Tim Van Mieghem

The outcome of monochorionic diamniotic twin gestations in the era of invasive fetal therapy: a prospective cohort study

OBJECTIVE The purpose of this study was to document pregnancy and neonatal outcome of monochorionic diamniotic twin pregnancies. STUDY DESIGN This observational study describes a prospective series included in the first trimester in 2 centers of the Eurotwin2twin project. RESULTS Of the 202 included twin pairs, 172 (85%) resulted in 2 survivors, 15 (7.5%) in 1 survivor, and 15 (7.5%) in no survivors. The mortality was 45 of 404 (11%), and 36 of 45 (80%) were fetal losses of 24 weeks or less, 5 of 45 (11%) between 24 weeks and birth, and 4 of 45 (9%) were neonatal deaths. Twin-to-twin transfusion syndrome (TTTS) occurred in 18 of 202 (9%). The mortality of TTTS was 20 of 36 (55%), which accounted for 20 of 45 (44%) of all losses. Severe discordant growth without TTTS occurred in 29 of 202 (14%). Its mortality was 5 of 58 (9%), which accounted for 5 of 45 (11%) of all losses. Major discordant congenital anomalies occurred in 12 of 202 (6%). Of the 178 pairs that continued after 24 weeks, 10 (6%) had severe hemoglobin differences at birth. After 32 weeks, the prospective risk of intrauterine demise was 2 in 161 pregnancies (1.2%; 95% confidence interval, 0.3-4.6). CONCLUSION Of the monochorionic twins recruited in the first trimester, 85% resulted in the survival of both twins, and 92.5% resulted in the survival of at least 1 twin. Most losses were at 24 weeks or less, and TTTS was the most important cause of death. After 32 weeks, the risk of intrauterine demise appears to be small.

Clinical outcome and placental characteristics of monochorionic diamniotic twin pairs with early-and late-onset discordant growth

OBJECTIVE The purpose of this study was to examine the clinical and placental characteristics of monochorionic diamniotic twin pregnancies with early-onset discordant growth diagnosed at 20 weeks, late-onset discordant growth diagnosed at 26 weeks or later, and concordant growth. STUDY DESIGN We studied a prospective cohort that underwent an ultrasound scan in the first trimester, at 16, 20, and 26 weeks. We excluded pregnancies complicated by twin-to-twin transfusion syndrome, miscarriage, fetal death less than 16 weeks, or severe congenital anomalies. Placental sharing and angioarchitecture were assessed by injection of each cord vessel with dyed barium sulphate. The 2 territories were delineated on an X-ray angiogram. The diameter of each intertwin anastomosis was measured on a digital photograph. RESULTS We included 178 twin pairs. Early onset discordant growth, late-onset discordant growth, and concordant growth occurred in 15, 13, and 150 pregnancies, respectively. Twin pairs with early-onset discordant growth had lower survival rates and were delivered at an earlier gestational age than pairs with late-onset discordant and concordant growth. The degree of birthweight discordance was similar in early- and late-onset discordant growth. Severe intertwin hemoglobin differences at the time of birth occurred in 0%, 38%, and 3% of pairs with early-onset discordant growth, late-onset discordant growth, and concordant growth, respectively. The placentas of pairs with early-onset discordant growth were more unequally shared and had larger arterioarterial anastomoses and a larger total anastomotic diameter as compared with placentas of pairs with late onset-discordant or concordant growth. CONCLUSION Unequal placental sharing appears to be involved in the etiology of early-onset discordant growth, whereas a late intertwin transfusion imbalance may be involved in some cases with late-onset discordant growth.

Morphological and Functional Adaptation of the Maternal Heart during Pregnancy

Background— Pregnancy provides a unique model to study the adaptation of the heart in a physiological situation of transient load changes. The aim of this study was to assess the performance of the left ventricle (LV) in normal, uncomplicated pregnancies while considering the actual LV load and shape. Methods and Results— Serial echocardiographic examinations were performed in 51 women in each pregnancy trimester and 3 to 6 months after delivery. Data from 10 nulliparous, age-matched women were used as the control. Conventional parameters of LV function (ejection fraction) as well as myocardial deformation (strain) were interpreted, taking into consideration maternal hemodynamics and LV shape. Cardiac output increased during pregnancy because of a higher stroke volume in early pregnancy and a late increase in heart rate, whereas total vascular resistance decreased. Progressive development of eccentric hypertrophy was observed, which subsequently recovered postpartum. Sphericity index decreased from the first to the third trimester (1.92±0.17 versus 1.71±0.17) and returned postpartum to values comparable to the control. Although higher LV stroke work was noted toward the third trimester (5.9±1.1 versus 5.3±1.0 Newton meter, P<0.001), ejection fraction showed no significant changes. LV strain decreased significantly in late pregnancy (−19.5±2% to −17.6±1.6%, P<0.001) and returned to baseline values after delivery (−19.5±2%). Conclusions— Pregnancy is a physiological process associated with increased cardiac performance and progressive LV remodeling. These changes are not directly reflected by parameters traditionally considered to describe systolic function, such as ejection fraction and longitudinal deformation. While ejection fraction was insensitive to the functional changes, the transient decrease in longitudinal deformation becomes only plausible when considering the changes in LV geometry.

Assessment of fetal cardiac function before and after therapy for twin-to-twin transfusion syndrome

OBJECTIVE We sought to assess fetal cardiac function in monochorionic twins before and after therapy for twin-to-twin transfusion syndrome (TTTS) and compare it with control subjects. STUDY DESIGN We conducted prospective longitudinal assessment of fetal cardiac function in cases undergoing curative fetal therapy for TTTS (n = 39) until 4 weeks postoperatively and in uncomplicated monochorionic twins (n = 23). Fetal cardiac function was assessed by the left and right ventricular myocardial performance index, atrioventricular valve flow pattern, ductus venosus a-wave, and umbilical vein pulsations. RESULTS Nomograms for the myocardial performance index were constructed. Fetal cardiac function was grossly abnormal in recipient twins of TTTS when compared with control subjects (P < .001 for all indices) but normalized by 4 weeks postoperatively. The donor developed abnormal ductus venosus flow and tricuspid regurgitation postoperatively that regressed within 4 weeks. CONCLUSION The cardiac dysfunction in the recipient twin of TTTS normalizes within 1 month after laser. The donor develops a transient impairment of cardiac function postoperatively.

Monochorionic Diamniotic Twin Pregnancies: Natural History and Risk Stratification

About 30% of monochorionic twin pregnancies are complicated by twin-to-twin transfusion syndrome (TTTS), isolated discordant growth, twin anemia-polycythemia sequence, congenital defects or intrauterine demise. About 15% will be eligible for invasive fetal therapy, either fetoscopic laser treatment for TTTS or fetoscopic or ultrasound-guided umbilical cord coagulation for a severe congenital defect in one twin or severe discordant growth with imminent demise of the growth-restricted twin. Ultrasound examination in the first and early second trimester can differentiate the monochorionic twins at high risk for adverse outcome from those likely to be uneventful, which may be useful for patient counselling and planning of care.

The role of ultrasound examination in the first trimester and at 16 weeks' gestation to predict fetal complications in monochorionic diamniotic twin pregnancies

OBJECTIVE The purpose of this study was to determine the value of ultrasound examination in the first trimester and at 16 weeks to predict fetal complications in monochorionic diamniotic (MCDA) twin pregnancies, defined as the occurrence of either twin-to-twin transfusion syndrome, severe discordant growth, or intrauterine death. STUDY DESIGN We identified risk factors to predict a complicated fetal outcome in the first trimester and at 16 weeks in a prospective cohort of 202 twin pregnancies recruited during the first trimester in 2 centers of the EuroTwin2Twin project. RESULTS Significant predictors in the first trimester were the difference in crown-rump length (odds ratio [OR], 11) and discordant amniotic fluid (OR, 10). At 16 weeks, significant predictors were the difference in abdominal circumference (OR, 29), discordant amniotic fluid (OR, 7), and discordant cord insertions (OR, 3). Risk assessment in the first trimester and at 16 weeks detected 29% and 48% of cases with a complicated fetal outcome, respectively, with a false-positive rate of 3% and 6%, respectively. Combined first-trimester and 16 week assessment identified 58% of fetal complications, with a false-positive rate of 8%. CONCLUSION Of the MCDA twin pregnancies classified as high risk on the combined first trimester and 16 weeks assessment (n = 41), 73% had a complicated fetal outcome with a survival rate of only 69%. In contrast, of the pregnancies classified as low risk (n = 154), 86% had an uneventful fetal outcome with a survival rate of 95%.

Prenatal diagnosis, prediction of outcome and in utero therapy of isolated congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) can be associated with genetic or structural anomalies with poor prognosis. In isolated cases, survival is dependent on the degree of lung hypoplasia and liver position. Cases should be referred in utero to tertiary care centers familiar with this condition both for prediction of outcome as well as timed delivery. The best validated prognostic indicator is the lung area to head circumference ratio. Ultrasound is used to measure the lung area of the index case, which is then expressed as a proportion of what is expected normally (observed/expected LHR). When O/E LHR is < 25% survival chances are < 15%. Prenatal intervention, aiming to stimulate lung growth, can be achieved by temporary fetal endoscopic tracheal occlusion (FETO). A balloon is percutaneously inserted into the trachea at 26–28 weeks, and reversal of occlusion is planned at 34 weeks. Growing experience has demonstrated the feasibility and safety of the technique with a survival rate of about 50%. The lung response to, and outcome after FETO, is dependent on pre‐existing lung size as well gestational age at birth. Early data show that FETO does not increase morbidity in survivors, when compared to historical controls. Several trials are currently under design. Copyright

Methods for prenatal assessment of fetal cardiac function

Fetal cardiac function is increasingly recognized as a marker of disease severity and prognosis in selected fetal conditions. Magnetic resonance imaging (MRI) has been used in experimental (animal) fetal cardiology but the lack of a noninvasive fetal electrocardiogram (ECG) to trigger image acquisition remains a major limiting factor precluding its application in humans. Fetal medicine specialists are therefore limited to ultrasound to evaluate human fetal cardiac function. In this review, we aim to provide a complete overview of the different ultrasound techniques that can be used for fetal cardiac function assessment and we discuss their (theoretical) strengths and shortcomings. Conventional methods include M‐mode assessment of ventricular contractility and Doppler assessment of the precordial veins and cardiac output (CO). More recent techniques such as the measurement of the myocardial performance index (MPI), myocardial motion analysis with tissue Doppler, speckle tracking and three‐dimensional (3D) ultrasound techniques are also discussed. Copyright

Results of Fetal Endoscopic Tracheal Occlusion for congenital diaphragmatic hernia and the set up of the randomized controlled TOTAL trial

In isolated congenital diaphragmatic hernia, lung size and/or the position of the liver are predictive of neonatal outcome. Percutaneous Fetal Endoscopic Tracheal Occlusion (FETO) by a balloon can be undertaken to prompt lung growth in the worst cases. The feasibility and safety of FETO is no longer at stake, and it is associated with an apparent increase in neonatal survival. The gestational age at birth, the pre-existing lung size, the ability to remove the balloon prior to birth, and the lung response are predicting outcome. The most frequent complication is preterm premature rupture of the membranes, and as a consequence preterm delivery, which also complicates balloon removal. We have set up a randomized trial for the formal evaluation of FETO in Europe, including criteria for fetoscopy centers. Training of European as well as North American centers is taking place, so that the procedure could be safely and more widely offered.

Changing Perspectives on the Perinatal Management of Isolated Congenital Diaphragmatic Hernia in Europe

Congenital diaphragmatic hernia (CDH) should be diagnosed in the prenatal period and prompt referral to a tertiary referral center for imaging, genetic testing, and multidisciplinary counseling. Individual prediction of prognosis is based on the absence of additional anomalies, lung size, and liver herniation. In severe cases, a prenatal endotracheal balloon procedure is currently being offered at specialized centers. Fetal intervention is now also offered to milder cases within a trial, hypothesizing that this may reduce the occurrence of bronchopulmonary dysplasia in survivors. Postnatal management has been standardized by European high-volume centers for the purpose of this and other trials.