Congenital infection and newborn prophylaxis

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Pathogens reach the fetus transplacentally, ascend through membranes, contact the infant during birth or transmit after birth. Earlier fetal infection often causes malformation or growth disturbance; later infection more often causes inflammation, organ disease or asymptomatic infection with delayed sequelae.

Congenital CMV is a leading infectious cause of sensorineural hearing loss. Most affected babies appear well, while symptomatic disease can cause microcephaly, periventricular calcification, thrombocytopenia, hepatitis, chorioretinitis and developmental impairment.

HSV is usually acquired intrapartum, particularly with newly acquired maternal genital infection near delivery. It presents as skin-eye-mouth disease, CNS disease or disseminated multiorgan disease; absence of vesicles does not exclude it.

Untreated maternal syphilis can cause fetal loss, hydrops, prematurity, rash, rhinitis, hepatosplenomegaly, bone disease and later neurological or dental sequelae. Maternal penicillin is the only established treatment preventing congenital disease.

Rubella classically affects hearing, eyes and heart, but UK vaccination has made indigenous disease rare. Maternal or infant diagnosis requires UKHSA coordination; there is no antiviral treatment that reverses congenital injury.

Toxoplasma infection may cause chorioretinitis, hydrocephalus and intracranial calcification. A normal newborn examination does not exclude later eye or neurological disease, so specialist testing and prolonged follow-up are required.

HIV and hepatitis B are distinctive because prompt newborn post-exposure prophylaxis can prevent infection. Antenatal screening, maternal treatment and reliable handover to the birth team are the first steps.

For HIV, neonatal regimen intensity reflects maternal viral load, adherence, timing of therapy, delivery circumstances and resistance. Feeding advice is part of the specialist plan and must follow current BHIVA guidance rather than generic advice.

For hepatitis B, HBIG provides immediate passive antibody for selected high-risk infants while vaccine generates active protection. The two injections are given at separate sites and neither substitutes for completion testing.

Diagnosis and prevention span maternal and neonatal records. Results, doses, follow-up appointments and responsible clinicians must be visible across maternity, neonatal, primary-care and public-health services.

Key points

Congenital infection crosses the placenta; perinatal infection is acquired around delivery. Timing determines phenotype, tests and prevention.
Common patterns overlap: growth restriction, microcephaly, petechiae or blueberry-muffin lesions, jaundice, hepatosplenomegaly, eye disease, intracranial abnormality and hearing loss.
Do not order an indiscriminate TORCH screen. Use maternal history, examination and organ pattern to select pathogen-specific PCR, serology, culture and imaging.
For congenital CMV, test saliva PCR and confirm a positive result with urine PCR within 21 days of birth; after that, postnatal acquisition becomes difficult to distinguish.
HIV prophylaxis begins as soon as possible, and no later than 4 hours. BHIVA uses 2 weeks of zidovudine alone for low-risk infants; standard high-risk combination prophylaxis is zidovudine plus lamivudine for 4 weeks with nevirapine for 2 weeks, using Appendix 4 doses.
Follow the current BHIVA infant virological-testing schedule; antibody testing alone cannot diagnose HIV in a young exposed infant because maternal antibody persists.
For maternal hepatitis B, give monovalent hepatitis B vaccine within 24 hours and add HBIG at a separate site for high-risk exposure, then complete the current selective neonatal schedule.
The post-2025 hepatitis B schedule is birth and 4-week monovalent doses, routine hexavalent vaccine at 8, 12 and 16 weeks, an 18-month dose, and HBsAg testing at 12–18 months; verify current UKHSA updates.
Suspected neonatal HSV requires IV aciclovir 20 mg/kg every 8 hours: 14 days for skin, eye and mouth disease and 21 days for CNS or disseminated disease, with specialist confirmation tests.
Congenital syphilis prevention depends on adequate maternal penicillin completed at least 4 weeks before delivery; at-risk infants need examination, serology, CSF and treatment through BASHH or specialist pathways.
Symptomatic congenital CMV, especially CNS or moderate-to-severe disease, may benefit from 6 months of valganciclovir started in the first month after specialist assessment, with blood-count, liver and renal monitoring.
Every exposed infant needs closed-loop follow-up: medicines, PCR or serology schedule, hearing and eye assessment, immunisation, family testing and safeguarding or public-health communication.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Transplacental infection

CMV, syphilis, toxoplasma, rubella and other pathogens cross the placenta and disrupt developing organs or cause fetal inflammation.

Intrapartum acquisition

HSV, HIV and hepatitis B can transmit through blood, secretions or mucosal contact during labour and birth.

Postnatal acquisition

Breast milk, household contact, blood products and caregivers can transmit selected pathogens; implications depend on gestation and organism.

Maternal risk state

Primary infection, high viral load, untreated disease, late therapy and membrane or delivery factors modify transmission probability.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Developmental disruption
Infection during fetal organogenesis can alter brain, eye, ear, heart and skeletal formation and significantly restrict intrauterine growth.
2
Fetal inflammation
Viral or bacterial replication triggers fetal hepatitis, marrow suppression, placental dysfunction, vasculitis, tissue necrosis and sometimes hydrops.
3
Immune immaturity
Limited fetal and neonatal responses permit dissemination while maternal antibody can both protect and complicate diagnostic serology.
4
Post-exposure prevention
Antiretrovirals suppress early HIV replication, while hepatitis B vaccine and HBIG establish active and passive protection before infection becomes established.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Maternal screening and illness

Review antenatal HIV, hepatitis B, syphilis and rubella screening, maternal seroconversion symptoms, travel, ultrasound, fever or rash, genital HSV, treatment and viral-load or serology results.

Exposure history

Ask about household infections, cat and undercooked-meat exposure, transfusion, immunisation, rupture of membranes, delivery lesions and breast-milk or postnatal exposure.

Structured newborn examination

Measure weight, length and head circumference and examine skin, eyes, red reflex, palate, heart, abdomen, liver, spleen, tone, movement, hearing response and bone tenderness.

Congenital infection pattern

Look for petechiae, purpura, jaundice, hepatosplenomegaly, microcephaly, cataract, chorioretinitis, murmur, snuffles, vesicles and abnormal neurological behaviour.

Asymptomatic exposure

A well appearance does not exclude CMV, HIV, hepatitis B, syphilis or toxoplasmosis; follow exposure-specific tests rather than waiting for symptoms.

Identity and handover

Confirm maternal and infant identity across specimens and records because a missed dose or incorrectly attributed result can permanently compromise prevention.

Red flags requiring action

Vesicles, keratoconjunctivitis, seizures, lethargy, hepatitis, coagulopathy or sepsis in the first weeks raises neonatal HSV even without known maternal lesions.
Microcephaly, intracranial calcification, chorioretinitis, sensorineural hearing loss, hepatosplenomegaly, petechiae or growth restriction suggests congenital infection.
Maternal HIV with detectable or unknown viral load near delivery requires immediate high-risk neonatal prophylaxis planning; start as soon as possible, ideally within 4 hours.
A baby born to a mother with hepatitis B requires monovalent vaccine, and when high-risk criteria apply HBIG, within 24 hours; missed prophylaxis needs urgent public-health advice.
Maternal syphilis untreated, inadequately treated, treated with a non-penicillin regimen or completed less than 4 weeks before delivery makes congenital infection possible regardless of neonatal appearance.
Pale stool, dark urine, severe jaundice, bleeding, hydrops or anaemia points to clinically significant hepatic or haematological involvement and urgent specialist care.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
First-line: pathogen-specific maternal and infant testingFirst stepFirst line
Why
Confirm exposure and diagnose infection within the relevant biological window.
Interpretation and limitations
Select PCR, serology or culture according to organism. Maternal IgG often crosses the placenta, so a positive infant antibody result may reflect exposure rather than infection.
02
Confirmatory congenital CMV testingConfirmatory
Why
Distinguish congenital from later postnatal CMV acquisition.
Interpretation and limitations
Use saliva PCR for screening and confirm positive saliva with urine PCR, both within 21 days. Breast-milk contamination can make an unconfirmed saliva result misleading.
03
HIV nucleic-acid testing
Why
Diagnose or exclude infection in an HIV-exposed infant while maternal antibody persists.
Interpretation and limitations
Follow the exact current BHIVA virological schedule, with additional testing after prophylaxis and feeding exposure; conventional antibody testing is used later to confirm seroreversion.
04
Hepatitis B completion testing
Why
Detect infection after vaccination and HBIG pathway completion.
Interpretation and limitations
UKHSA recommends HBsAg testing between 12 and 18 months in the current selective pathway; document every vaccine and HBIG dose before interpreting risk.
05
Syphilis evaluation
Why
Compare infant and maternal non-treponemal titres and identify CNS, blood, liver or bone involvement.
Interpretation and limitations
Examination, quantitative serology, FBC, liver tests, long-bone imaging and CSF are selected by maternal treatment and infant risk; passive maternal antibody falls over time.
06
Organ assessment and reference imaging
Why
Define congenital-infection severity and establish a baseline for treatment and prognosis.
Interpretation and limitations
FBC, bilirubin and liver tests, coagulation, renal function, cranial ultrasound or MRI, formal audiology and ophthalmology are directed by organism and phenotype.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Bacterial sepsis

Shock, thrombocytopenia, jaundice and neurological change require conventional cultures and antibiotics even when congenital infection is suspected.

Genetic or metabolic disease

Microcephaly, cataract, liver disease and growth restriction can reflect important chromosomal, mitochondrial, genetic and inherited metabolic conditions.

Haemolytic or hepatic disease

Immune haemolysis, biliary atresia and neonatal hepatitis can mimic congenital infectious jaundice, anaemia, liver dysfunction and hepatosplenomegaly.

Perinatal brain injury

HIE, stroke and haemorrhage cause seizures and imaging abnormalities but differ in history, pattern and laboratory findings.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01At deliveryDeliver planned prophylaxisFirst stepMaternal HIV or hepatitis B is known or discovered around birth.

1Alert neonatal infection and pharmacy before delivery where possible and verify maternal results and risk category.
2Start HIV prophylaxis as soon as possible, ideally within 4 hours, using the BHIVA gestation- and weight-based regimen.
3Give hepatitis B monovalent vaccine within 24 hours and add HBIG at a separate site when UKHSA high-risk criteria apply.

02Unwell infantTreat while defining pathogenThe newborn has sepsis, vesicles, neurological signs, hepatitis or coagulopathy.

1Stabilise and send blood culture, HSV PCR and other directed tests; obtain CSF when safe.
2Start IV aciclovir immediately when HSV is possible and empirical antibacterial therapy when sepsis remains possible.
3Adjust therapy to PCR, culture, organ involvement and specialist advice; monitor renal, liver, blood and coagulation function.

03CMVUse the 21-day diagnostic windowMaternal infection, failed hearing screen or compatible signs raise congenital CMV.

1Obtain saliva PCR promptly and confirm a positive result with urine PCR before 21 days.
2Assess FBC, liver function, brain imaging, ophthalmology and formal audiology.
3Discuss antiviral treatment in the first month for symptomatic disease and establish long-term hearing and developmental surveillance.

04Follow-upClose the prevention loopThe infant is discharged after exposure, prophylaxis or confirmed infection.

1Provide exact medicine duration, test and vaccine dates, feeding advice and responsible team in writing.
2Track virology, serology, hearing, vision, growth and development to completion, recalling missed appointments actively.
3Offer maternal, partner and family testing or treatment and notify public health where required.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

First-line prevention after perinatal HIV exposure, with intensity matched to transmission risk by the specialist HIV pregnancy team.

Neonatal HIV post-exposure prophylaxis

Start as soon as possible and no later than 4 hours. BHIVA recommends zidovudine monotherapy for 2 weeks in a low-risk infant. Standard high-risk combination prophylaxis is zidovudine plus lamivudine for 4 weeks with nevirapine for 2 weeks. Select every dose and interval from current BHIVA Appendix 4 using gestation, weight, maternal resistance and feeding plan.

Do not improvise paediatric doses or delay pending routine ward review. Prematurity changes zidovudine interval; monitor FBC and organ function and check interactions. High-risk components and resistance require specialist confirmation.

Active vaccine prophylaxis for every infant in the maternal hepatitis B pathway; HBIG adds immediate passive protection for high-risk exposure.

Monovalent hepatitis B vaccine and hepatitis B immunoglobulin

Give monovalent hepatitis B vaccine intramuscularly within 24 hours of birth. When UKHSA high-risk criteria apply, also give HBIG 200 IU intramuscularly within 24 hours at a separate injection site, then complete the current selective immunisation schedule.

Verify maternal HBeAg, anti-HBe, HBV DNA, timing of acute infection and infant weight. Do not mix products or omit later doses and HBsAg testing. Seek urgent UKHSA advice if birth prophylaxis was missed.

First-line time-critical antiviral therapy for possible neonatal HSV; begin before confirmation when the clinical syndrome is compatible.

Aciclovir intravenous

20 mg/kg IV every 8 hours for suspected or confirmed neonatal HSV, adjusted for renal function and gestation. Treat skin-eye-mouth disease for 14 days and CNS or disseminated disease for 21 days, subject to end-of-treatment CSF PCR and specialist advice.

Ensure hydration and monitor creatinine, urine output, FBC and IV site; crystalluria and neutropenia occur. CNS disease usually requires repeat CSF PCR and treatment extension if still positive. Arrange ophthalmology and suppressive therapy decisions with specialists.

Specialist antiviral treatment for moderate-to-severe symptomatic congenital CMV, particularly CNS disease; UK national guidance is limited and local tertiary protocols apply.

Valganciclovir oral

For selected symptomatic congenital CMV, an internationally supported specialist regimen is 16 mg/kg orally twice daily for 6 months, started in the first month; recalculate monthly with weight. Use IV ganciclovir 6 mg/kg every 12 hours initially when enteral absorption is unreliable or disease is severe.

Both uses require paediatric infection oversight and may be off-label. Monitor FBC, neutrophils, platelets, liver and renal function closely; interrupt or adjust for toxicity. Evidence does not support routine treatment of every asymptomatic infection.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Sensory loss

CMV, rubella, toxoplasma, syphilis and meningitic infection can cause delayed or progressive hearing and visual impairment.

Neurodevelopmental disability

Microcephaly, seizures, motor impairment and cognitive or language difficulty may emerge over years and require sustained multidisciplinary developmental support.

Chronic infection and organ disease

Untreated HIV, hepatitis B and congenital infection can cause ongoing replication, liver disease, immune failure or inflammation.

Treatment toxicity

Antivirals can cause neutropenia, anaemia, renal or hepatic injury and require weight-based recalculation and laboratory monitoring.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

For HIV prophylaxis monitor FBC and organ function according to the BHIVA regimen and check growth, adherence, feeding exposure and every virology result.
Record hepatitis B vaccine and HBIG product, batch, time and injection site, then reconcile 4-week, routine infant and 18-month doses and HBsAg testing.
During IV aciclovir maintain hydration, monitor creatinine and urine output, inspect IV access and adjust interval for renal impairment.
During valganciclovir or ganciclovir monitor neutrophils, platelets, liver and renal function frequently and recalculate dose with weight gain.
Confirmed CMV requires repeated audiology because hearing loss can emerge or progress after a normal newborn screen.
Syphilis serology is followed quantitatively until the expected decline or seroreversion; failure to fall prompts reassessment for infection or inadequate treatment.
Monitor vision, hearing, head growth, tone, seizures, feeding and development across all clinically significant congenital infections.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Maternal antibody complicates serology

Infant IgG can reflect placental transfer; direct detection, IgM where validated and serial titre behaviour are pathogen-specific diagnostic tools.

CMV has a clock

PCR after 21 days can detect infection but usually cannot prove it was congenital; arrange testing promptly after a failed hearing screen.

No maternal HSV history is reassuring only weakly

Many mothers of affected infants had unrecognised infection, so neonatal phenotype should drive aciclovir treatment.

HBIG and vaccine do different jobs

Passive antibody covers immediate high-risk exposure; active vaccination provides durable protection and needs every scheduled dose and final infection testing.

Prophylaxis is a pathway

A correct birth dose can still fail operationally if later tests, vaccines, feeding advice or specialist ownership are lost at discharge.

11Common pitfallsFrequent interpretation and management errors.

01
Do not request an undirected TORCH screen and assume it excludes all congenital infection.
02
Do not wait for vesicles before treating a septic or encephalopathic newborn for possible HSV.
03
Do not delay HIV prophylaxis while waiting for a repeat maternal result when high-risk exposure is credible.
04
Do not give HBIG in the same syringe or site as hepatitis B vaccine.
05
Do not diagnose congenital CMV from saliva PCR alone or from a sample first taken after 21 days.
06
Do not interpret a newborn's positive treponemal antibody as proof of congenital syphilis without maternal treatment and titre context.
07
Do not prescribe valganciclovir without specialist confirmation, baseline assessment and planned toxicity monitoring.
08
Do not discharge until every prophylaxis, test, feeding and follow-up responsibility has a named owner.