MULTIPLE BIRTHS MULTIFETAL PREGNANCIES

The term multiple births is defined as more than one fetus being born of a pregnant woman. Since 1970, 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 a number of 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. Two sperm fertilizing 2 ova produce dizygotic twins, which sometimes are called fraternal twins. Separate amnions, chorions, and placentas are formed in dizygotic twins. The placentas in dizygotic twins may fuse if the implantation sites are proximate. The fused placentas can be separated easily after birth.

Monozygotic twins develop when a single fertilized ovum splits during the first 2 weeks after conception. Monozygotic twins also are called identical twins. An early splitting (ie, within the first 2 days 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, during days 3-8 after fertilization) results in monochorionic/diamniotic placentation. Approximately 70% of monozygotic twins are monochorionic/diamniotic. If splitting occurs even later (ie, during days 9-12 after fertilization), then monochorionic/monoamniotic placentation occurs. 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 beyond 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 1 split result in a vanished fetus and monozygotic triplets. It is important to evaluate the placenta(s) after the birth of all multifetal pregnancies in order to determine zygosity.

Frequency:
• In the US: 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 in women younger than 20 years to 14 in 1000 in women aged 35-40 years, declining thereafter) and parity. In the United States, the overall prevalence of twins is approximately 12 per 1000, and two thirds are dizygotic. The birth rate of dizygotic twinning is highest for African Americans (10-40 per 1000 births), followed by Caucasians (7-10 per 1000 births) and Asian Americans (3 per 1000 births). The rate of higher order multiple births has also increased recently, 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.

• Internationally: 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 frequency of 45 twins per 1000 live births, and approximately 90 percent 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 6 times more than the neonatal mortality rate for single births. Higher order multiple births have even greater mortality rates in comparison to 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, and TTTS.

Race: The frequency of naturally occurring twin births varies by race. Black women have the highest birth rate of twins, followed by Caucasian and Hispanic women. Asian women have the lowest birth rate of twins. There is a racial disparity in the United States between black and Caucasian twin stillbirths. Risk of stillbirth is elevated in black fetuses compared with white fetuses among twins but not 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 diagnosed prenatally. 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 inconsistently large for dates and may experience accelerated weight gain. On 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:
In TTTS the donor twin is frequently anemic at birth. The recipient twin is polycythemic at birth.
• Calcium:
Hypocalcemia is common in premature infants, especially the donor twin in TTTS.
• Glucose:
Hypoglycemia is common in premature infants, especially if TTTS is present.
• Bilirubin:
Hyperbilirubinemia may develop in polycythemic infants from TTTS.

Imaging Studies:
• Maternal ultrasonography confirms most multiple gestation pregnancies.
• Neonatal head ultrasound: Premature infants from multifetal pregnancies are susceptible to intraventricular hemorrhage and periventricular leukomalacia.