Multiple birth

Identical triplet brothers at graduation. Identical triplets are extremely rare.

A multiple birth is the culmination of one multiple pregnancy, wherein the mother delivers two or more offspring, one for each fetus. A term most applicable to placental species, multiple births occur in most kinds of mammals, with varying frequencies. Such births are often named also according to the number of offspring, as in twins and triplets. In non-humans, the whole group may also be referred to as a litter, and multiple births may be more common than single births. Multiple births in humans are the exception, and can be exceptionally rare in the largest mammals.

Each single fertilized egg (zygote) may produce a single embryo, or it may split into two or more embryos, each carrying the same genetic material. Fetuses resulting from different zygotes are called fraternal and share only 50% of their genetic material, as ordinary full siblings from separate births do. Fetuses resulting from the same zygote share 100% of their genetic material, and are hence called identical and are always of the same sex (except in cases of sex reassignment or, much more rarely, Turner syndrome).

A multiple pregnancy may be the result of the fertilization of a single egg that then splits to create identical fetuses, or it may be the result of the fertilization of multiple eggs that create fraternal fetuses, or it may be a combination of these two. A multiple pregnancy from a single zygote is called monozygotic, from two zygotes is called dizygotic, or from two or more zygotes is called polyzygotic.

Similarly, the siblings themselves from a multiple birth may be referred to as monozygotic if they are identical, or as polyzygotic if they are fraternal.

Terminology

Fraternal twins at two weeks old. The technical term for "fraternal" is "polyzygotic".

Fraternal twin sisters taking a nap. Nonidentical twins, the most common kind of multiple birth among humans, occur in about 1 out of every 80 pregnancies.

Terms used for multiple births or the genetic relationships of their offspring:

• Monozygotic – multiple (typically two) fetuses produced by the splitting of a single zygote
• Dizygotic – multiple (typically two) fetuses produced by two zygotes
• Polyzygotic – multiple fetuses produced by two or more zygotes

Terms used for the number of offspring in a multiple birth:

• Two offspring - twins
• Three offspring - triplets
• Four offspring - quadruplets
• Five offspring - quintuplets
• Six offspring - sextuplets
• Seven offspring - septuplets
• Eight offspring - octuplets
• Nine offspring - nonuplets

Human multiple births

In humans, the average length of pregnancy (two weeks less than gestation) is 38 weeks with a single fetus. This average decreases for each additional fetus: to thirty-six weeks for twin births, thirty-two weeks for triplets, and thirty weeks for quadruplets. With the decreasing gestation time, the risks from immaturity at birth and subsequent viability increase with the size of the sibling group. Only as of the twentieth century have more than four all survived infancy.

Recent history has also seen increasing numbers of multiple births. In the United States, it has been estimated that by 2011, 36% of twin births and 78% of triplet and higher-order births resulted from conception by assisted reproductive technology.

Twins

Twins are by far the most common form of multiple births in humans. The U.S. Centers for Disease Control and Prevention report more than 132,000 sets of twins out of 3.9 million births of all kinds each year, about 3.4%, or 1 in 30.

Triplets

Identical triplets like these three sisters occur when a single fertilized egg splits in two and then one of the resulting two eggs splits again.

Identical triplets come from a monozygotic pregnancy, three fetuses from one egg. The commonest set, strictly fraternal triplets, comes from a polyzygotic pregnancy of three eggs. Between these types, triplets that include an identical (monozygotic) pair of siblings plus a fraternal sibling are the result of a dizygotic pregnancy, where one zygote divides into two fetuses and the other doesn't. The Kübler triplets (see Elisabeth Kübler-Ross) were of this type.

Triplets are far less common than twins, according to the U.S. Centers for Disease Control and Prevention, accounting for only about 4300 sets in 3.9 million births, just a little more than 0.1%, or 1 in 1000. According to the American Society of Reproductive Medicine, only about 10% of these are identical triplets: about 1 in ten thousand.

Quadruplets

Quadruplets are much rarer than twins or triplets. As of 2007, there were approximately 3500 sets recorded worldwide. Quadruplet births are becoming increasingly common due to fertility treatments. There are around 70 sets of all-identical quadruplets worldwide. Many sets of quadruplets contain a mixture of identical and fraternal siblings, such as three identical and one fraternal, two identical and two fraternal, or two pairs of identicals. One famous set of identical quadruplets was the Genain quadruplets, all of whom developed schizophrenia. Quadruplets and quintuplets are sometimes referred to as "quads" and "quins" in Britain or "quints" in the USA.

Quintuplets

The Canadian Dionne sisters, seen in this 1947 photograph, were the first quintuplets known to survive infancy.

Quintuplets occur naturally in 1 in 55,000,000 births. The first quintuplets known to survive infancy were the all-female Canadian Dionne Quintuplets, born in 1934.

Very high-order multiple births

In 1997, the McCaughey septuplets were born in Carlisle, Iowa. Multiple births of as many as eight babies have been born alive, the first set on record to the Chukwu family in Texas in 1998; one died and seven survived. In 2009, a second set, the Suleman octuplets, was born in Bellflower, California. The most recent report that all were still alive was shortly before their fifth birthday.

There have been a few sets of nonuplets (nine) in which a few babies were born alive, though none lived longer than a few days. There have been cases of human pregnancies that started out with ten, eleven, twelve or fifteen fetuses, but no instances of live births. The pregnancies of the 10, 11 and 15 fetuses have all resulted from fertility medications and assisted reproductive technology (ART). However there has been one documented case when 12 fetuses were conceived naturally.

Causes and frequency

The frequency of N multiple births from natural pregnancies has been given as approximately 1:89^N-1 (Hellin's law) and traditionally as about 1:80^N-1 (1:80 means 1 time in 80). This gives:

• 1:89 (= 1.1%) or 1:80 (= 1.25%) for twins
• 1:89² (= 1:7921, about 0.013%) or 1:80² (= 1:6400) for triplets
• 1:89³ (= approx. 0.000142%, less than 1:700,000) or 1:80³ for quadruplets

North American dizygotic twinning occurs about once in 83 conceptions, and triplets about once in 8000 conceptions. US figures for 2010 were:

• Twins, 132,562, 3.31%
• Triplets, 5,503, 0.14%
• Quadruplets, 313, 0.0078%
• Quintuplets and more, 37, 0.00092%

Human multiple births can occur either naturally (the woman ovulates multiple eggs or the fertilized egg splits into two) or as the result of infertility treatments such as IVF (several embryos are often transferred to compensate for lower quality) or fertility drugs (which can cause multiple eggs to mature in one ovulatory cycle).

For reasons that are not yet known, the older a woman is, the more likely she is to have a multiple birth naturally. It is theorized that this is due to the higher level of follicle-stimulating hormone that older women sometimes have as their ovaries respond more slowly to FSH stimulation.

The number of multiple births has increased over the last decade. For example, in Canada between 1979 and 1999, the number of multiple birth babies increased 35%. Before the advent of ovulation-stimulating drugs, triplets were quite rare (approximately 1 in 8000 births) and higher-order births much rarer still. Much of the increase can probably be attributed to the impact of fertility treatments, such as in-vitro fertilization. Younger patients who undergo treatment with fertility medication containing artificial FSH, followed by intrauterine insemination, are particularly at risk for multiple births of higher order.

The Gosselin sextuplets with their parents and sisters, cover of KoreAm, May 2008

Certain factors appear to increase the likelihood that a woman will naturally conceive multiples. These include:

• mother's age: women over 35 are more likely to have multiples than younger women
• mother's use of fertility drugs: approximately 35% of pregnancies arising through the use of fertility treatments such as IVF involve more than one child

The increasing use of fertility drugs and consequent increased rate of multiple births has made the phenomenon of multiples more frequent and hence more visible. In 2004 the birth of sextuplets, six children, to Pennsylvania couple Kate and Jon Gosselin helped them to launch their television series, originally Jon & Kate Plus 8 and (following their divorce) Kate Plus 8, which became the highest-rated show on the TLC network.

Risks

Premature birth and low birth weight

Babies born from multiple-birth pregnancies are much more likely to result in premature birth than those from single pregnancies. 51% of twins and 91% of triplets are born preterm, compared to 9.4% in singletons. 14% of twins and 41% of triplets are even born very preterm, compared to 1.7% in singletons.

The preterm births also result in multiples tending to have a lower birth weight compared to singletons.

Some evidence indicates that only 1.10% of singletons are born with a very low birth weight and 10.12% twins and 31.88% triplets were found to be born with very low birth weight. This study was conducted by looking at the statistics from the U.S. Natality Files (5).

Among the exceptions are the Kupresak triplets of Mississauga, Ontario, Canada; their combined weight at birth in 2008, of 17 lbs, 2.7 ounces, set a world record.

Cerebral palsy

Cerebral palsy is more common among multiple births than single births, being 2.3 per 1,000 survivors in singletons, 13 in twins, and 45 in triplets in North West England. This is likely a side effect of premature birth and low birth weight.

Incomplete separation

Further information: Twin § Degree of separation

Multiples may be monochorionic, sharing the same chorion, with resultant risk of twin-to-twin transfusion syndrome. Monochorionic multiples may even be monoamniotic, sharing the same amniotic sac, resulting in risk of umbilical cord compression and nuchal cord. In very rare cases, there may be conjoined twins, possibly impairing function of internal organs.

Mortality rate (stillbirth)

Multiples are also known to have a higher mortality rate. It is more common for multiple births to be stillborn, while for singletons the risk is not as high. A literary review on multiple pregnancies shows a study done on one set each of septuplets and octuplets, two sets of sextuplets, 8 sets of quintuplets, 17 sets of quadruplets, and 228 sets of triplets. By doing this study, Hammond found that the mean gestational age (how many weeks when birthed) at birth was 33.4 weeks for triplets and 31 weeks for quadruplets. This shows that stillbirth happens usually 3–5 weeks before the woman reaches full term and also that for sextuplets or higher it almost always ends in death of the fetuses. Though multiples are at a greater risk of being stillborn, there is inconclusive evidence whether the actual mortality rate is higher in multiples than in singletons.

Prevention in IVF

Today many multiple pregnancies are the result of in vitro fertilisation (IVF). In a study in 1997 of 2,173 embryo transfers performed as part of in vitro fertilisation (IVF), 34% were successfully delivered pregnancies. The overall multiple pregnancy rate was 31.3% (24.7% twins, 5.8% triplets, and .08% quadruplets). Because IVFs are producing more multiples, a number of efforts are being made to reduce the risk of multiple births- specifically triplets or more. Medical practitioners are doing this by limiting the number of embryos per embryo transfer to one or two. That way, the risks for the mother and fetuses are decreased.

The appropriate number of embryos to be transferred depends on the age of the woman, whether it is the first, second or third full IVF cycle attempt and whether there are top-quality embryos available. According to a guideline from The National Institute for Health and Care Excellence (NICE) in 2013, the number of embryos transferred in a cycle should be chosen as in following table:

Age	Attempt No.	Embryos transferred
<37 years	1st	1
	2nd	1 if top-quality
	3rd	No more than 2
37–39 years	1st & 2nd	1 if top-quality
		2 if no top-quality
	3rd	No more than 2
40–42 years		2

Also, it is recommended to use single embryo transfer in all situations if a top-quality blastocyst is available.

Management of multiple pregnancy

Selective reduction

Main article: Selective reduction

Selective reduction is the termination of one or more, but not all, of the fetuses in a multiple pregnancy. This is often done in pregnancies with multiple gestations to increase the likelihood that one child may live a healthy life. Armour reported a loss rate of 5.4% in a review of 1,000 cases of selective reduction. Fifteen percent of the losses occurred within 4 weeks of the procedures and more than 50% occurred after 8 weeks. This suggests that the reduction was successful at reducing the embryos from multiple gestations to single.

Though selective reduction seems to be effective, mothers of multiples who undergo this procedure are at a higher risk of miscarrying compared to that of an unreduced multiple pregnancy. A study done by looking at 158 pregnant women who underwent selective reduction from higher order multiples to twins showed that the mother had a 10.6% chance of miscarriage. Mothers of twin pregnancies without reduction only had a 9.5% chance of miscarriage. A study by Antsaklis showed a small increase in mortality for reduced twin pregnancies versus unreduced twin pregnancies.

Competition among fertility clinics does not appear to increase rates of multiple births from fertility treatment by promoting more aggressive embryo transfer decisions.

Cesarean section or vaginal delivery

A study in 2013 involving 106 participating centers in 25 countries came to the conclusion that, in a twin pregnancy of a gestational age between 32 weeks 0 days and 38 weeks 6 days, and the first twin is in cephalic presentation, planned Cesarean section does not significantly decrease or increase the risk of fetal or neonatal death or serious neonatal disability, as compared with planned vaginal delivery. In this study, 44% of the women planned for vaginal delivery still ended up having Cesarean section for unplanned reasons such as pregnancy complications. In comparison, it has been estimated that 75% of twin pregnancies in the United States were delivered by Cesarean section in 2008. Also in comparison, the rate of Cesarean section for all pregnancies in the general population varies between 40% and 14%.

Cesarean delivery is needed when first twin is in non cephalic presentation or when it is a monoamniotic twin pregnancy.

Neonatal intensive care

Multiple-birth infants are usually admitted to neonatal intensive care immediately after being born. The records for all the triplet pregnancies managed and delivered from 1992-1996 were looked over to see what the neonatal statistics were. Kaufman found from reviewing these files that during a five-year period, 55 triplet pregnancies, which is 165 babies, were delivered. Of the 165 babies 149 were admitted to neonatal intensive care after the delivery.

Insurance coverage

A study by the U.S. Agency for Healthcare Research and Quality found that, in 2011, pregnant women covered by private insurance in the United States were older and more likely to have multiple gestation than women covered by Medicaid.

Cultural aspects

Certain cultures consider multiple births a portent of either good or evil.

Mayan culture saw twins as a blessing, and was fascinated by the idea of two bodies looking alike. The Mayans used to believe that twins were one soul that had fragmented.

In Ancient Rome, the legend of the twin brothers who founded the city (Romulus and Remus) made the birth of twin boys a blessing, while twin girls were seen as an unlucky burden, since both would have to be provided with an expensive dowry at about the same time.

In Greek mythology, fraternal twins Castor and Polydeuces, and Heracles and Iphicles, are sons of two different fathers. One of the twins (Polydeuces, Heracles) is the illegitimate son of the god Zeus; his brother is the son of their mother's mortal husband. A similar pair of twin sisters are Helen (of Troy) and Clytemnestra (who are also sisters of Castor and Polydeuces). The theme occurs in other mythologies as well, and is called superfecundation.

In certain medieval European chivalric romances, such as Marie de France's Le Fresne, a woman cites a multiple birth (often to a lower-class woman) as proof of adultery on her part; while this may reflect a widespread belief, it is invariably treated as malicious slander, to be justly punished by the accuser having a multiple birth of her own, and the events of the romance are triggered by her attempt to hide one or more of the children. A similar effect occurs in the Knight of the Swan romance, in the Beatrix variants of the Swan-Children; her taunt is punished by giving birth to seven children at once, and her wicked mother-in-law returns her taunt before exposing the children.

See also

• Biological reproduction
• Conjoined twins
• Half a Dozen Babies a 1999 drama film, about the 1993 born Dilley sextuplets.
• List of multiple births
• List of twins
• Only child
• Superfecundation (multiple pregnancy resulting from separate sexual intercourses)
• Twin
• Feodor Vassilyev

External links

• Facts About Multiples
• Incredible Births, list of multiple births
• HFEA consultation on multiple births after IVF
• D. L. Ashliman, Multiple Births in Legend and Folklore
• Twins and Multiple Births Association