Suzano C E S, Amaral E, Sato H K, Papaiordanou P M
State University of Campinas (UNICAMP), Rua Alexander Fleming 101, Cid. Universitária, Campinas, São Paulo, CEP 13083-881, Brazil.
Vaccine. 2006 Feb 27;24(9):1421-6. doi: 10.1016/j.vaccine.2005.09.033. Epub 2005 Oct 3.
This study describes the consequences of the inadvertent immunization of pregnant women during a mass vaccination campaign in the Campinas region of the state of São Paulo, Brazil, in February and March 2000. The study was carried out by the Women's Comprehensive Healthcare Center (CAISM), at the State University of Campinas (UNICAMP). The objective of the study was to evaluate the possible effects of the vaccine on pregnancy and conceptus, and to assess congenital infection resulting from immunization.
Pregnant women who received the YF vaccine were identified at primary health clinics and referred to the study site, a public reference, high-risk clinic, serving 42 towns in a region with a population of 3,000,000. A 12-month serological follow-up for newborns (PRNT), and an examination to detect congenital abnormalities was offered to pregnant women, who signed a consent form. In a sub-sample of women who were delivered at the study site, additional exams were proposed: neonatal fontanel ultrasound, funduscopy, audiometry, neuro-pediatric follow-up until 12 months of age, and IgM detection at birth. Fifteen blood samples from placentas and umbilical cords were tested for PCR.
A total of 480 pregnant, immunized women were identified, who had received the vaccine at a mean of 5.7 weeks (95% CI 5.2-6.2) of gestation. The great majority of women were unaware of their pregnancy at the time they were vaccinated, and only 46.7% were counseled to avoid immunization if pregnant. After a minimum 6-week interval, 98.2% pregnant women were IgG positive. A total of 19.6% of women reported mild adverse events (headache, fever or myalgia). No IgM antibodies were detected at birth and no placental or umbilical cord blood was positive according to PCR. The frequency of malformations (2.3% or 7/304 babies), miscarriages (2.5% or 11/441 pregnancies), stillbirths (0.7%) and premature delivery (7.8%) was similar to that found in the general population. At 12 months follow-up, 7% of samples were reactive to PRNT. However, after 12 months, only one child was seropositive.
Contrary to a previous study, maternal seroconversion was very high when immunization was carried out in early pregnancy. Vaccine applied during the first trimester does not appear to cause malformations, complications to the central nervous system, nor adverse perinatal results as represented by premature deliveries or perinatal deaths. The 12-month serological follow-up is inconclusive and should be extended to 24 months. Evaluation of the risk of miscarriage was hindered by late presentation at the study clinic.
本研究描述了2000年2月和3月在巴西圣保罗州坎皮纳斯地区开展大规模疫苗接种运动期间，孕妇意外接种疫苗的后果。该研究由坎皮纳斯州立大学（UNICAMP）的妇女综合保健中心（CAISM）进行。研究目的是评估疫苗对妊娠和胎儿的可能影响，并评估免疫接种导致的先天性感染。
在初级保健诊所识别出接种黄热病疫苗的孕妇，并将其转介至研究地点，即一家为300万人口的地区的42个城镇服务的公共参考高危诊所。为签署了知情同意书的孕妇提供为期12个月的新生儿血清学随访（PRNT）以及检测先天性异常的检查。在研究地点分娩的妇女亚样本中，还建议进行其他检查：新生儿囟门超声检查、眼底镜检查、听力测定、直至12个月大的神经儿科随访以及出生时的IgM检测。对15份胎盘和脐带血样本进行了PCR检测。
共识别出480名接种疫苗的孕妇，她们接种疫苗时的平均孕周为5.7周（95%CI 5.2 - 6.2）。绝大多数妇女在接种疫苗时并不知道自己已怀孕，只有46.7%的妇女在怀孕时被告知应避免接种疫苗。经过至少6周的间隔后，98.2%的孕妇IgG呈阳性。共有19.6%的妇女报告有轻微不良事件（头痛、发热或肌痛）。出生时未检测到IgM抗体，根据PCR检测，胎盘和脐带血均为阴性。畸形（2.3%或7/304名婴儿）、流产（2.5%或11/441次妊娠）、死产（0.7%）和早产（7.8%）的发生率与普通人群相似。在12个月的随访中，7%的样本对PRNT呈反应性。然而，12个月后，只有一名儿童血清学呈阳性。
与之前的一项研究相反，在妊娠早期进行免疫接种时，母体血清转化非常高。孕早期接种疫苗似乎不会导致畸形、中枢神经系统并发症，也不会导致以早产或围产期死亡为代表的不良围产期结局。12个月的血清学随访结果尚无定论，应延长至24个月。研究诊所就诊较晚阻碍了对流产风险的评估。
