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Genetic determination of islet cell autoimmunity in monozygotic twin, dizygotic twin, and non-twin siblings of patients with type 1 diabetes: prospective twin study.

OBJECTIVE: To test the hypothesis that non-diabetic dizygotic and monozygotic twin siblings of patients with type 1 diabetes have a similar high prevalence of islet cell autoantibodies, thus suggesting that islet cell autoimmunity is mainly environmentally determined. DESIGN: Prospective twin study. SETTING: Two specialist centres for diabetes in the United States. PARTICIPANTS: Non-diabetic monozygotic twin (n=53), dizygotic twin (n=30), and non-twin (n=149) siblings of patients with type 1 diabetes; 101 controls. MAIN OUTCOME MEASURES: Analysis of progression to diabetes and expression of anti-islet autoantibodies. RESULTS: Monozygotic twin siblings had a higher risk of progression to diabetes (12/53) than dizygotic twin siblings (0/30; P<0.005). At the last follow up 22 (41.5%) monozygotic twin siblings expressed autoantibodies compared with 6 (20%) dizygotic twin siblings (P<0.05), 16 (10.7%) non-twin siblings (P<0.0001), and 6 (5.9%) controls (P<0.0001). Monozygotic twin siblings expressed multiple (>/=2) antibodies more often than dizygotic twin siblings (10/38 v 1/23; P<0.05). By life table analysis the probability of developing positive autoantibodies was higher among the monozygotic twin siblings bearing the diabetes associated HLA DQ8/DQ2 genotype than in those without this genotype (64.2% (95% confidence interval 32.5% to 96%) v 23.5% (7% to 40%) at 10 years of discordance; P<0.05). CONCLUSION: Monozygotic and dizygotic twins differ in progression to diabetes and expression of islet cell autoantibodies. Dizygotic twin siblings are similar to non-twin siblings. These two observations suggest that genetic factors play an important part in determination of islet cell autoimmunity, thus rejecting the hypothesis. In addition, there is a high penetrance of islet cell autoimmunity in DQ8/DQ2 monozygotic twin siblings.

Adolescent↗

Twin reversed arterial perfusion sequence in twin-to-twin transfusion syndrome after the death of the donor co-twin in the second trimester.

A twin-to-twin transfusion syndrome was diagnosed in a monochorionic-diamniotic pregnancy at 18 weeks' gestation without any malformation, especially heart defect. In spite of the aggressive treatment (serial amnioreduction, digoxin treatment) the donor twin died at 25 weeks and twin reversed arterial perfusion (TRAP) sequence developed and was documented by Doppler ultrasound. In the TRAP-twin, the route of the reversed blood flow from the umbilical arteries was as follows: descending aorta, aortic arch, ascending aorta, aortic valve, left ventricle, mitral valve, left atrium, foramen ovale, right atrium, inferior vena cava, ductus venosus; and back to the placenta through the umbilical vein. After a 12-h observation period the twin reversed arterial perfusion sequence disappeared. During this period ultrasound and fetal blood sampling revealed no sign of fetal anemia or disseminated intravascular coagulation in the surviving twin. Based on our observations, we propose, that the death of one of the twins in monochorionic pregnancy can result in twin reversed arterial perfusion sequence, which is an ultimately rare phenomenon in the second trimester. To our knowledge, this is the first reported case of twin reversed arterial perfusion sequence subsequent to the intrauterine demise of one twin in twin-to-twin transfusion syndrome in which the TRAP-twin had no cardiac malformation.

Adult↗

Rapid development of hydrops fetalis in the donor twin following death of the recipient twin in twin-twin transfusion syndrome.

Intrauterine death of one fetus in monochorionic twinning is associated with high rates of perinatal morbidity and mortality in the surviving fetus. Subsequent development of hydrops fetalis in the donor twin after fetal demise of the recipient twin has been described in only two case reports and pathophysiology remains unclear. We report on a monochorionic-diamniotic twin pregnancy complicated by severe twin-twin transfusion syndrome. Ultrasound examination at 20 weeks of gestation showed discrepant twins with oligohydramnios in the smaller twins' sac and polyhydramnios in that of the larger twin. Repeated amniocenteses permitted prolongation of the pregnancy. However, the recipient twin developed deteriorating hydrops fetalis and died at 28 weeks of gestation. After this event, subsequent development of hydrops fetalis in the surviving donor twin could be observed, as well as an increase of amniotic fluid. An elective cesarean section was performed at 29 weeks of gestation. Initial hypoxemia could be effectively treated by high frequency oscillatory ventilation, surfactant therapy and inotropic support. The infant was discharged in good condition at the age of 2 months. Although rare, antenatal demise of the recipient twin in a monochorionic pregnancy can be associated with the subsequent development of hydrops fetalis in the surviving donor twin. We speculate that this phenomenon is due to ischemia-reperfusion injury of the previously poorly perfused twin.

Adult↗

Risk for surviving twin after fetal death of co-twin in twin-twin transfusion syndrome.

OBJECTIVE: To determine neonatal outcome of surviving twins in pregnancies complicated by twin-twin transfusion syndrome and fetal deaths of co-twins. METHODS: We retrospectively reviewed medical records of 11 women seen during 1990-1996 in our hospital who had pregnancies complicated by twin-twin transfusion syndrome and death of one fetus. RESULTS: The median interval between fetal death and delivery (six by cesarean delivery and five vaginally) was 2 weeks (range, 1 day to 7 weeks). Three of the 11 surviving twins died soon after birth (gestational ages at birth 32, 31, and 34 weeks; fetal death-delivery intervals 3, 7, and 7 weeks, respectively). Two survivors were severely handicapped (gestational ages at birth 29 and 33 weeks; fetal death-delivery interval 1 and 2 weeks, respectively). Two children showed cerebral echodensities on ultrasound after birth but developed normally, and four did not show any abnormalities on cerebral and abdominal ultrasound and developed normally. Five of 11 surviving twins, each born 1 week or more after fetal death of the co-twin, either died or experienced serious morbidity. In the two infants born within 1 day of fetal death, no problems were detected. CONCLUSION: In monochorionic twin gestations complicated by twin-twin transfusion syndrome, approximately half of surviving twins will experience mortality or serious morbidity when co-twins die in utero.

Female↗

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.

Adult↗

Effect of twin-to-twin delivery interval on umbilical cord blood gas in the second twins.

OBJECTIVE: To examine the effect of twin-to-twin delivery interval on the umbilical cord blood gas status of the second twin following vaginal delivery. DESIGN: A retrospective study. SETTING: The department of obstetrics and gynaecology in a university teaching hospital. POPULATION: Twin deliveries at or beyond 34 weeks of gestation over a period of five years, with the first twin delivered vaginally. Twins with any antepartum complications including discordant growth, intrauterine growth restriction, intrauterine death, fetal malformations and pre-eclampsia were excluded. METHODS: The correlation between the twin-to-twin delivery interval, and both the umbilical arterial and venous blood gas parameters of the second twin, including pH, partial pressure of CO2 and base excess, were studied. RESULTS: A total of 118 cases were reviewed. The mean gestation at delivery was 37.1 weeks. The median twin-to-twin delivery interval was 16.5 minutes. There were significant negative correlations between twin-to-twin delivery interval and both the umbilical cord arterial and venous pH and base excess of the second twin (P <0.05). There were also significant positive correlations between both arterial and venous partial pressure of CO2 and the delivery interval (P <0.05). Similar changes were found even if the analyses were limited to those who had normal vaginal deliveries. The umbilical arterial pH of Twin 2 was <7.00 in none of the cases delivered within 15 minutes of the birth of Twin 1, 5.9% if within 16-30 minutes, and 27% if more than 30 minutes. Among those with an inter-twin delivery interval of more than 30 minutes, 73% had cardiotocographic evidence of fetal distress which required operative delivery. CONCLUSIONS: Umbilical cord arterial and venous values of pH, partial pressure of CO2 and base excess of the second twin deteriorate with increasing twin-to-twin delivery interval. Risks of fetal distress and acidosis in the second twin are high when the twin-to-twin delivery interval is beyond 30 minutes.

Adult↗

Haemoglobin differences at birth in monochorionic twins without chronic twin-to-twin transfusion syndrome.

OBJECTIVES: To determine the haemoglobin (Hb) differences at birth in monochorionic (MC) twins without chronic twin-to-twin transfusion syndrome (TTTS) in relation to birth order and placental vascular anatomy. METHODS: All consecutive cases of MC twins without chronic TTTS and dichorionic (DC) twins delivered at our centre and admitted to our neonatal nursery between June 2002 and December 2004 were included in our study. We analysed Hb differences at birth and on day 2, in relation to birth order and placental vascular anatomy. RESULTS: Forty-five pairs of MC twins and 71 pairs of DC twins were included. Mean Hb differences at birth in MC and DC twins were similar, respectively 1.5 and 1.4 g/dL. Hb differences >5 g/dL at birth were found in 2% (1/45) of MC twins compared to 8% (6/71) in DC twins. On day 2, mean Hb differences in MC twins increased to 3.8 g/dL, and the rate of MC twins with Hb differences >5 g/dL increased to 27% (12/45) (p < 0.001). Mean Hb differences and the percentage of twins with Hb differences >5 g/dL in DC twins did not change on day 2. In MC twins, Hb levels measured on day 2 were significantly higher in second-born twins than in first-born twins, respectively 17.7 and 15.5 g/dL (p = 0.002). Hb differences on day 2 were significantly higher in MC twins with superficial vascular anastomoses than those without superficial anastomoses, respectively 4.0 g/dL and 1.5 g/dL (p = 0.036). CONCLUSIONS: Hb differences occur more frequently in MC twins without chronic TTTS than in DC twins, but only when measured on the second day of life. Hb differences in MC twins are associated with birth order and superficial vascular anastomoses.

Case-Control Studies↗

The derivation of twin laws in non-merohedric twins. Application to the analysis of hybrid twins.

An algorithm is presented to derive the twin laws in non-merohedric twins through the systematic search for quasi-perpendicular lattice planes/directions. The twin lattice, i.e. the sublattice common to the whole crystalline edifice built by the twinned individuals, is based on a supercell of the individual defined by a pair of quasi-perpendicular lattice elements (hkl)/[uvw]. Starting from a (real or supposed) twin element, (hkl) or [uvw], the set of quasi-perpendicular lattice elements with user-defined limits on the twin index and obliquity is explored. The degree of lattice quasi-restoration is commonly measured by the classical twin index but in some cases, especially for large supercells, this index represents only a first approximation of the degree of lattice quasi-restoration, because more than one pair (hkl)/[uvw] may exist, and more than one concurrent sublattices of nodes, based on the same twin element, may be quasi-restored, although within different obliquities. These twins, whose existence has been recently recognized, are termed hybrid twins. In hybrid twins, the degree of lattice quasi-restoration is measured by the effective twin index n(E), a generalization of the classical twin index: in the limiting case of only one (quasi-)restored sublattice, the effective twin index and the classical twin index coincide. A number of examples previously reported simply as 'non-Friedelian' twins (with a twin index higher than the empirical limit of 6 established by Friedel) are analysed and reinterpreted as hybrid twins. A Fortran program is made available, which derives the possible twin laws according to this algorithm and analyses the pseudosymmetry of the concurrent sublattices defined by each pair (hkl)/[uvw]. The occurrence of hybrid concurrent components in twinning does not affect the normal procedures of dealing with diffraction patterns of twinned crystals.

Journal Article↗

Search for hemodynamic compromise at 11-14 weeks in monochorionic twin pregnancy: is abnormal flow in the ductus venosus predictive of twin-twin transfusion syndrome?

BACKGROUND AND OBJECTIVES: Twin-twin transfusion syndrome is a devastating complication of monochorionic twin pregnancies. The presence of increased nuchal translucency thickness (NT) in one of the monochorionic twins has been associated with an increased risk of developing this syndrome. One of the most plausible mechanisms for increased nuchal translucency is heart failure, indirectly manifested by abnormal blood flow in the ductus venosus. We aimed to clarify the pathophysiology of increased NT found more frequently in monochorionic twins prone to develop twin-twin transfusion syndrome. DESIGN: We present 50 cases of monochorionic twin pregnancies in which nuchal translucency thickness was measured and ductus venosus blood flow evaluation was performed at 11-14 weeks of gestation. RESULTS: Whenever the fetuses of a twin pregnancy were found to have discrepant nuchal translucency thickness measurements and abnormal flow in the ductus venosus was found in the fetus with increased nuchal translucency thickness, twin-twin transfusion syndrome eventually developed. Progression to twin-to-twin transfusion syndrome was not observed in the twins displaying no intertwin difference in nuchal translucency thickness measurements and it was not observed in those with discrepant nuchal translucency thickness but normal flow in the ductus venosus of both fetuses. In the two cases which developed twin-to-twin transfusion syndrome, fetoscopic laser coagulation of the vascular anastomoses was successfully carried out at 18 weeks and normalization of the venous return was recorded. CONCLUSIONS: Both increased nuchal translucency and abnormal flow in the ductus venosus in monochorionic twins may be early manifestations of haemodynamic imbalance between donor and recipient. The combined evaluation of both parameters in monochorionic twin pregnancies may constitute an effective method for identifying those at risk of developing twin-to-twin transfusion syndrome.

Adolescent↗

Twins with implanted pacemakers: Is there an increased mortality risk for the co-twin? A follow-up study based on the Danish Twin Registry and the Danish Pacemaker Register.

BACKGROUND: The main indications for implanting a cardiac pacemaker are either acquired atrio-ventricular block (AVB) or sick sinus syndrome (SSS). In general, the exact aetiology of these conditions is unknown. Genetic factors may play a role. Untreated AVB is associated with increased mortality but SSS seems to have a good prognosis. The present study was designed to assess whether first-degree relatives of these patients have an increased mortality risk. METHODS: We investigated the survival pattern of the co-twins of twins who have had a cardiac pacemaker implanted, by linking two nationwide registries in Denmark: the Danish Pacemaker Register and the Danish Twin Registry. For each "pacemaker-twin" four control-twins matched with respect to age, sex, and zygosity were selected among the twins who were alive at the time of the pacemaker implantation. A total of 159 twins with a pacemaker treated bradycardia of unknown aetiology were identified of which 73 had AVB and 64 had SSS. A total of 622 matched control-twins could be identified. The survival from age six of the co-twins of the "pacemaker-twins" was compared with that of the co-twins of the control-twins. The follow-up period ended January 1st, 2000. FINDINGS: The survival curves for the co-twins of the "pacemaker-twins" were virtually identical to those of the co-twins of the control-twins. This finding was consistent for both AVB and SSS and for monozygotic as well as dizygotic twins. CONCLUSION: No increased mortality risk could be demonstrated for first-degree relatives--including monozygotic twins--of patients with a cardiac pacemaker implanted due to either acquired AVB or SSS.

Aged↗

Intrauterine death of one twin, with rescue of the other, in twin-twin transfusion syndrome.

Single intrauterine death may occur in twin-twin transfusion syndrome. We investigated why the outcome of the surviving twin is fairly good when the donor twin dies first compared with when the recipient twin dies first. A detailed hemodynamic study was performed using Doppler ultrasound in a twin pregnancy affected by twin-twin transfusion syndrome before and after a single intrauterine death that occurred in the donor twin at 26 weeks' gestation. The recipient twin was expected to die due to severe right cardiac failure with functional stenosis of the pulmonary artery 2 days before the cotwin's death. The donor twin's death caused a prompt resolution of cardiac failure and improvement in other indices, including flow velocity waveform patterns of the umbilical vein, the middle cerebral artery and the ductus venosus. A healthy, premature female neonate weighing 1630 g with a hemoglobin concentration of 17.8 g/dL was delivered by Cesarean section following rupture of the fetal membranes 28 days after the episode. Hemorrhaging from the surviving twin to the dead twin that occurred just before or after the cotwin's death may have contributed to the decrease in volume overload in the recipient twin, leading to a prompt amelioration of the critical hemodynamic indices. The early death of the donor twin may thus have played a significant role in improving the status of the recipient twin in this case of twin-twin transfusion syndrome.

Adult↗

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 arterio-arterial anastomoses. DESIGN: Forty monochorionic pregnancies were prospectively recruited for an ultrasonographic survey of the chorionic plate using colour Doppler energy. Arterio-arterial anastomoses were identified by their characteristic bidirectional interference pattern on spectral Doppler. Angioarchitecture was confirmed by postnatal injection study. SETTING: Fetal medicine tertiary referral centre in London. MAIN OUTCOME MEASURES: Presence of arterio-arterial anastomoses, development of twin-to-twin transfusion syndrome, survival. RESULTS: Arterio-arterial anastomoses were detected by colour Doppler energy in 21 pregnancies (53%), and there were no false positives. An arterio-arterial anastomosis was more commonly found in unaffected (n=28) compared to pregnancies affected by twin-to-twin transfusion syndrome (n=12), both by colour Doppler energy [20/28 (71%) is 1/12 (8%); delta=63%, 95% CI 40%-86%] and by postnatal injection study [25/28 (89%) vs 3/12 (25%); delta=64%, 95% CI 37%-91%]. In pregnancies in which no arterio-arterial anastomoses were detected, a diagnosis of twin-to-twin transfusion syndrome was made in 58%, and the perinatal loss rate was 40%, compared with one case of twin-to-twin transfusion syndrome (5%) (P < 0.001) and a loss rate of 12% (P=0.005) in pregnancies in which an arterio-arterial anastomosis was detected. CONCLUSION Twin-to-twin transfusion syndrome is associated with an absence of functional arterio-arterial anastomoses in vivo in monochorionic twin pregnancies. This contributes to our understanding of the pathophysiology of twin-to-twin transfusion syndrome and confirms ex vivo studies demonstrating that twin-to-twin transfusion syndrome is associated with a paucity of superficial anastomoses. Prospective studies are indicated to determine the utility of colour Doppler energy for arterio-arterial anastomoses in predicting risk in monochorionic pregnancies.

Arterio-Arterial Fistula↗

Discordant amino acid profiles in monochorionic twins with twin-twin transfusion syndrome.

To test the hypothesis that discordant growth in monochorionic (MC) twins occurs at least in part due to disparity in placental amino acid transporter function, we measured plasma amino acid levels by HPLC in maternal and fetal blood samples collected at birth from gestational age matched twins with (n = 12) and without (n = 12) twin-twin transfusion syndrome (TTTS). In the donor twin, fetal plasma concentrations and feto-maternal ratios of five essential amino acids-valine (p < 0.001), leucine (p < 0.001), iso-leucine (p < 0.05), histidine (p < 0.001) and L-arginine (p < 0. 001)-were lower than the recipient and non-TTTS twin pairs. Fetal concentrations of the nonessential amino acids taurine (p < 0.001), serine (p < 0.01), glycine (p < 0.001) and tyrosine (p < 0.05) were also markedly lower in the donor than the recipient and non-TTTS twin pairs. In contrast, the fetal alanine level in the donor twin was higher than the recipient (664 +/- 64 versus 396 +/- 23 microM; p < 0.001) and the non-TTTS twin pairs (p < 0.01). No such differences between amino acid profiles in non-TTTS MC twin pairs were found. Maternal plasma amino acid levels between TTTS and non-TTTS groups were comparable. This study provides the first evidence that certain amino acids in the donor twin of chronic TTTS differ significantly from those of the co-twin while others were comparable between twin pairs. These data, therefore, argue against inter-twin transfusion as the sole cause of growth restriction of the donor twin and suggests instead that impaired placental transport of amino acids may be a likely mechanism.

Amino Acids↗

Placental regulation of insulin-like growth factor axis in monochorionic twins with chronic twin-twin transfusion syndrome.

To test the hypothesis that severe growth restriction (intrauterine growth retardation) in donor twins with chronic twin-twin transfusion syndrome (TTTS), a common complication of monochorionic twin pregnancy, is due to an aberration in the insulin-like growth factor (IGF) axis, we studied 25 sets of monochorionic twins with (n = 13) and without (n = 12) TTTS. Maternal and cord blood samples were collected at birth and analyzed for IGF-I, IGF-II, IGF-binding protein-1 (IGFBP-1), and IGFBP-1 phosphorylation status. Fetal IGF-II levels in the recipient twins with TTTS were higher than those in the donor twins (829 +/- 45 vs. 543 +/- 60 ng/mL; P < 0.001), but were comparable with those in the non-TTTS twin pairs. IGF-I levels in recipient and donor twin pairs were similar. The total IGFBP-1 concentration was higher in the donor twins than in the recipients (1153 +/- 296 vs. 419 +/- 108 ng/mL; P < 0.001) and non-TTTS twin pairs (P < 0.01). The percent less phosphorylated IGFBP-1 was higher in the recipients than in the donor twins (P < 0.05). There were no differences in IGF-I, IGF-II, and IGFBP-1 levels between non-TTTS twin pairs. Maternal levels of IGFs were comparable in the two groups. In the TTTS group, fetal birth weight gave a positive correlation with serum IGF-II levels (y = 0.25x + 361.1; r = 0.47; P < 0.05), and a negative association with IGFBP-1 levels (y = -0.72x + 1593.6; r = 0.58; P < 0.01). Our data argue against intertwin transfusion as the cause of intrauterine growth retardation in the donor twin and provide evidence that the placenta is the key regulator of the fetal IGF axis, especially when fetal genotype and maternal environments are similar.

Female↗

Iron metabolism in monochorionic twin pregnancies in relation to twin--twin transfusion syndrome.

Fetal iron metabolism was investigated in monochorionic (MC) twin pregnancies in relation to twin-twin transfusion syndrome (TTTS). Matched maternal and fetal blood samples were obtained both in utero and at birth from MC twins with TTTS (n = 23) and without TTTS (n = 18). In a second group of 30 twin pairs (15 with and 15 without TTTS), liver iron content was assessed by using archived paraffin wax-embedded blocks. Serum ferritin was determined by radioimmunoassay and values are given as gestation independent Z-scores and expressed as mean with 95% confidence intervals. Ferritin concentrations in the recipients were higher than in the donors both in utero (P < 0.01) and at birth (P < 0.01). Fetal serum ferritin in non-TTTS twins were similar to the recipient twins but higher than the donor twins (P < 0.05). A significant association was found between ferritin concentrations, the total red blood cell count and haemoglobin in the TTTS twin pairs (P < 0.01) and the non-TTTS twins as a group (P < 0.01). The total stainable liver iron was comparable between twin pairs in the TTTS and non-TTTS groups. This study fails to provide evidence of iron overload in the recipient and depletion in the donor twins and, thereby, questions the validity of the conventional theory of inter-twin transfusion as the cause of TTTS.

Erythrocyte Count↗

Color Doppler ultrasonography in the identification of communicating vessels in twin-twin transfusion syndrome and acardiac twins.

This study evaluates the role of color Doppler ultrasonography in the identification of the communicating placental vessels in pregnancies with twin-twin transfusion syndrome and acardiac twins. In 18 pregnancies with twin-twin transfusion syndrome and two with an acardiac twin, color Doppler studies of the placental vasculature were performed before fetoscopy for laser coagulation of the communicating vessels. In six cases of twin-twin transfusion syndrome the placental attachment of the intertwin membrane could be visualized. Pulsatile arterial blood flow was observed from the donor to the recipient twin that disappeared after laser therapy. In both cases of acardiac twins, one communicating vessel with pulsatile and another vessel with nonpulsatile blood flow in the opposite direction could be identified. Color Doppler imaging is unlikely to play a major role in assisting endoscopic laser separation of chorioangiopagus in patients with acute polyhydramnios, but it may prove to be useful in the early identification of pregnancies at risk of developing twin-twin transfusion syndrome.

Acute Disease↗

Fetal urine and amniotic fluid in monochorionic twins with twin-twin transfusion syndrome: simulations of therapy.

OBJECTIVE: Therapy for twin-twin transfusion syndrome includes amnioreduction, septostomy, and laser ablation, but there is no accepted standard of care. Mechanisms for the reported improvement in survival are incompletely understood. We sought to model the mechanisms and predict the response of varying severities of twin-twin transfusion syndrome and placental angioarchitectures to current therapies to determine optimal clinical interventions. STUDY DESIGN: We used our mathematic model of twin-twin transfusion syndrome that predicts fetal and amniotic fluid abnormalities that are related to the placental angioarchitecture. Amnioreduction was modeled as reduction in amniotic fluid volume; septostomy was modeled as the merging of donor and recipient amniotic fluid, and laser ablation was modeled as the cessation of all placental anastomotic blood flows. RESULTS: Amnioreduction reduces amniotic fluid pressure, which improves transplacental fluid flow from mother to fetus and increases both donor and recipient blood volume. However, net arteriovenous transfusion increases, because of increased donor arterial pressure, which negates, in part, the benefit of amnioreduction. Septostomy allows amniotic fluid to be swallowed by the donor, with minimal effects on donor growth and blood volume. Laser ablation eliminates anastomotic exchange of blood and reduces discordant fetal growth. CONCLUSION: Amnioreduction may be effective in milder twin-twin transfusion syndrome pregnancies but ineffective in severe cases. Septostomy is unlikely to offer significant therapeutic efficacy. Laser ablation is equally effective in mild and severe twin-twin transfusion syndrome but has a higher spontaneous abortion rate than amnioreduction. The model indicates improved outcomes with the use of amnioreduction in mild twin-twin transfusion syndrome cases and with laser ablation in severe cases.

Amniocentesis↗

Erythropoietin in monochorionic twin pregnancies in relation to twin--twin transfusion syndrome.

Fetal erythropoietin (Epo) concentrations were studied in monochorionic (MC) twin pregnancies in relation to twin-twin transfusion syndrome (TTTS). Matched maternal and fetal blood samples in utero were obtained from MC twins with TTTS (n = 15) and without TTTS (n = 6). In a second group of five sets of twin pairs with or without TTTS, immunolocalization of Epo was performed in archived paraffin wax sections of liver and kidney collected at autopsy. Epo was measured using a chemiluminescence assay and expressed as gestation independent Z-scores and given as mean +/- 95% confidence intervals (CI). Fetal Epo concentrations in utero were higher in MC twins with TTTS than the non-TTTS as a group (P < 0.001). There was no difference in Epo concentrations between TTTS and non-TTTS twin pairs. Fetal Epo concentrations were correlated with pO(2) in the recipient (r = 0.64; P < 0.01), donor (r = 0.64; P < 0.01) and control twins (r = 0.76; P < 0.01). Immunostaining of the fetal kidney localized Epo primarily to the cytoplasm of the proximal convoluted tubules. The intensity of staining in the kidney and liver was comparable between TTTS and non-TTTS twin pairs. Fetal Epo concentrations were higher in the TTTS than non-TTTS twin pairs and were correlated with the degree of hypoxaemia. However, Epo concentrations were comparable between donor and recipient twins, perhaps due to similar production rather than inter-twin transfusion of blood.

Acid-Base Equilibrium↗