Viral Infections of the Fetus and Newborn

Viral infection of the fetus and newborn is common, and it hides inside other problems: poor intrauterine growth, an unexplained rash or low platelet count, a baby who looks septic but grows no bacteria. The decisive variable is timing. A virus reaching the fetus during organogenesis tends to deform; the same virus acquired around delivery tends to overwhelm a host with no immunological memory and little transferred antibody; a virus acquired after birth is usually milder because maternal antibody has had time to cross. The single most useful question in a suspected congenital infection is not which virus, but when in pregnancy or delivery it was acquired, because that predicts both the agent and the pattern of damage.

Two principles follow and run through the whole topic. First, the long-standing TORCH grouping (toxoplasmosis, other, rubella, cytomegalovirus and herpes simplex virus) has outlived its usefulness: it implies a single clinical picture when each agent in fact has a distinct signature, a distinct test and, increasingly, a distinct treatment, so a specific diagnosis matters. Second, diagnosis in the infant is virological, not serological. Maternal immunoglobulin G (IgG) crosses the placenta, so a positive IgG in a newborn usually reflects the mother’s past exposure rather than the baby’s infection, and finding it is neither diagnostic nor reassuring. Detection of the virus itself, by culture or polymerase chain reaction (PCR) on the right specimen at the right time, is the basis of neonatal diagnosis for almost every agent here.

Routes and timing of vertical transmission

A virus reaches the fetus or newborn by one of three routes, and most agents favour one of them. Intrauterine (congenital) infection crosses the placenta during maternal viraemia and can occur at any gestation, with the consequences depending heavily on the trimester. Perinatal infection is acquired during labour and delivery, from cervicovaginal secretions, maternal blood or faeces, and is the dominant route for herpes simplex virus, hepatitis B virus and the enteroviruses. Postnatal infection follows delivery, through breast milk, contact or respiratory spread, and is usually the mildest because transferred maternal antibody is now working in the infant’s favour. Several agents use more than one route, and the route often determines the severity: intrauterine varicella deforms, while varicella acquired around delivery can kill.

Timing of acquisition by route

Timing	Predominant viruses
Prenatal (intrauterine)	Cytomegalovirus; Zika; parvovirus B19; varicella-zoster; rubella; lymphocytic choriomeningitis virus; HIV
Perinatal (intrapartum)	Herpes simplex; HIV; hepatitis B and C; enteroviruses; varicella-zoster; cytomegalovirus
Postnatal	Respiratory syncytial virus; enteroviruses; cytomegalovirus (breast milk); varicella-zoster; hepatitis viruses

The trimester of an intrauterine infection shapes the result. Infection during organogenesis, in the first trimester, produces the structural malformations of the classic congenital syndromes, as in rubella and varicella. Infection later in gestation is more likely to cause active organ inflammation, growth restriction and the haematological picture of disseminated disease, as in cytomegalovirus. For the teratogenic agents the window of greatest risk is narrow and early, and it largely closes by the midpoint of pregnancy.

Recognising congenital infection

The congenital infections share a clinical vocabulary, which is why they were once lumped together and why none of the shared signs is diagnostic on its own. Intrauterine growth restriction, a petechial or purpuric rash, jaundice with a raised conjugated bilirubin, hepatosplenomegaly, thrombocytopenia, a haemolytic anaemia, microcephaly and intracranial calcification recur across the group. Some are visible before birth on ultrasound: non-immune hydrops fetalis, echogenic bowel, ventriculomegaly and placental enlargement. The “blueberry muffin” rash of dermal extramedullary haematopoiesis is identical in congenital rubella and congenital cytomegalovirus, so the rash narrows the field but does not name the agent.

Within that shared picture, particular findings point more strongly to one cause, and a deliberate look for them directs the first tests.

Clinical findings that point to a specific congenital infection

Finding	Suggested agent
Cataracts, congenital heart disease, deafness	Rubella
Periventricular calcification with microcephaly; deafness	Cytomegalovirus
Skin vesicles, keratoconjunctivitis, seizures	Herpes simplex
Microcephaly with intracranial calcification; retinopathy	Zika
Hydrops and anaemia	Parvovirus B19
Cicatricial (scarring) skin lesions in a dermatomal pattern, limb hypoplasia	Varicella-zoster
Hydrocephalus with chorioretinitis	Lymphocytic choriomeningitis virus

Neuroimaging refines this but rarely settles it: brain calcification and microcephaly are shared by cytomegalovirus, toxoplasmosis, lymphocytic choriomeningitis virus, the parechoviruses and Zika, so imaging guides the workup while virology makes the diagnosis. The location of calcification gives a hint, being characteristically periventricular in cytomegalovirus and more diffusely scattered in toxoplasmosis, but the distinction is not reliable enough to act on alone.

The diagnostic principle is constant. Detect the virus, in the infant, early. For most agents the specimen is urine, saliva, a surface or lesion swab, blood or cerebrospinal fluid, tested by PCR. For the congenital infections there is a hard time limit: virus found in the first two to three weeks of life proves intrauterine acquisition, whereas the same virus found later may simply have been picked up during or after birth, a distinction that matters most for cytomegalovirus. Serology retains a role chiefly in the mother, where dating her infection and establishing her immune status guides the assessment of risk to the fetus.

Herpes simplex virus

Unlike rubella, cytomegalovirus and varicella, herpes simplex virus rarely reaches the fetus in utero. Neonatal herpes is overwhelmingly a perinatal infection, acquired from the maternal genital tract at delivery in around 85 per cent of cases, and it is rare but catastrophic, complicating roughly 1 in 2,500 to 1 in 8,000 births, most often through herpes simplex virus type 2. The risk is set by the mother’s infection type. A first (primary) genital infection acquired late in pregnancy, when the mother has not yet made antibody to pass on, carries an infant attack rate of 33 to 60 per cent; a recurrence in a woman with established antibody carries a rate of only 1 to 3 per cent. The trap is that around 90 per cent of mothers who transmit have no recognised history of genital herpes, because primary infection is often silent and shedding is asymptomatic, so a reassuring maternal history does not exclude the diagnosis.

The three syndromes of neonatal herpes

Most affected newborns are well at birth and declare themselves after the first few days of life. Disease in the first 72 hours points away from herpes. The infection takes one of three forms, and which form predominates governs both the treatment and the outlook.

The three presentations of neonatal herpes

Presentation	Share	Typical onset	Features	Mortality with treatment
Skin, eye and mouth	About 45 per cent	End of first week	Vesicles on skin, eye or oral mucosa; no organ or brain disease at this stage	Low, but may progress if untreated
Central nervous system	About 30 per cent	Second to third week	Seizures, lethargy; skin vesicles absent in up to a third	About 6 per cent, but over 70 per cent of survivors have neurological sequelae
Disseminated	About 25 per cent	Towards end of first week	Sepsis picture with hepatitis, pneumonitis and coagulopathy; vesicles may be absent	About 30 per cent

Roughly half of all neonatal herpes involves the central nervous system once the disseminated cases with brain involvement are counted. The absence of a rash is treacherous: up to a third of babies with herpes encephalitis never develop skin vesicles, so the diagnosis must be considered in any neonate with seizures, unexplained sepsis or hepatitis, and the disease pursued even when the skin is clear.

Diagnosis and treatment

Diagnosis rests on detecting the virus. Surface swabs of the mouth, conjunctivae, nasopharynx and rectum, swabs of any vesicle, and blood and cerebrospinal fluid are sent for PCR, with skin and conjunctival samples giving the highest yield. A lumbar puncture is mandatory in every case, including skin-eye-mouth disease, because central nervous system involvement can be subclinical; a negative cerebrospinal fluid PCR does not exclude herpes, since many infected infants have no neurological involvement to detect. Liver transaminases and a full blood count identify disseminated disease.

Treatment is high-dose intravenous aciclovir, and the dose and duration are decided by the disease form: a longer course for central nervous system and disseminated disease, a shorter one for skin-eye-mouth disease, with persistent viraemia at the end of treatment prompting an extension. The earlier standard of low-dose aciclovir was inferior, and the move to high-dose intravenous therapy cut the mortality of central nervous system disease from around half to under 10 per cent. After the intravenous course, six months of oral aciclovir suppression improves neurodevelopmental outcomes and reduces skin recurrences, and is now recommended after every form of neonatal herpes; the neutrophil count must be monitored, because suppression causes neutropenia in a large minority. There is no role for oral or topical aciclovir as initial treatment.

Prevention at delivery

Prevention turns on the delivery. A caesarean section is advised when active genital lesions are present at the onset of labour, particularly if the membranes are intact or have been ruptured for less than four hours. Routine antibody screening of pregnant women is not standard practice, and suppressive aciclovir in late pregnancy reduces the chance of lesions at delivery without being proven to prevent neonatal herpes. A glycoprotein D subunit vaccine has shown efficacy only in women seronegative for both herpes simplex types, and no herpes vaccine is licensed.

Suppressive regimens for recurrent genital herpes in pregnancy

Drug	Regimen
Aciclovir	400 mg orally three times a day
Valaciclovir	500 mg orally twice a day

Either regimen is started at 36 weeks of gestation.

Varicella-zoster virus

Maternal chickenpox is uncommon where childhood varicella vaccination is established, since over 95 per cent of women of childbearing age were immune even before vaccination, but it matters because primary maternal varicella, not zoster, produces two clinically separate diseases according to its timing: a prenatal disease, congenital varicella syndrome, after infection in early pregnancy, and a perinatal disease, neonatal varicella, after infection around delivery. Reactivation as shingles does not transmit to the fetus in any meaningful way.

Congenital varicella syndrome compared with neonatal varicella

Feature	Congenital varicella syndrome	Neonatal varicella
Timing of maternal infection	First or second trimester	Five days before to two days after delivery (severe form)
Mechanism	Intrauterine infection with fetal reactivation	Peripartum transmission without transferred maternal antibody
Manifestations	Cicatricial scarring, limb hypoplasia, eye and brain defects	Disseminated vesicular disease with visceral involvement
Risk	About 1 to 2 per cent of first-trimester infections	High morbidity; 23 to 30 per cent mortality in the severe window

Congenital varicella syndrome (prenatal)

Congenital varicella syndrome follows maternal chickenpox in the first or, less often, second trimester, complicating roughly 1 to 2 per cent of first-trimester maternal infections; third-trimester infection lies outside the teratogenic window and does not cause it. It is thought to represent a zoster-like reactivation in the infected fetus rather than the primary infection itself, which explains its strikingly dermatomal pattern. Its signature is cicatricial scarring of the skin in a dermatomal distribution with hypoplasia of the underlying limb, accompanied by eye defects (chorioretinitis, microphthalmia, cataracts), neurological damage (cortical atrophy, microcephaly, seizures) and, in 15 to 23 per cent, gastrointestinal malformations.

Diagnosis during pregnancy uses PCR of amniotic fluid, chorionic villi or fetal blood, which outperforms serology, with ultrasound looking for limb defects, hydrops and growth restriction. After birth, varicella IgG persisting beyond the six to seven months that passive maternal antibody would last confirms congenital infection. No antiviral alters established congenital varicella syndrome, which is managed supportively; the preventive effort is directed at the mother.

Neonatal varicella (perinatal)

Neonatal varicella follows maternal chickenpox around the time of delivery, and its severity is dictated by the timing of the maternal rash. When the rash appears more than five days before delivery, the mother has time to make and transfer antibody, and the neonatal illness, if it occurs, is usually mild. When the maternal rash appears in the window from five days before to two days after delivery, the infant is exposed to virus without transferred antibody, and the resulting neonatal varicella carries a mortality of 23 to 30 per cent. Disease then begins five to ten days after birth as recurrent crops of vesicles with visceral dissemination to liver, lung and brain, resembling varicella in an immunosuppressed host.

Diagnosis is clinical, confirmed where needed by PCR or direct immunofluorescence on a vesicle, which is high-yield in this acquired infection, unlike the low yield of lesion sampling in the congenital syndrome. The high-risk neonate is treated with intravenous aciclovir, and an exposed susceptible newborn is a candidate for post-exposure prophylaxis.

Treatment and prophylaxis in the mother

A pregnant woman who develops chickenpox is given oral aciclovir, ideally within 24 hours of the rash appearing and from 20 weeks of gestation, with earlier use weighed case by case. Varicella pneumonia is a medical emergency with a high maternal mortality, and demands immediate intravenous aciclovir. Aciclovir is not licensed in pregnancy, but extensive registry data show no specific pattern of fetal malformation, so the maternal benefit outweighs the theoretical risk.

Post-exposure prophylaxis protects the woman or infant with no immunity. Varicella-zoster immunoglobulin (VariZIG) is given after significant exposure to a susceptible pregnant woman, to a newborn whose mother developed chickenpox in the five-days-before to two-days-after window, and to exposed hospitalised preterm infants, as soon as possible and up to ten days after exposure. It does not abolish the risk: about half of immunoglobulin-treated infants still develop varicella, although usually attenuated. Where varicella-zoster immunoglobulin is unavailable, intravenous immunoglobulin is the alternative. The durable preventive measure for the population is universal childhood varicella vaccination, with pregnancy avoided for a month after immunisation.

Treatment and post-exposure prophylaxis of varicella in pregnancy

Scenario	Intervention	Regimen
Uncomplicated maternal varicella	Oral aciclovir	800 mg five times a day for seven days
Varicella pneumonia	Intravenous aciclovir	10 mg/kg every eight hours
Post-exposure prophylaxis	Varicella-zoster immunoglobulin, intramuscular	Within ten days of exposure (125 units per 10 kg, maximum 625 units)
Prophylaxis when immunoglobulin unavailable	Intravenous immunoglobulin	400 mg/kg as a single dose

Cytomegalovirus

Cytomegalovirus is the commonest congenital viral infection and the leading non-genetic cause of childhood sensorineural hearing loss, affecting 0.5 to 2 per cent of all live births. Its danger is almost entirely prenatal: congenital infection acquired across the placenta causes the lasting damage, whereas the virus acquired perinatally or postnatally is usually harmless except in the preterm infant.

Congenital cytomegalovirus (prenatal)

Risk to the fetus is set by the type of maternal infection. A primary maternal infection transmits to the fetus in 30 to 50 per cent of cases, whereas a non-primary infection (reactivation or reinfection in an already immune woman) transmits in only 0.5 to 3 per cent. Because most women in high-seroprevalence populations are already immune, most congenitally infected infants are nonetheless born to immune mothers, each pregnancy carrying only a small individual risk but the population producing the larger share of cases.

Of all congenitally infected newborns, 85 to 90 per cent are asymptomatic at birth and 10 to 15 per cent are symptomatic. Symptomatic disease presents with growth restriction, microcephaly, petechiae with thrombocytopenia, hepatosplenomegaly, jaundice and intracranial (characteristically periventricular) calcification, and carries a first-year mortality above 10 per cent with neurodevelopmental disability in 50 to 90 per cent of survivors. Sensorineural hearing loss is the hallmark sequela and is not confined to symptomatic infants: it occurs in 10 to 15 per cent of those who were asymptomatic at birth, may be delayed in onset and progressive, and is the reason every infected infant needs prospective audiological follow-up.

Diagnosis must capture the virus in the first two to three weeks of life. Urine and saliva are the specimens of choice, tested by PCR; virus found after three weeks cannot be distinguished from infection acquired through the birth canal or breast milk, and so cannot prove congenital infection. Infant serology is unhelpful because maternal IgG crosses the placenta. Symptomatic disease, particularly with central nervous system involvement, is treated with six months of oral valganciclovir, which improves hearing and neurodevelopmental outcomes; the principal toxicity is neutropenia. No vaccine is licensed, so prevention rests on hygiene advice to seronegative pregnant women, chiefly hand-washing after contact with the saliva and urine of young children, who are the main source of maternal infection.

Perinatal and postnatal cytomegalovirus

Cytomegalovirus is also acquired at delivery from cervicovaginal secretions and, most often, after birth through breast milk. In the healthy term infant this acquired infection is typically asymptomatic and carries no demonstrable neurodevelopmental harm. In the very preterm or very-low-birth-weight infant, breast-milk cytomegalovirus can instead cause a sepsis-like illness with hepatitis, neutropenia and thrombocytopenia, a risk reduced by freezing or pasteurising expressed milk from seropositive mothers.

Rubella

Rubella is a mild illness in the mother and a devastating one in the first-trimester fetus, and it is the model of a vaccine-preventable congenital infection. The risk to the fetus falls steeply through gestation. Maternal rubella with rash in the first 12 weeks transmits to the fetus in 70 to 85 per cent of cases and causes the full congenital syndrome; infection at 13 to 16 weeks transmits less often and tends to cause isolated deafness; after 17 weeks the teratogenic risk is negligible, so the timing of maternal infection both predicts and bounds the damage.

Congenital rubella syndrome is dominated by a triad of sensorineural deafness, cataracts and congenital heart disease, with deafness the commonest isolated defect. Cardiac lesions, present in 45 to 70 per cent, are typically patent ductus arteriosus and branch pulmonary artery stenosis. The wider picture adds pigmentary retinopathy, microphthalmia and glaucoma, microcephaly and psychomotor retardation, growth restriction, hepatosplenomegaly, the blueberry muffin rash, thrombocytopenic purpura and the long-bone lucencies sometimes called celery stalking. Some manifestations are delayed for years, including a late-onset diabetes and thyroid disease and, rarely, a progressive rubella panencephalitis, so a child infected in utero needs long-term surveillance even when normal at birth. In one series, 85 per cent of affected infants were not diagnosed until after nursery discharge.

Diagnosis in the first year rests on a positive rubella IgM, a significant change in IgG, or detection of virus by culture or reverse-transcription PCR from throat, urine or cerebrospinal fluid; infected infants shed virus from the oropharynx for months and are a hazard to susceptible contacts. There is no specific antiviral, and management is supportive and multidisciplinary, with cardiac and cataract surgery and lifelong audiological and developmental care. Prevention is the entire story: the live attenuated vaccine, given as the measles, mumps and rubella (MMR) combination or as a measles-rubella product, confers near-complete protection, and the priority is to immunise girls and women before pregnancy. The vaccine is avoided in pregnancy on theoretical grounds, although no case of congenital rubella syndrome has been attributed to inadvertent vaccination of over 500 monitored pregnancies.

Parvovirus B19

Parvovirus B19 threatens the fetus not through malformation but through anaemia. The virus uses the blood group P antigen as its receptor and replicates in erythroid progenitor cells, halting red-cell production. In the fetus, with its short red-cell lifespan and rapidly expanding blood volume, this causes severe anaemia, high-output cardiac failure and non-immune hydrops fetalis, the major fetal presentation. Parvovirus B19 is the commonest infectious cause of non-immune hydrops and accounts for the majority of virus-related fetal deaths before birth.

Most maternal infections in pregnancy do not harm the fetus. Around a quarter to a half of maternal infections transmit, and the serious outcomes cluster when infection occurs before 20 weeks: in a large series of maternal infections, fetal hydrops occurred in 3.9 per cent and fetal death in 6.3 per cent, with deaths confined to infection before the twentieth week. The mother may have the classic “slapped cheek” rash of erythema infectiosum or an arthropathy, or no symptoms at all. By the time the rash appears the viraemia has usually passed, which is why post-exposure immunoglobulin is not recommended.

Diagnosis uses maternal PCR, which is highly sensitive, and serology, while fetal IgM is detected in only about a fifth of infected fetuses and is unreliable. After maternal infection the fetus is monitored with serial ultrasound for one to two months, including middle cerebral artery Doppler velocimetry, which detects the fetal anaemia before hydrops is established. About a third of hydropic fetuses recover spontaneously; for the rest, intrauterine red-cell transfusion is the intervention that changes the outcome, taking survival in severe hydrops from near zero to over 80 per cent. Most survivors develop normally, and the long-term risk of major abnormality is under 1 per cent. No vaccine is available.

Neonatal enteroviral and parechoviral sepsis

The enteroviruses (chiefly the coxsackieviruses and echoviruses) and the human parechoviruses cause a neonatal illness that mimics bacterial sepsis, and they do so far more often than their profile suggests. Enterovirus is a more common reason for admission of a febrile neonate with suspected sepsis than group B streptococcus, herpes simplex virus and cytomegalovirus combined, and accounts for the majority of such admissions during the late-summer enterovirus season. The virus is acquired transplacentally from a viraemic mother, intrapartum, or postnatally, and the presence or absence of transferred maternal antibody governs how severe the illness becomes.

Most infected newborns are mildly ill or asymptomatic, with fever, poor feeding and irritability resolving over a few days. A minority, usually those infected peripartum before maternal antibody could transfer, develop overwhelming disease: a viral sepsis syndrome with disseminated intravascular coagulation, refractory hypotension, and the combination of severe hepatitis, coagulopathy and myocarditis that carries the highest mortality. The combination of severe hepatitis and coagulopathy is particularly grave, with mortality reported between 30 and 80 per cent. The parechoviruses, type 3 especially, produce a similar sepsis-like picture with prominent white-matter brain injury on imaging.

Diagnosis is by reverse-transcription PCR of blood, cerebrospinal fluid, and stool or rectal swabs. A point worth holding is that enteroviral and parechoviral meningitis can occur without cerebrospinal fluid pleocytosis, so the cerebrospinal fluid must be sent for PCR even when the cell count is normal. Treatment is supportive, since no antiviral is licensed for neonatal enteroviral disease; intravenous immunoglobulin and the investigational agent pleconaril have been used in severe disease with inconsistent evidence of benefit.

Other congenital agents

Several further viruses cause congenital disease that is rare, geographically restricted or under-recognised, and each carries a single point worth knowing.

Zika virus, a mosquito-borne flavivirus, came to prominence in the 2015 to 2016 American epidemic as a cause of congenital microcephaly. It infects fetal neural progenitor cells directly, killing them and disrupting cortical development, and produces a congenital Zika syndrome of microcephaly, intracranial calcification, a pigmentary retinopathy and hearing loss, with the greatest risk after first-trimester infection. Diagnosis is by reverse-transcription PCR of serum, positive only in the brief viraemic window of three to seven days, and of urine, which stays positive longer, with serology and plaque-reduction neutralisation used when PCR is negative. The epidemiology is specific to regions with the Aedes vector and to the epidemic period, and southern Africa has not reported autochthonous congenital Zika disease.

Lymphocytic choriomeningitis virus is an arenavirus carried by rodents, acquired by a pregnant woman from contact with mouse or hamster excreta, and it is easily missed because only half of mothers recall an illness. It targets the fetal brain and retina, causing hydrocephalus, chorioretinitis and microcephaly, and unlike most agents here it is diagnosed serologically because the population seroprevalence is low. Congenital lymphocytic choriomeningitis virus infection belongs in the differential of any neonate with unexplained hydrocephalus and chorioretinitis, where it can be mistaken for congenital toxoplasmosis or cytomegalovirus.

Human herpesvirus 6 is acquired by almost all children in the first two years of life and causes roseola, but its relevance to the newborn is a diagnostic pitfall: around 90 per cent of vertical transmission occurs through germline-integrated viral DNA present in every cell, so a positive blood PCR can reflect chromosomally integrated virus rather than active infection. Epstein-Barr virus and Kaposi sarcoma-associated herpesvirus (human herpesvirus 8) cross the placenta rarely and are not established causes of a defined congenital syndrome.

Bloodborne viruses: hepatitis B, hepatitis C and HIV

Three bloodborne viruses are transmitted from mother to infant chiefly around delivery, and for all three the obstetric and neonatal management is where transmission is prevented.

Hepatitis B

Hepatitis B virus (HBV) is transmitted predominantly at labour and delivery rather than across the placenta, and the consequence of perinatal infection is dictated by the age at acquisition: infection at birth becomes chronic in about 90 per cent of cases, against under 5 per cent for infection in adulthood, and 15 to 25 per cent of those chronically infected will eventually die of cirrhosis or hepatocellular carcinoma. The risk of transmission tracks maternal infectivity. A mother positive for the hepatitis B e antigen (HBeAg), a marker of high replication, transmits to 80 to 90 per cent of infants in the absence of prophylaxis, whereas an HBeAg-negative, hepatitis B surface antigen (HBsAg) positive mother transmits to 5 to 20 per cent. Maternal viral load is the underlying driver. The infant is well at birth; without intervention, surface antigenaemia and mild enzyme elevation appear over the following months.

Prevention is highly effective and rests on doing two things quickly. Every infant of an HBsAg-positive mother receives both the hepatitis B vaccine and hepatitis B immunoglobulin (HBIG) within 12 hours of birth, combining active and passive immunisation, and the vaccine course is completed on schedule. Where the maternal status is unknown, the surface antigen is checked immediately and the birth-dose vaccine given at once, with immunoglobulin added as soon as a positive result returns. This strategy sits within universal infant hepatitis B immunisation from birth.

Prophylaxis is not infallible: around 5 to 10 per cent of infants of HBeAg-positive mothers become chronically infected despite correct prophylaxis, the failures concentrated among the most viraemic and the few infected in utero. For that reason a highly viraemic mother is offered an antiviral in the third trimester, with tenofovir given when the maternal HBV DNA exceeds 200,000 international units per millilitre to lower the viral load and the residual transmission risk. Caesarean section is not indicated to prevent transmission, and breastfeeding is not contraindicated once the infant is immunised.

Hepatitis C

Hepatitis C virus (HCV) is transmitted vertically far less efficiently than hepatitis B, in about 5 to 11 per cent of pregnancies, and the rate roughly doubles when the mother is co-infected with the human immunodeficiency virus (HIV). There is no immunoglobulin, no vaccine and no proven intrapartum intervention that reduces hepatitis C transmission, so management is identification and follow-up rather than prophylaxis. Maternal viral load and HIV co-infection are the main risk factors; prolonged rupture of membranes and invasive fetal monitoring add to the risk, and caesarean section is not recommended for hepatitis C alone. Breastfeeding has not been shown to transmit the virus and is not contraindicated, with abstention advised only if the nipples are cracked or bleeding.

Diagnosing the infant requires patience. Maternal IgG antibody crosses the placenta and persists, so confirmatory anti-HCV antibody testing is deferred to 15 to 18 months of age, by which time maternal antibody has cleared; before then only a positive HCV RNA PCR, which may be negative at birth and become positive within the first weeks, confirms infection. A quarter or more of infected children clear the virus spontaneously by school age. The direct-acting antivirals that have transformed adult hepatitis C are increasingly licensed for children, replacing the older interferon-based regimens, and curative treatment is deferred until the child is old enough to be eligible.

HIV

In the absence of intervention, HIV is transmitted from mother to child in around a quarter of pregnancies, across the antepartum, intrapartum and breastfeeding periods, with the intrapartum period and breast milk carrying much of the risk. A bundle of measures (maternal antiretroviral therapy, an appropriately timed mode of delivery, infant prophylaxis and informed infant-feeding choices) reduces transmission to under 2 per cent. Maternal viral load is the dominant determinant, and a mother on suppressive antiretroviral therapy with an undetectable load transmits rarely. The newborn receives antiretroviral prophylaxis started within hours of birth, intensified when the mother was not virally suppressed, and early infant diagnosis uses HIV nucleic-acid testing rather than antibody testing, because transferred maternal antibody persists for months.

South African context

South Africa carries a distinctive version of this topic, shaped by high seroprevalence of several agents, a large antenatal HIV burden, and a programme that has changed substantially in the last few years. Cytomegalovirus is acquired in early childhood by most of the population, so the great majority of women enter pregnancy already immune and the congenital burden is driven less by maternal primary infection than by non-primary infection in immune women, a low per-pregnancy risk applied across very many pregnancies, and amplified by high maternal HIV prevalence.

HIV remains the dominant vertically transmitted infection nationally, and the prevention of mother-to-child transmission programme is a central activity of the antenatal services, with universal maternal antiretroviral therapy and early infant diagnosis having reduced transmission rates markedly. Regimen selection, maternal treatment and the prevention of mother-to-child transmission programme are set out in South Africa’s national HIV management guidelines.

The hepatitis B birth dose is currently targeted to infants born to mothers who are HBsAg-positive or HBeAg-positive. HBIG is advised for the most vulnerable newborns, but it remains difficult to access within public healthcare facilities, so the prevention of mother-to-child transmission of hepatitis B is hindered by these logistical gaps.

The most significant recent change concerns rubella. For decades the public programme contained no rubella vaccine, so rubella circulated and congenital rubella syndrome remained a live risk, in contrast to countries that had eliminated it. In 2024 South Africa introduced rubella-containing vaccine into the Expanded Programme on Immunisation, switching from a measles-only to a measles-rubella vaccine at 6 and 12 months, supported by a wide-age-range catch-up campaign. The epidemiology of congenital rubella in South Africa should therefore be expected to change over the coming years. Suspected congenital rubella is a category 2 notifiable medical condition.

References and recommended reading

• Schleiss MR, Marsh KJ. Viral Infections of the Fetus and Newborn. In: Gleason CA, Juul SE, editors. Avery’s Diseases of the Newborn, 10th edition, Chapter 37. Elsevier; 2018. The principal source for the timing-based approach to fetal and neonatal viral infection, the agent-by-agent clinical syndromes, their diagnosis and the antiviral and immunoprophylactic management described here.
• Workowski KA, Bachmann LH, Chan PA, et al. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recommendations and Reports 2021;70(RR-4). Centers for Disease Control and Prevention. The current source for the suppressive antiviral regimen for recurrent genital herpes in pregnancy given above.
• Royal College of Obstetricians and Gynaecologists. Chickenpox in Pregnancy. Green-top Guideline No. 13. London: RCOG; 2015. The source for the treatment of maternal varicella, including the oral and intravenous aciclovir regimens and the gestational threshold for oral treatment.
• National Department of Health, South Africa. National Guidelines for the Management of Viral Hepatitis. Pretoria: NDoH; 2019. The source for the South African approach to perinatal hepatitis B prevention, including the birth-dose vaccine and immunoglobulin strategy.
• National Department of Health, South Africa. 2026 National Consolidated Guidelines for the Prevention of Mother-to-Child Transmission of HIV and the Management of HIV in Children, Adolescents and Adults. Pretoria: NDoH; 2026. The source for the South African prevention of mother-to-child transmission programme and early infant diagnosis.
• National Department of Health, South Africa. Standard Treatment Guidelines and Essential Medicines List, Primary Healthcare: Immunisation (Chapter 13). Pretoria: NDoH; 2024. The source for the 2024 introduction of rubella-containing vaccine into the Expanded Programme on Immunisation and the South African infant hepatitis B schedule.