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Pregnancy and infant outcome of 80 consecutive cord coagulations in complicated monochorionic multiple pregnancies
American Journal of Obstetrics and Gynecology (2006) 194, 782–9
www.ajog.org
Pregnancy and infant outcome of 80 consecutive cord coagulations in complicated monochorionic multiple pregnancies Liesbeth Lewi, MD,a Eduardo Gratacos, MD, PhD,b Els Ortibus, MD,a Dominique Van Schoubroeck, MD,a Elena Carreras, MD,b Teresa Higueras, MD,b Josep Perapoch, MD,b Jan Deprest, MD, PhDa,* UZ-Gasthuisberg, Leuven, Belgiuma; Hospital Vall d’Hebron, Barcelona, Spainb Received for publication May 1, 2005; revised September 9, 2005; accepted September 29, 2005
KEY WORDS Cord coagulation Monochorionic Multiple pregnancy Selective feticide
Objective: This study was undertaken to document pregnancy and infant outcome after cord coagulation with laser and/or bipolar as a technique for selective feticide in complicated monochorionic multiple pregnancies. Study design: Prospective follow-up study in 2 tertiary fetal medicine centers. Results: Eighty cases were included in the study (73 twins, 7 triplets). The survival rate was 83% (72/87). There were 9 intrauterine fetal deaths (10%), 5 within 24 hours and 4 between 4 and 10 weeks after the procedure. There was 1 termination of pregnancy because of chorioamnionitis. Median gestational age at delivery was 35.4 weeks, with 79% of patients delivering after 32 weeks. Preterm prelabor rupture of the membranes before 25 weeks accounted for all perinatal deaths (n = 5). Of the children older than 1 year of age (n = 67), 62 (92%) have a normal development. Conclusion: Cord coagulation is an effective method for selective feticide in monochorionic multiple pregnancies. Ó 2006 Mosby, Inc. All rights reserved.
In monochorionic (MC) multiple pregnancies, the fetuses share a single placenta and in almost all cases vascular anastomoses connect the fetal circulations.1 Dr Lewi is the recipient of a grant from the 5th Framework Program of the European Commission (no. QLG1-CT-2002-01632 EuroTwin2Twin). Presented in abstract form at the 2003 International Fetal-Maternal Medicine Society Meeting, San Francisco, CA, and the 2003 ISUOG Meeting, Paris, France. * Reprint requests: Jan Deprest, MD, PhD, Department of Obstetrics and Gynecology, UZ Leuven, B-3000 Leuven, Belgium. E-mail: [email protected] 0002-9378/$ - see front matter Ó 2006 Mosby, Inc. All rights reserved. doi:10.1016/j.ajog.2005.09.013
This shared fetal circulation accounts for some unique complications, such as feto-fetal transfusion syndrome (FFTS), twin reversed arterial perfusion (TRAP), and acute feto-fetal hemorrhage of the survivor after single intrauterine fetal death (IUFD).2 MC multiplets are also at higher risk of structural anomalies, with usually only 1 fetus affected.3 Selective feticide in MC pregnancies may be considered if 1 fetus threatens the well-being of the other(s) and/or has a severe anomaly. However, the conventional method of fetal intravascular potassium chloride injection as used in multichorionic pregnancies is unsuitable, as the substance may embolize
Lewi et al to the healthy fetus(es) and patent anastomoses may cause acute feto-fetal hemorrhage of the survivor into the demised fetus’ circulation. Therefore, a number of minimally invasive procedures were developed to produce complete circulatory confinement of the affected fetus.4 Fetoscopic laser cord coagulation can be performed already at 16 weeks and allows optimal visual control, but may fail in the late second or early third trimester because of increasing size of the cord vessels.5,6 At later gestational ages, ultrasound guided bipolar cord coagulation is the preferred method.7-9 Cord coagulation is now performed by an increasing number of fetal medicine units. However, data on pregnancy outcome are limited to small case series, and the developmental outcome of survivors has not been documented yet. We therefore evaluated pregnancy and infant outcome in a prospective series of 80 cord coagulations.
Patients and methods Design and study population This is a prospective follow-up study of MC pregnancies that underwent laser and/or bipolar cord coagulation as a primary procedure in 2 tertiary fetal medicine centers. The patients were operated on by 2 surgeons (J.D.P. and E.G.), who started the fetoscopy program together in Leuven between 1997 and 2000. During the study, Dr Gratacos was promoted to Barcelona, and the patients treated there were also included. Cord coagulation was offered for the following conditions in MC pregnancies: (1) TRAP, (2) severe discordant anomaly, (3) selected cases of FFTS, and (4) severe discordant growth. Cases with FFTS in which cord coagulation was performed after failed laser coagulation of the vascular anastomoses, were not included. The treatment protocol was approved by the 2 local ethical committees. All patients were counseled about alternative management options and gave informed consent.
Interventions Preoperatively, patients received 2 g cefazolin intravenously and 100 mg indomethacin suppositories. From January 2002 onward, indomethacin was replaced by 20 mg nifedipin orally to avoid a potential adverse effect on fetal diuresis in cases with FFTS. Cefazolin was repeated every 8 hours for 24 hours and the patient stayed on indomethacin suppositories or nifedepin orally every 12 hours for 48 hours. The procedures were performed under combined spinal-epidural anesthesia, except for the first 11, which were under general anesthesia. The site of port insertion was chosen according to the position of the placenta, the amniotic sac of the affected fetus and its cord insertion. Preferentially, entry was in
783 the sac of the target fetus. A 1.2-mm double lumen needle (Karl Storz, Tuttlingen, Germany) or a 9-10 F cannula (Cook Surgical, Bloomington, IN) was inserted under ultrasound vision. Whenever necessary, amniodrainage or amnioinfusion with warmed Hartmann’s solution was performed. Septostomy was performed by laser, when direct access to the target sac was not possible and coagulation through the intertwin septum failed. Fetoscopic laser coagulation was used as a primary technique, except in cases with hydropic cord or advanced gestational age (GA) (eg, after 24 weeks), where laser was expected to fail. Coagulation was performed by a Nd:YAG laser (Sharplan Medical, London, UK) or diode laser (Dornier MedTech, Wessling, Germany) with 400 to 600 mm fibers. The umbilical arteries and vein were coagulated over a distance of 5 to 10 cm, with the use of a nontouch technique at 30 to 50 W. Absence of flow distal to the occlusion was confirmed by color Doppler. Bipolar coagulation was always available, using either a disposable 3.0 mm forceps (Everest Medical, Maple Grove, MN) or a reusable 2.4 or 3 mm forceps (Karl Storz). Under ultrasound guidance, a portion of the umbilical cord was grasped at the fetal abdominal wall, at its placental insertion or any other appropriate place as to ensure correct identification and enhance stability. Direct contact with the placenta, fetus or membranes was avoided. Coagulation started at 15 W and applied for 15 seconds with progressive increments of 5 W until the appearance of steam bubbles indicative of local heat production and hence tissue coagulation between the forceps’ blades (usually between 30-45 W). Confirmation of arrest of flow was performed by color Doppler distal to the occlusion after the forceps was freed from the cord. Two additional cord segments were coagulated (preferentially more proximal towards the target fetus) as a safety precaution, even if there was no longer any visible flow. Patients were kept in the hospital for 48 hours and an ultrasound scan was performed 24 and 48 hours after the procedure to confirm fetal well-being. Middle cerebral artery (MCA) Dopplers to detect postoperative fetal anemia were performed from 2001 onward.10 Subsequent prenatal care, delivery, and neonatal care were provided by the referring hospitals. Data on principal indication, GA, technique, and immediate postoperative outcome were entered in the Eurofoetus fetoscopy registry, whereas details on pregnancy and neonatal outcome were obtained from the referring hospitals. All children 1 year or older were invited to the treatment center for a developmental assessment. Children between 1 to 2.5 years were assessed with the mental and motor Bayley score (BSID-II), whereas for the older children, SON-R and Peabody score were used for mental and motor development assessment, respectively. Parents living in other countries
784 were requested to visit their local pediatrician for a neurologic and developmental assessment by the same scores or if not available, by the local standards. If this was not an option, written information on the child’s neurologic development was requested via the general practitioner.
Outcome variables Primary outcome measures studied were success rate of the procedure, survival, pregnancy, and maternal complications and developmental outcome. Procedures were considered successful if arrest of flow distal to the occlusion was confirmed by color Doppler. Survival rates were defined as the number of children alive at 28 days in relation to the number of fetuses remaining after the procedure (1 for twins, 2 for triplets). IUFD was divided into early and late IUFD, occurring within 24 hours and after 24 hours of the procedure, respectively. Perinatal death was defined as demise during labor, delivery, or during the first 28 days of life. Pregnancy complications included preterm prelabor rupture of the membranes (PPROM) before 37 weeks, preterm labor, and any fetal complication detectable by ultrasound scan, such as fetal anemia requiring intrauterine transfusion. Postoperative maternal complications included severe bleeding, placental abruption, chorioamnionitis, or any other postoperative complication requiring hospitalization. Mental and motor development was classified as normal, mild, moderate, or severe delay by the pediatric neurologists at the treatment centers, the local pediatrician, or by information provided by the general practitioner. As a secondary outcome measure, survival rates according to indication, technique, amnionicity, GA, and learning curve were analyzed in twins only. Triplets were excluded from this secondary analysis, as survival of the 2 remaining fetuses is interrelated. The effect of a learning curve was examined by comparing survival and pregnancy complications in the first half of our experience with the second half. Statistical analysis involved Fisher exact or Mann-Whitney U test when appropriate at significance levels of P ! .05 (Statistica, Statsoft, Tulsa, OK).
Results Study population and principal indications Between September 1996 and January 2004, 80 patients underwent cord coagulation, including 73 MC twins (67 diamniotic-MCDA and 6 monoamniotic-MCMA), 4 MC triamniotic (MCTA), and 3 dichorionic triamniotic (DCTA) triplets (Table I). Ten cases in this series were already included in earlier reports.7,11,12 Fifty-two cases were operated on in Leuven and 28 in Barcelona.
Lewi et al
Technical details Median gestational age at surgery was 21 weeks (15-29.5 weeks). All port insertions were percutaneous through a 3-mm skin incision, apart from the first 8, which were by minilaparotomy. In 67% (54/80), the target sac could be entered. In 25% (20/80), the procedure was performed through the sac of the nontarget fetus. In about half of these (11/20), coagulation through the intertwin septum failed and a septostomy was necessary. The remaining 8% (6) were MCMA. In 7 cases (9%), an additional port was used. Median operating time was 55 minutes (range: 10-160). In 55 cases (69%), laser was used as the primary energy, but in half (27/55), additional bipolar coagulation was necessary to achieve arrest of flow. Median GA at surgery was lower for primary laser (19.4 weeks, range: 15-26) as compared with primary bipolar coagulation (22.4 weeks, range: 17-29.5; P ! .0001). In addition, cases in which laser alone was successful (18.1 weeks, range: 15-22.6) had an earlier median GA at the time of surgery as compared with cases in which laser failed (21 weeks, range: 17-26; P ! .001). All procedures were successful, except for 1 case of TRAP, in which bipolar coagulation was complicated by cord perforation, immediately followed by intraoperative IUFD. In retrospect, the initial energy was set at a higher level (50 W) than requested by the surgeon. In the 6 MCMA twins, transsection of the cord with laser or scissors was successful in 4 cases. It failed in 1 case of TRAP because of an unfavorable angle, a short umbilical cord, and the close proximity of the pump twin. In another case of TRAP, cord transsection was not attempted.
Survival, pregnancy, and maternal complications The survival rate was 83% (72/87). In twins and triplets, survival rates were comparable, 84% (61/73) and 79% (11/14), respectively (NS). There were 9 IUFDs (10%); 5 early and 4 late (Table II). There was 1 termination of pregnancy (TOP) at 23 weeks for chorioamnionitis. Finally, 5 perinatal deaths occurred because of persistent PPROM before 25 weeks (Table III). MCA Dopplers to detect fetal anemia was performed since 2001 in 49 cases and detected 1 case of fetal anemia on the first postoperative day (Hb: 7.1 g/dL), which was successfully treated with a single intrauterine blood transfusion. Median GA at delivery in ongoing pregnancies (at least 1 fetus alive at the time of delivery; n = 71) was 35.4 weeks (range: 24-40.4) and median birth weight was 2250 g (range: 617-3800). Delivery before 28 weeks occurred in 8% (6/71) and between 28-32 weeks in 13% (9/71). As such, 79% of patients delivered after 32 weeks: 41% (29/71) between 32 and 37 weeks and 38% (27/71) after 37 weeks. PPROM occurred in 38% (27/ 71). Cases with PPROM delivered at an earlier GA (32 weeks; range: 24-40 weeks) than those without PPROM
Lewi et al Table IA
785 Description of the study population, according to chorionicity and amnionicity and indication for cord occlusion
Amnionicity and chorionicity
Discordant anomaly
TRAP
Severe discordant growth
FFTS
Twin, MCDA Twin, MCMA Triplet, DCTA Triplet, MCTA Number (%)
25 3 0 0 28 (35%)
16 3 0 3 22 (27.5%)
6 0 0 0 6 (7.5%)
20 0 3 1 24 (30%)
Numbers between brackets are % where applicable. MCDA, Monochorionic diamniotic; MCMA, monochorionic monoamniotic; DCTA, dichorionic triamniotic; MCTA, monochorionic triamniotic; TRAP, twin reversed arterial perfusion; FFTS, feto-fetal transfusion syndrome; PPROM, preterm prelabor rupture of the membranes; IUGR, intrauterine growth restriction.
Table IB
Further details on the indication for feticide in discordant anomalies and FFTS
n
Discordant anomalies
8 5 5 3 3 2 1 1
Hydrocephaly Unexplained hydrops Heterokaryotypic twins Complex cardiopathies Isolated or combined abdominal wall defects Neural tube defects Megacystis Caudal regression
n
FFTS
9 7 7 1
Terminal cardiac failure (2 donors, 7 recipients) Discordant structural anomaly (5 donors: 4 hydrocephaly, 1 complex cardiopathy; 2 recipients: anencephaly) Technical limitations precluding laser (4 donors with severe IUGR, 3 recipients with abnormal Dopplers) PPROM recipient’s sac
11 donor cords
In 6, entry via donor’s sac after amnioinfusion of 200 to 750 mL In 5, entry via recipient’s sac: cord coagulation through the intertwin septum with laser (n = 3) or with bipolar coagulation (n = 2) after septostomy In all cases entry via recipient’s sac
13 recipient cords
(37 weeks; range: 29-40; P ! .0001). Also, PPROM was associated with all spontaneous deliveries before 31 weeks. Nine patients (13%) experienced PPROM before 25 weeks, but in 3 amniotic fluid leakage stopped spontaneously and in 1 after the intra-amniotic injection of platelets and cryoprecipitate (‘‘amniopatch’’)13 with delivery between 31 and 40 weeks. This leaves 5 patients (4 twins/1 triplet) with persistent PPROM before 25 weeks, accounting for all 5 perinatal deaths in this series with only 1 surviving infant born at 27 weeks with a normal motor and mental development at the age of 3. There was 1 serious maternal complication after a difficult laser and bipolar cord coagulation for severe discordant growth in MC twins at 22 weeks. Five days later, the patient presented with spiking fever and because of chorioamnionitis the pregnancy was terminated. She developed a septic shock and was admitted to the intensive care unit for 6 days with transient renal failure. S epidermidis was later diagnosed. She made a full recovery, except for a residual 30% loss of kidney function. There was 1 maternal mirror syndrome, present already before the procedure in a
patient with unexplained fetal hydrops. Mild pulmonary edema and oliguria resolved after fluid restriction and furosemide.
Developmental outcome Follow-up was available on all 72 survivors, with 67 (93%) 1 year or older. Fifty-five (82%) were assessed by a pediatrician at a median age of 1.3 years (1-6 years), of which 35 (52%) at the 2 treatment centers. Of 12 children (18%), information was provided by the general practitioner. Of the 67 children, 5 had some form of developmental delay (8%), of whom 2 were diagnosed at the treatment centre (Table III). Four were born before 29 weeks, whereas nearly all children born at a later GA developed normally (4/11 vs 1/56; P ! .01). In 3 children with delay, cord coagulation was performed after 23 weeks for TRAP with cardiac decompensation of the pump twin. As such, survivors treated for TRAP after 23 weeks more commonly had developmental problems (3/4) than those treated before 23 weeks (0/15; P ! .01). Of the 72 survivors, 5 are currently younger
786
Lewi et al
Table II
Details of cases complicated with early and late IUFD Chorionicity amnionicty
GA at procedure (wks)
Coagulation technique
Operative details
TRAP TRAP
MCDA MCDA
23 15
Bipolar Laser
Cord perforation Uncomplicated procedure
0 1
TRAP
MCTA
18
Laser
Uncomplicated procedure
1
Discordant anomaly Discordant anomaly
MCDA
22
Laser
Uncomplicated procedure
1
Fetal hemorrhage Severe cardiac failure pump preoperatively Unexplained death of the non-pump twin Unexplained
MCDA
21
Laser
Uncomplicated procedure
1
Unexplained
Indication
IUFD (days after procedure)
Presumed cause IUFD
Early IUFD
Late IUFD Discordant anomaly Severe FFTS
MCDA
16
Laser
Septostomy
28
Unexplained
MCDA
19
Septostomy
35
TRAP
MCMA
18
Laser/ Bipolar Bipolar
35
TRAP
MCDA
17
Laser
Cords entwined, not sectioned Bifurcation cord, failed transsection
Cord constriction diagnosed at birth Cord entanglement diagnosed at birth Cord entanglement diagnosed at birth
70
MCDA, Monochorionic diamniotic; MCMA, monochorionic monoamniotic; DCTA, dichorionic triamniotic; MCTA, monochorionic triamniotic; TRAP, twin reversed arterial perfusion; FFTS, feto-fetal transfusion syndrome; IUFD, intrauterine fetal death.
than 1 year. All 5 were born between 31 and 37 weeks and their neonatal course was uneventful.
Survival according to indication, technique, amnionicity, GA, and learning curve in twins only Survival rates in twins did not differ according to indication: 74% for TRAP (14/19); 86% for discordant anomaly (24/28); 90% for FFTS (18/20); and 83% (5/6) for discordant growth (NS). For FFTS, survival was similar between cord coagulation of the donor (8/9) and recipient (10/11; NS). Survival with laser only was 17 of 23 (74%) compared with 44 of 50 (88%) with bipolar as primary (22/25, 88%) or secondary technique (22/25, 88%; NS). However, all IUFDs diagnosed on the first postoperative day had cord coagulation with laser only, compared with none in the group with bipolar as primary or secondary technique (3/23 vs 0/50; P ! .05). In MCDA twins (n = 67), septostomy with subsequent iatrogenic monoamnionicity (n = 9) was associated with late IUFD in 2 pregnancies (22%), whereas no late IUFDs occurred if no septostomy was performed (0/58; P ! .05). For MCMA twins, survival rate was 67% (4/6). In 2 cases, transsection of the umbilical cord was not performed. In the first case, late IUFD occurred and cord entanglement was noted at birth, whereas in the second
case, cord entanglement caused fetal bradycardia, perinatal asphyxia, and early neonatal death after PPROM at 25.2 weeks and vaginal delivery 4 days afterward. Six bipolar cord coagulations were performed after 26 weeks (26-29.5 weeks). Indications were 1 case of TRAP, 2 FFTS, and 3 discordant anomalies. One patient developed PPROM and delivered at 31 weeks. This patient also had an intrauterine blood transfusion, as mentioned previously. Survival rate was 100% with median GA at delivery of 36 weeks (31-40 weeks). Five children (including the child with postoperative anemia) are currently 1 year or older and have a normal development. As to ascertain an effect of a learning curve, the initial 36 cord coagulations in twins were compared with the last 37. Median GA at the time of surgery was similar in both groups, 21 weeks (15-28 weeks) versus 21 weeks (15-29 weeks; NS). The median operating time did not decrease significantly over time (59 minutes [range: 20160] vs 50 minutes [range: 10-160]; NS). However, fetoscopies of more than 60 minutes were twice as common in the first compared with the second cohort (16/36 [44%] vs 8/37 [21%]; P ! .05). Also, survival rates did not improve significantly (28/36 [78%] vs 33/37 [89%] infants; NS), and the number of IUFDs was similar with 4 cases in each cohort. Although the number of infants with normal development was comparable (24/28 [86%] vs 27/28 [96%] infants; NS), 4 of the 5 children with delay
Lewi et al Table III
Indication
787 Details of cases complicated by perinatal death and /or developmental delay in survivors GA at Chorionicity procedure Coagulation technique Amnionicty (wks)
Postoperative GA at complications birth (wks) Details on perinatal death and developmental delay (wks GA)
Perinatal deaths Discordant MCDA anomaly TRAP MCMA Severe FFTS MCDA
18
Laser/bipolar PPROM (19)
24
Intrapartum death: chorioamnionitis
24 20
Bipolar Laser
PPROM (25) PPROM (25)
26 26
Neonatal death: asphyxia with cord entanglement Neonatal death: necrotising enterocolitis
Severe FFTS DCTA
22
Laser
PPROM (25)
25
Neonatal death: recipient: cardiac failure, Neonatal death: noninvolved fetus: necrotizing enterocolitis Gr 2 leucomalacia on early brain scan, mild mental and motor delay at 1.5 y according to Bayley score Gr 2 leucomalacia on early brain scan, severe mental delay at 5 y according to pediatrician Unilateral mild ventriculomegaly on early brain scan, mild motor delay at 1.5 y according to Bayley score Gr 3 intraventricular hemorrhage on early brain scan, mild motor delay at 1 y according to Bayley score Normal early brainscan, mild motor delay at 1.5 y according to pediatrician
Survivors with developmental delay TRAP
MCDA
23
Laser/bipolar PPROM (28)
28
TRAP
MCDA
25
Laser/bipolar PPROM (29)
29
TRAP
MCDA
23.5
29
24
Laser/bipolar Fetal distress (29) Laser/bipolar PPROM (26)
28
19
Bipolar
34
Discordant MCDA growth Severe FFTS MCDA
Severe IUGRabnormal CTG (34)
MCDA, Monochorionic diamniotic; MCMA, monochorionic monoamniotic; DCTA, dichorionic triamiotic; MCTA, monochorionic triamiotic; TRAP, twin reversed arterial perfusion; FFTS, feto-fetal transfusion syndrome; PPROM, preterm prelabour rupture of the membranes; IUGR, intrauterine growth restriction; CTG, cardiotocography.
were treated in the first cohort. Significantly, PPROM before 31 weeks occurred in 13 of 31 (42%) ongoing pregnancies in the first compared with 2 of 33 (6%) pregnancies in the last cohort (P ! .001), in which both cases occurred at 30 weeks. Also, all perinatal deaths with persistent PPROM before 25 weeks were in the first cohort. Although median GA at delivery was similar in both cohorts, 35 weeks (24-40 weeks) and 36 weeks (30-40 weeks), the number of deliveries before 31 weeks was higher in the first cohort, 35% (11/31) versus 3% (1/33; P ! .001).
Comment In this series of 80 cord coagulations, the survival rate was 83% and 92% of infants had a normal development. This is the first large prospective study that reports not only on pregnancy but also on infant outcome, with a 100% follow-up rate. So far, cord coagulation with laser energy has only been described for the management of TRAP (n = 5).5,6 Also, only small case series have reported on the pregnancy outcome after bipolar cord coagulation: 1 series for the management of FFTS (n = 15)9 and 2 other (n = 10, n = 17)7,8 for similar indications as in our study, with survival rates of 90%, 80%, and 76%, respectively.
In dichorionic twins, the mortality of selective feticide for discordant anomalies is less than 10% and largely attributable to miscarriage or severe preterm delivery.14 In MC twins, the mortality of cord coagulation caused by severe preterm delivery was 4% (3/73). However, there was an additional 11% (8/73) loss because of IUFD, which rarely complicates selective feticide in dichorionic twins. The more complex technique of cord coagulation and the shared circulation with possible feto-fetal hemorrhage may account for this extra loss. Half were early IUFDs and had laser coagulation only, whereas the other half were late IUFDs, with 3 of 4 most likely related to cord complications. Late IUFD was more common after septostomy. Indeed, iatrogenic disruption of the intertwin septum may lead to cord entanglement and sudden IUFD as in naturally occurring monoamniotic twins.15 Also, in 1 case of TRAP in MCDA twins, the cord of the acardiac originated directly from the pump’s cord, which led to late IUFD with entangled cords at birth. Septostomy should therefore be avoided where possible and transsection of the cord may be beneficial in MCMA twins, after septostomy as well as in cases of TRAP where the acadiac’s cord originates directly from the pump’s cord. Laser was used as primary energy source in 69%, but in about half of cases additional bipolar coagulation was
788 required to achieve arrest of flow, especially after 21 weeks. Also, all IUFDs diagnosed on the first postoperative day had cord coagulation with laser only. If the cord vessels are large, laser may only partly or temporarily occlude the vessels. Here, Doppler may give a false impression of complete cord occlusion, either because of asystole in the target fetus or only temporary occlusion with later reopening of vessels. Bipolar cord coagulation appears to be a more reliable technique, although laser still has its specific indications. As such, for cord coagulation at an early GA (eg, 16 weeks), fetoscopic laser can be performed through a 1.2-mm double lumen needle, whereas bipolar coagulation is performed through a 3.3-mm cannula. Also, for coagulation of the donor’s cord in cases of FFTS where the only entry is via recipient’s sac, laser can often coagulate the cord through the interwin septum, whereas bipolar coagulation more commonly requires a septostomy. PPROM was associated with all spontaneous deliveries before 31 weeks and for all perinatal deaths. Therefore, PPROM and not preterm labor is the Achilles’ heel of this type of intervention. One patient with persistent PPROM before 25 weeks had no further amniotic fluid leakage after an amniopatch was administered and she delivered at 31 weeks. A therapeutic amniopatch procedure may therefore reduce the perinatal mortality associated with postoperative PPROM.13 Also, PPROM before 31 weeks decreased from 42% to 6% with increasing experience, probably partly related to a decrease in the number of lengthy procedures. This underscores the need to restrict this procedure to a limited number of hands. Finally, for isolated discordant anomalies with no immediate threat to the healthy twin, delay of the procedure until after 26 weeksdif legally and morally acceptabledobviates the risk of PPROM very early in gestation. In this series, cord coagulation after 26 weeks was associated with a 100% survival rate and all deliveries were between 31 and 40 weeks. Although larger series are required to assess the true incidence of severe maternal complications, this study illustrates that cord coagulation is in general a safe procedure for the mother. One patient had chorioamnionitis and septic shock develop after a difficult procedure. Severe chorioamnionitis has been reported after any invasive procedure, including amniocentesis and is estimated to be rare.16 Its true incidence after cord coagulation can only be established in larger series, and that is why we plead for ongoing registration of cases in the Eurofoetus registry (http://www.eurofoetus.org). Of the 67 children older than 1 year, 4 children had mild and 1 had severe developmental delay. Although 82% of the children were evaluated by a pediatrician, the assessment of developmental outcome in our series would have been more accurate if all children had been evaluated at the 2 treatment centers with the same
Lewi et al assessments tools. In this series, this was not possible, as many patients were referred from other countries. As 3 of the 5 patients with delay were diagnosed elsewhere, we believe our data give an accurate estimate of developmental delay in infancy, although more developmental problems may become apparent only at a later age. Developmental problems may arise from the underlying disease, the intervention as well as from severe preterm delivery. This series is too small to assess the relative contribution of each of these factors. All the children with delay were born before 29 weeks, except for 1 child born at 34 weeks. At the same time, 3 of the children with delay were treated for TRAP after 23 weeks and 2 had grade 2 leucomalacia on early brain scan. Cardiac failure or chronic hypoxemia may have caused brain damage before the procedure and thereby contributed to the observed developmental delay. This observation may favor prophylactic intervention in cases of TRAP, rather than await signs of cardiac decompensation later on. Because of the higher mortality of selective feticide in MC pregnancies compared with multichorionic pregnancies, indications must be carefully balanced. For TRAP, the survival rate of cord coagulation was 74%. The natural history of TRAP remains poorly documented, and reported survival rates vary widely between 14% and 90%.17,18 Data on long-term outcome of pump twins are not available, although the risk of cardiac19 and neurodevelopmental20 complications may be high because of chronic hemodynamic imbalances in utero and severe preterm delivery. As mentioned previously, there may be a place for prophylactic cord coagulation before cardiac decompensation of the pump twin occurs, but a larger series will need to confirm this. For severe discordant anomalies, cord occlusion is a valid alternative to termination of the whole pregnancy. For anomalies with a high likelihood of spontaneous IUFD, expectant management may be preferable in dichorionic twins. However, in MC pregnancies this specifically warrants a selective feticide, as IUFD of 1 twin will lead to demise of the co-twin in 10% to 25%, and cerebral damage in 25% to 45% because of acute feto-fetal hemorrhage in addition to the risks of severe prematurity.21,22 For discordant anomalies that do not threaten the well-being of the other fetus(es), delay of the procedure until after 26 weeks may reduce the risks for the healthy twin. For FFTS, laser coagulation of the vascular anastomoses remains the preferred first line treatment,23 although selective feticide may be indicated in selected cases. Finally, for severe discordant growth, umbilical cord coagulation may be considered, when there are signs of imminent IUFD before viability. Two recent series24,25 highlight the risks of severe discordant growth in MC twins. In 1 series (n = 13),24 42% of children had an abnormal development and 19% had cerebral palsy. There were 4 IUFDs and all 3 surviving children had cerebral palsy. In the other series (n = 42),25 12% of neonates had
Lewi et al parenchymal brain lesions on postnatal brain scan and the IUFD rate was 10%. As a conclusion, cord coagulation is an effective procedure for selective feticide in complicated MC twins as well as triplets. The information provided in this article may be useful for fetal medicine specialists who actually perform this procedure as well as for patients who are confronted with a complicated MC pregnancy.
References 1. Denbow ML, Cox P, Taylor M, Hammal DM, Fisk NM. Placental angioarchitecture in monochorionic twin pregnancies: relationship to fetal growth, fetofetal transfusion syndrome, and pregnancy outcome. Am J Obstet Gynecol 2000;182:417-26. 2. Lewi L, Van Schoubroeck D, Gratacos E, Witters I, Timmerman D, Deprest J. Monochorionic diamniotic twins: complications and management options. Curr Opin Obstet Gynecol 2003;15:177-94. 3. Bryan E, Little J, Burn J. Congenital anomalies in twins. Baillieres Clin Obstet Gynecol 1987;1:697-721. 4. Challis D, Grataco´s E, Deprest J. Selective termination in monochorionic twins. J Perinat Med 1999;27:327-38. 5. Hecher K, Hackeloer BJ, Ville Y. Umbilical cord coagulation by operative microendoscopy at 16 weeks’ gestation in an acardiac twin. Ultrasound Obstet Gynecol 1997;10:130-2. 6. Ville Y, Hyett JA, Vandenbussche FP, Nicolaides KH. Endoscopic laser coagulation of umbilical cord vessels in twin reversed arterial perfusion sequence. Ultrasound Obstet Gynecol 1994;4:396-8. 7. Deprest JA, Audibert F, Van Schoubroeck D, Hecher K, MahieuCaputo D. Bipolar cord coagulation of the umbilical cord in complicated monochorionic twin pregnancy. Am J Obstet Gynecol 2000;182:340-5. 8. Nicolini U, Poblete A, Boschetto C, Bonati F, Roberts A. Complicated monochorionic twin pregnancies: experience with bipolar cord coagulation. Am J Obstet Gynecol 2000;185:703-7. 9. Taylor MJ, Shalev E, Tanawattanacharoen S, Jolly M, Kumar S, Weiner E, et al. Ultrasound-guided umbilical cord occlusion using bipolar diathermy for Stage III/IV twin-twin transfusion syndrome. Prenat Diagn 2002;22:70-6. 10. Senat MV, Loizeau S, Couderc S, Bernard JP, Ville Y. The value of middle cerebral artery peak systolic velocity in the diagnosis of fetal anemia after intrauterine death of one monochorionic twin. Am J Obstet Gynecol 2003;189:1320-4. 11. Van Schoubroeck D, Lewi L, Ryan G, Jani J, Deprest J, Gratacos E. Fetocopic surgery in monochorionic and dichorionic triplet pregnancyda multicenter case series. Am J Obstet Gynecol 2004;191:1529-32.
789 12. Lewi L, Van Schoubroeck D, Van Ranst M, Bries G, Edmonds M-P, Arabin B, et al. Successful patching of iatrogenic rupture of the fetal membranes. Placenta 2004;25:352-6. 13. Quintero RA, Morales WJ, Allen M, Bornick PW, Arroyo J, LeParc G. Treatment of iatrogenic previable premature rupture of membranes with intra-amniotic injection of platelets and cryoprecipitate (amniopatch): preliminary experience. Am J Obstet Gynecol 1999;181:744-9. 14. Evans MI, Goldberg JD, Horenstein J, Wapner RJ, Ayoub MA, Stone J, et al. Selective termination for structural, chromosomal, and mendelian anomalies: international experience. Am J Obstet Gynecol 1999;181:893-7. 15. Feldman DM, Odibo A, Campbell WA, Rodis JF. Iatrogenic monoamniotic twins as a complication of therapeutic amniocentesis. Obstet Gynecol 1998;91:815-6. 16. Elchalal U, Shachar IB, Peleg D, Schenker JG. Maternal mortality following diagnostic 2nd-trimester amniocentesis. Fetal Diagn Ther 2004;19:195-8. 17. Sogaard K, Skibsted L, Brocks V. Acardiac twins: pathophysiology, diagnosis, outcome and treatment. Six cases and review of the literature. Fetal Diagn Ther 1999;14:53-9. 18. Sullivan AE, Varner MW, Ball RH, Jackson M, Silver RM. The management of acardiac twins: a conservative approach. Am J Obstet Gynecol 2003;189:1310-3. 19. Chandra S, Crane JM, Young DC, Shah S. Acardiac twin pregnancy with neonatal resolution of donor twin cardiomyopathy. Obstet Gynecol 2000;96(Pt 2):820-1. 20. Kosno-Kruszewska E, Deregowski K, Schmidt-Sidor B, WierzbaBobrowicz T, Pawlowska B, Lechowicz W, et al. Neuropathological and anatomopathological analyses of acardiac and ‘‘normal’’ siblings in an acardiac-twin pregnancy. Folia Neuropathol 2003; 41:103-9. 21. Bajoria R, Wee LY, Anwar S, Ward S. Outcome of twin pregnancies complicated by single intrauterine death in relation to vascular anatomy of the monochorionic placenta. Hum Reprod 1999;14: 2124-30. 22. Nicolini U, Poblete A. Single intrauterine death in monochorionic twins pregnancies. Ultrasound Obstet Gynecol 1999;14:297-301. 23. Senat MV, Deprest J, Boulvain M, Paupe A, Winer N, Ville Y. Endoscopic laser surgery versus serial amnioreduction for severe twin-to-twin transfusion syndrome. N Engl J Med 2004;351: 136-44. 24. Adegbite AL, Castille S, Ward S, Bajoria R. Neuromorbidity in preterm twins in relation to chorionicity and discordant birth weight. Am J Obstet Gynecol 2004;190:156-63. 25. Gratacos E, Carreras E, Becker J, Lewi L, Enriquez G, Perapoch J, et al. Prevalence of neurological damage in monochorionic twins with selective intrauterine growth restriction and intermittent absent or reversed end-diastolic umbilical artery flow. Ultrasound Obstet Gynecol 2004;24:159-63.
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Pregnancy and infant outcome of 80 consecutive cord coagulations in complicated monochorionic multiple pregnancies Liesbeth Lewi, MD,a Eduardo Gratacos, MD, PhD,b Els Ortibus, MD,a Dominique Van Schoubroeck, MD,a Elena Carreras, MD,b Teresa Higueras, MD,b Josep Perapoch, MD,b Jan Deprest, MD, PhDa,* UZ-Gasthuisberg, Leuven, Belgiuma; Hospital Vall d’Hebron, Barcelona, Spainb Received for publication May 1, 2005; revised September 9, 2005; accepted September 29, 2005
KEY WORDS Cord coagulation Monochorionic Multiple pregnancy Selective feticide
Objective: This study was undertaken to document pregnancy and infant outcome after cord coagulation with laser and/or bipolar as a technique for selective feticide in complicated monochorionic multiple pregnancies. Study design: Prospective follow-up study in 2 tertiary fetal medicine centers. Results: Eighty cases were included in the study (73 twins, 7 triplets). The survival rate was 83% (72/87). There were 9 intrauterine fetal deaths (10%), 5 within 24 hours and 4 between 4 and 10 weeks after the procedure. There was 1 termination of pregnancy because of chorioamnionitis. Median gestational age at delivery was 35.4 weeks, with 79% of patients delivering after 32 weeks. Preterm prelabor rupture of the membranes before 25 weeks accounted for all perinatal deaths (n = 5). Of the children older than 1 year of age (n = 67), 62 (92%) have a normal development. Conclusion: Cord coagulation is an effective method for selective feticide in monochorionic multiple pregnancies. Ó 2006 Mosby, Inc. All rights reserved.
In monochorionic (MC) multiple pregnancies, the fetuses share a single placenta and in almost all cases vascular anastomoses connect the fetal circulations.1 Dr Lewi is the recipient of a grant from the 5th Framework Program of the European Commission (no. QLG1-CT-2002-01632 EuroTwin2Twin). Presented in abstract form at the 2003 International Fetal-Maternal Medicine Society Meeting, San Francisco, CA, and the 2003 ISUOG Meeting, Paris, France. * Reprint requests: Jan Deprest, MD, PhD, Department of Obstetrics and Gynecology, UZ Leuven, B-3000 Leuven, Belgium. E-mail: [email protected] 0002-9378/$ - see front matter Ó 2006 Mosby, Inc. All rights reserved. doi:10.1016/j.ajog.2005.09.013
This shared fetal circulation accounts for some unique complications, such as feto-fetal transfusion syndrome (FFTS), twin reversed arterial perfusion (TRAP), and acute feto-fetal hemorrhage of the survivor after single intrauterine fetal death (IUFD).2 MC multiplets are also at higher risk of structural anomalies, with usually only 1 fetus affected.3 Selective feticide in MC pregnancies may be considered if 1 fetus threatens the well-being of the other(s) and/or has a severe anomaly. However, the conventional method of fetal intravascular potassium chloride injection as used in multichorionic pregnancies is unsuitable, as the substance may embolize
Lewi et al to the healthy fetus(es) and patent anastomoses may cause acute feto-fetal hemorrhage of the survivor into the demised fetus’ circulation. Therefore, a number of minimally invasive procedures were developed to produce complete circulatory confinement of the affected fetus.4 Fetoscopic laser cord coagulation can be performed already at 16 weeks and allows optimal visual control, but may fail in the late second or early third trimester because of increasing size of the cord vessels.5,6 At later gestational ages, ultrasound guided bipolar cord coagulation is the preferred method.7-9 Cord coagulation is now performed by an increasing number of fetal medicine units. However, data on pregnancy outcome are limited to small case series, and the developmental outcome of survivors has not been documented yet. We therefore evaluated pregnancy and infant outcome in a prospective series of 80 cord coagulations.
Patients and methods Design and study population This is a prospective follow-up study of MC pregnancies that underwent laser and/or bipolar cord coagulation as a primary procedure in 2 tertiary fetal medicine centers. The patients were operated on by 2 surgeons (J.D.P. and E.G.), who started the fetoscopy program together in Leuven between 1997 and 2000. During the study, Dr Gratacos was promoted to Barcelona, and the patients treated there were also included. Cord coagulation was offered for the following conditions in MC pregnancies: (1) TRAP, (2) severe discordant anomaly, (3) selected cases of FFTS, and (4) severe discordant growth. Cases with FFTS in which cord coagulation was performed after failed laser coagulation of the vascular anastomoses, were not included. The treatment protocol was approved by the 2 local ethical committees. All patients were counseled about alternative management options and gave informed consent.
Interventions Preoperatively, patients received 2 g cefazolin intravenously and 100 mg indomethacin suppositories. From January 2002 onward, indomethacin was replaced by 20 mg nifedipin orally to avoid a potential adverse effect on fetal diuresis in cases with FFTS. Cefazolin was repeated every 8 hours for 24 hours and the patient stayed on indomethacin suppositories or nifedepin orally every 12 hours for 48 hours. The procedures were performed under combined spinal-epidural anesthesia, except for the first 11, which were under general anesthesia. The site of port insertion was chosen according to the position of the placenta, the amniotic sac of the affected fetus and its cord insertion. Preferentially, entry was in
783 the sac of the target fetus. A 1.2-mm double lumen needle (Karl Storz, Tuttlingen, Germany) or a 9-10 F cannula (Cook Surgical, Bloomington, IN) was inserted under ultrasound vision. Whenever necessary, amniodrainage or amnioinfusion with warmed Hartmann’s solution was performed. Septostomy was performed by laser, when direct access to the target sac was not possible and coagulation through the intertwin septum failed. Fetoscopic laser coagulation was used as a primary technique, except in cases with hydropic cord or advanced gestational age (GA) (eg, after 24 weeks), where laser was expected to fail. Coagulation was performed by a Nd:YAG laser (Sharplan Medical, London, UK) or diode laser (Dornier MedTech, Wessling, Germany) with 400 to 600 mm fibers. The umbilical arteries and vein were coagulated over a distance of 5 to 10 cm, with the use of a nontouch technique at 30 to 50 W. Absence of flow distal to the occlusion was confirmed by color Doppler. Bipolar coagulation was always available, using either a disposable 3.0 mm forceps (Everest Medical, Maple Grove, MN) or a reusable 2.4 or 3 mm forceps (Karl Storz). Under ultrasound guidance, a portion of the umbilical cord was grasped at the fetal abdominal wall, at its placental insertion or any other appropriate place as to ensure correct identification and enhance stability. Direct contact with the placenta, fetus or membranes was avoided. Coagulation started at 15 W and applied for 15 seconds with progressive increments of 5 W until the appearance of steam bubbles indicative of local heat production and hence tissue coagulation between the forceps’ blades (usually between 30-45 W). Confirmation of arrest of flow was performed by color Doppler distal to the occlusion after the forceps was freed from the cord. Two additional cord segments were coagulated (preferentially more proximal towards the target fetus) as a safety precaution, even if there was no longer any visible flow. Patients were kept in the hospital for 48 hours and an ultrasound scan was performed 24 and 48 hours after the procedure to confirm fetal well-being. Middle cerebral artery (MCA) Dopplers to detect postoperative fetal anemia were performed from 2001 onward.10 Subsequent prenatal care, delivery, and neonatal care were provided by the referring hospitals. Data on principal indication, GA, technique, and immediate postoperative outcome were entered in the Eurofoetus fetoscopy registry, whereas details on pregnancy and neonatal outcome were obtained from the referring hospitals. All children 1 year or older were invited to the treatment center for a developmental assessment. Children between 1 to 2.5 years were assessed with the mental and motor Bayley score (BSID-II), whereas for the older children, SON-R and Peabody score were used for mental and motor development assessment, respectively. Parents living in other countries
784 were requested to visit their local pediatrician for a neurologic and developmental assessment by the same scores or if not available, by the local standards. If this was not an option, written information on the child’s neurologic development was requested via the general practitioner.
Outcome variables Primary outcome measures studied were success rate of the procedure, survival, pregnancy, and maternal complications and developmental outcome. Procedures were considered successful if arrest of flow distal to the occlusion was confirmed by color Doppler. Survival rates were defined as the number of children alive at 28 days in relation to the number of fetuses remaining after the procedure (1 for twins, 2 for triplets). IUFD was divided into early and late IUFD, occurring within 24 hours and after 24 hours of the procedure, respectively. Perinatal death was defined as demise during labor, delivery, or during the first 28 days of life. Pregnancy complications included preterm prelabor rupture of the membranes (PPROM) before 37 weeks, preterm labor, and any fetal complication detectable by ultrasound scan, such as fetal anemia requiring intrauterine transfusion. Postoperative maternal complications included severe bleeding, placental abruption, chorioamnionitis, or any other postoperative complication requiring hospitalization. Mental and motor development was classified as normal, mild, moderate, or severe delay by the pediatric neurologists at the treatment centers, the local pediatrician, or by information provided by the general practitioner. As a secondary outcome measure, survival rates according to indication, technique, amnionicity, GA, and learning curve were analyzed in twins only. Triplets were excluded from this secondary analysis, as survival of the 2 remaining fetuses is interrelated. The effect of a learning curve was examined by comparing survival and pregnancy complications in the first half of our experience with the second half. Statistical analysis involved Fisher exact or Mann-Whitney U test when appropriate at significance levels of P ! .05 (Statistica, Statsoft, Tulsa, OK).
Results Study population and principal indications Between September 1996 and January 2004, 80 patients underwent cord coagulation, including 73 MC twins (67 diamniotic-MCDA and 6 monoamniotic-MCMA), 4 MC triamniotic (MCTA), and 3 dichorionic triamniotic (DCTA) triplets (Table I). Ten cases in this series were already included in earlier reports.7,11,12 Fifty-two cases were operated on in Leuven and 28 in Barcelona.
Lewi et al
Technical details Median gestational age at surgery was 21 weeks (15-29.5 weeks). All port insertions were percutaneous through a 3-mm skin incision, apart from the first 8, which were by minilaparotomy. In 67% (54/80), the target sac could be entered. In 25% (20/80), the procedure was performed through the sac of the nontarget fetus. In about half of these (11/20), coagulation through the intertwin septum failed and a septostomy was necessary. The remaining 8% (6) were MCMA. In 7 cases (9%), an additional port was used. Median operating time was 55 minutes (range: 10-160). In 55 cases (69%), laser was used as the primary energy, but in half (27/55), additional bipolar coagulation was necessary to achieve arrest of flow. Median GA at surgery was lower for primary laser (19.4 weeks, range: 15-26) as compared with primary bipolar coagulation (22.4 weeks, range: 17-29.5; P ! .0001). In addition, cases in which laser alone was successful (18.1 weeks, range: 15-22.6) had an earlier median GA at the time of surgery as compared with cases in which laser failed (21 weeks, range: 17-26; P ! .001). All procedures were successful, except for 1 case of TRAP, in which bipolar coagulation was complicated by cord perforation, immediately followed by intraoperative IUFD. In retrospect, the initial energy was set at a higher level (50 W) than requested by the surgeon. In the 6 MCMA twins, transsection of the cord with laser or scissors was successful in 4 cases. It failed in 1 case of TRAP because of an unfavorable angle, a short umbilical cord, and the close proximity of the pump twin. In another case of TRAP, cord transsection was not attempted.
Survival, pregnancy, and maternal complications The survival rate was 83% (72/87). In twins and triplets, survival rates were comparable, 84% (61/73) and 79% (11/14), respectively (NS). There were 9 IUFDs (10%); 5 early and 4 late (Table II). There was 1 termination of pregnancy (TOP) at 23 weeks for chorioamnionitis. Finally, 5 perinatal deaths occurred because of persistent PPROM before 25 weeks (Table III). MCA Dopplers to detect fetal anemia was performed since 2001 in 49 cases and detected 1 case of fetal anemia on the first postoperative day (Hb: 7.1 g/dL), which was successfully treated with a single intrauterine blood transfusion. Median GA at delivery in ongoing pregnancies (at least 1 fetus alive at the time of delivery; n = 71) was 35.4 weeks (range: 24-40.4) and median birth weight was 2250 g (range: 617-3800). Delivery before 28 weeks occurred in 8% (6/71) and between 28-32 weeks in 13% (9/71). As such, 79% of patients delivered after 32 weeks: 41% (29/71) between 32 and 37 weeks and 38% (27/71) after 37 weeks. PPROM occurred in 38% (27/ 71). Cases with PPROM delivered at an earlier GA (32 weeks; range: 24-40 weeks) than those without PPROM
Lewi et al Table IA
785 Description of the study population, according to chorionicity and amnionicity and indication for cord occlusion
Amnionicity and chorionicity
Discordant anomaly
TRAP
Severe discordant growth
FFTS
Twin, MCDA Twin, MCMA Triplet, DCTA Triplet, MCTA Number (%)
25 3 0 0 28 (35%)
16 3 0 3 22 (27.5%)
6 0 0 0 6 (7.5%)
20 0 3 1 24 (30%)
Numbers between brackets are % where applicable. MCDA, Monochorionic diamniotic; MCMA, monochorionic monoamniotic; DCTA, dichorionic triamniotic; MCTA, monochorionic triamniotic; TRAP, twin reversed arterial perfusion; FFTS, feto-fetal transfusion syndrome; PPROM, preterm prelabor rupture of the membranes; IUGR, intrauterine growth restriction.
Table IB
Further details on the indication for feticide in discordant anomalies and FFTS
n
Discordant anomalies
8 5 5 3 3 2 1 1
Hydrocephaly Unexplained hydrops Heterokaryotypic twins Complex cardiopathies Isolated or combined abdominal wall defects Neural tube defects Megacystis Caudal regression
n
FFTS
9 7 7 1
Terminal cardiac failure (2 donors, 7 recipients) Discordant structural anomaly (5 donors: 4 hydrocephaly, 1 complex cardiopathy; 2 recipients: anencephaly) Technical limitations precluding laser (4 donors with severe IUGR, 3 recipients with abnormal Dopplers) PPROM recipient’s sac
11 donor cords
In 6, entry via donor’s sac after amnioinfusion of 200 to 750 mL In 5, entry via recipient’s sac: cord coagulation through the intertwin septum with laser (n = 3) or with bipolar coagulation (n = 2) after septostomy In all cases entry via recipient’s sac
13 recipient cords
(37 weeks; range: 29-40; P ! .0001). Also, PPROM was associated with all spontaneous deliveries before 31 weeks. Nine patients (13%) experienced PPROM before 25 weeks, but in 3 amniotic fluid leakage stopped spontaneously and in 1 after the intra-amniotic injection of platelets and cryoprecipitate (‘‘amniopatch’’)13 with delivery between 31 and 40 weeks. This leaves 5 patients (4 twins/1 triplet) with persistent PPROM before 25 weeks, accounting for all 5 perinatal deaths in this series with only 1 surviving infant born at 27 weeks with a normal motor and mental development at the age of 3. There was 1 serious maternal complication after a difficult laser and bipolar cord coagulation for severe discordant growth in MC twins at 22 weeks. Five days later, the patient presented with spiking fever and because of chorioamnionitis the pregnancy was terminated. She developed a septic shock and was admitted to the intensive care unit for 6 days with transient renal failure. S epidermidis was later diagnosed. She made a full recovery, except for a residual 30% loss of kidney function. There was 1 maternal mirror syndrome, present already before the procedure in a
patient with unexplained fetal hydrops. Mild pulmonary edema and oliguria resolved after fluid restriction and furosemide.
Developmental outcome Follow-up was available on all 72 survivors, with 67 (93%) 1 year or older. Fifty-five (82%) were assessed by a pediatrician at a median age of 1.3 years (1-6 years), of which 35 (52%) at the 2 treatment centers. Of 12 children (18%), information was provided by the general practitioner. Of the 67 children, 5 had some form of developmental delay (8%), of whom 2 were diagnosed at the treatment centre (Table III). Four were born before 29 weeks, whereas nearly all children born at a later GA developed normally (4/11 vs 1/56; P ! .01). In 3 children with delay, cord coagulation was performed after 23 weeks for TRAP with cardiac decompensation of the pump twin. As such, survivors treated for TRAP after 23 weeks more commonly had developmental problems (3/4) than those treated before 23 weeks (0/15; P ! .01). Of the 72 survivors, 5 are currently younger
786
Lewi et al
Table II
Details of cases complicated with early and late IUFD Chorionicity amnionicty
GA at procedure (wks)
Coagulation technique
Operative details
TRAP TRAP
MCDA MCDA
23 15
Bipolar Laser
Cord perforation Uncomplicated procedure
0 1
TRAP
MCTA
18
Laser
Uncomplicated procedure
1
Discordant anomaly Discordant anomaly
MCDA
22
Laser
Uncomplicated procedure
1
Fetal hemorrhage Severe cardiac failure pump preoperatively Unexplained death of the non-pump twin Unexplained
MCDA
21
Laser
Uncomplicated procedure
1
Unexplained
Indication
IUFD (days after procedure)
Presumed cause IUFD
Early IUFD
Late IUFD Discordant anomaly Severe FFTS
MCDA
16
Laser
Septostomy
28
Unexplained
MCDA
19
Septostomy
35
TRAP
MCMA
18
Laser/ Bipolar Bipolar
35
TRAP
MCDA
17
Laser
Cords entwined, not sectioned Bifurcation cord, failed transsection
Cord constriction diagnosed at birth Cord entanglement diagnosed at birth Cord entanglement diagnosed at birth
70
MCDA, Monochorionic diamniotic; MCMA, monochorionic monoamniotic; DCTA, dichorionic triamniotic; MCTA, monochorionic triamniotic; TRAP, twin reversed arterial perfusion; FFTS, feto-fetal transfusion syndrome; IUFD, intrauterine fetal death.
than 1 year. All 5 were born between 31 and 37 weeks and their neonatal course was uneventful.
Survival according to indication, technique, amnionicity, GA, and learning curve in twins only Survival rates in twins did not differ according to indication: 74% for TRAP (14/19); 86% for discordant anomaly (24/28); 90% for FFTS (18/20); and 83% (5/6) for discordant growth (NS). For FFTS, survival was similar between cord coagulation of the donor (8/9) and recipient (10/11; NS). Survival with laser only was 17 of 23 (74%) compared with 44 of 50 (88%) with bipolar as primary (22/25, 88%) or secondary technique (22/25, 88%; NS). However, all IUFDs diagnosed on the first postoperative day had cord coagulation with laser only, compared with none in the group with bipolar as primary or secondary technique (3/23 vs 0/50; P ! .05). In MCDA twins (n = 67), septostomy with subsequent iatrogenic monoamnionicity (n = 9) was associated with late IUFD in 2 pregnancies (22%), whereas no late IUFDs occurred if no septostomy was performed (0/58; P ! .05). For MCMA twins, survival rate was 67% (4/6). In 2 cases, transsection of the umbilical cord was not performed. In the first case, late IUFD occurred and cord entanglement was noted at birth, whereas in the second
case, cord entanglement caused fetal bradycardia, perinatal asphyxia, and early neonatal death after PPROM at 25.2 weeks and vaginal delivery 4 days afterward. Six bipolar cord coagulations were performed after 26 weeks (26-29.5 weeks). Indications were 1 case of TRAP, 2 FFTS, and 3 discordant anomalies. One patient developed PPROM and delivered at 31 weeks. This patient also had an intrauterine blood transfusion, as mentioned previously. Survival rate was 100% with median GA at delivery of 36 weeks (31-40 weeks). Five children (including the child with postoperative anemia) are currently 1 year or older and have a normal development. As to ascertain an effect of a learning curve, the initial 36 cord coagulations in twins were compared with the last 37. Median GA at the time of surgery was similar in both groups, 21 weeks (15-28 weeks) versus 21 weeks (15-29 weeks; NS). The median operating time did not decrease significantly over time (59 minutes [range: 20160] vs 50 minutes [range: 10-160]; NS). However, fetoscopies of more than 60 minutes were twice as common in the first compared with the second cohort (16/36 [44%] vs 8/37 [21%]; P ! .05). Also, survival rates did not improve significantly (28/36 [78%] vs 33/37 [89%] infants; NS), and the number of IUFDs was similar with 4 cases in each cohort. Although the number of infants with normal development was comparable (24/28 [86%] vs 27/28 [96%] infants; NS), 4 of the 5 children with delay
Lewi et al Table III
Indication
787 Details of cases complicated by perinatal death and /or developmental delay in survivors GA at Chorionicity procedure Coagulation technique Amnionicty (wks)
Postoperative GA at complications birth (wks) Details on perinatal death and developmental delay (wks GA)
Perinatal deaths Discordant MCDA anomaly TRAP MCMA Severe FFTS MCDA
18
Laser/bipolar PPROM (19)
24
Intrapartum death: chorioamnionitis
24 20
Bipolar Laser
PPROM (25) PPROM (25)
26 26
Neonatal death: asphyxia with cord entanglement Neonatal death: necrotising enterocolitis
Severe FFTS DCTA
22
Laser
PPROM (25)
25
Neonatal death: recipient: cardiac failure, Neonatal death: noninvolved fetus: necrotizing enterocolitis Gr 2 leucomalacia on early brain scan, mild mental and motor delay at 1.5 y according to Bayley score Gr 2 leucomalacia on early brain scan, severe mental delay at 5 y according to pediatrician Unilateral mild ventriculomegaly on early brain scan, mild motor delay at 1.5 y according to Bayley score Gr 3 intraventricular hemorrhage on early brain scan, mild motor delay at 1 y according to Bayley score Normal early brainscan, mild motor delay at 1.5 y according to pediatrician
Survivors with developmental delay TRAP
MCDA
23
Laser/bipolar PPROM (28)
28
TRAP
MCDA
25
Laser/bipolar PPROM (29)
29
TRAP
MCDA
23.5
29
24
Laser/bipolar Fetal distress (29) Laser/bipolar PPROM (26)
28
19
Bipolar
34
Discordant MCDA growth Severe FFTS MCDA
Severe IUGRabnormal CTG (34)
MCDA, Monochorionic diamniotic; MCMA, monochorionic monoamniotic; DCTA, dichorionic triamiotic; MCTA, monochorionic triamiotic; TRAP, twin reversed arterial perfusion; FFTS, feto-fetal transfusion syndrome; PPROM, preterm prelabour rupture of the membranes; IUGR, intrauterine growth restriction; CTG, cardiotocography.
were treated in the first cohort. Significantly, PPROM before 31 weeks occurred in 13 of 31 (42%) ongoing pregnancies in the first compared with 2 of 33 (6%) pregnancies in the last cohort (P ! .001), in which both cases occurred at 30 weeks. Also, all perinatal deaths with persistent PPROM before 25 weeks were in the first cohort. Although median GA at delivery was similar in both cohorts, 35 weeks (24-40 weeks) and 36 weeks (30-40 weeks), the number of deliveries before 31 weeks was higher in the first cohort, 35% (11/31) versus 3% (1/33; P ! .001).
Comment In this series of 80 cord coagulations, the survival rate was 83% and 92% of infants had a normal development. This is the first large prospective study that reports not only on pregnancy but also on infant outcome, with a 100% follow-up rate. So far, cord coagulation with laser energy has only been described for the management of TRAP (n = 5).5,6 Also, only small case series have reported on the pregnancy outcome after bipolar cord coagulation: 1 series for the management of FFTS (n = 15)9 and 2 other (n = 10, n = 17)7,8 for similar indications as in our study, with survival rates of 90%, 80%, and 76%, respectively.
In dichorionic twins, the mortality of selective feticide for discordant anomalies is less than 10% and largely attributable to miscarriage or severe preterm delivery.14 In MC twins, the mortality of cord coagulation caused by severe preterm delivery was 4% (3/73). However, there was an additional 11% (8/73) loss because of IUFD, which rarely complicates selective feticide in dichorionic twins. The more complex technique of cord coagulation and the shared circulation with possible feto-fetal hemorrhage may account for this extra loss. Half were early IUFDs and had laser coagulation only, whereas the other half were late IUFDs, with 3 of 4 most likely related to cord complications. Late IUFD was more common after septostomy. Indeed, iatrogenic disruption of the intertwin septum may lead to cord entanglement and sudden IUFD as in naturally occurring monoamniotic twins.15 Also, in 1 case of TRAP in MCDA twins, the cord of the acardiac originated directly from the pump’s cord, which led to late IUFD with entangled cords at birth. Septostomy should therefore be avoided where possible and transsection of the cord may be beneficial in MCMA twins, after septostomy as well as in cases of TRAP where the acadiac’s cord originates directly from the pump’s cord. Laser was used as primary energy source in 69%, but in about half of cases additional bipolar coagulation was
788 required to achieve arrest of flow, especially after 21 weeks. Also, all IUFDs diagnosed on the first postoperative day had cord coagulation with laser only. If the cord vessels are large, laser may only partly or temporarily occlude the vessels. Here, Doppler may give a false impression of complete cord occlusion, either because of asystole in the target fetus or only temporary occlusion with later reopening of vessels. Bipolar cord coagulation appears to be a more reliable technique, although laser still has its specific indications. As such, for cord coagulation at an early GA (eg, 16 weeks), fetoscopic laser can be performed through a 1.2-mm double lumen needle, whereas bipolar coagulation is performed through a 3.3-mm cannula. Also, for coagulation of the donor’s cord in cases of FFTS where the only entry is via recipient’s sac, laser can often coagulate the cord through the interwin septum, whereas bipolar coagulation more commonly requires a septostomy. PPROM was associated with all spontaneous deliveries before 31 weeks and for all perinatal deaths. Therefore, PPROM and not preterm labor is the Achilles’ heel of this type of intervention. One patient with persistent PPROM before 25 weeks had no further amniotic fluid leakage after an amniopatch was administered and she delivered at 31 weeks. A therapeutic amniopatch procedure may therefore reduce the perinatal mortality associated with postoperative PPROM.13 Also, PPROM before 31 weeks decreased from 42% to 6% with increasing experience, probably partly related to a decrease in the number of lengthy procedures. This underscores the need to restrict this procedure to a limited number of hands. Finally, for isolated discordant anomalies with no immediate threat to the healthy twin, delay of the procedure until after 26 weeksdif legally and morally acceptabledobviates the risk of PPROM very early in gestation. In this series, cord coagulation after 26 weeks was associated with a 100% survival rate and all deliveries were between 31 and 40 weeks. Although larger series are required to assess the true incidence of severe maternal complications, this study illustrates that cord coagulation is in general a safe procedure for the mother. One patient had chorioamnionitis and septic shock develop after a difficult procedure. Severe chorioamnionitis has been reported after any invasive procedure, including amniocentesis and is estimated to be rare.16 Its true incidence after cord coagulation can only be established in larger series, and that is why we plead for ongoing registration of cases in the Eurofoetus registry (http://www.eurofoetus.org). Of the 67 children older than 1 year, 4 children had mild and 1 had severe developmental delay. Although 82% of the children were evaluated by a pediatrician, the assessment of developmental outcome in our series would have been more accurate if all children had been evaluated at the 2 treatment centers with the same
Lewi et al assessments tools. In this series, this was not possible, as many patients were referred from other countries. As 3 of the 5 patients with delay were diagnosed elsewhere, we believe our data give an accurate estimate of developmental delay in infancy, although more developmental problems may become apparent only at a later age. Developmental problems may arise from the underlying disease, the intervention as well as from severe preterm delivery. This series is too small to assess the relative contribution of each of these factors. All the children with delay were born before 29 weeks, except for 1 child born at 34 weeks. At the same time, 3 of the children with delay were treated for TRAP after 23 weeks and 2 had grade 2 leucomalacia on early brain scan. Cardiac failure or chronic hypoxemia may have caused brain damage before the procedure and thereby contributed to the observed developmental delay. This observation may favor prophylactic intervention in cases of TRAP, rather than await signs of cardiac decompensation later on. Because of the higher mortality of selective feticide in MC pregnancies compared with multichorionic pregnancies, indications must be carefully balanced. For TRAP, the survival rate of cord coagulation was 74%. The natural history of TRAP remains poorly documented, and reported survival rates vary widely between 14% and 90%.17,18 Data on long-term outcome of pump twins are not available, although the risk of cardiac19 and neurodevelopmental20 complications may be high because of chronic hemodynamic imbalances in utero and severe preterm delivery. As mentioned previously, there may be a place for prophylactic cord coagulation before cardiac decompensation of the pump twin occurs, but a larger series will need to confirm this. For severe discordant anomalies, cord occlusion is a valid alternative to termination of the whole pregnancy. For anomalies with a high likelihood of spontaneous IUFD, expectant management may be preferable in dichorionic twins. However, in MC pregnancies this specifically warrants a selective feticide, as IUFD of 1 twin will lead to demise of the co-twin in 10% to 25%, and cerebral damage in 25% to 45% because of acute feto-fetal hemorrhage in addition to the risks of severe prematurity.21,22 For discordant anomalies that do not threaten the well-being of the other fetus(es), delay of the procedure until after 26 weeks may reduce the risks for the healthy twin. For FFTS, laser coagulation of the vascular anastomoses remains the preferred first line treatment,23 although selective feticide may be indicated in selected cases. Finally, for severe discordant growth, umbilical cord coagulation may be considered, when there are signs of imminent IUFD before viability. Two recent series24,25 highlight the risks of severe discordant growth in MC twins. In 1 series (n = 13),24 42% of children had an abnormal development and 19% had cerebral palsy. There were 4 IUFDs and all 3 surviving children had cerebral palsy. In the other series (n = 42),25 12% of neonates had
Lewi et al parenchymal brain lesions on postnatal brain scan and the IUFD rate was 10%. As a conclusion, cord coagulation is an effective procedure for selective feticide in complicated MC twins as well as triplets. The information provided in this article may be useful for fetal medicine specialists who actually perform this procedure as well as for patients who are confronted with a complicated MC pregnancy.
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