Child and Adolescent Psychiatry Department, Robert Debre Hospital, APHP, Paris, France.
Immunology-Immunopathology-Immunotherapy (i3), UMRS 959, INSERM, Paris, France.
Transl Psychiatry. 2022 Mar 18;12(1):112. doi: 10.1038/s41398-022-01843-y.
Epidemiological studies have raised concerns about the risk of neurodevelopmental disorders (NDD) in children of patients with autoimmune or inflammatory disorders (AID). The pathophysiological pathways underlying this association are still unknown and little is known about the specific and distinct risk of each AID. To explore these questions, we investigated the association between the occurrences of several NDD in the offspring of mothers or fathers with different IDA. We conducted a meta-analysis-PROSPERO (CRD42020159250)-examining the risk of NDD in the offspring of mothers or fathers with AID. We performed specific analyses separately in fathers or mothers of NDD patients as well as subgroup analyses for each NDD and AID. We searched MEDLINE, Embase, PsycINFO, Cochrane Central Register of Controlled Trials, and Web of Science Core Collection published until December 2021. From an initial pool of 2074 potentially relevant references, 14 studies were included, involving more than 1,400,000 AID and 10,000,000 control parents, 180,000 children with NDD and more than 14,000,000 control children. We found AID in mothers (Adjusted OR 1.27 [95% CI 1.03; 1.57] p = 0.02, [I = 65%, Tau = 0.03 p = 0.01] and adjusted OR 1.31 [95% CI 1.11; 1.55] p = 0.001, [I = 93%, Tau = 0.13 p = 0.001] and, although in a lesser extent, in fathers (adjusted OR 1.18 [95% CI 1.07; 1.30] p = 0.01, [I = 15.5%, Tau = 0.002 p = 0.47]) and adjusted OR 1.14 [95% CI 1.10; 1.17] p < 0.0001, [I = 0%, Tau = 0 p = 0.29]) to be associated with ASD and ADHD in the offspring. This difference in the strength of the association was found in the AID-specific analyses, suggesting that AID increase the risk of NDD by a shared mechanism but that a specific maternal route appears to represent an additional excess risk. Inflammatory bowel disease were not associated with an additional risk (neither in fathers nor in mothers) of NDD in offspring. Our results suggest that complex and multiple AID-specific pathophysiological mechanisms may underlie the association of AID and NDD in offspring. Further, comprehensive studies of the different AID and NDD are needed to draw definitive conclusions about the pathophysiological links between parental AID and NDD in children.
流行病学研究引起了人们对自身免疫或炎症性疾病（AID）患者的子女患神经发育障碍（NDD）风险的关注。这种关联的病理生理途径尚不清楚，对于每种 AID 的具体和独特风险知之甚少。为了探讨这些问题，我们研究了不同自身免疫性疾病（IDA）母亲或父亲的后代中出现的几种 NDD 之间的关联。我们进行了一项荟萃分析-PROSPERO（CRD42020159250）-研究了 AID 母亲或父亲的后代患 NDD 的风险。我们分别对 NDD 患者的母亲或父亲进行了特定分析，以及对每种 NDD 和 AID 的亚组分析。我们检索了 MEDLINE、Embase、PsycINFO、Cochrane 对照试验中心注册库和 Web of Science 核心合集，截至 2021 年 12 月。从最初的 2074 篇潜在相关文献中，纳入了 14 项研究，涉及超过 140 万例 AID 和 1000 万例对照父母、18 万例 NDD 患儿和超过 1400 万例对照患儿。我们发现母亲的 AID（调整后的 OR 1.27 [95%CI 1.03; 1.57] p=0.02，[I=65%，Tau=0.03 p=0.01]和调整后的 OR 1.31 [95%CI 1.11; 1.55] p=0.001，[I=93%，Tau=0.13 p=0.001]）和，尽管程度较小，父亲的 AID（调整后的 OR 1.18 [95%CI 1.07; 1.30] p=0.01，[I=15.5%，Tau=0.002 p=0.47]）和调整后的 OR 1.14 [95%CI 1.10; 1.17] p<0.0001，[I=0%，Tau=0 p=0.29]）与后代的 ASD 和 ADHD 相关。在特定于 AID 的分析中发现了这种关联强度的差异，表明 AID 通过共同的机制增加了 NDD 的风险，但特定的母体途径似乎代表了额外的超额风险。炎症性肠病与后代 NDD 的额外风险（无论是父亲还是母亲）无关。我们的结果表明，复杂和多种 AID 特异性病理生理机制可能是 AID 和后代 NDD 之间关联的基础。此外，需要对不同的 AID 和 NDD 进行综合研究，以得出关于父母 AID 和儿童 NDD 之间病理生理学联系的明确结论。
