CHAPTER 26

Caring for Twins and Higher-Order Multiples

Soina Kaur Dargan, MD, FAAP, and Lynne M. Smith, MD, FAAP

With the advent of artificial reproductive therapy 40 years ago, the incidence of twins and higher-order multiples has increased. Counseling the parents of multiples provides a unique opportunity for pediatricians. Much of what is known about caring for multiples comes from work with twins.

Parents of multiples often have many questions about the care of their children, but they rarely pose them to health care professionals. In a study in which 18 out of 29 mothers breastfed their twins, only 3 received information about breastfeeding from their physicians. One mother had been told by her obstetrician that she could not breastfeed her twins. Physicians should become knowledgeable about caring for multiples and the unique challenges they present to parents related to feeding, sleeping, and behavior.

Epidemiology

On July 25, 1978, Louise Brown was the first baby born as a result of in vitro fertilization (IVF). Since then, improved prenatal care and IVF methods have contributed to the increase in multiple births. According to the American Society for Reproductive Medicine, the rate of twins has increased more than 75% over the last 40 years in the United States. Twin rates have also increased in Finland, Norway, Austria, Sweden, Australia, Hong Kong, Japan, Canada, Singapore, and Israel, with the highest rate increase in Nigeria. A major contributor to the increase in multiple births is that women are starting their families later than in previous generations. The Centers for Disease Control and Prevention reports that from 1980 to 2009, twin birth rates increased 76% for women aged 30 to 34 years, nearly 100% for women aged 35 to 39 years, and more than 200% for women aged 40 years and older.

Because of the increased risk of infertility with advanced maternal age, more couples are choosing to conceive with assisted reproductive technologies, including ovulation-stimulating drugs, IVF, and intracytoplasmic sperm injection. More than one-third of twins and more than three-quarters of triplets and higher-order multiples in the United States resulted from conception assisted by fertility treatments.

The overall natural prevalence of twin births is about 33 in 1,000. Twins account for just slightly more than 1% of all births, and 20% of neonates born at fewer than 30 weeks’ gestation are twins. The average prevalence of monozygotic or identical twins, which is the same for all women regardless of race and age, is about 1 in 300 births. The incidence of dizygotic or fraternal twins varies among different groups and by method of conception. In the United States, blacks and whites have comparable incidences of live-born twin deliveries, and both have significantly higher rates than Hispanic women. A maternal family history of dizygotic twins correlates most strongly with an increased incidence of twins. A family history of monozygotic twins or a paternal family history of dizygotic twins does not increase the likelihood of twins.

Pathophysiology

Higher-order multiples, conceived naturally or via artificial reproductive technology, may be fraternal or a combination of monozygotic twins and fraternal siblings. Monozygotic twins result from the splitting of a single egg. They may share a placenta (monochorionic) (Figure 26.1A and 26.1B) and, in rare cases, may also share an amniotic sac (monoamnionic). When splitting occurs early (after several cell divisions of the zygote), each fetus develops its own chorion and amnion, leading to dichorionic and diamnionic placentas. Dizygotic twins result from 2 eggs, with each egg fertilized by a different sperm. Dizygotic twins have 2 placentas (Figure 26.1C). Although these placentas may fuse together like 2 pancakes, they are almost always dichorionic and diamnionic (Figure 26.1D). Ultrasonography at 14 weeks or sooner has been found to be 96% predictive of monochorionic twins and can also predict monoamnionic twins, anomalies, and syndromes.

Figure 26.1. Variations in placentas in twin births. A, Monochorionic placenta, cords close together. B, Monochorionic placenta, cords farther apart. C, Dichorionic placentas, separate. D, Dichorionic placentas, fused.

Following birth, many parents want to determine whether twins are monozygotic or dizygotic. Different-sex twins are almost always dizygotic, although monozygotic twins of different sexes have been reported in the literature. This occurs when 1 twin loses a Y chromosome and becomes a phenotypic female with Turner syndrome (XO). Occasionally, the male twin may have an XXY chromosome complement and have Klinefelter syndrome.

To determine whether twins are monozygotic or dizygotic after birth, a number of procedures can be undertaken. Visual or pathological examination of the placenta is helpful. About two-thirds of monozygotic twins have a common chorion and share 1 placenta. Finding a single chorion usually means the twins are monozygotic, unless the placentas of dizygotic twins have fused together. DNA testing is the preferred method for determining zygosity. Most commercially available testing, often referred to as zygosity testing, involves examining DNA obtained from buccal swabs from each child. Identification of short tandem repeats via polymerase chain reaction is typically accurate 99% of the time and is similar to techniques used in forensic medicine. Commercial laboratory charges range from $100 to $200, although prices vary significantly depending on the company and whether zygosity is being tested for twins or higher-order multiples.

Recent research on monozygotic twins has also focused on the effect of epigenetics, or how the environment affects genetics. By analyzing the DNA of monozygotic twins, researchers are hoping to identify epigenetic tags that mark a change in gene expression. Although DNA cannot be altered, DNA methylation, which affects the strength of gene expression, may be a process that, in the future, can be manipulated to reverse some complex disorders, such as autism spectrum disorder.

Differential Diagnosis

Diagnosing multiples is not difficult, but physicians should be aware of the problems these newborns may experience.

Perinatal Complications

Multiple births are associated with a significantly higher risk of perinatal complications relative to singleton births. The maternal complication most commonly reported with multiples is pregnancy-induced hypertension. Maternal preeclampsia rates are higher in twins and increase nearly 5-fold with triplets. In addition, mothers of twins who conceived via IVF have a higher rate of preeclampsia than mothers of twins who conceived naturally. Other maternal complications include placenta previa, antepartum hemorrhage, gestational diabetes mellitus, anemia, uterine atony, and maternal death.

Monozygotic twins are at increased risk for death and cerebral palsy because of complications such as severe birth weight discordance and twin transfusion syndrome (TTS). Twin transfusion syndrome is seen in 10% to 15% of monochorionic pregnancies and results from unbalanced blood flow due to vascular anastomoses within the shared placenta. The diagnosis is suspected by ultrasound when 1 fetus is growth restricted with oligohydramnios and the other fetus has evidence of volume overload with polyhydramnios. Both twins are ultimately at risk for fetal hydrops or death. Without treatment, TTS-induced death of at least 1 twin is as high as 80% to 100%. Of additional concern, the death of 1 twin is associated with neurologic damage or subsequent death of the surviving twin, with 1 in 10 surviving twins developing cerebral palsy.

Until recently, treatment was drainage of amniotic fluid in the twin with polyhydramnios to reduce the risk of preterm delivery. Endoscopic laser ablation of placental anastomoses has emerged as the treatment of choice for severe TTS pregnancies diagnosed and treated prior to 26 weeks’ gestation. Laser ablation addresses the primary pathology and results in an average gestation at delivery of 33 weeks, which is a significant improvement from the average 29 weeks with serial amniotic fluid reductions. Laser ablation is not without risks, however; reported complications include premature rupture of membranes, amniotic fluid leakage into the maternal peritoneal cavity, vaginal bleeding, and chorioamnionitis.

One percent of monozygotic twins are monochorionic– monoamnionic. Although monoamnionic twins have a lower risk of TTS, they are at very high risk for cord accidents. Monoamnionic pregnancies are monitored closely, and once the fetuses reach viability, emergent delivery is indicated if fetal distress is noted to avoid fetal death. Because fetal death significantly increases the risk of cerebral palsy and other neurologic disorders in the surviving twin, it is no longer recommended to allow fetal death in 1 monoamnionic twin to lengthen the gestation of the non-distressed twin.

Congenital Malformations

Twins and higher-order multiples have an increased risk of anomalies. Monochorionic twins have a higher risk of cardiac anomalies than dichorionic twins, increasing their need for fetal echocardiograms. Multiples conceived via IVF or intracytoplasmic sperm injection have increased risk for anomalies and aneuploidy. Disorders of genetic imprinting (eg, Beckwith-Wiedemann syndrome, Angelman syndrome) are also increased with intracytoplasmic sperm injection. These genetic complications are thought to be secondary to the underlying cause of infertility instead of artificial reproductive technologies. Because the costs associated with infertility treatments are substantial, many couples choose not to obtain a comprehensive chromosomal analysis looking for deletions or translocations on themselves prior to using reproductive technologies. Nuchal translucency and chorionic villus sampling can be used to detect and confirm suspected aneuploidy as early as the first trimester.

In addition to increased risks of malformations, multiples are at risk for deformations secondary to crowding, including torticollis, hip dislocation, plagiocephaly, and foot deformities. Monochorionic twins are also at risk for becoming conjoined twins, estimated to occur in 1 in 50,000 to 200,000 gestations, with more than 50% dying in utero or being stillborn and 35% dying within the first 24 hours after birth. Although monochorionic twins are more commonly males, conjoined twins are often female. Conjoining occurs because of incomplete splitting of the embryo or after a secondary fusion between 2 previously separate embryos. Prenatal ultrasonography is commonly used to diagnose this condition; more recently, prenatal magnetic resonance imaging has been used to evaluate specific anomalies. Due to surgical advances, some parents continue the pregnancy with hopes the live-born neonates can be separated.

Postnatal Complications

Approximately 60% of twins and 90% of triplets are born preterm, increasing the risk of morbidity and mortality. On average, most single pregnancies last 39 weeks, twin pregnancies 36 weeks, triplets 32 weeks, quadruplets 30 weeks, and quintuplets 29 weeks. The most common cause of preterm delivery in these neonates is premature rupture of membranes.

Although growth in twins tends to be normal until 30 to 34 weeks’ gestation, growth restriction is commonly associated with multiple births. Twins conceived by IVF are more likely to be born at a low birth weight than spontaneously conceived twins. Smaller twins have an increased incidence of hypoglycemia in the newborn period and have higher rates of targeted learning deficits and school failures during childhood. In addition, children born with growth restrictions have an increased risk for obesity and diabetes in later life. Selective intrauterine growth restriction (IUGR), when only 1 twin is affected by IUGR, occurs in 10% of monochorionic twins. This occurs when the twin with IUGR has reversed flow or persistent absent flow in the umbilical artery.

Neonatal mortality is 4-fold higher in twins and 15-fold higher in higher-order multiples. Neonatal morbidity is much higher in multiple births because of the increased incidence of preterm birth and growth restriction. The risk of these complications increases with the number of fetuses. The perinatal mortality of monozygotic twins is 8 times that of singletons and 4 times that of dizygotic twins. Twins and higher-order multiples are also at increased risk for cerebral palsy.

Evaluation History

A general medical history should be obtained, including a history of the pregnancy. Any specific medical concerns should also be addressed (Box 26.1).

Physical Examination

The initial evaluation of newly born twins involves assessment of gestational age and determination of the presence of any medical problems or anomalies (see Chapter 23). Older twins may undergo health supervision visits at which routine as well as specific concerns are addressed.

Laboratory Tests

Newborns should be assessed for the presence of anemia or polycythemia with a hemoglobin level determination. Hypoglycemia may occur in the newborn period and should be assessed frequently until glucose levels are stable. If the twins are preterm, they may have many of the problems seen in singleton preterm newborns, such as neonatal respiratory distress syndrome and necrotizing enterocolitis.

Older children should receive an appropriate evaluation for age, with a specific focus on any behavioral concerns.

Management

The focus of the management of multiples involves counseling parents about issues related to routine care and anticipated stress of caring for more than 1 newborn simultaneously. Parents often care for 2 or more children at the same time, but multiples present unique issues related to multiple children who are developmentally and chronologically at the same point. Many parents experience anxiety about the upcoming challenges they will face. Baby care books that specifically discuss birthing and raising multiples are available. Support groups and websites also provide information for families of multiples.

Feeding multiple newborns is often an exhausting challenge for parents, and consultation with a lactation expert is recommended. The physical demands of feeding multiple newborns are often compounded by women recovering from prenatal complications such as preeclampsia. Because preterm birth is common, newborns may have an immature suck reflex, making feeding more challenging. Few multiples are still exclusively breastfed by 4 months of age, and common reasons cited for unsuccessful breastfeeding of multiples include maternal stress, depression, fatigue, perceiving they were producing insufficient milk, and time burden. Despite these obstacles, parents should know that breastfeeding is possible even for triplets and understand the benefits of breastfeeding to the newborns’ health. It is recommended that mothers begin breastfeeding as soon as possible to establish their milk supply. An electric pump is a useful adjunct to help establish and continue breastfeeding. If supplemental nutrition is needed, utilizing a medicine dropper, syringe, spoon, cup, or finger feeding instead of a bottle will reduce the risk of newborns developing a preference for an artificial nipple.

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