Chung K C, Kowalski C P, Kim H M, Buchman S R
Department of Surgery at the University of Michigan Medical Center, Ann Arbor 48109-0340, USA.
Plast Reconstr Surg. 2000 Feb;105(2):485-91. doi: 10.1097/00006534-200002000-00001.
Maternal cigarette smoking during pregnancy as a risk factor for having a child with cleft lip/palate has been suggested by several epidemiologic studies. However, most of these studies contained small sample sizes, and a clear association between these two factors could not be established. The U.S. Natality database from 1996 and a case-control study design were used to investigate the association between maternal smoking during pregnancy and having a child with cleft lip/palate. The records of 3,891,494 live births from the 1996 U.S. Natality database were extracted to obtain cleft lip/palate cases and random controls. The National Center for Health Statistics collects maternal and newborn demographic and medical data from the birth certificates of all 50 states. New York (excluding New York City), California, Indiana, and South Dakota did not collect smoking data, and the data from these states were excluded from the analysis. A total of 2207 live births with cleft lip/palate cases were identified, and 4414 controls (1:2 ratio) were randomly selected (using the SAS program) from live births with no congenital defects. Odds ratios and 95 percent confidence intervals were determined from logistic regression models, adjusting for confounding variables, including maternal demographic and medical risk factors. A significant association was found between any amount of maternal cigarette use during pregnancy and having a child with cleft lip/palate [unadjusted odds ratio 1.55 (1.36, 1.76), p < 0.001]. Univariate analysis showed that maternal education level, age, race, and maternal medical conditions (diabetes and pregnancy-associated hypertension) were potential confounders. After adjusting for these confounders, the odds ratio remained significant [Mantel-Haenszel odds ratio 1.34 (1.16, 1.54), p < 0.001]. To determine the dose response of cigarette smoking during pregnancy, the cigarette consumption per day was divided into four groups: none, 1 to 10, 11 to 20, and 21 or more. A dose-response relationship was found when comparing each smoking category with the no smoking reference group: 1.50 (1.28, 1.76), 1.55 (1.23, 1.95), and 1.78 (1.22, 2.59), respectively. This means that increased cigarette smoking during pregnancy resulted in increased odds of having a child with cleft lip/palate. This is the largest study to date to test the association between maternal cigarette smoking during pregnancy and having a newborn with cleft lip/palate. The significant trend in the dose-response relationship strongly suggests the association of smoking tobacco and this common congenital deformity. These results emphasize the public health risks associated with smoking during pregnancy. To prevent this devastating craniofacial anomaly, educational initiatives should be considered that will alert expectant mothers to the association between smoking during pregnancy and the occurrence of cleft lip/palate.
多项流行病学研究表明，孕期母亲吸烟是孩子患唇腭裂的一个风险因素。然而，这些研究大多样本量较小，无法明确这两个因素之间的关联。本研究利用1996年美国出生数据库及病例对照研究设计，调查孕期母亲吸烟与孩子患唇腭裂之间的关联。从1996年美国出生数据库中提取了3,891,494例活产记录，以获取唇腭裂病例和随机对照。美国国家卫生统计中心从所有50个州的出生证明中收集母亲和新生儿的人口统计学及医学数据。纽约（不包括纽约市）、加利福尼亚、印第安纳和南达科他州未收集吸烟数据，这些州的数据被排除在分析之外。共确定了2207例唇腭裂活产病例，并从无先天性缺陷的活产中随机选取了4414例对照（比例为1:2）（使用SAS程序）。通过逻辑回归模型确定比值比和95%置信区间，并对包括母亲人口统计学和医学风险因素在内的混杂变量进行调整。研究发现孕期母亲任何程度的吸烟与孩子患唇腭裂之间存在显著关联[未调整比值比为1.55(1.36, 1.76)，p < 0.001]。单因素分析表明，母亲的教育水平、年龄、种族以及母亲的医学状况（糖尿病和妊娠相关高血压）是潜在的混杂因素。在对这些混杂因素进行调整后，比值比仍然显著[Mantel-Haenszel比值比为1.34(1.16, 1.54)，p < 0.001]。为确定孕期吸烟的剂量反应，将每日吸烟量分为四组：不吸烟、1至10支、11至20支以及21支或更多。将每个吸烟类别与不吸烟参照组进行比较时发现了剂量反应关系：分别为1.50(1.28, 1.76)、1.55(1.23, 1.95)和1.78(1.22, 2.59)。这意味着孕期吸烟量增加会导致孩子患唇腭裂的几率增加。这是迄今为止检验孕期母亲吸烟与新生儿患唇腭裂之间关联的最大规模研究。剂量反应关系中的显著趋势有力地表明了吸烟与这种常见先天性畸形之间的关联。这些结果强调了孕期吸烟相关的公共卫生风险。为预防这种严重的颅面畸形，应考虑开展教育活动，提醒准妈妈们孕期吸烟与唇腭裂发生之间的关联。
