## INCIDENCE

In 1895, Hellin described a mathematically simple rule for estimation of the rates of twinning and conception of higher order multiples in the general population. This rule, which has been widely cited and accepted, proposes the following rates of multiple pregnancy:

Several authors have attempted to refine this law, which has been demonstrated to be inexact, especially when higher order multiples and older mothers are concerned. The explosion in reproductive technologies, the societal trend of delayed childbearing, and the observation of an increase in spontaneous twinning on the multiple birth rate also render this law mostly of historic interest.

Since the 1970s, there has been a phenomenal rise in twinning rates by about 80 percent in some countries. France, for example, reports rates of approximately 17 in 1000 live births. In 2006 in the United States, twins comprised approximately 32 in 1000 live births. Triplet and higher order multiple births had demonstrated similar trends until the later 1990s with a leveling off after that time, likely because of better control of reproductive cycles. The estimated contribution of reproductive technologies to the multiple birth rates is dramatic, increasing the twin birth rate 20-fold and the triplet and quadruplet rate 400-fold. Approximately two-thirds of this increase is attributed to infertility treatment and the remaining third to the trend of delayed childbearing.

Although the etiology of multiple pregnancy is unknown in most cases, it is recognized that excessive gonadotropic stimulation leading to superovulation is a factor in dizygous twinning. This phenomenon is evident in older mothers up to approximately age 37 years.

Whatever the etiology, the impact of the multiples epidemic reverberates throughout the health care system in terms of health care costs and suboptimal perinatal outcome. In the patient census of any tertiary level neonatal unit, multiples are overrepresented. It has been estimated that the annual cost of caring for multiples born prematurely after in vitro fertilization is in excess of $1 billion U.S. annually or$52,000 per infant. Morbidity and mortality figures among multiples are also staggering. Population-based studies have reported the stillbirth and neonatal mortality rates in twins in the order of 18 in 100 births and 23 in 1000, respectively. Survival rates among multiples are also not uniformly distributed, and the effects of chorionicity on survival are both sobering and profound. Rates of fetal loss are substantially higher in monochorionic twins (44.4 in 1000 stillbirths rates) than dichorionic twins (12.2 in 1000 births; relative risk [RR], 3.6) and neonatal losses (32.4 in 1000 monochorionic vs. 21.4 in 1000 dichorionic; RR, 1.5) in dichorionic twins. The prospective risk of stillbirth was higher in monochorionic at all gestational ages and highest before 28 weeks of gestation. Survival rates decline dramatically as the number of fetal occupants of ...

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