DOI: 10.1002/pd.4643
ORIGINAL ARTICLE
Outcome of monochorionic diamniotic twin pregnancies followed at a single center Anna Fichera1*, Federico Prefumo1, Valentina Stagnati1, Daria Marella1, Adriana Valcamonico1 and Tiziana Frusca1,2 1
Maternal-Fetal Medicine Unit, Department of Obstetrics and Gynecology, University of Brescia, Brescia, Italy Department of Obstetrics and Gynecology, University of Parma, Parma, Italy *Correspondence to: Anna Fichera. E-mail: anna.fi
[email protected] 2
ABSTRACT Objective We aim to evaluate the outcome of a cohort of monochorionic diamniotic twin pregnancies followed from the first trimester onwards at a single center. Method This was a retrospective analysis of prospectively collected data from a series of 300 monochorionic diamniotic twin pregnancies referred to our twin clinic between 2001 and 2012. Pregnancies were followed from the first trimester and fortnightly after 16 weeks of gestation. Data on pregnancy and neonatal outcome were analyzed.
Results There were two surviving infants in 259/300 (86.4%) pregnancies, one survivor in 22/300 (7.3%) and no survivors in 19/300 (6.3%) with an overall mortality of 60/600 (10%). Twin–twin transfusion syndrome was diagnosed in 33 cases (11%), isolated intertwin weight discordance ≥ 25% in 35 (11.6%) and major congenital structural anomalies in ten (3.3%). After 32 weeks, the prospective risk of spontaneous fetal intrauterine death was one in 248 (0.4%) per pregnancy.
Conclusions Despite specific prenatal fetal monitoring and management, monochorionic diamniotic twin pregnancies have still to be considered at high risk of mortality, although the prospective risk of intrauterine death after 32 weeks is low. Twin–twin transfusion syndrome and congenital anomalies were the main risk factors for mortality. © 2015 John Wiley & Sons, Ltd.
Funding sources: None Conflicts of interest: None declared
INTRODUCTION Monochorionic diamniotic twin pregnancies (MCDA) account for 20% of all twin gestations and are known to be at higher risk of mortality and morbidity compared with dichorionic ones.1 The peculiar characteristics of monochorionic placentation are considered responsible for the excess of risks. Monochorionic twins shared in utero a single placenta and fetal circulations thorough placental vascular anastomoses: these particular features are associated with specific complications such as twin–twin transfusion syndrome (TTTS), and potential sequelae in one twin following the intrauterine demise (IUD) of the cotwin. Furthermore, other complications as birthweight discordance and congenital structural anomalies are reported more frequently in these pregnancies.2 In the last 15 years, medical attention has been focused on chorionicity as a fundamental prognostic factor in twin pregnancies: a correct diagnosis of monochorionicity and close surveillance of these pregnancies have been recommended by international guidelines, and new therapies have been developed, such as fetoscopic laser ablation of placental anastomoses, in order to improve the outcome of pregnancies complicated by TTTS.3–5 Prenatal Diagnosis 2015, 35, 1057–1064
Since 2001, a specialized prenatal clinic for twin gestations was set up in our unit, in order to provide specific information and care to these pregnancies, as suggested by previous studies to improve perinatal outcomes.6,7 The aim of this study was to review our experience and to report the pregnancy and neonatal outcome of a cohort of MCDA twin pregnancies followed from the first trimester onwards at a single center over an 11-year period.
METHODS This was a retrospective analysis of prospectively collected data from a series of consecutive MCDA twin pregnancies, referred to our twin clinic between May 2001 and December 2012. We excluded women referred after 14 weeks of gestation, cases with a single or double demise at the time of presentation and pregnancies with a diagnosis of twin-reverse arterial perfusion sequence. Given the retrospective nature of the analysis, based on clinical data presented in anonymized form, no ethical committee approval was necessary according to national regulations. The diagnosis of monochorionicity was established by ultrasound criteria in the first trimester and confirmed by pathological examination of the placenta after birth.8 During © 2015 John Wiley & Sons, Ltd.
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the first assessment, gestational age was confirmed by ultrasound and measurement of nuchal translucency was performed; from 2011, combined measurement of biochemical markers (pregnancy associated plasma protein A and free β-human chorionic gonadotropin) for screening of chromosomal anomalies was also offered. A close ultrasonographic surveillance to exclude TTTS was performed for all patients at our center fortnightly from 16 weeks of gestation until delivery [measurement of maximum vertical pocket (MVP) in each amniotic sac, evaluation of bladder filling and fetal Doppler studies]; fetal biometry was measured monthly, and a detailed anomaly scan (including fetal echocardiography) was carried out at 19 to 22 weeks of gestation.9 TTTS was diagnosed in the presence of polyhydramnios in one sac, with an MVP ≥8 cm before 20 weeks or ≥10 cm after 20 weeks, and oligohydramnios (MVP ≤ 2 cm) in the other sac, and it was classified using the Quintero staging system.5,10 Patients with a diagnosis of TTTS before 26 weeks were treated with serial amnioreductions or cord occlusion of one fetus was offered until 2004; after this year, fetoscopic laser ablation of placental anastomoses or umbilical cord occlusion of one fetus was offered. Both procedures were performed at Vittore Buzzi Hospital (Milan, Italy) between 2005 and 2008 and at our center between 2008 and 2012. Intrauterine growth restriction (IUGR) was defined as an estimated fetal weight less than the tenth percentile for gestational age between 16 and 36 weeks, while severe discordant growth was considered as a difference in birthweight of more than 25% for live-born twins without signs of TTTS; in cases with fetal IUD, discordant growth was calculated considering estimated fetal weight discordance. Conservative management or selective feticide by umbilical cord occlusion of the IUGR fetus was proposed differently in these cases, on the basis of gestational age at the diagnosis, severity of growth restriction and/or fetal Doppler findings. Umbilical cord occlusion was offered in pregnancies discordant for severe structural abnormalities in one twin in case the woman requested selective termination of pregnancy. Twin anemia polycythemia sequence (TAPS) was diagnosed postnatally in case of anemia in one twin and polycythemia in the other at birth.11 According to our policy, cervical cerclage was offered to those patients with an ultrasound cervical length less than 20 mm measured transvaginally or cervical dilatation at clinical examination before 25 weeks.12 Alternatively, in a few recent cases, an Arabin cervical pessary was placed.13 Delivery of uncomplicated pregnancies was generally planned at 36 weeks of gestation, preferably by cesarean section to avoid the risk of acute twin–twin transfusion in labor3,14 and considering also the organization of care in our labor ward. Vaginal delivery was considered in women with both fetuses in a cephalic presentation with a favorable Bishop score. Prophylactic corticosteroids (betamethasone 12 mg intramuscularly, two doses 24 h apart) were administered routinely in case of elective delivery before 37 weeks. In complicated pregnancies, delivery was carried out case by case, on the basis of the maternal and fetal conditions. Data on demographic characteristics, ultrasound measurements, Prenatal Diagnosis 2015, 35, 1057–1064
management, therapeutic options and pregnancy outcome were recorded in a dedicated computerized database. Neonatal data were collected from clinical notes. Information on delivery and neonatal outcome of those patients delivered at their local hospital was obtained from the referring physicians. In our analysis, we investigated the following variables: maternal age; parity; mode of conception (spontaneous or assisted); mode of delivery (vaginal or cesarean section); gestational age at delivery and preterm birth rate; preterm premature rupture of membranes; placement of cervical cerclage or pessary; onset of TTTS and treatment modality, growth disorders (intrauterine growth < tenth centile (IUGR) and/or the interfetal growth discordance greater than 25% without TTTS); congenital structural abnormalities; and diagnosis of TAPS at birth. To describe the neonatal outcome, we reported neonatal mortality, birthweight of live-born twins, admission to the neonatal intensive care unit, Apgar score less than 7 after 5 min from birth, endotracheal intubation, sepsis, intraventricular hemorrhage grades III to IV and/or periventricular leukomalacia at the neonatal cranial scan. We calculated the rate of fetal loss before 24 weeks (which includes the cases of IUD of both fetuses or miscarriage and termination of pregnancy before 24 weeks), perinatal mortality (including the number of IUD after 24 weeks, the birth-related deaths and neonatal deaths in the first week of life per total number of fetuses alive after 24 weeks) and neonatal mortality (deaths in the first 28 days after birth per total number of live births). The prospective risk of IUD for pregnancies continuing after 24 weeks was calculated using the same method previously reported by Barigye et al.15 Continuous variables were described as means (±standard deviation) or medians with ranges as appropriate, and categorical variables as percentage (%). A multivariable logistic regression analysis was performed to identify risk factors that could predict independently mortality per pregnancy for one or both twins, and the following predictive variables, known from the literature to be associated with increased perinatal mortality, were included: maternal age, parity, mode of conception, onset of TTTS, IUGR, severe growth discordance without TTTS, congenital anomalies and preterm birth before 32 weeks of gestation for pregnancies with at least one twin alive at birth. Given the known association between TTTS and preterm birth, an interaction term between TTTS and preterm birth before 32 weeks was also included in the analysis. Backward stepwise selection was used to refine the model with a threshold p value of 0.10 for including variables in the final model. Statistical analysis was performed with the SPSS software package (release 16.0.1, SPSS Inc., Chicago, IL, USA).
RESULTS A total of 640 MCDA twin pregnancies were referred to our twin clinic during the 11-year study period. Following the exclusion criteria, data of 300 pregnancies were included in the final analysis (Figure 1). The mean maternal age was 32.2 ± 4.7 years: 134 patients were nulliparous (44.7%) and 289 pregnancies (96.3%) were conceived spontaneously. Clinical details on the pregnancy outcome are reported in Table 1. © 2015 John Wiley & Sons, Ltd.
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Monochorionic diamniotic twin pregnancies referred to the twin clinic n=640 TRAP sequence
Pregnancies referred after 14 weeks
n=12
n=314 Pregnancies seen from the first trimester n=314 Intrauterine death of one or both twins during the first trimester at initial ultrasound examination n=7
Lost at the follow up n=7
Pregnancies analysed n=300
Figure 1 Flow chart of the study population. TRAP, twin-reverse arterial perfusion
Twin–twin transfusion syndrome was diagnosed in 33 patients (11%) at a mean gestational age of 20.6 ± 3.7 weeks (range 16.0 to 31.3): six cases were at stage I, four cases at stage II, 22 cases at stage III and one case at stage IV. Seven pregnancies (21%) were treated with amnioreductions, 16 patients (49%) with fetoscopic laser ablation of vascular anastomoses; delivery by cesarean section was chosen in two pregnancies (6%) with a diagnosis at 29+6 and 31+2 weeks; three patients (9%) opted for termination of pregnancy (in one case after laser therapy and a single IUD with signs of brain damage). No therapy was performed in one case at stage I because of spontaneous regression, in another pregnancy because of miscarriage and in four cases because spontaneous IUD of one or both twins occurred (in two pregnancies, the day before the laser procedure was scheduled). Mean gestational age at delivery in pregnancies complicated by TTTS with ≥1 live birth was 32.3 ± 3.6 weeks of gestation (range 25.4 to 39.1). Of the 33 pregnancies with TTTS, 25 (76%) resulted in at least one survival, 18 (55%) in a double survival, seven (21%) in a single survival and eight (24%) in no survivors: the overall survival rate was 43 of 66 (65%). In the laser and amnioreduction groups, the survival rates of at least one twin were 14/16 (87.5%) and 7/7 (100%), of both twins 8/16 (50%) and 6/7 (85.7%) and of a single twin 6/16 (37.5%) and 1/7 (14.3%), respectively. In particular, among the patients treated with laser ablation, preterm premature rupture of membranes within 28 days after the initial procedure occurred in two cases (12.5%), single IUD in six pregnancies (37.5%) and mean gestational age at delivery in those with at least one twin alive at birth was 32.6 ± 4.3 weeks of gestation (range 25.4–39.1). In the same group, there were two neonatal deaths and severe intraventricular hemorrhage was diagnosed in three twins. Prenatal Diagnosis 2015, 35, 1057–1064
Isolated severe growth discordance ≥25% without TTTS complicated 35 out of 300 pregnancies (11.6%) with a mortality rate of 5/70 (7.1%), including two cases with a single spontaneous IUD, two selective terminations with cord occlusion due to severe IUGR and signs of imminent fetal death and one neonatal death. Major congenital structural anomalies occurred in 3.3% of pregnancies (10/300). In all pairs, only one twin was affected. In a case of body stalk anomaly, termination of the entire pregnancy was requested. A selective termination was performed in one case of severe bilateral ventriculomegaly and in one of Dandy–Walker variant with omphalocele. Spontaneous IUD was observed in a case of anencephaly. In the remaining six cases, there was a live birth of the affected twin: one case each of arthrogryposis, multicystic dysplastic kidneys and aortic valve dysplasia; two cases with pulmonary stenosis; and one fetus with tetralogy of Fallot and unilateral clubfoot. Chromosomal abnormalities were present in two pregnancies (0.7%): in one, both twins had trisomy 21; in the other, twins were discordant for monosomy X (45,X and 46,XX). Mean gestational age at delivery in pregnancies with at least one twin alive at birth (281 patients) was 34.9 ± 2.5 weeks of gestation (range 25.4–40.4) (Table 1). In this group, preterm delivery between 24 and 32 weeks occurred in 33/281 pregnancies (11.7%): there was a spontaneous preterm labor in 18 patients (6.4%), and it was indicated for maternal (one case of preeclampsia) and/or fetal reasons (in six cases for non reassuring traces at cardiotocography, two for IUGR and six for TTTS) in 15 (5.3%) cases. In the group of patients who delivered before 32 weeks and with ≥1 twin live birth, ten pregnancies were complicated by TTTS (30%), six (18.1%) had isolated growth discordance and six (18.1%) had a single fetal IUD. © 2015 John Wiley & Sons, Ltd.
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Table 1 Clinical details of pregnancy and neonatal outcome Fetal complications IUD of one fetus
17/300 (5.7%)
IUD of both fetuses
9/300 (3%)
TTTS
33/300 (11%)
Severe isolated growth discordance
35/300 (11.7%)
Selective IUGR < 10th centile
40/300 (13.3%)
IUGR