Celiac.com 01/17/2011 - Women with latent celiac disease, those who test positive for celiac antibodies but show normal small bowel biopsies, may develop more reproductive problems, according to a report by Indian published in the World Journal of Gastroenterology.

"Women having unexplained infertility, recurrent abortions, stillbirths or intrauterine growth retardation could have subclinical celiac disease, which can be detected by serological screening tests," Dr. Ashok Kumar told Reuters Health by email.

Improved diagnostic tools, and greater access to screening have led to greater meant more latent or subclinical celiac disease, says Dr. Kumar, of Maulana Azad Medical College & Lok Nayak Hospital in New Delhi.

Doctors know that women with full, biopsy-proven, untreated celiac disease have more reproductive problems if they don't follow a gluten-free diet.

Until now, there have been "very few studies regarding the effect of latent celiac disease on reproductive performance; the association has never before been investigated in India," say the authors.

To study the effect of latent celiac disease on reproductive performance, the researchers examined 893 women.

They found that a total of 104 women had undergone idiopathic recurrent abortion, 104 had unexplained stillbirth, 230 had unexplained infertility, and 150 were pregnant, but showed idiopathic intrauterine growth restriction. The remaining 305 women, with normal obstetric histories, and served as control subjects.

Based on IgA tTG antibody titers, latent celiac disease was 5.43 times more common in the group with recurrent spontaneous abortion than in the control group.

Rates of latent celiac disease for the group with stillbirth were 4.61 times greater than the control group.

Rates for the group with intrauterine growth restriction were 7.75 times greater than control subjects, while rates for those with unexplained infertility were 4.51 higher.

The researchers also found that women with positive blood screens showed higher rates of  previous early births, low-weight births, and cesarean sections than did seronegative subjects.

Not every study shows a clear reduction in fertility, the researchers admit, but a number do show a higher risk of adverse pregnancy outcomes for women with latent celiac disease.

Spotting the celiac disease and treating it with a gluten free diet may reduce these associated risks.

Moreover, the researchers note that "the classic presentation of diarrhea and malabsorption is now less common, and atypical and silent presentations are increasing."

As a result of their findings, Dr. Kumar and his colleagues are recommending celiac disease blood screens for women with idiopathic cases of poor reproductive performance.

Source:

• World J Gastroenterol. 2010 Dec 14;16(46):5810-4

In 2008, a case-controlled study in Italy was executed to determine the association between female reproductive health and celiac disease. The study evaluated 62 celiac women, and 186 healthy control patients between the ages of 15 and 49.

Of the celiac women evaluated, the average age when diagnosed with celiac disease was about 24 years old. Most of the women, 69.3% exhibited a bloated stomach, 61.3% exhibited anemia, 51.6% exhibited weight loss, 40.3%  exhibited diarrhea, and 17.7% exhibited vomiting as their main symptom during onset of celiac disease. 40.3% of the women evaluated claimed to have other symptoms at the time they were diagnosed for celiac disease, including menstrual cycle disorders.

Of the celiac women evaluated, 47.6% reported that they noticed the onset of their menstrual cycle disorders before they noticed any other classic celiac symptoms, 28.6% noticed the onset of the menstrual symptoms after the  other celiac related symptoms presented, and 19% noticed menstrual problems at the same time as other celiac symptoms.  19.4% of celiac women exhibited menstrual disorders.

Exactly 50% of the celiac women tested and 50% of the controls tested had been pregnant at least once prior to entering the study. Celiac women reported 63 total pregnancies and 49 of those were brought to full term. The control group reported 203 pregnancies with 179 brought to full term. While only 11.8% of the control groups pregnancies ended in miscarriages, 22.2% of the women with celiac disease had miscarriages.

Additionally, the average birth rate of the children born from the celiac mothers was lower than the birth rate of the control group babies.

This study confirmed the association between celiac disease and pregnancy disorders. However, there have not been enough studies yet to determine the exact correlation between celiac disease and female related reproductive issues.

It has been hypothesized that the connection  might be due to the fact that celiac disease can cause malabsorbtion and therefor malnutrition in some individuals, which could possibly play a role in ovarian dysfunction. Although from this study and others, the connection between celiac disease and reproductive disorders has been demonstrated to be significant enough that women exhibiting reproductive issues are recommended to undergo celiac screenings.

Source:

• Open Original Shared Link

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.

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Celiac.com 08/11/2005 - A large study by Swedish and American researchers has determined that untreated celiac disease is associated with an increased risk of adverse fetal outcome. In contrast to several small studies that have been done in the past that produced conflicting results, this study looked at 2,078 births to women who were diagnosed with celiac disease—1,149 were diagnosed prior to their child’s birth, while 929 were diagnosed after. The researches employed a national register-based cohort study (1964-2001) that was restricted to women between 15-44 years old who had a single live birth. The researchers measured intrauterine growth retardation, low birth weight, very low birth weight, preterm birth, very preterm birth and birth by caesarean section for each child in the study.

The results of the study indicate that undiagnosed celiac disease is associated with an increased risk of intrauterine growth retardation (OR = 1.62; 95% CI: 1.22-2.15), low birth weight (OR = 2.13; 95% CI: 1.66-2.75), very low birth weight (OR =2.45; 95% CI: 1.35-4.43), preterm birth (OR = 1.71; 95% CI: 1.35-2.17), and caesarean section (OR = 1.82; 95% CI: 1.27-2.60). In contrast, those diagnosed with celiac disease before their births were not at increased risk for these adverse fetal outcomes.

The researchers conclude that undiagnosed celiac disease increases the risk of unfavorable fetal outcomes—a risk that is reduced in those with diagnosed celiac disease, presumably because they have been treated with a gluten-free diet.

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.

Gut. 2004 Jan;53(1):149-51

Celiac.com 12/31/2003 – Italian researchers report in the journal Gut that their previous hypothesis which was based on their hospital study that reported a 1 in 80 incidence of celiac disease in pregnant women and an unfavorable pregnancy outcome for them needs to be revised. With the goal of proving their initial research the group conducted a "large population based study on a stratified sample from the whole Campania region" in Italy. The study looked at 5,055 pregnant women and tested them for IgA class anti-tissue transglutaminase (TGASE) antibodies using the ELISA method. In addition "Endomysial antibodies (EMA) were investigated on thin sections of human cord blood by an immunofluorescence test. The HLA class II DQA1*0501/DQB1*02 and DQA1*0301/DQB1*0302 haplotypes were assessed using the Eurospital Eu-DQ kit."

The researchers found that 51 of the 5,055 patients tested positive for celiac disease, and 12 women with known celiac disease were added to the results which yielded a ratio of 1 in 80 pregnant women with celiac disease, results that matched the groups first study. When the celiac-positive groups birth outcomes were compared with the normal group the researchers did "not observe an excess risk of abortion, premature delivery, small birth weight, or intrauterine growth retardation," although anemia was more frequent in the celiac disease group.

The researchers conclude that "undiagnosed coeliac disease is frequent among pregnant women (>1%) but is not associated with an unfavorable outcome of pregnancy."

Lancet 2000;356:399-400.

(Celiac.com 08/13/2000) According to a recent study by Dr. Antonio Gasbarrini and colleagues from Gemelli Hospital, Catholic University, in Rome, celiac disease may play a role in recurrent spontaneous abortion and intrauterine fetal growth retardation. The researchers studied 44 patients who had a history of spontaneous abortion, 39 patients who had fetuses with intrauterine growth retardation and 50 normal controls. For each group the researchers measured serum concentrations of IgA anti-endomysial and IgG anti-transglutaminase.

According to Dr. Antonio Gasbarrini: The patients with recurrent spontaneous abortion and those with intrauterine fetal growth retardation had a significantly higher frequency of serological markers of celiac disease than controls, as reported in the July 29th issue of The Lancet. Further, they found that three patients with recurrent spontaneous abortion (8%) and six patients whose fetuses had growth retardation (15%) tested positive for celiac disease. In addition, nine of the patients also underwent an endoscopy (jejunal biopsy), and eight were positive for celiac disease. Of the positive endoscopy group three patients showed duodenal mucosa with chronic inflammation and
subtotal villous atrophy and five patients presented with severe mucosal atrophy.

The researchers also point out that while about 1 in 1000 people in Europe have some symptomatic gluten-sensitivity, it is now becoming clear that a greater proportion of individuals have a clinically silent form of the
disease, and probably many others have a minor form of enteropathy. Their research shows that it is important to recognize celiac disease as a possible risk factor for recurrent spontaneous abortion and intrauterine fetal growth retardation, but it remains to be seen whether the removal of gluten from the diet will decrease the incidence of both problems for women with celiac disease.