MULTIFETAL PREGNANCY → Conjoined twins result if division initiated
 May result from:
→ 2 or more fertilization events
→ From a single fertilization followed by an
“erroneous” splitting of the zygote
→ From a combination of both
 Increased risk for mother and child
→ Increases as number of offspring increases
– 60% of twins, 90% of triplets, almost all
quadruplets are born preterm
→ Infant mortality rate for multiple births is 5x
the rate for singletons
→ Risk for preeclampsia, postpartum
hemorrhage, and maternal death increased
twofold (or more)
→ Increased risk for postpartum depression
 Twinning rate rose from 18.9 to 32.1% in 2009
MECHANISMS OF MULTIFETAL GESTATIONS
Dizygotic vs Monozygotic Twinning
DIZYGOTIC TWINS
 Fraternal twins
 Due to fertilization of two ova during a single
ovulatory cycle
MONOZYGOTIC TWINS
 Identical twins
 Arise from a single fertilized ovum
 May still be discordant for genetic mutations
→ Due to postzygotic mutations or marked
variability in expression
 In a sense a teratogenic event
→ Increased incidence of often discordant
malformations
GENESIS OF MONOZYGOTIC TWINS
 Mechanisms are poorly understood
→ Minor trauma to blastocyst during assisted
reproductive technology (ART) increases
incidence
 Outcome depends on when division occurs
→ If zygotes divide within 72 hours of
fertilization:
– 2 embryos, 2 amnions, 2 chorions
– Diamnionic, dichorionic twin
– 2 distinct placentas or a single, fused
placenta may develop
→ If division occurs in the 4th-8th day:
– Diamnionic, monochorionic twin
→ If division occurs after 8 days:
– Chorion and amnion have already
differentiated
– 2 embryos within a common amnion
– Monoamnionic, monochorionic twin
later (more than 12 days)
 Monochorionic twins may be dizygotic
→ Possibly due to ART procedures
SUPERFETATION
 An interval as long as or longer than a menstrual
cycle intervenes between fertilizations
 Requires ovulation and fertilization during the
course of an established pregnancy
 Not known to occur spontaneously in humans
→ Alleged cases result from markedly
unequal growth and development of twin
fetuses with same gestational age
SUPERFECUNDATION
 Fertilization of 2 ova within the same menstrual
cycle but not at the same coitus (thus not
necessarily from the same male)
FREQUENCY OF TWINNING
 Dizygotic twinning more common than
monozygous splitting of a single oocyte
→ Incidence influenced by race, heredity,
maternal age, parity, fertility treatment
 Monozygotic twinning frequency is relatively
constant worldwide (1 in 250 births)
→ Generally independent of race, heredity,
age, and parity
THE “VANISHING TWIN”
 Incidence of twins in 1st trimester much greater
than incidence of twins at birth
→ 1 twin is lost before 2nd trimester (10-40%)
 Monochorionic twins have a greater risk of
abortion than dichorionic twins
 Spontaneous reduction of a twin
→ 36% in twin pregnancies, 53% in triplets,
and 65% in quadruplets
 Pregnancy duration and birthweight are
inversely related to the initial gestational sac
number
 Higher levels of pregnancy-associated plasma
protein A (PAPP-A) and free beta-HCG identified
if reduction diagnosed after 9 weeks gestation
FACTORS THAT INFLUENCE TWINNING
 Race
→ Highest in African-Americans, lowest in
Hispanic, Asian, and Native Americans
→ May be due to racial variations in FSH
levels
 Maternal age
 → Dizygotic twinning increases 4x between
15-37 years
– Maximal FSH stimulation increases the
rate of multiple follicles developing
→ Also increases with maternal age due to
use of ART
→ Paternal age of little effect
 Parity
→ Increasing parity  increased incidence
→ Eightfold increase if parity 4 or less, 20-fold
increase if parity 5 or more
 Heredity
→ Maternal family history more important than
paternal
→ 4 potential linkage peaks
– Highest peak at the long arm of
chromosome 6
– Others include chromosomes 7, 9, 16
 Nutritional factors
→ Taller, heavier women with 25-30% more
twinning rate than short, nutritionally-
deprived women
→ Correlated more with nutrition than body
size
 Pituitary gonadotropin
→ Associated with FSH levels
→ Paradox of declining fertility but
increasing twinning with increasing
maternal age
– Due to exaggerated pituitary release of
FSH in response to decreased
negative feedback from impending
ovarian failure
 Infertility therapy
→ Ovulation induction with FSH + chorionic
gonadotropin or clomiphene citrate
enhances likelihood of multiple ovulations
→ Mainstay infertility therapy is ovarian
stimulation followed by timed intrauterine
insemination
→ In IVF, the greater the number of embryos
transferred, the greater the risk of twins
and multiple fetuses
SEX RATIOS WITH MULTIPLE FETUSES
 As the number of fetuses per pregnancy
increases, the percentage of male conceptuses
decreases
 More females in twins from late twinning events
 2 explanations
→ Beginning in utero and extending
throughout the life cycle, mortality rates are
lower in females
→ Female zygotes have a greater tendency to
divide
DETERMINATION OF ZYGOSITY
 Twins of opposite sex are almost always
dizygotic
 Monozygotic twins may have different
karyotype or phenotype
→ Related to postzygotic loss of the Y
chromosome in 1 46,XY twin
– Results in Turner syndrome (45,X)
 Risk for twin-specific complications vary wth
zygosity and chorionicity
→ Increased perinatal mortality and
neurological injury in monochorionic
diamnionic twins
 Sonographic determination of chorionicity
→ Can be done in first trimester (10-14 wks)
→ Dichorion
– Thick dividing membrane (>2 mm)
– 2 separate placentas
– Twin peak sign seen
» Point of origin of the dividing
membrane on the placental
surface
» Peak seen as triangular projection
of placental tissue extending a
short distance between the layers
of the dividing membrane
→ Monochorion
– Thin dividing membrane, may not be
seen until second trimester
» Less than 2 mm thick
» Only 2 layers
– T sign
» Membranes and placenta at a
right angle with each other
» No apparent extension of placenta
between the dividing membranes
 Placental examination
→ Visual examination of placenta postpartum
– When first neonate delivered, clamp is
placed on a portion of its cord
– As second neonate is delivered, two
clamps placed on that cord
– Until delivery of last fetus, each cord
segment must remain clamped to
prevent fetal hypovolemia and anemia
caused by blood leaving the placenta
via anastomoses and then through an
unclamped cord
 – Placenta carefully delivered to
preserve attachment of amnion and
chorion
» Monozygotic if 1 common
amnionic sac or if not separated
by chorion
» Dizygotic (or less commonly
monozygotic) if adjacent amnions
are separated by chorion
→ Blood typing
– Different blood types confirm
dizygosity but same blood type does
not confirm monozygosity
Diagnosis of Multiple Fetuses
CLINICAL EVALUATION
 Fundal height
→ Uterine size larger than expected at 2nd
trimester (5 cm greater than singletons)
 Difficult to diagnose twins by palpation of fetal
parts before 3rd trimester
→ Also if 1 twin overlies the other, the mother
is obese, or if there is hydramnios
 Late 1st trimester
→ Heart rate may be identified with Doppler
SONOGRAPHY
 Each fetal head should be seen in 2
perpendicular spaces so as not to mistake a
cross section of the fetal trunk for a 2nd head
 2 fetal heads or 2 abdomens should be seen in
the same image plane
 Higher-order multifetal gestations more difficult to
evaluate
OTHER DIAGNOSTIC AIDS
 Radiography
→ If fetal number uncertain
→ May lead to an incorrect diagnosis if there
is hydramnios, obesity, fetal movement
during exposure, or inappropriate exposure
time
→ Fetal skeletons before 18 weeks AOG
insufficiently radiopaque and poorly seen
 Magnetic resonance imaging
→ Not typically used but may help delineate
complications in monochorionic tiwns
 Biochemical tests
→ No test reliably identifies multiple fetuses
→ Serum and urine beta HCG and maternal
serum AFP higher in twin pregnancy
MATERNAL ADAPTATION TO MULTIFETAL
PREGNANCY
 Maternal complications more likely
 During the first trimester, more nausea and
vomiting than singletons
→ Associated with higher serum beta HCG
 Blood volume expansion at 50-60% (compared
to 40-50% in singletons)
 RBC mass increases disproportionately less
→ Predisposes to anemia (along with
increased iron and folate requirements)
 Blood pressure changes
→ DBP lower with twins at 8 weeks AOG but
increases to a greater degree at term
 Cardiac output increased by another 20%
→ Due to greater stroke volume and to
increased heart rate (to a lesser extent)
→ Vascular resistance lower
 Uterine growth greater
→ Additional 10 L or more in excess of 20 lbs
 Excess amniotic fluid may accumulate
→ Maternal abdominal viscera and lungs
compressed and displaced
 Maternal renal function may be affected
→ Obstructive uropathy due to hydramnios
– May do therapeutic amniocentesis for
relief
– Acute onset with rapid reaccumulation
PREGNANCY COMPLICATIONS
Spontaneous Abortion
 7.3% in multiple pregnancies while only 0.9% in
singletons
 More common in monochorionic placentation
 More risk if pregnancy achieved through ART
Congenital Malformations
 406 per 10,000 twins (vs 238 per 10,000 singles)
→ Twice the rate in monochorionic twins
than in dichorionics
 Structural defects more common in
monozygotic twins
Low Birthweight
 Due to restricted fetal growth and preterm
delivery
 Degree of growth restriction increases with fetal
number
→ Abnormal growth diagnosed only if fetal
size is less than expected for multifetal
gestation, not for singletons
 Degree of growth restriction in monozygotic twins
is greater than in dizygotic pairs
→ Allocation of blastomeres may be unequal
 Vascularity may cause unequal distribution
→ →
of nutrients and oxygen
 Unequal placentation causing size discordancy
→ May also result from fetal malformations,
genetic syndromes, infection, or umbilical
cord abnormalities
Hypertension
 Pre-pregnancy BMI and egg donation are
additional independent risk factors for
preeclampsia
 Preeclampsia – 2-fold increased risk if with GDM
 Fetal number and placental mass are involved
in preeclampsia pathogenesis
→ Higher levels of antiangiogenic soluble fms-
like tyrosine kinase-1 (sFlt-1)
 Hypertension develops more often, earlier, and
more severe in multifetal gestation
Preterm Birth
 Gestation duration decreases as fetal number
increases
→ Prematurity increased 6-fold in twins and
10-fold in triplets
 Increased incidence of premature rupture of
membranes
 Cervical length measurement as predictor
Prolonged Pregnancy
 Twin pregnancy of 40 weeks or more considered
post-term
Long-term infant Development
 Cognitive delay, risk for cerebral palsy increased
in twins
→ Related to increased risk of fetal growth
restriction, congenital anomalies, twin-twin
transfusion syndrome, and fetal demise of
a co-twin
UNIQUE FETAL COMPLICATIONS
Monoamnionic Twins
 1 in 20 monochorionic twins are monoamnionic
→ High fetal death rate due to cord
entanglement, congenital anomalies,
preterm birth, or twin-twin transfusion
syndrome
→ No management available
 Women with monoamnionic twins recommended
to undergo 1 hour daily FHR monitoring
starting at 26-28 weeks
→ Betamethasone given to promote
pulmonary maturation
If FHR is reassuring, CS performed at 34
weeks after 2nd course of betamethasone
Aberrant Twinning Mechanisms
 Due to incomplete splitting of an embryo into 2
separate twins, or due to early secondary fusion
of 2 separate embryos
CONJOINED TWINS
 Thoracopagus most common
 Identified at midpregnancy via UTZ
→ MRI to evaluate connection of organs
 Delivered via CS
→ If for pregnancy termination, vaginal
delivery possible (dystocia common)
 Surgical separation may be successful if
essential organs not shared
EXTERNAL PARASITIC TWINS
 Grossly defective fetus or fetal parts attached
externally to a relatively normal twin
→ Usually consists of supernumerary limbs,
often with some viscera but without a
functional heart or brain
 Result from demise of a defective twin
 More frequent in male fetuses
FETUS-IN-FETU
 One embryo may be enfolded within its twin
→ Usually arrests in 1st trimester
→ Vertebral or axial bones found but no heart
or brain
Monochorionic Twins and Vascular Anastomoses
 Monozygotic twinning with 2 amnionic sacs and a
common surrounding chorion
→ Sharing of placental arteries and veins
→ Vascular anastomoses averaging at 8 but
may be 4-14
 Artery-to-artery anastomoses most common;
seen in 75% of cases
→ Vein-to-vein and artery-to-vein found in
half of cases
→ May be superficial or deep (reaches
capillary bed of villus)
 Risk to fetuses depend on degree to which they
are hemodynamically balanced
TWIN-TWIN TRANSFUSION SYNDROME
 1-3 per 10,000 births
 Blood transfused from a donor twin to its
recipient sibling
→ Donor may become anemic and have
growth restriction; pale
 → Recipient may become polycythemic
(leading to severe hyperbilirubinemia and
kernicterus) and develop circulatory
overload (hydrops); plethoric
 Pathophysiology
→ Due to unidirectional flow through
arteriovenous anastomoses
– Deoxygenated blood from donor’s
artery is pumped into a cotyledon
shared with the recipient
– Oxygen exchange occurs in the
chorionic villus
– Oxygenated blood leaves via
recipient’s vein
– Lead to imbalance in blood volumes
→ Typically presents in midpregnancy when
donor becomes oliguric from decreased
renal perfusion
– Develops oligohydramnios
» Prevents fetal motion
» Stuck twin or poly-oli syndrome
– Recipient develops severe hydramnios
→ Associated with growth restriction,
contractures, pulmonary hypoplasia in
donor, and PROM and heart failure in
recipient
 Fetal brain damage
→ Likely caused by ischemic necrosis
leading to cavitary brain lesions
→ Hypotension in surviving twin if the other
twin dies
 Diagnosis
→ Based on
– Presence of monochorionic diamnionic
pregnancy
– Hydramnios defined as largest vertical
pocket >8 cm in 1 twin and
oligohydramnios defined as largest
vertical pocket <2 cm in other twin
→ Quintero staging system
– Stage I: discordant amniotic fluid
volumes but urine still visible on UTZ
within bladder of donor twin
– Stage II: same as stage I but urine not
visible within donor bladder
– Stage III: same as stage II and
abnormal Doppler UTZ of umbilical a.,
ductus venosus, or umbilical v.
– Stage IV: ascites or frank hydrops in
either twin
– Stage V: demise of either fetus
→ Myocardial performance index (MPI) or
Tei index evaluates cardiac function
– Doppler index of ventricular function
calculated for each ventricle
 Management and Prognosis
→ Surveillance starts at 16 weeks and done
every 2 weeks
→ Quintero Stage I cases remain stable or
regress without intervention
→ Stage III or higher, perinatal loss 70-100%
→ Laser ablation of anastomoses preferred
for severe TTTS (Stage II-IV)
– Surveillance necessary post-procedure
→ Amnioreduction vs septostomy
– To decreases amniotic fluid?
→ Feticidal techniques to occlude
anastomoses (and termination of a twin)
– Radiofrequency ablation, fetoscopic
ligation, coagulation with laser, or
monopolar or bipolar cauterization
TWIN ANEMIA POLYCYTHEMIA SEQUENCE
(TAPS)
 Chronic fetofetal transfusion in monochorionics
 Significant Hgb differences between donor and
recipient twin without amniotic fluid volume
discrepancies
 Diagnosis by middle cerebral artery peak
systolic velocity (PSV) >1.5 multiples of the
median (MoM) in the donor and <1.0 MoM in the
recipient twin
 Occurs in up to 13% of pregnancies after laser
photocoagulation
→ Spontaneous TAPS occurs after 26 weeks
→ Iatrogenic TAPS within 5 weeks of
procedure
TWIN-REVERSED ARTERIAL PERFUSION (TRAP)
SEQUENCE
 Aka acardiac twin
 Rare (1 in 35,000 births)
 Serious complication of monochorionic multifetal
gestation
 Normal donor twin with features of heart failure
and a recipient twin without a heart and other
structures
→ Cardiomegaly and high-output heart
failure since donor must support its own
circulation as well as the recipient twin’s
 Hypothesized to be due to a large artery-to-artery
placental shunt (usually with vein-to-vein shunt)
→ Arterial perfusion pressure greater in donor
twin while recipient receives reverse blood
flow of deoxygenated arterial blood from its
co-twin
– “Used” arterial blood preferentially
goes to iliac vessels of recipient twin
 » Only lower body is perfused,
upper body has disrupted growth
and development
» Acardius acephalus (no head
growth)
» Acardius myelacephalus (partial
head growth & identifiable limbs)
» Acardius amorphous (no
recognizable structure formed)
 Prognosis
→ Pump twin died before intervention at 16-
18 weeks in 1/3 of cases
→ Spontaneous cessation of flow to acardiac
twin in ½ of cases  death or neurological
injury in 85% of normal twin
 In utero treatment
→ Radiofrequency ablation (90% survival)
– Umbilical vessels in malformed twin
are cauterized
Complete Hydatidiform Mole with Coexisting Normal
Fetus
 Twin molar pregnancy
 Due to a complete diploid molar pregnancy and a
normal fetus as twins
→ Partial molar pregnancy: anomalous
singleton fetus with molar tissue
 Termination of pregnancy includes removal of
mole and normal fetus
→ Risk of persistent trophoblastic disease
afterwards – may be fatal
 Continuation of pregnancy recommended if
→ Normal and nonanomalous twin, no early
preeclampsia, and declining HCG levels
 Preterm delivery frequently required due to
persistent and heavy bleeding or severe
preeclampsia
DISCORDANT GROWTH OF TWIN FETUSES
 Size inequality of twin fetuses
→ Sign of pathological growth restriction
→ Larger twin as index
→ Usually develops in late 2nd or early 3rd
trimester
Etiopathogenesis
 Different in monochorionic and dichorionic twins
 In monochorionic twins, it is due to placental
vascular anastomoses that cause hemodynamic
imbalance between twins
→ Unequal placental sharing as the most
important determinant of discordant growth
in monochorionics
 In dichorionic twins, it may be due to:
→ Different genetic growth potential
→ Suboptimal implantation site for one
placenta
→ In utero crowding
→ Histological placental abnormalities
Diagnosis
 Sonographic fetal biometry to computed
estimated weight for each twin
→ Percent discordancy = (larger twin
weight – smaller twin weight) / larger
twin weight
→ Abdominal circumference reflects fetal
nutrition
 Weight discordancy >25-30% most accurately
predicts adverse perinatal outcome
→ Associated with incidence of respiratory
distress, IVH, seizures, periventricular
leukomalacia, sepsis, and necrotizing
enterocolitis
Management
 Mainstay management includes sonographic
monitoring of growth and calculating discordancy
→ Monochorionics more frequently monitored
due to higher risk of death
→ Serial sonographic surveillance every 2
weeks (q4 in some) in monochorionic twins
→ Dichorionic twins evaluated every 6 weeks
 Nonstress testing, biophysical profile scores, and
umbilical a. Doppler studies recommended
 Royal College of Obsetricians and
Gynecologists recommend delivery by 37
weeks in monochorionics and 38 weeks in
dichorionic twins
FETAL DEMISE
Death of One Fetus
 Vanishing twin if occurs early in pregnancy
 Barely identifiable twin delivered at term
→ Fetus compressus (compressed greatly)
→ Fetus papyraceus (flattened greatly
through dessication)
 Risk higher in monochorionic twins before 32 wks
 Higher risk of co-twin demise after one twin dies
in monochorionic twins
 Factors that affect prognosis for surviving
twin include gestational age at time of demise
and duration between demise and delivery of
surviving twin
 Neurological prognosis of surviving twin
depends on chorionicity
→ Increased risk in monochorionic twins
 May trigger coagulation defects in the mother
MANAGEMENT
 Based on gestational age, cause of death, and
risk to surviving fetus
 If death occurs in 1st trimester, usually harmless
 If death after 1st trimester, risk of death to other
twin limited to monochorionic twins
→ Due to vascular anastomoses
→ Pregnancy termination considered if
surviving twin not viable
 If death occurs in late 2nd or early 3rd trimester,
surviving twin at greatest risk
→ Risk of preterm birth same in mono- or di-
→ Delivery within 3 weeks of diagnosis
→ Antenatal corticosteroids for lung
maturation given
Impending Death of One Fetus
 Delivery for compromised fetus but may result in
death from immaturity of other twin
 Amniocentesis for fetal karyotyping
PRENATAL CARE AND ANTEPARTUM
MANAGEMENT
 Primary goals are (1) to provide close
observation of mother and fetuses to prevent
complications and to (2) prevent preterm delivery
of markedly immature neonates
Diet
 BMI-specific weight gain goals
→ 37-54 lbs weight gain in those with normal
BMI
 Supplementation with macro- and micronutrients
→ Ca, Mg, Zinc, Vit C, D, E
 Carbohydrate-controlled diets
→ Daily recommended increased caloric
intake of 40-45 kcal/kg/d
– 20% protein, 40% carbs, 40% fats
Surveillance of Fetal Growth and Health
 Cornerstone of fetal assessment is
identification of abnormal fetal growth or
discordancy
→ Serial UTZ throughout 3rd trimester
 Amniotic fluid volume assessment
→ Amniotic fluid index (AFI) highest at 26-28
weeks, declines until delivery
→ Single deepest vertical pocket measured
– Oligohydramnios if <2 cm
– Hydramnios if >8 cm
TESTS OF FETAL WELL-BEING
 Nonstress test
 Biophysical profile
 Umbilical artery Doppler velocimetry
→ To reduce perinatal mortality
PULMONARY MATURATION
 Amniocentesis to verify pulmonary maturity
before delivery between 36-38 weeks
 Lecithin-sphingomyelin ratio measured
Pseudo-amnionicity  diamnionic but becomes
monoamnionic
Cord entanglement
- Pathognomonic in monochorionic
monoamnionics
- Major cause of fetal demise
Monitor monochorionic pregnancies in-hospital by
28 weeks
Vaginal delivery not recommended in
monochorionic monoamnionic pregnancies due
to risk of cord entanglement
Chorionicity can be diagnosed at 12 weeks
- Anencephaly also seen at 10-14 weeks
Monoamnionic – daily NST, do CS
1st trimester advice
- Iron increase
- Folic acid increase
- Nutritional intake increase
- WOF severe nausea and vomiting
- Establish chorionicity
2nd trimester
- Start monitoring for growth
- Congenital abnormality scan
o Done for all types of twinning due to
increased cardiac abnormalities
o Monochorionic monoamnionic – check
for embolus, periventricular
leukomalacia
- Measure cervical length (at 18-24 weeks)
o If short, can give micronized
progesterone
o Tocolytics not recommended due to
risk of pulmonary edema
20% chance that both monochorionic
monoamnionic twins have congenital
abnormalities
Clomiphene citrate – hyperstimulates ovaries to
release eggs; results in dizygotic twinning; can
be given again in this case if there are indications
Disadvantage of selective termination
 - Not sure if terminated fetus is the abnormal or
normal one

Should aspirin be started in this case?

- If risk of preeclampsia

Delivery depends on chorionicity, age of gestation

Gestational sac can be used to determine

chorionicity as early as 5 weeks
300-3500 kcal/day (additional 300 kcal/day) in
caloric requirement

Monochorionic monoamnionic twins delivered at

32-34 weeks to prevent cord entanglement

TUESDAY: Prenatal care