Multifetal Pregnancies: Epidemiology, Clinical Characteristics, and Management



Multifetal Pregnancies: Epidemiology, Clinical Characteristics, and Management


Lucas Otaño

César Meller

Horacio Aiello



Introduction

A multifetal gestation is a high-risk pregnancy because it is associated with an increased rate of maternal, perinatal, and infant morbidity and mortality compared to singleton pregnancies.1,2 Multifetal pregnancies account for 2% to 3% of all live births but are responsible for around 25% of the neonatal intensive care unit admissions. One of the main problems is preterm birth and its short- and long-term consequences.1


Epidemiology

The twin birth rate has significantly increased in most regions of the world during the last decades. In the United States, it rose around 75% in 35 years, from 19/1000 births in 1980 to 334/1000 births in 2016.3 The main reasons for this are delayed childbirth, advanced maternal age at conception, and the widespread use of assisted reproduction techniques (ART).

The incidence of monozygotic twins is around 1 in 250 pregnancies, and it is quite constant across the world,4 showing a slight increase in cases of ART. The incidence of dizygotic twins varies with race (it is more frequent in African ethnicity, intermediate in white European, and lower in East Asian), with maternal age (it increases with maternal age), and with family history (specially with maternal history), and it is highly influenced by the use of ART.4

ART plays an important role in twins, especially in dizygotic twins. In 2016, among infants conceived by ART, 30.4% were twins and 1.1% were triplets and higher order infants, with the consequent increase in adverse maternal and perinatal outcomes.5


Classification

Multifetal pregnancies can be classified according to the number of fetuses, zygosity, or chorionicity. According to the number of fetuses, multiple pregnancies can be twins, triplets, quadruplets, etc. In clinical practice, most are twins. According to zygosity, multiple pregnancies can be classified as dizygotic or monozygotic. Dizygotic twins result from the fertilization of two oocytes by two sperms that produce two genetically different embryos. Monozygotic twins result from the fertilization of one oocyte and one sperm and the early splitting of the resulting embryo in two genetically identical twins.6

According to chorionicity and amnionicity, twin pregnancies can be dichorionic (DC) or monochorionic (MC). In DC twins, each fetus has its own placenta and its own amniotic sac (diamniotic [DA]), whereas in MC, both fetuses shared the same placenta and can be DA (˜99%) or monoamniotic (MA; ˜1%).7

The relationship between zygosity, chorionicity, and amnionicity is described in Algorithm 5.1. Around 70% of twins are dizygotic, and all of them are DCDA. Monozygotic twins are the result of the cleavage of a single inner cell mass. If this cleavage occurs before the fourth day after conception, the twin pregnancy will be DCDA (˜30% of all monozygotic twins). If the cleavage occurs after the third day, the pregnancy will be MC (˜70% of monozygotic twins). In 99% of those MC twins, the cleavage of the inner cell mass will take place between the fourth and eighth day, and it will result in MCDA twins. Only in 1% of MC pregnancies the cleavage will occur after the eighth day resulting in MCMA
twins. In rare cases, the twinning process will take place after the 12th day producing an incomplete inner cell mass cleavage that results in conjoined twins.7






From an obstetrical standpoint, the most important distinction is if the twin pregnancy is DC or MC. MC twins have a significantly higher morbidity and mortality, and they also have complications exclusive for MC placentation. Knowledge of the chorionicity is crucial for prenatal screening and diagnosis of fetal anomalies, for choosing the optimal strategy of surveillance, for the appropriate management of complications, and for perinatal decision-making. In clinical practice, it is no longer acceptable to talk about “twin pregnancy”—it must be classified as MC or DC.


Ultrasound Diagnosis and Surveillance

Reliable diagnosis of multiple pregnancy is performed by ultrasound, ideally during the first trimester.1,8 Ultrasonography has become an integral clinical tool for appropriate screening, diagnosis, surveillance, and optimization of care in multifetal pregnancies.9

The ultrasound assessment of multiple pregnancies includes



  • Determining gestational age (dating of the pregnancy)


  • Determining chorionicity and amnionicity


  • Twin labeling


  • Ultrasound surveillance


  • Detection and management of complications


Determining Gestational Age

As in singletons, gestational age of multifetal pregnancies conceived spontaneously should be dated ideally during the first trimester, based on the fetus with the larger crown-rump length (CRL) at the 11- to 14-week scan. In cases of twins conceived by ART, dating should be based on the embryonic age from fertilization.8 For spontaneous twin pregnancies with first consultation after 14 weeks, gestational age is estimated based on the fetus with the larger head circumference.8



Determining Chorionicity and Amnionicity

Diagnosis of chorionicity is the most important goal for prenatal care and management of a twin pregnancy. Chorionicity is determined by ultrasound, and it is based on different features depending on the gestational age. It is usually best performed during the first trimester (sensitivity ≥98%), and it becomes more difficult during the second and third trimesters.10 Algorithm 5.2A and B and Figure 5.1 summarize the most important features for chorionicity and amnionicity assessment.







First Trimester

Before 10 weeks of gestation, determining chorionicity is usually easy. The first structures that can be seen at 5 to 6 weeks are the gestational sacs. In a panoramic view of the uterus, if one gestational sac with two embryos is observed (Figure 5.2A-D), the diagnosis of MC twin pregnancy is established.
Conversely, if two gestational sacs are identified with one embryo in each sac (Figure 5.2C and D), DC twin pregnancy is diagnosed. An ultrasound image showing the chorionicity should be documented and kept in the patient’s records for future reference.8






All DC twin pregnancies are DA. However, if an MC twin pregnancy is diagnosed, the next step is establishing amnionicity. Of note, more than 99% of MC twins are DA. To establish amnionicity in MC twins before 10 weeks, the amniotic membranes have to be identified. In early pregnancies, the amnion is seen as a very thin membrane that surrounds the embryo. From 8 to 9 weeks onward, a thin intertwin membrane dividing both amniotic sacs can be observed (Figure 5.3).

If the amniotic membranes cannot be identified, amnionicity can be inferred through the assessment of the yolk sacs. Usually, the number of yolk sacs correlates with the number of amniotic cavities. Therefore, if two yolk sacs are observed, it is more likely to be an MCDA (Figure 5.4). However, this concept has been challenged because several exceptions have been reported11,12 (Figure 5.5A). If monoamnionicity is suspected, confirmation can be obtained by the observing entanglement of the cords by color Doppler (Figure 5.5B).

At the 11- to 14-week scan, determining chorionicity and amnionicity is based on the assessment of the number of placental masses, and the characteristics of the membranes at the placental insertion sites. When two chorionic masses are identified, a DC twin pregnancy is diagnosed (Figure 5.6). If a single mass is observed, it could mean either an MC twin or a DC twin with fused placentas (Figure 5.7). In this circumstance, chorionicity is established by exploring the intertwin membranes at the site of the placental insertion. In DC twins, the intertwin membrane is thick and easily observed, and the placental insertion is thicker and shows a typical feature known as the “λ” (lambda) sign (Figure 5.8) produced due to the presence of chorionic tissue between membranes. Membrane insertion in MC twins shows a very thin membrane that

ends in a “T” form (Figures 5.7B and 5.8). Use of lambda sign predicts chorionicity with a high degree of accuracy before 14 weeks.13 Moreover, the combination of number of placentas, “T” sign, and “lambda” sign have shown more than 99% of sensitivity and specificity.14





















Other ultrasound features related to chorionicity are the thickness and the number of layers of the intertwin membrane (Figure 5.8). In MC twins, the membrane is made of two layers of amnion, is thin, and is sometimes even difficult to identify by ultrasound. In DC twins, the membranes have four layers—two chorionic and two amniotic—that are thicker and usually easily identifiable by ultrasound.

If chorionicity cannot be determined by abdominal ultrasound, a transvaginal approach should be attempted. If chorionicity cannot be determined during a first-trimester scan in a routine setting, a second opinion should be sought from a specialist. If MCMA is diagnosed, the patient should be referred to a tertiary center.8

Occasionally, there are pitfalls in determining chorionicity.15 For instance, a single bilobulated
placenta or different phenotypic sex in heterokaryotypic fetuses could be a source of a misdiagnosis.







Second and Third Trimesters

The performance in determining chorionicity decreases with increasing gestational age. Sometimes it becomes extremely difficult to establish a definite diagnosis. It has to be assessed using the number of placental masses and concordance or discordance of twins’ sex. If chorionicity cannot be established (DA with a single placental mass, twins of the same sex, and lack of first-trimester images), the pregnancy should be managed as MC.8







Twin Labeling

When referring to a twin pregnancy, it is desirable to differentiate each twin throughout the pregnancy. Thus, labeling the fetuses is a major process in the prenatal care of multifetal pregnancies. Labeling includes a description of each twin’s location (left-right, superior-inferior, anterior-posterior) and any other information that could help discriminate both twins: discordant sex, cord insertion sites, any discordant ultrasound marker, or anomaly.Usually, the lower twin is labeled as “A” or “1” and the other as “B” or “2.” For example, “twin A, at right side of the uterus, female, and with an intracardiac echogenic focus.” However, if during the pregnancy one twin changes position, it is useful to keep the original nomenclature.8

A consistent labeling is important for a better assessment and follow-up of complicated twin pregnancies. For example, in the first trimester when interpreting an abnormal genetic test, during the second and third trimesters when monitoring an abnormal condition (ie, intrauterine growth restriction [IUGR], a structural defect, etc). or for cases in which one twin is affected by a condition that requires special management (ie, congenital heart defect, diaphragmatic hernia, fetal anemia, etc).


Ultrasound Surveillance of Twin Pregnancies

The role of ultrasound in the follow-up of twin pregnancies has been mostly standardized during
the last decade, with several clinical guidelines published.1,8,16






Ultrasound assessment of twin pregnancies includes a first-trimester scan between 11 and 14 weeks. During the second and third trimesters, the ultrasound surveillance of an uncomplicated twin pregnancy varies according to chorionicity.


Ultrasound Examination at 11 to 13 6/7 Weeks and Screening for Chromosomal Anomalies

Ideally, every pregnant woman should undergo an ultrasound examination between 11 and 13 6/7 weeks. This is the optimal time for dating the pregnancy, establishing chorionicity and amnionicity, estimating aneuploidy risk, and screening for major structural anomalies (Figures 5.1A and B).

In dizygotic twins, the aneuploidy risk for each fetus is similar to single pregnancies. Thus, the probability of identifying an aneuploid fetus is two times the risk of a single pregnancy.1 On the other hand, in monozygotic twins, where fetuses are genetically identical, the likelihood of finding an aneuploidy is similar to single gestations.6 However, when an aneuploidy is diagnosed, usually both fetuses are affected. In rare cases, monozygotic twins have discordant karyotypes, which is known as heterokaryotypic twins.6,15

However, in clinical practice, the distinction between dizygosity and monozygosity is not always feasible. When assessing twins by ultrasound, it is important to bear in mind a few basic concepts: all MC twins are monozygotic, while all DC with discordant sex are dizygotic. DC twins with concordant sex are mostly dizygotic, but around 20% are monozygotic (Algorithm 5.1).

Current recommendations for first-trimester combined screening are as follows: in DC twins, an individual risk for each fetus is estimated according to nuchal translucency (NT) measurement and eventually according to other secondary markers such as nasal bone, ductus venosus (DV), or mitral valve regurgitation. In MC twins (always monozygotic), a unique risk is estimated for both fetuses based on the average NT of each fetus.8

Regarding the use of biochemical markers, such as free beta-hCG and PAPP-A, their performance is lower compared to singleton, but they still increase the detection rate for aneuploidies in twins. In higher order multiple pregnancies—three or more fetuses—biochemical markers are not useful.1,6

The risk for structural anomalies is also higher than in singletons, especially in monozygotic twins. Screening for structural anomalies is traditionally performed in the second trimester, but with the progressive improvement in imaging quality and standardization of anatomical assessment, a significant number of major anomalies can be detected at 12 to 13 weeks.17


Surveillance During Second and Third Trimesters

The ultrasound surveillance in second and third trimesters will depend on chorionicity.


DC Twins

In DC twins, it is recommended to perform a detailed scan between 20 and 22 weeks and one scan every 4 weeks thereafter. Routine cervical length (CL) measurement around 20 weeks is still
a matter of controversy, and it is not considered in every guideline.1,8


MC Twins

In MC twins, after the first-trimester scan, it is recommended to conduct ultrasound surveillance every 2 weeks starting at 16 weeks. Basic ultrasound measurments include amniotic fluid assessment and estimated fetal weight (EFW), with a detailed scan at 22 to 22 weeks.1,8,16 The purpose of closer surveillance in MC twins is that early detection of severe complications, including twin-to-twin transfusion syndrome (TTTS) and selective intrauterine growth restriction (sIUGR), can occur. Around 10% to 15% of MC twins will develop a TTTS and ˜15% will have sIUGR.

The minimal contents in the ultrasound surveillance in MC twins vary among the different guidelines, but there is consensus that (Figure 5.1):



  • Every MC has to be assessed every 2 weeks, beginning at 16 weeks until delivery.


  • Every scan must include the maximum vertical pocket (MVP) of amniotic fluid of each sac for early diagnosis of TTTS and the EFW of each fetus for detection of sIUGR or discordant growth.


  • Every MC twin pregnancy should have a detailed scan at 20 to 22 weeks, including a cardiac screening assessment.


  • Women with uncomplicated MC twins should be delivered around 36 to 37 weeks—34 to 37 6/7 weeks—according to the 2014 American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin.

There are some other aspects that differ among guidelines, like the use of Doppler and CL measurement. Regarding the use of Doppler in uncomplicated twins, there is no consensus on when, how often, and which vessels should be assessed. The measurement of CL is also suggested in the second trimester in the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) guidelines,8 but it is not recommended in the ACOG Practice Bulletin1 or in the Royal College of Obstetricians and Gynaecologists (RCOG) guidelines.16


Complications in Multifetal Pregnancies

Complications in multiple pregnancies, either maternal or fetal, are more frequent than in singletons. In addition, the higher the number of fetuses, the higher the complication rate.




Jun 19, 2022 | Posted by in OBSTETRICS | Comments Off on Multifetal Pregnancies: Epidemiology, Clinical Characteristics, and Management
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