Background: Partial amniotic carbon dioxide insufflation (PACI) during fetoscopic interventions greatly improves visualization of intraamniotic contents. The purpose of this study was to assess any histologically discernable effects from this approach on the fetal brain after long-term survival in sheep. Methods: Six pregnant ewes between 63 and 92 days of gestation underwent PACI after fetoscopic intraamniotic access. Insufflation pressures ranged between 7 and 15 mm Hg (mean 11.7; median 12.5). Insufflation times ranged between 45 and 80 minutes (mean 55.8 minutes; median 52.5) and depended on the duration of various percutaneous fetoscopic maneuvers (e.g., posturing, fetal transesophageal electrocardiography, and chronic fetal vascular access) that were tested during these studies. After fetal spontaneous delivery between 147 and 150 days of gestation, 5 of the lambs were observed for abnormal neurological symptoms. The last ewe and her sheep were terminated at 133 days of gestation for humane reasons. All six brains were examined for hemorrhage, embolism, infarctions, inflammatory changes, and abnormal cortical maturation. An unoperated sibling was available as a control. Results: The 5 sheep that were spontaneously delivered exhibited no abnormal neurological findings. In all 6 sheep, PACI did not result in any histologically discernable damage to their brain in these long-term studies. Maternal and fetal complications were not observed during or after the approach. Conclusion: The application of PACI during minimally invasive fetoscopic interventions seems safe for the fetal brain. Due to the still limited clinical experience with PACI, continued assessment of its maternal and fetal risks as well as management are required.

Background: Microbiome dysbiosis can have long-lasting effects on our health and induce the development of various diseases. Bronchopulmonary dysplasia (BPD) is a multifactorial disease with pre- and postnatal origins including intra-amniotic infection as main risk factor. Recently, postnatal pathologic lung microbiota colonization was associated with BPD. The objectives of this prospective observational cohort study were to describe differences in bacterial signatures in the amniotic fluid (AF) of intact pregnancies without clinical signs or risk of preterm delivery and AF samples obtained during preterm deliveries and their variations between different BPD disease severity stages. Methods: AF samples were collected under sterile conditions during fetal intervention from intact pregnancies (n = 17) or immediately before preterm delivery < 32 weeks (n = 126). Metabarcoding based approaches were used for the molecular assessment of bacterial 16S rRNA genes to describe bacterial community structure. Results: The absolute amount of 16S rRNA genes was significantly increased in AF of preterm deliveries and detailed profiling revealed a reduced alpha diversity and a significant change in beta diversity with a reduced relative abundance of 16S rRNA genes indicative for Lactobacillus and Acetobacter while Fusobacterium, Pseudomonas, Ureaplasma and Staphylococcus 16S rRNA gene prevailed. Although classification of BPD by disease severity revealed equivalent absolute 16S rRNA gene abundance and alpha and beta diversity in no, mild and moderate/severe BPD groups, for some 16S rRNA genes differences were observed in AF samples. Bacterial signatures of infants with moderate/severe BPD showed predominance of 16S rRNA genes belonging to the Escherichia-Shigella cluster while Ureaplasma and Enterococcus species were enriched in AF samples of infants with mild BPD. Conclusions: Our study identified distinct and diverse intrauterine 16S rRNA gene patterns in preterm infants immediately before birth, differing from the 16S rRNA gene signature of intact pregnancies. The distinct 16S rRNA gene signatures at birth derive from bacteria with varying pathogenicity to the immature lung and are suited to identify preterm infants at risk. Our results emphasize the prenatal impact to the origins of BPD.

Fetal surgery has become a lifesaving reality for hundreds of fetuses each year. The development of a formidable spectrum of safe and effective minimally invasive techniques for fetal interventions since the early 1990s until today has led to an increasing acceptance of novel procedures by both patients and health care providers. From his vast personal experience of more than 20 years as one of the pioneers at the forefront of clinical minimally invasive fetal surgery, the author describes and comments on old and new minimally invasive approaches, highlighting their lifesaving or quality-of-life-improving potential. He provides easy-to-use practical information on how to perform partial amniotic carbon dioxide insufflation (PACI), how to assess lung function in fetuses with pulmonary hypoplasia, how to deal with giant CPAMS, how to insert shunts into fetuses with LUTO and hydrothorax when conventional devices are not available, and how to resuscitate a fetus during fetal cardiac intervention. Furthermore, the author proposes a curriculum for future fetal surgeons, solicits for the centralization of patients, for adequate maternal counseling, for adequate pain management and adequate hygienic conditions during interventions, and last but not least for starting the process of academic recognition of the matured field as an independent specialty. These steps will allow more affected expectant women and their unborn children to gain access to modern minimally invasive fetal surgery and therapy. The opportunity to treat more patients at dedicated centers will also result in more opportunities for the research of rare diseases and conditions, promising even better pre- and postnatal care in the future.

Purpose To evaluate pre- and post-procedure myocardial function in monochorionic twins with TTTS who underwent laser ablation of placental anastomoses using pulsed wave tissue Doppler imaging (pw TDI). Materials and Methods 20 monochorionic twin gestations with TTTS were included and underwent laser ablation at our center between 2011 and 2014. Prior to and after the intervention, cardiac function was assessed by measuring the mitral annular plane systolic excursion (MAPSE), the tricuspid annular plane systolic excursion (TAPSE), Tei index, isovolumetric contraction time (ICT), ejection time (ET), isovolumetric relaxation time (IRT) for the left ventricle in pulsed wave Doppler (pw D) ultrasound as well as ICT, ET, IRT and Tei index in pw TDI for the left and right ventricle. E-, A-, E´- and A´-wave peak velocity and the systolic downward motion (S´) were measured for both ventricles and the E/A, E/E´ and E´/A´ ratios were calculated. In a mean of 1.3 (SD 0.6) days after laser ablation, this measurement protocol was repeated. Results Pre-intervention recipients had longer ICT, ET and IRT in pw D and pw TDI compared to donors not reaching statistical significance for most parameters. Statistically significant were prolonged ICT in pw D (p 0.01) and ET (p 0.01) in pw TDI in recipients. In donor fetuses preoperative myocardial function did not differ significantly from postoperative myocardial function except in increased left ventricular ejection time of the left ventricle in pw TDI (p 0.04) and an increased E´/A´ratio (p 0.01). After laser coagulation, myocardial function was slightly altered in recipients as ICT and IRT shortened and Tei indices decreased but only reaching statistical significance in shortened IRTs in pw TDI for both ventricles. Conclusion Laser ablation of placental anastomoses in TTTS might influence myocardial function in the postoperative period. Shortened IRT intervals may reflect an improvement of diastolic function in recipients.