Azathioprine (AZA), an oral immunosuppressant, is safe during pregnancy. Some reports suggested different impairments in the offspring of mothers with autoimmune diseases (AI) exposed in utero to AZA. These observations are available from retrospective studies or case reports. However, data with respect to the long-term safety in the antenatally exposed child are still lacking. The aim of this study is to summarize the current knowledge in this field and to focus on the need for a prospective study on this population. We performed a PubMed search using several search terms.

The actual data show that although the risk of congenital anomalies in offspring, as well as the infertility risk, are similar to those found in general population, there is a higher incidence of prematurity, of lower weight at birth and an intra-uterine delay of development. There is also an increased risk of materno- fetal infections, especially cytomegalovirus infection. Some authors raise the interrogations about neurocognitive impairment. Even though the adverse outcomes might well be a consequence of maternal illness and disease activity, interest has been raised about a contribution of this drug. However, the interferences between the external agent (in utero exposure to AZA), with the host (child genetic susceptibility, immune system anomalies, emotional status), environment (public health, social context, availability of health care), economic, social, and behavioral conditions, cultural patterns, are complex and represent confounding factors.

In conclusion, it is necessary to perform studies on the medium and long-term outcome of children born by mothers with autoimmune diseases, treated with AZA, in order to show the safety of AZA exposure. Only large-scale population studies with long-term follow-up will allow to formally conclude in this field.

Take home messages

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There is no study on a significant number of subjects concerning the medium and long-term outcome of children born by mothers with autoimmune disease treated with AZA.

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As AZA use is related to underlying disease and disease activity and many confounders interfere with AZA treatment, there is a major difficulty to distinguish between the influence of the disease itself on the risk of adverse birth outcome and potential AZA effects in offspring at medium and long term.

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Data need to be implemented with large, multicenter studies.

中文翻译：

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在子宫内暴露于硫唑嘌呤的自身免疫性疾病。我们站在哪里？

口服免疫抑制剂硫唑嘌呤（AZA）在怀孕期间是安全的。一些报告表明，子宫内暴露于AZA的患有自身免疫性疾病（AI）的母亲的后代有不同的损伤。这些意见可从回顾性研究或病例报告中获得。但是，仍然缺乏有关产前暴露儿童长期安全性的数据。这项研究的目的是总结该领域的当前知识，并着重于对该人群进行前瞻性研究的需要。我们使用多个搜索词进行了PubMed搜索。

实际数据表明，尽管后代先天异常的风险以及不孕风险与普通人群相似，但早产发生率较高，出生时体重较低，子宫内延迟发展。胎儿感染，尤其是巨细胞病毒感染的风险也增加了。一些作者提出了关于神经认知障碍的质疑。尽管不良后果很可能是孕产妇疾病和疾病活动的结果，但人们对该药物的作用已经引起了兴趣。但是，外部因素（在子宫内暴露于AZA中）与宿主之间的干扰（儿童遗传易感性，免疫系统异常，情绪状态），环境（公共卫生，社会环境，卫生保健的可用性），

总之，有必要对接受AZA治疗的自身免疫性疾病母亲所生的孩子的中期和长期结局进行研究，以显示AZA暴露的安全性。只有长期随访的大规模人群研究才能在该领域正式得出结论。

带回家的消息

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尚未有大量关于由AZA治疗的患有自身免疫性疾病的母亲所生孩子的中期和长期结局的研究。

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由于使用AZA与潜在疾病和疾病活动有关，并且许多混杂因素干扰AZA治疗，因此很难区分疾病本身对不良出生结局风险的影响与中，长期后代对AZA的潜在影响术语。

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数据需要通过大型的多中心研究来实施。