Abnormal Development - Twinning

From Embryology

Introduction

File:Twinning-historic embryology.jpg
Historic drawing of twins by William Smellie (1697-1763)

While singleton human births are the most common, there are also several different forms of twinning that may arise in the early weeks (first two weeks) of development. The two major twinning forms are monozygotic (from one fertilised egg and a single spermatazoa) or dizygotic (from two eggs fertilised by two different spermatazoa).

In addition to the zygosity, the additional twinning classifying terms refer to the type of placenta and fetal membranes, either separate or shared by the twins. Twinning has both a higher incidence of mortality in twins, due mainly to preterm delivery, and of incidence of birth defects.


Abnormality Links: abnormal development | abnormal genetic | abnormal environmental | Unknown | teratogens | ectopic pregnancy | cardiovascular abnormalities | coelom abnormalities | endocrine abnormalities | gastrointestinal abnormalities | genital abnormalities | head abnormalities | integumentary abnormalities | musculoskeletal abnormalities | limb abnormalities | neural abnormalities | neural crest abnormalities | placenta abnormalities | renal abnormalities | respiratory abnormalities | hearing abnormalities | vision abnormalities | twinning | Developmental Origins of Health and Disease |  ICD-11
Historic Embryology  
1915 Congenital Cardiac Disease | 1917 Frequency of Anomalies in Human Embryos | 1920 Hydatiform Degeneration Tubal Pregnancy | 1921 Anencephalic Embryo | 1921 Rat and Man | 1966 Congenital Malformations

Some Recent Findings

  • Birth weight in a large series of triplets[1] "There was no effect of assisted reproductive techniques on triplet birth weight. At gestational age 24 to 40 weeks triplets gained on average 130 grams per week; boys weighed 110 grams more than girls and triplets of smoking mothers weighted 104 grams less than children of non-smoking mothers. Monozygotic triplets had lower birth weights than di- and trizygotic triplets and birth weight discordance was smaller in monozygotic triplets than in dizygotic and trizygotic triplets. The correlation in birth weight among monozygotic and dizygotic triplets was 0.42 and 0.32, respectively. In nearly two-thirds of families, the heaviest and the lightest triplet had a birth weight discordance over 15%."
  • The impact of fetal gender on prematurity in dichorionic twin gestations after in vitro fertilization.[2] "Fetal gender mix serves as risk factor for more significant prematurity in dichorionic-diamniotic twins after assisted reproduction with opposite sex twins at higher risk than same sex-twins."
  • Increased prevalence of cardiovascular defects among 56,709 California twin pairs.[3] "An increased prevalence was observed in twins compared to singletons in all 16 cardiovascular categories. Seven of the cardiovascular categories had at least double the prevalence in twins compared to singletons. Like-sex twins, as a proxy of monozygosity, had an increased prevalence of cardiovascular defects compared to unlike sex twins. Probabilities of concordance for flow lesions were higher among monozygotic than dizygotic twins."
  • Maternal immunologic rejection: lessons from discordant dizygotic twin placentas.[4] "We describe a series of dizygotic twin placentas where the more severe the chronic villitis, the more affected the placenta and fetus. Since the maternal environment was constant for each of these twins, differences in villitis severity appears to be attributable to differences in the ability of each placenta to induce a maternal immune response."

Twinning Prevalence

The prevalence of spontaneous livebirth monozygotic twinning is relatively constant, with variability in dizygotic twinning around the world.[5]

  • Asia 6 in 1000
  • Europe/USA 10-20 in 1000
  • African-Americans 26 in 1000
  • Africa 40 in 1000
  • Japan 1 in 250
  • Nigeria 1 in 11

Monozygotic conjoined twins - 1 in 100,000 births (more female)


United States of America - 2.7% of all confinements resulted in a multiple birth in 1996 (U.S. Census Bureau, 1999, p.80)

New Zealand - 1.6% in 1998 (Statistics New Zealand, 2000, p.70)

Australia - 1.5% in 1998 (ABS, see below)

Australian Twinning Prevalence

Data from the Year Book Australia (2002) looking at pregnancies (confinements) shows the number resulting in a singleton live birth has been declining while the number resulting in multiple births has been increasing. This has been attributed to increased number of births to older women and the increasing use of assisted conception technologies.

"While the number of confinements resulting in multiple births remains relatively low, there has been a steady increase since the 1970s."

Multiple Births

1980 - 1.0% (2,249 of 223,318; 2,219 twins, 30 triplets or higher)
1990 - 1.2% (3,168 of 259,435; 3,074 twins, 94 triplets or higher)
2000 - 1.6% (3,900 of 245,700; 3,800 twins, 100 triplets or higher)

"Among older women this trend is more pronounced. In 1980, there were 730 confinements resulting in multiple births to women aged 30 years and over, constituting 1% of all confinements among women over 30. By 2000, this number had increased to 2,300 (2%)." [6]

Dizygotic Twinning

Dizygotic twins (DZ, fraternal, non-identical) arise from separate fertilization events involving two separate oocyte (egg, ova) and spermatozoa (sperm). These twins may also implant at different sites within the uterus. Maternal factors such as genetic history, advanced age, increased parity, elevated FSH concentrations, maternal height (taller) and maternal body mass index (30>) increase the risk of dizygotic twins.[7] There are also theories that suggest that non-in vitro fertilization dizygotic twins may have more in common with monozygotic mechanisms and not be due to purely twin ovulatory events.[8]

Monoygotic Twinning

Monoygotic twins (MZ, identical) produced from a single fertilization event (one fertilised egg and a single spermatozoa, form a single zygote), these twins therefore share the same genetic makeup. Occurs in approximately 3-5 per 1000 pregnancies, more commonly with aged mothers. The later the twinning event, the less common are initially separate placental membranes and finally resulting in conjoined twins.

Week Week 1 Week 2
Day 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Cell Number 1 1 2 16 32 128 bilaminar
Event Ovulation fertilization First cell division Morula Early blastocyst Late blastocyst

Hatching

Implantation starts X inactivation
Follicle 001 icon.jpg Early zygote.jpg Human embryo day 2.jpg Human embryo day 3.jpg Human embryo day 5.jpg CSt3.jpg Week2 001 icon.jpg
Monoygotic

Twin Type

Diamniotic

Dichorionic

Diamniotic

Monochorionic

Monoamniotic

Monochorionic

Conjoined

Table based upon recent Twinning Review.[5]

Triplets

Triplet and higher birth rates for mothers 25 years of age and older: United States, 1980, 1990, 1998, and 2006.

Triplet birth incidence is rare (1 / 10,000 births) though this number increased (6 / 10,000 births) during the early stages of assisted reproductive technologies (ART) and has since dropped again with single embryo transfer (SET) policies. Triplets are often born premature and with a low birth weight. A recent large study in the Netherlands has characterised birth weight, zygosity and environmental effects [1]

"There was no effect of assisted reproductive techniques on triplet birth weight. At gestational age 24 to 40 weeks triplets gained on average 130 grams per week; boys weighed 110 grams more than girls and triplets of smoking mothers weighted 104 grams less than children of non-smoking mothers. Monozygotic triplets had lower birth weights than di- and trizygotic triplets and birth weight discordance was smaller in monozygotic triplets than in dizygotic and trizygotic triplets. The correlation in birth weight among monozygotic and dizygotic triplets was 0.42 and 0.32, respectively. In nearly two-thirds of families, the heaviest and the lightest triplet had a birth weight discordance over 15%."

Twin-twin Transfusion Syndrome

Twin-twin transfusion syndrome (TTTS) can occur in both monochorionic and diamniotic twins that results from an unbalanced blood flow from one to the other in utero. Monozygotic twin pregnancies carry a 10-20% risk of twin-twin transfusion syndrome. Diagnosis of TTTS is generally by ultrasound: single placenta, same fetal sex, a “T-sign” and the amniotic fluid volume on either side of the dividing fetal membranes.

  • Twin-to-twin transfusion syndrome, vein of galen malformation, and transposition of the great arteries in a pair of monochorionic twins: coincidence or related association? [9] "The development of TTTS, VGM, and TGA in a single monochorionic pregnancy could be pure coincidence, but there might also be a causative link. We discuss the possible contribution of genetic factors, fetal flow fluctuations, vascular endothelial growth factors, and the process of twinning itself to the development of these congenital anomalies."


Quintero Staging System

Quintero and others in 1999 established a sonographic and clinical parameter staging system for TTTS.[10]

  • Stage I - The fetal bladder of the donor twin remains visible sonographically.
  • Stage II = The bladder of the donor twin is collapsed and not visible by ultrasound.
  • Stage III - Critically abnormal fetal Doppler studies noted. This may include absent or reversed end-diastolic velocity in the umbilical artery, absent or reverse flow in the ductus venosus, or pulsatile flow in the umbilical vein.
  • Stage IV - Fetal hydrops present.
  • Stage V - Demise of either twin.

This Quintero staging system efficacy has been recently suggested as not providing accurate information about prognosis.[11][12] An alternative Children's Hospital of Philadelphia (CHOP) cardiovascular score, appears to also be "not of clinical use as a prognostic marker in TTTS".[13]

Acardiac Twins

Historically called chorioangiopagus parasiticus. Acardia, also called twin reversed-arterial perfusion (TRAP) sequence, is an extreme form of twin-twin transfusion syndrome. In a twinned human fetal development where monozygotic twinning or higher multiple births have an artery-to-artery and a vein-to-vein anastomosis in the monochorial placenta.[14]

The incidence of this condition is 1% of monochorionic twin pregnancies (approx. 1 of 35,000 pregnancies).

Premature Ovarian Failure

Both forms of twinning have been shown to be at higher risk of Premature Ovarian Failure (POF).[15] The same study also showed that the menopausal ages were more concordant than for dizogotic twin-pairs, confirming that the timing of menopause has a heritable component.

Additional Images

References

  1. 1.0 1.1 <pubmed>21453554</pubmed>| BMC Pediatr.
  2. <pubmed>20534177</pubmed>| Reprod Biol Endocrinol.
  3. <pubmed>19353581</pubmed>
  4. <pubmed>18598117</pubmed>
  5. 5.0 5.1 <pubmed>12957099</pubmed>
  6. Australian Bureau of Statistics Year Book Australia 2002
  7. <pubmed>18024802</pubmed>
  8. <pubmed>19252194</pubmed>
  9. <pubmed>16808639</pubmed>
  10. <pubmed>10645517</pubmed>
  11. <pubmed>18044824</pubmed>
  12. <pubmed>19283655</pubmed>
  13. <pubmed>20582931</pubmed>
  14. <pubmed>10072652</pubmed>
  15. <pubmed>17065173</pubmed>| Hum Reprod.

Journals

Twin Research and Human Genetics "A quality peer-reviewed journal of the International Society for Twin Studies (ISTS). Founded in Rome in 1974, ISTS is an international, nonpolitical, nonprofit, multidisciplinary scientific organisation. Its purpose is to further research and public education in all fields related to twins and twin studies, for the mutual benefit of twins and their families and of scientific research in general."

Reviews

<pubmed>19363805</pubmed> <pubmed>18577552</pubmed> <pubmed>17391087</pubmed> <pubmed>16283408</pubmed> <pubmed>16045531</pubmed>

Articles

<pubmed>20522324</pubmed> <pubmed>16954162</pubmed>

Search Pubmed

Search Pubmed: Twinning | Monozygotic Twinning | Diygotic Twinning | Twin-twin Transfusion Syndrome

External Links

External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.

  • International Society for Twin Studies
  • Australian Twin Registry
  • The Danish Twin Registry "The Danish Twin Registry (DTR) is one of the oldest twin registries in the world. It was established in the 1950's with the aim of studying causes of cancer and it comprises now twins born through more than 130 years."
  • Berlin Twin Register
  • United Kingdom - Department of Twin Research & Genetic Epidemiology "The Department of Twin Research and Genetic Epidemiology (DTR) encompasses the biggest UK adult twin registry of 12,000 twins used to study the genetic and environmental aetiology of age related complex traits and diseases."
  • USA - National Academy of Sciences-National Research Council (NAS-NRC) Twin Registry "It consists of 15,924 white male twin pairs born in the years 1917 to 1927 (inclusive), both of whom served in the armed forces, mostly during World War II."

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Cite this page: Hill, M.A. (2020, July 2) Embryology Abnormal Development - Twinning. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Twinning

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© Dr Mark Hill 2020, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G