2. Medical issues associated to twin pregnancy and twin birth

increase in the female employment rate. There is evidence indicating that the incidence of twin pregnancies is known to rise with mother's age [3]. This pattern has been attributed both to an increase in the level of gonadotropins with the age and to the rise of medically assisted

This extraordinary growth in twinning rates in different developed countries must be considered as an important public health issue since twin pregnancies are generally associated with greater risk for both infants and mothers. Twin babies are more fragile, have lower birth weight and born preterm more often than singleton babies. In addition, many of the risks to the mother are also risks to the child-to-be, since they can lead to premature labor, complications or, in the worst cases, fetal death. For these reasons, twin babies are more frequently admitted to neonatal intensive care units (NICUs) and subjected to more prolonged hospitalization with potential negative effects both on infants and parental behavior. Other complications for the mother are

Moreover, twin births can have negative effects on parents' adjustment as well. In fact, although it is possible to identify similarities in pregnancy and parenthood for twin and singleton births, the experience of expecting and parenting twins seems to be very different [4]. The responses to a multiple pregnancy and parenthood by most of the parents may be associated with ambivalence and surprise, even if the pregnancy resulted from infertility treatment [5], as well as with higher levels of anxiety, distress and higher risk of depression in the postpartum period both in the case of twins conceived naturally and in the case of twins conceived with ART [4, 6]. In addition, due to the medical risk associated, twin pregnancies need to be closely monitored [7, 8]. On one hand, this frequent and intensive monitoring could reassure parents, but, on the other, it constantly reminds them that their pregnancies could be associated with serious risks for the babies and the mothers. Different researches tried to evaluate the association between the presence of mood disorders and stress in parents and twin pregnancies. Researchers that focused on parental experience associated to twin pregnancy that occurs both naturally or with ART investigated either the joint experience of mothers and fathers [9–12] or of mothers alone [13–16]. It was observed that the risks usually associated to twin pregnancy lead to higher level of stress [17] and seemed to increase the incidence of depression and anxiety in parents of twins and especially in mothers [6, 9–11, 16, 18]. In addition, it was also observed that the presence of medical risk as well as psychological suffering in mothers during twin pregnancy is generally associated to higher level of fatigue,

gestational diabetes, hypertension, preeclampsia and acute polyhydramnios.

loss of energy, depressed mood and feelings of worthlessness and guilt [14].

Another important aspect related to the mothers' psychological adjustment during twin pregnancies is related to the building process of the relationship between the mother and the childto-be [19]. During pregnancy, mothers use to think about their child-to-be, and they start to create representation of themselves as mothers. During twin pregnancies, the mother-to-be has to deal with an identification process with two children at the same time and have to create a mental space that allow her to make representation of both children. These processes include representations of physical and emotional characteristics of two different fetuses and of the interactions between the mother and her future babies, as well as dreams and expectations about both the children-to-be. For these reasons, it is possible to infer that the building process

reproductive technologies (ART) among older women.

82 Multiple Pregnancy - New Challenges

#### 2.1. Twin pregnancy: fertilization, intrauterine growth and associated fetal risk factors

Twin pregnancy can be the result of multiple ovulations with fertilization of any oocyte by a sperm and in that case we have dizygotic twins (DZ) or a consequence of the fertilization of an oocyte by a sperm with subsequent division of the single zygotes and in this case we will have monozygotic twins (MZ). All DZ pregnancies are dichorionic (two placentas) and diamniotic (two amniotic cavities). MZ pregnancies, in relation to the gestational age in which the division into two embryos occurs, may be dichorionic and diamniotic (about 1/3 of the cases) if the division takes place between the first and the third day of gestation or monochorionic (single placenta) and diamniotic (about 2/3 of cases) if the division takes place between the fourth and the eighth day of gestation. Finally, the division could rarely occur between the ninth and the thirteenth day of gestation, resulting in monochorionic monoamniotic pregnancy (about 1% of the MZ pregnancies). Overall, DZ twins represent 70% of twin pregnancies and MZ twins represent 30% [20, 21]. From the genetic point of view, DZ twins (fraternal twins) can be assimilated to natural brothers, while MZ twins (identical twins) have always been thought to have the same genetic heritage. However, epigenetic alterations and environmental factors may be responsible for different phenotypic expressions at physical, neuropsychological and behavioral levels, in the absence of variations in the genetic sequence.

In twin pregnancies, it is essential to define if twins share or not placenta as soon as possible. Chorionicity determination in the first trimester is almost 100% accurate [20]. The most reliable signs to determine chorionicity are the number of gestational sacs between 7 and 10 weeks of gestation and the presence of lambda sign (a subtle triangular strip of cortical tissue separating the two placenta) between 11 and 14 weeks of gestation [21, 22]. The determination of chorionicity is particularly important from a clinical and prognostic point of view, since monochorionic (MC) twin pregnancies are complicated by an incidence of 10–15% of twin-to-twin transfusion syndrome (TTTS). TTTS is a chronic midtrimester complication of MC twin pregnancies that causes significantly higher perinatal mortality and morbidity rates in monochorionic than in dichorionic twins [23]. MC twins share their placenta and their blood circulation is connected by vascular anastomoses at the placenta surface. Placenta vascular anastomoses allow acute or chronic inter-twin blood transfusions between the circulations of the two fetuses. Imbalanced inter-twin blood flow can lead to a severe complication such as TTTS. In TTTS, imbalanced blood flow from one twin (the donor) to the other twin (the recipient) results in hypovolemia and oligohydramnios in the donor and hypervolemia and polyhydramnios in the recipient twins with transient or persistent right ventricular hypertrophy [24].

Another important issue related to twin pregnancy concerns fetal growth. In single pregnancies, progressive and linear fetal growth is observed until the 37th week of gestation, whereas in twin pregnancies the overlap is observed with single pregnancy only in the first two trimesters. Recent data from an Italian sample compared the twin birth weight curves with those of single birth ones, indicating differences in 3, 50 and 97 percentiles, starting from 32 weeks of gestational age and increasing according to gestational age: at 37 weeks, twins' weight differs by about 9% compared to single babies' weight. Similar differences were observed for length, whereas for the cranial circumference differences occur later, around the 36 weeks of gestation [25]. Fetal growth depends on fetal genetic inheritance and on factors related to the uterine-placental development environment that can impair placental circulation with fetal hypoperfusion. The anomalies in placental circulation establish a high risk of fetal hypoxia and reduced amount of nutrients (e.g. glucose and amino acids) essential for fetal growth. In the case of twin pregnancies and in the absence of genetic-metabolic fetal abnormalities, a proper maternal nutritional input is crucial for proper development. From a physiological point of view, twin pregnancy provides, compared to single pregnancy, an estimated weight gain of 3.5 kg higher. Although the weight is different, the feeding regime to follow is similar in both types of pregnancy. Neonatal weight of twins also depends on their zygosis and chorionicity. MZ twins weigh less than DZ twins and MC twins weigh less than dichorionic twins (DC). Intrauterine growth is also negatively influenced by IVF with multiple embryo transfer. Also during TTTS, it is common that the donor twin weighs 25% less than the other twin. Another situation defined as selective intrauterine growth restriction (sIUGR) could lead to a high risk of intrauterine death or extreme prematurity [24, 26].

[7] while, since risks are significantly higher in monochorionic compared with dichorionic pregnancy [8], antenatal assessment should be scheduled more often, usually every 15 days or less when decided by the gynecologists, in order to prevent adverse perinatal outcomes

Prenatal Attachment in Twin Pregnancy http://dx.doi.org/10.5772/intechopen.79365 85

Moreover, since twin pregnancies are associated with an increase in mortality and morbidity rates, a careful planning of delivery and adequate neonatal care in the delivery room are needed [21]. It has long been recognized that the timing of delivering twins constitutes a significant issue [34]. Despite in high-risk pregnancies there is the temptation to be reassured by increasing gestational age as the potential complications of prematurity, different studies suggest that the offspring of a twin gestation may benefit from delivering prior to their expected date of delivery [35, 36]. Several studies have focused on the "prospective risk of foetal death" to help determine by which gestational age a twin pregnancy should be delivered [37]. For twins, the prospective risk of fetal death appears to be equivalent to that of post-term singletons at about 37–38 weeks of gestation [35, 37]. The prospective risk of fetal death for twins intersects with neonatal death at about 39 week of gestation, showing that it may be reasonable to consider delivery of uncomplicated twins before 40 weeks of gestation [36]. These studies, however, did not address the impact of chorionicity on the decision to deliver a twin pregnancy. Other research focused on this aspect, indicating that in the case of dichorionic and diamniotic twin pregnancies, delivery should be scheduled from 38 weeks, while in uncomplicated monochorionic twins delivery should be

Additionally, obstetrics and gynecologists broadly recognized that the delivery of twins constitutes an area of significant risk [34]. Perinatal mortality is five times higher in twins than in singletons [39]. In fact, the conduct of a twin delivery remains one of the most challenging events in the daily practice of obstetrics [34]. In particular, an important issue related to twin birth is associated with the choice of the mode of delivery. Although approximately 60% of twins are delivered by cesarean section [40], choosing the mode of delivery, spontaneous or cesarean, depends on multiple factors linked to both maternal and fetal characteristics [21]. Spontaneous delivery is generally used when both twins are vertex at the moment of childbirth. However, in this case, ultrasonographic examination is a useful adjunct after delivery of the first twin in order to establish the presentation of the second twin. In fact, after the delivery of the first twin, up to 20% of the second baby spontaneously changes presentation [41]. This emphasizes that, in case of a vaginal delivery in twin pregnancy, it is necessary to monitor all the process since the situation can rapidly change from a relatively low-risk delivery to one fraught with complications for mother and baby [34]. As regards the choice of cesarean delivery, there are few absolute indications to planned cesarean section. It seems that cesarean section without a trial of labor should be performed in cases of monoamniotic twins. The other indications are not dissimilar to those of a singleton pregnancy and include placenta previa and antenatal evidence of significant fetal compromise (e.g. severe selective IUGR) likely to worsen during labor. In addition, Cesarean section is generally the recommended method of

Twin delivery constitutes a challenge in daily obstetric practice, which becomes even more difficult in cases with preterm birth, the main perinatal risk factors associated with twin pregnancy [43]. Advancement of gestational age is crucial to achieve acceptable fetal growth

associated to this type of twin pregnancy.

scheduled from 36 weeks of gestation [22, 38].

delivery in twin gestations when one twin is non-vertex [42].

The presence of discordant anomalies, which occur more frequently in elderly women with twins, is another important risk factor. In fact, it is well documented that, if discordant anomaly is noted, the likelihood of adverse outcomes both for the discordant twin and for the normal twin is increased [27, 28]. Particularly, it was observed that the presence of discordant anomalies is significantly associated with preterm birth, lower birth weight, IUGR and neonatal and infant death. Moreover, it was observed that discordant twins showed higher physiological and behavioral dysregulation [29, 30].

Finally, an additional factor for fetal risk concerns the phenomenon of the "vanishing twin." Early prenatal ultrasound for fetal monitoring has shown that at 8 weeks of gestation the incidence of multiple pregnancies is 3.3–4.5% that spontaneously evolves in single pregnancy in 21–30% of cases, after the reabsorption of an embryo by the placenta or of the other twin. This event is a potential risk factor for the development of complications in the surviving fetus [31]. Data from the Danish nationwide registers have demonstrated that IVF singleton babies born from vanished twin pregnancies had higher rates of small for gestational age (SGA) and term low birth weight (LBW) compared with IVF singleton pregnancies [32]. Furthermore, studies have noted an association with cerebral palsy in IVF children when the number of gestations at delivery was less than the number of embryos transferred compared with pregnancies in which the number of gestations at delivery was the same as the number of embryos transferred [33].

#### 2.2. Twin delivery and perinatal risk factors

In twin pregnancies, antenatal care involves more intensive monitoring and protocols that are usually different to those for a singleton pregnancy. Ultrasound assessment of fetal biometry, anatomy and Doppler velocimetry is used to monthly monitor dichorionic twin pregnancies [7] while, since risks are significantly higher in monochorionic compared with dichorionic pregnancy [8], antenatal assessment should be scheduled more often, usually every 15 days or less when decided by the gynecologists, in order to prevent adverse perinatal outcomes associated to this type of twin pregnancy.

in twin pregnancies the overlap is observed with single pregnancy only in the first two trimesters. Recent data from an Italian sample compared the twin birth weight curves with those of single birth ones, indicating differences in 3, 50 and 97 percentiles, starting from 32 weeks of gestational age and increasing according to gestational age: at 37 weeks, twins' weight differs by about 9% compared to single babies' weight. Similar differences were observed for length, whereas for the cranial circumference differences occur later, around the 36 weeks of gestation [25]. Fetal growth depends on fetal genetic inheritance and on factors related to the uterine-placental development environment that can impair placental circulation with fetal hypoperfusion. The anomalies in placental circulation establish a high risk of fetal hypoxia and reduced amount of nutrients (e.g. glucose and amino acids) essential for fetal growth. In the case of twin pregnancies and in the absence of genetic-metabolic fetal abnormalities, a proper maternal nutritional input is crucial for proper development. From a physiological point of view, twin pregnancy provides, compared to single pregnancy, an estimated weight gain of 3.5 kg higher. Although the weight is different, the feeding regime to follow is similar in both types of pregnancy. Neonatal weight of twins also depends on their zygosis and chorionicity. MZ twins weigh less than DZ twins and MC twins weigh less than dichorionic twins (DC). Intrauterine growth is also negatively influenced by IVF with multiple embryo transfer. Also during TTTS, it is common that the donor twin weighs 25% less than the other twin. Another situation defined as selective intrauterine growth restriction (sIUGR) could lead

The presence of discordant anomalies, which occur more frequently in elderly women with twins, is another important risk factor. In fact, it is well documented that, if discordant anomaly is noted, the likelihood of adverse outcomes both for the discordant twin and for the normal twin is increased [27, 28]. Particularly, it was observed that the presence of discordant anomalies is significantly associated with preterm birth, lower birth weight, IUGR and neonatal and infant death. Moreover, it was observed that discordant twins showed higher physio-

Finally, an additional factor for fetal risk concerns the phenomenon of the "vanishing twin." Early prenatal ultrasound for fetal monitoring has shown that at 8 weeks of gestation the incidence of multiple pregnancies is 3.3–4.5% that spontaneously evolves in single pregnancy in 21–30% of cases, after the reabsorption of an embryo by the placenta or of the other twin. This event is a potential risk factor for the development of complications in the surviving fetus [31]. Data from the Danish nationwide registers have demonstrated that IVF singleton babies born from vanished twin pregnancies had higher rates of small for gestational age (SGA) and term low birth weight (LBW) compared with IVF singleton pregnancies [32]. Furthermore, studies have noted an association with cerebral palsy in IVF children when the number of gestations at delivery was less than the number of embryos transferred compared with pregnancies in which the number of gestations at delivery was the same as the number of embryos transferred [33].

In twin pregnancies, antenatal care involves more intensive monitoring and protocols that are usually different to those for a singleton pregnancy. Ultrasound assessment of fetal biometry, anatomy and Doppler velocimetry is used to monthly monitor dichorionic twin pregnancies

to a high risk of intrauterine death or extreme prematurity [24, 26].

logical and behavioral dysregulation [29, 30].

84 Multiple Pregnancy - New Challenges

2.2. Twin delivery and perinatal risk factors

Moreover, since twin pregnancies are associated with an increase in mortality and morbidity rates, a careful planning of delivery and adequate neonatal care in the delivery room are needed [21]. It has long been recognized that the timing of delivering twins constitutes a significant issue [34]. Despite in high-risk pregnancies there is the temptation to be reassured by increasing gestational age as the potential complications of prematurity, different studies suggest that the offspring of a twin gestation may benefit from delivering prior to their expected date of delivery [35, 36]. Several studies have focused on the "prospective risk of foetal death" to help determine by which gestational age a twin pregnancy should be delivered [37]. For twins, the prospective risk of fetal death appears to be equivalent to that of post-term singletons at about 37–38 weeks of gestation [35, 37]. The prospective risk of fetal death for twins intersects with neonatal death at about 39 week of gestation, showing that it may be reasonable to consider delivery of uncomplicated twins before 40 weeks of gestation [36]. These studies, however, did not address the impact of chorionicity on the decision to deliver a twin pregnancy. Other research focused on this aspect, indicating that in the case of dichorionic and diamniotic twin pregnancies, delivery should be scheduled from 38 weeks, while in uncomplicated monochorionic twins delivery should be scheduled from 36 weeks of gestation [22, 38].

Additionally, obstetrics and gynecologists broadly recognized that the delivery of twins constitutes an area of significant risk [34]. Perinatal mortality is five times higher in twins than in singletons [39]. In fact, the conduct of a twin delivery remains one of the most challenging events in the daily practice of obstetrics [34]. In particular, an important issue related to twin birth is associated with the choice of the mode of delivery. Although approximately 60% of twins are delivered by cesarean section [40], choosing the mode of delivery, spontaneous or cesarean, depends on multiple factors linked to both maternal and fetal characteristics [21]. Spontaneous delivery is generally used when both twins are vertex at the moment of childbirth. However, in this case, ultrasonographic examination is a useful adjunct after delivery of the first twin in order to establish the presentation of the second twin. In fact, after the delivery of the first twin, up to 20% of the second baby spontaneously changes presentation [41]. This emphasizes that, in case of a vaginal delivery in twin pregnancy, it is necessary to monitor all the process since the situation can rapidly change from a relatively low-risk delivery to one fraught with complications for mother and baby [34]. As regards the choice of cesarean delivery, there are few absolute indications to planned cesarean section. It seems that cesarean section without a trial of labor should be performed in cases of monoamniotic twins. The other indications are not dissimilar to those of a singleton pregnancy and include placenta previa and antenatal evidence of significant fetal compromise (e.g. severe selective IUGR) likely to worsen during labor. In addition, Cesarean section is generally the recommended method of delivery in twin gestations when one twin is non-vertex [42].

Twin delivery constitutes a challenge in daily obstetric practice, which becomes even more difficult in cases with preterm birth, the main perinatal risk factors associated with twin pregnancy [43]. Advancement of gestational age is crucial to achieve acceptable fetal growth rates and better perinatal conditions after birth [44]. Compared to term twin pregnancies, preterm twin pregnancies increase the risk of complications such as neonatal mortality, respiratory distress syndrome (RDS), sepsis, periventricular leukomalacia (PVL) and intraventricular hemorrhage (IVH). In addition, population-based studies from large databases have shown a higher risk of cerebral palsy in twins than in singletons. Studies found different risk profiles in relation to gestational age at birth. In particular, it was found that the presence of one or more of the above complications is present in 30% of moderately preterm infants (born between 32 and 33 + 6 weeks of GA), in 13% of late preterm infants (born between 34 and 36 + 6 weeks of GA) and only in 0.5% of twins born at term [21]. Therefore, all the complicated twin pregnancies have to be managed in tertiary level perinatal centers with both skilled gynecologists and neonatologists in this field.

types: secure and insecure [51]. The first would be those children who could use their mother (the caregiver) as a "safe base" that allow the children to explore the environment. These children usually cry at the time of separation, but they are capable to comfort themselves at the time of the reunion with the mother, returning to play. On the other hand, children with insecure attachment explore the environment less and are anxious when a stranger stays with them in the same room, even if the caregiver is near them; moreover, they become anxious also at the moment of separation from their caregiver and they usually cannot be consoled at the moment of the reunion with their caregiver. On the basis of the attachment relationship experienced, children would build a sort of primary mental "representations," the Internal Working Models (IWMs), that will regulate their peculiar interactive patterns [56]. The IWMs develop from the internalization of recurring interactive experiences between the children and their caregiver and the quality of their organization depends on the quality of care received during childhood. In the secure attachment pattern, IWMs would consist of representing the attachment figure as available to respond positively and consistently to requests for help and comfort, while in insecure attachment patterns, the IWMs would be organized starting from the representation of the caregiver as not available to respond properly at the requests of help and comfort, an attachment figure that is not attuned to the needs of the child, that are usually distant and, sometimes, even hostile. In reality, further studies pointed out that IWMs does not depend exclusively on the quality of the care received, but in a more complex way on the meanings that the caregiver communicate to

Prenatal Attachment in Twin Pregnancy http://dx.doi.org/10.5772/intechopen.79365 87

While the theory of neonatal attachment places the emphasis on the child, the theory of prenatal attachment emphasized the type of affective investment that parents, and especially mothers, have towards the child-to-be, an investment that begins and developed during the different stages of pregnancy. In fact, it was observed that the very early relationship between the mother and her babies does not start at birth [57], but it was recognized that it begins while the child is still a fetus [58]. With the perception of the fetal movements, the pregnant woman starts a process of psychological separation from the fetus and begins to view herself as a "mother" [59]. In particular, the concept of prenatal attachment is defined as "the unique relationship that develops between a woman and her fetus" [60] and "the emotional tie or bond which

Different studies on prenatal attachment investigated its intensity during different period of gestation. Research that used a longitudinal design demonstrated a significant increase in terms of level of prenatal attachment measures during the entire course of the pregnancy [60, 62–64]. It was observed that immediately after the beginning of pregnancy, the level of prenatal attachment may depend on some situational factors, for example, if the woman has perceived fetal movement or if has seen an ultrasound image of the fetus [63]. It was also found that prenatal attachment develops in an orderly sequential way during the course of pregnancy [57, 58, 65]. In the first trimester, relatively low levels of prenatal attachment were observed, while with the increasing of gestational age, mothers start talking to the fetus, call the child-to-be per name [63] and, in the second and third trimesters, increase "nesting" behaviors. Also in a recent literature review on maternal-fetal attachment, Yarcheski et al. [66] suggested that the

magnitude of this relationship is strongest during the third trimester of pregnancy.

normally develops between the pregnant parent and her unborn infant" [61].

the child with their behavior and conduct.

Finally, another relevant aspect that needs to be taken into account is breastfeeding. Mothers of risk infants, as some twins are, may not have the opportunity to experience breastfeeding. Additionally, also in the case of healthy twins, breastfeeding can result a challenge for mothers. It is documented that a mother's feelings and attitudes on breastfeeding can considerably influence on its initiation [45]. For mothers of twins, breastfeeding may be physically uncomfortable; some of them are not able to establish an adequate milk support for two babies [46]. Moreover, several mothers of twins find that their experience of breastfeeding two children is stressful and fraught. Additionally, Mitra et al. [47] observed that those mothers who were well prepared for the realities of breastfeeding had a more successful experience in terms of its duration. Mothers of twins usually feel ill-prepared for breastfeed their twins and reported a lack of information and support during pregnancy [4, 48].
