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Keywords:

  • monochorionic twin;
  • reversal of twin–twin transfusion syndrome;
  • twin anemia-polycythemia sequence (TAPS);
  • twin oligo-polyhydramnios sequence (TOPS);
  • twin–twin transfusion syndrome (TTTS)

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. CASE REPORT
  5. DISCUSSION
  6. REFERENCES

ABSTRACT  Antenatal sonographic diagnosis of twin–twin transfusion syndrome (TTTS) is based on findings of a twin oligo-polyhydramnios sequence (TOPS) observed in monochorionic twin fetuses. However, TTTS can develop without a significant characteristic intertwin discordance in the amniotic fluid volumes. We report an uncommon form of TTTS without TOPS showing severe anemia in one twin and polycythemia in the other. Based on sonographic findings, it is considered that the recipient twin became the donor later in gestation, and vice versa. It is concluded therefore that even in the absence of TOPS, the possibility of severe TTTS with a suspected reversal of donor-recipient phenotypes during pregnancy should not be excluded, and serial Doppler studies including the measurement of the middle cerebral artery peak systolic velocity should be routinely performed even in seemingly uncomplicated monochorionic twin fetuses without TOPS.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. CASE REPORT
  5. DISCUSSION
  6. REFERENCES

Twin–twin transfusion syndrome (TTTS) is a serious complication affecting 10–15% of monochorionic twin pregnancies (Sebire et al. 1997). On the basis of placental vascular anastomoses between the two circulations, an unbalanced intertwin transfusion can develop (Lopriore et al. 1995; Huber & Hecher 2004). The donor twin shows hypovolemia and oligo-/anuria (small bladder), and results in oligohydramnios (‘stuck twin’ syndrome). In contrast, the recipient becomes hypervolemic and polyuric leading to polyhydramnios, and because of volume overload, gradually shows cardiac dysfunction with cardiomegaly, hypertrophic cardiomyopathy, biventricular regurgitation, and venous overload resulting in hydrops. Another characteristic of TTTS is a fetal growth discrepancy in favor of the recipient.

The problem of TTTS is the high perinatal morbidity and mortality. When single intrauterine death occurs, nearly 50% of the remaining twin dies or survives with permanent disabilities (Bajoria et al. 1999). Current treatment options include amnioreduction and laser coagulation of vascular anastomoses, both of which achieve improved survival rates.

In the antenatal period, the stage of TTTS is determined using Quintero's classification based on ultrasound criteria (Quintero et al. 1999). According to this, a diagnosis of TTTS is made when a sonographic evidence of twin oligo-polyhydramnios sequence (TOPS) is observed in monochorionic twin fetuses. TOPS is defined by deepest vertical depths of ≤2 cm and ≥8 cm in the donor's and recipient's amniotic sac, respectively (stage I). Therefore, diagnosis and treatment of TTTS are usually considered after TOPS becomes evident in monochorionic twin fetuses.

In the following report, we present an uncommon form of TTTS without TOPS showing severe anemia in one twin and polycythemia in the other, with a reversal of donor-recipient phenotypes during the pregnancy period. Our case may suggest a further need for a careful management of possible TTTS even in seemingly uncomplicated monochorionic twin fetuses without TOPS.

CASE REPORT

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. CASE REPORT
  5. DISCUSSION
  6. REFERENCES

A 37-year-old Japanese woman, gravida 2, para 2, was referred to our hospital at 29+4 weeks of gestation for perinatal management of a monochorionic-diamniotic twin pregnancy. Although no abnormalities were noted by ultrasound (US) examination before her first visit to our hospital, our first US showed that twin 1 had a mildly dilated right cardiac atrium and ventricle with mild pericardial effusion (Fig. 1A), and a tricuspid regurgitation (Fig. 1B). The estimated fetal weight of twins 1 and 2 was 1443 g and 1340 g, respectively. Both fetuses had a normally filled bladder and a normal amniotic fluid volume (the deepest vertical depth of twin 1 and 2 was 3.4 cm and 3.2 cm, respectively). No malformations were noted in either of the twins. The patient was admitted for close perinatal management at 29+6 weeks. Because of increased uterine activity, the intravenous administration of ritodrine hydrochloride was initiated.

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Figure 1. (A) Twin 1 shows a mildly dilated right cardiac atrium and ventricle at 29+4 weeks. An arrow indicates mild pericardial effusion. (B) Twin 1 shows a tricuspid regurgitation.

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During the antenatal US follow-up, no remarkable changes were observed in the size of the heart and the amount of pericardial effusion in twin 1. The estimated fetal weight of both twins was within normal limits (Fig. 2) and they had a normally filled bladder and a normal amniotic fluid volume throughout the pregnancy period. Resistance index of the umbilical and the middle cerebral artery in both fetuses also remained within normal limits. Cardiotocogram demonstrated a reassuring fetal heart rate pattern in both fetuses until 32+1 weeks.

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Figure 2. Estimated fetal body weight of both twins during pregnancy.

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At 32+2 weeks', although both twins had a normal amniotic fluid volume demonstrated by US examination, the fetal heart rate monitoring of twin 1 showed loss of variability (Fig. 3). Because of non-reassuring fetal status of twin 1, two female infants were delivered by cesarean section. Infant 1 weighed 1420 g and was pale, whereas infant 2 weighed 1696 g and was plethoric. The birth weight discordance of these infants was 16%. Apgar scores at 1 and 5 minute after birth were 2/4 and 6/6 for infant 1 and 2, respectively. Umbilical arterial pH of these infants were 7.25 and 7.30, respectively, and hemoglobin contents were 4.7 g/dL and 24.9 g/dL (with absolute reticulocyte count 390 × 103 and 56 × 103), respectively. As demonstrated in the antenatal period, however, US examination of infant 1 also revealed a mildly dilated right cardiac atrium and ventricle with mild pericardial effusion and a tricuspid regurgitation in spite of severe anemic condition. In contrast, no pathological changes were noted in the heart of infant 2 who showed polycythemia. Although no symptoms of acute hemorrhagic hypovolemic shock were present in infant 1 at birth (heart rate 140 bpm, blood pressure 44/35 mmHg), she required a blood transfusion. Cranial US examination in both infants revealed no abnormalities. No serious complications were observed in either of the infants, and they were discharged from hospital 9 weeks after birth.

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Figure 3. Fetal heart rate monitoring at 32+2 weeks of gestation. The thick line indicates the heart rate of twin 1, and the thin line indicates that of twin 2.

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The placenta was monochorionic-diamniotic, with a velamentous insertion of the edematous umbilical cord of twin 2 (Fig. 4A). Obvious vascular anastomosis between the twins could not be confirmed by visual inspection of the placenta. The placental territory of twin 1 was pale, and three times larger than that of twin 2, which was plethoric (Fig. 4B). Histologic examination revealed edematous villi in the placental territory of twin 1 (Fig. 4C) and severe vascular congestion in that of twin 2 (Fig. 4D). Unfortunately, the placenta was formalin-fixed without an injection study using colored dye. This made it difficult to investigate vascular structure and anastomosis in detail, and DNA fragment analysis of the placental tissues could not be performed.

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Figure 4. (A) The placenta was monochorionic-diamniotic, with a velamentous insertion of the edematous umbilical cord of twin 2. (B) The placental territory of twin 1 was pale, and three times larger than that of twin 2, which was plethoric. (C) Histological examination revealed edematous villi in the placental territory of twin 1. Hematoxylin-eosin staining (HE), ×40. (D) Histological examination revealed severe vascular congestion in the placental territory of twin 2. Hematoxylin-eosin staining (HE), ×100.

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DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. CASE REPORT
  5. DISCUSSION
  6. REFERENCES

Based on antenatal and neonatal findings, twin 1, who initially presented with symptoms of the recipient fetus in TTTS (that is, the fetus whose placental territory was three times larger than that of the other fetus and who had a mildly dilated right cardiac atrium and a ventricle with mild pericardial effusion and a tricuspid regurgitation, without any cardiac structural abnormalities), was ultimately found to have symptoms of the donor (a pale infant who showed severe anemia with very high reticulocyte counts) at birth, whereas infant 2 presented with typical symptoms of the recipient (a plethoric infant who showed polycythemia). It is unlikely that this could have been due to mislabeling of the two fetuses, because the twins were discordant for fetal abnormality, that is, only twin 1 showed a cardiomegaly and pericardial effusion throughout the pregnancy period.

The phenomenon of such a reversal of the donor-recipient phenotype could be explained by hemodynamic changes in the fetus, for example, because of primary cardiac problems in the fetus, or by the placental angioarchitecture (arterio-arterial anastomoses compensating unbalanced transfusion), not only due to velamentous insertion of the edematous umbilical cord of twin 2. During fetal development, the rate of transfusion is probably constantly changing and is highly sensitive to fluctuations in the fetal blood pressure. In contrast, the placental volume increases during pregnancy, possibly ameliorating the unbalance in the placental share between the twins (Meyberg-Solomayer et al. 2004). Regardless of several hypotheses, the explanation of reversal TTTS is clearly still incomplete. Unfortunately, pathological examination could not reveal the type of anastomoses (arterio-arterial, veno-venous or arterio-venous connections) in our case. Wee et al. described five cases with a reversal of the direction of TTTS among a large cohort of 96 prospectively studied cases having TTTS (Wee et al. 2004).

The present case indicates that monochorionic twin fetuses can actually develop TTTS without TOPS resulting in severe fetal or neonatal hematological complications. Differential diagnosis in such monochorionic twins with highly discordant hemoglobin values at birth includes acute peripartum TTTS and chronic TTTS. The common form of chronic TTTS, however, can be ruled out because of the absence of typical findings of TOPS.

In acute peripartum TTTS, the anemic infant generally has clinical symptoms of hemorrhagic hypovolemic shock, such as pallor, tachycardia and hypotension (Lopriore et al. 2005). Also, reticulocyte counts after acute blood loss are typically not increased due to lack of time for compensatory hematopoiesis. In the present case, the typical clinical symptoms of acute perinatal blood loss were not observed in the anemic infant 1. Moreover, very high reticulocyte counts were measured in this infant (Lopriore et al. 2005), suggestive of chronic rather than acute blood loss.

Other possible causes of isolated anemia or polycythemia can also be ruled out. Chronic anemia in a newborn may result from a partial placental abruption, infection or chronic fetomaternal hemorrhage. The associated combination with polycythemia in the cotwin clearly suggests a form of fetofetal transfusion rather than fetomaternal transfusion. Common causes of polycythemia, such as chronic hypoxia associated with intrauterine growth restriction can also be excluded. Reticulocyte counts in polycythemic infant 2 were normal for gestational age (Lopriore et al. 2005), suggesting that polycythemia in this infant resulted from chronic TTTS rather than from the increased erythropoiesis secondary to chronic hypoxia.

The placental territory of twin 1 was three times larger than that of twin 2. It is supposed that the placenta of twin 1 had original superiority over that of twin 2 in blood flow distribution. However, the placental territory of twin 1 was pale, while that of twin 2 was plethoric with severe vascular congestion. It is considered therefore that superiority in blood flow distribution changed during the pregnancy period. This implies that twin 1 was initially a recipient and later became a donor. In contrast, twin 2 might initially have been a donor and changed to become a recipient.

Lopriore et al. suggested that atypical forms of chronic TTTS without TOPS, associated with anemia in one twin and polycythemia in the other, should be referred to as twin anemia-polycythemia sequence (TAPS) (Lopriore et al. 2007). It is not clear why the intertwin amniotic fluid discordance did not develop in our case. These twins may have been born before TOPS had become evident. It is reported that the intertwin hemoglobin and amniotic fluid discordance varies with the state of progression of chronic TTTS (Denbow et al. 1998). It is conceivable that some twins with chronic TTTS may first develop TAPS and then TOPS.

TAPS differs significantly in terms of diagnosis and management from the typical form of chronic TTTS with the characteristic signs of TOPS. The presence of TOPS is considered to be the major antenatal diagnostic criterion for chronic TTTS. Although marked fetal growth discordance and hemoglobin difference may also be present, these features are not considered to be the key elements in the diagnosis of chronic TTTS (Jain & Fisk 2004). Routine Doppler studies are a standard requirement to determine Quintero's staging once the diagnosis of chronic TTTS is made, and measurement of the middle cerebral artery peak systolic velocity (MCA-PSV) is helpful in the diagnosis of fetal anemia after single intrauterine fetal death (acute peripartum TTTS) (Senat et al. 2003) and laser surgery (Robyr et al. 2006). Lopriore et al. further suggested that Doppler studies including MCA-PSV measurement should be performed during each follow-up visit in all uncomplicated monochorionic twin pregnancies, even in the absence of TOPS.

In conclusion, perinatologists involved in the care of monochorionic twins should keep the differential diagnosis of acute or chronic TTTS in mind, even in the absence of TOPS. TAPS can occur in the absence of the characteristic intertwin discordance of the amniotic fluid volume. Indeed, the present case suggests a further need for a careful management of possible TTTS with a suspected reversal of donor-recipient phenotypes during pregnancy in monochorionic twin fetuses even without TOPS.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. CASE REPORT
  5. DISCUSSION
  6. REFERENCES