Abstracts

Introduction

Syphilis in pregnancy, when untreated, results in a high proportion of stillbirths and early neonatal deaths ¹1 . Goldenberg RL. Culhane JF, Johnson DC. Maternal infection and adverse fetal and neonatal outcomes. Clin Perinatol 2005; 32:523-59.. Maternal syphilis poses a threat to the fetus, given the high likelihood of vertical (mother-to-child) transmission of the disease, especially in the primary and secondary stages, increasing the risk of perinatal deaths ²2 . Sanchez PJ, Wendel GD. Syphilis in pregnancy. Clin Perinatol 1997; 24:71-90.. In Brazil, considering 3,059,402 deliveries per year and a 1.6% prevalence rate for syphilis in pregnancy, there were an estimated 48,950 cases of pregnant women with syphilis in 2004 ³3 . Departamento Nacional de DST, Aids e Hepatites Virais, Secretaria de Vigilância em Saúde, Ministério da Saúde. Dados epidemiológicos sífilis em gestantes. Boletim Epidemiológico AIDS e DST 2010; 1:34-6.. However, in 2005, the year after the above estimate, Brazil reported only 1,863 pregnant women with syphilis, increasing to 8,755 in 2009, but still far below the expected figure ³3 . Departamento Nacional de DST, Aids e Hepatites Virais, Secretaria de Vigilância em Saúde, Ministério da Saúde. Dados epidemiológicos sífilis em gestantes. Boletim Epidemiológico AIDS e DST 2010; 1:34-6.. Congenital syphilis can be prevented by adequate diagnosis and treatment during pregnancy ⁴4 . Schmid G. Economic and programmatic aspects of congenital syphilis prevention. Bull World Health Organ 2004; 82:402-9.. In Brazil, the conditions for such prevention are provided by the public healthcare system at the municipal level and can help eliminate the disease, since vertical transmission of syphilis can occur in up to 25% of cases of infected mothers ⁵5 . Secretaria de Assistência à Saúde/Secretaria de Vigilância em Saúde, Ministério da Saúde. Plano operacional – redução da transmissão vertical do HIV e da sífilis. Brasília: Ministério da Saúde; 2007.^,66 . Saraceni V, Leal MC. Avaliação da efetividade das campanhas para eliminação da sífilis congênita na redução da morbi-mortalidade perinatal. Município do Rio de Janeiro, 1999-2000. Cad Saúde Pública 2003; 19: 1341-9..

Congenital syphilis has been subject to compulsory notification in Brazil since 1986 ⁷7 . Brasil. Portaria no 542 de 22 de dezembro de 1986. Diário Oficial da República Federativa do Brasil 1986; 24 dez., with its own case definition, periodically revised ⁸8 . Paz LC, Pereira GI, Matida LH, Saraceni V, Ramos Jr. AN. Vigilância epidemiológica da sífilis no Brasil: definição de casos, 2004. Boletim Epidemiológico AIDS e DST 2004; XVII:10-5.. Information on miscarriage, stillbirth, and live birth with congenital syphilis must be reported to the Information System on Diseases of Notification (SINAN) ⁹9 . Departamento de Vigilância Epidemiológica, Secretaria de Vigilância em Saúde, Ministério da Saúde. Sistema de Informação de Agravos de Notificação – SINAN: normas e rotinas. Brasília: Ministério da Saúde; 2007.. Syphilis in pregnancy has been subject to compulsory notification since 2005 according to the same principles as congenital syphilis ¹⁰10 . Ministério da Saúde. Portaria MS/SVS no 33, de 15 de julho de 2005. Diário Oficial da República Federativa do Brasil 2005; 15 jul.. Epidemiological surveillance of both diseases is essential for eliminating congenital syphilis, providing the necessary information for planning and intervention ³3 . Departamento Nacional de DST, Aids e Hepatites Virais, Secretaria de Vigilância em Saúde, Ministério da Saúde. Dados epidemiológicos sífilis em gestantes. Boletim Epidemiológico AIDS e DST 2010; 1:34-6.^,55 . Secretaria de Assistência à Saúde/Secretaria de Vigilância em Saúde, Ministério da Saúde. Plano operacional – redução da transmissão vertical do HIV e da sífilis. Brasília: Ministério da Saúde; 2007.^,66 . Saraceni V, Leal MC. Avaliação da efetividade das campanhas para eliminação da sífilis congênita na redução da morbi-mortalidade perinatal. Município do Rio de Janeiro, 1999-2000. Cad Saúde Pública 2003; 19: 1341-9..

The Mortality Information System (SIM) was created in 1975 by the Brazilian Ministry of Health to gather regular mortality data in the country ¹¹11 . Ministério da Saúde. Manual de procedimentos do Sistema de Informações sobre Mortalidade. Brasília: Fundação Nacional de Saúde/Ministério da Saúde; 2001.. The SIM can serve as an alternative source for measuring perinatal mortality (stillbirth plus early neonatal mortality) from congenital syphilis, particularly relevant when assessing the quality of prenatal care ¹²12 . Saraceni V, Guimarães MHSF, Theme Filha MM, Leal MC. Mortalidade perinatal por sífilis congênita: indicador da qualidade da atenção à mulher e à criança. Cad Saúde Pública 2005; 21:1244-50..

The lack of a mechanism to integrate the large health information systems in Brazil makes database linkage an important tool for integrating the various bases. Database linkage has been applied in public health for the last 50 years, since publication of the study by Newcombe et al. ¹³13 . Newcombe HB, Kennedy JM, Axford SJ, James AP. Automatic linkage of vital records. Science 1959; 130:954-9.. Recent decades have witnessed growing recognition of the importance of assessing the results of probabilistic or deterministic record linkage ¹⁴14 . Silveira DP, Artmann E. Acurácia em métodos de relacionamento probabilístico de bases de dados em saúde: revisão sistemática. Rev Saúde Pública 2009; 43:875-82..

The objectives of this study were to describe the epidemiological profile of reported cases of syphilis in pregnancy and congenital syphilis in Amazonas State from 2007 to 2009, verify underreporting of such cases in the SINAN databases, and verify perinatal deaths associated with congenital syphilis not recorded in the SIM using probabilistic record linkage.

Methodology

This was a descriptive cross-sectional study of cases of congenital syphilis and syphilis in pregnancy included in the SINAN (version SINANNET) from 2007 to 2009 in Amazonas State, Brazil. Data on stillbirths (fetal losses after the 22^nd week of pregnancy or greater than 500 grams) and early neonatal deaths (up to 7 days of life) related to congenital syphilis, coded in the International Classification of Diseases, 10^th Revision (ICD-10) as A50.0 to A50.9 were identified in SIM for 2007-2009 through a search for multiple causes of death, using Stata version 9 (Stata Corp., College Station, USA).

After selecting cases reported to SINAN, we conducted probabilistic linkage of the databases for syphilis in pregnancy and congenital syphilis and subsequently for the SINAN-Congenital Syphilis and SIM databases, using the variable “pregnant woman’s name” in the SINAN-Syphilis in Pregnancy base and “mother’s name” in the SINAN-Congenital Syphilis and SIM databases to identify cases, with Reclink (version 1) ¹⁵15 . Camargo Jr. KR, Coeli CM. Reclink: aplicativo para o relacionamento de bases de dados, implementando o método probabilistic record linkage. Cad Saúde Pública 2000; 16:439-47. supported by Stata (version 9) to analyze cases present in the 3 databases.

In the SINAN-Congenital Syphilis database, recording of cases of miscarriage was preceded by the word “miscarriage by” before the name of the mother in the patient’s name variable. This term was used to identify cases of miscarriage in the SINAN. The search in SIM identified one such case as stillbirth rather than miscarriage. For cases of stillbirths, we searched for the words “stillbirth of” or “fetal death of” before the mother’s name in the SIM and SINAN-Congenital Syphilis databases in the patient name variable. The first blocking step was performed with “pregnant women’s name - mother’s name”. Given the small number of cases, we then proceeded to a manual search. Mother’s age, mother’s municipality of residence, and temporal correspondence of cases were used in the manual revision of the probabilistic linkage.

After probabilistic linkage of the databases, a final base was constructed in which the variables related to the pregnant woman (or mother of the case of congenital syphilis) were year of diagnosis, age, race, schooling, prenatal care, timing of syphilis diagnosis, clinical classification of the maternal syphilis, and treatment of the pregnant woman and her partner. For cases of congenital syphilis, the study variables were sex, age at diagnosis of congenital syphilis, presence of symptoms at diagnosis of congenital syphilis in the child, long-bone x-rays, cerebrospinal fluid analysis, and final case classification.

We began with a descriptive analysis, including frequency distributions of categorical variables and measures of central tendency and dispersion for continuous variables. The detection rate for syphilis in pregnancy was calculated as the number of notifications of syphilis in pregnancy divided by the number of live births in the same year, and the incidence rate for congenital syphilis was calculated as the number of notifications divided by the live births in the same year, according to the Brazilian Ministry of Health’s definitions for these indicators ¹⁶16 . Departamento Nacional de DST, Aids e Hepatites Virais, Secretaria de Vigilância em Saúde, Ministério da Saúde. Boletim Epidemiológico de Sífilis 2012; 1:3-8..

Data were provided by the Amazonas State STD/AIDS Division and the Health Surveillance Foundation (FVS). The study was approved by the Ethics Research Committee of the Amazonas State University/Amazonas Foundation for Tropical Medicine, case n. 1993/2010.

Results

Cases of syphilis in pregnancy

As for reporting of syphilis in pregnancy to the SINAN database, there were 666 notifications during the period, 224 of which in 2007, or a detection rate of 3.8/1,000 live births, 244 (4.5/1,000 live births) in 2008, and 198 (4.0/1,000 live births) in 2009. Table 1 shows the pregnant women’s demographic and clinical data. Most were brown/mixed-race (75.1%), less than 30 years old (80.6%), and had low schooling (66.2%). Sixty-four percent of notifications were for women residing in Manaus, the State capital. Staging of the disease showed 56.8% classified as primary syphilis, 82.9% with a reactive VDRL test at notification, and 58.7% treated with single-dose benzathine penicillin G, 2.4 million units.

Cases of congenital syphilis

A total of 486 cases of congenital syphilis were notified to SINAN from 2007 to 2009 in the Amazonas State, of which 153 cases were in 2007, or an incidence rate of 2.1/1,000 live births, 193 (2.6/1,000) in 2008, and 140 (2.0/1,000) in 2009. Seventy-eight per cent of notifications referred to mothers residing in the State capital. In 252 reports of congenital syphilis (51.9%), the diagnosis of maternal syphilis occurred late (at childbirth or post-miscarriage curettage), while 144 (29.6%) cases were diagnosed during prenatal care. Only 17% of the women were adequately treated. Less than one-fourth of the mothers’ partners were treated (Table 2). Only 25 infants were reported as symptomatic at notification, 56.6% presented reactive peripheral blood VDRL, 20.6% underwent long-bone x-rays, and 6% cerebrospinal fluid analysis for syphilis (Table 2).

Deaths related to congenital syphilis

The SIM listed 4,905 perinatal deaths from 2007 to 2009 in Amazonas State, of which 57.8% were stillbirths. Of the total, only six presented congenital syphilis coded as A50 (ICD-10), five as the underlying causes and one as an associated cause. The proportion of stillbirths from congenital syphilis was 0.04%.

Probabilistic record linkage

After probabilistic record linkage between the databases for syphilis in pregnancy and congenital syphilis, 237 pregnant women (35.6%) were found with resulting cases of congenital syphilis notified during the period, of which 3 women were recorded twice, in different years, and were thus considered as 2 cases of diagnosis of syphilis in pregnancy, resulting in 2 cases of congenital syphilis in distinct periods (Figure 1).

Probabilistic linkage of the SIM and SINAN-Congenital Syphilis databases yielded 13 cases in which the mother’s name was recorded on both the Death Certificate and the notification of congenital syphilis. Nine were stillbirths, none of these made any mention of congenital syphilis among the causes leading to death, and only two cases were notified in the SINAN-Congenital Syphilis database. Two cases of early neonatal deaths were in the SINAN database, one of which with congenital syphilis as the underlying cause and another as associated cause; a third early neonatal death was not notified, although congenital syphilis was listed as the underlying cause of death (Figure 2). Meanwhile, of the 20 cases listed as stillbirths in the SINAN-Congenital Syphilis database, only two were located in the SIM.

Estimated underreporting of syphilis in pregnancy and congenital syphilis

Approximately 60% of the women diagnosed with syphilis in pregnancy were treated with single-dose penicillin G, considered inadequate for controlling congenital syphilis. One could thus expect 25% of these mothers to transmit the disease, with an additional 100 cases of congenital syphilis during the period.

Meanwhile, some 50% of mothers of cases of congenital syphilis were not reported, which could have added 243 cases of syphilis in pregnancy during the period.

Discussion

The current study showed far fewer reported cases of pregnant women with syphilis than estimated for the North of Brazil in 2004 ³3 . Departamento Nacional de DST, Aids e Hepatites Virais, Secretaria de Vigilância em Saúde, Ministério da Saúde. Dados epidemiológicos sífilis em gestantes. Boletim Epidemiológico AIDS e DST 2010; 1:34-6., or some 1,200 pregnant women per year. Meanwhile, the study found an incidence rate of congenital syphilis ranging from 2.0 to 2.6 cases per 1,000 live births in the State of Amazonas, still above the target of elimination of the disease and indicating possible flaws in primary care ¹⁷17 . Secretaria de Políticas de Saúde, Ministério da Saúde. Sífilis congênita: diretrizes para o controle. Brasília: Ministério da Saúde; 2010.. In Brazil, congenital syphilis is still an important health problem, with rates around 2.0 per 1,000 live births in the study period ¹⁶16 . Departamento Nacional de DST, Aids e Hepatites Virais, Secretaria de Vigilância em Saúde, Ministério da Saúde. Boletim Epidemiológico de Sífilis 2012; 1:3-8., thus highlighting the need for a high-priority policy for its control ¹⁸18 . Saraceni V, Miranda AE. Relação entre a cobertura da Estratégia Saúde da Família e o diagnóstico de sífilis na gestação e sífilis congênita. Cad Saúde Pública 2012; 28:490-6..

The characteristics of the pregnant women reported with syphilis feature the high proportion of cases of primary syphilis (56.8%). The primary lesion (hard chancre) in women almost always presents with internal genital localization ²2 . Sanchez PJ, Wendel GD. Syphilis in pregnancy. Clin Perinatol 1997; 24:71-90., and most cases of syphilis in pregnancy are diagnosed in the latent phase, without signs or symptoms, only through serological screening with the nontreponemal test (VDRL) ¹⁹19 . Krakauer Y, Pariente G, Sergienko R, Wiznitzer A, Sheiner E. Perinatal outcome in cases of latent syphilis during pregnancy. Int J Gynaecol Obstet 2012; 118:15-7.. Logically, one would not expect such a diagnostic percentage of chancre in women submitted to serological screening tests for diseases with risk of vertical transmission. In addition, since most of the women were probably treated inadequately, we were not able to assess treatment of the partners ²⁰20 . Hildebrand VLPC. Sífilis congênita: fatores associados ao tratamento das gestantes e seus parceiros [Dissertação de Mestrado]. Rio de Janeiro: Escola Nacional de Saúde Pública Sergio Arouca; Fundação Oswaldo Cruz; 2010.. When verifying the quality of the mother’s treatment in the report of congenital syphilis, the failure becomes evident since only 16.7% of the women received adequate treatment, even though 67.3% attended prenatal care. For the same years in Brazil as a whole, slightly more than 70% of mothers reported having attended prenatal care ¹⁶16 . Departamento Nacional de DST, Aids e Hepatites Virais, Secretaria de Vigilância em Saúde, Ministério da Saúde. Boletim Epidemiológico de Sífilis 2012; 1:3-8..

As for cases of congenital syphilis reported in Amazonas State, 1.4% were classified as miscarriage due to syphilis and 4.2% as syphilitic stillbirth. In the year 2007, Brazil showed 1.7% as miscarriage and 12.3% as stillbirth ¹⁶16 . Departamento Nacional de DST, Aids e Hepatites Virais, Secretaria de Vigilância em Saúde, Ministério da Saúde. Boletim Epidemiológico de Sífilis 2012; 1:3-8.. In a study in the city of Nova Iguaçu, Rio de Janeiro State, 11.7% of recorded stillbirths were related to maternal syphilis ²¹21 . Nascimento MI, Cunha AA, Guimarães EV, Alvarez FS, Oliveira SR, Villas Bôas EL. Gestações complicadas por sífilis materna e óbito fetal. Rev Bras Ginecol Obstet 2012; 34:56-62.. In the current study, only 5.1% of cases were symptomatic at birth, a very low proportion, which should lead to immediate case investigation based on the Brazilian national protocol ⁵5 . Secretaria de Assistência à Saúde/Secretaria de Vigilância em Saúde, Ministério da Saúde. Plano operacional – redução da transmissão vertical do HIV e da sífilis. Brasília: Ministério da Saúde; 2007.^,2222 . Departamento de Atenção Básica, Secretaria de Atenção Básica, Ministério da Saúde. HIV/Aids, hepatites e outras DST. Brasília: Ministério da Saúde; 2006. (Cadernos de Atenção Básica, 18).. However, the data showed a low rate of long-bone x-rays (20.6%) and an even lower rate of cerebrospinal fluid analysis (6%) to assess involvement of the central nervous system.

Probabilistic record linkage of the databases found 237 women with syphilis in pregnancy whose newborns were also reported to the SINAN-Congenital Syphilis database during the same period. This corresponds to 35.6% of the pregnant women that were reported. One would not expect that all cases of syphilis in pregnancy would be followed by notification of congenital syphilis, since adequate treatment of the pregnant woman and partner should avoid the case ¹⁸18 . Saraceni V, Miranda AE. Relação entre a cobertura da Estratégia Saúde da Família e o diagnóstico de sífilis na gestação e sífilis congênita. Cad Saúde Pública 2012; 28:490-6.. Still, as discussed above, adequate treatment was only provided in a very low proportion of the pregnant women with syphilis, suggesting that there was underreporting of congenital syphilis, approximately 100 cases in the current study, as shown in another study in Rio de Janeiro ²³23 . Saraceni V, Vellozo VRO, Leal MC, Hartz ZMA. Estuda da confiabilidade do SINAN a partir das campanhas para a eliminação da sífilis congênita no município do Rio de Janeiro. Rev Bras Epidemiol 2005; 8:419-24.. Meanwhile, not all the mothers had been reported in the SINAN-Syphilis in Pregnancy database.

Considering the detection rate for syphilis in pregnancy of approximately 2 per 1,000, the proportion of stillbirths due to syphilis was extremely low (0.04%). The World Health Organization considers a proportion of less than 2% tolerable ²⁴24 . Blencowe H, Cousens S, Kamb M, Berman S, Lawn JE. Lives saved tool supplement detection and treatment of syphilis in pregnancy to reduce syphilis related stillbirths and neonatal mortality. BMC Public Health 2011; 11 Suppl 3:S9.. Of the 20 cases recorded as stillbirths in the SINAN-Congenital Syphilis database, only 2 were located in SIM. Many stillbirths are not claimed for burial by the families at the maternity hospitals and may not receive a Death Certificate. However, with the establishment of Committees for the Investigation of Infant and Fetal Mortality ²⁵25 . Secretaria de Vigilância em Saúde/Secretaria de Atenção à Saúde, Ministério da Saúde. Manual de vigilância do óbito infantil e fetal e do Comitê de Prevenção do Óbito Infantil e Fetal. Brasília: Ministério da Saúde; 2009., all such cases should be investigated, and when necessary an “epidemiological” death certificate should be issued to permit burial.

In this study, probabilistic record linkage of different databases containing data on congenital syphilis was a useful tool for evaluating the quality of information contained in these large national systems. In general, probabilistic record linkage is important for monitoring target events ²⁶26 . Zingmond DS, Ye Z, Ettner SL, Liu H. Linking hospital discharge and death records accuracy and sources of bias. J Clin Epidemiol 2004; 57:21-9.^,2727 . Coutinho ESF, Coeli CM. Acurácia da metodologia de relacionamento probabilístico de registros para identificação de óbitos em estudos de sobrevida. Cad Saúde Pública 2006; 22:2249-52.^,2828 . Rogot E, Sorlie P, Johnson NJ. Probabilistic methods in matching census samples to the National Death Index. J Chronic Dis 1986; 39:719-34.^,2929 . van den Bradt PA, Schouten L, Gold-Bohm RA, Dorant E, Hunen PMH. Development of a record linkage protocol for use in the Dutch Cancer Registry for epidemiological research. Int J Epidemiol 1990; 19:553-8. or for upgrading information in different databases ¹³13 . Newcombe HB, Kennedy JM, Axford SJ, James AP. Automatic linkage of vital records. Science 1959; 130:954-9.^,3030 . Coutinho RGM, Coeli CM, Faerstein E, Chor D. Sensibilidade do linkage probabilístico na identificação de nascimentos informados: Estudo Pró- Saúde. Rev Saúde Pública 2008; 42:1097-100..

The use of secondary databases such as SINAN and SIM may not reflect the total magnitude of the respective diseases, given the need for adequate completion of notification forms and/or death certificates according to the prevailing national protocols and by responsible health professionals. Nevertheless, these health information systems can provide the basis for monitoring and analyzing the health situation in municipalities and states, with a view towards health planning and management.

Final remarks

Two issues are essential for a better understanding of the current study’s findings and their extension to other locations. The first is adequate prenatal care provided in the municipalities and states, where diagnosis and treatment of syphilis in pregnancy can be the sentinel event for the quality of services, avoiding cases of congenital syphilis. The current study’s findings corroborate this issue. The second issue is training for health professionals in epidemiological surveillance and for physicians in the completion of death certificates, in addition to the implementation of inquiries into stillbirths and infant deaths according to Ministry of Health criteria. With the development of more reliable information systems with broader coverage, the analysis of the health situation can contribute more robustly to the control of diseases such as syphilis.

References

Publication Dates

History