sfgr - mcda sfgr - dcda ttts - mcda taps - mcda trap - … · 2019. 6. 3. · dear asma, thank you...

Asma KhalilSt George’s Hospital, University of London, UK

sFGR - MCDA sFGR - DCDA TTTS - MCDA TAPS - MCDA TRAP - MCDA

Complications in Twins

How should we monitor, diagnose and manage TTTS?

Complications in twins

Complications in twins

Polyhydramnios oligohydramnios

Deepest vertical point:16-20 weeks: >8cm AND <2cm>20 weeks: >10cm AND <2cm

Diagnosis

TTTS: Diagnosis

Modified Diagnostic Criteria of TTTS

• <18 weeks• Oligohydramnios (DVP ≤ 2cm)• Polyhydramnios (DVP ≥ 6cm)

• 18-20 weeks• Oligohydramnios (DVP ≤ 2cm)• Polyhydramnios (DVP ≥ 8cm)

•>20 weeks• Oligohydramnios (DVP ≤ 2cm)• Polyhydramnios (DVP ≥ 10cm)

DVP in MCDA twins

Khalil UOG 2017

I: Bladder donor visibleII: Donor empty bladderIII: Critically abnormal DopplersIV: Hydrops in one or both twinsV: IUFD of one twin

Quintero Staging

TTTS: Staging

Twin Pregnancy: TTTS

What is the treatment of choice for TTTS?

• Laser ablation is the treatment of choice for TTTS atQuintero stage ≥II.

A

• Conservative management with close surveillance orlaser ablation can be considered for Quintero stage I.

B

• When laser expertise is not available, serial

amnioreduction is an acceptable alternative after 26weeks.

A

Twin Pregnancy: TTTS

Evolution of Stage 1 TTTS: Systematic Review and Meta-Analysis

Progression 27%

Expectant

At least 1 survival 87%

Amnioreduction

86%

Overall survival

Double survival

79%

70%

77%

67%

Laser

81%

68%

54%

Khalil et al TRHG 2016

Twin Pregnancy: TTTS

North American Fetal Therapy Network: intervention vs expectant

management for stage I twin-twin transfusion syndrome

Emery et al AJOG 2016

010

20

30

40

50

60

70

80

90

100

Expectant

(n=49)

Amnioreduction

(n=30)

Laser surgery

(n=45)

Su

rviv

al (%

)

Double survival

At least one survival (p=0.02)

No survival (p=0.01)

• Retrospective multicentre cohort study

• Stage I TTTS was associated with

substantial fetal mortality

• Progression in 30%

• Both amnioreduction and laser therapy ↓

the chance of no survivors

• Laser was protective against poor

outcome independent of multiple factors

Twin Pregnancy: TTTS

What is the protocol for screening for TTTS?

• Start at 16 weeks and repeat every 2 weeks thereafter

What is the prognosis for MC twin pregnancies with

amniotic fluid discordance?

• Follow up on a weekly basis for progression to TTTS

• Good outcome (93% overall survival)

• Low risk of progression to severe TTTS (14%)

How should TTTS be followed-up and what is the optimal GA for delivery?

• Weekly ultrasound assessment for the first two weeks

after treatment, reducing to alternate weeks followingclinical evidence of resolution.

• In case of sIUD (post-laser)

• Brain imaging in 4-6 weeks

• Neurodevelopmental assessment at 2 years of age

Twin Pregnancy: TTTS

GA at delivery: 34 weeks

Stirnemann et al AJOG 2012

What to look for at the follow-up after Laser for

TTTS?

• Biometry + EFW discordance

• Amniotic fluid volume (DVP)

• Doppler (UA and MCA +/- Ductus venosus)

• Anomaly: heart, brain and limbs

Twin Pregnancy: TTTS

A case of missed TTTS resulting in single intrauterine demise

Complications in twins

• 28 years old, P1• Husband is studying medicine in the UK• Spontaneous MCDA twin pregnancy • First scan at 12 weeks: no concern• Next scan booked at 20 weeks

• 20+4 weeks• Twin 1: sIUD, oligohydramnios• Twin 2: alive, polyhydramnios

• Urgent referral to SGH:• Twin 1 (demised) has oligohydramnios• Twin 2 had polyhydramnios + severe

anaemia • Planned for urgent IUT• Fetal brain MRI in 5 weeks

• Follow-up scans: no concern• Fetal brain MRI at 26 weeks

irregularity at the superior aspect of the bodies of the lateral ventricles, representing focal subependymal cystic changes. This could be due to infection or focal white matter injury (due to hypoxia either arterial or venous). Fissuration is lagging 1-2 weeks. We could organize a follow up scan to monitor the changes.

• Follow-up scans: no concern• Repeat Fetal brain MRI at 30 weeks

The repeat fetal brain MRI has confirmed evidence of periventricular white matter injury, which might be associated with neurological disability. However the brain has matured since the previous MRI, with normal sulcation for gestational age.

The parents remain committed to this pregnancy and will not consider the option of termination of the pregnancy. In fact, they are moving to Canada in approximately 10 days. We would be happy to be contacted if there is any concern.

Dear Asma,

Thank you for all the help and support you gave us to give this baby a chance to be with us today. we truly appreciate. like i promised to inform you, the baby is here. I was induced on the 28th of October, was already 2cm dilated as at the time i got to the hospital. The induction started at 11am and he arrived 7.31pm at 7 pounds 4.4ounces. He was checked by the piediatrician and they feel he is meeting all milestones so far but we keep an eye on him. But i truly beleive all is fine with him.

I will bring him in to visit you once we return to London. we are still in the hospital treating Jaundicr with photo therapy and he is getting better. I have attached his picture to this email. Tank you so much once again.

Kind regards,Ndidiamaka

11-14 week• Dating, labelling

• Chorionicity

• Screening for trisomy 21

20-22 week

• Detailed anatomy

• Biometry

• Amniotic fluid volume

• Cervical length

24-26 week

28-30 week

• Assessment of fetal growth

• Amniotic fluid volume

• Fetal Doppler

36-37 week

Delivery

32-34 week

• Assessment of fetal growth

• Amniotic fluid volume

• Fetal Doppler

• Assessment of fetal growth

• Amniotic fluid volume

• Fetal Doppler

• Assessment of fetal growth

• Amniotic fluid volume

• Fetal Doppler

Dichorionic Twin Pregnancy Monochorionic Twin Pregnancy

11-14 week• Dating, labelling

• Chorionicity

• Screening for trisomy 21

20 week

• Detailed anatomy

• Biometry, DVP

• UA PI, MCA PSV

• Cervical length

28 week

30 week

34 week

32 week

16 week• Fetal growth, DVP

• UA PI

18 week• Fetal growth, DVP

• UA PI

• Fetal growth, DVP

• UA PI, MCA PSV

• Fetal growth, DVP

• UA PI, MCA PSV

• Fetal growth, DVP

• UA PI, MCA PSV

• Fetal growth, DVP

• UA PI, MCA PSV

22 week

24 week

26 week• Fetal growth, DVP

• UA PI, MCA PSV

• Fetal growth, DVP

• UA PI, MCA PSV

• Fetal growth, DVP

• UA PI, MCA PSV

36 week• Fetal growth, DVP

• UA PI, MCA PSV

Twin Pregnancy: ultrasound monitoring

Twin Pregnancy: Single fetal death

MC

PN brain abn

Neurological abn

34%

26%

DC

16%

2%

Death of co-twin

Preterm delivery

15%

68%

3%

54%

Senat MV et al. AJOG 2003

Hillman SC et al. Obstet Gynecol.2011

Hillman SC et al. Semin Fetal Neonatal Med 2010

sIUD in MC twin pregnancy

Referral to Fetal Medicine Centre:

• Detailed scan

• Umbilical, MCA PSV, DV Doppler

• Counselling (15% IUD, 25% neurological

morbidity vs 2% in DC)

Fetal biometry + Dopplers /2weeks

Fetal brain MRI 4-6 weeks after sIUD

Delivery at 34-36 wk after steroids

• TOP if abnormal

• PM (fetus + placenta)

Death of one fetus

Twin Pregnancy: Single fetal death

How should we monitor, diagnose and manage TAPS (Twin Anaemia Polycythaemia Sequence)?

Complications in twins

Diagnostic Criteria

TAPS

POSTNATAL

• Intertwin Hb difference >8.0 g/dl

and

• at least one of the following:

• Reticulocyte count ratio >1.7

• Placenta with only small (<1mm)

vascular anastomoses

ANTENATAL

• MCA-PSV >1.5 MoM in the donor

and

• MCA-PSV <1.0 MoM in the recipient

Incidence• Spontaneous: 3-5% MC twin pregnancies

• Post-laser: 2-13% TTTS cases

Placenta: minute (<1mm) AV anastomoses

Slaghekke et al, Fetal Diagn Therap 2010Lopriore et al, Prenat Diagn 2010

AN staging

Stage 1: Donor MCA-PSV >1.5 MoM and recipient MCA-PSV <1.0 MoM,

without other signs of fetal compromise

Stage 2: Donor MCA-PSV >1.7 MoM and recipient MCA-PSV <0.8 MoM,

without other signs of fetal compromise

Stage 3: Stage 1 or 2 and cardiac compromise in donor

(UA AREDF, UV pulsatile flow, DV increased or reversed flow)

Stage 4: Hydrops of donor

Stage 5: Death of one or both fetuses preceded by TAPS

Stage Intertwin Hb

difference (g/dL)

1 >8.0

2 >11.0

3 >14.0

4 >17.0

5 >20.0

PN staging

Slaghekke et al, Fetal Diagn Therap 2010Lopriore et al, Prenat Diagn 2010

TAPS

Management

• Expectant

• Delivery

• Intrauterine transfusion

• Selective feticide

• Fetoscopic laserLopriore et al, AJOG 2008

Herway et al, UOG 2009Slaghekke et al, Fetal Diagn Ther 2010

Lopriore et al, Placenta 2007

Genova et al, Fetal Diagn Ther 2013 Slaghekke et al, UOG 2014

Lopriore et al, Prenat Diagn 2010

TAPS

• Screening: MCA PSV should be measured in all MC twins andduring the follow-up of treated TTTS cases

• Prevention: Solomon fetoscopic laser ablation technique

TAPS

A case of post-Laser TAPS

Complications in twins

37 years old

1 previous uncomplicated singleton pregnancy

Spontaneous MCDA twin pregnancy

18 weeks

TTTS

Laser

One week post-Laser

One week post-Laser

One week post-Laser

Post-Laser TAPS

Post-Laser TAPSRepeat Laser

Follow-up scansNo recurrenceFetal brain MRI 28 weeksNormal

OutcomeLivebirth x 2

How should we monitor, diagnose and manage FGR in twins?

Complications in twins

• Estimate fetal weight discordance at each scan from 20 wk.

• Do not scan more than 28 days apart.

• Consider a ≥25% difference in size as clinically important

and refer woman to a 3ry level fetal medicine centre.

NICE 2011

The Fetal Medicine

Foundation sFGR Delphi

Diagnostic features

Solitary: EFW <3rd centile

Contributory: at least 2/3

• EFW <10th centile

DC twins MC twins

• EFW discordance ≥25%

• Umbilical PI >95th centile

Solitary: EFW <3rd centile

Contributory: at least 2/4

• EFW <10th centile

• EFW discordance ≥25%

• Umbilical PI >95th centile

• AC <10th centile

NEW

Khalil et al UOG 2018

What is the management of sFGR?• DC twins: sFGR can be followed as in FGR singletons

• MC twins: limited evidence to guide themanagement

Twin Pregnancy: sFGR

sFGR - MCDA sFGR - DCDAOptions include:

• Conservative management

followed by early delivery

• Laser ablation

• Cord occlusion

What is the follow-up protocol for sFGR?

• In DC sFGR fetal Dopplers should be assessed every two

weeks depending on the severity. In MC sFGR

pregnancies fetal Dopplers should be assessed at least

weekly.

Twin Pregnancy: sFGR

How should sFGR in MC twins be classified?• depends on the pattern of the end-diastolic velocity

in the umbilical artery Doppler.

Type 1 Type 2 Type 3

When should we deliver twins with sFGR?

• In DC sFGR: avoid delivery <30-32 weeks

• In MC sFGR:

If there is a substantial risk of fetal demise of the smaller

twin (e.g. reversed a-wave in DV)

• >26 weeks: consider delivery

• <26 weeks: consider selective termination

D

Delivery

• sFGR type 1: 34-36 weeks

• sFGR type 2 and 3: 32 weeks or earlier if deterioration

Twin Pregnancy: sFGR

How should we manage discordant anomaly in twins?

Complications in twins

Discordant anomaly in twins

How common are structural or genetic anomaly in twins?6% in total birth vs 3% newborn

Most of the anomalies affect only one twin (>80%)

Do anomalies in twins differ according to chorionicity?• 1% DC vs 4% MC twins• MC twins 4 x singletons

The Fetal Medicine

Foundation Congenital anomalies in twins

What is the detection rate of anomalies in twins in the 1st trimester? 27%

What are the risk factors? • Monochorionicty• CRL discordance • NT discordance

Discordant anomaly in twins

Which anomalies affect twins?• Heart and CNS (Brain and NTD)• Midline anomalies in MC twins

The Fetal Medicine

FoundationCongenital anomalies unique to twins

Midline structural defects (twinning process) Conjoined twins

The Fetal Medicine

Foundation Congenital anomalies unique to twins

• Brain abnormalities • PVL• Ventriculoemegaly• Cerebral atrophy

• Bowel atresia• Renal dysplasia• Limb amputation

Malformations resulting from vascular event (hypotension and/or ischaemia with vascular anastomoses)

The Fetal Medicine

Foundation

Management of Discordant Anomaly

Expectant TOP entire pregnancy

Counselling• Risk of intrauterine death• Risk of miscarriage• Risk of preterm birth

Discordant Anomaly

Selective TOP

The Fetal Medicine

Foundation Discordant Anomaly

What should we consider when we see a twin pregnancy with discordant anomaly?• Chorionicity• Amnionicity• Type of anomaly• Gestational age• Parents’ wishes• Technical and legal matters

Twin Pregnancy: Discordant anomaly

How should twin pregnancies discordant for fetal anomaly

be managed?

• Twin pregnancies discordant for fetal anomaly should

be referred to a regional fetal medicine center.

• lethal abnormality with a high risk of

intrauterine demise:

• DC twins: conservative management

• MC twin: selective termination to

protect the healthy cotwin against

the adverse effects of spontaneous

demise.

Twin Pregnancy: Discordant anomaly

Selective Feticide in Twin Pregnancies

• Dichorionic: intracardiac or intrafunicular injection of

KCl or lignocaine, preferably in the first trimester.B

• When the diagnosis is made in the second trimester,

women might opt for late selective termination in the

third trimester, if the law permits.

MC pregnancies: cord occlusion, intrafetal coagulation (laser or

radiofrequency ablation)

• Survival >80%

• Premature rupture of the membranes and PTB <32 weeks 20%

• Adverse neurological sequelae

Khalil et al UOG 2016

Trisomy 21 – Meta-analysis

NIPT in Twin Pregnancies

Lau et al 2013; Huang et al 2014; Benachi et al 2015; Sarno 2016; Tan 2016; Gil et al UOG 2017

all12

Total DR (%)

Lau et al 2013 100

Huang et al 2014 9 100

FPR (%)

0

1 0

all12Benachi et al 2015 100

Sarno et al 2016 8 100

Tan et al 2016 4 100

0

0

2 0

Pooled analysis 24 100 0

Non-Trisomy 21

Study

12

Total

180

10

12

409

506

5

1110

Trisomy 21

Trisomy 18/13

NIPT in Twin Pregnancies

Detection Rate False Positive Rate

67% (2/3) 0% (0/254)

Sarno et al UOG 2016

Study

Sarno et al 2016

63% (5/8) 0.15% (1/658)Published studies

Singletons

Twins

Log fetal fraction

Fre

qu

en

cy

Fre

qu

en

cy

Median Fetal fraction

11% 8%

Singletons Twins

Sarno et al UOG 2016

Although the total fetal fraction

in twins is 1.6 x singletons, the

average fetal fraction per twin is

lower.

Fetal fraction

NIPT in Twin Pregnancies

Risk factors for Failed

NIPT:

• Maternal BMI (dilutional)

• IVF (impaired placentation)

Twins ----

Singleton

IVF

Non-IVF

MA 35 years

Caucasian

CRL 55 mm

Maternal BMI (Kg/m2)

cfD

NA

failu

re r

ate

(%

)

Sarno et al UOG 2016

NIPT in Twin Pregnancies

How should we diagnose and manage Twin Reversed Arterial Perfusion?

Complications in twins

Ultrasound findings• Absence of normal cardiac structure • Cardiac movement • Variable structural abnormalities

Twin reversed Arterial Perfusion

Heart failureIntrauterine demisePolyhydramniosPreterm birth

TRAP sequence

Controversy on timing of intervention

• Risks: demise of the co-twin; preterm birth

• Spontaneous cessation of the flow in theacardiac twin

• High loss rate (54%) between diagnosis in thefirst trimester and planned intervention at 16weeks

• Prenatal intervention: 80% survival rate

• Lower very preterm birth rates with early vs lateintervention

Lewi L, AJOG 2010; Chaveeva P, Fet Diagn Ther 2014

Pagani G, UOG 2013

A: Spontaneous demise at 13-16 weekB: Spontaneous arrest of flow at 14-17 weekC: Pump twin alive at 16-18 week with reversed flow

Management of TRAP• The chances of survival of the pump twin are increased by the

use of minimally invasive techniques (preferably <16 weeks)

• Intrafetal Laser

• Cord coagulation/ligation

• Laser photocoagulation of the anastomoses

D

Twin Pregnancy: TRAP

Take-home Messages

Thank you

• DC twins: US every 4 weeks after 20 weeks• MC twins: US every 2 weeks after 16 weeks

• sFGR in DC twins: avoid delivery <30 weeks• sFGR in MC twins: Gratacos classification

•TTTS: Polyhydramnios • TAPS: MCA PSV discordance

• TTTS: US every 2 weeks from 16 weeks• TAPS: MCA PSV from 20 weeks and follow-up after Laser (TTTS)

• TTTS: Laser surgery (Soloman) at 16-26 weeks (≥stage 2)• TAPS: Individualised management options (no guidance)

Complications in Twins

Twin reversed Arterial Perfusion

Radiofrequency ablation

Twin reversed Arterial Perfusion

Intrafetal interstitial Laser

35 years old

IVF MCDA twin pregnancy

TRAP mass; 50% size of the pump twin

Normal NT and ductus venosus Doppler

Prognosis

Size of the TRAP mass

NT and ductus venosus Doppler of the pump twin

Twin reversed Arterial Perfusion

Intrafetal interstitial Laser

Laser at 13 weeks

Follow-up scans

Follow-up scan at 28 weeks

Follow-up scan at 28 weeks

Fetal brain MRI 29 weeksNormal

TRAP mass

Follow-up scan at 29 weeks

Weekly monitor

Delivery by CS

35+ weeks

Take-home Messages

Thank you

• DC twins: US every 4 weeks after 20 weeks• MC twins: US every 2 weeks after 16 weeks

• sFGR in DC twins: avoid delivery <30 weeks• sFGR in MC twins: Gratacos classification

•TTTS: Polyhydramnios • TAPS: MCA PSV discordance

• TTTS: US every 2 weeks from 16 weeks• TAPS: MCA PSV from 20 weeks and follow-up after Laser (TTTS)

• TTTS: Laser surgery (Soloman) at 16-26 weeks (≥stage 2)• TAPS: Individualised management options (no guidance)

Complications in Twins

Twin reversed Arterial Perfusion