Key points:

1. Early clinical suspicion and rapid diagnosis of parvovirus B19 is critical.
2. Tertiary level follow-up with serial MCA Doppler assessment up to 12 weeks post infection is essential to detect fetal anaemia.
3. Timely intra-uterine transfusion can be lifesaving in cases of parvovirus B19-associated non-immune anaemia and hydrops.
4. Fetal brain MRI in the third trimester may detect subtle changes not seen on fetal neurosonography.

A 32-year-old woman (G2P1) was referred to the Westmead Hospital Maternal-Fetal Medicine Unit (MFM) following an incidental finding of fetal hydrops at 18+5 weeks. Fortnightly transvaginal cervical length surveillance had been instigated following the detection of a cervical length of 25 mm at 16+5 weeks. No other concerns were noted on that ultrasound. At 18+5 weeks, ultrasound revealed fetal hydrops including generalised anasarca, ascites, pericardial effusion, placentomegaly, and a moderately elevated middle cerebral artery peak systolic velocity (MCA PSV, 33.3 cm/s, 1.39 MoM). On questioning, the patient reported a flu-like illness four weeks earlier. She was Rhesus positive with no relevant medical or surgical history. Non-invasive prenatal testing was low risk for the common aneuploidies.

Following counselling, amniocentesis was performed, and samples were sent for cytogenetics, DNA storage, and urgent PCR testing for cytomegalovirus (CMV), toxoplasmosis, syphilis, and parvovirus B19. Maternal serology was also obtained to assess for recent infection. A follow-up scan at 19+0 weeks showed progression of fetal anaemia, with the MCA PSV rising to 46.3 cm/s (1.90 MoM). The patient was counselled for intrauterine transfusion (IUT). Transfusion was briefly delayed pending confirmation of rapid PCR for parvovirus. Chromosomal microarray later returned with no evidence of chromosomal copy number variants, and maternal serology was positive for both parvovirus IgG and IgM.

IUT was performed in two stages due to severe hydrops. A small-volume “snack” transfusion of 10 mL was administered at 19+0 weeks, reducing the MCA PSV to 33 cm/s (1.36 MoM). The patient was followed up closely with a scan every 2 days (19+1 to 19+6 weeks). MCA PSV values remained between 33–41 cm/s (1.36-1.69 MoM). Ascites, scalp oedema, and pericardial effusion persisted, but ventricular function remained preserved. A second IUT was performed at 20+0 weeks (pre-procedure MCA PSV 46 cm/s, 1.89 MoM; fetal Hb 21.7 g/L). A 20 mL transfusion reduced the MCA PSV to 25 cm/s (1.0 MoM). Serial ultrasounds documented gradual improvement. Generalised oedema had resolved by 21+6 weeks, with ascites steadily decreasing. Continued improvement was seen in two to three weekly ultrasounds, with complete resolution of ascites at 33+1 weeks and appropriate fetal growth throughout. A fetal brain MRI at 31 weeks showed subtle parieto-occipital white matter signal loss. The patient was subsequently seen by a paediatric neurologist, who considered the findings reassuring and unlikely to result in adverse neonatal outcome. Follow-up was arranged, with the option of postnatal review and repeat MRI if concerns arose. At 38+2 weeks, the patient delivered vaginally after spontaneous rupture of membranes. The neonate was well at birth (Apgars 9, 9, 9; birthweight 2.6 kg), with no evidence of anaemia (day 1 Hb 193 g/L). Both mother and baby were discharged home the following day for ongoing midwifery in the home care.

Parvovirus B19 infection, also known as fifth disease or “slapped cheek”, is a common, self-limiting childhood illness caused by a single-stranded DNA virus transmitted through respiratory droplets and hand-to-mouth contact. In adults, infection is usually mild or   asymptomatic, though flu-like symptoms, rash and symmetric peripheral arthropathy may occur. Approximately 40% of Australian women are non-immune.¹ If acquired during pregnancy, there is a 50% risk of vertical transmission, which can, in rare cases, lead to severe fetal anaemia and life-threatening hydrops .¹ The virus targets erythroid precursor cells in the liver, suppressing erythropoiesis and inducing apoptosis. There is currently no intervention to prevent fetal infection, nor is there a role for routine screening in pregnancy, making it crucial to remain vigilant and ensure timely diagnosis.

In suspected cases, maternal serology for IgG and IgM antibodies should be performed, with consideration for repeat testing in two to four weeks after possible exposure in susceptible women. Urgent referral must be made to a tertiary care MFM centre if infection is suspected. Serial ultrasound for 12 weeks from time of probable exposure is crucial.¹ Amniocentesis in asymptomatic intrauterine fetal infection is not recommended, however, in cases of unexplained fetal hydrops or anaemia where amniocentesis is performed, the sample can be sent for parvovirus PCR, as in this case. Other rare causes of fetal anaemia and hydrops to consider include CMV, toxoplasmosis, coxsackie virus, and syphilis infections.² We emphasise the importance of early communication with the local health laboratory to understand processing times and potentially expedite results.

The greatest risk of parvovirus B19 to the fetus is prior to 20 weeks gestation, where there is a 10% excess risk of pregnancy loss, and 3% risk of hydrops between 9-20 weeks gestation.² Hydrops carries a high risk of intrauterine death. Spontaneous resolution occurs in 32% of non-hydropic fetuses, but in only 5% of hydropic cases.¹ When hydrops or severe fetal anaemia (MCA PSV value >1.5 MoM) is present, IUT substantially reduces the risk of fetal death and markedly improves prognosis.³ However, large-volume transfusion in severely anaemic fetuses <24 weeks may worsen outcomes due to parvovirus-induced myocarditis and reduced cardiac reserve.^{2, 4} The Society for Maternal-Fetal Medicine (SMFM) recommend a stepwise approach, whereby an initial partial transfusion is followed by a second IUT within 48 hours to achieve a near-normal fetal haematocrit, with a third procedure scheduled seven to ten days later if required.² In this case, close follow-up in our MFM unit with serial ultrasounds every two days confirmed good fetal tolerance (including ventricular function) following the first IUT, with the second transfusion performed after seven days.

There is a paucity of data on the long-term neurodevelopmental outcomes of children born after IUT for fetal anaemia due to parvovirus B19 infection. A recent MRI study suggested higher rates of abnormal fetal neuroimaging findings at 28-32 weeks, including cerebellar hypoplasia and intracranial haemorrhage, however the long-term significance of these findings remains unclear.⁵ MRI may detect subtle brain abnormalities, or white matter changes that may not be apparent on ultrasound, which can aid parental counselling and early neonatal management. Data from the LOTUS study,⁶ which evaluated the long-term neurodevelopmental outcomes in 291 children aged 2-17 years of age who had undergone IUT for haemolytic disease of the newborn, found that the overall incidence of neurodevelopmental impairment was low (4.8%). However, those with severe hydrops were at higher risk, as it was independently associated with neurodevelopmental impairment.⁶ Severe fetal anaemia and hydrops may contribute to cerebral injury either through ischaemic events, or haemodynamic changes in cerebral blood flow during IUT,⁸ but further studies are required to clarify these associations.

We report a case of congenital parvovirus B19 infection that illustrates how early referral, monitoring, and timely intervention can lead to excellent outcomes. With the recent surges of parvovirus B19 cases across Europe and the USA in 2023–2024,⁹ we stress the importance of heightened awareness and antenatal education in Australia. Additionally, our case underscores the importance of fetal brain MRI and neurological follow up.