人乳头瘤病毒6/11/16/18型疫苗临床试验中的妊娠及婴儿结局：五项随机对照试验的综合分析

Pregnancy and infant outcomes in the clinical trials of a human papillomavirus type 6/11/16/18 vaccine: a combined analysis of five randomized controlled trials.

作者信息

Garland Suzanne M, Ault Kevin A, Gall Stanley A, Paavonen Jorma, Sings Heather L, Ciprero Karen L, Saah Alfred, Marino Deborah, Ryan Desmond, Radley David, Zhou Haiping, Haupt Richard M, Garner Elizabeth I O

机构信息

From the Microbiology and Infectious Diseases Department, Royal Women's Hospital and Department of Obstetrics and Gynecology, University of Melbourne, Melbourne, Victoria, Australia; Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia; Department of Obstetrics, Gynecology, and Women's Health, University of Louisville, Louisville, Kentucky; Department of Obstetrics and Gynecology, University Central Hospital, Helsinki, Finland; Merck Research Laboratories, West Point, Pennsylvania.

出版信息

Obstet Gynecol. 2009 Dec;114(6):1179-1188. doi: 10.1097/AOG.0b013e3181c2ca21.

DOI:10.1097/AOG.0b013e3181c2ca21

PMID:19935017

Abstract

OBJECTIVE

To present a combined analysis of the pregnancy outcomes for women aged up to 45 years enrolled in five phase III clinical studies of the prophylactic quadrivalent human papillomavirus 6/11/16/18 vaccine.

METHODS

Twenty thousand five hundred fifty-one women aged 15-45 years received quadrivalent HPV vaccine or placebo at day 1 and months 2 and 6. Urine pregnancy tests were performed immediately before each injection; participants testing positive were not vaccinated. Women who became pregnant after enrollment were discontinued from further vaccination until resolution of pregnancy. All pregnancies were followed for outcomes.

RESULTS

During the studies, 1,796 vaccine and 1,824 placebo recipients became pregnant, resulting in 2,008 and 2,029 pregnancies with known outcomes. No significant differences were noted overall for the proportions of pregnancies resulting in live birth, fetal loss, or spontaneous abortion. A total of 40 neonates born to vaccinated women and 30 neonates born to women given placebo had one or more congenital anomalies (P=.20). The anomalies were diverse and consistent with those most commonly observed in the general population. The vaccine was well tolerated among women who became pregnant.

CONCLUSION

Administration of quadrivalent human papillomavirus vaccine to women who became pregnant during the phase III clinical trials did not appear to negatively affect pregnancy outcomes. The vaccine is a U.S. Food and Drug Administration pregnancy category B medication (animal studies revealed no evidence of fetal harm, but there are no adequate and well-controlled studies in pregnant women); however, vaccination is not recommended during pregnancy. Postlicensure surveillance is ongoing.

CLINICAL TRIAL REGISTRATION

ClinicalTrials.gov, www.clinicaltrials.gov, NCT00092521, NCT00092534, NCT00092495, NCT00092547 and NCT00090220.

LEVEL OF EVIDENCE

II.

摘要

目的

对纳入预防性四价人乳头瘤病毒6/11/16/18疫苗五项III期临床研究的45岁及以下女性的妊娠结局进行综合分析。

方法

2551名年龄在15 - 45岁的女性在第1天、第2个月和第6个月接受了四价人乳头瘤病毒疫苗或安慰剂。每次注射前立即进行尿妊娠试验；检测呈阳性的参与者未接种疫苗。入组后怀孕的女性停止进一步接种，直至妊娠结束。对所有妊娠进行结局随访。

结果

在研究期间，1796名接种疫苗者和1824名接受安慰剂者怀孕，分别有2008例和2029例妊娠有已知结局。在活产、胎儿丢失或自然流产的妊娠比例方面，总体未观察到显著差异。接种疫苗的女性所生的40名新生儿和接受安慰剂的女性所生的30名新生儿有一个或多个先天性异常（P = 0.20）。这些异常多种多样，与普通人群中最常见的异常一致。怀孕女性对疫苗耐受性良好。