus, or other autoimmune conditions.
References
- Ludvigsson JF, et al. Celiac disease and risk of adverse fetal outcome: A population-based cohort study. Gastroenterology 2005;129:454-463.
- Nistico L, et al. Concordance, disease progression, and heritability of coeliac disease in Italian twins. Gut 2006;55:803-808.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content