M. J. O. Taylor

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.

Influence of twin-twin transfusion syndrome on fetal cardiovascular structure and function: prospective case–control study of 136 monochorionic twin pregnancies

Objective: To test the hypothesis that identical twins show no inter-twin differences in cardiovascular structure or physiology in fetal life unless there has been twin-twin transfusion syndrome. Design: Unselected prospective case–control observational study of fetoplacental haemodynamics including echocardiography at a median of 24 (16.7 to 32.3) weeks, with postnatal confirmation of congenital heart disease or normality. Setting: Fetal medicine unit. Patients: 136 women with monochorionic diamniotic twin pregnancies, of which 47 fetal twin pairs (35%) had twin-twin transfusion syndrome. Results: There were no haemodynamic differences between the bigger fetus (twin 1) and the smaller co-twin (twin 2) in uncomplicated monochorionic diamniotic pairs. In twin-twin transfusion syndrome, recipient fetuses had increased aortic and pulmonary velocities compared with their donor co-twins (mean (SD): 0.73 (0.23) m/s and 0.63 (0.14) m/s), respectively, v 0.53 (0.16) m/s and 0.48 (0.10) m/s in donor twins; p = 0.003 (aortic) and < 0.0001 (pulmonary)), and also in comparison with twin 1 and twin 2. The overall prevalence of congenital heart disease was increased above that in singletons (3.8% v 0.56%; 6.9% in twin-twin transfusion v 2.3% in uncomplicated monochorionic diamniotic twins), with inter-twin discordance for defects. The prevalence in recipient twins was 11.9% (p = 0.014 v uncomplicated control twins). Conclusions: Fetuses with an identical genome but no circulatory imbalance have similar cardiovascular physiology but discordant phenotypic expression of congenital heart disease. The high prevalence of congenital heart disease in monochorionic diamniotic twins merits detailed fetal echocardiography.

Fetal origins of reduced arterial distensibility in the donor twin in twin-twin transfusion syndrome

Twin-twin transfusion syndrome permits investigation of vascular programming independent of genetic influence. Arterial distensibiity was lower in the donor twin during infancy, implying the intrauterine vascular remodelling might result in raised cardiac afterload and could influence later cardiovascular health.

Validation of the Quintero staging system for twin-twin transfusion syndrome

OBJECTIVE To validate an established staging system for twin‐twin transfusion syndrome. METHODS Prospective observational study in a tertiary referral fetal medicine center of 52 consecutive cases of twin‐twin transfusion syndrome. Each pregnancy was assessed longitudinally for a variety of prognostic factors including fetal biometry, amniotic fluid volume, arterial and venous Doppler sonogram abnormalities, and the presence of hydrops. Data were used to determine stage at diagnosis and first treatment, and worst stage throughout pregnancy. Perinatal outcome was assessed by stage. Management comprised serial amnioreduction, septostomy, selective reduction, or delivery, alone or in combination. RESULTS Median gestation at presentation and first treatment were both 21 weeks (range 14–34 and 15–34), and at delivery it was 29 weeks (range 16–40). Sixty‐three percent of pregnancies (33 of 52) were at least stage III at presentation. Forty‐five percent of pregnancies (22 of 49) progressed to a more advanced stage. Overall survival was 47% (47 of 100), with no difference between donor and recipient fetuses (40% [20 of 50] versus 54% [27 of 50] [χ2 P < .5]). Survival rates were 58% (15 of 26), 60% (six of ten), 42% (20 of 48), 43% (six of 14), and 0% (none of two) for stages I–V, respectively, with no significant influence of stage at presentation on survival. Survival was poorer where stage increased, versus decreased (27% [12 of 44] versus 94% [17 of 18] χ2 P < .001). Kaplan‐Meier survival curves indicated that staging at presentation identified pregnancies at greater risk of earlier rather than later gestational perinatal loss. CONCLUSION The Quintero staging system did not distinguish good from bad outcome at presentation, and thus should be used with caution in guiding initial management of twin‐twin transfusion syndrome. However, prognosis was influenced by a change in stage, and pregnancies progressing to higher stage disease were at increased risk of earlier perinatal loss. Staging may thus be more useful in monitoring disease progression.

Non-invasive fetal electrocardiography in singleton and multiple pregnancies

Objectives To document the duration of fetal cardiac time intervals in uncomplicated singleton pregnancies using a novel non‐invasive fetal electrocardiography (fECG) system and to demonstrate this techniques ability to acquire recordings in twin and triplet pregnancies.

Twin-twin transfusion syndrome: the influence of intrauterine laser photocoagulation on arterial distensibility in childhood.

Background—In twin-twin transfusion syndrome (TTTS), the donor and recipient fetus are exposed to differing volume loads and show discordant intertwin vascular compliance in childhood despite identical genotype. We hypothesized that discordance is prevented by intrauterine endoscopic laser ablation of placental anastomoses, which abolishes intertwin transfusion. We tested this by examining pulse wave velocity (PWV) in brachial arteries of twin survivors of TTTS treated with and without laser therapy. Methods and Results—One hundred children (50 twin pairs, 27 with TTTS) were studied. Group 1 comprised 14 monochorionic (MC) twin pairs with TTTS treated symptomatically; group 2 comprised 13 MC twin pairs with TTTS treated by laser. The control groups comprised 12 MC twin pairs without TTTS (group 3) and 11 dichorionic twin pairs (group 4). Fetal cardiovascular data, predictive factors for, and duration of TTTS and cord blood were collected prospectively. We measured blood pressure and PWV photoplethysmographically at a median corrected postnatal age of 11 months (range, 1 week to 66 months). Both TTTS groups showed marked intertwin PWV discordance, unlike MCDA control subjects. The PWV discordance seen in laser treated twin pairs resembled that of dichorionic control subjects (heavier individual with higher PWV), whereas group 1 showed the opposite (negative) intertwin discordance (ANOVA F (1,45)=4.5, P =0.04). No significant differences in blood pressure or intrauterine growth were observed between TTTS groups. Conclusions—Vascular programming is evident in monozygotic twins with intertwin transfusion and is altered but not abolished by intrauterine therapy to resemble that seen in dichorionic twins.

Transmitted arterio-arterial anastomosis waveforms causing cyclically intermittent absent/reversed end-diastolic umbilical artery flow in monochorionic twins.

OBJECTIVES To characterize the phenomenon of retrograde transmission of arterio-arterial anastomosis (AAA) interference patterns on umbilical artery (UA) waveform by (a) documenting the periodicity, (b) correlation with in vivo and in vitro demonstration of AAAs and (c) reproducing these patterns by computer modelling. METHODS Monochorionic twins (MC) twins underwent placental and umbilical Doppler studies. AAAs were sought by pulse wave Doppler of their bi-directional interference pattern and confirmed by postnatal injection studies. The periodicity of transmitted patterns in the UA was determined. Determinants of the transmitted patterns were ascertained by computer modelling of physiological and fetal variables. RESULTS Among 83 prospectively studied MC twin pregnancies; a transmitted pattern was observed in 6 (7 per cent) patients for 15-114 days. This was found in 20 per cent (6/30) of smaller MC twins discordant for growth restriction but in no appropriately grown twins. It was only observed in association with AAAs validated both in vivo and in ex vivo. Computer modelling demonstrated that this pattern could be reproduced by summating end diastolic flow with a high pulsatility index in the UA in the presence of a large AAA. Consistent with this, MC twins with a transmitted pattern had larger AAAs (median diameter 4.3 mm interquartile range 4.1-5.2) compared to MC twins discordant for intrauterine growth restriction (2.1 mm interquartile range 1.5 to 2.8) (P<0.05) without a transmitted pattern. Perinatal mortality was similar in the fetuses with and without transmitted patterns (0/12 vs. 2/48 P=0.7).

Doppler for artery-artery anastomosis and stage-independent survival in twin-twin transfusion.

OBJECTIVE: Treatment selection in twin–twin transfusion syndrome is increasingly determined by disease severity. We investigated whether detection of arterio-arterial anastomoses predicts perinatal survival. METHODS: An artery–artery anastomosis was sought by Doppler and disease stage was determined in 105 cases of twin–twin transfusion syndrome at presentation, first treatment, and worst stage. Outcome measures were perinatal, double, and any (1 or more babies) survival rates. RESULTS: After exclusion of 10 noninformative pregnancies, perinatal, double, and any survival rates were 61%, 44%, and 77%, respectively. When an anastomosis was detected at each of the 3 time points, perinatal and double survival rates were higher than when one was not (at first treatment, perinatal survival 83% versus 53%, respectively, P = .003; double survival 78% versus 33%, P < .001). Perinatal and double survival (P ≤ .01) were poorer with more advanced stage, but any survival rates were not influenced by stage or anastomosis detection. Multiple logistic regression demonstrated that anastomosis detection at treatment increased the chance of perinatal (odds ratio [OR] 5.1, 95% confidence interval [CI] 1.6, 15.9) and double survival (OR 19.3, 95% CI 2.7, 138), independently of stage. For stages I–III at treatment, anastomosis detection predicted better perinatal (100% versus 63%, 100% versus 59%, and 83% versus 44%, respectively) and double survival rates (100% versus 52%, 100% versus 46%, and 78% versus 26%). Stage III, with anastomoses detected, had better perinatal (83% versus 63%) and double survival (78% versus 52%) than did stage I without detection. CONCLUSION: Antenatal detection of artery-to-artery anastomosis predicts higher perinatal and double survival in twin–twin transfusion syndrome, independently of disease stage. LEVEL OF EVIDENCE: II-3

Interstitial laser: a new surgical technique for twin reversed arterial perfusion sequence in early pregnancy

Current treatments for twin reversed arterial perfusion sequence are associated with significant morbidity and most are not feasible in early gestation. We report the use of an interstitial laser in two pregnancies complicated by this sequence at 14 and 15 weeks, respectively. A 600μm laser fibre was introduced via a 17 gauge needle into the abdomen of the perfused twin close to the vitelline artery and umbilical vein, which were occluded by neodymium:yttrium aluminium garnet (Nd:YAG) laser. Both pregnancies continued uneventfully and each resulted in the birth of a healthy baby at term.

Fetal ECG: A Novel Predictor of Atrioventricular Block in Anti-Ro Positive Pregnancies

Objective: Approximately 2.8% of pregnancies are Ro/La antibody positive. 3–15% of fetuses develop complete heart block (CHB). First-degree atrioventricular heart block (1° AVB) is reported in a third of Ro/La fetuses but as most have a normal postnatal ECG this may reflect inadequacies of Doppler measurement techniques. Methods: Comparison was made between mechanical (mPR) and electrical (ePR) intervals obtained prospectively using Doppler and non-invasive fetal ECG (fECG) in 52 consecutive Ro/La pregnancies in 46 women carrying 54 fetuses in an observational study at a fetal medicine unit. 121 mPR and 37 ePR intervals were recorded in 49 Ro/La fetuses. Five were referred with CHB and excluded. ePR was measured successfully in 35/37 (94%) and mPR was measured in all cases. 1° AVB was defined as PR >95% CI. Logistic regression predicted abnormal final fetal rhythm from first mPR or ePR. Results: The ePR model gave 66.7% sensitivity (6 of 8 final abnormal fetal rhythm cases were predicted correctly in fetuses >20 weeks) and 96.2% specificity. mPR gave 44.4% sensitivity (4 of 9 cases) and 88.5% specificity. Z scores for ePR (zPR) were calculated from 199 normal fetuses. The area under the receiver operator characteristic (ROC) curve was 0.88 (95% CI, 0.754 to 1.007). A cut-off of 1.65 gave a sensitivity of 87.5% and specificity of 95% for those with prolonged and normal ePR intervals, respectively. Conclusion: zPR is better than mPR at differentiating between normal and prolonged PR intervals, suggesting that fECG is the diagnostic tool of choice to investigate the natural history and therapy of conduction abnormalities in Ro/La pregnancies.