Kurt Hecher

Preliminary experience with endoscopic laser surgery for severe twin-twin transfusion syndrome

Background In monozygotic twin pregnancies, there are placental vascular communications between the two fetuses. In 15 percent of such pregnancies there is an imbalance in net blood flow between the twins, resulting in the twin–twin transfusion syndrome. The recipient twin may have severe hydramnios during the second trimester of pregnancy, and there is a high risk of perinatal death and cerebral palsy in survivors. This condition can now be treated by endoscopic coagulation of the vascular anastomoses responsible for fetofetal transfusion with a neodymium:yttrium–aluminum–garnet (Nd:YAG) laser. Methods We performed intrauterine surgery in 45 pregnant women carrying twins at 15 to 28 weeks of gestation (median, 21); in each case there was severe hydramnios in one fetus due to the twin–twin transfusion syndrome. With the use of local anesthesia and continuous ultrasound visualization, a rigid fetoscope 2 mm in diameter, housed in a 2.7-mm cannula, was introduced transabdominally into the amniotic cavity of...

Predictors of neonatal outcome in early-onset placental dysfunction

OBJECTIVE: To identify specific estimates and predictors of neonatal morbidity and mortality in early onset fetal growth restriction due to placental dysfunction. METHODS: Prospective multicenter study of prenataly diagnosed growth-restricted liveborn neonates of less than 33 weeks of gestational age. Relationships between perinatal variables (arterial and venous Dopplers, gestational age, birth weight, acid-base status, and Apgar scores) and major neonatal complications, neonatal death, and intact survival were analyzed by logistic regression. Predictive cutoffs were determined by receiver operating characteristic curves. RESULTS: Major morbidity occurred in 35.9% of 604 neonates: bronchopulmonary dysplasia in 23.2% (n=140), intraventricular hemorrhage in 15.2% (n=92), and necrotizing enterocolitis in 12.4% (n=75). Total mortality was 21.5 % (n=130), and 58.3% survived without complication (n=352). From 24 to 32 weeks, major morbidity declined (56.6% to 10.5%), coinciding with survival that exceeded 50% after 26 weeks. Gestational age was the most significant determinant (P<.005) of total survival until 266/7 weeks (r2=0.27), and intact survival until 292/7 weeks (r2=0.42). Beyond these gestational-age cutoffs, and above birth weight of 600 g, ductus venosus Doppler and cord artery pH predicted neonatal mortality (P<.001, r2=0.38), and ductus venosus Doppler alone predicted intact survival (P<.001, r2=0.34). CONCLUSION: This study provides neonatal outcomes specific for early-onset placenta-based fetal growth restriction quantifying the impact of gestational age, birth weight, and fetal cardiovascular parameters. Early gestational age and birth weight are the primary quantifying parameters. Beyond these thresholds, ductus venosus Doppler parameters emerge as the primary cardiovascular factor in predicting neonatal outcome. LEVEL OF EVIDENCE: II

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.

ENDOSCOPIC LASER COAGULATION IN THE MANAGEMENT OF SEVERE TWIN-TO-TWIN TRANSFUSION SYNDROME

Objective To assess the clinical effectiveness of endoscopic laser coagulation of placental vessels in the

Fetal venous, intracardiac, and arterial blood flow measurements in intrauterine growth retardation: Relationship with fetal blood gases☆

OBJECTIVE Our purpose was to investigate arterial, venous, and intracardiac blood flow in growth-retarded fetuses and to relate the Doppler results to blood gases in umbilical venous blood obtained by cordocentesis. STUDY DESIGN A cross-sectional, pulsed-wave color Doppler ultrasonographic study of 23 severely growth-retarded fetuses undergoing cordocentesis and measurement of blood gases was performed. Blood velocity waveforms were recorded from the descending thoracic aorta, middle cerebral artery, inferior vena cava, ductus venosus, and atrioventricular valves. RESULTS The Doppler studies demonstrated evidence of redistribution in the arterial system with increased impedance to flow in the aorta and decreased impedance in the cerebral circulation. The velocity of flow in the venous system and across the atrioventricular valves was decreased, whereas pulsatility of waveforms in the inferior vena cava and ductus venosus was increased. The mean umbilical venous blood PO2 and pH were decreased, and there were significant associations between blood gases and Doppler parameters in the thoracic aorta, middle cerebral artery, and ductus venosus. CONCLUSION In severe intrauterine growth retardation the degree of fetal acidemia can be estimated from Doppler measurements of pulsatility in both the arterial system and the ductus venosus.

Relationship between monitoring parameters and perinatal outcome in severe, early intrauterine growth restriction

To investigate whether pathological changes in the umbilical artery (UA), ductus venosus (DV) and short‐term fetal heart variation are related to perinatal outcome in severe, early intrauterine growth restriction (IUGR).

Fetomaternal immune cross-talk and its consequences for maternal and offspring's health

An improved mechanistic understanding of the adaptational processes mounted during mammalian reproduction is emerging. Intricate pathways occurring at the fetomaternal interface, such as the formation of a functional synapse between invading fetal trophoblast cells, and the involvement of various maternal immune cell subsets and epigenetically modified decidual stromal cells have now been identified. These complex pathways synergistically create a tolerogenic niche in which the semiallogeneic fetus can develop. New insights into fetomaternal immune cross-talk may help us to understand the pathogenesis of pregnancy complications as well as poor postnatal health. Moreover, the effects of maternal immune adaptation to pregnancy on autoimmune disease activity are becoming increasingly evident. Thus, insights into fetomaternal immune cross-talk not only advance our understanding of pregnancy-related complications but also may be informative on how immune tolerance can be modulated in clinical settings outside the context of reproduction.

Endoscopic laser coagulation of placental anastomoses in 200 pregnancies with severe mid-trimester twin-to-twin transfusion syndrome

OBJECTIVE To investigate perinatal outcome after endoscopic laser coagulation of the placental vascular anastomoses in severe mid trimester twin-to-twin transfusion syndrome (TTTS). STUDY DESIGN In a prospective study between January 1995 and September 1999, we performed laser therapy in 200 consecutive pregnancies with TTTS between 16 and 25 weeks of gestation. We compared outcome of the first group of 73 pregnancies whose outcome has been reported previously in a study comparing laser surgery and serial amniodrainages [Am J Obstet Gynecol 1999;180:717-24], with the following group of 127 patients. RESULTS The overall survival rate increased from 61% (89/146) in group 1 to 68% (172/254) in group 2. The percentage of pregnancies with survival of both fetuses was 42% (31/73) in group 1 and increased to 54% (69/127) in group 2 (P=0.142). The survival rate for at least one fetus was 81% (103/127) in group 2. The median gestational age at delivery of liveborn babies was 33.7 weeks in group 1 and 34.4 weeks in group 2 with a median interval of 13 weeks between the intervention and delivery. CONCLUSION This study of a large population of pregnancies with severe second trimester twin-to-twin transfusion syndrome confirms the improvements of outcome after laser therapy as compared to serial amniodrainages reported previously. Furthermore, it shows a trend towards an increase in survival rates with growing experience in this technique, most likely attributable to a more selective identification and efficient coagulation of the placental vascular anastomoses.

Perinatal morbidity and mortality in early‐onset fetal growth restriction: cohort outcomes of the trial of randomized umbilical and fetal flow in Europe (TRUFFLE)

Few data exist for counseling and perinatal management of women after an antenatal diagnosis of early‐onset fetal growth restriction. Yet, the consequences of preterm delivery and its attendant morbidity for both mother and baby are far reaching. The objective of this study was to describe perinatal morbidity and mortality following early‐onset fetal growth restriction based on time of antenatal diagnosis and delivery.

2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): A randomised trial

BACKGROUND No consensus exists for the best way to monitor and when to trigger delivery in mothers of babies with fetal growth restriction. We aimed to assess whether changes in the fetal ductus venosus Doppler waveform (DV) could be used as indications for delivery instead of cardiotocography short-term variation (STV). METHODS In this prospective, European multicentre, unblinded, randomised study, we included women with singleton fetuses at 26-32 weeks of gestation who had very preterm fetal growth restriction (ie, low abdominal circumference [<10th percentile] and a high umbilical artery Doppler pulsatility index [>95th percentile]). We randomly allocated women 1:1:1, with randomly sized blocks and stratified by participating centre and gestational age (<29 weeks vs ≥29 weeks), to three timing of delivery plans, which differed according to antenatal monitoring strategies: reduced cardiotocograph fetal heart rate STV (CTG STV), early DV changes (pulsatility index >95th percentile; DV p95), or late DV changes (A wave [the deflection within the venous waveform signifying atrial contraction] at or below baseline; DV no A). The primary outcome was survival without cerebral palsy or neurosensory impairment, or a Bayley III developmental score of less than 85, at 2 years of age. We assessed outcomes in surviving infants with known outcomes at 2 years. We did an intention to treat study for all participants for whom we had data. Safety outcomes were deaths in utero and neonatal deaths and were assessed in all randomly allocated women. This study is registered with ISRCTN, number 56204499. FINDINGS Between Jan 1, 2005 and Oct 1, 2010, 503 of 542 eligible women were randomly allocated to monitoring groups (166 to CTG STV, 167 to DV p95, and 170 to DV no A). The median gestational age at delivery was 30·7 weeks (IQR 29·1-32·1) and mean birthweight was 1019 g (SD 322). The proportion of infants surviving without neuroimpairment did not differ between the CTG STV (111 [77%] of 144 infants with known outcome), DV p95 (119 [84%] of 142), and DV no A (133 [85%] of 157) groups (ptrend=0·09). 12 fetuses (2%) died in utero and 27 (6%) neonatal deaths occurred. Of survivors, more infants where women were randomly assigned to delivery according to late ductus changes (133 [95%] of 140, 95%, 95% CI 90-98) were free of neuroimpairment when compared with those randomly assigned to CTG (111 [85%] of 131, 95% CI 78-90; p=0.005), but this was accompanied by a non-significant increase in perinatal and infant mortality. INTERPRETATION Although the difference in the proportion of infants surviving without neuroimpairment was non-significant at the primary endpoint, timing of delivery based on the study protocol using late changes in the DV waveform might produce an improvement in developmental outcomes at 2 years of age. FUNDING ZonMw, The Netherlands and Dr Hans Ludwig Geisenhofer Foundation, Germany.