四价人乳头瘤病毒疫苗接种与不良妊娠结局的风险。

Quadrivalent HPV Vaccination and the Risk of Adverse Pregnancy Outcomes.

机构信息

From the Department of Epidemiology Research, Statens Serum Institut, Copenhagen (N.M.S., B.P., D.M.-N., H.S., A.H.); and the Clinical Epidemiology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm (B.P.).

出版信息

N Engl J Med. 2017 Mar 30;376(13):1223-1233. doi: 10.1056/NEJMoa1612296.

DOI:10.1056/NEJMoa1612296

PMID:28355499

Abstract

BACKGROUND

The quadrivalent human papillomavirus (HPV) vaccine is recommended for all girls and women 9 to 26 years of age. Some women will have inadvertent exposure to vaccination during early pregnancy, but few data exist regarding the safety of the quadrivalent HPV vaccine in this context.

METHODS

We assessed a cohort that included all the women in Denmark who had a pregnancy ending between October 1, 2006, and November 30, 2013. Using nationwide registers, we linked information on vaccination, adverse pregnancy outcomes, and potential confounders among women in the cohort. Women who had vaccine exposure during the prespecified time windows were matched for propensity score in a 1:4 ratio with women who did not have vaccine exposure during the same time windows. Outcomes included spontaneous abortion, stillbirth, major birth defect, small size for gestational age, low birth weight, and preterm birth.

RESULTS

In matched analyses, exposure to the quadrivalent HPV vaccine was not associated with significantly higher risks than no exposure for major birth defect (65 cases among 1665 exposed pregnancies and 220 cases among 6660 unexposed pregnancies; prevalence odds ratio, 1.19; 95% confidence interval [CI], 0.90 to 1.58), spontaneous abortion (20 cases among 463 exposed pregnancies and 131 cases among 1852 unexposed pregnancies; hazard ratio, 0.71; 95% CI, 0.45 to 1.14), preterm birth (116 cases among 1774 exposed pregnancies and 407 cases among 7096 unexposed pregnancies; prevalence odds ratio, 1.15; 95% CI, 0.93 to 1.42), low birth weight (76 cases among 1768 exposed pregnancies and 277 cases among 7072 unexposed pregnancies; prevalence odds ratio, 1.10; 95% CI, 0.85 to 1.43), small size for gestational age (171 cases among 1768 exposed pregnancies and 783 cases among 7072 unexposed pregnancies; prevalence odds ratio, 0.86; 95% CI, 0.72 to 1.02), or stillbirth (2 cases among 501 exposed pregnancies and 4 cases among 2004 unexposed pregnancies; hazard ratio, 2.43; 95% CI, 0.45 to 13.21).

CONCLUSIONS

Quadrivalent HPV vaccination during pregnancy was not associated with a significantly higher risk of adverse pregnancy outcomes than no such exposure. (Funded by the Novo Nordisk Foundation and the Danish Medical Research Council.).

摘要

背景

四价人乳头瘤病毒（HPV）疫苗推荐用于所有 9 至 26 岁的女性。一些女性在妊娠早期会无意中接触到疫苗，但关于这种情况下四价 HPV 疫苗的安全性的数据很少。

方法

我们评估了一个包括丹麦所有在 2006 年 10 月 1 日至 2013 年 11 月 30 日期间结束妊娠的女性的队列。我们使用全国性登记册，将疫苗接种、妊娠结局不良和队列中女性的潜在混杂因素相关信息进行了关联。在指定的时间窗口内有疫苗暴露的女性与在同一时间窗口内没有疫苗暴露的女性按照倾向评分进行 1:4 比例匹配。结局包括自然流产、死胎、主要出生缺陷、胎儿生长受限、低出生体重和早产。

结果

在匹配分析中，与无暴露相比，四价 HPV 疫苗暴露并未显著增加主要出生缺陷的风险（1665 例暴露妊娠中有 65 例，6660 例未暴露妊娠中有 220 例；优势比，1.19；95%置信区间 [CI]，0.90 至 1.58）、自然流产（463 例暴露妊娠中有 20 例，1852 例未暴露妊娠中有 131 例；风险比，0.71；95%CI，0.45 至 1.14）、早产（1774 例暴露妊娠中有 116 例，7096 例未暴露妊娠中有 407 例；优势比，1.15；95%CI，0.93 至 1.42）、低出生体重（1768 例暴露妊娠中有 76 例，7072 例未暴露妊娠中有 277 例；优势比，1.10；95%CI，0.85 至 1.43）、胎儿生长受限（1768 例暴露妊娠中有 171 例，7072 例未暴露妊娠中有 783 例；优势比，0.86；95%CI，0.72 至 1.02）或死胎（501 例暴露妊娠中有 2 例，2004 例未暴露妊娠中有 4 例；风险比，2.43；95%CI，0.45 至 13.21）。