Clinical characteristics and factors contributing to transmission of congenital syphilis in England, 2015–24: a national surveillance study

Summary

Background

Congenital syphilis has re-emerged in England despite near-universal antenatal screening coverage, indicating that important opportunities for prevention continue to be missed. We aimed to characterise the clinical presentation, diagnostic findings, and factors contributing to transmission among congenital syphilis cases in England to inform strategies for earlier diagnosis and prevention.

Methods

We reviewed probable and confirmed congenital syphilis cases in England (January 2015 to June 2024) reported through the Integrated Screening Outcomes Surveillance Service, including maternal and infant demographic, clinical, laboratory, treatment, and outcome data.

Findings

Among 67 cases there were 54 livebirths, including five neonatal deaths, and 13 stillbirths. Common manifestations included hepatosplenomegaly, rash, bone abnormalities, thrombocytopaenia and jaundice. Neonatal IgM was positive in 81% (34/42), whereas only 24% (10/41) of mother–infant pairs demonstrated the expected four-fold higher non-treponemal titre in the infant. PCR was positive in 87% (13/15) of those tested but was used infrequently. Nearly half of cases (32/67, 48%) occurred in infants whose mothers had screened negative antenatally but acquired syphilis during pregnancy. Maternal symptoms were often overlooked, and some infants were initially treated for presumed sepsis without syphilis testing. Other cases were associated with late antenatal booking, incomplete treatment, difficulties engaging with maternity services, and complex social circumstances.

Interpretation

Congenital syphilis in England remains associated with substantial morbidity and mortality. Maternal infection acquired during pregnancy, missed diagnostic opportunities, and social vulnerability contribute to transmission. Greater clinical vigilance, wider use of PCR, improved engagement with vulnerable women, and consideration of universal third-trimester screening could strengthen prevention efforts.

Funding

Funding was received from the Sexually Transmitted Infection Research Foundation, United Kingdom.

Research in context.

Evidence before this study

We searched PubMed for articles published on or before February 28, 2026, using the terms “congenital syphilis” with “surveillance” or “clinical presentation” or “symptoms” or “stillbirth” or “diagnosis” or “prevention”. We also reviewed relevant national and international guidelines and surveillance reports. Existing evidence shows that congenital syphilis has re-emerged globally as a major yet preventable cause of stillbirth, neonatal death, and infant morbidity, driven by increasing syphilis incidence among adults of reproductive age. Studies describe wide clinical heterogeneity, frequent absence of symptoms at birth, and diagnostic challenges related to interpretation of neonatal serology. Most evidence derives from single-centre case series or regional datasets, with limited national-level analyses linking maternal infection pathways, infant presentation, diagnostics, and health system factors in high-income settings with established antenatal screening programmes. Evidence to inform policy decisions on repeat antenatal syphilis screening in low-prevalence countries remains limited.

Added value of this study

This study provides a comprehensive description of confirmed and probable congenital syphilis cases in England over a ten-year period, combining enhanced surveillance with expert multidisciplinary clinical review. Despite near-universal antenatal screening coverage, we demonstrate substantial morbidity and mortality, including stillbirths and neonatal deaths. Nearly half of cases occurred in infants born to mothers who screened negative early in pregnancy but acquired syphilis subsequently, highlighting the limitations of risk-based repeat testing strategies. We provide detailed descriptions of infant clinical presentations, showing that diagnosis was frequently delayed because clinicians were reassured by a negative antenatal screening result. Infants often presented at or shortly after birth with non-specific multisystem manifestations, including irritability and respiratory compromise, which frequently led to an initial diagnosis of presumed neonatal sepsis. However, almost all affected infants had additional features uncommon in sepsis, such as hepatosplenomegaly or rash, which should prompt consideration of congenital syphilis. We further identify important diagnostic gaps, including the infrequent use of PCR testing and the limited utility of infant-to-maternal non-treponemal titre comparisons in establishing the diagnosis. The study also underscores the contribution of social vulnerability and barriers to care across the prevention pathway.

Implications of all the available evidence

Congenital syphilis in high-income settings remains uncommon but is increasing and is associated with severe and preventable adverse outcomes. Clinicians should maintain a high index of suspicion for congenital syphilis in infants presenting with hepatosplenomegaly, rash, or thrombocytopaenia, even when antenatal screening was negative, and make greater use of adjunctive diagnostics such as PCR. Greater awareness that maternal infection can be acquired after an initial negative screen is needed across all clinical settings. The findings support consideration of additional strategies to prevent vertical transmission, including repeat antenatal screening later in pregnancy, improved recognition of maternal symptoms suggestive of syphilis, and enhanced support for women experiencing social exclusion and barriers to healthcare engagement. Strengthening these interventions will be important for preventing congenital syphilis and supporting progress towards elimination targets.

Introduction

In England, antenatal screening for syphilis, hepatitis B, and human immunodeficiency virus (HIV) is offered during pregnancy¹ although in 1999 it was proposed that syphilis be removed from the list, as there were almost no cases of congenital syphilis reported in England.² Over the last 20 years, this has changed significantly; there has been a global re-emergence of syphilis in adults,³ and this has led to a rise in cases of syphilis in pregnancy and congenital syphilis, including in England.⁴ Importantly, pregnant women and infants bear a significant disease burden from syphilis, with the high risk of spontaneous abortion, stillbirth, preterm delivery, neonatal death, and infant morbidity. Worldwide, syphilis is the second most common infectious cause of stillbirth after malaria.⁵ This concerning change in epidemiology has occurred at a time when the World Health Organization (WHO) is aiming for worldwide triple elimination of syphilis, hepatitis B and HIV in infants by 2030.⁶

In 2024, 9535 cases of early (infectious) syphilis were reported in England, the highest number since the 1940s, mostly in gay and bisexual men.⁷ However, between 2015 and 2024, infections in women tripled, from 273 to 830 diagnoses.⁸ Antenatal screening for syphilis is recommended for all women when they present for antenatal care, with very high coverage (99.8% in 2022–2023, with around 1100 women screening positive and 44% requiring treatment in the same period) and urgent screening for women who present in labour.^1,4 Guidance also recommends that repeat testing for syphilis in pregnancy should be offered based on risk identification: change in sexual partner; a partner who is sexually active with other people; is diagnosed or has a partner who is diagnosed with a sexually transmitted infection; injects recreational drugs; or undertakes sex work.⁴

National surveillance of congenital syphilis in England is carried out by the Integrated Screening Outcomes Surveillance Service (ISOSS), part of NHS England's Infectious Diseases in Pregnancy Screening Programme and started in 2020 with a look-back to 2015.⁴ Prior to this, a prospective study identified 17 cases in England between February 2010 and January 2015, with 10 of the 17 cases born in 2010, and 1–2 cases per year until 2015.⁹ Since then cases have been increasing, to an average of 10 cases per year since 2019.⁴ However the incidence of congenital syphilis in England of 0.023 per 1000 live births remains below the WHO elimination threshold of less than 0.5 per 1000 live births. Of the 79 infants born 2015–2024 and diagnosed with congenital syphilis, half were born preterm (<37 weeks gestation) and 18% were stillbirths.⁴ Identified reasons for congenital syphilis included: maternal infection acquired later in pregnancy after a negative screen in early pregnancy; late booking for maternity care and/or delivery before treatment completion; re-infection; and declined or incorrect treatment. Some pregnant women presented with symptoms or signs of syphilis but these were not identified by clinicians, leading to a lack of re-testing and missed opportunities for curative penicillin treatment.⁴

The aim of this paper is to use national enhanced surveillance data to highlight the clinical presentations of syphilis in pregnancy and in infants. We wish to alert clinicians who may be assessing women and infants presenting in primary and community care, emergency departments, maternity services or neonatal and paediatric departments so that timely diagnosis and appropriate treatment may prevent vertical transmission and/or long-term health consequences for women and their infants.

Methods

ISOSS has conducted population-based active surveillance of syphilis in pregnancy in England since January 2020. Data on all pregnancies in women who screen positive for syphilis are reported prospectively to ISOSS by antenatal newborn and screening teams at each maternity unit nationally via a secure online portal. Data collected include demographic, clinical and social inequalities, and submitting data is required as part of the Infectious Diseases in Pregnancy Screening Programme services specification with 100% completeness to date recorded. Screening algorithms and protocols are defined by the Screening Programme.¹⁰ Paediatric follow-up is undertaken for infants born to women who require treatment for syphilis in pregnancy in line with national guidelines.

ISOSS also carries out enhanced surveillance of all vertical transmissions in infants born in England since 2015, including whose mothers are diagnosed postnatally: all suspected or confirmed cases of congenital syphilis among infants are notified to ISOSS by clinicians across England. The ISOSS team interview and collect key data items from the health care professionals involved in the care of the woman and infant during and after pregnancy by phone and secure email in order to build a chronology of the case covering the woman's medical/social history, antenatal care and child's diagnosis. Multiple services contribute to this process depending on the case including maternity, sexual health, neonatology, paediatrics, microbiology and paediatric pathology. Anonymised case summaries are reviewed by the Screening Programme Clinical Expert Review Panel, which consists of representation from relevant clinical specialities including maternity services, sexual health services, paediatric infectious diseases, screening quality assurance, microbiology and paediatric pathology. The purpose of the panel is to establish circumstances surrounding the transmission, identify contributing factors and learning points, and feed recommendations into the Screening Programme to inform national guidelines, policy and quality assurance processes. The panel classifies the cases as possible, probable or confirmed congenital syphilis according to defined clinical-pathological criteria developed by the panel (Table 1). Complete treatment during pregnancy is defined as completing therapy at least four weeks before delivery.

Table 1.

Definition used to categorise cases of congenital syphilis by the Clinical Expert Review Panel. RPR, rapid plasma reagin.

Congenital Syphilis—livebirth

Possible case: Includes all the following: •Woman had untreated or inadequately treated syphilis at delivery •A reactive infant serum RPR (or no serology results available for infant) •Infant has no features of probable or confirmed congenital syphilis

Probable case: Woman had untreated or inadequately treated syphilis at delivery, a reactive infant serum RPR and at least one of the following in the infant: •Any evidence of congenital syphilis on physical examination •Any evidence of congenital syphilis on radiographs of long bones •A positive cerebrospinal fluid RPR •Infant RPR titre four-fold or greater than that of mother

Confirmed case: A probable case plus at least one of the following: •Treponema pallidum identified by PCR or dark-field microscopy from: umbilical cord, placenta, neonatal nasal discharge, body fluids or skin lesion swabs AND/OR •Detection of Treponema pallidum specific IgM in the infant serum

Congenital Syphilis—stillbirth

Possible case Foetal death in which the mother had untreated or inadequately treated syphilis where no post mortem or placental examination were undertaken

Probable case Pathological features on post-mortem examination of foetus and/or placenta consistent with congenital syphilis

Confirmed case Treponema pallidum identified by PCR or dark-field microscopy or histological identification of spirochaetes in specimens from placenta and/or post-mortem foetal tissue sample(s)

Data were collated from the ISOSS dataset for all cases classified by the panel as ‘Probable’ and ‘Confirmed’ cases of congenital syphilis born between 1 January 2015 and 30 June 2024, reported to ISOSS by 30 September 2024 and reviewed by 31 March 2025. Maternal data included: timing of syphilis diagnosis, syphilis serology results, syphilis treatment in pregnancy, gestation at antenatal booking, symptoms of syphilis prior to diagnosis, complex social factors, ethnicity, and gestation at and outcome of delivery. Types of complex social factors included social services involvement, mental health issues, insecure housing, drug/alcohol misuse, intimate partner violence, sex work and immigration issues.

Infant data included: birthweight, age at diagnosis, clinical signs around the time of diagnosis, syphilis PCR and serology results, other blood and cerebrospinal fluid test results and radiology reports. Preterm delivery was defined as delivery before 37 completed weeks of pregnancy, low birthweight as <2.5 kg, and neonatal death as death of a liveborn infant within the first 28 days of life (early neonatal death, within the first seven days).

Ethics

ISOSS collects data without patient consent under legal permissions granted to the Infectious Diseases in Pregnancy Screening Programme under Regulation 3 of the Health Service (Control of Patient Information) Regulations 2002. Ethical approval for data release for this study was granted by the NHS England Screening Research, Innovation and Development Advisory Committee (Ref: ANNB-2425-002 D).

Role of the funding source

Funding was received from the Sexually Transmitted Infection Research Foundation, United Kingdom, for ISOSS to collate and analyse the data. The funder of the study had no role in study design, data collection, data analysis, data interpretation, writing of the report or decision to submit for publication.

Results

Description of cases

There were 79 cases of congenital syphilis in infants reviewed by the Clinical Expert Review Panel, with 67 classified as confirmed or probable cases. These 67 infants were born to 65 women, including two sets of twins. Of the 67 infants, 54 were liveborn (including five neonatal deaths due to syphilis) and 13 were stillborn (Fig. 1).

Fig. 1.

Congenital syphilis cases by birth outcome (n = 67), January 2015–June 2024. Note counts for 2023 and 2024 are likely to increase, as they are incomplete due to delayed diagnosis and notification.

The median maternal age at delivery was 26 years (IQR 22–30 years) and 79% (51/65) of women were White British. Nearly half of women (27/65, 42%) booked (i.e. registered for antenatal care) after 12 weeks gestation, with an overall median gestational age at antenatal booking of 11 weeks (IQR 9–23 weeks), and nearly one in 10 were unbooked. Of the livebirths, over half (37/67, 55%) were preterm and half (27/54, 50%) were low birthweight (Table 2).

Table 2.

Maternal characteristics and birth outcomes of the 65 women and their 67 infants with confirmed and probable congenital syphilis.

	Pregnancies ending in livebirth (n = 52)	Pregnancies ending in stillbirth (n = 13)	Total (n = 65)
	N (%)
Maternal characteristics
Gestation at antenatal booking
<12 weeks	26 (50.0%)	6 (46.2%)	32 (49.2%)
12–20 weeks	13 (25.0%)	0	13 (20.0%)
>20 weeks	8 (15.4%)	6 (46.2)	14 (21.5%)
No antenatal care	5 (9.6%)	1 (7.7%)	6 (9.2%)
Ethnic origin
White British	42 (80.8%)	9 (69.2%)	51 (78.5%)
White Other	5 (9.6%)	3 (23.1%)	8 (12.3%)
Asian	3 (5.8%)	1 (7.7%)	4 (6.2%)
Other	2 (3.8%)	0	2 (3.1%)
Syphilis diagnosis timing
Antenatal
Booking screen positive	19 (36.5%)	7 (53.4%)	26 (40.0%)
Postnatal
Screened in labour	8 (15.4%)	1a (7.7%)	9 (13.8%)
Postnatal (booking screen negative)	25 (48.1%)	5 (38.5%)	30 (46.2%)
Syphilis treatment in pregnancyb
No	5 (26.3%)	5 (71.4%)	10 (38.5%)
Yes—incomplete	5 (26.3%)	1 (14.8%)	6 (23.1%)
Yes—complete (at least 4 weeks before delivery)	9 (47.4%)c	1 (14.8%)d	10 (38.5%)
Syphilis treatment type	(n = 14)	(n = 2)	(n = 16)
Benzathine penicillin	8 (57.1%)	1 (50%)	9 (56.3%)
Macrolide	6 (42.9%)	1 (50%)	7 (43.8%)
Complex social factors
None	26 (50.0%)	5 (38.5%)	31 (47.7%)
At least one	26 (50.0%)	8 (61.5%)	34 (52.3%)
Birth outcomes (in 54 liveborn and 13 stillborn infants)
Gestational age at delivery
<32 weeks	11 (20.4%)	8 (61.5%)	19 (28.4%)
32–36 weeks	15 (27.8%)	3 (23.1%)	18 (26.9%)
≥37 weeks	28 (51.9%)	2 (15.4%)	30 (44.8%)
Birthweight
<1500 g	7 (13.0%)
1500–2499 g	20 (37.0%)
≥2500 g	27 (50.0%)

^aRe-screened in labour, booking screen negative.

^bAmong women with known diagnosis in pregnancy.

^c6/9 women with complete treatment received a macrolide; 3/9 had reinfection in pregnancy following treatment.

^dTreated with a macrolide.

Most women (39/65, 60%) were diagnosed postnatally, either because they first presented for antenatal care in labour and were screened then (5/65, 8%), declined screening in pregnancy due to needle phobia, but accepted during labour when cannulation was required (3/65, 5%) or acquired syphilis infection during pregnancy after a negative antenatal screen and were not re-rested later in gestation (30/65, 46%). One additional woman had a negative antenatal screen but tested positive for syphilis when re-tested in labour (Table 2). Among these 31 women who acquired syphilis later in pregnancy, 11 (35%) had symptoms consistent with syphilis during pregnancy or at time of postnatal diagnosis: four had vulval lesions in pregnancy (three were diagnosed with herpes and one with candida infection), six had skin rash (four during pregnancy), and one was reported to have had lesions (site unknown) at diagnosis.

Clinical presentation of congenital syphilis cases

Of the 54 livebirths with confirmed or probable congenital syphilis there were 20 infants born to mothers who were diagnosed antenatally with syphilis and eight infants born to women who were diagnosed with syphilis in labour. All these infants were tested as part of routine follow-up. The remaining 26 infants born to mothers who had screened negative at booking and subsequently acquired syphilis later during pregnancy were tested for syphilis due to symptoms or following postnatal syphilis diagnosis in the mother.

Maternal antenatal diagnosis or diagnosed with syphilis in labour

Of the 28 livebirths in this group, eight infants had no symptoms at birth, one of whom subsequently developed symptoms within the first month of life. There were four deaths, all within the first two weeks of birth (three within 48 h of birth). There were also seven stillbirths.

The most common signs were hepatosplenomegaly (11 infants), rash and/or skin/mucosal lesions and/or desquamation (7 infants), and bone abnormalities (5 infants). Most infants (16/20) had at least one of these signs, predominantly in combination with thrombocytopaenia, anaemia or jaundice (13/16). Only three infants had suspected ‘sepsis’ or respiratory distress but no hepatosplenomegaly, rash/lesion or bone involvement.

Additional signs in some infants included respiratory distress (7 infants), hydrops (4 infants), hydrocephalus (2 infants), nephrotic syndrome (2 infants), and meningitis (1 infant).

Postnatal syphilis diagnosis

Of the 32 confirmed or probable cases where the mother had screened negative at booking and subsequently acquired syphilis later during pregnancy, 26 were livebirths and six were stillbirths. Syphilis was often not considered in the differential diagnosis of the unwell infant until relatively late in the investigations and clinicians reported to be falsely reassured by a negative antenatal screening result. There was one neonatal death which occurred within 24 h of birth; the infant had respiratory symptoms, thrombocytopaenia and anaemia but was not tested for syphilis. The diagnosis of congenital syphilis was made at postmortem.

Infant diagnosis within 48 h of birth

Seven infants were tested for syphilis based on signs/symptoms present at birth. The most common abnormality was thrombocytopaenia (6/7 infants). Three of these infants also had hepatosplenomegaly and a rash or skin/mucosal lesions. Another three infants had respiratory distress with thrombocytopaenia and/or jaundice. Additional signs in some infants included hydrops (2 infants), nephrotic syndrome (1 infant), anaemia (1 infant), and hydrocephalus (1 infant). Two infants were suspected to have sepsis. Only one infant had thrombocytopaenia but no other signs or symptoms.

Infant diagnosis >48 h after birth

There were 14 infants who were diagnosed in the first year of life based on signs that did not manifest, or were not recognised, at birth. Of these, 11 were diagnosed before three months of age, and three were diagnosed between four and 12 months of age. All infants had at least one of rash or skin/mucosal lesions or desquamation (9 infants), bone abnormalities (8 infants), or hepatosplenomegaly (7 infants). Additional signs included anaemia (6 infants), thrombocytopaenia and jaundice (1 infant), nephrotic syndrome (2 infants) and respiratory distress (3 infants).

An additional four children were diagnosed between 12 and 24 months of age. Three of these were only tested for syphilis following maternal diagnosis as part of antenatal screening in a subsequent pregnancy. Of these three infants, two had multiple symptoms since the neonatal period including a rash and hepatosplenomegaly but had not been tested for syphilis and one was asymptomatic. The fourth infant was tested for syphilis as part of investigations for mouth lesions but had no other signs.

Social risk factors

Fifty-two percent (34/65) of women had at least one complex social issue reported in pregnancy. These included Social Service involvement (25), insecure housing (19), mental health issues (14), issues engaging with healthcare services (14), drug/alcohol misuse (12), intimate partner violence (9), and sex work (6). Many women (26/34) experienced multiple complex social factors at the time of the pregnancy, and numbers are likely to be underreported as this information is what was known to the clinical team.

Syphilis diagnostics

There were 41 mother–infant pairs with RPR titres available for comparison, where both specimens were taken at the time of congenital syphilis diagnosis. Overall, only 24% (10/41) of pairs had an infant RPR titre four or more times higher than that of the mother. However, this was more common where the mother had acquired syphilis during pregnancy after a negative screen at booking, occurring in 50% (8/16) of cases compared with 12% (2/17) in the antenatal diagnosis group (p = 0.042). Among these 41 mother–infant pairs, 35 infants had IgM test results, with 30 (86%) having a positive IgM, including all those where maternal syphilis was acquired during pregnancy (Table 3). Overall, there were 42 infants with IgM results available (34 IgM positive, 8 IgM negative); 37.5% (3/8) of the infants with IgM negative results were asymptomatic versus 11.8% (4/34) of the infants with IgM positive results.

Table 3.

Comparison of maternal and infant RPR titres and infant IgM results, by time of maternal diagnosis (41 mother–infant pairs).

	Antenatal diagnosis (n = 17)		Postnatal diagnosis following negative screen at booking (n = 16)		Unbooked/screened in labour (n = 8)
	Infant RPR titre ≥4 × maternal RPR titre (n = 2)	Infant RPR titre <4 × maternal RPR titre (n = 15)	Infant RPR titre ≥4 × maternal RPR titre (n = 8)	Infant RPR titre <4 × maternal RPR titre (n = 8)	Infant RPR titre≥4 × maternal RPR titre (n = 0)	Infant RPR titre <4 × maternal RPR titre (n = 8)
IgM positive	2	10	6	5	0	7
IgM negative	0	4	0	0	0	1
IgM not done	0	1	2	3	0	0

Of the 54 livebirths, only 11 infants had ≥1 sample taken for Treponema pallidum PCR. Of these, eight children were positive in a single sample (3 nose/throat swabs, 2 skin swabs, 1 blood, 1 placenta and 1 bone biopsy) and one had positive results from both a nose/throat swab and a blood sample. For the remaining two infants, one was PCR-negative in nasal, blood and CSF samples and the other in nose/throat and CSF samples. Of the 13 stillbirths, there were PCR results available for four, all of which were positive (1 lung and liver tissue, 1 liver and spleen tissue, 1 placenta plus infant tissue (unspecified) and 1 placenta).

Twelve infants had a lumbar puncture performed, of whom three had abnormal cerebrospinal fluid parameters (positive RPR, raised white blood cell count or high protein).

Discussion

Cases of congenital syphilis reported to national surveillance in England were associated with poor clinical outcomes, including five neonatal deaths and 13 stillbirths. Among infants born to mothers diagnosed antenatally or in labour, nearly a third were asymptomatic at birth, while symptomatic infants mostly presented with hepatosplenomegaly, rash or skin/mucosal lesions, and bone abnormalities, usually accompanied by thrombocytopaenia, anaemia, or jaundice. Nearly half of infants were born to mothers who screened negative for syphilis at booking and acquired syphilis during pregnancy. Diagnosis was prompted by infant symptoms or maternal diagnosis after delivery, with syphilis frequently not considered initially because clinicians were reassured by the negative antenatal screen. The most common clinical features were thrombocytopaenia, rash, hepatosplenomegaly, and bone abnormalities. Most cases were diagnosed within the first three months of life, although several infants experienced significant diagnostic delays despite persistent symptoms, with some not identified until 12–24 months of age.

It is unknown how many infants with congenital syphilis in England remain undetected, and the long-term consequences for those children who may develop signs of late congenital syphilis in future. It is reported that up to two-thirds of infants with congenital syphilis may be asymptomatic at birth, with 65% developing symptoms within the first two months of life.¹¹ Between 2014 and 2018, 55.5% (2120/3834) of live-born infants in the United States who had congenital syphilis were reported to be asymptomatic.¹² Common manifestations included anaemia and thrombocytopaenia (37%), hepatobiliary dysfunction (33–100%), bullous or mucocutaneous lesions (40%), osteochondritis or periostitis (75%), and up to 60% of symptomatic cases had neurosyphilis.¹³ In 61 congenital syphilis cases in Argentina, 78% were asymptomatic at birth but 83% of these developed symptoms within two months; the main clinical findings were bone abnormalities (59%), hepatosplenomegaly (54.1%), anaemia (62.8%), and skin lesions (50.8%).¹⁴ However, in a review of 17 congenital syphilis cases in Western Australia, 10/12 (83%) livebirths were symptomatic at delivery, and one developed symptoms at 3 months. They also reported five stillbirths and one neonatal death.¹⁵

Neonatal serology can be difficult to interpret due to the transplacental passage of maternal IgG antibodies. However, neonatal IgM is a useful marker, as maternal IgM does not cross the placenta, indeed, 81% of those tested in our case series had a positive IgM. A non-treponemal antibody titre more than four times higher than the maternal titre is generally regarded as diagnostic of congenital syphilis, as such a high ratio is unlikely to be due to passive transfer of maternal antibodies, although lower ratios do not exclude congenital syphilis. Of our cases where a result was available, only 24% of maternal–infant pairs had an infant RPR titre four times higher than the maternal titre, although this profile was more likely to be seen in those who had acquired syphilis during pregnancy after a negative screen at booking (50%). This possibly reflects the lack of any antibiotic treatment in the latter group. In a case series from Los Angeles 1/35 infants had an RPR titre that was 4-fold higher than the maternal RPR, and in most cases the infant RPR titre was less than the maternal RPR titre.¹⁶ In the case series from Western Australia, 2/12 cases had a four-fold greater RPR titre and 55% had a positive IgM.¹⁵ In the Argentinian cases, 60.5% had non-treponemal titres equal to or less than fourfold the maternal titre.¹⁴

Although there is only limited published data available to support the use of syphilis PCR in diagnosing congenital syphilis,¹⁷ we found PCR to be a very useful adjunct to diagnosis, as the direct detection of T. pallidum has a greater specificity than the serological tests. Clinical and laboratory guidance were strengthened to recommend PCR from suspected cases, which is provided free of charge to all laboratories across the United Kingdom (UK) by the UK Health Security Agency (UKHSA) Sexually Transmitted Infections Reference laboratory.^18,19 Suitable specimens include nasal discharge, naso-pharyngeal aspirates, throat swabs, lesion swabs, blood, CSF and placental tissue. In our case series, there was a high PCR positivity, although less than a quarter of infants had a specimen taken for syphilis DNA detection.

Despite high antenatal screening coverage for syphilis in England, cases of congenital syphilis have continued to rise over the past decade. Among infants with confirmed or probable congenital syphilis, 40% of mothers had a positive antenatal screening result at booking. Transmission to the infant most often occurred because of late booking, resulting in treatment not being completed at least four weeks before delivery, or due to difficulties engaging with healthcare services to receive treatment. Pregnant women who screen positive for syphilis are disproportionately affected by complex social factors and barriers to engagement compared with the wider antenatal population, with 38% of the former having complex social factors reported compared to 10% in the general antenatal population.^4,20 This disparity is even more pronounced among mothers of infants with congenital syphilis. In our study, around half of women were known to experience social exclusion—including experiences of homelessness, drug use, and sex work.

In some cases, mothers had been treated with a macrolide antibiotic, a regimen now known to be associated with treatment failure because of the high prevalence of macrolide-resistant T. pallidum strains.¹⁶ Historically in the UK macrolide treatment was an alternative option for patients with penicillin allergy, and a randomised controlled trial in Tanzania had previously shown 2g azithromycin to be as effective as Benzathine penicillin for the treatment of early syphilis.²¹ For these reasons the 2008 and 2015 British Association for Sexual Health and HIV guidelines for the management of syphilis included macrolides as an alternative option. However, following reports from ISOSS of congenital syphilis cases in which mothers had received macrolide therapy, the guideline was amended in 2019 to remove macrolides as a recommended treatment.²² Awareness of this change, though, may not have been optimal among clinicians. The 2024 guideline now clearly states that macrolides should not be used.¹⁸

Nearly half of cases (48%) were born to mothers who had a negative antenatal screening result and acquired syphilis during pregnancy. Syphilis is known as ‘the great imitator’ due the diversity of symptoms it may cause, and this is also true for congenital syphilis infection. Many of the cases presented at birth or soon after with non-specific systemic features such as irritability and respiratory compromise which were frequently misdiagnosed as ‘sepsis’. However, nearly all these infants had additional signs not usually associated with sepsis, such as hepatosplenomegaly or rash, and this should alert clinicians to the possibility of congenital syphilis. Even in those cases where a congenital infection was suspected, clinicians had initially requested a ‘TORCH’ screen: toxoplasmosis, ‘other’, rubella, cytomegalovirus and herpes simplex virus, but had not specifically requested syphilis testing (data not shown), often falsely reassured by a negative antenatal screen. Penner et al. have proposed that the investigation of infants with suspected congenital infection should be broadened to ‘SCORTCH’ to particularly highlight syphilis along with cytomegalovirus, ‘other’, rubella, toxoplasmosis, chickenpox, herpes simplex and blood borne viruses.²³

The approach of offering repeat testing for syphilis in pregnancy based on risk relies on disclosure of risk—and assumes awareness of risk. Several infants with congenital syphilis were born to women who did not have identifiable risk factors for acquiring syphilis and would only have been diagnosed during pregnancy if universal repeat screening was offered at 28 weeks gestation, as is the case in high prevalence regions in the United States and Europe.²⁴ This is currently under review by the UK National Screening Committee; a previous review in 2019 concluded that universal repeat screening would not be cost-effective.²⁵

In our case series, several mothers had symptoms consistent with syphilis such as vulval lesions or a rash but were not offered repeat testing for syphilis. Following communication from ISOSS, the UKHSA's guidance on the management of viral rashes in pregnancy was expanded to include syphilis.²⁶ Additionally, the ‘Negative Now’ message, explaining that a negative screening result does not confer protection throughout pregnancy, has been included in professional and patient maternity resources, including negative screening laboratory reports.⁴

A strength of our study is that our dataset includes all reported congenital syphilis cases in England from the past ten years collected through the ISOSS national surveillance system. For context, in England during the study period there were around 4.96 million live births and around 19,900 stillbirths based on Office for National Statistics data.²⁷ A further strength is that we have included detailed information on the epidemiology, clinical presentation, investigation and management of all cases. One limitation of the study is that prospective data collection only began in 2020, with retrospective data collection for 2015–2020, which likely resulted in an underestimation of cases during that period. Additionally, reporting of congenital syphilis was voluntary until April 2025, when congenital syphilis became a Notifiable Disease in England under the Health Protection (Notification) Regulations 2025.²⁸ There is also the likelihood that these cases were skewed to the more severe end of the spectrum, and an unknown number of infants, asymptomatic in the early months of life, remain undiagnosed.

In summary, the congenital syphilis cases described here reflect missed opportunities for prevention, diagnostic challenges, and maternal infection acquired during pregnancy. Despite high antenatal screening coverage, delayed booking, reliance on risk-based repeat testing, and difficulties engaging women with complex social needs continue to drive avoidable transmission. A routine 28-week repeat syphilis screen could have identified many cases in this series. Because treatment must be completed at least four weeks before delivery, the increased risks of preterm birth and of late presentation among socially vulnerable women further narrow the window for effective intervention. Nearly half of affected mothers experienced social exclusion, underscoring the importance of closer collaboration with Inclusion health services–including housing, drug and outreach services–to promote awareness, support early testing and treatment, and facilitate earlier engagement with maternity care. The UKHSA Syphilis Response Plan highlights the need for targeted interventions to reduce inequalities across the care pathway and identify missed opportunities for the timely detection and treatment of syphilis in pregnancy.²⁹

Clinical presentations of congenital syphilis remain broad and often non-specific, necessitating a high index of suspicion even with negative antenatal screening and greater use of adjunctive diagnostics such as PCR, including in the investigation of stillbirths. Strengthening systems to ensure timely screening, treatment and follow-up will be critical to reversing current trends and protecting maternal and infant health.

Contributors

HF, MK and HL designed the study. HP and KF collated and analysed the data and made the Figures. HF wrote the first draft with input from MK, HL and CT. All authors edited and reviewed the final draft.

Data sharing statement

The data are not publicly available because of information governance and patient confidentiality restrictions. Deidentified data may be made available to researchers upon request and subject to the appropriate regulatory approvals.

Declaration of interests

We declare no competing interests.