Although being easily detectable and treatable during pregnancy for many years, syphilis remains an important cause of perinatal death [13]. Pregnancy with syphilis could be transmitted to the fetus through cord blood and placenta, causing terrible harm to children. Worse, mothers with high RPR baseline titers, refused to receive treatments, and later treatments are most at risk of delivering an adverse outcome [23]. Pregnancy syphilis often has no obvious clinical symptoms, and latent syphilis accounts for the vast majority. This may be related to the temporary inhibition of the immune system in pregnant women during pregnancy. However, no matter it was active syphilis or latent syphilis, miscarriage, premature birth, stillbirth, congenital syphilis, and even neonatal death could happen [24]. The result of our study revealed that maternal syphilis could cause extremely high risk of adverse outcome events, especially premature birth, stillbirth and congenital syphilis.
The results in our study indicated that perinatal adverse outcome is closely related to the RPR titer baseline of their mothers. Additionally, high RPR baseline together with none treatment could increase the risk of adverse perinatal outcome [14]. We also found that the infection degree of mothers directly influenced it of their babies to a certain degree, with the trending of higher the titer of RPR in mother, higher RPR titer and adverse pregnancy outcome in their infants. The RPR seropositive rate at birth is significantly higher in RPR ≥ 1:8 group than RPR < 8 group and TPPA positive group, which needed to be highly valued that when the RPR titer rises above 1:8, the possibility of adverse pregnancy outcome and high RPR titer of the newborn should be informed, especially when the treatment is not effective. Not only that, we also found that double negative (RPR = 0 and TPPA negative) newborns at 12 months decreased extremely if they have higher RPR titers, especially those obtain RPR ≥ 8. None of the newborns with RPR ≥ 8 turned double negative. In the study in Tanzania, they revealed that Tanzanian women who were RPR negative and TPHA positive or who had low RPR titers and a positive specific treponemal test result, didn’t increased the risk of adverse birth outcomes when compared with seronegative women; but they demonstrated that the adverse outcome mainly occurred in 1:32 RPR [13].
Among all the possible adverse outcomes, neonatal death, premature delivery, congenital syphilis and stillbirth occurred frequently. The perinatal deaths represented 0.99% in our study encounter with syphilis, which was higher than 0.4% of all pregnancies in Beijing in the 2013–2015 period [14]. The incidence of neonatal death and stillbirth increased in the pregnant women with RPR titer ≥ 1:8, compared with those in RPR < 1:8. We sought that the number of enrolled samples should response for the insignificant difference. Moreover, the frequency of congenital syphilis was 0.66% during the study period, compared with 3.48% among treated mothers from Shenzhen Province [20], 0.90% from Beijing [14] in recent years.
Most of the factors assumed as potential confounders in our study failed to alter the relationship between adverse outcomes and maternal age, and high-titer active syphilis at birth. The result in our study was consistent with the study in Tanzania [13].
For the terrible consequence of high RPR titer in syphilis pregnancy women, adequate treatment should be implemented once discovered. Timely diagnosis and early definitive penicillin treatment are the most important components of syphilis management during pregnancy [25, 26]. Many researches have revealed that untreated syphilis in pregnancy carries significant risk for stillbirth or fetal loss, premature birth, low birth weight, congenital syphilis and neonatal death [10, 27, 28]. Studies consistently show that the earlier the treatment starts, the lower the risk of adverse pregnancy outcomes [26]. The risk of congenital syphilis could be raised by approximately 10% if there was one-week delay [29]. However, there were only 65% of the women had been treated adequately in the study of Zhang et al [14]. Delightful, the number of patients accepted treatment increased, with proportion of 84.17% in our study. However, the patients without treatment still occupied larger number, which highlighting the need to improve the implementation of the Chinese guidelines.
In the study of Moline et al [30], penicillin was considered as the only known effective treatment during pregnancy. However, some studies have put focus on alternative treatment on syphilis, including ceftriaxone, amoxicillin, and doxycycline [31–34]. In our study, penicillin is the first choice for anti-syphilis, except those allergic patients. In the study of Liang et al [21] they revealed that ceftriaxone compared with penicillin for the treatment of syphilis has insignificant effective. The result in our study revealed that the effect increased with the addition of courses, and the effect achieve best when combined with ceftriaxone. In addition, we also found that the higher the RPR titer was, the more efficacy it could be. Regrettably, the intention-to-treat patients enrolled in our study is still not enough.