NTP Monogr. 2013 May(2):i-214.
The National Toxicology Program (NTP) Office of Health Assessment and Translation (OHAT) conducted an evaluation of the developmental effects and pregnancy outcomes associated with cancer chemotherapy use during pregnancy in humans. The final NTP monograph was completed in May 2013 (available at http:// ntp.niehs.nih.gov/go/36495). The incidence of cancer during pregnancy has been reported to occur from 17 to 100 per 100,000 pregnant women. Chemotherapy is a common treatment for cancer; however, most chemotherapy agents are classified as known or suspected human teratogens. Cancer chemotherapy use during pregnancy was selected for evaluation by the NTP because of the: (1) paucity of comprehensive reviews on the pregnancy outcomes following cancer chemotherapy use during pregnancy in humans, including the integration of the developmental animal toxicology literature with the observational studies in humans, and (2) growing public interest in the developmental effects of chemotherapy on offspring exposed to cancer chemotherapy during gestation due to the expected incidence of cancer diagnosed during pregnancy as women delay pregnancy to later ages. Of the approximately 110 cancer chemotherapeutic agents currently in use, the NTP monograph includes data on 56 agents used during 1,261 pregnancies for which pregnancy outcomes were documented. Overall, the NTP evaluation found that treatment with chemotherapy for cancer appeared to be associated with: (1) a higher rate of major malformations following exposure during the first trimester compared to exposure in the second and/or third trimester; (2) an increase the rate of stillbirth following exposure in the second and/ or third trimester; abnormally low levels of amniotic fluid (primarily attributable to Trastuzumab); and (3), also data are insufficient, impaired fetal growth and myelosuppression. Treatment with chemotherapy for cancer during pregnancy did not appear to increase spontaneous preterm birth, or impair normal growth and development of offspring during early life. In addition, the NTP monograph provides background materials on individual cancer chemotherapeutic agents (e.g., evidence for placenta and breast milk transport, developmental toxicity in animals), and a brief review of the prevalence and prognosis of seven frequently diagnosed cancers in women during pregnancy. Finally, the NTP monograph identifies challenges in interpreting the health outcomes from this observational literature base and discussed possible actions to improve the understanding of the developmental effects of chemotherapy treatment for cancer administered during pregnancy.
美国国家毒理学计划（NTP）健康评估与转化办公室（OHAT）对孕期使用癌症化疗药物对人类发育影响及妊娠结局进行了评估。NTP的最终专著于2013年5月完成（可在http://ntp.niehs.nih.gov/go/36495获取）。据报道，孕期癌症的发病率为每10万名孕妇中有17至100例。化疗是癌症的常见治疗方法；然而，大多数化疗药物被归类为已知或疑似人类致畸剂。NTP选择评估孕期使用癌症化疗药物是因为：（1）缺乏关于孕期使用癌症化疗药物后妊娠结局的全面综述，包括将发育动物毒理学文献与人类观察性研究相结合；（2）由于女性推迟生育年龄导致孕期诊断出癌症的预期发病率，公众对化疗对孕期接触癌症化疗药物后代的发育影响的兴趣日益增加。在目前使用的约110种癌症化疗药物中，NTP专著纳入了1261例记录了妊娠结局的妊娠中使用的56种药物的数据。总体而言，NTP评估发现，癌症化疗治疗似乎与以下情况相关：（1）与孕中期和/或孕晚期接触相比，孕早期接触后严重畸形的发生率更高；（2）孕中期和/或孕晚期接触后死产率增加；羊水过少（主要归因于曲妥珠单抗）；（3）胎儿生长受损和骨髓抑制的数据也不足。孕期癌症化疗治疗似乎不会增加自发早产，也不会损害后代早期的正常生长发育。此外，NTP专著提供了关于个别癌症化疗药物的背景材料（例如，胎盘和母乳转运的证据、动物发育毒性），并简要回顾了孕期女性中七种常见诊断癌症的患病率和预后。最后，NTP专著确定了解释该观察性文献基础中的健康结局所面临的挑战，并讨论了可能采取的行动，以增进对孕期癌症化疗治疗发育影响的理解。
