“Ultrasound Imaging in Multifetal Pregnancies:

Its More than Chorionicity”

Anthony Johnson, DO Professor, UTHSC, Houston, TX

Co-Director, Texas Fetal Center, CMHH

1

Disclosures

• I have no relationships with commercial companies that could be perceived as a conflict of interest.

• I will not be discussing the use of products that are investigational or approved devices that are being used “off label”

Perinatal mortality MC vs. DC twins

Dutch cohort study 1995-2004

Outcome MC (n = 198)

DC (1107)

Hazard Risk (95%CI)

Perinatal Mortality

11.6% 5.0% 2.44 (1.73-3.44)

Stillbirth 7.6% 1.5% 5.21 (3.18-8.51)

Screening protocol: -  1st trimester ultrasound for chorionicity -  20 wks anatomic survey -  Serial ultrasounds (fortnightly) for growth, AFV and Doppler assessment

Hack KEA et al BJOG 2008;115:58-67

Survival Twin live births 172 85% Singleton 15 7% Double demise 15 7% Complication TTTS 18 9%

sIUGR 30 15% Losses Total 11% (TTTS ~ 42%) < 24 weeks 84%

> 24 weeks 16% > 32 weeks 1%

Lewi et al., 2008

Outcome of MCDA twin gestations in the era of invasive fetal therapy

Extra loss in MC twins is due to complications placental anastomoses

Complications in Monochorionic Multi-Fetal Pregnancies

•  Twin-Twin Transfusion Syndrome - Oligo/Polyhydramnios Sequence ~ TOPS - Twin Anemia Polycythemia Sequence ~ TAPS

•  Twin Reverse Arterial Perfusion •  Growth Discordance •  Discordant malformations -  Structural - Chromosomal

•  Monoamnioitc

Diagnosis

"There is NO diagnosis of twins.”

K Nicolaides, 02/27/09

“The only diagnosis is a monochorionic or dichorionic twin gestation. This should be written in capital red letters on the front of the chart at 8 - 10 weeks".

Multifetal Pregnancies Ultrasound Determination of Amnionicity & Chorionicity

1st Trimester Ultrasound Examination: -  Amnionicity and chorionicity should be documented for all

multiple gestations when possible.

2nd & 3rd Trimester Ultrasound Examination: -  Multiple gestations require the documentation of additional

information: chorionicity, amnionicity, comparison of fetal sizes, estimation of amniotic fluid volume on each side of the membrane, and fetal genitalia (when visualized).

AIUM PRACTICE GUIDELINES, Oct 2007

ACOG PRACTICE GUIDELINES, #101, Reaffirmed 2011

Ultrasound techniques for determining chorionicity & amnionicity

First trimester Second Trimester Third Trimester

No. of gestational sacs

No. of yolk sacs

Umbilical cord entanglement

Fetal sex

Separate placental discs

No. of layers in membrane

Membrane thickness

Lambda or Twin Peaks or T-sign

J Robinson & AZ Abuhamad Modern Medicine 2002

amnionicity

chorionicity

Multifetal Pregnancies Chorionicity

Moise KJ Texas Medicine 2007

Monochorionic “T” sign

Dichorionic Lambda or Twin Peak sign

Multifetal Pregnancies ~ Establish chorionicity 10 - 14 weeks

“T” sign Monochorionic

Twin Peak (lambda) Dichorionic

Accuracy of Ultrasonographic Chorionicity Classification*

Pathologic Evaluation Misclassification Total 545 6.4% Dichorionic 455 4% Monochorionic 90 19%

*Classified by ultrasound < 20 weeks

Sensitivity Specificity PPV NPV 96% 81% 96% 80%

< 14 wks vs. 15-20 wks Odds Ratio: 0.47; 95% CI 0.23, 0.96

Blumenfeld Y AIUM 2013; Cleary-Goldman J et al 2004

58% ACOG optimal time for Dx chorionicity 1st trimester 62% Manage all twins without MFM consultation

Accuracy of referral vs. tertiary diagnosis of amnionicity and chorionicity Center DADC DAMC MOMO Total

Twins DADC DAMC MOMO

Referring Tertiary

Referring Tertiary

Referring Tertiary

45% 98%

49% 96%

50% 83%

83

167 40 72 8 5

Triplets TATC TADC TAMC

Referring Tertiary

Referring Tertiary

Referring Tertiary

28% 96%

24% 92%

0

100%

8

25 4

13 1 1

Wan JJ et al Prenat Diagn 2011

Accurate diagnosis of A/C can be obtained by assessment of key sonographic findings Emphasis on need to enhance diagnostic skills in the general community & referral if dx ambiguous

Take home message Two is better than one !!

 

Bipartite Monochorionic Placentation

•  Twin Pregnancies with two separate placental masses can still be monochorionic and have vascular anastomoses

•  Lopriore E, et al 2006 ~ 3/109

•  Machin GA et al 2002 ~ 8/600

If is looks like TTTS ~ it is until proven otherwise

Monozygotic Twins Incidence of Anomalies

– 845 pairs of twins w/evaluation of zygosity: •  483 monozygotic •  252 dizygotic •  110 zygosity unconfirmed

–  Anomalies: •  MZ: 2.7% (82% discordant) •  DZ: 1% (100% discordant) •  Singletons: 0.6%

Chen et al. Acta Genet Med Gememol 1992;41:197-203

Bahityar MO, J Ultrasound Med 2007;26:1491

Monochorionic Twins Management of Anomalies

•  Old theory of “bad humors’ crossing to the live twin discounted

•  Acute hemodynamic changes the more likely etiology •  No benefit from acute delivery •  15% of cases associated with IUFD of co-twin

–  ↑ 5X over dichorionic twins

•  34% abnormal postnatal cranial imagine with IUFD co-twin •  26% of survivors with neurologic sequelae

–  ↑ 12X over dichorionic twins

Risk of death or longterm compromise co-twin

Fusi et al. Obstet Gynecol 1991;78:517-20 Ong et al. BJOG 2006;113:992-8 Hillman et al Obstet Gynecol 2011;118:928-40

Observation Intervention

Maternal-Fetal Surgery: Balancing Risks Discordant Fetal Malformation Multifetal Gestations

Perinatal Outcomes of Twin Pregnancies Discordant for Major Fetal Anomalies

Category Normal Twins Discordant Twins*

P

Number 235 13 GA_Delivery 34

(16-40) 32

(24-37) 0.029

Birth Weight 2030 (180 – 3680)

1640 (520-3320)

0.022

Perinatal Survival

91% 69% 0.018

Gul A et al, Fetal Diagno Ther 2005;20:244

*2/3 cotwin in MCDA set end as IUFD

Dilemmas in Management of twins discordant for anencephaly diagnosed at 11-14 weeks

Chorionicity # Hydramnios Livebirth GA Delivery

Delivery < 33 wks

DICHORIONIC Expectant Obs Reduction

35 9

57%

0

97% 89%

36 37

18% 13%

Monochorionic Expectant Obs

19

52%

84%*

33

38%

MC Intervention Laser coagulation Cord Ligation Bipolar

6

24 92

100% 54% 77%

33% 69% 31%

* IUFD of affected Twin with co-twin demise in 3/4

Vandecruys H Ultrasound Obstet Gynecol 2006;28:653

Acardiac Twin Incidence 1/35,000

Earliest form of TTTS

Reverse Arterial Perfusion ~‘acardiac”

Co-twin anomaly ~ 10%

Perinatal M&M ~ 50%

Growth AT:PUMP 70%

Polyhydramnios

Cardiac decompensation in pump twin

Acardiac Twin

Acardiac Twin

Outcome in TRAP Pregnancies Observation vs. Intervention

Acardiac size < 50% of Pump

Group N Acardiac Size

MOMO Pump Survival

GA Delivery

Observation 8 27% 38% 88% 34

Intervention (RFA)

7 49% 0% 100% 36

Jelin E et al Fetal Diagn Therp 2010:27;138

IUFD of pump twin, 33% Arrest of Flow Acardiac, 24% Pump alive Flow In Acardiac, 46%

Liesbeth L et al, AJOG, 2010; 203,213.e1 - 213.e4

Outcome of TRAP sequence diagnosed in the first trimester

Survival Rate 1st Tri DX 46% 11/24 3/5 Pump twins Demise or Abnl CNS Following arrest of flow to acardiac Intervention need 12-16 weeks

Twin-twin Transfusion Syndrome

Dickinson et al. Am J Obstet Gynecol 2000;182:706-12 Saunders et al. Am J Obstet Gynecol 1992;166:820-4

•  Complicates 9 – 15% of MCDA twins •  1 in 58 twin pregnancies •  1 in 4,170 pregnancies •  Presentation < 26 weeks ~ 90% perinatal mortality

Monochorionic Twins Epidemiology of TTTS

Twin Twin Transfusion Syndrome Diagnosis

Single placenta Polyhydramnios (8cm) / oligohydramnios (2cm) Concordant for sex Discordant for size and placental echogenicity Recipient persistent enlarged bladder Donor small or non-visible bladder

Prediction of Twin Twin Transfusion

Nuchal Translucency Folding Intertwin Membrane Arterio-arterial anastomoses

*Sueters M et al Ultrasound Obstet Gynecol. 2006 Oct;28(5):659-64

Discordant AFV*

Twin-Twin Transfusion Syndrome Staging (TOPS)

Stage I Oligohydramnios(<2cm) with Polyhydramnios(>8cm)

Stage II Discordant fluid volume No bladder in the donor twin

Stage III Doppler flow- absent or reversed in umbilical artery or ductus venosus, pulsatile flow in the umbilical vein

Stage IV Hydrops in one or both fetuses

Stage V One or both fetuses have died

Quintero R et al J. Perinatol 1999;19:55

Quintero Stage Related Outcomes in TTT Following Laser Photocoagulation

Report N I II III IV

Quintero, 2003 Both > 1

95 67% 86%

49% 86%

25% 79%

46% 82%

Huber, 2006 Both > 1

200 76% 93%

61% 83%

54% 83%

50% 70%

Suspected TTTS How often Dx Correct & Referral Timely

N % Confirmed Dx TTTS 249 77% Stage 1 2 3 4 5

28 50

150 15 10

11% 20% 60% 6% 4%

No TTTS 75 23% Discordant AFV sIUGR

42 33

56% 44%

Gandhi M et al, 2012

Twin Anemia-Polycythemia Sequence (TAPS)

Study N Post-laser Robyr, 2006 101 13% Habli, 2009 152 2% Slagehekke,2010 276 8%

Spontaneous* Lewi et al, 2009 202 5% Lopriore, 2010 113 5%

Slagehekke F et al Fetal Diagn Therapy 2010

•  Larger intertwin hemoglobin difference w/o signs of TOPS

•  Intertwin blood transfusion w/o hormonal imbalance

•  Post laser: ex-recipient anemic w/ ex-donor polycythemic ~ 77%

•  Spontaneous reported as early as 16 weeks

TAPS Optimal Management is Unclear

•  Expectant observation •  Induction of labor •  Selective reduction •  Laser photocoagulation •  Intrauterine transfusion

Intravascular/intraperitoneal IV / exchange transfusion

•  Perinatal mortality and morbidity unknown

•  Majority Dual Survivors •  IUFD (dual & single) •  Thrombosis, CNS

Infarct; Hydrops

Delivery 32 wks 4 days Dual survivors Single AA at placental edge

Herway C et al Ultrasound Obstet Gynecol 2009;33:592

Schrey S et al AJOG 2012

Vascular Occlusion Injuries in TTTS

•  95% recipient •  85% lower limb

•  71% right sided

•  Intestinal atresia •  Mechanism

•  Polycythemia •  Hyperviscosity •  Hypertension •  Vascoconstriction

Discordant Growth & Selective IUGR

Discordant Growth in Twin Pregnancies Associated Outcomes

•  Anomalies •  IUGR •  Preterm Birth •  Intrauterine infection •  Stillbirth •  UA cord ph < 7.10 •  NICU Admission •  RDS •  Neonatal Death

•  Detection efficacy •  Significant threshold •  Co-morbidities •  Management strategy

ACOG Practice Bulletin #56, reaffirmed 2009

Debate

Factors Affecting Fetal Growth Discordance

Maternal •  Tobacco •  Vascular disease •  Poor prenatal care •  Low Maternal wt gain

Placental* •  Vascular anastomoses •  Placental sharing •  Placental weight •  Velamentous insertion

Fetal •  Aneuploidy •  Sex-discordance •  Viral Infection

* Major component of discordance in MC twinning

Definition & Impact of Discordant Fetal Growth in MC Twins

•  Discordant Growth - (Largest – Smallest) / Largest * 100 - EFW or birthweight -  ACOG defines discordance 15-25% -  SOGC – > 20% EFW or [AC large – AC small] > 20 mm

31 publications > 1.1 million twins 16% discordance

137,000 US twin births/yr 22,000 discordant twins/yr

Martin JA CDC NCHS data brief 80;2012 Miller J et al AJOG 2012:206;10

Discordant growth = selective growth restriction

First trimester prediction Twin complications & adverse outcome

Study # Placenta Bwt > 20%

sIUGR Early IUFD

Perinatal Mortality

Sebire, 1998 549 MC/DC - - + -

Kalish, 2004 159 DC + - + -

Tai, 2007 178 MC/DC + - - -

Banks, 2008 135 DC - - - -

Memmo, 2011 242 MC +

D’Antonio, 2013 2155 MC/DC - - - -

In the absence of aneuploidy or structural malformations CRL discordance is a poor predictor for adverse perinatal outcome in MC and DC twin pregnancies

D’Antonio F, Ultrasound Obstet Gynecol.2013; Feb 14. doi: 10.1002/uog.12430

Discordant Growth in Twin Pregnancies 2nd Trimester Ultrasound Predictive Accuracy

Screening Test Sensitivity Specificity

AC 65-83% 65-90%

EFW 50-93% 80-93%

Discordance > 20%

Miller J et al AJOG. 2012;206:10-20

Discordance & Adverse Outcome by Chorionicity

Choriionicity HR (95% CI) P HR (95% CI) P

Monochorionic 2.6 (1.4-4.7) <0.003 2.6 (1.6-4.3)<0.001

Dichorionic 1.0 (0.7-1.6) NS 2.2 (1.6-2.9) <0.001

SGA 5% 18% BW

Discordance

DC 18% discordance = Uncomplicated MC MC 18% discordance double risk of adverse outcome

Breathnach FM et al Obstet Gynecol 2011;118:94

MCDA Discordant Growth* Clinical

Early (15)

Late (13)

Concordant (150)

Discordance EFW > 20% < 20 wks > 26 wks

UA Doppler abnl 73% 0 3%

IUFD 27% 8% 1%

TAPS 0 38% 3% GA_Delivery 33 35 35

Birthwt discordance 30% 31% 9%

Overall Survival Rate 83% 96% 99% Placenta

Placenta Territory ratio 2.55 1.6 1.4

Total Anastomotic Diameter (mm)

14 6 9

Lewi L AJOG 2008;199:511.e1

* Bwt Discordance > 25%

Monochorionic Twins Selective IUGR

•  10-15% of monochorionic twins •  Smaller twin EFW < 10%tile for gestational age • Unequal placental sharing • +/- Unbalanced intertwin vascular flow •  Perinatal mortality & long term morbidity

-  Smaller twin: IUFD 30-40% Neurologic 15-40% -  Cotwin twin: IUFD 25-30% Neurologic 20-30%

-  iatrogenic prematurity -  acute feto-feto transfusion

Monochorionic Twins Classification sIUGR

Type Umbilical Artery

IUFD Neurologic Compromise

In Utero Deterioration

GA Delivery

I Normal 2-4% <5% Rare 34-35

II 30-40% 14% 90% Ductus

Venosus Dopplers

< 30

III 15% 15-40% Rare 32+

Perinatal outcome with expectant observation in sIUGR by Umbilical Artery Doppler Classification

0

10

20

30

40

50

60

70

80

90

100

Type I Type II Type III

Both One None

33%

26%

41%

96%

2% 2%

38%

23%

38%

Intact Survivors

Ishii K et al Fetal Diagn Ther 2009;26:157 (23) (27) (13)

Monochorionic Twins Selective IUGR

Expectant Observation •  Fetal monitoring

-  Biophysical profile

-  Ductus venosus Doppler blood flow studies in Type II

•  Early delivery

•  Selective reduction •  Laser ablation placental anastomoses ~ RCT

Monochorionic Diamniotic Twins Frequency of Ultrasound Evaluations

•  Serial sonographic evaluations every 2 weeks, beginning at 16 weeks, until delivery, should be considered for all twins with MCDA placentation

•  Screening for congenital heart disease is warranted in all

MC twins, in particular those complicated with TTTS

SMFM Committee Opinion Am J Obstet Gynecol. 2013;208(1):3-18

Lewi L et al Am J Obstet Gynecol 2008;199:511.e1-7

Two Step Screening Strategy for Complicated Outcomes in MC Twins

Twins Ultrasound Surveillance All twins

-  Ultrasound for anomalies at 18 – 20 weeks -  Placental Cord Insertions

-  Weekly Biophysical profile > 32 weeks Dichorionic

-  Ultrasounds Q 4 weeks for serial growth -  Change in AFV and Doppler UA may precede discordant growth

Monochorionic twins -  Ultrasounds alternate limited and growth, Q 2 weeks, 16 wks

-  Amniotic fluid volume, bladder -  Fetal growth -  Doppler blood flow studies

-  UA, UV, DV and MCA baseline 20 weeks -  Repeat if > 20% discordance with smaller < 10% -  Uncomplicated or late discordance MCA

- Fetal echocardiography

Conclusion Increase awareness of risks associated with MC pregnancies by healthcare providers and patients

– “No Dx Twins” • Establish chorionicity early • Risk stratify multifetal pregnancies DC vs. MC

– MC pregnancies serial ultrasound beginning at 16 weeks • Limited (MVP, UA and bladder) • Growth studies with Doppler assessment

– MFM/Fetal Treatment Center referral consultation for • Targeted ultrasound/echo • Signs of discordance growth or AFV

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Update ACOG Practice Bulletin #56 October, Multiple Gestation: Complicated Twins, Triplets and High-Order Multifetal Pregnancy