Literature Review of Syphilis in Pregnant Women Pdf

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Enquiry Article

Global Estimates of Syphilis in Pregnancy and Associated Adverse Outcomes: Analysis of Multinational Antenatal Surveillance Information

• Lori Newman,
• Mary Kamb,
• Sarah Hawkes,
• Gabriela Gomez,
• Lale Say,
• Armando Seuc,
• Nathalie Broutet

10

• Published: February 26, 2013
• https://doi.org/10.1371/journal.pmed.1001396

Figures

Abstract

Background

The World Health System initiative to eliminate mother-to-child transmission of syphilis aims for ≥90% of significant women to exist tested for syphilis and ≥ninety% to receive handling by 2015. We calculated global and regional estimates of syphilis in pregnancy and associated adverse outcomes for 2008, too equally antenatal care (ANC) coverage for women with syphilis.

Methods and Findings

Estimates were based upon a health service commitment model. National syphilis seropositivity data from 97 of 193 countries and ANC coverage from 147 countries were obtained from World Health Organization databases. Proportions of adverse outcomes and effectiveness of screening and treatment were from published literature. Regional estimates of ANC syphilis testing and treatment were examined through sensitivity assay. In 2008, approximately one.36 million (range: i.xvi to 1.56 one thousand thousand) pregnant women globally were estimated to have probable active syphilis; of these, lxxx% had attended ANC. Globally, 520,905 (best case: 425,847; worst case: 615,963) adverse outcomes were estimated to be caused by maternal syphilis, including approximately 212,327 (174,938; 249,716) stillbirths (>28 wk) or early fetal deaths (22 to 28 wk), 91,764 (76,141; 107,397) neonatal deaths, 65,267 (56,929; 73,605) preterm or low birth weight infants, and 151,547 (117,848; 185,245) infected newborns. Approximately 66% of agin outcomes occurred in ANC attendees who were not tested or were not treated for syphilis. In 2008, based on the middle case scenario, clinical services likely averted 26% of all adverse outcomes. Limitations include missing syphilis seropositivity information for many countries in Europe, the Mediterranean, and Due north America, and use of estimates for the proportion of syphilis that was "probable agile," and for testing and treatment coverage.

Conclusions

Syphilis continues to touch on large numbers of pregnant women, causing substantial perinatal morbidity and mortality that could exist prevented by early testing and handling. In this analysis, almost agin outcomes occurred among women who attended ANC only were not tested or treated for syphilis, highlighting the need to ameliorate the quality of ANC as well as ANC coverage. In addition, improved ANC data on syphilis testing coverage, positivity, and treatment are needed.

Please see later in the article for the Editors' Summary

Editors' Summary

Background

Syphilis—a sexually transmitted bacterial infection caused by Treponema pallidum—tin pass from a female parent who is infected to her unborn kid. Screening pregnant women for syphilis during routine antenatal intendance by looking for a reaction to T. pallidum in the blood (seropositivity) and then treating any detected infections with penicillin injections has been feasible for many years, fifty-fifty in low-resource settings. Notwithstanding, because coverage of testing and treatment of syphilis remains depression in many countries, mother-to-child transmission of syphilis—"congenital syphilis"—is still a global public health problem. In 2007, the World Health Organization (WHO) estimated that there were two million syphilis infections among meaning women annually, 65% of which resulted in adverse pregnancy outcomes: the baby'south expiry during early or late pregnancy (fetal death and stillbirth, respectively) or before long after birth (neonatal decease), or the nativity of an infected baby. Babies born with syphilis often have a low birth weight and develop problems such every bit blindness, deafness, and seizures if not treated.

Why Was This Report Washed?

In 2007, WHO launched an initiative to eliminate congenital syphilis that gear up targets of at least 90% of significant women existence tested for syphilis and at least xc% of seropositive meaning women receiving acceptable treatment by 2015. To appraise the initiative's progress and to guide policy and advocacy efforts, authentic global data on the burden of syphilis in pregnancy and on associated agin outcomes are needed. Unfortunately, even in developed countries with good laboratory facilities, definitive diagnosis of congenital syphilis is hard. Estimates of the global brunt can be obtained, yet, using mathematical models. In this study, the researchers generate global and regional estimates of the burden of syphilis in pregnancy and associated adverse outcomes for 2008 using a health services delivery model.

What Did the Researchers Exercise and Find?

The researchers developed a mathematical model to approximate the number of syphilis-infected pregnant women in each country and in each region, and to approximate the regional and global numbers of adverse pregnancy outcomes associated with syphilis. They used national syphilis seropositivity data and information on antenatal care coverage from WHO and estimates of the effectiveness of screening and treatment from published literature. Using these information and their model, the researchers estimated that, in 2008, one.4 million pregnant women, 80% of whom had attended antenatal intendance services, had an active syphilis infection. Bold a scenario in which the percentage of pregnant women tested for syphilis and adequately treated ranged from xxx% for Africa and the Mediterranean region to lxx% for Europe (a scenario defined in consultation with WHO advisors), the researchers estimated that maternal syphilis caused 520,000 adverse outcomes in 2008, including 215,000 stillbirths or fetal deaths, xc,000 neonatal deaths, 65,000 preterm or low birth weight infants, and 150,000 infants with congenital disease. Most 66% of these adverse furnishings occurred in women who had attended antenatal care but were either not tested or not treated for syphilis. Finally, the researchers estimated that in 2008, clinical services averted 26% of all adverse outcomes.

What Practice These Findings Hateful?

These findings, which update and extend previous estimates of the global brunt of congenital syphilis, indicate that syphilis continues to affect a large number of pregnant women and their offspring. The current findings, which cannot be directly compared to previous estimates because of the unlike methodologies used, are probable to be afflicted by the accuracy of the information fed into the researchers' model. In particular, the information on the per centum of the population infected with syphilis in individual countries used in this report came from the HIV Universal Access reporting arrangement and may not be nationally representative. Nevertheless, these findings suggest that syphilis continues to be an important cause of adverse outcomes of pregnancy, partly because pregnant women ofttimes do non receive syphilis screening and prompt treatment during routine antenatal intendance. The researchers recommend, therefore, that all countries should ensure that all pregnant women receive an essential package of high-quality antenatal care services that includes routine and like shooting fish in a barrel access to syphilis testing and treatment. Congenital syphilis, they conclude, can only be eliminated if conclusion-makers at all levels prioritize the provision, quality, and monitoring of this bones antenatal care service, which has the potential to reduce infant mortality and amend maternal health.

Commendation: Newman 50, Kamb M, Hawkes S, Gomez One thousand, Say L, Seuc A, et al. (2013) Global Estimates of Syphilis in Pregnancy and Associated Adverse Outcomes: Assay of Multinational Antenatal Surveillance Information. PLoS Med 10(2): e1001396. https://doi.org/10.1371/periodical.pmed.1001396

Bookish Editor: Clara Menendez, Hospital Dispensary, Barcelona, Spain

Received: Baronial 29, 2012; Accepted: January 15, 2013; Published: February 26, 2013

This is an open up-admission article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Eatables CC0 public domain dedication.

Funding: GBG was funded by The Wellcome Trust (#WPIA-P30479) while working at Imperial College London. The funders had no office in written report design, data drove and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors accept declared that no competing interests exist.

Abbreviations: ANC, antenatal care; MTCT, mother-to-child transmission; WHO, World Health Organization

Introduction

Syphilis is a severe bacterial disease that in pregnancy may manifest as stillbirth, early on fetal expiry, low nascence weight, preterm delivery, neonatal death, or infection or disease in the newborn. Both archaeological and literary prove suggest that mother-to-kid manual (MTCT) of syphilis, usually referred to as "congenital syphilis," is an ancient scourge [1],[two]. In modern times the effectiveness of syphilis testing and handling in preventing MTCT of syphilis is well-recognized [three]. Diagnosis and prevention of MTCT of syphilis is feasible, inexpensive, and cost-constructive in nearly every situation evaluated [iv]. Nevertheless, despite the tools beingness available for over 60 y, MTCT of syphilis persists as a public health trouble.

It is unknown exactly what proportion of pregnant women globally receives adequate testing and treatment for syphilis. The Globe Wellness Organization (WHO) has begun to monitor syphilis testing and treatment coverage through the HIV Universal Access reporting organization, but quality data are not yet available from all countries. In 2011, 63 of 149 low- and middle-income countries reported on coverage of syphilis testing within antenatal care (ANC), with a median of 68% of women in the reporting countries existence tested for syphilis at start ANC visit [5]. However, this coverage guess may be an overestimate of syphilis testing coverage in depression- and middle-income countries, every bit those countries without a functional syphilis screening program are unlikely to take a functional reporting arrangement. A recent multi-country study to appraise introduction of rapid signal-of-care tests institute that ANC syphilis testing at baseline was nonexistent in the Amazonas region of Brazil, 1.7% in Kampala Hospital and rural ANC centers in Uganda, 17.viii% in the district hospital and 51 health facilities in Geita District, Tanzania, 51% in a motherhood hospital in Lima and ANC centers in Callao, Peru, and 79.9% in Lusaka Hospital and rural ANC centers in Mongu District, Zambia [6]. Other individual state reports take besides documented a low coverage of testing and treatment of syphilis in pregnant women. For instance, a written report in southern Mainland china establish that 57% of pregnant women were tested for syphilis from 2004 to 2008 [7]. Some other written report in two provinces in South Africa constitute that although 71% of significant women were tested for syphilis at first ANC visit, only 74% of women who tested positive for syphilis had treatment documented, and just 36% of seropositive women with documented treatment received the recommended three doses of intramuscular penicillin [viii].

In 2007, WHO launched its Initiative for the Global Elimination of Congenital Syphilis, with the goal that by 2015 at least ninety% of significant women are tested for syphilis and at least ninety% of seropositive pregnant women receive adequate treatment [4]. The elimination initiative was designed effectually improving four public wellness "pillars": political advocacy and community engagement; acceptable coverage and quality of ANC; admission to and quality of syphilis testing in ANC; and routine surveillance, monitoring, and evaluation. The regions of the Americas and the Asia Pacific have also launched elimination initiatives, in both cases initiatives integrated with elimination of MTCT of HIV [9],[x].

In gild to assess progress in elimination of MTCT of syphilis and to guide policy and advocacy efforts, global data on the burden of syphilis in pregnancy and associated adverse outcomes are needed. Unfortunately, MTCT of syphilis cannot exist easily measured globally because definitive diagnosis is difficult, fifty-fifty in developed countries with robust laboratory infrastructure. Thus, estimating the brunt of disease must rely on modeled data. In 2007 WHO reported global estimates for congenital syphilis burden based on a review of published data from 1997 through 2003. This work estimated that annually there were two,036,753 syphilis infections amongst pregnant women, of which 65% (i,323,889; range: 728,547 to ane,527,565) resulted in adverse pregnancy outcomes [11]. The 1997–2003 estimates were based upon 45 published studies representing 31 countries. All included studies had a sample size of at to the lowest degree 100 women and determined syphilis seropositivity using both treponemal and non-treponemal tests. The 1997–2003 estimates excluded studies from the U.s., Canada, and virtually of Europe considering syphilis is rare in these countries and they would non contribute meaningful numbers of congenital syphilis. The 1997–2003 estimates also did not take existing treatment services into account and did non remove background bloodshed and morbidity (i.e., expected agin outcomes that would occur in uninfected women).

In guild to support the global initiative for emptying of congenital syphilis, WHO has adult 2008 global estimates of maternal syphilis and associated adverse pregnancy outcomes. The 2008 numbers are intended non just to update the earlier 1997–2003 estimates, merely also to utilize a stronger methodology to have into account existing treatment services, remove background bloodshed, and contain information from a greater number of countries. These updated estimates tin be used to guide global and regional policy, plan, and advocacy efforts to strengthen maternal and child health services and to monitor progress to eliminate MTCT of syphilis.

Methods

The objective of this analysis was to gauge for 2008 the global and regional number of pregnant women infected with probable active syphilis, too as the number of associated adverse outcomes of syphilis in pregnancy. This analysis is based upon a health service delivery model that involved four interpretation steps (Figure 1): calculation of the number of pregnant women with likely active syphilis in each country, adding of the number of pregnant women with probable active syphilis in each region, calculation of the number of adverse pregnancy outcomes associated with syphilis in each region, and calculation of the global number of agin pregnancy outcomes related to syphilis.

Wherever possible, this analysis was done using data provided routinely by countries to United nations organizations (state-specific data points are available in Dataset S1). Countries were allocated to one of 6 regions based on WHO regional classifications [12]. For this analysis we defined "likely active syphilis infection" every bit seropositivity on both treponemal and not-treponemal tests, because women without confirmed exam results may have had false positive tests or onetime or untreated disease that would be unlikely to pose a risk of syphilis transmission to the fetus. Nosotros defined "stillbirth" every bit expiry of a fetus of at least 28 wk gestation or at least one,000 g weight, and "early fetal death" every bit fetal death occurring from 22 to 28 wk gestation (i.east., second and early third trimester); nosotros did not include get-go trimester losses (miscarriages) [thirteen].

Step A: Guess the Number of Pregnant Women with Likely Agile Syphilis in Each Country

For Step A_i, data on syphilis seropositivity among ANC attendees for each state were those information reported through the WHO HIV Universal Admission reporting system for 2008 (data available at the WHO Global Health Observatory Data Repository: http://apps.who.int/gho/data/?theme=main). If 2008 information were not bachelor, we used data reported for 2009 (Figure 2). In 2008 and 2009, data were reported for 97 of 193 countries (50.three%). A regional median was used for countries that did not report data in 2008 or 2009. Countries could report either ANC lookout survey results or routinely conducted antenatal plan data to the HIV Universal Access reporting system. In this reporting system, type of syphilis exam used is not reported; thus, it was non possible to distinguish whether reported seropositivity was based upon treponemal, non-treponemal, or combined test results.

Figure 2. Syphilis seropositivity among antenatal care attendees reported by countries through the WHO HIV Universal Access reporting system in 2008 or 2009, and regional median for non-reporting countries.

https://doi.org/x.1371/journal.pmed.1001396.g002

The estimated number of meaning women in Stride A₂ was calculated for each land as the sum of the number of alive births per United nations Population Division estimates for 2008, stillbirths (after 28 wk gestation) per 2008 published estimates, and early fetal deaths (22–28 wk gestation) [xiv]. Estimates of early fetal deaths are not available for many countries; thus, nosotros estimated these to be approximately xx% of stillbirths based on the early on to tardily fetal decease human relationship in a limited number of studies mainly in high-income countries [15],[16]. Estimations of fetal deaths did not include get-go trimester losses (miscarriages).

Pace A_iii included an estimation of the proportion of seropositive meaning women with probable active syphilis infection. A value of 65% was used as a correction factor to estimate the proportion of seropositive women with both treponemal and not-treponemal syphilis test positivity for the data reported through the HIV Universal Access reporting system. The correction factor was based on data from a literature review of 45 studies on syphilis in pregnancy from 2004 to 2008 [17]. Of these, three studies reported results of treponemal and non-treponemal tests for all significant women [18]–[twenty]. Among all women with either syphilis test positive, the proportion of women with both the treponemal exam and the non-treponemal test positive was found to be 63.9% in Mozambique, 61.7% in Bolivia, and 68.0% in Tanzania.

Step A₄ involved estimating for each land the proportion of pregnant women with and without at least ane ANC visit. We used the almost recent information for a country available in the WHO Global Health Observatory from 2000 to 2010; data were available for 147 countries [21]. A regional median was used for countries for which data were not available. The four values in Step A were multiplied to obtain the estimated number of pregnant women infected with likely active syphilis attending and not attending ANC in each state.

An approximate doubt range for the global number of significant women with probable agile syphilis was calculated using the delta method and a 10% relative error at the national level for three input variables: syphilis seropositivity, number of pregnancies, and the correction cistron for the estimated proportion of women with syphilis with likely active disease.

Stride B: Approximate the Number of Meaning Women Infected with Likely Active Syphilis in Each Region

Step B involved summing the country values to provide regional estimates of the number of pregnant women with likely agile syphilis not attention ANC (B_one), as well as the number attention ANC (B_ii).

Stride C: Estimate the Number of Adverse Pregnancy Outcomes Associated with Syphilis in Each Region

The objective of Stride C was to estimate for each region the total number of adverse pregnancy outcomes related to maternal syphilis. We calculated the number of specific adverse pregnancy outcomes in five categories: any adverse outcome, stillbirth or early fetal death, neonatal decease, prematurity or low nascence weight, and an infected newborn. Considering of the express availability of data on the proportion of pregnant women tested in ANC and, of those found to be positive, the proportion treated fairly, nosotros devised a unproblematic sensitivity analysis that considered three testing and treatment coverage scenarios defined in consultation with WHO regional advisors: worst, middle, and best example (Table 1). In addition, we considered the scenario proposed as a target for 2015 in the WHO Initiative for the Global Elimination of Congenital Syphilis, in which at least 90% of pregnant women are tested for syphilis at start antenatal visit, and at least 90% of seropositive significant women are adequately treated (i.e., testing and treatment coverage T = 81% for all regions, except Europe, which was assumed to maintain T = 90%).

Table one. Estimated proportion of antenatal care attendees tested and treated in different scenarios for 2008, and proposed Initiative for the Global Elimination of Built Syphilis target for 2015.

https://doi.org/10.1371/journal.pmed.1001396.t001

In Step C_ane, the total number of adverse outcomes in meaning women with likely active syphilis who did not attend ANC was calculated every bit the production of the regional number of infected pregnant women not attending ANC and the proportion P of those women expected to have a syphilis-related agin effect without treatment. P for each adverse outcome category was obtained from a meta-analysis of published clinical literature assessing adverse pregnancy outcomes amongst women with probable active syphilis without adequate treatment: P _{any adverse outcome} = 0.52, P _{stillbirth/early fetal expiry} = 0.21, P _{neonatal death} = 0.09, P _{prematurity/low nascency weight} = 0.06, and P _{infected newborn} = 0.16 [22].

Nosotros also estimated the number of adverse outcomes in pregnant women with likely active syphilis who attended ANC (Step C₂ and Footstep C_iii). Not all women who attend ANC are tested for syphilis and fairly treated if seropositive. Therefore, we estimated agin outcomes for women who were both tested and treated (T) (Tabular array i), likewise every bit for those who were non (1−T). In women who are not both tested and treated, the number of adverse outcomes is the number non tested and treated multiplied past the proportion expected to have an agin issue (P). Fifty-fifty amidst women who are both tested and treated, a small number of adverse events can be expected, especially if syphilis cases are identified late in pregnancy. A systematic review by Blencowe et al. found that the effectiveness E of screening and treatment with penicillin in reducing adverse outcomes was every bit follows: E _{neonatal decease} = 0.80, East _{prematurity/low birth weight} = 0.64, and E _{infected newborn} = 0.97 [23]. For this analysis, E _{stillbirth/early on fetal death} = 0.82 was based on the judge of effectiveness for stillbirth alone, and E _{any adverse effect} = 0.84 was based on the weighted hateful of E _{neonatal death}, Eastward _{prematurity/low birth weight}, East _{infected newborn}, and E _{stillbirth/early fetal death}, using equally weights the proportion of women with the respective adverse outcome.

Step D: Estimate the Global Number of Adverse Pregnancy Outcomes Related to Syphilis

Footstep D summed the regional estimates for each adverse effect to produce a global estimate of the number of adverse pregnancy outcomes related to syphilis.

Finally, nosotros calculated the number of adverse pregnancy outcomes averted past electric current services by subtracting the number of adverse outcomes in the middle case testing-and-treatment-coverage scenario from a baseline number of adverse outcomes estimated in the absence of any services.

Results

We estimated that in 2008 in that location were 1,360,485 (range i,160,195–1,560,776) meaning women with probable active syphilis infections, and of these women, 1,085,637 (79.8%) attended ANC. The estimated number of infected pregnant women by region was 535,203 in Africa (39.3%), 106,500 in the Americas (vii.8%), 603,293 in Asia (44.3%), 21,602 in Europe (1.vi%), 40,062 in the Mediterranean (three.0%), and 53,825 (4.0%) in the Pacific. Without any screening or treatment services, these meaning women with probable active syphilis would have had 707,452 adverse pregnancy outcomes, including 285,702 stillbirths or early fetal deaths, 122,444 neonatal deaths, 81,629 premature or low birth weight infants, and 217,678 infected newborns. Thus, in the absence of whatever antenatal syphilis screening and treatment, an estimated 408,146 fetal or perinatal deaths and 299,307 infants at risk for early on decease would have resulted from maternal syphilis infection.

Figure 3 shows the estimated number of adverse outcomes in 2008 associated with syphilis globally and past region for the worst, middle, and best instance scenarios of testing and treatment of women who are seropositive. Because the middle instance scenario, we estimated that globally in that location were 520,905 (best: 425,847; worst: 615,963) adverse outcomes associated with syphilis in pregnancy, which included 212,327 (all-time: 174,938; worst: 249,716) stillbirths or early fetal deaths, 91,764 (best: 76,141; worst: 107,397) neonatal deaths, 65,267 (best: 56,929; worst: 73,605) preterm or depression birth weight infants, and 151,547 (best: 117,848; worst 185,245) infected newborns. In summary, globally in 2008 in a middle instance scenario, untreated maternal syphilis resulted in approximately 304,091 fetal or perinatal deaths and 216,814 syphilis-infected infants at chance for early decease. Exam of any adverse outcome by region showed that the majority of adverse outcomes (87%) were in Africa and Asia. Of notation, 66% of all adverse outcomes occurred in women who had attended ANC.

In 2008, using the eye case scenario for antenatal screening and handling, approximately 186,548 (26%) of all adverse outcomes of syphilis in pregnancy were averted. Specifically, the averted outcomes were 73,375 stillbirths or early fetal deaths, 30,679 neonatal deaths, 16,362 preterm or depression nascency weight infants, and 66,131 infected newborns (Tabular array 2). Past region, the number of all agin outcomes averted in 2008 in the middle instance scenario was estimated as 54,676 in Africa, 26,318 in the Americas, 82,949 in Asia, 6,447 in Europe, iii,398 in the Mediterranean, and 12,758 in the Pacific. If the elimination initiative targets for 2015 of at least xc% testing and 90% treatment had been reached in 2008, then 385,815 (55%) of all agin outcomes could accept been averted: 151,753 stillbirths or early fetal deaths, 63,451 neonatal deaths, 33,840 preterm or low nativity weight infants, and 136,771 infected newborns.

Table ii. Estimated number of adverse outcomes associated with syphilis in pregnancy averted in the middle scenario in 2008, and if Initiative for the Global Elimination of Congenital Syphilis targets for 2015 for testing and treatment had been met in 2008.

https://doi.org/10.1371/journal.pmed.1001396.t002

Word

Globally, nearly 1.4 million pregnant women in 2008 had probable active syphilis infection and were at gamble of transmitting the illness perinatally to their unborn children. This is lower than previously reported 1997–2003 WHO estimates of approximately 2 million meaning women annually with untreated syphilis infection, and suggests some progress may take been made over the by decade in syphilis prevention and control. Even so, the extent of progress is difficult to determine, equally the estimates used differing methodological approaches. In comparison to the 1997–2003 estimates, the 2008 estimates were intended to take into account existing treatment services, remove background mortality and morbidity unrelated to syphilis, and better account for the predictable increasing availability of testing and treatment over time. In addition, considering of the paucity of published cross-exclusive survey data since 2003 on syphilis in pregnancy, the 2008 estimates were based on data reported to WHO routinely by countries through the HIV Universal Access reporting system rather than on information from a literature review.

Despite differences in methodology, both the 1997–2003 and the 2008 estimates indicate that syphilis in pregnancy continues to be an important cause of mortality and morbidity in pregnancy. This is unsettling given the fact that universal syphilis screening in ANC and prompt treatment of women testing positive are basic interventions that have been proven to be cost-effective even in low prevalence settings. Additionally, rapid point-of-care syphilis tests allowing testing and treatment in almost whatsoever clinical setting were non widely available in 2003, just certainly should have been by 2008. These 2008 estimates back up that countries in every region of the world should scale up screening and handling for syphilis in pregnancy, and that doing and then could essentially reduce preventable perinatal decease and disability.

Our estimates suggest that over 520,000 adverse pregnancy outcomes due to syphilis occurred in 2008, of which approximately 215,000 were stillbirths or early on fetal deaths, ninety,000 were neonatal deaths, 65,000 were premature or low birth weight infants, and another 150,000 were infected newborns. Our estimates exercise non include boosted deaths that would exist expected to occur after the first month of life due to prematurity, depression birth weight, or built infections, estimated in i report to result in approximately 10% mortality by 1 y (i.due east., approximately 21,500 additional infant deaths) [24].

Approximately one-fifth (20%) of all pregnant women with syphilis did not nourish ANC. Thus, efforts to ensure universal admission to early on ANC are primal in eliminating congenital syphilis, every bit well equally other causes of preventable infant mortality. Simply importantly, our information suggest that 2-thirds of the agin outcomes due to syphilis occurred in women who had attended ANC at least once, but either were not screened or, if they were screened and tested positive, did not receive appropriate treatment with intramuscular benzathine penicillin. The vast majority of outcomes that occurred in 2008 could have been prevented had the women received quality early ANC that included syphilis testing and access to effective therapies, as recommended by WHO. Syphilis testing and handling are relatively cheap compared with other interventions, with tests typically costing less than US$1, and treatment slightly less than that. To reduce cases of congenital syphilis, information technology will exist important to incorporate syphilis testing and treatment into routine procurement and distribution systems to ensure that pregnant women receive an essential minimal package of ANC interventions.

Existing health care services were able to avert 1 out of every four expected agin outcomes in 2008. However, if the proposed testing and treatment targets for 2015 outlined in the Initiative for the Global Elimination of Congenital Syphilis had been reached in 2008, over one-half of all expected adverse outcomes could have been averted. Further research is needed to define how many cases and what level of service delivery is needed to attain the ultimate goal of "emptying of congenital syphilis equally a public health problem." However, given that screening and treatment for preventing MTCT of syphilis is non 100% effective, primary prevention of syphilis in significant women is likewise an important strategy that needs to exist addressed to truly eliminate congenital syphilis.

While substantial progress has been made in the utilization of ANC (in 2009 WHO estimated that approximately 81% of all pregnant women had attended at to the lowest degree one ANC visit) [25], built syphilis nevertheless occurred for a multifariousness of reasons: many of these visits were too late to avert an adverse outcome, clinics may not take offered testing, testing may not accept been affordable, women may not take followed up or received their exam results, handling may not have been bachelor, or treated women may accept been reinfected by untreated sexual partners [26].

Our estimates are field of study to some limitations. First, there are no global data on estimated numbers of early on fetal deaths; national estimates of early fetal deaths had to exist crudely extrapolated from estimated numbers of stillbirths using a correction factor based mainly on data from high-income countries. Improved information on early fetal expiry, in particular in low- and eye-income countries, is necessary to sympathise the total extent of the impact of this limitation.

In addition, these estimates rely on data reported through the HIV Universal Access reporting system and do not include separate published studies of syphilis seropositivity, every bit was previously done for the 1997–2003 estimates. The advantage of HIV Universal Access information is that they are reported by most developing countries on a routine basis, involve a larger sample size than most published studies, and are less field of study to a publication bias. Notwithstanding, several countries did not report through the HIV Universal Admission system, including some loftier-income countries in North America, Europe, and the Mediterranean with depression syphilis seropositivity, as well as some particularly low resource countries without organized screening programs and with high syphilis seropositivity. It is unclear how this underreporting would bear on the overall estimates.

Although countries are asked to report nationally representative data, it is possible that these data are over-representative of urban populations with greater admission to syphilis prevention and treatment services than rural populations. If syphilis seropositivity is higher in rural settings (and programs are less effective), our calculations may underestimate the truthful brunt of syphilis-associated adverse outcomes.

In addition, HIV Universal Access data practise not include information on testing methodologies, test titer, phase of disease, or treatment history, and therefore it is unclear whether or not a state'south data includes women with latent or previously treated disease. This assay applied a correction factor for "probable active" disease to the unabridged dataset to account for this; however, adjustment may not take been necessary in all cases and may accept led to underestimation of the true burden of active illness.

Because of a lack of representative data on electric current testing and treatment coverage, these estimates relied on expert opinion of current testing and treatment coverage, and the experts may have miscalculated. In order to explore the validity of these estimates, nosotros nowadays a basic sensitivity analysis of testing and treatment coverage to business relationship for the uncertainty related to this approximation. Although WHO is working to improve collection of information on syphilis testing and treatment through the HIV Universal Admission reporting arrangement, these testing and treatment data are non nonetheless felt to be accurate and representative at a global level (the highest performing countries are more probable to written report service delivery indicators). Thus, more work with countries to strengthen surveillance and monitoring systems is needed.

Finally, these estimates practice not account for the timing of treatment of syphilis in pregnancy. Although syphilis manual has been documented to occur very early in pregnancy, existing data suggest that catastrophic outcomes due to syphilis crave development of the fetal allowed system (i.due east., after xviii–20 wk gestation) [27]. It is also recognized that the effectiveness of screening and treatment is lower in the third trimester than in the showtime and second trimesters [28].

The limitations of these estimates highlight the urgent need for improved data through stronger national surveillance and monitoring systems. All countries should know at least the three core indicators related to MTCT of syphilis in their population: what proportion of ANC attendees are tested for syphilis, what proportion are seropositive, and what proportion of syphilis seropositive ANC attendees are fairly treated [29]. WHO hopes to work with countries to improve capacity to monitor and report on these three core indicators through the WHO HIV Universal Access reporting arrangement. Meliorate national data are likewise needed on how early pregnant women seek intendance and how many women have early fetal deaths, equally well as how estimates of adverse outcomes such as congenital syphilis and stillbirth attributable to syphilis compare to actual reported cases of congenital syphilis and stillbirth attributable to syphilis.

In summary, this assay indicates that syphilis continues to be an important cause of adverse outcomes of pregnancy, including substantial numbers of perinatal deaths and disabilities. Given that an increasing proportion of the infant mortality that Millennium Development Goal four aims to address by 2015 occurs during the offset month of life, investing in elimination of MTCT of syphilis is a low-hanging fruit for reducing neonatal bloodshed, as well as stillbirths. Primary prevention of syphilis in people of reproductive historic period is an important kickoff step towards reducing these deaths. Better information are needed to raise local awareness of the burden of syphilis in pregnancy, an old scourge that is oftentimes overlooked in modernistic day public health programs. Countries likewise need to ensure that quality-assured syphilis testing is available in all ANC settings, now possible even in remote care settings with the introduction of rapid point-of-care diagnostics. In add-on, efforts are needed to ensure universal admission to early ANC, likewise as improved quality of ANC, so that all pregnant women receive an essential package of services that includes routine and early access to point-of-care testing and adequate treatment for syphilis if seropositive. MTCT of syphilis can simply be eliminated if determination-makers at all levels prioritize the provision and quality of this bones ANC service.

Elimination of MTCT of syphilis directly supports attainment of Millennium Evolution Goals four, 5, and 6 through reduction in infant mortality, improved maternal health, and primary prevention of HIV [xxx]. With just a short amount of time left to achieve the Millennium Development Goals, the United Nations Secretary-General launched the Global Strategy for Women's and Children's Wellness, which calls for improved coordination around maternal and newborn health issues [31]. Bringing ministries of health and partners together to provide universal coverage of antenatal syphilis screening and to ensure handling of all pregnant women infected with syphilis is a specific example of an activity that would greatly support the Global Strategy for Women'south and Children's Health.

Supporting Data

Acknowledgments

The authors would like to admit the assistance of the following regional advisors who provided input on methodology, assumptions, and information quality: Iyanthi Abeyewikreme, Monica Alonso, Hamida Khattabi, Lali Khotenashvili, Assimawe Pana, Suzanne Serruya, and Teodora Wi. In addition, the authors thank the following consultants for their input on methodology through the Child Health Epidemiology Research Group: Hannah Blencowe, Cynthia Boschi-Pinto, Simon Cousens, Geoff Garnett, Joy Backyard, Colin Mathers, and Neff Walker. The authors are also grateful for the following colleagues who provided input: Txema Garcia Calleja, Harrell Chesson, Jennifer Mark, Igor Toskin, Brad Stoner, and George Schmid.

Writer Contributions

Conceived and designed the experiments: LN MK SH LS NB. Performed the experiments: LN GG AS. Analyzed the data: LN GG AS. Contributed reagents/materials/analysis tools: LN MK SH GG LS Equally. Wrote the first draft of the manuscript: LN. Contributed to the writing of the manuscript: LN MK SH GG AS NB. ICMJE criteria for authorship read and met: LN MK SH GG LS Equally NB. Agree with manuscript results and conclusions: LN MK SH GG LS Equally NB.

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