Advertisement
JOGC

No. 262-Prenatal Screening for and Diagnosis of Aneuploidy in Twin Pregnancies

      Abstract

      Objective

      To provide a Canadian consensus document with recommendations on prenatal screening for and diagnosis of fetal aneuploidy (e.g., Down syndrome and trisomy 18) in twin pregnancies.

      Options

      The process of prenatal screening and diagnosis in twin pregnancies is complex. This document reviews the options available to pregnant women and the challenges specific to screening and diagnosis in a twin pregnancy.

      Outcomes

      Clinicians will be better informed about the accuracy of different screening options in twin pregnancies and about techniques of invasive prenatal diagnosis in twins.

      Evidence

      PubMed and Cochrane Database were searched for relevant English and French language articles published between 1985 and 2010, using appropriate controlled vocabulary and key words (aneuploidy, Down syndrome, trisomy, prenatal screening, genetic health risk, genetic health surveillance, prenatal diagnosis, twin gestation). Results were restricted to systematic reviews, randomized controlled trials, and relevant observational studies. Searches were updated on a regular basis and incorporated in the guideline to August 2010. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The previous Society of Obstetricians and Gynaecologists of Canada guidelines regarding prenatal screening were also reviewed in developing this clinical practice guideline.

      Values

      The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1).

      Benefits, harms, and costs

      There is a need for specific guidelines for prenatal screening and diagnosis in twins. These guidelines should assist health care providers in the approach to this aspect of prenatal care of women with twin pregnancies.

      Summary Statements

      • 1.
        Fetal nuchal translucency combined with maternal age is an acceptable first trimester screening test for aneuploidies in twin pregnancies (II-2).
      • 2.
        First trimester serum screening combined with nuchal translucency may be considered in twin pregnancies. It provides some improvement over the performance of screening by nuchal translucency and maternal age by decreasing the false-positive rate (II-3).
      • 3.
        Integrated screening with nuchal translucency plus first and second trimester serum screening is an option in twin pregnancies.Further prospective studies are required in this area, since it has not been validated in prospective studies in twins (III).
      • 4.
        Non-directive counselling is essential when invasive testing is offered (III).
      • 5.
        When chorionic villus sampling is performed in non-monochorionic multiple pregnancies, a combination of transabdominal and transcervical approaches or a transabdominal only approach appears to provide the best results to minimize the likelihood of sampling errors (II-2).

      Recommendations

      • 1.
        All pregnant women in Canada, regardless of age, should be offered, through an informed counselling process, the option of a prenatal screening test for the most common clinically significant fetal aneuploidies. In addition, they should be offered a second trimester ultrasound for dating, assessment of fetal anatomy, and detection of multiples (I-A).
      • 2.
        Counselling must be non-directive and must respect a woman's right to accept or decline any or all of the testing or options offered at any point in the process (III-A).
      • 3.
        When non-invasive prenatal screening for aneuploidy is available, maternal age alone should not be an indication for invasive prenatal diagnosis in a twin pregnancy (II-2A). If non-invasive prenatal screening is not available, invasive prenatal diagnosis in twins should be offered to women aged 35 and over (II-2B).
      • 4.
        Chorionicity has a major impact on the prenatal screening process and should be determined by ultrasound in the first trimester of all twin pregnancies (II-2A).
      • 5.
        When screening is done by nuchal translucency and maternal age, a pregnancy-specific risk should be calculated in monochorionic twins. In dichorionic twins, a fetus-specific risk should be calculated (II-3C).
      • 6.
        During amniocentesis, both amniotic sacs should be sampled in monochorionic twin pregnancies, unless monochorionicity is confirmed before 14 weeks and the fetuses appear concordant for growth and anatomy (II-2B).
      • 7.
        Prior to invasive testing or in the context of twins discordant for an abnormality, selective reduction should be discussed and made available to those requesting the procedure after appropriate counselling (III-B).
      • 8.
        Monitoring for disseminated intravascular coagulopathy is not indicated in dichorionic twin pregnancies undergoing selective reduction (II-2B).

      Key Words

      Abbreviations:

      AFP (alpha fetoprotein), CVS (chorionic villus sampling), DR (detection rate), FPR (false-positive rate), hCG (human chorionic gonadotropin), NT (nuchal translucency), PAPP-A (pregnancy-associated plasma protein A), uE3 (unconjugated estriol)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Obstetrics and Gynaecology Canada
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Public Health Agency of Canada
        Canadian Perinatal Health Report, 2008. Edition.
        PHAC, Ottawa2008
        • Hall J.G.
        Twinning.
        Lancet. 2003; 362: 735-743
        • Aston K.I.
        • Peterson C.M.
        • Carrell D.T.
        Monozygotic twinning associated with assisted reproductive technologies: a review.
        Reproduction. 2008; 136: 377-386
        • Blickstein I.
        Estimation of iatrogenic monozygotic twinning rate following assisted reproduction: pitfalls and caveats.
        Am J Obstet Gynecol. 2005; 192: 365-368
        • Blickstein I.
        • Jones C.
        • Keith L.G.
        Zygotic-splitting rates after single-embryo transfers in in vitro fertilization.
        N Engl J Med. 2003; 348: 2366-2367
        • Morin L.
        • Lim K.
        • SOGC Diagnostic Imaging Committee; SOGC Genetics Committee; SOGC Maternal Fetal Medicine Committee
        Ultrasound for twin pregnancies. SOGC Clinical Practice Guideline No. 260, June 2011.
        J Obstet Gynaecol Can. 2011; 33: 643-656
        • Machin G.A.
        Why is it important to diagnose chorionicity and how do we do it?.
        Best Pract Res Clin Obstet Gynaecol. 2004; 18: 515-530
        • Sepulveda W.
        • Sebire N.J.
        • Hughes K.
        • et al.
        The lambda sign at 10–14 weeks of gestation as a predictor of chorionicity in twin pregnancies.
        Ultrasound Obstet Gynecol. 1996; 7: 421-423
        • Shetty A.
        • Smith A.P.
        The sonographic diagnosis of chorionicity.
        Prenat Diagn. 2005; 25: 735-739
        • Dube J.
        • Dodds L.
        • Armson B.A.
        Does chorionicity or zygosity predict adverse perinatal outcomes in twins?.
        Am J Obstet Gynecol. 2002; 186: 579-583
        • Sebire N.J.
        • Snijders R.J.
        • Hughes K.
        • et al.
        The hidden mortality of monochorionic twin pregnancies.
        Br J Obstet Gynaecol. 1997; 104: 1203-1207
        • Hannelius U.
        • Gherman L.
        • Makela V.V.
        • et al.
        Large-scale zygosity testing using single nucleotide polymorphisms.
        Twin Res Hum Genet. 2007; 10: 604-625
        • Rodis J.F.
        • Egan J.F.
        • Craffey A.
        • et al.
        Calculated risk of chromosomal abnormalities in twin gestations.
        Obstet Gynecol. 1990; 76: 1037-1041
        • Summers A.M.
        • Langlois S.
        • Wyatt P.
        • et al.
        • SOGC Genetics Committee; CCMG Committee on Prenatal Diagnosis; SOGC Diagnostic Imaging Committee
        Prenatal screening for fetal aneuploidy. SOGC Clinical Practice Guideline No. 187, February 2007.
        J Obstet Gynaecol Can. 2007; 29: 146-179
        • Cuckle H.
        Down's syndrome screening in twins.
        J Med Screen. 1998; 5: 3-4
        • Cleary-Goldman J.
        • Berkowitz R.L.
        First trimester screening for Down syndrome in multiple pregnancy.
        Semin Perinatol. 2005; 29: 395-400
        • Cleary-Goldman J.
        • D'Alton M.E.
        • Berkowitz R.L.
        Prenatal diagnosis and multiple pregnancy.
        Semin Perinatol. 2005; 29: 312-320
        • Sebire N.J.
        • Snijders R.J.
        • Hughes K.
        • et al.
        Screening for trisomy 21 in twin pregnancies by maternal age and fetal nuchal translucency thickness at 10–14 weeks of gestation.
        Br J Obstet Gynaecol. 1996; 103: 999-1003
        • Wald N.J.
        • Rish S.
        • Hackshaw A.K.
        Combining nuchal translucency and serum markers in prenatal screening for Down syndrome in twin pregnancies.
        Prenat Diagn. 2003; 23: 588-592
        • Sebire N.J.
        • D'Ercole C.
        • Hughes K.
        • et al.
        Increased nuchal translucency thickness at 10–14 weeks of gestation as a predictor of severe twin-to-twin transfusion syndrome.
        Ultrasound Obstet Gynecol. 1997; 10: 86-89
        • Sebire N.J.
        • Souka A.
        • Skentou H.
        • et al.
        Early prediction of severe twin-to-twin transfusion syndrome.
        Hum Reprod. 2000; 15: 2008-2010
        • Vandecruys H.
        • Faiola S.
        • Auer M.
        • et al.
        Screening for trisomy 21 in monochorionic twins by measurement of fetal nuchal translucency thickness.
        Ultrasound Obstet Gynecol. 2005; 25: 551-553
        • Snijders R.J.
        • Thom E.A.
        • Zachary J.M.
        • et al.
        First-trimester trisomy screening: nuchal translucency measurement training and quality assurance to correct and unify technique.
        Ultrasound Obstet Gynecol. 2002; 19: 353-359
        • Chasen S.T.
        • Perni S.C.
        • Kalish R.B.
        • et al.
        First-trimester risk assessment for trisomies 21 and 18 in twin pregnancy.
        Am J Obstet Gynecol. 2007; 197: e1-e3
        • Gonce A.
        • Borrell A.
        • Fortuny A.
        • et al.
        First-trimester screening for trisomy 21 in twin pregnancy: does the addition of biochemistry make an improvement?.
        Prenat Diagn. 2005; 25: 1156-1161
        • Spencer K.
        • Kagan K.O.
        • Nicolaides K.H.
        Screening for trisomy 21 in twin pregnancies in the first trimester: an update of the impact of chorionicity on maternal serum markers.
        Prenat Diagn. 2008; 28: 49-52
        • Spencer K.
        • Nicolaides K.H.
        Screening for trisomy 21 in twins using first trimester ultrasound and maternal serum biochemistry in a one-stop clinic: a review of three years experience.
        BJOG. 2003; 110: 276-280
        • Bersinger N.A.
        • Noble P.
        • Nicolaides K.H.
        First-trimester maternal serum PAPP-A, SP1 and M-CSF levels in normal and trisomic twin pregnancies.
        Prenat Diagn. 2003; 23: 157-162
        • Garchet-Beaudron A.
        • Dreux S.
        • Leporrier N.
        • et al.
        Second-trimester Down syndrome maternal serum marker screening: a prospective study of 11 040 twin pregnancies.
        Prenat Diagn. 2008; 28: 1105-1109
        • Muller F.
        • Dreux S.
        • Dupoizat H.
        • et al.
        Second-trimester Down syndrome maternal serum screening in twin pregnancies: impact of chorionicity.
        Prenat Diagn. 2003; 23: 331-335
        • Noble P.L.
        • Snijders R.J.
        • Abraha H.D.
        • et al.
        Maternal serum free beta-hCG at 10 to 14 weeks of gestation in trisomic twin pregnancies.
        Br J Obstet Gynaecol. 1997; 104: 741-743
        • Wald N.J.
        • Rish S.
        Prenatal screening for Down syndrome and neural tube defects in twin pregnancies.
        Prenat Diagn. 2005; 25: 740-745
        • Watt H.C.
        • Wald N.J.
        • George L.
        Maternal serum inhibin-A levels in twin pregnancies: implications for screening for Down's syndrome.
        Prenat Diagn. 1996; 16: 927-929
        • Neveux L.M.
        • Palomaki G.E.
        • Knight G.J.
        • et al.
        Multiple marker screening for Down syndrome in twin pregnancies.
        Prenat Diagn. 1996; 16: 29-34
        • Spencer K.
        • Salonen R.
        • Muller F.
        Down's syndrome screening in multiple pregnancies using alpha-fetoprotein and free beta hCG.
        Prenat Diagn. 1994; 14: 537-542
        • Maymon R.
        • Dreazen E.
        • Rozinsky S.
        • et al.
        Comparison of nuchal translucency measurement and second-trimester triple serum screening in twin versus singleton pregnancies.
        Prenat Diagn. 1999; 19: 727-731
        • Wald N.J.
        • Watt H.C.
        • Hackshaw A.K.
        Integrated screening for Down's syndrome on the basis of tests performed during the first and second trimesters.
        N Engl J Med. 1999; 341: 461-467
        • Malone F.D.
        • Canick J.A.
        • Ball R.H.
        • et al.
        First-trimester or second-trimester screening, or both, for Down's syndrome.
        N Engl J Med. 2005; 353: 2001-2011
        • Bush M.C.
        • Malone F.D.
        Down syndrome screening in twins.
        Clin Perinatol. 2005; 32 (vi): 373-386
        • Lynch L.
        • Berkowitz G.S.
        • Chitkara U.
        • et al.
        Ultrasound detection of Down syndrome: is it really possible?.
        Obstet Gynecol. 1989; 73: 267-270
        • Spencer K.
        Screening for trisomy 21 in twin pregnancies in the first trimester using free beta-hCG and PAPP-A, combined with fetal nuchal translucency thickness.
        Prenat Diagn. 2000; 20: 91-95
        • Maymon R.
        • Jauniaux E.
        • Holmes A.
        • et al.
        Nuchal translucency measurement and pregnancy outcome after assisted conception versus spontaneously conceived twins.
        Hum Reprod. 2001; 16: 1999-2004
        • Geipel A.
        • Berg C.
        • Katalinic A.
        • et al.
        Different preferences for prenatal diagnosis in pregnancies following assisted reproduction versus spontaneous conception.
        Reprod Biomed Online. 2003; 8: 119-124
        • Yaron Y.
        • Bryant-Greenwood P.K.
        • Dave N.
        • et al.
        Multifetal pregnancy reductions of triplets to twins: comparison with nonreduced triplets and twins.
        Am J Obstet Gynecol. 1999; 180: 1268-1271
        • Jenkins T.M.
        • Wapner R.J.
        The challenge of prenatal diagnosis in twin pregnancies.
        Curr Opin Obstet Gynecol. 2000; 12: 87-92
        • Taylor M.J.
        • Fisk N.M.
        Prenatal diagnosis in multiple pregnancy.
        Baillieres Best Pract Res Clin Obstet Gynaecol. 2000; 14: 663-675
        • Levy R.
        • Mirlesse V.
        • Jacquemard F.
        • et al.
        Prenatal diagnosis of zygosity by fetal DNA analysis, a contribution to the management of multiple pregnancies. A series of 31 cases.
        Fetal Diagn Ther. 2002; 17: 339-342
      1. The Canadian Early and Mid-trimester Amniocentesis Trial (CEMAT) Group. Randomised trial to assess safety and fetal outcome of early and midtrimester amniocentesis.
        Lancet. 1998; 351: 242-247
        • Delisle M.F.
        • Brosseuk L.
        • Wilson R.D.
        Amniocentesis for twin pregnancies: is alpha-fetoprotein useful in confirming that the two sacs were sampled?.
        Fetal Diagn Ther. 2007; 22: 221-225
        • Kidd S.A.
        • Lancaster P.A.
        • Anderson J.C.
        • et al.
        A cohort study of pregnancy outcome after amniocentesis in twin pregnancy.
        Paediatr Perinat Epidemiol. 1997; 11: 200-213
        • Wapner R.J.
        Genetic diagnosis in multiple pregnancies.
        Sem Perinatol. 1995; 5: 361-362
        • Kidd S.A.
        • Lancaster P.A.
        • Anderson J.C.
        Fetal death after exposure to methylene blue dye during mid-trimester amniocentesis in twin pregnancy.
        Prenat Diagn. 1996; 16: 39-47
        • van der Pol J.G.
        • Wolf H.
        • Boes K.
        • et al.
        Jejunal atresia related to the use of methylene blue in genetic amniocentesis in twins.
        Br J Obstet Gynaecol. 1992; 99: 141-143
        • McFadyen I.
        The dangers of intra-amniotic methylene blue.
        Br J Obstet Gynaecol. 1992; 99: 89-90
        • Cragan J.D.
        • Martin M.L.
        • Khoury M.J.
        • et al.
        Dye use during amniocentesis and birth defects.
        Lancet. 1993; 341: 1352
        • Pruggmayer M.R.
        • Jahoda M.G.
        • van der Pol J.G.
        • et al.
        Genetic amniocentesis in twin pregnancies: results of a multicenter study of 529 cases.
        Ultrasound Obstet Gynecol. 1992; 2: 6-10
        • Brandenburg H.
        The use of synthetic dyes for identification of the amniotic sacs in multiple pregnancies.
        Prenat Diagn. 1997; 17: 281-282
        • Weisz B.
        • Rodeck C.
        Invasive diagnostic procedures in twin pregnancies.
        Prenat Diagn. 2005; 25: 751-758
        • Antsaklis A.
        • Souka A.P.
        • Daskalakis G.
        • et al.
        Second- trimester amniocentesis vs. chorionic villus sampling for prenatal diagnosis in multiple gestations.
        Ultrasound Obstet Gynecol. 2002; 20: 476-481
        • Jeanty P.
        • Shah D.
        • Roussis P.
        Single-needle insertion in twin amniocentesis.
        J Ultrasound Med. 1990; 9: 511-517
        • Buscaglia M.
        • Ghisoni L.
        • Bellotti M.
        • et al.
        Genetic amniocentesis in biamniotic twin pregnancies by a single transabdominal insertion of the needle.
        Prenat Diagn. 1995; 15: 17-19
        • van Vugt J.M.
        • Nieuwint A.
        • van Geijn H.P.
        Single-needle insertion: an alternative technique for early second-trimester genetic twin amniocentesis.
        Fetal Diagn Ther. 1995; 10: 178-181
        • Cirigliano V.
        • Cañadas P.
        • Plaja A.
        • et al.
        Rapid prenatal diagnosis of aneuploidies and zygosity in multiple pregnancies by amniocentesis with single insertion of the needle and quantitative fluorescent PCR.
        Prenat Diagn. 2003; 23: 629-633
        • Sebire N.J.
        • Noble P.L.
        • Odibo A.
        • et al.
        Single uterine entry for genetic amniocentesis in twin pregnancies.
        Ultrasound Obstet Gynecol. 1996; 7: 26-31
        • Megory E.
        • Weiner E.
        • Shalev E.
        • et al.
        Pseudomonoamniotic twins with cord entanglement following genetic funipuncture.
        Obstet Gynecol. 1991; 78: 915-917
        • Bahado-Singh R.
        • Schmitt R.
        • Hobbins J.C.
        New technique for genetic amniocentesis in twins.
        Obstet Gynecol. 1992; 79: 304-307
        • Schmid O.
        • Trautmann U.
        • Ashour H.
        • et al.
        Prenatal diagnosis of heterokaryotypic mosaic twins discordant for fetal sex.
        Prenat Diagn. 2000; 20: 999-1003
        • Shalev S.A.
        • Shalev E.
        • Pras E.
        • et al.
        Evidence for blood chimerism in dizygotic spontaneous twin pregnancy discordant for Down syndrome.
        Prenat Diagn. 2006; 26: 782-784
        • Cahill A.G.
        • Macones G.A.
        • Stamilio D.M.
        • et al.
        Pregnancy loss rate after mid-trimester amniocentesis in twin pregnancies.
        Am J Obstet Gynecol. 2009; 200: 257.e1-257.e6
        • Millaire M.
        • Bujold E.
        • Morency A.M.
        • et al.
        Mid-trimester genetic amniocentesis in twin pregnancy and the risk of fetal loss.
        J Obstet Gynaecol Can. 2006; 28: 512-518
        • Ghidini A.
        • Lynch L.
        • Hicks C.
        • et al.
        The risk of second- trimester amniocentesis in twin gestations: a case-control study.
        Am J Obstet Gynecol. 1993; 169: 1013-1016
        • Yukobowich E.
        • Anteby E.Y.
        • Cohen S.M.
        • et al.
        Risk of fetal loss in twin pregnancies undergoing second trimester amniocentesis.
        Obstet Gynecol. 2001; 98: 231-234
        • McLean L.K.
        • Evans M.I.
        • Carpenter Jr., R.J.
        • et al.
        Genetic amniocentesis following multifetal pregnancy reduction does not increase the risk of pregnancy loss.
        Prenat Diagn. 1998; 18: 186-188
        • Stephen J.A.
        • Timor-Tritsch I.E.
        • Lerner J.P.
        • et al.
        Amniocentesis after multifetal pregnancy reduction: is it safe?.
        Am J Obstet Gynecol. 2000; 182: 962-965
        • Rochon M.
        • Stone J.
        Invasive procedures in multiple gestations.
        Curr Opin Obstet Gynecol. 2003; 15: 167-175
        • Casals G.
        • Borrell A.
        • Martinez J.M.
        • et al.
        Transcervical chorionic villus sampling in multiple pregnancies using a biopsy forceps.
        Prenat Diagn. 2002; 22: 260-265
        • Appelman Z.
        • Furman B.
        Invasive genetic diagnosis in multiple pregnancies.
        Obstet Gynecol Clin N Am. 2005; 32: 97-103
        • Wapner R.J.
        • Johnson A.
        • Davis G.
        • et al.
        Prenatal diagnosis in twin gestations: a comparison between second-trimester amniocentesis and first-trimester chorionic villus sampling.
        Obstet Gynecol. 1993; 82: 49-56
        • Brambati B.
        • Terzian E.
        • Tognoni G.
        Randomized clinical trial of transabdominal versus transcervical chorionic villus sampling methods.
        Prenat Diagn. 1991; 11: 285-293
        • Pergament E.
        • Schulman J.D.
        • Copeland K.
        • et al.
        The risk and efficacy of chorionic villus sampling in multiple gestations.
        Prenat Diagn. 1992; 12: 377-384
        • De Catte L.
        • Liebaers I.
        • Foulon W.
        Outcome of twin gestations after first trimester chorionic villus sampling.
        Obstet Gynecol. 2000; 96: 714-720
        • Fiddler M.
        • Frederickson M.C.
        • Chen P.X.
        • et al.
        Assessment of fetal status in multiple gestation pregnancies using interphase FISH.
        Prenat Diagn. 2001; 21: 196-199
        • Evans M.
        • Ciorica D.
        • Britt D.W.
        • et al.
        Update on selective reduction.
        Prenat Diagn. 2005; 25: 807-813
        • Brandenburg H.
        • van der Meulen J.H.
        • Jahoda M.G.
        • et al.
        A quantitative estimation of the effect of prenatal diagnosis in dizygotic twin pregnancies in women of advanced maternal age.
        Prenat Diagn. 1994; 14: 243-256
        • van den Berg C.
        • Braat A.P.G.
        • Van Opstal D.
        • et al.
        Amniocentesis or chorionic villus sampling in multiple gestations? Experience with 500 cases.
        Prenat Diagn. 1999; 19: 234-244
        • Lynch L.
        • Berkowitz R.L.
        • Stone J.
        • et al.
        Preterm delivery after selective termination in twin pregnancies.
        Obstet Gynecol. 1996; 87: 366-369
        • Berkowitz R.L.
        • Stone J.
        • Eddleman K.A.
        One hundred consecutive cases of selective termination of an abnormal fetus in a multifetal gestation.
        Obstet Gynecol. 1997; 90: 606-610
        • Evans M.I.
        • Goldberg J.D.
        • Horenstein J.
        • et al.
        Selective termination for structural, chromosomal, and mendelian anomalies: international experience.
        Am J Obstet Gynecol. 1999; 181: 893-897
        • Eddleman K.A.
        • Stone J.L.
        • Lynch L.
        • et al.
        Selective termination of anomalous fetuses in multifetal pregnancies: two hundred cases at a single center.
        Am J Obstet Gynecol. 2002; 187: 1168-1172
        • Woolf S.H.
        • Battista R.N.
        • Angerson G.M.
        • et al.
        Canadian Task Force on Preventive Health Care. New grades for recommendations from the Canadian Task Force on Preventive Health Care.
        CMAJ. 2003; 169: 207-208

      Linked Article