Original cartoon by Alex Martin
Source: Original cartoon by Alex Martin

Multiple births  — twins, triplets or even more  —  can be both a blessing and a curse. Mercifully, a steep decline from twins to nonuplets fits a simple probability progression. Births of nine (usually non-viable) womb mates are exceedingly rare and no higher multiples have been recorded. Following an even simpler principle, pregnancy duration and newborn size decrease as the number of womb mates increases. A greater likelihood of prematurity, with many accompanying health disadvantages, is hence inevitable with multiple births. Multiple pregnancies also have other downsides, such as a doubled divorce rate reported following twins. Ironically, though, multiples are seemingly associated with greater fertility.

A basic pattern for multiple births

Undeservedly, German physician Dionys Hellin is usually credited with identifying in 1895 a regular pattern in human multiple birth rates. “Hellin’s Law” (actually just a rule of thumb) runs thus: If twins occur at a rate a rate of (say) 1 in 85 births, triplets will occur at a rate of 1 in 85 squared (one in 7,225), quadruplets at a rate of 1 in 85 cubed (one in 614,125), and so on. Accordingly, the rate of octuplets should be 1 in 85 raised to the power 7, only once in over 30 trillion births. A simple explanation of “Hellin’s” rule is that a standard probability of having an extra fetus in the womb is multiplied for every one added.

Adapted from a figure in Jonczyk 2015.
Illustration of the mathematical progression embodied in “Hellin’s Law”
Source: Adapted from a figure in Jonczyk 2015.

The “law” is just a rule of thumb for several reasons. Firstly, multiple birth rates differ markedly between regions. A comprehensive 2011 survey of twinning rates across the developing world by Jeroen Smits and Christiaan Monden revealed that twinning rates are generally low throughout South and Southeast Asia, averaging one set of twins per 130 births. Twinning rates in Latin America are similarly low. In stark contrast, strikingly high rates are generally typical across the African continent, with an overall average of one set of twins for every 60 births. The twinning capital of the world, with one set for every 35 births, is Benin. Because of its high rates, Africa alone accounts for almost half of the world’s twin births every year. Twinning rates in Europe and North America, roughly 1 for every 85 births (as in “Hellin’s” rule), are intermediate between African and Asia plus Latin America. Although twinning rates vary fourfold around the globe, however, multiple births do show a regular progression within each individual region.

Adapted from a figure in Pison et al. 2015.
Changing rates of twinning between 1900 and 2010 for various European countries and the USA, along with partial data for some Asian nations. Note the general decline from 1930 to 1980 in Europe and the USA and the steep increase from 1980 onwards (also seen in Asia).
Source: Adapted from a figure in Pison et al. 2015.

A second complication is that rates of multiple birth can change over time within a region. A 2015 paper, with Gilles Pison joining Smits and Monden as co-author, revealed a complex pattern shared by various European countries and the USA: Twinning rates declined steadily between 1930 and 1980 before rising steeply up to the present day. Over the 30-year period 1980–2010, twinning rates in Europe and the USA approximately doubled. Average rates also doubled over that same period in Asian nations, although they remained consistently lower than in Europe and the USA.

Why are multiple births increasingly common?

Two main factors contributed to the sharp rise in twinning rates in industrialized countries since 1980. Firstly, because multiple births trend upwards with a women’s age, an increased tendency to delay childbirth has played a major part in rising rates. But there is a complicating factor. As in other contexts, investigators have commonly examined only maternal age. But partners in a couple grow old together, so father’s age may at least partly influence multiple pregnancy. Karine Kleinhaus and colleagues specifically investigated this in a 2008 paper drawing on data for over 90,000 births collected in the Jerusalem Perinatal Study. After controlling for mother’s age, they found that paternal age was independently associated with increasing frequency of multiple pregnancy.

Adapted from a figure in Pison et al. 2015.
Twinning rates rise along with maternal age, as shown by data from France, England + Wales and the USA for 1900-2010. Note that in the past rates were generally quite low in pre-menopausal women with ages exceeding 45, but that after 1980 a steep rise occurred. That change is doubtless due to increasing use of artificial reproductive technology.
Source: Adapted from a figure in Pison et al. 2015.

But another main contributor to booming multiple births has been proliferation of assisted reproduction, including hormonal stimulation of ovulation as well as the more complicated procedure of in vitro fertilization (IVF) followed by embryo transfer. Hormone treatment is widely used both to trigger ovulation without other intervention and to increase numbers of eggs harvested as a prelude to IVF. Until recently, it was common practice with IVF procedures to transfer several embryos together to maximize the chances of success. To date, only 20 cases of octuplet births have been reported, and at least 13 of them resulted from treatment with fertility drugs. To reduce the incidence of multiple pregnancies, most fertility clinics now restrict numbers of embryos transferred. But some cases occurred regardless, as with notorious “octomom” Nadya Suleman, who gave birth to octuplets in 2009 after her physician transferred 12 embryos.

Hazards of multiple births

Multiple births necessarily face problems that increase with the number of babies. Although the womb shows remarkable flexibility, its capacity to expand is limited. As the number of fetuses increases, pregnancy length declines and average size at birth decreases. In 1952, Thomas McKeown and Reginald Record provided a classic review of basic statistics. Following the medical convention of calculating pregnancy length from the onset of the last menstrual period, average duration is 40 weeks for single births. But this is reduced to around 37 weeks with twins, 35 weeks with triplets, and 34 weeks with quadruplets. As the number of babies mounts, they are hence increasingly likely to be born premature. The standard medical threshold for preemies is 37 weeks, and with normal singletons only one in ten is premature. With twins, however, average pregnancy length is only 37 weeks, so half of them are preemies. Already with triplets, nine out of ten are born premature.

Adapted from a figure in McKeown & Record 1952.
Reduction in average pregnancy length and decline in average birth weight as the number of babies increases from singletons to quadruplets.
Source: Adapted from a figure in McKeown & Record 1952.

Average birth weight decreases in tandem with pregnancy length. So the escalating proportion of preemies with multiple births is a severe handicap, as being born too small has numerous side-effects throughout life. McKeown and Record reported averages of 7.5 pounds for singletons, 5.25 pounds for twins, 4 pounds for triplets, and a little over 3 pounds for quadruplets. Hence, the average singleton at birth weighs more than twice as much as an individual quadruplet. Nevertheless, although babies from multiple births are individually smaller, their combined weight increases with their number: 7.5 pounds for a singleton, 10.5 pounds for twins, 12 pounds for triplets, and 12.5 pounds for quadruplets.

Multiple pregnancies with five or more fetuses  —  quintuplets, sextuplets, septuplets, octuplets, and nonuplets  —  are very rare, so no average figures for pregnancy lengths and birth weights are available. “Octomom” Nadya Suleman gave birth to her octuplets  —  only the second recorded case in the USA  —  after a pregnancy lasting just over 30 weeks, almost 10 weeks less than for a singleton. The average birth weight of Suleman’s babies, all of which survived to celebrate their eighth birthday earlier this year, was only 2.5 pounds, just one third of the weight expected with a routine singleton birth.

Multiple births and greater fertility

Adapted from a figure in Ferrari et al. 2007.
Greater fertility, as indicated by shorter time-to-pregnancy, is seen in couples that have twins as opposed to those that have singletons.
Source: Adapted from a figure in Ferrari et al. 2007.

Intriguingly, some evidence indicates that couples with multiple pregnancies have higher-than-average fertility. Two papers published in 2007 provide examples. The first, by Renee Ferrari and colleagues, analysed data for time-to-pregnancy (TTP) from the US Collaborative Perinatal Project. 81 women that gave birth to twins or triplets, carefully matched for maternal age, were compared to 243 control women with singletons. It emerged that women with a relatively short TTP of 6 months or less were about twice as likely to have a multiple birth than women with a TTP exceeding 6 months. The second study, by Camilla Asklund and colleagues, examined semen quality in 37 fathers of naturally conceived twins, comparing them to a reference group of 349 men with normal fertility. It emerged that average sperm concentration was around 20% higher in fathers of twins. Moreover, percentages of motile sperm cells and of sperm cells with normal appearance were also higher. It has been suggested that the greater fertility reported for couples with multiple births is due to a higher probability of ovulation in female partners. However, the evidence reported by Asklund and colleagues shows, once again, that both sexes must be considered.

References

Asklund, C., Jensen, T.K., Jørgensen, N., Tabor, A., Sperling, L. & Skakkebaek, N.E. (2007) Twin pregnancy possibly associated with high semen quality. Human Reproduction 22:751-755.

Fauser, B.C.J.M., Devroey, P. & Macklon, N.S. (2005) Multiple birth resulting from ovarian stimulation for subfertility treatment. Lancet 365:1807-1816.

Fellman, J. & Eriksson, F.J. (2009) On the history of Hellin's law. Twin Research & Human Genetics 12:183-190.

Ferrari, R.M., Cooney, M.A., Vexler, A., Liu, A. & Louis, G.M.B. (2007) Time to pregnancy and multiple births. Human Reproduction 22:407-413.

Hoekstra, C., Zhao, Z.Z., Lambalk, C.B., Willemsen, G., Martin, N.G., Boomsma, D.I. & Montgomery, G.W. (2008) Dizygotic twinning. Human Reproduction Update 14:37-47.

Jena, A.B., Goldman, D.P. & Joyce, G. (2011) Association between the birth of twins and parental divorce. Obstetrics & Gynaecology 117:892-897.

Jonczyk, P. (2015) Superfecundation  —  from ancient to modern times. Ginekologia i Położnictwo Medical Project 4,38:32-38.

Kleinhaus, K., Perrin, M.C., Manor, O., Friedlander, Y., Calderon-Margalit, R., Harlap, S. & Malaspina, D. (2008) Paternal age and twinning in the Jerusalem Perinatal Study. European Journal of Obstetrics, Gynecology & Reproductive Biology 141:119-122.

McKeown, T. & Record, R.G. (1952) Observations on foetal growth in multiple pregnancy in man. Journal of Endocrinology 8:386-401.

Pison, G. (2000) Nearly half of the world’s twins are born in Africa. Population & Societies 360:1-4.

Pison, G., Monden, C. & Smits, J. (2015) Twinning rates in developed countries: Trends and explanations. Population & Development Review 41:629-649.

Smits, J. & Monden, C. (2011) Twinning across the developing world. PLoS One 6(9), e25239:1-5.

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