Jump to ContentJump to Main Navigation

Journal of Perinatal Medicine

Official Journal of the World Association of Perinatal Medicine

Editor-in-Chief: Dudenhausen, Joachim W.

Editorial Board Member: / Bancalari, Eduardo / Greenough, Anne / Genc, Mehmet R. / Chervenak, Frank A. / Chappelle, Joseph / Bergmann, Renate L. / Bernardes, J.F. / Bevilacqua, G. / Blickstein, Isaac / Cabero Roura, Luis / Carbonell-Estrany, Xavier / Carrera, Jose M. / D`Addario, Vincenzo / D'Alton, MD, Mary E. / Dimitrou, G. / Grunebaum, Amos / Hentschel, Roland / Köpcke, W. / Kawabata, Ichiro / Keirse, M.J.M.C. / Kurjak M.D., Asim / Levene, Malcolm / Lockwood, Charles J. / Marsal, Karel / Makatsariya, Alexander / Nishida, Hiroshi / Papp, Zoltán / Pejaver, Ranjan Kumar / Pooh, Ritsuko K. / Saugstad, Ola D. / Schenker, Joseph G. / Sen, Cihat / Seri, MD, PhD, HonD, Istvan / Vetter, Klaus / Winn, MD, Hung N. / Young, Bruce K. / Zimmermann, Roland

6 Issues per year

Increased IMPACT FACTOR 2012: 1.949
Rank 29 out of 77 in category Obstretics & Gynecology and 39 out of 121 in category Pediatrics in the 2012 Thomson Reuters Journal Citation Report/Science Edition

Access brought to you by:

provisional account



The prevalence and clinical features of twin-twin transfusion syndrome with onset during the third trimester

1 / Keisuke Ishii1 / Takako Taguchi1 / Aki Mabuchi1 / Haruna Kawaguchi1 / Ryo Yamamoto1 / Shusaku Hayashi1 / Nobuaki Mitsuda1

1Department of Maternal Fetal Medicine, Osaka Prefectural Hospital Organization, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan

Corresponding author: Masaharu Murata, MD, PhD, Department of Maternal Fetal Medicine, Osaka Prefectural Hospital Organization, Osaka Medical Center and Research Institute for Maternal and Child Health, 840 Murodo-cho, Izumi, Osaka 594-1101, Japan, Tel.: +81-752-56-1220, Fax: +81-725-57-3207, E-mail:

Citation Information: Journal of Perinatal Medicine. Volume 42, Issue 1, Pages 93–98, ISSN (Online) 1619-3997, ISSN (Print) 0300-5577, DOI: 10.1515/jpm-2013-0101, August 2013

Publication History

Published Online:


Objective: To describe the incidence and clinical features of twin-twin transfusion syndrome (TTTS) with third trimester onset.

Methods: We performed a retrospective chart review of monochorionic diamniotic (MD) twin pregnancies delivered during a recent 4-year period. The inclusion criterion was women who received prenatal care at our center from the first trimester onward. Serial ultrasound examinations were performed at least every 2 weeks until delivery to evaluate fetal growth as well as to estimate amniotic fluid volume. The prevalence of TTTS onset after 28 weeks of gestation and clinical features, including neonatal outcomes and placental findings, were elucidated.

Results: Meeting our inclusion criterion were 143 MD twin pregnancies, including 15 TTTS cases (10%). Five cases (4%) developed TTTS during the third trimester and underwent a cesarean section immediately after the diagnosis. All of these women exhibited either abdominal distension or uterine contractions. Recipient twins tended to require more intensive cardiopulmonary treatment than donors, however, neither a recipient nor a donor twin suffered neonatal death or neurological impairment. Placental arterio-arterial anastomoses were detected in three out of five cases. Arteriovenous anastomoses were present in all cases, however, venovenous anastomoses were not found in any case.

Conclusions: TTTS is a relatively rare complication during the third trimester. It is imperative to be observant for the development of TTTS in MD twin pregnancies with any abdominal symptoms, even if they appear insignificant.

Keywords: Monochorionic diamniotic twin pregnancy; perinatal outcome; third trimester; twin-twin transfusion syndrome


Twin-twin transfusion syndrome (TTTS) occurs at a frequency of 8%–10% in monochorionic twin pregnancies [1, 9, 15], and the majority of those cases are diagnosed during the second trimester [25]. In the last two decades, the overall prognosis of TTTS cases diagnosed before 26 weeks of gestation has dramatically improved by the introduction of fetoscopic laser photocoagulation (FLP) for placental communicating vessels [18–20]. Recently, several studies have shown that FLP for cases with TTTS after 26 weeks of gestation resulted in outcomes equal to, or superior to, those undergoing conventional treatment strategies [3, 14, 26]. However, there have been only a few studies focused on the clinical features of TTTS developing after 28 weeks of gestation [3, 10, 14, 26], and it is currently unclear which management option minimizes adverse outcomes.

The aim of this study was to describe the incidence and clinical features of TTTS onset during the third trimester. To clarify the natural course of the cases, we performed a single-center cohort study and limited it to the cases managed at our center throughout pregnancy.


This was a retrospective cohort study performed at a tertiary perinatal care center in Japan, providing fetal treatment, including around 30 fetoscopic laser therapies per year. We conducted a retrospective chart review of all monochorionic diamniotic (MD) pregnancies managed from the first trimester onward that delivered at our center between January 2009 and December 2012. The cases with single or double fetal demise before 14 weeks of gestation, fetuses with major anomalies, and twin reversed arterial perfusion sequence (TRAPs) were excluded.

The diagnosis of monochorionicity and the decision of an accurate gestational age were made at first trimester by ultrasound examination. Serial sonographic examinations were performed until delivery at least every 2 weeks to evaluate fetal growth and amniotic fluid volume. Doppler measurements of the umbilical artery and the ductus venous (DV) were performed at 18–19 weeks of gestation, and additional Doppler evaluations were done at the attending physician’s discretion when impaired fetal growth or discordant amniotic fluid volume between twins were found. Inpatient management was initiated only for obstetrical indications. The diagnosis of TTTS was based on the sonographic criteria of polyhydramnios with amniotic fluid volume (AFP) of 8 cm or greater in the recipient fetus and oligohydramnios with AFP of 2 cm or less in the donor fetus. Staging of the disease was done according to the Quintero’s staging system [17]. We examined the prevalence of TTTS during the second and third trimesters.

Concerning cases with TTTS onset during the third trimester, we reviewed maternal demographics as well as the clinical course of these pregnancies. The data of neonatal clinical course, including the need of intratracheal intubation, the administration of catecholamine, transfusion, and neurological findings at 1 month and 6 months of life were also documented. Furthermore, placental findings were reviewed to investigate the features of placental anastomoses evaluated by a color dye injection test.


Initially included in the study were 152 MD twin pregnancies; subsequently, nine cases (three cases with TRAPs, two with spontaneous abortion before 14 weeks of gestation, and four with major anomalies) were excluded (Figure 1). A total of 143 sets of MD twin pregnancies met our criteria and were analyzed. Table 1 shows baseline characteristic of this population. TTTS occurred in 15 cases (10%), 10 cases (6%) diagnosed during the second trimester, and five cases (4%) during the third trimester. Among 10 TTTS cases during the second trimester, eight cases underwent FLP, one underwent a cesarean section to transition to neonatal treatment, and one was a pregnancy termination.

No. of pregnancies, n143
Maternal age, median (range)31 (18–42)
Primipara, n (%)78 (55)
Spontaneous conception, n (%)120 (85)
Ovulation induction, n (%)10 (7)
IVF/ICSI, n (%)13 (9)
Delivery <22 weeks of gestation, n (%)8 (6)
 Both IUFD5
 Termination of pregnancy2
 Spontaneous abortion1
IUFD, n (%)9 (7)
 Single IUFD, n5
 Both IUFD, n4
TTTS, n (%)15 (11)
 Diagnosed <28 weeks of gestation10
 Diagnosed >28 weeks of gestation5
Table 1

Baseline characteristics.

Figure 1

Diagram of study profile.

The five cases with TTTS during the third trimester are summarized in Table 2. Gestational age at TTTS diagnosis ranged from 31+2 to 35+5 weeks. Two cases were Quintero’s stage I and the other three were stage III or IV. Two cases (cases 1 and 3) were inpatients due to threatened preterm labor (TPL) followed by the diagnosis of TTTS. In case 1, amniotic fluid discordance expanded to meet the TTTS criteria; this occurred 2 days after the ultrasonographic evaluation, which revealed isolated oligohydramnios at 31+0 weeks of gestation. In case 3, estimated amniotic volume of both twins was noted to be normal at 33+2 weeks of gestation, however, the patient complained of uterine contractions. Severe polyhydramnios and oligohydramnios with a pericardial effusion and ascites in the recipient fetus were demonstrated 3 days later.

TTTS diagnosis
AgeParityGA (w)Quintero stageComments
133031+2IInpatient due to TPL from 27 weeks of gestation

Amniotic fluid discordance was detected at 31 weeks by chance
229031+4IIIRaaOutpatient as uncomplicated MD twin until 30 weeks without amniotic fluid discordance

Abdominal distension was started a couple of days before the date of TTTS diagnosis
330133+5IVInpatient due to TPL from 28 weeks

Amniotic fluid discordance was detected at 33 weeks by chance
422034+5IVOutpatient as uncomplicated MD twin until 33 weeks without amniotic fluid discordance

Abdominal distension was started a couple of days before the date of TTTS diagnosis
533035+5IOutpatient as selective IUGR type I until 34 weeks without amniotic fluid discordance

Abdominal distension was started a couple of days before the date of TTTS diagnosis
Table 2

Five cases with twin-twin transfusion syndrome (TTTS) onset during the third trimester: pregnancy course.

The other three cases (cases 2, 4, and 5) were managed as outpatients without obstetrical complications. All three women presented at our outpatient department and complained of abdominal distension, which began a few days before the diagnosis of TTTS. In case 2, sonographic evaluation exhibited TTTS with reversal of DV flow in the recipient twin despite normal sonographic findings 9 days before the diagnosis of TTTS. In case 4, polyhydramnios, pleural effusion, and ascites in the recipient twin together with anhydramnios in the donor twin were found at an examination 7 days after the previous scan in which the amniotic fluid volume was noted to be normal. In case 5, amniotic fluid volume was found to be normal in both twins 14 days before the patient was diagnosed at 33+5 weeks with TTTS.

All cases underwent cesarean section immediately after diagnosis of TTTS without any fetal intervention, and subsequently, neonatal care was initiated by neonatologists. Neonatal and placental findings of the five cases are presented in Table 3. All five recipient neonates and two donor neonates required intratracheal intubation. Four out of five recipients required administration of catecholamine, whereas no donors required this therapy. Two recipient neonates required fresh frozen plasma transfusions to sustain hemodynamic status; one donor required red cell concentrate due to severe anemia. There was neither neonatal death nor abnormal neurological findings at the first month and 6 months after birth.

GA (weeks)Quintero stageBirth weight (g)Hb (g/dL)Comments
FetusIntratracheal intubationCatecholamineTransfusionNeurological findings
at 1 monthat 6 months
131+2I160220.0RecipientDay 0–1Day 0–2NoNormalNormalYesYesNo
231+4IIIRa179420.5RecipientDay 0–3Day 0–2FFP: day 0–2NormalNormalYesYesNo
115810.0DonorDay 0–3NoRCC: day 1–3NormalNormal
333+5IV237614.0RecipientDay 0–7NoFFP: day 3–4NormalNormalNoYesNo
434+5IV227013.9RecipientDay 0–1Day 0–4NoNormalNormalNoYesNo
190116.0DonorDay 0–1NoNoNormalNormal
535+5I215220.4RecipientDay 0–4Day 1–5NoNormalNormalYesYesNo
Table 3

Five cases with TTTS onset during the third trimester: neonatal and placental findings.

In regard to placental findings, arterioarterial anastomoses (AAA) were detected in three cases (cases 1, 2, and 5), and arteriovenous anastomoses were detected in all cases, however, venovenous anastomoses were not found in any case.


The prevalence of TTTS onset after 28 weeks of gestation was 4% among the MD twin pregnancies uniformly managed at a single perinatal center from the first trimester onward. This prevalence is less than half that of previous reports including the typical onset of TTTS during the second trimester [1, 9, 15]. Thorson et al. reported five cases that were diagnosed after 28 weeks among 42 TTTS pregnancies (12%) [25]; however, that series consisted of patients referred from a number of hospitals at an unspecified stage of gestation.

It is well-known that placental angioarchitecture [4, 6, 8] and endocrinologic mechanisms [2, 7, 12] are involved in the pathogenesis of TTTS. It has been suggested that thrombosis could cause hemodynamic changes between the twins leading to late onset TTTS [16, 24]. However, it remains to be fully clarified why TTTS develops during the third trimester after a previously uncomplicated prenatal course.

As twin pregnancies tend to be accompanied with threatened preterm labor, especially after the mid-trimester, uterine contractions might play some role in the development of TTTS. In animal studies, it has been demonstrated that non-labor uterine contractions cause significantly increased arterial and venous pressure in fetuses with oligohydramnios [21]. This could amplify blood transfusion from twins with relatively less amniotic fluid volume to co-twins. Moreover, it has been reported that uterine contractions could also affect fetal hemodynamic status in both normal and TTTS conditions [22, 23]. It appears to be imperative to explore the development of TTTS closely in MD twin pregnancies with clinical manifestations of TPL. However, the use of prophylactic tocolysis cannot be endorsed, considering that our five TTTS cases included two patients under medical treatment with intravenous tocolytic for TPL.

Several studies have shown that the presence of placental AAA plays a protective role against TTTS [5, 6]. In our series, AAA was detected in three out of five cases. Although our series is too small to verify the pathological significance of the presence of AAA, it is presumed that AAA may play a protective role against development of TTTS before the third trimester unless additional events, such as thrombosis and uterine contractions occur.

Recently, several studies have been published concerning cases treated with FLP outside the customary period [3, 14, 26]. Middeldrop et al. demonstrated that FLP performed after 26 weeks of gestation prolonged gestational age and reduced neonatal morbidity compared to serial amnioreduction (AR) [14]. Baud et al. reported FLP performed between 26+1 and 30+3 weeks of gestation resulted in an improved survival rate with similar surgical feasibility compared to the customary period [3]. Conversely, the neonatal care of TTTS survivors is challenging because of hemodynamic aberrations in addition to prematurity [11]. In our series, recipient fetuses tended to require more intensive cardiopulmonary treatment than donor fetuses; however, neither neonatal death nor neurological impairment were seen in our series. Although serial amnioreduction is related to a low survival rate and high neuromorbidity rate [10, 13], the expectant management including strict monitoring, antenatal corticosteroid administration and amnioreduction would be a option, especially stage I TTTS in early third trimester. In contrast, for the TTTS cases with advanced staging or in late third trimester, the most reasonable option appears to be intensive fetal surveillance, to deliver promptly the patient when fetal status deteriorates, and to initiate intense neonatal treatment. In order to determine the optimal management of TTTS during the third trimester, a larger series of cases and long-term outcome must be evaluated.

In conclusion, TTTS occurs during the third trimester in 4% of MD twin gestations. Although the current study includes a case number too small to derive enough clinical considerations, it appears to be important to closely monitor women with MD twin pregnancies for the development of TTTS when they develop symptoms of threatened preterm labor even if their pregnancy has been uneventful until that point. Currently, therapeutic preterm delivery might be a primary option for third trimester TTTS.


  • [1]

    Acosta-Rojas R, Becker J, Munoz-Abellana B, Ruiz C, Carreras E, Gratacos E. Twin chorionicity and the risk of adverse perinatal outcome. Int J Gynaecol Obstet. 2007;96:98–102.

  • [2]

    Bajoria R, Ward S, Chatterjee R. Brain natriuretic peptide and endothelin-1 in the pathogenesis of polyhydramnios-oligohydramnios in monochorionic twins. Am J Obstet Gynecol. 2003;189:189–94. [CrossRef]

  • [3]

    Baud D, Windrim R, Keunen J, Kelly EN, Shah P, van Mieghem T, et al. Fetoscopic laser therapy for twin-twin transfusion syndrome before 17 and after 26 weeks’ gestation. Am J Obstet Gynecol. 2013;208:197.e1–7.

  • [4]

    Bermudez C, Becerra CH, Bornick PW, Allen MH, Arroyo J, Quintero RA. Placental types and twin-twin transfusion syndrome. Am J Obstet Gynecol. 2002;187:489–94. [Web of Science]

  • [5]

    de Villiers SF, Slaghekke F, Middeldorp JM, Walther FJ, Oepkes D, Lopriore E. Arterio-arterial vascular anastomoses in monochorionic placentas with and without twin-twin transfusion syndrome. Placenta. 2012;33:652–4. [Web of Science]

  • [6]

    Denbow ML, Cox P, Taylor M, Hammal DM, Fisk NM. Placental angioarchitecture in monochorionic twin pregnancies: relationship to fetal growth, fetofetal transfusion syndrome, and pregnancy outcome. Am J Obstet Gynecol. 2000;182:417–26.

  • [7]

    Galea P, Barigye O, Wee L, Jain V, Sullivan M, Fisk NM. The placenta contributes to activation of the renin angiotensin system in twin-twin transfusion syndrome. Placenta. 2008;29:734–42. [PubMed] [Web of Science] [CrossRef]

  • [8]

    Hack KE, Nikkels PG, Koopman-Esseboom C, Derks JB, Elias SG, van Gemert MJ, et al. Placental characteristics of monochorionic diamniotic twin pregnancies in relation to perinatal outcome. Placenta. 2008;29:976–81. [PubMed] [CrossRef] [Web of Science]

  • [9]

    Lewi L, Jani J, Blickstein I, Huber A, Gucciardo L, Van Mieghem T, 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;199:514.e1–8. [Web of Science]

  • [10]

    Li X, Morokuma S, Fukushima K, Otera Y, Yumoto Y, Tsukimori K, et al. Prognosis and long-term neurodevelopmental outcome in conservatively treated twin-to-twin transfusion syndrome. BMC Pregnancy Childbirth. 2011;11:32. [PubMed] [Web of Science]

  • [11]

    Lopriore E, Oepkes D, Walther FJ. Neonatal morbidity in twin-twin transfusion syndrome. Early Hum Dev. 2011;87:595–9. [Web of Science]

  • [12]

    Mahieu-Caputo D, Muller F, Joly D, Gubler MC, Lebidois J, Fermont L, et al. Pathogenesis of twin-twin transfusion syndrome: the renin-angiotensin system hypothesis. Fetal Diagn Ther. 2001;16:241–4. [CrossRef]

  • [13]

    Mari G, Roberts A, Detti L, Kovanci E, Stefos T, Bahado-Singh RO, et al. Perinatal morbidity and mortality rates in severe twin-twin transfusion syndrome: results of the International Amnioreduction Registry. Am J Obstet Gynecol. 2001;185:708–15.

  • [14]

    Middeldorp JM, Lopriore E, Sueters M, Klumper FJ, Kanhai HH, Vandenbussche FP, et al. Twin-to-twin transfusion syndrome after 26 weeks of gestation: is there a role for fetoscopic laser surgery? Br J Obstet Gynecol. 2007;114:694–8.

  • [15]

    Nakayama S, Ishii K, Kawaguchi H, Hayashi S, Hidaka N, Murakoshi T, et al. Perinatal outcome of monochorionic diamniotic twin pregnancies managed from early gestation at a single center. J Obstet Gynaecol Res. 2012;38:692–7. [Web of Science]

  • [16]

    Nikkels PG, van Gemert MJ, Sollie-Szarynska KM, Molendijk H, Timmer B, Machin GA. Rapid onset of severe twin-twin transfusion syndrome caused by placental venous thrombosis. Pediatr Dev Pathol. 2002;5:310–4. [CrossRef] [PubMed]

  • [17]

    Quintero RA, Dickinson JE, Morales WJ, Bornick PW, Bermudez C, Cincotta R, et al. Stage-based treatment of twin-twin transfusion syndrome. Am J Obstet Gynecol. 2003;188:1333–40.

  • [18]

    Roberts D, Gates S, Kilby M, Neilson JP. Interventions for twin-twin transfusion syndrome: a Cochrane review. Ultrasound Obstet Gynecol. 2008;31:701–11.

  • [19]

    Sago H, Hayashi S, Saito M, Hasegawa H, Kawamoto H, Kato N, et al. The outcome and prognostic factors of twin-twin transfusion syndrome following fetoscopic laser surgery. Prenat Diagn. 2010;30:1185–91. [PubMed] [CrossRef] [Web of Science]

  • [20]

    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;351:136–44.

  • [21]

    Shields LE, Brace RA. Fetal vascular pressure responses to nonlabor uterine contractions: dependence on amniotic fluid volume in the ovine fetus. Am J Obstet Gynecol. 1994;171:84–9.

  • [22]

    Takahashi Y, Iwagaki S, Nakagawa Y, Kawabata I, Tamaya T. Uterine contractions increase fetal heart preload. Ultrasound Obstet Gynecol. 2003;22:53–6. [CrossRef] [PubMed]

  • [23]

    Takahashi Y, Iwagaki S, Nakagawa Y, Kawabata I, Tamaya T. Uterine contractions might increase heart preload in the recipient fetus in early-onset twin-twin transfusion syndrome: an ultrasound assessment. Prenat Diagn. 2004;24:977–80. [CrossRef] [PubMed]

  • [24]

    Tan TY, Denbow ML, Cox PM, Talbert D, Fisk NM. Occlusion of arterio-arterial anastomosis manifesting as acute twin-twin transfusion syndrome. Placenta. 2004;25:238–42. [CrossRef] [PubMed]

  • [25]

    Thorson HL, Ramaeker DM, Emery SP. Optimal interval for ultrasound surveillance in monochorionic twin gestations. Obstet Gynecol. 2011;117:1227.

  • [26]

    Valsky DV, Eixarch E, Martinez-Crespo JM, Acosta ER, Lewi L, Deprest J, et al. Fetoscopic laser surgery for twin-to-twin transfusion syndrome after 26 weeks of gestation. Fetal Diagn Ther. 2012;31:30–4. [Web of Science]

The authors stated that there are no conflicts of interest regarding the publication of this article.

Comments (0)

Please log in or register to comment.