['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.', '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.', '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.'] Does partial amniotic carbon dioxide insufflation during minimally invasive fetoscopic interventions seem safe for the fetal brain in sheep?