Multiple Pregnancy: Boon or Bane – An Indian Perspective

*R. Kishore Kumar and B.R. Usha*

#### **Abstract**

In the era of rising multiple pregnancy, it is important for us to analyse the recent trends. Assisted reproductive technology has brought hope to many childless couples. But it comes with a price. The prevalence of multiple gestation globally at present is 32 per 1000 deliveries. Recent studies from India report an incidence of 30.5 per 1000 deliveries. The most important complication associated with multiple gestation is prematurity. From the neonatology point of view, the increase in multiple gestation has opened an additional opportunity for the neonatologists to see and manage more preterm babies. Infants born after a multifetal pregnancy are associated with an increased risk of prematurity, cerebral palsy, learning disabilities, slow language development, behavioural difficulties, chronic lung disease, developmental delay, and death. The relative risk of cerebral palsy in twins and triplets compared to a singleton is 4.9 and 12.7, respectively. Foetal reduction as a routine should be discussed with all couples with multiple gestation including twins, to improve the pregnancy and neonatal outcome. Any multifetal gestation is a high-risk pregnancy should be managed efficiently by a multidisciplinary team involving Senior Obstetricians, neonatologists, intensivists, anaesthesiologists, physicians and nursing team in a well-equipped centre.

**Keywords:** multiple pregnancy, foetal reduction, prematurity

#### **1. Introduction**

In the era of rising multiple pregnancy, it is important for us to analyse the recent trends. This chapter will highlight the same and the recent updates in the management from an Indian perspective.

The prevalence of multiple gestation globally at present is 32 per 1000 deliveries [1]. Recent studies from India report an incidence of 30.5 per 1000 deliveries [2]. These again vary with respect to private and government sectors, with more spontaneous multiple pregnancies in the government and more ART (assisted reproductive technology)-associated multiple pregnancies seen in the private sector.

Due to the changes in lifestyle, delayed age of childbearing and stressful life, we see a lot of increase in infertility. At least one in five couples are known to have fertility issues these days. These ART techniques including ovulation induction with or without IUI are associated with a risk of multiple pregnancy of 8–10%. This increases up to 30% with IVF and two blastocyst transfer.

Assisted reproductive technology has brought hope to many childless couples. But it comes with a price. Each blastocyst of good quality can potentially give rise to four foetuses. There are many case reports of multiple pregnancy after a single-embryo transfer. With the routine trend of many ART specialists adopting two or more embryo transfer to achieve better pregnancy rates, the incidence of multiple gestation is known to increase.

From the neonatology point of view, the increase in multiple gestation has opened an additional challenge to the neonatologists to manage more preterm babies. Gone are those days, when extremely premature babies less than 28 weeks were not considered viable and were not resuscitated. Extremely premature babies with less as 24 weeks or 450 gm rate are being resuscitated and managed efficiently in NICU and successfully sent home. Perinatal outcomes may not be optimum with extremely premature babies, but over the last few decades, we have learnt a lot about extremely premature new-born care. This has helped us to analyse the data and improvise our protocols in the management.

#### **2. Causes of multiple gestation**


#### **2.1 Types of multiple gestation**


Depending on the timing of cell division after fertilisation, chorionicity and amnionicity develop in monozygotic twins. After fertilisation, when the division happens.


#### **2.2 Multiple pregnancy boon or bane**

It may be very nice to have twin babies, triplets might be fancy, and quadruplets would be a burden. But any multiple gestation is termed a high-risk pregnancy.

The most important complication associated with multiple gestation is prematurity (Kamlesh Kumari et al. [3]). 65.7% increased chances of preterm labour and 61.4% increased chances of having a caesarean section have been reported with multiple pregnancies – with most common reason being malpresentation of one of the fetuses.

#### **2.3 Maternal complications**

The maternal complications with multiple pregnancy include preterm labour, PPROM, anaemia, gestational hypertension, gestational diabetes, polyamnios, oligoamnios, haemorrhage including post-partum, and more incidence of caesarean delivery.

#### **2.4 Foetal complications**

Infants born after a multifetal pregnancy are associated with the increased risk of prematurity, cerebral palsy, learning disabilities, slow language development, behavioural difficulties, chronic lung disease, developmental delay, and death. The relative risk of cerebral palsy in twins and triplets compared to a singleton is 4.9 and 12.7, respectively.

Determination of chorionicity is very important in these pregnancies.


The other complications include single foetal demise, congenital anomalies, discordant twins, conjoint twins, birth asphyxia, low birth weight, birth trauma, still birth, perinatal death and prolonged NICU stay. In India, 10% of the perinatal mortality can be attributed to twin pregnancies (**Table 1**).

The above comparison reports various descriptive Indian studies done in recent years with respect to multiple pregnancy. The mean age of women in these studies was in the range of 25–27 yrs. So, they are all young women mostly conceptions with ART. Preterm labour was the most common complication with incidence going up to 84.31%, and in them, preterm premature rupture of membranes was noted in up to 23.52%. Among the medical complications, anaemia was the most common complication ranging from 30.7 to 91.67%. This is due to nutritional deficiency developed due to increased demand of twins or triplets or due to hyperemesis associated with these pregnancies. Incidence of gestational diabetes is up to 13.73%, and gestational hypertension is seen up to 37.5%, which can be explained by a larger placenta seen in these pregnancies. Antepartum haemorrhage was seen in up to 5.95% patients. Most of these patients present with lowlying placenta mainly due to a larger placental surface and develop intermittent spotting


#### **Table 1.**

*Demographics of multiple gestation studies in India.*

or bleeding creating panic in patients. Many of them also develop abruption associated with hypertension. There is an increased incidence of postpartum haemorrhage also in multiple gestation mainly due to overdistended uterus and post-partum atony. It would be wise to be prepared for it with active management of the third stage of labour and keeping blood and blood products cross-matched and ready.

Caesarean delivery is the most common of delivery in multiple pregnancy seen in up to 64.3% mainly due to malpresentation (in up to 47%). Normal delivery is an option only in twin deliveries and not on triplets or higher orders. In twins, cephaliccephalic position is the most common presentation where vaginal delivery is feasible. The second most common is cephalic and second breech position where vaginal delivery also can be done. However, in these cases, there is a small risk of the requirement of Caesarean for second twin due to malpresentation or non-progress of labour. In cases of transverse lie or both breech or other presentations, Caesarean would be the option. In the breech and second cephalic presentation, there is risk of the first twin's head getting locked against the second twin (interlocking twin) and hence vaginal deliveries should be thought about only when the first twin is in cephalic presentation.

#### **3. Foetal reduction**

It has been developed since the 1980s, as a method to reduce the multiple gestation to twin or singleton gestation to reduce the complications. It involves preliminary

#### *Multiple Pregnancy: Boon or Bane – An Indian Perspective DOI: http://dx.doi.org/10.5772/intechopen.105839*

screening of foetuses at NT scan and reduction of foetuses that are abnormal or relatively abnormal. If there are no abnormal foetuses, then a decision is taken based on the most accessible foetus for the procedure. Gender selection is not allowed in India as per PCPNDT rules and hence shall not be a criterion to decide. It is done as a day-care procedure with some minimal local anaesthesia. It involves transabdominal ultrasound-guided injection of KCl into the foetal heart to stop its function. Some studies report doing chorionic villus sampling of foetuses and FISH before reduction. The procedure is ideally done between 12 and 14 weeks after the NT scan to allow for spontaneous reductions to happen till then and NT screening to be done. In up to 20 to 60%, spontaneous reduction to singleton pregnancy happens [6]. The demised twin disappears as a vanishing twin. There has been an increasing trend of reducing even twins to singleton to avoid the complications associated with multiple births.

Jung Ryeol Lee et al. [7] report early foetal reduction at 6–8 weeks by transvaginal ultrasound guidance using a 19G needle. Cardiac puncture and amniotic fluid aspiration is done to produce foetal reduction, which may be added on with KCl injection. However, this study reports better pregnancy and foetal outcomes with early foetal reduction at 6–8weeks without using KCl.

The foetal reduction procedure is therefore not limited to triplets or quadruplet gestations. Twin gestation reduced to singleton, do better according to studies. We do see patients refusing reduction on moral or religious grounds, thinking about foeticide or about the risk of miscarriage.

The procedure is associated with a small risk of miscarriage and infection, which should be explained to the couple against the risks involved in continuing with the multiple gestation.

Foetal reduction as a routine should be discussed with all couples with multiple gestation, including twins to improve the pregnancy and the neonatal outcome. This counselling should involve an explanation of the risks specifically with multiple pregnancy and the option to reduce the pregnancy. The moral and ethical background should be kept in mind before counselling the couple about the procedure.

#### **4. Interventions to reduce multiple gestation**


#### **5. Antenatal care**

It is important to determine the chorionicity with a good transvaginal ultrasound at the time of the dating scan (7–10 weeks). According to the chorionicity, the pregnancy is categorised, and the antenatal visit schedule is planned. All women should be offered screening for trisomy 21 at 11–13 + 6 weeks of gestation. This ultrasound can be combined with first-trimester biochemistry (serum PAPP-A and beta-Hcg) to make it combined screening with the better detection rates. For triplets or higherorder pregnancies, only nuchal translucency screening should be done.

The next level of ultrasound screening is an anomaly scan, which is offered between 18 and 22 weeks. Monochorionic pregnancies should be scanned at 16–17, 19–20, and 21–22 weeks. Monoamniotic twins should be screened from 15 to 16 weeks and 18 to 20 weeks. A five-chamber view of the heart should be carried out at 18–19 weeks and 21–22 weeks. Further growth scan shall include complete documentation of full biometry, foetal weight, liquor, and bladder size. Scans should be performed at a frequency dictated by the chorionicity (**Table 2**) [8].

It is important for the obstetrician to be well versed with the complications associated with multiple gestation. Accordingly, the antenatal visits should be scheduled, and the pregnancy closely monitored. Where required, a multidisciplinary team involving foetal medicine consultants, neonatologists and physicians should be involved in the management. Routine antenatal visits should include screening for anaemia, hypertension, diabetes, and foetal heartbeat assessment.

#### **5.1 Cervical length screening**

It is done by transvaginal ultrasound at 12 weeks, 16 weeks, 20 weeks and 24 weeks. Cervical length less than 2.5 cm is considered short. Prophylactic cervical cerclage in multiple gestation is controversial. Evidence suggests that cervical length is a moderate predictor of spontaneous preterm labour in twin pregnancy. Vaginal progesterone may reduce this risk in women with a twin pregnancy. However, in patients with ART conception especially with polycystic ovaries that are known to be associated with cervical insufficiency, prophylactic cervical cerclage would be beneficial. It is ideally applied after NT scan between 13 and 14 weeks or if history indicated, at least 2 weeks before the previous miscarriage.


**Table 2.**

*Suggested ultrasound scans for multiple gestation pregnancies.*

#### **5.2 Antenatal corticosteroids**

If elective delivery or Caesarean is planned before 38 weeks, antenatal corticosteroids are warranted to be given, either betamethasone or dexamethasone. This is according to the present data available. A lot of newer studies are ongoing with respect to the assessment of newborn adverse effects due to antenatal steroids. The present protocols suggest two doses of betamethasone, 12 mg given intramuscular, 24 hrs apart. Similarly, dexamethasone can be given 6 mg, 12th hourly four doses 6 hrs apart.

#### **5.3 Antenatal magnesium sulphate**

BEAM trial [9] in 2002 first proposed the beneficial effects of antenatal magnesium sulphate in women at imminent preterm delivery. All pregnancies that are at risk of premature delivery shall be given an intravenous infusion of magnesium sulphate over 24 hrs. It is given as a loading dose of 4 g slow IV over 5 minutes followed by 1 g/ hour infusion for 24 hrs. Magnesium sulphate is a weak tocolytic. It is very efficient in preventing cerebral palsy in preterm newborns (RR 0.70, 95% CI 0.55–0.89). It also has a neuroprotective role in preventing intra-ventricular haemorrhage.

#### **5.4 Tocolysis**

Preterm labour being the most common complication with multiple pregnancy, it is essential to provide tocolysis to the patient at least to have antenatal steroid cover for 48 hrs. This would improve neonatal neurological and respiratory outcomes. The most effective tocolysis available is Atosiban, which is an oxytocin antagonist and should be the first choice of drug. It is started as a 0.9 ml (6.75MG) loading dose intravenous and followed by a high-dose infusion of 300 mcg per minute for 3 hrs. This is followed by a low-dose maintenance infusion of 100 mcg per minute for the next 45 hrs. The total dose infused shall not exceed 330.75 mg. The second-best drug for tocolysis is nifedipine given as a loading dose of 30–40 mg followed by 10 mg sixth hourly. Nifedipine being a calcium channel blocker relaxes the smooth muscle of the uterus and induces tocolysis. The main aim of tocolysis is to safely transfer the mother to a tertiary care centre well equipped for multiple gestation and preterm newborn care and also to allow for the antenatal steroid prophylaxis to act. Hence, it should not be prolonged for more than 48 hrs. Tocolysis should be weighed against the maternal risks of sepsis and pulmonary oedema before continuing the therapy.

#### **6. Delivery plan**

It is essential to have institutional deliveries for all multiple pregnancies. The centre should be well equipped for emergency Caesarean facilities, blood bank, tertiary NICU care, and a multidisciplinary team involving intensivists, physicians, endocrinologists, and foetal medicine consultants. The timing of delivery is crucial to optimise the neonatal outcomes. The mode of delivery again should be individualised, and the main deciding factor is the foetal presentation (**Table 3**).

#### **6.1 Intrapartum monitoring**

Monitoring twin foetuses in labour can be difficult at times. They should be monitored with twin foetal heart probes to avoid the same foetal heart being traced twice on cardiotocography. Always perform a portable ultrasound bedside to ascertain the presentation at the start of labour.

#### **6.2 Post-partum period**

There is more incidence of post-partum haemorrhage in these women, mainly due to an overdistended uterus in pregnancy. The obstetric team should be prepared with oxytocics, blood and blood products at the time of delivery to efficiently manage it. Active management of the third stage of labour should be routinely done in all women to reduce the incidence of haemorrhage.

#### **6.3 Breastfeeding**

It can be a challenge with respect to demand in twin and triplets gestation. Most of these babies are born prematurely with poor suckling or latching, and hence, there can be difficult establishing the feeding. More so many of these babies stay in the NICU in the initial few days or weeks when rooming in and breastfeeding could be difficult to establish. As suckling is the most important stimulus for further breast milk production, when the baby is away from the mother breastfeeding establishment becomes a challenge. Feeding both babies simultaneously is another technique to increase the milk output in the mother.


#### **Table 3.**

*Recommended time table for delivery of multiple pregnancies.*

#### **7. Conclusion**

Multiple pregnancy is a high-risk pregnancy to be always managed by an efficient and experienced multidisciplinary team. Foetal reduction is an option to be explained to all couples with multiple pregnancy to reduce the neonatal and childhood morbidity. Foetal reduction is more common in LMIC countries than in developed world because of the higher morbidity and cost of healthcare associated with multiple pregnancies.

### **Author details**

R. Kishore Kumar1,2\* and B.R. Usha3

1 Senior Consultant Neonatologist and Paediatrician, Cloudnine Hospitals, Bangalore, India

2 Adjunct Professor in Neonatology and Paediatrics, Notre Dame University, Perth, Australia

3 Consultant Obstetrician, Gynaecologist and Laparoscopic Surgeon Cloudnine Hospitals, Jayanagar, Bangalore, India

\*Address all correspondence to: drkishore@cloudninecare.com

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

#### **References**

[1] El-Toukhy T, Bhattacharya S, Akande V. A on behalf of the Royal College of Obstetricians and Gynaecologists. Multiple pregnancies following assisted conception. Scientific Impact Paper No. 22. BJOG. 2018

[2] Madan A, Meena JKS, Puri A. Maternal and fetal outcome in multiple pregnancy. International Journal of Health and Clinical Research. 2020;**3**(12):221-226

[3] Kumari K, Mishra M, Jhanwar A, Kumari A. Fetomaternal outcome in twin pregnancies: A retrospective analysis from a tertiary care centre. Journal of Clinical and Diagnostic Research. 2020;**14**(7):QC01-QC05

[4] Yadav N, Alwani M, Singh A. Incidence and perinatal outcome of multiple pregnancy in a tertiary care centre in Central India. International Journal of Reproduction, Contraception, Obstetrics and Gynecology. 2018;**7**(5):1912-1917

[5] Upreti P. Twin pregnancies: Incidence and outcomes in a tertiary health centre of Uttarakhand, India. International Journal of Reproduction, Contraception, Obstetrics and Gynecology. 2018;**7**(9):3520-3525

[6] Beriwal S, Impey L, Ioannou C. Multifetal pregnancy reduction and selective termination. The Obstetrician & Gynaecologist. 2020;**22**:284-292. Available from: https://obgyn.onlinelibrary.wiley. com/doi/10.1111/tog.12690

[7] Lee JR, Ku S-Y, Jee BC, Suh CS, Kim KC, Kim SH. Pregnancy outcomes of different methods for multifetal pregnancy reduction: A comparative study. Journal of Korean Medical Science 2008;**23**:111-116. The Korean Academy ISSN 1011-8934 of Medical Sciences. DOI: 10.3346/jkms.2008.23.1.111

[8] Antenatal management of multiple pregnancies: NICE guidelines. March 2013

[9] Rouse, Dwight. Beneficial effects of antenatal magnesium sulfate (BEAM Trial)

## **Chapter 3** Types of Multiple Pregnancy

*Tshililo Mashamba*

#### **Abstract**

Multiple pregnancy is condition where more than one offsprings are formed. This result from either fertilization of more than one ovum individually by separate sperms or division of fertilized ovum. The implantation sites may be in different part of the genital organs and even the peritoneal cavity. The physiology of monozygotic multiple pregnancy is not fully understood as the trigger has not yet been identified. The incidence of multiple pregnancy is increasing, and this is as a result of assisted reproductive technologies.

**Keywords:** multiple pregnancy, dichorionic, monochorionic, twin, heretopic

#### **1. Introduction**

Multiple pregnancy refers to a pregnancy with more than one embryo. The embryos may grow in the same uterine pregnancy as a result of either two or three separate ova were fertilized or one ovum fertilized, and the embryo divided two or more embryos developed. Where two or more ova are fertilized individually the resultant pregnancy is called dizygous if two ova were fertilized and multizygous multiple pregnancy if three or more ova were fertilized. The implantation site also determines the naming of the type of multiple pregnancy. The dizygous or multizygous multiple pregnancies result in each embryo having its own placenta and amniotic sac and are independent of each other. Where one ovum is fertilized, and the embryo divides it is called monozygous multiple pregnancy. Zygosity is the degree of identity in the genome.

The incidence of multiple pregnancy is increasing as a result of increasing use of assisted reproductive technology [1, 2]. Twin pregnancy account for 2–4% of the total number of births. Spontaneous twin pregnancy rates vary worldwide [3]. The incidence of higher order multiple pregnancy is not fully reported but there are lot of case reports noted. The incidence of triplet pregnancies has been estimated to be one in thousand pregnancies [4]. Different types of multiple pregnancy will be discussed.

#### **2. Dizygous multiple pregnancy**

Dizygotic multiple pregnancy is derived from fertilization of two ova by two sperms and they may be of same sex or different sex. Their genetic composition is different because it comes from different ova and different sperms. These are just two siblings in the same patient. Dizygotic multiple pregnancy contributes two thirds of all multiple pregnancies. The implantation may be at the same site or different sites. Each of the embryo has its own chorion (placenta) and amniotic membrane as in **Figure 1**. They are also called fraternal multiple pregnancy [5]. Fertilization may occur during the same sexual activity or different sexual activities during the same


#### **Table 1.**

*Subtypes of multiple pregnancy.*

menstrual cycle. Fertilization of the second ovum during different sexual exposure is called superfecundation. This means that fertilization of the ovum when there is an existing early embryo. If fertilization of the second ovum and implantation occurs in subsequent menstrual cycle, this is superfetation. Upregulation of hypothalamicpituitary-ovarian axis by luteal progesterone and then placental progesterone in the first trimester of pregnancy suppresses ovulation and makes the possibilities of superfetation unlikely [5, 6]. The physiology of superfetation is not well understood.

#### **3. Intra uterine dizygotic multiple pregnancy**

Implantation of all the embryos inside the endometrial cavity. This is the most common type of all multiple pregnancies. There may be two or more fetuses. The naming of the subtype depends on the number of fetuses (see **Table 1**).

#### **4. Dicavitary multiple pregnancy**

This is a type of multiple pregnancy occurring in a woman with embryological developmental malformation of the Mullerian or Wolffian ducts, characterized by complete failure of Mullerian ducts to fuse, resulting in two separate uterine cavities and cervices (**Figures 2** and **3**). There may associated vaginal anomalies like septum which may be longitudinal or transverse [7]. The anomalies may of different degrees with either fully developed or under developed and each with separate fallopian tube and endometrial cavity [8, 9]. Both uterine horns achieve a pregnancy at the same time when double ovulation has taken place (**Figure 4**). This only follows dizygotic multiple pregnancy and not possible with monozygotic pregnancy.

#### **5. Heterotopic pregnancy**

This refers to the occurrence of two pregnancies in different implantation sites simultaneously, mostly manifested as intrauterine and ectopic pregnancies 9ampullary in 80%). Heterotopic pregnancy is rare and estimated to occur in about 1 per

**Figure 2.** *Uterine didelphus.*

**Figure 3.** *Uterine anomaly.*

**Figure 4.** *Pregnancy on each uterus.*

30,000 (0.006%–0.001%) spontaneous pregnancies while a higher prevalence may occur in assisted reproductive techniques that may reach up to 1 case per 100 cases (1–3%) (**Figure 5**) [10, 11].

**Figure 5.** *Heterotopic oregnancy.*

**Figure 6.** *Different sites for heterotopic pregnancy.*

Another rare combination of heterotopic pregnancy is a combination of intrauterine and ovarian [12]. The occurrence of an ovarian heterotopic pregnancy is a singular event as it comprises only 2.35 of all heterotopic pregnancies. However, in the last decade there has been a significant increase of ectopic pregnancy and subsequent increase in heterotopic pregnancy. This increase has been attributed to higher incidence of pelvic inflammatory disease and the extended use of assisted reproductive technologies [12]. The implantation outside the endometrial cavity can be anywhere including any part of the fallopian tube, ovary and any part of peritoneal cavity as indicated on **Figure 6**.

#### **6. Twin ectopic pregnancy**

In ectopic pregnancy, the implantation occurs outside the uterine cavity post fertilization, either in singleton or multi-gestational ectopic pregnancy. The incidence of twin ectopic pregnancies is quite rare and is estimated to be 1 in 125,000

**Figure 7.** *Twin ectopic pregnancy.*

pregnancies and that of twin tubal pregnancies to be 1 in 200 ectopic pregnancies (**Figure 7**) [13–15].

#### **7. Monozygotic multiple pregnancy**

Monozygotic (MZ) twins, also called identical twins, occur when a single egg cell is fertilized by a single sperm cell. The resulting zygote splits into two very early in development, leading to the formation of two separate embryos. MZ twins occur in 3–4 per 1000 births worldwide. Research suggests that most cases of MZ twinning are not caused by genetic factors. However, a few families with a larger-than-expected number of MZ twins have been reported, which indicates that genetics may play a role. It is possible that genes involved in sticking cells together (cell adhesion) may contribute to MZ twinning, although this hypothesis has not been confirmed. Most of the time, the cause of MZ twinning is unknown [16].

The theory proposes that monozygotic twin are formed when the blastocyst contains two inner cell masses, each of which lead to a separate fetus rather than by the embryo splitting while hatching from the zona pellucida. Monozygotic twins may be created artificially by embryo splitting. Monozygotic twins are genetically nearly identical and are always of the same sex unless there has been a mutation during development [16]. The timing of the division determines the chorionicity and amnionicity. Chorionicity refers to the placenta and amnionicity to amniotic sac on whether they are shared by the twins or not as indicated on **Figure 8**.

When the division occurs within 3 days of fertilization, a dichorionic twin pregnancy results, when the division occurs between 4 and 8 days a monochorionic diamniotic twin pregnancy develops and when division occurs from day 8 until day 12 or 13 the monochorionic mono amniotic twin pregnancy develops. After day 13 the division leads to conjoined twins. All this means is that the placenta is determined within 3 days otherwise no further division could take place after this period in regard to the placenta. Amniotic sac is determined between day 4 and day 8 after fertilization and complete fetal division within 12–13 days [17].

#### **Figure 8.**

*Dichorionic diamniotic multiple pregnancy from monozygotic twins.*

Monozygotic multiple pregnancies are not genetically inherited. The twinning is random, due to the splitting of the embryo, so all parents have equal chance of conceiving these types of twins [18]. The rate of monozygotic twins is 2,25 times higher in assisted conceptions than natural conceptions. Monozygotic twins have a chorionicity that relates to how early the fertilized egg divides. Of the live born twins 70–75% are monochorionic diamniotic, 25–30% are dichorionic diamniotic and 1% are monochorionic monoamniotic [19, 20].

Division of the fertilized ovum occurs within 3 days. Placental development is independent of each other, though genetic material is identical. This constitutes 25 to 30 percent of monozygotic twins [19].

#### **8. Monochorionic diamniotic multiple pregnancy**

This is the commonest type of twin pregnancy arising from monozygotic multiple pregnancy as its occurrence is 70–75%. The fetuses share a placenta but have different amniotic sacs. The division takes place between 4 and 8 days after fertilization. Overall 1 in 3 spontaneous twins or 1 in 300 pregnancies become monochorioninic diamniotic.

#### **9. Monochorionic monoamniotic twins**

This is the least common type of multiple pregnancies as it is just around 1% of all monochorionic multiple pregnancies. This type of multiple pregnancy is associated the highest rate of congenital anomalies starting with vascular malformation to conjoined twins.

#### **10. Conclusion**

Multiple pregnancy refers to conception with more than one embryo. There are different types of multiple pregnancy depending on the site of implantation and the number of embryos. Multiple pregnancy can develop from fertilization of more than one embryo (dizygotic) or from division of a single fertilized embryo (monozygotic). Dizygotic embryos have different genetic makeup while monozygotic embryos have almost the same genetic makeup unless mutation has taken place during development. Dizygotic multiple pregnancy is more common than monozygotic pregnancies because of assisted reproductive technology. The division of the embryo is guided by the time of division to achieve a particular type of monozygotic multiple pregnancy. Monochorionic multiple pregnancy is the commonest type of monozygotic multiple pregnancy compared to dichorionic and monoamniotic types.

#### **Author details**

Tshililo Mashamba Department of Obstetrics and Gynaecology, Sefako Makgatho University Pretoria, South Africa

\*Address all correspondence to: tjmashamba@yahoo.com

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

#### **References**

[1] Yayla M, Baytur Y. Multicentric multiple pregnancy study 1-Epidemiology. Perinatal Journal. 2008;**16**

[2] Mackie F, Morris R. Multiple gestation: Biology and epidemiology. Global Library Women. 2016;**40**:1756-2228

[3] Santana DS, Surita FG, Cecatti JG. Multiple pregnancy: Epidemiology and association with maternal and perinatal morbidity. Revista Brasileria de Ginecologia Obstetricia. 2018;**40**:554-562

[4] Smith LK, Manktelow BN, Draper ES, et al. Trends in the incidence and mortality of multiple births by socioeconomic deprivation and maternal age in England: Population-based cohort study. BMJ Open. 2014;**4**:e004514. DOI: 10.1136/bmjopen-2013-004514

[5] Painter JN, Hall JG. Twins and twinning. In: Emery and Rimoin's Principles and Practice of Medical Genetics. 2013

[6] Umstad MP, Craig JM. Superfetaion. In: Emery and Rimoin's Principles and Practice of Medical Genetics. 2019

[7] Al Yaqoubi HN, Fatema N. Successful vaginal delivery of naturally conceived dicavitary twin in didelphus uterus: A rare reported case. Hindawi Case Reports in Obstetrics and Gynecology. 2017

[8] Doruk A, Gozukara I, Burkaş G, Bilik E, Dilek TUK. Spontaneous twin pregnancy in uterus bicornis unicollis. Case Reports in Obstetrics and Gynecology. 2013;**2013**:3. Article ID: 834952

[9] Ilyas M, Dar M, Rafiq S, Khan I. Twin pregnancy in bicornuate uterus-one fetus in each horn. Journal of Fetal Medicine. 2018;**5**. DOI: 10.1007/s40556-018-0156-4

[10] Ali T, Tawab MA, ElHariri MAG, Ayad AA. Hetrotopic pregnancy: A case report. Egyptian Journal of Radiology and Nuclear Medicine. 2020;**51**:214

[11] Nabi U, Yousaf A, Ghaffar F, Salid S, Ahmed MMH. Heterotopic pregnancy—A diagnostic challenge. Six case reports and literature review. Cureus. 2019;**11**:11

[12] Basile F, Cesare DC, Quagliozzi L, Donati L, Bracaglia M, Caruso A, et al. Spontaneous heterotopic pregnancy simultaneous ovarian and intrauterine: A case report. Case Reports in Obstetrics and Gynecology. 2012. Article ID: 509694

[13] Madaan S, Jaiswal A, Banode P, Dhok A, Dewani D. Spontaneous twin ectopic pregnancy managed successfully with methotrexate-mediated ultrasound guided fetal reduction: A fertilitypreserving approach. Cureus. 2021;**13**(8)

[14] Rolle CJ, Wai CY, Bawdon R, Santos-Ramos R, Hoffman B. Unilateral twin ectopic pregnancy in a patient with a history of multiple sexual transmitted infections. Infectious Diseases in Obstetrics and Gynecology. 2006:1-3

[15] Seak CJU, Goh ZNL, Wong AC, Seak JCY, Seak CK. Unilateral live twin tubal ectopic pregnancy presenting at 12 weeks of gestation. Medicine. 2019;**98**:38

[16] Available from: https://en.wikipedia. org/wiki/Twin

[17] Chitkara U, Berkowitz RL. Multiple Gestations, Obstetrics, Normal and Problem Pregnancies. 4th ed. 2002

[18] de Bellefonds C. Are Twins Hereditary? 2021. Retrieved from: https://www.whattoexpect.com/ pregnancy/twins-and-multiples/ do-twins-really-run-in-families/

[19] Visintin C, Mugglestone MA, James D, Kilby MD, Guideline Development Group. Antenatal care for twin and triplet pregnancies: Summary of NICE guidance. BMJ (Clinical Research ed.). 2011;**343**:d5714. DOI: 10.1136/bmj.d5714

[20] Robinson J, Peat B, Dodd J, Atkinson E. South Australian Perinatal Practice Guideline: Twin pregnancy. 5th ed. 2014

## **Chapter 4** Multiple Gestation

*Mandefro Yilma Asfaw*

#### **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.

**Keywords:** multiple pregnancy, chorionicity, zygosity, antenatal care, morbidity, mortality

#### **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 higherorder 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.

	- I.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.
	- II.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.
	- III.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.
	- IV.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.


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]:


#### **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].


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


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.


## **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.


## **10. Perinatal morbidity and mortality related to multiple pregnancies**

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


*Multiple Gestation DOI: http://dx.doi.org/10.5772/intechopen.104836*


#### **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 [1–3].

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.


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


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].

*Multiple Gestation DOI: http://dx.doi.org/10.5772/intechopen.104836*

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]:


#### **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:


#### **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 Gestation DOI: http://dx.doi.org/10.5772/intechopen.104836*

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.

I.Mode of delivery in diamniotic twins


II.Monoamniotic twins–cesarean delivery

III.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**



## **Author details**

Mandefro Yilma Asfaw Hawassa University, Ethiopia

\*Address all correspondence to: ymande23@gmail.com

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

#### **References**

[1] Cunningham, Leveno, Bloom, Dashe, Hoffman, Casey, Sheffield. Multifetal Pregnancy. In: Cunningham FG, Leveno KJ, Bloom SL, Spong CY, Dashe JS, Hoffman BL, Casey BM, Sheffield JS, editors. Williams Obstetrics. 24th ed. 2014. pp. 891-920

[2] Newman RB and Unal ER. Multiple gestations. In: Gabbe, Niebly, Simpson, Landon, Galan, Jauniaux, Driscoll, Berghella, Grobman, editors. Obstetrics Normal And Problem Pregnancies. 7th ed. 2017. pp. 706-733

[3] Moore TR. Multifetal gestation and malpresentation. In: Hacker, Moore, Gambone, editors. Essentials of Obstetrics and Gynecology. 4th ed. 2007. pp. 183-188

[4] Dutta DC. Multiple pregnancy, amniotic fluid disorders, abnormalities of placenta and cord. In: Konar H, editors. DC Dutta's Textbook of Obstetrics including Perinatology and Contraception. 8th ed. 2015. pp. 233-245

[5] Bush MC and Pernoll ML. Multiple gestation. In: Dechrney AH, Nathan L, Laufer N and Roman AS, editors. Current Diagnosis and Treatment –Obstetrics and Gynecology. 11th ed. 2013. pp. 301-309

[6] Benirschke K. Multiple gestation: The biology of twinning. In: Creasy RK, Resnik R, Iams JD, Lockwood CJ, Moore TR, Greene MF, editors. Creasy and Resnik's Maternal-Fetal Medicine. 7th ed. 2014. pp. 53-65

[7] Newman RB and Rittenberg C. Multiple gestation. In: Gibbs RS, Karlan BY, Haney AF, Nygaard IE, editors. Danforth's Obstetrics and Gynecology. 10th ed. 2008. pp. 221-244

Section 2
