Systematic Review of the Manifestations of Congenital Rubella Syndrome

Abstract

Congenital rubella syndrome (CRS) continues to cause disability among unvaccinated populations, particularly in the 62 countries yet to introduce rubella vaccine and in immunized populations with insufficient vaccine coverage to prevent transmission. We systematically reviewed the literature on birth outcomes associated with CRS to estimate the duration, severity, and frequency of combinations of morbidities. We searched PubMed, the Science Citation Index, and references from relevant articles for studies in English with primary data on the frequency of CRS manifestations for ≥20 cases and identified 65 studies representing 66 study populations that met our inclusion criteria. We abstracted available data on CRS cases with one or more hearing, heart, and/or eye defects following maternal rubella infection during the period of 0-20 weeks since the last menstrual period. We assessed the quality and weight of the available evidence using a modified GRADE approach. Most of the evidence originates from studies in developed countries of cohorts of infants identified with CRS in the 1960s and 1970s, prior to the development of standardized definitions for CRS and widespread use of vaccine. We developed estimates of undiscounted disability-adjusted life-years (DALYs) lost per CRS case for countries of different income levels. The estimates ranged from approximately 26 to 38 for high-income countries assuming optimal treatment and approximately 29 to 39 DALYs lost per CRS case in low- and lower middle-income countries assuming minimal treatment, with the lower bound based on 2010 general global burden of disease disability weights and the upper bound based on 1990 age-specific and treatment-specific global burden of disease disability weights.