Department of Preventive Medicine, Keck School of Medicine, University of Southern California.
Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California.
J Epidemiol. 2019 Jan 5;29(1):18-25. doi: 10.2188/jea.JE20170159. Epub 2018 Sep 29.
Inherited factors and maternal behaviors are thought to play an important role in the etiology of several congenital malformations. Twin studies can offer additional evidence regarding the contribution of genetic and lifestyle factors to common birth anomalies, but few large-scale studies have been reported.
We included data from twins (20,803 pairs) from the population-based California Twin Program. We compared concordance in monozygotic (MZ) to dizygotic (DZ) twins for the following birth anomalies: clubfoot, oral cleft, spina bifida, muscular dystrophy, deafness, cerebral palsy, strabismus, and congenital heart defects. Each birth anomaly was also examined for the associations with birth characteristics (birthweight and birth order) and parental exposures (age, smoking, and parental education).
The overall prevalence of any selected birth anomaly in California twins was 38 per 1,000 persons, with a slightly decreasing trend from 1957-1982. For pairwise concordance in 6,752 MZ and 7,326 like-sex DZ twin pairs, high MZ:DZ concordance ratios were observed for clubfoot (CR 5.91; P = 0.043) and strabismus (CR 2.52; P = 0.001). Among the total 20,803 pairs, parental smoking was significantly associated with risk of spina bifida (OR 3.48; 95% CI, 1.48-8.18) and strabismus (OR 1.61; 95% CI, 1.28-2.03). A significant quadratic trend of increasing risk for clubfoot, spina bifida, and strabismus was found when examining whether father smoked, mother smoked, or both parents smoked relative to non-smoking parents (P = 0.029, 0.026, and 0.0005, respectively).
Our results provide evidence for a multifactorial etiology underlying selected birth anomalies. Further research is needed to understand the biological mechanisms.
遗传因素和产妇行为被认为在多种先天性畸形的发病机制中起着重要作用。双胞胎研究可以为遗传和生活方式因素对常见出生异常的贡献提供额外的证据，但很少有大规模的研究报告。
我们纳入了来自基于人群的加利福尼亚双胞胎计划的双胞胎数据（20803 对）。我们比较了单卵（MZ）双胞胎和双卵（DZ）双胞胎在以下先天性畸形方面的一致性：马蹄内翻足、口腔裂、脊柱裂、肌肉营养不良、耳聋、脑瘫、斜视和先天性心脏病。还检查了每种先天畸形与出生特征（出生体重和出生顺序）和父母暴露（年龄、吸烟和父母教育）的关联。
加利福尼亚双胞胎中任何一种选定的先天畸形的总患病率为每千人 38 例，从 1957 年至 1982 年呈略有下降趋势。在 6752 对 MZ 和 7326 对同性别 DZ 双胞胎中，马蹄内翻足（CR5.91；P=0.043）和斜视（CR2.52；P=0.001）的 MZ：DZ 一致性比值较高。在总共 20803 对双胞胎中，父母吸烟与脊柱裂（OR3.48；95%CI，1.48-8.18）和斜视（OR1.61；95%CI，1.28-2.03）的风险显著相关。当检查父亲吸烟、母亲吸烟或父母双方吸烟相对于非吸烟父母时，发现马蹄内翻足、脊柱裂和斜视的风险呈显著二次趋势增加（P=0.029、0.026 和 0.0005）。
我们的研究结果为一些先天性畸形的多因素病因提供了证据。需要进一步的研究来了解生物学机制。
