Multifetal Pregnancy

Multifetal Pregnancy

No Results

No Results


The term multifetal gestation includes twins, triplets, and higher-order multiples. Multiple births are increasing in the United States and account for a large proportion of neonatal morbidity and mortality. In addition, these pregnancies often present a challenge in management for the obstetrician

Twins can be classified as monozygotic, originating from the fertilization and subsequent division of one egg, or dizygotic, originating from the fertilization and development of two eggs. Approximately one third of twins are thought to be monozygotic in the United States. [1]

Twins can be further classified by their chorionicity. Dizygotic twins are almost always dichorionic, diamniotic. The chronicity of monozygotic twins depends on the timing of division of the fertilized egg. Dichorionic, diamniotic twins result if the fertilized egg splits 0-3 days after fertilization. This is thought to occur in approximately 20-30% of monozygotic twins. Monochorionic, diamniotic twins occur at days 4-8 after fertilization and account for approximately 70% of monozygotic twins. Monochorionic, monoamniotic twins are rare (1-5% of monozygotic twins) and result secondary to division 8-12 days postfertilization. Conjoined twins occur with division 13 days or later; this is extremely rare.

The etiology of monozygotic twinning is unknown. Dizygotic twins are thought to result from the ovulation of multiple follicles caused by elevations in serum gonadotropin levels. Hence, advanced maternal age is associated with an increased prevalence of twin birth.

The availability of assisted reproductive technology has contributed to the increase in multiple gestations seen over the past 20 years. During ovulation induction treatment, the ovaries are stimulated to produce several follicles, thus increasing the risk of multiple eggs being released and subsequently fertilized. The risk of multiple gestations during in-vitro fertilization is directly related to maternal age and number of embryos transferred. With two embryos transferred, the risk of a multiple gestation was found to be 22.7% and 19.7% for women aged 20-29 years and 30-34 years, respectively. This risk increased to 45.7% in women aged 20-29 years and 39.8% for women aged 30-34 years if 3 embryos were transferred. [2]

Dizygotic twinning can occur more frequently in some families. This is thought to be secondary to genetic factors leading to ovulation of several eggs during the menstrual cycle. In contrast, monozygotic twinning has not been shown to have a familial inheritance.

The incidence of multiple gestations varies by country due to regional variations in dizygotic twin rates; monozygotic twinning rates are fairly constant across nations. In Nigeria, the rate of twinning has been reported as high as 49 per 1000 births. [3] In contrast, in Japan, the rate of twinning is 1.3 per 1000 births. [4] The incidence of spontaneous twins is thought to be approximately 1 in 80 pregnancies. [5] For spontaneous triplets, the incidence is estimated at 1 in 8,000. [5] In the United States, the twin birth rate was 33.3 per 1,000 births in 2009. [6] This rate had risen 70% from 1980-2004 and is thought to be secondary to older maternal age at childbirth and the use of fertility treatment. The rate of triplet and higher order multiple births was 1.5 per 1,000 total births in 2009. This number had initially increased during the 1980s and 1990s but has since declined.

Twin birth rates in 2005-2006 for non-Hispanic whites were 36 per 1,000, for non-Hispanic blacks, 36.8 per 1,000, and for Hispanics, 21.8 per 1,000. Since 1990, rates have risen 57% for non-Hispanic whites, 38% for non-Hispanic blacks, and 21% for Hispanic women. [6]

As maternal age increases, the risk of dizygotic twinning also increases. This is thought to be due to increased levels of follicle-stimulating hormone with advancing maternal age. [7] From 1980-2006, twin birth rates rose 27% for mothers younger than 20 years compared with 80% for women in their thirties. In 2006, 20% of births to women aged 45-54 were twins, compared with approximately 2% of births to women aged 20-24 years. [6] This increase can also be attributed in part to the use of assisted reproductive technology.

Although the frequency of multiple gestations is lower than singleton gestations, multiple gestations account for a disproportionate share of neonatal morbidity and mortality. Much of this can be attributed to a higher rate of preterm delivery for multiple gestations. The mean gestational age at delivery is 35 weeks for twins, 32 weeks for triplets and 29 weeks for quadruplets.  [1]  As a result, 25% of twins and 75% of triplets require admission to the neonatal intensive care unit (NICU). [8] Neurologic outcomes also appear to be worse in multiple births. When matched for gestational age at delivery, infants born from multifetal pregnancies have an approximately 3-fold increase in cerebral palsy [9] (see the Gestational Age from Estimated Date of Delivery calculator).  There is an approximate fivefold increased risk of stillbirth and sevenfold increased risk of neonatal death.  [10]

Monochorionic gestations are at risk for twin twin transfusion syndrome (TTTS) which can occur about 15% of monochorionic pregnancies.  [1]  TTTS is thought to be caused by vascular anastomoses within the placenta causing one twin to become underperfused (the “donor” twin) and the other twin to show signs of overperfusion (the “recipient” twin).  Pregnancies complicated by TTTS are at significantly increased risk of neonatal morbidity and mortality.

Maternal morbidity is also increased in a multifetal gestation. Women with multiples are more likely to be hospitalized with complications including preterm labor, preterm premature rupture of membranes, preeclampsia, placental abruption, pulmonary embolism, and postpartum hemorrhage. As a result, hospital costs are higher in these pregnancies. [10]

Malone FD, D’Alton ME. Multiple gestation: clinical characteristics and management. Creasy RK, Resnik R. Maternal Fetal Medicine, Principles and Practices. Sixth edition. Philadelphia, PA: Saunders; 2009. 454-476.

Schieve LA, Peterson HB, Meikle SF, Jeng G, Danel I, Burnett NM, et al. Live-birth rates and multiple-birth risk using in vitro fertilization. JAMA. 1999 Nov 17. 282(19):1832-8. [Medline].

Nylander PP. The factors that influence twinning rates. Acta Genet Med Gemellol (Roma). 1981. 30(3):189-202. [Medline].

Soma H, Takayama M, Kiyokawa T, Akaeda T, Tokoro K. Serum gonadotropin levels in Japanese women. Obstet Gynecol. 1975 Sep. 46(3):311-2. [Medline].

Benirschke K, Kim CK. Multiple pregnancy. 1. N Engl J Med. 1973 Jun 14. 288(24):1276-84. [Medline].

Martin JA, Hamilton BE, Osterman MJ. Three decades of twin births in the United States, 1980-2009. NCHS Data Brief. 2012.

Lambalk CB, De Koning CH, Braat DD. The endocrinology of dizygotic twinning in the human. Mol Cell Endocrinol. 1998 Oct 25. 145(1-2):97-102. [Medline].

Ettner SL, Christiansen CL, Callahan TL, Hall JE. How low birthweight and gestational age contribute to increased inpatient costs for multiple births. Inquiry. 1997-1998 Winter. 34(4):325-39. [Medline].

Grether JK, Nelson KB, Cummins SK. Twinning and cerebral palsy: experience in four northern California counties, births 1983 through 1985. Pediatrics. 1993 Dec. 92(6):854-8. [Medline].

American College of Obstetricians and Gynecologists, Society for Maternal-Fetal Medicine. ACOG Practice Bulletin No. 144: Multifetal gestations: twin, triplet, and higher-order multifetal pregnancies. Obstet Gynecol. 2014 May. 123 (5):1118-32. [Medline].

Shetty A, Smith AP. The sonographic diagnosis of chorionicity. Prenat Diagn. 2005 Sep. 25(9):735-9. [Medline].

Evans MI, Dommergues M, Wapner RJ, Goldberg JD, Lynch L, Zador IE. International, collaborative experience of 1789 patients having multifetal pregnancy reduction: a plateauing of risks and outcomes. J Soc Gynecol Investig. 1996 Jan-Feb. 3(1):23-6. [Medline].

Haas J, Hourvitz A, Dor J, et al. Pregnancy outcome of early multifetal pregnancy reduction: triplets to twins versus triplets to singletons. Reprod Biomed Online. 2014 Dec. 29(6):717-21. [Medline].

Shinagawa S, Suzuki S, Chihara H, Otsubo Y, Takeshita T, Araki T. Maternal basal metabolic rate in twin pregnancy. Gynecol Obstet Invest. 2005. 60(3):145-8. [Medline].

Weight gain during pregnancy: reexamining the guidelines. Institute of Medicine of the National Academies. May 28, 2009.

Goodnight W, Newman R,. Optimal nutrition for improved twin pregnancy outcome. Obstet Gynecol. 2009 Nov. 114(5):1121-34. [Medline].

Blake GD, Knuppel RA, Ingardia CJ, Lake M, Aumann G, Hanson M. Evaluation of nonstress fetal heart rate testing in multiple gestations. Obstet Gynecol. 1984 Apr. 63(4):528-32. [Medline].

Lodeiro JG, Vintzileos AM, Feinstein SJ, Campbell WA, Nochimson DJ. Fetal biophysical profile in twin gestations. Obstet Gynecol. 1986 Jun. 67(6):824-7. [Medline].

Curnow KJ, Wilkins-Haug L, Ryan A, et al. Detection of triploid, molar, and vanishing twin pregnancies by a single-nucleotide polymorphism-based noninvasive prenatal test. Am J Obstet Gynecol. 2015 Jan. 212(1):79.e1-9. [Medline].

Minakami H, Sato I. Reestimating date of delivery in multifetal pregnancies. JAMA. 1996 May 8. 275(18):1432-4. [Medline].

Whitworth NS, Magann EF, Morrison JC. Evaluation of fetal lung maturity in diamniotic twins. Am J Obstet Gynecol. 1999 Jun. 180(6 Pt 1):1438-41. [Medline].

Hack KE, Derks JB, Elias SG, Franx A, Roos EJ, Voerman SK. Increased perinatal mortality and morbidity in monochorionic versus dichorionic twin pregnancies: clinical implications of a large Dutch cohort study. BJOG. 2008 Jan. 115(1):58-67. [Medline].

Lee YM, Wylie BJ, Simpson LL, D’Alton ME. Twin chorionicity and the risk of stillbirth. Obstet Gynecol. 2008 Feb. 111(2 Pt 1):301-8. [Medline].

Glinianaia SV, Obeysekera MA, Sturgiss S, Bell R. Stillbirth and neonatal mortality in monochorionic and dichorionic twins: a population-based study. Hum Reprod. 2011 Jul 4. [Medline].

Hogle KL, Hutton EK, McBrien KA, Barrett JF, Hannah ME. Cesarean delivery for twins: a systematic review and meta-analysis. Am J Obstet Gynecol. 2003 Jan. 188(1):220-7. [Medline].

Chasen ST, Spiro SJ, Kalish RB, Chervenak FA. Changes in fetal presentation in twin pregnancies. J Matern Fetal Neonatal Med. 2005 Jan. 17(1):45-8. [Medline].

Chauhan SP, Roberts WE, McLaren RA, Roach H, Morrison JC, Martin JN Jr. Delivery of the nonvertex second twin: breech extraction versus external cephalic version. Am J Obstet Gynecol. 1995 Oct. 173(4):1015-20. [Medline].

Glinianaia SV, Rankin J, Wright C. Congenital anomalies in twins: a register-based study. Hum Reprod. 2008 Jun. 23(6):1306-11. [Medline].

Cameron AH, Edwards JH, Derom R, Thiery M, Boelaert R. The value of twin surveys in the study of malformations. Eur J Obstet Gynecol Reprod Biol. 1983 Feb. 14(5):347-56. [Medline].

Meyers C, Adam R, Dungan J, Prenger V. Aneuploidy in twin gestations: when is maternal age advanced?. Obstet Gynecol. 1997 Feb. 89(2):248-51. [Medline].

Sibai BM, Hauth J, Caritis S, Lindheimer MD, MacPherson C, Klebanoff M. Hypertensive disorders in twin versus singleton gestations. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. Am J Obstet Gynecol. 2000 Apr. 182(4):938-42. [Medline].

Roach VJ, Lau TK, Wilson D, Rogers MS. The incidence of gestational diabetes in multiple pregnancy. Aust N Z J Obstet Gynaecol. 1998 Feb. 38(1):56-7. [Medline].

Effect of corticosteroids for fetal maturation on perinatal outcomes. NIH Consens Statement. 1994 Feb 28-Mar 2. 12(2):1-24. [Medline].

Mauldin JG, Newman RB. Neurologic morbidity associated with multiple gestation. Female Pat. 1998. 23(4):27-8, 30, 35-6, passim.

Roberts D, Neilson JP, Kilby M, Gates S. Interventions for the treatment of twin-twin transfusion syndrome. Cochrane Database Syst Rev. 2008 Jan 23. CD002073. [Medline].

Rouse DJ, Caritis SN, Peaceman AM, Sciscione A, Thom EA, Spong CY, et al. A trial of 17 alpha-hydroxyprogesterone caproate to prevent prematurity in twins. N Engl J Med. 2007 Aug 2. 357 (5):454-61. [Medline].

Caritis SN, Rouse DJ, Peaceman AM, Sciscione A, Momirova V, Spong CY, et al. Prevention of preterm birth in triplets using 17 alpha-hydroxyprogesterone caproate: a randomized controlled trial. Obstet Gynecol. 2009 Feb. 113 (2 Pt 1):285-92. [Medline].

Garchet-Beaudron A, Dreux S, Leporrier N, Oury JF, Muller F, ABA Study Group, et al. Second-trimester Down syndrome maternal serum marker screening: a prospective study of 11 040 twin pregnancies. Prenat Diagn. 2008 Dec. 28 (12):1105-9. [Medline].

Committee Opinion No. 640: Cell-Free DNA Screening For Fetal Aneuploidy. Obstet Gynecol. 2015 Sep. 126 (3):e31-7. [Medline].

Asha J Heard, MD, MPH, FACOG Assistant Professor of Obstetrics and Gynecology, Associate Residency Director, Director of Clinical Ultrasound, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center

Asha J Heard, MD, MPH, FACOG is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, Society for Maternal-Fetal Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Ronald M Ramus, MD Professor of Obstetrics and Gynecology, Director, Division of Maternal-Fetal Medicine, Virginia Commonwealth University School of Medicine

Ronald M Ramus, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, Medical Society of Virginia, Society for Maternal-Fetal Medicine

Disclosure: Nothing to disclose.

Jordan G Pritzker, MD, MBA, FACOG Adjunct Professor of Obstetrics/Gynecology, Hofstra North Shore-LIJ School of Medicine at Hofstra University; Attending Physician, Department of Obstetrics and Gynecology, Long Island Jewish Medical Center; Medical Director, Aetna, Inc; Private Practice in Gynecology

Disclosure: Nothing to disclose.

Steven J Ralston, MD Associate Professor of Obstetrics and Gynecology, Harvard Medical School; Consulting Staff in Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center

Steven J Ralston, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Society of Law, Medicine & Ethics, Association of Professors of Gynecology and Obstetrics, Society for Maternal-Fetal Medicine

Disclosure: Nothing to disclose.

Multifetal Pregnancy

Research & References of Multifetal Pregnancy|A&C Accounting And Tax Services