Multifetal Pregnancy

S. Grisaru-Granovsky MD PhD

Shaare Zedek MC Jerusalem, 2013

Multiple pregnancies

monozygotic (so-called

‘identical’) polyzygotic (‘non-

identical’ or ‘fraternal’)

Dizygotic twins2 ovum are fertilized. have separate amnions, chorions, and placentas

The 2 types of twin pregnancies: dizygotic and monozygotic.Monozygotic multiple pregnancies result from a zygote being formed from the union of one ovum and one sperm which then divides to form two ‘genetically identical’ individuals

Underlying mechanism :1. ‘splitting’ of a single cell mass (‘splitting

theory’), 2. the development

of more than one organising axis (‘co-dominant axis theory’)

The pattern of placentation in monozygotic twins

depends primarily upon the timing of the underlying twinning:

early division, within the first three days post

fertilisation, results in dichorionic placentation,

approximately three to nine days post fertilisation results in monochorionic twin

placentation splitting after around nine days post

fertilisation results in monoamniotic twins.

(A)Two placentas, two amnions, two chorions (from either dizygotic twins or monozygotic twins with cleavage of zygote during first 3 days after fertilization)

(B)One placenta, one chorion, two amnions (monozygotic twins with cleavage of zygote from the fourth to the eighth day after fertilization)

(C)One placenta, one chorion, one amnion (monozygotic twins with cleavage of zygote from the eighth to the twelfth day after fertilization)

Figure: Transvaginal ultrasonography of dichorionic twin pregnancy at 6 2/7 weeks' gestation. Note separate gestational sacs.

Crown-rump length measurements were concordant (both measured 49 mm).

From: Sherer: Obstet Gynecol Surv, Volume 53(11).November 1998.715-726

20-30% post ART

•The birthrate of monozygotic twins is constant

world wide (approx 4 /1000 births)

•Birth rates of dizygotic twins vary by race:

highest birth rate of dizygotic twinning in Africa

lowest birth rate of dizygotic twinning occurs in

Asia

The Yorubas of western Nigeria have a birth rate

of 45 twins /1000 live births; approx. 90%

dizygotic

MATERNAL High-risk pregnancy Hyperemesis gravidarum

Hypertensive diseases x2.3

Anemia [all types of defic]x2.5

Acute fatty liver of pregnancy

Preterm labor, premature rupture of membranes,abruptionx3

UTIx3

Placenta previa

Polyhydramnios

Delivery complications (eg, Cesarean delivery, placental

abruption, operative delivery, malpresentation, cord

accidents, postpartum hemorrhage)

• Congenital malformations : concordance rate of major congenital

malformations 20% for monozygotic twinsDizygotic twin pairs discordant

• Early pregnancy loss• Specific multifetal pregnancy complication [TTTS, sFGR etc]

• Preterm delivery• Low birth weight,

• Intrauterine growth retardation

United States (2006):Premature: 11% of singletons (< 37 weeks' gestation) vs 61%

multiples LBW(< 2500 g) 6% of singletons vs 59% multiples

very low birthweight neonates (< 1500 g)1% singletons vs 11% multiples

FETAL HIGH RISK PREGNANCY

Maternal Adaptation

Increased progesterone, estradiol,estriol, human placental lactogen (hPL), human chorionic gonadotropin (hCG), and alpha-fetoprotein (AFP)

Third trimester multifetal gravidas have increased heart rate and strokevolume compared to singleton gravidas, making cardiac output high: •plasma volume increases by 50-100% for multigravida mothers.

Term singleton uterine volume is reached by twins in the 25th week:

Caloric intake per day:

SingletonTwins2400 kcal/day2800 kcal/day

Weight gain per week:

SingletonTwins0.88 lbs/wk1-1.5lbs/wk

(25-35lbs for(35-45 total lbs) BMI = 19.8 -26.0 pre-pregnancy)

Preterm labor: >40% of twin & >70% triplet gestations

Cervical length of 25 mm at 20-24 weeks : positive likelihood ratio of 5.02 (95% CI: 3.31-7.61) and a negative summary likelihood ratio of 0.75 (95% CI: 0.54- 1.06) for deliverybefore 34 weeks: correlates with a change from a pretest probability of preterm birth of 18.5% to a post-test probability of 14.2% (95% CI: 12.9-15.9) with a negative test, and 47.6% (95% CI:38.9-56.4) with a positive test.

Pre-eclampsia:Scheduled evaluation of signs and symptoms

Low dose aspirin or calcium supplementation

has not been shown to prevent or reduce incidence

25%-60% of triplet gestations with earlier onset

that is more severe or atypical

Interventions???

Cerclage should be reserved for selected patientswith an incompetent cervix and is not for prophylaxis [may increase risk: Berghella V, Odibo AO, To MS, Rust OA, Althuisius SM. Cerclage for short cervix on ultrasonography: meta-analysis of trials using individual patient-level data.Obstet Gynecol 2005;106:181-9.]

Prophylactic tocolysis is not beneficial considering therisk of vascular or pulmonary morbidity for the motherIV magnesium sulfate may be used to delay delivery for 48 hours for betamethasoneadministration or transport to facilities with neonatal intensive care

Bed rest at home may be recommended for higher order multiple gestation starting at 20 weeks

Standardized bed rest is not defined and effectiveness has not been proven

Home Uterine Activity Monitoring (HUAM): no significant benefit in preventing preterm deliveryPossible role in predicting preterm delivery for patients with early cervical change, previous history of preterm delivery, or post-fetal reduction procedure.

PROGESTERONE 1. TWINS: no effect on the primary outcome ofdelivery or fetal death before 35 completed weeks (RR: 1.1; 95% CI:0.9-1.3), TRIPLETS: no reduction in PTB <35 weeks (RR: 1.0; 95% CI: 0.9-1.1)

Rouse DJ, Caritis SN, Peaceman AM, et al. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. A trial of 17alpha-hydroxyprogesterone caproate to prevent prematurity in twins. N Engl JMed 2007;357:454-61.Norman JE, Mackenzie F, Owen P, et al. Progesterone for the prevention ofpreterm birth in twin pregnancy (STOPPIT): a randomised, double-blind,placebo-controlled study and meta-analysis. Lancet 2009;373(9680):2034-40 Caritis SN, Rouse DJ, Peaceman AM, et al. Eunice Kennedy Shriver NationalInstitute of Child Health and Human Development (NICHD), Maternal-FetalMedicine Units Network (MFMU). Prevention of preterm birth in triplets using17 alpha-hydroxyprogesterone caproate: a randomized controlled trial. ObstetGynecol 2009;113(2 Pt 1):285-92.

Seminars in Fetal & Neonatal Medicine 15 (2010) 336-341

Potential mechanisms :‘Supra-physiological’ levels of stimuli to parturition including stretch, placental corticotrophinreleasing hormone (CRH) production and lung maturity factors may result from the increased fetal and placental mass of multiple pregnancy, leading to increased myometrial andfetal membrane activation.

More than 50% of women with twin pregnancy deliver before 37 weeks.

Progesterone is ineffective in preventing preterm birth

in twins. Cervical cerclage may increase

preterm birth in twins.

Performed between 10-13 weeksIndicated for “higher-order” multifetal gestations

viable fetuses have significant risk of delivery prior to 28 weeks with risk serious neonatal morbidity:

triplets have 20% risk of total loss prior to 24 wks with 8% risk of delivery from 24-28 wks

quadruplets have 12% risk of delivery between 24-28 weeks

MFPR is best performed at around 13 weeks after NT

assessment of the risk of T21 and early anomaly scan

and if necessary following CVS.

In trichorionic triplets, although outcome is good with

conservative management, reduction to dichorionic

twins significantly reduces risk of severe preterm labour

and low birth weight with no increase in risk of

miscarriage.

Reduction to a singleton increases risk of miscarriage,

but overall appears to have lowest risk of preterm labour

Anomalies of monozygotic duplication

Twin-twin transfusion syndrome

imbalance in the net flow of blood leads to development : the

donor fetus suffers from

hypovolaemia and hypoxia, while the recipient becomes

polycythaemic and polyuric, with high cardiac output and

polyhydramnios

Congenital abnormalities more prevalent in monochorionic

infants with TTTS[x3]: structural congenital heart defects (VSD,

ASD, PulSt)Seminars in Fetal & Neonatal Medicine 15 (2010) 313-318

A monochorionic twin placenta following vascular injection studies, demonstrating multiple vascular anastomoses, including both clear arterioarterial and arteriovenous communications (Courtesy of Dr L Wee).

Quintero staging systemStage I Both bladders are still visibleNo Doppler anomaliesStage IIThe bladder is invisible in the donor twinNo Doppler anomaliesStage III Doppler anomalies in either twin:AREDF in the UAAbsent or negative ‘a’ wave in the DVPulsatile flow in the UVStage IV Pleural effusion, pericardial effusion, ascitis or hydropsin either twinStage V Death of one twinAREDF, absent/reversed end diastolic flow; UA, uterine artery; DV,; UV,.

G.E. Chalouhi et al. / Seminars in Fetal & Neonatal Medicine 15 (2010) 349-356

Treatment options in TTTS

Fetoscopic laser coagulation of placental anastomoses[ Q 2-4]:

-most cases are diagnosed at around 20-21 weeks,-iatrogenic risks and technical difficulties, most centers generally agree on a 26 week upper limit to perform SLCPV-survival rates of at least one twin following SLPCV range between 65% and 85%, whereas survival of both twins ranges between 35% and 50%-(PPROM) <34 weeks : 28% of cases and mostly during the 3-4 weeksfollowing the procedure-miscarriage, defined by a delivery <24 weeks, occurs in 5-23% of cases

Amnioreduction

Septostomy

Cord coagulation

The Eurofoetus multicentre randomized trial : in severe TTTS treated before 26 weeks of gestation, laser therapy resulted in higher survival rates and better neurologic outcomes than did amnioreduction, both in the perinatal period and during the first 6 months of life Senat M, 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

004;351:136-44.

‘Selective intrauterine growth restriction’

in monochorionic pregnancies

Definition: •the estimated fetal weight (EFW) of the small fetus falls below the 10th percentile•significant fetal weight discordance is an important element of the clinical picture, but not necessary for diagnosis =

Discordance between the EFW of two fetuses>25 [calculatedas the difference between the EFW of the larger twin and the smaller twin divided by the EFW of the larger twin]

• the clinical significance of both twins’ EFW below the 10th percentile without discordance or discordance exists but the smaller fetus’ EFW is above the 10th percentile???

Intrauterine death of a fetus in a monochorionic twin pregnancy

Associated with death or disability of the co-twin in 20-40%due to hypotensive episodes as a result of placental vascular

Anastomoses

Neurologically damaged twin infants vsnormal twin infants:

• death of one co-twin later in gestation• shorter interval between co-twin

death and delivery• delivery earlier in gestation

Expert consensus guidelines for timing of delivery of twin gestations:

according to a clinical scenarioperinatal mortality (PNM) occurs at an earlier

gestational age and at lower birth weight in twins than in singletons

twins lowest PNM was at 37 to 39 weeks

uncomplicated dichorionic twins: 37- 38 weeks/ ACOG up to 39+0uncomplicated monochorionic diamniotic twins : 34-37/ ACOG up to 38+0Monoamniotic twin pregnancy — earlier in the third trimester may (30 - 70 % PNM, which is likely due to cord entanglement), CS

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the Society for Maternal-Fetal Medicine (SMFM) , National Institute for Health and Clinical Excellence (NICE) , ACOG

Ultrasonography performed upon delivery room entry to confirm position & prior to delivery of second twinContinuous lumbar epidural anesthesia for labor Delivery room should be an operating roomDelivery should be by 40 weeks from LMP in DI DI

VERTEX-VERTEX40-50%

Vaginal deliveryClamp first cord &

sonography to exclude 2nd twin funic

presentationC/S rate increases with

increased time interval to delivery of second twin

VERTEX-NONVERTEX35-40%

C/S if twin#2 is significantly larger or if the staff is not experienced in assisted

breech delivery or internal podalic version & total breech extraction;

External cephalic version of twin 2 is 70% successful & total breech extraction is

95% successful

NONVERTEX-VERTEX15-20%

C/S to avoid interlocked heads in

breech/ vertex presentation

(rare)

A randomized trial of planned cesarean or vaginal delivery for twin pregnancy. Barrett JF, et al. N Engl J Med. 2013 Oct 3; 369(14):1295-305.

Thank You

Sorina@szmc.org.il