Infection with parvovirus B19 and the maternal, mirror syndrome

Abstract

In 2024, an extreme increase in the number of parvovirus B19 (B19V) infections occurred worldwide, including in the pregnant population, resulting in severe foetal morbidity and mortality. We describe the case of a 37-year-old patient (G2/P1) who was 26 weeks 0 days pregnant at admission and who presented with foetal hydrops and mirror syndrome due to B19V infection and sudden onset of acute perimyocarditis in the mother, possibly triggered by the foetal situation and severe anaemia.

Foetal hydrops is a life-threatening manifestation of foetal infection with B19V. Independent of whether it is immune or nonimmune, hydrops fetal is occurs in 1 : 1500 to 4000 pregnancies. In 6.1% of foetal hydrops cases, the hydrops mirrors the symptoms between the mother and the child. Mirror syndrome was defined as foetal hydrops and/or placentomegaly associated with the maternal development of pronounced oedema with or without preeclampsia symptoms. Due to the increase in infections and the potentially foetal consequences for the unborn child, the possible therapy, which requires well coordinated multidisciplinary cooperation, is relevant for anaesthesiologists as demonstrated in the following case.

The patient underwent two foetal transfusions and one foetal ascites puncture; consequently, she required anaesthesiological care on multiple occasions. We emphasise the importance of ensuring that patients with this condition are closely monitored, not only by the obstetrician but also by the anaesthesiologist, so that the clinical deterioration of the mother and/or the child can be quickly recognised and treated appropriately.

Introduction

A marked upsurge in acute parvovirus B19 (B19V) infection rate was recorded in Europe and in the United States in 2024. Although up to 50% of cases B19V infection in pregnant women remains asymptomatic, severe manifestations with severe anaemia, foetal hydrops and death may occur.^1–3 Foetal hydrops is a life-threatening consequence of foetal infection with B19V,^3,4 with hydrops fetalis occurring in 3.9% with an overall foetal death rate of 6.3%. It was shown that early intrauterine transfusion reduces mortality.^4,5 In 6.1% of foetal hydrops cases, the symptoms of the hydrops are mirrored between the mother and the child.⁶ Treating this potentially foetal condition in the unborn child requires well coordinated multidisciplinary cooperation and makes this case relevant for obstetric anaesthesiologists.

Only a few case reports have described severe cardiac involvement in adults.^7,8 Overall, the literature on cardiac manifestations triggered by B19V infection in adults is scarce, and we were unable to identify any studies on pregnant women. Hence our interest in this case of a pregnant woman with foetal hydrops, mirror syndrome due to B19V infection with the cardiac manifestation probably triggered by generalised endothelial dysfunction.

Case description

In August 2023, a 37-year-old patient (77 kg, 165 cm, BMI 28.3 kg m⁻²), ASA 2 (G2P1), who was at 26 weeks and 0 days gestation was referred to us for foetal hydrops therapy.

The patient's consent was obtained. Her medical history was uneventful, and taking no regular medication except for prenatal vitamins. A few weeks earlier, her first child acquired a B19V infection. The maternal serological test for active B19V infection was diagnosed by PCR in the foetal blood (789 billion copies ml⁻¹, cut-off <1000 copies ml⁻¹) obtained by cordocentesis. Foetal ultrasound revealed foetal hydrops with a pericardial effusion, cardiomyopathy, massive ascites and skin oedema (Fig. 1). Additionally, placentomegaly and reduced ammonic fluid levels were observed. The arteria cerebri media peak velocity (ACM PSV) was 80 cm s⁻¹ corresponding to 2.4 Multiples of Median (MoM, Fig. 2), which is highly suspicious for severe anemia.⁹ Severe anaemia was suspected and then confirmed by cordocentesis.

Fig. 1.

Prenatal sonographic images of the foetus demonstrating hydrops fetalis at 26 weeks of gestation.

(a) Cross section at the level of the cardiac four chamber view: cardiomegaly with pericardial effusion and thickened myocardium. (b) Perihepatic ascites (∗); (c) massive skin oedema around the head (double arrow).

Fig. 2.

The x-axis is gestational age in weeks.

The y-axis corresponds to the MoM values of the measured ACM PSV assessed by Doppler sonography. The red line represents the 1.5 MoM threshold defining the threshold to suspect severe foetal anaemia¹²; the black arrows indicate the moments of cordocentesis with IUT. ACM PSV, arteria cerebri media peak velocity; MoM, multiples of Median; IUTs, intrauterine transfusions.

Two intrauterine transfusions (IUT) were performed under tocolysis in single-shot spinal anaesthesia without any anaesthesiological complications. Betamethasone for foetal lung maturation was administered along with intravenous magnesium to ensure neuroprotection of the potentially preterm infant. The foetal haemoglobin level improved from 2.3 g dl⁻¹ at the first IUT to 13.8 g dl⁻¹ after the second IUT. In addition to severe foetal aplastic anaemia, thrombocytopenia was noted at 38 000 μl⁻¹ (reference value >150 000 μl⁻¹).

On day 4, the patient complained of tremor, dizziness, headache, shortness of breath, left-sided chest pain and minor flu symptoms. A nasopharyngeal swab for COVID-19 and a respiratory panel PCR were negative. B19V was detected in the maternal blood via PCR (942 000 copies ml⁻¹; cutoff <1000 copies ml). On day 5, there was increased shortness of breath and left-sided chest pain, and a productive cough was also observed. Other vital parameters were unremarkable at this time. However, the patient was unable to tolerate the supine position due to dyspnoea with a correspondingly low SpO₂ at 92%. An ECG showed no abnormalities (Fig. 3). Troponin-T was slightly elevated at 47 ng l⁻¹ (cut-off <14 ng l⁻¹), and creatine kinase and creatine kinase myocardial band levels were within the normal range. NT-proBNP and D-dimer levels were raised at 6171 pg ml⁻¹ (cut-off: <202 pg ml⁻¹) and 8087 μg l⁻¹ (cut-off: <500 μg l⁻¹), respectively. A transthoracic echocardiogram (TTE) showed minor pericardial effusion without haemodynamic restriction but otherwise unremarkable results (Fig. 4). There were no signs of cardiomyopathy or left ventricular heart failure. Thoracic computed tomography (CT) ruled out pulmonary embolism but revealed bilateral bronchopneumonia. The symptoms and results were interpreted as being indicative of perimyocarditis. Correspondingly, therapy consisting of colchicine twice a day, paracetamol and antibiotic treatment for pneumonia was started. The patient was transferred to the intermediate care unit (ICU), and regular nonstress tests were performed for foetal surveillance.

Fig. 3.

The ECG of the 37-year-old patient showed no PQ and ST segment changes or abnormalities.

Fig. 4.

The image shows the maternal four-chamber view at 26 weeks of gestation with normal biventricular function and no relevant valvular heart disease.

Biatrial dilatation and a small pericardial effusion (yellow arrow) were noted.

During the stay in the ICU, she developed hypertension with proteinuria and increased hepatic transaminase levels. Preeclampsia was suspected, and antihypertensive therapy with Labetalol was initiated. She also developed oedema, and her body weight increased from 77 kg to 82.3 kg. The angiogenic ratio of soluble Feline McDonough Sarcoma-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) was assessed.¹⁰ The sFlt-1 : PlGF ratio was 99. An sFlt-1 : PlGF quotient greater than 85 before the 34th week of pregnancy indicates a high risk that patient will or has developed preeclampsia.¹⁰ During the following days, the sFlt-1 : PlGF ratio decreased from 99 to 7. Given this development and the lack of other clinical features of preeclampsia, there was strong suspicion that mirror syndrome was an issue. No additional IUT was necessary, and the ACM PSV remained less than 1.5 MoM (Fig. 2).⁹

Foetal cardiomegaly with pericardial effusion was normalised, although massive foetal ascites persisted. For this reason, an ascites puncture with 300 ml fluid was performed. A high concentration of parvovirus was detected in ascites fluid. Subsequently, the foetal oedema and pericardial effusion improved significantly.

At 37th gestational week, an elective Caesarean section with spinal anaesthesia was performed. The male infant delivered presented with an Apgar score of 7/9/10 (pH of 7.28, birth weight of 2995 g, P49). The only residual sign of B19V infection in the child was confluent erythema on the left arm, but the clinical paediatric assessment at birth was otherwise unremarkable. PCR in the neonatal blood showed persistent B19V with 9 252 000 copies ml⁻¹ (normal <1000 copies ml⁻¹). Haemoglobin and platelet counts were in the normal range. Both mother and baby were discharged without any residual clinical concerns.

Discussion

Most B19V infections are asymptomatic or mild in immunocompetent adults. The clinical presentation associated with B19V infection varies greatly, with foetal infection leading to foetal hydrops at the life-threatening end of the spectrum. There are also unconfirmed disease associations including pericarditis and myocarditis. A causal link has not been definitively established,¹¹ and pericarditis as a manifestation of B19V infection is not typically described in the literature. This may be due to the fact that more than half of the cases of acute pericarditis in Western Europe are classified as idiopathic. Actually, the significance of the perimyocardial involvement of B19V also remains unclear. However, it is commonly suspected that they are of viral aetiology, but due to the typically benign course of the illness and the lack of clinical sequelae, proof of viral infection is not typically obtained.

In 2024, an increase in the number of B19V infections (including in the pregnant population) was reported in Europe. Clinical monitoring of both the babies and the mothers must be ensured so that any deterioration in particular can be diagnosed and treated at an early stage.^1,3

Mirror syndrome

In 1892, John W. Ballantyne described the association between maternal oedema in pregnancy and foetal and placental hydrops due to rhesus isoimmunisation. By definition, mirror syndrome refers to a maternal state in which symptoms reflect foetal hydrops. The literature currently suggests that it occurs in 5 to 30% of hydrops cases.¹² Maternal symptoms include excessive weight gain, oedema, hypertension, haemodilution, dyspnoea and proteinuria.^13–15 The pathophysiology of this manifestation of symptoms remains poorly understood, although some authors have suggested that placental disease with leakage of antiangiogenic factors into the maternal circulation may play an important role, thus displaying similarities with preeclampsia pathogenesis.¹⁶ Furthermore, the identification of mirror syndrome remains challenging, because its symptoms overlap with those of preeclampsia, and no uniform diagnostic criteria currently exist.¹⁷

A recent retrospective study by Sichitiu et al. has shown a perinatal mortality rate of 44.4% in foetal hydrops cases that were complicated by maternal mirror syndrome.¹⁵ Foetal therapy, whose primary goal is to reverse foetal hydrops, has been shown to alleviate or prevent maternal mirror syndrome. In contrast, during the period before the development of foetal therapy, only preterm delivery of the hydropic foetus and its placenta led to maternal recovery.

Synopsis

Given that an average of 10 days is necessary for the resolution of maternal mirror syndrome, and that acute pericarditis can take up to 6 weeks to resolve, close (postinterventional) monitoring should be emphasised in such cases.¹² Additionally, it should be kept in mind that a case of maternal mirror syndrome might become apparent only after foetal therapy, and that a patient with mirror syndrome, not unlike a patient with preeclampsia, can deteriorate rapidly. Possible maternal complications include postpartum haemorrhage, heart failure, pulmonary oedema and renal dysfunction.^12,17 Furthermore, the course of the acute pericarditis should be monitored, as pericardial tamponade is a possible complication, as is progression to perimyocarditis with left ventricular failure and arrhythmias. We would also like to emphasise that a woman with a hydropic infant should be referred to a tertiary care facility with an experienced maternal foetal medicine specialist and neonatology unit. The eventual delivery should be thoroughly coordinated between the obstetrician, neonatologist and anaesthesiologist, with the decision being made on a case-by-case basis. Anaesthesiological considerations related to the management of Caesarean delivery include the choice of neuraxial vs. general anaesthesia, consideration to extended haemodynamic monitoring, and other supportive therapy.

Conclusion

We report a rare combination of pathologies in a pregnant woman resulting from infection with B19V, which had a favourable outcome for both the mother and child. In our opinion, this report is even more relevant in light of the worldwide increase in B19V infections, especially in pregnant women. As the aetiology of mirror syndrome is still a matter of debate, we cannot exclude the possibility that a direct, virally induced cardiac insult to the mother or (auto-)immunopathy may explain these transient preeclampsia-like clinical findings. Longitudinal surveillance of the sFlt-1 : PlGF ratio could be helpful in cases of suspected mirror syndrome, not only in ruling out preeclampsia but also in detailing the recovery from the altered angiogenic imbalance, as seen in our case. There needs to be an especial awareness that an acute deterioration of both the mother and the child(ren) can occur. Consequently, these patients should be cared for within a multidisciplinary team, choosing suitable strategies for both anaesthesiological and obstetric strategies for the mother and her child(ren) and, if necessary, initiating a preterm delivery of the baby, as this may significantly influence the outcome.