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Twins and Multiple Gestation

The incidence of twin and higher-order multiple gestations has increased significantly over the past 15 years primarily because of the availability and increased use of ovulation-inducing drugs and newly developed assisted reproductive technologies such as in vitro fertilization. Multiple pregnancies and their various complications have, therefore, become more common (1). The incidence of twins, triplets, and higher-order multiple gestations now has reached approximately 3% of all pregnancies (2). When considering only those pregnancies resulting from assisted reproductive techniques, the rate of twin deliveries is from 25% to 30%; triplets account for 5% of deliveries, whereas the rate of higher-order multiple gestations is 0.5-1%.

Multifetal gestation is associated with an increased risk of perinatal morbidity and mortality (see Tables 1-3). Women who are undergoing treatment for infertility should be aware of the risks and potential fetal and maternal complications of multiple gestation. Such women can benefit from preconceptional counseling.

Obstetrician-gynecologists should be prepared to manage, with consultation when necessary, the special problems and complications of twin and higher-order multiple gestations. Because of the many variables associated with higher-order gestations and the need for specialized care based on individual circumstances, this Educational Bulletin will focus on twin gestations.

Antepartum Management

Nutritional Considerations

It is recommended that maternal dietary intake in a multiple gestation be increased daily by approximately 300 kcal above that for a singleton pregnancy (4). Supplementation should include iron and folic acid. Although optimal weight gain for women with multiple gestations has not been determined, it has been suggested that women with twins gain 35-45 pounds (5).

Prenatal Diagnosis

The usual indications for prenatal diagnosis and counseling in a singleton pregnancy apply to twin and higher-order gestations. Because the incidence of twin gestation increases with maternal age, women with multiple gestations often are candidates for prenatal genetic diagnosis. Genetic counseling should make clear to the patient the need to obtain a sample from each fetus, the risk of a chromosomal abnormality, potential complications of the procedure, the possibility of discordant results, and the ethical and technical concerns when one fetus is found to be abnormal. Some research has shown that the combined risk of fetal chromosome abnormality is higher in dizygotic twin gestations than in a singleton gestation (6, 7). Structural anomalies are more common in monozygotic twins.

Maternal Serum Screening

Maternal serum alpha-fetoprotein (MSAFP) screening programs contribute to the detection of multiple gestations. Multiple gestation is the second most common reason after incorrect dating for the reported increase in the MSAFP level during the second trimester. Maternal serum alpha-fetoprotein screening will identify approximately 60% of unsuspected twin gestations and virtually all higher-order gestations. About 10% of pregnancies with an elevated MSAFP level will be explained by the presence of more than one fetus. The median value of MSAFP levels in twins from 14 to 20 weeks of gestation is 2.5 times that for singleton pregnancies (8). The levels in triplets and quadruplets are three and four times as high, respectively (9). Genetic screening programs, therefore, redefine an elevated MSAFP level for a twin gestation because there are two fetuses and a larger volume of placenta. Depending on the laboratory, a value greater than 4.5 multiples of the median in an uncomplicated twin gestation is abnormal, requiring further comprehensive ultrasound evaluation by an experienced ultrasonographer and possible amniocentesis for the detection of amniotic fluid alpha-fetoprotein and acetylcholinesterase.

Although maternal serum screening for neural tube defects can be useful in the twin pregnancy, its effectiveness in screening for trisomy 21 is not well defined (10). Further investigation is necessary to determine the clinical usefulness of multiple marker screening for Down syndrome in twin and higher-order pregnancies.

Amniocentesis

Although the risks may be increased, amniocentesis, using continuous ultrasound guidance, of both sacs can be performed successfully in most patients with a twin gestation (11 ). One technique is ultrasound-guided amniocentesis of each sac with approximately 1-2 mL of a dilute (approximately 0.08%) indigo carmine dye instilled into the first amniotic sac (12). A second amniocentesis of clear fluid confirms specimens from each sac. Methylene blue dye, which is associated with fetal bowel atresia and other complications, should not be used (13). If the twins are without question monozygotic, there is no reason to tap more than one sac.

Chorionic Villus Sampling

Chorionic villus sampling (CVS) is an appropriate method of first-trimester prenatal diagnosis in multiple gestations (14). The procedure is best performed by or under the supervision of an experienced operator who samples both placentas under ultrasound guidance between 10.0 and 12.9 weeks of gestation. Difficulties that can arise with CVS in twin gestations include the inability to obtain an adequate sample and contamination of one sample with tissue from the second. In approximately 1% of patients, tissue can be obtained only from one placenta. When CVS is performed at centers with experienced operators, twin-twin contamination occurs in approximately 4-6% of samples, causing prenatal diagnostic errors. When CVS or amniocentesis is performed in the twin gestation, documentation of the location of the fetuses and the membrane separating the sacs is important because discordant results can occur, and the location of the abnormal fetus may need to be known for future management.

Multifetal Reduction

The greater the number of fetuses within the uterus, the greater the risk for preterm delivery and adverse perinatal outcome. Multifetal pregnancy reduction may be performed to decrease the risk of serious perinatal morbidity and mortality associated with preterm delivery by reducing the number of fetuses. Preferably, this problem can be avoided by carefully monitoring patients receiving ovulation-inducing drugs and by minimizing the number of embryos transferred during in vitro fertilization or embryo transfer programs. The ethical dilemmas can be considerable. Patients with higher-order multiple gestations may be faced with the possibility of terminating the entire pregnancy, continuing the pregnancy and taking the risk of delivering severely preterm infants, or reducing the pregnancy in an effort to decrease the risk of perinatal morbidity and mortality.

Pregnancy loss is the main risk of multifetal pregnancy reduction and ranges from 10% to 26%. The benefit of this procedure is most clear in quadruplet and higher-order gestations because it increases the length of gestation of the surviving fetuses. It is unclear and remains to be determined whether multifetal pregnancy reduction improves long-term neonatal outcome of a triplet gestation reduced to twins. Elevations in MSAFP levels occur after selective reduction to twins; nonetheless, these patients should undergo a detailed ultrasound examination of the surviving fetuses in the middle of the second trimester.

Dizygotic twins can be discordant for congenital anomalies. Selective fetal termination allows a pregnancy to continue with a normal twin after the termination of an abnormal twin. In one study, selective fetal termination was performed successfully in 183 multifetal pregnancies, most of which were twin gestations (20). Indications for selective fetal termination were twins discordant for chromosomal abnormalities, fetal structural anomalies, or one twin affected by a Mendelian disorder. The preferred method for selective fetal termination was intracardiac injection of potassium chloride. The procedure caused loss of the entire pregnancy if there was a monochorionic placentation. The pregnancy loss rate before 24 weeks of gestation was 12.6%; an additional 3.8% of patients gave birth between 24 and 28 weeks of gestation. The authors of this study concluded that selective fetal termination for an abnormal pregnancy is a safe procedure when performed by experienced physicians provided there is a dichorionic placenta-tion. Ligation of the umbilical cord under endoscopic visualization has been performed for selective termination in a monochorionic pregnancy, but the safety and efficacy of this procedure requires further study.

Ultrasonography

Ultrasonography can be useful in both prenatal diagnosis and antepartum surveillance. With its use, less than 10% of twin gestations are undiagnosed before labor and delivery. Although the value of routine screening to promote early diagnosis is subject to debate, ultrasonography has a role in evaluating the progress of pregnancy once the diagnosis is established.

Screening

In the randomized clinical Routine Antenatal Diagnostic Imaging With Ultrasound (RADIUS) trial, special attention was given to multiple gestation. In the study, 129 multiple gestations were included. The RADIUS study concluded that multiple pregnancies were consistently diagnosed at an earlier gestational age in the screened group; however, this finding did not result in any overall alteration in management improving adverse perinatal outcome. This conclusion is not consistent with findings of other studies. In a 10-year study of 22,400 women having 43,000 routine ultrasound examinations involving 249 multiple gestations, earlier detection improved perinatal outcome. When multiple gestation is suspected on the basis of clinical examination, family history, a history of assisted reproduction, or an elevated MSAFP value, an ultrasound examination should be performed. Often, ultrasound examinations are performed early in gestation in twins to document viability; this examination also can be helpful in defining chorionicity.

Evaluation

A detailed ultrasound evaluation of a multiple gestation should be performed during the second trimester. This examination should include determination of placentation, amnionicity, and chorionicity; the number of fetuses; evaluation for fetal amniotic fluid or placental abnormalities; and an assessment of the growth of each fetus. If two separate placentas are identified or if the fetuses are of different sex, the placentation is dichorionic. A thick membrane also suggests dichorionicity. When a thin, wispy membrane is seen between two sacs with a single placenta, and the fetuses are of the same sex, monochorionicity is suggested. "Stuck twin syndrome," where there is polyhydramnios for one twin and extreme oligohydramnios for the other, can be very difficult to differentiate from a monochorionic pregnancy because the membrane may be so near the stuck twin that it is difficult to detect. Determination of chorionicity is most accurate in the first trimester; as the pregnancy progresses, it becomes less accurate.

Visualization of a membrane confirms the diagnosis of a diamniotic gestation. When dichorionicity is diagnosed, the pregnancy must also be diamniotic. The number of fetuses should be identified; this number, however, may decrease as the pregnancy progresses. Until the third trimester, twins follow the same growth curves that apply to singleton pregnancies. There is no clear clinical advantage to the use of twin- or triplet-specific ultrasound growth tables. Evaluation of serial fetal growth should include estimated fetal weight of each fetus and appropriate and concordant interval growth.

Routine Cervical Evaluation

Routine cervical evaluation by either clinical or ultra-sonographic assessment has been investigated as an approach to predict preterm birth in the multiple gestation. A cervical scoring system, calculated as cervical length (in centimeters) minus cervical dilatation at the internal os (in centimeters) has been used. This system has been associated with a positive predictive value of 75%, which is associated with a fourfold increased relative risk of preterm delivery. Weekly digital cervical examination for clinical assessment of the cervix has not been associated with adverse maternal or fetal outcome.