Obstetric Management of Multiple Gestation and Birth

Biology

Most human conceptions (>99.2%) emerge from a single zygote (i.e., monozygotic [MZ]), resulting from the fertilization of a single egg by a single spermatozoon. In the remaining cases, more than one egg is ovulated and fertilized, resulting in polyzygotic conceptions (i.e., dizygotic [DZ], trizygotic). This phenomenon occurs more often in taller, older, parous, heavier, and black women. Although direct and indirect evidence points to a genetic predisposition, the exact mechanism whereby the ovary is naturally stimulated to release more than one egg per cycle is unknown. All infertility treatments are associated, however, with ovarian stimulation and polyovulation. The contribution of infertility treatments to polyzygotic gestations has become extremely significant since the 1970s.

Most MZ conceptions result in singleton births. In a small fraction of cases (0.4% of all natural conceptions), the zygote splits to form an MZ twin gestation. The mechanism of zygotic splitting is unclear. It has been postulated (but never completely established) that all forms of assisted reproduction produce a breach in the integrity of the zona pellucida—the acellular layer of the egg—resulting in herniation of the part of the early embryo through that gap and splitting of the embryo.

The frequency of MZ splitting is also increased with all methods of assisted reproduction. The true incidence of zygotic splitting after assisted reproduction is unknown. In a large study of single-embryo transfers, a sixfold increase in zygotic splitting was found. The frequency was not influenced by using fresh versus frozen-thawed embryos or by performing embryo transfers during a spontaneous versus an induced cycle. A later hypothesis suggests that the potential to undergo splitting might be an inherent characteristic of the oocyte.

Two points related to the issue of DZ and MZ twinning warrant further discussion. The first is the change of overall frequency of MZ conceptions. In a population comprising mainly of spontaneous gestations, the usual quoted frequency of MZ twinning is about one-third of the twin population, whereas in a population comprising a sizable proportion of iatrogenic pregnancies, one should expect one MZ pregnancy in 15-20 twin gestations.

The second point to consider is the placental arrangement (see Chapter 26 ). Dizygotic twins have two placentas (separate or fused), each with chorion and amnion, forming the so-called dichorionic (DC) placenta. Placentation of the MZ twins is postulated to depend, however, on the stage of embryonic development at which the split occurs. It is believed that early splits (about one-third) result in DC placentas, whereas later splits result in monochorionic (MC) placentas. If the amnion has not yet differentiated, the MC placenta includes two amniotic sacs: the MC-diamniotic placenta (about two-thirds of the cases). If the split occurs later than 8 days after fertilization, an MC-monoamniotic placenta develops. Finally even later splits result in all varieties of conjoined twins. However, one should remember that this well-known theory has never been proved.

When describing a multiple gestation, one must differentiate between zygosity and chorionicity. Because MZ conceptions with a DC placenta cannot be differentiated clinically from same-sex DZ twins (half of DZ conceptions) who also have a DC placenta, zygosity can be determined with certainty only in the DC—unlike sex twins (all must be DZ conceptions) and in twins with an MC placenta (all must be MZ conceptions). Simple calculation reveals that we are blind to zygosity in about 45% of the cases, and zygosity determination must be performed by DNA testing. Thus nothing should be said about zygosity to parents of same-sex twins with a DC placenta.

Maternal Consequences

When discussing maternal complications during multiple gestation, two important issues should be considered. The first issue involves the significant changes in the roles of women in Western societies witnessed after World War II. The new roles in society were facilitated by effective contraception, allowing ample time to achieve education and a career. This change resulted in increased maternal age at first delivery. Because age and fecundity are inversely related, however, infertility treatment to achieve a pregnancy often becomes inevitable. Because all infertility treatments carry an increased risk of multiple gestations, the end result of these sociomedical trends is an increased age of the cohort of mothers of multiples. US data clearly show that the increase in maternal age is more striking in high-order multiple gestations than in twins and in twins than in singletons, with a net result of multiples being more often delivered to older mothers in whom chronic disease conditions have already accumulated.

The second issue involves the overwhelmed maternal homeostasis. Consider the fact that the average singleton, twin, and triplet have a similar birth weight until 28 weeks (≈1000 g). By 28 weeks, the mother of twins and the mother of triplets have accumulated twice and three times the fetal mass of singletons. This excess of fetal mass must come from either existing maternal resources or from supplemental energy. During the third trimester, all maternal systems are overwhelmed, and some may be only a step away from clinical insufficiency.

Two examples vividly demonstrate the situation. The first is the increased frequency of clinically significant anemia as a result of depleted maternal iron stores or inadequate iron supplementation. The incidence of anemia is significantly increased among mothers of multiples. A second example relates to the increased cardiac output. It has been estimated that in the worst-case scenario (i.e., preterm labor because of infection in a multiple gestation), the cardiac output may exceed 10 L/min (two to three times the normal value). It is understandable why cardiac function so easily turns into dysfunction when additional load—in the form of β-sympathomimetic tocolysis—is administered to a patient with multiples who experience premature contractions.

Regardless of the inherent changes in maternal physiology resulting from the multiple gestation, there are some maternal disease conditions that are more frequent in these gestations. Hypertensive disorders are two to three times more frequent, and their most dangerous complication—eclampsia—is six times more frequent among mothers of multiple gestations. Preeclamptic toxemia occurs earlier in multiples than in singletons and often occurs in a more severe form. Because triplets and other high-order multiples were rare in the past, there were scant data related to hypertensive disorders in high-order multiple gestations. With the current epidemic dimensions of multiple gestations, it has been shown that the risk of hypertensive disorders depends on plurality: The risk in triplets is higher than that in twins, and the risk in twins is higher than that in singletons.

Although the data are still conflicting, the frequency of gestational diabetes also seems to be increased among mothers of multiples. Critical reading of the literature suggests that most stimulation tests to detect glucose intolerance of various degrees showed a diabetogenic effect of multiple gestations, whereas demographic analyses failed to show increased rates of gestational diabetes. The latter analyses were conducted in the era before the epidemic of iatrogenic multiples, however, and before the effect of older maternal age could be documented. Sivan and colleagues showed that the risk of gestational diabetes depends on plurality, as is the case for hypertensive disorders. The correlation of multiple gestation with hypertensive disorders and gestational diabetes seems to point, at least in a teleologic way, to the increased placental size—hyperplacentosis—as a potential common denominator. Simões and coworkers showed that pregravid obesity appears to predispose women to gestational diabetes during twin pregnancy and that there is no advantage in terms of birth weight in twins born to diabetic mothers.

All mothers of multiples are at considerably greater risk of preterm labor and delivery. Preterm contractions with or without cervical changes quite often necessitate tocolytic treatment. Many prophylactic measures, including progestogens, cervical suture (cerclage), β-sympathomimetics, bed rest, and hospitalization, were proposed to reduce preterm birth rates (see Chapter 19 ). All prophylactic measures failed to reduce significantly this common complication of multiple gestation. A cervical pessary has been proposed to help in cases of preterm birth in twins. Expecting mothers of multiples are frequently asked to leave work and to conduct a more sedentary lifestyle. Box 21.1 lists the most common maternal complications during multiple gestations.

Fetal and Neonatal Consequences

Animal models, similar to humans, show an inverse relationship between litter size and gestational age and birth weight. In humans, the average gestational age at birth is around 40 weeks for singletons, 36 weeks for twins, 32 weeks for triplets, and 29 weeks for quadruplets. Although multiple gestations exhibit many specific complications, the consequences of prematurity are the most common.