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Abnormal Development - Twinning

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Contents
1 Introduction
2 Some Recent Findings
3 Twinning Prevalence
3.1 USA Data 2012
3.2 World Data 2003
3.3 Australian Data 2002
4 Dizygotic Twinning
5 Monoygotic Twinning
6 Conjoined Twinning
7 Triplets
8 Twin-twin Transfusion Syndrome
9 Quintero Staging System
10 Acardiac Twins
11 Premature Ovarian Failure
12 Additional Images
13 References
13.1 Books and Journals
13.2 Reviews
13.3 Articles
13.4 Search Pubmed
13.4.1 Pubmed Books
14 External Links
15 Glossary Links
Introduction

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"
(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.[1] Monozygotic twinning is thought to occur at a relatively constant rate of 3.54 per 1000
births across human populations, with assisted reproductive technologies possibly contributing to recent
changes.[2][3]
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,[4] and there are more maternal risks involved
with multiple pregnancies.

Abnormality Links: Introduction | Genetic | Environmental | Unknown | Teratogens | Cardiovascular |
Coelomic Cavity | Endocrine | Gastrointestinal Tract | Genital | Head | Integumentary | Musculoskeletal
| Limb | Neural | Neural Crest | Renal | Respiratory | Placenta | Sensory | Twinning | Developmental
Origins of Health and Disease | ICD-10 | Week 2
Some Recent Findings
Trends and correlates of monozygotic twinning after assisted reproductive technology[3] "Monozygotic
twinning, associated with increased infant morbidity and mortality, is more common after assisted
reproductive technology (ART) than in the general population. Although multiple factors have been
proposed as contributors, studies seeking to define causality have been underpowered or inconclusive.
We analyzed 392,136 pregnancies resulting from fresh, nondonor embryo transfers conducted between
2000 and 2011 and reported to the National ART Surveillance System. ...Monozygotic twin pregnancy
incidence after ART has increased over the past decade. Day-5 transfer and assisted hatching are
associated with increased monozygotic twinning risk." Assisted Reproductive Technology
Birth weight in a large series of triplets[5] "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.[6]
"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.[7] "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.[8] "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."
More recent papers
Mark Hill.jpg
This table shows an automated computer PubMed search using the listed sub-heading term.
Therefore the list of references do not reflect any editorial selection of material based on content or
relevance.
References appear in this list based upon the date of the actual page viewing.
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.
Links: References | Discussion Page | Pubmed Most Recent
Search term: Twinning
Yinyin Zhang, Nicolas Brodusch, Sylvie Descartes, Richard R Chromik, Raynald Gauvin Microstructure
Refinement of Cold-Sprayed Copper Investigated By Electron Channeling Contrast Imaging. Microsc.
Microanal.: 2014;1-8 PMID:24960434 Shinjiro Fujiyama, Shintaro Seino, Natsumi Kamiya, Koji Nishi,
Kenji Yoza, Yoshinobu Yokomori Adsorption structures of non-aromatic hydrocarbons on silicalite-1
using the single-crystal X-ray diffraction method. Phys Chem Chem Phys: 2014; PMID:24954128 S
Baragou, E Goeh-Akue, M Pio, Y M Afassinou, B Atta [Hypertension and pregnancy in Lome (sub-Saharan
Africa): Epidemiology, diagnosis and risk factors.] [Hypertension artrielle et grossesse Lom (Afrique
sub-saharienne) : aspects pidmiologiques, diagnostiques et facteurs de risque.] Ann Cardiol Angeiol
(Paris): 2014; PMID:24951092 Pongsathorn Chaiyasap, Supasak Kulawonganunchai, Chalurmpon
Srichomthong, Sissades Tongsima, Kanya Suphapeetiporn, Vorasuk Shotelersuk Whole Genome and
Exome Sequencing of Monozygotic Twins with Trisomy 21, Discordant for a Congenital Heart Defect and
Epilepsy. PLoS ONE: 2014, 9(6);e100191 PMID:24950249 Lingyan Ruan, Hadi Ramezani-Dakhel, Chain
Lee, Yongjia Li, Xiangfeng Duan, Hendrik Heinz, Yu Huang A Rational Biomimetic Approach to Structure
Defect Generation in Colloidal Nanocrystals. ACS Nano: 2014; PMID:24937767
Twinning Prevalence

Twinning in Low and Middle Income Countries Map[1]
USA Data 2012
A recent study of twinning in developed countries[9]
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.[10]
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."
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%)." [11]
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.[12] 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.[13]
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 (GA week 3) Week 2 (GA week 4)
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 Macaque
Xi at interphase 02.jpg
Monoygotic
Twin Type
Diamniotic
Dichorionic
Diamniotic
Monochorionic
Monoamniotic
Monochorionic
Conjoined
Table based upon recent a recent twinning review.[10] (More? Twinning)
Conjoined 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.[14]
Both ischiopagus and pygopagus conjoined twins have a range of variable spinal abnormalities.[15]
Conjoined twins 02.jpg Conjoined twins 03.jpg Conjoined twins 01.jpg
Conjoined twins ultrasound[16] Conjoined twins MRI[16] Conjoined twins after birth[17]
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 [5]
"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? [18] "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.[19]
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.[20][21] An alternative Children's Hospital of Philadelphia (CHOP) cardiovascular score,
appears to also be "not of clinical use as a prognostic marker in TTTS".[22]
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.[23]
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).[24]
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

Historic drawing - Twinning in fish embryo
References
1.0 1.1 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.: 2013; PMID:24373946
3.0 3.1 Jessica R Kanter, Sheree Boulet, Jennifer F Kawwass, Denise J Jamieson, Dmitry Kissin Trends
and correlates of monozygotic twinning after assisted reproductive technology. Obstet Gynecol: 2014,
123 Suppl 1;6S PMID:24770255
Isaac Blickstein, Sharon Perlman Single fetal death in twin gestations. J Perinat Med: 2012;1-5
PMID:22752835
5.0 5.1 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
PMID: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 PMID: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 PMID: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 PMID:18598117
Cande V Ananth, Suneet P Chauhan Epidemiology of twinning in developed countries. Semin.
Perinatol.: 2012, 36(3);156-61 PMID:22713495
10.0 10.1 Judith G Hall Twinning. Lancet: 2003, 362(9385);735-43 PMID:12957099
Australian Bureau of Statistics Year Book Australia 2002
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
PMID: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 PMID:19252194
Gaurav Sharma, Sheila S Nazarian Mobin, Michael Lypka, Mark Urata Heteropagus (parasitic) twins: a
review. J. Pediatr. Surg.: 2010, 45(12);2454-63 PMID: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 PMID:15278384
16.0 16.1 Lynn J Shepherd, Graeme N Smith Conjoined twins in a triplet pregnancy: a case report.
Case Rep Obstet Gynecol: 2011, 2011;235873 PMID:22567498 | PMC3335527 | Case Rep Obstet
Gynecol.
Tayyab Batool, Jamshed Akhtar Conjoined twins: the flip side. APSP J Case Rep: 2010, 1(2);23
PMID:22953266
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 PMID:16808639
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 PMID:10645517
Y Ville Twin-to-twin transfusion syndrome: time to forget the Quintero staging system? Ultrasound
Obstet Gynecol: 2007, 30(7);924-7 PMID: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 PMID: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 PMID:20582931
K Sgaard, 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 PMID: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
PMID: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
Reviews
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 PMID: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 PMID: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 PMID: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 PMID: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 PMID:16045531

Articles
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 PMID: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 PMID:16954162

Search Pubmed
Search Pubmed: Twinning | Monozygotic Twinning | Diygotic Twinning | Twin-twin Transfusion
Syndrome
Pubmed Books
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
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.
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."
Glossary Links
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| Symbols
Cite this page: Hill, M.A. (2014) Embryology Abnormal Development - Twinning. Retrieved June 27,
2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Abnormal_Development_-
_Twinning
What Links Here?
Dr Mark Hill 2014, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No.
00098G
Retrieved from https://php.med.unsw.edu.au/embryology/index.php?title=Abnormal_Development_-
_Twinning&oldid=136348
Categories:
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Types of Twins : Identical, Fraternal & Unusual Twinning
The term twin most notably refers to two individuals (or one of two individuals) who have shared the
same uterus (womb) and are usually. but not necessarily. born on the same day. A fetus alone in the
womb is called a singleton.
Due to the limited size of the mother's womb. multiple pregnancy is much less likely to carry to full term
than singleton birth (twins usually around 34 to 37 weeks).
Since some premature births often have health consequence to the babies. twin births are more often
handled with special procedures than regular births.
Fraternal Twins
Fraternal Twins (commonly known as "non-identical twins") usually occur when two fertilised eggs are
implanted in the uterine wall at the same time that is when the mother releases two eggs and both
become fertilized by two different sperms. The two eggs form two zygotes. and these twins are
therefore also known as dizygotic.
Dizygotic twins. like any siblings. have a very small chance of having the exact same chromosone profile.
but most likely have a number of different chromosones that distinguish them. Dizygotic twins may be a
different sex or the same sex. just as with any other siblings. Like singleton siblings. they share 50% of
their DNA.
Studies show that there is a genetic basis for fraternal twinning ;that is. non-identical twins do run in
families. However. it is only the female that has any influence on the chances of having fraternal twins
as the male cannot make her release more than one ovum. Your likelihood of having fraternal twins is
dependent upon the woman carrying a fraternal twin gene and can also be affected by heredity. race.
marital age and number of children previously born. Two-thirds of all twin births result in same sex
fraternal twins and one-third are different sex fraternal twins. About two-thirds of all twin births are
fraternal.
Identical Twins
Identical Twins occur when a single egg is fertilized by a single sperm to form one zygote (monozygotic)
but the zygote then divides into two separate embryos. The biological mechanisms that prompt the
single fertilized egg to split in two remain a mystery. The two embryos develop into foetuses sharing the
same womb. Depending on the stage at which the zygote divides. identical twins may share the same
amnion (in which case they are known as monoamniotic) or not (diamniotic). Diamniotic identical twins
may share the same placenta (known as monochorionic) or not (dichorionic). All monoamniotic twins
are monochorionic.
The later in pregnancy that twinning occurs. the more structures will be shared. Zygotes that twin at the
earliest stages will be diamniotic and dichorionic ("di-di"). Twinning between 4 to 8 days after
fertilization typically results in monochorionic-diamniotic ("mono-di") twins. Twinning between 8 to 12
days after fertilization will usually result in monochorionic-monoamniotic ("mono-mono") twins.
Twinning after 12 days post-fertilization will typically result in conjoined twins.
Dichorionic/Diamniotic : each twin has his/her own placenta, chorion and amniotic sac
Monochorionic/Diamniotic: twins share placenta and chorionic sac but have their own amniotic sac
Monoamniotic/Monochorionic : twins share placenta, chorionic and amniotic sac
Monoamniotic / Monochorionic Twins
Sharing the same amnion (or the same amnion and placenta) can cause complications in pregnancy. For
example. the umbilical cords of monoamniotic twins can become entangled. reducing or interrupting
the blood supply to the developing foetus. Monochorionic twins. sharing one placenta. usually also
share the placental blood supply. These twins may develop such that blood passes disproportionately
from one twin to the other through connecting blood vessels within their shared placenta. leading to
twin-to-twin transfusion syndrome. About 50% of mono-mono twins die from umbilical cord
entanglement.
Monozygotic twins are genetically identical unless there has been a mutation in development. and they
are almost always the same gender. (On extremely rare occasions. an original XXY zygote may form
monozygotic boy/girl twins by dropping the Y chromosome for one twin and the extra X chromosome
for the other.) Monozygotic twins generally look alike. although sometimes they appear as mirror
images of each other. Identical twins will also share the same blood type. eye and hair colour.
Examination of details such as fingerprints and teeth marks can tell them apart. As they mature.
identical twins often become less alike because of lifestyle choices or external influences such as scars.
While it was originally thought that identical twins do not run in families. but occur more or less
randomly. some recent research has suggested that a genetic predisposition may exist. The exact cause
for the splitting of a zygote or embryo is unknown.
Behaviour & Environmental Influences
Identical twins can behave as differently as any other siblings (a matter of much interest to
psychologists). They develop their own individual personalities to enable themselves to be identified as
individual persons. Many identical twins spend most of their time together (especially as children). so
people often assume that they will behave alike just as they look alike; however. this is not the case.
Twins are unique individuals that establish their own individual likes and dislikes. There are usually
obvious signs of differences when the identical twins are observed separately or together.
Identical twins have identical DNA but differing environmental influences throughout their lives affect
which genes are switched on or off. This is called epigenetic modification. A study of 80 pairs of twins
ranging in age from 3 to 74 showed that the youngest twins have relatively few epigenetic differences.
The number of differences between identical twins increases with age. 50-year-old twins had over 3
times the epigenetic difference that the 3-year-old twins had. Twins who had spent their lives apart
(such as those adopted by two different sets of parents at birth) had the greatest difference. (Fraga. et
al.. 2005).
Mirror Twins
Mirror twins. also called Mirror Image Twins. are a subset of identical twins and are identical twins with
opposite features. that is one will be right handed and the other will be left handed. One quarter (1/4)
of all identical twins may be mirror twins. These mirrors are literally reflections of each other and may
possess matching or almost matching fingerprints and share the same DNA. They result form a late split
of the fertilized egg at around 9-12 days. The one mirror may or may not have situs reverus or situs
inversus. This is where the organs will be on the opposite side of the body. heart being on the right. etc.
Half Identical Twins (Polar Body Twinning)
Polar body twinning occurs when an egg splits prior to fertilization and each half receives a separate
sperm. The twins share 75% of their DNA. This type (although not fully accepted as an "official" type of
twins by scientists yet) theorizes that twins aren't exactly identical and aren't exactly fraternal. but half
identical/half fraternal. It can happen when the oocyte (primary egg cell) divides twice on its way to
maturity. yielding egg cells and polar bodies at different stages along the way. Usually these smaller
polar bodies don't play a meaningful role in reproduction. But now scientists believe that some twins
could be the result of two of these egg cells and larger polar bodies being pregnated by two sperm. The
twins would most likely share all of their mother's genes but only half of their father's genes.
Twins of Two
Two eggs are released by the ovaries and each egg is fertilized by a different father. These fraternal
twins are genetically half-siblings and share 25% of their DNA.
Unusual Twinnings
There are some patterns of twinning that are exceedingly rare: while they have been reported to
happen. they are so unusual that most obstetricians or midwives may go their entire careers without
encountering a single case.
Among fraternal twins. in rare cases. the eggs are fertilised at different times with two or more acts of
sexual intercourse. either within one menstrual cycle (superfecundation) or. even more rarely. later on
in the pregnancy (superfetation). This can lead to the possibility of a woman carrying fraternal twins
with different fathers (that is. half-siblings). One 1992 study estimates that the frequency of
heteropaternal superfecundation among dizygotic twins whose parents were involved in paternity suits
was approximately 2.4%.
Among monozygotic twins. in extremely rare cases. twins have been born with opposite sexes (one
male. one female). The probability of this is so vanishingly small (only 3 documented cases) that
multiples having different genders is universally accepted as a sound basis for a clinical determination
that in utero multiples are not monozygotic. When monozygotic twins are born with different genders it
is because of chromosomal birth defects. In this case. although the twins did come from the same egg. it
is incorrect to refer to them as genetically identical. since they have different karyotypes.
Complications of Twin Pregnancy
Vanishing twins
Researchers suspect that more pregnancies start out as multiples than come to term that way. Early
obstetric ultrasound exams sometimes reveal an "extra" fetus. which fails to develop and instead
disintegrates and vanishes. This topic is discussed in more detail under a separate article.
Miscarried twin
Occasionally. a woman will suffer a miscarriage early in pregnancy. yet the pregnancy will continue; one
twin was miscarried but the other was able to be carried to term. Similar to vanishing twin.
Conjoined twins / Siamese twins
Conjoined twins are monozygotic twins (Monoamniotic-Monochorionic) whose bodies are joined
together at birth. This occurs where the single zygote of identical twins fails to separate completely.
perhaps because they split very late in development (12 days or later since conception). Most conjoined
twins are also mirror twins. This condition occurs in about 1 in 100.000 pregnancies.
Parasitic twins
Sometimes one twin fetus will fail to develop completely and continue to cause problems for its
surviving twin. One fetus acts as a parasite towards the other. Sometimes the parasitic twin just
becomes an almost indistingishiable part of the other.
A chimera is a person who is a complete normal human with no extra parts. but some of the parts
actually came from his or her twin. A chimera may be from either from identical twin fetuses (where it
would be impossible to detect). or from dyzygotic fetuses. which could be identified by chromosonal
comparisons from various parts of the body.
Human Twins - Twinning Rate
Historically, about 1 in 80 human births (1.2%) has been the result of a twin pregnancy. The rate of
twinning varies greatly among ethnic groups. ranging as high as about 6% for the Yoruba (Nigeria) or
10% for a tiny Brazilian village. The widespread use of fertility drugs causing hyperovulation (stimulated
release of multiple eggs by the mother) has caused what some call an "epidemic of multiple births". In
2001. for the first time ever in the US. the twinning rate exceeded 3% of all births. Thus. approximately
6% of children born in the US in 2001 were twins. In the UK approx 1.5% of all multiple births are twins
(3% of the total UK population). this has increased by almost 50% over the last 20 years. The primary
reasons for this are increase in maternal age. assisted conception techniques eg IVF and the
improvement in neo-natal care.
Nevertheless. the rate of identical twins remains at about 1 in 250 across the globe. further suggesting
that pregnancies resulting in identical twins occur randomly.
Multiple births
Sometimes multiple births may involve more than two fetuses. If there are three, they are called
triplets; four. quadruplets; five. quintuplets; six. sextuplets. seven. septuplets. and so on. Before the
advent of ovulation-stimulating drugs. triplets were quite rare (approximately 1 in 8000 births) and
higher order births so rare as to be almost unheard of. Multiple pregnancies are usually delivered before
the full term of 40 weeks gestation: the average length of pregnancy is around 37 weeks for twins. 34
weeks for triplets and 32 weeks for quadruplets.
Predisposing factors
The cause of monozygotic twinning is unknown. Fewer than 20 families have been described with an
inherited tendency towards monozygotic twinning (people in these families have nearly a 50% chance of
delivering monozygotic twins). Some evidence suggests that the environment of the womb causes the
zygote to split in most cases.
Dizygotic twin pregnancies are slightly more likely when the following factors are present in the woman:
She is of African descent
Between the age of 30 and 40 years
Greater than average height and weight
Conception is soon after the cessation of oral contraceptives
Several previous pregnancies.
Women undergoing certain fertility treatments may have a greater chance of multiple births. This can
vary depending on what types of fertility treatments are used. With in vitro fertilisation (IVF). this is
primarily due to the insertion of multiple embryos into the uterus. Some other treatments such as the
drug Clomid can stimulate a woman to release multiple eggs. allowing the possibility of multiples. Many
fertility treatments have no effect on the likelyhood of multiple births. Currently around 25% of IVF
treatment results in a multiple birth.
Twin Studies
Twin studies are studies that assess identical (monozygotic) twins for medical. genetic. or psychological
characteristics to try to isolate genetic influence from environmental influence. Twins that have been
separated early in life and raised in separate households are especially sought-after for these studies.
which have been invaluable in the exploration of human nature.
Zygosity Testing:
It is difficult to tell if twins are identical or fraternal at birth. Some identical twins may be born with
individual sets of membranes, which may lead to the mistaken assumption that the babies are fraternal.
One way to tell the difference is to have the twins DNA tested. Identical twins share the same genetic
information. while fraternal twins share around half. The test can be done with a sample of cheek cells.
collected painlessly. Contact The Multiple Births Foundation for more information on DNA testing.
Article by: Delyth Raffell, Founder of TwinsUK and mum to fraternal twins.
Looking for more information on Twins & Multiples Statistics, Facts & Trivia

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Complications specific to multiple pregnancy
Some pregnancy complications only occur in twin and multiple pregnancies. These include selective
intrauterine growth restriction (IUGR), Twin-to-Twin Transfusion Syndrome (TTTS) and cord
entanglement in twins who share an amniotic sac.
Twin-to-Twin Transfusion Syndrome (TTTS)
Twin-to-Twin Transfusion Syndrome (TTTS) is a rare complication of twins and higher gestation
pregnancies. The lives of both twins are endangered by this condition, and complications for surviving
babies can include cerebral palsy. Treatment of TTTS with the laser fetoscope, available at Auckland
Hospital, improves the survival rate of both twins to 50-60%, with a 75% chance that at least one twin
will survive.
Early diagnosis of chorionicity is vital to detect TTTS. Dr Emma Parry, the NZMBA medical advisor,
emphasises the need for early diagnosis of twin type (chorionicity) and regular scanning to identify the
potential for problems early in the pregnancy:
About one-quarter of all twin pregnancies share a placenta. If you have a scan that shows you are having
twins or higher-order multiples, it is important to find out if they are sharing a placenta before 16 weeks
gestation, because after this scans are not accurate enough to diagnose whether the placenta is shared.
Dr Parry has devised a Guideline for the Management of Monochorionic Twins, where she discusses
TTTS, and indicates that women who have been diagnosed with a monochorionic twin or multiple
pregnancy need to have regular scans beginning at 16 weeks gestation, not the usual 20 weeks for twins
who do not share a placenta. Dr Parry states that women also need to know the warning signs for TTTS:
Between 16 to 28 weeks, watch for a sudden increase in the size of your abdomen and shiny red skin,
with a feeling of it being stretched or tight. If this happens, your doctor or midwife needs to arrange an
urgent scan to assess what is happening.
To find out more about TTTS, click here.
Selective intra-uterine growth restriction (sIUGR)
Intrauterine growth restriction (IUGR) occurs in 3-10% of singleton pregnancies, 9% of twin pregnancies
and 9.9% of monochorionic twin pregnancies. A fetus suffering from IUGR will be small for its gestational
age and not growing at the normal, expected rate. IUGR, thought to be a result of problems with the
placenta, can also be caused by health problems in the mother. It is diagnosed by ultrasound scanning of
the babies growth. A difference in the rate of growth between the babies (growth discordance) in the
first trimester may also indicate anatomical and chromosomal abnormalities.
Up to 32 weeks gestation, the growth rate for twins should be the same as for singletons, but after 32
weeks growth slows due to the restricted space in the womb/uterus and placental insufficiencyit is
overworked growing twins! In triplets, this process starts earlier. The degree of difference in growth
(growth discordance) between twin or multiple babies can indicate the degree of the IUGR:
Mild is less than 15% difference
Moderate is between 15-30% difference
Severe is more than 30% difference.
When evaluating the babies growth in a multiple pregnancy, it is important to know whether the twins
are identical (chorionicity), as they are at a greater risk of IUGR which may be due to placental
insufficiency, unequal placental sharing (ITP), placental cord abnormalities and TTTS. IUGR may affect
one twin in 12-25% of pregnancies, especially with TTTS, where the difference in growth in the donor
twin can be can be up to 85%. The complications of growth restriction that affects only one twin
(selective IUGR, or sIUGR), include intrauterine death, which may cause the death or disability of the co-
twin, or premature labour.
Abnormal growth discordance can occur in up to 30% of twin pregnancies, but most twins do well
despite it. In the second trimester, treatment options include selective termination if one twin is
abnormal, so that there is less risk of adverse impact on the co-twin. Should one twin die in-utero, the
specialist team aims to get the pregnancy to 34 weeks before delivering the co-twin.
The management of a multiple gestation with severe growth discordance in the third trimester is fairly
complex, and involves:
Serial growth scans (ultrasounds every 1-2 weeks)
Doppler blood flow studies (ultrasound procedure to measure the blood flow through the placental
blood vessels)
Cardiotocographs (CTG fetal monitoring)
Possible admission for surveillance
Giving steroids between 24 and 34 weeks for fetal lung development.
If TTTS or placental cord abnormalities are involved, there are two main treatment options:
Umbilical cord occlusion (via laser, bipolar coagulation or fetoscopy) for selective reduction (feticide) in
order to save the co-twin from death or harm
Selective Laser Photocoagulation of Communicating Vessels (SLPCV), a new treatment for severe TTTS,
which may allow both twins to survive, and benefit the smaller twin. Studies into this area of fetal
medicine continue.
To find out more about Intrauterine growth restriction, click here.
Cord entanglement in identical twins who share the same sac (monoamniotic twins)
The umbilical cords run from each baby to the placenta, on the wall of the uterus. They feed nutrients,
oxygen and blood flow between the babies and the mother. By the time a fetus is full-term, its umbilical
cord is around 50 cm long, allowing freedom for the fetus to move inside the womb. Any baby can get
tangled in their own cord and there is a risk of compressing the cord (thus, cutting off the supply of
nutrients, oxygen and blood) once the membranes have ruptured (during labour) and there is no longer
as much fluid to cushion the cord. This risk occurs for each baby during a multiple birth.
So long as each baby in a multiple pregnancy has its own amniotic sac, they are at no risk of becoming
tangled in their siblings cord. In a monoamniotic pregnancy, however, because the babies share a sac,
the risk of cord entanglement is greater, as each baby is not only at risk of getting tangled in their own
cord, but of also getting tangled in their siblings cord. Cord entanglements (also called Cord Accidents)
are the number one risk in this type of pregnancy.
To put this danger in perspective, virtually all cases of monoamniotic twins will have tangled cords. In
order for entanglement to become dangerous, there must also be cord compression. It is very possible
to have entanglement apparent as early as 10 weeks (and probably even earlier), and still have both
babies born safely at 34 weeks with no complications. Nevertheless, as cord entanglement is the first
sign of possible problems, expect the obstetricians to be on high-alert for it.
There are many pictures of cord entanglement on the Monoamniotic Monochorionic Support website
(www.monoamniotic.org) that show the level of entanglement that babies can survive through. It may
be comforting for some expectant parents to view these, but keep in mind that the pictures are graphic
and disturbing.
The only treatment doctors can offer is expediting the birth. If serious problems are discovered before
24-26 weeks (the point of viability outside the womb), there is, sadly, nothing that can be done. After
that point, if life-threatening problems are discovered, the babies can be bornalthough the earlier the
birth occurs, the higher chance that the babies may suffer from complications due to extreme
prematurity.
While some cord accidents are sudden, it appears that the majority of fatal cord accidents are gradual.
Ultrasound, Doppler-imaging (a way of seeing actual blood flow through the cords), and fetal monitoring
(CTGs) enable early detection of possible problems. This means that if you are watching often enough,
signs of cord compression may be detected early enough to perform an emergency birth, before it is too
late.
So, the key to managing a monoamniotic pregnancy is frequent assessment and monitoring. How
much, and how often, is a question that you will have to address with your obstetrician. Generally
speaking, more is better.
For more information about the management of monoamniotic pregnancy, click here.
You may also be interested to read Jocastas storyMonoamniotic Twins.
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Our long experience with prenatal diagnosis and planning for optimum care allows us to offer the
highest quality treatment whether intervention is indicated before or after birth.
Under the direction of Dr. Michael Harrison, the Fetal Treatment Center was the first institution to
develop fetal surgery techniques. The first open fetal surgery in the world was performed at UCSF since
the early 1980's. We presently have more experience with fetal surgery and endoscopic fetal
intervention (FETENDO fetal surgery) than any other institution in the world. We are dedicated to twin
complication research and treatment innovation.
What are twin pregnancy complications?
watch video
A single placenta normally supports a single fetus. When the situation arises in which two fetuses have
to share a single placenta, complications may sometimes develop. Identical twins that share a single
placenta are called monochorionic twins (MC). Chorion is the Latin root that refers to the placenta,
while the word amnion refers to the sac, or membranes that surround each fetus. While fraternal
twins (2 eggs and 2 sperm) are always surrounded in their own sacs and have their own individual
placentas, 70% of identical twins may end up sharing a single placenta. Only 1% of identical twins share
both a single placenta and a single sac, and this poses significant risk.
medical illustration of normal monochorionic twins - chrisgralapp.comWhen two fetuses share one
placenta, their umbilical cords may implant anywhere there is no set or predictable pattern and
depending on where they implant, one fetus may get less of a share of the placenta than its co-twin,
resulting in less blood flow and nutrition to one fetus, with more to the other (unequal placental
sharing). As a result, although identical twins usually share the same genetic material, they may actually
grow differently. Like the roots of a tree, the blood vessels that run from each implanted cord may
connect with each other beneath the surface, as there is nothing separating them within a single
placenta. Depending on which types of vessels connect to which, one fetus may transfuse blood to the
other. We will discuss each of these complications, their risks, and potential treatments, below.
Monochorionic Twins Recommendations
Thumbnail of Monochorionic Twin Brochure
The following recommendations are meant for both patients and their providers as guidance during a
pregnancy with monochorionic twins. For questions and referrals please call us at 1-800-RX-FETUS.
You can also download and print this information with our Monochorionic Twins Recommendations PDF
brochure.
Monochorionic Twins Recommendations
Complications Unique to Monochorionic Twins
Amniotic fluid discordance
Growth discordance ( > 20%)
Unequal placental sharing
Selective intrauterine growth restriction (S-IUGR) in one fetus
TTTS - clinically defined as a deepest vertical pocket of > 8 cm in one twin and < 2 cm in in the other
twin, simultaneously. Note: growth discordance may also be seen but not necessary for the diagnosis.
Anomalies in on fetus
TRAP Sequence
Components of UCSF Evaluation
Level II anatomic survey for fetal anomalies
Special attention paid to cord insertions and vascular mapping
Fetal echocardiagraphy both for the structural integrity and functional (systolic and diastolic) pathology
Fetal brain MRI > 22 weeks when indicated and appropriate
Potential Surgical Procedures
Selective fetoscopic laser ablation
Radiofrequency ablation (RFA) cord occlusion
Timeframe for Referrals to UCSF
Consider Referral
Significant amniotic fluid discordance
While TTTS is defined as having a DVP > 8 cm and < 2 cm simultaneously, we encourage referral for
evaluation if the fluid pockets become significantly discordant even before TTTS criteria are met
Significant growth discordance defined as > 20% difference
Polyhydramnios in one twin with normal fluid in the other
Suspicion of discordant anomaly
We encourage you to call our center to discuss your findings if you have concerns at 1-800-RX-FETUS
Call for Timely Referral (need to see patient within 1 week)
DVP > 8 cm and < 2 cm with bladder visualized in donor and normal umbilical artery dopplers
Call for Urgent Referral (need to see patient within a couple days)
DVP > 8 cm and < 2 cm with no visible bladder in donor and/or abnormal umbilical doppler
Suspected Hydrops
What is Needed For Referral
Patients referred to UCSF for an evaluation should have the following faxed to 415-502-0660:
Demographic information
A copy of the front/back of their health insurance card
All OB/Perinatal medical records
If insurance authorization is required, please download the Monochorionic Evaluation Codes PDF for the
proper codes.
What is Twin to Twin Transfusion Syndrome (TTTS)?
watch video
Because there is no barrier separating the two fetuses from each other, there are almost always blood
vessel connections in the placenta shared by two fetuses in monochorionic twin (MC) pregnancies. As a
result of these connections, in about 10-15% of monochorionic twins (sharing one placenta) an
imbalance in the circulations of the fetuses can develop. In these instances, there may be significant
transfer of blood from one twin (the so-called donor) to the other twin (the so-called recipient),
resulting in twin-to-twin transfusion syndrome (TTTS).
medical illustration of normal monochorionic twins - chrisgralapp.commedical illustration of stuck
twin syndrome - chrisgralapp.commedical illustration of TTTS - chrisgralapp.comTwin-to-Twin
Transfusion Syndrome (TTTS) is a serious, progressive disorder. The twins do not have malformations,
but one transfuses the other through abnormal or imbalanced blood vessel connections in the shared
placenta. More specifically, an artery branches off from the donor twins umbilical cord, entering the
placenta in order to obtain oxygen and nutrients for the blood from the mothers circulation.
Unfortunately, the corresponding vein that would normally bring the now nutrient-rich blood back to
that same fetus instead is directed toward the other twin via this abnormal arterio-venous connection.
As a result, if there are no connections flowing in the opposite direction, one twin receives too much
blood and the other too little.
How Does This Blood Imbalance Affect the Fetus?
When a fetus is anemic, or doesnt have enough blood and oxygen, it tries to use what it has most
efficiently. This is accomplished by emphasizing the blood flow to the most important organs (the brain
and the heart) and shutting down less vital organs, such as the kidneys. Thus, the donor twin will make
a lot less and sometimes no urine. Meanwhile, the recipient twin is overloaded with blood and
volume, and is urinating excessively as a result.
Low amniotic fluid is termed oligohydramnios, while a high level of amniotic fluid is called
polyhydramnios. TTTS is diagnosed by the ultrasound findings of high amniotic fluid (polyhydramnios)
in the amniotic sac of one twin (the recipient) and low amniotic fluid (oligohydramnios) around the
other twin (the donor). The recipients blood can become thick and difficult to pump around the body.
The recipient twin, having to pump the thick extra volume of blood, can develop heart failure,
generalized soft tissue swelling (hydrops), and, in some cases, fetal death.
The donor twin is at risk for developing failure of the kidneys and other organs because of inadequate
blood flow. Because of the blood vessels that connect the circulations of the two fetuses across the
shared placenta, if one twin dies, the other twin faces significant risk of death or damage to vital organs.
If the other twin survives, there is up to a 40% risk of some form of brain injury. Unfortunately, without
treatment, approximately 7080% of twins with TTTS will die. Survivors may have injuries to their brains,
hearts and/or kidneys.
Although technically speaking the diagnosis of TTTS is based on the amniotic fluid levels in each sac, the
twins may be significantly different in their weights/sizes as well. Some of the size differences may be
due to the TTTS process. However, much of the difference in size results from the fact that the portion
of the placenta devoted to each twin differs (unequal placental sharing). The majority of MC twins that
develop TTTS also have some unequal placental sharing, with smaller placental portion assigned to the
donor twin. Further, many twins that only have unequal placental sharing (but are not transfusing one
another) may be incorrectly diagnosed as having TTTS. Differences may be subtle, but outcomes are
dependent on accurate diagnosis, and the treatment and management are different for these
conditions.
What is the outcome for a fetus with TTTS?
watch video
In Twin-to-Twin Transfusion Syndrome (TTTS), the donor twin responds to anemia and low volume by
trying to make the most efficient use of the blood it does have. Blood is shunted preferentially to the
most vital organs (the brain and the heart), and away from other, less vital, internal organs such as the
kidneys. This partial shutdown of the kidneys results in the fetus making less urine. Because amniotic
fluid is mostly comprised of fetal urine, the reduced urine output results in low amniotic fluid level, or
oligohydramnios.
As the kidneys make less and less urine and the degree of oligohydramnios worsens, the fetal bladder
may become empty and no longer visible by ultrasound (as it is not being filled with urine). Meanwhile,
the recipient becomes overloaded with fluid as a result of the on-going blood transfusion from the
donor twin, and responds by producing large amounts of urine in an effort to reduce all of its excess
volume. This leads to very large amounts of amniotic fluid in the recipients sac (polyhydramnios). It is
the combination of oligohydramnios and polyhydramnios in a MC twin pair seen by ultrasound that
indicates the diagnosis of TTTS. Careful obstetric ultrasound is crucial for correctly detecting and
diagnosing TTTS during pregnancy. The ultrasound exams at our center are performed by specialists,
widely renowned for their diagnostic skills and expertise in this field, who have written textbooks and
many scientific articles about fetal conditions, such as TTTS and unequal placental sharing.
In cases of TTTS, in addition to abnormal amniotic fluid volumes, the twins are often discrepant in size as
well, with significant discordance in their estimated fetal weights. The recipients blood can become
thick and difficult to pump around the body. The recipient twin, having to pump the thick extra volume
of blood, can develop heart failure, generalized soft tissue swelling (hydrops), and, in some cases, fetal
death. The donor twin is at risk for developing failure of the kidneys and other organs because of
inadequate blood flow. Because of the blood vessels that connect the circulations of the two fetuses
across the shared placenta, if one twin dies, the other twin faces significant risk of death or damage to
vital organs. If the other twin survives, there is up to a 40% risk of some form of brain injury.
Unfortunately, without treatment, approximately 7080% of twins with TTTS will die. Survivors may
have injuries to their brains, hearts and/or kidneys.
Maternal Mirror Syndrome
In cases with extreme fetal tissue swelling, or hydrops, the pregnant woman may be at risk for
maternal mirror syndrome, the term used to describe the process in which the mothers condition
mimics that of the sick fetus. Because of a high-flow, high-volume cardiovascular state, the mother may
develop symptoms that are similar to pre-eclampsia which may include vomiting, hypertension,
generalized body swelling (more so than usual), excessive protein in the urine (proteinuria), and
dangerous build-up of fluid in her lungs (pulmonary edema). While this is a rare occurrence, it is
imperative that the pregnant woman be carefully followed. Management must include continued
optimal obstetric/prenatal care with surveillance for such maternal conditions, while attention is paid to
the complicated twin pregnancy.
How serious is my fetuss condition?
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The severity of Twin-to-Twin Transfusion Syndrome (TTTS) is partially based on the stage in pregnancy at
which the condition becomes evident (the earlier it presents, the more serious it is). In addition, the
degree of fluid imbalance between the twins is important in grading or staging the problem. True TTTS
occurs when one twin of a monochorionic pair is shown by ultrasound to have a deepest pocket of
amniotic fluid in its sac of less than 2cm (the donor), while at the same time, the deepest pocket of
amniotic fluid measures greater than 8cm in the other twins sac (the recipient).
A bladder that remains empty in the donor twin is a concerning sign, indicating a more advanced stage
of TTTS. The situation worsens further when, in addition to abnormal discrepant fluid volumes,
abnormal blood flow patterns are shown by ultrasound in the umbilical cord vessels of either or both
twins. Finally, evidence of heart failure and tissue swelling (hydrops) in either twin, usually the recipient,
is an indication of a very serious, advanced stage.
Dr. Ruben Quintero developed the widely used staging system for TTTS (see below). Many patients in
whom TTTS is suspected may, on further investigation, be found to have twins with discrepant fluid
volumes but do not meet the definition for stage I TTTS. Still, all patients carrying MC twins with
significantly unequal amniotic fluid volumes and/or fetal weights should be evaluated and followed very
carefully for changes, as true TTTS can develop and worsen rapidly.
Fetal Echocardiogram
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To further evaluate the severity of TTTS, fetal echocardiography is often performed at our institution.
Fetal echocardiograms are specialized, targeted ultrasound studies of the heart, performed by pediatric
cardiologists with special expertise in this area.
Early changes of heart failure are usually seen first in the recipient twin, as its heart has to work hard to
pump the extra blood. These exams may reveal increased size of some of the heart chambers, and
changes in flow across the heart valves (for example, tricuspid regurgitation). If the stress and overload
on the recipient continues untreated, progressive changes may include decreased function of the heart
chambers, and possible development of narrowing of one of the heart valves (pulmonary stenosis).
Umbilical Artery Blood Flow
Finally, using information from both the echocardiogram and obstetric ultrasound exam, we look for
blood flow patterns in the umbilical artery and vein and other major fetal blood vessels. Blood in the
umbilical artery (UA) normally flows away from the fetus and toward the placenta, in an attempt to
obtain fresh oxygen and nutrients from the mothers circulation. If a placental condition worsens, it
becomes harder for the blood to flow toward and within the placenta. With each heartbeat, the fetus
pushes blood toward the placenta (the systole phase) through the umbilical artery, and normally, that
beat is strong enough for blood to keep flowing forward, toward the placenta, even as the heart re-fills
for its next beat (the diastole phase).
In some cases, as TTTS progresses, forward flow in the umbilical artery of the donor may diminish
between heartbeats. If the condition worsens, there may be no flow or even reversal of flow direction
during the re-filling (diastole phase) of the fetal heart.
All of the echocardiogram and ultrasound exam findings are considered in determining the severity of
TTTS for each individual pregnancy.
What treatment choices do I have and is laser the only option?
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Because Twin-to-Twin Transfusion Syndrome (TTTS) is a progressive disorder, early treatment may
prevent complications, including preterm labor and premature rupture of membranes due to excessive
fluid (polyhydramnios). Treatment for TTTS depends on the severity of the condition and the current
stage of your pregnancy.
Fetoscopic Laser Intervention
All patients with stage II, III or IV TTTSand some patients with stage Ishould learn about and
consider fetal intervention. In most instances, the appropriate, optimal therapy will be fetoscopic laser
intervention. Our center was one of the first in the world to perform fetoscopic laser to treat TTTS.
Survival rates for at least one twin are greater than 85% and for both twins is approximately 60% at our
center.
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The fetal laser procedure is performed by introducing a thin fiber-optic scope through the mothers
abdominal wall, through the wall of the uterus and into the amniotic cavity of the recipient twin. By
examining the blood vessels on the placental surface directly, the abnormal vascular connections
between the twins can be found and eliminated by directing a laser beam at them. Only those vessels
that go from one twin to the other are coagulated by the laser beam. The normal blood vessels that help
nourish each twin are left intact.
A detailed ultrasound examination prior to the procedure demonstrates the sites where the umbilical
cords attach to the shared placenta and may help locate abnormal inter-twin connections, making it
quicker and easier to identify with the fetoscope. After the laser procedure is completed, an
amnioreduction (removing extra amniotic fluid) is performed, to decrease the chance of early labor and
help make the pregnancy more comfortable.
What About Amnioreduction?
Many families ask whether amnioreduction is a potential treatment option for TTTS. Some of our most
expert European colleagues attempted to address the question whether laser or amnioreduction was
the best therapy for TTTS. In a randomized prospective trial, they found 76% survival of at least one
fetus and 36% survival of both twins with laser, compared with 51% survival of at least one fetus and
26% survival of both twins with amnioreduction. For many researchers and experts in this field, this
study showed that laser was the preferred therapy for TTTS.
At our center, however, we have found a group of patients with early TTTS that respond well to
amnioreduction, a less invasive therapy. In a small percentage of pregnancies that develop TTTS, an
artery to artery (A-A) connection between the twins on the surface of the placenta can be found using
ultrasound. The twin-pairs in whom these connections are demonstrated by ultrasound, have been
shown to have better outcomes overall, and in our experience, over 80% survival of both twins after
being treated with amnioreduction. Thus, although laser is the appropriate therapy for the vast majority
of patients with TTTS, we occasionally offer amnioreduction to patients with TTTS who meet criteria for
this therapy.
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With our multidisciplinary team of expert radiologists and surgeons the Fetal Treatment Center is
uniquely qualified to evaluate which treatment is best for you. To find out more best please contact our
center.
Learn More
What is as acardiac twin or the TRAP sequence?
How serious is my fetuss condition?
What options do I have?
What is and acardiac twin or the TRAP sequence?
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Twin reversed arterial perfusion (TRAP) sequence or acardiac twinning is a very rare problem, occurring
in approximately 1% of monochorionic twins (MC, twins sharing one placenta). One twin is usually
structurally completely normal. The other is an abnormal mass of tissue, consisting usually of legs and a
lower body, but no upper body, head or heart. Because of the absent heart, the term acardiac twin
was been used to describe this mass. The normal fetus is referred to as the pump twin because its
heart is used to pump blood to the abnormal mass. The acardiac twin has no chance of survival.
Due to the absence of a beating heart, the acardiac does not send blood to any portion of the placenta,
and all of its blood supply comes from and goes back to the circulation of the pump twin through unique
vascular connections on the surface of the shared placenta. Arteries usually carry blood away from the
fetus and toward the placenta to receive oxygen from the mothers circulation. When there is an
acardiac twin, the unique vascular connections allow blood in the artery to flow in the reversed
direction (toward the acardiac fetus rather than away from it). Thus, the phrase twin reversed arterial
perfusion (TRAP) sequence has been used to describe this condition.
The normal pump twin faces the excess burden of having to send and receive blood to the acardiac
mass as well as to its own growing tissues. As such, the normal twins heart has to work extra hard and is
under a lot of stress. This can result in heart failure for the normal twin. Left untreated, up to 50% of
these otherwise normal twins may die in utero (stillbirth) or die shortly after birth.
How serious is my fetuss condition?
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The risk of the normal or pump twin going into heart failure and dying seems to depend on the size of
the acardiac. The larger the acardiac compared to the pump twin the greater the risk. The amount of
blood flow into the acardiac also seems to play a role. The more blood flow the higher the risk. The
harder the pump twin's heart is working, the greater the risk of heart failure also. All of these things can
be looked for with ultrasound tests. In critical cases these tests may have to be repeated frequently.
What options do I have?
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The condition may only require monitoring in low risk cases where the acardiac twin is small and there is
little cardiac stress on the pump twin. With frequent ultrasounds, we can keep and eye on the health of
the normal twin and identify signs of heart failure in the acardiac twin. If heart failure of the acardiac
twin is identified, and the pregnancy is far enough along then the normal pump twin would simply be
delivered.
Fetal Treatment: Radio-Frequency Ablation (RFA)
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Over the years, many efforts have been made to treat TRAP sequence, focused on finding a way to
safely stop flow to the acardiac mass, so that the normal pump twin is protected and is no longer in
danger of heart failure or death. Our center pioneered the most successful form of treatment, taking
advantage of advanced technology termed radiofrequency ablation (RFA) to stop blood flow into the
acardiac mass.
TRAP sequence treatment illustrationThe major benefit of the radiofrequency ablation technique, as
compared to others such as laser or bipolar coagulation, is the size of the instrument used. The RFA
technique uses a small 17-gauge needle, which is approximately 1 mm diameter in size (whereas as
other procedures require 3 mm diameter instruments). Use of this smaller device leads to fewer
complications, such as preterm labor, and less trauma to the pregnant patient. The procedure is
performed using real-time ultrasound guidance.
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Having pioneered this technique, our center has the worlds largest experience with this approach. We
have published our experience using RFA, and have shown over 90% success in treating
monochorionic/diamniotic TRAP sequence pregnancies with an average gestational age at delivery of
approximately 35 weeks. This compares favorably with other reported techniques that have been
described for the treatment of TRAP, and has dramatically improved the outcome for pump twins in
these pregnancies.
What is unequal placental sharing?
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Although Twin-Twin Transfusion Syndrom (TTTS) is one of the most common diagnoses made in
monochorionic twins (MC), not all MC twin pregnancies in which there are unequal fluid levels or a
difference in size of the twins have TTTS. These findings can also be seen in a condition called unequal
placental sharing.
When two fetuses share one placenta, their umbilical cords may implant anywhere there is no set or
predictable pattern and depending on where they implant, one fetus may get less of a share of the
placenta than its co-twin, resulting in less blood flow and nutrition to one fetus, with more to the other
(unequal placental sharing). As a result, although identical twins usually share the same genetic material
(split from one egg/sperm), they may actually grow differently. The normally grown twin typically has
normal or generous (but not excessive, or polyhydramnios) amniotic fluid level. The other twin may
have a smaller placental share, resulting in a smaller size. The smaller twin may have either normal
amniotic fluid volume or, if its growth becomes progressively restricted, can develop low fluid
(oligohydramnios).
How serious is my fetuss condition?
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Ultrasound evaluations provide us with the information to determine the severity of the situation. The
greater the degree of size/weight difference between the twin fetuses the more serious the problem is.
Also the less fluid present in the sac of the smaller twin, the more serious the situation. We also monitor
the blood flow in the umbilical cords of the fetuses using Doppler ultrasound. A high resistance pattern
is characteristic in the smaller, sicker one, and a normal one in the larger.
Unequal Placental Sharing Vs TTTS
Differentiating unequal placental sharing from TTTS can be challenging as many pregnancies with TTTS
have some element of unequal sharing, and many pregnancies with unequal sharing may have some
element of TTTS. However, when unequal sharing is the more significant aspect of the problem,
amniotic fluid discrepancies do not typically reach the levels seen with severe TTTS, and the issue is
more pointedly about the size/weight discrepancy. TTTS is defined by a deepest vertical pocket (or
DVP) of 8cm or greater in the recipient twins sac, with a simultaneously low DVP of 2cm or less in the
donor twins sac. With unequal placental sharing, the fluid for each twin may be normal, or the smaller
twin may exhibit some degree of low-fluid related to its restricted growth. The difference in size
between the twins may be marked and may reach 40% or greater (a difference of up to 20% is
considered within the normal range for MC twins).
Twin pregnancies with unequal placental sharing have to be followed very closely for possible
development of TTTS. Serial ultrasound exams are performed to calculate the weights, watch the
growth and fluid levels of each twin. Although the smaller fetus may be somewhat restricted in its
growth, it is still typically possible for that twin to grow well enough to sustain normal function. The goal
is to help get that fetus safely to a gestational age when early delivery would be an acceptable
alternative to continued (or worsening) growth restriction in the womb while remaining mindful of the
other, normally grown twins best interests.
Vascular Connections: Arteries Vs Veins
As mentioned in the TTTS section, virtually all MC twin pairs have vascular connections within the single
shared placenta. Importantly, there are different kinds of connections, because there are different kinds
of blood vessels. Specifically, each twin sends arteries and veins from the base of its umbilical cord
toward and away from the placenta. When vessels from each twins circulation erroneously connect
within the placenta, they may do so in any combination: an artery to an artery, a vein to a vein, or an
artery to a vein. The culprit in TTTS is the abnormal connection between an artery from one twin and a
vein from the other. Arteries are surrounded by a muscular layer within the wall and therefore have the
ability to pump blood in one direction. Veins, on the other hand, are more flaccid, without any
surrounding muscular layer, and accept whatever blood is pumped into them.
When an artery and a vein connect, the blood will flow from the powerful artery into the vein, heading
in one direction or from one twin (the one giving rise to the feeding artery) to the other (the one
receiving the draining vein). This leads to a net transfusion from one twin to the other. In some
instances, an artery may connect with an artery from the other twin. When this happens, both vessels
are powerful and can pump blood in either direction. In this type of connection, blood typically flows
back and forth between the twin circulations, rather than exclusively from one toward the other. This
type of connection seems to offer a protective effect and in some cases will balance out the worrisome
one-way flow that an arterial-venous (AV) pair can cause. We are currently actively studying the effects
of an AA connection to better understand its role. We are now able to look for these types of
connections using ultrasound. We tend to find arterial-arterial (AA) connections more often when there
is unequal placental sharing rather than true TTTS which might help explain why these twin pairs are
at less risk. The main concern in these cases is the size and weight discrepancy, and specifically, focuses
on at determining the critical point when the smaller twins smaller share of placenta will no longer be
enough to safely allow it to grow and thrive in the uterus.
What options do I have?
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There are no treatments that can be performed to improve the situation in this case, because the
amount of placental share for each twin is fixed and cannot be changed. Amnioreduction and laser
treatment are not beneficial, and could make things worse (as the underlying problem is not a matter of
transfusion between the twins). Management is based on keeping a very close watch on the smaller
twin. This may allow us to see when the smaller one is starting to show signs of difficulty. Depending on
the stage of the pregnancy this may lead to hospitalization for closer monitoring or delivery. It is very
important to keep very close vigilance on the smaller twin because stillbirth in that twin could possibly
lead to serious problems even in the survivor (due to the vascular connections between them). In
severe, early cases of unequal sharing in which the smaller twin is severely growth restricted and at
significant risk for demise before a viable gestational age is attainable, radio-frequency ablation (RFA) of
umbilical cord flow to that twin may be an option, in order to protect the normally grown twin from the
adverse effects stillbirth of the other twin could have.
At our center, we offer close monitoring by a combination of ultrasound and non-stress tests up to 3
times/week, and in some cases, in-hospital continuous monitoring and watching the pregnancy for signs
of danger to the smaller twin. In this way, we maximize the benefits of longer gestation and maturity of
the fetuses while maintaining close surveillance of the small twin for signs necessitating delivery.