Multiple Births
Yvette R. Johnson
I. CLASSIFICATION
Zygosity. Monozygotic (MZ) twins originate and develop from a single fertilized egg (zygote) as a result of division of the inner cell mass of the blastocyst. MZ twins are of the same sex and are genetically identical. Dizygotic (DZ) or fraternal twins originate and develop from two separately fertilized eggs. Triplets and higher order pregnancies (quadruplets, quintuplets, sextuplets, septuplets, etc.) can be multizygotic, MZ and identical, or rarely, a combination of both.
Placenta and fetal membranes. A major portion of the placenta and the fetal membranes originate from the zygote. The placenta consists of two parts: (i) a larger fetal part derived from the villous chorion and (ii) a smaller maternal part derived from the deciduas basalis. The chorionic and amniotic sacs surround the fetus. The chorion begins to form at day 3 after fertilization, and the amnion begins to form between days 6 and 8. The two membranes eventually fuse to form the amniochorionic membrane.
MZ twins commonly have one placenta with one chorion and two amnions (monochorionic diamniotic) or, rarely, one placenta with one chorion and one amnion (monochorionic monoamniotic).
If early splitting occurs before the formation of the chorion and amnion (day 0—3), MZ twins can end up having two placentas with two chorions and two amnions (dichorionic diamniotic).
DZ twins always have two placentas with two chorions and two amnions (dichorionic diamniotic); however, the two placentas and chorions may be fused.
II. EPIDEMIOLOGY
Incidence. The twin birth rate in 2006 was 32.1 per 1,000 live births and had been stable for the previous 2 years.
The rate of MZ twinning has remained relatively constant (3.5 per 1, 000 births).
The rate of DZ twinning is approximately 1 in 100 births. This rate is influenced by several factors such as ethnicity (1 in 500 Asians, 1 in 125 in whites, and as high as 1 in 20 in African populations) and maternal age. The frequency of DZ twinning has a genetic tendency that is affected by the genotype of the mother and not that of the father. In the United States, approximately twothirds of twins are DZ.
The birth rate of triplet and higher order multiples peaked in 1998 at 194 per 100,000 live births. The rate declined to 153 per 100,000 live births in 2006. The rates for other higher order multiples (quadruplets and higher)
declined by 21% in 2006 compared to peak rates in 1998 (194 per 100, 000 live births).
Causative factors. Two main factors account for the increase in multiple births over the last 2 decades: (i) increased use of fertility-enhancing therapies, including assisted reproductive technologies (ARTs) such as in vitro fertilization (IVF), and non-ART therapies such as ovulation-inducing drugs and artificial insemination, and (ii) older maternal age at childbearing (peak at 35—39 years), which is associated with an increase in multiples.
III. ETIOLOGY
MZ pregnancies result from the splitting of a single egg between day 0 and day 14 postfertilization. The type of placenta that forms depends on the day of embryo splitting.
A dichorionic diamniotic placenta results when early splitting occurs at day 0 to 3 before chorion formation (which usually occurs about day 3) and before implantation. A monochorionic diamniotic placenta results when splitting occurs about day 4 to 7, at which time the blastocyst cavity has developed and the chorion has formed. Amnion formation occurs at day 6 to 8, and splitting of the egg after this time (day 4 to 7) results in a monochorionic monoamniotic placenta. At day 14 and thereafter, the primitive streak begins to form, and late splitting of the embryo at this time results in conjoined twins.
DZ or multizygous pregnancies result when more than one dominant follicle has matured during the same menstrual cycle and multiple ovulations occur. Increased levels of follicle-stimulating hormone (FSH) in the mother have been associated with spontaneous DZ twinning. FSH levels increase with advanced maternal age (peak at age 37). A familial tendency toward twinning has also been shown to be associated with increased levels of FSH.
IV. DIAGNOSIS.
Multiple gestational sacs can be detected by ultrasonography as early as 5 weeks and cardiac activity can be detected from more than one fetus at 6 weeks.
Placentation. First-trimester ultrasonography can best determine the chorionicity of a multiple gestation; chorionicity is more difficult to determine in the second trimester. From weeks 10 to 14, a fused dichorionic placenta may often be distinguished from a true monochorionic placenta by the presence of an internal dividing membrane or ridge at the placental surface (lambda sign). The dividing septum of a dichorionic placenta appears thicker and includes two amnions and two chorionic layers. In contrast, the dividing septum of a monochorionic placenta consists of two thin amnions. One placenta, same-sex fetuses, and absence of a dividing septum suggest monoamniotic twins, but absence of a dividing septum may also be due to septal disruption. Both conditions have a poor prognosis.
Zygosity. Deoxyribonucleic acid (DNA) typing can be used to determine zygosity in same-sex twins. Prenatally, DNA can be obtained by chorionic villus sampling (CVS) or amniocentesis. Postnatally, DNA typing should optimally be performed on umbilical cord tissue, buccal smear, or a skin biopsy specimen rather than blood. There is evidence that DZ twins, even in the absence of vascular connections, can also carry hematopoietic stem cells (HSCs) derived from
their twin. HSCs are most likely transferred from one fetus to the other through maternal circulation.
Pathologic examination of the placenta(s) at birth is important in establishing and verifying chorionicity.
V. PRENATAL SCREENING AND DIAGNOSIS
Zygosity determines the degree of risk of chromosomal abnormalities in each fetus of a multiple gestation. The risk of aneuploidy in each fetus of an MZ pregnancy is the same as a singleton pregnancy, and except for rare cases of genetic discordancy, both fetuses are affected. In a DZ pregnancy, each twin has an independent risk of aneuploidy; thus, the pregnancy has twice the risk of having a chromosomal abnormality compared with a singleton.
Second-trimester maternal serum screening for women with multiples is limited because each fetus contributes variable levels of these serum markers. When levels are abnormal, it is difficult to identify which fetus is affected.
First-trimester ultrasonography to assess for nuchal translucency is a more sensitive and specific test to screen for chromosomal abnormalities. A secondtrimester ultrasonography exam is important in surveying each fetus for anatomic defects. Second-trimester amniocentesis and first-trimester CVS can be safely performed on multiples and are both accurate diagnostic procedures for determining aneuploidy.
VI. MATERNAL COMPLICATIONS
Gestational diabetes has been shown in some studies to be more common in twin pregnancies.
Spontaneous abortion occurs in 8% to 36% of multiple pregnancies with reduction to a singleton pregnancy by the end of the first trimester (“vanishing twin”). Possible causes include abnormal implantation, early cardiovascular developmental defects, and chromosomal abnormalities. Before fetal viability, the management of the surviving co-twin in a dichorionic pregnancy includes expectant management until term or close to term, in addition to close surveillance for preterm labor, fetal well-being, and fetal growth. The management of a single fetal demise in a monochorionic twin pregnancy is more complicated. The surviving co-twin is at high risk for ischemic multiorgan and neurologic injury that is thought to be secondary to hypotension or thromboembolic events. Fetal imaging by ultrasonography or magnetic resonance imaging (MRI) may be useful in detecting neurologic injury. Termination of pregnancy may be offered as an option when single fetal demise occurs in a previable monochorionic twin pregnancy.
Incompetent cervix occurs in up to 14% of multiple gestations.
Placental abruption risk rises as the number of fetuses per pregnancy increases. In a large retrospective cohort study, the incidence of placental abruption was 6.2, 12.2, and 15.6 per 1,000 pregnancies in singletons, twins, and triplets, respectively.
Preterm premature rupture of membranes complicates 7% to 10% of twin pregnancies compared with 2% to 4% of singleton pregnancies. Preterm labor and birth occur in approximately 57% of twin pregnancies and in 76% to 90% of higher order multiple gestations.
Pregnancy-induced hypertension (PIH) and preeclampsia are 2.5 times more common in multifetal pregnancies compared with singleton pregnancies.
Cesarean delivery. Approximately 66% of patients with twins and 91% of patients with triplets have cesarean delivery. Breech position of one or more fetuses, cord prolapse, and placental abruption are factors that account for the increased frequency of cesarean deliveries for multiple gestations.
VII. FETAL AND NEONATAL COMPLICATIONS
Prematurity and low birth weight. The average duration of gestation is shorter in multifetal pregnancies and further shortens as the number of fetuses increases. The mean gestational age at birth is 36, 33, and 29 and one-half weeks, respectively, for twins, triplets, and quadruplets. In developed countries, the incidence of preterm birth in twins was 60.4% in 2006, compared with 11.1% in singletons. Although most of this increased incidence is due to mild prematurity, multifetal pregnancy increases the risk of severe prematurity and very low birth weight (VLBW). The likelihood of a birth weight <1,500 g is 8 and 33 times greater in twins and triplets or higher order multiples, respectively, compared with singletons. In two multicenter surveys, multiples occurred in 21% to 24% of births <1,500 g and in 30% of births <1,000 g.
Intrauterine growth restriction (IUGR).
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