False-negative syphilis screening: the prozone phenomenon, nonimmune hydrops, and diagnosis of syphilis during pregnancy.

The prevalence of congenital syphilis is rapidly rising in several areas of the United States. Efforts to control the disease depend on the effectiveness of established screening strategies and treatment of infected pregnant women. False-negative test results hinder these efforts and leave the fetus at risk for acquiring congenital syphilis. Recently we encountered four cases of false-negative syphilis serologic results in women who gave birth to infants with congenital syphilis. The false-negative results were caused by the prozone phenomenon. The prozone phenomenon, seen during primary and secondary syphilis, occurs because a higher than optimal amount of antibody in the tested sera prevents the flocculation reaction typifying a positive result in reagin tests. Serum dilution is necessary to make the correct diagnosis. We recommend that for any pregnant woman with apparently negative syphilis serologic results in whom fetal compromise of unknown etiology exists, particularly nonimmune hydrops, nontreponemal testing should be repeated using serum dilutions to prevent a missed diagnosis of syphilis. We further recommend serum dilution as a routine procedure for all pregnant women in areas of high syphilis prevalence.