MULTIFETAL

PREGNANCY
NANCY MARGARETTE C. ROXAS
FIRST YEAR RESIDENT
ETIOLOGY
◦ Dizygotic or fraternal twin—due to fertilization of 2
separate ova

◦ Monozygotic or identical twin—single fertilized ovum

that subsequently divides

◦ Either or both process may be involved in the

formation of higher numbers, ex: quadruplets
FRATERNAL vs. IDENTICAL TWIN
Dizygotic is not in a strict sense true twins because they result from the maturation and
fertilization of two ova during a single ovulatory cycle
Monozygotic twins are usually not identical—division of one zygote doesn’t necessarily
result in EQUAL sharing of protoplasmic materials
-They may be discordant for genetic mutations as the result of postzygotic mutation,
or have same genetic disease but with marked variability in expression
-Process of M- twinning is in a sense a teratogenic event
increased incidence of often discordant malformations (ex: asymmetrical organs)
Dizygotic twins may appear more nearly identical at birth than MT
GENESIS OF MONOZYGOTIC TWINS
◦ 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
- possible until the uterine cavity is obliterated by fusion of the decidua
capsularis to the decidua parietalis
- unproven in humans; most authorities believe that alleged cases result
from markedly unequal growth and development of twin fetuses with same
gestational age

SUPERFECUNDATION
-fertilization of two ova within the same menstrual cycle but not at the
same coitus, nor necessarily by sperm from the same male
FACTORS AFFECTING TWINNING
Monozygotic twinning
- 1/250 births
- Increased following ART
- Independent of demographic factors

Dizygotic twinning
◦ -Influenced remarkably by race, heredity, maternal age, parity and fertility
treatment
FACTORS AFFECTING TWINNING
RACE
-Marked difference may be the consequences of racial variations in levels of
FSH
HEREDITY
- Family hx of mother is more important than father
- Women who themselves are DT gave birth to twin at a rate of 1/58 births
- Women whose husbands were DT gave birth to twin at a rate of 1/116
pregnancies
- Contribution of genetic variants that increase rate of DT is likely small
MATERNAL AGE AND PARITY
- Rate of natural twinning peaks at 37 years, when maximal FSH stimulation
increases the risk of multiple follicles developing
- The fall of incidence thereafter probably reflects physiological follicle
depletion
- Increasing parity has also been shown to increase incidence of twinning
independently in all populations
FACTORS AFFECTING TWINNING
NUTRITIONAL FACTORS
- Increasing gradient in twinning rate related to greater nutritional status as reflected
by maternal size
- Taller, heavier women have twinning rate 25-30% greater than short, nutritionally
deprived women
- DT is more common in large and tall women
PITUITARY GONADOTROPIN
- The Common factor linking race, age, weight and fertility to MG may be FSH levels
- Increased fecundity and higher rate of DT in women who conceive within 1 month
after stopping oral contraceptives
- may be due to sudden release of pituitary gonadotropin in amounts greater than
usual during 1st spontaneous cycle after stopping hormonal contraception.
INFERTILITY THERAPY
-Ovulation induction with FSH plus chorionic gonadotropin or CLOMIPHENE CITRATE
enhances likelihood of multiple ovulations
SEX RATIOS WITH MULTIPLE FETUSES
- As the number of fetuses per pregnancy increases, the percentage of male
conceptus decreases
- Females predominate even more in twins from late twinning events
- 68% of thoracopagus conjoined twins are females

2 explanations:
1. Beginning in utero and extending throughout the lifecycle, mortality rates
are lower in females
2. Female zygotes have greater tendency to divide
DETERMINING THE ZYGOSITY
- Twins of opposite sex are almost always dizygotic
- In rare instances, due to somatic mutations or chromosome aberration, the
karyotype or phenotype of monozygotic twin gestation can be different
DETERMINING THE CHORIONICITY
- Risk for twin-specific complications varies in relation to ZYGOSITY and
CHORIONICITY, with the latter being the more important determinant

- Monochorionic diamnionic twins have higher rates of perinatal mortality and

neurologic injury compared with dichorionic pairs.

- Risk of fetal demise in one or both monochorionic twin was twice that in
dichorionic multifetal gestation

- Chorionicity differences do not significantly affect maternal outcomes

Sonographic evaluation
Accuracy is greatest in the first trimester and diminishes as gestational age advances
Chorionicity determined using four features:
1. Number of placental masses
2. Thickness of the membrane dividing the sac (≥ 2 mm –dichorionicity)
3. Presence of an intervening membrane
4. Fetal gender

TWIN PEAK SIGN/DELTA/LAMBDA SIGN

-triangular projection of placenta extending beyond the
chorionic surface between the layers of the dividing
membrane
-seen at the point of origin of dividing membrane on
the placental surface
-Confirms dichorionic twinning
T –SIGN
—right angle relationship between the membranes and
placenta with no apparent extension of placenta
between the dividing membrane
-Monochorionic diamnionic pregnancies with thin
dividing membrane that may not be seen until 2nd
trimester
-Less than 2mm thick, and magnification only reveals
2 layers (the juxtaposed amnion of each twin)
Placental examination
Visual examination of the placenta and membranes following delivery to establish zygosity and chorionicity:
- As the first neonate is delivered, one clamp is placed on a portion of its cord
- Cord blood is not collected until after delivery of the other twin, unless it has been shown prior to delivery that
there are two placentas
- As the second neonate is delivered, 2 clamps are placed on that cord
- Three clamps are used to mark the cord of the 3rd neonate, and so on
- Until the delivery of the 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
- Deliver the placenta carefully to preserve attachment of the amnion and chorion, because identification of the
relationship to each other is critical
- With one common amnionic sac, or with juxtaposed amnions not separated by chorion arising between the
fetuses, the fetuses are monozygotic
- If adjacent amnions are separated by chorion, then the fetuses could either by dizygotic or monozygotic, but DT
is more common
- If the neonates are of same sex, blood typing of cord blood samples may be helpful
- difference confirms DT
- For definitive dx: DNA fingerprinting
DIAGNOSIS OF MULTIFETAL GESTATION
HISTORY AND CLINICAL EXAM

Maternal personal or family history of twins, advanced maternal age, high parity and large maternal size are weakly
associated
Recent administration of clomiphene citrate or gonadotropins or pregnancy accomplished by ART are much stronger
associates
Uterine size typically larger during 2nd trimester (20 to 30 weeks) than expected (approx 5cm greater) -In general, it is
difficult to diagnose twins by palpation of fetal parts before 3rd trimester
- Even late in pregnancy, it may be difficult to identify by abdominal palpation, especially if:
One twin overlies the other
Woman is obese
There is hydramnios
- If uterine palpation leads to dx of twins, it most often because 2 fetal heads have been detected, often in different
uterine quadrants
- Doppler detection of fetal heart beats—late in 1st trimester
- Aural fetal stethoscope can identify fetal heart sounds in twins as early as 18-20 weeks

SONOGRAPHY
- Separate gestational sacs can be identified early
- Each fetal head must be seen in 2 perpendicular planes so as not to mistake a cross section of a fetal trunk for a 2nd
head
- Ideally: 2 fetal heads or 2 abdomens should be seen in the same image plane
- Can early identify multiple fetuses; but higher order multiple fetal gestations are more difficult
OTHER DX AIDS
-Radiologic examination
-X-ray of maternal abdomen can be helpful if the number of fetuses in higher-order MG is uncertain
-However, generally not useful and may lead to incorrect dx if there is hydramnios, obesity, fetal
movement during exposure, or inappropriate exposure time
-Fetal skeletons before 18 weeks are insufficiently radiopaque and may be poorly seen
-MRI may help delineate complications in MT

Biochemical test
- No biochemical test reliably identifies MG
- Serum and urine Levels of hCG and maternal serum levels of AFP are higher than with singleton
pregnancy, but not so high as to allow definite dx
MATERNAL PHYSIOLOGIC ADAPTATIONS
- N/V in excess of women with singleton pregnancy (higher serum B-hCG levels)
-Maternal blood volume expansion is greater (40-50-% inc in singleton; 50-60% in MG)
-Red cell mass increases as well
-Both the increase in blood volume and increased iron and folate requirements predispose to greater
prevalence of anemia
- Diastolic pressure is lower as early as 8 weeks compared to singleton mothers, but increases more by
delivery (increase of at least 15mmHg in 95% of women carrying twins, 54% of women with singleton)
- Uterine growth is substantively greater , may achieve volume of 10L or more and weigh in excess of 20
pounds
-Increased cardiac output due to greater stroke volume rather than higher heart rate
-Vascular resistance is significantly lower
-If hydramnios develops, maternal renal function may become seriously impaired, more likely as a
consequence of obstructive uropathy
- Therapeutic amniocentesis may be used to provide relief and improve obstructive uropathy, if severe
- However, hydramnios is often characterized by acute onset remote from term and by rapid
reaccumulation following amniocentesis
PREGNANCY COMPLICATIONS
SPONTANEOUS ABORTION
- more likely with MF (MT > DT)
CONGENITAL MALFORMATIONS
-Incidence appreciably higher
- high incidence of structural defects in MT
LOW BIRTHWEIGHT
-due to restricted fetal growth and preterm delivery (MT >DT)
HYPERTENSION
-pregnancy-related hypertensive disorders more likely to develop, placental mass and fetal number
involved in pathogenesis (2x sFlt-1)
PRETERM BIRTH
-6 fold increase in twins, 10 fold in triplets
LONG TERM INFANT DEVELOPMENT
-considered cognitively delayed compared to singletons (inc. cerebral palsy risk)
UNIQUE FETAL COMPLICATIONS
MONOAMNIONIC TWINS
- 1% of MT
- Associated high fetal death rate may result from:
1. Cord entanglement/intertwining—complicate at least half of cases
2. Congenital anomaly
3. Preterm birth
4. TTTS
- Diamnionic twins can become monoamnionic if the dividing membrane ruptures

Management:
- Women may be managed with 1 hour of daily fetal heart rate monitoring beginning at 26 to 28 weeks
- With initial testing, a course of bethamethasone is given to promote pulmonary maturation
- Scheduled CS at 32 to 34 weeks if tests remain reassuring
UNIQUE AND ABBERANT TWINNING

CONJOINED TWINS/ SIAMESE TWINS may result from aberration in twinning process
-incomplete splitting of an embryo into 2 separate twins
-An alternative hypothesis is early secondary fusion of 2 originally separate embryos
- thoracopagus is the most common
-frequently identified using sonography at mid pregnancy
-separation may be successful if essential organs are not shared
EXTERNAL PARASITIC TWIN
-A grossly defective fetus or merely fetal parts, attached externally to a relatively normal twin
-Usually consist of externally attached supernumerary limbs, often with some viscera
- Classically, a functional heart or brain is absent
- Believed to result from demise of the defective twin, with its surviving tissue attached to and
vascularized by its normal twin
FETUS-IN-FETU
- Early in development, one embryo may be enfolded inside its twin
- Normal development of this rare parasitic twin usually arrests at the first trimester
- Classically, vertebral or axial bones are found in this fetiform mases, whereas heart and brain are
lacking
- These masses are typically supported by their host by a few large parasitic vessels
MONOCHORIONIC TWINS AND VASCULAR ANASTOMOSES
- Present only in monochorionic twin placentas
- One vessel may have several connections, sometimes to both arteries and veins
- Artery-to-artery anastomoses are most common and are found on the chorionic surface of the
placenta in 75%
- Vein-to-vein and artery-to-vein communications are each found in approximately half
- deep artery-to-vein communications extend through the capillary bed of a given villus
- These deep AV anastomoses create a common villous compartment or third circulation that has
been identified in approximately half of monochorionic twin placentas
- Chronic fetofetal transfusion may result in several clinical syndromes a. twin-twin transfusion
syndrome (TTTS), twin anemia polycythemia sequence (TAPS), and acardiac twinning

TWIN-TWIN TRANSFUSION SYNDROME

- Blood is transfused from a donor twin to its recipient sibling such that the donor becomes
anemic and its growth may be restricted
- The recipient becomes polycythemic and may develop circulatory overload manifested as
hydrops
- Donor is pale and recipient is plethoric
- One portion of the placenta often appears pale compared to the remainder
- In the recipient twin, neonatal period may be complicated by:circulatory overload with heart
failure, if severe hypervolemia and hyperviscosity are not identified promptly and treated
- Occlusive thrombosis, also much more likely to develop
- Polycythemia may lead to severe hyperbilirubinemia and kernicterus
MONOCHORIONIC TWINS AND VASCULAR ANASTOMOSES
TWIN-TWIN TRANSFUSION SYNDROME
Pathophysiology
-Chronic TTTS results from unidirectional flow through AV anastomoses.
-deoxygenated blood from donor is pumped into a cotyledon shared by the
recipient -> Oxygenated blood may leave via a placental vein of the recipient
twin -> imbalance in fluid volumes

-Clinically important TTTS frequently is chronic and results from significant

vascular volume differences

-Typically presents in midpregnancy when donor fetus becomes oliguric from

decreased renal perfusion ->develops oligohydramnios
-Recipient fetus develops severe hydramnios, presumably due to inc. urine
production
- Virtual absence of AF in the donor sac prevents fetal motion ->stuck twin or
hydramnios-oligohydramnios—“poly-oli” syndrome
-Associated with growth restriction, contractures and pulmonary hypoplasia in
donor twin, and PROM and heart failure in the recipient
MONOCHORIONIC TWINS AND VASCULAR ANASTOMOSES
FETAL BRAIN DAMAGE
- 1. CP 2. Microcephaly 3. Porencephaly 4. Multicystic encephalomalacia : serious complications assoc.
with placental vascular anastomoses in MG
-Neuro damage is most likely caused by ischemic necrosis leading to cavitary brain lesions
- In the donor twin, ischemia results from hypotension, anemia, or both
- In the recipient, ischemia develops from blood pressure instability and episodes of severe hypotension
- Cerebral anomalies develop in 8% in TTTS pregnancies

Diagnosis: based on 2 sonographic criteria

1. Monochorionic diamniotic is identified
2. Hydramnios defined by a largest vertical pocket >8cm in one sac and oligohydramnios defined by a largest vertical
pocket <2cm in the other twin is found

QUINTERO STAGING SYSTEM (spectrum of severity)

Stage I—discordant AF as described above, but urine still visible sonographically within donor’s bladder
Stage II—criteria of stage I, but urine is not visible
Stage III—criteria of stage II and abnormal Doppler studies of the umbilical artery, ductus venosus or
umbilical vein
Stage IV—ascites or frank hydrops in either twin
Stage V—demise of either fetus

Cardiac dysfunction of the recipient twin correlated with fetal outcome  thus CV function is assessed
with echocardiography
MONOCHORIONIC TWINS AND VASCULAR ANASTOMOSES
MANAGEMENT AND PROGNOSIS
- Prognosis is related to Quintero Staging and gestational age at presentation
- Stage 1 have been reported stable or regress without intervention while stage III or
higher are much worse, 70-100% perinatal loss without intervention

Therapies used for TTTS:

1. Amnioreduction- needle drainage of excess amniotic fluid
2. Laser ablation of vascular anastomoses—preferred for severe TTTS (arrest shunting
of blood from the donor to recipient also halts transfer of potential vasoactive
mediators)
3. Selective feticide—if severe AF and growth disturbances develop before 20 weeks
4. Septostomy—intentionally creating a hole in the dividing amnionic membrane
 DISCORDANT GROWTH OF TWIN FETUSES
- Fetal size inequality (15%) may reflect pathologic growth restriction in one fetus
- As the weight difference increases, perinatal mortality rates increase
- Restricted growth of one twin fetus(selective fetal- growth restriction) usually develops
late in the 2nd and early third trimester
- Earlier discordancy is usually symmetrical and indicates higher risk of fetal demise
- The earlier the discordancy develops, the more serious the sequelae

Etiopathogenesis:

MT - Discordance usually attributed to placental vascular anastomoses that cause

hemodynamic imbalance between the twins. Reduced pressure and perfusion of the donor
twin likely cause diminished placental and fetal growth.
UNEQUAL PLACENTAL SHARING- most important determinant

DT- Due to variety of factors. May have different growth potential, especially if they are
opposite gender
Placenta are separate (requires more implantation space) One placenta may have
suboptimal implantation site
DISCORDANT GROWTH OF TWIN FETUSES
DIAGNOSIS:
Computation of weight of each twin and comparison of weight of smaller twin with that of larger twin

Percent discordancy— weight of larger twin - weight of smaller twin x 100

weight of larger twin

Abdominal circumference differ by more than 20mm

Estimated fetal weight difference is 20% or more

Weight discordance greater than 25-30% most accurately predicts an adverse perinatal outcome:

Respiratory distress, intraventricular hemorrhage, seizures, periventricular leukomalacia, sepsis and

NEC increased directly with degree of weight discordancy

MANAGEMENT:
1. Serial Sonography - mainstay in management
2. Fetal surveillance may be indicated, especially if one or both fetuses exhibit growth restriction.

Delivery is usually not performed for size discordancy ALONE, except occasionally at advanced
gestational age
FETAL DEMISE
DEATH OF ONE FETUS
- Related to zygosity, chorionicity and growth concordance

Fetus compressus—dead fetus may be identifiable but may be compressed appreciably

Fetus papyraceus—fetus flattened remarkably through loss of fluid and most of the soft tissue

Prognosis for surviving fetus depends on: gestational age at time of demise
duration between demise and delivery of surviving twin

neurologic prognosis for surviving twin depends ALMOST EXCLUSIVELY on chorionicity

IMPENDING DEATH OF ONE FETUS

- delivery may be the best option for compromised fetus yet may result in death from immaturity of the
second
- if fetal lung maturity confirmed, salvage of both healthy fetus and its jeopardized sibling is possible
- performing amniocentesis for fetal karyotyping in women of advanced age carrying twin pregnancies
is advantageous
PRENATAL CARE
RECOMMENDATIONS:

1. Unless there are already complications, prenatal visits of twins or higher order multiple (HOM)
gestation can be done monthly until 24 weeks, every 2 to 3 weeks until 32 weeks then weekly
thereafter (Level I, Grade A)

2. A weight gain of 37-54 lbs at term is recommended for women of normal pre pregnancy weight while
31-50 lbs. for women who are overweight and 25-41 lbs. for those who are obese. (Level II-1, Grade B)

3. The recommended total energy needs of a pregnant woman should be based on physical stature and
physical activity level and are given as follows: for underweight women 35 kcal/kg/day is recommended
if sedentary, 40 kcal/kg/day if having light activity and 45kcal/kg/day for moderate activity (Level III,
Grade C)

4. For women within normal weight range 30 kcal/kg/day is recommended if sedentary, 35 kcal/kg/day if
having light activity and 40 kcal/kg/day for moderate activity (Level III, Grade C)

5. For overweight women, 25 kcal/kg/day is recommended if sedentary, 30 kcal/kg/day if having light

activity and 35 kcal/kg/day for moderate activity (Level III, Grade C)
ANTEPARTUM FETAL SURVEILLANCE
RECOMMENDATIONS:

1. ALL women with twin pregnancies should be offered an utz exam at 10-13 weeks AOG to assess
viability, chronicity, major congenital malformation and nuchal translucency (Level II-2, Grade A)

2. A careful sonographic survey of fetal anatomy, including extended view of the fetal heart is
recommended bet 18-22 weeks (Level III, Grade B)

3. Patterns of fetal growth are more important than absolute measurements and serial ultrasonographic
eval every 3 to 4 weeks is indicated (Level I, Grade B)

4. The diagnosis of twin discordance should be based on the following: an AC difference of 20mm and an
EFW difference based on BPD and AC or AC and FL > 20% (Level II-2, Grade B)

5. Doppler velocimetry may provide added value in screening for growth disturbances, however supportive
evidence is limited (Level II-2, Grade C)

6. Although BPP is commonly performed in high risk pregnancies there is insufficient data to determine
its value in MG (Level II-3, Grade C )

7. Although there is limited evidence to support the use of NST in twin gestation, the available studies on
twin gestation suggest that NST has screening performance similar to singleton (Level II-2, Grade B)
PREVENTION OF PRETERM DELIVERY
Preterm labor is common in multifetal pregnancies and may complicate up to 50% of twin, 75% of triplet,
and 90% of quadruplet

Bed Rest
- Most evidence suggest that routine hospitalization is not beneficial in prolonging multifetal pregnancy
- Limited physical activity, early work leave, more frequent health care visits and sonographic
examinations, and structured maternal education on preterm delivery risks have been advocated, but
there is little evidence that these substantially change outcome

Prophylactic Tocolysis
- No evidence that it improves outcome

Progesterone Therapy
- Weekly injections of 17-a hydroxyprogesterone caproate fail to reduce birth rates in women carrying
twins or triplets

Corticosteroids
-Less studied in multifetal gestations
-Guidelines are not different for singleton

Cervical cerclage
-Prophylactic cerclage has been shown to improve perinatal outcome (but may worsen outcomes in women
with shortened cervix)
PRETERM BIRTH PREDICTION
- Only cervical length and fetal fibronectin levels predicted preterm birth
- At 24 weeks, a cervical length of 25mm or less was the best predictor of birth before 32 weeks
- At 28 weeks, elevated fetal fibronectin level was the best predictor
- Rates of preterm delivery:
66% with cervical length 10mm
24% with 20mm
12% for 25mm
1% for 40mm
-Low risks for 24 weeks AOG to deliver at 32 weeks if:
-Closed internal os on digital cervical exam
-Normal cervical length by sonography
-Negative fetal fibronectin test
- A closed internal os by digital exam was as predictive as the combination of normal measured cervical
length and negative fibronectin test results

Pulmonary Maturation
- Pulmonary maturation is usually synchronous to twins
- Ratio often exceeds by approximately 32 weeks—however, pulmonary function may be markedly
different, with the smallest, most stressed fetus being more mature
PRETERM PROM
-Managed expectantly
-Labor ensued earlier in twins
-Median time from rupture to delivery was 1.1 days in twins compared to 1.7 days in
singletons
-90% delivered within 7 days of membrane rupture

DELAYED DELIVERY OF 2ND TWIN

-It may be advantageous for undelivered fetus to remain in utero
-Reduced mortality of 2nd twin if the first twin was delivered between 22-23 weeks
and 2nd twin was delayed for 1-3 weeks
-Avoidance of delivery from 23-26 weeks seems most beneficial
-Good candidates for delayed delivery are rare
LABOR AND DELIVERY
Labor complications: Preterm birth, Uterine contractile dysfunction, Abnormal presentation,
Umbilical cord prolapsed, previa, abruption, emergent operative delivery and postpartum hemorrhage
from atony

Recommendations for intrapartum management:

1.An appropriately trained OB attendant should remain with the mother throughout labor—CEM, or
simultaneous monitoring of presenting part by internal EM and remaining sibling by external monitor
2. Blood transfusion products readily available
3.IV infusion system capable of delivering fluid rapidly. If no hge: LR or aqueous dextrose solution
infusion at rate of 60-125ml/hr
4. An OB skilled in intrauterine identification of fetal parts and in intrauterine manipulation of a fetus
should be present
5. Sonography machine made readily available to help evaluate position and status of remaining fetus
6. Experienced anesthesia personnel immediately available—in the event that intrauterine
manipulation or CSD is necessary
7. For each fetus, 2 attendants skilled in resuscitation and care of newborn are immediately available
8.Delivery area should provide adequate space for all team members, and appropriately equipped to
provide maternal and neonatal resuscitation
LABOR AND DELIVERY
PRESENTATION AND POSITION

All possible combinations of fetal position may be encountered

Most common:
-Cephalic-cephalic (42%)
-Cephalic-breech (27%)
-Cephalic-transverse (18%)
-Breech-breech (5%)
-Others (8%)

Latter two are unstable before and during labor and delivery
Compound, face, brow, and footling breech presentations are common, especially if: Fetuses are small,
AF is excessive, Maternal parity is high
Cord prolapsed is also common
Presentations ascertained by sonography
For any confusion, a single AP radiograph of the abdomen may be helpful

INDUCTION OR STIMULATION OF LABOR

Labor is generally shorter in twins
ANALGESIA AND ANETHESIA
- Use may be complicated by problems imposed by:
-Preterm labor
-Preeclampsia
-Desultory labor
-Need for intrauterine manipulation
-Postpartum uterine atony
-hemorrhage

Labor epidural anesthesia – ideal because it provides excellent pain relief and can be rapidly extended
cephalad if internal podalic version or cesarean delivery is required.

Sometimes, GA is necessary for intrauterine manipulation, uterine relaxation is needed (intravenous/

sublingual nitroglycerin, intravenous terbutaline or halogenated inhalation agents)