111: Multiple Gestation

A multiple gestation occurs when more than one fetus is carried during a pregnancy.

In 2008, the overall rate of twin births was 32.6 in 1000 live births, and the rate of triplet births was 147.6 in 100,000 live births. The incidence of multiple gestation pregnancies is probably underestimated. Fewer than half of twin pregnancies diagnosed by ultrasonography during the first trimester are delivered as twins, a phenomenon that has been termed vanishing twin. Two gestational sacs can be identified with ultrasonography by 6 weeks' gestation. In addition, routine screening for maternal α-fetoprotein (AFP) may identify pregnancies with multiple gestations at an early gestational age. Between 1980 and 2004, the twinning rate climbed 70% (18.9–32.2/100 live births). The rate was stable between 2004 and 2007 but climbed 1% between 2007 and 2008. The rate of triplet births escalated more rapidly, increasing 400% during the 1980s and 1990s with a peak in 1998. Since 1998 there has been a steady reduction in triplet and other higher order multiple births. About a third of twins in the United States are monozygotic. The incidence of monozygotic twinning is constant at 3–5 per 1000 pregnancies, whereas the rate for dizygotic twinning varies from 4–50 per 1000 pregnancies.

Placental classification and determination of zygosity are important in the pathophysiology of twins.

1. Classification. Placental examination affords a unique opportunity to identify two-thirds to three-fourths of monozygotic twins at birth.

   1. Twin placentation is classified according to the placental disk (single, fused, or separate), number of chorions (monochorionic or dichorionic), and number of amnions (monoamniotic or diamniotic) (Figure 111–1).

   2. Heterosexual (assuredly dizygotic) twins always have a dichorionic placenta.

   3. Monochorionic twins are always of the same sex. All monochorionic twins are believed to be monozygotic. In 70% of monozygotic twin pregnancies, the placentas are monochorionic, and the possibility exists for commingling of the fetal circulations. Less than 1% of twin pregnancies are monoamniotic.

2. Placental complications. Twin gestations are associated with an increased frequency of anomalies of the placenta and adnexa, for example, a single umbilical artery or velamentous or marginal cord insertion (6–9 times more common with twin gestation). The cord is more susceptible to trauma from twisting. The vessels near the insertion are often unprotected by Wharton jelly and are especially prone to thrombosis when compression or twisting occurs. Intrapartum fetal distress from cord compression and fetal hemorrhage from associated vasa previa are potential problems with velamentous insertion of the cord.

3. Determination of zygosity. The most efficient way to identify zygosity is as follows:

   1. Gender examination. Male-female pairs are dizygotic. The dichorionic placenta may be separate or fused.

   2. Placental examination. Twins with a monochorionic placenta (monoamniotic or diamniotic) are monozygotic. Care should be taken not to confuse apposed fused placentas for a single chorion. If doubt exists on a gross inspection of the dividing membranes, a transverse section should be studied. The zygosity of twins of the same sex with dichorionic membranes cannot be immediately known. Genetic studies are needed (eg, blood typing, human leukocyte antigen typing, DNA markers, and chromosome marking) to determine zygosity.

Use of assisted reproductive technology is a major risk factor for multiple births. The incidence of dizygotic twinning increases with a family history of twins, maternal age (peak at 35–39 years), previous twin gestation, increasing parity, maternal height, fecundity, social class, frequency of coitus, and exposure to exogenous gonadotropins, clomiphene, or in vitro fertilization. The risk of twinning decreases with undernourishment. Ethnic background (African Americans > Caucasians > Asians) is a preconception risk factor for naturally conceived multiple gestation births.

Twins are more likely to have prematurity, intrauterine growth restriction, congenital anomalies, and twin-twin transfusion.

1. Prematurity and uteroplacental insufficiency. The major contributors to perinatal complications. In 2008, 1% of singletons, 10% of twins, and 36% of triplets had birthweights of <1500 g.

2. Intrauterine growth restriction (IUGR). The incidence of low birthweight in twins is ∼50–60%, a figure that is 5–7 times higher than the incidence of low birthweight in singletons. In general, the more fetuses in a gestation, the smaller their weight for gestational age (Figure 111–2). Twins tend to grow at normal rates up to about 30–34 weeks' gestation when they reach a combined weight of 4 kg. Thereafter, they grow more slowly. Two-thirds of twins show some signs of growth restriction at birth.

3. Uteroplacental insufficiency. The incidence of acute and chronic uteroplacental insufficiency is increased in multiple gestations. Five-minute Apgar scores of 0–3 are reported for 5–10% of twin gestations. These low scores may relate to acute stresses of labor, cord prolapse (1–5%), or trauma during delivery superimposed on chronic uteroplacental insufficiency.

4. Congenital anomalies. Birth defects are 2 to 3 times more common in monozygotic twins than in singletons or dizygotic twins, who have a 2–3% incidence of major defects diagnosed at birth. Three mechanisms are postulated for the increased frequency of structural defects in monozygotic twins: deformations caused by intrauterine space constraint, disruption of normal blood flow secondary to placental vascular anastomoses, and defects in morphogenesis. Such defects are usually discordant in monozygotic twins; however, in purely genetic conditions (eg, chromosomal abnormalities or single-gene defects), concordance would be the rule. Twins conceived by in vitro fertilization have twice the risk of major congenital anomalies compared with twins conceived naturally.

   1. Anomalies unique to multiple pregnancies. Certain anomalies, such as conjoined twins and acardia, are unique to multiple pregnancies.

   2. Deformations. Twins are more likely to suffer from intrauterine crowding and restriction of movement, leading to synostosis, torticollis, facial palsy, positional foot defects, and other defects.

   3. Vascular disruptions. Disruptions related to monozygotic vascular shunts may result in birth defects. Acardia occurs from an artery-to-artery placental shunt, in which reverse flow leads to the development of an amorphous recipient twin. In utero death of a co-twin may result in a thromboembolic phenomenon, including disseminated intravascular coagulation, cutis aplasia, porencephaly or hydranencephaly, limb reduction defects, intestinal atresias, or gastroschisis.

5. Twin-twin transfusion syndrome

   1. Vascular anastomoses. Almost all monochorionic placentas demonstrate vascular anastomoses, whereas dichorionic placentas rarely do. Vascular anastomoses may be superficial direct communications easily visible on inspection between arteries (most common) or veins (uncommon), deep connections from arteries to veins via villi, or combinations of superficial and deep connections.

   2. Incidence. Despite the high frequency of vascular anastomosis in monochorionic placentation, the twin-twin transfusion syndrome is relatively uncommon (∼15% of monochorionic gestations).

   3. Clinical manifestations. Clinically, the twin-twin transfusion syndrome is diagnosed when twins have a hemoglobin difference of >5 g/dL and is due to artery-to-vein anastomoses.

      1. The donor twin tends to be pale and have a low birthweight, oligohydramnios, anemia, hypoglycemia, decreased organ mass, hypovolemia, and amnion nodosum. Donor twins often require volume expansion, red blood cell transfusion, or both.

      2. The recipient twin is frequently plethoric and has a high birthweight, polyhydramnios, polycythemia or hyperviscosity, increased organ mass, hypervolemia, and hyperbilirubinemia. Recipient twins often require partial exchange transfusion.

      3. Infants born with twin-twin transfusion syndrome have an increased risk of being diagnosed with antenatally acquired severe cerebral lesions and are at an increased risk of neurodevelopmental sequelae, even when treatment is initiated antenatally. Antenatal treatment with fetoscopic selective laser coagulation may reduce the risk of death or long-term impairment.

      4. Very low birthweight infants who are multiple births may have an increased risk of mortality and intraventricular hemorrhage compared with singletons.

Multiple gestation is usually diagnosed prenatally by ultrasound as early as 5 weeks (can see gestational sacs) and by an increased AFP (in twin pregnancies, the average AFP is double that found in a singleton pregnancy).

1. Site of delivery. When a complicated twin gestation has been identified, delivery should ideally be conducted at a high-risk perinatal center with experienced pediatric delivery teams in attendance.

2. Physical examination. Infants should be examined for evidence of intrauterine growth restriction, congenital anomalies, and twin-twin transfusion syndrome. Central hematocrits should be obtained in both infants. When one of the infants has a congenital anomaly, the other twin is at increased risk for complications. In particular, death of one fetus puts the others at risk for fetal disseminated intravascular coagulation.

3. Complications in newborn period. The second-born twin is more likely to develop respiratory distress syndrome, bronchopulmonary dysplasia, and die.

4. Co-bedding of multiples (controversial). Coincident with the rise in multiple births has been an interest in co-bedding of multiples. Although co-bedding multiples has become common practice, the safety or the benefit of this practice has not been definitively established.

5. Economic considerations. It has been estimated that the care of assisted reproductive-related preterm infants born in the United States is approximately $1 billion annually.

6. Risks beyond the neonatal period

   1. Catch-up growth. In monozygotic twins, birthweight differences may be as much as 20%, but the lighter twin has a remarkable ability to make up intrauterine growth deficits.

   2. Social problems. Parents of multiple births may have an increased level of stress and may respond differently to their children compared with singletons. Counseling for parents of twins may be invaluable.

Although perinatal mortality rates for singleton pregnancies have continued to fall during the last decade, there has been little change in mortality rates for multiple pregnancies.

1. Twins. The perinatal death rate for twins is 9 times the rate for first-born singletons and 11 times the rate for second-born singletons.

   1. Monoamniotic twins. Monoamniotic twins have the highest mortality rate among the different types of twins, largely because of cord entanglement.

   2. Monozygotic twins. Monozygotic twins have a perinatal mortality and morbidity rate that is 2 to 3 times that of dizygotic twins. Diamniotic monochorionic twins have a mortality rate of 25%, and dichorionic twins have a mortality rate of 8.9%.

   3. Fetal death in twins. When the cause of death is intrinsic to one dichorionic fetus and does not threaten the other fetus, complications are rare. Hazardous intrauterine environments threaten both twins, whether monochorionic or dichorionic. With monochorionic placentas, the incidence of major complications or death in the surviving twin is ∼50%.

2. Triplets. The neonatal mortality rate for triplets is 18.8%, and the perinatal mortality rate is 25.5%. The risk of death or neurodevelopmental impairment has been shown to be increased in extremely low birthweight triplets and other higher-order multiples compared to singletons (adjusted odds 1.7, 95% confidence intervals 1.3–2.2).