Congenital syphilis : management of babies born to mothers with syphilis infection

Routine antenatal screening for infectious diseases includes tests for syphilis, along with HIV and Hepatitis B. Most cases of maternal syphilis are detected this way. Particular attention must be paid when managing neonates born to mothers who have booked late or present with no antenatal care to ensure all necessary tests are taken and acted upon.

Syphilis screening in pregnancy in NHSGGC is done with an automated enzyme immunoassay (EIA). Around 25% of initial screen-positive EIAs in NHSGGC are actually false positives due to the low prevalence of real infection, with approximately 50% representing previously treated infection. Supplementary testing is undertaken for all positive EIAs and will include:

• RPR: (Rapid Plasma Reagin test) non-treponemal (indirect) antibodies. This test detects biomarkers given off by cells damaged by the syphilis spirochaete. This reflects current disease activity and falls in response to adequate treatment
• TP Syphilis IgM (EIA): This is a direct antibody to the syphilis spirochate. This is positive in early infection and falls slowly (>2years). It does not cross the placenta.
• TPHA: (Treponema Pallidum Haemagglutination test) a specific treponemal antibody which confirms the EIA is genuine. The exact titre doesn’t really matter.
• InnoLIA Blot test: useful where the markers are discrepant, Needs specialist interpretation
• Syphilis PCR: may be positive from lesions of early syphilis (genital ulcers, mucous patches, condylomata lata)

It is important to determine the stage of maternal illness as this gives an assessment of the risk to the fetus as outlined above. The maternal staging should be assessed by an experienced clinician in Sexual Health. All maternal positive results in NHSGGC and NHS AA are forwarded to the sexual health team. The results are reviewed and a clinical interpretation will be shared with the mother's Obstetrician and GP. All antenatal treatment of Syphilis infection should be managed in sexual health services. It is important to check the maternal record when reviewing a neonate. Advice can be obtained from your local genito-urinary medicine team (see box 1).

Maternal treatment is very effective at preventing congenital syphilis if a full course is given early in the pregnancy. Adequate treatment is defined as a parenteral penicillin preparation given for the required duration for the stage of disease. Parenteral penicillin is very safe for the mother (expected anaphylaxis risk of 0-3 per 100,000). There is a possible increased risk of pre-term delivery when treating early symptomatic syphilis in later pregnancy, due to the Jarisch Herxheimer reaction. The recommended treatment course should have been completed more than 30 days before delivery and a fall in the RPR titre should have been documented following treatment if this was detectable at diagnosis. N.B. if there is any doubt about whether satisfactory treatment has been completed the Genito-Urinary Medicine team in charge of the mother’s treatment should be consulted.   

Inadequate maternal treatment includes the following:

1. Treatment for less than the required period of therapy (see above) with a parenteral penicillin preparation. N.B. If more than one day of therapy is missed the course is inadequate and must be recommenced.
2. Treatment with a non-penicillin regimen
3. Infant delivered <30 days after completion of the antibiotic course
4. Maternal RPR titres do not respond (if positive at diagnosis)
5. Risk of re-infection from untreated partner or recurrent clinical signs

The mother’s HIV status must be determined (and result verified) as this has been shown to affect the course of syphilis infection both in the mother and neonate and make neonatal infection more likely.

The GUM team will classify the infant as ‘low risk’ or ‘high risk’ depending on the factors above and will communicate this to the GP, obstetric and neonatal teams using the template letter in appendix 1.  Ideally, this should also be documented on maternal clinical portal and badger record (under specialist review).

If mother has had a false positive syphilis result or has been confirmed to have previously treated syphilis, the infant needs no further examination above routine and needs no serology (bloods) performed at birth.

Sometimes maternal syphilis infection is not identified either because the mother was infected after booking bloods or was not tested during pregnancy. The first signs of infection are when the child is symptomatic, this can be months or even years after delivery. If a child is found to have syphilis this should be discussed with the local sexual health team to determine appropriate treatment and follow up and to arrange testing and treatment of parents.

All infants (low risk and high risk) whose mother has a true positive serological test for syphilis in this pregnancy need to be reviewed by the paediatrician shortly after delivery. Paediatrics need not attend delivery unless there are other indications. A detailed clinical evaluation is essential to look for signs of congenital syphilis as described above, recognising that two-thirds of infected infants will be asymptomatic.

All infants (low risk and high risk) should have syphilis serology performed on infant serum (not cord blood) for TP Syphilis IgM (specific IgM suggests congenital infection as fetus can produce IgM from 24 weeks gestation) and RPR – this requires 2ml of blood in EDTA tube. These should be accompanied by a maternal venous bloods sample for comparison (for IgM and RPR).

High risk infants
Infants born to mothers with primary, secondary or early latent phase maternal disease are at high risk in the following circumstances:

Neonate:

1. Signs of congenital syphilis (see above)
2. Infant TP Syphilis IgM test is positive, together with corroborative history, clinical signs
3. Infant has positive dark ground microscopy (see below)
4. Infant has positive T pallidum PCR test (see below) together with corroborative history, clinical signs

Maternal factors - these will be highlighted in birth plan from GUM (appendix 1):

1. High maternal RPR titres e.g. a titre of 1:16 or greater
2. Inadequate course of maternal treatment as defined above
3. Mothers with symptoms of primary syphilis shortly before delivery irrespective of the serological results.

These infants need the following investigations:

• FBC,U+E, LFTs
• HIV antibody if not known from maternal booking bloods.
• Lumbar puncture for CSF WCC, protein, RPR, TPHA (For RPR and TPHA: CSF fluid into white topped virology tube)
• Long bone X-rays for osteochondritis and periostitis
• Chest X-ray for cardiomegaly
• Cranial U/S scan
• Ophthalmology assessment for interstitial keratitis
• Audiology for 8th nerve deafness

If baby is symptomatic on examination, also perform:

• T pallidum polymerase chain reaction (PCR) test – This test is done on any secretion or fluid from skin or oral lesions and fluid should be put into the white topped virology tube - discuss with the laboratory regarding sampling requirement prior to sending.
• Dark ground microscopy (DGM) – this is a test of fluid from a lesion on the skin. Fluid needs to be immediately placed on a slide and requires immediate interpretation so If this is required, discuss with the laboratory regarding sampling technique.

When samples are sent to the lab for TP Syphilis Antibody and RPR, the result can be interpreted as follows:

• TP Syphilis IgM: This is a direct antibody to the syphilis spirochaete and is positive in early infection and falls slowly (>2years). This test as reported as positive or negative. It does not cross the placenta so is a good marker for congenital syphilis infection if positive in neonate. A positive test indicates a need for treatment.
  • The ‘IgM ratio’ is a supplement to this result and gives an indication to how recent the syphilis infection was. This is not important in management.
• RPR: (Rapid Plasma Reagin test) to non-treponemal (indirect) antibodies. This test detects biomarkers given off by cells damaged by the syphilis spirochaete. This reflects current disease activity and falls in response to adequate treatment. This test is reported as a titre. An RPR positive in ‘neat serum’ indicates a weakly positive test before dilution. If the test remains positive with dilution, this indicates a more convincingly positive test. If the RPR is positive at a dilution >4 fold compared to the mother (e.g. the mother is positive at 1:4 and the baby at 1:16), then this is a significantly positive test and indicates a requirement for treatment.  
• TPHA: (Treponema Pallidum Haemagglutination test): A specific treponemal antibody. The exact titre doesn’t really matter.
• TP-syphilis antibody (IgG): This is a direct antibody to the syphilis spirochete. The IgG will remain positive for life in anyone who has ever had syphilis infection, even after adequate treatment. This is not usually checked in the neonatal period.

(see flowchart below for interpretation)

A diagnosis of congenital syphilis is confirmed:

• If the infant’s serum is TP Syphilis IgM positive and/or
• There is a sustained elevation (two samples - the original screening sample and, if the original is positive, a repeat) showing a four-fold or greater difference of RPR titre above that of the mother (e.g mother RPR 1:4 and infant RPR 1:16 or greater).  

Treat all symptomatic infants, and all infants meeting the criteria of a serological diagnosis of syphilis (see flowchart above) with a full 10 day course of IV Benzylpenicillin. All infants commence on 50mg/kg/dose twice daily increasing to 50mg/kg/dose three times a day for term infants once >7days old.

High Risk Infants or those diagnosed with congenital syphilis infection

Follow up for high risk infants is essential at 3, 6 and 12 months or until RPR is negative, to ensure adequate treatment or absence of vertical infection. Negative RPR at 6 months excludes congenital syphilis. If the RPR does not fall or increases then repeat treatment with the above course is necessary. Successful treatment is defined as a 4 fold fall in RPR titres by 3 months following treatment and RPR negative at one year.

Those infants in whom CSF was indicative of neurosyphilis will also require repeat examination of CSF at six months of age. If CSF RPR is not negative after six months then a further course of treatment is indicated and a repeat CSF should be tested in a further 6 months.

Low Risk Infants

Low risk infants are defined above. These infants need serological tests for syphilis as above, performed shortly after delivery. No treatment is required for this group; however, serology should be repeated at 3, 6 and 12 months or until all tests become negative. Neonatal RPR should be negative by 6 months of age.

Summary of Follow-up Serological tests Required

All maternal siblings to new born infant should be assessed and screened for congenital syphilis infection taking into account any previous syphilis testing of the mother. Any uncertainties if testing is needed should be discussed with sexual health. Serological testing can be arranged via your local general paediatrics team. 

Letter to GP, Obstetrics & Neonatal team re: Antenatal Syphilis Diagnosis & Management (pdf)