Although we have focused our discussion of multiple gestations to this point on twins, higher order multiples (i.e., triplets, quadruplets, quintuplets, etc) also occur but, fortunately, much less often than twins. The hypothesis of Hellin predicts that if the frequency of twinning (n) in a population is known, the frequency of triplets can be estimated as n-squared, the frequency of quadruplets as n-cubed, the frequency of quintuplets as n-to the 4th power, etc. For example, if 1 in 30 pregnancies is twins then about 1 in 1100 would be triplets, and 4 in 100,000 would be quadruplets. Actual findings of higher order multiples in the population support these predicted distributions.
The incidence of twins has increased steadily over the past two decades in the U.S. Although assisted reproductive technologies have contributed to an increase in all multiples and, especially, high order multiples, better monitoring of the infertility patient and general agreement among reproductive endocrinologists to recommend the transfer of no more than two embryos in in vitro fertilization cycles, has stabilized the rise in the latter in recent years. Specific issues related to ‘placentation’ as discussed for twins in the previous post also apply to higher order multiples as do proportionate increases in pregnancy complications.
The most common fetal and neonatal complications in multiple gestations are related to premature delivery. The mean gestational age for delivery of twins is about 35 weeks, triplets about 32 weeks, and quadruplets about 29 weeks. In the U.S., as we mentioned previously, multiples account for about 3% of all deliveries, but they also contribute to about 25% of the very low birth weight (VLBW; < 1500 g) babies that are born. In 2001, 57% of twins and 92% of triplets were born at less than 37 weeks compared to only 10% of singletons. In that same year, 10% of twins, 35% of triplets, and more than 70% of higher order multiples resulted in VLBW babies. Martin and colleagues (National Center for Health Statistics Report 2003;42) reviewed birth weight data from 2002 and found the mean birth weight for singletons was 3,332 g, whereas that for twins was 2,347 g, triplets 1,687 g, and quadruplets 1,309 g. It is significant to note that 80% of the triplets and higher pregnancies were the results of the ‘successes of infertility programs throughout the country. It is also interesting to note that women who require infertility treatment to conceive are at even greater risk for preterm and low birth weight babies than women who spontaneously conceive multiple gestations (Schieve, et al., NEJM 2002;346:741; Dhont, et al., Am J Obstet Gynecol 1999;181:688; McElrath, et al., Obstet Gynecol 1997;90:600).
Early gestational age at delivery, low birth weight, and intrauterine growth restriction at these early gestational ages contribute to the morbidity and mortality accompanying multiple gestations. U.S. Vital Statistics data indicate that twins are about 7 times more likely than singletons to die during the first month of life (and 5 times more likely to die during the first year) and triplets are about 20 times more likely to die in the first month (and 12 times more likely during the first year). Multiple gestations require a high rate of admission to neonatal intensive care units and are at risk for all of the common complications of prematurity, both acute and chronic, such as respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage, retinopathy of prematurity, and chronic lung disease. Despite the dramatic advances that have been made in early neonatal care, worldwide data suggests that multiples are 4 to 10 times more likely to result in cerebral palsy and permanent handicaps than singleton pregnancies. The short- and long-term costs of health care for multiples are staggering when compared on a per baby basis to singleton pregnancies.
Maternal complications during pregnancies with multiples also contribute to morbidity, mortality, and health care costs above that seen for singletons at every stage of pregnancy. There are greater risks for miscarriage in first and second trimesters, severe nausea and vomiting of pregnancy (hyperemesis gravidarum), bladder and kidney infections, iron deficiency anemia (and frank maternal malnutrition with higher order pregnancies), thromboembolic complications, gestational diabetes, hypertensive disorders of pregnancy, including severe preeclampsia syndromes, acute fatty liver of pregnancy, as well as premature rupture of membranes, early, and cesarean deliveries. Abnormalities of placentation and uterine overdistention increase the risk for bleeding complications both during the pregnancy and at the time of delivery. If a woman with multiples has previously had a cesarean delivery, she may also be at greater risk for uterine rupture prior to the onset of, or during, labor. Multiple, and sometimes prolonged, hospitalizations related to any of these complications contribute to the increased costs of health care for these pregnancies and are characteristic of high order multiples. Indeed, the higher the order of the multiple pregnancy, the greater the risk for each of these complications…