OBJECTIVE: To assess antenatal, birth, and infant outcomes for pregnant women, fetuses, and infants after antenatal vaccination with any antigen present in combination pertussis vaccines.
DATA SOURCES: PubMed, EMBASE, Literature in the Health Sciences in Latin America and the Caribbean, ClinicalTrials.gov, Cochrane Library, and World Health Organization (inception to May 5, 2016).
METHODS OF STUDY SELECTION: Studies reporting outcomes for pregnant women, their fetus, or infant after antenatal exposure to either monovalent or combined tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) or inactivated polio vaccines were considered for inclusion.
RESULTS: A total of 21 studies were included in this review. Point estimates ranged from 0.47 to 1.50 for preterm birth (less than 37 weeks of gestation), 0.65–1.00 for small for gestational age (birth weight less than the 10th percentile), 0.36–0.85 for stillbirth, 0.16–1.00 for neonatal death, 0.76–1.20 for low birth weight (less than 2,500 g), and 0.20–0.91 for congenital anomalies. All lower 95% confidence intervals (CIs) were less than 1.0. Of three retrospective studies assessing chorioamnionitis after vaccination, one showed a small but statistically significant increase. Point estimates for all anomalies after antenatal tetanus toxoid vaccination ranged from 1.20 to 1.60 and had 95% CIs that crossed 1.0. There was substantial clinical and methodologic heterogeneity from mainly retrospective observational studies with an overall high risk of bias. Objective rates of fever were low, 3% or below, and more common systemic events observed included headache, malaise, and myalgia.
CONCLUSION: Evidence suggests that antenatal combined Tdap administered during the second or third trimester of pregnancy is not associated with clinically significant harms for the fetus or neonate. Medically attended events in pregnant women are similar between vaccinated and unvaccinated groups.
Combined tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccines administered during the second or third trimester of pregnancy are not associated with clinically significant harms.
Vaccinology and Immunology Research Trials Unit, Women's and Children's Hospital, School of Medicine and Robinson Research Institute, the University of Adelaide, North Adelaide, Australia; Children's Hospital of Eastern Ontario Research Institute and University of Ottawa, Ottawa, Ontario, Canada; and the Immunisation, Hepatitis, and Blood Safety Department, Public Health England, London, United Kingdom.
Corresponding author: Mark McMillan, MClSc, Vaccinology and Immunology Research Trials Unit, Women's and Children's Hospital, School of Medicine, University of Adelaide, 72 King William Road, North Adelaide 5006, South Australia; email: email@example.com.
Financial Disclosure Research grants from vaccine manufacturers GSK and Sanofi Pasteur for investigator-led research have been provided to the institution at which Mr. McMillan, Ms. Clarke, Dr. Parrella, and Dr. Marshall are employees. Dr. Marshall has been an investigator for studies funded by pharmaceutical companies including GSK and Sanofi-Pasteur. Travel support has been provided to her institutions by GSK for Dr. Marshall to present scientific data at international meetings. Mr. McMillan and Dr. Parrella received travel support from GSK in 2014 to present at the Australian National Immunisation Conference. Ms. Amirthalingam has received accommodation costs covered by Medscape Education (sponsored by an unrestricted grant from GSK) to present on the maternal pertussis program at the ESPID 2016 meeting. Dr. Fell did not report any potential conflicts of interest.
Each author has indicated that he or she has met the journal’s requirements for authorship.