ISUOG Practice Guidelines: role of ultrasound in congenital infection

Key points

• Ultrasound signs such as ventriculomegaly, calcifications, hyperechogenic bowel, growth restriction or hydrops are suggestive, not diagnostic, of congenital infection and should trigger maternal testing; in hydrops or fetal anemia, parvovirus testing is added.
• Fetal infection is confirmed by PCR of amniotic fluid; for cytomegalovirus (CMV), amniocentesis should wait at least 8 weeks after maternal infection and until after 20 weeks, for Toxoplasma at least 4 weeks and after 18 weeks.
• A confirmed fetal infection does not necessarily mean the fetus will be affected, and normal prenatal imaging does not exclude later sequelae such as hearing loss.
• After parvovirus B19 infection, serial ultrasound every 1–2 weeks looks for fetal anemia; fetal blood sampling with preparation for transfusion is indicated when the middle cerebral artery peak systolic velocity (MCA-PSV) is above 1.5 MoM or there is ascites or hydrops.
• For CMV, high-dose valaciclovir and hyperimmune globulin should be given only in the context of research.

Overview

These ISUOG Practice Guidelines, peer reviewed by the society's Clinical Standards Committee, explain how ultrasound helps diagnose congenital infection, estimate fetal prognosis and guide management. They cover six pathogens: CMV, Toxoplasma, parvovirus B19, rubella, varicella-zoster virus (VZV) and Zika virus. Prevention and routine screening are not addressed because practice differs between countries; recommendations are graded, and those lacking evidence are labelled good practice points.

Cytomegalovirus

CMV is the most common viral cause of congenital infection, affecting 0.2–2.2% of live births. Primary maternal infection is diagnosed by new CMV IgG in a previously seronegative woman or by IgM with low IgG avidity; non-primary infection cannot be excluded serologically. After primary infection, vertical transmission is around 30–40% on average and rises with gestation, while the likelihood of severe symptoms at birth in an infected fetus is about 70% after periconceptional, 20% after first-trimester and 5% after second-trimester infection. Ultrasound abnormalities can appear 12 weeks or more after maternal infection, so scans every 2–4 weeks are advised; normal brain ultrasound and MRI indicate a low risk of disability but not the hearing outcome.

Toxoplasma

Amniotic fluid PCR detects at most 90% of infections. After maternal infection, spiramycin 1 g orally three times daily should start without delay, within 3 weeks of seroconversion. If fetal infection is confirmed, spiramycin is given for 1 week, followed by pyrimethamine 50 mg once daily, sulfadiazine 1 g three times daily and folinic acid 50 mg weekly for the rest of the pregnancy, with the infant treated for 1 further year. Scans every 4 weeks focus on the brain, eyes and growth; even with normal imaging the risk of long-term sequelae, especially chorioretinitis, is approximately 30%.

Parvovirus B19 and rubella

For parvovirus B19, ultrasound monitoring starts 4 weeks after infection and continues every 1–2 weeks until 12 weeks after infection; MCA Doppler should not be measured during or immediately after fetal activity. The risk of perinatal death is approximately 30% for hydropic and 6% for non-hydropic infected fetuses, and cerebral imaging should be considered after hydrops or severe anemia. Rubella IgM has a 15–50% false-positive rate; after primary infection before 12 weeks, termination can be considered even without invasive testing, and amniocentesis within 6 weeks of infection may be falsely negative.

Varicella-zoster and Zika virus

The risk of congenital varicella syndrome is estimated at 0.5% for maternal infection in the first 13 weeks and 2% between weeks 13 and 20; infection after 36 weeks carries a 25% risk of clinical neonatal varicella, and maternal shingles has not been associated with fetal harm. Exposed non-immune women should be offered varicella zoster immunoglobulin within 10 days, and oral acyclovir is offered within 24 h of the rash. For Zika, travel history should be asked routinely and the primary test is real-time reverse transcription PCR (rRT-PCR) of serum and urine; microcephaly is diagnosed at a head circumference 2 SD or more below the mean, and head circumference should not be used for dating in exposed pregnancies. Amniocentesis for Zika should not be done before 20 weeks, and when congenital Zika syndrome is suspected, follow-up after birth until at least 12 months of age is recommended.

Frequently asked questions

Does a positive amniotic fluid test mean the baby will be affected?

No. The guideline stresses that a confirmed fetal infection does not necessarily mean the fetus will develop abnormalities, although infected fetuses with normal imaging may still have long-term sequelae.

Why is amniocentesis delayed after maternal infection?

Amniotic fluid PCR usually turns positive only 6–8 weeks after maternal infection, and fetal urination, which carries the virus into the fluid, is not well established until 18–20 weeks, so earlier testing risks false-negative results.

Is antiviral or immunoglobulin treatment recommended for fetal CMV?

Not as routine care. High-dose valaciclovir and CMV hyperimmune globulin should be given only within research, because randomized evidence for valaciclovir is lacking and one randomized trial of hyperimmune globulin showed no significant benefit.

Source

Khalil A, Sotiriadis A, Chaoui R, da Silva Costa F, D'Antonio F, Heath PT, et al. ISUOG Practice Guidelines: role of ultrasound in congenital infection. Ultrasound Obstet Gynecol 2020;56(1):128-151. doi:10.1002/uog.21991. Produced on behalf of the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) and peer reviewed by its Clinical Standards Committee. Summary prepared by Medpresso from the original publication; it is not a substitute for the full text or for medical advice.