Pitfalls in the diagnosis of congenital rubella syndrome in the first trimester of pregnancy

Abstract

A 29-year-old woman, gravida 3 para 0, was referred at 19 weeks of gestation because of a maternal rubella infection during the first trimester of pregnancy. She consulted at 5 weeks for a rash, which, at that time, was considered to be urticaria. Her serological status for rubella was unknown at that time, and as rubella infection was not considered, serological investigations were not conducted. At 6 weeks, toxoplasma and rubella testings were performed as recommended by the French High Health Authority [Haute Autorité de Santé (HAS)]. HAS only recommends IgG testing for routine Rubella screening and both IgG and IgM testings for toxoplasma.1 Her results were negative for rubella-specific IgG and positive for toxoplasma-specific IgG [104 IU/mL (cutoff: 10.5 IU/mL)] and IgM [5.23 (cutoff: 1), Access 2, Beckman Coulter, Fullerton, CA, USA]. Because these findings suggested a recent toxoplasma infection, spiramycine was started pending the results of the IgG avidity test. The avidity index was high, 0.48 (cutoff: 0.30; Vidas bioMérieux, Marcy-l'Étoile, France), thus making postconceptional toxoplasma seroconversion very unlikely, and spiramycine was stopped. As recommended by HAS, all rubella seronegative patients have a subsequent rubella testing at around 20 weeks. Her second serology performed at 16 weeks indicated a seroconversion leading to IgM testing: rubella-specific IgG, 181.6 IU/mL (cutoff: 10 IU/mL; Architect Abbott, Wiesbaden Germany) and rubella-specific IgM, 1.48 (cutoff: 1.2; Vidas bioMérieux). Retrospective analysis of the serum collected at 6 weeks indicated that rubella-specific IgM was already positive at that time (3.15). The IgG avidity index was measured using our in-house urea wash method. This method is based on adding 6 M urea as a denaturing agent to the washing buffer to prevent the binding of low-avidity antibody to the antigen. Results are expressed as a ratio of absorbance of a single serum dilution with and without denaturing agent. An avidity index of <30% is considered as very low, between 30% and 70% as low, between 70% and 90% as moderate, and >90% as high.2 The IgG avidity index was 78% (moderate) at 16 weeks. Together with the analysis of IgM kinetics on both samples,2 the primary infection was dated at around 5 weeks, coinciding with the rash described by the patient. The ultrasound at 16 weeks was unremarkable. Amniocentesis at 18 weeks detected rubella viral RNA by RT-nested-PCR analysis3 indicating congenital rubella infection. The ultrasound scan at 19 weeks revealed intrauterine growth restriction, together with asymmetric bilateral microphthalmia (below the 5th percentile),4 opacity of the right lens (Figures 1 and 2), and an isolated hyperechogenic mitral focus. Because these signs indicated symptomatic fetal rubella infection, the couple asked for termination of pregnancy. The male fetus weighed 190 g (below the 5th percentile for 20 weeks). The pathology examination confirmed bilateral microphthalmia and the fetal infection with biopsies from the liver and the brain being positive for rubella viral RNA.