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Neonatal outcome, complications, and management of multiple births

George T Mandy, MD
Section Editor
Leonard E Weisman, MD
Deputy Editor
Melanie S Kim, MD


Multiple births are increasing in the United States and contribute disproportionately to perinatal and neonatal mortality and morbidity. (See "Perinatal mortality", section on 'Multifetal pregnancies'.)

The incidence, mechanisms, complications, and pediatric management of multiple births are reviewed here. The antepartum and intrapartum management of twins and monoamniotic twin pregnancy are discussed separately. (See "Twin pregnancy: Prenatal issues" and "Twin pregnancy: Labor and delivery" and "Monoamniotic twin pregnancy".)


Twins and triplets naturally occur in approximately 1 in 80 and 1 in 8000 pregnancies, respectively, in the United States [1,2]. The incidence of spontaneous twins varies by country. The incidence of twins is lower in Japan and higher in Nigeria. (See 'Zygosity' below.)

Multiple pregnancies comprise an increasing proportion of the total pregnancies in the developed world due to older maternal age at childbirth and the expanded use of fertility treatments [3,4]. In countries with high rates of multiple births, 30 to 50 percent of twin pregnancies and 75 percent of triplet pregnancies occur after infertility treatment [5].

From the 1980 to 2008, the number of twin pregnancies has doubled in the United States with a birth rate of 32.6 per 1000 births in 2008 [6]. The peak incidence of triplet, quadruplets, or higher order pregnancies occurred in 1998 at a rate of 193.5 per 100,000 live births, and has decreased to a rate of 147.6 per 100,000 births in 2008 [6].


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Literature review current through: Jun 2015. | This topic last updated: Nov 5, 2013.
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  1. Benirschke K, Kim CK. Multiple pregnancy. 1. N Engl J Med 1973; 288:1276.
  2. Benirschke K, Kim CK. Multiple pregnancy. 2. N Engl J Med 1973; 288:1329.
  3. Luke B. The changing pattern of multiple births in the United States: maternal and infant characteristics, 1973 and 1990. Obstet Gynecol 1994; 84:101.
  4. Blondel B, Kogan MD, Alexander GR, et al. The impact of the increasing number of multiple births on the rates of preterm birth and low birthweight: an international study. Am J Public Health 2002; 92:1323.
  5. Blondel B, Kaminski M. Trends in the occurrence, determinants, and consequences of multiple births. Semin Perinatol 2002; 26:239.
  6. Martin JA, Hamilton BE, Sutton PD, et al. Births: Final Data for 2006. Natl Vital Stat Rep 2010; 59:1. http://www.cdc.gov/nchs/data/nvsr/nvsr59/nvsr59_01.pdf (Accessed on October 26, 2011).
  7. Russell RB, Petrini JR, Damus K, et al. The changing epidemiology of multiple births in the United States. Obstet Gynecol 2003; 101:129.
  8. Hamilton BE, Martin JA, Ventura SJ. Births: preliminary data for 2005. Natl Vital Stat Rep 2006; 55:1.
  9. Lambalk CB, De Koning CH, Braat DD. The endocrinology of dizygotic twinning in the human. Mol Cell Endocrinol 1998; 145:97.
  10. Cameron AH, Edwards JH, Derom R, et al. The value of twin surveys in the study of malformations. Eur J Obstet Gynecol Reprod Biol 1983; 14:347.
  11. Cameron AH. The Birmingham twin survey. Proc R Soc Med 1968; 61:229.
  12. Bulmer MG. The Biology of Twinning in Man, Oxford University Press, London 1970.
  13. Cunnigham FG, Gant NF, Leveno KJ, et al. Williams Obstetrics, 20th ed, Appleton & Lange, Stamford, CT 1997.
  14. Vermesh M, Kletzky OA. Follicle-stimulating hormone is the main determinant of follicular recruitment and development in ovulation induction with human menopausal gonadotropin. Am J Obstet Gynecol 1987; 157:1397.
  15. Martin NG, Olsen ME, Theile H, et al. Pituitary-ovarian function in mothers who have had two sets of dizygotic twins. Fertil Steril 1984; 41:878.
  16. Nylander PP. Serum levels of gonadotrophins in relation to multiple pregnancy in Nigeria. J Obstet Gynaecol Br Commonw 1973; 80:651.
  17. Soma H, Takayama M, Kiyokawa T, et al. Serum gonadotropin levels in Japanese women. Obstet Gynecol 1975; 46:311.
  18. Marshall JR. Ovulation induction. Obstet Gynecol 1970; 35:963.
  19. Källén B, Olausson PO, Nygren KG. Neonatal outcome in pregnancies from ovarian stimulation. Obstet Gynecol 2002; 100:414.
  20. Schachter M, Raziel A, Friedler S, et al. Monozygotic twinning after assisted reproductive techniques: a phenomenon independent of micromanipulation. Hum Reprod 2001; 16:1264.
  21. Schieve LA, Peterson HB, Meikle SF, et al. Live-birth rates and multiple-birth risk using in vitro fertilization. JAMA 1999; 282:1832.
  22. Pijnenborg JM, Oei SG. The monoamniotic twin: a riskful event. Eur J Obstet Gynecol Reprod Biol 1999; 86:51.
  23. Aisenbrey GA, Catanzarite VA, Hurley TJ, et al. Monoamniotic and pseudomonoamniotic twins: sonographic diagnosis, detection of cord entanglement, and obstetric management. Obstet Gynecol 1995; 86:218.
  24. Derom C, Vlietinck R, Derom R, et al. Population-based study on sex proportion in monoamniotic twins. N Engl J Med 1988; 319:119.
  25. Slotnick RN, Ortega JE. Monoamniotic twinning and zona manipulation: a survey of U.S. IVF centers correlating zona manipulation procedures and high-risk twinning frequency. J Assist Reprod Genet 1996; 13:381.
  26. Dubecq F, Dufour P, Vinatier D, et al. Monoamniotic twin pregnancies. Review of the literature, and a case report with vaginal delivery. Eur J Obstet Gynecol Reprod Biol 1996; 66:183.
  27. Su LL. Monoamniotic twins: diagnosis and management. Acta Obstet Gynecol Scand 2002; 81:995.
  28. Suzuki S, Kaneko K, Shin S, Araki T. Incidence of intrauterine complications in monoamniotic twin gestation. Arch Gynecol Obstet 2001; 265:57.
  29. Spellacy WN, Handler A, Ferre CD. A case-control study of 1253 twin pregnancies from a 1982-1987 perinatal data base. Obstet Gynecol 1990; 75:168.
  30. Roberts WE, Morrison JC, Hamer C, Wiser WL. The incidence of preterm labor and specific risk factors. Obstet Gynecol 1990; 76:85S.
  31. Bodeau-Livinec F, Zeitlin J, Blondel B, et al. Do very preterm twins and singletons differ in their neurodevelopment at 5 years of age? Arch Dis Child Fetal Neonatal Ed 2013; 98:F480.
  32. Rydhstroem H, Heraib F. Gestational duration, and fetal and infant mortality for twins vs singletons. Twin Res 2001; 4:227.
  33. Donovan EF, Ehrenkranz RA, Shankaran S, et al. Outcomes of very low birth weight twins cared for in the National Institute of Child Health and Human Development Neonatal Research Network's intensive care units. Am J Obstet Gynecol 1998; 179:742.
  34. Grennert L, Persson PH, Gennser G. Intrauterine growth of twins judged by BPD measurements. Acta Obstet Gynecol Scand Suppl 1978; 78:28.
  35. Alexander GR, Kogan M, Martin J, Papiernik E. What are the fetal growth patterns of singletons, twins, and triplets in the United States? Clin Obstet Gynecol 1998; 41:114.
  36. Grumbach K, Coleman BG, Arger PH, et al. Twin and singleton growth patterns compared using US. Radiology 1986; 158:237.
  37. Hamilton EF, Platt RW, Morin L, et al. How small is too small in a twin pregnancy? Am J Obstet Gynecol 1998; 179:682.
  38. Devoe LD, Ware DJ. Antenatal assessment of twin gestation. Semin Perinatol 1995; 19:413.
  39. Monset-Couchard M, de Bethmann O, Relier JP. Long term outcome of small versus appropriate size for gestational age co-twins/triplets. Arch Dis Child Fetal Neonatal Ed 2004; 89:F310.
  40. Hartley RS, Hitti J, Emanuel I. Size-discordant twin pairs have higher perinatal mortality rates than nondiscordant pairs. Am J Obstet Gynecol 2002; 187:1173.
  41. Demissie K, Ananth CV, Martin J, et al. Fetal and neonatal mortality among twin gestations in the United States: the role of intrapair birth weight discordance. Obstet Gynecol 2002; 100:474.
  42. Branum AM, Schoendorf KC. The effect of birth weight discordance on twin neonatal mortality. Obstet Gynecol 2003; 101:570.
  43. Victoria A, Mora G, Arias F. Perinatal outcome, placental pathology, and severity of discordance in monochorionic and dichorionic twins. Obstet Gynecol 2001; 97:310.
  44. American College of Obstetricians and Gynecologists. Special problems of multiple gestation. In: ACOG Educational Bulletin 253, American College of Obstetricians and Gynecologists, Washington, DC 1998.
  45. Mathews TJ, Menacker F, MacDorman MF. Infant mortality statistics from the 2000 period linked birth/infant death data set. Natl Vital Stat Rep 2002; 50:1.
  46. Martin JA, MacDorman MF, Mathews TJ. Triplet births: trends and outcomes, 1971-94. Vital Health Stat 21 1997; :1.
  47. Kaufman GE, Malone FD, Harvey-Wilkes KB, et al. Neonatal morbidity and mortality associated with triplet pregnancy. Obstet Gynecol 1998; 91:342.
  48. Blickstein I, Keith LG. Outcome of triplets and high-order multiple pregnancies. Curr Opin Obstet Gynecol 2003; 15:113.
  49. Imaizumi Y. Perinatal mortality in triplet births in Japan: time trends and factors influencing mortality. Twin Res 2003; 6:1.
  50. Francois K, Alperin A, Elliott JP. Outcomes of quintuplet pregnancies. J Reprod Med 2001; 46:1047.
  51. Ronalds GA, De Stavola BL, Leon DA. The cognitive cost of being a twin: evidence from comparisons within families in the Aberdeen children of the 1950s cohort study. BMJ 2005; 331:1306.
  52. Christensen K, Petersen I, Skytthe A, et al. Comparison of academic performance of twins and singletons in adolescence: follow-up study. BMJ 2006; 333:1095.
  53. Lorenz JM. Neurodevelopmental outcomes of twins. Semin Perinatol 2012; 36:201.
  54. Feldman R, Eidelman AI. Triplets across the first 5 years: the discordant infant at birth remains at developmental risk. Pediatrics 2009; 124:316.
  55. Wadhawan R, Oh W, Vohr BR, et al. Neurodevelopmental outcomes of triplets or higher-order extremely low birth weight infants. Pediatrics 2011; 127:e654.
  56. Natalucci G, Iten M, Hofmann J, et al. Health-related quality of life and behavior of triplets at adolescent age. J Pediatr 2012; 161:495.
  57. Sebire NJ, Snijders RJ, Hughes K, et al. The hidden mortality of monochorionic twin pregnancies. Br J Obstet Gynaecol 1997; 104:1203.
  58. Bermúdez C, Becerra CH, Bornick PW, et al. Placental types and twin-twin transfusion syndrome. Am J Obstet Gynecol 2002; 187:489.
  59. Arias F, Sunderji S, Gimpelson R, Colton E. Treatment of acardiac twinning. Obstet Gynecol 1998; 91:818.
  60. Gonsoulin W, Moise KJ Jr, Kirshon B, et al. Outcome of twin-twin transfusion diagnosed before 28 weeks of gestation. Obstet Gynecol 1990; 75:214.
  61. Bajoria R, Ward S, Sooranna SR. Atrial natriuretic peptide mediated polyuria: pathogenesis of polyhydramnios in the recipient twin of twin-twin transfusion syndrome. Placenta 2001; 22:716.
  62. Zosmer N, Bajoria R, Weiner E, et al. Clinical and echographic features of in utero cardiac dysfunction in the recipient twin in twin-twin transfusion syndrome. Br Heart J 1994; 72:74.
  63. Jones KL. Smith's recognizable patterns of human malformation, 6th ed, Elsevier Saunders, Philadelphia 2006.
  64. Schinzel AA, Smith DW, Miller JR. Monozygotic twinning and structural defects. J Pediatr 1979; 95:921.
  65. Spitz L, Kiely EM. Conjoined twins. JAMA 2003; 289:1307.
  66. Métneki J, Czeizel A. Conjoined twins in Hungary, 1970-1986. Acta Genet Med Gemellol (Roma) 1989; 38:285.
  67. Spencer R. Anatomic description of conjoined twins: a plea for standardized terminology. J Pediatr Surg 1996; 31:941.
  68. Mackenzie TC, Crombleholme TM, Johnson MP, et al. The natural history of prenatally diagnosed conjoined twins. J Pediatr Surg 2002; 37:303.
  69. Cywes S, Millar AJ, Rode H, Brown RA. Conjoined twins--the Cape Town experience. Pediatr Surg Int 1997; 12:234.
  70. O'Neill JA. Conjoined twins. In: Pediatric Surgery, 5th ed, O'Neill JA, Rowe M, Grosfeld JL, et al (Eds), Mosby Year Book, St Louis 1998. Vol 2, p.1925.
  71. Spitz L, Kiely E. Success rate for surgery of conjoined twins. Lancet 2000; 356:1765.
  72. Aggarwal N, Suri V, Saxena S, et al. Acardiac acephalus twins: a case report and review of literature. Acta Obstet Gynecol Scand 2002; 81:983.
  73. Coulam CB, Wright G. First trimester diagnosis of acardiac twins. Early Pregnancy 2000; 4:261.
  74. Tsao K, Feldstein VA, Albanese CT, et al. Selective reduction of acardiac twin by radiofrequency ablation. Am J Obstet Gynecol 2002; 187:635.
  75. Sullivan AE, Varner MW, Ball RH, et al. The management of acardiac twins: a conservative approach. Am J Obstet Gynecol 2003; 189:1310.
  76. Bajoria R, Kingdom J. The case for routine determination of chorionicity and zygosity in multiple pregnancy. Prenat Diagn 1997; 17:1207.
  77. Gaucherand P, Rudigoz RC, Piacenza JM. Monofetal death in multiple pregnancies: risks for the co-twin, risk factors and obstetrical management. Eur J Obstet Gynecol Reprod Biol 1994; 55:111.
  78. Johnson CD, Zhang J. Survival of other fetuses after a fetal death in twin or triplet pregnancies. Obstet Gynecol 2002; 99:698.
  79. Bajoria R, Wee LY, Anwar S, Ward S. Outcome of twin pregnancies complicated by single intrauterine death in relation to vascular anatomy of the monochorionic placenta. Hum Reprod 1999; 14:2124.
  80. Landy HJ, Weiner S, Corson SL, et al. The "vanishing twin": ultrasonographic assessment of fetal disappearance in the first trimester. Am J Obstet Gynecol 1986; 155:14.
  81. Benirschke K. Intrauterine death of a twin: mechanisms, implications for surviving twin, and placental pathology. Semin Diagn Pathol 1993; 10:222.
  82. Fusi L, McParland P, Fisk N, et al. Acute twin-twin transfusion: a possible mechanism for brain-damaged survivors after intrauterine death of a monochorionic twin. Obstet Gynecol 1991; 78:517.
  83. Petterson B, Nelson KB, Watson L, Stanley F. Twins, triplets, and cerebral palsy in births in Western Australia in the 1980s. BMJ 1993; 307:1239.
  84. Pharoah PO, Cooke T. Cerebral palsy and multiple births. Arch Dis Child Fetal Neonatal Ed 1996; 75:F174.
  85. Larroche JC, Droullé P, Delezoide AL, et al. Brain damage in monozygous twins. Biol Neonate 1990; 57:261.
  86. Scheller JM, Nelson KB. Twinning and neurologic morbidity. Am J Dis Child 1992; 146:1110.
  87. Weig SG, Marshall PC, Abroms IF, Gauthier NS. Patterns of cerebral injury and clinical presentation in the vascular disruptive syndrome of monozygotic twins. Pediatr Neurol 1995; 13:279.
  88. Bejar R, Vigliocco G, Gramajo H, et al. Antenatal origin of neurologic damage in newborn infants. II. Multiple gestations. Am J Obstet Gynecol 1990; 162:1230.
  89. Pharoah PO. Twins and cerebral palsy. Acta Paediatr Suppl 2001; 90:6.
  90. Pharoah PO. Cerebral palsy in the surviving twin associated with infant death of the co-twin. Arch Dis Child Fetal Neonatal Ed 2001; 84:F111.
  91. Glazebrook C, Sheard C, Cox S, et al. Parenting stress in first-time mothers of twins and triplets conceived after in vitro fertilization. Fertil Steril 2004; 81:505.
  92. Leonard LG. Depression and anxiety disorders during multiple pregnancy and parenthood. J Obstet Gynecol Neonatal Nurs 1998; 27:329.
  93. Choi Y, Bishai D, Minkovitz CS. Multiple births are a risk factor for postpartum maternal depressive symptoms. Pediatrics 2009; 123:1147.
  94. Ellison MA, Hotamisligil S, Lee H, et al. Psychosocial risks associated with multiple births resulting from assisted reproduction. Fertil Steril 2005; 83:1422.
  95. Olivennes F, Golombok S, Ramogida C, et al. Behavioral and cognitive development as well as family functioning of twins conceived by assisted reproduction: findings from a large population study. Fertil Steril 2005; 84:725.
  96. Bryan E. The impact of multiple preterm births on the family. BJOG 2003; 110 Suppl 20:24.
  97. Malone FD, Chelmow D, Athanassiou A, D'Alton ME. Impact of gestational age at delivery of the economics of triplet pregnancy. J Matern Fetal Med 1999; 8:256.
  98. Callahan TL, Hall JE, Ettner SL, et al. The economic impact of multiple-gestation pregnancies and the contribution of assisted-reproduction techniques to their incidence. N Engl J Med 1994; 331:244.
  99. Leonard LG. Breastfeeding higher order multiples: enhancing support during the postpartum hospitalization period. J Hum Lact 2002; 18:386.
  100. Leonard LG. Breastfeeding rights of multiple birth families and guidelines for health professionals. Twin Res 2003; 6:34.
  101. Robin M, Josse D, Tourrette C. Forms of family reorganization following the birth of twins. Acta Genet Med Gemellol (Roma) 1991; 40:53.
  102. Harrigan R, Naber MM, Jensen KA, et al. Perinatal grief: response to the loss of an infant. Neonatal Netw 1993; 12:25.
  103. Swanson PB, Pearsall-Jones JG, Hay DA. How mothers cope with the death of a twin or higher multiple. Twin Res 2002; 5:156.
  104. Friedman S, Flidel-Rimon O, Lavie E, Shinwell ES. The effect of prenatal consultation with a neonatologist on human milk feeding in preterm infants. Acta Paediatr 2004; 93:775.
  105. Czeszyńska MB, Kowalik K. Multiple pregnancy: factors contributing to early infant's breast-feeding--own experience. Acta Genet Med Gemellol (Roma) 1998; 47:191.
  106. Flidel-Rimon O, Shinwell ES. Breast feeding twins and high multiples. Arch Dis Child Fetal Neonatal Ed 2006; 91:F377.
  107. Damato EG, Dowling DA, Standing TS, Schuster SD. Explanation for cessation of breastfeeding in mothers of twins. J Hum Lact 2005; 21:296.
  108. Berlin CM. "Exclusive" breastfeeding of quadruplets. Breastfeed Med 2007; 2:125.
  109. Mead LJ, Chuffo R, Lawlor-Klean P, Meier PP. Breastfeeding success with preterm quadruplets. J Obstet Gynecol Neonatal Nurs 1992; 21:221.
  110. Saint L, Maggiore P, Hartmann PE. Yield and nutrient content of milk in eight women breast-feeding twins and one woman breast-feeding triplets. Br J Nutr 1986; 56:49.