Cornel M C, Erickson J D, Khoury M J, James L M, Liu Y
Department of Medical Genetics, University of Groningen, Ant. Deusinglaan 4, 9713 AW Groningen, The Netherlands, Tel.: +31 50 363 32 38; Fax: +31 50 318 72 68. E-mail:
Int J Risk Saf Med. 1996;8(3):197-209. doi: 10.3233/JRS-1996-8302.
In many countries, birth defect monitoring systems have been set up in order to identify new teratogens as soon as possible. The usual approach to monitoring involves analysis of the frequency of specific birth defects over time. This approach has been criticized as having poor statistical power to detect epidemics due to new rare teratogenic exposures. A proposed alternative approach is the on-going analysis of risk-factor data with a case-control approach. In this paper, we present birth-defects and risk-factor surveillance data from the Northern Netherlands (NNL). For years of birth 1981-1994, 4014 cases had been registered. We investigated combinations of 32 diagnostic categories and 77 risk factors. For 10 combinations a P value < 0.01 was found; for another 25, the P value was between 0.01 and 0.05. We then checked these positive associations against data from the Metropolitan Atlanta Congenital Defects Program (MACDP) and the MAternal DRug Exposure surveillance project (MADRE). In all three data sets, an association between maternal use of psychotropic drugs (psycholeptics) and cleft lip with or without cleft palate (CLP) was present. The highest odds ratio was found for CLP and maternal use of oxazepam in the NNL data (OR = 8.17, 95% CI 1.26-42.2). Both in the MACDP data and in the NNL data, an association between maternal smoking and clubfoot was found. Although the odds ratios were low, the attributable fraction derived from the NNL data was 11%. Methodologic issues that should be considered in this approach include exposure ascertainment and classification, outcome specificity, and type I errors. The strengths of this approach include its population-based nature and the ability of users to check results against results from other similar systems.
在许多国家，已经建立了出生缺陷监测系统，以便尽快识别新的致畸物。通常的监测方法包括分析特定出生缺陷随时间的发生频率。这种方法被批评为在检测因新的罕见致畸物暴露导致的流行病方面统计效力不足。一种提议的替代方法是采用病例对照方法对风险因素数据进行持续分析。在本文中，我们展示了荷兰北部（NNL）的出生缺陷和风险因素监测数据。对于1981 - 1994年出生的年份，共登记了4014例病例。我们研究了32种诊断类别和77种风险因素的组合。发现10种组合的P值<0.01；另外25种组合的P值在0.01至0.05之间。然后，我们对照大亚特兰大先天性缺陷项目（MACDP）和母亲药物暴露监测项目（MADRE）的数据检查了这些阳性关联。在所有三个数据集中，母亲使用精神药物（抗精神病药物）与唇裂伴或不伴腭裂（CLP）之间均存在关联。在NNL数据中，CLP与母亲使用奥沙西泮的比值比最高（OR = 8.17，95% CI 1.26 - 42.2）。在MACDP数据和NNL数据中，均发现母亲吸烟与马蹄内翻足之间存在关联。尽管比值比很低，但从NNL数据得出的归因分数为11%。这种方法应考虑的方法学问题包括暴露的确定和分类、结局特异性以及I型错误。这种方法的优点包括其基于人群的性质以及用户能够对照其他类似系统的结果检查结果。
