JAMA：研究揭示H1N1疫苗接种后的出生缺陷及神经系统疾病的风险

芝加哥–据7月11日刊《美国医学会杂志》JAMA上的两项研究披露，在检测接种A型流感（H1N1）疫苗后不良后果风险的研究中，在子宫内接触该疫苗的婴儿的严重出生缺陷、早产或胎儿生长受限风险没有明显的增加；而在另外一项研究中，研究人员发现在疫苗接种后的4-8周中，成年人的神经系统疾病和格林-巴利综合征的罹患风险会有小幅的增加。

在第一则研究中，丹麦哥本哈根市国家血清研究所（Statens Serum Institut）的Bj？rn Pasternak， M.D.， Ph.D.及其同事对在妊娠期间接触某种佐剂A型流感（H1N1）pdm09疫苗是否与严重的出生缺陷、早产和胎儿生长受限的风险增加有关进行了调查。根据文章的背景资料，2009年的A型流感（H1N1）大流行使得孕妇的患病、死亡和不良妊娠后果的风险增加。“孕妇属于要优先接种A型流感（H1N1）pdm09疫苗的主要目标群体之一，仅在美国，预计有240万名妇女在怀孕期间接种过该疫苗。然而，在妊娠期间对H1N1接种的胎儿安全性的评估一直局限于一些药物警惕报告和描述性的群组研究。”

该基于登记的研究包括了在2009年11月2日至2010年9月30日间的所有在丹麦出生的活产单个婴儿。研究人员通过比较妊娠期间接触过及未接触过AS03佐剂A型流感（H1N1）pdm09疫苗的婴儿来评估其不良胎儿后果的流行几率比。经过排除法之后，研究人员发现了一群为数5.3432万人的活产婴儿，其中6989（13.1%）人在妊娠期间接触过该疫苗。

在一项对在妊娠头3个月内接触过该疫苗的330个婴儿及330个未接触过该疫苗的婴儿所做的倾向得分匹配分析中，在那些接触过该疫苗的人中有18个婴儿（5.5%）被诊断患有一种严重的出生缺陷，而在那些未接触过该疫苗的人中有15个婴儿（4.5%）被诊断患有一种严重的出生缺陷。在妊娠头3个月中接触过该H1N1疫苗的婴儿中，有31人（9.4%）在出生时为早产，而在未接触该疫苗的婴儿中出生时为早产者有24人（7.3%）。在妊娠第二或第三孕中期中接触过该疫苗的6543名婴儿中有302人（4.6%）为早产，而在6366名未接触过该疫苗的婴儿中有295人（4.6%）为早产。研究人员写道：“将胎龄纳入考虑的话，没有发现与接触疫苗相关的在第一孕中期（25名[7.6%]接触者vs. 31名[9.4%]未接触者）或第二或第三孕中期（641名[9.7%]接触者vs. 657名[9.9%]未接触者）的低于正常胎龄婴儿尺码的风险的增加。”

“总之，这一在丹麦的全国性的群组研究中，人们没有发现在妊娠期间接触一种AS03佐剂A型流感（H1N1）pdm09疫苗与包括严重出生缺陷、早产及胎儿生长受限等不良胎儿后果之间有明显的关系。尽管该数据为与第二或第三孕中期接触该疫苗的有关结果提供了强有力的安全性证据，但来自第一孕中期疫苗接触的分析结果应被视作是初步的并需要得到确认。还需要做进一步的研究来探讨妊娠中的特异性的出生缺陷风险及H1N1疫苗接种的有效性。”

doi:10.1001/jama.2012.6131
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Risk of Adverse Fetal Outcomes Following Administration of a Pandemic Influenza A(H1N1) Vaccine During Pregnancy

Björn Pasternak, MD, PhD; Henrik Svanström, MSc; Ditte Mølgaard-Nielsen, MSc; Tyra G. Krause, MD, PhD; Hanne-Dorthe Emborg, DVM; Mads Melbye, MD, DrMedSci; Anders Hviid, MSc, DrMedSci

Context Assessment of the fetal safety of vaccination against influenza A(H1N1)pdm09 in pregnancy has been limited. Objective To investigate whether exposure to an adjuvanted influenza A(H1N1)pdm09 vaccine during pregnancy was associated with increased risk of adverse fetal outcomes. Design, Setting, and Participants Registry-based cohort study based on all liveborn singleton infants in Denmark, delivered between November 2, 2009, and September 30, 2010. In propensity score–matched analyses, we estimated prevalence odds ratios (PORs) of adverse fetal outcomes, comparing infants exposed and unexposed to an AS03-adjuvanted influenza A(H1N1)pdm09 vaccine during pregnancy. Main Outcome Measures Major birth defects, preterm birth, and small size for gestational age. Results From a cohort of 53 432 infants (6989 [13.1%] exposed to the influenza A[H1N1]pdm09 vaccine during pregnancy [345 in the first trimester and 6644 in the second or third trimester]), 660 (330 exposed) were included in propensity score–matched analyses of adverse fetal outcomes associated with first-trimester exposure. For analysis of small size for gestational age after second- or third-trimester exposure, 13 284 (6642 exposed) were included; for analyses of preterm birth, 12 909 (6543 exposed) were included. A major birth defect was diagnosed in 18 of 330 infants (5.5%) exposed to the vaccine in the first trimester, compared with 15 of 330 unexposed infants (4.5%) (POR, 1.21; 95% CI, 0.60-2.45). Preterm birth occurred in 31 of 330 infants (9.4%) exposed in the first trimester, compared with 24 of 330 unexposed infants (7.3%) (POR, 1.32; 95% CI, 0.76-2.31), and in 302 of 6543 infants (4.6%) with second- or third-trimester exposure, compared with 295 of 6366 unexposed infants (4.6%) (POR, 1.00; 95% CI, 0.84-1.17). Small size for gestational age was observed in 25 of 330 infants (7.6%) with first-trimester exposure compared with 31 of 330 unexposed infants (9.4%) (POR, 0.79; 95% CI, 0.46-1.37), and in 641 of 6642 infants (9.7%) with second- or third-trimester exposure, compared with 657 of 6642 unexposed infants (9.9%) (POR, 0.97; 95% CI, 0.87-1.09). Conclusions In this Danish cohort, exposure to an adjuvanted influenza A(H1N1)pdm09 vaccine during pregnancy was not associated with a significantly increased risk of major birth defects, preterm birth, or fetal growth restriction.