Reduced telomere length in amniocytes: an early biomarker of abnormal fetal development?

Telomeres protect chromosome ends and control cell division and senescence. During organogenesis, telomeres need to be long enough to ensure the cell proliferation necessary at this stage of development. Previous studies have shown that telomere shortening is associated with growth retardation and congenital malformations. However, these studies were performed in newborns or postnatally, and data on telomere length (TL) during the prenatal period are still very limited. We measured TL using quantitative PCR in amniotic fluid (AF) and chorionic villi (CV) samples from 69 control fetuses with normal ultrasound (52 AF and 17 CV) and 213 fetuses (165 AF and 48 CV) with intrauterine growth retardation (IUGR) or congenital malformations diagnosed by ultrasound. The samples were collected by amniocentesis at the gestational age (GA) of 25.0 ± 5.4 weeks and by CV biopsy at 18.1 ± 6.3 weeks. In neither sample type was TL influenced by GA or fetal sex. In AF, a comparison of abnormal versus normal fetuses showed a significant telomere shortening in cases of IUGR (reduction of 34%, P < 10-6), single (29%, P < 10-6) and multiple (44%, P < 10-6) malformations. Similar TL shortening was also observed in CV from abnormal fetuses but to a lesser extent (25%, P = 0.0002; 18%, P = 0.016; 20%, P = 0.004, respectively). Telomere shortening was more pronounced in cases of multiple congenital anomalies than in fetuses with a single malformation, suggesting a correlation between TL and the severity of fetal phenotype. Thus, TL measurement in fetal samples during pregnancy could provide a novel predictive marker of pathological development.

Temperature Elevation in an Instrumented Phantom Insonated by B-Mode Imaging, Pulse Doppler and Shear Wave Elastography.

Diagnostic ultrasound is the gold standard for obstetric scanning and one of the most important imaging techniques for perinatal and neonatal monitoring and diagnosis. Ultrasound provides detailed real-time anatomic information, including blood flow measurements and tissue elasticity. The latter is provided through various techniques including shear wave elastography (SWE). SWE is increasingly used in many areas of medicine, especially in detection and diagnosis of breast, thyroid and prostate cancers and liver disease. More recently, SWE has found application in gynaecology and obstetrics. This method mimics manual palpation, revealing the elastic properties of soft biological tissues. Despite its rising potential and expanding clinical interest in its use in obstetrics and gynaecology (such as for assessment of cervical ripening or organ development and structure during pregnancy), its effects on and potential risks to the developing fetus remain unknown. Risks should be evaluated by regulatory bodies before recommendations are made on the use of SWE. Because ultrasound is known to produce thermal and mechanical effects, this study measured the temperature increase caused by B-mode, pulse Doppler (PD) and SWE, using an instrumented phantom with 11 embedded thermocouples. Experiments were performed with an Aixplorer diagnostic ultrasound system (Supersonic Imagine, Aix-en-Provence, France). As expected, the greatest heating was detected by the thermocouple closest to the surface in contact with the transducer (2.9°C for SWE, 1.2°C for PD, 0.7°C for B-mode after 380-s excitation). Both conduction from the transducer face and direct heating owing to ultrasound waves contribute to temperature increase in the phantom with SWE associated with a larger temperature increase than PD and B-mode. This article offers a methodological approach and reference data for future safety studies, as well as initial recommendations about SWE safety in obstetrics and gynaecology.

Factors associated to early intrauterine fetal demise after laser for TTTS by preoperative fetal heart and Doppler ultrasound.

OBJECTIVE: To determine the prognostic value of fetal Doppler and echocardiographic parameters for intrauterine fetal demise (IUFD) within 24 hours and within 1 week after laser coagulation in monochorionic pregnancies complicated by twin-twin transfusion syndrome. METHOD: This retrospective study correlated the preoperative hemodynamic and echocardiography parameters to the outcome in fetuses with twin-twin transfusion syndrome undergoing laser therapy. RESULTS: One hundred and twelve laser coagulations were performed between February 2006 and June 2015. The total (single and double) IUFD rate was 27.7%. Further, 59% of IUFD occurred within 24 hours and 74.4% occurred within 1 week after laser. The following were associated to IUFD within 24 hours: the middle cerebral arterial pulsatility index in the donor, abnormal umbilical artery (UA) end diastolic flow, increased middle cerebral artery peak systolic velocity, and right ventricular myocardial performance index (RV-MPI) z-score in the recipient. For IUFD within 1 week were the pulsatility index in the donor UA and the recipient abnormalities in UA, ductus venosus, middle cerebral artery-peak systolic velocity, and RV-MPI z-score. CONCLUSION: Following laser was early IUFD that was associated with Doppler findings suggesting donor cerebroplacental redistribution, and recipient overload cardiomyopathy, such as abnormal ductus venosus and UA Dopplers as well as an increase of RV-MPI.

Retinoic acid and tracheal occlusion for diaphragmatic hernia treatment in rabbit fetuses.

INTRODUCTION: Lung hypoplasia and pulmonary arterial hypertension in congenital diaphragmatic hernia lead to a high perinatal mortality. Although sustained fetoscopic tracheal occlusion (TO) improves lung development, a major side effect is abnormal pneumocyte differentiation. This study evaluated the potential ability of intratracheal retinoic acid (RA) administration to reduce adverse effects of sustained TO in a rabbit model of diaphragmatic hernia. METHODS: A left diaphragmatic defect was created on day 23 in time-dated pregnant rabbits. On day 28, the same rabbits underwent sham surgery or TO, with an injection of empty or RA-loaded liposomes. On day 30, the fetuses were harvested, and the lungs were processed for histology, immunohistochemistry, and gene expression quantification. RESULTS: A tracheal RA injection at the time of TO had no effect on the lung-to-body-weight ratio, radial alveolar count or lung connective tissue composition. Retinoic acid plus TO had synergic effects on vascular measurements, proportional medial thickness, and endothelin-1 receptor type-A gene expression. The most noticeable effect was recovery of normal pneumocyte differentiation. CONCLUSION: Retinoic acid plus TO prevented abnormal pneumocyte differentiation and seemed to have a beneficial effect on pulmonary vascularization.

Aortic Isthmus Flow Recording Predicts the Outcome of the Recipient Twin after Laser Coagulation in Twin-Twin Transfusion Syndrome.

INTRODUCTION: The objective was to assess the prognostic value of the systolic flow through the aortic isthmus in monochorionic pregnancies complicated by twin-twin transfusion syndrome (TTTS) treated by placental laser ablation. MATERIAL AND METHODS: Fetal echocardiography and outcome data of 105 cases of TTTS treated by laser photocoagulation of placental anastomoses were reviewed. Hemodynamic parameters were collected before and after treatment. The isthmic systolic index (ISI) was calculated as the peak systolic velocity/systolic nadir ratio. RESULTS: A total of 105 laser coagulations were studied. Fetal echocardiography pre- and post-laser were available in 68 cases, including 55 with data on aortic isthmic Doppler. Survival rates were 17, 22, and 61% for 0, 1, or 2 twins, respectively. At least 1 twin was delivered alive in 83% of the pregnancies. The mean gestational age at surgery was 21 weeks (range 16-26). Median ISI values were similar for donor and recipient twins, before and after laser ablation (all p > 0.05). A lower recipient ISI before laser was related to early recipient demise within 24 h (p = 0.04). DISCUSSION: A lower ISI before placental laser ablation for TTTS is associated with postoperative demise of the recipient twin.