Etiology and clinical presentation of birth defects: population based study.
Etiology and clinical presentation of birth defects: population based study.
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DOI：
10.1136/bmj.j2249
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发表时间：
2017-05-30
期刊：
影响因子：
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通讯作者：
Botto LD
中科院分区：
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作者：
Feldkamp ML;Carey JC;Byrne JLB;Krikov S;Botto LD
目的探讨重大出生缺陷的病因及临床表现。 设计基于人群的病例队列。 通过犹他州基于人口的监测系统确定的2005-09年出生于居民妇女的儿童出生缺陷病例。对所有记录进行了临床重新审查。 研究对象270878例新生儿中5504例（患病率2.03%），排除轻度孤立性疾病（如肌性室间隔缺损、远端尿道下裂）。 主要结局指标主要结局是已知病因（染色体、遗传、人类致畸剂、孪生）或未知病因的出生缺陷比例，按形态学（孤立、多发、仅未成年人）和发病机制（序列、发育领域缺陷或已知的出生缺陷模式）分类。 结果20.2%（n=1114）的病例确定病因：染色体或遗传因素占94.4%（n=1052），致畸因素占4.1%（n=46，大多数控制不良的妊娠前糖尿病），双胞胎占1.4%（n=16，连体或无心）。其余79.8%（n=4390）被归类为病因不明;其中88.2%（n=3874）为孤立性出生缺陷。4.8%（n=266）记录了家族史（受类似影响的一级亲属）。在该队列中，92.1%（5067/5504）为活产婴儿（孤立和非孤立出生缺陷）：75.3%（4147/5504）被归类为具有孤立出生缺陷（病因未知或已知）。 结论这些发现强调了我们对出生缺陷原因的认识存在差距。对于已知的原因，如吸烟或糖尿病，在个别情况下分配因果关系仍然具有挑战性。然而，这些暴露对胎儿发育的持续影响突出了基于人群的预防性干预措施的紧迫性和益处。对于仍然未知的原因，需要更好的策略。这些可以包括将病因学，形态学和发病机制的关键要素更好地整合到流行病学研究中;研究人员（如发育生物学家），临床医生（如医学遗传学家）和流行病学家之间的更大合作;以及更好的方法来客观地测量胎儿暴露（超越母体自我报告）和更接近（产前）器官形成的关键时期。
Objective To assess causation and clinical presentation of major birth defects. Design Population based case cohort. Setting Cases of birth defects in children born 2005-09 to resident women, ascertained through Utah’s population based surveillance system. All records underwent clinical re-review. Participants 5504 cases among 270 878 births (prevalence 2.03%), excluding mild isolated conditions (such as muscular ventricular septal defects, distal hypospadias). Main outcome measures The primary outcomes were the proportion of birth defects with a known etiology (chromosomal, genetic, human teratogen, twinning) or unknown etiology, by morphology (isolated, multiple, minors only), and by pathogenesis (sequence, developmental field defect, or known pattern of birth defects). Results Definite cause was assigned in 20.2% (n=1114) of cases: chromosomal or genetic conditions accounted for 94.4% (n=1052), teratogens for 4.1% (n=46, mostly poorly controlled pregestational diabetes), and twinning for 1.4% (n=16, conjoined or acardiac). The 79.8% (n=4390) remaining were classified as unknown etiology; of these 88.2% (n=3874) were isolated birth defects. Family history (similarly affected first degree relative) was documented in 4.8% (n=266). In this cohort, 92.1% (5067/5504) were live born infants (isolated and non-isolated birth defects): 75.3% (4147/5504) were classified as having an isolated birth defect (unknown or known etiology). Conclusions These findings underscore the gaps in our knowledge regarding the causes of birth defects. For the causes that are known, such as smoking or diabetes, assigning causation in individual cases remains challenging. Nevertheless, the ongoing impact of these exposures on fetal development highlights the urgency and benefits of population based preventive interventions. For the causes that are still unknown, better strategies are needed. These can include greater integration of the key elements of etiology, morphology, and pathogenesis into epidemiologic studies; greater collaboration between researchers (such as developmental biologists), clinicians (such as medical geneticists), and epidemiologists; and better ways to objectively measure fetal exposures (beyond maternal self reports) and closer (prenatally) to the critical period of organogenesis.