Best Practice & Research Clinical Obstetrics and Gynaecology 28 (2014) 319–326
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Best Practice & Research Clinical Obstetrics and Gynaecology journal homepage: www.elsevier.com/locate/bpobgyn
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Timing of birth in multiple pregnancy Tiran Dias, MBBS MD (Obs & Gyn) MRCOG MD (London) Dip (Fetal Med), Consultant Obstetrician and Gynaecologist a, *, Ranjit Akolekar, MBBS MRCOG b, c a b c
Department of Obstetrics and Gynecology, District General Hospital, Ampara, Sri Lanka Fetal Medicine Unit, Medway NHS Foundation Trust, Gillingham, Kent, UK Fetal Medicine Unit, St George’s Hospital, Blackshaw Road, Tooting, London, UK
Keywords: monochorionic dichorionic risk of stillbirth optimum timing of birth
Timing of delivery of twins should be decided when the benefit of prolonging the pregnancy outweighs the risk of stillbirth. Perinatal mortality of singletons is increased significantly after 42 weeks, whereas perinatal mortality in twins starts to increase significantly after 37 weeks. Recent, large cohort studies have showed significantly higher stillbirth rates near term even in apparently low-risk monochorionic twin pregnancies. Stillbirth risk in monochorionic twins is three-fold higher than in dichorionic twins, and this risk remains high throughout the pregnancy. In uncomplicated monochorionic twins between 32 and 37 weeks, no statistically significant increase of stillbirth occurs between 32 and 37 weeks; these pregnancies are usually monitored until delivery at 37 weeks. The risk of stillbirth in dichorionic twins does not seem to be different between 28 and 38 weeks, justifying a differential policy for the timing of delivery in monochorionic compared with dichorionic twin pregnancies. Therefore, uncomplicated dichorionic twins should be managed expectantly, and delivery can be arranged from 38 weeks. In cases of discordant fetal wellbeing at preterm gestations, timing of delivery should be based mainly on parameters and outlook for the healthy twin balanced against the condition of the compromised fetus. The threshold for early delivery may be lower in monochorionic twins because of the high mortality and morbidity in surviving twins with co-twin death. Ó 2013 Elsevier Ltd. All rights reserved.
* Corresponding author. Tel.: þ94 632222261; Fax: þ94 632223928. E-mail address: [email protected] (T. Dias). 1521-6934/$ – see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.bpobgyn.2013.11.001
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Introduction The management of multiple pregnancies forms an important cornerstone of modern antenatal care. In the past 3 decades, the incidence of multiple pregnancies has increased, mainly because of increasing use of assisted reproduction techniques, with more than one- quarter of in-vitro fertilisation pregnancies resulting in multiple gestations [1–5]. This increase in the incidence of multiple pregnancies after assisted reproduction techniques has been associated with dizygotic and monozygotic pregnancies [6,7]. The necessity of having evidence-based management strategies in multiple pregnancies is because they are at a higher risk of complications, such as preterm labour, fetal growth restriction, and preeclampsia, and they are also associated with a significantly increased risk of stillbirth compared with singleton pregnancies [8–11]. Therefore, timing of delivery in multiple pregnancies is crucial to mitigate the risk of these complications. This chapter will focus on the available evidence in deciding the appropriate timing of delivery in multiple pregnancies, with reference to twin pregnancies. Accurate dating and assessment of chorionicity Twin pregnancies are at increased risk of perinatal morbidity and mortality, compared with singleton pregnancies, mainly as a consequence of preterm delivery and fetal growth restriction [10]. An accurate estimation of the gestational age is vital to manage these complications. Considerable evidence suggests that twin pregnancies can be reliably dated using singleton crown–rump length charts between 11 and 14 weeks, and by fetal head circumference thereafter [12,13]. Biometry of the larger twin is more pragmatic than smaller twin in dating of twin pregnancy, as fetal growth restriction could exist even in an early stage [14]. No uniform policy of dating in in-vitro fertilisation (IVF) pregnancies exists and, as such, some chose the date of oocyte retrieval whereas others use the embryo replacement date for pregnancy dating [12,15]. To overcome this limitation, crown–rump length measurement between 11 and 14 weeks has been suggested, even in IVF pregnancies [16]. Perinatal mortality and morbidity among twins are determined by chorionicity, with a higher prevalence of complications in monochorionic compared with dichorionic twins [17–19]. Therefore, determination of chorionicity is the most important step in managing twin pregnancies. First-trimester markers of two different placental masses and lambda or ‘T’ sign are more reliable in determining chorionicity, as some of the other markers disappear with advancing gestation [20,21]. Mechanism for differing risks of pregnancy loss in monochorionic and dichorionic twins The higher mortality in monochorionic twins is attributed to the effects of placental vascular characteristics and degree of placental sharing of each twin. Vascular anastomosis between both fetuses at the level of placenta is always present in monochorionic twins, and blood flow in these is often balanced. Up to 15% of monochorionic twins could be complicated by chronic twin-to-twin transfusion syndrome (TTTS) and selective fetal growth restriction caused by haemodynamic imbalance between these anastomoses and unequal placental sharing, respectively [22]. These complications of monochorionic twins are responsible for high early fetal loss rate, and it has been estimated in early research that pregnancy loss rate of monochorionic twins is 12 times higher than dichorionic twins before 26 weeks [17]. With the increasing use and experience of fetoscopic laser techniques, however, early fetal loss rate in monochorionic twins has been significantly reduced [23] (Fig. 1). Late pregnancy loss in monochorionic twins is not as high as in early pregnancy, but remains higher than dichorionic twins at term. Reasons for term fetal loss in monochorionic twins are not well studied; however, twin anemia–polycythaemia sequence, acute fetal transfusions, congenital anomalies, and hidden fetal growth restriction are thought to be possible contributory factors. Twin anemia–polycythaemia sequence is characterised by large inter-twin haemoglobin differences without signs of twin oligo–polyhydramnios sequence [24]. Twin anemia–polycythaemia sequence may occur spontaneously or after laser surgery for TTTS. The spontaneous form complicates about 3–5% of monochorionic twin pregnancies [25]. The acute form of TTTS is unlikely in the antenatal period, and usually occurs during labour in monochorionic twins. A two- to four-fold increased risk of structural anomalies occurs
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Fig. 1. Perinatal loss rates in monochorionic compared with dichorionic twins. Adapted with permission [23].
in monochorionic twins, particularly congential heart disease. The incidence of congenital heart defects is six times higher in monochorionic twins than in dichorionic twins, which may be an additional contributory factor [26]. Fetal growth restriction is associated with an increased risk of late pregnancy loss in twin pregnancies. Regardless of chorionicity, twins grow at the same rate as singletons up to 32 weeks’ gestation [27,28], and thereafter the growth rate is slowed. This may be related to reduced intrauterine physical space or to uteroplacental insufficiency. Discordance in fetal growth of more than 25% is associated with higher mortality in twins [18,23]. In a large study that included more than 2000 twin pregnancies, D’Antonio et al. [23] showed that perinatal loss in twins with a birth-weight discordance of more than 25% was significantly greater (60.9 per 1000 fetuses) compared with those with a discordance less than 25% (8.6 per 1000 fetuses). Their analysis further showed that birth-weight discordance and gestational age but not chorionicity and individual fetal size percentile were the only independent predictors of perinatal mortality in twin pregnancies [23]. These data highlight that, in monochorionic twin pregnancies, the mechanism of fetal loss before 26 weeks is primarily related to complications such as TTTS and selective fetal growth restriction. After this gestation, the main determinants of pregnancy loss in monochorionic twins are complications such as twin anemia–polycythaemia sequence, acute fetal transfusions, congenital anomalies, and fetal growth restriction [23]. In dichorionic pregnancies, the predominant factor contributing to fetal loss relates to fetal growth restriction manifested by discordance in fetal size, and this assumes significant importance when the degree of discordance is more than 25%. In addition to fetal loss caused by factors previously mentioned, other important contributors to perinatal mortality in both monochorionic and dichorionic twins is gestational age at delivery [23]. Risk of fetal and neonatal mortality with advancing gestation in monochorionic and dichorionic twins The contribution of preterm delivery and prematurity towards neonatal mortality after 32 weeks of gestation is significantly reduced in recent years as a result of improved neonatal care facilities [27]. Prospective risk of fetal death in twin pregnancies, however, increases with advancing gestation, and it ranges between 0.2% and 0.4% per gestational week between 32 and 38 weeks’ gestation [28]. Evidence suggests that the risk of stillbirths in twins equaled that of post-term singletons by 36–37 weeks’ gestation [29]. Therefore, appropriate management of this late gestational age period is critical because twins are known to experience significantly greater stillbirth rates compared with singleton gestations near term. The main limitation of these population-based studies is the lack of data on chorionicity
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[29], and, although it is clear that twins have an increased risk of mortality compared with singletons, it also true that the mechanisms and causes of such an increased rate of pregnancy loss differ in chorionicity of the pregnancy. It is, therefore, vital that decisions about the optimal timing of delivery for term and near-term twins should be based on chorionicity. Dichorionic twins Evidence on rates of fetal death in dichorionic twins is consistent. Recent, large cohort studies have shown that risk of stillbirth in dichorionic twins remains below 3.5 per 1000 ongoing fetuses between 26 and 36 weeks (Fig. 2). In a large, retrospective cohort study, based on 4912 dichorionic twin pregnancies, Dias et al. [30] reported that the risk of stillbirth in dichorionic twins after 26 weeks remained static at around 1 per 1000 ongoing fetuses in each 2-week epoch, with a total stillbirth rate of 6.5 per 1000 (95% CI 4.8 to 9.8) ongoing fetuses [30]. These data are similar to those reported by Hack et al. [31], in which the total stillbirth rate after 26 weeks was reported to be 6.6 (95% CI 3.9 to 11.0). Therefore, the current evidence suggests that the stillbirth rate in dichorionic twins is fairly constant after 26 weeks but only up until 38–39 weeks, as evidence shows that rates of fetal death significantly increase once a gestational age of 38–39 weeks is reached [32]. Hack et al. [31] reported that most of late deaths in dichorionic twins in their study were a result of either diagnosed small for gestational age with normal fetal well-being tests, or by undiagnosed small for gestational age [31]. Therefore, it is rational to have expectant management until 38 weeks and plan elective delivery at 38 weeks in uncomplicated dichorionic twin pregnancies. Women who intend to prolong the pregnancy beyond 38 weeks should have fetal growth and wellbeing assessed; if fetal growth restriction is diagnosed, then recommendations should be made for delivery; if it is not diagnosed, and even in the presence of reassuring assessment of fetal wellbeing beyond this gestation, adverse outcome may still be a risk. In the case of dichorionic twin pregnancies, timing of delivery is important. Discordant fetal complications, such as congenital defects, should be individualized, and management focused on optimising outcome for the healthy co-twin. Monochorionic twins
Prospective risk (per 1000 ongoing pregnancies)
The risk of fetal death in monochorionic twins is higher than in dichorionic twins, and this risk is not just confined to early pregnancy; higher rates have been documented even after 32 weeks [30,33] (Fig. 2). Relative low prevalence of monochorionic twins has resulted in a paucity of epidemiological evidence on which to base clinical decisions about the optimal timing of monochorionic twin birth to avoid intrauterine fetal death. The optimal timing of delivery in monochorionic twins has been much
10 9 8 7 6 5 4 3 2 1 0
26 + 0 to 27 + 6
28 + 0 to 29 + 6
30 + 0 to 31 + 6 32 + 0 to 33 + 6 Gestational age (weeks)
34 + 0 to 35 + 6
> 36 + 0
Fig. 2. The gestational specific risk of stillbirth expressed per 1000 continuing pregnancies in monochorionic (-) and dichorionic (C) in combined data [22,25,30,33–38].
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debated, with some suggesting expectant management in uncomplicated monochorionic twins until 36 weeks, and others recommending an early delivery at around 32 weeks (Table 1), owing to presumed risk of unexplained late fetal loss after this gestation [3,25,30,32–40]. Tul et al. [33] evaluated 387 monochorionic twin pregnancies that were delivered after 24 weeks in Slovenia between 1997 and 2007, and reported that the prospective risk of stillbirth per pregnancy after 34 weeks of gestation was as high as 16.5 (95% CI 9.0 to 30.2). The weakness of this study was that it lacked a standardised ultrasound surveillance protocol for monochorionic twins, and the frequency of assessments was based on decisions of the attending obstetrician rather than the current evidence-based fortnightly assessments, thus introducing a degree of bias in their results [33]. In contrast, in another retrospective study by Hack et al. [31], the investigators reported that the delivery of monochorionic twins should be at or before 37 weeks, as the prospective risk of stillbirth after 36 weeks for monochorionic twins is significantly increased 21.6 (8.4 to 54.3), and is almost nine times higher than in dichorionic twins (2.3, 95% CI 0.8 to 6.8) at that gestation [31]. In this study, the investigators reported a standardised protocol for the monitoring of twin pregnancies consisted of fortnightly scans for growth, amniotic fluid and Doppler assessments [31]. They reported that, in the group of monochorionic twins, six stillbirths occurred after 32 weeks gestation, but they were all caused by complications of TTTS [31]. The same group examined a larger cohort of twin pregnancies in a further study and reported that, after excluding cases with TTTS, the risk of stillbirth was low, between 32 and 36 weeks [39]. Six neonatal deaths occurred, three early and three late, most of which were caused by complications of prematurity related to delivery before 36 weeks. This led them to conclude that, in uncomplicated monochorionic twins, planned delivery should be undertaken at or after 36 weeks as, before these gestations, the complications of prematurity can be substantial [39]. Considerable evidence suggests that late preterm delivery is not without risks, and is known to significantly increase the risk of neonatal morbidity and mortality [39], thus adding further support to the practice of delivering uncomplicated monochorionic twins at or after 36 weeks. The support for later delivery in uncomplicated monochorionic pregnancies was reported in a large study based on 549 twins, in which the investigators reported that, in monochorionic twins delivered after 26 weeks, the total risk of stillbirth was 19.1 per 100 fetuses, which was significantly higher than in dichorionic twins; 6.5 per 1000 fetuses, with an odds ratio of 2.97 (95% CI 1.71 to 5.18) [30]. The risk of stillbirth in monochorionic twins did not change significantly between 26 weeks (1.8 per 1000 fetuses) and 36 weeks (3.4 per 1000 fetuses), with an odds ratio of 1.85 (95% CI, 0.3 to 13.2) [30]. Moreover, in a recent study, Smith et al. [38], observed that increased mortality at or after 32 weeks in monochorionic twins can be attributed to TTTS and severe growth discordance. They suggested that, in these complicated monochorionic twins, the timing of delivery is often intuitive owing to clinical indications, but prolonging pregnancy to 36–37 weeks should be considered in uncomplicated monochorionic twins, where a clear indication for delivery is absent [38]. A recent systematic review [41]
Table 1 Prospective risk of stillbirth in monochorionic diamniotic twins at 32 weeks and after 36 weeks. Reference
Number of monochorionic twins
Country
Prospective risk of stillbirths at 32 weeks (per 1000 ongoing fetuses)
Prospective risk of stillbirths after 36 weeks (per 1000 ongoing fetuses)
Dias et al., 2012 Farah et al., 2012 Tul et al., 2011 Hack et al., 2011
549 144 387 465 after excluding TTTS 234 111 189 178 188 193 151
UK Ireland Slovenia Netherlands
6.09 0.0 7.42 5.4
(2.8–13.2) (0.0–14.8) (3.2–17.2) (2.3–12.5)
3.37 16.7 10.90 1.7
USA Portugal USA Belgium and Germany Netherlands Portugal UK
4.18 6.33 0.00 3.11 6.83 0.00 7.19
(1.1–15.1) (1.1–35.0) (0.0012.1) (0.5–17.4) (1.9–24.5) (0.0–11.4) (2.0–25.8)
0.00 (0.0–14.9) No data 8.30 (1.5–45.7) 0.00 (0.0–20.5) 21.60 (8.4–54.3) 0.00 (0.0–22.0) 5.38 (0.9–29.8)
Smith et al., 2010 Domingues et al., 2009 Lee et al., 2008 Lewi et al., 2008 Hack et al., 2008 Simoes et al., 2006 Barigye et al., 2005
(0.9–12.2) (5.7–47.8) (4.7–25.3) (0.3–9.4)
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Table 2 Prospective risk of stillbirth for monochorionic and dichorionic twins per 1000 continuing fetuses in combined data. Monochorionic twins Gestational age (weeks) 26þ0 – 28þ0 – 30þ0 – 32þ0 – 34þ0 – >36þ0 Total
27þ6 29þ6 31þ6 33þ6 35þ6
Dichorionic twins
Ongoing fetuses
Fetal losses
Risk of stillbirth
95% CI
Ongoing fetuses
Fetal losses
Risk of stillbirth
95% CI
4479 4357 4164 3835 3248 2505 4479
16 18 14 18 18 13 97
3.57 4.13 3.36 4.69 5.54 5.19 21.66
2.2–5.8 2.6–6.5 2.0–5.6 3.0–7.4 3.5–8.7 3.1–8.9 17.8–26.3
9174 9022 8745 8205 7401 6641 9174
7 11 13 11 8 11 61
0.76 1.22 1.49 1.34 1.08 1.66 6.65
0.4–1.6 0.7–2.2 0.9–2.5 0.8–2.4 0.6–2.1 0.9–2.9 5.2–8.5
looked at timing of delivery in twin pregnancies, and concluded that elective delivery at 36 weeks may be the best current strategy to decrease fetal mortality in monochorionic twins. It is, however, likely that their analysis is undermined because investigators failed to include data from two large studies that reported on risk of stillbirth in twin pregnancies [3,30] and, additionally, they failed to consider the heterogenicity of studies in their metaanalysis [41]. It is evident from studies that the risk of stillbirth for uncomplicated monochorionic twins does not increase significantly in the third trimester between 32 and 36 weeks (Table 2). Late complications, however, caused by vascular anastomoses, can still occur in monochorionic twins. On the basis of these concerns, a policy of routine fetal surveillance in the last trimester is indicated, and elective delivery from 36 weeks’ gestation can be justified.
Risk of fetal and neonatal morbidity with advancing gestation in monochorionic and dichorionic twins Neonatal morbidity with advancing gestation of twins has not been studied much. In a retrospective study by Hack et al. [31], the investigators reported that 80% of monochorionic twins and 66% of dichorionic twins were admitted to the neonatal unit [31]. The proportion of twins admitted to the neonatal intensive care unit was also higher for monochorionic twins than for dichorionic twins (29.4 and 19.5%, respectively). Furthermore, they also reported that, overall, neonatal morbidity was considerably higher in monochorionic twins but, after adjustment for gestational age and birthweight, only necrotising enterocolitis occurred significantly more often in monochorionic twins than in dichorionic twins (OR 4.05, 95% CI 1.97 to 8.35) [31]. There is a trend towards higher neonatal neuromorbidity (periventricular leukomalacia, intraventricular haemorrhage, or both) in monochorionic twins compared with dichorionic twins [31]. In a recent study comparing the rate of neonatal respiratory morbidity in singletons with twins delivered by pre-labour caesarean section, the investigators reported that the overall neonatal respiratory morbidity was comparable between singletons (25 out of 241 [11.7%] and 7 out of 100 [7%]; P ¼ 0.331) [42]. The risk, however, was higher among singletons than twins (15 out of 46 [32.6%] v 6 out of 72 [8.3%]; P < 0.001) between 34 þ 0 and 36 þ 6 weeks [42]. Furthermore, after adjusting for confounders in a multiple regression analysis, dichorionicity, gestational age at delivery greater than 37 weeks, and female sex independently decreased the risk of neonatal respiratory morbidity [42].
Conclusion The stillbirth rate of singletons at 42 weeks is equivalent to that of twins at 38 weeks, suggesting delivery of twins should be considered around 38 weeks. Among twins, pregnancy outcome is determined by chorionicity. Risk of stillbirth of dichorionic twins does not increase from 28 weeks to 38 weeks. Therefore, expectant management is justifiable for uncomplicated dichorionic twins until 38 weeks. In contrast, risk of stillbirth in monochorionic twins is higher in all gestations than dichorionic counterparts. This risk does not change significantly between 32 weeks and 37 weeks, indicating that
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apparently healthy monochorionic twins could be monitored until 37 weeks, and elective delivery should be planned around 37 weeks. Conflict of interest None declared.
Practice points
Chorionicity is the most important determinant of pregnancy outcome in twin pregnancy. Uncomplicated monochorionic twins should not be delivered electively before 36 weeks. Conservative management until 38 weeks is justified in uncomplicated dichorionic twins. In the case of discordant fetal wellbeing or discordant fetal anomaly, timing of delivery should be based on optimising outcome for the healthy co-twin. To prevent consequences of co-twin death in monochorionic twins, timing of delivery should be considered on the basis of the viability of the healthy twin, and the condition of the compromised co-twin.
Research agenda Assessing neonatal morbidity of late preterm delivery in twins. To determine optimum time of delivery in the case of co-twin death in monochorionic and dichorionic twins. To determine optimum method and frequency of fetal monitoring in monochorionic and dichorionic twins.
References [1] Verberg MFG, Macklon NS, Heijnen EMEW, et al. Iatrogenic multiple pregnancy? Best Pract Res Clin Obstet Gynaecol 2007;21:129–43. [2] Martin JA, Hamilton BE, Sutton PD, et al. Births: final data for 2006, in national vital statistics reportsvol. 57, No 7. Hyattsville, MD: National Center for Health Statistics; 2009. [3] Oldenburg A, Rode L, Bødker B, et al. Influence of chorionicity on perinatal outcome in a large cohort of Danish twin pregnancies. Ultrasound Obstet Gynecol 2012;39:69–74. *[4] National Institute for Health and Clinical Excellence. Multiple pregnancy: the management of twin and triplet pregnancies in the antenatal period [CG129]. London: National Institute for Health and Clinical Excellence; 2011. [5] Nakhuda GS, Sauer MV. Addressing the growing problem of multiple gestations created by assisted reproductive therapies. Semin Perinatol 2005;29:355–62. [6] Aston KI, Peterson CM, Carrell DT. Monozygotic twinning associated with assisted reproductive technologies: a review. Reproduction 2008;136:377–86. [7] Vitthala S, Gelbaya TA, Brison DR, et al. The risk of monozygotic twins after assisted reproductive technology: a systematic review and meta-analysis. Hum Reprod Update 2009;15:45–55. *[8] Sairam S, Costeloe K, Thilaganathan B. Prospective risk of stillbirth in multiple-gestation pregnancies: a population-based analysis. Obstet Gynecol 2002;100:638–41. [9] Ehsanipoor RM, Haydon ML, Lyons Gaffaney C, et al. Gestational age at cervical length measurement and preterm birth in twins. Ultrasound Obstet Gynecol 2012;40:81–6. [10] Elliott JP, Istwan NB, Collins A, et al. Indicated and nonindicated preterm delivery in twin gestations: impact on neonatal outcome and cost. J Perinatol 2005;25:4–7. [11] Luke B, Brown MB, Hediger ML, et al. Perinatal and early childhood outcomes of twins versus triplets. Twin Res Hum Genet 2006;9:81–8. *[12] Dias T, Mahsud-Dornan S, Thilaganathan B, et al. First-trimester ultrasound dating of twin pregnancy: are singleton charts reliable? BJOG 2010;117:979–84. *[13] Dias T, Arcangeli T, Bhide A, et al. Second-trimester assessment of gestational age in twins: validation of singleton biometry charts. Ultrasound Obstet Gynecol 2011;37:34–7. [14] Memmo A, Dias T, Mahsud-Dornan S, et al. Prediction of selective fetal growth restriction and twin-to-twin transfusion syndrome in monochorionic twins. BJOG 2012;119:417–21.
326
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[15] Salomon LJ, Hourrier S, Fanchin R, et al. Is first-trimester crown–rump length associated with birthweight? BJOG 2011; 118:1223–8. [16] Dias T, Thilaganathan B. Is first-trimester crown-rump length associated with birthweight? BJOG 2012;119:380. author reply 381. [17] Sebire NJ, Snijders RJ, Hughes K, et al. The hidden mortality of monochorionic twin pregnancies. Br J Obstet Gynaecol 1997;104:1203–7. [18] Dias T, Bhide A, Thilaganathan B. Early pregnancy growth and pregnancy outcome in twin pregnancies. Ceylon Med J 2010;55:80–4. [19] Bhide A, Sankaran S, Sairam S, et al. Relationship of intertwin crown-rump length discrepancy to chorionicity, fetal demise and birth-weight discordance. Ultrasound Obstet Gynecol 2009;34:131–5. [20] Sepulveda W, Sebire NJ, Nicolaides KH. The lambda sign in twin pregnancies. Ultrasound Obstet Gynecol 1996;8:429. *[21] Dias T, Arcangeli T, Bhide A, et al. First-trimester ultrasound determination of chorionicity in twin pregnancy. Ultrasound Obstet Gynecol 2011;38:530–2. [22] Hack KE, Nikkels PG, Koopman-Esseboom C, et al. Placental characteristics of monochorionic diamniotic twin pregnancies in relation to perinatal outcome. Placenta 2008;29:976–81. *[23] D’Antonio F, Khalil A, Dias T, et al., Southwest Thames Obstetric Research Collaborative (STORK). Early fetal loss in monochorionic and dichorionic twin pregnancies: analysis of the Southwest Thames Obstetric Research Collaborative (STORK) multiple pregnancy cohort. Ultrasound Obstet Gynecol 2013;41:632–6. [24] Lopriore E, Middeldorp JM, Oepkes D, et al. Twin anemia-polycythemia sequence in two monochorionic twin pairs without oligopolyhydramnios sequence. Placenta 2007;28:47–51. *[25] Lewi L, Jani J, Blickstein I, et al. The outcome of monochorionic diamniotic twin gestations in the era of invasive fetal therapy: a prospective cohort study. Am J Obstet Gynecol 2008;199:514–8. [26] Pasquini L, Wimalasundera RC, Fisk NM. Management of other complications specific to monochorionic twin pregnancies. Best Pract Re Res Clin Obstet Gynaecol 2004;18:577–99. [27] Senoo M, Okamura K, Murotsuki J, et al. Growth pattern of twins of different chorionicity evaluated by sonographic biometry. Obstet Gynecol 2000;95:656–61. [28] Kingdom JC, Nevo O, Murphy KE. Discordant growth in twins. Prenat Diagn 2005;25:759–65. lu E, et al. Neonatal morbidity and mortality of late-preterm babies. J Matern Fetal Neonatal [29] Kalyoncu O, Aygün C, Cetinog Med 2010;23:607–12. *[30] Dias T, Patel D, Bhide A, et al. Prospective risk of late stillbirth in monochorionic twins: a regional cohort study. Southwest Thames Obstetric Research Collaborative (STORK). Ultrasound Obstet Gynecol 2012;39:500–4. [31] Hack KE, Derks JB, Elias SG, et al. Increased perinatal mortality and morbidity in monochorionic versus dichorionic twin pregnancies: clinical implications of a large Dutch cohort study. BJOG 2008;115:58–67. [32] Kahn B, Lumey LH, Zybert PA, et al. Prospective risk of fetal death in singleton, twin, and triplet gestations: implications for practice. Obstet Gynecol 2003;102:685–92. *[33] Tul N, Verdenik I, Novak Z, et al. Prospective risk of stillbirth in monochorionic-diamniotic twin gestations: a population based study. J Perinat Med 2011;39:51–4. [34] Lee YM, Wylie BJ, Simpson LL, et al. Twin chorionicity and the risk of stillbirth. Obstet Gynecol 2008;111:301–8. [35] Simões T, Amaral N, Lerman R, et al. Prospective risk of intrauterine death of monochorionic-diamniotic twins. Am J Obstet Gynecol 2006;195:134–9. [36] Barigye O, Pasquini L, Galea P, et al. High risk of unexpected late fetal death in monochorionic twins despite intensive ultrasound surveillance: a cohort study. PLoS Med 2005;2:e172. [37] Domingues AP, Fonseca E, Vasco E, et al. Should apparently uncomplicated monochorionic twins be delivered electively at 32 weeks? J Matern Fetal Neonatal Med 2009;22:1077–80. [38] Smith NA, Wilkins-Haug L, Santolaya-Forgas J, et al. Contemporary management of monochorionic diamniotic twins: outcomes and delivery recommendations revisited. Am J Obstet Gynecol 2010;203:e1–6. [39] Hack KE, Derks JB, Elias SG, et al. Perinatal mortality and mode of delivery in monochorionic diamniotic twin pregnancies 32 weeks of gestation: a multicentre retrospective cohort study. BJOG 2011;118:1090–7. [40] Farah N, Hogan J, Johnson S, et al. Prospective risk of fetal death in uncomplicated monochorionic twins. Acta Obstet Gynecol Scand 2012;91:382–5. [41] Danon D, Sekar R, Hack KE, et al. Increased stillbirth in uncomplicated monochorionic twin pregnancies: a systematic review and meta-analysis. Obstet Gynecol 2013;121:1318–26. *[42] Ghi T, Nanni M, Pierantoni L, et al. Neonatal respiratory morbidity in twins versus singletons after elective prelabor caesarean section. Eur J Obstet Gynecol Reprod Biol 2013;166:156–60.
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Timing of birth in multiple pregnancy Tiran Dias, MBBS MD (Obs & Gyn) MRCOG MD (London) Dip (Fetal Med), Consultant Obstetrician and Gynaecologist a, *, Ranjit Akolekar, MBBS MRCOG b, c a b c
Department of Obstetrics and Gynecology, District General Hospital, Ampara, Sri Lanka Fetal Medicine Unit, Medway NHS Foundation Trust, Gillingham, Kent, UK Fetal Medicine Unit, St George’s Hospital, Blackshaw Road, Tooting, London, UK
Keywords: monochorionic dichorionic risk of stillbirth optimum timing of birth
Timing of delivery of twins should be decided when the benefit of prolonging the pregnancy outweighs the risk of stillbirth. Perinatal mortality of singletons is increased significantly after 42 weeks, whereas perinatal mortality in twins starts to increase significantly after 37 weeks. Recent, large cohort studies have showed significantly higher stillbirth rates near term even in apparently low-risk monochorionic twin pregnancies. Stillbirth risk in monochorionic twins is three-fold higher than in dichorionic twins, and this risk remains high throughout the pregnancy. In uncomplicated monochorionic twins between 32 and 37 weeks, no statistically significant increase of stillbirth occurs between 32 and 37 weeks; these pregnancies are usually monitored until delivery at 37 weeks. The risk of stillbirth in dichorionic twins does not seem to be different between 28 and 38 weeks, justifying a differential policy for the timing of delivery in monochorionic compared with dichorionic twin pregnancies. Therefore, uncomplicated dichorionic twins should be managed expectantly, and delivery can be arranged from 38 weeks. In cases of discordant fetal wellbeing at preterm gestations, timing of delivery should be based mainly on parameters and outlook for the healthy twin balanced against the condition of the compromised fetus. The threshold for early delivery may be lower in monochorionic twins because of the high mortality and morbidity in surviving twins with co-twin death. Ó 2013 Elsevier Ltd. All rights reserved.
* Corresponding author. Tel.: þ94 632222261; Fax: þ94 632223928. E-mail address: [email protected] (T. Dias). 1521-6934/$ – see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.bpobgyn.2013.11.001
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Introduction The management of multiple pregnancies forms an important cornerstone of modern antenatal care. In the past 3 decades, the incidence of multiple pregnancies has increased, mainly because of increasing use of assisted reproduction techniques, with more than one- quarter of in-vitro fertilisation pregnancies resulting in multiple gestations [1–5]. This increase in the incidence of multiple pregnancies after assisted reproduction techniques has been associated with dizygotic and monozygotic pregnancies [6,7]. The necessity of having evidence-based management strategies in multiple pregnancies is because they are at a higher risk of complications, such as preterm labour, fetal growth restriction, and preeclampsia, and they are also associated with a significantly increased risk of stillbirth compared with singleton pregnancies [8–11]. Therefore, timing of delivery in multiple pregnancies is crucial to mitigate the risk of these complications. This chapter will focus on the available evidence in deciding the appropriate timing of delivery in multiple pregnancies, with reference to twin pregnancies. Accurate dating and assessment of chorionicity Twin pregnancies are at increased risk of perinatal morbidity and mortality, compared with singleton pregnancies, mainly as a consequence of preterm delivery and fetal growth restriction [10]. An accurate estimation of the gestational age is vital to manage these complications. Considerable evidence suggests that twin pregnancies can be reliably dated using singleton crown–rump length charts between 11 and 14 weeks, and by fetal head circumference thereafter [12,13]. Biometry of the larger twin is more pragmatic than smaller twin in dating of twin pregnancy, as fetal growth restriction could exist even in an early stage [14]. No uniform policy of dating in in-vitro fertilisation (IVF) pregnancies exists and, as such, some chose the date of oocyte retrieval whereas others use the embryo replacement date for pregnancy dating [12,15]. To overcome this limitation, crown–rump length measurement between 11 and 14 weeks has been suggested, even in IVF pregnancies [16]. Perinatal mortality and morbidity among twins are determined by chorionicity, with a higher prevalence of complications in monochorionic compared with dichorionic twins [17–19]. Therefore, determination of chorionicity is the most important step in managing twin pregnancies. First-trimester markers of two different placental masses and lambda or ‘T’ sign are more reliable in determining chorionicity, as some of the other markers disappear with advancing gestation [20,21]. Mechanism for differing risks of pregnancy loss in monochorionic and dichorionic twins The higher mortality in monochorionic twins is attributed to the effects of placental vascular characteristics and degree of placental sharing of each twin. Vascular anastomosis between both fetuses at the level of placenta is always present in monochorionic twins, and blood flow in these is often balanced. Up to 15% of monochorionic twins could be complicated by chronic twin-to-twin transfusion syndrome (TTTS) and selective fetal growth restriction caused by haemodynamic imbalance between these anastomoses and unequal placental sharing, respectively [22]. These complications of monochorionic twins are responsible for high early fetal loss rate, and it has been estimated in early research that pregnancy loss rate of monochorionic twins is 12 times higher than dichorionic twins before 26 weeks [17]. With the increasing use and experience of fetoscopic laser techniques, however, early fetal loss rate in monochorionic twins has been significantly reduced [23] (Fig. 1). Late pregnancy loss in monochorionic twins is not as high as in early pregnancy, but remains higher than dichorionic twins at term. Reasons for term fetal loss in monochorionic twins are not well studied; however, twin anemia–polycythaemia sequence, acute fetal transfusions, congenital anomalies, and hidden fetal growth restriction are thought to be possible contributory factors. Twin anemia–polycythaemia sequence is characterised by large inter-twin haemoglobin differences without signs of twin oligo–polyhydramnios sequence [24]. Twin anemia–polycythaemia sequence may occur spontaneously or after laser surgery for TTTS. The spontaneous form complicates about 3–5% of monochorionic twin pregnancies [25]. The acute form of TTTS is unlikely in the antenatal period, and usually occurs during labour in monochorionic twins. A two- to four-fold increased risk of structural anomalies occurs
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Fig. 1. Perinatal loss rates in monochorionic compared with dichorionic twins. Adapted with permission [23].
in monochorionic twins, particularly congential heart disease. The incidence of congenital heart defects is six times higher in monochorionic twins than in dichorionic twins, which may be an additional contributory factor [26]. Fetal growth restriction is associated with an increased risk of late pregnancy loss in twin pregnancies. Regardless of chorionicity, twins grow at the same rate as singletons up to 32 weeks’ gestation [27,28], and thereafter the growth rate is slowed. This may be related to reduced intrauterine physical space or to uteroplacental insufficiency. Discordance in fetal growth of more than 25% is associated with higher mortality in twins [18,23]. In a large study that included more than 2000 twin pregnancies, D’Antonio et al. [23] showed that perinatal loss in twins with a birth-weight discordance of more than 25% was significantly greater (60.9 per 1000 fetuses) compared with those with a discordance less than 25% (8.6 per 1000 fetuses). Their analysis further showed that birth-weight discordance and gestational age but not chorionicity and individual fetal size percentile were the only independent predictors of perinatal mortality in twin pregnancies [23]. These data highlight that, in monochorionic twin pregnancies, the mechanism of fetal loss before 26 weeks is primarily related to complications such as TTTS and selective fetal growth restriction. After this gestation, the main determinants of pregnancy loss in monochorionic twins are complications such as twin anemia–polycythaemia sequence, acute fetal transfusions, congenital anomalies, and fetal growth restriction [23]. In dichorionic pregnancies, the predominant factor contributing to fetal loss relates to fetal growth restriction manifested by discordance in fetal size, and this assumes significant importance when the degree of discordance is more than 25%. In addition to fetal loss caused by factors previously mentioned, other important contributors to perinatal mortality in both monochorionic and dichorionic twins is gestational age at delivery [23]. Risk of fetal and neonatal mortality with advancing gestation in monochorionic and dichorionic twins The contribution of preterm delivery and prematurity towards neonatal mortality after 32 weeks of gestation is significantly reduced in recent years as a result of improved neonatal care facilities [27]. Prospective risk of fetal death in twin pregnancies, however, increases with advancing gestation, and it ranges between 0.2% and 0.4% per gestational week between 32 and 38 weeks’ gestation [28]. Evidence suggests that the risk of stillbirths in twins equaled that of post-term singletons by 36–37 weeks’ gestation [29]. Therefore, appropriate management of this late gestational age period is critical because twins are known to experience significantly greater stillbirth rates compared with singleton gestations near term. The main limitation of these population-based studies is the lack of data on chorionicity
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[29], and, although it is clear that twins have an increased risk of mortality compared with singletons, it also true that the mechanisms and causes of such an increased rate of pregnancy loss differ in chorionicity of the pregnancy. It is, therefore, vital that decisions about the optimal timing of delivery for term and near-term twins should be based on chorionicity. Dichorionic twins Evidence on rates of fetal death in dichorionic twins is consistent. Recent, large cohort studies have shown that risk of stillbirth in dichorionic twins remains below 3.5 per 1000 ongoing fetuses between 26 and 36 weeks (Fig. 2). In a large, retrospective cohort study, based on 4912 dichorionic twin pregnancies, Dias et al. [30] reported that the risk of stillbirth in dichorionic twins after 26 weeks remained static at around 1 per 1000 ongoing fetuses in each 2-week epoch, with a total stillbirth rate of 6.5 per 1000 (95% CI 4.8 to 9.8) ongoing fetuses [30]. These data are similar to those reported by Hack et al. [31], in which the total stillbirth rate after 26 weeks was reported to be 6.6 (95% CI 3.9 to 11.0). Therefore, the current evidence suggests that the stillbirth rate in dichorionic twins is fairly constant after 26 weeks but only up until 38–39 weeks, as evidence shows that rates of fetal death significantly increase once a gestational age of 38–39 weeks is reached [32]. Hack et al. [31] reported that most of late deaths in dichorionic twins in their study were a result of either diagnosed small for gestational age with normal fetal well-being tests, or by undiagnosed small for gestational age [31]. Therefore, it is rational to have expectant management until 38 weeks and plan elective delivery at 38 weeks in uncomplicated dichorionic twin pregnancies. Women who intend to prolong the pregnancy beyond 38 weeks should have fetal growth and wellbeing assessed; if fetal growth restriction is diagnosed, then recommendations should be made for delivery; if it is not diagnosed, and even in the presence of reassuring assessment of fetal wellbeing beyond this gestation, adverse outcome may still be a risk. In the case of dichorionic twin pregnancies, timing of delivery is important. Discordant fetal complications, such as congenital defects, should be individualized, and management focused on optimising outcome for the healthy co-twin. Monochorionic twins
Prospective risk (per 1000 ongoing pregnancies)
The risk of fetal death in monochorionic twins is higher than in dichorionic twins, and this risk is not just confined to early pregnancy; higher rates have been documented even after 32 weeks [30,33] (Fig. 2). Relative low prevalence of monochorionic twins has resulted in a paucity of epidemiological evidence on which to base clinical decisions about the optimal timing of monochorionic twin birth to avoid intrauterine fetal death. The optimal timing of delivery in monochorionic twins has been much
10 9 8 7 6 5 4 3 2 1 0
26 + 0 to 27 + 6
28 + 0 to 29 + 6
30 + 0 to 31 + 6 32 + 0 to 33 + 6 Gestational age (weeks)
34 + 0 to 35 + 6
> 36 + 0
Fig. 2. The gestational specific risk of stillbirth expressed per 1000 continuing pregnancies in monochorionic (-) and dichorionic (C) in combined data [22,25,30,33–38].
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debated, with some suggesting expectant management in uncomplicated monochorionic twins until 36 weeks, and others recommending an early delivery at around 32 weeks (Table 1), owing to presumed risk of unexplained late fetal loss after this gestation [3,25,30,32–40]. Tul et al. [33] evaluated 387 monochorionic twin pregnancies that were delivered after 24 weeks in Slovenia between 1997 and 2007, and reported that the prospective risk of stillbirth per pregnancy after 34 weeks of gestation was as high as 16.5 (95% CI 9.0 to 30.2). The weakness of this study was that it lacked a standardised ultrasound surveillance protocol for monochorionic twins, and the frequency of assessments was based on decisions of the attending obstetrician rather than the current evidence-based fortnightly assessments, thus introducing a degree of bias in their results [33]. In contrast, in another retrospective study by Hack et al. [31], the investigators reported that the delivery of monochorionic twins should be at or before 37 weeks, as the prospective risk of stillbirth after 36 weeks for monochorionic twins is significantly increased 21.6 (8.4 to 54.3), and is almost nine times higher than in dichorionic twins (2.3, 95% CI 0.8 to 6.8) at that gestation [31]. In this study, the investigators reported a standardised protocol for the monitoring of twin pregnancies consisted of fortnightly scans for growth, amniotic fluid and Doppler assessments [31]. They reported that, in the group of monochorionic twins, six stillbirths occurred after 32 weeks gestation, but they were all caused by complications of TTTS [31]. The same group examined a larger cohort of twin pregnancies in a further study and reported that, after excluding cases with TTTS, the risk of stillbirth was low, between 32 and 36 weeks [39]. Six neonatal deaths occurred, three early and three late, most of which were caused by complications of prematurity related to delivery before 36 weeks. This led them to conclude that, in uncomplicated monochorionic twins, planned delivery should be undertaken at or after 36 weeks as, before these gestations, the complications of prematurity can be substantial [39]. Considerable evidence suggests that late preterm delivery is not without risks, and is known to significantly increase the risk of neonatal morbidity and mortality [39], thus adding further support to the practice of delivering uncomplicated monochorionic twins at or after 36 weeks. The support for later delivery in uncomplicated monochorionic pregnancies was reported in a large study based on 549 twins, in which the investigators reported that, in monochorionic twins delivered after 26 weeks, the total risk of stillbirth was 19.1 per 100 fetuses, which was significantly higher than in dichorionic twins; 6.5 per 1000 fetuses, with an odds ratio of 2.97 (95% CI 1.71 to 5.18) [30]. The risk of stillbirth in monochorionic twins did not change significantly between 26 weeks (1.8 per 1000 fetuses) and 36 weeks (3.4 per 1000 fetuses), with an odds ratio of 1.85 (95% CI, 0.3 to 13.2) [30]. Moreover, in a recent study, Smith et al. [38], observed that increased mortality at or after 32 weeks in monochorionic twins can be attributed to TTTS and severe growth discordance. They suggested that, in these complicated monochorionic twins, the timing of delivery is often intuitive owing to clinical indications, but prolonging pregnancy to 36–37 weeks should be considered in uncomplicated monochorionic twins, where a clear indication for delivery is absent [38]. A recent systematic review [41]
Table 1 Prospective risk of stillbirth in monochorionic diamniotic twins at 32 weeks and after 36 weeks. Reference
Number of monochorionic twins
Country
Prospective risk of stillbirths at 32 weeks (per 1000 ongoing fetuses)
Prospective risk of stillbirths after 36 weeks (per 1000 ongoing fetuses)
Dias et al., 2012 Farah et al., 2012 Tul et al., 2011 Hack et al., 2011
549 144 387 465 after excluding TTTS 234 111 189 178 188 193 151
UK Ireland Slovenia Netherlands
6.09 0.0 7.42 5.4
(2.8–13.2) (0.0–14.8) (3.2–17.2) (2.3–12.5)
3.37 16.7 10.90 1.7
USA Portugal USA Belgium and Germany Netherlands Portugal UK
4.18 6.33 0.00 3.11 6.83 0.00 7.19
(1.1–15.1) (1.1–35.0) (0.0012.1) (0.5–17.4) (1.9–24.5) (0.0–11.4) (2.0–25.8)
0.00 (0.0–14.9) No data 8.30 (1.5–45.7) 0.00 (0.0–20.5) 21.60 (8.4–54.3) 0.00 (0.0–22.0) 5.38 (0.9–29.8)
Smith et al., 2010 Domingues et al., 2009 Lee et al., 2008 Lewi et al., 2008 Hack et al., 2008 Simoes et al., 2006 Barigye et al., 2005
(0.9–12.2) (5.7–47.8) (4.7–25.3) (0.3–9.4)
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Table 2 Prospective risk of stillbirth for monochorionic and dichorionic twins per 1000 continuing fetuses in combined data. Monochorionic twins Gestational age (weeks) 26þ0 – 28þ0 – 30þ0 – 32þ0 – 34þ0 – >36þ0 Total
27þ6 29þ6 31þ6 33þ6 35þ6
Dichorionic twins
Ongoing fetuses
Fetal losses
Risk of stillbirth
95% CI
Ongoing fetuses
Fetal losses
Risk of stillbirth
95% CI
4479 4357 4164 3835 3248 2505 4479
16 18 14 18 18 13 97
3.57 4.13 3.36 4.69 5.54 5.19 21.66
2.2–5.8 2.6–6.5 2.0–5.6 3.0–7.4 3.5–8.7 3.1–8.9 17.8–26.3
9174 9022 8745 8205 7401 6641 9174
7 11 13 11 8 11 61
0.76 1.22 1.49 1.34 1.08 1.66 6.65
0.4–1.6 0.7–2.2 0.9–2.5 0.8–2.4 0.6–2.1 0.9–2.9 5.2–8.5
looked at timing of delivery in twin pregnancies, and concluded that elective delivery at 36 weeks may be the best current strategy to decrease fetal mortality in monochorionic twins. It is, however, likely that their analysis is undermined because investigators failed to include data from two large studies that reported on risk of stillbirth in twin pregnancies [3,30] and, additionally, they failed to consider the heterogenicity of studies in their metaanalysis [41]. It is evident from studies that the risk of stillbirth for uncomplicated monochorionic twins does not increase significantly in the third trimester between 32 and 36 weeks (Table 2). Late complications, however, caused by vascular anastomoses, can still occur in monochorionic twins. On the basis of these concerns, a policy of routine fetal surveillance in the last trimester is indicated, and elective delivery from 36 weeks’ gestation can be justified.
Risk of fetal and neonatal morbidity with advancing gestation in monochorionic and dichorionic twins Neonatal morbidity with advancing gestation of twins has not been studied much. In a retrospective study by Hack et al. [31], the investigators reported that 80% of monochorionic twins and 66% of dichorionic twins were admitted to the neonatal unit [31]. The proportion of twins admitted to the neonatal intensive care unit was also higher for monochorionic twins than for dichorionic twins (29.4 and 19.5%, respectively). Furthermore, they also reported that, overall, neonatal morbidity was considerably higher in monochorionic twins but, after adjustment for gestational age and birthweight, only necrotising enterocolitis occurred significantly more often in monochorionic twins than in dichorionic twins (OR 4.05, 95% CI 1.97 to 8.35) [31]. There is a trend towards higher neonatal neuromorbidity (periventricular leukomalacia, intraventricular haemorrhage, or both) in monochorionic twins compared with dichorionic twins [31]. In a recent study comparing the rate of neonatal respiratory morbidity in singletons with twins delivered by pre-labour caesarean section, the investigators reported that the overall neonatal respiratory morbidity was comparable between singletons (25 out of 241 [11.7%] and 7 out of 100 [7%]; P ¼ 0.331) [42]. The risk, however, was higher among singletons than twins (15 out of 46 [32.6%] v 6 out of 72 [8.3%]; P < 0.001) between 34 þ 0 and 36 þ 6 weeks [42]. Furthermore, after adjusting for confounders in a multiple regression analysis, dichorionicity, gestational age at delivery greater than 37 weeks, and female sex independently decreased the risk of neonatal respiratory morbidity [42].
Conclusion The stillbirth rate of singletons at 42 weeks is equivalent to that of twins at 38 weeks, suggesting delivery of twins should be considered around 38 weeks. Among twins, pregnancy outcome is determined by chorionicity. Risk of stillbirth of dichorionic twins does not increase from 28 weeks to 38 weeks. Therefore, expectant management is justifiable for uncomplicated dichorionic twins until 38 weeks. In contrast, risk of stillbirth in monochorionic twins is higher in all gestations than dichorionic counterparts. This risk does not change significantly between 32 weeks and 37 weeks, indicating that
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apparently healthy monochorionic twins could be monitored until 37 weeks, and elective delivery should be planned around 37 weeks. Conflict of interest None declared.
Practice points
Chorionicity is the most important determinant of pregnancy outcome in twin pregnancy. Uncomplicated monochorionic twins should not be delivered electively before 36 weeks. Conservative management until 38 weeks is justified in uncomplicated dichorionic twins. In the case of discordant fetal wellbeing or discordant fetal anomaly, timing of delivery should be based on optimising outcome for the healthy co-twin. To prevent consequences of co-twin death in monochorionic twins, timing of delivery should be considered on the basis of the viability of the healthy twin, and the condition of the compromised co-twin.
Research agenda Assessing neonatal morbidity of late preterm delivery in twins. To determine optimum time of delivery in the case of co-twin death in monochorionic and dichorionic twins. To determine optimum method and frequency of fetal monitoring in monochorionic and dichorionic twins.
References [1] Verberg MFG, Macklon NS, Heijnen EMEW, et al. Iatrogenic multiple pregnancy? Best Pract Res Clin Obstet Gynaecol 2007;21:129–43. [2] Martin JA, Hamilton BE, Sutton PD, et al. Births: final data for 2006, in national vital statistics reportsvol. 57, No 7. Hyattsville, MD: National Center for Health Statistics; 2009. [3] Oldenburg A, Rode L, Bødker B, et al. Influence of chorionicity on perinatal outcome in a large cohort of Danish twin pregnancies. Ultrasound Obstet Gynecol 2012;39:69–74. *[4] National Institute for Health and Clinical Excellence. Multiple pregnancy: the management of twin and triplet pregnancies in the antenatal period [CG129]. London: National Institute for Health and Clinical Excellence; 2011. [5] Nakhuda GS, Sauer MV. Addressing the growing problem of multiple gestations created by assisted reproductive therapies. Semin Perinatol 2005;29:355–62. [6] Aston KI, Peterson CM, Carrell DT. Monozygotic twinning associated with assisted reproductive technologies: a review. Reproduction 2008;136:377–86. [7] Vitthala S, Gelbaya TA, Brison DR, et al. The risk of monozygotic twins after assisted reproductive technology: a systematic review and meta-analysis. Hum Reprod Update 2009;15:45–55. *[8] Sairam S, Costeloe K, Thilaganathan B. Prospective risk of stillbirth in multiple-gestation pregnancies: a population-based analysis. Obstet Gynecol 2002;100:638–41. [9] Ehsanipoor RM, Haydon ML, Lyons Gaffaney C, et al. Gestational age at cervical length measurement and preterm birth in twins. Ultrasound Obstet Gynecol 2012;40:81–6. [10] Elliott JP, Istwan NB, Collins A, et al. Indicated and nonindicated preterm delivery in twin gestations: impact on neonatal outcome and cost. J Perinatol 2005;25:4–7. [11] Luke B, Brown MB, Hediger ML, et al. Perinatal and early childhood outcomes of twins versus triplets. Twin Res Hum Genet 2006;9:81–8. *[12] Dias T, Mahsud-Dornan S, Thilaganathan B, et al. First-trimester ultrasound dating of twin pregnancy: are singleton charts reliable? BJOG 2010;117:979–84. *[13] Dias T, Arcangeli T, Bhide A, et al. Second-trimester assessment of gestational age in twins: validation of singleton biometry charts. Ultrasound Obstet Gynecol 2011;37:34–7. [14] Memmo A, Dias T, Mahsud-Dornan S, et al. Prediction of selective fetal growth restriction and twin-to-twin transfusion syndrome in monochorionic twins. BJOG 2012;119:417–21.
326
T. Dias, R. Akolekar / Best Practice & Research Clinical Obstetrics and Gynaecology 28 (2014) 319–326
[15] Salomon LJ, Hourrier S, Fanchin R, et al. Is first-trimester crown–rump length associated with birthweight? BJOG 2011; 118:1223–8. [16] Dias T, Thilaganathan B. Is first-trimester crown-rump length associated with birthweight? BJOG 2012;119:380. author reply 381. [17] Sebire NJ, Snijders RJ, Hughes K, et al. The hidden mortality of monochorionic twin pregnancies. Br J Obstet Gynaecol 1997;104:1203–7. [18] Dias T, Bhide A, Thilaganathan B. Early pregnancy growth and pregnancy outcome in twin pregnancies. Ceylon Med J 2010;55:80–4. [19] Bhide A, Sankaran S, Sairam S, et al. Relationship of intertwin crown-rump length discrepancy to chorionicity, fetal demise and birth-weight discordance. Ultrasound Obstet Gynecol 2009;34:131–5. [20] Sepulveda W, Sebire NJ, Nicolaides KH. The lambda sign in twin pregnancies. Ultrasound Obstet Gynecol 1996;8:429. *[21] Dias T, Arcangeli T, Bhide A, et al. First-trimester ultrasound determination of chorionicity in twin pregnancy. Ultrasound Obstet Gynecol 2011;38:530–2. [22] Hack KE, Nikkels PG, Koopman-Esseboom C, et al. Placental characteristics of monochorionic diamniotic twin pregnancies in relation to perinatal outcome. Placenta 2008;29:976–81. *[23] D’Antonio F, Khalil A, Dias T, et al., Southwest Thames Obstetric Research Collaborative (STORK). Early fetal loss in monochorionic and dichorionic twin pregnancies: analysis of the Southwest Thames Obstetric Research Collaborative (STORK) multiple pregnancy cohort. Ultrasound Obstet Gynecol 2013;41:632–6. [24] Lopriore E, Middeldorp JM, Oepkes D, et al. Twin anemia-polycythemia sequence in two monochorionic twin pairs without oligopolyhydramnios sequence. Placenta 2007;28:47–51. *[25] Lewi L, Jani J, Blickstein I, et al. The outcome of monochorionic diamniotic twin gestations in the era of invasive fetal therapy: a prospective cohort study. Am J Obstet Gynecol 2008;199:514–8. [26] Pasquini L, Wimalasundera RC, Fisk NM. Management of other complications specific to monochorionic twin pregnancies. Best Pract Re Res Clin Obstet Gynaecol 2004;18:577–99. [27] Senoo M, Okamura K, Murotsuki J, et al. Growth pattern of twins of different chorionicity evaluated by sonographic biometry. Obstet Gynecol 2000;95:656–61. [28] Kingdom JC, Nevo O, Murphy KE. Discordant growth in twins. Prenat Diagn 2005;25:759–65. lu E, et al. Neonatal morbidity and mortality of late-preterm babies. J Matern Fetal Neonatal [29] Kalyoncu O, Aygün C, Cetinog Med 2010;23:607–12. *[30] Dias T, Patel D, Bhide A, et al. Prospective risk of late stillbirth in monochorionic twins: a regional cohort study. Southwest Thames Obstetric Research Collaborative (STORK). Ultrasound Obstet Gynecol 2012;39:500–4. [31] Hack KE, Derks JB, Elias SG, et al. Increased perinatal mortality and morbidity in monochorionic versus dichorionic twin pregnancies: clinical implications of a large Dutch cohort study. BJOG 2008;115:58–67. [32] Kahn B, Lumey LH, Zybert PA, et al. Prospective risk of fetal death in singleton, twin, and triplet gestations: implications for practice. Obstet Gynecol 2003;102:685–92. *[33] Tul N, Verdenik I, Novak Z, et al. Prospective risk of stillbirth in monochorionic-diamniotic twin gestations: a population based study. J Perinat Med 2011;39:51–4. [34] Lee YM, Wylie BJ, Simpson LL, et al. Twin chorionicity and the risk of stillbirth. Obstet Gynecol 2008;111:301–8. [35] Simões T, Amaral N, Lerman R, et al. Prospective risk of intrauterine death of monochorionic-diamniotic twins. Am J Obstet Gynecol 2006;195:134–9. [36] Barigye O, Pasquini L, Galea P, et al. High risk of unexpected late fetal death in monochorionic twins despite intensive ultrasound surveillance: a cohort study. PLoS Med 2005;2:e172. [37] Domingues AP, Fonseca E, Vasco E, et al. Should apparently uncomplicated monochorionic twins be delivered electively at 32 weeks? J Matern Fetal Neonatal Med 2009;22:1077–80. [38] Smith NA, Wilkins-Haug L, Santolaya-Forgas J, et al. Contemporary management of monochorionic diamniotic twins: outcomes and delivery recommendations revisited. Am J Obstet Gynecol 2010;203:e1–6. [39] Hack KE, Derks JB, Elias SG, et al. Perinatal mortality and mode of delivery in monochorionic diamniotic twin pregnancies 32 weeks of gestation: a multicentre retrospective cohort study. BJOG 2011;118:1090–7. [40] Farah N, Hogan J, Johnson S, et al. Prospective risk of fetal death in uncomplicated monochorionic twins. Acta Obstet Gynecol Scand 2012;91:382–5. [41] Danon D, Sekar R, Hack KE, et al. Increased stillbirth in uncomplicated monochorionic twin pregnancies: a systematic review and meta-analysis. Obstet Gynecol 2013;121:1318–26. *[42] Ghi T, Nanni M, Pierantoni L, et al. Neonatal respiratory morbidity in twins versus singletons after elective prelabor caesarean section. Eur J Obstet Gynecol Reprod Biol 2013;166:156–60.
