Medical Express

ISSN (print): 2318-8111

ISSN (online): 2358-0429

Issue: 3.6 - 6 Articles

Back to summary

x

How to cite


 

Lopes IMD, Aragão JA, Lopes AD, Almeida-Santos M, Lima SO, Fonseca V, et al. Adhesion to the monitoring of newborns from VDRL positive mothers. MEDICALEXPRESS 2016;3(6):M160602 http://www.dx.doi.org/10.5935/MedicalExpress.2016.06.02

 

ORIGINAL RESEARCH http://www.dx.doi.org/10.5935/MedicalExpress.2016.06.02

Adhesion to the monitoring of newborns from VDRL positive mothers

Izailza Matos Dantas Lopes1; José Aderval Aragão1,2; Adriana Dantas Lopes1; Marcos Almeida-Santos1; Sônia Oliveira Lima1; Vania Fonseca3; Vera Lúcia Corrêa Feitosa2; Francisco Prado Reis1

1. Universidade Tiradentes, Departamento de Medicina , Aracaju, SE, Brazil
2. Universidade Federal de Sergipe, Departamento de Morfologia, Aracaju, SE, Brazil
3. Universidade Estadual Paulista Julio de Mesquita Filho, Departamento de Geografia, São Paulo, SP, Brazil

E-mail: izailzamatos@hotmail.com

Received in August 1 2016.
First Review in August 29 2016.
Accepted in November 14 2016.

Abstract

OBJECTIVE: Treponema pallidum is the etiological agent of congenital syphilis, which results from fetal contamination by the infected mothers, who were not treated or were inadequately treated during pregnancy.
METHODS: An observational, prospective and longitudinal study, was performed (2010-2014), through the evaluation of 428 newborns during 18 months in a syphilis clinic from a Philanthropic Maternity Hospital in Aracaju, capital city of the Northeastern state of Sergipe, Brazil. The findings were statistically expressed as descriptive data and the statistical program used was SPSS (Statistical Package for Social Sciences).
RESULTS AND CONCLUSIONS: The prevalence of congenital syphilis was 10.02/1,000 live births. A total of 120 (28%) of newborns did not attend the first appointment. During the observational period, at 18 months, the rate of abandonment was 75%. The average interval of healing of the newborns was 4.25 months. A high prevalence of congenital syphilis was found with low adhesion to the first consultation and monitoring period; 67.1% of newborns were treated with Crystalline Penicillin (Penicillin G) and only 3% of them required a repeat treatment.

Keywords: Congenital syphilis; prenatal care; prevalence.

Resumo

OBJETIVO: A sífilis congênita tem como agente etiológico o Treponema pallidum e resulta da contaminação do feto pela gestante infectada sem tratamento ou com tratamento inadequado.
MÉTODO: Foi realizado um estudo observacional, prospectivo, longitudinal, com a participação de 428 recém-nascidos que foram acompanhados durante 18 meses em um ambulatório de sífilis de uma Maternidade Filantrópica em Aracaju. Os achados foram estatisticamente expressos de maneira descritiva e o programa estatístico utilizado foi o SPSS.
RESULTADOS E CONCLUSÕES: A prevalência de sífilis congênita para 1000 nascidos vivos foi de 10,02 casos. Não compareceram à primeira consulta 28,2% dos recém-nascidos. Durante o acompanhamento, aos 18 meses, o percentual de abandono foi de 75%. O intervalo médio de cura dos recém-nascidos foi de 4,25 meses. Foi encontrada uma alta prevalência de sífilis congênita com baixas adesões à primeira consulta e ao acompanhamento; 67,1% foram tratados com penicilina cristalina e apenas 3% necessitaram repetir o tratamento.

Palavras-chave: Sífilis congênita; Pré-natal; Prevalência

 

INTRODUCTION

Since 2004 in Brazil, congenital syphilis has been assumed to be present in every live birth, abortion or stillborn of a mother with clinical and/or laboratory evidence of syphilis and VDRL (Venereal Disease Research Laboratory) positive test, who has not been treated or who has received inadequate treatment.1-4 Syphilis is still considered one of the main diseases responsible for high morbidity and mortality in the intrauterine and neonatal periods.5 Its incidence rates have been used as a development indicator of countries because it is treatable with penicillin and can be prevented by condom use.3 In 1993, The Ministry of Health (MOH) and The Pan American Health Organization (PAHO) implemented a congenital syphilis elimination plan in order to reduce the high prevalence of the disease. This plan established the right of all pregnant women to carry out the VDRL test in the first prenatal consultation, third trimester of pregnancy and on admission for childbirth.6

Despite the implementation of these WHO recommended actions, some studies have shown that, in the last decade, the incidence of congenital syphilis has increased globally, even in developed countries. These studies indicate, according to regions or countries, some factors that may or may not have contributed to its occurrence: the difficult access to prenatal care and/or its low quality; early sexual initiation; low income; use of legal and illegal drugs; sex professionals; low education, the non-partner treatment, among others.5,7-11

Even in countries that have implemented eradication plans for congenital syphilis, the disease remains a threat to maternal and child health. Only about one-third of pregnant women attending prenatal care in 22 countries of sub-Saharan Africa are tested for syphilis, although 17 of these countries have policy recommendations requiring this triage.12

A basic and essential action for the health of newborns with congenital syphilis has been the recommendation of monitoring of newborns and their parents through a medical specialized service.6 Thus, this study was conducted in order to monitor newborns diagnosed with congenital syphilis, to determine the prevalence of the disease, adherence to follow-up and therapeutic management. The study was conducted in the Aracaju (population 570,000, high Human Development Index - 0.777), the capital of the northeastern Brazilian state of Sergipe (population, 2,200,000 Average HDI - 0.665)

 

MATERIAL E METHODS

An observational, descriptive, prospective and longitudinal study was conducted between 2010 and 2014, from medical records data of a syphilis clinic at a Philanthropic Maternity Hospital Santa Izabel in Aracaju, Sergipe, Brazil. The study was approved by the Ethics Committee of Universidade Tiradentes (case # 525.002/2010).

A total of 595 mothers of live newborns were interviewed in order to establish criteria as to the suitability of the treatment they had received for syphilis. The treatment was considered suitable (a) when the mother and her partner received benzathine penicillin, according to the clinical phase of the disease, and the treatment was completed thirty days before childbirth; (b) if the couple used condom during the treatment period; (c) if the mother had a monthly performance of VDRL test from the positive finding in pregnancy; (d) if documental evidence proving the completion of treatment by both was offered. These strategies have been applied in accordance with the guidelines recommended by the 2008 Elimination of Congenital Syphilis Program.13

The VDRL test in peripheral blood was performed in all newborns. Those whose mothers were considered adequately treated, who had no symptoms and had negative VDRL were referred for ambulatory follow-up. In case of doubt regarding this monitoring, they received a dose of benzathine penicillin. When the newborn had positive VDRL, radiographs of long bones, blood count and CSF collection were performed. Babies were treated with penicillin for ten days when they presented: (a) symptoms; (b) VDRL greater than their mothers; (c) radiographic alterations of long bones; (d) positive VDRL for Cerebrospinal Fluid. In cases where VDRL was positive and less than or equal to the mother's they were treated with benzathine penicillin and, if there were doubts as to the follow-up, they were treated with penicillin for ten days.

In cases of newborns whose mothers received no treatment or inadequate treatment, X-ray of long bones, blood count and CSF collection for determination of VDRL were performed. In the presence of positivity in any of these examinations and/or signs of the disease, newborns were treated with penicillin for ten days. Those who had negative tests and no signs of disease were treated with a dose of benzathine penicillin. Whenever a child had not healed he or she was hospitalized and again treated with penicillin for ten days; if any doubt about the follow-up remained, they were hospitalized and treated with penicillin for ten days. All patients were referred to the clinic at the age of 1 month for clinical examination and measurement of VDRL levels in peripheral blood were performed during the monitoring period of newborns at the age of 1, 3, 6, 12, 18 months. Whenever (a) they had symptoms of the disease, (b) their VDRL levels were four times higher compared with the previous test or (c) remained equal to or greater than 1:8, the newborn was hospitalized for ten days to perform a new treatment with crystalline penicillin. Healing and medical release from the program were determined by the following criteria: the absence of signs and symptoms of the disease; two consecutive negative VDRL test results in peripheral blood; x-ray of long bones unchanged; and negative VDRL in CSF.

All findings were statistically expressed descriptively through simple frequency and percentage, with their respective confidence intervals. The statistical program used was SPSS (Statistical Package for Social Sciences).

 

RESULTS

During the study period we searched through 41,720 records of obstetric proceedings from which we retrieved 595 live births from 740 mothers with a positive VDRL test; we recorded 23 dead fetuses and 122 miscarriages. Thus, was found a rate of 1.77% of congenital syphilis. Out of the 595 newborns, 428 attended the first consultation of the monitoring program while 167 failed to attend without any explanation. Out of the 428 newborns who attended first consultation, only 379 exhibited weight gain as evaluated in the first month of life. The frequency distribution of newborn by sex, birth weight and weight gain in the first month of life are presented in Table 1. The following can be observed: (i) there was a similar frequency in the sex distribution; (ii) 42.5% were born with 1,500 to 2,500g weight, while 43.3% exhibited weight > 2,500g; (iii) similar percentages exhibited weight gains of 15 to 30 g or greater than 30 g per day, respectively, during the first month of life.

 

 

All values VDRL levels in newborn infants from birth to 18 months of age are shown in Table 2. VDRL levels above a high level of 1:8, had a frequency of 22.6% at child birth, by the 1st month this was down to 7.9%.

 

 

Values of VDRL continued to decline gradually: at 3 months 11 newborns had VDRL values above 1:8; by six months this number was down to two; at 12 months down to zero.

Regarding the therapeutic approach used for the 428 newborns referred for follow-up: 287 (67.1%) were treated with penicillin at birth; 131 (30.6%) received prophylactic benzathine penicillin; 10 (2.3%) did not require treatment. Treatment with crystalline penicillin was used up to 12 months after the start of monitoring. 2.1% of newborns needed to be hospitalized for further treatment in the first month of life, 0.8% in the third, 0.8% in the sixth and 4.5% in the twelfth. The average healing time was 4.25 months.

Out of the 427 newborns who attended the first consultation, only 285 attended the third month consultation. At 18 months, the newborn noncompliance rate reached 75%. In terms of medical discharge, 51.2% of newborns were cured in the third month and the percentage reached 100% at 18 months. Table 3 shows that the monitoring program had a progressive increase of the noncompliance rate.

 

 

DISCUSSION

Despite decades of epidemiological and clinical experience with maternal congenital and syphilis, Cooper et al.,14 reported that both remain major public health problems not only in Brazil but in the rest of the Americas. The World Health Organization estimates that globally 1.5 - 1.9 million pregnant women are infected with syphilis annually and half of them have children with adverse outcomes.15

In Brazil congenital syphilis has been on the increase, resulting in a substantial level of neonatal deaths. In 2004, a rate of 1.7/1,000 live births of congenital syphilis was reported to the Ministry of Health and PAHO, while in 2013 the number of cases increased to 13,705 (4.70/1,000 live births). Preliminary reports indicate an increase in 2014 to 16,165 cases (5.5/1,000 live births). According to the Information System for Notifiable Diseases (SINAN), in the northeastern state of Sergipe (population 2.2 million), the incidence rate was 11.2/1,000 live births second only to Rio de Janeiro, where the incidence rate was 11.5/1,000 live births16 in 2013.

At the present study, conducted in the largest maternity hospital of the state of Sergipe, by analyzing protocols of 41,720 obstetric procedures was found a rate of 1.77% of congenital syphilis. Studies of similar shape and objectives conducted in maternity hospitals in different regions of Brazil, reported congenital syphilis rates varying from 1.3% to 14.5%.17-22 Domingues et al.,23 in a national hospital based study in a sample of 450 newly delivered mothers, found a rate of 6.2% of congenital syphilis in the northeast of Brazil, where the state of Sergipe is inserted. The Northeast was behind only the Southeast, the most developed area of Brazil.

SINAN data for 2014 in reference to the incidence of congenital syphilis in Brazilian state capitals, recorded levels of up to twice as many as found in the respective states as a whole. Sergipe has a prevalence of congenital syphilis (11.2/1,000) which is still far above the goal estimated by WHO (less than 0.5 cases per 1000 live births).12,25,26 Countries such as Canada, United States, Chile and Cuba already have these rates.21

Based on the 2012 guidelines of the Scientific Department of Nutrology,28 86.8% of newborns in this study gained weight daily in their first month of life, greater than 15g per day. Only 14.2% gained less than 15g daily. It should be noted that, besides the similarity in distribution between sexes, 43.3% of newborns had birth weight greater than 2,500g. This finding was similar to those described elsewhere.26,27,29

In this study, at birth and in the sixth month of life, 29.7% and 88.6% of newborns, respectively, had negative VDRL. The average time to newborn healing was 4.25 months of age. VDRL levels equal to or greater than 1:8 occurred at childbirth in 22.6% of newborns and at 6 months in only 2.3%. Lago et al.,21 found 17.5% of newborns with congenital syphilis, who were negative for VDRL at birth. Vanegas-Castillo et al.,30 and Galeno-Cardona et al.,24 found VDRL levels greater than 1:8 at birth in 12% and 41.6% of cases, respectively. In newborns treated at a later stage after birth, the decrease of VDRL levels decreased more slowly and with a higher incidence of mortality and morbidity.³

Newborns in this study were treated with penicillin intravenously (67.1%) for ten days in hospitalization; 30.6% received one dose of benzathine penicillin; and 3% received further treatment. In newborns studied by Lago et al.,21 77.6% were treated with penicillin intravenously for 10 to 14 days; 21.9% with benzathine penicillin, a single dose intramuscularly; and 0.5% received procaine penicillin intramuscularly for ten days. A prospective study conducted in Italy from 2000 to 2007 accompanied newborns of mothers inadequately treated or untreated for syphilis, at birth, three, six, nine to 12 months old. Infants exhibiting prematurity, radiographically altered long bones, IGM specific to the Treponema pallidum and cerebrospinal fluid with positive VDRL were treated with crystalline penicillin from birth until 14 days of age; infants with negative serology and no signs of the disease received a single dose of penicillin benzatine.31

A number of reports have shown the value of penicillin in the treatment of syphilis in pregnant women and newborns with a positive VDRL. These data support the statement from Ingraham (1951), who said that "the value of penicillin in the treatment and prevention of syphilis transmission from mother to newborn approaches perfection and is valid until today".32 This also ratifies the concept that, despite seven decades of use, Treponema pallidum, up to the present, has no penicillin resistance.

Short term adhesion

In terms of adhesion to the first appointment by newborns with congenital syphilis in Porto Alegre (population, 1.5 million high HDI - 0.805), Lago et al21 reported a frequency of 50.3%. In our study, despite the completion of a schedule and an explanation of the program to mothers about the importance of returning to the clinic, adhesion to the first consultation was 71.8%. Mesquita et al33 in the city of Sobral (population 200,000 high HDI), in the northeastern state of Ceará, reported an adhesion of only 10% at the first appointment.

Follow-up records of newborns from mothers with congenital syphilis have been precarious. Magalhães et al6 reported a lack of monitoring of 67 pregnant/puerperal women notified in SINAN, between 2009 and 2010 from public hospitals in Distrito Federal. Costa et al.,34 in Ceará analyzed 2,930 cases of congenital syphilis registered in SINAN from 2000 to 2009 and confirmed the need of follow-up records.

Long term adhesion

In this study, 75% of mothers abandoned the follow-up at 18 months. Lago et al21 observed that the follow-up frequency of newborns with congenital syphilis over 60 months had a gradual decrease, reaching 21% between 3 and 5 years old. Rawstron et al.,35 in New York found 17% at 6 months and London Sothinathan et al.,36 found a 14% frequency in African Caribbean at 3 months and 8% at 6 months. In Florida, Ricci et al.,37 reported a noncompliance of 51.7%.

In most of these observations, as in the present study, reduction in appearance was increasing over the follow-up program duration. This low rate may be due to the presence of some social vulnerability factor in the current study population, such as transport difficulties, lack of financial resources, location address, the disbelief that the newborn is really sick and even lack of a phone contact.

 

CONCLUSION

In spite of the proposed Congenital Syphilis Elimination Program by the Ministry of Health, a high prevalence of this disease and low adhesion to the follow-up program carried out over 18 months were found in a Philanthropic Maternity in Aracaju. This appears to be a problem prevalent throughout Brazil.

 

AUTHOR CONTRIBUTION

Lopes IMD: conception and design, acquisition of data, analysis and interpretation of data; critical revision of the manuscript for intellectual content; final approval of the submitted manuscript. Lopes AD: literature review, acquisition of data; final approval of the submitted manuscript. Almeida-Santos MA: analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for intellectual content and final approval of the submitted manuscript. Lima SO: methodological design, critical revision of the manuscript for intellectual content, drafting of the manuscript and final approval of the submitted manuscript. Fonseca V: literature review, critical revision of the manuscript for intellectual content and final approval of the submitted manuscript. Feitosa VLC: reviewing the manuscript and final approval of the submitted manuscript. Aragão JA: substantial contribution to conception and design, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for intellectual content and final approval of the submitted manuscript. Reis FP: conception and design, acquisition of data, analysis and interpretation of data; critical revision of the manuscript for intellectual content; final approval of the submitted manuscript.

 

CONFLICTS OF INTEREST

Authors declare no conflicts of interest regarding this project.

 

REFERENCES

1. Brasil. Ministério da Saúde. Secretaria de vigilância em saúde. Programa nacional de DST e AIDS. Diretrizes para o controle de sífilis congênita. Guia de bolso. 2. ed. Brasília: Ministério da Saúde; 2006. p. 1-72.

2. Brasil. Ministério da Saúde. Doenças Infecciosas e Parasitárias: Guia de Bolso. 8. ed. Revista. Brasília: Ministério da Saúde; 2010. p. 1-444.

3. Brasil. Ministério da Saúde. Atenção à saúde do recém-nascido: guia para os profissionais de saúde. 2. ed. Brasília: Ministério da Saúde; 2012. p. 1-195.

4. Kingston M, French P, Goh B, Goold P, Higgins S, Sukthankar A, Stott C, Turner A, Tyler C, Young H; Syphilis Guidelines Revision Group 2008, Clinical Effectiveness Group. UK National Guidelines on the Management of Syphilis 2008. Int J STD AIDS. 2008 Nov;19(11):729-40.

5. Hebmuller MG, Fiori HH, Lago EG. Gestações subsequentes em mulheres que tiveram sífilis na gestação. Ciênc. Saúde coletiva. 2015;20(9):1590-98. http://dx.doi.org/10.1590/1413-81232015209.20332014

6. Magalhães DMS, Kawaguchi IAL, Dias A, Calderon IMP. Maternal and congenital syphilis: a persistent challenge. Cad Saúde Pública. 2013;20(9):1109-20. http://dx.doi.org/10.1590/S0102-311X2013001000008

7. Saraceni V, Miranda AE. Relação entra a cobertura da Estratégia Saúde da Família e o diagnóstico de Sífilis na gestação e Sífilis congênita. Cad Saúde Pública. 2012;28(3):490-6. http://dx.doi.org/10.1590/S0102-311X2012000300009.

8. Lomotey CJ, Lewis J, Gebrian B, Bourdeau R, Dieckhaus K, Salazar JC. Maternal and congenital syphilis in rural Haiti. Rev Panam Salud Publica. 2009; 26(3):197-202. http://dx.doi.org/10.1590/S1020-49892009000900002

9. Rodolfo LC, Rodriguez M, Rivas J. Articulo de revision Sífilis y embarazo:? Cómo diagnosticar y tratar oportunamente? Revista colombiana de Obstetricia y Ginecologia. 2009; 60(1):49-56.

10. Campos ALA, Araújo MAL, Melo SP, Gonçalves MLC. Epidemiology of gestational syphilis in Fortaleza, Ceará State, Brazil: an uncontrolled disease. Cad. Saúde Pública. 2010;26(9):1747-55. http://dx.doi.org/10.1590/S0102-311X2010000900008.

11. Domingues RMSM, Lauria LM, Saraceni V, Leal MC. Manejo da sífilis na gestação: conhecimentos, práticas e atitudes dos profissionais pré-natalistas da rede SUS do município do Rio de Janeiro. Rev Ciênc Saúde Coletiva. 2013;18(5):1341-51.

12. WHO. Investment case for eliminating mother-to-child transmission of syphilis: promoting better maternal and child health and stronger health systems. WHO [Internet] 2012 [cited 2016 August 1]; Available from: http://apps.who.int/iris/bitstream/10665/75480/1/9789241504348_eng.pdf

13. Organização Mundial de Saúde (OMS). Eliminação mundial da sífilis congênita: fundamento lógico e estratégia para ação. OMS [Internet] 2008 [acessado em 01 de agosto de 2016] Available from: http://apps.who.int/iris/bitstream/10665/43782/4/9789248595851_por.pdf

14. Cooper JM, Michelow IC, Wozniak PS, Sánchez PJ. Em tempo: a persistência da sífilis congênita no Brasil – Mais avanços são necessários!. Rev Paul Pediatr. 2016;34(3):251-53. http://dx.doi.org/10.1016/j.rpped.2016.06.001

15. Gomez GB, Kamb ML, Newman LM, Mark J, Broutet N, Hawkes SJ. Untreated maternal syphilis and adverse outcomes of pregnancy: a systematic review and meta-analysis. Bull World Health Organ. 2013;91:217-26. http://dx.doi.org/10.2471/BLT.12.107623

16. Ministério da Saúde (BR). Sífilis. Boletim Epidemiológico. 2015;4(1):1-32.

17. Schetini J, Ferreira DC, Passos MRL, Salles EB, Santos DDG, Rapozo DCM. Estudo da prevalência de sífilis congênita em um hospital da rede SUS de Niterói – RJ. J Bras Doenças Sex Transm. 2005;17(1):18-23.

18. Fernandes RCSC, Fernandes PGCC, Nakata TY. Análise de casos de sífilis congênita na maternidade do hospital da sociedade portuguesa de beneficência de Campos, RJ. J Bras Doenças Sex Transm. 2007;19(3-4):157-61.

19. Fernandes RSC, Fernandes RSC, Fernandes RCSC. Aspectos epidemiológicos da sífilis congênita em uma maternidade do município de Campos do Goytacazes, RJ. Ver Cient Faculdade Med Campos. 2006;1(1):15-19.

20. Magalhães DMS, KawaguchiI IAL, Dias A, Calderon IMP. Maternal and congenital syphilis: a persistent challenge. Cad Saúde Pública. 2013;29(6):1109-20. http://dx.doi.org/10.1590/S0102-311X2013000600008.

21. Lago EG, Vaccari A, Fiori RM. Clinical features and follow-up of congenital syphilis. Sex Transm Dis. 2013;40(2):85-94. http://dx.doi.org/10.1097/OLQ.0b013e31827bd688

22. Rojas MM, Dias RM, Araújo EC. Dez anos de sífilis congênita em maternidade de referência na Amazônia brasileira. Rev Para Med. 2015;29(1):7-10.

23. Domingues RMSM, Leal MC. Incidência de sífilis congênita e fatores associados à transmissão vertical da sífilis: dados do estudo Nascer no Brasil. Rev Saúde Pública. 2013; 32(6): e00082415. http://dx.doi.org/10.1590/0102-311X00082415.

24. Galeno-Cardona CL, Garcia-Gutiérrez WD, Congote-Arango LM, Vélez-Garcia MA, Martinez-Buitrago DM. Prevalencia de Sífilis Gestacional e Incidencia de Sífilis Congénita, Cali, Colombia, 2010. Rev Colomb Obstet Ginecol 2012;63(4):321-26.

25. Lima MG, Santos RFR, Barbosa GJA, Ribeiro GS. Incidência e fatores de risco para sífilis congênita em Belo Horizonte, Minas Gerais, 2001-2008. Ciênc Saúde Coletiva. 2013;18(2):499-506. http://dx.doi.org/10.1590/S1413-81232013000200021.

26. Qin J, Yang T, Xiao S, Tan H, Feng T, Fu H. Reported estimates of adverse pregnancy outcomes among women with and without syphilis: a systematic review and meta-analysis. PLoS One. 2014;9(7):e102203. http://dx.doi.org/10.1371/journal.pone.0102203

27. Melo NGDO, Filho DAM; Ferreira LOC. Diferenciais intraurbanos de sífilis congênita no Recife, Pernambuco, Brasil (2004-2006). Epidemiol Serv Saúde. 2011 Abr-Jun;20(2):213-22. http://dx.doi.org/10.5123/S1679-49742011000200010

28. Sociedade Brasileira de Pediatria. Manual de orientação para alimentação do lactente, do pré-escolar, do escolar, do adolescente e na escola. Sociedade Brasileira de Pediatria [Internet] 2012 [acessado em 01 de agosto de 2016] Available from: https://www.sbp.com.br/img/manuais/manual_alim_dc_nutrologia.pdf

29. Holanda MT, Barreto MA, Machado KM, Pereira RC. Perfil epidemiológico da sífilis congênita no Município do Natal, Rio Grande do Norte – 2004 a 2007. Epidemiol Serv Saúde. 2011;20(2):203-12. http://dx.doi.org/10.5123/S1679-49742011000200009.

30. Vanegas-Castillo N, Caceres-Buitrago YN, Jaimes-gonzalez CA, Ángel-Mulle E, Rubio-Romero JA. Tratamiento de la Sífilis gestacional y Prevención de la sífilis congénita en un Hospital público en Bogotá, 2010. Rev Fac Med. 2011;59(3):167-89.

31. Marangoni A, Moroni A, Tridapalli E, Capretti MG, Farneti G, Faldella G, D'Antuono A, Cevenini R. Antenatal syphilis serology in pregnant women and follow-up of their infants in northern Italy. Clin Microbiol Infect. 2008;14(11):1065-8. http://dx.doi.org/10.1111/j.1469-0691.2008.02066.x

32. Jacinto S, Henriques M, Ferreira T, Carvalho G, Costa T, Valido AM. A sífilis congênita ainda existe. Análise retrospectiva de 12 anos de uma grande maternidade. Acta Pediatr Port. 2007;38(2):65-8.

33. Mesquita KO, Lima GK, Filgueira AA, Flôr SMC, Freitas CASL, Linhares MSC, Gubert FA. Análise dos Casos de Sífilis Congênita em Sobral, Ceará: Contribuições para Assistência Pré-Natal. J Bras Doenças Sex Transm 2012;24(1):20-27. http://dx.doi.org/10.5533/2177-8264-201224107

34. Costa CC, Freitas LV, Sousa DMN, Oliveira LL, Chagas ACMA, Lopes MVO, Damasceno AKC. Congenital syphilis in Ceará: epidemiological analysis of one decade. Rev Esc Enferm USP. 2013;47(1):152-9. http://dx.doi.org/10.1590/S0080-62342013000100019.

35. Rawstron SA, Mehta S, Marcellino L, Rempel J, Chery F, Bromberg K. Congenital syphilis and fluorescent treponemal antibody test reactivity after the age of 1 year. Sex Transm Dis. 2001;28(7):412-6.

36. Sothinathan U, Hannam S, Fowler A, Zuckerman M, Reeves I, Tenant-Flowers M. Detection and follow up of infants at risk of congenital syphilis. Arch Dis Child. 2006 Jul;91(7):620.

37. Ricci JM, Fojaco RM, O'Sullivan MJ. Congenital syphilis: the University of Miami/Jackson Memorial Medical Center experience, 1986-1988. Obstet Gynecol. 1989 Nov;74(5):687-93.