Comparative performance of the traditional and reverse diagnostic algorithms for syphilis in pregnancy

Congenital syphilis rates in the United States have increased significantly over the past decade. Syphilis is a curable infection with the potential for lifelong sequelae in the absence of timely diagnosis and treatment. Routine serologic syphilis screening is universally recommended during prenatal care with the traditional or the reverse diagnostic algorithm. False positive syphilis serologic testing in pregnancy can occur and comparative performance data for recommended algorithms in pregnancy are limited.

To compare the performance of the traditional algorithm and the reverse algorithm for the diagnosis of syphilis in pregnancy.

This retrospective analysis included pregnant women who delivered at our tertiary care center in the Southeastern United States during a period of increasing syphilis rates with testing performed between November 1, 2012 and December 31, 2019. We evaluated results according to the diagnostic algorithm used by facility laboratories at the time of syphilis screening (traditional 2012-2014 and reverse 2015-2019). Screen positivity, false positive test results, confirmed infection, and pregnancy outcomes were compared between the two periods. For secondary outcomes, multivariable logistic regression models were conducted to identify factors associated with false positive screening results and confirmed infection including maternal age, race, insurance status, test timing and location, and human immunodeficiency virus/sexually transmitted infection coinfection.

Of 26,519 pregnant women tested for syphilis during the study period, 8781 were evaluated using the traditional algorithm and 17,738 were evaluated using the reverse algorithm. Mean age was 27.9 years, 85.3% of women were initially screened in the first trimester, and the mean number of syphilis testing episodes in pregnancy was 2.3. Screen positivity was 0.6% among women screened using the traditional algorithm compared to 1.6% for those tested with the reverse algorithm (p < 0.001). The proportion diagnosed with confirmed infection was similar in both algorithms: 0.2% traditional algorithm versus 0.3% reverse algorithm. Among those who screened positive with follow-up testing performed, 52.4% and 60.4% were classified as falsely positive with negative confirmatory testing with the traditional algorithm and the reverse algorithms, respectively. In an adjusted model, delayed testing in pregnancy (odds ratio [OR], 22.8; 95% confidence interval [CI], 14.1-36.8 for ≥28 weeks compared to <14 weeks), inpatient or ER screening location (OR, 22.7; 95% CI, 13.4-38.4 vs. clinic), Black race (OR, 5.4; 95% CI, 3.2-9.2) compared to White, other sexually transmitted infection in pregnancy (OR, 2.2; 95% CI, 1.2-4.1]), and lack of private insurance (OR, 1.8; 95% CI, 1.2-2.9) were associated with false positive syphilis screening. The same factors were associated with confirmed syphilis in pregnancy except for STI coinfection. The reverse algorithm was only associated with false positive screening in the crude model (OR, 2.2; 95% CI, 1.4-3.5).

Syphilis screen positivity rates in pregnancy were nearly twice as high with the reverse algorithm compared to the traditional algorithm. Since false positive screening tests were common, improved diagnostic testing for active infection in pregnancy is needed.