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AUTHOR AND EDITOR INFORMATION
Section 1 of 10  
Author: Terence Zach, MD, Department Vice-Chair, Professor, Department of Pediatrics, Section of Newborn Medicine, Creighton University
Terence Zach is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, and Nebraska Medical Association
Coauthor(s):
Arun K Pramanik, MD, Professor, Department of Pediatrics, Division of Neonatology, Louisiana State University Health Science Center;
Susannah P Ford, MD, Fellow, Department of Pediatrics
Editors: David N Sheftel, MD, Director, Division of Neonatology, Clinical Associate Professor, Department of Pediatrics, Lutheran General Children's Hospital of Park Ridge, Chicago Medical School; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; David A Clark, MD, Chairman, Professor, Department of Pediatrics, Albany Medical College; Carol L Wagner, MD, Professor of Pediatrics, Medical University of South Carolina; Ted Rosenkrantz, MD, Head, Division of Neonatal-Perinatal Medicine, Professor, Departments of Pediatrics and Obstetrics/Gynecology, University of Connecticut School of Medicine
Author and Editor Disclosure
Synonyms and related keywords:
multiple births, multifetal pregnancy, twins, triplets, quadruplets, dizygotic twins, fraternal twins, monozygotic twins, identical twins, dichorionic/diamniotic twins, monochorionic/diamniotic twins, monochorionic/monoamniotic twins, conjoined twins, monozygotic triplets, dizygotic triplets, trizygotic triplets, twin-to-twin transfusion syndrome, TTTS, placenta previa, abruptio placenta, preeclampsia, cord accidents, hyaline membrane disease
Background
Multiple births occur when multiple fetuses are carried during one pregnancy. Since 1970, the prevalence of multiple births has been increasing because of more widespread use of assisted reproductive technologies to treat infertility. Multifetal pregnancies are high-risk pregnancies with numerous associated fetal and neonatal complications. Researchers have studied twins in an attempt to separate the influence of genetic and environmental factors on both fetal and postpartum development.
Pathophysiology
Multiple births include twins and higher-order multiples (eg, triplets, quadruplets). The 2 types of twins are monozygotic and dizygotic. Dizygotic twins, which sometimes are called fraternal twins, are produced when 2 sperm fertilize 2 ova. Separate amnions, chorions, and placentas are formed in dizygotic twins (see Media file 1). The placentas in dizygotic twins may fuse if the implantation sites are proximate. The fused placentas can be easily separated after birth. Monozygotic twins develop when a single fertilized ovum splits during the first 2 weeks after conception. Monozygotic twins are also called identical twins. An early splitting (ie, within the first 2 d after fertilization) of monozygotic twins produces separate chorions and amnions (see Media file 1). These dichorionic twins have different placentas that can be separate or fused. Approximately 30% of monozygotic twins have dichorionic/diamniotic placentas. Later splitting (ie, 3-8 d after fertilization) results in monochorionic/diamniotic placentation (see Media file 2). Approximately 70% of monozygotic twins are monochorionic/diamniotic. If splitting occurs even later (ie, during 9-12 d after fertilization), monochorionic/monoamniotic placentation occurs (see Media file 3). Monochorionic/monoamniotic twins are rare; only 1% of monozygotic twins have this form of placentation. Monochorionic/monoamniotic twins have a common placenta with vascular communications between the 2 circulations. These twins can develop twin-to-twin transfusion syndrome (TTTS). If twinning occurs more than 12 days after fertilization, then the monozygotic pair only partially split, resulting in conjoined twins. Triplets can be monozygotic, dizygotic, or trizygotic. Trizygotic triplets occur when 3 sperm fertilize 3 ova. Dizygotic triplets develop from one set of monozygotic cotriplets and a third cotriplet derived from a different zygote. Finally, 2 consecutive zygotic splittings with one split results in a vanished fetus and monozygotic triplets. Although the evaluation of the placenta or placentas after the birth is important in all multifetal pregnancies, the examination may not always help determine zygosity, as in the case of monozygotic twins, in which 30% have a dichorionic/diamniotic placentation.
Frequency
United States
The birth rate of monozygotic twins is constant worldwide (approximately 4 per 1000 births). In contrast, dizygotic twinning is associated with multiple ovulation, and its frequency varies among races within countries and is affected by maternal age (increases from 3 in 1000 births in women younger than 20 y to 14 in 1000 births in women aged 35-40 y, declining thereafter) and parity. In the United States, the overall prevalence of twins is approximately 12 per 1000 births, and two thirds are dizygotic. The birth rate of dizygotic twinning is highest in African Americans (10-40 per 1000 births), followed by whites (7-10 per 1000 births) and Asian Americans (3 per 1000 births). The rate of higher-order multiple births has also recently increased, which has been attributed to in vitro fertilization and embryo transfer. Naturally occurring triplet births occur in approximately 1 per 7000-10,000 births; naturally occurring quadruplet births occur in 1 per 600,000 births.
International
The birth rate of monozygotic twins is constant worldwide (approximately 4 per 1000 births). Birth rates of dizygotic twins vary by race. The highest birth rate of dizygotic twinning occurs in African nations, and the lowest birth rate of dizygotic twinning occurs in Asia. The Yorubas of western Nigeria have a birth rate of 45 twins per 1000 live births, and approximately 90% are dizygotic.
Mortality/Morbidity
Multifetal pregnancies are high-risk pregnancies. The fetal mortality rate for twins is 4 times the fetal mortality rate for single births. The neonatal mortality rate for twins is more than 5 times greater than the neonatal mortality rate for single births. Higher-order multiple births have even greater mortality rates than twin and single births. A high prevalence of low birth weight infants, due to prematurity and intrauterine growth retardation (IUGR) and their associated complications, contribute to this problem. Twins have increased frequency of congenital anomalies, placenta previa, abruptio placenta, preeclampsia, cord accidents, and malpresentations, as well as asphyxia/perinatal depression, group B streptococcal (GBS) infections, hyaline membrane disease (HMD), and TTTS.
Race
The frequency of naturally occurring twin births varies by race. Black women have the highest birth rate of twins, followed by white and Hispanic women. Asian women have the lowest birth rate of twins. A racial disparity between black and white twin stillbirths is observed in the United States. Risk of stillbirth is elevated in black fetuses compared with white fetuses among twins but not among triplets.
Age
Maternal age has no effect on monozygotic twin births. Advanced maternal age (>35 y) is associated with increased risk of dizygotic twins. Prevalence of naturally occurring twin births has increased recently because of the trend to delay childbearing to later years.
History
Most multifetal pregnancies are prenatally diagnosed. Maternal complaints of excessive weight gain, hyperemesis gravidarum, and/or sensation of more than one moving fetus; use of ovulation-inducing drugs; or family history of dizygotic twins should alert caregivers to the possibility of a multifetal pregnancy.
Physical
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 agents or gamete/zygote transfer.
Lab Studies
- CBC count: In TTTS, the donor twin is frequently anemic at birth. The recipient twin is polycythemic at birth.
- Calcium level: Hypocalcemia is common in premature infants, especially the donor twin in TTTS.
- Glucose level: Hypoglycemia is common in premature infants, especially if TTTS is present.
- Bilirubin level: Hyperbilirubinemia due to TTTS may develop in polycythemic infants.
Imaging Studies
- Maternal ultrasonography: This study confirms most multifetal pregnancies.
- Neonatal head ultrasonography: Premature infants from multifetal pregnancies have a higher incidence of intraventricular hemorrhage and periventricular leukomalacia than singleton infants of the same gestational age.
Medical Care
Medical care of the woman with multifetal pregnancy is beyond the scope of this article. - The specific medical care required by infants from multifetal births varies and is dictated by whatever complications may be present. Many require only routine newborn care, whereas those with significant prematurity or other complications may require high-level intensive care in specialized centers.
- The usual method of delivery for higher-order multiple births (eg, triplets, quadruplets) is cesarean delivery. Cesarean delivery is also the usual method of delivery for twins in the following situations:
- Breech/vertex presentation with the possibility of interlocking twins
- Monoamniotic twins
- Conjoined twins
- Congenital anomalies that threaten increased neonatal morbidity in a twin
- Delayed interval delivery: Delayed interval delivery of remaining fetuses in multifetal pregnancies at the border of viability is becoming more common. Before 30 weeks’ gestation, delayed delivery for 2 or more days is associated with improved survival in the second twin.
- Delivery room management of infants from multifetal pregnancies requires adequate personnel skilled in neonatal resuscitation. Infants from multifetal pregnancies are at increased risk of birth asphyxia and respiratory distress syndrome (RDS). Such infants may require bag mask ventilation and endotracheal intubation in the delivery room.
- Partial exchange transfusion may be necessary in donor or recipient twins from TTTS.
- Partial exchange transfusions are used to increase hemoglobin concentrations in anemic donor twins while maintaining euvolemia. Small aliquots (5-15 mL) of packed RBCs are infused (usually via an umbilical venous catheter) following removal of an equal volume of the infant's blood until a desired hemoglobin is attained. The transfused packed RBCs should be appropriately cross-matched, cytomegalovirus (CMV) negative, and irradiated. For more information, see Anemia of Prematurity.
- Partial exchange transfusions are used to decrease hemoglobin concentrations in polycythemic recipient twins while maintaining euvolemia. Small aliquots (5-10 mL) of either a colloid such as fresh frozen plasma or a crystalloid such as a 0.9% saline solution are infused (usually via an umbilical venous catheter) following removal of an equal volume of the infant's blood until a desired hemoglobin level is attained. For more information, see Polycythemia of the Newborn.
Consultations
A woman with multiple gestation pregnancy may benefit from a consultation with a perinatologist. A neonatologist may be involved in the postnatal care of multiple birth infants, particularly if the births are premature or if congenital anomalies are present.
Medication requirements vary depending on specific comorbidities. Refer to the eMedicine topics for the specific complication.
Complications
- Prematurity: Infants from multifetal pregnancies are more likely to be born prematurely and are more likely to require neonatal intensive care. Approximately 50% of twin deliveries occur before 37 weeks' gestation. The length of gestation inversely decreases with the number of fetuses present. Infants from multifetal pregnancies represent 20% of very low birth weight infants.
- Hyaline membrane disease: Twins born at fewer than 35 weeks' gestation are twice as likely to develop HMD as single birth infants born at fewer than 35 weeks' gestation. The prevalence of HMD is greater in monozygotic twins than in dizygotic twins. The concordance rate for HMD (ie, both twins have HMD) is greater in monozygotic twins than in dizygotic twins. If only one of a pair of twins develops HMD, then the second twin is more likely to develop HMD than the first twin.
- Birth asphyxia/perinatal depression: Newborns from multifetal pregnancies have an increased frequency of perinatal depression and birth asphyxia due to various causes. Umbilical cord entanglement, locked twins, a prolapsed umbilical cord, placenta previa, and uterine rupture can occur and result in asphyxiation of an infant. Cerebral palsy is 6 times more common in twin births and 30 times more common in triplet births than in single births. Monochorionic/monoamniotic twins are at highest risk for cord entanglement. The second-born twin is at greatest risk for birth asphyxia/perinatal depression.
- Group B streptococcal infections: Early onset GBS infections in low birth weight infants are nearly 5-fold greater than in average weight singletons.
- Vanishing twin syndrome: Early ultrasonography diagnosis has revealed that as many as one half of all twin pregnancies result in the delivery of only a single fetus; the second twin vanishes. Intrauterine demise of one twin can result in neurologic sequelae in the surviving twin. Acute exsanguination of the surviving twin into the relaxed circulation of the deceased twin can result in intrauterine CNS ischemia.
- Congenital anomalies, acardia, twin reversed arterial perfusion sequence: Congenital anomalies are more common in twins than in a single fetus. CNS, cardiovascular, and GI defects occur with increased frequency. Monozygotic twins have increased prevalence of deformations secondary to intrauterine space constraints. Common deformations in twins include limb defects, plagiocephaly, facial asymmetry, and torticollis. Acardia is a rare anomaly unique to multifetal pregnancy. In this condition, one twin has an absent or rudimentary heart. Twin reversed arterial perfusion (TRAP) sequence occurs when an acardiac twin receives all of the blood supply from the normal "pump" twin. This only occurs in monochorionic twins. Blood enters the acardiac twin in a reversed perfusion manner. Blood enters this fetus via an umbilical artery and exits via the umbilical vein. The excessive demands on the normal "pump" twin can cause cardiac failure in that twin.
- TTTS: This syndrome occurs in monochorionic/monoamniotic or monochorionic/diamniotic twins. Vascular anastomoses in the monochorionic placenta result in transfusion of blood from one twin (ie, donor) to the other twin (ie, recipient). Polyhydramnios develops in the sac of the recipient twin because of volume overload and increased fetal urine output. Oligohydramnios develops in the sac of the donor twin because of hypovolemia and decreased urine output. Severe oligohydramnios can result in the stuck twin phenomena, in which the twin appears in a fixed position against the uterine wall.
- Conjoined twins
- Incomplete late division of monozygotic twins produces conjoined twins.
- Conjoined twins are connected at identical points and are classified according to site of union, as follows:
- Thoracopagus - Joined at chest (40%)
- Xiphopagus/omphalopagus - Joined at abdomen (34%)
- Pygopagus - Joined at buttocks (18%)
- Ischiopagus - Joined at ischium (6%)
- Craniopagus - Joined at head (2%)
- IUGR: The birth weights are smaller in infants from multifetal pregnancies than weights in corresponding singletons. However, when combined, birth weights of twins are greater than weights of corresponding singletons. Most of the deficit of birth weight occurs in the final 8-11 weeks of pregnancy. Average birth weights are similar between twins and singletons until 32 weeks’ gestation. Average birth weights are similar between triplets and singletons until 29 weeks’ gestation. Birth weight discrepancies of more than 20-25% are considered discordant. Discordant birth weights occur in 10% of twins. The cause of discordant birth weight among twins is the difference between each twin's placental surface area or TTTS. Discordant birth weights among triplets are more common than discordant birth weights between twins. Approximately 30% of pregnancies with triplets have a birth weight discordance of more than 25%.
Prognosis
The prognosis of infants born from multifetal pregnancies depends on the complications that develop. Some studies have reported that the risks of death, chronic lung disease, and grade III/IV intracranial hemorrhage were similar in twins and singletons. Other studies have reported a higher prevalence of complications such as necrotizing enterocolitis, retinopathy of prematurity, and patent ductus arteriosus in infants from multifetal pregnancies versus singletons.
Medical/Legal Pitfalls
- Most problems that could result in medical legal action against the health professional involve prenatal and intrapartum care issues.
Special Concerns
- Multiple births have significant economic implications. Twins and triplets have more frequent and longer duration hospitalizations than singletons. Multiple births contribute disproportionately to inpatient hospital costs in the first 5 years of life.
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Multiple Births excerpt Article Last Updated: Oct 2, 2007
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