Multiple Gestation

Abstract

Multiple pregnancies mean when the woman carries more than one fetus at a time. Multiple pregnancy, multiple gestation, and multifetal pregnancy are synonyms. These can be twins, triplets, quadruplets, or more. These types of pregnancy have become one of the most common high-risk pregnancies encountered by obstetricians. It is associated with an increased risk of both maternal and perinatal morbidity and mortality. The incidence of multiple pregnancies has risen significantly over the last four decades, primarily due to increased use of ovulation induction drugs. The symptoms and signs of multiple pregnancies include excessive nausea and vomiting, larger uterus than expected for the date of pregnancy, and excessive weight gain. The aim of this chapter is to discuss the occurrence, causes, epidemiology, maternal and perinatal morbidity and mortality, antepartum, and intrapartum management of multiple pregnancies.

1. Introduction

Multiple pregnancies are the presence of more than one fetus at a time. Simultaneous development of two fetuses, three fetuses, and four fetuses is called as twins, triplets, quadruplets, respectively, and so on. These types of pregnancies may result from two or more fertilization or from single fertilization followed by cleavage of the zygote or combination of both [1]. Such pregnancies are associated with increased maternal and perinatal morbidity and mortality compared to that singleton gestations. They can cause almost every potential complication of pregnancy except post-term delivery and macrosomia [2, 3]. Twins’ pregnancy is the most common variety of multiple pregnancies and the rate of occurrence of multiple pregnancies decreases with an increased number of fetuses [4]. The rate and the number of both twin and higher-order multi-fetal births have increased dramatically over the last four decades, mainly due to ovulation induction and early detection by ultrasound [1, 5]. According to Hellin’s rules, the mathematical frequency of multiple births is 1 in 80 ⁽ⁿ⁻¹⁾ pregnancies, where n is the number of fetuses [4]. For example, twins 1 in 80 pregnancies, triplets 1 in 6400, quadruplets 1 in 512,000, etc. [4, 5].

2. Zygosity and chorionicty

Zygosity refers to the genetic makeup of the twin pregnancy while chorionicty indicates the placenta’s membrane status [4]. Early determination of chorionicity is essential because it is a major factor in determining obstetrical risks, management, and outcomes [2, 3].

Twins can be either monozygotic or dizygotic.

• Dizygotic (DZ) or fraternal twins result from fertilization of two ova by two sperms during a single ovarian cycle.

• Monozygotic (MZ) or identical twins are the result of fertilization of a single ovum by single sperm and followed by splitting of the zygote. Chorionicity will depend on the timing of the division of the embryo. The following possibilities may occur:

1. If the division takes place within 72 hours after fertilization, the resulting embryos will have two separate placenta, chorions, and amnions, that is, a thick four-layered intervening membrane. It accounts for 25 to 30% of MZ twins.

2. If the division takes place between the 4th and 8th days of fertilization when the chorion is already formed, monochorionic, diamniotic twins will evolve with a thin two-layer dividing membrane. It accounts 70–75% of MZ twins.

3. If the division occurs between 8th and 12th days of fertilization, the result will be a monochorionic and monoamniotic twin. It accounts 1–2% of MZ twins.

4. If the division occurs after 13th day of fertilization, the result will be a monochorionic, monoamniotic, and conjoined twins. It is a rare type of MZ and occurs in less than 1%.

The following table shows the relationship between the timing of division and the nature of membranes in twin pregnancy.

Time of cleavage	Nature of membranes
0–72 hours	Dichorionic, diamniotic
4–8 days	Monochorionic, diamniotic
9–12 days	Monochorionic, monoamniotic
After 13 days	Monochorionic, monoamniotic (conjoined twins)

The following figures show placentation in twin pregnancies [2].

3. Rates and causes of monozygotic and dizygotic twinning

Dizygotic twins occur in about 1% to 1.5% and monozygotic twins 1 in 250 pregnancies among natural conception [2]. The rates of spontaneous DZ twinning are influenced by maternal age, family history, and race [2, 3, 6]. The frequency of MZ twinning is constant in all populations studied at about 1 in 250 births [3].

The risk for DZ twinning increases with maternal age, peaking at 37 years of age. Maternal family history also increases the chance of spontaneous DZ twinning, while paternal family history contributes little or nothing to this risk [2, 7]. The frequency of multiple pregnancies varies significantly among different races and ethnic groups. Women of African descent have higher rates of DZ twinning than white women, who in turn have higher rates than women of Asian descent [2]. In Japan, 1 in 250 newborns is a twin, whereas in Nigeria, 1 in 11 babies is a result of a twin gestation [2, 6]. Ovulation induction increases the occurrence of multiple pregnancies, including both dizygotic and monozygotic [4, 7].

4. Superfecundation and superfetation

Superfecundation is the fertilization of two different ova released in the same cycle, by separate acts of coitus within a short period of time. Sexual intercourse may not necessary with the same man [1, 4].

Superfetation is the fertilization of two ova released in different menstrual cycles. The implantation and development of one fetus over another fetus are theoretically possible until the uterine cavity is obliterated by 12 weeks of pregnancy. In other words, superfetation requires ovulation and fertilization during the course of an established pregnancy [1, 4].

5. Diagnosis of multiple pregnancies

5.1 Clinical evaluation

With multiple fetuses, a woman may experience excessive nausea and vomiting during the first trimester. The uterine size is typically larger than expected during the second and third trimesters.

In general, it is difficult to diagnose twins by palpation of fetal parts before the third trimester. In obese women, presence of hydramnios and overlapping fetuses are factors that make it difficult to identify twins by abdominal palpation. Palpating two or more fetal heads and or fetal poles supports a diagnosis of multiple pregnancies.

Identification of two fetal heartbeats suggests that their rates are clearly distinct from each other and from that of the mother suggests twin pregnancy.

6. Sonography

Routine prenatal ultrasound scan has proved important for early detection of multiple pregnancies. Before the advent of routine prenatal ultrasound, many twins were not diagnosed until late in gestation or delivery [2]. Separate gestational sacs with individual yolk sacs can be visualized as early as 5 weeks from the first day of the last menstrual period, and embryos with cardiac activity can usually be seen by 6 weeks by transvaginal ultrasound [2]. Prenatal sonography in multiple pregnancies is useful for the following [6]:

• Confirming a diagnosis of multiple gestations

• Determining chorionicty

• Detecting fetal anomalies

• Evaluating fetal growth

• For fetal well-being

7. Determination of chorionicity

Accurate determination of chorionicity early in pregnancy is essential to optimal obstetrics care [4]. It is a major determinant of pregnancy outcome and its determination is easiest and most reliable when assessed in the first trimester [2].

• The presence of two separate gestational sacs, each containing the fetus, and a thick dividing membrane strongly suggests dichorionic diamniotic pregnancy.

• When there is one gestational sac and a thin dividing membrane (< 2 mm) suggests monochorionic diamniotic pregnancy.

• A single gestational sac that contains two fetuses without dividing membrane suggests monochorionic monoamniotic pregnancy.

Examination of the base of the intertwin membrane is also useful for the determination of chorionicity.

• The twin peak sign appears as a triangular projection of placental tissue extending a short distance between the layers of the dividing membrane, suggesting dichorionic pregnancy.

• The T sign is the right-angle relationship between the membranes and placenta and no apparent extension of the placenta between the dividing membranes suggests monochorionic pregnancy.

The determination of chorionicity and amnionicity in the second and third trimesters can be made based on sex of fetuses, number of placentas, and thickness of the dividing membrane.

• For instance, different gender, two separate placentas, and thick dividing membrane strongly suggest dichorionic pregnancy.

After delivery, a careful visual examination of the placenta and membranes serves to establish zygosity and chorionicity in approximately two-thirds of cases [4].

8. Maternal adaptation to multiple pregnancies

The degree of maternal physiologic changes during pregnancy is exaggerated with multiple gestations. The levels of maternal hormones related to pregnancy are higher in multiple gestations than in singleton. Compared to singleton pregnancies, multiple pregnancies are associated with an increased risk of the following conditions.

• Nausea and vomiting

• Weight

• Blood volume

• Cardiac output

• Glomerular filtration rate

• Tidal volume

• Mechanical distress

9. Maternal morbidity and mortality related to multiple pregnancies

Rates of essentially every obstetrical complication are elevated with multiple pregnancies with the exception of macrosomia and post-term pregnancy. In general, these complications rise proportionally with increasing the number of fetuses.

• Hyperemesis gravidarum

• Spontaneous abortion

• Anemia

• Hypertensive disorder of pregnancy

• Abruption placentae

• Placenta previa

• Gestational diabetics

• Polyhydramnios

• Thromboembolism

• Postpartum hemorrhage

• Cesarean delivery

10. Perinatal morbidity and mortality related to multiple pregnancies

Babies who are products of multiple gestations have higher rates of:

• Low birth weight

• Preterm birth

• Malpresentation

• Premature rupture of membranes

• Umbilical cord prolapse

• Intrauterine growth restriction

• Congenital anomalies

• Neonatal and infant death and cerebral palsy

11. Fetal complications unique to multiple pregnancies

11.1 “Vanishing twin”

It refers to the loss of one member of a twin or other higher-order gestations early in pregnancy. This is typically either asymptomatic or associated with spotting or mild bleeding [2, 7]. It is responsible for lower frequency of twin or higher-order multiple gestations during the second trimester than the first trimester. For instance, if two gestational sacs are confirmed by the first-trimester ultrasound, the chance of delivering twins is 63% for women younger than 30 years and 52% for women 30 years or older [2]. Monochorionic twin gestations are at higher risk for a vanishing twin than dichorionic twins. Vanishing twin is even more common in higher-order pregnancies [2, 7]. This condition can be diagnosed with serial ultrasound with the loss of one or more fetus/fetuses.

11.2 Twin-twin transfusion syndrome (TTTS)

TTTS is exclusively a complication of monochorionic multiple pregnancies that occur in 10–15% of monochorionic diamniotic gestations [2, 5, 7]. This syndrome is characterized by unbalanced anastomoses in the placenta which leads to under perfusion of the donor twin and over perfusion of the recipient. The donor twin develops oligohydramnios and intrauterine growth restriction; the recipient experiences volume overloads which result in polyhydramnios [1, 2, 3].

TTTS can be present at any gestational age. The earlier the onset is associated with a poorer prognosis. If untreated, the mortality rates range from 80–100% [2, 7]. Both twins are at risk of demise from circulatory derangement, and the pregnancy is predisposed further for preterm delivery due to uterine overdistention with hydramnios [2].

There are three types of possible vascular anastomosis in the monochorionic placenta [1, 2, 5,]. Arteriovenous (AV), arterioarterial (AA), and venovenous (VV).

11.3 Diagnosis and staging

The two classic criteria required for antenatal diagnosis of TTTS are monochorionic diamniotic twin gestation and oligohydramnios in one amniotic sac and polyhydramnios in the other sac [1].

Once identified, TTTS is typically staged by the quintero staging system:

• Stage I- oligohydramnios, polyhydramnios sequence. Donor twin bladder is visible.

• Stage II- oligohydramnios, polyhydramnios sequence. The donor twin bladder is not visible and the doppler scan is normal.

• Stage III- oligohydramnios, polyhydramnios sequence. Donor twin bladder is not visible and doppler scans are abnormal.

• Stage IV- ascites or frank hydrops in either twin.

• Stage V- one or both fetuses have died.

When TTTS diagnosed management, it depends on gestational at diagnosis and the severity of clinical findings. There are five management options available [2]:

• Expectant management

• Septostomy

• Serial amnioreduction

• Selective termination/cord occlusion

• Fetoscopic laser photocoagulation

Generally, expectant management is not recommended in stage II or greater TTTS and selective termination is only offered in extreme cases of advanced TTTS [2].

11.4 Conjoined twins

This is a very rare event of MZ twinning resulting when the division occurs after the embryonic disc has completely formed, that is, after 13 days. It occurs with a frequency of about 1 in 50,000 pregnancies. Most conjoined twins are female, with a reported female-to-male ratio of 2:1 or 3:1 [2].

Conjoined twins are classified according to the anatomic location of the incomplete splinting [3]. The most common location is the chest (thoracopagus), followed by the anterior abdominal wall (omphalopagus), the buttocks (pygopagus), the ischium (ischiopagus), and the head (cephalopagus) [2, 3].

Conjoined twins can be diagnosed by ultrasound as early as the first trimester based on visualization of monoamnionicity and a bifid fetal pole [2].

The pregnancy termination should be offered when the diagnosis is confirmed before the age of viability. The prognosis for survival and successful separation depends on the degree of organ and vascular sharing between the two fetuses. For a better outcome, women with conjoined twins should be cared for by a multidisciplinary team [1, 2].

11.5 Intrauterine death of one fetus

Intrauterine death of one fetus in a multiple gestation can occur at any gestation. This condition is more common during the first trimester and has no or little effect on the prognosis of the surviving fetus or fetuses. After the death of one twin in a monochorionic gestation, approximately 15% of the remaining fetus also dies, while approximately 3% of remaining fetus dies in a dichorionic gestation [2].

The risk for significant neurologic morbidity is increased after intrauterine death of one fetus in a monochorioic, but not in a dichorionic gestation. The surviving twin runs the risk of cerebral palsy, microcephaly, renal cortical necrosis, and disseminated intravascular coagulation. The DIC is due to thromboplastin liberated from the dead twin that crosses via placental anastomosis to the living twin. In such cases, the maternal coagulation profile should be followed once a week to identify possible coagulation abnormalities. The dead fetus is reabsorbed if the death occurs prior to 12 weeks gestation, while the fetus shrinks and becomes dehydrated beyond this time [1, 2].

11.6 Twin reversed arterial perfusion (TRAP)

The TRAP sequence is also known as acardiac twinning and occurs only in monochorionic pregnancies. It is characterized by an acardiac-perfused twin having blood supply from a normal cotwin via arterio-arterial or vein-to-vein connection. In majority, the cotwin dies due to high output failure. The arterial pressure of the donor twin is high, the recipient twin receives the used blood from the donor. The perfused twin is often chromosomally abnormal and an extremely malformed fetus with either no heart at all or only rudimentary cardiac tissue [1, 2].

The management of TRAP is controversial. The options for management are [2, 4]:

• Expectant management

• Delivery

• Occlusion of the acardiac twin’s umbilical cord by bipolar cord coagulation or laser ablation.

11.7 Twin anemia polycythemia sequence (TAPS)

This is a form of chronic fetofetal transfusion that is characterized by significant hemoglobin differences between donor and recipient twins without discrepancies in amniotic fluid volumes. The spontaneous form complicates from 3–5% of monochorionic pregnancies and it occurs in up to 13% of pregnancies after laser photocoagulation.

It is diagnosed antenatally by middle cerebral artery peak systolic velocity of more than 1.5 multiples of median (MoM) in the donor and less than 1.0 MoM in the recipient twin [1].

The options for management include expectant management and intrauterine transfusions both intraperitoneal and intravenous.

11.8 Complete hydatidiform mole with coexisting normal fetus

One of the fetuses is either complete or partial molar pregnancy, whereas the cotwin is normal fetus. The prevalence rates range from 1 in 22,000 to 100,000 pregnancies [1].

The diagnosis is usually made in the first half of pregnancy and using similar diagnostic modalities.

The possible complications are persistent and heavy bleeding, preeclampsia, preterm delivery, and persistent trophoblastic disease.

Optimal management is not known for this twin gestation. The possible options of management are termination at the time of diagnosis, and observation and pregnancy progression [1].

12. Antepartum management of multiple pregnancies

Gestational age at delivery and the adequacy of fetal growth are two important factors that most influence pregnancy outcomes [2].

The care provider should understand and advise on the following issues during antenatal care:

• Increased dietary supplement is needed for increased energy supply to the extent of 300 Kcal/day above that needed in a singleton pregnancy. Dietary supplementation includes both macronutrients and micronutrients [4].

• Increased rest at home and early cessation of work.

• Interval of antenatal contact should be more frequent.

• Multiple gestations are an increased risk for uteroplacental insufficiency. So, fetal surveillance is mandatory. It should be started at 28 weeks for triplets and higher-order pregnancies, while at 32 and 34 weeks for monochorionic twins and dichorionic twins, respectively [1, 2, 4]. The non-stress test and biophysical profile can be used and the interpretation is similar to singleton pregnancy.

• Fetal growth is monitored by ultrasound every 4 to 6 weeks beginning at 24 weeks. Twins grow at the same rate as singletons until 30 to 32 weeks gestation, after which their growth velocity slows compared with singletons. Institute of Medicine recommends women with twins and normal body mass index gain a total of 37–54 lb. weight during the pregnancy [2].

• Assess the risk for preterm birth using a transvaginal cervical length of 20 mm or less between 20- and 24-weeks’ gestation and fetal fibronectin sampling [2].

• Routine use of tocolytic agents to prevent preterm delivery has no significant benefit. However, short-term use of these agents for acute tocolysis in preterm labor is helpful to gain time for administration of corticosteroids and allow transport to a tertiary care facility. Tocolytic use in multiple gestations needs careful monitoring of maternal condition as these women are at higher risk for cardiovascular complications due to exaggerated maternal cardiovascular adaptations [1, 2].

• As the numbers of fetuses increases, the prognosis of multiple pregnancies gets poorer. Now a day, there is a practice of selective fetal reduction to improve the outcome of the remaining fetus or fetuses.

13. Timing of delivery in multiple pregnancies

The timing of delivery depends on maternal and fetal complications. The available data suggest that nadir perinatal complications occur at earlier gestational ages in multiple gestations compared with singletons [2]. There is an increased risk in twin pregnancies that extend past 38 to 39 weeks gestation. Allowing a dichorionic twin gestation to go beyond 38 weeks requires convincing evidence of normal fetal growth, reassuring fetal condition as well as a woman’s desire to extend the pregnancy. It is not advisable to prolong twin pregnancy past 39 weeks because of clear risk without any known benefit.

The ACOG, NICHD, and SMFM recommend the delivery of uncomplicated dichorionic twins at 38 weeks and uncomplicated monochorionic twins between 34 and 37 weeks [2].

Based on experts’ opinions, it is reasonable to offer delivery of uncomplicated triples anytime between 35 and 36 weeks.

14. Mode of delivery in multiple pregnancies

Mode of delivery for patients with multiple gestations depends on the gestational age, estimated weight of the fetuses, number of fetuses, presentation of fetuses, presence or absence of complications, etc.

1. Mode of delivery in diamniotic twins

• Both twins are vertex presentation, vaginal delivery in the absence of obstetric indications for cesarean delivery.

• Twin A vertex and twin B non-vertex presentation, vaginal delivery is possible if the estimated fetal weight is 1500 g–3500 g

• Twin A non-vertex cesarean delivery is indicated.

1. Monoamniotic twins–cesarean delivery

2. Triplet and higher-order gestation–cesarean delivery

15. Intrapartum management of twin vaginal delivery

Twin pregnancy is considered high risk and needs careful preparation and multidisciplinary cooperation among obstetrics, anesthesia, nursing, and neonatology.

Both fetuses should be monitored continuously. Use of analgesic drugs is to be limited as the babies are small and rapid delivery may occur. The third stage of labor should be managed actively as these women are at high risk for postpartum hemorrhage.

Abbreviations

ACOG	American College of Obstetricians and Gynecologist
DIC	Disseminated intravascular coagulation
DZ	Dizygotic
MZ	Monozygotic
MoM	Multiples of the median
NICHD	The national institute of child health and human development
SMFM	Society for maternal-fetal medicine
TAPS	Twin anemia polycythemia sequence
TTTS	Twin-twin transfusion syndrome
TRAP	Twin reversed arterial perfusion