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    Overall Fertility Normal in Celiac Women, but Lower Last Two Years Before Diagnosis


    Jefferson Adams
    Image Caption: Photo: CC- sean dreilinger

    Celiac.com 10/07/2011 - A number of studies suggest that women with celiac disease have reproductive difficulties, but data have been inconclusive and contradictory.


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    A research team recently set out to assess fertility in women with biopsy-verified celiac disease. The study team included Daniela Zugna, Lorenzo Richiardi, Olof Akre, Olof Stephansson, and Jonas F Ludvigsson.

    Photo: CC- sean dreilingerThey are affiliated variously with the Cancer Epidemiology Unit at the Centre for Experimental Research and Medical Studies and Centre for Oncologic Prevention at the University of Turin in Turin, Italy, the Department of Paediatrics at Örebro University Hospital in Örebro, Sweden, and with Clinical Epidemiology Unit of the Department of Medicine, the Department of Molecular Medicine and Surgery, the Division of Obstetrics and Gynaecology, and the Department of Women's and Children's Health at the Karolinska Institutet in Karolinska, Sweden.

    For their Swedish population-based cohort study, the team gathered data all 28 pathology departments in Sweden on 18,005 biopsy-proven duodenal/jejunal biopsy, using Marsh III, villous atrophy as their baseline.

    They also established a control group of 51,109 age-matched women without celiac disease.

    They then found 11,495 women with celiac disease who were aged 18–45 years.

    The team used multinomial logistic regression and Cox regression to estimate fertility in these women compared with the age-matched reference women.

    The team defined 'fertility' as the number of children according to the Swedish Multi-Generation Register.

    Their results showed that women with celiac disease had 16,309 births compared with 69,245 for the reference group.

    Overall, the total number of children in the group of women with celiac disease was slightly higher compared with the reference group.

    Adjusting for age, calendar period and parity and stratifying by education, the overall fertility hazard ratio (HR) for women with celiac disease was 1.03 (95% CI 1.01 to 1.05).

    Specifically, the fertility HR was 1.05 (95% CI 0.96 to 1.14) for celiac disease diagnosed in women under 18-years of age, 1.04 (95% CI 1.01 to 1.07) for celiac disease diagnosed in women between 18 and 45 years, and 1.02 (95% CI 0.99 to 1.04) for celiac disease diagnosed in women >45 years of age.

    Factoring in the dates of celiac disease diagnosis, fertility was decreased 0–2 years before time of diagnosis (HR=0.63; 95% CI 0.57 to 0.70),

    but was identical to that of controls 0–5 years subsequent to diagnosis and increased to 1.12 (95% CI 1.03 to 1.21) thereafter.

    The data for this study show that women with celiac disease had a normal fertility, but their fertility was decreased in the last two years before diagnosis.

    Interestingly, fertility in women with celiac disease was also slightly higher after five years, comported to the control group.

    Stay tuned...

    Source:

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  • Related Articles

    Scott Adams
    Gastroenterology, 2005; 128: 849-855
    Celiac.com 04/29/2005 – In contrast to previous studies, the findings of a study by researchers in the United Kingdom indicate that women with celiac disease do not have an increased risk of infertility. Their study compared computerized primary care data on 1,521 women with celiac disease, and, unlike past studies, compared that data with 7,732 age and practice-matched women without celiac disease. They found that fertility rates were 48.2 live births per 1,000 person-years for women without celiac disease, while those with the disease had 47.7 live births. Interestingly the researchers found that women with celiac disease had lower fertility rates when they were younger, and higher rates when they were older, compared to the non-celiac group, and the increase in fertility seen in older women with the disease was not affected by whether they were on a gluten-containing vs. gluten-free diet. The researchers noted a slightly higher risk of miscarriage and delivery by cesarean section in the group of women with celiac disease, while all other negative outcomes occurred at a level similar to that of the healthy control group. The researchers conclude that women with celiac disease have similar fertility rates to that of the normal female population, and they tend to have their babies at an older age.

    Jefferson Adams
    10/05/2009 - Pregnant women with celiac disease suffer early pregnancy loss more often than women without celiac disease. A team of Italian researchers recently set out to look at a possible role of genetic pro-thrombotic variants in early pregnancy loss in women with celiac disease.
    The research team was made up of C. Ciacci, R. Tortora, O. Scudiero, R. Di Fiore, F. Salvatore, and G. Castaldo. The team looked at 39 women with celiac disease, who had experienced at least two early pregnancy losses within the first 3 months of pregnancy, a control group of 72 celiac women with a history of one or more normal pregnancies with no pregnancy loss.
    Each of the women were enrolled in the study immediately upon diagnosis for celiac disease, whereupon, the researchers obtained a clinical history obtained from each woman.
    The researchers then screened leukocyte DNA for factor V Leiden (mutation G1691A), factor V R2 (H1299R), factor II (G20210A), methylenetetrahydrofolate reductase
    (MTHFR) (C677T and A1298C), beta-fibrinogen (−455 G>A), PAI-1 alleles 4G/5G, factor XIII (V34L), and HPA-1 (L33P).
    Women with pregnancy losses were notably older (p = 0.002) among the celiacs than in controls. Of the gene variants examined, the allelic frequency of 4G variant of PAI-1, and the frequency of mutant genotypes were significantly more frequent in the group of celiac women with early pregnancy loss (p = 0.00003 and 0.028, respectively).
    Interestingly, the beta-fibrinogen −455 G>A genotype distribution differs substantially between the two groups, though frequency of the variant allele remains the same. The control group showed more frequent variant genotypes (p = 0.009).
    Based on these data, the research team believes the 4G variant of the PAI-I gene may predispose some celiac women who carry the gene to early pregnancy loss, though they note that their data should be confirmed on larger populations.

    Digestive and Liver DiseaseVolume 41, Issue 10, October 2009, Pages 717-720


    Jefferson Adams
    Celiac.com 03/04/2015 - Women with infertility face higher rates of celiac disease, according to a recent data analysis.
    Until now, data connecting celiac disease and infertility has been contradictory. There are currently no recommendations regarding celiac disease screening in female patients with infertility.
    A research team recently conducted a meta-analysis to find out whether women with infertility have a higher risk for celiac disease. The team included Prashant Singh MBBS; Shubhangi Arora MBBS; Suman Lal MD; Tor A. Strand MD, PhD; and Govind K. Makharia MD, DM, DNB, MNAMS.
    To source information for their analysis, the team performed a literature search using the MeSH keywords "celiac disease," "gluten," and "infertility." They based celiac diagnosis on positive patient serology and biopsies showing villous atrophy. The team extracted celiac disease data in 3 groups of women with "all cause" infertility, unexplained infertility, and a group of control subjects. They then calculated pooled odds ratio (OR) and prevalence, with 95% confidence intervals (CI).
    Of 105 relevant studies, they included five studies for calculation of pooled odds ratio. Four additional studies, where data on controls were not available, were also considered for calculation of pooled rates of celiac disease.
    The analysis showed that women with infertility had 3.5 times higher odds of having celiac disease compared with the control group (OR=3.5; 95% CI, 1.3-9; P<0.01). Similarly, odds for celiac disease in women with "unexplained infertility" were 6 times greater than for control subjects (OR=6; 95% CI, 2.4-14.6).
    Of 884 women with infertility, 20 had celiac disease indicating a pooled prevalence of 2.3% (95% CI, 1.4-3.5).
    Of 623 women with "unexplained infertility," 20 had celiac disease. The pooled prevalence of celiac disease in women with unexplained infertility was 3.2% (95% CI, 2-4.9).
    Celiac disease is more common in women with what is called "all-cause" infertility and "unexplained" infertility, than in general population.
    Infertility and unexplained infertility can point to hidden celiac disease.
    Source:
    Journal of Clinical Gastroenterology. doi: 10.1097/MCG.0000000000000285

    Jefferson Adams
    Celiac.com 04/27/2015 - We know that women with infertility have higher rates of celiac disease than women who are not infertile.
    There's been some evidence to suggest that celiac disease might have impact women's reproductive health. However, the quest for more solid answers continues.
    A team of researchers recently set out to assess fertility and outcomes of pregnancy among women with celiac disease. The research team included Stephanie M. Moleski, Christina C. Lindenmeyer, J. Jon Veloski, Robin S. Miller, Cynthia L. Miller, David Kastenberg, and Anthony J. DiMarino. The team crafted a retrospective cohort study in which they analyzed information gathered from patients at a tertiary care celiac center, along with information gathered from members of two national celiac disease awareness organizations.
    A group of women without celiac disease served as control subjects. Both groups answered an anonymous online survey of 43 questions about menstrual history, fertility, and pregnancy outcomes. The group included 329 women with small bowel biopsy-confirmed celiac disease and 641 control subjects. Of the 970 women included in the study, 733 (75.6%) reported that they had been pregnant at some point.
    In terms of pregnancy, there was no significant difference between women with celiac disease (n=245/329, 74.5%) and controls (488/641, 76.1%; P=0.57). However, fewer women with celiac disease than controls (79.6% vs. 84.8%) reported giving birth following 1 or more pregnancies (P=0.03).
    Women with celiac disease had higher rates of spontaneous abortion than did control subjects (50.6% vs. 40.6%; P=0.01). Women with celiac disease also had higher rates of premature delivery, at 23.6% compared to 15.9% among controls (P=0.02).
    The average age at menarche was a bit higher in the celiac disease group, at 12.7 years, than in the control group, which came in at 12.4 years (P=0.01).
    This retrospective cohort analysis examining reproductive features of women with celiac disease, found that celiac disease was associated with significant increases in spontaneous abortion, premature delivery, and later age of menarche.
    Source:
    Ann Gastroenterol 2015; 28 (2): 236-240

  • Recent Articles

    Jefferson Adams
    Celiac.com 06/19/2018 - Could baking soda help reduce the inflammation and damage caused by autoimmune diseases like rheumatoid arthritis, and celiac disease? Scientists at the Medical College of Georgia at Augusta University say that a daily dose of baking soda may in fact help reduce inflammation and damage caused by autoimmune diseases like rheumatoid arthritis, and celiac disease.
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    Read more at: Sciencedaily.com

    Jefferson Adams
    Celiac.com 06/18/2018 - Celiac disease has been mainly associated with Caucasian populations in Northern Europe, and their descendants in other countries, but new scientific evidence is beginning to challenge that view. Still, the exact global prevalence of celiac disease remains unknown.  To get better data on that issue, a team of researchers recently conducted a comprehensive review and meta-analysis to get a reasonably accurate estimate the global prevalence of celiac disease. 
    The research team included P Singh, A Arora, TA Strand, DA Leffler, C Catassi, PH Green, CP Kelly, V Ahuja, and GK Makharia. They are variously affiliated with the Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Lady Hardinge Medical College, New Delhi, India; Innlandet Hospital Trust, Lillehammer, Norway; Centre for International Health, University of Bergen, Bergen, Norway; Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Gastroenterology Research and Development, Takeda Pharmaceuticals Inc, Cambridge, MA; Department of Pediatrics, Università Politecnica delle Marche, Ancona, Italy; Department of Medicine, Columbia University Medical Center, New York, New York; USA Celiac Disease Center, Columbia University Medical Center, New York, New York; and the Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.
    For their review, the team searched Medline, PubMed, and EMBASE for the keywords ‘celiac disease,’ ‘celiac,’ ‘tissue transglutaminase antibody,’ ‘anti-endomysium antibody,’ ‘endomysial antibody,’ and ‘prevalence’ for studies published from January 1991 through March 2016. 
    The team cross-referenced each article with the words ‘Asia,’ ‘Europe,’ ‘Africa,’ ‘South America,’ ‘North America,’ and ‘Australia.’ They defined celiac diagnosis based on European Society of Pediatric Gastroenterology, Hepatology, and Nutrition guidelines. The team used 96 articles of 3,843 articles in their final analysis.
    Overall global prevalence of celiac disease was 1.4% in 275,818 individuals, based on positive blood tests for anti-tissue transglutaminase and/or anti-endomysial antibodies. The pooled global prevalence of biopsy-confirmed celiac disease was 0.7% in 138,792 individuals. That means that numerous people with celiac disease potentially remain undiagnosed.
    Rates of celiac disease were 0.4% in South America, 0.5% in Africa and North America, 0.6% in Asia, and 0.8% in Europe and Oceania; the prevalence was 0.6% in female vs 0.4% males. Celiac disease was significantly more common in children than adults.
    This systematic review and meta-analysis showed celiac disease to be reported worldwide. Blood test data shows celiac disease rate of 1.4%, while biopsy data shows 0.7%. The prevalence of celiac disease varies with sex, age, and location. 
    This review demonstrates a need for more comprehensive population-based studies of celiac disease in numerous countries.  The 1.4% rate indicates that there are 91.2 million people worldwide with celiac disease, and 3.9 million are in the U.S.A.
    Source:
    Clin Gastroenterol Hepatol. 2018 Jun;16(6):823-836.e2. doi: 10.1016/j.cgh.2017.06.037.

    Jefferson Adams
    Celiac.com 06/16/2018 - Summer is the time for chips and salsa. This fresh salsa recipe relies on cabbage, yes, cabbage, as a secret ingredient. The cabbage brings a delicious flavor and helps the salsa hold together nicely for scooping with your favorite chips. The result is a fresh, tasty salsa that goes great with guacamole.
    Ingredients:
    3 cups ripe fresh tomatoes, diced 1 cup shredded green cabbage ½ cup diced yellow onion ¼ cup chopped fresh cilantro 1 jalapeno, seeded 1 Serrano pepper, seeded 2 tablespoons lemon juice 2 tablespoons red wine vinegar 2 garlic cloves, minced salt to taste black pepper, to taste Directions:
    Purée all ingredients together in a blender.
    Cover and refrigerate for at least 1 hour. 
    Adjust seasoning with salt and pepper, as desired. 
    Serve is a bowl with tortilla chips and guacamole.

    Dr. Ron Hoggan, Ed.D.
    Celiac.com 06/15/2018 - There seems to be widespread agreement in the published medical research reports that stuttering is driven by abnormalities in the brain. Sometimes these are the result of brain injuries resulting from a stroke. Other types of brain injuries can also result in stuttering. Patients with Parkinson’s disease who were treated with stimulation of the subthalamic nucleus, an area of the brain that regulates some motor functions, experienced a return or worsening of stuttering that improved when the stimulation was turned off (1). Similarly, stroke has also been reported in association with acquired stuttering (2). While there are some reports of psychological mechanisms underlying stuttering, a majority of reports seem to favor altered brain morphology and/or function as the root of stuttering (3). Reports of structural differences between the brain hemispheres that are absent in those who do not stutter are also common (4). About 5% of children stutter, beginning sometime around age 3, during the phase of speech acquisition. However, about 75% of these cases resolve without intervention, before reaching their teens (5). Some cases of aphasia, a loss of speech production or understanding, have been reported in association with damage or changes to one or more of the language centers of the brain (6). Stuttering may sometimes arise from changes or damage to these same language centers (7). Thus, many stutterers have abnormalities in the same regions of the brain similar to those seen in aphasia.
    So how, you may ask, is all this related to gluten? As a starting point, one report from the medical literature identifies a patient who developed aphasia after admission for severe diarrhea. By the time celiac disease was diagnosed, he had completely lost his faculty of speech. However, his speech and normal bowel function gradually returned after beginning a gluten free diet (8). This finding was so controversial at the time of publication (1988) that the authors chose to remain anonymous. Nonetheless, it is a valuable clue that suggests gluten as a factor in compromised speech production. At about the same time (late 1980’s) reports of connections between untreated celiac disease and seizures/epilepsy were emerging in the medical literature (9).
    With the advent of the Internet a whole new field of anecdotal information was emerging, connecting a variety of neurological symptoms to celiac disease. While many medical practitioners and researchers were casting aspersions on these assertions, a select few chose to explore such claims using scientific research designs and methods. While connections between stuttering and gluten consumption seem to have been overlooked by the medical research community, there is a rich literature on the Internet that cries out for more structured investigation of this connection. Conversely, perhaps a publication bias of the peer review process excludes work that explores this connection.
    Whatever the reason that stuttering has not been reported in the medical literature in association with gluten ingestion, a number of personal disclosures and comments suggesting a connection between gluten and stuttering can be found on the Internet. Abid Hussain, in an article about food allergy and stuttering said: “The most common food allergy prevalent in stutterers is that of gluten which has been found to aggravate the stutter” (10). Similarly, Craig Forsythe posted an article that includes five cases of self-reporting individuals who believe that their stuttering is or was connected to gluten, one of whom also experiences stuttering from foods containing yeast (11). The same site contains one report of a stutterer who has had no relief despite following a gluten free diet for 20 years (11). Another stutterer, Jay88, reports the complete disappearance of her/his stammer on a gluten free diet (12). Doubtless there are many more such anecdotes to be found on the Internet* but we have to question them, exercising more skepticism than we might when reading similar claims in a peer reviewed scientific or medical journal.
    There are many reports in such journals connecting brain and neurological ailments with gluten, so it is not much of a stretch, on that basis alone, to suspect that stuttering may be a symptom of the gluten syndrome. Rodney Ford has even characterized celiac disease as an ailment that may begin through gluten-induced neurological damage (13) and Marios Hadjivassiliou and his group of neurologists and neurological investigators have devoted considerable time and effort to research that reveals gluten as an important factor in a majority of neurological diseases of unknown origin (14) which, as I have pointed out previously, includes most neurological ailments.
    My own experience with stuttering is limited. I stuttered as a child when I became nervous, upset, or self-conscious. Although I have been gluten free for many years, I haven’t noticed any impact on my inclination to stutter when upset. I don’t know if they are related, but I have also had challenges with speaking when distressed and I have noticed a substantial improvement in this area since removing gluten from my diet. Nonetheless, I have long wondered if there is a connection between gluten consumption and stuttering. Having done the research for this article, I would now encourage stutterers to try a gluten free diet for six months to see if it will reduce or eliminate their stutter. Meanwhile, I hope that some investigator out there will research this matter, publish her findings, and start the ball rolling toward getting some definitive answers to this question.
    Sources:
    1. Toft M, Dietrichs E. Aggravated stuttering following subthalamic deep brain stimulation in Parkinson’s disease--two cases. BMC Neurol. 2011 Apr 8;11:44.
    2. Tani T, Sakai Y. Stuttering after right cerebellar infarction: a case study. J Fluency Disord. 2010 Jun;35(2):141-5. Epub 2010 Mar 15.
    3. Lundgren K, Helm-Estabrooks N, Klein R. Stuttering Following Acquired Brain Damage: A Review of the Literature. J Neurolinguistics. 2010 Sep 1;23(5):447-454.
    4. Jäncke L, Hänggi J, Steinmetz H. Morphological brain differences between adult stutterers and non-stutterers. BMC Neurol. 2004 Dec 10;4(1):23.
    5. Kell CA, Neumann K, von Kriegstein K, Posenenske C, von Gudenberg AW, Euler H, Giraud AL. How the brain repairs stuttering. Brain. 2009 Oct;132(Pt 10):2747-60. Epub 2009 Aug 26.
    6. Galantucci S, Tartaglia MC, Wilson SM, Henry ML, Filippi M, Agosta F, Dronkers NF, Henry RG, Ogar JM, Miller BL, Gorno-Tempini ML. White matter damage in primary progressive aphasias: a diffusion tensor tractography study. Brain. 2011 Jun 11.
    7. Lundgren K, Helm-Estabrooks N, Klein R. Stuttering Following Acquired Brain Damage: A Review of the Literature. J Neurolinguistics. 2010 Sep 1;23(5):447-454.
    8. [No authors listed] Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 43-1988. A 52-year-old man with persistent watery diarrhea and aphasia. N Engl J Med. 1988 Oct 27;319(17):1139-48
    9. Molteni N, Bardella MT, Baldassarri AR, Bianchi PA. Celiac disease associated with epilepsy and intracranial calcifications: report of two patients. Am J Gastroenterol. 1988 Sep;83(9):992-4.
    10. http://ezinearticles.com/?Food-Allergy-and-Stuttering-Link&id=1235725 
    11. http://www.craig.copperleife.com/health/stuttering_allergies.htm 
    12. https://www.celiac.com/forums/topic/73362-any-help-is-appreciated/
    13. Ford RP. The gluten syndrome: a neurological disease. Med Hypotheses. 2009 Sep;73(3):438-40. Epub 2009 Apr 29.
    14. Hadjivassiliou M, Gibson A, Davies-Jones GA, Lobo AJ, Stephenson TJ, Milford-Ward A. Does cryptic gluten sensitivity play a part in neurological illness? Lancet. 1996 Feb 10;347(8998):369-71.

    Jefferson Adams
    Celiac.com 06/14/2018 - Refractory celiac disease type II (RCDII) is a rare complication of celiac disease that has high death rates. To diagnose RCDII, doctors identify a clonal population of phenotypically aberrant intraepithelial lymphocytes (IELs). 
    However, researchers really don’t have much data regarding the frequency and significance of clonal T cell receptor (TCR) gene rearrangements (TCR-GRs) in small bowel (SB) biopsies of patients without RCDII. Such data could provide useful comparison information for patients with RCDII, among other things.
    To that end, a research team recently set out to try to get some information about the frequency and importance of clonal T cell receptor (TCR) gene rearrangements (TCR-GRs) in small bowel (SB) biopsies of patients without RCDII. The research team included Shafinaz Hussein, Tatyana Gindin, Stephen M Lagana, Carolina Arguelles-Grande, Suneeta Krishnareddy, Bachir Alobeid, Suzanne K Lewis, Mahesh M Mansukhani, Peter H R Green, and Govind Bhagat.
    They are variously affiliated with the Department of Pathology and Cell Biology, and the Department of Medicine at the Celiac Disease Center, New York Presbyterian Hospital/Columbia University Medical Center, New York, USA. Their team analyzed results of TCR-GR analyses performed on SB biopsies at our institution over a 3-year period, which were obtained from eight active celiac disease, 172 celiac disease on gluten-free diet, 33 RCDI, and three RCDII patients and 14 patients without celiac disease. 
    Clonal TCR-GRs are not infrequent in cases lacking features of RCDII, while PCPs are frequent in all disease phases. TCR-GR results should be assessed in conjunction with immunophenotypic, histological and clinical findings for appropriate diagnosis and classification of RCD.
    The team divided the TCR-GR patterns into clonal, polyclonal and prominent clonal peaks (PCPs), and correlated these patterns with clinical and pathological features. In all, they detected clonal TCR-GR products in biopsies from 67% of patients with RCDII, 17% of patients with RCDI and 6% of patients with gluten-free diet. They found PCPs in all disease phases, but saw no significant difference in the TCR-GR patterns between the non-RCDII disease categories (p=0.39). 
    They also noted a higher frequency of surface CD3(−) IELs in cases with clonal TCR-GR, but the PCP pattern showed no associations with any clinical or pathological feature. 
    Repeat biopsy showed that the clonal or PCP pattern persisted for up to 2 years with no evidence of RCDII. The study indicates that better understanding of clonal T cell receptor gene rearrangements may help researchers improve refractory celiac diagnosis. 
    Source:
    Journal of Clinical Pathologyhttp://dx.doi.org/10.1136/jclinpath-2018-205023