An association between advanced paternal age at birth and risk for autism spectrum disorders and the underlying biological mechanisms

父亲出生时高龄与自闭症谱系障碍风险之间的关联及其潜在的生物学机制

• 批准号: 20591396
• 负责人: TSUCHIYA Kenji
• 金额: $ 2.91万
• 依托单位: Hamamatsu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20591396/
• 关键词: 自閉症スペクトラム; 言語; 生殖補助医療; 疫学; コホート研究; 父親; ロジスティック回帰分析; 母子手帳

Background and aim. Paternal age at birth has been suggested to be associated with autism spectrum disorder (ASD). In this study, we aimed at replicating the association in a Japanese sample in a retrospective manner, and at investigating biological mechanisms underlying this association using a birth cohort. A potential candidate for this mechanism is a use of artificial reproductive technique.Method 1. "Retrospective study" : 84 individuals with high-functioning ASD and 208 typically developed control individuals were enrolled. A statistical association was sought between diagnosis of ASD and paternal age at birth, while controlling for gender, parity, and maternal age at birth.Method 2. "Prospective study" : 780 pregnant women and their babies were enrolled as a part of an ongoing birth cohort study who were born during the period of 19 November, 2007 and 1 July, 2009. The participating mother-and-child dyads were followed up until the end of 2010 to examine whether any aberrant dev … More elopmental trajectories would be found ; such outcome measures include scores of Mullen Scales of Early Learning, developmental milestones, and suspected diagnosis of ASD. We also examined a risk of suspected ASD in association with paternal age at birth, and artificial reproductive technique as well. Result 1. "Retrospective study" : The association between paternal age at birth and a risk for ASD was confirmed after controlling for covariates. The dose-response relationship was also found.Result 2. "Prospective study" : In univariate analyses, paternal age at birth did not predict delay in motor/language development, in achievement of developmental milestones, and suspected diagnosis of ASD. On the other hand, artificial reproductive technique appeared to predict delayed development and ASD, although the associations did not reach statistical significance. Due to lack of statistical power, we were unable to seek for interaction between paternal age at birth and artificial reproductive therapy in association with a risk for ASD.Conclusion. Although firm conclusions are awaited, this study suggested relevance of artificial reproductive techniques as an underlying biological mechanism for the association between paternal age at birth and ASD. Less

背景和目标。父亲出生时的年龄被认为与自闭症谱系障碍（ASD）有关。在这项研究中，我们的目的是在日本样本中复制的协会在回顾性的方式，并在调查的生物学机制，这种协会使用的出生队列。这种机制的一个潜在候选者是使用人工生殖技术。“回顾性研究”：84名高功能ASD患者和208名典型发展的对照个体入组。在控制性别、产次和母亲出生年龄的同时，寻找ASD诊断与父亲出生年龄之间的统计学关联。“前瞻性研究”：780名孕妇及其婴儿入组，作为正在进行的出生队列研究的一部分，他们在2007年11月19日至2009年7月1日期间出生。参与研究的母子二人组被随访至2010年底，以检查是否有任何异常发育。 ...更多信息 将找到发育轨迹;这些结果指标包括马伦早期学习量表评分、发育里程碑和疑似自闭症谱系障碍诊断。我们还研究了疑似ASD的风险与父亲出生时的年龄和人工生殖技术的关系。结果1.“回顾性研究”：在控制协变量后，证实了父亲出生时年龄与ASD风险之间的关联。并发现了剂量-反应关系。“前瞻性研究”：在单变量分析中，父亲出生时的年龄并不能预测运动/语言发育延迟、发育里程碑的实现以及ASD的疑似诊断。另一方面，人工生殖技术似乎可以预测发育延迟和ASD，尽管这种关联没有达到统计学意义。由于缺乏统计学把握度，我们无法寻求父亲出生年龄和人工生殖治疗与ASD风险之间的相互作用。虽然确切的结论还在等待中，但这项研究表明，人工生殖技术作为父亲出生年龄与ASD之间关联的潜在生物学机制的相关性。少

项目成果

Perinatal asphyxia reduces dentate granule cells and exacerbates methamphetamine induced hyperlocomotion in adulthood

围产期窒息减少齿状颗粒细胞并加剧甲基苯丙胺引起的成年期过度运动

• 发表时间: 2008
• 期刊: PLoS ONE 3
• 作者: Wakuda T;Matsuzaki H;Suzuki K;Iwata Y;Shinmura C;Suda S;et al.
• 通讯作者: et al.

Mother's unintended pregnancy associated with lower ponderal index at 4 months of the infant : the HBC Study.

母亲的意外怀孕与婴儿 4 个月时体重指数较低相关：HBC 研究。

• 发表时间: 2010
• 作者: Takahashi S;Tsuchiya KJ;Matsumoto K;Mori T;Takabayashi R;Suzuki Y;Sato R;Narumiya M;Seno Y;Suda S;Matsuzaki H;Suzuki K;Mori N;Takei N;the HBC Study Team.
• 通讯作者: the HBC Study Team.

Unwanted pregnancy and its detrimental effect on early language development in the offspring : the HBC Study.

意外怀孕及其对后代早期语言发育的不利影响：HBC 研究。

• 发表时间: 2009
• 作者: Matsumoto K;Tsuchiya KJ;Miyachi T;Itoh H;Kanayama N;Takei N;the HBC Study Team.
• 通讯作者: the HBC Study Team.

Validating a Japanese version of the Ritvo Autism and Asperger's Diagnostic Scale : a pilot study.

验证日本版 Ritvo 自闭症和阿斯伯格诊断量表：一项试点研究。

• 发表时间: 2008
• 作者: Matsumoto K;Tsuchiya KJ;Ritvo ER;Tsujii M.
• 通讯作者: Tsujii M.

Age-specific 3-month cumulative incidence of postpartum depression : The Hamamatsu Birth Cohort Study(HBC).

特定年龄的产后抑郁症 3 个月累积发病率：滨松出生队列研究 (HBC)。

• 期刊: Journal of Affective Disosrders
• 作者: Matsumoto K;Tsuchiya KJ;Itoh H;Kanayama N;Suda S;et al.
• 通讯作者: et al.