The rate of twin pregnancies in the United States has stabilized at 32 per 1000 births in 2006. Aside from determining chorionicity, first-trimester screening and second-trimester ultrasound scanning should ascertain whether there are structural or chromosomal abnormalities. Compared with singleton births, genetic amniocentesis–related loss at <24 weeks of gestation for twin births is higher (0.9% vs 2.9%, respectively). Selective termination for an anomalous fetus is an option, although the pregnancy loss rate is 7% at experienced centers. For singleton and twin births for African American and white women, approximately 50% of preterm births are indicated; approximately one-third of these births are spontaneous, and 10% of the births occur after preterm premature rupture of membranes. From 1989-2000, the rate of preterm twin births increased, for African American and white women alike, although the perinatal mortality rate has actually decreased. As with singleton births, tocolytics should be used judiciously and only for a limited time (<48 hours) in twin births. Administration of antenatal corticosteroids is an evidence-based recommendation.
On October 10, 2009, there was an article entitled, “21st Century Babies: The Gift of Life, and Its Price,” which started with 2 succinct sentences: “Scary. Like aliens.” The article could have been dismissed easily were it not published in The New York Times and were the topic something other than twins. Because this article is the first in a series called “21st Century Babies: The Twins Dilemma,” twinning will be a part of patient lexicon and a source of concern. Thus, a review of antepartum complications with twin pregnancies is useful not only for the concerned patient but also because recent publications on the topic may influence our practice.
A Google search with the word “twin” yields 116,000,000 results in 0.21 seconds; a PubMed search with the words “twin pregnancy” found 24,982 publications (November 12, 2009). Therefore, although it is not feasible to summarize the voluminous literature on this topic, this review article will focus on: twin birth rate, common antenatal problems, and preterm births, which are the bane of modern obstetrics.
Twin birth rate
In the United States, between 1980 and 2006, the twin rate climbed 101% ( Figure 1 ). There were 68,339 twins born in 1980; 27 years later, 137,085 twins were born. The twinning rates have also increased in Austria, Finland, Norway, Sweden, Canada, Australia, Hong Kong, Israel, Japan, and Singapore. There are multiple causes for the change in the rate of twin pregnancies: use of assisted reproductive techniques (ARTs) and non-ART procedures, maternal age, ethnicity, variation among the 50 states, and a decreasing rate of triplets and higher order multiple gestation.
Approximately 1% of infants born in the United States in 2006 were conceived with the use of ARTs and account for 18% of the multiple births nationwide. Of 54,566 infants who were born with the use of ARTs, 48% were multiple birth deliveries. The International Committee for Monitoring Assisted Reproductive Technology analyzed ARTs for the year 2002 from 53 countries. For conventional in vitro fertilization and intracytoplasmic sperm injection, the overall twin rate was 26%. In the United States, the twin rate was 32%; in Latin America, it was 25%; in Europe, it was 23%; in Asia and the Middle East, it was 22%, and in Australia/New Zealand, it was 21%.
The rate of twin pregnancies varies by maternal age and ethnicity ( Figure 2 ). Between 1980 and 2006, twin birth rates rose 27% for mothers <20 years (compared with 80% for women in their 30s) and 190% for mothers who were ≥40 years old. In 2006, 20% of births to women 45-54 years old were twins, compared with approximately 2% of births to women 20-24 years old. Twin birth rates were essentially unchanged among the 3 largest racial groups for 2005-2006: non-Hispanic white (36.0 per 1000 births in 2006), non-Hispanic black (36.8 per 1000 births), and Hispanic (21.8 per 1000 births). Since 1990, rates have risen 57% for non-Hispanic white and 38% and 21% for non-Hispanic black and Hispanic women, respectively.
The rate of twin pregnancies also varies among the states ( Figure 3 ). In 2004-2006, the rate of twin pregnancies in the United States was 32.2 per 1000 live births, with <25% being 29.5 per 1000 live births; median, 31.8 per 1000 live births, and >75% being 34.0 per 1000 live births. In Connecticut, Massachusetts, and New Jersey, 4% of all births were twins. In contrast, <2.5% of births to New Mexico residents were twin pregnancies.
The likelihood of twin pregnancies is also increasing because the rate of triplets and higher-order gestations is decreasing. Thus, twin pregnancies constitute a greater proportion of multiple pregnancies. In 1989, for example, there were 110,670 twin deliveries, which constituted 93.6% of 118,296 multiple births; in 2006, the corresponding numbers were 137,085 twin pregnancies and 95.4%. During these 9 years, the rate of triplets and higher-order gestations decreased by 29%.
The rapid rise, however, in twin rates over the last several decades may have ended. From 1935-1980, the twinning rate declined. After that, there has been a steady increase: in 1980, the twin rate was 18.9 per 1000 births; in 1990, it was 22.6 per 1000 births, and in 2000, it was 29.3 per 1000 births ( Figure 1 ). The rate reached 32 per 1000 births in 2004 and has stabilized since then; the rate was 32.1 per 1000 births in 2006.
To summarize, the rate of twin pregnancies varies in the United States for several reasons and has stabilized, despite the recent alarm by public press.
Identification of chorionicity and anomaly
Because of risks that are associated with monochorionicity, an important aspect of first-trimester ultrasound scans in twin gestation is the determination of chorionicity. It has been demonstrated that chorionicity is best determined by sonography in the first or early second trimester. In a single large tertiary center, the sensitivity, specificity, and positive and negative predictive values of prediction of monochorionicity at ≤14 weeks was found to be 89.8%, 99.5%, 97.8%, and 97.5%, respectively. If only 1 placenta is visualized, the presence of an extension of chorionic tissue from the fused dichorionic placentas suggests dichorionicity. If only 1 placenta is visualized, the absence of an extension of chorionic tissue into the intertwin membrane suggests monochorionicity. In monochorionic twin pregnancies, the absence of an intertwin membrane suggests monoamniotic gestation. Monochorionic diamniotic twin gestation is associated with a 10-15% risk of twin-to-twin transfusion syndrome. Although monoamnionicity is somewhat protective against the development of twin-to-twin transfusion syndrome, monoamniotic gestations are associated with a 6% incidence of twin-to-twin transfusion. Because of the breadth of the topic, this article will not address risks, associations, or management of unique aspects of monochorionic gestations, namely twin-to-twin transfusion syndrome and monoamnionicity.
In addition to the determination of chorionicity and amnionicity, the goal of sonographic examination with twin gestations is to identify anomalies and/or syndromes. This should allow for the modification of pregnancy management in efforts to optimize outcome for mother and newborn infants or to identify risk factors that may suggest a need for active or prophylactic therapy to decrease the likelihood of adverse pregnancy outcome. Depending on the severity and/or lethality of the identified anomalies or syndromes, pregnancy management options include (1) continued conservative management, (2) termination of pregnancy in efforts to decrease maternal morbidity and death, especially in cases in which lethal syndromes are suspected, (3) selective reduction to prevent the birth of an adversely affected child and/or to optimize likelihood of survival for an apparently normal fetal sibling, or (4) placental (vascular) and/or fetal and/or neonatal therapy in efforts to optimize outcome for 1 or both the neonates.
Risks that are associated with selective termination of dichorionic twin pregnancies with structural, chromosomal, and Mendelian anomalies are known for centers with experience. Evans et al reported on 345 cases of selective termination with twins, of whom 7% delivered at <24 weeks of gestation and 93% ended in a viable singleton. Unlike multifetal reduction for multifetal pregnancies, in which outcomes are related to experience, over 15 years, termination for an anomalous fetus was not associated with improvement in losses or prematurity. The loss rate also was not influenced by the gestational age of the procedure, even when done at >24 weeks of gestation, and by the indication for selective termination.
For many reasons, the likelihood of aneuploidy is higher in twin pregnancies than in singleton pregnancies. In dizygotic gestations, the background risk for each twin is the same as it would be in a singleton gestation for that mother; however, the number of fetuses results in a 2-fold increase in risk for that gestation when compared with singleton pregnancies. Because ARTs are often used in older women, the risk of aneuploidy should be approximately twice her age-related risk, unless donor oocytes are used. In monozygous twins, the risk of both twins being affected should be similar to that of a singleton gestation.
First-trimester screening for aneuploidy in twin pregnancies has many nuances that limit its capabilities as a screening tool. Although monochorionicity has been associated with increased nuchal translucency, nuchal translucency alone has been shown to be an effective marker for aneuploidy in twin gestations. The addition of serum biochemistry to age and nuchal translucency measurement in twin gestation has a very high sensitivity for detecting trisomy 18 or 21. In that series of 535 sets, maternal (or egg donor) age alone was associated with a 33% detection rate for trisomy 18 or 21. The addition of nuchal translucency increased the sensitivity to 83%; combined age and nuchal translucency and biochemistry (free or total beta human chorionic gonadotropin and pregnancy-associated pregnancy protein A) increased sensitivity to 100%. The authors did acknowledge that, with larger numbers, the combined detection rate would be <100%.
As alluded to earlier, early diagnosis is important to minimize the complications that are associated with intervention. Chorionic villus sampling (CVS) is the standard first-trimester approach to the confirmation of suspected aneuploidy. CVS is performed by 2 general approaches: transabdominal vs transcervical, depending on operator experience and placental location/accessibility. In the hands of experienced clinicians, first-trimester CVS has been found to be at least as safe and effective as second-trimester amniocentesis for prenatal diagnosis in twin gestations. De Catte et al summarized the outcomes of CVS with 3 earlier studies and their own experience with 262 cases. Overall outcomes of 614 twins who had CVS were known. The likelihood of total loss was 4.6% (95% confidence interval [CI], 3.5–6.0). Furthermore, Ferrara et al confirmed that CVS does not increase the pregnancy loss rate before multifetal pregnancy reduction.
Compared with singleton pregnancies, twin pregnancy is associated with an increased incidence of anomalies, although the rate of anomalies in dizygotic twins is not likely increased per twin. Hardin et al, for example, compared the prevalence of cardiovascular defects in 56,709 California twin pairs with singleton pregnancies. They categorized cardiac anomalies into 16 groups; twins had a higher incidence for all 16 categories. For 7 of the cardiovascular categories, the prevalence was 2 times higher for twin pregnancies than singleton pregnancies. Like-sex twins, a proxy for monozygosity, had a higher prevalence of cardiac defects than unlike sex twins. Bahtiyar et al reviewed the literature and noted that congenital heart defects were prevalent significantly more among monochorionic, diamniotic twins than the general population (relative risk [RR], 9.18; 95% CI, 5.51–15.29). Ventricular septal defects are the most frequent heart defects.
Fortunately, detection of anomalies in twin gestation does not seem to be compromised by its multifetal nature. Edwards et al confirmed a sensitivity of 82% and negative predictive value of 98% for anatomic surveys among 245 consecutive twins, with a 4.9% prevalence of anomalies. Among 495 monochorionic twins, Sperling et al reported severe structural abnormalities in 2.6%; two-thirds of the abnormalities were cardiac. With first-trimester nuchal translucency and anatomy scan at <20 weeks of gestation, 83% of anomalies and aneuploidy were detected. Earlier reports on detection of congenital anomalies in twin pregnancies noted a lower detection rate. In 1991, Allen et al reported that, among 157 pair of twins (314 newborn infants), anomalies occurred in 9.5%. Antenatal ultrasonography detected only 39% of all major anomalies, 55% of noncardiac anomalies, and 69% of major anomalies for which routine prenatal management would be altered. For detection of cardiac anomalies, their ultrasound protocol was limited to a 4-chamber view, and they detected no major cardiac lesions. Thus, it is understandable why the American College of Obstetrics and Gynecology (ACOG) practice bulletin on ultrasonography recommends that, as part of cardiac screening examination, the views of the outflow tracts should be obtained, if technically feasible. Twins should have fetal echocardiograms, especially if they are monochorionic or a result of assisted reproduction.
Importantly, if discordant anomaly is noted, the likelihood of adverse outcome for the normal twin is increased. Sun et al used the 1995-1997 matched multiple births dataset from the United States and noted that 1 fetus had an anomaly in 2.5% of the cases and both fetuses had anomalies in 1.0%. They identified 3307 twins and matched them with 12,813 nonanomalous twins. Compared with the control subject, the presence of an anomalous cotwin significantly increased the risk of (1) preterm birth at <32 weeks of gestation (odds ratio [OR], 1.85; 95% CI, 1.65–2.07), (2) birthweight <1500 g (OR, 1.88; 95% CI 1.67–2.12), (3) small for gestational age (10% vs 12%; OR, 1.21; 95% CI, 1.07–1.36), (4) fetal death (OR, 3.75; 95% CI, 2.61–5.38), (5) neonatal death (OR, 2.08; 95% CI 1.47–2.94), and (6) infant death (OR, 1.97; 95% CI,1.49–2.61).
In summary, once twin pregnancies are detected, sonographic examination should be done to determine chorionicity, first trimester screening should be done to identify fetuses with aneuploidy, targeted ultrasound should be done for the detection of major anomalies, and fetal echocardiography should be done for identification of congenital heart defect. As recommended by the ACOG practice bulletin on ultrasonography in pregnancy, every patient should be informed about the limitation of the detection of all major birth defects. If 1 fetus has a major structural or chromosomal abnormality, selective termination should be discussed.
Genetic amniocentesis
Compared with singleton pregnancies, twin pregnancies are at higher risk for fetal anomalies and for chromosomal abnormalities. Rodis et al calculated that a 33-year-old woman with twins has an equivalent risk of a child with Down syndrome as a 35-year-old woman with a singleton infant. Thus, the importance of genetic amniocentesis with twins can be seen.
Among the 6 publications that reported on loss rate after genetic amniocentesis with twins, the needle gauge varied, but all investigators used 2 separate needle insertions ( Table 1 ). Although the rate of loss at <24 weeks of gestation varied from 0.4-4.1%, the cumulative experience with >1700 amniocenteses indicates that the fetal loss rate is 2.9% (95% CI, 2.3–3.8) or 1 per 34 (95% CI, 26–43). It is noteworthy that a systematic review that summarized the results of 29 articles calculated that, for singleton pregnancies who undergo genetic amniocentesis, the loss rate at <24 weeks of gestation is 0.9% (95% CI, 0.6–1.3) or 1 per 111 procedures (95% CI, 76–111). The differential loss rate between singleton and twin pregnancies may result from the fact that the spontaneous loss rate at <24 weeks of gestation is higher with multiples. Only 3 of these reports provided data for twins who were treated at a similar time who did not have a genetic amniocentesis. For the twins who did not have the invasive procedure, the overall loss rate was 1.1% (95% CI, 0.6–2.0). A comparison of spontaneous loss rate vs after loss rate genetic amniocentesis indicates that the fetal losses are approximately 160% higher after the procedure (1.1% vs 2.9%; Table 1 ). It should be noted that loss subsequent to genetic amniocentesis is similar among twins who are conceived spontaneously or with ART and those who had undergone multifetal reduction.
