Coeliac disease (CD) is diagnosed twice as frequently amongst women compared to men. Amongst the non-classical presentations of CD, a wide-range of female reproductive disorders have been described, including infertility and adverse pregnancy outcomes.
The pathogenetic mechanisms underlying these conditions are fairly unknown. Micro- and macronutrient deficiencies as a result of intestinal malabsorption, as well as a direct role for tTG in damaging the placental throphoblast, thus leading to miscarriages and other pregnancy complications, have been proposed. Currently, consensus is lacking regarding which categories of obstetric and gynaecological disorders warrant testing amongst affected individuals. The aim if this review was to critically summarise the current literature in this field and provide practical proposals that may help clinicians involved in the management of their female patients.
Infertility and CD
The majority of studies in this area have considered the prevalence of undiagnosed/ untreated coeliac disease amongst women with explained or unexplained infertility. In the papers that demonstrated a positive association between CD and infertility, the prevalence of untreated CD amongst women with explained infertility (infertility owing to a known cause) was between 2.10 and 3.03%. The prevalence of untreated CD was higher amongst women with unexplained infertility, ranging between 2.50 and 10.30%. Three meta-analyses concordantly found a higher prevalence of untreated CD in women with infertility. Pooled prevalence of CD was 2.3% in all-cause infertility and 3.2% in unexplained infertility. A positive effect of a gluten-free diet in infertile women with CD was demonstrated by seven papers. In contrast, the prevalence of infertility amongst women with diagnosed CD has only been considered within 3 population studies. In all three papers, the prevalence of infertility was not significantly different from that of the general population, however the limitations of data derived from large population-based studies must be taken in to consideration.
Miscarriages
A recent meta analysis found that the odds ratio for untreated CD amongst women experiencing miscarriage was 5.82 (95% CI: 2.3-14.74). At the same time, women with CD were found to be at increased risk of miscarriage (OR=1.39, 95% CI: 1.15-1.67), however a gluten-free diet is able to reduce this risk significantly.
Other adverse outcomes/ complications
To date, 13 studies have investigated the occurrence of other poor pregnancy outcomes and obstetric complications. In women with CD, there is an increased risk of intrauterine growth restriction (IUGR), low-birth weight (LBW) babies, small-for-gestational age (SGA) babies and preterm births. Results for still births and post-partum haemorrhages are conflicting. No increased risk of pre-eclampsia and ectopic pregnancies have been reported. The studies that evaluated the role of a gluten-free diet found a positive protective effect in reducing risk of poor pregnancy outcomes for women with CD. The prevalence of untreated CD in women who had experienced poor pregnancy outcomes has been considered by 6 studies. Three of these found an increased prevalence of CD amongst those who experienced IUGR (4.4-15%). A meta analysis found the OR for CD amongst women experiencing IUGR to be 8.73 (95% CI: 3.23-23.58).
Implications for clinical practice
- Women with recurrent, unexplained miscarriages, unexplained IUGR and unexplained infertility should be investigated for CD, even in the absence of gastrointestinal symptoms/ biochemical alternations.
- In women with un-investigated iron-deficiency anaemia, gastrointestinal symptoms, autoimmune disorders or first-degree familiarity for CD, it is vital to rule out CD before trying to conceive.
- Widespread screening of women who want to start a pregnancy is unlikely to provide benefits in terms of cost-effectiveness.
- Up to now, the best cost-effective strategy for pregnancy planning in newly diagnosed women with CD is undefined. It would seem that a strategy based on serological check-up may be the best cost-effective option, although this may be a poor predictor of dietary adherence.
- Women with coeliac disease who wish to conceive should be provided with information regarding the necessity of consuming a strict gluten-free diet to mimimise the risk of poor pregnancy outcomes. Assessment of nutritional status should be performed by a skilled dietitian and screening for common associated autoimmune conditions should be offered before conception
- A proposal for a clinical algorithm for pregnancy programming in women with coeliac disease has been proposed by the authors. Key considerations include: age at diagnosis, type of clinical presentation, previous history of miscarriages/ other poor pregnancy outcomes, tTG/ EMA normalisation.
Schiepatti A, Sprio E, Sanders D.S et al. Eur J Gastroenterol & Hepatol 2019 Apr;31(4):425-433