Publikationen

Application of video-endoscopic surgery to the gravid uterus provides a new treatment option for the fetus with a correctable congenital anomaly. “Fetendo” surgery requires temporary enlargement of the uterine cavity to create a working space. Volume expansion of the amniotic space raises intrauterine pressure, which could increase placental vascular resistance and thereby reduce placental blood flow. To test this hypothesis, the authors developed a fetal sheep model to examine the relationship between insufflating pressure and flow in the placental circulation. Fetoplacental blood flow was measured via ultrasonic flow probes placed around the fetal common umbilical artery and the maternal uterine artery in five anesthetized 120-day-gestation ewes. Invasive feto-maternal monitoring permitted synchronous measurement of fetal mean arterial pressure, fetal central venous pressure, maternal mean arterial pressure, amniotic pressure, and fetal oxygen saturation, with calculated values for fetal and maternal placental vascular resistance. Amniotic pressure was raised from 10 mm Hg to 40 mm Hg in 5-mm Hg increments by a combination of saline amnioinfusion and external uterine compression. At amniotic pressures of 20 mm Hg or less, placental blood flow was preserved; however, elevation of amniotic pressure above 20 mm Hg resulted in a significant decrease in placental flow, with concomitant fetal hypoxia. The authors conclude that the relationship between intrauterine pressure, flow in the placental circulation, and fetal oxygen delivery must be considered when selecting intrauterine insufflation pressures for hysteroscopic intervention.

Journal: Journal of Pediatric Surgery (Volume 30, Issue 8, Pages 1165-1168)

Fetal skin heals by regeneration rather than by adult-type scarring. Prior studies indicate that scarless healing is an intrinsic property of fetal tissue.

Journal: Surgery (Volume 118, Issue 1, Pages 82-86)

A recent study in human fetuses with myelomeningocele (MMC) suggested that the primary malformation is not neural but a failed closure of the posterior vertebral column and paraspinal soft tissue, which leads to exposure and secondary destruction of the spinal cord. The goal of this study was to test whether chronic exposure of the normal spinal cord to the amniotic space produces a lesion similar to human MMC. In fetal sheep at 75 days' gestation (group A) and 60 days' gestation (group B) (term = 150 days), the lumbar spinal cord was exposed to the amniotic cavity by excising skin and paraspinal soft tissues, and by performing a laminectomy. Some animals from both groups were fetectomized and assessed morphologically at 100 days' gestation. The remainder were delivered near term and assessed clinically, electrophysiologically, and morphologically. In group A, all animals showed MMC-type pathology. The exposed spinal cord was herniated out of the spinal canal and rested on the dorsal membranes of a cystic sac. The neural tissue was stretched and flattened out. Histologically, the hallmarks of the spinal cord were not discernable and the cytoarchitecture was lost. These changes were less severe at 100 days than at term. The three survivors in group A were paraplegic. In group B, the two survivors and two fetuses harvested at 100 days had healed skin wounds and near normal spinal cord histology. The other animal harvested at 100 days had a MMC-type lesion with less severe histological changes. The two survivors had a mild paraparesis. In conclusion, surgical exposure of the normal spinal cord to the amniotic space in a 75-day sheep fetus results in a MMC-type pathology at birth, which clinically and morphologically resembles human MMC. The creation of a spina bifida-type lesion in a 60-day-old fetus may result in spontaneous healing and minimal neurological deficit at birth. This “healing experiment of nature” suggests that in utero repair of MMC might prevent spinal cord damage and spare neurological function.

Journal: Journal of Pediatric Surgery (Volume 30, Issue 7, Pages 1028-1033)

In utero surgery rescues neurological function at birth in sheep with spina bifida

We hypothesize that the neurologic deficit associated with open spina bifida is not directly caused by the primary defect but rather is due to chronic mechanical and chemical trauma since the unprotected neural tissue is exposed to the intrauterine environment. We report here that exposure of the normal spinal cord to the amniotic cavity in midgestational sheep fetuses leads to a human-like open spina bifida with paraplegia at birth, indicating that the exposed neural tissue is progressively destroyed during pregnancy. When open spina bifida was repaired in utero at an intermediate stage, the animals had near-normal neurologic function. The spinal cord was deformed but largely preserved. These findings suggest that secondary neural tissue destruction during pregnancy is primarily responsible for the functional loss and that timely in utero repair of open spina bifida might rescue neurologic function.

Journal: Nature Medicine 1, 342-347 (1995)

The aim of this study was to determine whether the fetal alimentary tract shares the unique scarless healing properties of fetal skin. Full-thickness incisional gastric wounds were created and sutured closed in fetal lambs at 60, 75, and 120 days' gestation (full term, 145 days), and in adult control sheep. At the time of harvest, 14 days postwounding, dense fibrous adhesions were found intraperitoneally in all fetal and adult animals. Histologically, all fetal and adult gastric wounds healed with pronounced scar formation. In contrast to the adult wound, there was no significant inflammatory response in the fetal wounds. Because scar formed in the absence of inflammation in fetal gastric wounds, there is no obvious relation between scarring and the inflammatory response at this location. This study shows that not all fetal tissues exhibit scarless repair properties.

Journal: Journal of Pediatric Surgery (Volume 30, Issue 3, Pages 392-395)