**4. Diagnosis of a multifetal pregnancy**

Before the introduction of modern infertility treatments, the prevalence of monozygotic twinning was relatively constant among different origins, oscillating between 3 and 5 per 1000 live births [27]. On the other hand, the prevalence of dizygotic twinning differs concerning race, maternal age, and family history of twinning. Black women have the highest rate of dizygotic twins followed by Asian women and finally white women. Moreover, women with a family history for dizygotic twinning, such as a previous dizygotic pregnancy or being part of or related to a set of dizygotic twins, have greater probability to conceive dizygotic twins

Since the early 1970s, maternal age was considered an important factor that could influence the conception of a multiple pregnancy, with a reported fourfold increase of dizygotic twinning rate between the ages of 15 and 37 [28]. Maternal age does not seem to affect monozygotic multiple pregnancy rates, as shown in multiple studies [29]. Women between the ages of 35 and 41 are more likely to have a multiple gestation. The increment in multifetal pregnancies is probably related to higher basal FSH levels for women over the age of 35 compared to younger women. Higher levels of FSH can be associated with the maturation of multiple follicles in natural cycles and consequently the occurrence of a multiple pregnancy [30].

There is evidence that a woman's somatometric parameters are associated with a multiple pregnancy. Women with a BMI over 30 are more likely to conceive more than one babies compared to women with normal BMI [31–34]. Noteworthy, a higher BMI increases the probability of multizygotic pregnancies but not monozygotic ones. Women's height has been associated with multiple pregnancies, even though its impact is less important than weight [34]. Women who are taller than 173 cm seem to have higher probability for dizygotic twinning

Some lifestyle choices have also been proposed as predisposing factors for multiple pregnancy. Multivitamins and folic acid supplementation have been associated with an increased incidence of multiple gestation, even though the results were not statistically significant [35]. In order to confirm that the use of folic acid increases the rates of multiple pregnancies (up to 40%), more trials have to be performed [36]. Coffee consumption, smoking, and alcohol have also been evaluated for their possible positive correlation with multiple pregnancy without fertility treatments [37]. This observation is surprising, since smoking and alcohol are known to have negative effects on the fetus and the pregnancy outcome. Kapidaki in 1995 [38] showed that for each cup of coffee per day there was an increase in the odds for multifetal pregnancy. Parazzini in 1996 [37], on the other hand, found no relation between multiple pregnancy and the extent of coffee drinking. In the same study, however, they found that women who were drinking ≥15 alcohol units per week and those who were smoking ≥10 cigarettes per day were more likely to conceive a multifetal pregnancy. In any case, more studies are necessary

The use of contraceptive pill and the time after its discontinuation are associated with multiple pregnancy. The theory behind this affirmation is an increase in the secretion of gonadotropins shortly after the cessation of the pill that could result in multiple pregnancies. Many studies, since the 1970s [39–42], have denoted an increase in twin pregnancies after the cessation of oral contraceptive pills. A study by Campbell in 1987 [43], however, found no statistical

compared to women with no family history [14].

162 Multiple Pregnancy - New Challenges

compared to women shorter than 165 cm [31, 33].

in order to have results that are more reliable.

Early diagnosis of a multiple pregnancy is crucial for achieving the best outcome and for preventing as many complications as possible, either maternal or fetal [53]. The preferred method to diagnose a multifetal gestation is by ultrasonography. This method is accurate enough to reveal a multiple pregnancy by the fourth week of gestation, although the number of yolk or gestational sacs can be misleading as early in pregnancy [54].

The term "vanishing fetus" or "natural fetal reduction" is used to describe the loss, through miscarriage, of one or more fetuses during a multiple gestation. This phenomenon can be observed up to the 16th week of pregnancy, and it can be either asymptomatic or it can present with bleeding, pain, or abdominal cramps. Before the introduction of ultrasound, a vanishing fetus could only be diagnosed after delivery [55]. Dickey et al. estimated that the prevalence of a vanishing fetus before the 12th week of a quadruplet pregnancy could be as high as 65% with great variability among different researchers [56]. They also showed that the probability of a spontaneous absorption in a multiple pregnancy was directly related to the initial number of gestational sacs and to maternal age (p < 0.001 and p < 0.01, respectively). In the same study, they concluded that the average duration of reduced twin pregnancies with initially four sacs was 11 days shorter when compared to the duration of unreduced twin pregnancies (254 days–243 days, p < 0.001). In addition, the birth weight of naturally reduced twins was lower compared to the weight of unreduced twins (2024 ± 668 g compared to 2453 ± 575 gr, p < 0.003).

relationship can be found for certain complications of the pregnancy. Wen et al. [44] in 2004 compared the outcomes in women with twins, triplets, quadruplets, and high-order pregnancies from 1995 to 1997. They concluded that women with triplets and more were in greater risk for pregnancy associated hypertension, eclampsia, anemia, diabetes mellitus, placental abruption, premature rupture of the membranes, and cesarean delivery, even after the adjustment for important confounding factors. Wen also compared the maternal health outcomes. Women with triplets, quadruplets, and higher order are predisposed to develop pregnancyassociated hypertension and diabetes mellitus (7.68% for twins, 10.32% for triplets, and 11.57% for quadruplets and higher order for hypertension, while for diabetes mellitus the rates were 3.34% for twins, 5.97% for triplets, and 6.75% for quadruplets and higher order). Twins were less frequently delivered by cesarean section (51.21% compared to 86.78 and 84.87% for triplets and quadruplets or higher, respectively) and had less chances for a premature rupture of the membranes (6.66% for twins, 11.17% for triplets, and 10.65 for quadruplets and more). The rise in rates for cesarean delivery as the number of fetuses increases could also explain the low rates of induction of labor and use of forceps and vacuum among triplets and quadruplets compared to twin pregnancies. The study by Luke and Brown in 2008 [45] also came to the same results that quadruplet pregnancies have greater chances for pregnancy-associated complications when compared to twin pregnancies. In the study by Luke and Brown, the p-value was <0.0001 for diabetes mellitus, incompetent cervix, induction of labor, stimulation of labor, tocolysis, cesarean delivery, premature rupture of the membranes, infant death of ≥1 baby, birth at ≤29 weeks of pregnancy, and <0.05 for pregnancy-associated hypertension

Quadruplets and Quintuplets

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http://dx.doi.org/10.5772/intechopen.80338

Multiple pregnancies present increased spontaneous loss rates, and these rates increase in parallel with the increase of the number of the fetuses. The authors estimate that a quadruplet pregnancy has a 25% chance for a spontaneous loss, while a quintuplet has three times more, up to 75%. This rise is more obvious when these rates are compared with the ones for a twin

Preterm labor has been proven the most common maternal complication in high-order pregnancies [67], and it is directly associated with the increased perinatal morbidity and mortality observed in these pregnancies, while the rates of pregnancy complications seem to be raised alongside the increase of the number of fetuses [14]. More than 90% of highorder pregnancies are born prematurely, with the approximate gestational age at delivery for quadruplets to be estimated around 29.5 weeks, while for quintuplets this point is up to 29 weeks of gestation [17]. In USA, in 2016, the 93% of quadruplets (217 cases) and the 100% of quintuplets and higher order pregnancies (31 cases) have been born before the 34th week

In order to prolong the pregnancy, several methods have been used. Bed rest, either hospitalization or home rest, is a method still widely used. Although some researchers considered bed rest the most important mode of treatment and it was used to be advised to all patients [53], Crowther in 2001 [68] for a Cochrane review synthesized seven controlled trials including twin and triplet gestations. Bed rest has been proven ineffective to reduce preterm labor,

and eclampsia.

of gestation [12].

and a triplet pregnancy (8 and 15 respectively) [66].

while on the same time it was psychologically distressing.

Ultrasonography plays an important role in the diagnosis of chorionicity and placentation of a pregnancy. Determining chorionicity is crucial, since twin and triplet pregnancies with at least one monochorionic pair have greater perinatal morbidity and mortality [57, 58]. Perinatal mortality in quadruplets tends to be five times higher when a monochorionic set is present compared to quadra-chorionic [57]. Adeghite et al. in 2007 [59] compared the differences in neonatal complications between quadra-chorionic quadramniotic and trichorionic newborns. There was statistically significant higher incidence for almost all complications considered within the trichorionic group. This group also had statistically significant higher rates in neonatal death when compared to the quadra-chorionic group. Furthermore, trichorionic infants were born much earlier and weighed less compared to the quadra-chorionic ones: 28 vs. 32 weeks and 69% <1000 g vs. 13% <1000 g (p < 0.001), respectively. There was no difference between the groups in regard to the mode of delivery. Some data suggest that the use of modern infertility treatment methods is associated with monozygotic twinning, although the data for some of these methods are conflicting [60]. Since 75% of monozygotic twins are also monochorionic [61], women who have undergone such treatments and have a multifetal gestation must be suspected for monochorionicity. Chow et al. in 2001 in a study of 464 multiple gestations showed that in multiple gestations arising from artificial reproduction treatments, there is a correlation between the number of fetuses and the rates of monochorionic pairs [62]. Monochorionic pairs were present in only 2.1% of twin pregnancies, while in quadruplet and quintuplet pregnancies the rates were as high as 25% (p < 0.05). Chow et al. finally confirmed the observation made in earlier studies that a monochorionic pair is more likely to be found in a naturally conceived gestation.

Early ultrasound evaluation can identify placentation correctly in over 90% of multiple gestations, and in case this is not possible, the gestation should be treated as monochorionic [17]. The data regarding the incidence of placenta previa in a multiple gestation are conflicting. Some of them suggest that placenta previa is up to 40% more common in twin pregnancies [63], probably due to limited space in the endometrial cavity [64], whereas others argue that the incidence of placenta previa is not correlated with the number of embryos [65].
