Our model suggests that prenatal syphilis screening coverage is the single most important component of CS control, but several other strategies, including earlier screening and improved treatment completion, are needed to achieve targets established by the Chinese government. Increasing prenatal screening coverage to 95% resulted in an estimated 78 (95% CI: 73, 83) CS cases per 100,000 live births, compared to the estimated 184 (95% CI: 172, 196) CS cases per 100,000 live births with current screening coverage (57%). Catalyzed by momentum from the NSCP and subsequent increased local resources for syphilis control, China is uniquely positioned to implement far-reaching CS control programs that could have a major impact on maternal and child health 
. While previous studies have analyzed the relationship between screening coverage and CS cases 
, to our knowledge this is the first study to analyze the relative contribution of individual and comprehensive strategies to overall syphilis control, and the first syphilis control model with empirical validation datasets available, representing a substantial improvement on earlier studies.
Our analysis suggests that improving prenatal syphilis screening is the most important individual component of CS control. This is likely related to suboptimal baseline screening and the critical position of screening in downstream control efforts 
. Although there have been reports of duplicate reporting of cases and misdiagnosis in China 
, our findings are consistent with net underreporting, with an estimated reporting rate of 75.5%. Some reasons for underreporting include misdiagnosis, lack of CS testing, and non-hospital deliveries. Our model input parameters were conservative and did not account for the underreporting of adult syphilis cases or birth rates 
, and hence CS case outcomes are likely to be an underestimation. While other studies have modeled syphilis screening as part of a comprehensive strategy 
, the relative contribution of screening has not been investigated to date. Achieving 95% screening coverage rates in prenatal settings exceeds the Chinese policy goals of 60% screening coverage in rural areas and 80% screening coverage in urban areas. The 95% screening coverage target is not only necessary but feasible, and has been implemented in similar rural and urban settings. The pilot study in urban Shenzhen City achieved 94% prenatal screening coverage, while another study conducted in rural Guangdong achieved 96% prenatal screening coverage 
. Globally, greater than 90% prenatal screening coverage rates have been implemented in pilot programs in several low- and middle-income countries 
. A simple, inexpensive, rapid on-site syphilis test has been rolled out in China and could help realize the universal syphilis screening required at hygiene stations and other low-level prenatal clinics that may not be able to implement non-treponemal syphilis screening 
, but improvement in point-of-care test sensitivity is needed. A United Nations report in 2010 estimated that there is 92% antenatal care coverage across China and suggested the feasibility of expanding syphilis screening coverage across China 
Next, earlier syphilis treatment is a critical variable for averting CS burden. Previous models of syphilis control have not explicitly targeted first and second trimester syphilis screening 
. Many pregnant women in China initiate prenatal care late in pregnancy 
. Earlier prenatal care would be useful not only for syphilis screening, but also for routine prenatal care 
. Treatment in the third trimester is minimally effective in reducing CS transmission to the infant 
because much of vertical syphilis transmission occurs prior to the third trimester 
. At the same time, there are benefits to third trimester screening that include detection of reinfection and prevention of subsequent transmission, in addition to early treatment of infected infants. Early syphilis screening has been proven feasible in resource-constrained settings. A Zambian study successfully implemented earlier prenatal screening through educational campaigns, increasing prenatal syphilis screening before the first 16 wk of gestation from 9.4% to 42.5% 
. Earlier prenatal screening in Mongolia also resulted in reduced CS cases 
. Delayed prenatal care is a particular problem among migrant women in China, many of whom have an increased risk of syphilis 
. The WHO Global Strategy for the Elimination of Congenital Syphilis also calls for early, high-quality prenatal care to increase the impact of syphilis screening 
. More operational research is needed in order to implement earlier routine prenatal care, especially among migrant women in China.
Treatment completion was also found to reduce CS cases, and previous studies in global settings have demonstrated the potential feasibility of attaining high treatment completion rates in low-income settings 
. In the Shenzhen intervention trial, the treatment completion rate was 92% 
. Increasing treatment completion rates will require the strengthening of local health systems in order to enhance health professional training and identify sustainable financing. Mistrust of syphilis test results, physicians, and clinics has been observed in China, and may contribute to incomplete treatment 
. In addition, suboptimal test kits were problematic in the past in Guangdong Province. Newly available point-of-care testing provides a higher sensitivity and specificity than many existing test technologies 
There are limitations as to how effective small pilot studies can be applied on a larger scale in China and across diverse populations around the world. The presence of existing infrastructure and political will, as well as public acceptance of health outreach programs are critical components for attaining high screening coverage and completion of treatment. Widespread scale-up of successful prenatal syphilis screening pilot programs and clinical services that are trusted among pregnant women within most-at-risk populations are needed in order to overcome these challenges 
. The NSCP consists of policies targeted at decreasing adult syphilis rates and educational campaigns aimed at increasing test-seeking probabilities. These interventions may decrease adult syphilis cases, but appear to have a limited effect on reducing CS rates, as one-way sensitivity analysis results demonstrated that they avert no more than 7% of the estimated CS case burden, and two-way sensitivity analysis with increased screening coverage demonstrated that they avert no more than 3% of estimated CS case burden. Nonetheless, the additional benefits of reducing the incidence of syphilis among the adult population should not be overlooked—improved sexual health and possibly reduced HIV transmission risk.
The most effective three-pronged strategy fell slightly short of the Chinese Ministry of Health target of <30 cases per 100,000 births, but the four-pronged strategy consisting of increased prenatal syphilis screening coverage, earlier prenatal testing, increased treatment completion rates, and increased test specificity and sensitivity managed to surpass that target, with a model-estimated CS outcome of 27 cases per 100,000 live births. This particular four-pronged strategy was also the most successful of all the combinations: no five-pronged strategy resulted in more CS case aversions. The model suggests that this combination strategy is the strategy that would most likely be associated with achieving the Chinese Ministry of Health goals.
This study has several important limitations. First, as with any model-based analysis, there are inherent uncertainties associated with the structure and necessary simplifying assumptions used for model analysis of a complex problem. In particular, pregnant women and non-pregnant women may have different clinical presentations or test-seeking behaviors. No model can simulate all aspects of real-world interactions. However, simplified models provide a useful tool for understanding the dynamics of relationships between interacting components, which facilitates greater understanding of complex phenomena. Based on current understanding and data from the literature, we included key aspects of syphilis natural history and treatment as well as critical features of intervention strategies, both those laid out in the NSCP and other proven intervention strategies. Confidence intervals for each model estimate were calculated, and the resulting uncertainty in the model did not affect the results. Second, this study generated estimates only for Guangdong Province in China and so may not be applicable to other regions with different syphilis epidemiology, health-seeking behaviors, or other health systems issues. At the same time, our estimates could potentially be applied to similar Chinese urban settings where , as in Guangdong Province, there is a substantial burden of syphilis. Third, our model addresses the impact of syphilis control strategies on the number of CS cases averted, but it does not include other adverse outcomes avoided and all the benefits associated with syphilis control policies in pregnancy. There was a lack of data from Chinese studies that described other adverse outcomes associated with syphilis such as stillbirths and prematurity. Fourth, this study did not collect or evaluate costing data, but other Guangdong research has shown that prenatal syphilis screening is highly cost-effective 
. Prenatal syphilis testing has also been found to be cost-effective in a variety of settings from Europe to Africa and across a range of syphilis prevalence settings 
. Lastly, this study could not quantify the health systems strengthening and improved case management that are also likely to play an important role in syphilis control programs 
. Health systems strengthening would be useful for CS prevention as well as stemming the syphilis epidemic among pregnant women.
While our analysis specifically focuses on Guangdong Province, these results have broader implications within China and for other middle-income nations. Our analysis illustrates the importance of using multi-pronged approaches to address the complex problem of syphilis control and to reduce the number of CS cases. Reducing the burden of CS would also help achieve child and maternal health goals established by the United Nations 
and the Asian Development Bank 
CS control is a solvable public health problem, but critical details about metrics and screening strategies are required for successful implementation. China's high level of commitment to syphilis control and extensive public health infrastructure create unparalleled opportunities for progress. The targets in the NSCP are consistent with WHO recommendations and represent useful goals. However, our model suggests that achieving these goals may require broadening and further refining of public health strategies for syphilis control.