Abnormal Development - Twinning
|Embryology - 30 Mar 2017 Expand to Translate|
|Google Translate - select your language from the list shown below (this will open a new external page)|
العربية | català | 中文 | 中國傳統的 | français | Deutsche | עִברִית | हिंदी | bahasa Indonesia | italiano | 日本語 | 한국어 | မြန်မာ | Pilipino | Polskie | português | ਪੰਜਾਬੀ ਦੇ | Română | русский | Español | Swahili | Svensk | ไทย | Türkçe | اردو | ייִדיש | Tiếng Việt These external translations are automated and may not be accurate. (More? About Translations)
- 1 Introduction
- 2 Some Recent Findings
- 3 Dizygotic Twinning
- 4 Monoygotic Twinning
- 5 Conjoined Twinning
- 6 Triplets
- 7 Twinning Prevalence
- 8 Placenta
- 9 Twin-twin Transfusion Syndrome
- 10 Quintero Staging System
- 11 Acardiac Twins
- 12 Premature Ovarian Failure
- 13 Trisomy 21
- 14 Additional Images
- 15 References
- 16 External Links
- 17 Glossary Links
While singleton human births are the most common, there are also several different forms of "twinning" (multiple pregnancy) that may arise in the early weeks (first two weeks) of development. The two major twinning forms are dizygotic (from two eggs fertilised by two different spermatazoa) and monozygotic (from one fertilised egg and a single spermatazoa). Higher multiple pregnancies (triplets, quadruplets, etc.) are generally dizygotic with ultrasound acting as the earliest diagnostic test for all multiple pregnancies.
Dizogotic twinning can be described following the normal developmental sequence, while monozygotic twinning requires a perturbation of developmental event(s) to occur in the first weeks following fertilisation. The later stages of monozygotic embryonic development may well follow the normal pattern of differentiation, though growth during the fetal period can be lower.
Twinning rate differences over time and between countries are thought due to variation in dizygotic twinning. Monozygotic twinning is thought to occur at a relatively constant rate of 3.5–4 per 1000 births across human populations, with assisted reproductive technologies possibly contributing to recent changes.
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. Single fetal mortality also occurs in 3.7 - 6.8% of all twin pregnancies, and there are more maternal risks involved with multiple pregnancies. As a positive, twins do appear to have a lower incidence of trisomy 21.
Some Recent Findings
|More recent papers|
This table shows an automated computer PubMed search using the listed sub-heading term.
References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.
Margaret Dziadosz, Mark I Evans Re-Thinking Elective Single Embryo Transfer: Increased Risk of Monochorionic Twinning - A Systematic Review. Fetal. Diagn. Ther.: 2017; PubMed 28351027
Jialin Liu, Zaiwang Huang, Zhiliang Pan, Qiuming Wei, Xiaodong Li, Yue Qi Atomistic Origin of Deformation Twinning in Biomineral Aragonite. Phys. Rev. Lett.: 2017, 118(10);105501 PubMed 28339258
I Ariel, D Goldman-Wohl, S Yagel, E Gazit, R Loewenthal Triple paternal contribution to a normal/complete molar chimeric singleton placenta. Hum. Reprod.: 2017;1-6 PubMed 28333325
Surbhi Grover, Shivakumar Gudi, Ajeet Kumar Gandhi, Priya M Puri, Adam C Olson, Danielle Rodin, Onyi Balogun, Preet K Dhillon, Daya Nand Sharma, Goura Kishor Rath, Shyam Kishore Shrivastava, Akila N Viswanathan, Umesh Mahantshetty Radiation Oncology in India: Challenges and Opportunities. Semin Radiat Oncol: 2017, 27(2);158-163 PubMed 28325242
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. 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.
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 (GA week 3)||Week 2 (GA week 4)|
|Event||Ovulation||Fertilization||First cell division||Morula||Early blastocyst|| Late blastocyst
|Implantation starts||X inactivation|
Table based upon recent a recent twinning review. (More? Twinning)
- Diprosopus - two faces are located on the same side of a single head. A form of parapagus (less than 1% of conjoined twins).
- Parapagus - side-by-side connection with a shared pelvis and variable cephalic sharing (28 % of conjoined twins).
- Ischiopagus - conjoined pelvis (6 –11 % of conjoined twins).
- Heteropagus - asymmetrical form of twinning when one of the twins monopolizes the placental blood at the expense of other fetus.
Both ischiopagus and pygopagus conjoined twins have a range of variable spinal abnormalities.
|Conjoined twins ultrasound||Conjoined twins MRI||Conjoined twins after birth|
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 
- "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%."
USA Data 2012
A recent study of twinning in developed countries
- Twins constitute 2% - 4% of all births
- Rate of twining has increased by 76% between 1980 and 2009.
- Rate of preterm birth (<37 weeks) among twins is about 60%.
- Of all twin preterm births in the United States
- roughly half are indicated
- a third are due to spontaneous onset of labor
- about 10% are due to preterm premature rupture of membranes.
- recent decline in neonatal morbidity (one or more of 5-minute Apgar score <4, neonatal seizures or assisted ventilation for ≥ 30 minutes) among twin gestations.
- ART twins are more likely to deliver at <37 weeks.
World Data 2003
The prevalence of spontaneous livebirth monozygotic twinning is relatively constant, with variability in dizygotic twinning around the world.
- 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 Data 2002
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."
- 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%)." 
| Monochorionic Twin Placenta
| Monochorionic Triamniotic Triplet Placenta
- Links: Placenta Development
| Dichorionic diamniotic
GA 13 week = 11 week
| Monochorionic diamniotic
GA 12 week = 10 week
|Thick dividing membrane and "lambda" or twin peak sign at the junction with the placenta.||Thin dividing membrane and "T" sign at the junction with the placenta.|
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?  "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."
Fetoscopic Laser Therapy
Quintero Staging System
Quintero and others in 1999 established a sonographic and clinical parameter staging system for TTTS.
- 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. An alternative Children's Hospital of Philadelphia (CHOP) cardiovascular score, appears to also be "not of clinical use as a prognostic marker in TTTS".
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.
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). 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.
A recent 2014 study  of European data for the period 1990-2009 (14.8 million births 2.89% multiple births) showed the risk of trisomy 21 (Down Syndrome) per fetus/baby is lower in multiple than singleton pregnancies. The authors suggest that these estimates can be used for genetic counselling and prenatal screening.
- Links: Trisomy 21
- 21980404</pubmed>| PLoS One.
- Rebekah E Gee, Richard P Dickey, Xu Xiong, Latoya S Clark, Gabriella Pridjian Impact of monozygotic twinning on multiple births resulting from in vitro fertilization in the United States, 2006-2010. Am. J. Obstet. Gynecol.: 2014, 210(5);468.e1-6 PubMed 24373946
Cite error: Invalid
<ref>tag; name "PMID24770255" defined multiple times with different content
- B Boyle, J K Morris, R McConkey, E Garne, M Loane, M C Addor, M Gatt, M Haeusler, A Latos-Bielenska, N Lelong, R McDonnell, C Mullaney, M O'Mahony, H Dolk Prevalence and risk of Down syndrome in monozygotic and dizygotic multiple pregnancies in Europe: implications for prenatal screening. BJOG: 2014, 121(7);809-19; discussion 820 PubMed 24495335
- Simi Gupta, Nathan S Fox, Jessica Feinberg, Chad K Klauser, Andrei Rebarber Outcomes in twin pregnancies reduced to singleton pregnancies compared to ongoing twin pregnancies. Am. J. Obstet. Gynecol.: 2015; PubMed 26071922
- Diane J Lamb, Christel M Middeldorp, Catharina E M van Beijsterveldt, Jacqueline M Vink, Monique C Haak, Dorret I Boomsma Birth weight in a large series of triplets. BMC Pediatr: 2011, 11;24 PubMed 21453554 | BMC Pediatr.
- Andrea Weghofer, Katharina Klein, Maria Stammler-Safar, Christof Worda, David H Barad, Peter Husslein, Norbert Gleicher The impact of fetal gender on prematurity in dichorionic twin gestations after in vitro fertilization. Reprod. Biol. Endocrinol.: 2010, 8;57 PubMed 20534177 | Reprod Biol Endocrinol.
- J Hardin, S L Carmichael, S Selvin, E J Lammer, G M Shaw Increased prevalence of cardiovascular defects among 56,709 California twin pairs. Am. J. Med. Genet. A: 2009, 149A(5);877-86 PubMed 19353581
- Kamran Yusuf, Harvey J Kliman The fetus, not the mother, elicits maternal immunologic rejection: lessons from discordant dizygotic twin placentas. J Perinat Med: 2008, 36(4);291-6 PubMed 18598117
- Chantal Hoekstra, Zhen Zhen Zhao, Cornelius B Lambalk, Gonneke Willemsen, Nicholas G Martin, Dorret I Boomsma, Grant W Montgomery Dizygotic twinning. Hum. Reprod. Update: 2007, 14(1);37-47 PubMed 18024802
- Charles E Boklage Traces of embryogenesis are the same in monozygotic and dizygotic twins: not compatible with double ovulation. Hum. Reprod.: 2009, 24(6);1255-66 PubMed 19252194
- Judith G Hall Twinning. Lancet: 2003, 362(9385);735-43 PubMed 12957099
- Gaurav Sharma, Sheila S Nazarian Mobin, Michael Lypka, Mark Urata Heteropagus (parasitic) twins: a review. J. Pediatr. Surg.: 2010, 45(12);2454-63 PubMed 21129567
- A Graham Fieggen, Robert N Dunn, R Dick Pitcher, Alastair J W Millar, Heinz Rode, Jonathan C Peter Ischiopagus and pygopagus conjoined twins: neurosurgical considerations. Childs Nerv Syst: 2004, 20(8-9);640-51 PubMed 15278384
- Lynn J Shepherd, Graeme N Smith Conjoined twins in a triplet pregnancy: a case report. Case Rep Obstet Gynecol: 2011, 2011;235873 PubMed 22567498 | PMC3335527 | Case Rep Obstet Gynecol.
- Tayyab Batool, Jamshed Akhtar Conjoined twins: the flip side. APSP J Case Rep: 2010, 1(2);23 PubMed 22953266
- Cande V Ananth, Suneet P Chauhan Epidemiology of twinning in developed countries. Semin. Perinatol.: 2012, 36(3);156-61 PubMed 22713495
- Australian Bureau of Statistics Year Book Australia 2002
- S B de Haseth, M C Haak, A A W Roest, M E B Rijlaarsdam, D Oepkes, E Lopriore Right ventricular outflow tract obstruction in monochorionic twins with selective intrauterine growth restriction. Case Rep Pediatr: 2012, 2012;426825 PubMed 23050183 | PMC3462376 | Case Rep Pediatr.
- Ahmet Gul, Halil Aslan, Altan Cebeci, Yavuz Ceylan, Ali Ismet Tekirdag Monochorionic triamniotic triplet pregnancy with a co-triplet fetus discordant for congenital cystic adenomatoid malformation of the lung. Reprod Health: 2005, 2(1);2 PubMed 15819977 | PMC1082912 | Reprod Health.
- Sylke Steggerda, Enrico Lopriore, Marieke Sueters, Margot Bartelings, Frank Vandenbussche, Frans Walther 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? Pediatr. Dev. Pathol.: 2005, 9(1);52-5 PubMed 16808639
- Nahla Khalek, Mark P Johnson, Michael W Bebbington Fetoscopic laser therapy for twin-to-twin transfusion syndrome. Semin. Pediatr. Surg.: 2013, 22(1);18-23 PubMed 23395141
- C A Walsh, F M McAuliffe Recurrent twin-twin transfusion syndrome after selective fetoscopic laser photocoagulation: a systematic review of the literature. Ultrasound Obstet Gynecol: 2012, 40(5);506-12 PubMed 22378622
- R A Quintero, W J Morales, M H Allen, P W Bornick, P K Johnson, M Kruger Staging of twin-twin transfusion syndrome. J Perinatol: 1999, 19(8 Pt 1);550-5 PubMed 10645517
- Y Ville Twin-to-twin transfusion syndrome: time to forget the Quintero staging system? Ultrasound Obstet Gynecol: 2007, 30(7);924-7 PubMed 18044824
- A Cristina Rossi, Vincenzo D'Addario The efficacy of Quintero staging system to assess severity of twin-twin transfusion syndrome treated with laser therapy: a systematic review with meta-analysis. Am J Perinatol: 2009, 26(7);537-44 PubMed 19283655
- J J Stirnemann, B Nasr, F Proulx, M Essaoui, Y Ville Evaluation of the CHOP cardiovascular score as a prognostic predictor of outcome in twin-twin transfusion syndrome after laser coagulation of placental vessels in a prospective cohort. Ultrasound Obstet Gynecol: 2010, 36(1);52-7 PubMed 20582931
- K Søgaard, L Skibsted, V Brocks Acardiac twins: pathophysiology, diagnosis, outcome and treatment. Six cases and review of the literature. Fetal. Diagn. Ther.: 1999, 14(1);53-9 PubMed 10072652
- R G Gosden, S A Treloar, N G Martin, L F Cherkas, T D Spector, M J Faddy, S J Silber Prevalence of premature ovarian failure in monozygotic and dizygotic twins. Hum. Reprod.: 2007, 22(2);610-5 PubMed 17065173 | Hum Reprod.
Books and 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."
Multiple Pregnancy: The Management of Twin and Triplet Pregnancies in the Antenatal Period. National Collaborating Centre for Women's and Children's Health (UK). London: RCOG Press; 2011 Sep. (NICE Clinical Guidelines, No. 129.) Bookshelf PMID 22855972
Geoffrey Machin Non-identical monozygotic twins, intermediate twin types, zygosity testing, and the non-random nature of monozygotic twinning: a review. Am J Med Genet C Semin Med Genet: 2009, 151C(2);110-27 PubMed 19363805
K I Aston, C M Peterson, D T Carrell Monozygotic twinning associated with assisted reproductive technologies: a review. Reproduction: 2008, 136(4);377-86 PubMed 18577552
Evelyne E Muggli, Jane L Halliday Folic acid and risk of twinning: a systematic review of the recent literature, July 1994 to July 2006. Med. J. Aust.: 2007, 186(5);243-8 PubMed 17391087
N Prapas, I Kalogiannidis, I Prapas, P Xiromeritis, A Karagiannidis, G Makedos Twin gestation in older women: antepartum, intrapartum complications, and perinatal outcomes. Arch. Gynecol. Obstet.: 2006, 273(5);293-7 PubMed 16283408
Gordon C S Smith, Imran Shah, Ian R White, Jill P Pell, Richard Dobbie Mode of delivery and the risk of delivery-related perinatal death among twins at term: a retrospective cohort study of 8073 births. BJOG: 2005, 112(8);1139-44 PubMed 16045531
Gerardo Vela, Martha Luna, Jason Barritt, Benjamin Sandler, Alan B Copperman Monozygotic pregnancies conceived by in vitro fertilization: understanding their prognosis. Fertil. Steril.: 2011, 95(2);606-10 PubMed 20522324
James S Palmer, Zhen Zhen Zhao, Chantal Hoekstra, Nicholas K Hayward, Penelope M Webb, David C Whiteman, Nicholas G Martin, Dorret I Boomsma, David L Duffy, Grant W Montgomery Novel variants in growth differentiation factor 9 in mothers of dizygotic twins. J. Clin. Endocrinol. Metab.: 2006, 91(11);4713-6 PubMed 16954162
- National Collaborating Centre for Women's and Children's Health (UK). Multiple Pregnancy: The Management of Twin and Triplet Pregnancies in the Antenatal Period. London: RCOG Press; 2011 Sep. (NICE Clinical Guidelines, No. 129.) Available from: http://www.ncbi.nlm.nih.gov/books/NBK83105/ "This guideline contains recommendations specific to twin and triplet pregnancies and covers the following clinical areas: optimal methods to determine gestational age and chorionicity; maternal and fetal screening programmes to identify structural abnormalities, chromosomal abnormalities and feto-fetal transfusion syndrome (FFTS), and to detect intrauterine growth restriction (IUGR); the effectiveness of interventions to prevent spontaneous preterm birth; and routine (elective) antenatal corticosteroid prophylaxis for reducing perinatal morbidity. The guideline also advises how to give accurate, relevant and useful information to women with twin and triplet pregnancies and their families, and how best to support them."
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
- Norwegian Twin Registry PMID 22947319
- 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."
- A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols
Cite this page: Hill, M.A. 2017 Embryology Abnormal Development - Twinning. Retrieved March 30, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Twinning
- © Dr Mark Hill 2017, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G