A risk factor for female fertility and pregnancy: Celiac disease

Laboratory of Comparative Toxicology and Ecotoxicology, Istituto Superiore di Sanità, Rome, Italy.
Gynecological Endocrinology (Impact Factor: 1.33). 01/2001; 14(6):454-63. DOI: 10.3109/09513590009167719
Source: PubMed


Celiac disease is a genetically-based intolerance to gluten. In the past, celiac disease has been considered a rare disease of infancy characterized by chronic diarrhea and delayed growth. Besides the overt enteropathy, there are many other forms which appear later in life; target organs are not limited to the gut, but include liver, thyroid, skin and reproductive tract. It is now recognized that celiac disease is a relatively frequent disorder; the overall prevalence is at least 1:300 in Western Europe. Celiac disease may impair the reproductive life of affected women, eliciting delayed puberty, infertility, amenorrhea and precocious menopause. Clinical and epidemiological studies show that female patients with celiac disease are at higher risk of spontaneous abortions, low birth weight of the newborn and reduced duration of lactation. No adequate studies are available on the rate of birth defects in the progeny of affected women; however, celiac disease induces malabsorption and deficiency of factors essential for organogenesis, e.g. iron, folic acid and vitamin K. The overall evidence suggests that celiac disease patients can be a group particularly susceptible to reproductive toxicants; however, the pathogenesis of celiac disease-related reproductive disorders still awaits clarification. At present, like the other pathologies associated with celiac disease, the possible prevention or treatment of reproductive effects can only be achieved through a life-long maintenance of a gluten-free diet.

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    • "Moreover, it is intriguing that despite the high frequency of folate deficiency in untreated celiac patients [16], the suspected association between maternal CD and an increased risk of nonsyndromic structural malformations in CD patient offspring has received no support from large studies focused on unfavourable outcomes of pregnancy in untreated CD women [17, 18]. The suspected association was considered to be a consequence of hyperhomocysteinemia due to folate deficiency [19–21]. "
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    ABSTRACT: Celiac disease (CD) is a polygenic chronic enteropathy conferring an increased risk for various nutrient deficiency states. Hyperhomocysteinemia is a frequent finding in CD and may be related to the development of venous thrombosis, cardiovascular disease, and stroke in untreated CD patients. Recently, a possible excess in the frequency of the MTHFR c.677C>T (rs1801133) gene variant in CD patients was reported. The purpose of this study was to determine if there exist differences in the distribution of polymorphic variants of genes involved in homocysteine/methyl group metabolism between CD patients and the general population. A set of 10 gene polymorphisms (MTHFR rs1801133, MTR rs1805087, MTHFD1 rs2236225, MTRR rs1801394, CBS 844ins68, BHMT1 rs7356530 and rs3733890, BHMT2 rs526264 and rs625879, and TCN2 rs1801198) was tested in 134 patients with CD and 160 matched healthy controls. The frequency of the MTR rs1805087 GG genotype in CD patients was lower than in controls (0.01 and 0.06, respectively), although statistical significance was not achieved (P = 0.06). For the other analyzed polymorphisms, there was no evidence of difference in both allelic and genotypic distribution between cases and controls. The exhaustive Multifactor Dimensionality Reduction analysis revealed no combination of interactive polymorphisms predicting the incidence of CD. In contrast to the well-documented clinical observations of increased risks of vascular disease in patients with longstanding untreated CD, in our group of patients no significant association with CD was found for all tested polymorphic variants of genes involved in homocysteine metabolism. These findings should be replicated in studies with a larger sample size. Electronic supplementary material The online version of this article (doi:10.1007/s11033-011-1077-7) contains supplementary material, which is available to authorized users.
    Full-text · Article · Jun 2011 · Molecular Biology Reports
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    • "Several studies have shown an association between celiac disease and women's fertility disorders or pregnancy and puerperal disorders [10-18,22], whereas some other studies have assumed a potential role for celiac disease among the other causes of women's infertility [23]. Instead in a study published in 2005, Tata et al. affirmed that, women with celiac disease have fertility similar to that of the general female population, but they have their babies at an older age [24]. "
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    ABSTRACT: The aim of this study is to explore the association between celiac disease and menstrual cycle, gestation and puerperal disorders. The association between celiac disease and menstrual cycle, gestation and puerperal disorders in a sample of 62 childbearing age women (15-49 age) was assessed within an age and town of residence matched case-control study conducted in 2008. Main outcome measures were the presence of one or more disorders in menstrual cycle and the presence of one or more complication during pregnancy. 62 celiac women (median age: 31.5, range: 17-49) and 186 healthy control (median age: 32.5, range: 15-49) were interviewed. A higher percentage of menstrual cycle disorders has been observed in celiac women. 19.4% frequency of amenorrhea was reported among celiac women versus 2.2% among healthy controls (OR = 33, 95% CI = 7.17-151.8;, p = 0.000). An association has been observed between celiac disease and oligomenorrhea, hypomenorrhea, dysmenorrhea and metrorrhagia (p < 0.05). The likelihood of having at least one complication during pregnancy has been estimated to be at least four times higher in celiac women than in healthy women (OR = 4.1, 95% CI = 2-8.6, p = 0.000). A significant correlation has emerged for celiac disease and threatened abortion, gestational hypertension, placenta abruption, severe anaemia, uterine hyperkinesia, intrauterine growth restriction (p < 0.001). A shorter gestation has on average been observed in celiac women together with a lower birth weight of celiac women babies (p < 0.001). The occurrence of a significant correlation between celiac disease and reproductive disorders could suggest to consider celiac disease diagnostic procedures (serological screening) in women affected by these disorders.
    Full-text · Article · Aug 2010 · BMC Gastroenterology
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    • "People suffering from coeliac disease react with inflammation of the small intestine, leading to malabsorption of several important nutrients including iron, folate, calcium and fat soluble vitamins (Feighery, 1999; Murray, 1999). Clinical and epidemiological studies have showed coeliac disease to be a risk factor for cancer (Silano et al., 2007), osteoporosis (Sategna-Guidetti et al., 2000), thyroid disease (Sategna-Guidetti et al., 1998), female infertility (Stazi & Mantovani, 2000), neurological and psychiatric disorders (Ludvigsson, Osby, Ekbom, & Montgomery, 2007; Tengah, Wills, & Holmes, 2002). Therefore a strict gluten-free diet – without cereals containing gluten proteins (wheat, barley, rye, triticale, dinkel and kamut) is essential (Gallagher, Gormley, & Arendt, 2004). "
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    ABSTRACT: Folate content in some gluten-free cereal products and their main ingredients was determined using a validated method based on reversed-phase high performance liquid chromatography (HPLC) with fluorescence and diode array detection. The main folate forms found in gluten-free products were 5-methyl-tetrahydrofolate and tetrahydrofolate. Starches and low protein flours commonly used as main components in gluten-free products appeared to be poor folate sources with folate content ⩽6 μg/100 g fresh weight. Folate content in gluten-free breads was higher (15.1–35.9 μg folate/100 g fresh weight) due to use of bakery yeast which is a rich folate source. Overall, folate content in gluten-free products was lower than in their gluten-containing counterparts. Therefore, fortification of gluten-free products with folic acid or enrichment of these products with nutrient-dense fractions of cereals naturally free from gluten (such as buckwheat, quinoa, amaranth or millet) can be of interest.
    Full-text · Article · Nov 2008 · Food Chemistry
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