Multiple Pregnancy

Multiple pregnancy, or multifetal gestation, is a pregnancy with more than 1 fetus. Multiple pregnancy with more than 2 fetuses is referred to as a higher-order multiple pregnancy and the most common type of multiple pregnancy is a twin pregnancy. Due to advanced maternal age and evolving assisted reproductive technology, the rates of multiple pregnancies have steadily increased over the past 3 decades. However, rates have slowly plateaued with the increase of the single embryo Embryo The entity of a developing mammal, generally from the cleavage of a zygote to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the fetus. Fertilization and First Week transfer. The perinatal mortality and morbidity rates of twin pregnancies are 3–7x higher than singleton pregnancies primarily because of higher rates of preterm delivery. Multiple pregnancies also carry a higher risk of obstetric complications such as congenital anomalies, preeclampsia, and gestational diabetes. Multiple pregnancies are classified as high-risk and require astute obstetric care.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Overview

Definition

Multiple pregnancy is a pregnancy with more than 1 fetus.

Table: Important terminology of multiple pregnancy
Term Definition
Zygosity Refers to the genetic makeup of a twin pregnancy
Monozygotic twins
  • Result from division of a single zygote
  • Share the same genetic material
  • Identical twins
Dizygotic twins
  • Result from 2 separate eggs fertilized by 2 separate sperm
  • Share approximately 50% of the genetic material
  • Fraternal twins
Chorionicity The number of chorions (equal to the number of placentas)
Amnionicity The number of amnions surrounding the fetuses

Epidemiology

Statistics of the United States:

  • Twin births account for: 
    • 3% of live births 
    • 97% of multiple births
    • Dizygotic twins: 70% of all twin gestations in the absence of assisted reproductive technology
    • ↑ Rate of monozygotic twins with assisted reproduction
  • Triplet and higher-order multiple births: 
    • 87.7 per 100,000 births
    • Approximately 80% are associated with medically assisted conception.

Risk factors

  • Prior history of multiple pregnancies
  • History of twins in the maternal family
  • Maternal weight and height: Women with a BMI ≥ 30 kg/m2 and ≥ 165 cm are at ↑ risk for dizygotic twin births.
  • ↑ Maternal age
  • ↑ Parity
  • Racial and ethnic variation:
    • ↑ In Nigeria 
    • ↓ In Japan
  • Assisted reproductive technology or ovulation induction drugs

Classification and Diagnosis

Classification

  • Dizygotic twins are always dichorionic-diamniotic.
  • Monozygotic twins are classified based on the timing of cleavage after fertilization Fertilization To undergo fertilization, the sperm enters the uterus, travels towards the ampulla of the fallopian tube, and encounters the oocyte. The zona pellucida (the outer layer of the oocyte) deteriorates along with the zygote, which travels towards the uterus and eventually forms a blastocyst, allowing for implantation to occur. Fertilization and First Week (timing of cleavage determines chorionicity and amnionicity). 
Table: Classification of monozygotic twins
Time of cleavage after fertilization Fertilization To undergo fertilization, the sperm enters the uterus, travels towards the ampulla of the fallopian tube, and encounters the oocyte. The zona pellucida (the outer layer of the oocyte) deteriorates along with the zygote, which travels towards the uterus and eventually forms a blastocyst, allowing for implantation to occur. Fertilization and First Week Classification Prevalence
1–3 days Dichorionic-diamniotic 20%–25%
4–8 days Monochorionic-diamniotic 70%–75%
9–12 days Monochorionic-monoamniotic 1%–5%
≥ 13 days Monochorionic-monoamniotic (conjoined twins) Very rare

Diagnosis

Signs and symptoms:

  • Exaggerated early pregnancy symptoms (e.g., hyperemesis gravidarum)
  • Symphyseal-fundal height is greater than expected for gestational age.
  • ↑ Abdominal girth
  • ↑ Weight gain compared to singleton pregnancies

Ultrasound findings:

  • ≥ 2 fetuses and ≥ 2 heart activities 
  • Dichorionic-diamniotic:  
    • Lambda sign: a thick, triangular protrusion of tissue leading up to the intertwin membrane
    • Thick intertwin membrane
    • 2 separate placentas
  •  Monochorionic-diamniotic:
    • T sign: the interface between 2 amniotic membranes
    • Thin intertwin membrane
    • Single placenta Placenta The placenta consists of a fetal side and a maternal side, and it provides a vascular communication between the mother and the fetus. This communication allows the mother to provide nutrients to the fetus and allows for removal of waste products from fetal blood. Placenta, Umbilical Cord, and Amniotic Cavity
  • Monochorionic-monoamniotic:
    • No intertwin membrane
    • Single placenta Placenta The placenta consists of a fetal side and a maternal side, and it provides a vascular communication between the mother and the fetus. This communication allows the mother to provide nutrients to the fetus and allows for removal of waste products from fetal blood. Placenta, Umbilical Cord, and Amniotic Cavity

Management

General care

Multiple pregnancy is considered a high-risk pregnancy.

  • Prenatal care Prenatal care Prenatal care is a systematic and periodic assessment of pregnant women during gestation to assure the best health outcome for the mother and her fetus. Prenatal care prevents and identifies maternal and fetal problems that adversely affect the pregnancy outcome. Prenatal Care requires: 
    • More frequent prenatal visits
    • More frequent ultrasounds to monitor fetal growth
    • Adequate maternal nutrition
    • Monitoring for maternal complications (e.g., gestational diabetes and preeclampsia)
    • Monitoring for fetal complications (e.g., congenital anomalies)
  • Chorionicity determination is essential in the 1st trimester:
    • Aids AIDS Chronic HIV infection and depletion of CD4 cells eventually results in acquired immunodeficiency syndrome (AIDS), which can be diagnosed by the presence of certain opportunistic diseases called AIDS-defining conditions. These conditions include a wide spectrum of bacterial, viral, fungal, and parasitic infections as well as several malignancies and generalized conditions. HIV Infection and AIDS in appropriate counseling of associated risks
    • Becomes less accurate after the beginning of the 2nd trimester

Mode of delivery

  • Depends on several factors, including:
    • Prior obstetric history
    • Current obstetric history
    • Fetal presentation Fetal presentation Fetal presentation describes which part of the fetus will enter through the cervix first, while position is the orientation of the fetus compared to the maternal bony pelvis. Presentations include vertex (the fetal occiput will present through the cervix first), face, brow, shoulder, and breech. Fetal Malpresentation and Malposition of the twin closest to the birth canal (cephalic, or head presenting, is favorable for a vaginal delivery)
    • The expertise of the obstetric provider
  • Multiple pregnancies with > 2 fetuses are almost always delivered by cesarean section.
  • Triplet pregnancies may be delivered vaginally by experienced obstetricians.

Timing of delivery in uncomplicated cases

For twins the timing for delivery depends on chorionicity and amnioniticy:

  • Dichorionic-diamniotic: 38 0/7 weeks–38 6/7 weeks
  • Monochorionic-diamniotic: 34 0/7 weeks–37 6/7 weeks
  • Monochorionic-monoamniotic: 32 0/7 weeks–34 0/7 weeks

Maternal Complications

Multiple pregnancy presents higher risk to develop complications such as:

  • Hyperemesis gravidarum
  • Gestational diabetes mellitus Diabetes mellitus Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus 
  • Hypertensive pregnancy disorders Hypertensive pregnancy disorders Hypertensive disorders of pregnancy include chronic hypertension, preeclampsia/eclampsia, gestational hypertension, and hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. These syndromes pose a significant risk to the pregnant woman and her fetus. Hypertensive Pregnancy Disorders (e.g., preeclampsia)
  • Anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview
  • Excessive weight gain
  • Postpartum hemorrhage Postpartum hemorrhage Postpartum hemorrhage is one of the most common and deadly obstetric complications. Since 2017, postpartum hemorrhage has been defined as blood loss greater than 1,000 mL for both cesarean and vaginal deliveries, or excessive blood loss with signs of hemodynamic instability. Postpartum Hemorrhage (due to uterine atony or lacerations)
  • Miscarriages
  • Placental abnormalities Placental abnormalities Normal placental structure and function are essential for a healthy pregnancy. Some of the most common placental abnormalities include structural anomalies (such as a succenturiate lobe or velamentous cord insertion), implantation anomalies (such as placenta accreta and placenta previa), and functional anomalies (such as placental insufficiency). Placental Abnormalities (e.g., placenta Placenta The placenta consists of a fetal side and a maternal side, and it provides a vascular communication between the mother and the fetus. This communication allows the mother to provide nutrients to the fetus and allows for removal of waste products from fetal blood. Placenta, Umbilical Cord, and Amniotic Cavity previa)
  • Increased risk for cesarean delivery Cesarean Delivery Cesarean delivery (CD) is the operative delivery of ≥ 1 infants through a surgical incision in the maternal abdomen and uterus. Cesarean deliveries may be indicated for a number of either maternal or fetal reasons, most commonly including fetal intolerance to labor, arrest of labor, a history of prior uterine surgery, fetal malpresentation, and placental abnormalities. Cesarean Delivery

Fetal Complications

Affecting all multiple pregnancies

  • Preterm labor and birth Preterm labor and birth Preterm labor refers to regular uterine contractions leading to cervical change prior to 37 weeks of gestation; preterm birth refers to birth prior to 37 weeks of gestation. Preterm birth may be spontaneous due to preterm labor, preterm prelabor rupture of membranes (PPROM), or cervical insufficiency. Preterm Labor and Birth:
    • Resulting in prematurity and associated complications such as:
      • Respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure
      • Intracranial hemorrhage
      • Sepsis Sepsis Organ dysfunction resulting from a dysregulated systemic host response to infection separates sepsis from uncomplicated infection. The etiology is mainly bacterial and pneumonia is the most common known source. Patients commonly present with fever, tachycardia, tachypnea, hypotension, and/or altered mentation. Sepsis and Septic Shock
      • Cerebral palsy Cerebral palsy Cerebral palsy (CP) refers to a group of conditions resulting in motor impairment affecting tone and posture and limiting physical activity. Cerebral palsy is the most common cause of childhood disability. It is caused by a nonprogressive CNS injury to the fetal or infant brain. Cerebral Palsy
    • Women with multifetal gestation are 6x more likely to give birth preterm.
  • Congenital anomalies 
  • Low birth weight
  • Discordant growth
  • Neonatal death

Monochorionic twins

Twin-to-twin transfusion syndrome:

  • Occurs in 10%–15% of monochorionic twins
  • Due to arterio-venous anastomosis with imbalanced blood flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure
  • Blood flows in a fixed direction from 1 fetus (donor) to another (recipient)
  • Donor twin: 
    • Anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview
    • Growth restriction
    • Oligohydramnios Oligohydramnios Oligohydramnios refers to amniotic fluid volume less than expected for the current gestational age. Oligohydramnios is diagnosed by ultrasound and defined as an amniotic fluid index (AFI) of ‰¤ 5 cm or a single deep pocket (SDP) of < 2 cm in the 2nd or 3rd trimester. Oligohydramnios 
  • Recipient twin: 
    • Polycythemia
    • Polyhydramnios Polyhydramnios Polyhydramnios is a pathological excess of amniotic fluid. Common causes of polyhydramnios include fetal anomalies, gestational diabetes, multiple gestations, and congenital infections. Patients are often asymptomatic but may present with dyspnea, extremity swelling, or abdominal distention. Polyhydramnios
  • 5 stages (each stage is progressively worse)
  • Management depends on the stage and severity of compromise and may include:
    • Monitoring
    • Amnioreduction
    • Fetoscopic laser occlusion of placental vessels
    • Selective feticide of 1 twin 

Twin anemia polycythemia sequence (TAPS):

  • A form of atypical chronic twin-to-twin transfusion syndrome 
  • Due to sparse vascular anastomoses
  • Characterized by: 
    • Large difference in hemoglobin and reticulocyte levels between the twins
    • Absence of oligohydramnios and polyhydramnios
  • May occur either: 
    • Spontaneously 
    • Iatrogenically (after laser treatment for twin-to-twin transfusion syndrome) 
  • Management: In the absence of poor prognostic factors, expectant management is appropriate.

Twin reversed arterial perfusion (TRAP):

  • Approximately 1% of  monochorionic twins
  • Occurs when a twin with an absent/rudimentary heart is perfused by the other twin via abnormal placental anastomoses (artery-to-artery shunt) 
  • Donor twin: 
    • Also called the “pump twin” 
    • Suffers from high-output heart failure (e.g., polyhydramnios and cardiomegaly)  
  • Recipient twin: 
    • Also called the “acardiac twin”
    • Normally developed lower body, underdeveloped upper body
  • Management:
    • Focus on maximizing the outcome for the structurally normal pump twin.
    • Delivery is recommended for signs of cardiac compromise.

Monoamniotic twins

  • Umbilical cord entanglement 
  • Conjoined twins:
    • Very rare: approximately 1 per 50,000–100,000 births
    • Requires expert care during pregnancy and after delivery 
    • Separation after birth may be feasible but is associated with significant morbidity and mortality.

References

  1. Gabbe, S. G. (2017). Obstetrics: normal and problem pregnancies. (7th ed.). Elsevier. 
  2. Resnik, R., et al. (2019). Creasy and Resnik’s maternal-fetal medicine: Principles and practice. Elsevier.
  3. Cunningham, F. G. (2018). Williams obstetrics. New York: McGraw Hill Medical.
  4. Chasen, S. (2021). Twin pregnancy: Overview. In Barss, V.A. (Ed.), UpToDate. Retrieved August 22, 2021, from https://www.uptodate.com/contents/twin-pregnancy-overview
  5. Mandy, G. T. (2020). Neonatal complications, outcome, and management of multiple births. In Kim, M.S. (Ed.), UpToDate. Retrieved August 24, 2021, from https://www.uptodate.com/contents/neonatal-complications-outcome-and-management-of-multiple-births 
  6. Hayes, E. J. (2021). Triplet pregnancy. In Barss, V.A. (Ed.), UpToDate. Retrieved September 15, 2021, from https://www.uptodate.com/contents/triplet-pregnancy
  7. Multifetal Gestations: Twin, Triplet, and Higher-Order Multifetal Pregnancies (2021). Obstetrics & Gynecology, 137(6). Retrieved September 15, 2021, from doi:10.1097/aog.0000000000004397 
  8. Moldenhauer, J. S. (2021). Multifetal pregnancy. MSD Manual Professional Version. Retrieved September 15, 2021, from https://www.msdmanuals.com/professional/gynecology-and-obstetrics/abnormalities-and-complications-of-labor-and-delivery/multifetal-pregnancy

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