Repeat karyotyping showed normal 46,XY chromosomes for both babies.
The small twin developed respiratory distress, which relapsed to mild to moderate chronic lung disease in the next days. He was extubated by day of life #5. His hematocrit and complete blood count was normal at birth. He later developed anemia of prematurity and received numerous blood transfusions. The physical exam showed hypospadias and bilateral undescended testes, as well as a wide anterior fontanel. From his regular screen tests only elevated TSH was found, without clinical symptoms of hypothyroidism, and was treated accordingly. Since then the TSH normalized. He was finally discharged after 99 days in the Neonatal Intensive Care Unit.
The big twin was extubated by day of life # 2. His hematocrit and complete blood count was within normal limits at birth. He later developed anemia of prematurity requiring two transfusions of packed red blood cells. He also developed Staphylococcus Epidermis septicemia, with secondary thrombocytopenia. He was treated accordingly. The regular laboratory screen was within normal limits. On physical exam no structural anomalies were found. He was discharged 7 days after delivery.
The placenta was submitted to gross and microscopic evaluation and was found to be of the dichorionic diamniotic type (it was also a “fused” one). It was a single oval disk that weighted 449 gr. The umbilical cord of the small twin was attached to the margin of the placenta. The diameter of the two umbilical cords was the same. Although the parenchyma was disrupted in the region of the small twin, there was no obvious evidence of missing cotyledons. There was no evidence of inflammatory or other histopathologic abnormality.
Prevalence: Discordant fetal growth (more than 20%) has been reported to complicate 15% to 29% of twin gestations1,6,16,17. In a large collaborative study18, birth weights differed between 500 and 999gr in 18% of the twin sets and were in excess of 1000gr in 3%. In another large study19, discordancy in birth weights more than 750gr was seen in 8,9% of the twin sets.
Etiology of growth discrepancy:6
Prevalence 25% (10 times greater than singletons).
17% of all IUGR are twins.
Twin-to twin transfusion syndrome.
Pathogenesis: Although the birth differences in monochorionic twins have been attributed to hemodynamic factors, the etiology of discordance in dichorionic twins remains elusive2 . Possible etiological factors are genetic potential, fetal sex, environmental factors and congenital anomalies2 ,3 , 12 . It has been postulated that the smaller twin might have a genetic predisposition for a lower birth weight and becomes compounded by a crowded intrauterine environment and/or uteroplacental insufficiency that results in greater divergence in growth rate1
Sonographic findings: The standard care for twin pregnancy includes serial sonographic evaluations to assess the growth of each fetus20,21 . Findings suggestive of growth discrepancy include:
Estimated fetal weights discordant by more than 20%7,22,23,24,25,26,27,28,29,30,31,32,33,34. It can be classified as mild (15-25%) or severe (>25%). Cases of pre-term twin gestations with severe discrepancy are associated with a higher morbidity rate35,36,37.
Abdominal circumference diverging by 20 mm or more37,38,39,40.
Difference in biparietal diameter greater than 6 mm, with the smaller biparietal diameter less than 2 standard deviations below the mean5.
Head perimeter diverging by more than 5%.
Umbilical artery S/D ratios discordant by more than 15% and elevated umbilical artery S/D ratio (³0.4) in one or both twins41,42,43,44,45,46,47.
Differential diagnosis: Includes, in monochorionic diamniotic twin pregnancies, twin-to-twin transfusion syndrome (twin oligohydramnios-polyhydramnios sequence, stuck twin syndrome).
2.5 risk of perinatal mortality.
6.5 risk of stillbirth
Small twin mortality: 20% (6 times more than in concordant twins).
Discussion: According to Erkkola et al6, growth discrepancy in twins can be attributed to IUGR, twin-to twin transfusion syndrome and to anomalies. In this case-report twin-to-twin transfusion syndrome was excluded from the diagnosis because of the normal amniotic fluid in the small twin. Moreover, the small twin had the greater hematocrit (56%) of the pair at birth. In addition, major anomalies were not found in either of the twins.
In this case report the discordancy between the two fetuses was actually due to IUGR in one of the fetuses. IUGR has a prevalence of 25% in twins, which is 10 times greater than in singletons. Moreover, 17% of all IUGR are twins6. Especially for the dizygotic twins, significant differences in growth rates have been attributed to selective intrauterine growth retardation of one twin2.
In a study of 147 dichorionic twin pairs, birth weight discordance was attributable not to differences in placental weight but to a greater number of placental lesions in the lighter twin than in the heavier twin2. In another study of 382 twin pregnancies48, the most frequent findings in the placentas of severely discordant twins were small placental weight and umbilical cord abnormalities. Vascular-thrombotic lesions, particularly infarcts, acute atherosis of spiral arteries, thrombosis of fetal vessels, intraplacental hematomas and perivillous fibrin deposition are common in the placentas of growth restricted fetuses48. In our case, however, none of the above lesions were found. The only possibly significant finding was that the umbilical cord of the smallest fetus had a marginal insertion, although its diameter was same as in the big twin. Moreover, in a recent study49, marginal placental cord insertion was not associated with increased risk of growth impairment, although it was limited in singleton pregnancies.
There were no statistically significant differences observed between discordant and nondiscordant twins with respect to length of gestation, race, education, occupation, smoking, alcohol use, hypertension, diabetes, maternal age, gravidity, and autoimmune disease2. Moreover, these factors are common to each member of a twin pair15.
The overall risk of fetal death in discordant twins (>25% weight discrepancy) is 6,5-fold greater than in concordant twins1,6. However, when there is discordancy with an appropriate for gestational age twin and a small for gestational age twin there is no increased morbidity or mortality.
In a large study of 15066 twin pregnancies19, like-sexed pairs experienced significant excess in pregnancy loss when discordance exceeded 20% to 30%. In the same study the pregnancy loss rate for like-sexed pairs was more than twice as high as for unlike-sexed pairs. This increase in the rate of pregnancy loss was attributed to monochorionic twin pregnancies. In addition, discordancy greater than 750 gr was noted in 10,4% of unlike-sexed twins and in 8,3% of like-sexed twins. In another study of 147 twin pairs, however, sex did not play a significant role in birth weight discordance2.
According to Rydhstrom19, a malformed twin has a tendency to intrauterine growth retardation, leading to an increased discordance even in cases when the malformation does not prove lethal.
This was a case report of a dichorionic twin pregnancy with discordance between the pair approaching 50% that had a favorable outcome. It is important that the counseling of patients with so greatly discordant twin pairs will include not only the definition of the possibility of pregnancy loss, but also the possibility of malformations, prolonged stay in the Neonatal Intensive Care Unit and the possible neurological damage. It would be also useful to know how many of these babies will eventually have a sufficiently normal life.
Reviewer: Antony Vintzileos, MD
1.Rodis JF, Vintzileos AM, Campbell WA, Nochimson DJ. Intrauterine fetal growth in discordant twin gestations.J Ultrasound Med. 1990 Aug;9(8):443-8. 2. Eberle AM, Levesque D, Vintzileos AM, Egan JF, Tsapanos V, Salafia CM. Placental pathology in discordant twins.Am J Obstet Gynecol. 1993 Oct;169(4):931-5 3.Blickstein I, Weissman A. Birth weight discordancy in male-first and female-first pairs of unlike-sexed twins. Am J Obstet Gynecol. 1990 Mar;162(3):661-3. 4.O"Brien WF, Knuppel RA, Scerbo JC, Rattan PK. Birth weight in twins: an analysis of discordancy and growth retardation. Obstet Gynecol. 1986 Apr;67(4):483-6. 5.Crane JP, Tomich PG, Kopta M. Ultrasonic growth patterns in normal and discordant twinsObstet Gynecol. 1980 Jun;55(6):678-83 6.Erkkola R, Ala-Mello S, Piiroinen O, Kero P, Sillanpaa M. Growth discordancy in twin pregnancies: a risk factor not detected by measurements of biparietal diameter. Obstet Gynecol. 1985 Aug;66(2):203-6. 7.Storlazzi E, Vintzileos AM, Campbell WA, Nochimson DJ, Weinbaum PJ. Ultrasonic diagnosis of discordant fetal growth in twin gestations.Obstet Gynecol. 1987 Mar;69(3 Pt 1):363-7. 8.Blickstein I, Friedman A, Caspi B, Lancet M. Ultrasonic prediction of growth discordancy by intertwin difference in abdominal circumference. Int J Gynaecol Obstet. 1989 Jun;29(2):121-4. 9.Guaschino S, Spinillo A, Stola E, Pesando PC. Growth retardation, size at birth and perinatal mortality in twin pregnancy. Int J Gynaecol Obstet. 1987 Oct;25(5):399-403 10.Keet MP, Jaroszewicz AM, Lombard CJ. Follow-up study of physical growth of monozygous twins with discordant within-pair birth weights. Pediatrics. 1986 Mar;77(3):336-44. 11.Vetter K. Considerations on growth discordant twins.J Perinat Med. 1993;21(4):267-72. Review. 12.Blickstein I, Lancet M. The growth discordant twin. Obstet Gynecol Surv. 1988 Sep;43(9):509- Review. 13.Blickstein I. The twin-twin transfusion syndrome. Obstet Gynecol. 1990 Oct;76(4):714-22. Review. 14.Fisk NM, Borrell A, Hubinont C, Tannirandorn Y, Nicolini U, Rodeck CH. Fetofetal transfusion syndrome: do the neonatal criteria apply in utero?Arch Dis Child. 1990 Jul;65(7 Spec No):657-61. 15.Westwood M, Gibson JM, Sooranna SR, Ward S, Neilson JP, Bajoria R. Genes or placenta as modulator of fetal growth: evidence from the insulin-like growth factor axis in twins with discordant growth. Mol Hum Reprod. 2001 Apr;7(4):387-95. 16.Leveno KJ, Santos- Ramos R, Duenhoelter JH, et al: Sonar cefalometry in twin pregnancy: Discordancy of the biparietal diameter after 28 weeks’ gestation. Am J Obstet Gynecol 138:615, 1980. 17.Barnea ER, Romero R, Scott D, et al: The value of biparietal diameter and abdominal perimeter in the diagnosis of growth retardation in twin gestation.Am J Perinatol 2:221, 1985. 18.Kohl SG, Casey G. Twin gestation. Mt Sinai J Med 1975 Nov-Dec;42(6):523-39 19.Rydhstrom H. Discordant birthweight and late fetal death in like-sexed and unlike-sexed twin pairs: a population-based study. Br J Obstet Gynaecol. 1994 Sep;101(9):765-9. 20.Citkara U, Berkowitz GS, Levine R, Riden DJ, Fagerstrom RM Jr, Chervenak FA, Berkowitz RL. Twin pregnancy: routine use of ultrasound examinations in the perinatal diagnosis of intrauterine growth retardation and discordant growth. Am J Perinatol 1985 Jan;2(1):49-54. 21.Divon MY, Weiner Z. Ultrasound in twin pregnancy. Semin Perinatol 1995 Oct;19(5):404-12. 22.Blickstein I, Goldman RD, Smith-Levitin M, Greenberg M, Sherman D, Rydhstroem H. The relation between inter-twin birth weight discrepancy and total twin birth weight. Obstet Gynecol 1999 Jan;93(1):113-6. 23.Lemery DR, Santolaya-Forgas J, Serre AF, Besse GH, Jacquetin B. Fetal serum erythropoietin in twin pregnancies with discordant growth. A clue for prenatal diagnosis of monochorionic twins with vascular communications. Fetal Diagn Ther 1995 Mar-Apr;10(2):86-91. 24.Hsieh TT, Chang TC, Chiu TH, Hsu JJ, Chao A. Growth discordancy, birth weight, and neonatal adverse events in third trimester twin gestations. Gynecol Obstet Invest 1994;38(1):36-40. 25.Chauhan SP, Washburne JF, Martin JN Jr, Roberts WE, Roach H, Morrison JC. Intrapartum assessment by house staff of birth weight among twins. Obstet Gynecol 1993 Oct;82(4):523-6. 26.Sayegh SK, Warsof SL. Ultrasonic prediction of discordant growth in twin pregnancies. Fetal Diagn Ther 1993 Jul-Aug;8(4):241-6. 27.Mordel N, Benshushan A, Zajicek G, Laufer N, Schenker JG, Sadovsky E. Discordancy in triplets. Am J Perinatol 1993 May;10(3):224-5. 28.Jakobovits AA. The significance of birth weight discrepancy in twins. Acta Med Hung 1992-93;49(3-4):195-200. 29.Chamberlain P, Murphy M, Comerford FR. How accurate is antenatal sonographic identification of discordant birth weight in twins?. Eur J Obstet Gynecol Reprod Biol 1991 Jul 1;40(2):91-6. 30.Blickstein I, Shoham-Schwartz Z, Lancet M. Growth discordancy in appropiate for gestational age, term twins. Obstet Gynecol 1988 Oct;72(4):582-4. 31.Blickstein I, Shoham-Schwartz Z, Lancet M, Borenstein R. Characterization of the growth-discordant twin. Obstet Gynecol 1987 Jul;70(1):11-5. 32.Philip AG. Term twins with discordant birth weights: observations at birth and one year. Acta Genet Med Gemellol 1981;30(3):203-12. 33.Devoe LD, Ware DJ. Antenatal assessment of twin gestation. Semin Perinatol 1995 Oct;19(5):413-23. 34.Fraser D, Picard R, Picard E, Leiberman JR. Birth weight discordance, intrauterine growth retardation and perinatal outcomes in twins. J Reprod Med 1994 Jul;39(7):504-8. 35.Blickstein I, Manor M, Levi R, Goldchmit R, Weissman A. The intrauterine ponderal index in relation to birth weight discrepancy in twin gestations. Int J Gynaecol Obstet 1995 Sep;50(3):253-5. 36.Cheung VY, Bocking AD, Dasilva OP. Preterm discordant twins: what birth weight difference is significant?. Am J Obstet Gynecol 1995 Mar;172(3):955-9. 37.Blickstein I. The definition, diagnosis, and management of growth-discordant twins: an international census survey. Acta Genet Med Gemellol 1991;40(3-4):345-51. 38.Blickstein I, Manor M, Levi R, Goldsmith R. Is intertwin birth weight discrepancy predictable?. Gynecol Obstet Invest 1996;42(2):105-8. 39.Divon MY, Girz BA, Sklar A, Guidetti DA, Langer O. Discordant twins-a prospective study of the diagnostic value of real-time ultrasonography combined with umbilical artery velocimetry. Am J Obstet Gynecol 1989 Sep;161(3):757-60. 40.Brown CE, Guzick DS, Leveno KJ, Santos-Ramos R, Whalley PJ. Prediction of discordant twins using ultrasound measurement of biparietal diameter and abdominal perimeter. Obstet Gynecol 1987 Nov;70(5):677-81. 41.Chittacharoen A, Leelapattana P, Phuapradit W. Umbilical Doppler velocimetry prediction of discordant twins. J Obstet Gynaecol Res 1999 Apr;25(2):95-8. 42.Grab D, Hutter W, Haller T, Sterzik K, Terinde R. Discordant growth in twin pregnancy-value of Doppler ultrasound. Geburtshilfe Frauenheilkd 1993 Jan;53(1):42-8. 43.Giles WB. Doppler ultrasound in multiple pregnancies. Baillieres Clin Obstet Gynaecol 1998 Mar;12(1):77-89. 44.Clode N, Casal E, Graca LM. Umbilical flowmetry in twin pregnancy. A method for identifying discordant fetal growth?. Acta Med Port 1992 Oct;5(9):483-4. 45.Behrens O, Wedeking-Schohl H, Mesrogli M, Degenhardt F, Schneider J. Doppler ultrasound in monitoring twin pregnancies with early discordant growth. Z Geburtshilfe Perinatol 1992 Sep-Oct;196(5):209-12. 46.Gerson AG, Wallace DM, Bridgens NK, Ashmead GG, Weiner S, Bolognese RJ. Duplex Doppler ultrasound in the evaluation of growth in twin pregnancies. Obstet Gynecol 1987 Sep;70(3):419-23. 47.Giles WB, Trudinger BJ, Cook CM. Fetal umbilical artery flow velocity-time waveforms in twin pregnancies. Br J Obstet Gynaecol 1985 May;92. 48.Victoria A, Mora G, Arias F. Perinatal outcome, placental pathology, and severity of discordance in monochorionic and dichorionic twins. Obstet Gynecol. 2001 Feb;97(2):310-5. 49.Liu C. C., Pretorius D., Scioscia A. L., Hull A.D. Sonografic Prenatal Diagnosis of Marginal Placental Cord Insertion. J Ultrasound Medicine 2002 June;21(6):627-32.