William Polzin

Early manifestations and spectrum of recipient twin cardiomyopathy in twin–twin transfusion syndrome: relation to Quintero stage

To examine cardiac structural and functional changes in twin–twin transfusion syndrome (TTTS), relative to Quintero stage, as a means of evaluating the spectrum of cardiomyopathy in TTTS.

Incidence of complications in twin-twin transfusion syndrome after selective fetoscopic laser photocoagulation: a single-center experience

OBJECTIVE The purpose of this study was to evaluate the incidence of complications after selective fetoscopic laser photocoagulation for twin-twin transfusion syndrome (TTTS). STUDY DESIGN One hundred fifty-two cases of TTTS were treated with selective fetoscopic laser photocoagulation from 2005-2008. Complications were TTTS recurrence, amniotic band syndrome, iatrogenic monoamnionicity, and twin anemia-polycythemia sequence. Data were placed in the following categories: no complications; early complications < or =7 days; late complications >7 days; both early and late complications. RESULTS The incidence of early, late, and both early and late complications was 31%, 39%, and 10%. Complications included 2 cases (1.3%) of monoamnionicity, 3 cases (2.0%) of recurrent TTTS, 3 cases (2.0%) of twin anemia-polycythemia sequence, and 5 cases (3.3%) of amniotic band syndrome. Cases with TTTS with early complications had a lower number of superficial arteriovenous vascular anastomoses and 1 or both fetus survival (70.2% vs 96.7%; P < .001), compared with no complications. Fetal survival was 238 of 307 cases (77.5%), with 1 or both twins surviving in 134 of 152 (88%) of pregnancies. CONCLUSION The incidence of early, late, and both early and late complications was 31%, 39%, and 10%, respectively. Close postoperative surveillance is important.

High-risk fetal congenital pulmonary airway malformations have a variable response to steroids

BACKGROUND/PURPOSE Anecdotal reports suggest that maternal steroids may arrest the growth of congenital pulmonary airway malformations (CPAMs), preventing or reversing hydrops. We reviewed our experience with CPAMs to determine the fetal response to steroid therapy. METHODS This study is a retrospective review of all fetal CPAMs from 2004 to 2008. Fetuses with high-risk CPAMs that received at least one course of steroids were identified. Fetal magnetic resonance imaging and ultrasound data were used to classify the CPAMs, identify hydrops fetalis and follow the fetuses poststeroid dosing. RESULTS Forty-four fetuses with CPAM were identified. Fifteen patients were found to have received at least one course of steroids. Thirteen were hydropic and 2 were nonhydropic. Seven of the 13 hydropic fetuses (54%) showed an initial response to steroid administration, whereas the 2 nonhydropic high-risk fetuses progressed to birth without developing hydrops. Seven of the 15 patients, however, resulted in fetal demise or early postnatal death, giving a survival rate of 53%. CONCLUSIONS High-risk CPAMs have a variable response to steroids. This variable response demonstrates the need for a placebo-controlled randomized study to more accurately determine the effect of steroids on hydrops and CPAM growth rates. Repeated steroid courses may not be helpful, and progression in CPAM volume to head circumference ratio (CVR) or hydrops should prompt open fetal surgery to prevent irreversible fetal insult.

Acute effects of selective fetoscopic laser photocoagulation on recipient cardiac function in twin-twin transfusion syndrome

OBJECTIVE This study evaluated the acute effects of selective fetoscopic laser photocoagulation (SFLP) on recipient cardiovascular function in a twin-twin transfusion syndrome (TTTS) pregnancy. STUDY DESIGN This was a retrospective chart review of echocardiographic data in TTTS including right (RV) and left (LV) ventricular Doppler myocardial performance index (MPI); LV and RV end diastolic wall thickness; and umbilical artery (UA), vein (UV), and ductus venosus (DV) Dopplers. The primary outcome measures were improved MPI defined as greater than 10% interval decrease in left and/or right MPI. Data were analyzed by Student t test and Fishers exact test. RESULTS Sixty-five patients met inclusion criteria. SFLP results in a significant improvement in UV and DV Doppler and an increase in both RV and LV wall thickness. A 10% or greater improvement in recipient LV MPI after SFLP is associated with improved recipient survival as compared with unimproved LV MPI (100% vs 86.1%, P = .05). CONCLUSION Improved recipient myocardial performance index after SFLP is associated with improvement in recipient survival.

THE ETIOLOGY OF PREMATURE RUPTURE OF THE MEMBRANES

The etiology of PROM is multifactorial. It is clear that maternal enzymes, maturational and mechanical forces, chorionicamniotic membrane phospholipid content, collagen disruption, amniotic cell cytokines induced by fetal signals, and bacterial phospholipases and collagenases all play major and interrelated roles. It is also clear that the production of oxytocic prostaglandins is a major, if not exclusive, common pathway leading to PROM and preterm delivery. The increasing awareness of the fetal role, i.e., fetal interleukins, fetal polymorphonuclear leukocytes and type V collagenase, make this area of research ripe for further investigation. The complex host defense mechanisms and biologic variability make any universal treatment impossible. Even with a specific etiology determined, the reduced availability of pharmacologic interventions for the fetal compartment portend suboptimal success. Therefore, it appears that continued research and aggressive measures to optimize the quality and availability of prenatal care are the best foci of our efforts.

Prevalence and progression of recipient-twin cardiomyopathy in early-stage twin–twin transfusion syndrome

The management of twin–twin transfusion syndrome (TTTS) in its early stages (Quintero Stages I and II) is controversial. We describe the prevalence, severity, incidence and rate of progression of recipient‐twin cardiomyopathy in Stages I and II TTTS.

Congenital High Airway Obstruction Syndrome due to Complete Tracheal Agenesis: An Accident of Nature with Clues for Tracheal Development and Lessons in Management

Congenital high airway obstruction syndrome (CHAOS) is a life-threatening condition characterized by complete blockage of the fetal airways associated with hydrops. We present a case of CHAOS due to the rare cause of complete tracheal agenesis. The ex utero intrapartum therapy (EXIT) strategy was employed to allow for neck and mediastinal exploration. Thymectomy allowed dissection to the level of the carina demonstrating the confluence of dilated mainstem bronchi but no trachea and no connection to the esophagus. A 2.5 endotracheal tube was inserted into the right mainstem bronchus and secured to the left clavicle. At 3 months of age, the infant succumbed to sepsis from Enterobacter mediastinitis due to friction between the tracheostomy tube and the nasogastric tube resulting in erosion of the esophagus. Complete tracheal agenesis, as seen in this case, is consistent with the failure of normal tracheal elongation as suggested by newer theories of foregut development. This case illustrates the most severe form of tracheal atresia causing CHAOS ever salvaged by the EXIT procedure at birth. The subsequent postnatal course highlights the need for early tracheal replacement in this particularly challenging form of CHAOS.

Severe micrognathia: indications for EXIT-to-Airway.

The ex utero intrapartum treatment (EXIT) procedure has become an important management option in cases of fetal airway obstruction. Select cases of severe micrognathia may be candidates for EXIT-to-Airway due to high-risk of airway obstruction at birth. Here we present three successful EXIT-to-Airway procedures for the management of congenital micrognathia in its most severe manifestations. Case 1: A 23-year-old G3P1011 with a pregnancy complicated by severe micorgnathia, jaw index <5th percentile, as well as polyhydramnios. At 36 weeks EXIT-to-Airway was performed utilizing a bronchoscopically positioned laryngeal mask airway (LMA) during 23 min of uteroplacental support followed by tracheostomy. Case 2: A 26-year-old G4P0120 with a pregnancy complicated by severe micrognathia, jaw index <5th percentile, and an obstructed oropharynx associated with polyhydramnios. At 37 weeks EXIT-to-Airway was performed with placement of tracheostomy. Case 3: A 36-year-old G6P3023 with fetal magnetic resonance imaging (MRI) revealing esophageal atresia, polyhydramnios, and severe micrognathia with a jaw index <5th percentile. At 35 weeks the patient underwent EXIT-to-Airway with formal tracheostomy during 35 min of uteroplacental bypass. In the most severe cases of fetal micrognathia, EXIT-to-Airway provides time to evaluate and secure the fetal airway prior to delivery. We propose indications for EXIT-to-Airway in micrognathia to include a jaw index <5%, with indirect evidence of aerodigestive tract obstruction such as polyhydramnios, glossoptosis or an absent stomach bubble.

The relationship between amniotic fluid levels of brain-type natriuretic peptide and recipient cardiomyopathy in twin-twin transfusion syndrome.

OBJECTIVE We sought to evaluate amniotic fluid brain natriuretic peptide (BNP) levels as a biomarker of recipient twin (RT) cardiomyopathy (RTCM) in twin-twin transfusion syndrome. STUDY DESIGN Amniotic fluid samples were obtained from 157 twin-twin transfusion syndrome RTs and from 6 singletons (controls) from 2007 through 2009. N-terminal prohormone BNP (NT-proBNP) levels were quantified by enzyme-linked immunosorbent assay. RTCM was classified as mild (IIIA), moderate (IIIB), or severe (IIIC) by fetal echocardiography. The relationship between NT-proBNP and RTCM was evaluated using analysis of variance. The ability of NT-proBNP to predict moderate or greater RTCM was evaluated by receiver operating characteristic analysis. RESULTS There is a significant positive correlation between NT-proBNP levels and worsening RTCM (r = 0.33; P < .001). NT-proBNP thresholds of 569 fmol/mg and 369 fmol/mg had a sensitivity of 70% and 87%, and specificity of 67% and 42%, respectively, in predicting moderate or greater RTCM. CONCLUSION This is the first large case series that demonstrates a relationship between NT-proBNP and RTCM. This pathophysiologic insight supports ongoing efforts to develop screening biomarkers.

Hypoplastic left heart syndrome is associated with structural and vascular placental abnormalities and leptin dysregulation.

INTRODUCTION Hypoplastic left heart syndrome (HLHS) is a severe cardiovascular malformation (CVM) associated with fetal growth abnormalities. Genetic and environmental factors have been identified that contribute to pathogenesis, but the role of the placenta is unknown. The purpose of this study was to systematically examine the placenta in HLHS with and without growth abnormalities. METHODS HLHS term singleton births were identified from a larger cohort when placenta tissue was available. Clinical data were collected from maternal and neonatal medical records, including anthropometrics and placental pathology reports. Placental tissues from cases and controls were analyzed to assess parenchymal morphology, vascular architecture and leptin signaling. RESULTS HLHS cases (n = 16) and gestational age-matched controls (n = 18) were analyzed. Among cases, the average birth weight was 2993 g, including 31% that were small for gestational age. When compared with controls, gross pathology of HLHS cases demonstrated significantly reduced placental weight and increased fibrin deposition, while micropathology showed increased syncytial nuclear aggregates, decreased terminal villi, reduced vasculature and increased leptin expression in syncytiotrophoblast and endothelial cells. DISCUSSION Placentas from pregnancies complicated by fetal HLHS are characterized by abnormal parenchymal morphology, suggesting immature structure may be due to vascular abnormalities. Increased leptin expression may indicate an attempt to compensate for these vascular abnormalities. Further investigation into the regulation of angiogenesis in the fetus and placenta may elucidate the causes of HLHS and associated growth abnormalities in some cases.