Treatment evaluation to improve preventing mother to child transmission among women with syphilis

The aim of this study was to evaluate the effectiveness of preventing mother to child syphilis transmission to improve pregnancy outcomes. We performed a retrospective analysis of municipal databases of mother-to-child syphilis transmission. Pregnant women with syphilis were included. Group specific pregnancy outcomes were analyzed according to treatment. A total of 28 pregnant women were diagnosed with syphilis in 2012; 321 were diagnosed with syphilis in 2018. A prevalence of 0.14% was observed amongst pregnant women in Suzhou city from 2012–2018. Primary treatments included benzathine penicillin, ceftriaxone sodium or erythromycin when patients were allergic to Benzathine penicillin. The treatment coverage was 81.57%, and only 52.86% of pregnant women were adequately treated. Adverse pregnant outcomes were higher amongst untreated women. Expanding early screening coverage and promoting treatment were key to improving pregnancy outcomes amongst women with syphilis.

pregnant women were local residents, and 879 (70.49%) were migrants. Amongst the 10 reported districts, the incidence was highest in Kunshan city and lowest in the Suzhou industrial park. The number of hospitalized live births decreased from 120,343 to 116,399, but the number of pregnant women diagnosed with syphilis increased from 28 to 321 from 2012 to 2018. Approximately 86.45% of pregnant women were diagnosed during prenatal examinations. In total, 12.27% were diagnosed during delivery. The demographic information of the pregnant women with syphilis infection was showed in Table 2.
A total of 106 spontaneous abortions occurred, of which 11 died within 7 days of birth and 17 stillbirths occurred. Adverse pregnancy outcomes were higher amongst untreated women (χ2 = 213.96, p < 0.001). Detailed information is shown in Table 4.

Discussion
According to the National Statutory Infectious diseases reports, the prevalence of adult syphilis and maternal syphilis infections have increased in China since 2011. The prevention of syphilis transmission from mother to children is therefore of high priority. In this study, the average prevalence of syphilis in pregnant women was 0.14%, which was similar to the reported prevalence of Europe (0.16%) 11 . The rate of maternal syphilis in Suzhou was 0.28% in 2018, which was higher than China (0.24%) 12 and the Mediterranean (0.06%), but lower than Latin America (1.1%) and India (0.57-0.78%) 11,13,14 . The increased prevalence of maternal syphilis was partly due to the accumulation of the previously infected women and the inflow of the migrant pregnant women with syphilis infections. According to the requirement of PMTCT of syphilis program, free syphilis screening should be provided to all pregnant women during initial prenatal care examinations, but full coverage was not achieved. Based on our studies, most syphilis cases in infected pregnant women occur in migrants and the unemployed, in which educational background are junior school or below. These women do not value prenatal care and lack access to effective treatment. In addition, women with syphilis infections suffer from the stigma and sociological discrimination that occur for other sexually transmitted diseases (STDs). This physiological status restricts the awareness of pregnant women seeking professional medical healthcare.
Vertical transmission is dependent on the stages of maternal infection, for which the risk is highest during the primary and secondary stages of infection, followed by asymptomatic syphilis during pregnancy 1,15 . Adverse outcomes in pregnant women with syphilis infections are common, particularly for those who are inadequately treated [16][17][18] . A single dose of penicillin is the first-line treatment and most cost-effective treatment for women with syphilis during pregnancy 19,20 . Since the launch of the global initiative of eliminating the MTCT of syphilis, the Chinese government has integrated the PMTCT of HIV and syphilis with maternal healthcare management. The screening and surveillance of prenatal syphilis has improved in Suzhou city. From 2012 to 2018, the number of infants diagnosed with congenital syphilis has decreased. However, due to deliberate concealment and avoidance of syphilis detection, delayed diagnosis leads to delayed treatment. Consistent with previous studies [21][22][23] , to improve patient compliance, a efforts to promote the importance of pregnant syphilis screening and the benefits of standardized treatment have been employed. The syphilis screening rates at the first trimester have improved from 82.14% to 87.85% during the past 7 years in Suzhou. However, treatment rates of 16.32% were recorded in 2018 which were lower than those of 2012. The adverse pregnancy outcomes amongst women lacking treatment were higher than those treated with standard care.
Despite the prevalence of syphilis in Suzhou city being lower than high-epidemic cities in China, the Jiangsu province was highly afflicted due to the large migrant population. Migrants are attracted by economic development. These relationships should be assessed in more detail in future studies.
This was the first study investigating the prevalence of syphilis and its characteristics amongst pregnant women in Suzhou, There were several limitations. Firstly, we could not compare pregnancy outcomes between healthy women and women with syphilis due to the lack of data availability. Secondly, the influence of a partner's infection status on infant health was not assessed due to limited information. Finally, only selected adverse pregnancy outcomes were recorded in the PMTCT system, meaning the effectiveness of PMTCT was not fully evaluated. www.nature.com/scientificreports www.nature.com/scientificreports/ In summary, we demonstrate that full-course and adequate treatment improves pregnancy outcomes and infant health. The priority of PMTCT of syphilis is to improve early screening coverage and the compliance of pregnant women with medication in Suzhou city, particularly in the migrant population.

Methods
Data collection. Data were extracted from the municipal PMTCT system from 2012 to 2018. According to the requirements of the PMTCT program, syphilis counseling and testing were combined with routine prenatal healthcare. All pregnant women underwent syphilis counseling and testing upon their initial prenatal healthcare appointment. Positive results in syphilis rapid plasma regain (RPR)/toluidine red unheated serum test (TRUST) and treponemal pallidum particle agglutination (TPPA)/enzyme linked immunosorbent assay (ELISA) tests led to a diagnosis of maternal syphilis infection. Syphilis infected women were provided free penicillin in the first and the third trimester, respectively. All pregnant women were screened prior to delivery. For children born to syphilis infected women, syphilis screening and preventive treatment were performed if the mothers failed to receive two courses of full-time penicillin during the first and third trimester of pregnancy, or if their mothers received fulltime penicillin treatment during pregnancy. Newborns maintained reactive TRUST or RPR serum titers that were 4-times lower than the mothers prior to delivery. Exposed children were followed up every three months until a   www.nature.com/scientificreports www.nature.com/scientificreports/ syphilis diagnosis was excluded. Information on infected pregnant women, pregnancy outcomes and follow ups of exposed children were recorded in the PMTCT system. Statistical analysis. The database was exported in Excel and analyzed using SPSS 17.0 software (Chicago Illinois, USA). Demographic characteristics of syphilis infected women were described. Categorical variables are presented as numbers and frequencies. Statistically significant differences between the groups were evaluated using the χ 2 -test or Fisher's exact test as appropriate. P < 0.05 was considered statistically significant. ethical considerations. This study was approved by the Ethics committee of Suzhou Municipal Hospital.
All infected mothers were required to complete a routine questionnaire upon receiving syphilis screening and testing at their first antenatal care or delivery. Informed consent was obtained from syphilis infected mothers. Prenatal syphilis screening and testing processes followed the guidelines and regulations of the integrated National Preventing Mother to Child Transmission Program of HIV, Syphilis and Hepatitis B. In the final database, only mothers and infant numbers were listed. All personal information was kept confidential.

Data availability
The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.