Syphilis During Pregnancy

All women should be screened serologically for syphilis at the first prenatal care visit (174), which is mandated by the majority of states (142). Among populations for whom receipt of prenatal care is not optimal, serologic screening and treatment (if serologic test is reactive) should be performed at the time of pregnancy testing (632). Antepartum screening can be performed by manual nontreponemal antibody testing (e.g., RPR) by using the traditional syphilis screening algorithm or by treponemal antibody testing (e.g., immunoassays) using the reverse sequence algorithm.

Pregnant women with positive treponemal screening tests (e.g., EIA, CIA, or immunoblot) should have additional quantitative nontreponemal testing because titers are essential for monitoring treatment response. Serologic testing should also be performed twice during the third trimester: at 28 weeks’ gestation and at delivery for pregnant women who live in communities with high rates of syphilis and for women who have been at risk for syphilis acquisition during pregnancy.

Maternal risk factors for syphilis during pregnancy include sex with multiple partners, sex in conjunction with drug use or transactional sex, late entry to prenatal care (i.e., first visit during the second trimester or later) or no prenatal care, methamphetamine or heroin use, incarceration of the woman or her partner, and unstable housing or homelessness (174,633–636). Moreover, as part of the management of pregnant women who have syphilis, providers should obtain information concerning ongoing risk behaviors and treatment of sex partners to assess the risk for reinfection.

Any woman who has a fetal death after 20 weeks’ gestation should be tested for syphilis. No mother or neonate should leave the hospital without maternal serologic status having been documented at least once during pregnancy. Any woman who at the time of delivery has no prenatal care history or has been at risk for syphilis acquisition during pregnancy (e.g., misuses drugs; has had another STI during pregnancy; or has had multiple sex partners, a new partner, or a partner with an STI) should have the results of a syphilis serologic test documented before discharge.

Diagnostic Considerations

Pregnant women seropositive for syphilis should be considered infected unless an adequate treatment history is clearly documented in the medical records and sequential serologic antibody titers have decreased as recommended for the syphilis stage. The risk for antepartum fetal infection or congenital syphilis at delivery is related to the syphilis stage during pregnancy, with the highest risk occurring during the primary and secondary stages. Quantitative maternal nontreponemal titer, especially if >1:8, might be a marker of early infection and bacteremia. However, risk for fetal infection is still substantial among pregnant women with late latent syphilis and low titers. Pregnant women with stable, serofast low nontreponemal titers who have previously been treated for syphilis might not require additional treatment; however, increasing or high antibody titers in a pregnant woman previously treated might indicate reinfection or treatment failure, and treatment should be offered.

If an automated treponemal test (e.g., EIA or CIA) is used for antepartum syphilis screening, all positive tests should be reflexed to a quantitative nontreponemal test (e.g., RPR or VDRL). If the nontreponemal test is negative, the results are considered discrepant and a second treponemal test (TP-PA is preferred) should be performed, preferably on the same specimen.

If the second treponemal test is positive (e.g., EIA positive, RPR negative, or TP-PA positive), current or previous syphilis infection can be confirmed. For women with a history of adequately treated syphilis who do not have ongoing risk, no further treatment is necessary. Women without a history of treatment should have the syphilis stage determined and should be treated accordingly with a recommended penicillin regimen.

If the second treponemal test is negative (e.g., EIA positive, RPR negative, or TP-PA negative), the positive EIA or CIA is more likely to represent a false-positive test result for women who are living in communities with low rates of syphilis, have a partner who is uninfected, and have no history of treated syphilis (637,638). If the woman is at low risk for syphilis, lacks signs or symptoms of primary syphilis, has a partner with no clinical or serologic evidence of syphilis, and is likely to follow up with clinical care, repeat serologic testing within 4 weeks can be considered to determine whether the EIA or CIA remains positive or if the RPR, VDRL, or TP-PA result becomes positive. If both the RPR and TP-PA remain negative, no further treatment is necessary. If follow-up is not likely, women with an isolated reactive treponemal test and without a history of treated syphilis should be treated according to the syphilis stage.

Treatment

Penicillin G is the only known effective antimicrobial for treating fetal infection and preventing congenital syphilis (639). Evidence is insufficient to determine the optimal penicillin regimen during pregnancy (640).

Other Management Considerations

The following recommendations should be considered for pregnant women with syphilis infection:

• Certain evidence indicates that additional therapy is beneficial for pregnant women to prevent congenital syphilis. For women who have primary, secondary, or early latent syphilis, a second dose of benzathine penicillin G 2.4 million units IM can be administered 1 week after the initial dose (641–643).
• When syphilis is diagnosed during the second half of pregnancy, management should include a sonographic fetal evaluation for congenital syphilis. However, this evaluation should not delay therapy. Sonographic signs of fetal or placental syphilis (e.g., hepatomegaly, ascites, hydrops, fetal anemia, or a thickened placenta) indicate a greater risk for fetal treatment failure (644); cases accompanied by these signs should be managed in consultation with obstetric specialists. A second dose of benzathine penicillin G 2.4 million units IM after the initial dose might be beneficial for fetal treatment in these situations.
• Women treated for syphilis during the second half of pregnancy are at risk for premature labor or fetal distress if the treatment precipitates the Jarisch-Herxheimer reaction (590). These women should be advised to seek obstetric attention after treatment if they notice any fever, contractions, or decrease in fetal movements. Stillbirth is a rare complication of treatment; however, concern for this complication should not delay necessary treatment. No data are available to support that corticosteroid treatment alters the risk for treatment-related complications during pregnancy.
• Missed doses >9 days between doses are not acceptable for pregnant women receiving therapy for late latent syphilis (613). An optimal interval between doses is 7 days for pregnant women. If a pregnant woman does not return for the next dose on day 7, every effort should be made to contact her and link her to immediate treatment within 2 days to avoid retreatment. Pregnant women who miss a dose of therapy should repeat the full course of therapy.
• All women who have syphilis should be offered testing for HIV at the time of diagnosis.

Follow-Up

Coordinated prenatal care and treatment are vital because providers should document that women are adequately treated for the syphilis stage and ensure that the clinical and antibody responses are appropriate for the patient’s disease stage. If syphilis is diagnosed and treated at or before 24 weeks’ gestation, serologic titers should not be repeated before 8 weeks after treatment (e.g., at 32 weeks’ gestation) but should be repeated again at delivery. Titers should be repeated sooner if reinfection or treatment failure is suspected. For syphilis diagnosed and treated after 24 weeks’ gestation, serologic titers should be repeated at delivery.

A majority of women will not achieve a fourfold decrease in titers before delivery, although this does not indicate treatment failure (645). However, a fourfold increase in titer after treatment (e.g., from 1:8 to 1:32) that is sustained for >2 weeks is concerning for reinfection or treatment failure. Nontreponemal titers can increase immediately after treatment, presumably related to the treatment response. Therefore, unless symptoms and signs exist of primary or secondary syphilis, follow-up titer should not be repeated until approximately 8 weeks after treatment. Inadequate maternal treatment is likely if delivery occurs within 30 days of therapy, clinical signs of infection are present at delivery, or the maternal antibody titer at delivery is fourfold higher than the pretreatment titer.

Management of Sex Partners

See Syphilis, Management of Sex Partners.

Special Considerations

Penicillin Allergy

No proven alternatives to penicillin are available for treatment of syphilis during pregnancy. Pregnant women who have a history of penicillin allergy should be desensitized and treated with penicillin G. Skin testing or oral graded penicillin dose challenge might be helpful in identifying women at risk for acute allergic reactions (see Management of Persons Who Have a History of Penicillin Allergy).

Tetracycline and doxycycline are to be avoided in the second and third trimesters of pregnancy (431). Erythromycin and azithromycin should not be used because neither reliably cures maternal infection nor treats an infected fetus (640). Data are insufficient to recommend ceftriaxone or other cephalosporins for treatment of maternal infection and prevention of congenital syphilis (646,647).

HIV Infection

Placental inflammation from congenital syphilis infection might increase the risk for perinatal transmission of HIV. All women with HIV infection should be evaluated for syphilis and receive a penicillin regimen appropriate for the syphilis stage. Data are insufficient to recommend any alternative regimens for pregnant women with syphilis and HIV infection (see Syphilis Among Persons with HIV).

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