A Few Too Many Sonography of Multiple Gestations

Ivana M Vettraino, MD, MBA Maternal Fetal Medicine Director, Perinatal Center, Genetics and Outreach Mercy – St Louis Disclosures

 Speakers bureau  March of Dimes  Hologic, Inc  Trainer  Nexplanon

 I will not be discussing any of these organizations or products in this presentation

2 Objectives

 Define and describe the categories of multiple gestations  Describe the keys to ultrasound assessment of multiple gestation  Describe sonographic complications of twin gestation and other higher order multiples  Introduce management of twin gestation in the prenatal period Introduction

 Account for 3 % of all pregnancies  Incidence human pregnancies  Approximately 1 in 90 births  Rate varies from country to country  Highest numbers - Nigeria (45 twins per 1000 live births)  Lowest in Japan (4 twins per 1000 live births)  United States (2016) – 33.4 twins per 1000 live births  Vary by ethnic group  Hispanic women  19.5 per 1000 births  Non-Hispanic black women  30.0 per 1000 births  Non-Hispanic white women  28.8 per 1000 births Multiple Gestation

 Overall rise in multiple gestations  Older age at childbearing  1/3  Increasing use of infertility therapies  2/3 Triplet Data Twinning

 Monozygotic twins (“identical”)  Develop from a single fertilized ovum  Have same genetic material  Rate is constant worldwide  3.5 to 4 per 1000 births  30 percent of twins

 Dizygotic twins (“fraternal”)  Develop from more than one fertilized ovum  Genetically similar as any full siblings  Rate varies by ethnic background, maternal age, parity, family history, use of ART  70 percent of twins Placentation

 Splitting within first 2 days after fertilization  Separate chorion and amnion - Dichorionic/diamniotic  Different placentas that can be separate or fused  30% of monozygotic twins  Splitting during days 3-8 after fertilization  One chorion and two amnions - Monochorionic/diamniotic  70% of monozygotic twins  Can have vascular communications between the 2 circulations and develop twin-to-twin transfusion syndrome  Splitting during days 9-12 after fertilization  One chorion and one amnion - Monochorionic/monoamniotic  1% of monozygotic twins Placentation

 Conjoined twins  Incomplete embryonic division  Splitting 13 to 15 days after conception  1 in 50,000 births  Classified according to site of union  Thoracopagus - Chest (40%)  Xiphopagus/omphalopagus - Abdomen (34%)  Pygopagus - Buttocks (18%)  Ischiopagus - Ischium (6%)  Craniopagus - Head (2%)

Placentation

 Ascertainment of chorionicity extremely important  Monochorionic twins account for 20% to 33% of twin gestations  Relative risk of perinatal mortality of 2.5  Neurologic morbidity  4 to 5 times dichorionic twins  25 to 30 times singleton pregnancies  Optimal time to ascertain is in the 1st trimester Placentation Diagnosis

 At or after 14 weeks  Discordance of fetal gender by sonogram  Positive predictive value approaches 100%  Only 55% of all twins discordant for gender  Rarely, post-zygotic disjunction can result in a female fetus with 45,X karyotype and a normal male co-twin  Two separate placental masses  Only one-third of twin gestations  Beware the succenturiate placental lobe  Thickness of the intertwin membrane  2 mm or greater had 90% sensitivity and 76% specificity Placentation Placentation Placentation The Yolk Sacs

 Two yolk sacs  Diamniotic twins  One yolk sac  Follow-up sonogram should be suggested as could be monoamniotic or diamniotic Placentation

 35% of twins divide between 2-8 cell stage

 Two babies, two amnions, and two chorions, and one fused or two separate placentas

 Cannot tell difference between these twins unless genetic testing is done

 If two placentas are present – twin could still be identical Placentation

 Ascertainment of chorionicity extremely important  Monochorionic pairs account for 20% to 33% of twin gestations  Relative risk of perinatal mortality of 2.5  Optimal time to ascertain is in the 1st trimester Dating the Pregnancy

 Optimally assigned in 1st trimester using CRL

 Twins conceived by ART

 Embryo age

 Date of transfer

 Discrepancy between CRLs or dates by LMP

 Use size of larger twin

 Decreases risk of missing fetal growth restriction Complications - Antepartum

 Miscarriage

 Premature labor

 Congenital malformations

 Higher incidence of IUGR

 Higher incidence of maternal anemia

 Increased risk for PROM

 Twin-to-twin transfusion syndrome

 Pregnancy induced hypertension

 Hydramnios Complications - Antepartum

 “Vanishing Twin”

 Miscarriage more common in multifetal pregnancies

 One twin lost prior to 2nd trimester in 10 to 40 percent of pregnancies

 Incidence high in pregnancies conceived by assisted reproductive technologies (ART)

 Monochorionic at greater risk than dichorionic

 The more fetuses – the more common Complications - Antepartum

 Spontaneous reduction of one or more gestational sac before the 12th week

 36% of twin

 53% of triplet

 65% of quadruplet pregnancies Complications - Antepartum

 Death of one twin in utero

 2% to 7% in spontaneously conceived pregnancies

 25% in gestations conceived by ART

 After the 1st trimester

 Intrauterine growth restriction

 Preterm labor

 Perinatal mortality Complications - Antepartum

 Premature delivery

 Duration of pregnancy decreases with increasing fetal number

 Indicated preterm deliveries far more common that those by spontaneous preterm labor

 Preeclampsia

 Discordant growth

 Worsening maternal medical condition Complications - Antepartum

 Average length of pregnancy

 Singleton 39-41 weeks

 Twins 35-37 weeks

 Triplets 33- 35 weeks

 Quadruplets 29 -31 weeks Complications - Antepartum

 Cervical length assessments  No longer recommended  Don’t place a cerclage in women with short cervix who are pregnant with twins

 Does not reduce actual rate of preterm births Complications - Antepartum

 Congenital malformations

 Twice as high as singleton

 Monochorionic twins approximately twice dichorionic twins

 Greater risk in pregnancies conceived by ART

 Can be discordant

 One twin may be normal appearing and the other anomalous Images

Twin Gestation with Co-existent Normal Fetus and Complete Hydatidiform Mole Images Molar degeneration

Normal appearing placenta Images “Twin Molar Pregnancy”

 Prevalence

 1 in 22,000 to 1 in 100,000 pregnancies

 Must be differentiated from partial molar pregnancy

 Presence of triploid fetus with multiple anomalies and early onset severe fetal growth restriction

 Continuation can place mother at risk for persistent trophoblastic disease which can be fatal

 1/3 of pregnancies complicated by vaginal bleeding and severe preeclampsia

 Live birth in approximately 35 % of pregnancies Images

10 5/7 weeks’ gestation Images Images

Monochorionic diamniotic

14 4/7 weeks’ gestation Images

Nuchal hygroma Skin edema Complications - Antepartum

 Higher incidence of IUGR  Prevalence of 26% in dichorionic and 46% in monochorionic twins  Monochorionic twins  Disproportionate placental sharing  15 percent of pregnancies  Associated with 5 to 10 percent of the perinatal mortality  Management options depending on gestational age  Selective termination  Strict antepartum surveillance  Consideration of early delivery Complications Monochorionic Twins

 Twin to twin transfusion syndrome (TTTS)

 Selective intrauterine fetal growth restriction (sIUGR)

 Discordant fetal growth

 Twin anemia polycythemia sequence (TAPS)

 Twin reverse arterial perfusion (TRAP)

 Monochorionic monoamniotic twinning Complications - TTTS

 Complicates 10 to 15 % of monochorionic twins  Usually presents in the second trimester (16 to 26 weeks’)  1/3 of perinatal deaths in monochorionic pregnancies  Ablation of placental anastomoses prior to 26 weeks’ gestation

 Perinatal survival 50 to 70 percent Early Sonographic Findings

 First Trimester  CRL discordance

 Nuchal translucency

 Greater than the 95th percentile

 Discordance of greater than 20 percent between each fetus

 Reversal or absence of A wave of the ductus venosus

 Subjectively discordant fluid volumes TTTS – Staging Criteria Images Images

MVP = 8.02 cm

MVP = 1.89 cm Images

Demise of One Fetus Complications – sIUGR Early

 10 percent of monochorionic twins  Discordant growth  Mean EFW less than 10th percentile in one fetus  Mean EFW discordance greater than or equal to 25%

 Calculation

 (larger weight – smaller weight)/larger weight Complications – sIUGR Late

 5 percent of monochorionic twins  Discordant growth

 Mean EFW less than 10th percentile in one fetus

 Progressive discordance in the 3rd trimester  Outcomes usually good unlike early onset sIUGR Categories

SIUGR Type Clinical Features Timing of Delivery

• Good prognosis with mild 1 growth discordance 34-35 weeks’ gestation Normal umbilical artery • Low risk of IUFD Doppler – Diastolic flow • Low risk brain injury co-twin

2 • High risk for progression 26-32 weeks’ gestation Reversed or absent end and IUFD of IUGR twin diastolic flow in the • Low risk brain injury co-twin umbilical artery Doppler • Low risk of hypoxic 3 deterioration of IUGR twin Intermittent reversed or • 10 to 15 % risk unexpected 30 weeks’ gestation absent end diastolic flow demise IUGR twin in the umbilical artery • 10 to 15 % risk brain injury Doppler co-twin Ultrasound Obstet Gynecol 2007;30:28-34 sIUGR Management Considerations

Fetal Diagn Ther 2014

sIUGR Management

 Type 1  Weekly to twice weekly sonograms to assess fetal growth and progression to Type 2 or 3  Type 2 and Type 3  May necessitate consideration for fetal therapy  Selective cord occlusion  Improve outcome for normally growing twin by stopping blood flow to growth-restricted twin  Bipolar cord coagulation (BCC) or radiofrequency ablation (RFA) Complications - TAPS

 3 to 5 % of monochorionic twins (3rd trimester)  Chronic fetofetal transfusion leads to anemia/polycythemia  Complications of incomplete laser treatment for TTTS  2 to 6 percent of cases  More aggressive  Significant hemoglobin differences between fetuses  Elevated middle cerebral artery peak systolic velocity indicating severe fetal anemia in one twin  Fetal hydrops in the absence of TTTS  Management  Intrauterine blood transfusion of anemic fetus  Repeat laser procedure  Cord coagulation  Early delivery Diagnosis - TAPS Fetal Diagn Ther 2010;27:181-190

 Prenatal  MCA-PSV greater than 1.50 MOM - Donor  MCA-PSV less than 0.8 MOM – Recipient  Postnatal  Intertwin hemoglobin difference of greater than 8 mg/dl  Intertwin reticulocyte count ratio greater than 1.7 donor/recipient NEJM 2000;342:9-14 Complications - TRAP

 1 % of monochorionic twins  Presence of a normal fetus and an anomalous (acardiac) fetus  Placental arterio-arterial connection from pump twin to anomalous fetus  Cardiac hypertrophy and failure develop in pump twin  50 to 75 percent of casesof demise of pump twin without treatment  Risk to rises as the size of the anomalous fetus increases  Fetal therapy  Bipolar cord coagulation  Radiofrequency ablation Complications - Antepartum Twin Reversed Arterial Perfusion Sequence Complications Monochorionic Monoamniotic

 Both fetuses in one amniotic sac  1 in 20 monochorionic twins  Survival 90 % with aggressive management  Complications  Cord entanglement  Cord compression  Twin-to-twin transfusion syndrome  Difficult to diagnose  Growth discordance most important feature Complications Monochorionic Monoamniotic

 Management

 Inpatient management with continuous fetal monitoring controversial

 1 hour of monitoring daily beginning at 26 to 28 weeks’ gestation either as outpatient or inpatient

 Cesarean section following betamethasone at 32 to 34 weeks’ gestation

 Some studies suggest following umbilical artery Doppler for notching Images Images

J Matern Fetal Neonatal Med, 2013; 26(15): 1559–1561. Complications

 Demise of one fetus in monochorionic placentation  Intraplacental connections place co-twin at risk  Death of remaining twin 15% of cases versus 3% for dichorionic gestations  Injury to the brain following death of co-twin  26% versus about 2% in dichorionic gestations

 Etiology  Acute hypotension in dying fetus results in loss of blood volume of remaining fetus resulting in death or survival with potential neurologic injury  Immediate or emergent delivery offers no benefit Management

 12-14 weeks’ gestation  Assess chorionicity  Assess for major anomalies  15 to 28 weeks’ gestation  Twin to twin surveillance every 2 weeks  Detailed fetal anatomic survey  Assess for selective fetal growth restriction  29 to 36 weeks’ gestation  Surveillance for twin complications  Asses for late onset twin to twin transfusion syndrome  Assess for TAPS MISCELLANEOUS Higher Order Multiples

 Frequency increasing in North America secondary to reproductive technologies

 Unique complications of a monchorionic set in a multifetal gestation

 Dichorionic Triamniotic triplets

 Frequency of quadruplets, quintuplets decreasing secondary to selective reduction

 Most recommend C-section delivery regardless of presentation of first fetus Fetal Reduction

 Old term – “selective termination”

 Benefits, Risks, and Complications

 Prenatal genetics Diagnostic Methods

 Preimplantation genetics (PID)  Implies IVF  8 cell stage  Blastomere day 3  Set apart 1-2 cells (embryobiopsy)  Tested by FISH  Implant embryos with favorable test results

Take Home

 Determine chorionicity in multifetal gestations as early as possible

 Ideally by 10 to 13 weeks of gestation

 Monochorionic diamniotic twin pregnancies

 Sonographic exams every 2 weeks beginning at 16 weeks’ gestation for assessment of TTTS

 Sonographic growth assessments every 3 to 4 weeks

 Assess for umbilical cord insertion and other placental abnormalities