Mark L. Denbow

Placental angioarchitecture in monochorionic twin pregnancies: Relationship to fetal growth, fetofetal transfusion syndrome, and pregnancy outcome ☆ ☆☆

OBJECTIVE We sought to correlate placental vasculature with fetal growth and outcome in monochorionic twins. STUDY DESIGN Eighty-two patients with consecutive monochorionic pregnancies underwent biweekly ultrasonography for determination of fetal growth and well-being. After delivery, blinded placental injection studies delineated vascular anastomoses and territory share. Degree of balance in arteriovenous anastomoses equaled the number of arteriovenous anastomoses in one direction minus the number in the other. RESULTS Pregnancies affected by fetofetal transfusion syndrome (n = 21) had numbers of arteriovenous and venovenous anastomoses that were similar to those in pregnancies without fetofetal transfusion syndrome but fewer arterioarterial anastomoses (P <.0001). Fetofetal transfusion syndrome occurred in 78% of pregnancies with >/=1 arteriovenous and no arterioarterial anastomoses. Birth weight discordancy correlated with placental territory discordancy (P <.0001) and the degree of balance in arteriovenous anastomoses (P =.004). The larger placental share twin had a greater growth velocity than its smaller placental share co-twin (P =.008) for all but one anastomotic pattern. Where arteriovenous anastomoses were aligned with the net venous outflow to the fetus with the smaller territory, co-twins had similar birth weights and growth velocities irrespective of placental share. Fetal survival was higher in pregnancies with an arterioarterial anastomosis (P =.01) but lower with a venovenous anastomosis (P =. 01). Survival of both fetuses was inversely associated with birth weight discordancy (P <.0001). CONCLUSION Although interrelationships among the various types of anastomoses are complex, our data suggest that the placental territory share and the pattern of arteriovenous anastomoses influence fetal growth, that arterioarterial anastomoses protect against fetofetal transfusion syndrome, and that venovenous anastomoses reduce perinatal survival.

Colour Doppler energy insonation of placental vasculature in monochorionic twins: absent arterio‐arterial anastomoses in association with twin‐to‐twin transfusion syndrome

Objective To determine in vivo whether monochorionic pregnancies complicated by twin‐to‐twin transfusion syndrome are associated with absence of haemodynamically‐compensatory arterioarterial anastomoses.

Neonatal cranial ultrasonographic findings in preterm twins complicated by severe fetofetal transfusion syndrome

OBJECTIVE To investigate cranial ultrasonographic findings in survivors of monochorionic pregnancies complicated by fetofetal transfusion syndrome. STUDY DESIGN Case details of all monochorionic twin pregnancies complicated by fetofetal transfusion syndrome were obtained from the Centre for Fetal Care database for a 3-year period. Fetofetal transfusion syndrome was diagnosed according to ultrasonographic criteria. Eligible for entry were twin pregnancies resulting in live-born preterm infants and complicated by fetofetal transfusion syndrome severe enough to require amnioreduction. Cranial ultrasonographic scans performed within 48 hours of birth were reviewed for evidence of abnormality. RESULTS Seventeen pregnancies were eligible for inclusion in the study. Median gestational age was 25 weeks (between 17 and 29 weeks) at diagnosis and 30 weeks (between 25 and 35 weeks) at delivery. Three infants died before ultrasonography could be performed. The remaining 31 twin infants received an early cranial ultrasonographic scan. One of the 31 had a major cerebral infarct; 10 others had evidence of other, more minor, antenatally acquired lesions. CONCLUSIONS Both donor and recipient survivors from pregnancies complicated by fetofetal transfusion syndrome are at significant risk for antenatally acquired cerebral lesions. Long-term neurologic follow-up studies are indicated to determine the clinical significance of these lesions.

The aetiology and management of twin-twin transfusion syndrome.

Twin‐to‐twin transfusion syndrome presents in the mid‐trimester with gross discordance in amniotic fluid volume, and complicates 10–15 per cent of monochorionic twins. Recent studies suggest a primary vascular basis in which a paucity of the bidirectional superficial anastomoses normally found in monochorionic twins is unable to compensate for haemodynamic imbalance resulting from unidirectional transfusion along deeper arterio‐venous anastomoses. It is associated with high rates of perinatal mortality from ruptured membranes, hydrops and growth restriction, and a significant morbidity from cardiac and neurological sequelae in particular. Serial aggressive amnioreduction is the current treatment of choice, with survival in around two thirds of cases. In the remaining third, with features suggesting a poor outcome, selective fetocide may have a role. Current attempts at vascular ablative therapies have been associated with inferior survival rates, but the long term therapeutic goal remains the identification and ablation of the shared chorionic vasculature.

Vascular occlusion using focused ultrasound surgery for use in fetal medicine

OBJECTIVE Focused ultrasound surgery (FUS) is being developed clinically for the non-invasive treatment of soft tissue tumours of the prostate, bladder, liver, kidney, muscle and breast. In the work described in this paper, the application of FUS is extended to investigate the potential to induce vascular occlusion, with the aim of applying the technique to problems in fetal medicine and oncology. METHODS In this feasibility study the occlusion of femoral blood flow in vivo is demonstrated using an array of multiple single exposures of 1.7 MHz focused ultrasound. These were placed in two rows of four lesions at a focal depth of 5 mm. The 4660-W cm-2 (free field spatial peak intensity) 2-s exposures were placed 2 mm apart. Vascular patency was assessed using a Siemens Vision (1.5T) magnetic resonance (MR) imaging scanner with an extremity coil, and intravenous gadolinium contrast agent. FLASH and FISP MR sequences were used to obtain full 3D data sets providing information on soft tissue damage and perfusion. RESULTS AND CONCLUSION Total vascular occlusion was achieved in four of nine cases and significant vascular disruption in five of nine cases. Refinement of the FUS technique and long-term studies are now indicated prior to initial clinical application in fetal medicine.

Haematological indices at fetal blood sampling in monochorionic pregnancies complicated by feto-fetal transfusion syndrome

36 MCDA twin pregnancies with FFTS investigated by fetal blood sampling (FBS) were studied over a 10‐year period (1988–1997). The haematological data obtained at FBS were compared between the donor and recipient fetuses. It was shown that the donor fetus had a significantly lower haematocrit (35·7 per cent versus 47·2 per cent; p<0·001), haemoglobin (12·2 gs/dl versus 15·8 g/dl; p<0·001), and red blood cell count (2·9×1012/l versus 3·8×1012/l; p=0·006) compared with the recipient fetus. A haematocrit discordancy of >15 per cent, however, was found in only 25 per cent of twin pairs. There were no significant inter twin differences in the remaining indices. The study concluded that although there are significant differences in haematocrit and red cell mass between the donor and recipient fetuses, only a minority of fetuses will have degrees of discordancy suggested in the literature to be diagnostic. We suggest that FBS does not have a role in establishing the diagnosis of FFTS, although its role in determining the degree of haematocrit discordancy to assist in timing of delivery remains to be evaluated.

High failure rate of umbilical vessel occlusion by ultrasound-guided injection of absolute alcohol or enbucrilate gel

The success rate for injected umbilical vascular occlusion in the published literature exceeds 85 per cent. In this study we assessed the efficacy of two forms of injected sclerosants in achieving umbilical vessel occlusion. 12 cases of attempted ultrasound‐guided occlusion over a 2½ year period were reviewed. These were monochorionic (MC) twins (n=6), dichorionic twins (n=3) and singletons (n=3) undergoing fetocide for severe anomalies, or impending fetal demise. Absolute alcohol (n=6), enbucrilate gel (n=5) or both (n=1) were used in an attempt to achieve vascular occlusion. Complete vessel occlusion was achieved in only a third of cases (4/12), three with absolute alcohol and one with enbucrilate gel. In MC twins occlusion was successful in two of six cases. In contrast to previously published data, this large series, containing more cases than the total previously reported, shows considerably poorer success rates for injected umbilical vascular occlusion. Injection of currently available sclerosants can no longer be recommended for umbilical vascular occlusion in human fetuses. Copyright

Preclinical development of noninvasive vascular occlusion with focused ultrasonic surgery for fetal therapy

OBJECTIVE This study was undertaken to investigate the ability of focused ultrasonic surgery to occlude blood flow in vivo. STUDY DESIGN A 5-mm linear track exposure of 1.7-MHz focused ultrasound was applied across the femoral vessels for 5 seconds. Free field spatial peak intensities in the range of 1,000 to 4,660 W x cm(-2) were used. Vascular occlusion was confirmed after demonstration of an absent distal arterial pulse and an absent flow signal on magnetic resonance angiography and subtracted (after minus before) contrast-enhanced dual-echo steady-state sequences. RESULTS The minimum intensity for consistent vascular occlusion was 1,690 W x cm(-2) at a focal depth of 5 mm when the transducer was moved at 1 mm x s(-1) orthogonal to the direction of blood flow. CONCLUSIONS This study demonstrates that focused ultrasonic surgery can achieve reproducible vascular occlusion in vivo. Potential obstetric applications include noninvasive ultrasonographically guided occlusion of placental vessels mediating interfetal transfusion in monochorionic twins.

Ultrasound microbubble contrast angiography in monochorionic twin fetuses

microbubble ultrasound contrast agent Levovist (Schering Health Care, UK) in an attempt to determine chorionicity. Levovist has been widely used to enhance colour doppler blood flow within various organs, but not previously in pregnancy. Levovist contains galactose microparticles which dissolve in water to release air as microbubbles, which are small enough (99% <8 μm diameter) to pass through capillaries but large enough to preclude transmembranous passage. Palmitic acid prolongs their longevity by lowering surface tension, to extend enhancement for 2–10 min. Colour doppler energy-gain settings were reduced to just sub-threshold (ie, no signal in the absence of microbubbles). After aspiration of blood for investigations, a bolus of Levovist (0·15 mL [100 μL/kg estimated fetoplacental weight]) was given intravenously. Presence of contrast was clearly seen within the sampled twin and then later within the cardiac chambers of the other twin (figure) where it reached a maximum intensity after 65 s. Monochorionicity was thus confirmed. The procedure was uncomplicated, and fetal heart rate and doppler studies were unaltered. Acid-base, haematological, and karyotypic results were normal, hence delivery was indicated. Two male infants were born by Caesarean section and required only supportive neonatal care. Placental examination confirmed monochorionicity with intertwin vascular anastomoses. The use of microbubble contrast agent in this case prevented an unnecessary invasive procedure in a healthy fetus. It enabled accurate determination of chorionicity, and hence altered clinical management. Early confirmation of chorionicity would have obviated the need for contrast injection, but is only 100% accurate before 12 weeks gestation, when the number of extraembryonic coeloms can be counted. However, many spontaneous twin pregnancies are not scanned until the midtrimester, when chorionicity is of insufficient reliability to inform management decisions. Ultrasound enhancement may prove a useful adjunct in multiple pregnancies, not just for late determination of chorionicity, but also for quantification and placental localisation of intertwin transfusion.

Selective termination by intrahepatic vein alcohol injection of a monochorionic twin pregnancy discordant for fetal abnormality

A 33 year old woman was referred with a twin pregnancy discordant for fetal abnormality. Initial ultrasound at 17 weeks of gestation confirmed, in one of the twins, a lumbo-sacral myelomeningocoele associated with an absent cerebellum, a lemon shaped head, and bilateral talipes. The other twin appeared normal. The ultrasound appearances of concordant external genitalia, indeterminate septa1 thickness (1.7 mm), and absent ‘twin peak’ sign, were suggestive of monochorionic placentation. Placental vascular anastomoses between the twins, and therefore monochorionic placentation, were confirmed by injecting donor adult red cells into the intrahepatic vein of the normal twin, and then demonstrating their substantial intertwin passage on Kleihauer testing of fetal blood sampled from the abnormal twin ( 1 6% adult cells) after a delay of 30 min. The parents received detailed counselling but remained adamant that they would not consider continuing the pregnancy. In the absence of alternative options, they requested that both twins be terminated. After discussing this at length, they consented to experimental selective fetocide which was performed at 18 weeks of gestation. One millilitre 100% alcohol (Martindale Pharmaceuticals, Essex UK) was injected under ultrasound control into the lumen of the abnormal twin’s intrahepatic vein, resulting in immediate asystole. In the healthy twin, umbilical and cerebral arterial Doppler waveforms showed no evidence of haemodynamic instability on continuous monitoring over the first 15 min, intermittent monitoring over the next 90 min, and then again 24 h later. The pregnancy progressed without incident, with