Excerpt from Multiple Births

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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.

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