Intrauterine transfusion in monochorionic twins with parvovirus B19 infection: Evidence of intertwin blood exchange

Abstract

Background

Parvovirus B19 infection can cause severe fetal anemia. Management in monochorionic twin pregnancies is challenging due to placental vascular connections.

Case

We report a case of severe fetal anemia in both fetuses of a monochorionic diamniotic twin pregnancy following maternal parvovirus B19 infection. Elevated middle cerebral artery peak systolic velocity (MCA‐PSV) was first detected at 16 weeks in twin A and reached 2.32 multiples of the median (MoM) in twin A and 2.30 MoM in twin B at 21+6 weeks. These findings were associated with polyhydramnios in both fetuses and ascites in twin B. Intrauterine transfusion was performed at 22+1 weeks, revealing hemoglobin levels of 3 g/dL in both fetuses. Transfusion of twin B resulted in an unexpected spontaneous increase in hemoglobin in twin A, suggesting intertwin blood transfer.

Results

Following minimal additional transfusion in twin A, MCA‐PSV normalized in both fetuses. The pregnancy was subsequently complicated by preeclampsia without severe features, and vaginal delivery occurred at 36+3 weeks. Both neonates had normal and identical hemoglobin levels at birth. Placental examination after delivery, with dye injection, demonstrated a single large arterio‐arterial anastomosis that had not been visualized prenatally.

Conclusion

Transfusion of one twin was followed by an immediate rise in hemoglobin in the co‐twin, indicating major intertwin blood exchange through a large arterio‐arterial anastomosis. Because such exchange cannot be predicted prenatally, both fetuses require individual assessment before and after transfusion.

1. INTRODUCTION

Parvovirus B19 infection is a well‐known cause of fetal anemia, which may lead to hydrops and fetal demise. In monochorionic twins, shared placental anastomoses can influence the severity and distribution of anemia between fetuses.

We report a case of severe fetal anemia in both fetuses of a monochorionic diamniotic twin pregnancy, highlighting the role of intertwin vascular exchange during intrauterine transfusion.

2. CASE PRESENTATION

The patient was a 34‐year‐old woman followed at Toulouse University Hospital, a tertiary care center in France. She had no significant personal or family medical history and was Rhesus D positive. Her obstetric history included one previous cesarean section in 2019 for failure to progress in labor, followed by the birth of a healthy infant.

This spontaneous twin pregnancy was monochorionic diamniotic, confirmed on first‐trimester ultrasound. The first‐trimester scan was unremarkable, with no crown‐rump length discordance or increased nuchal translucency. Cell‐free DNA screening for trisomies 13, 18, and 21 was negative. At 16 weeks' gestation, routine monitoring identified a borderline elevation of middle cerebral artery peak systolic velocity (MCA‐PSV) in twin A (1.50 multiples of the median [MoM]), while MCA‐PSV remained within the normal range in twin B (1.23 MoM), without other ultrasound signs of fetal anemia. No ultrasound features suggestive of twin‐to‐twin transfusion syndrome (TTTS) or twin anemia‐polycythemia sequence (TAPS) were observed. Doppler surveillance initially included MCA‐PSV measurement every 2 weeks. By 18 weeks' gestation, MCA‐PSV exceeded 1.5 MoM in both fetuses, and surveillance was intensified to weekly assessments when values subsequently increased to approximately 1.9 MoM. Given the technical challenges of transfusion at this early gestational age and the risks of repeated cordocenteses, expectant management with close ultrasound surveillance was preferred. At 21+6 weeks, MCA‐PSV reached 2.32 MoM in twin A and 2.30 MoM in twin B, prompting reassessment 48 h later and the decision to perform intrauterine transfusion at 22+1 weeks. Elevated MCA‐PSV values were associated with polyhydramnios (maximum vertical pockets of 81 mm in twin A and 74 mm in twin B) and ascites in twin B, consistent with early hydrops. Maternal serology showed seroconversion for parvovirus B19 between 12+5 and 17+5 weeks, with negative IgG and IgM at 12+5 weeks and positive IgG and IgM at 17+5 weeks. Kleihauer testing and irregular antibody screening were negative, ruling out fetomaternal hemorrhage and red blood cell alloimmunization.

Following the rapid development of ascites in twin B, severe fetal anemia was considered highly likely, and intrauterine transfusion by cordocentesis was proposed. After informed consent, the procedure was performed under combined spinal‐epidural anesthesia at 22+1 weeks.

2.1. Intervention details

Under ultrasound guidance, fetal blood sampling was performed in both twins at the placental cord insertion sites before transfusion because the severity of anemia in each fetus could not be reliably inferred from Doppler findings alone. Hemoglobin levels were 3 g/dL in both fetuses, confirming severe anemia. Once severe anemia had been confirmed in both fetuses, twin B was transfused immediately, without returning first to twin A, to limit the number of cordocenteses. The packed red blood cells used for transfusion had a hematocrit greater than 70%. The transfusion volume was calculated taking into account the estimated fetal blood volume (approximately 37 mL based on an estimated fetal weight of 370 g) and the risk of circulatory overload. Although the theoretical target hemoglobin level for this gestational age was approximately 13.5 g/dL, a more conservative initial target was chosen. An initial transfusion of 10 mL into twin B was performed, followed by iterative hemoglobin measurements, allowing adjustment of the final transfusion volume to 14.5 mL. A repeat blood sampling from twin A revealed a spontaneous increase in hemoglobin from 3.0 to 6.6 g/dL, likely due to intertwin blood transfer. Twin A then received 6 mL of packed red blood cells, of which 4.5 mL were withdrawn for the final laboratory assessments, resulting in a net transfused volume of 1.5 mL and a final hemoglobin of 9.4 g/dL; continued intertwin transfer from twin B during the procedure probably also contributed to this increase.

At the end of the procedure, MCA‐PSV values were 1.48 MoM in twin A and 1.30 MoM in twin B. Pre‐ and post‐transfusion data are summarized in Table 1. Parvovirus B19 Polymeras Chain Reaction (PCR) performed on the fetal blood sample from twin A showed a high viral load of 7.14 log copies/mL, confirming fetal infection. PCR testing of the amniotic fluid was therefore not considered necessary. A Kleihauer test performed on the pre‐transfusion fetal blood sample from twin A showed 100% fetal cells. Post‐transfusion Kleihauer testing could not be performed because repeat sampling was unsuccessful. Hemoglobin electrophoresis was not performed. PCR testing was not performed in twin B because obtaining an additional blood volume in the setting of severe anemia was considered potentially harmful. Given the monochorionic placentation, confirmed infection in twin A, maternal seroconversion, and similar hematological involvement of both fetuses, infection of twin B was considered highly likely, although it could not be formally confirmed.

TABLE 1.

Pre‐ and post‐transfusion hematologic parameters in both fetuses.

	Pre‐transfusion		Post‐transfusion
	Hb (g/dL)	Platelets (G/L)	Hb (g/dL)	Platelets (×109/L)
Twin A	3.1	168	9.4	99
Twin B	3.1	162	8.8	119

Abbreviations: CBC, complete blood count; Hb, hemoglobin.

2.2. Postoperative course

Postoperative monitoring included daily assessment of MCA‐PSV and fetal heart activity for 3 days, followed by weekly surveillance. MCA‐PSV remained stable between 1.3 and 1.5 MoM in both fetuses. No features of TTTS or TAPS were observed. Fetal growth remained appropriate. Fetal brain Magnetic Resonance Imaging at 32+1 weeks was normal in both fetuses.

The pregnancy was subsequently complicated by preeclampsia without severe features, diagnosed according to the 2020 ACOG criteria based on blood pressure at least 140/90 mmHg and a urine protein‐to‐creatinine ratio of 0.30, without any clinical or laboratory severe features [1]. Blood pressure was controlled with antihypertensive treatment. Delivery occurred vaginally at 36+3 weeks after cervical ripening with a Foley catheter. Twin A weighed 2310 g and twin B weighed 2550 g. The neonatal course was uneventful. Both neonates had identical hemoglobin levels at birth (16 g/dL). Placental examination with dye injection demonstrated a single large‐caliber arterio‐arterial anastomosis within a monochorionic diamniotic placenta (Figure 1). This anastomosis had not been identified on prenatal color Doppler ultrasound and was only demonstrated after delivery. At 6 months of age, both infants were in good health.

FIGURE 1.

Monochorionic diamniotic placenta after delivery, injected with colored dye (red, arteries; blue, veins). The green arrow indicates the single large‐caliber arterio‐arterial anastomosis (yellow arrowheads), which connects the arterial territory of twin A with that of twin B (yellow dashed lines).

3. DISCUSSION

Several cases of parvovirus B19 infection in dichorionic diamniotic twin pregnancies have been reported, typically describing asymmetric involvement, with one fetus severely affected and the co‐twin relatively spared [2, 3, 4, 5, 6]. Although infection of both fetuses is often confirmed, the mechanisms underlying this discordance remain unclear.

In contrast, both fetuses in our case presented with similarly severe anemia (hemoglobin 3 g/dL), suggesting effective hemodynamic equilibration through anastomoses.

To our knowledge, only one previous case of intrauterine transfusion in monochorionic twins affected by parvovirus B19 infection has been reported. Von Kaisenberg et al. described a case diagnosed at 22+3 weeks with polyhydramnios and hydrops, requiring four intrauterine transfusions using intraperitoneal and intracardiac approaches [7]. However, intra‐procedural hemoglobin measurements were not performed, preventing assessment of immediate intertwin blood exchange.

In the previously published case by Maisonneuve et al. [8], suspected anemia in both twins of a monochorionic diamniotic twin pregnancy was managed in the context of anti‐D alloimmunization. Twin A had an initial hemoglobin level of 3.0 g/dL and first received a 30‐mL intrauterine transfusion. During the following 30 min, MCA‐PSV decreased not only in twin A, from 1.64 to 1.19 MoM, but also spontaneously in twin B, from 2.02 to 1.64 MoM, suggesting intertwin passage of transfused red blood cells. As MCA‐PSV remained above 1.5 MoM in twin B, fetal blood sampling was subsequently performed, showing a hemoglobin level of 8.1 g/dL, and twin B received a 15‐mL intrauterine transfusion. In addition, the Kleihauer test performed on the blood sample from twin B, after transfusion of twin A, showed that fetal cells accounted for only 17% of circulating cells, providing further evidence of intertwin blood exchange through a placental vascular anastomosis. Subsequent transfusions were performed in twin A only and were sufficient to correct anemia in both fetuses, with normalization of MCA‐PSV. The placenta showed multiple arterio‐arterial anastomoses. The three published cases are summarized in Table 2.

TABLE 2.

Reported cases of intrauterine transfusion in monochorionic twin pregnancies complicated by severe fetal anemia.

Characteristics	Von Kaisenberg et al. [7]	Maisonneuve et al. [8]	Present case
Chorionicity	Monochorionic diamniotic twin pregnancy	Monochorionic diamniotic twin pregnancy	Monochorionic diamniotic twin pregnancy
Etiology of fetal anemia	Parvovirus B19 infection	Maternal anti‐D red blood cell alloimmunization	Maternal parvovirus B19 infection
Gestational age at diagnosis and IUT	Diagnosis at 22+3 weeks; IUTs at 22+3, 22+5, 23+2, and 23+3 weeks	Diagnosis and first IUT at 24 weeks; subsequent IUTs at 25, 27, and 30 weeks	MCA‐PSV elevation detected from 16 weeks; IUT at 22+1 weeks
Fetal presentation	MCA‐PSV approximately 2.3 MoM in both fetuses, with progressive hydrops in one twin	Suspected severe anemia in both fetuses (MCA‐PSV 1.64 MoM in twin A and 2.0 MoM in twin B), with ascites in both fetuses	Severe anemia in both fetuses (MCA‐PSV 2.32 MoM in twin A and 2.30 MoM in twin B), with ascites in twin B, consistent with early hydrops
Initial fetal hemoglobin	Not reported	Twin A: 3.0 g/dL; twin B: not reported (8.1 g/dL mL after IUT to twin A)	3.0 g/dL in both twins
Transfusion approach	Intra‐abdominal transfusion followed by three intracardiac transfusions because umbilical cord access was not possible	Both fetuses were transfused during the first procedure; subsequent intravascular transfusions were performed in twin A only	Intravascular transfusion of twin B followed by a limited supplementary transfusion of twin A
Volume administered during the IUT	First IUT: 10 mL to twin A and 10 mL to twin B Second IUT: 20 mL to twin A and 18 mL to twin B Third IUT: 22 mL to twin B Fourth IUT: 10 mL to twin A	First IUT: 30 mL to twin A and 15 mL to twin B Second IUT: 44 mL to twin A Third IUT: 36 mL to twin A Fourth IUT: 65 mL to twin A	14.5 mL to twin B; 6 mL to twin A, of which 4.5 mL were withdrawn for laboratory assessments (net transfused volume 1.5 mL)
Immediate effect on the co‐twin	Not assessed by intraprocedural hemoglobin measurement	Improvement in twin B after transfusion of twin A, with an immediate decrease in MCA‐PSV in both fetuses	Spontaneous increase in twin A hemoglobin from 3.0 to 6.6 g/dL after transfusion of twin B
Evidence of intertwin blood exchange	Not reported	Improvement in the non‐transfused twin and fetal cells accounting for only 17% of circulating cells in twin B after transfusion of twin A	Immediate increase in twin A hemoglobin from 3.0 to 6.6 g/dL after transfusion of twin B
Placental vascular findings	Not reported	Multiple arterio‐arterial anastomoses	Single large‐caliber arterio‐arterial anastomosis, not visualized prenatally
Pregnancy and neonatal outcomes	Resolution of hydrops and normalization of MCA‐PSV in both fetuses; vaginal delivery at 33+2 weeks after preterm prelabor rupture of membranes; neonatal hemoglobin 14.5 and 15.5 g/dL; normal neurological examinations	Normalization of MCA‐PSV; delivery at 31 weeks for abnormal fetal heart rate monitoring; neonatal hemoglobin 11.3 and 11.5 g/dL	Normalization of MCA‐PSV; vaginal delivery at 36+3 weeks after preeclampsia without severe features; neonatal hemoglobin 16 g/dL in both twins; normal examination in both infants at 6 months of age

Abbreviations: IUT, intrauterine transfusion; MCA‐PSV, middle cerebral artery peak systolic velocity; MoM, multiples of the median.

Taken together with the two previous cases, our observation suggests that intrauterine transfusion is feasible when severe fetal anemia is suspected in both fetuses of a monochorionic diamniotic twin pregnancy, depending on gestational age and accessibility. Transfusion may be initiated in the most accessible or most severely affected twin, followed by reassessment of the co‐twin. No data are available on the volume required to treat both fetuses; we suggest transfusing the first twin up to the ceiling used in singletons, namely a post‐transfusion hemoglobin not exceeding three times the initial value when baseline hemoglobin is below 5 g/dL, postulating that part of the volume will be shared with the co‐twin.

Reassessment of the co‐twin may rely on repeat hemoglobin measurement or on MCA‐PSV. However, there may be a latency period before a significant decrease in MCA‐PSV can be demonstrated after transfusion, and MCA‐PSV may also be falsely elevated for other reasons; in the present case, MCA‐PSV was therefore measured repeatedly before the decision to transfuse. In monochorionic pregnancies without signs of complications such as TTTS or TAPS, there is usually at least one large‐caliber anastomosis or several small‐caliber anastomoses allowing for hemodynamic balance between the two fetuses. Consequently, transfusion of a single twin may partially correct anemia in both fetuses, potentially reducing procedural risks, although this remains to be demonstrated.

4. CONCLUSION

In monochorionic diamniotic twin pregnancies complicated by fetal anemia, placental anastomoses may allow major intertwin blood transfer, so that transfusion of one twin can partially correct anemia in the co‐twin. Because this exchange cannot be predicted prenatally, both fetuses should be assessed individually before and after the procedure, and this approach requires confirmation in larger series.

AUTHOR CONTRIBUTIONS

Ninon Dupuis: Writing—original draft. Louise Paret: Writing—review and editing. Christophe Vayssière: Supervision. Blandine Hervy: Writing—review and editing. Marlène Sohier‐Lépine: Writing—review and editing.

CONFLICT OF INTEREST STATEMENT

The authors declare no conflicts of interest.

FUNDING INFORMATION

The authors received no specific funding for this work.

ETHICS STATEMENT

Ethical approval has been obtained for this study. Written and oral informed consent for publication of this case report was obtained from the patient.

DATA AVAILABILITY STATEMENT

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.