Taguchi Nobuko, Rubin Evelyn T, Hosokawa Akiko, Choi Jacquelyn, Ying Angela Yating, Moretti Myla E, Koren Gideon, Ito Shinya
The Motherisk Program, Division of Clinical Pharmacology and Toxicology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Canada.
Reprod Toxicol. 2008 Oct;26(2):175-7. doi: 10.1016/j.reprotox.2008.06.009. Epub 2008 Jul 1.
Use of HMG-CoA reductase inhibitors (statins) is becoming increasingly common. However, a recent study based on a series of cases reported to FDA suggests possible teratogenic effects of statins on embryogenesis, such as limb defects and severe central nervous system anomalies.
In a prospective, observational cohort study with a comparison group to examine a fetal toxicity risk of statins, we followed 64 pregnant women taking statins, and 64 comparison group women without exposure to known teratogens. The statin group women were exposed to atorvastatin (n=46), simvastatin (n=9), pravastatin (n=6), or rosuvastatin (n=3) during the first trimester.
There was no difference in the rate of major malformations between the statin group (1/46 live birth: 2.2%) and the comparison group (1/52 live birth: 1.9%, p=0.93). Similarly, there were no statistical differences between the statin and comparison groups in live births (71.9% vs 81.2%), spontaneous abortions (14: 21.9% vs 11: 17.2%), therapeutic abortions (3: 4.7% vs 0: 0%) and stillbirths (1: 1.5% vs 1: 1.6%). Gestational age at birth (38.4+/-2.8 weeks vs 39.3+/-1.3 weeks: M+/-S.D., p=0.04) and birth weight (3.14+/-0.68kg vs 3.45+/-0.42kg, p=0.01) were lower in the statin group.
The absolute risk of teratogenicity of statins, if any, appears relatively small. A large-scale study is needed to further characterize the teratogenic potential.
HMG - CoA还原酶抑制剂（他汀类药物）的使用正变得越来越普遍。然而，最近一项基于向美国食品药品监督管理局（FDA）报告的一系列病例的研究表明，他汀类药物对胚胎发育可能有致畸作用，如肢体缺陷和严重的中枢神经系统异常。
在一项有对照组的前瞻性观察队列研究中，为了检验他汀类药物的胎儿毒性风险，我们追踪了64名服用他汀类药物的孕妇以及64名未接触已知致畸物的对照组女性。他汀类药物组的女性在孕早期接触了阿托伐他汀（n = 46）、辛伐他汀（n = 9）、普伐他汀（n = 6）或瑞舒伐他汀（n = 3）。
他汀类药物组（46例活产中有1例：2.2%）和对照组（52例活产中有1例：1.9%，p = 0.93）之间的严重畸形发生率没有差异。同样，他汀类药物组和对照组在活产率（71.9%对81.2%）、自然流产率（14例：21.9%对11例：17.2%）、治疗性流产率（3例：4.7%对0例：0%）和死产率（1例：1.5%对1例：1.6%）方面也没有统计学差异。他汀类药物组的出生孕周（38.4±2.8周对39.3±1.3周：均值±标准差，p = 0.04）和出生体重（3.14±0.68kg对3.45±0.42kg，p = 0.01）较低。
他汀类药物致畸的绝对风险（如果存在的话）似乎相对较小。需要进行大规模研究以进一步明确其致畸潜力。
