J Am Board Fam Pract: first published as 10.3122/jabfm.2.1.58 on 1 January 1989. Downloaded from The Recognition And Significance Of The Vanishing Twin Jo Jackson, M.D., and Kurt Benirschke, M.D.

Abstract: With the advent of sonography, a twin The distinction between monochorionic and dichor­ pregnancy may be diagnosed in early gestation. Se­ ionic twins is important in their management and rial sonographic examinations can show the disap­ for both maternal and fetal prognosis. Identification pearance of one of two twins. We offer evidence of an of dizygotic twins through chromosomal or sono­ early twin pregnancy with a "vanishing twin," re­ graphic studies, revealing separate placentas, sepa­ sulting in a liveborn singleton plus a fetus papyra­ rate membranes, or different sexes, theoretically al­ ceus. There is an increasing body of information lows the physician to predict a favorable outcome for I 'I about explanations, management, and complications the live twin and the mother. (J Am Bd Fam Pract I associated with a multiple gestation and fetal death. 1989; 2:58-63.) j The rate of multiple gestation is being redefined used birth control during the last 6 months. The 1 since the advent of sonography. It is now well last menstrual period began on December 5, 1983, ,I known that more twins are lost in early pregnancy and was described as a typical 5-day, moderate 1 than previously believed and that many appar­ flow associated with premenstrual tension. Persist­ ently singleton pregnancies began as a twin preg­ ent light spotting without cramping had occurred 1 nancy. A review of the literature by Landy, et al. since the last menstrual period and was a source of noted that the simultaneous occurrence of a fetus concern. Her day of delivery was estimated to be papyraceus and a live twin is extremely rare and September 11, 1984, on the basis of dates. reported to be 1: 12,000 live births. I In this re­ Her physical examination showed a uterine size port, we present a case of a twin gestation result­ consistent with 13 to 14 weeks' gestation; fetal I ing in the birth of a healthy singleton and a fetus heart rate, 140/minute; and a dosed cervical os. l papyraceus. Sonographic study with amniocentesis was of­ I Fetus papyraceus is defined as the fetal death of fered because of advanced maternal age. one fetus in a twin pregnancy, with compression The sonographic examination on March 27, I of the blighted twin by the growth of the living 1984, showed a twin gestation with a single fetal twin. The result is a flattened body resembling intrauterine death (Figure 1). The live twin had a http://www.jabfm.org/ parchment. Serial sonographic examinations al­ biparietal diameter of 3 cm, corresponding to a lowed the course of this pregnancy to be followed. gestational age of 15 to 16 weeks, while the dead Had the original sonogram not been done, the fetus's biparietal diameter (2.4 cm) correlated twin pregnancy could have been missed. Knowl­ with 13 weeks. Separate membranes and placen­ edgeable management of such pregnancies is of tas were identified. Under ultrasonic guidance, us­ increasing importance. ing the biopsy transducer, 20 mL of brown amni­ otic fluid were aspirated from the sac of the live on 27 September 2021 by guest. Protected copyright. twin and karyotyped as 46,XX. Case Report The identification of twins with one fetal death The mother was healthy, married, aged 37 years, in utero was discussed with the patient and her Rh-positive, gravida 3, para 2, spontaneous abor­ husband. The risk of complications from the dis­ tion 1. She was examined in March 1984 and semination of tissue thromboplastins from the reported intermittent spotting and irregular men­ dead fetus to the live one and to the mother was ses since a spontaneous abortion in August 1983 explained. Monthly sonographic studies were rec­ at approximately 7-weeks' gestation. She had not ommended to assess fetal growth. Although the exact magnitude of risk could not be determined, FrDm the Family Practice Residency. Swedish Hospital the patient and her husband elected to continue Medical Center. Seattle. and the Departments of PatholDgy and the pregnancy. The fact that the live twin ap­ Reproductive Medicine. University Df California. San DiegD. Address reprint requests to Jo Jackson. M.D .• Swedish Hospital peared structurally normal and was very active Family Practice Clinic. 700 Minor Avenue. Seattle. WA 98104. was considered encouraging.

58 The Journal of the American Board of Family Practice-Vol. 2 No. 1 / January - March 1989 J Am Board Fam Pract: first published as 10.3122/jabfm.2.1.58 on 1 January 1989. Downloaded from

ure 2). Thereafter, the remnant of the dead twin became virtually imperceptible. On September 15, 1984, pontaneous labor with intact membranes began and progres ed normally. A 3000 g, vigorous female infant was delivered in a birthing chair over a midline episiotomy under local ane the ia. Apgar cores were 8 for 1 minute and 9 for 5 minutes. A single placenta followed, which measured 19 x 2 cm and had a central umbilical cord insertion. A econd 8 cm infarcted placenta was adherent to the liveborn's placenta (Figure 3). This might have been interpreted as an a cessory Figure I. Gestational age at 13 weeks, with two visi­ lobe; however, because of the previous sonographk ble sacs.

In order to assure continuity of care for this patient, a team con i ting of the family physician and an obstetrician/gynecologist was e tablished, and biweekly office vi it were alternated between them. Weekly coagulation profiles, which includ­ ed a complete blood count, platelet count, pro­ thrombin time, partial thromboplastin time, fi­ brinogen and fibrin degradation products, were obtained, and all of these tudie remained within normal limits throughout the pregnancy. There was no fever, cramping, abdominal pain, or fur­ ther spotting on clinical follow-up. Fundal height grew consistently throughout ge tation and Figure 3. The mall infarcted placenta at delivery wa reached a maximum 36 cm at 39 weeks. Monthly adherent to the term liveborn's pia enta. sonograms showed normal fetal growth of the live twin and gradual degeneration of the dead one identification of twin, a se ond placenta wa. ex­ until approximately 27 week' gestation (Fig- pe ted. It showed extensive retroplacental clotting http://www.jabfm.org/ with membranous necrosis, supporting the u pi­ cion of fetal death due to placental infarction. The uterine cavity was explored to as ertain complete delivery of the intrauterine contents. A e ond fetus was not identified in tJ1e uterine avity. Both placentas were fixed in formalin, and a

compressed fetus papyraceus was later re ognized on 27 September 2021 by guest. Protected copyright. (Figure 4). Radiographs further defin d the fetal structure as an apparently normal fetus, having died at appro. "imately 13 weeks, with a femoral length of 11 mm (Figure 5). Figure 6 .,how. dis ection of the fetu papyraceu.

Discussion Landy, et al. in 1982 reported a well-organized in­ vestigation of the "vanishing twin ·yndrome."l Their summary of the literature and review of corre­ sponden e with members of the International Sod­ Figure 2. Twenty-seven weeks with a small disap­ ety of Twins Studies provided new insight about the pearing fetal remnant as marked + +. potential frequency of twinning and fetal death.

Vanishing Twin 59 J Am Board Fam Pract: first published as 10.3122/jabfm.2.1.58 on 1 January 1989. Downloaded from

The relative frequency of twins increases with maternal age and parity.2.3 The dizygotic twinning rate rises to a maximum at age 37 years and falls abruptly near menopause. Martin's study sup­ ported the hypothesis that mothers of dizygotic • twins have higher serum gonadotropin levels in the early follicular phase of the menstrual cycle than mothers of singletons. 4 This increase in ~in­ ning has been postulated to be due to the increase 5 of gonadotropins with increasing age. ,6 The sud­ den fall to zero near menopause is presumably related to aging and declining ovarian function. Physiological explanations for the vanishing Figure 4. Visual examination of the small placenta twin include reabsorption of an embryo or fetus shows several anatomical landmarks. H = Head, papyraceus. Fetus papyraceus occurs as the result R = Ribs. of a variety of lethal circumstances affecting one of the twins in the middle stages of pregnancy. Posner and Klein postulated that fetal deaths Twinning frequency and spontaneous abortion statistics are presumably inaccurate due to the un­ recognized loss of some multiple pregnancies in utero, resulting in a single, surviving twin. More­ over, such twin gestations do not appear in ordi­ nary birth statistics. Spontaneous abortion before 6 weeks may be clinically unrecognized. Lost or incomplete recovery of the products of conception in a spontaneous abortion at home, complete or partial expulsion of a second sac during spotting episodes with a surviving single gestation, thera­ peutic abortions without sonographic recognition of singleton versus multiple gestations, and unrec­

ognized placental evidence of multiple gestation http://www.jabfm.org/ contribute to inaccurate twinning and fetal death statistics. Indeed, this case could have gone unrec­ Figure 6. Dissection of the fetus papyraceus. ognized if prenatal sonographic studies had not been done or the placenta had not been scrutini­ zed closely. earlier than 3 months are resorbed, and later deaths fail to mummify in time? Fetal deaths of

twins may also be secondary to the transfusion on 27 September 2021 by guest. Protected copyright. syndrome, hemolytic disease, decidual vascular disease, velamentous cord insertion, cord en­ tanglement or infarct, anomalies, trisomies, utero­ placental compromise, placental abruptiO or infarct. or chronic maternal disease. Close exami­ nation of the placenta, cord, and membranes is essential to discern causes of death and also the presence of multiple gestati.on. Documentation of data is important if the rate of multiple gestation and the frequency of fetus papyraceus are to be identified. Fetal death may be suspected from the loss of Figure 5. Radiographic evidence of fetal bony struc­ fetal heart tones or fetal movement and vaginal ture compressed in the smaller infarcted placenta. bleeding and confirmed by amniocentesis, sonog-

60 The Journal of the American Board of Family Practice- Vol. 2 No. 1 / January - March J989 J Am Board Fam Pract: first published as 10.3122/jabfm.2.1.58 on 1 January 1989. Downloaded from raphy, or examination of the placenta following ine death was present in 20 percent, supporting delivery. Bleeding in the first trimester is common NeUInan's claim.22 Vascular anastomosis and cord with fetal death and should signal attempts to accidents, as well as velamentous cord insertions, identify a multiple gestation pregnancy, When are seen more frequently in monochorionic pla­ prenatal diagnosis has been made, sonographic centas. The number of placentas in ~ twin preg­ study should be used throughout the pregnancy to nancy depends in part on zygosity. Dizygotic detect possible complications of the live fetus, to twins develop two separate placentas, whereas assess intrauterine growth, and to follow the fetal the majority of monozygous twins share a single r~mnant. placenta through which their circulation commu­ There is a lack of accurate information about nicates. With two separate placentas there are the natural history of coagulopathy associated no shared vascular beds, and the risk of exchange with the death of one twin in utero. Maternal and transfusion does not exist. One must assess fetal consumptive coagulopathy may occur with the usefulness of sonographic identification of the absorption of thromboplastins released by the two separate placentas. In dichorionic pregnan­ dead fetus. There are no case reports of maternal cies that implant side by side, which makes it diffi­ hypo fibrin ogenemi a when fetal death of one twin cult to detect two separate circulations, the physi­ occurred before week 5. 8 Reversal of consump­ cian may be able to identify membranes tive coagulopathy has been reported with the separating the two twins. Sonographic identifica­ use of heparin.9 Typically, the clotting defect is tion of a male and female twin pregnancy can also characterized by decreasing plasma fibrinogen, clarify the issue of $eparate placentas. With two increasing fibrin degradation products, and de­ placentas, one can reason that the death of a fetus creased platelet count, often followed by vaginal follo"Yed by papyraceus formation would not be bleeding.10,1l directly responsible for morbidity or mortality in a Of more serious concern are the reported fre­ dizygous second twin and that a favorable out­ quencies of morbidity and mortality in the surviv­ come is likely. In our case, the sonographic studies 8 ing twin. -22 This, presumably, is related to the revealed two separate placentas and sacs. presence of vascular connections and coagulop­ Elevated maternal serum and amniotic fluid athy in the live fetus. 17 Maternal chronic illness alpha-fetoprotein, as well as the presence of a pos­ and placental insufficiency may also lead to fetal itive acetylcholinesterase band in fluid from the death, papyraceus formation, and the subsequent sac of a healthy fetus after the death of a co-twin death of the second twin because of a hostile in­ have been reported. 27,28. Early gestational sono­ trauterine environment. 12 graphic examination with attention to the placenta

Yet, the presence of fetal death does not consis­ may allow identification of a second gestational http://www.jabfm.org/ tently cause a negative outcome in the live fetus. sac or fetus, and therapeutic abortion of a normal Landy, et al., 1982, found that the prognosis for fetus because of persistently elevated alpha-feto­ the surviving twin is good. 1 Of 28 patients sus­ protein secondary to the death of a co-twin could pected of having a vanishing fetus, four pregnan­ be avoided. cies led to the death of the second fetus, leaving an . Multiple pregnancy can be diagnosed by so­ 86.7 percept survival rate. 23 As Enbom noted, this nography before 10 weeks.29 Nakano, in his

is overly optimistic and does not take into account study of multiple gestations and fetal loss using on 27 September 2021 by guest. Protected copyright. the potential rate of morbidity in the surviving ultrasonic tomography during 7-12 weeks' ges­ twin.24 Gindoff, et al. identified resorption of first tation, observed that misinterpretation may oc­ trimester empty sacs and found that one empty cur.30 Technical ultrasonic artifact, distortion, and sac does not adversely affect the development of a changing conditions in· pregnancy may account coexisting normal fetus, but mUltiple empty sacs for inaccurate diagnosis. Loss of an early pregnan­ seem to be associated with pregnancy loss.25 cy may result in plaque formation and appear son­ Neuman believed that the frequency of intra­ ographically similar to a fetus papyraceus. Skel­ uterine fetal death in monochorionic twins is etal formation can clarify this finding, except in three times more likely to occur than in dichor­ fetal death under 10 weeks of age. Moreover, if ionic twins. 26 Johnson's large-scale review of one fully examines a placenta, earlier sacs may be 34,677 deliveries showed a 64 percent survival identified. Accurate evaluation of multiple gesta­ rate for the co-twin associated with a single intra­ tions with fetal loss will require precise sono­ uterine death. Monochorionicity of the intrauter- graphic technique followed by thorough exami-

Vanishing Twin 61

-- J Am Board Fam Pract: first published as 10.3122/jabfm.2.1.58 on 1 January 1989. Downloaded from nation of the placenta and uterine contents after References delivery to confirm previous findings. 1. Landy HJ, Keith L, Keith D. The vanishing twin. Landy, et aI., 1986, attempted to establish a Acta Genet Med Gemellol (Roma) 1982; 31: 179- correct rate of disappearance of human fetuses 94. based on sonography in the first trimester in 2. Weinberg W. Beitrge zur physiologie und patholo­ 1000 pregnancies.23 Their conclusion was that gie der mehrlingsgeburten beim menschen. Arch Fuer Die Gesamte Physiologie Des Menschen und the frequency of multiple gestation is 3.29 per­ Der Tiere 1901; 88:346-430. cent to 5.39 percent greater than previously be­ 3. Bulmer MG. The biology of twinning in man. Ox­ lieved. This disparity was based in part on sono­ ford: Clarendon Press, 1970:78. graphic documentation of the vanishing twin, 4. Martin NG, Olsen ME, Theile H, EI Beaini JL, Han­ with a frequency of 21.2 percent. Two factors delsman D, Bhatnagar AS. Pituitary-ovarian func­ tion in mothers who have had two sets of dizygotic continue to prevent exact diagnosis ofthe multi­ twins. Ferti! Steril 1984; 41 :878-80. ple gestations in early pregnancy. Identifying 5. Milhan S Jr. Pituitary gonadotrophin and dizy­ gestational sacs before the 12th week of preg­ gotic twinning. Lancet 1964; 2:566. nancy is technically more difficult, and very early 6. Albert A, Randall RV, Stnith RA, et al. The urinary first trimester sonographic examinations are not excretion of gonadotrophin as a function of age. In: Engle ET, Pincus G, eds. Hormones and standard practice. One could postulate that the the aging process. New York: Acadetnic Press, true rate of twin conception is greater than is 1956:49-62. . currently recognized. 7. Posner AC, Klein MA. Fetus papyraceus. Obstet Gynecol 1954; 3: 106-10. 8. Hanna JH, Hill JM. Single intrauterine fetal demise in multiple gestation. Obstet Gynecol 1984; Conclusion 63:126-30. We believe that the vanishing twin phenomenon 9. Romero R, Duffy TP, Berkowitz R, Chang E, constitutes a definite clinical problem and have Hobbins JC. Prolongation of a preterm pregnancy reported here a patient in whom this occurred. complicated by death of a single twin in utero and Furthermore, we believe that this condition oc­ dissetninated intravascular coagulation. N Engl J Med 1984; 310:772-4. curs more frequently than has been known in the 10. Skelly H, Marivate M, Norman R, Kenoyer G, past. It occurs at the end of the first and the begin­ Martin R. Consumptive coagulopathy following ning of the second trimester of pregnancy and is fetal death in a triplet pregnancy. Am J Obstet more likely to occur in older women who are Gynecol1982; 142:595-6. multiparous. It should be suspected whenever 11. Pritchard JA, MacDonald PC, eds. Williams Ob­ stetrics. 16th ed. New York: Appleton-Century­ there is first trimester bleeding, and early sonogra­ Crofts, 1980:652. phy should be used to make the diagnosis. Such 12. Kindred JE. Twin pregnancies with one twin http://www.jabfm.org/ pregnancies should be considered high risk and blighted. Am J Obstet Gynecol 1944; 48:642-82. managed optimally with attention to repeated so­ 13. Catniel MR. Fetus papyraceus with intrauterine nography and tests for coagulopathy that might sibling death. JAMA 1967; 202:247. 14. Livnat EJ, Burd L, Cadkin A, Keh p, Ward AB. affect the surviving twin and the mother. Fetus papyraceus in twin pregnancy. Obstet Gyne­ The prognosis for the surviving twin is good and col 1978; 51:41s-45s. is improved in dizygotic pregnancies. A dizygotic 15. Moore CM, McAdams AJ, Sutherland J. Intrauter­ twin pregnancy may be identified with chromoso­ ine disseminated intravascular coagulation: a syn­ on 27 September 2021 by guest. Protected copyright. mal or sonographic studies looking for separate drome of multiple pregnancy with a dead twin fetus. J Pediatr 1969; 74:523-8. placentas or membranes and gender differences. It 16. Yoshioka H, Kadomoto y, Mino M, Morikawa Y, is worth noticing that a dead twin can cause in­ Kasubuchi Y, Kusunoki T. Multicystic encephalo­ creases in alpha-fetoprotein and acetylcholines­ malacia in liveborn twin with a stillborn macer­ terase in the amniotic fluid of the sllrvivor. ated co-twin. J Pediatr 1979; 95:798-800. Careful examination of placentas after delivery 17. Benirschke K. Twin placenta in perinatal mortal­ ity. New York State J Med 1961; 61:1499-508. can confirm the existence of a fetus that did not 18. Durkin MV, Kaveggia EG, Pendleton E, Neu­ survive, especially when a fetus papyraceus is hauser G, Opitz JM. Analysis of etiologic factors in identified. cerebral palsy with severe mental retardation. I. Analysis of gestational, parturitional and neonatal We gratefully acknowledge the assistance of Katherine data. Eur J Pediatr 1976; 81:67-81. Camacho Carr, R.N, C.M.N., M.S.; David Luthy, M.D.; and 19. Melnick M. Brain damage in survivor after in­ Robert Osborne, M.D., in the team management of this pa­ utero death of monozygous co-twin. Lancet 1977; tient, and Chris Sherman for providing photographic detail. 2:1287.

62 The Journal of the American Board of Family Practice-Vol. 2 No. 1 I January - March 1989 J Am Board Fam Pract: first published as 10.3122/jabfm.2.1.58 on 1 January 1989. Downloaded from 20. Hoyme HE, Higginbottom MC, Jones KL. Vascular 26. Newman HH. The physiology of twinning. Chi­ etiology of disruptive structural defects in mono­ cago: The University of Chicago Press, 1923: zygotic twins. Pediatrics 1981; 67:288-91. 147 21. Schinzel AA, Smith DW, Miller JR. Monozygotic 27. Winsor EJ, Brown BS, Luther ER, Heifetz SA, twinning and structural defects. J Pediatr 1979; Welch JP. Deceased co-twin as a cause of false 95:921-30. positive amniotic fluid AFP and ACHE. Prenat 22. Johnson S, Barss V, Driscoll S. Incidence and im­ Diagn 1987; 7:485-9. pact of single intrauterine death in multiple gesta­ 28. Bass HN, Oliver JB, Srinivasan M, et at. Persist­ tion. Lab Invest 1986; 54:29A. ently elevated AFP and ACHE in amniotic fluid 23. Landy HJ, Weiner S, Corson SL, Batzer FR, Bolog­ from a normal fetus following demise of its twin. nese RJ. The vanishing twin: ultrasonographic as­ Prenat Diagn 1986; 6:33-5. sessment of fetal disappearance in the first trimes­ 29. Levi S. Ultrasonic assessment of the high rate of ter. Am J Obstet Gyneco11986; 155:14-9 human multiple pregnancy in the first trimester. 24. Enbom JA. Twin pregnancy with intrauterine JCU 1976; 4:3-5. death of one twin. Am J Obstet Gynecol 1985; 30. Nakano H, Kubota S, Koyanagi T, Taki I. The 152:424-9. prognosis of multiple pregnancy assessed by ul­ 25. GindoffPR, Yeh MN, Jewelewicz R. The vanishing trasonic tomography. Acta Obstet Gynaecol Jpn sac syndrome. J Reprod Med 1985; 31:322-5. 1981; 33:839-43.

American Board of Family Practice Certification/Recertification Examination Dates

July 14, 1989 July 13, 1990 http://www.jabfm.org/ July 12, 1991 July 10, 1992 July 9, 1993 on 27 September 2021 by guest. Protected copyright.

Vanishing Twin 61