INSERM UMR 1153, Obstetrical, Perinatal and Pediatric Epidemiology Research Team (EPOPé), Center for Epidemiology and Statistics, Sorbonne Paris Cité (CRESS), DHU Risks in Pregnancy, Paris Descartes University, F-75004 Paris, France.
Department of Obstetrics and Gynecology, Centre hospitalier général de Saint-Denis, Saint-Denis, France.
Hum Reprod. 2020 Sep 1;35(9):2113. doi: 10.1093/humrep/deaa105.
Is there an association between advanced paternal age and congenital heart defects (CHD)?
Advanced paternal age is associated with a 16% increase in the overall odds of CHD.
CHD are the most common congenital malformations. Several risk factors for CHD have been identified in the literature, but the association between advanced paternal age and CHD remains unclear.
STUDY DESIGN, SIZE, DURATION: We conducted a systematic literature search on MEDLINE and EMBASE (1960-2019) to identify studies assessing the association between advanced paternal age (≥35 years) and the risk of CHD, unrestrictive of language or sample size. We used a combination of Medical Subject Headings (MeSH) terms and free text words such as 'paternal age', 'paternal factors', 'father's age', 'parental age', 'heart', 'cardiac', 'cardiovascular', 'abnormalities, congenital', 'birth defects', 'congenital malformations' and 'congenital abnormalities'.
PARTICIPANTS/MATERIALS, SETTING, METHODS: We included observational studies aiming at assessing the association between paternal age and CHD. The included population could be live births, fetal deaths and terminations of pregnancy for fetal anomaly. To be included, studies had to provide either odds ratios (OR) with their 95% confidence interval (CI) or sufficient information to recalculate ORs with 95% CIs per paternal age category. We excluded studies if they had no comparative group and if they were reviews or case reports. Two independent reviewers selected the studies, extracted the data and assessed risk of bias using a modified Newcastle-Ottawa Scale. We used random-effects meta-analysis to produce summary estimates of crude OR. Associations were also tested in subgroups.
Of 191 studies identified, we included nine studies in the meta-analysis (9 917 011 participants, including 34 447 CHD), including four population-based studies. Five studies were judged at low risk of bias. Only one population-based study specifically investigated isolated CHD. The risk of CHD was higher with advanced paternal age (summary OR 1.16, 95% CI, 1.07-1.25). Effect sizes were stable in population-based studies and in those with low risk of bias.
The available evidence did not allow to assess (i) the risk of isolated CHD in population-based studies, (ii) the association between paternal age and the risk for specific CHD and (iii) the association between paternal age and CHD after adjustment for other risk factors, such as maternal age.
Our findings suggest that advanced paternal age may be a risk factor for CHD. However, because the association is modest in magnitude, its usefulness as a criterion for targeted screening for CHD seems limited.
STUDY FUNDING/COMPETING INTEREST(S): None.
CRD42019135061.
父亲年龄较大与先天性心脏病（CHD）之间是否存在关联？
父亲年龄较大与 CHD 的总体患病风险增加 16%相关。
CHD 是最常见的先天性畸形。文献中已经确定了几个 CHD 的风险因素，但父亲年龄较大与 CHD 之间的关联仍不清楚。
研究设计、规模、持续时间：我们对 MEDLINE 和 EMBASE（1960-2019 年）进行了系统的文献检索，以确定评估父亲年龄较大（≥35 岁）与 CHD 风险之间关联的研究，不限制语言或样本量。我们使用了医学主题词（MeSH）术语和自由文本词的组合，例如“父亲年龄”、“父亲因素”、“父亲的年龄”、“父母年龄”、“心脏”、“心脏”、“心血管”、“先天异常”、“出生缺陷”、“先天性畸形”和“先天性异常”。
参与者/材料、设置、方法：我们纳入了旨在评估父亲年龄与 CHD 之间关联的观察性研究。纳入的人群可以是活产儿、胎儿死亡和因胎儿异常而终止妊娠。为了纳入研究，研究必须提供优势比（OR）及其 95%置信区间（CI），或者提供足够的信息，以便按每个父亲年龄类别重新计算 OR 和 95%CI。如果研究没有对照组，或者是综述或病例报告，我们将其排除。两名独立的审查员选择研究，提取数据，并使用改良的 Newcastle-Ottawa 量表评估偏倚风险。我们使用随机效应荟萃分析生成原始 OR 的汇总估计值。还在亚组中测试了关联。
在 191 项研究中，我们纳入了 9 项荟萃分析（9917011 名参与者，包括 34447 例 CHD），包括 4 项基于人群的研究。五项研究被认为具有低偏倚风险。只有一项基于人群的研究专门调查了孤立性 CHD。父亲年龄较大时 CHD 的风险更高（汇总 OR 1.16，95%CI，1.07-1.25）。基于人群的研究和低偏倚风险的研究中，效应大小稳定。
现有证据尚无法评估（i）基于人群的研究中孤立性 CHD 的风险，（ii）父亲年龄与特定 CHD 风险之间的关联，以及（iii）在调整其他风险因素（如母亲年龄）后，父亲年龄与 CHD 之间的关联。
我们的研究结果表明，父亲年龄较大可能是 CHD 的一个风险因素。然而，由于关联的幅度较小，因此其作为 CHD 靶向筛查标准的实用性似乎有限。
研究资助/利益冲突：无。
PROSPERO 注册号：CRD42019135061。
