Multiple Births 

Updated: Dec 20, 2019
Author: Garth E Fletcher, MD; Chief Editor: Dharmendra J Nimavat, MD, FAAP 

Overview

Background

The term "multiple births" refers to the delivery of twins and higher-order multiples (ie, triplets, quadruplets, etc). Multiple births occur when multiple fetuses are carried during a pregnancy with the subsequent delivery of multiple neonates. Pregnancies complicated by multiple births are associated with a higher rate of neonatal morbidity and mortality, paralleling the increased risk of preterm delivery, low birth weight, and other associated high-risk morbidities.[1] Maternal morbidity and mortality are also increased in pregnancies complicated by multiple gestations and multiple births.

Physiology/Pathophysiology

Placental physiology has a significant impact on fetal and neonatal outcome. Monochorionic twins have increased neonatal morbidities such as prematurity, intrauterine growth retardation, congenital anomalies, twin-to-twin transfusion syndrome, and increased perinatal mortality.[2] Twin-to-twin transfusion syndrome has been reported in 8-10% of monochorionic pregnancies. Triplet gestations with monochorionic placentation may also experience an increased complication rate.[1, 3]

Determination of placental chorionicity can be evaluated by obstetric ultrasonography during the first and early second trimester. Evaluation of the placenta(s) after birth may also be helpful in the perinatal evaluation process.

Monozygotic pregnancies involve the fertilization of a single ovum by a single sperm. Monozygotic twins develop when a single fertilized ovum splits after conception. An early splitting of the ovum (ie, within 2 days of fertilization) produces separate chorions and amnions. These dichorionic twins have different placentas, which can be separate or fused. Approximately 30% of monozygotic twins have dichorionic/diamniotic placentas.

Later splitting (ie, 3-8 days after fertilization) results in monochorionic/diamniotic placentation (see the image below).

Monochorionic/diamniotic placentation. Monochorionic/diamniotic placentation.

Approximately 70% of monozygotic twins are monochorionic/diamniotic. If splitting occurs later (ie, 9-12 days after fertilization), monochorionic/monoamniotic placentation occurs (see the image below).

Monochorionic/monoamniotic placentation. Monochorionic/monoamniotic placentation.

Monochorionic/monoamniotic twins are rare; only 1% of monozygotic twins have this form of placentation. Monochorionic/monoamniotic twins have a common placenta, with the possibility of significant vascular communication between the 2 fetal circulations. These twins can develop twin-to-twin transfusion syndrome. If twinning occurs more than 12 days after fertilization, then the monozygotic fertilized ovum only partially splits, resulting in conjoined twins.

Dizygotic, trizygotic, and other higher-order pregnancies involve the fertilization of multiple ova. Dizygotic twins, for example, develop when two ova are fertilized. Dizygotic twins have separate amnions, chorions, and placentas (see the image below).

Dichorionic/diamniotic placentation. Dichorionic/diamniotic placentation.

The placentas in dizygotic twins may fuse if the implantation sites are proximate. The fused placentas can be easily separated after birth.

Triplet pregnancies result from various fertilization, splitting, and development scenarios that involve ova and sperm. For example, triplets can be monozygotic, dizygotic, or trizygotic. Trizygotic triplets occur when three sperm fertilize three ova. Dizygotic triplets develop from one set of monozygotic cotriplets and a third cotriplet derived from a different zygote. Finally, two consecutive zygotic splittings with a vanished fetus can also result in monozygotic triplets. Zygosity in quadruplets and higher order multiples also varies.

Although the evaluation of the placenta(s) following birth is important in all multifetal pregnancies, the examination may not always help to determine zygosity.[4]

Epidemiology

The incidence of monozygotic twins is constant worldwide, approximately 4 per 1000 births. Approximately two thirds of twins are dizygotic. Birthrates of dizygotic twins vary by race (10-40 per 1000 births in blacks, 7-10 per 1000 births in whites, and approximately 3 per 1000 births in Asians) and maternal age (ie, the frequency has risen with increasing maternal age ≤40 years). Dizygotic-twin birthrates are also influenced by other factors, such as parity and mode of fertilization (ie, most artificially conceived twins are dizygotic; however, 6-10% are monozygotic). The highest birthrate of dizygotic twins occurs in African nations, and the lowest occurs in Asia.[5, 6] The incidence of multiple zygotic pregnancies varies in relation to maternal age, the use of assisted reproductive technology (ART), and ethnicity. Naturally occurring triplet births occur in approximately 1 per 7000-10,000 births; naturally occurring quadruplet births occur in approximately 1 per 600,000 births.

The incidence of multiple births increased significantly in the late 20th century in the United States and worldwide.[2, 7] A combination of factors contributed to this, the two most prominent of these being the use of ART and advanced maternal age at the time of conception.[2, 8, 9, 10]

In the United States, a plateau in the prevalence of multiple births was observed from 2004-2010. Statistics showed that the prevalence of twin deliveries in the United States remained stable at approximately 33 per 1000 live births, compared with a decreasing prevalence of higher-order multiple deliveries (see the graphs below).[2, 10] This trend continued until 2014, when the twin birth rate began to decline by an average of 1% a year from 33.9 in 2014 to 32.6 in 2018, for a total decrease of 4%.[11, 12, 13]

National Vital Statistics Reports, August 2012. Co National Vital Statistics Reports, August 2012. Courtesy of the US Department of Health and Human Services (HHS).
National Vital Statistics Reports, August 2012. Co National Vital Statistics Reports, August 2012. Courtesy of the US Department of Health and Human Services (HHS).

Prognosis

Even with advancements in perinatal/neonatal medicine, multifetus pregnancies present challenges in prenatal and postnatal care. Neonatal morbidity and mortality parallel the increased risk of preterm birth and low birth weight in these pregnancies.[14]

Improving the outcome of multifetal pregnancies involves decreasing the rate of preterm births, providing an optimal intrauterine environment for fetal growth, optimizing neonatal care in the delivery room, and neonatal ICU if required.[15]

Maternal morbidity

Multiple-gestation pregnancies are associated with a significantly higher maternal complication rate than are singleton gestations.[16] Multiple-gestation pregnancies carry an increased risk of hypertensive disorders of pregnancy; gestational diabetes mellitus; hyperemesis; preterm labor; premature rupture of membranes; anemia; placental abruption; postpartum hemorrhage; cardiac complications, such as myocardial infarction and left ventricular heart failure; operative deliveries, both vaginal and cesarean; required hysterectomy; and prolonged hospital stay.[2, 16]

Fetal/neonatal morbidity

The increase in fetal and neonatal morbidity and mortality associated with multiple-gestation/birth pregnancies correlates with an increased risk of preterm delivery, low birth weight, and intrauterine growth retardation. The neonatal mortality rate in multiple-fetus pregnancies is similar to singleton rates, increasing with decreasing gestational age.

The average gestational age for twin deliveries is 35.3 weeks; for triplet deliveries, 32.2 weeks; and for quadruplet deliveries, 29.9 weeks. Although the percentage of preterm multiple-birth deliveries in the United States declined between 2006 and 2010 (as did the incidence of preterm births in general),[10] the rate still remained significantly high; in 2011, approximately 60% of multiples delivered at less than 37 weeks' gestation (see the graph below).[2, 17]

Preterm by plurality, United States, 2011. Courtes Preterm by plurality, United States, 2011. Courtesy of March of Dimes (www.marchofdimes.org).

Birth weight is closely associated with gestational age, so the increased incidence of preterm delivery influences the rate of reduced birth weights in multiple-birth neonates. These neonates also have an increased incidence of intrauterine growth retardation. Divergence from singleton growth curves occurs at approximately 32-33 weeks in twin gestations, at 29-30 weeks in triplet gestations, and at 27-28 weeks in quadruplet gestations.

Comparing specific morbidities and mortality in multiple-gestation pregnancies is difficult due to the complexity of contributing factors. For example, some evidence suggests a link between ART and perinatal morbidity unrelated to the risks associated with multiple births.[18]  Chorionic-amniotic placentation also affects multiple-gestation outcomes.

Neonatal outcomes at specific gestational ages and birth weights are similar in multiple-birth neonates to those in singleton pregnancies. Neonates from multiple-gestation pregnancies may have a higher risk of acute respiratory morbidity, such as respiratory distress syndrome,[19] but do not have a higher incidence of chronic lung disease. Other major morbidities, including intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, necrotizing enterocolitis, patent ductus arteriosus, and nosocomial infection, as well as length of hospital stay, demonstrate no statistical difference between singletons and multiples.[8, 20]

The risk of cerebral palsy in multiple-fetus pregnancies parallels decreasing gestational age. A second association during the late preterm period (34-37 weeks' gestation) may correlate with the increasing maternal morbidities of multiple-fetus pregnancies during this time frame (ie, fetal growth restriction, hypertensive disorders, placental insufficiency).[9]

In a prospective cohort study of monochorionic twins followed from the first trimester to a mean age of 24 months, Ortibus et al found that twin-to-twin transfusion syndrome (a specific morbidity in multiple-gestation pregnancies) and assisted conception increased the risk of both death and neurodevelopmental impairment, whereas early onset discordant growth increased only the risk of death. Of the 136 pregnancies studied, 90% resulted in both twins surviving, 4% resulted in one survivor, and 6% resulted in no survivors. Overall mortality was 8%, and neurodevelopmental impairment occurred in 10% of infants.[21]

Patient Education

When multifetal pregnancy is diagnosed, parental education on specific issues of a multifetal pregnancy should take place.

Most outcomes from multifetal pregnancies require only routine pediatric care; however, some patients may require specialized follow-up coordinated through a neonatal ICU (NICU) follow-up clinic.

 

Presentation

History and Physical Examination

History

Most multifetal pregnancies are prenatally diagnosed.

Maternal complaints of excessive weight gain, hyperemesis gravidarum, the sensation of more than one moving fetus, the use of ovulation-inducing drugs, or a family history of dizygotic twins should alert caregivers to the possibility of a multifetal pregnancy.

Physical Examination

Women with multifetal pregnancies may have a uterine size that is inconsistently large for dates and may experience accelerated weight gain. Upon auscultation, more than one fetal heart rate may be heard.

Causes

Risk factors for multifetal pregnancy can be divided into natural and induced.

Risk factors for natural multifetal pregnancy include advanced maternal age, family history of dizygotic twins, and race.

Induced multifetal pregnancies occur following infertility treatment via the use of ovulation-inducing agent or multiple gamete/zygote transfer.

 

Workup

Laboratory Studies

The evaluation of a multifetal pregnancy involves routine prenatal and postnatal care, as well as specific assessment directed by the type of multiple pregnancy and neonatal complications. Guidelines for the evaluation of multifetal pregnancies have been established by American College of Obstetricians and Gynecologists, including the following laboratory studies[2] :

  • Obstetrical: Routine prenatal laboratory studies are indicated.

  • Neonatal: A CBC count is obtained to evaluate for anemia and polycythemia.

  • Neonatal arterial blood gas and cord blood gas: These are measured to evaluate for respiratory distress, hypoxia, acidosis, and perinatal depression.

  • Metabolic panel: Fluid status and electrolyte levels should be evaluated and metabolic status should be determined, including through screening for hypoglycemia and hypocalcemia.

  • Bilirubin level: This is obtained to screen for increased risk of hyperbilirubinemia associated with prematurity and polycythemia.

Imaging Studies

Several imaging studies are useful in the workup of multifetal pregnancy, including the following:

  • Obstetrical: Prenatal ultrasonography is used to confirm multifetal pregnancy and to monitor intrauterine fetal growth.

  • Fetal echocardiography: This is used to screen for congenital heart disease in neonates.

  • Fetal MRI: This is used to screen for fetal anomalies.

  • Neonatal: Chest radiography is used to evaluate respiratory distress.

  • Ultrasonography: This is used to screen for intraventricular hemorrhage, periventricular leukomalacia, and abdominal abnormalities.

  • Echocardiography: This is used to screen for congenital heart disease.

Other Tests

Obstetrical considerations: Antepartum surveillance is indicated.

Procedures are specific to the obstetrical or neonatal complications (ie, ablation procedure in twin-to-twin transfusion syndrome [TTTS], surgery in conjoined twins).

 

Treatment

Medical Care

Obstetric medical care is specific to the type of multifetal pregnancy. The highest risk is in monochorionic/monoamniotic pregnancies. An inherent risk of other conditions (ie, preterm labor, intrauterine growth retardation [IUGR], hypertensive diseases) is also found in multiple-fetus pregnancies.

In a systematic review and meta-analysis of 32 studies, Cheong-See et al investigated the risks of stillbirth and neonatal complications by gestational age in uncomplicated monochorionic and dichorionic twin pregnancies. They found that neonatal morbidity rates showed a consistent reduction with increasing gestational age in both monochorionic and dichorionic pregnancies. Based upon their findings, the investigators recommend that to minimize perinatal deaths, delivery should be considered at 37 weeks' gestation in uncomplicated dichorionic twin pregnancies and at 36 weeks in monochorionic pregnancies.[14]

In a retrospective, multicenter US cohort, Lappen et al compared the outcome of attempted vaginal delivery versus planned cesarean delivery of triplets. Eighty sets of triplets met inclusion criteria; 24 sets (30%) had an attempted vaginal delivery, with a success rate of 16.7%. Compared with planned cesarean delivery, attempted vaginal delivery was associated with a higher risk of maternal transfusion (20.8% vs 3.6%, P = 0.01) and neonatal mechanical ventilation (26.4% vs 7.7%; adjusted incidence rate ratio, 1.12; 95% confidence interval, 1.01-1.24).[22]

Neonatal medical care is dictated by general and specific morbidities. Many neonates require only routine newborn care; others require neonatal intensive care secondary to prematurity, low birth weight, and their associated complications. Refer to specific Medscape Drugs & Diseases neonatology articles for more information.

Medication requirements vary depending on specific comorbidities. Refer to the relevant Medscape Drugs & Diseases topics for specific complications.

Consultations

A woman with a multiple-gestation pregnancy may benefit from a consultation with a perinatologist.

A neonatologist may be involved during prenatal counseling and in the postnatal care of multiple-birth infants, particularly if the births are premature or congenital anomalies are present.

Special concerns

The impact of neonates from multifetal pregnancies on the family has been studied. Increased incidence of maternal depression, poor parent satisfaction with parenting, child abuse, and sibling behavior problems have all been associated with multifetal pregnancies.[23]