Department of Medicine, Horsens Regional Hospital, Sundvej 30, Horsens, Denmark.
Department of Public Health, Aarhus University, Bartholins Allé 2, Aarhus C, Denmark.
Hum Reprod. 2018 Aug 1;33(8):1538-1547. doi: 10.1093/humrep/dey214.
How does celiac disease (CD) influence women's reproductive life, both prior to and after the diagnosis?
Prior to the diagnosis of CD, an increased risk of adverse pregnancy outcomes was seen, whereas after the diagnosis, no influence on reproductive outcomes was found.
CD has been associated with several conditions influencing female reproduction and pregnancy outcomes including spontaneous abortion and stillbirth.
STUDY DESIGN, SIZE, DURATION: A nationwide matched cohort study following 6319 women diagnosed with CD and 63166 comparison women and identifying reproductive events between the ages of 15 and 50 years.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Through linkage of several Danish national health registers, we identified all women diagnosed with CD between 1977 and 2016. We identified an age- and sex-matched comparison cohort and obtained data on reproductive outcomes for both cohorts. Adjusted stratified Cox and logistic regression models were used to estimate differences in reproductive outcomes between women with and without CD.
Comparing women with diagnosed CD with the non-CD women, the chance of pregnancy, live birth and risk of stillbirth, molar and ectopic pregnancy, spontaneous abortion and abortion due to foetal disease was the same. However, prior to being diagnosed, CD women had an excess risk of spontaneous abortion equal to 11 extra spontaneous abortions per 1000 pregnancies (adjusted odds ratio (OR) = 1.12, 95% CI: 1.03, 1.22) and 1.62 extra stillbirths per 1000 pregnancies (adjusted OR = 1.57, 95% CI: 1.05, 2.33) compared with the non-CD women. In the period 0-2 years prior to diagnosis fewer pregnancies occurred in the undiagnosed CD group, equal to 25 (95% CI: 20-31) fewer pregnancies per 1000 pregnancies compared to the non-CD group and in addition, fewer undiagnosed CD women initiated ART-treatment in this period, corresponding to 4.8 (95% CI: 0.9, 8.7) fewer per 1000 women compared to non-CD women.
LIMITATIONS, REASONS FOR CAUTION: Validity of the diagnoses in the registers was not confirmed, but reporting to the registers is mandatory for all hospitals in Denmark. Not all spontaneous abortions will come to attention and be registered, whereas live- and stillbirths, ectopic and molar pregnancies and abortion due to foetal disease are unlikely not to be registered. We adjusted for several confounding factors but residual confounding cannot be ruled out.
These findings suggest that undiagnosed CD can affect female reproduction and the focus should be on early detection of CD in risk groups.
STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Health Research Fund of Central Denmark Region and The Hede Nielsens Foundation, Denmark. The authors report no conflicts of interest in this work.
乳糜泻（CD）如何影响女性的生殖生活，包括诊断前和诊断后？
在诊断 CD 之前，观察到不良妊娠结局的风险增加，而在诊断后，未发现对生殖结局有影响。
CD 与多种影响女性生殖和妊娠结局的情况有关，包括自然流产和死产。
研究设计、大小和持续时间：这是一项全国性匹配队列研究，随访了 6319 名诊断为 CD 的女性和 63166 名对照女性，并确定了 15 至 50 岁之间的生殖事件。
参与者/材料、设置、方法：通过链接几个丹麦国家健康登记处，我们确定了所有在 1977 年至 2016 年间被诊断为 CD 的女性。我们确定了一个年龄和性别匹配的对照组，并为两个队列获取了生殖结局数据。使用调整后的分层 Cox 和逻辑回归模型来估计患有 CD 和未患有 CD 的女性之间生殖结局的差异。
与未患 CD 的女性相比，患有确诊 CD 的女性怀孕、活产和死产、葡萄胎和异位妊娠、自然流产以及因胎儿疾病导致的流产的风险相同。然而，在诊断之前，CD 女性的自然流产风险增加，每 1000 次妊娠就有 11 次额外的自然流产（调整后的优势比（OR）=1.12，95%置信区间：1.03，1.22），每 1000 次妊娠就有 1.62 次额外的死产（调整后的 OR=1.57，95%置信区间：1.05，2.33）。在诊断前 0-2 年内，未确诊的 CD 组发生的妊娠较少，每 1000 次妊娠中就有 25 次（95%置信区间：20-31 次）妊娠较少，此外，在此期间，未确诊的 CD 女性接受辅助生殖技术（ART）治疗的人数也较少，每 1000 名女性中就有 4.8 次（95%置信区间：0.9，8.7 次）ART 治疗较少。
局限性、谨慎的原因：登记处的诊断有效性未经证实，但丹麦所有医院都必须向登记处报告。并非所有的自然流产都会引起注意并被登记，而活产和死产、异位妊娠和葡萄胎以及因胎儿疾病导致的流产则不太可能未被登记。我们调整了几个混杂因素，但不能排除残余混杂。
这些发现表明，未确诊的 CD 可能会影响女性的生殖能力，应重点关注在高危人群中尽早发现 CD。
研究资金/利益冲突：本研究由丹麦中央丹麦地区卫生研究基金和 Hede Nielsens 基金会资助。作者在这项工作中没有报告任何利益冲突。
