890 Taree Obstetrical Complications Pisone O, Vauloup-Fellos C, Cone AG, ea Asse of 298 oytomegalo vans primaryinfeions during pregoancy dcipson and outcome een Diagn 21,2013 Pat Es New>nan R Digs of TUGR- tudinal biomety. Semin Ptinatl 32(3)140, 2008 oer J, Maas AF, Birnie Fc a Seca depevation and adverse pinta ucomes among Western and non Western pregnant women in» Dutch turban popalition Soe Set Med 83:4, 2013 Peado EL, Alcock KJ, Muse H, et al: Maternal mukiple micronuen sup ements and ch copstion: randori tal in Indoveda, Pediatr 13036536, 2012 Redine RW: Vili of unknown eiloy:nonnfectoas chronc iit he pacnta, Ha Patol 38(10/1439, 2007 Riu E, Amaaa K, Koleanovs N, ea: Prenatal programming —elfects on "ood prema and eal function. Nat Rey Neplel (3137, 2011 Robere Peter J. Ho J, Valiapa J. ee ab Symp funda high (SFE) mestrement in pregnancy for detecting abnormal fal growth. Cochrane Database ye Rey 7CD008136, 2012 Rode’, Heguil HK, Kjcrgaad Hy e as Asocaon between aera ‘eight un and birth weight. Ose: Gypeol109(61309, 2007 ger MA Pda M, Claire M, ea Inher rombopis and pregnancy complications revised. Obser Gyaeent 112320, 2008, Roges BB, Bloom SL. Levene KJ. Atheros revisited: current concepts on the padhophysaiogy of implantation site sores, Ober Gyacol Su Saists9, 1999 Roos Hemdink JW, Rays TP, Sica Jl, et ak Outcome of pregnancy ia vient with arial or chsemic heat nee: eae of reget of he European Soceyof Crdioogy. Eur Heart) 3409657, 2013 Rowse DJ, Owen J Popes cesucan delivery for eal macrosomia dag owed by mea of lceonopapby-—s Faustian bungie? Am ) Oba Gynecol 1813332. 199) Rouse DJ, Oven J Goenberg Rly eli 'Theeftvenss and cos of ee: tive ceatean dvr or fel mcrosomia diagnosed by uleasound. JAMA, 276021480, 1996 ozs). Seegers EA, Veburg BO, csi Whats pared by fal brain sparing? eal cesatryralsribtion and behavioral problem in he gener pop sation Am J Fpigemio 16810)1145, 2008, Rudd E, Giloy M, Newbil Cet ak. Posive Cd immunosaining of Paczta villous yaeysotopobla suppor hostremar fal ecu a "lis af unknown elogy. Ped Dew Patol 167. 2013 Salaa CM, Minioe VK, Peo JC, ea Ieasterine growth rentiion fn infant of less han 33 week’ gestation: associated placental pathologie tags. Am J Obstet Gynecol 173):1049, 1995, Sandher Ramos 1, Beatin 5, Kaunte AMG: Expectant management versus Taher induction fer suspected etl macrosomia x syematc vow, Ob Gynecol 10013 pe 1997, 2002 Schemes G, Wapnet RJ ohuson A. cal: Fse-uimester growth pacens of ancupo fuses. Prenat Diagn 17Q)-155, 1997 Scholten RR, Sep 5, Pesce Ly ota: Prepregancylow-plases volume and repoion so preslampia snd el grow estcson, Obes Gynecl 715; 1085, 2011 Sends W: Impaired fel growth: definition and clinical diagnosis Obser ‘Gyoecl 6431303, 1988 Sheil JS, Sincher¥), Morte G, eta Cangentl phe afer maser teeement for syphilis ding pregnancy Am J Obser Gynec 1860356, 2002 ‘Sienpsoa JW, Lawless RW, Michell AC: Responsbily of dhe obsteiian the feu, Tlucnc of prepregnancy weight and pregnancy weight gala fon ith weight. Obstet Gyea 45(4)481, 1975 Smulian JC. Ananth CY, Vinelcos AM, ot as Feta deaths ia the United ‘Sater, Influence of high rik conditions and implicson for management, (Obsee Gypeca! 10061183, 2002 Sparks TN, Cheng YW, Mt auglin Bt a: Funal bight well secon tool or eal probe J Matern Fetal Neonatal Med 24().708, 2071 pong C¥: Add ili tothe it of outcomes o wary show aa pregnant ‘woman with &hicony of preter birch ot fea gowth resction bet Gynecol 119(3)495, 2012 ‘Spong CY, Meer BM, D'lion M, ea Timing of indicate late petr and ‘sep ccm bin. Obstet Gynecol 11802 Pe 1323, 2011 Stcin Z, Stuer M, Ssenger Gre al In Famine and Human Developmen: The Dutch Hunger Wine of 194471945, New York, Oxford Univesity Pass, 1975 Stonck F, HafkerE, Php K, et alt Meiveneteraydrofole redacese (C5771 polymorphism and pregnancy completions, Obet Gynec 1102 pe 0)363, 2007 ‘Setlnd NE, Caughey AB, Breed EM, ta: Risk fits and obstetric compl Caton asocated wit nazar Tne) Gynacal Obstet 873):220, 2004 Supplemenson with Mulsple MiceonetictIneretion Tel (SUMMIT) ‘ady Groupe Efics of maternal mulpe micronutiene supplementation fn fel oa and inane death in ndoneria: + double blind cheer random lad wi Lancet 371(9608) 215, 2008 “Tam Tar KB, Bi C, Penman AD, ele Fel gastscissepiemilogl- fal characte tod pregoancy ontcomer io Misistppl. Ar} Pentel 2500689, 20 Thornton JG, HornbucleJ Val Ay cal nfme well-being at 2 years oF agen he Growth Resuiction Inewendon Teal (GRIT) mulucene tandomed ‘entclled a. Lancet 364(9433)513, 2006, “Tongiong,T Sisupundit K, Lucwan S: Ousomes of pregnancies acted by Temogibin Hf dese In Gynscnl Ober 104(3:206, 209 ‘Turan OM, Turn 8, Gangot 8, ah, Pogreion of Doppler abnormalies in lorautesine growth rewiction, Utsound Obstet Gynecol 322160, 200 ‘Taal MG, Cal A, Sami D, et ai Comparative ficiency of mesures ‘of early Fal growth rion fr predicting advere perinatal ote Obsee Gynecol 117661331, 2011 “Tyson JE, Kennedy K, Broyles, et: The sll for gestational age inane tctersted or Aayed prlewoeary mantsoc?Tacresed or dectesed sot val Pesiatcs 95(0134, 1998 ‘Umber: A, Aiken EH, Rogeson 8): Malaria in pregnancy: sal babies, ig problem, Trends Paso 27(8):168, 2011 Unterchlder J, Dal 8, Gray MP, e als Optimising the defn of ina ‘sarne growth recon: the enlicenerproepectve PORTO sty. Am J Obst Gyrecal208(5}290., 2013 Usher Re McLean F: Inari gowth of ive horm Caucasian infin at ea evel andide obtained from meaurement in 7 dimensions of inane born beewecs 25 and #4 weeks’ gation, J Pdi 74(6):90, 1969 van Wyk, Boes KE, yan der Pos JA, eta Eason (eur developmeral ‘nd ebavioralourcme a 2 yeas of ae of induced bor compared wih ‘pectant management in iachuterne growthresited infants long.cerm ‘outcomes ofthe DIGITAT ural Am Obstet Gynecol 206(5)406.1, 2012 ‘Vartehpour A, RadalsT, Msi J eal Acdaton of phospholipase A2 is road wih generation of place pid sige and el obey. J Clin Endocrinol Mer 911):248, 2006 Vesco KK, Sharma AJ, Diew PM, ak Newborn size among obese women ids weight gus ouside the 2009 Inscute of Medicine recommenda, ‘Ober Gyecal 117812, 2001 ‘Vac AC. Blackall SC: Potential rks and bene of antenatal coticme- reid therapy prior fo preterm birth in pregnancies complicated by sree fel growin rescton. Obstet Gynecol Ci North Arm 38(2) 205,201 ‘Vida? AC, Yeomans ER, Ramin SM: Pegoaney in women with eal dese Part: general pins. Am J Petal 25(7):385, 2008 Vellore TG, Alger J Brower IA, ea: Matra tigicerde lve during ‘ary pregnaney are sncinted with bir welght snd poral grow] Padi 13905) 736, 20 ‘Waller DM, Maslow N, Upstone Let The Growth Resulcion Iteenton "Tei legen sutzooea in rrctoraed al aig of delivery in eal pow rnrision. Am J Ober Gynecol 204(1} S41, 2011 ‘Weismann Brenner A, Sincen M) ZberbergF ta Maer an neon. ta outcomes of maciesomic pregnancies Med Sei Monit 18(9%PH77, 2012 ‘Wea E, Tits AT: Fay cm bth conideralons in management, Obsct Gyoecol Clin North Am 39(089, 2012 ‘Wiles Haug L, Quade 8, Mosion CC: Confined placental mosicim as 2 tile for among newborns with feral goweh reiion,Prent Diagn 2615-128, 2006 ‘Willams JW: Obst: A Text Book for Student and Practones, Late Now York, Appleton, 1903, p 133 ‘Willams Rl Invaweine growth cures, nia and ternational compassons ‘with frenetic groups in Calon Prev Med 4163, 1975, Willams RL, Creasy RK, Cunningham GC, ea: Feal growth and petnata vile ia Caloris, Obses Gynecal 39:624, 1982 ‘Woo J, Lang ST, Lo RL: Sipaicnce ofan aber o severed end disalie flow ix Doppler sbi ery waveform J Ukesoand Med 6(6)291, 1987 ‘Wu YW, Coen LA, Sh Seal: Cerra ply in term infos, Plies (21590, 2006 ‘Yamamoto hi K, Shimada M, ea: Sigucance of maternal seeing for Toroplemosi, kal, cnomeglovca and hopes spl ve ifotion Incase of fea growth restriction. J Obstet Gynaecol Res 3963653, 2013 ang J Meal M, Phe LD, et sk Defining sorta and abgosmal fe \rowd: promises and challenges Am J Obsct Gyoecl 2026}522, 2010 “Zhang, Mise, Grewal). csk Prenatal pplication of he individ. in etal grow reference, Am J Epidemil 173(3)539, 2011 ‘Jl, Obe C. Hammer Bech By a fry, inferiny estment and Fel growehresiction, Obstet Gyacen!110():1326, 2007ea Naa) Multifetal Pregnancy (MECHANISMS OF MULTIFETAL GESTATIONS 892 DIAGNOSIS OF MULTIPLE FETUSES 896 MATERNAL ADAPTATION TO MULTIFETAL PREGNANCY 898 PREGNANCY COMPLICATIONS. 899 UNIQUE FETAL COMPLICATIONS 901 DISCORDANT GROWTH OF TWIN FETUSES. 909 FETAL DEMISE. s10 PRENATAL CARE AND ANTEPARTUM MANAGEMENT . . 912 PRETERM BIRTH o8 LABOR AND DELIVERY os TRIPLET OR HIGHER-ORDER GESTATION ne SELECTIVE REDUCTION OR TERMINATION os Muleifetal pregnancies may resule from two or more fertiliza- tion events, from a single fertilization followed by an “errone 04s” splitting of the zygote, or from a combination of both Sach pregnancies are associated with increased risk for both ‘mother and child, and his risk increases with che number of offspring. For example, 60 percent of twins, 90 percent of eiplets, and virtually all of quadruplets are born preterm (Martin, 2012). From these observations, i is apparent that women were not intended to concurrently bear more than one offspring. And although they are often viewed as a novelty or miracle, multifetal pregnancies represent a potentially perilous journey for the mother and her unborn childeen, Fueled largely by inferilty therapy, both the rate and the number of ewin and higher-order multifeal bigths have creased dramatically since 1980, Specifically, the «winning rate rose 76 percent from 18.9 to 32.1 per 1000 live births in 2009 (Martin, 2012). During the same time, the number of higher-order maltifeal births increased more than 400 per cent to a peak in 1998, Since chen, however, evolving infet ity management has resulted in decreased rates of higher-order ‘muliferal births to es lowest leve! in 15 years. Specifically, the rate of triplets or more decreased by 10 percent from 153 pet 100,000 births in 2009 ro 138 per 100,000 births in 2010 (Martin, 2012), ‘The overall increase in prevalence of multifeal births is of concern because the corresponding increase in the rate of pre- term birch compromises neonatal survival and increases the risk of lifelong disability. For example, inthis country, about a fourth of very-low-birthweight neonates—those born weigh- ing < 2500 g—are from multfetal gestations, and 15 percent of infants who die in the frst year after bisth are from multife- tal pregnancies (Martin, 2012). In 2009, che infant mortality rate for multiple births was five times the rate for singletons (Mathews, 2013). A comparison of singleton and win out comes from infants delivered at Parkland Hospital is shown in ‘Talble 45-1. These risks are magnified further with criplets or quadrupless. In addition co chese adverse outcomes, the risks for congenital malformations are increased with multiferal gestation. Importantiy, this increased risk is foreach ferus and is not simply because there are more feruses per pregnancy. “The mother may also experience higher obsterrcal morbid- ity and morality rates. "These also increase with the number of fetuses (Myre, 2012; Wen, 2004). In a study of more than 44,000 multifeal pregnancies, Walker and colleagues (2004) reported that, compared with singletons, che risk for preeclamp- sia, postpartum hemorshage, and maternal death were increased twofold or more. "The risk for peripartum hysterectomy is also increased, and Francois and associates (2005) reported this to 391392 Taree Obstetrical Complications TABLE 45-1. Selected Outcomes in Singleton and Twin Pregnancies Delivered at Parkland Hospital from 2002 through 2012 on ngletons (No.) _ Twins (No.) Pregnancies 78,879 850 Births® 78879 1700 stilbirths 406 (6.1) 24 (14.1) Neonatal deaths 253 32) 38 (22.4) Perinatal deaths 659 (8.4) 62 (365) Very low birthweight 895 (1.0) 196 (11.6) (< 1500 9) girth data are represented as number (oer 1000). Data courtesy of Dr. Don Mint. be threefold for ewins and 24-fold for eiples or quadruplets. Finally, these mothers are at increased risk for depression com- pared wich women with a singleron pregnaney (Choi, 2009) MECHANISMS OF MULTIFETAL GESTATIONS ‘Twin feruses usually resule fom fertilization of two separate ovadizygotic or fraternal twins, Less often, twins arise from 4a single fersilied ovum that divides-monosygotic or identical ‘wins, Eicher ot both processes may be involved in the forma- tion of higher numbers. Quadruplets for example, may arise from as few as one co as many as four ova Dizygotic versus Monozygotic Twinning Diaygotic twins are not ina stit sense true twins because chey| result from the maturation and fertilization of ewo ova dusing 4 single ovulatory cycle. Moreover, from a genetic perspective, 25 percent discardance were excluded, (Date courtesy of Dr. Don Maint.) birthweights progressively lagged (Vig. 45-8). Beginning at 35 to 36 weeks, swin biethweights clearly diverge from chose of singletons. In general, the degree of growth restriction inereases with fetal number. The caveat is that chis assessment is based on growth curves established for singletons. Several autho: ties argue that fetal growth in ewins is different from thac of singleton pregnancies, and thus abnormal growth should be diagnosed only when fetal site is less than expected for mul- tifetal gestation. Sccoxdingly, vwin and teiplet growth curves have been developed (Kim, 2010; Odibo, 2013; Vora, 2006). ‘The degree of growth restriction in monorygotic twins is likely to be greater than thac in dizygotic pais (Fig, 45-9). ‘With monochorionic embryos, allocation of blastomeres may rot be equal, vascular anastomoses within che placenta may cause unequal distribution of nutrienes and oxygen, and dis- cordant structural anomalies resulting from the ewinning event FIGURE 45-9 Marked growth discordance in monochotionic twins. (Photograph contributed by Dr. Laura Greer.) 899 EP EICL LP)900 Taree Obstetrical Complications FIGURE third ang fith neonates are from the same ovum. itself may affect growth. For example, the quintuplets shown in Figure 45-10 represent chee dizygotic and two monorygotic feruses. When delivered at 31 weeks, the three neonates from separate ova weighed 1420, 1530, and 1440 g, whereas the two derived from the same ovum weighed 990 and 860 g, In the third trimester, the larger feral mass leads to accel crated placental maturation and relative placental inswffi- ciency. In dizygotic pregnancies, marked size discordancy usually results from unequal placencation, with one placental site receiving more perfusion than the other. Size differences may also reflect different genetic fetal-growch potentials Diseordaney can also result from fetal malformations, genetic syndromes, infection, or umbilial cord abnormalities such 4s velamentous insertion, marginal insertion, oF vasa previa (Chap. 6, p. 122). Hypertension Hypertensive disorders due to pregnancy are mote likely to develop with multiple fetuses. The exact incidence atibutable to twin gestation is difficult to determine because «win preg nancies are more likely 10 deliver preterm before preeclamp- sia can develop and because women with twin pregnancies are often older and multiparous. The incidence of pregnancy. relaced hypertension in women with cwins is 20 percenc at Parkland Hospical. In their analysis of 513 twin pregnancies > 20 weeks’ gestation, Fox and coworkers 2014) also identified 20 percent of parcurienes with either gestational hypertension ‘or preeclampsia, Case-control analyses suggest chat prepreg- rnaney body mass index (BMI) > 30 ky/m* and egg dona- tion are additional independent risk factors for preeclampsia. Gonzaler and colleagues (2012) compared 257 women with twins and gestational diabetes with 277 nondiabetic women carrying twins. These researchers found a twofold increased risk of preeclampsia in women diagnosed with gestational dia- betes. Finally, in che Matched Multiple Birch Datasee for the 5-10 Davis quintuplets at 3 weeks follwing delivery. The fis, second, and fourth newooms fiom the left each arase from separate avs, whereas the National Center for Health Statistics, Luke and associates (2008) analyzed 316,696 twin, 12,193 wiplet, and 778 quadruple pregnancies. ‘These investigators found thatthe rsk for preg- naney-associated hypertension was significantly increased for triplets and quadruplets (11 and 12 percent, respectively) compared with thar for rwins (8 percent), “These data suggest thac feral number and placental mass are involved in. preeclampsia pathogenesis. Women with rwin pregnancies have levels of antiangiogenic soluble fisclike tyrosine kinase-1 (sEtel) thar are ewice that of singletons. Levels are ssemingly related to increased placental mass rather than primary placental pathology (Bdolah, 2008; Maynard, 2008). Rana and coworkers (2012) measured antiangiogenic sFlt-1 and proangiogenic pla ‘ental growth factor (PIGF) in 79 women with ‘wins referred for evaluation of preeclampsia. In the 58 women identified with either gesta- tional hypertension or preeclampsia, there was a stepwise increase in sFlt-1 concencrations, decrease in PIGF levels, and increase in sFlt-1/PIGF ratios compared with nor rmotensive twin pregnancies. With multfetal gestation, hyper tension not only develops more often but also tends to develop earlier and be more severe. In the analysis of angiogenic fac- rors mentioned above, more than one half presented before 34 ‘weeks, and in those who did, the sPlt-/PIGF ratio more striking (Rana, 2012). This relationship is discussed in Chapter 40 (p. 735) Preterm Birth “The duration of gestation decreases with increasing fetal num- ber (Fig. 45-11). According to Martin and colleagues (2012), more than five of every 10 twins and nine of 10 triplets bora in the United States in 2010 were delivered preterm. Delivery before term is a major reason for increased neonatal morbid ity and mortality rates in multifeal pregnaney. Premavuriy is increased sixfold and tenfold in wins and triples, respectively (Giuffe, 2012). In thei review, Chauhan and associates (2010) reported that, similar to singleton pregnancies, approximately 60 percentof preterm birthsin cwinsare indicated, abouta third result from spontaneous labor, and 10 percent follow prema cuely ruptured membranes, In their analysis oF most 300,000 live births in Ohio, Pakrashi and DeFranco (2013) found that the proportion of preterm birth associated with premature membrane rapture increased with gestational plurality from 13 percene with singletons to 20 percene with triplets oF more. “The preterm birth rate among multfetal gestations has increased during the past ewo decades. In an analysis of nearly 350,000 swin births, Kegan and coworkers (2000) showed that during the 16-year period ending in 1997, the tem birth rate among twins declined by 22 percent. Joseph and colleagues (2001) attributed this decline to an increased rate of indicated preterm deliveries. This wend is not necessarily negative, as it ‘was asociated with decreased perinatal morbidity and mortality100) 90 00 a) 2 0) £ 50 34 5 20 ce =i Singleton <0 Dew OM Gestational categories (weeks) FIGURE 45-11. Cumulative percent of singleton, twin, and triplet or higher-order multifetal births according to gestational age at elivery in the United States during 1990, (From Luke, 1994, with permission} rates among twins thac reached 34 weeks. Although the causes of preterm delivery in ewins and singletons may be different, no- natal outcome is generally the same at similar geseational ages (Gardner, 1995; Kilpatrick, 1996; Ray, 2009). Importantly, outcomes for preterm rwins who are markedly discordant may rot be comparable with those for singletons because whatever caused the discordance may have longelasting effecs. Prolonged Pregnancy More than 40 years ago, Bennett and Dunn (1969) suggested that a ewin pregnancy of 40 weeks or more should be consid- cred postterm. Twin stillborn neonates delivered at 40 weeks or beyond commonly had feaures similar to those of postma- ture singletons (Chap. 43, . 864). From an analysis of almost 300,000 twin births, Kahn and coworkers (2003) calculated that at and beyond 39 weeks, the rik of subsequent stilbith was greater than the risk of neonatal morality. At Parkland Hospital, twin gestations have empiti- cally been considered to be prolonged at 40 weeks Long-Term Infant Development Hiscorically, twins have been considered cognitively delayed compared with sin- tlecons (Record, 1970: Ronalds, 2005) However, in cobore studies evaluating rormal-birchweighe term infants, cog- nitive outcomes between swins and singletons are similar (Lorenz, 2012) Christensen and associates (2006) found similar national standardized test scores jn ninth grade in 3411 eins and 7796 singletons bom between 1986 and 1988. Tn contrast, among normal-brthweight infants, the cerebral palsy risk is higher among twins and higher-order muleipes Multietal Pregnancy For example, the cerebral palsy rate has been reported to be 2.3 per 1000 in singletons, 12.6 per 1000 in cwins, and 44.8, per 1000 in triplets (Giuffte, 2012). Much ofthis exces risk is thought to be related to an increased risk of feal-growch restriction, congenital anomalies, ewin-twin transfusion syn- drome, and fetal demise of a cotwin (Loren, 2012), UNIQUE FETAL COMPLICATIONS. Several unique and fascinating complications arse in multife- tal pregnancies, These have been best described in ewins but n be found in higher-order multfetal gestions. Most fetal »mplications due to the ewinning proces itself ate seen with ‘monozygotic twins. Their pathogenesis is best understood after reviewing the possibilities shown in Figure 45-1, Monoamnionic Twins Only about 1 percent ofall monozygotic twins will share an amnionic sac (Hall, 2003). Said another way, approximately 1 in 20 monochorionie rwins are monoamnionie (Lewi, 2013). “This configuration is associated with a high fetal death rate from cord entanglement, congenital anomalies, preterm birth, or ewin-twin-transfusion syndrome, which is described sub- sequently. In a comprehensive review, Allen and associates (2001) reported that monoamnionie «wins diagnosed antena- tally and alive at 20 weeks have approximately a 10-perceat risk of subsequent fetal demise. In a Dutch report of 98 monoamni- onic twin pregnancies, the perinatal mortality rate was 17 per- nt (Hack, 2009), Umbilical cord entanglement, a frequent cause of death, is estimated to complicate at least half of cases (Fig. 45-12), Diamnionic ewins can become monoamnionic if the dividing membrane ruptures and therefore have similar associated morbidity and moreaisy rats. FIGURE 45-12 Monozygotic Lins in a single amnionic sac, The smaller fetus appar ently died fist, and the second subsequently succubed when umbilical cores entwinee. 901 EP EICL LP)902 Taree Obstetrical Complications Unfortunately, there sre no management methods that guarantee good outcomes for either ot both twins. This is because ofthe unpredictability of fetal death feom card encan glement and the lack of an effective means of monitoring for it. Quion and colleagues (2011) retrospectively evaluated the feasibility of inpatient concinuous fetal heart monitoring in 17 secs of monoamnionic ewins. Acer review of more than 10,000 hours of fetal eracing, these investigators concluded chat this was posible in only 50 percent of cases. Importantly, an abnormal fetal hear rate racing prompred delivery in only six cases. Morbid cord entanglement appeas to occur eatly, and rmonoamnionic pregnancies that have succesfully reached 30 co 32 weeks ae a reduced risk In the Dutch series described above, the incidence of intrauterine demise dropped from 15 percent after 20 weeks to 4 percent when gestational age exceeded 32 weeks (Hack, 2009) ‘Although umbilical cords frequently entangle, actors chat lead to pathologies! umbilical vestel constriction ate unknove, Color-low Doppler sonography can be used to diagnose entan slement ( ). However, once identified, evidence to guide management is observational, reteospectve, and subject, {obiased reporting. One proposed management scheme is based on a study by Heyborne and coworkers (2005), who reported no stlbires in 43 «win pregnancies of women admitted at 26 «co 27 weeks’ gestation for daily fea surveillance. Convers, there were 13 sulbrchs in 44 women who were managed as ourpatienss and admitted only for an obstetrical indication Because ofthis report, women with monoamnionic wins are recommended to undergo I hour of daly feral hear ate moni- toring, cither as outpatients or as inpatients, beginning at 26 to 28 wocks. With initial testing, a course of betamethasone i given to promote pulmonary maturation (Chap. 42, p. 850). IF fetal ins reassuring, cesarean delivery is performed ac 34 weeks and after @ second course of betamethasone. This management scheme is used at Parkland Hospital and resulted the succesful 34-week delivery of the «wins depicted in Figure 45-13, Aberrant Twinning Mechanisms Several aberrations in the twinning process result in a spec: ‘eum of fetal malformations. These are traditionally ascribed to incomplete spliting of an embryo into ewo separate «wins. However, iti possible tac they may result from early second- ary fusion of rwo separate embryos. These separated embryos are cicher symmetrical or asymmetrical, and the spectrum of anomalies is shown in Conjoined Twins In the United States, unite © conjoined twins have been referred to as Siamete twins-afeer Chang and Eng Bunker of Siam (Thailand), who were displayed worldwide by P. T. Barnum. Joining of the «wins may begin at either pole and may produce characteristic forms depending on which body pats are joined or shared ( )., OF these, thoracopagus is the most common (Mutchinick, 2011), The frequency of conjoined twins is not well established. Ac Kandang Kerbau Hospital in Singapore, Tan and coworkers (1971) identified FIGURE 45-13 Monochorionic monoamnionic cord entanglement, ‘A. Despite marked knotting ofthe cov, vigorous twins were delivered by cesarean. B, Preoperative sonogram of this pregnancy shows entwined cords. €. This finding fs accentuated with applica lion of color Doppler. (hotogeaphs contributed by Dr. julie Lo} seven cases of conjoined twins among more than 400,000 Aeliveries-an incidence of 1 in 60,000. AAs reviewed by McHugh and associates (2006), con- joined cwins can frequently be identified using sonography at midpregnaney. This provides an opportunity for parents to decide whether to continue the pregnancy. As shown inMultitetal Pregnancy Cs FIGURE 45-14 Possible outcomes of monozygotic twinning, The asymmetrical category cantzns twinning types in which ene twin complement is substantially smaller and incompletely formed. Figure 45-16, identification of eases during the frst trimes- ter is also possible. A targeted examination, including a care- ful evaluation of the connection and the organs involved, is necessary before counseling can be provided. As shown in Figure 45-17, MR imaging can play an important adjunctive role in clarifying shared organs. Compared with sonography, MR imaging may provide superior views, especially in later pregnancy when amnionic fui is diminished and feral crowd ing is increased (Hibbeln, 2012) ‘Surgical separation of an almost completely joined win pair may be suecessfal if essential organs are nor shared (Spice, 2003; ‘Tannuri, 2013). Consultation with a pediatric surgeon often assists parental decision making. Conjoined twins may have discordant structural anomalies that further complicate decisions about whether to continue the pregnancy. Vertrat Viable conjoined twins should be delivered by cesarean. For the purpose of pregnancy termination, however, vaginal delivery is possible because the union is most often pliable (Fig, 45-18). Sill, dystocia is common, and ifthe fetuses are mature, vaginal delivery may be traumatic tothe uterus oF cervix. External Parasitic Twins “This is a grossly defective ecus or merely Fetal parts, attached externally to a relatively normal cwin, A parasitic twin usu- ally consists of externally attached supernumerary limbs, often swith some viscera. Classically, however, a functional heart of brain is absent. Attachment mirrors those sites described earlier for conjoined «wins (sce Fig. 45-14). Parasites are believed to result from demise of the defective twin, with its surviving ts- sues attached to and vascularized by ies normal ewin (Spencer, Dorsal L 1 1 Lateral RRASERAUY COmphalopagus Thoracopagus Cephalopagus Ischionagus Parapagus Parapagus dlpresopus dicephalus CCraniopagus RachipagusPygopagus FIGURE 45-15 Types of conjoined twins, (Rediawn fiom Spencer, 2000.) 903 EP EICL LP)904 Taree Obstetrical Complications FIGURE 45-16 Sonogram of a conjoined twin pregnancy at 13 weeks’ gestation, These tharacoomphalopagus twins have ‘ovo heads but a shared chest and abdon 2001). In a worldwide collaborative epidemiological study paras twins were found to account for 3.9 percent ofall conjoined twins and to occur more frequently in male fetuses (Mutchinick, 2010. Fetus-in-Fetu Early in development, one embryo may be enfolded within its ‘ovin, Normal development of this rate parasitic «win usually arests in che fist trimester. Asa result, normal spatial arrange: ‘ment of and presence of many organs is lst, Classically, verte bral or axial bones are found in these fesiform masses, whereas heart and brain are lacking. These masses are typically sup ported by cheir host by a few large parascie vessels (Spencer, 2000). Malignant degeneration is rare (Kaufman, 2007), FIGURE 45-17 Magnetic resonance imaging of conjoined twins This T2-weighted HASTE sagital image demonstrates fusion fram the level ofthe xiphoid process to just below the level ofthe umbi cus, that, omphalopagus twins. Below the fused vr (0, there is a midine cystic mass (arrow) within the tissue comecting the ‘wins. An omphalomesenteric cyst was favored given the location within the shared tissue. (mage connibuted by Or. Api Balle. FIGURE 45-18 Conjoined twins aborted at 17 weeks’ gestation (Photograph contributed by Dr. jonathan wills} Monochorionic Twins and Vascular Anastomoses [Another group of fascinating fetal syndromes can arise when monozygotic twinning results in two amnionic sacs and a common surrounding chorion. ‘This leads to anatomical sharing of the two fetal circulations through anastomoses of placental arteries and veins, All monochorionic placentas likely shaze some anastomotic connections. Howeve ace marked variations in the number, size, and direction of these seemingly haphazard connections (Fig. 45-19), In their analyses of more than 200 monochorionic placentas, Zhao and colleagues (2013) found the median number of anasto co be 8 with an incerquartile range of 4 to 14, With rare exceptions, anastomoses between (wins are unique to mono chorionic twin placentas, Arrery-to-arcery anastomoses are mast common and are identified on the chorionic surface of the placenta in up to 75 percent of monochorionic win placentas, Vein-to-vein and arcery-to-vein communications are each found in approximately half. One vessel may have several connections, sometimes to both arceries and veins. In contrast to these superficial vascu- 1¢ chorion, deep arte cations can extend through the capillary bed of a given villus (ig, 45-20). These deep arteriovenous anastomoses create & common villous compartment or thied circulation that has been identified in approximately half of monochorionie ‘win placentas, ‘Whether these anastomoses are dangerous co either «win depends on the degree to which they are hemodynamically balanced. In chose with significant pressure or fiow gradients, a shune will develop berween fetuses. This chronic fetofetal transfusion may result in several clinical syndromes that include ‘vin-swin transfusion syndrome (TTTS), twin anemia polyeythe- ‘mia sequence (TAPS), and acardiac twinning. there lar connections on the surfice of Twin-Twin Transfusion Syndrome (TTTS) The prevalence of this condition is approximately 1 to 3 per 10,000 births (Simpson, 2013). In this syndrome, blood is,Multietal Pregnancy 905 Shared placenta fram pregnancy compli ted by twin-twin transtusion syndrome. the fallowing color cade w. for injection, Left twin. yellow = artery, blue = vein; ight twins red = artery, green = vein, A. Pat of the arterial network ofthe right ‘win filled with yellow dye, due tothe presence of a small artery-to-artery anastomosis (aro¥). B. Close-up ofthe lower portion of ne placenta diplays the yelow dye-filed anastomosis. (From De Paeze, 2005, with permission } transfused from a donor ewin to its recipient sibling such tha The donor ewin is pale, and is recipient sibling is pletho- the donor may eventually become anemic and its growth may ric (Fig. 45-21). Similarly, one portion of the placenta ofien be restricted. In contrast the recipient becomes polycythemic appears pale compared with che remainder. and may develop circulatory overload manifest as hydrops. The recipient neonate may have circulatory overload from heart failure and severe hypervolemia and_hyperviscosty. (Occlusive thrombosis is another concern, Finally, polycythemia in the recipient twin may lead to severe hyperbilirubineria and kernicterus (Chap. 33, p. 644) Anastomases between twins may be artery-to- vein (AV), artery-to-artery (AA), or vein-to-vein (VW). Schematic Fepresentation of an AV anastomosis in twin-win transfusion syn rome that forms 3 “common villous dstct” or “thir circulation ‘deep within the vious tissue, Blood fram a donor twin may be Twin ransterted to 2 recipient twin through this shared circulation. This, Pale donor twin (690 g) also had oligohydrarnnins. 8. The ranste leads toa growth-restricted discordant donor twin with pletharic recipient twin (730 g) had hycramios. From Mahone, markedly reduced ammonic fluid, causing i to be “stuck 1993, with peimission. in translusion syndrome at 23 weeis,906 Taree Obstetrical Complications Pathophysiology. Any ofthe differnt types of vascular anas- tomoses discussed before may be found with monochorionic pla- centas. Classically, chronic TT'TS resls from unidirectional ow through arteriovenous anastomoses. Deoxygenated blood from a donor placensal artery is purmped into a coryidon shared by the recipient (ce Fig. 45-20). Once oxygen exchange is completed in the chorionic villus, the oxygenated blood leaves the cotyledon via a placenzal vein of the respint win. Unless compensated — typically through arterioarterial anastomoses—this unidsectional od volumes (Lewi, 2013). ¢ ovin-twin transfusion syndrome fre flow leads co an imbalance in Clinically import quently is chronic and results from significane vascular volume differences becween the cwins. Even so, the pathogenesis is ‘more complex than a net transfer of red blood cells from one ‘win to another, Indeed, in most monochorionic win preg: nancies complicated by the syndrome, chere is no difference in hemoglobin concentrations berween the donor and recipient wwin (Lewi, 2013) The syndrome typically presents in midpregnancy when the donor ferus becomes oliguric from decreased renal perfusion (Simpson, 2013). This ferus develops oligohydramnios, and the recipient fetus develops severe hydramnios, presumably. due to increased urine production. Vircual absence of amnionic uid in the donor sac prevents ftal motion, giving rise to the descriptive term stuck twin or polyhydramnias-oligohydramnios— gndrome—‘poly-oi.” ated with growth restriction, contractures, and pulmonary hypoplasia in the donor twin, and premature rupture of the membranes and heart failure in the recipient his amnionie uid imbalance is associ- Fetal Brain Damage. Cerebral palsy, microcephaly, porenceph- aly, and multicystic encephalomalacia are serious complication Coronal Intethemispheric Cavity Fissure Ventricle Age (days) 2 FIGURE 45-22 Cranial magnetic resonance imaging study of 2 clamnioni-ronachorionic twin performed on day 2 of He, large cavitary lesions inthe white matter adjacent to the ventricles, noid space and lateral ventricles are marked The bright signals (arowheads) inthe pevip permission) nlarged, The ¥ of the cavitary lesions most probably correspond to gloss. (Fi associated with placental vascular anastomoses in multifetal gesta- tion. The exact pathogenesis of neurological damage is not fully understood but leading to cavitary brain lesions (Fig. 45-22). Tn the donor ‘win, ischemia results from hypotension, anemia, or both. In the recipient, ischemia develops from blood pressure insta bility and episodes of severe hypotension (Lopriore, 2011). Cerebral lesions may also be due to postnatal injury asso axed with precerm delivery. Quarello and associates (2007) reviewed data from 315 liveborn fecuses from pregnancies ‘with cwin-twin-transfusion syndrome and reported cerebral abnormalities in 8 percent. fone twin of an affected pregnancy dies, cerebral pathol- ogy in the survivor probably results from acute hypoten- sion, A less likely cause is emboli of thromboplastic ma originating from che dead fetus. Fusi and coworkers (1990, 1991) observed that with the death of one twin, acute twit ‘win anastomotic transfusion feom the high-pressure vess of the living twin to ‘win leads rapidly to hypovolemia and ischemic antenatal brain damage in the survivor, In their systematic review of 343 cwin pregnancies complicated by single fetal demise, Hillman and colleagues (2011) caleulated a 26-percent risk of neurodevelopmencal morbidity in monochorionic wins compared with 2 percent in dichorionic twins. They also found that this morbidity was related to gestational age ax the death of the corwin. If the death occurred becween 28 and 33 weeks’ gestation, monochorionic twins had an almost cightfold risk of neurodevelopmental morbidity compared with dichorionic twins of the same gestational age. With fetal death after 34 weeks, the likelihood dramati- cally deereased—odds ratio 1.48. is likely caused by ischemic necrosis ial ¢ low-resistance vessels of the dead Parasagittal Subarachnoid Space Cavity Vanticle Cerebellum 2 he sul n Bejar, 1990, wih“The acuity of hypotension following the death of one twin with cwin-ewin-transfusion syndrome makes successful inter- vention for the survivor nearly impossible. Even with delivery immediately after a cowwin demise is recognized, the hypo- tension that occurs at the moment of death has likely already caused irreversible brain damage (Langer, 1997; Wada, 1998) Diagnosis. ‘There have been dramatic changes in the criteria used to diagnose and classify varying severities of ewin-twin transfusion syndrome. Previously, weight discordancy and hemoglobin differences in monochorionic twins were caleu- laced. However, i¢ was soon appreciated that in many cases these were late-onset findings. According to the Society for Maternal-Fetal Medicine (2013), TTS is diagnosed based on ‘wo criteria: (I) presence of a monochorionie diamnionie preg- saney, and (2) hydramnios defined ifthe largest vertical pocket i> 8 em in one twin and oligohydramnios defined ifthe larg est vertical pocket is < 2 em in the other twin. Only 15 percent of pregnancies complicated by esse degrees of fluid imbalance progress to TTTS (Huber, 2006) Once identified, TITS is typically staged by the Quintero (1999) staging system: + Stage I-liscordane amnionic uid volumes as described above, but urine is sll visible sonographically wichin the bladder of the donor ewin, + Stage Il—eritria of stage I. but urine isnot visible within the donor bladder. + Stage [ll—criteria of stage Il and abnormal Doppler studies of the umbilical artery, ductus venosus, or umbilical vin, + Stage IV—ascites or frank hydrops in either win, + Stage V—demise of ither fetus. In addition to these criteria, there is evidence that cardiac function of the recipient ewin coztelates with fetal outcome (Crombleholme, 2007). Although fetal echocardiographie find ings are not part of the staging system above, many centers rou cinely perform fetal echocardiography for TTTS. It has been theorized chat early diagnosis of cardiomyopathy inthe # ent ovin may identify pregnancies that would benefit from early intervention, One system for evaluating cardiac func- tion—the myocardial performance index (MP1) ot Tei index— is a Doppler index of ventricular function calculated for each vventicle (Michelfelder, 2007). Although scoring systems that include assessment of cardiac function have been developed, their usefulness in prediction of ourcomes remains controver- sial (Simpson, 2013). ‘At Parkland Memorial Hospital, evaluation before and during treatment includes anatomical and neurological fea assessment using echocardiography, MPI caleulaion, Doppler velocimetry, and MR imaging: genetic counseling and amaio- centesis; and placental mapping. ipt- Management and Prognosis. ‘Ihe prognosis for muliftal gsstations complicated by TTS is related to Quintero stage and gestational age at presotation. More than chree fourths of stage I cases remain stable or regress without incervention, Conversely, outcomes in those identified at stage III or higher are much worse, and che perinatal lss rate is 70 to 100 percent Multietal Pregnancy without intervention (Simpson, 2013). Several therapies are currently used for TTTS, including amnioreduction, laser abla- tion of vascular anastomoses, selective Feticide, and septostomy {intentional cretion of a communication inthe dividing ami conic membrane). Comparative data from randomized tials for some of these techniques ae discussed below. “The Euroferus trial included 142 women with severe ‘TTTS diagnosed before 26 weeks. Participants were randomly assigned to laser ablation of vascular anastomoses or to serial amnioreduction (Senat, 2004). These investigators reported an increased survival ate t0 age 6 months for at lease one ewin swith laser ablation compared with serial amnioreduction-76 ‘versus 51 percent, respectively. Moreover, analyses of random ized studies confirm beter neonatal outcomes with laser ther- apy compared with selective amnioreduetion (Roberts, 2008; Rossi, 2008, 2009). In contrast, Crombleholme and associates (2007), in a randomized trial of 42 women, found equivalent rates of 30-day survival of one or both twins treated with either amnioreduction or selective fetoscopic laser ablation-75 versus 65 percent, respectively. Furthermore, evaluation of ewins from the Eurofecus trial through 6 yeas of age did not demonstrate any addicional survival benefit beyond 6 months or improved neurological outcomes in those treated with laser (Salomon, 2010). [Ac tis time, laser ablation of anastomoses is prefered for severe TTTS (stages I-IV), although optimal therapy for stage I diseases controversial. After laser therapy, close ongoing,sur- veillance is necessary. Robyr and colleagues (2006) reported that a fourth of 101 pregnancies teated with laser required additional invasive therapy because of either recurrent TTS, or middle cerebral arery Doppler evidence of anemia or poly- cythemia, Recently, in a comparison of selective laser abla- tion of individual anastomoses versus ablation of the entire surface of chorionic plate along the vascular equator, Baschat and coworkers (2013) found that equatorial photocoagulation reduced the likelihood of recurrence. Meise and associates (2005) compared amnioreduction septostomy in a multicentered randomized tral of 73 wom Repeated procedures were performed for symptoms or ifthe ‘greatest vertical pocket of amnionic fluid met the original inclusion crieria of 8 to 12 em, depending on gestational age. Perinatal outcomes were the same in each group, with atleast one survivor in 80 percent of pregnancies, The average number of additional procedures was rwo in each group. Much of this is moor, however, because intentional septostomy has largely been abandoned as treatment (Simpson, 2013). Selective reduction has generally been considered if severe ampionic fluid and growth disturbances develop before 20 ‘weeks. In such cases, both feruses typically will die without intervention. Selection of which ewin is to be terminated is based on evidence of damage to ether fetus and comparison of their prognoses. Any substance injected into one «win may affect the other twin because of shared circulations. Therefore, feticidal techniques include methods to ocelude the circula- tion of the chosen fetal umbilical vein or by umbilical cord occlusion using radiofrequency ablation, fetescopic ligation, or coagulation with laser, monopolar, or bipolar cauterzation (Challis, 1999; Chang, 2009; Donner, 1997). Even after these ed 907 EP EICL LP)908 Taree Obstetrical Complications procedures, however, the risks to the remaining Fetus are still appreciable (Rossi, 2009). Twin Anemia Polycythemia Sequence (TAPS) This form of chronic fecofetal transfusion is characterized by significant hemoglobin differences between donor and recipi ‘ent wins withous the discrepancies in anionic fluid volumes typical of twin-twin-transfusion syndrome (Slaghekke, 2010). Ic is diagnosed antenataly by middle cerebral artery (MCA) peak systolic velocity (PSV) > 1.5 multiples of the median (MoM) in the donor and < 1.0 MoM in the recipient «win (Simpson, 2013).'The spontancous form reporcedly complicates 3 to 5 percent of monochorionic pregnancies, and ie occurs in up t0 13 percent of pregnancies after laser phosocoagulation ‘Spontancous TAPS usually occurs aftr 26 weeks and iatrogenic ‘TADS develops within 5 weeks of a procedure (Lewi, 2013) [Although a saging system has been proposed by Slaghekke and colleagues (2010), futher studies are necesary to better under- stand the natural history of TAPS and its management. Twin-Reversed Arterial Perfusion (TRAP) Sequence Also known as an acandiae twin, this is a rare—1 in 35,000 births—buc serious complication of monochorionic mauliferal gestation, In the TRAP sequence, there is usually a normally formed donor ewin chat has features of heart failure and a rec ient twin thac lacks a heart (acardius) and other structures. It has been hypothesized that the TRAP sequence is caused by a large artery-to-artery placental shunt, often also accomp: bya veincto-vein shunt (Vig. 45-23). Within he single, shared placenta, arterial perfusion pressure ofthe donor swin exceeds that in che recipient ewin, who thus receives reverse blood Bow ‘of deoxygenated arterial blood from its corwin (Lewi, 2013) “This “used” arterial blood reaches the recipient ewin through its umbilical arteries and preferentially goes to its iliac vessels “Thus, only the lower body is perfused, and diseupted growth and development of the upper body results. Failure of head ‘growth js called acardius acephatus; a partially developed head with identifiable limbs is called acardius myelacephalus and failure of any recognizable structure to form is aaurdius amorphous, which is shown in Figure 45-24 (Faye-Petersen, 2006). Because of this vascular connection, the normal donor ‘win must not only suppor its own circulation but also pump its blood through the underdeveloped acardac recipient. This may lead co cardiomegaly and high-ourpue hear failure in the normal rwin (Fox, 2007) Lewi and coworkers (2010) reviewed 26 cases of TRAP. sequence identified in the firs trimester. In one third, the pump twin died before planned intervention at 16 co 18 weeks. In more than half of all he cases, there was spontaneous exssation of ow to the acardiae ewin, and such flow arrest was associated with subsequent death or neurological injury in 85 percent of the nor- smal owins. Quintero and asociates (1994, 2006) have reviewed methods of fn utero teatment of acardiac twinning in which the goal is imetruption of aberrant vascular communication between the cwins. Of these methods, Le (2007), Lewi (2010), Livingston (2007), and cei colleagues found an approximate 9-percentsur- vival rate following second-trimestr radiofrequency ablation. This method cauterizes umbilical vessels in the malformed recipient FIGURE 45-23 win 1eversed-arterial perfusion sequence. In| the TRAP sequence, there is usually a notmally formed donor twin that has features of heart failure, and a recipient twin that lacks 2 heart. It has been hypothesize that the TRAP sequence is caused by a large artery-to-artery placental shunt, often also accompanied by 2 vein-to-vein shunt, Within the single, shared placenta, perfusion pressure of the danor twin overpowers that In the recipient twin, who thus receives reverse blood flow from its twin sibling, the “used” arterial blood (colored bie) that reaches the recipient twin preferentially goes to its ilac vessels and thus perfuses oly the lower body. This disupts grawth and evelopment of the upper body FIGURE 45-24 Photograph of an acardiac twin weighing 475 giams. the undeideveloped ead is indicated by the bleck arrow, and its details are shown in the inst, A yellaw clamp is seen an its umbilical card. Its viable donar catwin was delivered vaginaly at 36 weeks and weighed 2325 grams. (Photograph contributed by Dr. Michael 0. Hat.)‘vin to terminate blood flow from the donor. In @ review of 118 complicated monochorionic ewin gestations that underwent bipolar coed coagulation, Lanna and associates (2012) reported a fetal loss rate in those weated before 19 weeks of 45 percent com pared with 3 percent in those treated after 19 weeks. Prompted by the high morality rate of TRAP sequence in the first _mester, small ease series of early intervention have been reported (Donoghue, 2008; Scheiet, 2012). Importantly, eficacy and safery of incervention before fasion of che amnion and chorion has nor been demonstrated convincingly (Lewi, 2013). Complete Hydatidiform Mole with Coexisting Normal Fetus ‘Alo termed a twin molar pregnancy, this is due toa complete diploid molar pregnancy comprising one conceptus, whereas the coxwin isa normal fers. Reported prevalence rates range from 1 in 22,000 to 1 in 100,000 pregnancies (Dolapcioglu, 2009). Ie ‘must be differentiated fiom a pasal molar pregnancy in which an anomalous «ingleron fetus—uswally crplokd—is accompa died by molar tissue (Chap. 20, p. 398) (primal management is not known for this twin gestation, Diaggosis is usually made inthe first half of pregnancy, and ter- amination at tat time would remove the mole but also the nor- smal fetus, However, pregnancy progression exposes the woman co the later postpartum dangers of persistent trophoblastic dis- «ase that requires chemotherapy and may be fatal. Despite cis, pregnancy continuation is increasingly being recommended in cases with a karyorypically normal and nonanomalous ewin, no carly preeclampsia, and declining hCG levels (Sebire, 2002). If observation and pregnancy progression is chosen, preter delivery is frequently required because of persistent and. heavy bleeding or severe preeclampsia, Dolapcioglu and coworkers (2009) reviewed 159 reported cases and reporced a live birth in 35 percent. Preeclampsia and preterm birth each developed in a third. Niemann and colleagues (2007) reported thas persistent tro- hoblastic disease rates following such a ewin gestation were not increased compared with those ara singleton complete mole. DISCORDANT GROWTH OF TWIN FETUSES Size inequality of rwin fetuses, which can bea sign of pathologi cal growth restriction in one fetus, is calculated using the lager twin as the index. Generally, asthe weighe difference within a ‘win pair inereases, the perinatal moreality rate increases pro- Portionately. Because the single placenta is not always equally shared in monochorionie ewins, these twins have greater rates of discordant growth outside of TITS Ie develops in approximately 15 percent of ewin gestations (Lewi, 2013; Miller, 2012). As discussed furcher in Chapter 44 (p-879), restricted growth of one swin fetus usually develops late in the second and ealy third wrimester. Ealier dscordancy indi- cates higher risk for fetal demise in the smaller win. Specially, when discordant groweh i identified before 20 weeks, fetal death jccus in about 20 percent (Lewi, 2013). Importantly, differences in crown-rump length (CRL) are associated with fetal structural and chromosomal anomalies but are not reliable predictors for birthweight discordance (Miller, 2012). than dichorionic wins Multietal Pregnancy Etiopathogenesis “The cause of bisthweighe inequality in ewin fetuses is often unclear, but the etiology in monochorionic ewins likely difers from that in dichorionie ewins. Discordancy in monochorionic ‘wins s usually auibuced to placental vascular anastomoses that cause hemodynamic imbalance becween the owins. Reduced pressure and perfusion of the donor ewin can eause diminished placental and fetal growth. Even so, unequal placental shar ing is probably the most importanc determinant of discordant growth in monochorionic cwins (Lewi, 2013). Occasionally, rmonochorionic twins are discordant in size because they are discordant for structural anomalis Discordancy in dichorionic ewins may resule from vari- ous factors. Dizygotic feruses may have different genetic growth porential, especially if they are of opposite genders Alternatively, because the placentas are separate and require ‘more implantation space, one placenta might have a subopti- ‘mal implantation site. Bagehi and associates (2006) observed that the incidence of severe discordaney is twice as great in triplets as itis in wins. This Gnding lends credence co the view that in utero crowding isa factor in fetal-growth restric- tion, Placental pathology may play a role as well. Kent and coworkers (2012) evaluated placental abnormalities in 668 ‘win gestations. They observed a strong relationship beoween histological placental abnormalities and birthweight discor- daney with associated growth restriction in dichorionic, but nat monochorionic, rwin pregnancies. Diagnosis Size discondancy between swins can be determined sono- traphically in several ways. One common method uses sono- ‘graphic fetal biometry to compute an estimated weight for cach twin (Chap. 10, p. 198). The weight of the smaller win is then compared with that of the lager twin. Thus, percent discordancy = weight of larger ewin minus weight of smaller ‘win, divided by weight of larger ewin, Alternatively, cons ering that growth restriction is the primary concern and that abdominal citcumference (AC) reflects fetal nutrition, some use the sonographic AC value of each ewin, With these meth- ods, some specify discordance if the AC measurements differ more than 20 mm or if che estimated fetal weight difference is 20 percent or more. “That said, several diferent weight disparities between twins have been used to define discordancy. Accumulated data sug pest chat weight discordaney greater than 25 to 30 percent most accurately predicts an adverse perinaaal outcome. Hollier and coworkers (1999) retrospectively evaluated 1370 «win pairs delivered at Parkland Hospital and stratified twin weight dis- cordancy in S-pereent inerements within a range of 15 t0 40 percent, They found that the incidence of respiratory distress, intraventricular hemorthage, seizures, periventricular leukoma- aca, sepsis, and necrotizing enterocolitis increased directly with the degree of weight discordancy. These condivions increased substantially if discordancy was greater than 25 percent. The relative risk of fetal death increased significantly to 5.6 if there was more than 30-percent discordancy. It increased co 18.9 if there was greater than 40-percent discordancy.. 909 EP EICL LP)910 Taree Obstetrical Complications Management Sonographic monitoring of growch within a win pair and caleu- lating discordancy has become a mainstay in management. Other sonographic findings, suchas oigohydramnios, may be helpful ‘gauging feal risk, Monochorionic ewins ae generally monitored ‘more frequently. This is because thei isk of death is higher—3.6 percent versus 1.1 percent—and the risk of neurological damage inthe surviving twin i substantial compared with thas risks in dichorionic twins (Hillman, 2011; Lee, 2008). Thorson and cok leagues (2011) retrospectively analyzed 108 monochorionic twin pregnancies and found that a sonographic surveillance interval of greater chan 2 weeks was associated with detection of higher- stage swin-rwin transfusion syndrome. These findings have led some to recommend serial somographic surveillance every weeks in monochorionic swins (Simpson, 2013; Sociery for Maternal- Fetal Medicine, 2013). However, there have been no random- ized tials of the optimal frequency of sonographic surveillance in monochorionic twin pregnancies. At Parkland Hospital, rmonochorionic twins undergo sonographie evaluation to assess interval growth every 4 weeks. Dichorionic ewins are evaluated ‘every 6 weeks, Depending on the degre of discordaney and the ‘gestational ag, fetal surveillance may be indicated, especialy if ‘one or both fetuses exhibit restricted growth. Nonstess testing, biophysical profile scores, and umbilical artery Doppler assess- ‘ment have all een recommended in the management of owins, but none have been evaluated in appropriately sized prospective trials (Miler, 2012). ‘The American College of Obstetricians and Gynecologists (2010) recommends that antepartum testing be performed in rmultifetal gestions for the same indications as in singleton feruses (Chap 17, p. 345). Ar Parkland Hospital, all women swith rwin cordance of 25 percent or greater undergo daily ‘monitoring as an inpatient. There are limited data to establish the optimal timing of delivery of twins. Delivery is usually not prompted by size diseordancy alone, except occasionally at advanced gestational ages. The Royal College of Obstetricians and Gynecologists (2008) advocates delivery by 37 weeks! gestation in monochorionic twins and by 38 weeks in dicho- FETAL DEMISE ‘At-any time during multfetal pregnancy, one or more fetuses may die, either simultaneously or sequentially, The causes and incidence of fetal death are related to zygosity, chorionicity, and growth concordance Death of One Fetus In some pregnancies, one fecus dies remote from term, but pregnancy continucs with one or more live feruses. When this ‘occurs early in prognancy, it may manifest asa vanishing tin discussed on page 892. Fetal death in a slightly more advanced {station may go undetected until delivery of @ normal-appear- ing live infant along with a dead fers that is barely identifiable. le may be compresed appreciably-ferur compress, or ie may be flatened remarkably through desiccation —feus papyraceut ig, 45.29), FIGURE 45-25 This fetus papyraceus i a lan ovoid mass com pressed agains the etal membranes. Analamical pars can be identified as marked. Demise af this twin had beer roted dung Sonographic examination pesfrmed at 17 weeks’ gestation. Is viable cotwin deliver at 40 weeks. (Photog-aph contributed by Ot Michael. Zaretsky.) In a review of 9822 Japanese twin pregnancies, Morikawa and associates (2012) reported that 2.5 percent of mono- chorionic diamnionic ewins greater than 22 weeks’ gestation had a death of one or both twins compared with 1.2 percent of dichorionic «wins. As shown in Figure 45-26, the isk of ssilbiech is related to gestational age in all ewins, but is much higher for monochorionie twin pregnancies before 32 weeks, In this same review, women with monochorionic diamnionic ‘wins who last one cwin were 16 times more likely to expe rience death of the corwin chan women with dichorionic 30 ‘* Monachorionic diamnionic 6 * Dichorionie diarmnionic (per 1000 women) Prospective risk of 2 04 28 28 30 32 34 36 38 Gestational week FIGURE 45-26 Prospective risk of stibith among women who reached a given gestational week (pet 1000 women). (am ‘Markawa, 2012, with permission)twins who lost one twin (Morikawa, 2012). Similarly, in their analysis of 1094 twin pregnancies, Mahony and asso- ciates (2011) identified a threefold increased risk of death of one or both fetuses in monochorionic ewins compared with dichorionic pairs. Last in their systematic review and ‘metaanalyses, Hillman and colleagues (2011) concluded that after one twin dies, the odds of corwin demise was five times higher in monochorionic twins compared with dichorionic coins experiencing the same fate. Analyses of 701 criplets identified mortality rates to be 2.1 percent, 3.2 percent, and 5.3 pereent in trichorionie tiamnionic, dichorionic triam- aionic, and monochorionic triamnionic triplets, respectively (Kawaguchi, 2013) Other factors that affect the prognosis for the surviving cowin include gestaional age at the time of the demise and duration beeween the demise and delivery of the surviving covin, With demise of the vanishing rvin discussed earl afer the fist trimester, the risk of death is not increased for the survivor. However, when one fetus dies in the second tsi- ester or later, the effect of gestational age at the time of death and the mortality risk to the cotwin is less cleat. In the analysis by Hillman and colleagues (2011), cotwin demise rates wore unaffected regardless of whether the fist death occurred at 13 to 27 weeks or at 28 to 34 weeks. In cases with the death of one twin after the first trimester, however, the odds of spontaneous and iatrogenic preterm delivery of the remaining living twin were increased (Hillman, 2011). Preterm birth was five times more likely in monochorionic ‘win gestations complicated by demise of one twin between 28 and 33 weeks' gestation, Ifthe fetus died after 34 weeks, preterm delivery rates were similar. “The neurological prognosis for a surviving corwin depends almost exclusively on chorionicity. In thei comprehensive review, Ong and coworkers (2006) found an 18-percent rate of neurological abnormalicy in ewins with monochorionie pla- centation compared with only 1 percent in those with dicho- nic placentation, In another review, in twin pregnancies complicated by a single fetal demise before 34 weeks, a fivefold increased risk of neurodevelopmental morbidity was identified in monochorionic ewins compared with dichorionic «wins. If the one feus died after 34 weeks, the likelihood of neurological deficits was essentially the same between monachorionic and dichorionic twin pregnancies (Hillman, 201) Later in gestation, the death of one of multiple fetuses could theoretically trigger coagulation defects in the mother. Only a few cases of maternal coagulopathy after a single feral death in a ewin pregnancy have been reporced. ‘This is prob- ably because the surviving twin is usually delivered within a few weeks of the demise (Eddib, 2006). That said, we have observed transient, spontaneously corrected consumptive coagulopathy in multfetal gestations in which one fetus died and was retained in utero along with its surviving twin, ‘The plasma fibrinogen concentration initially decreased but then increased spontaneously, and the level of serum fibrinogen fibrin degradation products increased initially buc then returned to normal levels, At delivery, the portions of the placenta that supplied the living fetus appeared normal. In contrast the part that had once provided for the dead fecus Multietal Pregnancy was the site of massive Gbria deposition, ‘This is further dis- cussed and illuscrated in Chaprer 41 (p. 811). Management Decisions should be based on gestational age, the cause of death, and the rsk to the surviving fetus. As mentioned prev ously, if the loss occurs early in the first crimester, a vanishing twin is considered harmless co the survivor. If the loss occurs after the first trimester, the risk of death or damage co the survivor is largely limited to monochorionie twin gestations Morbidity in the monochorionic twin survivor is almost always due to vascular anastomoses, which often cause the demise of one twin followed by sudden hypotension in the other. IFone fetus of a monochorionic twin gestation dies after the fist ti- smester but before viability, pregnancy termination ean be eon- sidered (Blickstein, 2013). Occasionally, death of one but not all fexuses results from a maternal complication such as diabetic ketoacidosis or severe preeclampsia with abruption. Pregnancy management is based on the diagnosis and the stats of both the mother and surviving fetus. Ifthe death of one dichorionic ‘win is due to a discordant congenital anomaly, its death should not affect is surviving twin Single fetal death during late second and carly thied trimes- ter presents the greatest rsk to che surviving twin. Alchough the risks of subsequene death or neurological damage to the Surv ‘vor are comparatively increased for monochorionic twins at this gestational age, the risk of preterm birth is equally increased in mono- and dichorionie ewins (Ong, 2006). Delivery gener- ally occurs within 3 weeks of diagnosis of feel demise, thus antenatal corticosteroids for survivor lung macurity should be considered (Blckstein, 2013). Regardless, unless chere isa hos- tile intrauterine environment, the goal should be to prolong pregnancy. ‘Timing of eletive delivery aftr conservative management of a late second or early third urimester single etal death is a matter of debate. Dichorionie ewins can probably be safely delivered at term. Monochorionic ewin gestations are more dilficule co manage and are often delivered beoween 34 and 37 weeks’ gestation (Blickstein, 2013), In cases of single fetal death at term, especially when the etiology is unclear, most opt for delivery instead of expectant management, Impending Death of One Fetus Abnormal aneeparcum rest results of feral health in one ewin ferus, but not the other, pose a particular dilemma. Delivery ray be the best option for the compromised fetus yet may resale in death from immaturiey of the corwin. IF fel lung maturity is confirmed, salvage of both the healthy fetus and its jeopardized sibling is possible. Unfortunately, ideal man- agement if ewins are immature is problematic but should be based on the chances of intact survival for both fetuses. Often the compromised fetus is severely growth restricted or anoma- lous. Thus, performing amniocentesis for fetal karyotyping in women of advanced maternal age carrying twin pregnancies is advantageous, even for those who would continue their preg- nancies rogardiess of the diagnosis, Aneuploidy identification in one fers allows rational decisions regarding interventions. on EP EICL LP)12 Taree Obstetrical Complications PRENATAL CARE AND ANTEPARTUM MANAGEMENT. Primary goals of prenatal management of mulifetal pregnancy are to provide close observation of the mother and her fetuses to prevent or interdict complications as they develop. A major imperative i o prevent precerm delivery of markedly immature neonates, At Parkland Hospital, women with mulifetal gesta- tions are seen every 2 weeks beginning at 22 weeks’ gestion, and a digital cervical examination is performed ae each visi. Identification of other unique complications discussed above may also lead co interventions including easly delivery. We routinely perform sonographic studies to assess fetal growth and amnionic fluid every 4 weeks in monochorionic ewins or 6 weeks in dichorionie pairs Diet ‘Along with more frequent prenatal visits, it must be ensured that the maternal diet provides additional requirements for calories, protein, minerals, vitamins, and essential fatty aids. Achievement of BMI-specfic weight gain goals, supplementa- tion with macto- and micronutrients co meet the increased needs associated with a twin gestation, and carbohydrate controlled diets have been recommended (Goodnight, 2008), ‘The Instituce of Medicine guidelines for twin pregnancy rec- ‘ommend a 37- to 54¢-Ib weight gain for women wi mal BMI. In their extensive review of the topic, Goodnight and Newman (2009) recommend supplementation of micro- nutrients such as calcium, magnesium, zine, and vitamins C, 1D, and E based on upper intake levels from the Food and Nutrition Board of the Insticute of Medicine. ‘The daily ree- ‘ommended increased calorie intake for women with twins is 40 to 45 keal/kg/d, composed of 20 percent protein, 40 per- cent carbohydrate, and 40 percent fat divided into three meals and three snacks daly Surveillance of Fetal Growth and Health Because a cornerstone of fetal assessment in twin pregnancy is identification of abnormal fetal growth or discordancy, serial sonographic examinations are usually performed throughout the third trimester. Assessment of amnionic fluid volume is also important. Associated oligohydramnios may indicate uteropla ‘ental pathology and should prompt further evaluation of fetal well-being, That said, quantifying amnionic fluid volume in rmuliferal gestation is sometimes difficult. Some measure the deepest vertical pocket in each sac or assess the fluid subjec- tively. Measurement of the amnionic fluid index (AFI) may also be helpful. Using data from 488 diamnionic ewins with birthweighe berween the 10ch and 90ch percentiles, Hill and associates (2000) described a protocol for measuring the AFT in twin gestations. Each amnionie sac was divided into quadrants that extended along a vertical, horizontal, or oblique axis. The deepest vertical pocket free of umbilical cord in each quadrant was measured. They found a slightly lower median value in twins than singletons, The AFI was highest at 26 to 28 weeks’ gestation and declined until delivery. Magan and coworkers (2000) compared subjective assessment and several objective methods of assessing amnionie uid in 23 sets of ewins. They found all methods to be equally poor in predicting abnormal volumes in diamnonic twins. At Parkland Hospital, the single depest vertical pocket is measured in ach sa. A measurement < 2 cm is considered oligohydramnios and a measurement > 8 em is considered hydramnios (Hernandez, 2012). Tests of Fetal Well-Being [As described throughout Chapter 17, there are several meth- ods of assessing fetal health in singleton pregnancies. ‘The ronstress test or biophysical profile is commonly used in management of twin or higher-order mulifetal gestations Because of the complex complications associated with mul- tifeal gestations and the potential technical difficulties in dif- ferentiating fetuses during antepartum testing, the usefulness ‘of these methods appears limited. According to DeVoe (2008), the few exclusive studies of nonstress testing in twins suggest that the method performs the same as in singleton pregnan- es. Elliot and Finberg (1995) used the biophysical profile as the primary method for monitoring higher-order maleifetal sgestations. They reported that four of 24 monitored pregnan- ‘es had a poor outcome despite reassuring biophysical profile scores. Although biophysical csting is commonly performed in multifeal gestations, there are insufficient data to determine its efficacy (DeVoe, 2008). In an early study of 272 ewin sets, Giles and colleagues (1990) reported that availabilty of umbilical artery Doppler velocimetry led to a reduced perinatal morality rate Ina later randomized tial of 526 twin pregnancies by the same group, the addision of umbilical arery Doppler velocimetry to man- agement compared with fetal testing based on fetal-growth parameters alone resulted in no perinatal outcome improve- rent (Giles, 2003). Hack and associates (2008) investigated the utility of umbilical artery Doppler velocimeuy in 67 uncomplicated monochorionic win gestations. ‘They found similar morcality rates in those with abnormal pulsaiiy indi- ‘es of the umbilical artery compared with those with normal ies. Differences in neonatal morbidity were explained by gestational age at delivery. All esting schemes have high false-positive rates in single- tons, and daca sugges cha cesting in multifeal gestatons per forms no bexcer, In cases of abnormal cesting in one «win and ‘normal results in another, iatrogenic preterm delivery remains & major concer. Pulmonary Maturation ‘According to Robinson and coworkers (2012), beyond a strat- ‘egy of planned delivery of uncomplicated monochorionie twins at 38 weeks, a secondary strategy is amniocentesis to verily pulmonary maturity before delivery between 36 and 38 weeks. In cases of complicated twin gestations, amniocentesis may be performed eatlier. As measured by determination of the lecithin-sphingomyelin ratio, pulmonary maturation is usu ally synchronous in twins (Leveno, 1984). Moreover, although this ratio usually does not exceed 2.0 uncil 36 weeks in single- ton pregnancies, ic often exceeds this value by approximately 32. weeks in multiferal pregnancies, McElrath and colleagues (2000) reported similar increased values of surfactant in twinsafer 31 weeks gestation, In & comparison of respiratory mor- bidigy in 100 ewins and 241 singleton newborns delivered by cesarean before labor, Ghi and associates (2013) found less neonatal respiratory morbidity in twins, especially those del ered $ 37 weeks’ gestation. In some cases, howevet, pulmonary function may be markedly different, and the smallest, most setessed twin fetus is typically more mature, PRETERM BIRTH Preterm labor is common in mulifetal pregnancies and may complicate up to 50 percent of twin, 75 percent of tiplt, and 90 percent of quadruplet pregnancies (Eliot, 2007). The proportion of preterm births in multifetal gestatons, however, varies widely. For example, the preweem birth rate is 42 per- cent in Ireland but is 68 percent in Austria (Giulfre, 2012). “These differences likely reflect different clinical approaches to ‘management, Several techniques have been applied in attempts to prolong these pregnancies. Methods include bed rest—espe cially through hospitalization, prophylactic administration of B-mimetic drugs or progestins, prophylactic cervical cerclage, and pesary placement. Prediction of Preterm Birth [A major goal of multfecal pregnancy prenatal care is accurate prediction of women likely to experience preterm delivery, ‘with prediction followed by prevention. ‘This has heen an elu- sive goal, but some advances have been made. Goldenberg and coworkers (1996) prospectively screened 147 ewin preg nancies for more than 50 potential preterm birth risk fac- tors, These investigators found that cervical lenge and fetal fibronectin concentration in the cervical canal wete predictive of preterm birth (Chap. 42, p. 843). At 24 weeks, a cervi- cal length $ 25 mm was che best predictor of bisth before 32 weeks. At 28 weeks, an elevated fetal fibronectin level was the best predictor. Similarly, To and associates (2006) sono- sraphically measured cervical length in 1163 «win pregnancies at 22 c0 24 weeks. Rates of preterm delivery before 32 weeks ‘were 66 percent in those with cervical lengths of 10mm: 24 percent for lengths of 20 mm; 12 percent for 25 mm: and only { percent for 40 mm, McMahon and colleagues (2002) found that women wich muleiferal gestations at 24 weeks who had a closed internal 0s on digital cervical examination, 4 normal cervical length by sonographic examination, and a negative fetal bronectin test resule had a low risk to deliver before 32 weeks. Interestingly, a closed internal os by digital examination was as predictive of carly delivery as the com- bination of normal sonogeaphically measured cervical length and negative fetal fibronectin test results. In a systematic review and metaanalyss of transvaginal cervical length for the prediction of preterm birth, Conde- ‘Agudelo and coworkers (2010) concluded that cervical length between 20 and 24 weeks was a good predictor of spontaneous preterm birth in asympcomacic women with «win pregnancies, ‘These authors found chat a cervical length $ 20 mm was most accurate for predicting birth < 34 weeks, with a specificity of 97 percent and positive likelihood ratio of 9.0. Multietal Pregnancy Prevention of Preterm Birth Several schemes have been evaluated to prevent preterm labor and delivery. [a recent years, some have been shown to decrease the risk of preterm delivery in small subgroups of singleton pregnancies. Unfortunately, most have been disappointingly neffective. Bed Rest Most evidence suggests that routine hospitalization is not ben- efical in prolonging multifeal pregnancy. In a metaanalysis of seven trials of hospitalization with bed rest, Crovicher and Han (2010) concluded chat the practice did not reduce the risk of preterm birth or perinatal mortality. Also at Parkland Hospital, elective hospitalization was compared with outpa- tient management, and no advantages were found (Andrews, 1991). Importantly, however, almost half of the women requited admission for specific indications such as hyperten- sion or threatened preterm delivery. Limited physical activity, early work leave, more frequent health cae visits and sonographic examinations, and structured maternal education regarding preterm delivery risks have been advocated to reduce preterm birth rates in women with moul- tiple frases. Unforcunately, there is litle evidence that these ‘measures substantially change outcome, Prophylactic Tocolysis ‘Tocolytic therapy in multifetal pregnancies has not been exten- sively studied. In a Cochrane review of five randomized trials of prophylactic oral B-mimetie therapy that included 374 win pregnancies, Yamasmit and coworkers (2012) concluded that treatment did not reduce the rate of twins delivering before 37 or before 34 weeks. Especially in light of the recent Food and Drug Administration warning against the use of oral cerbu- taline, prophylactic use of B-mimecies in multifetal gestations seems especially unwarranted, Intramuscular Progesterone Therapy Although somewhat effective in reducing recurrent preterm birth in women with a singleton pregnancy, weekly injections of Wachydroxyprogesterone caproate (17-OHPO) are not effective for mulifetal gestations (Caritis, 2009; Rouse, 2007). “These results were corroborated in a more recent randomized trial in 240 ewin pregnancies (Combs, 2011). Moreover, women carrying twins and identified with a cervical length < 36 mm (25th percentile) did not benefit despite thee increased risk for preterm bizth (Durnwald, 2010). Senat and colleagues (2013) randomly assigned 165 asymptomatic women with twins and a cervical length < 25 mm to 17-OHPC and also found no reduction in delivery before 37 weeks. Caritis and associates (2012), in an evaluation of plasma drug concencrations in_a Maternal-Fetal Medicine Unics (MFMU) Neowork trial, reporced that higher concentrations of 17-OHPC were associated with earlier gestational age a deliv ery. They concluded that 17-OHPC may adversely lower the pestational age at delivery in women with win gestaions. When taken sogether, administration of intramuscular 17-OHPC to ‘women with twin pregnancies, even to those with a shortened cervix, does not lower the preterm birth risk. 13 EP EICL LP)4 Taree Obstetrical Complications Vaginal Progesterone Therapy Micronized progesterone administered vaginally to women ‘with ewins is of uncertain benefit. Cetingoz and coworkers (2011) gave 100 mg of micronized progesterone intravagi- rally daily from 24 to 34 weeks. These authors reported that this practice reduced rates of delivery before 37 weeks from 79 co 51 percent in 67 women with twins. In contrast, sev- ‘eral studies have filed to demonstrace any preterm bieth rate reduction in women receiving various formulations of vagi- nal progesterone, Norman and colleagues (2009) randomly assigned 494 women with ewins to 10 weeks of daily 90-mg intravaginal progesterone and filed to show reduced rates of delivery before 34 weeks. In the multicenter Prevention of Preterm Delivery in Twin Gestations (PREDICT) trial, Rode and associates (2011) randomly assigned 677 women ‘with rwins to receive prophylactic, 200-mg progesterone pes- saries or placebo pessaries. ‘These investigators also filed to demonstrate a reduction in delivery rates before 34 weeks In a subgroup analysis of this tral that included only women with a short cervix oF a history of prior preterm birth, Klein and associates (2011) also did not demonstrate a benefit. At Parkland Hospital, management of women with multife- tal gestations does not typically include progesterone in any formulation. Cervical Cerclage Prophylactic cerclage has not been shown to improve perinatal ‘outcome in women with multifetal pregnancies. Studies have included women who were not specially selected and those who ‘were selected because of a shortened cervix that was identified sonographically (Dor, 1982; Elimian, 1999; Newman, 2002; Rebarber, 2005). In the latter group, cerclage may actually ‘worsen outcomes (Berghella, 2005). Pessary ‘Avaginal pesary that enciteles and theoretically compresses the cervix, alters the inclination of the cervical canal, and relieves direct pressure on the internal cervical os has been proposed as an alternative to cerelage. The most popular is the silicone ‘Arabin pessry. In a study of pessary use in women with a short cervix between 18 and 22 weeks, a subgroup analysis of 23 ‘women with twins showed a significant reduetion in the dliv- ‘ery tate before 32 weeks compared with the rate in 23 con- trol pregnancies (Arabin, 2003). Liem and coworkers (2013) recently reported on the open-label Pessaries in. Multiple Pregnancy as a Prevention of Preterm Birth (ProTWIN) tt ‘completed at 40 centers throughout the Netherlands. These researchers randomized 813 unselected women with wins to receive either the Arabin pessary berween 12 and 20 weeks or no treatment. ‘The pessary failed ro reduce preterm birth ‘overall bur did decrease delivery rates before 32 weeks in a subsce of women with a cervical length < 38 mm—29 versus 14 percent. At this time, before such trearmene can be recom= mended, beneficial effects of pessary use in women with a short cervix need to be confirmed Treatment of Preterm Labor Although many advocate their use, therapy with tocolytie agents to forestall preterm labor in muleifetal pregnancy has rot resulted in measurably improved neonatal outcomes (Chauhan, 2010; Gyewai, 1999). They are similarly ineffec- tive in singleton pregnancy as discussed in further detail in Chapter 42 (p. 851). Another caveat is that tocolytic therapy in ‘women with a maltiferal pregnancy entails higher rsk chan in singleton pregnancy. This is in part because of the augmented pregnancy-induced hypervolemia and its increased. cardiac demands and susceptibility to iatrogenic pulmonary edema Gabriel and colleagues (1994) compared outcomes of 26 «win and six triplet pregnancies with those of 51 singlerons—all treated wich a Bomimetic drug for preterm labor. Women with 4 multifetal gestation had signifcandy more cardiovascular complications —43 versus 4 pereent—including three wich pul- monary edema. Ina recent retrospective analysis, Derbent and ‘coworkers (2011) evaluated nifedipine tocolysis in 58 singleton and 32 «win pregnancies. These authors reported higher inei- cdences of side effects such as maternal tachycardia in women with ewins—19 versus 9 percent, Glucocorticoids for Lung Maturation Administration of corticosteroids to stimulate fetal lung maturation has not been well studied in mulifetal gestation However, these drugs logically should be as beneficial for mul: tiples as they are for singletons (Roberts, 2006). Bartita and colleagues (2008) compared the efficacy of betamethasone ther apy in GO preterm twin pregnancies to 60 preterm singleson pregnancies. These researchers found no differences in neonatal morbidity, including respiratory dlseress. Morcover, Gyamfi and associates (2010) evaluated betamethasone concentrations in maternal and umbilical cord blood in 30 singleton and 15, twin pregnancies receiving weekly antenatal corticosteroids “They found no differences in levels beeween twins and single- tons. These treatments are discussed in Chapter 42 (p. 850). At this time, guidelines for the use of these agents are not difer- cent from those for singleton gestations (American College of Obstecricians and Gynecologists, 2010). Preterm Premature Membrane Rupture “The frequency of preterm premature rupture of membranes (PPROM) increases with increasing plurality. In a population- based retrospective cohort study of more than 290,000 live births in Ohio, Pakrashi and coworkers (2013) reported the proportion of precerm birth complicated by premature rupture ‘was 13.2 percent in singletons. This rate was compared with 17, 20, 20, and 100 percent in twins, ciplets, quadruplets, and higher-order multiples, respectively. Multifeal gestations with PPROM are managed expectantly much like singleton preg- nancies (Chap. 42, p. 846). Ehsanipoor and colleagues (2012) compared outcomes of 41 win and 82 singleton pregnancies, both with ruptured membranes berween 24 and 32 weeks. “They found the median latency was overall shorer for ewins— 3.6 days compared with 6.2 days for singletons. ‘This difference ‘was signifcane in pregnancies after 30 weeks—1.7 days and6.9 days. Importantly, latency beyond 7 days approximated 40 percent in both groups. Delayed Delivery of Second Twin Infrequently, after preterm birth of the presenting ferus, it may be advantageous for undelivered ferus(e) to remain in utero, Trivedi and Gillett (1998) reviewed che English ltera- ture and described 45 case reports of asynchronous birth in -multifetal gestation. Although likely biased, those pregnancies with a surviving retained twin or triplet continued for an aver- age of 49 days. No advantage was gained by management with cocolyties, prophylactic antimicrobials, or eerclage. In heir 10-year experience, Roman and associates (2010) reported a median latency of 16 days in 13 ewin and five triplet pregnan- cies with delivery of the frst fetus becween 20 and 25 weeks. Survival of the firstborn infant was 16 percent. Although 54 percent of the retained fetuses survived, only 37 percent of survivors did so without major morbidity. Livingston and coworkers (2004) described 14 pregnancies in. which an active attempt was made co delay delivery of 19 feruses after delivery of the ist neonate. Only one fetus survived without ‘major sequelae, and one mother developed sepsis syndrome swith shock. Arabin and van Eyck (2009) reported better out- comes in a few ofthe 93 ewin and 34 tiplee pregnancies thar qualifed for delayed delivery in their center during a 17-year period, If asynchronous birth is attempted, there must be careful evaluation for infection, abruption, and congenital anomalies “The mother must be thoroughly counseled, particularly regard- ing the potential for serious, life-threatening infection. ‘The range of gestational age in which the benefits ourweigh the risks for delayed delivery i likely narrow. Avoidance of delivery fom 23 wo 26 weeks would seem most beneficial. In our experience, ood candidates for delayed delivery ae rare. LABOR AND DELIVERY “There is litany of complications that may be encountered dur ing labor and delivery of multiple fetuses. In addition to precerm labor and delivery as already discussed, there are increased rates of uterine contractile dysfunction, abnormal feral presentation, umbilical cord prolapse, placenta previa, placental abruption, emergent operative delivery, and postpartum hemorthage from uterine atony. All of these must be anticipared and thus cer- tain precautions and special arrangements are prudent. These should include: 1. An appropriately trained obstetrical acendant should remain ‘with the mother throughout labor. Continuous external elec tronic monitoring is preferable, If membranes are ruptured and the cervix dilated, the presenting fetus is monitored internally. 2. An intravenous infusion system capable of delivering fuid rapidly is established. In the absence of hemorthage, lactated Ringer or an aqueous dextrose solution is infused at arate of 60 vo 125 mL/hr 3. Blood for transfusion is readily available if needed. Multietal Pregnancy 4, An obstetrician skilled in intrauterine identification of fetal parts and in intrauterine manipulation of a fetus should be present 5. A sonography machine is readily available to evaluate the presentation and position of the fetuses during labor and to image the remaining fetuses) after deivery ofthe first. 6. An anesthesia team is immediately available inthe event that emergent cesarean delivery is necessary or that intrauterine ‘manipulation is required for vaginal delivery. 7. For each fetus at least one attendant who is skilled in resus- citation and care of newborns and who has been appropri- ately informed of the case should be immediately available. 8. ‘Ihe delivery area should provide adequate space for the nursing, obstetrical, anesthesia, and pediatric team members to work effectively. Equipment must be on site to provide emergent anesthesia, operative intervention, and maternal and neonatal resuscitation, Evaluation upon Admission Fetal Presentation In addition to he standard preparations for the conduct of labor and delivery discussed in Chapter 22, there are special considerations for women with a mulifetal pregnancy. First, the positions and presentations of fetuses are best confirmed sonographically (American College of Obstetricians and Gynecologists, 2011). Although any possible combination of positions may be encountered, those most common at admis- sion for delivery are cephalic-cephalic, cephalic-breech, and cephalc-ansverse. At Parkland Hospital beoween 2008 and 2013,71 percent of ewin pregnancies had cephalic presentation ofthe first fetus a the time of admission ro labor and delivery. Importantly, with perhaps the exception of cephalic-cephalic presentations, these are all unstable before and during labor and delivery. Accordingly, compound, face, brow, and footling breech presentations are relacively common, and even moreso if fetuses are small, amnionic Aud is excessive, of maternal party is high. Cord prolapse is also frequent in chese circumstances ‘After his initial evaluation, if active labor is confirmed, then a decision is made to attempe vaginal delivery or t© pro- ceed with cesarean delivery. The latter is chosen in many cases because of feral presentations. Cephalic presencation ofthe frst fetus in a laboring woman with wins may be considered for ‘expectant management, Of the 547 women who presented like this at Parkland Hospital during 5 yeas, 32 percent delivered spontaneously. Nevertheless, the overall cesarean delivery rate ‘win pregnancies during chose years was 77 percent, Notably, percent of cesarean performed were for emergent delivery of the second «win following vaginal delivery of the frst twin. The desire to avoid this obstetrical dilemma has contributed to the increasing cesarean delivery rate in twin pregnancies across the United States (Antsaklis, 2013; Lee, 2011), Labor Induction or Stimulation According to a comparison of 891 reins with more chan 100,000 singleton pregnancies included in the Consortium of Safe Labor, Lefewich and colleagues (2013) concluded that 915 EP EICL LP)916 Taree Obstetrical Complications both nulliparas and multiparas with ewins had slower progres- sion of active labor. Women with twins required between 1 and 3 additional hours to complete first-stage labor. This was spite equivalent rates of labor induction or augmentation, Provided women with ovins meet all criteria for oxytocin administration, it may be used as described in Chapter 26 (p_ 529). Wolfe and associates (2013) evaluated the success of labor induction in 40 ses of twins compared with 80 singletons and found chat protocols for oxytocin alone or in combina tion with cervical ripening can safely be used in win gesations. ‘Taylor and coworkers (2012) reported that 100 women with ‘wins undergoing labor induction had similar labor lengths and cesarean delivery rates compared with those of 100 matched ‘women with singleton pregnancies. Sei, in an analysis of rwin bins in the United States between 1995 and 2008, Lee and colleagues (2011) reported that induction rates of ewin preg- nancies has decreased from a maximum of 13.8 percent in 1999 0 99 percent in 2008, Analgesia and Anesthesia During labor and delivery of multiple fetuses, decisions regard ing analgesia and anesthesia may be complicated by problems imposed by preterm labor, preeclampsia, desultory labor, need for intrauterine manipulation, and postpartum uterine atony and hemorrhage. Labor epidural analgesia is ideal because it provides excel {ent pain relief and can be rapidly extended cephalad if incernal podalic version or cesarean delivery is required. There are spe- «ial considerations for women with severe preeclampsia or with hhemorthage as discussed in their respective chapters. Because of these eventualicies, most recommend thar continuous epid- ral analgesia be performed by anesthesia personnel with special ‘expertise in obstetrics If general anesthesia. becomes necessary for intrauterine manipulation, then uterine relaxation can be accomplished rapidly wich one ofthe halogenated inhalation agents discussed in Chaprer 25 (p. 19}. Some clinieians use intravenous or sub- lingual nitroglycerin to achieve uerine relaxation yet avoid the aspiration and hypoxia risks associated with general anesthetics Delivery Route Regardless of fetal preseneation during labor, there muse be a readiness to deal with any change of fetal postion during deli ‘ery and expecially folowing delivery of the Grst ein. Ifthe first fetus is nonverte, cesarean delivery is ypicaly performed, ‘whereas cephalic-cephalic ewins are commonly considered for vaginal delivery (Peaceman, 2009; Ross, 2011). Importantly, ‘when comparing neonatal outcomes among all these options, second twins ac term as a group have worse composive neona- tal outcomes than those of their couwin regardless of delivery method Smith, 2007; Thomgren-Jeneck, 2001) Cephalic-Cephalic Presentation If the fitse ewin presents cephalic, delivery can usually be accomplished. spontaneously or with forceps. According to Alcon (2010), there i general consensus that a ttl of labor is reasonable in women with cephalic-cephalie ewins. Hogle and associates (2003) performed an extensive literature review and concluded that planned cesarean delivery doesnot improve neonatal outcome when both twins are cephalic. The recent randomized il by Barrett and coworkers (2013) affirms this conclusion, Muleba and colleagues (2005) identified increased rates of respiratory distress in the second twin of preterm pairs regardless of delivery mode or corticosteroid use Cephalic-Noncephalic Presentation “The optimal delivery route for cephalie-noncephalicewin pairs remains controversial (D'Alton, 2010). Patient selection is eru- cial, and options include cesarean delivery of both twins, o less ‘commonly, vaginal delivery with intrapartum external cephalic 1 second ewin. Longer interewin delivery time has been shown in some studies to be associated with poorer second ‘win outcome (Ears, 2006; Stein, 2008). ‘Thus, breech extrac- tion may be preferable to version. Least desirable, vaginal del ‘ery ofthe first bur cesarean delivery ofthe second twin may be requited due to intrapartum complications such as umbilical cord prolapse, placental abruption, contracting cervix, and fetal distress. Most, but nor al, studies show the worst composite fetal outcomes for this scenario (Alexander, 2008; Ross, 20115, ‘Wen, 2004) Several reports attest to the safety of vaginal delivery of sec- cond noncephalicrwins whose birthweight is > 1500 g. Recently, Fox and associates (2014) reported outcomes of 287 diamsnionic twin pregnancies between 2005 and 2009. Cesarean delivery was routinely performed forall women with a noncephalic present- ing twin fetus, a noncephalic second twin weighing < 1500 g, ‘ora second twin estimated o be 20 percent larger than the pre- senting twin All others without contraindications to labor were offered a vaginal delivery and were treated using a stice proto- col of second-stage labor management. This included vaginal delivery ofa second cephalic twin, breech extraction of a second rnoncephalic twin, and internal podalc version of an unengaged cephalic second twin followed by breech extraction, Of the 130 ‘who planned a vaginal delivery, only 15 percent underwent cesarean delivery. There was no difference in the rate of S-min: tute Apgar score <7 or of umbilical arterial pH < 7.20 in second twins, The daca are less informative concerning vaginal delivery of a second twin whose estimated fetal weight is < 1500 g. That sid, however, comparable or even better fetal outcomes with vaginal delivery have been reported with these smaller infants compared with those who weigh > 1500 g (Caukwell, 2002: Davidson, 1992; Rydhstrdm, 1990). Other investigators advocate cesarean delivery for both members of a cephalie-noncephalic ewin pair (Armson, 2006; Hoffmann, 2012). Yang and coworkers (2005a,b) studied 15,185 eephalic-noncephalic ewin pairs. The risk of asphyxia- related neonatal deaths and morbidity was increased in the group ‘which both ewins were delivered vaginally compared with the ‘up in which both ewins underwent cesarean delivery. version of | Randomized Trial of Planned Cesarean versus Vaginal Delivery. To add insight into che clinical complexities ds cussed above, a randomized trial was designed by the Twin Birth Study Collaborative Group from Canada. The studyTABLE 45-4, Maternal and Perinatal Outcomes cof Women with a Twin Pregnancy Randomized to Planned Cesarean versus Vaginal Delivery as) em [ie Pai med Maternal (No.) 13931393 Cesarean delivery 89.9% 39.6% Before labor 53.8% © 14.1% Serious morbidity 73% 85% 0.29 Death (No.) 1 1 Hemorrhage 6.0% 7.8% Blood Transfusion 47% 5.4% Thromboembolism 0.4% 0.19, Perinatal (No.) 27832782 Paimaty composite 22% 1.9% 0.49 outcome Perinatal mortality $ per 10006 per 1000 Serious morbidity 13% 1.34% Possible 05% 0.4% encephalopathy* Intubation 10% 0.6% “includes coma, stupor; hyperaert, drowsy or lethargic; or > 2 seizures Data from Barrett, 2013, results described by Barrett and colleagues (2013) included 2804 women carrying a presumed diamnionic twin preg- nancy with the frst fetus presenting cephalic. Women were randomly assigned between 32 and 38 weeks to planned cesarean of vaginal delivery. ‘The time from randomization to delivery—12.4 versus 13.3 days, the mean gestational age at delivery—36.7 versus 36.8 weeks, and use of regional analgesia—92 versus 87 percent was similar in both groups. Salient maternal and perinatal outcomes are shown in “Table 45-4, No significane diferences in outcomes were noted between the ewo groups of women. Although there were no increased risks to mother or fetuses with planned vagin delivery in these circumstances, we agree with Greene (2013) that chis tral will moderately affece the cesarean delivery rate of women with ewins. Breech Presentation of First Twin Problems with the firserwin presenting asa breech are similar co those encouncered with a singleton breech ferus. Thus, major problems may develop if; 1. The fetus is unusually large, and the aftercoming head is larger than the birth canal, 2, The fetal body is small, and delivery of the extremities and trunk through an inadequately effaced and dilated cervix causes the relatively larger head to become trapped above the cervix. This is more likely when there is disproportion beeween the feral buttocks or trunk and the head. This may Multietal Pregnancy be seen with preterm or growth: restricted fetuses or with a macrocephalic fetus due to hydrocephaly. 3. The umbilical cord prolapses. If these problems are anticipated or identified, cesarean delivery is often prefered with a viablesize fetus. But even without these problems, many obstetricians perform cesar can delivery if the firs ewin presents as breech. This is despite data that support the safety of vaginal delivery. Specifically, Blickstein and associates (2000) reported experiences from 13 European ceneers with 613 «win pairs and the fist ovin presenting breech. Vaginal delivery was attempted in 373 of these cases and was successful in 64 percent, Cesarean delivery of the second twin was done in 24 percent, There was no dif- ference in the rate of S-minute Apgar score <7 or of morality in breech-presentng first ewins who weighed at least 1500 g, Denals of techniques for delivery of a breech presentation are described in Chapter 28 (p. 563). Locked Twins. For ewin fecuses co become locked cogether dating delivery che frst muse present as breech and the second as cephalic. As the breech of the fist ewin descends chrough the birth canal, the chin locks between the neck and chin of the second cephalic-presenting corwin. ‘This phenomenon is rar, and Cohen and coworkers (1965) desribed it only once in 817 twin gestations. Cesarean delivery should be considered when the potential for locking is identified Vaginal Delivery of the Second Twin Following delivery of the frst ewin, the presenting pare of the second twin, is size, and its relationship to the birth canal should be quickly and carefully ascertained by combined abdominal, vaginal, and at times, intrauterine examination, Sonography may be a valuable aid. If the fetal head or the breech is fixed in the birth canal, moderate fundal pressure is applied and membranes are ruptured. Immediately afterward, digital examination of the cervix is repeated to exclude cord prolapse. Labor is allowed co resume. IF contractions do not begin within approximately 10 minutes, dilute oxytocin may be used to stimulate contractions In the past, the safest interval between delivery of the first and second twins was frequently cited as less than 30 min- tures, Rayburn and colleagues (1984), and others, have shown that if continuous fetal monitoring is used, a good ouscome is achieved even if his interval is longer. Several investigators have demonstrated a direct correlation beeween worsening umbilical cord blood gas values and increasing time between delivery of first and second ewins (Leung, 2002; Stein, 2008). Gourheux and associates (2007) retrospectively reviewed delivery intervals in 239 win gestations in France and determined that mean umbilical arterial pH was significantly lower after the interval ‘exceeded 15 minutes. Thus, vigilant monitoring for nonteas- suring fetal heart race or bleeding is required. Hemosthage may indicate clinically significane placental abruption. If the occiput or breech presents immediately over the pelvic inlet, bt is nor fixed in the birch canal, the presenting parc can often be guided inco the pelvis by one hand in the vagina, while a second hand on the uterine fundus exerts moderate pressure 917 EP EICL LP)18 Taree Obstetrical Complications ‘caudally. Alternatively, with abdominal manipulation, an assis tant can guide the presenting part into the pelvis. Sonography n aid guidance and allow heart rate monitoring, Intrapartum ‘exernal version of a noncephalic second twin has also been described, ‘A presenting shoulder may be gently converted into a cephalic presentation. If the occiput or breech is not over the pelvic inlet and cannot be so positioned by gentle pressure or if appreciable uterine bleeding develops, delivery of the second twin can be problematic. To obrain a favorable ourcome, itis essential ro have an ‘obstetrician skiled in intrauterine fetal manipulation and anes- thesia personnel skilled in providing anesthesia to effectively relax the uterus for vaginal delivery of a noncephalic second twin (American College of Obstetricians and Gynccologiss, 2010). To take maximum advantage of the dilated cervix before the uterus contracts and the cervix retracts, delay must be avoided. Prompt cesarean delivery ofthe second fetus is pre- ferred ifno one present is skilled in che performance of internal ppodalic version or if anesthesia that will provide effective uter- ine relaxation is not immediately available. Internal Podalic Version With this mancuver, a fetus is turned to a breech presen- tation using the hand placed into che urerus (Fig, 45-27). “The obstetrician grasps the fetal fet to then effect delivery by breech extraction, As mentioned earlier, Fox and col- leagues (2010) deseribed a seriee protocol for management of the delivery of the second twin, which included ineernal podalic version. They reported that none of the 110 women ‘who delivered the Gist twin vaginally underwent a cesarean delivery forthe second twin. Chauhan and coworkers (1995) compared outcomes of 23 second twins delivered by podalie version and breech extraction with those of 21 who under- ‘went external cephalic version. Breech extraction was con- sidered superior to external version because less fetal distress developed. The technique of breech extraction is described Chapter 28 (p. 567). FIGURE 45-27 Internal podalc version. Upward pressure on the head by an abdominal hand is applied as downward traction exerted on the feel, Vaginal Birth after Cesarean Delivery ‘Any attempt to deliver twins vaginally in a woman who has previously undergone one or more cesarean deliveries should be carefully considered. As discussed in Chapter 31 (p. 614), some studies support the safety of attempting a vaginal bieth alier cesarean delivery (VBAC) for selected women with ewi (Cahill, 2005; Ford, 2006; Varner, 2005). According to the American College of Obstetricians and Gynecologists (20136), there currently is no evidence of an increased risk of uterine rupture, and women with twins and one previous cesarean delivery with a low cransverse incision may be considered can- didaes for cal of labor. Ac Parkland Hospital, such women are generally offered repeat cesarean delivery. Cesarean Delivery for Multifetal Gestation There are several unusual intraoperative problems that can arise during cesarean delivery of twins or higher-order multiples. Supine hypotension is common, and thus these ‘women should be positioned in a left lateral tit co deflect uterine weight off the aorta (Chap. 4, p. 60). A low- transverse hysterocomy is preferable if the incision can be made large enough t0 allow atraumatic delivery of both fetuses. Piper forceps can be used if the second «win is presenting breech (Fig. 28-13, p. 568). In some eases, a vertical hysteror- ‘omy beginning as low as possible inthe lower ucerne segment may be advantageous. For example, if fers is transverse with its back down and the arms are inadvertently delivered fist, ivis much easice and safer to extend a vertical uterine incision upward than to extend a transverse incision laterally oF to make a “I” incision vertically. Cesarean Delivery of the Second Twin Te is not uncommon for cesarean delivery to become neces sary for delivery ofa second ewin after the frst has been deliv ered vaginally. As described earlier, this occurred in 32 of 770 women with twins at Parkland Hospital beeween 2008 and 2013. In these cases, prompe cesarean delivery is required and is fequenely emergenty indicated. Indications most often cited area second fetus chat is much larger than the first and is presenting brecch oF transverse. In other cass, che cer promptly contracts and thickens after delivery ofthe fst ein. “This may be followed by a nonreassuring fetal satus or bya cer- vix cht fl to completly dilate again despite adequate urine TRIPLET OR HIGHER-ORDER GESTATION Fetal hearc rate monitoring during labor with triplet pregnan- cies is challenging. A scalp electrode can be attached 10 the presenting fetus, but itis dificult co ensure chat the other two fetuses are each being monitored separately. With vag- inal delivery, the frse neonate is usually bora with licde or no manipulation, Subsequent fetuses, however, are delivered according to the presenting pare. This often requires comp! cated obstetrical mancuvers such as total breech extraction with or without internal podalic version or even cesarean livery. Associated with malposition of fetuses isan increasedincidence of cord prolapse, Moreover, reduced placental perfu- sion and hemorthage from separating placentas are more likely during delivery ‘or all these reasons, many clinicians believe that pregnan cies complicated by three or more fetuses are best delivered by cesarean. Vaginal delivery is reserved for those circum. stances in which survival is noc expected because fevuses are ‘markedly immacure or maternal complications make cesarean delivery hazardous to the mother. Others believe chat vaginal delivery is safe under certain circumstances. For example, Alamia and colleagues (1998) evaluated a protocol for vaginal delivery of triplet pregnancies in which the presenting feeus ‘was cephalic. A total of 23 sets of triplets were analyzed, and a third ofthese were delivered vaginally. Neonatal outcomes were the same in the vaginal and cesarean delivery groups, with no morbidity and 100-percent fetal survival. Grobman and asso- ciates (1998) and Alran and coworkers 2004) reported vaginal delivery completion rates of 88 and 84 percent, respectively, jn women carrying triplets who underwent 2 tial of labor. Neonatal outcomes did not differ from those of a matched proup of riplec pregnancies delivered by elective cesarean, Conversely, Vineeleos and colleagues (2005) reviewed more than 7000 triplex pregnancies and found that vaginal deliv cry was associated with an increased perinatal mortality rate. Importantly, the overall cesarean delivery race among triplets ‘was 95 percent. At Parkland Hospital, triplet gestatons are routinely delivered by cesarean, SELECTIVE REDUCTION OR TERMINATION In some cases of higher-order multifetal gestation, reduction of the fetal number to two or thee improves survival of the remaining fetuses, Selective reduction implies ealy pregnancy intervention, whereas selective termination is performed later. Selective Reduction Reduction ofa selected fetus or fetuses in a multichorionic mul tifeal gestation may be chosen as a therapeutic intervention to enhance survival of the remaining fetuses (American College of Obstecrcians and Gynecologists, 2013). There are no random- ined controled srials onthe effects of such reduction. However, :metaanalysis of nonrandomized prospective studies indicates chat pregnancy reduction to ewins compared with expectant manage- ‘ments associated with lower rates of maternal complications, pre- term birth, and neonatal death (Dodd, 2004, 2012). Pregnancy reduction ean be performed transcervially, eransvainally, or ceansabdominally, but the wansabdominal route is usually easiest, ‘Transabdominal feal reductions are typically performed beeween 10 and 13 weeks. This gestational age is chosen because most spontaneous abortions have already occurred, the remaining fetuses are large enough to be evaluated sonograpl cally, the amount of devitalized fetal issue remaining after the procedure is small, and the risk of aborting the entire preg- rnaney as a result of the procedute is low. ‘The smallest fetuses and any anomalous fetuses are chosen for reduction, Porasium chloride is then injected under sonographic guidance into the heart or thorax of each selected fetus. Care is used to not enter Multietal Pregnancy or traverse the sacs of fetuses selected for retention. In most cases, pregnancies ate reduced to twins to increase the chances of delivering at least one viable fetus vans and associates (2005) reported continued improve iment in fetal outcomes with this procedure. They analyzed ‘more than 1000 pregnancies managed in 11 centers from 1995 to 1998. The pregnancy loss rate varied from a low of 4.5 percent for triplets who were reduced co twins. The loss rate increased with each addition to the starting number of fetuses and peaked at 15 pereent for six or more fetuses (Evans, 2001). Operator skill and experience are believed responsible for the low and declining rates of pregnancy loss. Selective Termination ‘With the identification of multiple fetuses discordant for struc- cual or genetic abnormalities, chree options are available: abor- tion of al fetuses, selective termination of the abnormal fetus, or pregnancy continuation, Because anomalies are typically not discovered until the second trimester, selective termination is performed later in gestation than selective reduction and entails ‘greater risk, This procedure is therefore usually noc performed unless che anomaly is severe but not lethal. Thus, a riplec pregnancy in which one fetus has Down syndrome might be a candidate for selective termination, whereas a twin pregnancy in which one fetus has trisomy 18 might not. In some cases, termination is considered because che abnormal ferus may jeop- ardize the normal one. For example, pathological hydeamnios in a ewin with esophageal atresia could lead to preterm birth of is sibling. Prerequisites to selective termination include a precise diag- nosis for the anomalous fetus and absolute certain of fetal location. ‘Thus, if genetic amniocentesis is performed on a mul- tifeal gestation, a map of the uterus with locations ofall he fetuses cleaty labeled should be made atthe time of the diag- nostic procedure. Unless a special procedure such as umbili- cal cord interruption is used, selective termination should be performed only in multichorionic multifetal gestations to avoid damaging the surviving fecuses (Lewi, 2006). Roman and coworkers (2010) compared 40 cases of bipolar umbilical cord coagulation with 20 cases of radioftequency ablation for teat- ment of complicated monochorionic: multifeal gestations at ridpregnancy. They found similar survival rates of 87 and 88 percent, and a median gestational age > 36 weeks ar delivery in both. Prefumo and colleagues (2013) reported cher preliminary experience with microwave ablation of the umbilical cord for selective termination in two monochorionie rwin pregnancies, One pregnancy aborted within 7 days, and the other resulted in a term singleton delivered at 39 weeks’ gestation. vans and coworkers (1999) have provided the most compre- hensive results co date on second:-trimester selective termination for fetal abnormalities. A total of 402 cases were analyzed from eight centers worldwide. Included were 345 cwin, 39 rplet, and 18 quadruple pregnancies. Selective termination using potas- sium chloride resulted in delivery ofa viable neonate or neonates in more chan 90 percent of cases, with a mean age of 35.7 weeks a delivery. The entire pregnancy was losin 7.1 percent of preg nancies reduced to singletons and in 13 percent of those reduced 919 EP EICL LP)920 Taree Obstetrical Complications to twins. The gestational age at the time ofthe procedure did not appear co affect che pregnancy los rate, Several losses occurred because the pregnancy was actully monochorionie, and potas- sium chloride also killed the normal fetus through placental vas cular anastomoses. Ethics “The ethical issues associated with these techniques are almost less. There is a beneficence-based justification for offer- ng selective termination in cases in which continuation of the pregnancy poses a chreat to the life of coexistent fetuses. The final decision co continue the pregnancy without intervention, {co terminate the entre pregnancy, or to eect selective termina tion is solely the patients (Chervenak, 2013). ‘he interested reader is referred to the excellent reviews by Evans and cowork- ‘ers (1996, 2004) and Simpson and Carson (1996). Informed Consent Before selective termination or reduction, a discussion should include the morbidity and mortality rates expected if the pregnancy is continued; the morbidity and mortality rates ‘expected with surviving twins or criplets; and the risks of che procedure itself. Wich couples seeking infertility treatment, the issue of selec- tive reduction should ideally be discussed before conception, Grobman and associates (2001) reported that these couples ‘were generally unaware of the risks associated with mulsifetal gestation, and they were less desizous of having a multifetal _gestation once apprised of the risks Specific risks that are common to selective termination o reduction include: 1. Abortion of the remaining fetuses 2. Abortion of the wrong (normal) ferus(es) Retention of genetic or structurally abnormal fetuses after a reduction in number Damage without death to a fetus Preterm labor Discordant or growth-restricted fetuses ". Maternal infection, hemorthage, or possible disseminated intravascular coagulopathy because of retained products of| ‘conception. “the procedure should be performed by an operator skilled and experienced in sonographically guided procedures Psychological Reaction Women and their spouses who elect to undergo sclective termination or reduction find this decision highly sressfl Schciner-Engel and colleagues (1995) retospectively stud- ied the emotional reactions of 100 women following selective reduction. Although 70 percent of the women mourned for their dead fetus(s), most grieved only for I month. Persistent pressive symptoms were mild, although moderately severe sadness and guilt continued for many of them. Fortunately, most were reconciled to the termination of some Fewses to preserve the lives of 2 remaining few. Indeed, 93 percent of the women would have made the same decision again, REFERENCES ‘All EL, Keuger ML: Maternal and paternal age and twinning inthe United Str, 2004 2008 J Perinat Med 10237, 2012 ‘Alumis VJ, Royo AB, Jace RK ca: Prbminay expetince with 3 pro: ‘specie promcl for panned vagina delivery of wple gestions, Am Obs Gynecol 1791133, 1998 ‘Alezandr JM, Leveno KJ, Rouse D, etalk Coazean delivery for dhe second vin Obstet Gynecol 11204), 2008 Allen VM, Winds R, Base Je al Management of monoamioic msn Pregnancies a ce sees and tematic review ofthe Ine BJOG Yo83931, 2001 ‘Alea §, Sony O, ton Deak Maternal and neonatal outcome of 93 con teeter progences wth 7108 vagina deiney. Acta Obie Gyoccal Scand 85:56 2004 ‘American Coleg of Obseriins and Gynecologis: Mukiple geaon ormplicted twin, ple, and highorder mulatel pregrancy. Practice Bills No. 56, Octaber 2004, Refirsed 2010 ‘Amen Collge of Obseticiane and Gpocelogiec Ukramnogmphy in Pregnancy rsctice Bulletin No. 10, Febmsry 2009, Ream 201 ‘Amentan Callege of Obseticans and Gynecregits" Mlifealpegancy ‘eduction. Commit Opinion No 353, Febuary 20133 Ansan Calle of Obstet and Gyacclogi Vagal bith fr pevos entender, Practice Balen No.5, Agus 2010, Rearmed 20135 ‘American’ Society for Reproductive Medicine and Soiey for Atsived Repretctve Technology: Cre for number of mbes co tans. comune opinion. atl Stl 99(44, 2013 ‘Acanth CV. Chauhan SP: Epideminlogy of twicning in developed countries, Semin Perinatol 36156, 2012 ‘Andrews WW, Leno KJ, Sheoman ML, al: Elecvehopitalzation in che management of tin pegnanles, Obsee Gynecol 77826, 1991 ‘Anuabls A. Fotadacs M, Sides, M, eu a Tends in ewin pregnancies and ‘rode of deliery daring the at 30 year inconsitensy bowers guidlines ad lini prac J Perinat Med 41(0:399, 2013, ‘Arabin 8, Halbems Jy Vork F tal I estment wih vaginal peste an ‘pon in paens witha sonogephicly detected short ceri J Pelt Med 31:12, 2003 ‘Abin B, van Eye J: Delayed interel delivery in ewin and ple pogna ties: 17 peas of experience in I petal tect, Am | Onset Gyoecl 20002)154e1, 2008 ‘Ammon BA, O'Connell C, Pes V, ea: Determines of pital morta ieyand scious neonatal xb i the second twin, Obstet Gyacea! 108 (3 Fe3s6, 2006 ‘AszonK, Perron C, Carrel D: Monomgeric winning acoited with aed reproduce echnoogis: a eiew: Reproduction 13644):377, 2008, Bagel 8, Sabu HM: Birthweight diconlanc in muliple gestadons occu ‘ence and outcomes. Obact Gyaacel 26(4:291, 2006 Bart JPR, Hanah ME, Hoon FX, cal A randomised el of planed car ‘an or vaginal dlvery For twin pregnancy. N Bg) Med 3691295, 2013, Baschac A, Barber), Pderen Neal Outcome air feocnpe seesve se thlaion of pcenal anastomoses vs equatorial laser diotonzaon for the eaten of twia-trtn naaionsyndome. Arn J Obit Gyrecel 09:1, 2013 Batsea Ly Winovitch KC, Rumney PJs eta: A ese-contol comprivon of the efectveness of beumethasone ro prevent neonatal morbidity fd morality in preterm ewin and singleton pregnancies Am J Pein 2507449, 2008 Beolah¥, Lap C. Rapkumar A, et ak Twin pregnancy and che tof pre ‘clamps biger placenta o elves? Am J Ober Gees 198 ‘el, 2008 Beomuteboee SN, Homburg R, Gore: NA ca The palo of dediing, Tcl bu increasing ewaing sxe wth advancog tata ap. Hum Repend 21-1531, 2005, Bajar R, Vigaco G, Gramajo H, eta: Antenatal origin of nerlogcl “hamage in nestor infants 2. Mulipe gesasons Am J Obstet Gynecl 1: 1230, 1990 Bekins Fistowsks M, Herman Sackan I, Romaniulc Doron A at Daghontc probleme in ate of tin pregnancies US ve MA dy, Perna Mes 41(5}535, 2013 Benichie K Kim CK: Multiple pregnancy. N Eng) Med 288:1276, 1973 Bennet D, Dunn LC: Geneial snd embryloycl compton of vert tale row wil snnse populations. Gentes 61:41, 199Baral V, Odiko AO, To MS, et ak Cera for shore cenit om uta tography: meta ana of wing indivceal patient lee date Obes Gynecol 10601).181, 2005 Blckteis I, Godiman RD, Kupfermine Me Delivery of breech Bs wins a ‘ulucenierreuespecie study. Obstet Gynecol 95:37, 2000, Bltltcn I, PelmanS: Sige fal dent i win gettions Psat Med “065, 2013 Boyle B McConkey 8, Gane E Trends the petalencs, rik and prog ancy outcome of tuple bir with congealelsnomay a tgiuy-bsed stalin 14 Euopesn counts 1984-2007. BJOG 120-707, 2013 Brady PC. Conia KF, Miimer SA, etal: Early Shaman chorionic ponado- Tropin trends vanishing win pregancee. Feral Ser 1000116, 2013 Bulmer MG: The fot of parental age, pari and duration of masa on he ‘ving tate Hum Genet 25:45, 1959 Cll’, Sura DM, Pat Ee a Vaginal bith afer emp in rs pregnancies ek Amr] Ort: Gynec CCampbel DM Mera! aan n win pregnancy. Semin Perinatol 10 4 1986 (Cuts SN, Rouse Df, Peaceman AM, etal Prevention of pete bth i wp et using {7sipha hylsnypropeteone capri: a eadomalned contaed ‘a Ober Gynec 1132 Pe 1):285, 2009 (Cats SN, Simba FH, Zo ¥ «a Rltionship berwen 17-hydronyproge ‘wore ciproate concentrations and gestational age at delivery inten gs ton Am J Obsee Gynecol 2073961, 2012 Calo §, Marphy DJ: The cet of made of delivery and ptatonal age on neonatal usin ofthe non cephalc presenting xcond tin, mJ Ob Gynecol 18721356, 2002 CCeigor E, Can, Salah M, eal Progesterone tes on peters bi ia highria proguances: a candomiaed placchocontllel til. Arch Gyoecl Obsce 285425, 2011 Chale D, Gratacos Fy Deprest JA: Cond ocsion techniques for slctne ‘erminaion in monachvionic wins. }Pvinat Med 27327, 1999, (Chang, Park M, Kins Yak A case of sucess selective abortion using ‘alloeequeny ablation ia win pregnancy sling (om severe vin 1S ‘vin unsaonayadome, Korean Med Si 24519, 2009 (Chater ST Lio G, Peri SC, etal Ate in vio ferlzacon pegpanie wich ‘ary spontaneous redaction high ik? Am J Obser Gynecol 19536, 26 CChauhas SP, Rabers WE, McLaren RA, et a: Deliv of the noavertex ee ‘twin: breech exraction vets eral cephalic version, Ame] Obie Gynecol 1731015. 195 Chauhan SP, Sao JA, Tlayes Bet ak Twins prevalence, problems, and rtm Am J Obs Gynec! 203(4):303, 2010 (Cherenak FA McClough LB: Ethical challenges inthe management of ml ‘ple prouances: che profonal esponsbiny model af penal ties, 1 Perinat Med 4161, 2013, (Cot ¥, Bai D, Miakovie CS: Muleple bits areal att fr posta "un mata depressive symproms. Peas 123(0)1147, 2009 CChestersen K, Peanen 1 Shythe A, & als Compara of academic per- Formance of twine and singetns io adelecencefllow-up sad. BM) 333:1095, 2006 (Caen M, Koh SG, Rotel AH: Fe ineocking complicating evn get ton Am J Obsee Gynec 91-407, 1965 (Comb CA, Gare T, Mantel K, el 17 Hydrosypropescrone capone fo ‘vin pregnancy: 2 double lind, candomied cin si. Am | Obes Gynecol 304(3)21.e1, 2011 Conde-Agudel A, Rome R, Hassan SS, et ak Transaginl sonographic erie Leng forthe pecleson of spontancous preterm ish In la Prguanciar n gumath brew ted teamanlye. An} Obes Gyan 203312841, 2010 Coyselo G, Pte: The world ofrwins an update} Matern Fel Neonatal “Med 23(83)59, 2010 CCromlchelme TM, Shera D, Le H aA prospective candomized, mul enter el of aionducion vr sete Recep er photacagaaion, forthe reatment af severe tein avin ansfucionaydome, Am | Obie Gynecol 1973961, 2007 Crowther CA, Han 5: Hespalaaon and bed est for mulpe pregnany ‘Cochrane Due Sat Rev 72CD000110, 2010, D’Alton ME: Delay ofthe second evi, Obstet Gynecol 115(2)-221, 2010 Davidson, Fateing TR, Jackson JC, ea Brosh exracion of lowbih vcightscond ewint. Am J Obst Gynecol 166497, 1992 De Paspe ME, Dekoniack Pied RM: Vasu dstcbuton pacers ia ‘monechetioic ia pce. Pleats 26(6)471, 2005 DDetbent A, Sima S, Gumus I eal Nifiinefor he tatment of preterm Labor in win and singleton pregnancies. Arch Gynecol Obstet 286821, 2017 DeVoe LD" Antena fetal assessment) mula gevation—an orevew, ‘Sela Fviatl 32281, 2008 Multietal Pregnancy Diamond MP, Mitwally M, Carer Rl: Easimating rts of mall gc ion pregnanie sample see caeation fom the auexment of ape innaterinegnarons rom ovarian smaliton (AMIGOS) wal, Contemp Chin Teal 32902, 2011 Dieicy RF, Taylor SN, Lu PY, ea: Spontaneous eduction f mulple preg nancy incidence nd lfc om outcome, Arm] Obstet Gynecol 18677, 2002 Dead, Cher C: Mule pregnancy eduction of tpet and higher: eres mlpe pregnancies oevins, Perl Set 81(3)-142, 2008 Dodd JM, Crowther CA: Redaction ofthe number af fetuses fr women witha ‘ulpe pregnancy. Codan Database St Rev 10:CD003932, 2012 Delapeogla K. Gungoren A Hake S, ta Twin pregancy with 3 com- lee Bplatform mole and co-xstee lve feu owe cae separ and fevew ofthe tear. Asch Gynecol Obes 279431, 2009 Donner C, Sha 8, Thomas D, ev a Sdletve fede by embolization la ‘via-twin tapion syndrome. Arepor of two ces J Reprod Med 2 ve 997 Dor, Shale J, Mabiach , ea lee cers nse of sn pregnancies “gros ulzasoncally inthe is rimese following Induced ovulon, Gynecl Obs favese 13355, 1982 Drwald CP, MemioveV, Rowse D], eta Seon mene ceil and ‘lof preci in women wth win getatons eed wih 17 hory Progesterone epee } Mater Fea Neoaal Md 2312)1360, 210 adits A, Rodges B, Lawler J ec al: Monochoronie pseudomoncamnosc ‘win pregnancy wih fal dre of one win and devtlepmecn of atte onnumprive engulopathy. Lrwound Olste Gynccl 28:73, 2006 ts Fe Oppencimer L, Yang Q, et al Relasonship beret inteovin ‘very intel and metabolic doris inthe seca twin. Am | Penal 2308) 481, 2006 Ehsanpoor R Arora N, Laggew DC, et a Tia venus slagcon pregnancies, ‘coopcated by pretra premature rupee of membranes. J Mate Fel Neonatal Med 25(6):658, 2012 Bkeund CK, Skibsed Ly Sopa Ky ec al: Digotic monochovionic vin Pregnancy conceived following inacyoplasmic spe injection tearment End complicated ly ewi-twin vation syndrome and blood cies, Uleaound Obaer Gynca! 32282, 2008, Eimian A, Figueos Ry Nigam S, eal: Pesinatal outcome of ipl geen hoes prophylaiccercloge make dferene” | Mater Fetal Neoaal Med 119, 1999 Elle JP: Prete Labor in eins and highorder mull. Cli Pentel 34599, 2007 Eo JP, Finberg H): Biophysical profile rtng a an ndistor of Fl wel tring high-order mall gations, Am | Obstet Gynecol 172508, 1995 Econ A, Kalle B, Abe At Use of mula and fai ad i eal prsancy and multiple Bits ia Sweden Twan Res (2453, 2001 vane Ml Beskowis RL, Wapne J, ca: Improvement in outcomes of mal ‘etal pregnany redurion with incre experience Am] Ober Gynecol 18497, 2001, Evans Mf, Cio D, Butt DW, el: Update on eletve eduction, Prenat Diagn 2:07, 2005, vane Ml, Golderg JD, Horenstein et a lcsiveerminaon fr soc, ‘hromomomal, and mendelin anomalies inenationl experience. Am J Obs Gynecol 181893, 1999 vats Mf Johnson MP, Quintero RA, ta: ical ies suroundig mull regan rdacion and selene terminason. lin Pentel 253437, 1996 vane ML, Kaufman Ml, Urban A, et als Fea eduction fom rin 293 ‘ington a resonable consideration? Obstet Gynecol 1041423, 2004 FayePetenen OM, Heller DS, Joe VV: Handbook of Placental Pathology, “and ed London, Taylor & Francs, 2006 Feliman J, Eeson AW: Secondary or zal ip mulbple bits, Twin Res ‘Hum Gener 130.101, 2010, oud AA, Bateman BT Simon Ll: Vaginal hin afer ceacan delivery in twin gatos: alae, natonwide simple of deliveries, Am) Obstet Gyoeel 19521138, 2006, For H, Sebite NJ Pathology of she Placenta, 3d ed. Philp, Saunders, 2007 Fox NS, Roma AS, Sakaman DI ea: lk factors fr preeclampsia in ovin rghancies. Am J Petal 31(2163, 2014 Ft NS Siventcin M, Bender S, eta Active second-stage management in Trin preprence dexping planed vagina deiery in US. population, (ObseeGyen! 115229, 2010 FrapeoisK, One aris G, eal Is pespartu hysterectomy more common in multiple gestions? Ober Gynecol 105-1363, 2005 Fu L, Gordon H: Twin propnany complicated by singe intestine det Problems and outcome wih conserative management 8JOG 97511, 1999 us L, MeParand P, Fak N, et ab Acie win-win earfoson: a posible "occas for ban-damaged survivors after inuaterine deh of mono rience. Obst Gynecl 78517, 1991 921 EP EICL LP)