Journal of Perinatology (2014), 1–3 © 2014 Nature America, Inc. All rights reserved 0743-8346/14 www.nature.com/jp
ORIGINAL ARTICLE
Doppler abnormalities in monochorionic diamniotic twin pregnancies with discordant growth L Zuckerwise1, U Nayeri2, S Abdel-Razeq1, J Copel1 and MO Bahtiyar1 OBJECTIVE: We studied whether abnormal umbilical artery (UA) Doppler flow velocity waveforms occur with higher frequency in monochorionic diamniotic (MCDA) twin gestations with discordant fetal growth and whether this impacted neonatal outcome. STUDY DESIGN: We performed a retrospective study of MCDA twin pairs. We collected data from an electronic medical record. We classified pregnancies as discordant if there was at least 20% birth weight discordance. Abnormal UA Doppler velocity waveforms included absent or reversed end diastolic flow. We analyzed the data with chi square, Student’s t-test and analysis of variance as appropriate. RESULT: Seventy-three twin pairs met criteria for inclusion, including 16 with discordant growth. The discordant group was significantly more affected with twin-to-twin transfusion syndrome (TTTS) (P = 0.02). The smaller fetuses in discordant pairs were more likely to display abnormal UA Doppler flow velocity waveforms (P o 0.01). These neonates also had lower Apgar scores (P = 0.03) and were more likely to require care in a neonatal intensive care unit. Our findings persisted after excluding pregnancies with TTTS. CONCLUSION: In MCDA twin gestations complicated by discordant growth, there is an increased frequency of abnormal UA Doppler flow velocity waveforms in small fetuses, and these neonates face clinical challenges after birth. Journal of Perinatology advance online publication, 18 December 2014; doi:10.1038/jp.2014.223
INTRODUCTION Monochorionic diamniotic (MCDA) twin pregnancies are characterized by the presence of a single placenta that is functionally divided into separate portions supporting each individual fetus. Vascular communications between these portions normally maintain balance from net transfusion perspective; however, 10% to 15% of MCDA twin pregnancies are complicated by failure of proper development of this functional separation, with insufficient or abnormal communications, resulting in imbalanced distribution of blood between the two fetuses.1 Although twin-to-twin transfusion syndrome (TTTS) is the best-characterized result of a placental abnormality unique to MCDA twin pregnancies,2 other conditions of an imbalanced placenta and blood-sharing exist, including selective fetal growth restriction and twin anemiapolycythemia sequence (TAPS). These complications, which are unique to monochorionic placentation, share the principles of an unbalanced placenta and/or blood-sharing between fetuses but may have a different underlying pathophysiology. Discordant growth in twin gestations, usually defined as a difference of 420% or 25%, has been found in 7% to 15% of MCDA twin pregnancies3,4 and contributes to neonatal mortality and morbidity.5,6 Although there is a higher incidence of TTTS in MCDA twin pregnancies with discordant growth, this syndrome does not account for all instances of discordant growth. We studied whether abnormal umbilical artery (UA) Doppler flow velocity waveforms occur more often in MCDA twin pregnancies characterized by discordant growth compared with non-discordant twin pairs and characterize perinatal outcomes in these pregnancies.
METHODS This is a retrospective study of MCDA twin pregnancies that received antenatal care at a single academic center between January 2007 and January 2010 (n = 98). Cases with confirmed MCDA placentation were included for analysis. MCDA placentation was confirmed by review of first trimester ultrasound data to ensure that these pregnancies had a single placenta, thin dividing membrane and absence of twin peak sign, as well as by final placenta pathology results. Diagnosis of TTTS was made antenatally by standard ultrasound criteria.7,8 Abnormal UA Doppler flow velocity waveforms were defined as absent or reversed end diastolic flow. Estimated fetal weight (EFW) was calculated by standard methods.9 An MCDA twin pregnancy with discordant growth was defined as birth weight difference 420% ((EFWlarger twin − EFWsmaller twin)/EFWlarger twin). Cases without available delivery or neonatal information were excluded from analysis. This study received IRB approval. Data were collected by retrospective chart review from an electronic medical record and from an electronic ultrasound database. Information collected included maternal demographic and medical data, ultrasound data, placental pathology and pregnancy and neonatal outcomes. All MCDA twin pregnancies were monitored according to our institution’s protocol, which consists of first trimester determination of chorionicity, detailed anatomical survey ultrasound at 18 to 20 weeks gestation, fetal echocardiography at approximately 22 weeks gestation and assessment of growth and amniotic fluid volume every 2 to 4 weeks as clinically indicated. It is our policy to perform UA Doppler imaging in cases of discordant or low amniotic fluid volume, defined as one twin with a maximum vertical pocket o2.0 cm or discordant or abnormal growth in either fetus. Doppler studies were undertaken biweekly in cases of abnormal UA Doppler findings. Statistical analysis of the data was performed by chi square, Student’s t-test and analysis of variance as appropriate. We analyzed the data first
1 Department of Obstetrics and Gynecology, Yale School of Medicine, New Haven, CT, USA and 2Department of Obstetrics and Gynecology, Upstate Medical University, Syracuse, NY, USA. Correspondence: Dr L Zuckerwise, Department of Obstetrics and Gynecology, Yale School of Medicine, 333 Cedar Street, P.O. Box 208063, New Haven 06520-8063, CT, USA. E-mail: [email protected] Received 27 August 2014; revised 22 October 2014; accepted 4 November 2014
Doppler abnormalities in monochorionic diamniotic twins L Zuckerwise et al
2 Table 1.
Table 2. Antenatal and postnatal characteristics of MCDA twin pregnancies included
Demographic of the study groups
Study group characteristics Maternal age (range), years
Non-discordant (N = 57)
Discordant (N = 16)
P-value
30.0 (16–43)
33.5 (26–42)
0.08
Race/ethnicity (n (%)) Asian African-American Caucasian Hispanic Other Comorbidities (n (%)) Diabetes Hypertension Obesity Tobacco use IVF (n (%))
0.02 9 13 30 5 0
(16) (23) (53) (9) (0)
0 1 14 0 1
(0) (6) (88) (0) (6) 1.0
11 5 4 3
(19) (9) (7) (5)
6 (11)
2 2 1 1
(13) (13) (6) (6)
1 (6)
0.55
Abbreviation: IVF, in vitro fertilization. Non-discordant twin gestation with fetal growth discordance ⩽ 20%. Discordant twin gestation with fetal growth discordance 420%. IVF with or without intra cytoplasmic sperm injection.
with all MCDA twin pairs included and then again after excluding pregnancies complicated by TTTS.
RESULTS Seventy-three twin pairs met inclusion criteria, including 16 twin pairs with discordant fetal growth 420%. Table 1 lists the baseline pregnancy characteristics of the included cases. In the discordant group, there was a higher incidence of Caucasian race (P = 0.02). No difference was found in age, gravidity, parity or incidence of assisted reproductive technology. No difference was found in common co-morbidities that are associated with abnormal fetal growth. The discordant group was significantly more affected by TTTS (P = 0.02), though of the 13 cases of TTTS included, only 6 were characterized by discordant birth weight, comprising 38% of the discordant group, and 7 demonstrated concordant growth. Of the 57 concordant twin pairs, only 1 resulted in the birth of small for gestational age (SGA) neonates, defined as birth weight o10th percentile. In this case, both babies were SGA. In contrast, 9 of the 16 (56%) discordant twin pairs resulted in the birth of an SGA neonate, and in each case only the small twin met criteria for SGA. Table 2 demonstrates antenatal and postnatal findings of the MCDA pregnancies. The smaller twin in the discordant group was significantly more likely to have abnormal UA Doppler flow velocity waveforms (P o 0.01). After birth, the smaller twin in discordant pairs had significantly lower 1-min Apgar scores (P = 0.03), with a median score of seven, compared with nine in the smaller twin of non-discordant pairs. Additionally, both smaller and larger twins of discordant pairs were more likely to require neonatal intensive care unit (NICU) admission after birth as compared with non-discordant twin pairs (88% vs 58% and 81% vs 51%, respectively, P = 0.01), although the length of NICU stay in neonates who were admitted were not significantly different. When cases complicated by TTTS were excluded from analysis, these findings persisted. Although not achieving statistical significance, we found that discordant MCDA twin pairs were delivered approximately 2 weeks earlier than the non-discordant MCDA twin pairs (P = 0.06). Journal of Perinatology (2014), 1 – 3
Antenatal data TTTS (n (%)) AEDF or REDF in UA (%) Large twin Small twin
Nondiscordant (N = 57)
Discordant (N = 16)
7 (12)
6 (38)
− 1.8
− 31.3
P-valuea
0.02 o0.01
Post-natal data GA at delivery (mean ± s.d.) 34.6 ± 4.0 32.4 ± 4.6 0.06 BW (mean ± s.d.) Large twin 2306.8 ± 695.6 1928.1 ± 799.2 Small twin 2134.4 ± 663.9 1376.4 ± 679.3 BW discordance (median 8 (0–20%) 32 (20–51%) o0.001 (range)) Hgb at birth (mean ± s.d.) Large twin 16.6 ± 2.8 15.4 ± 4.3 0.31 Small twin 15.2 ± 2.8 15.6 ± 2.4 0.63 Apgar scores (median (range)) 1-minute Large twin 9 (1–9) 7.5 (1–9) 0.08 Small twin 9 (1–9) 7 (0-9) 0.03 5-minute Large twin 9 (4–9) 9 (5–9) 0.07 Small twin 9 (5–10) 9 (0-9) 0.06 NICU admission (%) 0.01 Large twin 39 81 Small twin 44 88 Length of NICU stay (median (range)) Large twin 13 (1–261) 19 (1–101) 0.17 Small twin 14 (1–126) 18 (1–113) ) 0.24 Abbreviations: AEDF, absent end diastolic flow; BW, birth weight; Hgb, hemoglobin; GA, gestational age; NICU, newborn intensive care unit; REDF, reverse end diastolic flow; TTTS, twin-to-twin transfusion syndrome; UA, umbilical artery. Non-discordant twin gestation with fetal growth discordance ⩽ 20%. Discordant twin gestation with fetal growth discordance 420%. aP-values corrected for gestational age.
DISCUSSION We assessed whether MCDA twin pregnancies with discordant growth are at an increased incidence of abnormal Doppler studies and whether these findings are related to adverse neonatal outcomes. We found that abnormal Doppler flow velocity waveforms occurred with higher frequency in MCDA twin pregnancies with discordant growth. We also demonstrated that pregnancies complicated by discordant growth were more likely to have adverse neonatal outcomes. As the prevalence of MCDA twin pregnancies is low, our study population was relatively small, and therefore we were unable to assess the risks for specific neonatal morbidities related to discordant growth and abnormal Doppler studies; however, we did demonstrate an increased requirement for NICU care, suggesting increased overall neonatal morbidity. Prior studies looking at Doppler assessment in twin pregnancies mostly include both dichorionic and monochorionic twin pregnancies. For example, Giles et al.10 found no difference in maternal or neonatal outcomes when Doppler assessment with biometry was compared with biometry. Importantly, this study did not identify chorionicity of the twin pairs, and based on prevalence of twin types, it is likely that the majority of subjects in this study were dichorionic twin pregnancies. As the placentation of monochorionic twin pregnancies is of utmost importance related to MCDA-specific complications, the data presented in this and © 2014 Nature America, Inc.
Doppler abnormalities in monochorionic diamniotic twins L Zuckerwise et al
similar studies cannot be extrapolated to monochorionic twin pregnancies. Looking specifically at Doppler assessment in monochorionic twins, studies have evaluated Doppler findings and implications in pregnancies complicated by TTTS, as Doppler flow is a component of the Quintero staging system for TTTS.7,11 These studies universally demonstrate that abnormal Doppler findings portend worse outcomes for MCDA twin pregnancies with TTTS, including, but not limited to, fetal or neonatal death, cerebral palsy and NICU admission. One study that focused on UA Doppler flow in monochorionic pregnancies with and without TTTS examined perinatal outcomes of MCDA twin pregnancies with abnormal UA Doppler studies, defined similarly to our study as absent or reversed end diastolic flow, diagnosed between 16 and 20 weeks gestation.12 This retrospective study included 84 MCDA twin pregnancies, all of which had UA Doppler assessment during a routine mid-trimester scan. The pregnancies were then divided into groups based on the presence or absence of MCDA-specific complications (selective intrauterine growth restriction, growth discordance, TTTS) and/or abnormal UA Doppler studies at intake. The authors reported that MCDA pregnancies with complications were more likely to demonstrate abnormal UA Doppler flow at intake. In addition, pregnancies with abnormal UA Doppler flow in the absence of apparent complications were at higher risk for developing complications, such as discordant growth and intrauterine growth restriction. The authors concluded that isolated abnormal UA Doppler flow between 16 and 20 weeks gestation indicates higher risk for development of MCDA-specific complications, even if the pregnancy appears otherwise normal in the mid-trimester. This study suggests a role for mid-trimester screening Doppler assessment of monochorionic twin pregnancies to determine those at risk for developing complications; however, it was underpowered to detect statistically significant differences in perinatal mortality and did not comment on other pregnancy or neonatal outcomes. Furthermore, our current study adds evidence for poor outcomes in MCDA twin pregnancies with abnormal UA Doppler assessment, including UA Doppler abnormalities diagnosed later in gestation. Our study contributes to the current literature that supports the use of UA Doppler waveform velocimetry as a valuable tool for predicting MCDA twin pregnancies at risk for perinatal complications. Our approach to serial Doppler imaging in MCDA twin pairs with abnormal fluid or growth, performed up until the time of delivery, found that MCDA twin pregnancies with discordant growth are at higher risk for adverse perinatal outcomes, and these discordant twin pairs are more likely to demonstrate abnormal UA Doppler waveform patterns during antenatal surveillance. In MCDA twin gestations complicated by discordant growth, there is a higher incidence of TTTS, but this syndrome does not account for all instances of discordant growth and also occurs in the absence of discordant growth. The increased frequency of
© 2014 Nature America, Inc.
abnormal UA Doppler flow velocity waveforms in smaller fetuses of discordant pairs supports the notion that dysfunctional placental vasculature is a possible cause of discordant growth and is a separate entity from TTTS. However, the causal relationship between Doppler abnormalities and discordant fetal growth and subsequent adverse perinatal outcomes in MCDA pregnancies is yet to be determined. Finally, although specific complications of monochorionic placentation, including TTTS, selective fetal growth restriction and TAPS, can affect the pregnancy individually, overlap in these diagnoses is frequent. Our current study showed that TTTS is more common among pregnancies complicated with fetal growth discordance. Interestingly, TAPS did not occur in our discordant growth group. This suggests that, while fetal growth discordance and TTTS might have similar placental angiostructure, TAPS may have a different underlying vascular abnormality. CONFLICT OF INTEREST The authors declare no conflict of interest.
REFERENCES 1 Society for Maternal-Fetal Medicine: Simpson LL. Twin-twin transfusion syndrome. Am J Obstet Gynecol 2013; 208(1): 3–18. 2 Quintero RA. Twin-twin transfusion syndrome. Clin Perinatol 2003; 30(3): 591–600. 3 Demissie K, Ananth CV, Martin J, Hanley ML, MacDorman MF, Rhoads GG. Fetal and neonatal mortality among twin gestations in the United States: the role of intrapair birth weight discordance. Obstet Gynecol 2002; 100(3): 474–480. 4 Lewi L, Gucciardo L, Huber A, Jani J, Van Mieghem T, Doné E et al. Clinical outcome and placental characteristics of monochorionic diamniotic twin pairs with early- and late-onset discordant growth. Am J Obstet Gynecol 2008; 199(5): 511, e511–e517. 5 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(2): 98–102. 6 Adegbite AL, Castille S, Ward S, Bajoria R. Neuromorbidity in preterm twins in relation to chorionicity and discordant birth weight. Am J Obstet Gynecol 2004; 190(1): 156–163. 7 Quintero RA, Morales WJ, Allen MH, Bornick PW, Johnson PK, Kruger M. Staging of twin-twin transfusion syndrome. J Perinatol 1999; 19(8 Pt 1): 550–555. 8 Huber A, Hecher K. How can we diagnose and manage twin-twin transfusion syndrome? Best Pract Res Clin Obstet Gynaecol 2004; 18(4): 543–556. 9 Hadlock F, Harrist R, Sharman R, Deter R, Park S. Estimation of fetal weight with the use of head, body, and femur measurements--a prospective study. Am J Obstet Gynecol 1985; 151(3): 333–337. 10 Giles W, Bisits A, O'Callaghan S, Gill A. The Doppler assessment in multiple pregnancy randomised controlled trial of ultrasound biometry versus umbilical artery Doppler ultrasound and biometry in twin pregnancy. BJOG 2003; 110(6): 593–597. 11 Zikulnig L, Hecher K, Bregenzer T, Baz E, Hackeloer BJ. Prognostic factors in severe twin-twin transfusion syndrome treated by endoscopic laser surgery. Ultrasound Obstet Gynecol 1999; 14(6): 380–387. 12 Pan M, Chen M, Leung TY, Sahota DS, Ting YH, Lau TK. Outcome of monochorionic twin pregnancies with abnormal umbilical artery Doppler between 16 and 20 weeks of gestation. J Maternal Fetal Neonatal Med 2012; 25(3): 277–280.
Journal of Perinatology (2014), 1 – 3
3
ORIGINAL ARTICLE
Doppler abnormalities in monochorionic diamniotic twin pregnancies with discordant growth L Zuckerwise1, U Nayeri2, S Abdel-Razeq1, J Copel1 and MO Bahtiyar1 OBJECTIVE: We studied whether abnormal umbilical artery (UA) Doppler flow velocity waveforms occur with higher frequency in monochorionic diamniotic (MCDA) twin gestations with discordant fetal growth and whether this impacted neonatal outcome. STUDY DESIGN: We performed a retrospective study of MCDA twin pairs. We collected data from an electronic medical record. We classified pregnancies as discordant if there was at least 20% birth weight discordance. Abnormal UA Doppler velocity waveforms included absent or reversed end diastolic flow. We analyzed the data with chi square, Student’s t-test and analysis of variance as appropriate. RESULT: Seventy-three twin pairs met criteria for inclusion, including 16 with discordant growth. The discordant group was significantly more affected with twin-to-twin transfusion syndrome (TTTS) (P = 0.02). The smaller fetuses in discordant pairs were more likely to display abnormal UA Doppler flow velocity waveforms (P o 0.01). These neonates also had lower Apgar scores (P = 0.03) and were more likely to require care in a neonatal intensive care unit. Our findings persisted after excluding pregnancies with TTTS. CONCLUSION: In MCDA twin gestations complicated by discordant growth, there is an increased frequency of abnormal UA Doppler flow velocity waveforms in small fetuses, and these neonates face clinical challenges after birth. Journal of Perinatology advance online publication, 18 December 2014; doi:10.1038/jp.2014.223
INTRODUCTION Monochorionic diamniotic (MCDA) twin pregnancies are characterized by the presence of a single placenta that is functionally divided into separate portions supporting each individual fetus. Vascular communications between these portions normally maintain balance from net transfusion perspective; however, 10% to 15% of MCDA twin pregnancies are complicated by failure of proper development of this functional separation, with insufficient or abnormal communications, resulting in imbalanced distribution of blood between the two fetuses.1 Although twin-to-twin transfusion syndrome (TTTS) is the best-characterized result of a placental abnormality unique to MCDA twin pregnancies,2 other conditions of an imbalanced placenta and blood-sharing exist, including selective fetal growth restriction and twin anemiapolycythemia sequence (TAPS). These complications, which are unique to monochorionic placentation, share the principles of an unbalanced placenta and/or blood-sharing between fetuses but may have a different underlying pathophysiology. Discordant growth in twin gestations, usually defined as a difference of 420% or 25%, has been found in 7% to 15% of MCDA twin pregnancies3,4 and contributes to neonatal mortality and morbidity.5,6 Although there is a higher incidence of TTTS in MCDA twin pregnancies with discordant growth, this syndrome does not account for all instances of discordant growth. We studied whether abnormal umbilical artery (UA) Doppler flow velocity waveforms occur more often in MCDA twin pregnancies characterized by discordant growth compared with non-discordant twin pairs and characterize perinatal outcomes in these pregnancies.
METHODS This is a retrospective study of MCDA twin pregnancies that received antenatal care at a single academic center between January 2007 and January 2010 (n = 98). Cases with confirmed MCDA placentation were included for analysis. MCDA placentation was confirmed by review of first trimester ultrasound data to ensure that these pregnancies had a single placenta, thin dividing membrane and absence of twin peak sign, as well as by final placenta pathology results. Diagnosis of TTTS was made antenatally by standard ultrasound criteria.7,8 Abnormal UA Doppler flow velocity waveforms were defined as absent or reversed end diastolic flow. Estimated fetal weight (EFW) was calculated by standard methods.9 An MCDA twin pregnancy with discordant growth was defined as birth weight difference 420% ((EFWlarger twin − EFWsmaller twin)/EFWlarger twin). Cases without available delivery or neonatal information were excluded from analysis. This study received IRB approval. Data were collected by retrospective chart review from an electronic medical record and from an electronic ultrasound database. Information collected included maternal demographic and medical data, ultrasound data, placental pathology and pregnancy and neonatal outcomes. All MCDA twin pregnancies were monitored according to our institution’s protocol, which consists of first trimester determination of chorionicity, detailed anatomical survey ultrasound at 18 to 20 weeks gestation, fetal echocardiography at approximately 22 weeks gestation and assessment of growth and amniotic fluid volume every 2 to 4 weeks as clinically indicated. It is our policy to perform UA Doppler imaging in cases of discordant or low amniotic fluid volume, defined as one twin with a maximum vertical pocket o2.0 cm or discordant or abnormal growth in either fetus. Doppler studies were undertaken biweekly in cases of abnormal UA Doppler findings. Statistical analysis of the data was performed by chi square, Student’s t-test and analysis of variance as appropriate. We analyzed the data first
1 Department of Obstetrics and Gynecology, Yale School of Medicine, New Haven, CT, USA and 2Department of Obstetrics and Gynecology, Upstate Medical University, Syracuse, NY, USA. Correspondence: Dr L Zuckerwise, Department of Obstetrics and Gynecology, Yale School of Medicine, 333 Cedar Street, P.O. Box 208063, New Haven 06520-8063, CT, USA. E-mail: [email protected] Received 27 August 2014; revised 22 October 2014; accepted 4 November 2014
Doppler abnormalities in monochorionic diamniotic twins L Zuckerwise et al
2 Table 1.
Table 2. Antenatal and postnatal characteristics of MCDA twin pregnancies included
Demographic of the study groups
Study group characteristics Maternal age (range), years
Non-discordant (N = 57)
Discordant (N = 16)
P-value
30.0 (16–43)
33.5 (26–42)
0.08
Race/ethnicity (n (%)) Asian African-American Caucasian Hispanic Other Comorbidities (n (%)) Diabetes Hypertension Obesity Tobacco use IVF (n (%))
0.02 9 13 30 5 0
(16) (23) (53) (9) (0)
0 1 14 0 1
(0) (6) (88) (0) (6) 1.0
11 5 4 3
(19) (9) (7) (5)
6 (11)
2 2 1 1
(13) (13) (6) (6)
1 (6)
0.55
Abbreviation: IVF, in vitro fertilization. Non-discordant twin gestation with fetal growth discordance ⩽ 20%. Discordant twin gestation with fetal growth discordance 420%. IVF with or without intra cytoplasmic sperm injection.
with all MCDA twin pairs included and then again after excluding pregnancies complicated by TTTS.
RESULTS Seventy-three twin pairs met inclusion criteria, including 16 twin pairs with discordant fetal growth 420%. Table 1 lists the baseline pregnancy characteristics of the included cases. In the discordant group, there was a higher incidence of Caucasian race (P = 0.02). No difference was found in age, gravidity, parity or incidence of assisted reproductive technology. No difference was found in common co-morbidities that are associated with abnormal fetal growth. The discordant group was significantly more affected by TTTS (P = 0.02), though of the 13 cases of TTTS included, only 6 were characterized by discordant birth weight, comprising 38% of the discordant group, and 7 demonstrated concordant growth. Of the 57 concordant twin pairs, only 1 resulted in the birth of small for gestational age (SGA) neonates, defined as birth weight o10th percentile. In this case, both babies were SGA. In contrast, 9 of the 16 (56%) discordant twin pairs resulted in the birth of an SGA neonate, and in each case only the small twin met criteria for SGA. Table 2 demonstrates antenatal and postnatal findings of the MCDA pregnancies. The smaller twin in the discordant group was significantly more likely to have abnormal UA Doppler flow velocity waveforms (P o 0.01). After birth, the smaller twin in discordant pairs had significantly lower 1-min Apgar scores (P = 0.03), with a median score of seven, compared with nine in the smaller twin of non-discordant pairs. Additionally, both smaller and larger twins of discordant pairs were more likely to require neonatal intensive care unit (NICU) admission after birth as compared with non-discordant twin pairs (88% vs 58% and 81% vs 51%, respectively, P = 0.01), although the length of NICU stay in neonates who were admitted were not significantly different. When cases complicated by TTTS were excluded from analysis, these findings persisted. Although not achieving statistical significance, we found that discordant MCDA twin pairs were delivered approximately 2 weeks earlier than the non-discordant MCDA twin pairs (P = 0.06). Journal of Perinatology (2014), 1 – 3
Antenatal data TTTS (n (%)) AEDF or REDF in UA (%) Large twin Small twin
Nondiscordant (N = 57)
Discordant (N = 16)
7 (12)
6 (38)
− 1.8
− 31.3
P-valuea
0.02 o0.01
Post-natal data GA at delivery (mean ± s.d.) 34.6 ± 4.0 32.4 ± 4.6 0.06 BW (mean ± s.d.) Large twin 2306.8 ± 695.6 1928.1 ± 799.2 Small twin 2134.4 ± 663.9 1376.4 ± 679.3 BW discordance (median 8 (0–20%) 32 (20–51%) o0.001 (range)) Hgb at birth (mean ± s.d.) Large twin 16.6 ± 2.8 15.4 ± 4.3 0.31 Small twin 15.2 ± 2.8 15.6 ± 2.4 0.63 Apgar scores (median (range)) 1-minute Large twin 9 (1–9) 7.5 (1–9) 0.08 Small twin 9 (1–9) 7 (0-9) 0.03 5-minute Large twin 9 (4–9) 9 (5–9) 0.07 Small twin 9 (5–10) 9 (0-9) 0.06 NICU admission (%) 0.01 Large twin 39 81 Small twin 44 88 Length of NICU stay (median (range)) Large twin 13 (1–261) 19 (1–101) 0.17 Small twin 14 (1–126) 18 (1–113) ) 0.24 Abbreviations: AEDF, absent end diastolic flow; BW, birth weight; Hgb, hemoglobin; GA, gestational age; NICU, newborn intensive care unit; REDF, reverse end diastolic flow; TTTS, twin-to-twin transfusion syndrome; UA, umbilical artery. Non-discordant twin gestation with fetal growth discordance ⩽ 20%. Discordant twin gestation with fetal growth discordance 420%. aP-values corrected for gestational age.
DISCUSSION We assessed whether MCDA twin pregnancies with discordant growth are at an increased incidence of abnormal Doppler studies and whether these findings are related to adverse neonatal outcomes. We found that abnormal Doppler flow velocity waveforms occurred with higher frequency in MCDA twin pregnancies with discordant growth. We also demonstrated that pregnancies complicated by discordant growth were more likely to have adverse neonatal outcomes. As the prevalence of MCDA twin pregnancies is low, our study population was relatively small, and therefore we were unable to assess the risks for specific neonatal morbidities related to discordant growth and abnormal Doppler studies; however, we did demonstrate an increased requirement for NICU care, suggesting increased overall neonatal morbidity. Prior studies looking at Doppler assessment in twin pregnancies mostly include both dichorionic and monochorionic twin pregnancies. For example, Giles et al.10 found no difference in maternal or neonatal outcomes when Doppler assessment with biometry was compared with biometry. Importantly, this study did not identify chorionicity of the twin pairs, and based on prevalence of twin types, it is likely that the majority of subjects in this study were dichorionic twin pregnancies. As the placentation of monochorionic twin pregnancies is of utmost importance related to MCDA-specific complications, the data presented in this and © 2014 Nature America, Inc.
Doppler abnormalities in monochorionic diamniotic twins L Zuckerwise et al
similar studies cannot be extrapolated to monochorionic twin pregnancies. Looking specifically at Doppler assessment in monochorionic twins, studies have evaluated Doppler findings and implications in pregnancies complicated by TTTS, as Doppler flow is a component of the Quintero staging system for TTTS.7,11 These studies universally demonstrate that abnormal Doppler findings portend worse outcomes for MCDA twin pregnancies with TTTS, including, but not limited to, fetal or neonatal death, cerebral palsy and NICU admission. One study that focused on UA Doppler flow in monochorionic pregnancies with and without TTTS examined perinatal outcomes of MCDA twin pregnancies with abnormal UA Doppler studies, defined similarly to our study as absent or reversed end diastolic flow, diagnosed between 16 and 20 weeks gestation.12 This retrospective study included 84 MCDA twin pregnancies, all of which had UA Doppler assessment during a routine mid-trimester scan. The pregnancies were then divided into groups based on the presence or absence of MCDA-specific complications (selective intrauterine growth restriction, growth discordance, TTTS) and/or abnormal UA Doppler studies at intake. The authors reported that MCDA pregnancies with complications were more likely to demonstrate abnormal UA Doppler flow at intake. In addition, pregnancies with abnormal UA Doppler flow in the absence of apparent complications were at higher risk for developing complications, such as discordant growth and intrauterine growth restriction. The authors concluded that isolated abnormal UA Doppler flow between 16 and 20 weeks gestation indicates higher risk for development of MCDA-specific complications, even if the pregnancy appears otherwise normal in the mid-trimester. This study suggests a role for mid-trimester screening Doppler assessment of monochorionic twin pregnancies to determine those at risk for developing complications; however, it was underpowered to detect statistically significant differences in perinatal mortality and did not comment on other pregnancy or neonatal outcomes. Furthermore, our current study adds evidence for poor outcomes in MCDA twin pregnancies with abnormal UA Doppler assessment, including UA Doppler abnormalities diagnosed later in gestation. Our study contributes to the current literature that supports the use of UA Doppler waveform velocimetry as a valuable tool for predicting MCDA twin pregnancies at risk for perinatal complications. Our approach to serial Doppler imaging in MCDA twin pairs with abnormal fluid or growth, performed up until the time of delivery, found that MCDA twin pregnancies with discordant growth are at higher risk for adverse perinatal outcomes, and these discordant twin pairs are more likely to demonstrate abnormal UA Doppler waveform patterns during antenatal surveillance. In MCDA twin gestations complicated by discordant growth, there is a higher incidence of TTTS, but this syndrome does not account for all instances of discordant growth and also occurs in the absence of discordant growth. The increased frequency of
© 2014 Nature America, Inc.
abnormal UA Doppler flow velocity waveforms in smaller fetuses of discordant pairs supports the notion that dysfunctional placental vasculature is a possible cause of discordant growth and is a separate entity from TTTS. However, the causal relationship between Doppler abnormalities and discordant fetal growth and subsequent adverse perinatal outcomes in MCDA pregnancies is yet to be determined. Finally, although specific complications of monochorionic placentation, including TTTS, selective fetal growth restriction and TAPS, can affect the pregnancy individually, overlap in these diagnoses is frequent. Our current study showed that TTTS is more common among pregnancies complicated with fetal growth discordance. Interestingly, TAPS did not occur in our discordant growth group. This suggests that, while fetal growth discordance and TTTS might have similar placental angiostructure, TAPS may have a different underlying vascular abnormality. CONFLICT OF INTEREST The authors declare no conflict of interest.
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