Maternal syphilis is a health threat to both pregnant women and children. The World Health Organization (WHO) estimated that about two million women suffer from maternal syphilis every year, 60% of whom could transmit the infection to their newborns [1
]. In 2008, there were nearly 521,000 adverse pregnant outcomes (APOs) associated with maternal syphilis and 66% of them occurred in those who were not screened or treated for syphilis during pregnancy [2
]. Maternal syphilis is a disease prevalent in low-income countries and poor populations, such as Malawi (prevalence of seropositivity: 5.56%) [3
], Uganda (4.0%) [4
] and Bangladesh (2.96%) [5
]. Since the establishment of the People’s Republic of China in 1949, syphilis had been well controlled and was once considered eliminated in the 1960s [6
]. However, it has reemerged since the 1980s [7
]. In 2013, the prevalence of maternal syphilis in China was 0.24%, which involved 30,520 infected pregnant women [8
The mother-to-child vertical transmission of syphilis mostly occurs within 16–28 gestational weeks (GW) [9
]. This indicates that early detection could be helpful in the prevention of congenital infection and other APOs. In 2007, the WHO launched the preventing mother-to-child transmission (PMTCT) program to eliminate congenital syphilis globally [9
]. Since then, multiple countries have integrated PMTCTs services into their routine antenatal care (ANC) and abundant evidence shows that PMTCT intervention is significantly cost-effective [10
]. In China, maternal syphilis was treated as a general sexual transmitted disease before the 2000s and its ominous effect on newborns went unheeded. In cooperation with the United Nations International Children’s Emergency Fund (UNICEF), China’s PMTCT program was initiated at the beginning of the 21st century for the purpose of tackling human immunodeficiency virus (HIV) infection [8
]. A pilot PMTCT of syphilis was conducted in some cities like Shanghai and Shenzhen at the same time. In 2011, China’s Ministry of Health called for the integrated PMTCT program of HIV, syphilis and hepatitis B virus (HBV) nationwide [8
As one of the most developed cities in China, the population in Shanghai has expanded from 11 million in 1978 to 24.3 million in 2015, consisting of 58.9% local registered residents and 41.1% non-residents. Along with the ongoing urbanization and what has been known as the “sexual revolution”, the notification rate of syphilis in Shanghai has risen from 0.48 per 100,000 in 1990 [11
] to 74.88 per 100,000 in 2016 [12
]. To prevent the vertical transmission of syphilis, the Shanghai health authority initiated the municipal PMTCT program of syphilis in its maternal and child health care system in 2001, together with the HIV intervention. This was a joint effort among local health care facilities for delivery, newborn care and sexually transmitted infection (STI) treatment. With the launch of the national integrated PMTCT program, this program has been intensified and upgraded since 2011, mainly through the enhancement of infrastructure, including a secured central government budget, quality assured laboratories for syphilis screening and diagnosis, and comprehensive training and supervision for capacity building in all maternity health facilities. Later on, an online reporting platform was developed under the program, which covers all participating institutions and health facilities.
It has been over 15 years since the initiation of the PMTCT syphilis program in Shanghai. The prevalence of maternal syphilis has dropped sharply and numerous associated APOs were avoided [13
]. Nonetheless, how the PMTCT program and the enhancement of maternal healthcare infrastructure improves maternal syphilis detection remains un-assessed. Therefore, this study aimed to compare the screening and diagnosis of maternal syphilis in two different periods of PMTCT implementation, and to understand whether the enhancement of healthcare infrastructure could bring about the early detection of maternal syphilis in Shanghai.
2. Materials and Methods
2.1. Definition of Study Periods
According to the PMTCT strategy, the first five years of Shanghai’s municipal PMTCT syphilis program (2002 to 2006) were defined as the “exploring period”. The following five years (2011 to 2015) after the initiation of the national integrated PMTCT program of HIV, syphilis and HBV were known as the “comprehensive period”. The two-month preparation period of the program in 2001 was not taken into consideration regarding data validity.
2.2. Study Design and Study Participants
This study was a longitudinal secondary data analysis study based on the PMTCT of a syphilis management system in Shanghai. The study participants were pregnant women diagnosed with syphilis at ANC visits during 2002–2006 and 2011–2015 in all health facilities providing maternal health services in Shanghai. A flow chart of participant selection is shown in Figure 1
2.3. Screening and Diagnosis of Maternal Syphilis
The serologic-based diagnosis of maternal syphilis used both treponemal and non-treponemal tests. Treponemal tests use a specific antigen, Treponema pallidum, whereas non-treponemal tests detect non-specific antibodies to reaginic antigens. The diagnosis of pregnant woman with maternal syphilis was restricted to those that presented with seropositivity in both tests. Upon the first ANC visit, either treponemal or non-treponemal tests were applied to screen for syphilis in pregnant women when registering at community health centers. If a screening test returned positive, the patient was then transferred to a delivery hospital in order to receive the other test as a confirmatory diagnosis. For those who had a delayed initial ANC visit, the syphilis screening and diagnosis tests were performed together. In addition, serological testing was also performed before delivery to monitor the antibody-titer levels of syphilis and to identify patients who had not attended a full ANC procedure.
2.4. Data Collection
Registration and clinical information for the eligible cases were exported from the PMTCT management system. Participants’ identifying information was replaced with codes before data extraction. The study collected information on demographics (age, residence, education, marriage status and occupation), pregnancy history, gestational weeks for maternal syphilis screening and diagnosis. This study was approved by the Institutional Review Board of School of Public Health, Fudan University (IRB#2016-03-0578).
2.5. Statistical Analysis
Continuous variables were described as mean ± standard deviation, whereas categorical data were presented as numbers and percentages. Student’s t-test was used for continuous variables, and the Pearson chi-square test and Cochran–Mantel–Haenszel chi-square test were applied to categorical variables. In the logistic regression model, the odds ratio (OR) and the 95% confidence interval (CI) were used to evaluate the factors influencing the early detection of maternal syphilis. Meanwhile, the impact of PMTCT policy on early syphilis detection in the two periods was assessed using a multivariate analysis, after adjusting for demographic factors. A histogram was used to delineate the health facilities for syphilis screening and designated delivery services in the two periods. The significant level (α) was set at 0.05. All data analysis was run by SPSS v19.0 (IBM Corporation, Armonk, NY, USA) and SAS v9.2 package (SAS Institute, Cary, NC, USA).
In this study, it was observed that the early detection of maternal syphilis has been improved remarkably in integrated PMTCT programs along with the enhancement of maternal healthcare infrastructure. Since 2011, the PMTCT program for HIV, syphilis and HBV has been comprehensively integrated into China’s current ANC system. A study conducted in Jinlin province of China found that the coverage of maternal syphilis screening increased from 77.4% in 2011 to 94.6% in 2014 [14
]. In Shanghai, women receiving syphilis screening increased from 625,235 in the exploring period to 1,268,827 in the comprehensive period. The screened population increased as the integrated PMTCT program was applied more widely, amplifying its impact. In addition, more efforts were made to ensure early detection. According to the present study, screening and diagnosis of syphilis in early gestational weeks has significantly increased, by 1.28 and 2.76 times, respectively, in the comprehensive period. The Shanghai health authority has defined pregnant women infected with syphilis as one of the high risk groups in the municipal “Early Warning and Management System for High Risk Pregnancy” in 2010 and are providing routine surveillance on diagnosis and treatment [15
Early detection is the key to preventing APOs and congenital syphilis as the mother-to-child transmission often occurs within 16–28 gestational weeks. In this study, the proportion of syphilis diagnoses within 12 GWs increased from 7.3% in the exploring period to 13.3% in the comprehensive period. About half of the infected cases were detected within 18 GWs. With the further application of the PMTCT policy across the whole country, similar enhancing effects were seen in other areas in China. For example, the detection of maternal syphilis within 12 GWs in Fujian Province reached 8.68% [16
]. However, nearly one third of infected cases remained undetected until 28 GWs in Shanghai, 2015. Delayed diagnosis may result in adverse pregnant outcomes to these women and their newborns, suggesting that the enhancing effect of the PMTCT policy still has space for improvement. This study found that if the infected women belonged to the non-resident population, which is persistently enlarging, they were less likely to receive early syphilis diagnosis. Several studies have reported that pregnant women from the non-resident population usually had limited knowledge of reproductive health [17
], were unfamiliar with the antenatal care system [18
], or remained uncovered by local health insurance [19
]. These factors hinder patients’ timely access to ANC services and other health services. A study in 2012 by Zhao, et al. reported that only 19.7% of Shanghai’s non-resident pregnant women visited ANC during the first trimester [20
]. Meanwhile, the similar distribution of GW in screening and diagnosis suggested that inaccessibility of the ANC visit, rather than referral delay, was the key weaknesses to achieving the early detection of maternal syphilis. The report from China’s national PMTCT program also pointed out that low ANC coverage and financial difficulties were the main factors hampering non-resident women from benefiting from the PMTCT program in eastern China [21
]. Fortunately, PMTCT programs operated in other countries brought new inspiration to optimize the management of maternal syphilis. A cluster-randomized trial in Mongolia demonstrated that one-stop services that provided syphilis screening, test results and treatment within the same day could increase the detection rate of syphilis, treat more positive women and their partners, and effectively reduce the rate of congenital syphilis [22
]. The utility of immune-chromatographic assay (SD BIOLINE Syphilis 3.0 test) as a rapid tool for syphilis screening also has been piloted in India to improve the acceptability and feasibility of a point of care syphilis test in women attending ANC visits [23
Indeed, the PMTCT programs enhance the healthcare infrastructure by facilitating early syphilis screening and diagnosis in pregnant women, thus reducing adverse outcomes. However, the efficiency of the PMTCT of syphilis is affected by several factors. According to the WHO, the dominant factors in this case were whether a good antenatal care system had been established, and whether the high risk population had timely access to ANC services [24
]. Nonetheless, even with secured financing and the existing establishment of healthcare service institutions, the quality of PMTCT programs is still affected by subtler factors. The present study found that amongst pregnant women with syphilis, those who had fewer school years or were unmarried or unemployed were less likely to receive early diagnosis within 16 GWs. This indicates that more efforts should be made to develop pro-vulnerable policies to improve equity in ANC utilization, to implementing tailored health education on maternal healthcare and syphilis prevention, and to expand accessibility via resource-integrated PMTCT interventions. In addition, timely access to antenatal care and early syphilis screening should be set as a priority for the most vulnerable pregnant women who are at high risk of maternal syphilis and vertical transmission to the next generation.
The study was limited with regard to certain aspects. For example, the PMTCT management system lacked some important information on the pregnant women, such as income, health insurance and knowledge of the ANC and PMTCT programs. Also, secondary data analysis was unable to identify the factors affecting the early detection of maternal syphilis directly. In future studies, field investigations are recommended to identify the barriers hindering patients’ access to the early detection of maternal syphilis. Stakeholder interviews with both the infected pregnant women and health providers should also be included.