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Keywords:

  • acute peripartum;
  • hemoglobin;
  • monochorionic twins;
  • twin–twin transfusion syndrome

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Disclosure
  8. References

Aim

The aim of this study was to examine the incidence, placental characteristics and outcome in acute peripartum twin–twin transfusion syndrome (TTTS).

Material and Methods

All consecutive cases of monochorionic (MC) twins admitted to our center were included in the study. We excluded cases with chronic TTTS or twin anemia polycythemia sequence. Acute peripartum TTTS was defined when the inter-twin hemoglobin difference at birth was >8 g/dL.

Results

A total of 241 MC twin pregnancies were included in the study. Acute peripartum TTTS was detected in six cases (2.5%, 6/241). Vaginal delivery occurred more often in the acute peripartum TTTS group compared to the control group of uncomplicated MC pregnancies, 100% (6/6) versus 57% (135/235) (P = 0.002), respectively. Acute anemia was detected only in firstborn twins. Placental angioarchitecture in acute peripartum TTTS was similar to the placentas in the control group.

Conclusions

The incidence of acute peripartum TTTS is low (2.5%). Birth order and mode of delivery appear to be associated with increased risk of acute peripartum TTTS.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Disclosure
  8. References

All monochorionic (MC) twins have placental vascular anastomoses connecting the circulation of both twins. Vascular anastomoses allow inter-twin blood transfusion during the course of the pregnancy and may lead to several disorders, including chronic twin–twin transfusion syndrome (TTTS) and spontaneous twin anemia-polycythemia sequence (TAPS). Chronic TTTS affects approximately 9% and is usually diagnosed in the second trimester of pregnancy.[1] Diagnosis of chronic TTTS is reached by demonstrating the characteristic twin oligo-polyhydramnios sequence (TOPS) on prenatal ultrasound. Spontaneous TAPS is a novel form of chronic feto-fetal transfusion characterized by the presence of large inter-twin hemoglobin (Hb) discordances without prenatal signs of TOPS.[2] Spontaneous TAPS occurs in approximately 5% of MC twin pregnancies.[3]

Anecdotal reports suggest that acute and large inter-twin blood transfusion may also occur during delivery.[4, 5] This form of TTTS, often referred to as acute peripartum (or perinatal) TTTS, leads to a large difference in Hb levels at birth between the donor and the recipient. Acute peripartum TTTS is thought to occur due to acute shifts of blood from one twin to the other due to blood pressure differences following uterine contractions or changes in fetal positions.[4, 6] Research data on acute peripartum TTTS is, however, extremely scarce. Knowledge on the incidence, pathophysiology, risk factors and neonatal outcome after acute peripartum TTTS is lacking.

The aim of our study was to estimate the incidence, risk factors, placental characteristics and neonatal outcome after acute peripartum TTTS.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Disclosure
  8. References

All consecutive MC diamniotic twins delivered at our center between April 2002 and April 2012 were included in this retrospective study. Perinatal outcome data on all MC twins delivered at our center are prospectively entered in our dedicated database. We used the database to retrieve all required medical information for this study. We included only MC twin pregnancies that delivered >24 weeks' gestation and resulted in two liveborn twins. Exclusion criteria were: MC twins with chronic TTTS, TAPS, acardiac twinning and MC triplets (or higher order). Diagnosis of chronic TTTS was based on the presence of TOPS according to internationally accepted standardized antenatal ultrasound criteria.[7] Diagnosis of TAPS was based on the presence at least two of the following three criteria: (i) inter-twin Hb difference > 8.0 g/dL; (ii) reticulocyte count ratio > 1.7; and (iii) placental injection with colored dye showing the presence of only minuscule (diameter < 1 mm) anastomoses.[3] The reticulocyte count ratio is calculated by dividing the reticulocyte count of the infant with the lower Hb level by the reticulocyte count of the co-twin.

For the purpose of this study, we defined acute peripartum TTTS in MC twins as an Hb difference > 8 g/dL at birth, without signs of chronic TTTS or spontaneous TAPS.

The angioarchitecture of all MC placentas was studied by injection with colored dye, as previously described.[8]

The following perinatal data were collected: gestational age at delivery, mode of delivery, sex, birthweight and inter-twin growth discordance. Growth discordance was calculated by dividing the difference in birthweights by the birthweight of the larger twin.

The following neonatal data were collected: respiratory distress syndrome (RDS), patent ductus arteriosus (PDA), necrotizing enterocolitis (NEC) and severe cerebral injury detected on neonatal cranial ultrasound examination. After birth, cranial ultrasound scans were performed routinely in all MC twins according to our previously described clinical protocol.[9] Intraventricular hemorrhages (IVH) were classified according to Volpe[10] and periventricular leukomalacia (PVL) was graded according to de Vries et al.[11] Severe cerebral lesions were defined as the presence of at least one of the following: IVH grade III or IV, PVL ≥ grade II, porencephalic cysts and ventricular dilatation. Ventricular dilatation was present when the width of one or both lateral ventricles exceeded the 97th percentile.[12]

Hb levels and reticulocyte count were routinely assessed at birth from umbilical cord blood. As Hb levels may not be reliable when measured shortly after acute blood volume shifts, a second venous Hb level was analyzed on day 2, when clinically indicated. Inter-twin Hb difference was defined as absolute Hb difference (higher Hb value minus lower Hb value). Hb levels were analyzed in relation to birth order (twin 1 vs twin 2). We recorded the use of blood transfusion and partial exchange transfusion during the first day of life. Acute hemorrhagic hypovolemic shock was defined as a combination of pallor, tachycardia (heart rate > 160 b.p.m.) and/or hypotension, requiring treatment with volume expanders, blood transfusion and/or inotropic support.[13] Hypotension was defined as a systolic blood pressure below the 3rd percentile for gestational age.[14]

We studied the incidence and risk factors of acute peripartum TTTS and investigated differences in placental angioarchitecture, neonatal mortality and morbidity between the group with acute peripartum TTTS and the control group of uncomplicated MC twins.

The study was exempt from Institutional Review Board Approval as ethical approval and informed consent in the Netherlands is not needed for anonymized studies with medical charts.

Statistics

Student t-tests were used to compare continuous variables between the two groups. Results of categorical variables were compared using Fisher's exact test. A P-value < 0.05 was considered to indicate statistical significance. All statistical data were analyzed using spss 17.0.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Disclosure
  8. References

A total of 483 consecutive MC twin pregnancies were delivered at our center during the study, of which 241 fulfilled our inclusion criteria. We excluded 242 MC twin pregnancies due to chronic TTTS (n = 229), spontaneous TAPS (n = 7), acardiac twinning (n = 2) and MC triplets (n = 4).

Acute peripartum TTTS was detected in six pregnancies (2.5%; 6/241). All cases of acute peripartum TTTS occurred after vaginal delivery (100%, 6/6), whereas 57% (135/235) of deliveries in the control group of uncomplicated MC pregnancies occurred through vaginal delivery (P = 0.002). In each of the six cases with acute peripartum TTTS, the anemic twin (donor twin) was the firstborn twin. Perinatal characteristics in the MC twin pregnancies with and without acute peripartum TTTS are shown in Table 1.

Table 1. Perinatal characteristics in 241 monochorionic twin pregnancies with and without acute peripartum TTTS
 Acute peripartum TTTS (n = 6 pregnancies; 12 fetuses)Control group (n = 235 pregnancies; 470 fetuses)P-value
  1. †Value given as mean ± standard deviation. TTTS, twin–twin transfusion syndrome.

Vaginal delivery n (%)12 (100%)270(57%)0.002
Gestational age at delivery (weeks)33.5 ± 3.433.8 ± 2.80.755
Birthweight (g)2060 ± 7992080 ± 6300.913
Birthweight discordance %17.6 ± 16.116.0 ± 12.50.783
Female n (%)10 (83%)238(51%)0.037

Detailed information on obstetrical and neonatal characteristics for the six cases of acute peripartum TTTS are presented in Table 2. Antenatal Doppler ultrasound measurements of the middle cerebral artery peak systolic velocity (MCA-PSV) were performed in only one of the six cases and showed normal values.

Table 2. Characteristics in the six cases with acute peripartum TTTS
Acute TTTSCardiotocographyGestational age at deliveryBirthweightMode of deliveryDonorHemoglobin level (reticulocyte count)Neonatal outcome
  1. CIF, caput in fundo; CTG, cardiotocogram; TTTS, twin–twin transfusion syndrome.

DonorRise in baseline, minimal variability35 weeks2163 gVertex position, vaginallyTwin 112.1 g/dL (4.3%)Blood transfusion Mild perinatal asphyxia
RecipientUneventful2130 gVertex position, vaginally22.1 g/dL (4.5%)Uneventful
DonorTachycardia with variable decelerations35 weeks1760 gVentouse due to suboptimal CTGTwin 112.7 g/dL (5.7%)Uneventful
RecipientUneventful2936 gVentouse due to suboptimal CTG23.8 g/dL (5.7%)Partial exchange transfusion
DonorTachycardia30 weeks915 gVertex position, vaginallyTwin 111.6 g/dL (5.9%)Died after resuscitation at birth
RecipientUneventful1230 gVertex position, vaginally20.9 g/dL (6.8%)Respiratory distress syndrome
DonorUneventful28 weeks1149 gVertex position, vaginallyTwin 113.3 g/dL (7.5%)Respiratory distress syndrome
RecipientUneventful1121 gCIF, breech extraction21.4 g/dL (6.9%)Respiratory distress syndrome
DonorRise in baseline, minimal variability36 weeks2515 gVertex position, vaginallyTwin 112.7 g/dL (6.1%)Uneventful
RecipientUneventful until birth of twin 1; from then on tachycardia and saltatory3310 gVentouse due to suboptimal CTG22.9 g/dL (5.6%)Uneventful
DonorMinimal variability, variable decelerations37 weeks2750 gVentouse due to suboptimal CTGTwin 110.0 g/dL (3.1%)Blood transfusion, Mild perinatal asphyxia
RecipientUneventful2665 gVentouse due to suboptimal CTG19.0 g/Dl (4.3%)Uneventful

Anastomotic pattern was examined in 100% (6/6) of placentas after acute peripartum TTTS and 91% (214/235) of placentas in the control group. Superficial arterio-arterial anastomoses were found in each placenta with acute peripartum TTTS. We detected no significant differences in placental angioarchitecture between the groups with and without acute peripartum TTTS (Table 3).

Table 3. Characteristics in placentas with and without acute peripartum TTTS
 Acute Peripartum TTTS (n = 6)Control group (n = 235)P-value
  1. †Value given as mean ± SD. AV, arterio-venous; AA, arterio-arterial; TTTS, twin–twin transfusion syndrome; VV, veno-venous.

AV anastomoses present n/N (%)6/6 (100%)205/214 (95.8%)0.776
AV anastomoses from twin 1 to twin 2 n6.0 ± 3.03.5 ± 3.00.097
AV anastomoses from twin 2 to twin 1 n6.0 ± 3.23.4 ± 3.00.101
Total number AV anastomoses n12.0 ± 5.76.9 ± 4.90.077
AA anastomoses present n/N (%)6/6 (100%)197/214 (92.1%)0.614
Total number of AA anastomoses n1.2 ± 0.41.0 ± 0.40.309
VV anastomoses present n/N (%)3/6 (50%)53/214 (24.7%)0.174
Total number of VV anastomoses n0.8 ± 1.00.3 ± 0.50.231
Total number of anastomoses n14.0 ± 6.38.1 ± 5.10.072
Velamentous cord insertion n/N (%)1/12 (8%)90/428 (21%)0.474

Hemoglobin level at birth in donor and recipient twins was 12.0 ± 1.2 g/dL and 21.7 ± 1.7 g/dL, respectively (P < 0.01). All donors had normal reticulocyte counts at birth (see Table 2). Two donors (33%) required an acute blood transfusion on day 1 and one recipient (17%) required a partial exchange transfusion on day 1. Neonates in the acute peripartum TTTS group required volume expansion or inotropics at birth more often (Table 4). One donor (delivered at 30 weeks' gestation) died at birth due to intractable respiratory failure. Autopsy was performed but did not reveal a clear cause of death.

Table 4. Morbidity and mortality in neonates with and without acute peripartum TTTS
 Acute peripartum TTTS (n = 12)Control group (n = 470)P-value
  1. †Value given as mean ± SD. Hb, hemoglobin; TTTS, twin–twin transfusion syndrome.

Hb level in first twin on day 1 (g/dL)12.0 ± 1.216.2 ± 2.7<0.001
Hb level in second twin on day 1 (g/dL)21.7 ± 1.717.0 ± 2.7<0.001
Inter-twin Hb difference on day 1 (g/dL)9.6 ± 1.12.1 ± 1.9<0.001
Hb level in first twin on day 2 (g/dL)10.3 ± 0.613.6 ± 3.7<0.001
Hb level in second twin on day 2 (g/dL)19.3 ± 1.914.5 ± 4.3<0.001
Inter-twin Hb difference on day 2 (g/dL)8.4 ± 2.43.2 ± 2.4<0.001
Reticulocyte count ratio1.0 ± 0.21.0 ± 0.10.405
Blood transfusion n (%)2 (17%)13 (3%)0.050
Partial exchange transfusion n (%)1 (8%)3 (1%)0.096
Volume expansion n (%)5 (42%)52/411 (12.5%)0.014
Inotropic medications n (%)4 (33%)27/410 (7%)0.008
Respiratory distress syndrome n (%)3 (25%)57 (13%)0.203
Patent ductus arteriosus n (%)0 (0%)7 (2%)0.827
Necrotizing enterocolitis n (%)0 (0%)13 (3%)0.710
Severe cerebral injury n (%)0 (0%)9 (2%)0.810
Neonatal death n (%)1 (8%)8 (2%)0.205

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Disclosure
  8. References

This study shows that the incidence of acute peripartum TTTS is low (2.5%, 6/241) and could be associated with mode of delivery and birth order. The incidence of acute peripartum TTTS found in this study is similar to the incidence of 1.5% (2/135) recently reported by Suzuki et al.[15] In each one of the six cases with acute peripartum TTTS detected in our study, delivery occurred vaginally and the firstborn twin was the donor twin. Whether birth order and mode of delivery could play a role in the development of acute peripartum TTTS could not reliably be assessed in this study due to the low occurrence rate.

A handful of case reports of MC twins with acute peripartum TTTS have been reported and these have also recently been summarized in the literature.[16] Diagnostic criteria for acute peripartum TTTS vary among the published case reports, but always include a significant Hb difference at birth. To reach the correct diagnosis in a twin pair with large Hb difference at birth, perinatologists should first rule out the presence of chronic TTTS and TAPS. Diagnosis of chronic TTTS is based on antenatal ultrasound findings of the characteristic oligo-polyhydramnios sequence,[17-21] whereas diagnostic criteria for TAPS are based on abnormal antenatal Doppler findings (suggestive of fetal anemia and fetal polycythemia, respectively) and/or abnormal postnatal hematological findings (large Hb difference with significant reticulocytosis in the donor twin) and typical placental characteristics after colored-dye injection. Unfortunately, most case reports of acute peripartum TTTS were incomplete and failed to mention the results of antenatal ultrasound examinations, reticulocyte count at birth and findings on placental injection studies.[16] Detailed information is essential to rule out more common causes of high Hb discordance at birth, such as chronic TTTS or TAPS.

The pathogenesis of acute peripartum TTTS remains unclear. Superficial vascular anastomoses have been suggested to be responsible for acute inter-twin blood transfusions.[22] In this study, superficial anastomoses were present in all cases with acute peripartum TTTS. However, these anastomoses are also present in the majority of uncomplicated MC pregnancies. Additional factors must therefore be responsible for the development of acute peripartum TTTS. In theory, acute fetal blood loss from the donor twin into the circulation of the recipient twin may occur as a result of variations in blood pressure due to uterine contractions or fetal positions, however strong evidence is not available. As shown in this study, birth order and mode of delivery may also play a role in the cause of acute peripartum TTTS. In agreement with previous studies, we found that the Hb levels in firstborn twins are lower than in second-born twins.[23-26] Hypothetically, after clamping of the firstborn's cord, uterine contractions may allow placental blood from the first twin's low-pressure placental bed to be transfused through the low-resistance superficial vascular anastomoses into the higher pressure circulation of the second twin.

Optimal obstetrical management in uncomplicated MC twins is not yet well established. Based on the data from this study we cannot determine if a planned cesarean delivery may avoid or reduce the risk of acute TTTS. Recommendations on the mode of delivery in MC twin pregnancies remain controversial. Nevertheless, although our study was not designed to address obstetrical management, perinatologists should be aware that acute peripartum TTTS is a rare complication in MC twins. Further studies are warranted to guide fetal medicine specialists and help determine the optimal obstetrical management in MC twin pregnancies, including mode and timing of delivery as well as optimization of diagnostic tools (Doppler ultrasound, cardiotocogram [CTG]).

In theory, fetal hemorrhage and severe anemia in the donor twin with acute peripartum TTTS should lead to increased fetal heart rate and/or sinusoidal CTG pattern. In our study, however, only two of the six donors had signs of fetal tachycardia. Suzuki et al. reported two cases with acute peripartum TTTS[15] in which in one case the donor showed tachycardia, whereas in the other the donor had a normal fetal heart rate. According to the authors, differences in CTG patterns in acute peripartum TTTS may be due to differences in amount of inter-twin blood transfusion and elapsed time.[15] Whether careful evaluation of fetal heart rate patterns on CTG may help timely detection of acute peripartum TTTS is not clear.

Our data should be interpreted with care due to the retrospective nature of the study and the relatively small sample size. In addition, due to the lack of international consensus on the definition of acute peripartum TTTS, we defined (for the purpose of this study) our own criteria to distinguish acute peripartum TTTS from chronic TTTS and TAPS. Any attempts to compare our findings with other case series may thus be unreliable due to the use of other (or no) definitions.

In conclusion, we report a low incidence (2.5%) of acute peripartum TTTS in MC twin pregnancies. All detected cases of acute peripartum TTTS occurred after vaginal delivery and firstborn twins were the donor twins. Although birth order and mode of delivery may play a role, the exact pathophysiology of this rare form of acute peripartum feto-fetal transfusion still needs to be elucidated.

Disclosure

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Disclosure
  8. References

The authors have no financial support or relationships that may pose potential conflict of interest.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Disclosure
  8. References
  • 1
    Lewi L, Jani J, Blickstein I et al. The outcome of monochorionic diamniotic twin gestations in the era of invasive fetal therapy: A prospective cohort study. Am J Obstet Gynecol 2008; 199: 514518.
  • 2
    Lopriore E, Middeldorp JM, Oepkes D, Kanhai HH, Walther FJ, Vandenbussche FP. Twin anemia-polycythemia sequence in two monochorionic twin pairs without oligo-polyhydramnios sequence. Placenta 2007; 28: 4751.
  • 3
    Slaghekke F, Kist WJ, Oepkes D et al. Twin anemia-polycythemia sequence: Diagnostic criteria, classification, perinatal management and outcome. Fetal Diagn Ther 2010; 27: 181190.
  • 4
    Sherer DM, Sinkin RA, Metlay LA, Woods JR, Jr. Acute intrapartum twin-twin transfusion. A case report. J Reprod Med 1992; 37: 184186.
  • 5
    Uotila J, Tammela O. Acute intrapartum fetoplacental transfusion in monochorionic twin pregnancy. Obstet Gynecol 1999; 94: 819821.
  • 6
    Wenstrom KD, Tessen JA, Zlatnik FJ, Sipes SL. Frequency, distribution, and theoretical mechanisms of hematologic and weight discordance in monochorionic twins. Obstet Gynecol 1992; 80: 257261.
  • 7
    Senat MV, Deprest J, Boulvain M, Paupe A, Winer N, Ville Y. Endoscopic laser surgery versus serial amnioreduction for severe twin-to-twin transfusion syndrome. N Engl J Med 2004; 351: 136144.
  • 8
    Lopriore E, Slaghekke F, Middeldorp JM et al. Accurate and simple evaluation of vascular anastomoses in monochorionic placenta using colored dye. J Vis Exp 2011; 55: e3208.
  • 9
    Lopriore E, Wezel-Meijler G, Middeldorp JM, Sueters M, Vandenbussche FP, Walther FJ. Incidence, origin, and character of cerebral injury in twin-to-twin transfusion syndrome treated with fetoscopic laser surgery. Am J Obstet Gynecol 2006; 194: 12151220.
  • 10
    Volpe JJ. Intracranial hemorrhage: Germinal matrix-intraventricular hemorrhage of the premature infant. In: Volpe JJ (ed.). Neurology of the Newborn, 4th edn. Philadelphia, PA: Saunders, 2001; 428493.
  • 11
    de Vries LS, Eken P, Dubowitz LM. The spectrum of leukomalacia using cranial ultrasound. Behav Brain Res 1992; 49: 16.
  • 12
    Levene MI. Measurement of the growth of the lateral ventricles in preterm infants with real-time ultrasound. Arch Dis Child 1981; 56: 900904.
  • 13
    Lubin B. Neonatal anaemia secondary to blood loss. Clin Haematol 1978; 7: 1934.
  • 14
    Hegyi T, Carbone MT, Anwar M et al. Blood pressure ranges in premature infants. I. The first hours of life. J Pediatr 1994; 124: 627633.
  • 15
    Suzuki S, Iwasaki N, Ono S, Igarashi M, Murata T. Fetal heart rate patterns in monochorionic twins following acute twin-twin transfusion. Obstet Gynecol Int 2009; 2009: 498530.
  • 16
    Skupski DW, Sylvestre G, Di Renzo GC, Grunebaum A. Acute twin-twin transfusion syndrome in labor: Pathophysiology and associated factors. J Matern Fetal Neonatal Med 2012; 25: 456460.
  • 17
    Duncan KR, Denbow ML, Fisk NM. The aetiology and management of twin-twin transfusion syndrome. Prenat Diagn 1997; 17: 12271236.
  • 18
    Wee LY, Fisk NM. The twin-twin transfusion syndrome. Semin Neonatol 2002; 7: 187202.
  • 19
    Jain V, Fisk NM. The twin-twin transfusion syndrome. Clin Obstet Gynecol 2004; 47: 181202.
  • 20
    Lopriore E, Vandenbussche FP, Tiersma ES, de Beaufort AJ, de Leeuw JP. Twin-to-twin transfusion syndrome: New perspectives. J Pediatr 1995; 127: 675680.
  • 21
    Huber A, Hecher K. How can we diagnose and manage twin-twin transfusion syndrome? Best Pract Res Clin Obstet Gynaecol 2004; 18: 543556.
  • 22
    Danskin FH, Neilson JP. Twin-to-twin transfusion syndrome: What are appropriate diagnostic criteria? Am J Obstet Gynecol 1989; 161: 365369.
  • 23
    Klebe JG, Ingomar CJ. The fetoplacental circulation during parturition illustrated by the interfetal transfusion syndrome. Pediatrics 1972; 49: 112116.
  • 24
    Faxelius G, Raye J, Gutberlet R et al. Red cell volume measurements and acute blood loss in high-risk newborn infants. J Pediatr 1977; 90: 273281.
  • 25
    Galea P, Scott JM, Goel KM. Feto-fetal transfusion syndrome. Arch Dis Child 1982; 57: 781783.
  • 26
    Lopriore E, Sueters M, Middeldorp JM, Vandenbussche FP, Walther FJ. Haemoglobin differences at birth in monochorionic twins without chronic twin-to-twin transfusion syndrome. Prenat Diagn 2005; 25: 844850.