Talk:Abnormal Development - Syphilis

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Cite this page: Hill, M.A. (2024, February 26) Embryology Abnormal Development - Syphilis. Retrieved from


Congenital Syphilis: A Discussion of Epidemiology, Diagnosis, Management, and Nurses' Role in Early Identification and Treatment

Adv Neonatal Care. 2018 Dec;18(6):438-445. doi: 10.1097/ANC.0000000000000534.

Rowe CR1, Newberry DM, Jnah AJ.

BACKGROUND: Syphilis is caused by the spirochete bacterium Treponema pallidum. Syphilis left untreated, or inadequately treated during pregnancy, can result in congenital syphilis (CS). Congenital syphilis can lead to severe sequelae or fetal, neonatal, or infant death. PURPOSE: To discuss the epidemiological trends, pathophysiology, diagnosis, and management of CS; the implications of CS upon the infant; as well as the importance of the nurse's role in the prompt identification of CS and the timely interventions needed to minimize sequelae. METHODS: A literature search was completed using ProQuest, CINAHL, Google Scholar, and PubMed. Articles published within the past 10 years were included. FINDINGS: Epidemiological trends of CS in the United States indicate that maternal syphilis infection and CS are on the rise. Risk factors include ethnicity, socioeconomic status, access to prenatal care, and sexual behaviors, as well as compliance with prenatal syphilis screening by prenatal providers. Risks of CS to the developing fetus begin at approximately 14 weeks. Timely treatment is necessary to minimize or eliminate mortality and morbidity. IMPLICATIONS FOR PRACTICE: Evidence-based, interprofessional strategies, which promote a collaborative perinatal/neonatal preventative approach to care of the pregnant female, are indicated to reverse the increasing incidence of CS within the United States. Strategies prioritizing early identification and treatment of at-risk neonates are necessary to reduce/eliminate the devastating long-term consequences of CS upon this vulnerable population. IMPLICATIONS FOR RESEARCH: The paucity of research, which focuses on CS, is most likely due to ethical concerns related to infants as research participants and provides an opportunity for future research. Future research could focus on factors that focus on maternal-fetal/maternal-child transmission of CS. PMID: 30020089 DOI: 10.1097/ANC.0000000000000534

Fetal and Placental Pathology in Congenital Syphilis: A Comprehensive Study in Perinatal Autopsy

Fetal Pediatr Pathol. 2018 Aug;37(4):231-242. doi: 10.1080/15513815.2018.1485798. Epub 2018 Sep 12.

Kittipornpechdee N1, Hanamornroongruang S1, Lekmak D1, Treetipsatit J1. Author information Abstract INTRODUCTION: At autopsy, without available serologic information, diagnosing congenital syphilis (CS) relies on identification of Treponema pallidum in tissues. Recognition of clues leading to detection of the organism is important. MATERIALS AND METHODS: Autopsy cases with CS were studied for fetal and placental abnormalities. RESULTS: Twenty-one cases were recruited: 12/21 with identifiable T. pallidum and 9/21 with positive serology and characteristics of CS. 20/21 (95%) demonstrated ≥1 fetal abnormalities. Chronic stress involution of thymus was most common. Hydrops and hepatosplenomegaly were found in >50%. Metaphyseal abnormalities and organ inflammation were found in <30%. Mucocutaneous lesions were lacking. Placental abnormalities were identified in 20/21 (95%). Placentomegaly was most common. Amniotic fluid infection (AFI) was noted in >50%. CONCLUSION: Common findings in CS at autopsy include chronic stress involution of thymus, hydrops, and hepatosplenomegaly. Mucocutaneous lesions are uncommon. Common placental findings in fetal deaths due to CS include placentomegaly and AFI. KEYWORDS: Congenital syphilis; fetal syphilis ; intrauterine syphilis infection PMID: 30207805 DOI: 10.1080/15513815.2018.1485798


Underreporting of Congenital Syphilis as a Cause of Fetal and Infant Deaths in Northeastern Brazil

PLoS One. 2016 Dec 12;11(12):e0167255. doi: 10.1371/journal.pone.0167255. eCollection 2016.

Cardoso AR1, Araújo MA1, Andrade RF1, Saraceni V2, Miranda AE3, Dourado MI4.

INTRODUCTION: Of all syphilis-related pregnancy outcomes, fetal death is certainly the most common one, being directly related to the availability, accessibility and quality of prenatal care. The present study aimed to analyze the underreporting of fetal and infant deaths and other maternal factors associated with congenital syphilis (CS) death. METHODS: This cross-sectional study integrated data of infants that were diagnosed and/or died of CS from the Sistema de Informação de Agravos de Notificação-Sinan (Notifiable Diseases Information System) and the Sistema de Informação de Mortalidade-SIM (Mortality Information System) in Fortaleza, Northeastern Brasil to identify unreported cases of congenital syphilis. We assessed data during the period from 2007 to 2013. RESULTS: The underreporting of CS as a cause of fetal or infant death increased from 41 to 415 cases (90.1%) during 2007-2013. Exactly 3,209 cases of CS were identified in Sinan and 6,578 deaths in SIM. After database linkage, we identified 382 cases that were reported in the SIM and SINAN databases consisting of 309 fetal deaths and 73 infant deaths related to CS. From the children notified at Sinan that born alive, 3.0% (78/2,542) died; Out of these, 39 (50.0%) were early and 25 (32.1%) were late neonatal deaths. The proportion of death by CS increased from 0.62 to 5.8 from 2007 to 2013. At logistic regression, the variable that maintained statistical significance with fetal and infant death outcomes was the presence of CS signs and/or symptoms at birth (OR = 3.20; IC 95% 1.54-6.62; p = 0.002). CONCLUSIONS: Neonatal and Infant deaths following CS-associated live births are underreported in Northeastern Brazil. Data base linkage identified unreported fetal and neonatal deaths due to CS leading to an increased awareness of fetal/infant mortality due to this infection. PMID: 27941983 PMCID: PMC5152812 DOI: 10.1371/journal.pone.0167255


Strategies of testing for syphilis during pregnancy

Cochrane Database Syst Rev. 2014 Oct 29;10:CD010385. doi: 10.1002/14651858.CD010385.pub2.

Shahrook S1, Mori R, Ochirbat T, Gomi H.


BACKGROUND: Each year about two million pregnant women are infected with preventable syphilis infection, mostly in developing countries. Despite the expansion of antenatal syphilis screening programmes over the past few decades, syphilis continues to be a major public health concern in developing countries. Point-of-care syphilis testing may be a useful strategy to substantially prevent syphilis-associated perinatal mortality and other negative consequences in resource-poor settings. However, the evidence on effectiveness has been generated mostly from observational study designs or has been reported as a mixed-intervention effect. OBJECTIVES: To assess the effectiveness of antenatal syphilis screening in improving the uptake of screening tests and treatment, and reducing perinatal mortality. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2014) and the reference lists of retrieved studies. SELECTION CRITERIA: Randomised (individual and cluster) controlled trials comparing different screening tests conducted during routine antenatal check-ups versus no screening test. Cross-over trials and quasi-randomised experimental study designs were not eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked for accuracy. MAIN RESULTS: We included two cluster-randomised controlled trials (three reports). Both trials assessed point-of-care syphilis testing with conventional testing methods and together involved a total of 8493 pregnant women. Data from these trials were not amenable to meta-analysis as the measure of effectiveness was assessed in a non-comparable way.One trial randomised 14 antenatal clinics (including 7700 pregnant women) and was carried out at in Ulaanbaatar, Mongolia. The trial assessed one-stop syphilis testing using a rapid treponemal test, and was judged to have unclear methods of random sequence generation, allocation concealment, selective reporting, and other bias and low risk of bias for incomplete outcome data. Blinding was not reported and was assessed as high risk. The point-of-care testing provided screening, test results and treatment within the same day. The trial appears to have adjusted their results to account for clustering. We entered the data into RevMan using the generic inverse variance method. The incidence of congenital syphilis was lower in the clusters receiving on-site screening (adjusted odds ratio (AOR) 0.09, 95% confidence interval (CI) 0.01 to 0.71) and the proportion of women tested for syphilis was higher in the clusters receiving on-site screening at both the first antenatal visit and at the third trimester visit (OR 989.80, 95% CI 16.27 to 60233.05; OR 617.88, 95% CI 13.44 to 28399.01). Adequate treatment and partner treatment was higher with the on-site screening (AOR 10.44, 95% CI 1.00 to 108.99; AOR 18.17, 95% CI 3.23 to 101.20) and more syphilis cases were detected at first and third trimester visits with the on-site screening (AOR 2.45, 95% CI 1.44 to 4.18; AOR 6.27, 95% CI 1.47 to 26.69). Perinatal mortality, incidence of HIV/AIDS, obstacles in uptake of screening, any other adverse effects, or healthcare resource usage were not reported in this trial.The second trial divided clinics into seven matched pairs (including 7618 pregnant women, although results were only presented for the positive cases (793 women)), and within each pair one clinic was randomised to receive the on-site screening and the other to continue routine laboratory testing. The trial was conducted in primary healthcare clinics in KwaZulu-Natal, South Africa. Random sequence generation were judged to be at low risk of bias, but allocation concealment and incomplete outcome data were judged to be high risk. Other bias and selective reporting bias remain unclear. Blinding was not reported and was assessed as high risk of bias. This trial assessed the primary outcome of this review (perinatal mortality) and the secondary outcomes (adverse outcomes; adequate treatment; syphilis prevalence) in the subset of women (793 women) who tested positive for syphilis. Only one outcome, adequate treatment, was adjusted to account for cluster design. However, not enough information was provided to include this in an analysis using the generic inverse variance method. Where possible, results have therefore been presented in forest plots (perinatal mortality; adequate treatment), as if the data are from a parallel randomised controlled trial. These results should therefore be interpreted with caution.The trial reported on perinatal mortality in women with positive test results and showed that on-site screening using a rapid plasma reagin test had no clear evidence of an effect on perinatal mortality reduction (odds ratio (OR) 0.63; 95% CI 0.27 to 1.48; 18/549 (3.3%) versus 8/157 (5.1%)). After loss to follow up, 396/618 (64.1%) women with positive test results received adequate treatment (two or more doses of 2.4 mega units of benzathine penicillin) in the intervention cluster versus 120/175 (68.6%) in the control (OR 0.82; 95% CI 0.57 to 1.17). It was not possible to include any other data on reported outcomes in forest plots (adverse outcomes; syphilis prevalence). Incidence of congenital syphilis, proportion of women test for syphilis, incidence of HIV/AIDS, obstacles in uptake of screening, partner treatment, or healthcare resource usage were not reported in this trial. AUTHORS' CONCLUSIONS: This review included evidence from two cluster-randomised trials at high or unclear risk of bias for most of the 'Risk of bias' domains. Data were not combined in meta-analysis because the trials used non-comparable measures of effectiveness.Point-of-care syphilis testing showed some promising results for syphilis detection and treatment rates and for use in different settings. In Mongolia point-of-care testing was found to be effective in increasing the proportion of pregnant women tested for syphilis and treatment provided, reducing congenital syphilis, and improving access to treatment for both women and their partners. In contrast, in rural South Africa, among women with positive test results, there was no clear evidence of an effect of point-of-care syphilis testing in increasing adequate syphilis treatment rates, and reducing perinatal mortality, but point-of-care testing was found to reduce delay in seeking treatment.More trials are therefore warranted to determine the effectiveness of available testing strategies for improving syphilis-associated adverse outcomes in pregnant women and neonates, especially in high-risk regions.

PMID 25352226

Progression of ultrasound findings of fetal syphilis after maternal treatment

Am J Obstet Gynecol. 2014 Oct;211(4):426.e1-6. doi: 10.1016/j.ajog.2014.05.049. Epub 2014 Jun 4.

Rac MW1, Bryant SN2, McIntire DD2, Cantey JB3, Twickler DM4, Wendel GD Jr2, Sheffield JS2.


OBJECTIVE: The purpose of this study was to evaluate ultrasound findings of fetal syphilis and to describe their progression after maternal treatment. STUDY DESIGN: This was a retrospective cohort study from September 1981 to June 2011 of seropositive women after 18 weeks of gestation who had an ultrasound before treatment to evaluate for fetal syphilis. Only those women who received treatment after the initial ultrasound scan, but before delivery, were included. If the initial ultrasound scan was abnormal, serial sonography was performed until resolution of the abnormality or delivery. Patient demographics, ultrasound findings, stage of syphilis, delivery, and infant outcomes were recorded. Standard statistical analyses were performed. Kaplan-Meier estimates were constructed to estimate time to resolution. RESULTS: Two hundred thirty-five women met the inclusion criteria; 73 of them (30%) had evidence of fetal syphilis on initial ultrasound scan. Abnormalities included hepatomegaly (79%), placentomegaly (27%), polyhydramnios (12%), ascites (10%) and abnormal middle cerebral arterial Doppler assessment (33%). After treatment, middle cerebral arterial Doppler assessment abnormalities, ascites, and polyhydramnios resolved first, followed by placentomegaly and finally hepatomegaly. Infant outcomes were available for 173 deliveries; of these, 32 infants (18%) were diagnosed with congenital syphilis. Congenital syphilis was more common when antenatal ultrasound abnormalities were present (39% vs 12%; P < .001). Infant examination findings at delivery were similar between women with and without an abnormal pretreatment ultrasound scan. However, in those infants with congenital syphilis, hepatomegaly was the most frequent abnormality found, regardless of antenatal ultrasound findings. CONCLUSION: Sonographic signs of fetal syphilis confer a higher risk of congenital syphilis at delivery for all maternal stages. Hepatomegaly develops early and resolves last after antepartum treatment. Copyright © 2014 Elsevier Inc. All rights reserved. KEYWORDS: fetal syphilis; pregnancy; resolution; ultrasound finding

PMID 24907700


Untreated maternal syphilis and adverse outcomes of pregnancy: a systematic review and meta-analysis

Bull World Health Organ. 2013 Mar 1;91(3):217-26. doi: 10.2471/BLT.12.107623. Epub 2013 Jan 17.

Gomez GB1, Kamb ML, Newman LM, Mark J, Broutet N, Hawkes SJ.


OBJECTIVE: To perform a systematic review and meta-analysis of reported estimates of adverse pregnancy outcomes among untreated women with syphilis and women without syphilis. METHODS: PubMed, EMBASE and Cochrane Libraries were searched for literature assessing adverse pregnancy outcomes among untreated women with seroreactivity for Treponema pallidum infection and non-seroreactive women. Adverse pregnancy outcomes were fetal loss or stillbirth, neonatal death, prematurity or low birth weight, clinical evidence of syphilis and infant death. Random-effects meta-analyses were used to calculate pooled estimates of adverse pregnancy outcomes and, where appropriate, heterogeneity was explored in group-specific analyses. FINDINGS: Of the 3258 citations identified, only six, all case-control studies, were included in the analysis. Pooled estimates showed that among untreated pregnant women with syphilis, fetal loss and stillbirth were 21% more frequent, neonatal deaths were 9.3% more frequent and prematurity or low birth weight were 5.8% more frequent than among women without syphilis. Of the infants of mothers with untreated syphilis, 15% had clinical evidence of congenital syphilis. The single study that estimated infant death showed a 10% higher frequency among infants of mothers with syphilis. Substantial heterogeneity was found across studies in the estimates of all adverse outcomes for both women with syphilis (66.5% [95% confidence interval, CI: 58.0-74.1]; I(2) = 91.8%; P < 0.001) and women without syphilis (14.3% [95% CI: 11.8-17.2]; I(2) = 95.9%; P < 0.001). CONCLUSION: Untreated maternal syphilis is associated with adverse pregnancy outcomes. These findings can inform policy decisions on resource allocation for the detection of syphilis and its timely treatment in pregnant women.

PMID 23476094


Lives Saved Tool supplement detection and treatment of syphilis in pregnancy to reduce syphilis related stillbirths and neonatal mortality

BMC Public Health. 2011 Apr 13;11 Suppl 3:S9.

Blencowe H, Cousens S, Kamb M, Berman S, Lawn JE.

SourceLondon School of Hygiene and Tropical Medicine, London, UK. Abstract

BACKGROUND:Globally syphilis is an important yet preventable cause of stillbirth, neonatal mortality and morbidity.OBJECTIVES:This review sought to estimate the effect of detection and treatment of active syphilis in pregnancy with at least 2.4 MU benzathine penicillin (or equivalent) on syphilis-related stillbirths and neonatal mortality.

METHODS:We conducted a systematic literature review of multiple databases to identify relevant studies. Data were abstracted into standardised tables and the quality of evidence was assessed using adapted GRADE criteria. Where appropriate, meta-analyses were undertaken.RESULTS:Moderate quality evidence (3 studies) supports a reduction in the incidence of clinical congenital syphilis of 97% (95% c.i 93 - 98%) with detection and treatment of women with active syphilis in pregnancy with at least 2.4 MU penicillin. The results of meta-analyses suggest that treatment with penicillin is associated with an 82% reduction in stillbirth (95% c.i. 67 - 90%) (8 studies), a 64% reduction in preterm delivery (95% c.i. 53 - 73%) (7 studies) and an 80% reduction in neonatal deaths (95% c.i. 68 - 87%) (5 studies). Although these effect estimates were large and remarkably consistent across studies, few of the studies adjusted for potential confounding factors and thus the overall quality of the evidence was considered low. However, given these large observed effects and a clear biological mechanism for effectiveness the GRADE recommendation is strong.CONCLUSION:Detection and appropriate, timely penicillin treatment is a highly effective intervention to reduce adverse syphilis-related pregnancy outcomes. More research is required to identify the most cost-effective strategies for achieving maximum coverage of screening for all pregnant women, and access to treatment if required.

PMID 21501460


Maternal and congenital syphilis in Shanghai, China, 2002 to 2006

Int J Infect Dis. 2010 Sep;14 Suppl 3:e45-8. Epub 2010 Feb 6.

Zhu L, Qin M, Du L, Xie RH, Wong T, Wen SW.

SourceShanghai First Maternity and Infant Hospital/Tongji University, Shanghai Women's Health Institute, Shanghai, China. AbstractOBJECTIVE:To assess the trends and determinants of maternal and congenital syphilis in Shanghai, China.METHODS:We conducted a prospective cohort study of maternal and congenital syphilis from 2002 to 2006 in Shanghai, China. We presented the trends of maternal syphilis and congenitalsyphilis rates and compared outcomes in infants born to mothers with complete versus incomplete treatment for maternal syphilis. We also assessed the determinants of compliance to treatment of maternal syphilis and examined the associations of initial maternal RPR antibody level and gestational age at initiation of treatment with occurrence of congenital syphilis.RESULTS:A total of 535 537 pregnant women were included in the analysis. During this period of time, 1471 maternal syphilis cases (298.7 per 100 000 live births) and 334 congenitalsyphilis cases (62.4 per 100 000 live births) were identified. Both maternal and congenital syphilis rates increased from 2002 until 2005, with a slight decrease in 2006. The rate of maternalsyphilis was 156.2 per 100 000 live births in Shanghai residents and 371.7 per 100 000 live births in the migrating population (p<0.001). The compliance to treatment for maternal syphiliswas poorer in women with a lower level of education. The rate of congenital syphilis in infants born to mothers with incomplete treatment (50.8%) was much higher than in infants born to mothers with complete treatment (12.5%). Rates of fetal death, neonatal death, and major birth defects were 30.4%, 11.0%, and 3.8%, respectively, in the incomplete treatment group; the corresponding figures were 5.5%, 0.56%, and 0.46%, respectively, in the complete treatment group. Infant outcome was also affected by initial maternal RPR antibody level and time of treatment, with much better outcomes in mothers with low antibody levels and earlier treatment.CONCLUSION:There has been a resurgence of congenital syphilis in Shanghai, China, especially in the migrating population and other populations with a lower socioeconomic status.Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

PMID 20137991

We keep forgetting maternal and congenital syphilis

Aust N Z J Obstet Gynaecol. 2010 Jun;50(3):306-7.

Jones IS, Jones AI.

PMID 20618256

Number of notifications of syphilis and congenital syphilis in Australia 2004 – 2007  

Year Syphilis Congenital syphilis
Male Female Total Male Female Unknown Total
2007 1231 150 1381 5 2 1 8
2006 689 182 871 6 7 - 13
2005 - - 653 8 6 1 15
2004 - - 636 11 2 - 13


Treatment for syphilis in antenatal care: compliance with the three dose standard treatment regimen

Sex Transm Infect. 2005 Jun;81(3):220-2.

Mullick S, Beksinksa M, Msomi S. Source Population Council, Frontiers in Reproductive Health, Hyde Park Lane Manor, EG001 Edinburgh Gate, Hyde Park, Box 411744, Craighall 2024, Johannesburg, South Africa.


BACKGROUND: In South Africa, three doses of benzathine penicillin 2.4 MU at weekly intervals are recommended for treating syphilis in pregnancy. Limited information is available on compliance with the recommended regimen, in terms of time to starting treatment, number of doses, and timing of treatment.

METHODS: The study was conducted to establish the degree of compliance with treatment for syphilis. Timing of treatment and the titres of the rapid plasma reagin (RPR) positive women were recorded. A retrospective record review was conducted of 18,128 antenatal records. These were records of women attending antenatal care clinics in a tertiary hospital catchment area in KwaZulu Natal between February 2001 and January 2002.

RESULTS: Treatment patterns showed that 15.9% received no treatment, 13.2% one dose, 5.8% received two doses, and 64.8% received three doses. In total, 188 women (1.03%) were found to be RPR positive. Of these 36% were found to be high titre positives (titre > or = 1:8).

CONCLUSION: Completed treatment was significantly associated with age of gestation at first visit (p = 0.029), with women attending later in pregnancy less likely to receive all three doses of treatment.

PMID 15923289


Maternal syphilis: pathophysiology and treatment

Bull World Health Organ. 2004 Jun;82(6):433-8.

Berman SM. Source Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA 30306, USA.


Despite the long history of medical interest in syphilis and its effects on pregnancy outcome, many fundamental questions about the pathophysiology and treatment of syphilis during pregnancy remain unanswered. However, understanding has been advanced by recent scientific reports such as those which delineate the complete sequence of the genome of the syphilis spirochaete, provide a more precise description of fetal and neonate infection by use of rabbit infectivity tests and describe the gestational age distribution of fetal death secondary to syphilis. It appears that fetal syphilitic involvement progresses in a rather predictable fashion, and although there is disagreement about the optimal prenatal treatment regimen, programmatic efforts to prevent fetal death must provide seropositive pregnant women with a recommended treatment early in pregnancy, and certainly before the third trimester.

PMID: 15356936