Multiple Births 

Multiple births refers to the delivery of twins and higher order multiples (eg, triplets, quadruplets). Multiple births occur when multiple fetuses are carried during a pregnancy with the subsequent delivery of multiple neonates.^[1]

The 2 types of twin pregnancies are dizygotic and monozygotic.

Dizygotic twins develop when 2 ovum are fertilized. Dizygotic twins have separate amnions, chorions, and placentas (see the image below).

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 after conception. An early splitting (ie, within 2 d after fertilization) of monozygotic twins produces separate chorions and amnions. 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 the image below).

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

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 fertilized ovum only partially splits resulting in conjoined twins.

Triplet pregnancies result from various fertilization, splitting, and development scenarios that involve ovum and sperm. For example, 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 a vanished fetus can also result in monozygotic triplets. Zygosity in quadruplets and higher order multiples also varies.

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.^[2]

Frequency

United States

The incidence of monozygotic twins is constant worldwide (approximately 4 per 1000 births). Approximately two thirds of twins are dizygotic. Birth rates of dizygotic twins vary by race (10-40 per 1000 in blacks, 7-10 per 1000 births in whites, and approximately 3 per 1000 in Asians), maternal age (ie, increasing frequency with increasing maternal age ≤ 40 y), and other factors such as parity and mode of fertilization (ie, most artificially conceived twins are dizygotic; however, 6-10% are monozygotic). 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.

Since 1970, the prevalence of multiple births has been increasing. A combination of factors including the widespread use of assisted reproductive techniques and advancing maternal age at conception are associated with this phenomenon. In the United States, a plateau in the prevalence of multiple births has been observed since 2004. From 2004–2006, the prevalence of twin deliveries in the United States has remained stable at approximately 32 per 1000 live births, compared with the decreasing prevalence of higher order multiple deliveries.^[3]

International

The birthrate of monozygotic twins is constant world wide (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. Multifetal pregnancies are complicated by a higher incidence of hypertensive diseases, anemia, preterm labor, premature rupture of membranes, hyperemesis gravidarum, placenta previa, polyhydramnios, and delivery complications (eg, Cesarean delivery, placental abruption, operative delivery, malpresentation, cord accidents, postpartum endometriosis).

Because of advancements in perinatal and neonatal care, the major issues that affect neonatal outcome of multiple fetal pregnancies include preterm delivery, low birth weight, and intrauterine growth retardation. In 2006 in the United States, 11% of singletons were premature (< 37 weeks' gestation) and 61% of multiples were premature, combining for a total preterm delivery rate of 12%; 6% of singletons had low birth weight (birth weight < 2500 g) and 59% of multiples had low birth weight, combining for a total low birth rate percentage of 8%.^[3] The percentage of very low birthweight neonates (birth weight < 1500 g) was 1% in singletons and 11% in multiples, combining for a frequency of 1%.

The mean gestational age at delivery is approximately 37 weeks for twins, 33 weeks for triplets and 28 weeks for quadruplets. Divergence from singleton growth curves occurs at approximately 32 weeks' gestation in twins, 29-30 weeks' gestation in triplets, and 27 weeks' gestation in quadruplets.

Specific morbidities in multiple fetal pregnancies are controversial. Neonatal outcomes at specific gestational ages and birth weights are similar to singleton pregnancies. Neonates born to multiple fetal pregnancies may have a higher risk of acute respiratory morbidities, such as respiratory distress syndrome^[4] 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, nosocomial infection ,and length of hospital stay, demonstrate no statistical difference between singletons and multiples.^{[5, 6]}

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 fetal pregnancies during this time frame (ie, fetal growth restriction, hypertensive disorders, placental insufficiency).^[7]

The neonatal mortality rate in multiple fetal pregnancies is similar to singleton rates and parallels decreasing gestational age.

In a prospective cohort study of monochorionic twins followed up from the first trimester until a mean age of 24 months, Ortibus et al found that twin-to-twin transfusion syndrome 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 1 survivor, and 6% resulted in no survivor. Overall, mortality was 8% and neurodevelopmental impairment occurred in 10% of infants.