Diagnose and manage congenital and perinatal infections, including TORCH and group B streptococcus

In one line

Congenital and perinatal infection is one disease problem with two questions — did the organism reach the fetus, and can anything change what it does once there — and the answer to the second is mostly "prevent transmission, not treat the fetus": cytomegalovirus is the commonest and most under-recognised, group B streptococcus is the one you actively prevent in labour, and syphilis is the one South Africa still fails despite a cheap, curable answer.

Mechanism & pathophysiology

Four routes carry an organism from mother to fetus or newborn, and the route determines both the timing of damage and what intervention is even possible.

• Transplacental (haematogenous) — the maternal organism crosses the villous trophoblast during a viraemia or parasitaemia. This is the route for cytomegalovirus (CMV), rubella, Toxoplasma gondii, parvovirus B19, varicella and the spirochaete of syphilis. Damage here is embryopathic/fetopathic — it injures organogenesis or established fetal tissue — and it is the route where antenatal antimicrobial treatment, if it works at all, works by reducing the chance the placenta is crossed rather than by reversing established fetal injury.
• Ascending — organisms track from the vagina through the cervix into the amniotic cavity, classically once membranes rupture but also with intact membranes. Group B streptococcus (GBS), the genital mycoplasmas and enteric organisms reach the fetus this way and cause chorioamnionitis, preterm birth and early-onset neonatal sepsis.
• Intrapartum (contact during passage through the genital tract) — the fetus meets the organism on the birth canal. This is the dominant route for neonatal herpes simplex (HSV), much early-onset GBS disease, and is one of the routes for hepatitis B and HIV. It is the route most amenable to a delivery decision — caesarean for active primary HSV lesions, intrapartum antibiotics for GBS.
• Postnatal / breast milk — CMV, HIV and HSV can be transmitted after birth, including through breast milk. For a term healthy infant, breast-milk CMV is usually trivial; in the very preterm it can cause symptomatic disease, which is the one setting where breast-milk CMV transmission is clinically weighed against the benefits of breastfeeding.

Gestation governs both the probability and the severity of transplacental infection, and the two move in opposite directions. The placental barrier becomes more permeable as pregnancy advances, so transmission rates rise with gestation; but the embryo and early fetus are most vulnerable to teratogenesis and tissue destruction, so the severity of damage falls with gestation. Rubella is the cleanest illustration — first-trimester maternal infection transmits to roughly 90% of fetuses and the defects are devastating and near-universal, whereas infection after 18–20 weeks rarely causes structural disease. CMV and toxoplasmosis follow the same logic: late-pregnancy infection is more often transmitted but more often produces a subclinically infected, normal-appearing neonate, while early infection is less often transmitted but more often catastrophic when it is. This single fact — high transmission/low harm late, low transmission/high harm early — is why timing of maternal seroconversion, not merely its presence, drives counselling.

The "TORCH" label (toxoplasmosis, others, rubella, CMV, HSV) is a historical mnemonic, not a diagnostic test; ordering "a TORCH screen" on a baby with non-specific findings is low-yield and has been abandoned in favour of pathogen-directed testing guided by the maternal history and the specific fetal/neonatal phenotype.

Assessment

The maternal serological pattern, the fetal ultrasound phenotype and (where it changes management) amniotic-fluid PCR are the three legs of antenatal diagnosis. The principle running through all of them: a positive IgM is a clue, never a diagnosis, and avidity testing on the IgG is what dates the infection.

Maternal serology and its traps.

• IgG present, IgM absent = past/immune. Reassuring for primary infection — but past infection does not exclude congenital disease for CMV (non-primary reactivation/reinfection still transmits) or for syphilis (a treponemal test stays positive for life; you need a non-treponemal titre — RPR/VDRL — to gauge activity and response).
• IgM present = recent infection or a false positive or persistent IgM lingering from an old infection (IgM can persist for months, particularly for toxoplasma and CMV). IgM alone must never trigger an irreversible decision.
• IgG avidity resolves the ambiguity. Low avidity indicates recent (typically <3–4 months) primary infection; high avidity effectively excludes infection acquired in the preceding 3–4 months and so, early in pregnancy, largely excludes a recent primary infection capable of harming the fetus. Avidity is the single most useful add-on test for CMV and toxoplasma and is how you date a seroconversion when only one sample exists.
• Seroconversion across paired sera (a documented IgG-negative→IgG-positive change, or a rising titre) is the gold standard but requires that a booking sample was stored — which is why CMV and toxoplasma, for which there is no routine antenatal screening, are usually diagnosed retrospectively or on avidity.

Fetal ultrasound markers raise suspicion and, more importantly, grade severity:

• Cerebral — ventriculomegaly, intracranial (especially periventricular) calcification, microcephaly, abnormal gyration. CMV and toxoplasma both calcify; CMV classically periventricular, toxoplasma more scattered/parenchymal.
• Hydrops / cardiomegaly / raised MCA peak systolic velocity — points to fetal anaemia, the signature of parvovirus B19, and also seen in severe CMV and syphilis.
• Hepatosplenomegaly, echogenic bowel, placentomegaly, ascites, FGR — non-specific markers of intrauterine infection across several organisms.
• A normal detailed scan and normal serial growth is reassuring but not exclusory for subclinical congenital CMV, which is precisely the infection most likely to look normal antenatally and declare itself postnatally as sensorineural hearing loss.

Amniocentesis with pathogen PCR is the antenatal confirmation of fetal infection for CMV and toxoplasma. Two conditions must be met for it to be reliable: it should be performed after ~20–21 weeks (the fetal kidney must be excreting virus/organism into the amniotic fluid) and at least ~6–8 weeks after maternal seroconversion, or a true fetal infection can be missed by a falsely negative result. Counselling — what a positive amniocentesis means for prognosis, and what options follow — is the harder half of the assessment and must precede the needle.

The counselling itself separates two questions that families collapse into one: is the fetus infected (the amniocentesis answers this) and is the fetus damaged (imaging answers this, imperfectly). A positive PCR with normal serial neuroimaging and growth carries a far better prognosis than a positive PCR with ventriculomegaly or calcification — most notably for CMV, where many PCR-positive but imaging-normal fetuses are born without symptoms and the residual risk is later-onset hearing loss rather than the severe syndrome. The procedure-related risks of amniocentesis, the imperfect predictive value of a normal scan, and the irreversibility of a termination decision all have to be set out before the test, not after a result has forced the conversation. For organisms with no fetal intervention available (rubella, established severe CMV), the counselling is honest about that limitation rather than offering false reassurance of "treatment".

Management

Organise each organism as immediate (this pregnancy/peripartum) → ongoing (fetal/neonatal) → long-term (prevention and the next pregnancy), and hold one unifying truth: for most of these infections the effective intervention is preventing transmission or its consequences, not curing the established fetal disease.

Cytomegalovirus — the commonest, and the one with new antenatal options

CMV is the commonest congenital infection and the leading non-genetic cause of childhood sensorineural hearing loss. Most congenitally infected infants are asymptomatic at birth; a minority have the classic syndrome (FGR, microcephaly, hepatosplenomegaly, thrombocytopenic petechiae, chorioretinitis), and of the asymptomatic group a meaningful fraction develop late-onset hearing loss — which is why congenital CMV is a hearing-surveillance diagnosis, not a one-look diagnosis.

• Diagnosis: maternal primary infection by seroconversion or low IgG avidity; fetal infection by amniotic-fluid PCR after 20–21 weeks and ≥6 weeks post-seroconversion; severity by serial neurosonography/MRI. Neonatal confirmation is CMV PCR on urine within the first 21 days of life (the definitive specimen); a saliva PCR is a convenient screen, but because CMV is shed in breast milk a positive saliva taken soon after a feed can be a false positive and must be confirmed on urine. After 3 weeks you cannot distinguish congenital from postnatally acquired infection.
• Antenatal treatment — the valaciclovir question. High-dose oral valaciclovir (8 g/day) started after a first-trimester or periconceptional primary maternal infection reduced the rate of fetal infection in a randomised trial (positive amniocentesis 11% vs 30% overall; 11% vs 48% in the first-trimester subgroup) — the first credible evidence that an antenatal antiviral can lower vertical transmission of CMV. It is increasingly offered to women with confirmed early primary infection, but it is not established as routine, the trial was small and single-centre, and it treats transmission, not established fetal disease. Letermovir and CMV hyperimmune globulin have not delivered convincing benefit (the hyperimmune-globulin randomised trials were negative).
• The screening debate. There is no routine antenatal CMV screening in the UK, SA or most of the world, and this is deliberate, not an oversight: no licensed vaccine, historically no proven antenatal treatment, imperfect tests (persistent IgM, avidity grey zones) and the spectre of terminating pregnancies that would have produced healthy infants together failed the criteria for a screening programme. The valaciclovir data have reopened the argument — if early treatment works, the case for at least first-trimester screening strengthens — and in December 2023 Italy's Ministry of Health became the first national body to recommend universal first-trimester CMV serological screening, while the UK, US and SA still do not screen, so that tension is now live. What is universally endorsed is hygiene-based primary prevention counselling for seronegative women, particularly those with a toddler at home (handwashing after nappies/saliva, not sharing utensils), because young children are the main source.