Multifetal gestation

Multifetal gestation is a pregnancy with two or more fetuses. Previous multifetal gestation and use of assisted reproductive technology increase the risk of multifetal gestation, which may be fraternal (multizygotic) or identical (monozygotic). The diagnosis is suspected in individuals who present with exaggerated features of pregnancy (e.g., hyperemesis gravidarum, excessive weight gain) and fundal height unusually large for the gestational age. Ultrasound is used to confirm the diagnosis and determine chorionicity. Increased prenatal care, including more frequent ultrasound surveillance, is recommended for multifetal gestations. Multifetal reduction may be recommended to improve outcomes in triplet or higher-order pregnancies; selective termination may be recommended for severe health problems in one fetus. Antepartum fetal surveillance is recommended in the third trimester, with delivery usually scheduled between 32 and 38 weeks' gestation for twin pregnancies. Pregnancies with more than one fetus are considered high-risk pregnancies and carry an increased risk of almost all complications of pregnancy, including hypertensive pregnancy disorders, pregnancy loss, and preterm labor. Monochorionic multifetal pregnancies are associated with a higher risk of complications and fetal anomalies than multichorionic pregnancies and should be monitored closely.

• Zygosity
  • The genetic classification of embryos in a multifetal gestation
  • Monozygotic multiples are genetically identical.
  • Multizygotic multiples are genetically distinct.
• Chorionicity
  • The type of placentation in multifetal gestations
  • In monochorionic placentation, all fetuses share one placenta.
  • In multichorionic placentation, each fetus has a separate placenta.
  • Does not reflect zygosity (e.g., monozygotic twins may be monochorionic or dichorionic)
• Amnionicity
  • The number of amniotic sacs in multifetal gestations
  • In monoamniotic pregnancies, all fetuses share one amniotic sac.
  • In multiamniotic pregnancies, each fetus has a separate amniotic sac (e.g., diamniotic twin pregnancies; triamniotic triplet pregnancies).

• The frequency of multiple births is calculated in accordance with Hellin's law. [1]
  • Twins: ∼ 1:89
  • Triplets: ∼ 1:89² (1:7,921)
  • Quadruplets: ∼ 1:89³ (1:704,969)
• The incidence of multifetal gestations (particularly dizygotic) has increased since the 1980s as assisted reproductive technology has become readily available.

Epidemiological data refers to the US, unless otherwise specified.

Predisposing factors include: [2]

• Advanced maternal age (≥ 35 years)
• Previous multifetal gestation
• Use of assisted reproductive technology
• Maternal family history of dizygotic twins

Twin gestations

Monozygotic vs. dizygotic twins [2]

Chorionicity in twin gestations [2]

• Dizygotic pregnancy results in a dichorionic-diamniotic pregnancy.
• In monozygotic pregnancies, there are various pathways in which the amniotic sac and placenta are shared.

A four-wheeler has SPACe for twins. 1^st four days (0–3): Separate placenta and amniotic sac; 2^nd four days (4–7): shared Placenta; 3^rd four days (8–11): shared Amniotic sac; day 12 and beyond: Conjoined twins.

Most twin pregnancies are dichorionic-diamniotic because most twins are dizygotic twins. Among monozygotic twins, however, the most common configuration is monochorionic-diamniotic. [2]

Higher-order multifetal gestations

• Higher-order multifetal gestations (e.g., triplets, quadruplets) may be fraternal (multizygotic) or identical (monozygotic). [4]
  • Multizygotic multiples are genetically distinct; monozygotic multiples are genetically identical.
  • In higher-order multifetal gestations, a combination of monozygotic and multizygotic multiples is common.
• Type of placentation: either monochorionic or multichorionic; and either monoamniotic or multiamniotic

Pregnancies with more than two fetuses may assume a variety of forms (e.g., triplets with two monochorionic fetuses and one fetus with its own placenta).

• Exaggerated symptoms of pregnancy (e.g., hyperemesis gravidarum, excessive weight gain) [5]
• Features of complications of pregnancy (e.g., preeclampsia, gestational diabetes, iron deficiency anemia) [5]
• Physical examination findings [6]
  • Fundal height and abdominal girth unusually large for the gestational age
  • More than one fetus felt on palpation
  • Two or more fetal heart rates heard on auscultation

• The diagnostic approach is similar for singleton and multifetal gestation.
• Ultrasound is confirmatory.
• Laboratory studies may provide supportive evidence.
• See also “Diagnosis of pregnancy” and “Prenatal ultrasound.”

Laboratory studies

The following parameters are elevated for gestational age in multifetal pregnancies compared to singleton pregnancies.

• HCG [7]
• Additional studies [5][8]
  • Maternal serum alpha-fetoprotein
  • Human placental lactogen

Ultrasound (transvaginal or transabdominal) [3][9][10]

• First-trimester ultrasound is used:
  • To confirm multifetal gestation
  • To determine chorionicity and amnionicity
  • As part of prenatal genetic testing
• Second-trimester ultrasound is used to monitor for complications and fetal anomalies (see “Management” section for details).

Diagnostic confirmation

Any of the following confirms multifetal gestation.

• Multiple gestational sacs and yolk sacs (in dichorionic pregnancies)
• Multiple embryos (fetal poles) and/or fetal cardiac activity

Determination of chorionicity and amnionicity

The findings are similar in twin and higher-order pregnancies.

• Chorionicity and amnionicity is best determined between 11 and 14 weeks' gestation. [3][10][11][12]
  • DCDA fetuses
    • The chorionic cavities are separated from one another.
    • Lambda sign: separation of the chorionic and amniotic sacs resembles the Greek symbol λ (lambda)
  • MCDA fetuses
    • One chorionic cavity is present, and each twin has an individual amniotic sac.
    • T-sign: Separation of the amniotic sacs resembles the letter T on ultrasound.
  • MCMA fetuses: single chorionic cavity gestational sac
• Findings on a second-trimester scan [11]
  • Monochorionic pregnancies
    • A single placenta is present.
    • Fetuses are of the same sex.
  • Multichorionic pregnancies
    • Each fetus has its own distinct placenta.
    • Sex of the fetuses may differ.

Monochorionic multifetal pregnancies are associated with a higher risk of complications and fetal anomalies than multichorionic pregnancies. Identification of chorionicity and amnionicity in the first trimester or early second trimester is recommended to facilitate close monitoring of this group of patients. [10][11][12]

General principles [10][11][12]

• Multifetal gestations are high-risk pregnancies and require appropriate prenatal care and delivery planning.
• Prenatal care may require referral to various specialists (e.g., obstetrician specialized in multifetal gestations, maternal-fetal medicine, neonatology). [9][13]
• Management of preterm labor is often required.

Spontaneous labor before 37 weeks' gestation occurs in 60% of twin pregnancies. [10]

Prophylactic measures to prevent preterm delivery (e.g., bed rest, hospitalization, cervical cerclage, tocolytics) are not routinely recommended in the management of uncomplicated multifetal gestations. [11]

Prenatal care [11][12]

Modifications to routine prenatal care for multifetal pregnancies include the following:

• Counseling regarding the complications of multifetal gestation, including spontaneous loss of a fetus [11][12]
• Discussion of the challenges of prenatal genetic screening, e.g.:
  • Typically less reliable in multifetal gestations
  • Risk of sampling the wrong fetus with amniocentesis or chorionic villus sampling
• Nondirective counseling on elective fetal termination ; [10][12][13]
  • Multifetal reduction to improve outcomes for the remaining fetus or fetuses and birthing parent; typically performed in the first trimester
  • Selective fetal termination if fetal anomalies are detected; typically performed in the second trimester
• Initiation of aspirin for preeclampsia prophylaxis
• Additional ultrasound monitoring includes regular assessment of: [9][10]
  • Fetal biometry
  • Umbilical artery Doppler velocimetry to assess for twin-to-twin transfusion syndrome in monochorionic pregnancies [10][14]
  • Third-trimester antepartum fetal surveillance [15]
• Consideration of increased nutritional requirements for multifetal gestations (e.g., additional iron and folate supplementation) [12]

Monitor uncomplicated dichorionic gestations with ultrasound every 4 weeks after the second-trimester scan and uncomplicated monochorionic gestations every 2 weeks after 16 weeks' gestation. Increase frequency of scans for patients with complicated multifetal gestation. [9][10][11]

Delivery planning [10][11][12]

Early delivery of multifetal gestations is recommended, as perinatal mortality increases after 38 weeks' gestation. There is a paucity of data on the optimal timing and route of delivery of triplet and higher-order gestations.

• Consider antenatal corticosteroid therapy for fetal maturation and schedule delivery: [11]
  • DCDA twins: 38 weeks' gestation
  • MCDA twins: 34–38 weeks' gestation
  • MCMA twins: 32–34 weeks' gestation
  • Higher-order gestations: Optimal timing is unknown. [12]
• Indications for cesarean delivery include: [11][12]
  • Presenting fetus in breech position
  • MCMA pregnancies
  • Lack of obstetrician experience in delivering multifetal gestations
• See also “Management of high-risk pregnancies” and “Preterm labor and birth.”

Multifetal gestations are associated with increased risk of maternal and fetal and/or neonatal morbidity and mortality. Nearly all complications associated with normal pregnancies are more likely in multifetal gestations.

Maternal complications [11][12]

• Antenatal complications
  • Hyperemesis gravidarum
  • Gestational diabetes
  • Hypertensive disorders of pregnancy
  • Cervical incompetence
• Intrapartum complications
  • Preterm labor and birth (most common complication)
  • Premature rupture of membranes [16]
  • Prolonged first stage of labor , premature placental abruption after birth of the first fetus, prolapsed cord [17]
  • Uterine atony
• Placenta previa [12][18]

Fetal complications [11][12]

• Intrauterine demise (spontaneous abortion)
• Vanishing twin syndrome: spontaneous fetal reduction; mostly occurs in the first trimester
• Twin-to-twin transfusion syndrome (in monochorionic pregnancies)
• Placental insufficiency, hypotrophy, and intrauterine malnutrition of at least one fetus
• Umbilical cord entanglement: can occur only in monoamniotic twin pregnancies
• Intrauterine growth restriction
• Congenital abnormalities

Neonatal or long-term complications [12]

• Complications of prematurity (e.g., neonatal respiratory distress syndrome, intraventricular hemorrhage)
• Cerebral palsy
• Blindness
• Deafness

We list the most important complications. The selection is not exhaustive.

• Affects 10–15% of monochorionic twin pregnancies (twins that share the placenta)
• Predominantly affects MCDA pregnancies but may also affect MCMA pregnancies [14]
• Blood is continuously shunted from one twin to the other through vascular anastomoses on the shared placenta, posing a risk to both fetuses.
• Recipient twin
  • Polycythemia
  • Hypervolemia
  • Polyhydramnios in diamniotic pregnancies
• Donor twin
  • Anemia
  • Fetal growth restriction
  • Hypovolemia, dehydration (stuck twin or cocooned appearance)
  • Oligohydramnios in diamniotic pregnancies
• Management options include: [14]
  • Suspected twin-to-twin transfusion syndrome : fetal surveillance (at least weekly)
  • Confirmed twin-to-twin transfusion syndrome
    • Termination of significantly affected fetus or complete pregnancy
    • Fetoscopic laser surgery of intertwin placental anastomoses at 16–26 weeks' gestation

Twin-to-twin transfusion syndrome may occur in monochorionic twins. [3]