Syphilis is a chronic infectious disease caused by the syphilis spirochete, which can cause multi-organ damage. Syphilis spirochetes can infect the fetus through the placenta, posing a serious risk to both the pregnant woman and the fetus and infant. Currently, many clinicians do not know enough about the diagnosis and management of syphilis in pregnancy, some concepts are unclear, and there is a problem of over-diagnosis and over-treatment of patients with syphilis in pregnancy and their newborns. In 2012, the Infectious Diseases Collaborative Group of the Obstetrics and Gynecology Branch of the Chinese Medical Association published the “Expert Consensus on the Diagnosis and Management of Syphilis in Pregnancy” (hereinafter referred to as the Consensus), which proposed that syphilis in pregnancy should be treated according to international standards, and since 2014, relevant guidelines have been published by professional societies in China, Europe and the United States. The progress of research on the diagnosis and management of syphilis in pregnancy is introduced. The incidence of syphilis in pregnancy in domestic Domestic is 2‰~5‰, accounting for 9.2% of female syphilis and 5.1% of all syphilis. Screening of 279,334 pregnant women revealed that 838 cases (3.0‰) were combined with syphilis; 8.2% (34/417) of infants delivered by mothers with syphilis were diagnosed with congenital syphilis and 24.7% (103/417) had adverse pregnancy outcomes. Compared with non-congenital syphilis and no adverse pregnancy outcome, high non-spirochete antibody titers, early syphilis stage, short interval between the start of first treatment and delivery, older gestational age at the time of treatment, cocaine use by the patient’s partner and syphilis infection were positively associated with congenital syphilis and adverse pregnancy outcome, whereas the presence of prenatal testing and completion of anti-syphilis treatment were negatively associated with congenital syphilis and adverse pregnancy outcome. There was a negative association between the presence of prenatal testing and completion of anti-syphilis treatment and the occurrence of congenital syphilis and adverse pregnancy outcomes. Older patient age, cocaine use, history of ectopic pregnancy, high non-spirochete antibody titers, short interval between the start of first treatment and delivery, older gestational age at the time of treatment, and infection of the patient’s spouse with syphilis were positively associated with poor pregnancy outcome; previous syphilis history, prenatal examination, and completion of anti-syphilis treatment were negatively associated with poor pregnancy outcome. Screening of 27 150 pregnant women in rural Guangzhou found that 106 (3.9 per 1000) were combined with syphilis, of which 78 (73.6%) received anti-syphilis treatment, and multifactorial analysis showed that the rate of syphilis infection was higher in pregnant women of advanced age and with a history of adverse delivery [7]. A meta-analysis of 54 papers in English and Chinese, including 11,398 patients with combined syphilis in pregnancy and 43,342 non-syphilitic pregnant women, found that the estimated incidence of adverse pregnancy outcomes among untreated syphilitic pregnant women was as high as 76.8%, including 36.0% for congenital syphilis, 23.2% for preterm birth, 23.4% for low birth weight infants, 26.4% for stillbirths, 14.9% for miscarriages 14.9%, and 16.2% of neonatal deaths. Among pregnant mothers with syphilis who started treatment late in pregnancy (after 28 weeks of gestation), 64.4% had adverse pregnancy outcomes, including 40.6% of congenital syphilis, 17.6% of preterm births, 12.4% of low birth weight babies, and 21.3% of stillbirths. Among pregnant mothers with high titers of positive antibodies (≥1:8) syphilis, 42.8% had adverse pregnancy outcomes, including 25.8% with congenital syphilis, 15.1% with preterm birth, 9.4% with low birth weight, 14.6% with stillbirth, and 16.0% with neonatal death. Among non-syphilitic pregnant women, the incidence of adverse pregnancy outcomes was 13.7%, including 7.2% of preterm births, 4.5% of low birth weight babies, 3.7% of stillbirths, 2.3% of miscarriages, and 2.0% of neonatal deaths; overall, the incidence of adverse pregnancy outcomes was significantly higher among pregnant women with combined syphilis than among pregnant women in general [8].From 2002 to 2011, 2,077,362 pregnant women were screened for syphilis in Shenzhen. pregnant women were screened for syphilis, and the screening rate increased from 89.8% in 2002 to 97.4% in 2011; 7,668 of these pregnant women with syphilis were treated. As a result, the incidence of adverse pregnancy outcomes (including spontaneous abortion, preterm delivery and stillbirth) decreased from 27.3% in 2003 to 8.2% in 2011; the incidence of congenital syphilis decreased from 115 per 100,000 (live births) in 2002 to 10 per 100,000 (live births) in 2011 [9].Gomez et al [10] analyzed 6 of 3,258 literature studies that met the criteria Gomez et al [10] analyzed 6 case-control studies from 3,258 publications that met the criteria and found that untreated pregnant women with syphilis had a 21% higher stillbirth rate, a 9.3% higher neonatal mortality rate, and a 5.8% higher incidence of preterm or low birth weight infants than non-syphilitic pregnant women; 15% of infants delivered by these women had congenital syphilis. It has also been demonstrated that standardized screening and treatment of syphilis in pregnancy can interrupt 99.1% of mother-to-child transmission. Screening and diagnosis of syphilis is performed on all pregnant women at the first antenatal visit after pregnancy, preferably within the first three months of pregnancy. For pregnant women in areas with a high prevalence of syphilis or pregnant women at high risk of syphilis, they need to be screened again in the last 3 months of pregnancy and before delivery. Stage I syphilis can be diagnosed by taking exudate directly from the skin mucosal damage of the lesion and seeing the syphilis spirochete under the dark field microscope. All stages of syphilis can be diagnosed by serology and cerebrospinal fluid examination. Pregnancy-associated syphilis is more common with latent syphilis, with emphasis on detection of syphilis based on serologic screening. Non-spirochetal tests include rapid plasma reagin circle card test (RPR) and venereal disease research laboratory test (VDRL), and spirochetal tests include spirochetal gelatin agglutination test (treponema pallidum particle test). treponema pallidum particle assay (TPPA) and fluorescent treponemal antibody absorption test (FTA-ABS). The non-spirochete test or the spirochete test can corroborate each other. Quantitative non-spirochete tests can also be used to determine efficacy. In cases of autoimmune disease, recent febrile illness, pregnancy, or drug addiction, the non-spirochete test may give a false positive reaction and further confirmation of the diagnosis is required with the spirochete test. The spirochete test detects anti-syphilis spirochete IgG, and most patients have a lifetime positive spirochete test, with or without treatment. Spirochete test antibody titers do not assess treatment response. Non-spirochete test antibody titers usually decline after treatment or become negative over time, but in some patients, the non-spirochete test can show persistent positive antibodies for a long time, called “serofixation”. In a 17-year cohort study that analyzed the pregnancy outcomes of 58,569 women, 113 cases (0.19%) were found to have syphilis in pregnancy; of the 17 patients who tested positive for non-spirochetes late in pregnancy, 10 were not screened late in pregnancy and tested positive during delivery. All newborns were serologically screened negative. Empirical penicillin treatment was applied to these 10 neonates. The cost of evaluating and treating neonates for syphilis was$11,079 at 2011 hospital rates. The cost of routinely applying VDRL for syphilis screening to all pregnant women at 28 to 32 weeks of gestation was$1,991,346 over the 17-year study period. The study concluded, based on a cost-benefit analysis, that routine re-screening for syphilis in late pregnancy lacks relevance. Re-screening at 28 to 32 weeks of gestation and before delivery is currently recommended only for pregnant women in areas with a high prevalence of syphilis or at high risk of syphilis. Of 235 cases of fetal syphilis, 73 (31.1%) showed signs of fetal syphilis on first ultrasound, including hepatomegaly, placenta enlargement, amniotic fluid, ascites and abnormal middle cerebral artery ultrasound Doppler assessment; after treatment, usually the middle cerebral artery ultrasound abnormalities, ascites and amniotic fluid first reduced, decreased or returned to normal, followed by placenta enlargement and finally hepatomegaly [15]. Of the 173 infants followed up to delivery outcome, 32 (18.5%) were diagnosed with congenital syphilis. Congenital syphilis was more common in those with prenatal ultrasound abnormalities than in those with normal ultrasound (39% and 12%, respectively). Fetuses with no pre-treatment ultrasound abnormalities and those with abnormal findings had similar findings on postnatal examination. In children with congenital syphilis, hepatomegaly was the most common, regardless of the prenatal ultrasound diagnosis. Treatment 1. Treatment principles: Early standardized treatment should be carried out. The purpose of standardized treatment is to treat pregnant women on the one hand, and to prevent or reduce congenital syphilis in infants on the other. Treatment in early pregnancy has the potential to avoid fetal infection, and treatment in mid to late pregnancy can allow the infected fetus to be cured before delivery. If a pregnant woman has a positive serologic test for syphilis and syphilis cannot be ruled out, she should be treated again for the protection of the fetus, despite having received anti-syphilis treatment. If a patient with syphilis is pregnant and has received regular treatment and follow-up, no further treatment is necessary. If there are doubts about the previous treatment and follow-up, or if this examination reveals signs of syphilis activity, the patient should receive 1 more course of treatment. The 2012 consensus did not follow the previous recommendation of “starting one course of regular anti-syphilis treatment upon detection of syphilis and another course of anti-syphilis treatment in late pregnancy” in China [1], mainly based on the following considerations: (1) the original recommendation was not supported by clear studies; (2) the original recommendation had the problem of misuse of antibiotics and was not in accordance with the principles of antibiotic application; (3) in the Chinese Obstetrics and Gynecology (2nd edition) (3) this recommendation is no longer used in the “syphilis treatment” of the Chinese Journal of Obstetrics and Gynecology (2nd edition), and some scholars have questioned the routine anti-syphilis treatment in late pregnancy; (4) in order to maximize the prevention of congenital syphilis, the consensus emphasizes strict follow-up after treatment and retreatment for those with indications for repeat treatment. The consensus lists the indications for repeat treatment, stating that “if the titer of non-spirochete antibody increases or does not decrease by 2 dilutions 3 months after treatment, repeat treatment should be given. However, for patients with low non-spirochete antibody titers, such as those with antibody titers of 1:4 or less, antibody titers usually do not achieve a “2 dilution drop”. For this group of patients, as long as the antibody titer does not increase, there is no need to repeat the treatment. Domestic experts have been following the recommendations of the STD Control Center of the Chinese Center for Disease Control and Prevention regarding the treatment of syphilis in pregnancy. Some recently published studies do not emphasize that anti-syphilis treatment should be routinely repeated in late pregnancy. Chinese Obstetrics and Gynecology (3rd edition) follows the internationally accepted norms and also does not recommend routine repeat anti-syphilis treatment in late pregnancy. The available evidence suggests that increasing the penicillin dose does not enhance the efficacy. There is a need to investigate the difference in effectiveness of routine repeat anti-syphilis treatment in late pregnancy versus no routine repeat treatment in the prevention of congenital syphilis. 2. treatment options: Clement et al [22] reviewed the advances in syphilis treatment and showed that injectable penicillin is still the preferred treatment for syphilis. The treatment of syphilis in pregnancy is similar to the treatment of syphilis in non-pregnancy. For stage I syphilis, stage II syphilis and latent syphilis of less than 1 year duration, benzathine penicillin 2.4 million U intramuscularly, 1 time/week for 2 weeks; or procaine penicillin 800,000 U intramuscularly, 1 time/d for 10-14 d. For latent syphilis, syphilitic dendritis and cardiovascular syphilis of more than 1 year duration or unclear duration, benzathine penicillin 2.4 million U intramuscularly, 1 time/ For the treatment of neurosyphilis, administer benzathine penicillin 3-4 million U intravenously once/4 h for 10-14 d. After that, continue with benzathine penicillin 2.4 million U intravenously once/week for 3 weeks (7.2 million U in total) or Procaine penicillin 2.4 million U intramuscular injection, 1 time/d, plus propofol 500 mg orally, 4 times/d, the two drugs together, for 10~14 d. 3. Special problems: For penicillin allergic patients, the reliability of their allergy history should be explored first, and penicillin skin allergy test should be redone if necessary. For those allergic to penicillin, oral or intravenous penicillin desensitization is preferred before treatment with penicillin. The data of 13 studies that met the criteria were selected from 2,765 retrospective studies, including a total of 3,466,780 patients, and the analysis revealed that of the 2,028,982 patients treated with benzathine penicillin, 56 (0.002%) developed allergic reactions and 4 patients died, all from severe allergic reactions. of the 3,465,322 non-pregnant patients, adverse reactions occurred in 6 377 cases (0.169%), and no serious adverse reactions occurred in 1,244 pregnant women who applied benzathine penicillin. If desensitization is ineffective, cephalosporin antibiotics or erythromycin can be used, such as ceftriaxone 500 mg intramuscularly once/d for 10 d or erythromycin 500 mg orally 4 times/d for 14 d. It should be noted that ceftriaxone may be cross-allergic to penicillin, and those with a history of severe penicillin allergy should not use ceftriaxone or should be desensitized to penicillin first. There is a lack of information on the pharmacokinetics of cephalosporin antibiotics from the placenta to the fetus and their effectiveness in preventing congenital syphilis. Doxycycline is the treatment of choice after delivery. Jarisch-Herxheimer reaction (JHR) is a strong metabolic reaction in the body caused by the release of large amounts of allogeneic proteins and endotoxin after the killing of syphilis spirochetes during anti-syphilis treatment, which manifests as fever, uterine contractions, decreased fetal movement, and temporary late fetal heart rate deceleration by fetal heart monitoring. Pregnant women and fetuses with severe syphilis infection have a high incidence of post-treatment gi-hai reaction, preterm delivery, stillbirth or stillbirth. Patients with high titers of non-spirochete test antibodies (e.g. RPR ≥ 1:32) in late pregnancy should be treated with oral prednisone 5 mg 4 times/d for 4 d before treatment to reduce the Gi-hai reaction; patients with early syphilis beyond 20 weeks of gestation should be hospitalized for observation if available. Tetracycline and doxycycline are contraindicated in pregnant women, and they need to be informed that treatment with erythromycin does not prevent congenital syphilis. Many treatment failures in pregnant women are associated with reinfection and sexual partners must be tested and treated at the same time. All pregnant women with syphilis in pregnancy should be screened for human immunodeficiency virus infection and other sexually transmitted diseases prior to treatment. 4. Obstetric management: syphilis in pregnancy is a high-risk pregnancy. During the ultrasound examination at 24-26 weeks of gestation, attention should be paid to the signs of congenital syphilis in the fetus, including fetal hepatosplenomegaly, gastrointestinal obstruction, ascites, fetal edema, fetal growth restriction and placenta enlargement and thickening, etc. Ultrasound examination reveals obvious fetal involvement, which often indicates a poor prognosis, and no termination of pregnancy is necessary if no fetal abnormality is found. The mode of delivery is determined by obstetric indications. Those who have received standard anti-syphilis treatment before delivery and responded well to the treatment can breastfeed after excluding fetal infection. Depending on whether the pregnant woman with syphilis in pregnancy is diagnosed or effectively treated before delivery, the newborn may have four conditions, namely, confirmed infection, probable infection, low chance of infection and almost no chance of infection. The newborns with confirmed infection and probable infection are treated as congenital syphilis, while those with low chance of infection and almost impossible infection may be followed up or given a single injection of benzathine penicillin 50,000 U/kg according to body weight. there is an overdiagnosis of congenital syphilis and the resulting overtreatment, which not only causes a waste of resources but also causes great stress to the mother and her family. Our scholars followed 42 reported congenital syphilis infants for 12 months and finally proved that none of these infants had congenital syphilis. Bradley et al. observed 328 infants, 87 of which were diagnosed with syphilis by their mothers and another 241 were suspected of syphilis by infant blood tests. The consensus recommended the management of neonates of pregnant women with syphilis in pregnancy based on the diagnosis, treatment and response to treatment during pregnancy and neonatal test results, emphasizing follow-up for neonates with indeterminate congenital syphilis and, if necessary, a single dose of benzathine penicillin 50,000 U/kg ( maximum dose of 2.4 million U) intramuscularly. Medical personnel need to update their knowledge to avoid overdiagnosis and overtreatment of newborns delivered by pregnant women with syphilis in pregnancy. V. Follow-up was studied in 166 patients, 93 of whom had early syphilis and a mean gestational age of (29.1±5) weeks at the time of treatment. The antibody titer of the non-spirochete test decreased after treatment in all cases, and in 63 patients the antibody titer decreased by 4 dilutions up to the time of delivery. Those whose antibody titers did not decrease by 4 dilutions at delivery were mainly seen in patients who were older, started treatment late in pregnancy, had late syphilis or syphilis with indeterminate latency, and those who had a short interval between treatment and delivery; the fact that antibody titers did not obtain the desired decrease after treatment does not necessarily mean treatment failure. After treatment for syphilis in pregnancy, non-spirochete antibodies should be tested every month before delivery; in patients with high antibody titers, treatment should be repeated if antibody titers rise or fall by less than 2 dilutions 3 months after treatment. In patients with low antibody titers (e.g., VDRL ≤ 1:2 or RPR ≤ 1:4), the decrease in antibody titers is often not obvious after treatment, and as long as antibody titers do not increase after treatment, there is usually no need for retreatment. All newborns delivered by pregnant women with syphilis in pregnancy should be followed up.