The effects of yellow fever immunization (17DD) inadvertently used in early pregnancy during a mass campaign in Brazil

Vaccine. 2006 Feb 27;24(9):1421-6. doi: 10.1016/j.vaccine.2005.09.033. Epub 2005 Oct 3.


Background: 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.

Methods: 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.

Findings: 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.

Interpretation: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Spontaneous
  • Adolescent
  • Adult
  • Antibodies, Viral / blood
  • Brazil
  • Child
  • Female
  • Fetal Blood / virology
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Infant, Newborn
  • Mass Vaccination*
  • Middle Aged
  • Neutralization Tests
  • Placenta / virology
  • Pregnancy
  • Pregnancy Complications, Infectious / immunology
  • Pregnancy Complications, Infectious / virology
  • Premature Birth
  • RNA, Viral / blood
  • Stillbirth
  • Yellow Fever / prevention & control*
  • Yellow Fever / transmission
  • Yellow Fever Vaccine / administration & dosage
  • Yellow Fever Vaccine / adverse effects*
  • Yellow fever virus / genetics


  • Antibodies, Viral
  • Immunoglobulin G
  • Immunoglobulin M
  • RNA, Viral
  • Yellow Fever Vaccine