Management of the fetus with congenital hydronephrosis II: Prognostic criteria and selection for treatment

Selecting appropriate management for the fetus with bilateral congenital hydronephrosis depends on our ability to accurately assess the severity of existing renal damage and to predict the potential for recovery of renal and pulmonary function if the obstruction is relieved. We reviewed our experience with 20 fetuses with congenital bilateral hydronephrosis to determine the prognostic value of various criteria used to assess functional potential, including temporary catheter exteriorization to measure fetal urine output and composition. Based on autopsy, biopsy, or clinical outcome, ten fetuses were classified retrospectively as "poor function," and ten fetuses as "good function." The good function group could be distinguished from the poor function group by the following criteria: Amniotic fluid (AF) status at presentation (P less than .001), ultrasound appearance of the fetal kidneys (P less than .05), fetal urine sodium and chloride concentration and osmolarity (P less than .001), and hourly urine output (P less than .02), but not by fetal urine iothalamate excretion or potassium and creatinine concentrations (P greater than .05). Based on these results, we have identified prognostic criteria that accurately identify the fetus with "good function" from the fetus with "poor function." We also reviewed the clinical management of our last 12 unreported cases. Ten fetuses had undergone diagnostic catheter placement and in utero renal function testing. This led to placement of a therapeutic indwelling catheter-shunt in seven fetuses (three required multiple shunts) and a suprapubic vesicostomy in another. Catheter related complications, including three cases of chorioamnionitis, emphasize the need for better methods of in utero decompression in selected cases. Our ability to select appropriate management has improved markedly.     

Effect of in utero vesicostomy on pulmonary hypoplasia in the fetal lamb with bladder outlet obstruction and oligohydramnios: a morphometric analysis

A model of early gestation bladder outlet obstruction and oligohydramnios in the fetal lamb is characterized by small, immature lungs (pulmonary hypoplasia). The current study examines how in utero relief of urinary tract obstruction produced early in gestation modifies pulmonary hypoplasia. Bladder obstruction was created at 60 days gestation in fetal sheep (term = 140 days); 11 fetuses then underwent in utero decompression at 95 to 100 days; six were left obstructed. Five normal fetuses served as controls and two underwent sham obstruction and vesicostomy. All were delivered and sacrificed near term (135 days), the right lung was inflation-fixed and its volume determined. Relative volumes of alveoli, alveolar ducts, and tissue, alveolar surface area, and alveolar numerical density were estimated morphometrically. Kidneys were examined histologically. In all animals persistent bladder obstruction produced oligohydramnios. Bladder obstruction to term produced pulmonary hypoplasia with a mean right lung volume-to-body weight ratio (LV:BW) of 14.3 cc./kg. (normal = 36.4, p less than 0.001). Structural immaturity was evidenced by an airspace fraction of only 57% (normal = 68%, p less than 0.05). Kidneys in these animals were not dysplastic; there was hydronephrosis or evidence of spontaneous urinary decompression. In eight of the 11 animals, decompression improved the LV:BW ratio to 28.4 cc./kg. (vs. obstructed, p less than 0.001; vs normal, p less than 0.05) and normalized maturity. All had increased amniotic fluid at delivery; kidneys in 7/8 animals were normal, and the other had moderate hydronephrosis. One of the 11 animals had normal kidneys, oligohydramnios, immature lungs, but with normal volume. Oligohydramnios was present in the other two of 11 fetuses despite successful decompression and they had markedly dysmorphic kidneys and profoundly hypoplastic and immature lungs (LV:BW 5.1 cc./kg.). Even after 35 days (25% gestation) of obstruction, in utero urinary tract decompression permits better lung growth and maturation than in persistently obstructed animals. The degree of renal damage from obstruction appears to be a critical determinant in the correction of pulmonary hypoplasia.     

Early experience with open fetal surgery for congenital hydronephrosis

The fetus with severe bilateral hydronephrosis and associated oligohydramnios in the second trimester is doomed at birth by ongoing pulmonary and renal damage. Since decompression with percutaneously placed catheters anesthetic, surgical, and tocolytic techniques for open fetal anesthetic, surgical, and tocolytic techniques for open fetal urinary tract decompression in animals, and have now applied those techniques to a small group of five patients. One had bilateral ureterostomies and the subsequent four had marsupialization of the bladder. All pregnancies proceeded to cesarean delivery at 32 to 35 weeks' gestation. There was no long-term maternal morbidity, and two mothers have since experienced normal pregnancies. Three fetuses had return of normal amniotic fluid dynamics, and all three had adequate pulmonary function at birth, suggesting that fatal pulmonary hypoplasia associated with early severe oligohydramnios had been reversed. Two neonates died at birth with pulmonary hypoplasia. One had no amniotic fluid even after decompression, and the other had some amniotic fluid after decompression but a tiny chest cavity due to the long period of severe oligohydramnios before decompression. Of the three surviving infants, one had normal renal function when she died of unrelated causes at 9 months of age. One has normal renal function at 23 months and the third had failing renal function at 2 1/2 years and has grown and developed normally, but will require renal transplantation. We have now developed selection criteria that would exclude from treatment the two fetuses who died of pulmonary hypoplasia and the one who developed renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intrauterine tracheal obstruction, a new treatment for congenital diaphragmatic hernia, decreases amniotic fluid sodium and chloride concentrations in the fetal lamb.

OBJECTIVE: To evaluate the effect of fetal tracheal occlusion on sodium and chloride concentrations in amniotic and tracheal fluid. SUMMARY BACKGROUND DATA: Intrauterine tracheal occlusion has been proposed to reverse pulmonary hypoplasia, an important prognostic factor in congenital diaphragmatic hernia. In early human trials, technical failure of the obstructive device has been reported. METHODS: Eight fetal lambs (gestational age = 95 days) were subjected to fetal tracheoscopy, and amniotic and tracheal fluid samples were taken. In multiple pregnancies (n = 6), amniotic fluid was also sampled from the contralateral amniotic sac and used as a control. Subsequently, endotracheal obstruction, using a detachable balloon, was performed. After 14 days, all fetuses were delivered, and sodium and chloride concentrations in amniotic and tracheal fluid were measured again. Statistical analysis was done using a two-tailed Student's t test, paired or unpaired as appropriate. RESULTS: In controls, between 95 and 109 days gestational age, no significant changes occurred in sodium or chloride concentrations in amniotic or tracheal fluid. After 2 weeks of tracheal obstruction, however, chloride and sodium concentrations in amniotic fluid decreased (chloride = 76.7 mEq/L vs. 107.6 mEq/L, p = 0.0003; sodium = 109.6 mEq/L vs. 125.9 +/- 5.2 mEq/L, p = 0.019). A concomitant increase in chloride and sodium concentration was observed in tracheal fluid (chloride = 145.4 mEq/L vs. 130.0 mEq/L, p = 0.047; sodium = 153.1 mEq/L vs. 142.9 mEq/L, p = 0.051). When comparing groups at 109 days, chloride and sodium concentrations in amniotic fluid were markedly lower in the treated group versus controls (p = 0.0004 and p = 0.05 for chloride and sodium, respectively). CONCLUSION: Complete tracheal occlusion in ovine fetuses results in a significant decrease of amniotic fluid sodium and chloride concentrations.     

The natural history of prenatal hydronephrosis with normal amounts of amniotic fluid

Thirteen cases of fetal hydronephrosis associated initially with normal volumes of amniotic fluid were diagnosed by maternal sonography. No invasive procedures were done in utero. Postnatal evaluation demonstrated 8 neonates with urinary tract obstruction and 5 normal neonates. Long-term followup of these 13 patients revealed that 12 are healthy and have normal renal function. The exception is a child whose amniotic fluid decreased during pregnancy. Our data suggest that fetuses with normal volumes of amniotic fluid do well. Treatment should be limited to frequent prenatal sonography and subsequent early postnatal evaluation. Caution should be exercised with the diagnosis of hydronephrosis, since 5 of our patients had false positive findings. In the rare instances when oligohydramnios develops during pregnancy fetal intervention may be warranted.     

Fetal uropathies: diagnostic pitfalls and management

Based on the experience of 63 antenatal diagnoses of fetal uropathic conditions we discuss the diagnostic problems, practical implications of antenatal diagnosis and potential indications of in utero intervention. A correct diagnosis was established in 43 of the 63 cases (70 per cent). Diagnostic problems were encountered in differentiating among multicystic dysplastic kidneys and ureteropelvic junction obstruction, dilatation owing to reflux or obstruction and lack of visualization of small hypoplastic kidneys. Transitory urinary tract dilatation was found in 14 cases (22 per cent) and can be responsible for additional false positive findings. Evaluation of the thoracic development and amniotic fluid must be part of the examination, since they are related to severe obstructive uropathy. Repeat examinations are necessary in these cases. During evaluation of the eventual benefit of an in utero decompression one should consider the diagnostic difficulties, mainly the time of onset of fetal uropathic conditions during morphogenesis and the absence of a clinically reliable method to evaluate fetal renal function. To date there are no real indications for in utero intervention in most detectable cases. The major benefit of prenatal echography is to allow early recognition of major uropathic conditions before postnatal infection worsens the prognosis.     

The effects of partial and total amniotic fluid exclusion on excisional fetal rabbit wounds

Previous studies have consistently demonstrated that fetal rabbit excisional wounds exposed to amniotic fluid do not heal in utero. This study examines fetal wounds covered to exclude amniotic fluid. Full-thickness excisional wounds were created on fetal rabbits on day 25 of gestation. The following three treatment groups were examined: uncovered (n = 19 live); covered, a silicone cover was sutured over the wound (n = 14 live); and donut, a silicone cover containing a 2-mm central hole was sutured over the wound (n = 6 live). Fetuses were returned to the uterus and harvested by cesarean section 72 hr postoperatively. Fetal (covered) wounds excluded from amniotic fluid contracted and reepithelialized up to confluence. Sixteen of 19 uncovered wounds expanded, 3 were unchanged; minimal reepithelialization was present in all wounds. Partially (donut) covered wounds exhibited an intermediate response. This study shows that excisional wounds in the rabbit fetus respond to injury by contracting and reepithelializing when excluded from amniotic fluid.     

Urological emergency in neonates with congenital hydronephrosis

OBJECTIVE: It is well described that unilateral pelviureteric junction obstruction (PUJO) is a benign condition, because the dilatation resolves spontaneously and the function does not decrease in most of the kidneys. However, there is exceptional PUJO that requires emergent treatment in neonatal periods. The aim of this article is to report the urological emergency and management in neonates with PUJO. MATERIALS AND METHODS: Nine children (seven boys and two girls) with PUJO who underwent neonatal emergent treatment during the last 13 years were reviewed. Renal function was evaluated according to decay curve of serum creatinine (SCr) levels corresponding to gestational age (GA) at delivery. Physical examination, ultrasonographic monitoring, and chest and abdominal plain radiographs were repeated in each neonate. RESULTS: Eight patients were detected prenatally. In five patients, multicystic dysplastic kidney (MCDK) was demonstrated on the contralateral side. Three patients underwent percutaneous puncture of fetal hydronephrosis. Decrease of amniotic fluid was evident in three fetuses. Indications for emergent treatment included mass effect from hydronephrosis in three patients, renal dysfunction in five, and severe urinary tract infection in one. During neonatal periods, a percutaneous nephrostomy tube was placed in seven, and open nephrostomy in one with anorectal malformation. Repeated punctures of the dilated renal pelvis were done in one patient. Renal function after pyeloplasty was stable in eight patients, while it was moderately decreased in one who was associated with oligohydramnios in utero. CONCLUSION: Indications for emergent treatment in neonates with PUJO included mass effect from giant hydronephrosis, renal dysfunction and severe urinary tract infection. At birth, respiratory and circulatory conditions must first be stabilized. In neonates with hydronephrosis of the solitary kidney or severe bilateral PUJO, serial SCr should be monitored to evaluate renal function. Decrease of amniotic fluid suggested renal functional compromise that would not recover after urological management.     

胎儿肾积水的超声诊断及转归分析

目的用超声方法检测胎儿肾积水程度与出生后积水肾的转归情况。方法选择2000年9月至2007年6月我院门诊就诊的单胎孕妇，应用超声检查筛选并随访肾积水胎儿163例（221侧）积水胎肾，随访时间最长为2．5年，同期测量15孕周至40孕周正常胎儿肾脏，记录肾脏集合系统内径及肾皮质厚度。结果正常胎儿的肾脏在孕28—32周可以测量到7mm左右集合系统的分离，肾脏皮质厚度均在5mm以上；本组胎肾集合系统前后径分离值10～15mm者：Ⅰ组，165侧，其中皮质厚度在5mm以下者37侧，6侧手术治疗；集合系统前后径〉15mm者：Ⅱ组，56侧，皮质厚度〉5mm的42侧中3侧手术治疗，皮质厚度5mm以下14侧，其中11例手术治疗。结论产前胎儿肾积水大部分都是生理性的，可随着个体的发育而自发消退，对于生后仍存在肾积水的患儿，应定期随访观察；超声检查显示肾集合系统前后径〉15mm，肾皮质厚度〈5mm的胎儿肾积水往往存在病理性梗阻，应高度重视。     

Feasibility of intracranial surgery in the rat fetus: model and surgical principles

The feasibility of intracranial surgery in the rat fetus is demonstrated by the use of a microsurgical model. In utero craniotomy and cerebral incision have been performed successfully without compromise of the fetal-maternal unit. Maternal and fetal survival rates of 95 and 93%, respectively, are reported. Several principles of fetal surgery have been established and are discussed. These include the inhibition of uterine contraction, monitoring of physiological variables, timing of operation, microsurgical technique, and preservation of amniotic fluid. The fetal rat model is amenable to antenatal research because it fulfills certain criteria, including accurately timed pregnancies, littermate controls, inexpensiveness, and animal availability.     

Correction of congenital hydronephrosis in utero IV: in utero decompression prevents renal dysplasia

Renal dysplasia (RD) is commonly seen in babies with urinary tract obstruction (UTO). Recent experimental evidence suggests that early fetal UTO leads to the development of RD. The RD seen in children with congenital UTO is usually not reversible, even when the obstruction is relieved soon after birth. Is the RD associated with congenital UTO preventable or reversible by decompression of the urinary tract early in gestation? If so, at what stage of development must this decompression be performed? We produced complete unilateral ureteral obstruction in 25 early second trimester (62 to 65 days) lamb fetuses, a procedure that results in ipsilateral RD at term (140 days). At a second operation, 20, 40, or 60 days after the initial procedure, we decompressed the obstructed kidney by a cutaneous end-ureterostomy. The contralateral unobstructed kidneys served as controls. Renal function (urine output and iothalamate clearance) and histopathology were evaluated after delivery at term. Recovery of renal function was directly proportional to the duration of in utero decompression and inversely proportional to duration of obstruction. In addition, in utero decompression prevented or greatly ameliorated the development of RD. However, some postobstructive changes persisted; these were proportional to the length of in utero obstruction. These results substantiate the clinical impression that some human fetuses with congenital UTO may benefit from early in utero decompression.     

Autologous transplantation of amniotic fluid-derived mesenchymal stem cells into sheep fetuses

Long-term engraftment and phenotype correction has been difficult to achieve in humans after in utero stem cell transplantation mainly because of allogeneic rejection. Autologous cells could be obtained during gestation from the amniotic fluid with minimal risk for the fetus and the mother. Using a sheep model, we explored the possibility of using amniotic fluid mesenchymal stem cells (AFMSCs) for autologous in utero stem cell/gene therapy. We collected amniotic fluid (AF) under ultrasound-guided amniocentesis in early gestation pregnant sheep (n = 9, 58 days of gestation, term = 145 days). AFMSCs were isolated and expanded in all sampled fetal sheep. Those cells were transduced using an HIV vector encoding enhanced green fluorescent protein (GFP) with 63.2% (range 38.3-96.2%) transduction efficiency rate. After expansion, transduced AFMSCs were injected into the peritoneal cavity of each donor fetal sheep at 76 days under ultrasound guidance. One ewe miscarried twin fetuses after amniocentesis. Intraperitoneal injection was successful in the remaining 7 fetal sheep giving a 78% survival for the full procedure. Tissues were sampled at postmortem examination 2 weeks later. PCR analysis detected GFP-positive cells in fetal tissues including liver, heart, placenta, membrane, umbilical cord, adrenal gland, and muscle. GFP protein was detected in these tissues by Western blotting and further confirmed by cytofluorimetric and immunofluorescence analyses. This is the first demonstration of autologous stem cell transplantation in the fetus using AFMSCs. Autologous cells derived from AF showed widespread organ migration and could offer an alternative way to ameliorate prenatal congenital disease.     

Primary fetal hydrothorax: natural history and management

Primary fetal hydrothorax presents a wide spectrum of severity ranging from small, harmless effusions, to life-threatening thoracic compression. To define natural history and management, we reviewed 32 cases seen at two large perinatal centers from 1980 to 1987. Spontaneous resolution of the effusions was seen in three fetuses, all of whom survived. Three fetuses were electively terminated. The overall mortality was 53%. In the 24 untreated fetuses, sex and the presence of polyhydramnios did not influence mortality, but hydrops, gestational age less than 35 weeks at delivery, and bilateral effusions were associated with a poor prognosis. Five fetuses underwent in utero decompression. In four, thoracentesis was performed, with rapid reaccumulation of the effusion. All four died from pulmonary insufficiency. In the fifth fetus, a thoracoamniotic shunt permanently decompressed the effusion, with resolution of the hydrops, and delivery of a normal viable infant. We conclude that (1) primary fetal hydrothorax may resolve or progress to hydrops, necessitating close follow-up with ultrasound; (2) pulmonary hypoplasia as a result of undrained large pleural effusions may result in neonatal mortality; (3) the gestational age at both diagnosis and delivery, the development of hydrops, and bilaterality of effusions are important prognostic predictors; and (4) the fetus with large effusions and hydrops has a poor prognosis, and thoracic decompression with a thoracoamniotic shunt may prove life saving.     

Uptake and distribution of continuously infused intraamniotic nutrients in fetal rabbits

Nutrient delivery via the fetal gastrointestinal tract may be a potential prenatal treatment for intrauterine growth retardation. Uptake from continuous intraamniotic infusions with nutrient incorporation into developing fetal tissues has not previously been shown. To study this, ovarian-end fetuses of 18 time-mated rabbit does underwent amniotic cavity catheterization and either esophageal ligation (EL) or sham operation (SH) on gestational day 23 (term, 33 days). Saline plus 14C D-glucose and 3H proline were infused into the amniotic fluid for 4 days. Nutrients absorbed by the EL fetus represent only those taken up into the maternal circulation and subsequently redelivered hematogenously to the fetus. Radioactivity of fetal blood and organs was determined using a liquid scintillation counter. All infused does and 10 of 18 infused fetuses (56%) survived the entire study period. In SH fetuses, uptake of 14C per mg of tissue was highest in the lung and significantly greater in the stomach, jejunum, ileum, and lung than in fetal blood (P less than .05). Uptake of 3H per mg of tissue was also highest in the lung and significantly greater than fetal blood in the stomach, small intestine, lung, and liver (P less than .05). Each organ's 14C and 3H uptake was greater in SH than in EL fetuses (P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Fetal hydronephrosis: selection and surgical repair

Newly developed diagnostic techniques allowed us to select a fetus with potentially reversible renal damage from the usually fatal group with bilateral hydronephrosis and severe oligohydramnios early in gestation. Fetal surgery to marsupialize the fetal bladder at 24 weeks gestation restored normal amniotic fluid dynamics and allowed sufficient pulmonary and renal development to insure survival after delivery near term.     

Correction of congenital diaphragmatic hernia in utero, V. Initial clinical experience

Review of our experience with 45 cases of prenatally diagnosed congenital diaphragmatic hernia (CDH) confirms that most fetuses (77%) will not survive despite optimal pre- and postnatal care. Polyhydramnios, associated anomalies, early diagnosis, and a large volume of herniated viscera (including liver) are associated with a particularly dismal prognosis. After extensive experimental work demonstrated the efficacy, feasibility, and safety of repair in utero, we attempted to salvage six highly selected fetuses with severe CDH by open fetal surgery. Five had liver incarcerated in the chest: three died at operation because attempts to reduce the liver compromised umbilical venous return. In one, a Goretex diaphragm was constructed around the liver, but the baby died after birth. The last two fetuses, one with incarcerated liver, were successfully repaired. Both demonstrated rapid growth of the lung in utero, had surprisingly good lung function after birth despite prematurity, had the abdominal patch removed at 2 weeks, and subsequently died of nonpulmonary problems (an unrelated nursery accident in one and intestinal complications in the other). The only maternal complication was amniotic fluid leak and preterm labor. All six women are well and four have had subsequent normal children. From this phase I experience, we conclude that fetal surgery appears safe for the mother and her reproductive potential, that fetal CDH repair is feasible in selected cases, and that the fetal lung responds quickly after decompression. However, fetal repair remains a formidable technical challenge.     

Experimental study concerning safety dosage of OK-432 for intrauterine treatment

OBJECTIVE: Clinical intrauterine treatment for fetal cystic hygroma has so far been performed in a few patients; however, it is still difficult to evaluate the results. The aim of this study is to establish the safe dosage of OK-432 in the intrauterine treatment of fetal cystic hygroma. METHODS: OK-432 was injected either subcutaneously behind the neck of the fetuses or into the amniotic cavity through the uterine wall of pregnant Japanese white rabbits at 27 days of gestation. Saline was administered to the controls. The dosage and the site of injection were as follows: group 1, OK-432, 0.01 KE (0.25 KE/kg) in 0.2 mL saline per fetus, subcutis; group 2, OK-432, 0.02 KE (0.5 KE/kg) in 0.2 mL saline per fetus, subcutis; group 3, OK-432, 0.04 KE (1 KE/kg) in 0.2 mL saline per fetus, subcutis; group 4, OK-432, 0.01 KE in 0.2 mL saline per fetus, amniotic cavity; group 5, OK-432, 0.04 KE in 0.2 mL saline per fetus, amniotic cavity; group 6, saline, 0.2 mL per fetus, subcutis; group 7, saline, 0.2 mL per fetus, amniotic cavity. All fetuses were delivered at 29 days of gestation. RESULTS: The mother's rectal temperature was mostly in the normal range throughout the experiment. There was no significant difference between any of the seven groups in fetal body weight. The C reactive protein values of all fetuses were negative. The appearance of the skin of all the fetuses was normal. The histopathological findings of the skin in the OK-432 groups showed a moderate infiltration of monocytes and plasma cells. No pathological changes were observed in the heart, lung, liver or kidneys of any of the fetuses. CONCLUSION: Based on this rabbit experiment, we determined that OK-432 may be safely used at a dose of up to 1 KE/1 kg of fetal body weight as an intrauterine treatment for fetal cystic hygroma.     

Fetoscopic placement of a transurethral stent for intrauterine obstructive uropathy

PURPOSE: Fetal urinary obstructive uropathy and consecutive oligohydramnios result in a poor outcome. Usually renal insufficiency and life threatening lung hypoplasia have developed at term. We report a case of in utero fetal cystoscopy and successful placement of a transurethral vesico-amniotic Double-J (Medical Engineering Corp., New York, New York) stent. Indications, results and the potential benefits of different techniques are discussed. MATERIAL AND METHODS: A 36-year-old woman (primipara) was evaluated at week 26 due to a male fetus with bilateral hydronephrosis, massive distended bladder and an open posterior urethra. Using local anesthesia the fetal bladder was punctured, a 2.6 mm endoscope was inserted and a wire was advanced antegrade through the penis. A 2.8Fr Double-J stent was then placed between the bladder and amniotic cavity. RESULTS: The bladder drained into the amnion, hydronephrosis disappeared and the lung developed normally. At week 37 a healthy infant was delivered who voided spontaneously. CONCLUSIONS: After careful selection of candidates for fetal intervention in obstructive uropathy direct vision fetoscopy and transurethral stent placement can be performed in patients with oligohydramnios, favorable urinary electrolytes and normal appearing kidneys.     

Fetoscopic surgery for the treatment of congenital anomalies.

Fetoscopic techniques may broaden the indications for prenatal surgical intervention by obviating the risks of hysterotomy. For example, congenital obstructive uropathy has been treated by open vesicostomy and percutaneous catheter placement. The open approach is appropriate only for highly selected fetuses because of the inherent risks, whereas catheter drainage, though a safer procedure, is only useful for short-term therapy late in gestation due to frequent catheter obstruction and migration. The natural history of congenital obstructive uropathy mandates the need for improved therapy earlier in gestation, in order to salvage fetuses who would otherwise die of renal failure and pulmonary hypoplasia. We have developed a potential solution to this problem in which surgery is performed on the fetus without the risks of hysterotomy. Endoscopic fetal surgery uses a telescopic lens and operating instruments that are passed through small "ports" in the uterus. A bubble of CO2 is used to displace amniotic fluid and provides excellent visualization in a magnified field. This approach is considerably less invasive than open fetal surgery and, therefore, is less likely to provoke preterm labor. In this study we corrected obstructive uropathy in midgestation fetal lambs using a new, expandable wire mesh stent that is placed endoscopically and should provide more reliable bladder drainage than existing catheters. The fetoscopic surgical approach can potentially expand the indications for in utero surgery by decreasing fetal risks, facilitating intervention earlier in gestation, and reducing preterm labor. As a consequence, the potential now exists to correct non-life-threatening malformations in utero.     

Feasibility of intracranial surgery in the primate fetus. Model and surgical principles

A research model for intracranial surgery in the primate fetus was developed and tested in 10 timed-pregnant rhesus monkeys. With general anesthesia and sterile surgical technique, a laparotomy followed by a lower uterine segment hysterotomy was performed at a site avoiding the placenta. The amnion was opened carefully by use of the operative microscope and the fetal head was exposed. A scalp incision was made over the frontal region and a small craniectomy and cortical incision were carried out. In three of the fetuses, ventricular shunts were also placed. A layered closure was performed and the uterus was returned to the peritoneal cavity. Placental integrity and fetal viability were assessed before surgery and 1 week postoperatively by ultrasonography. The survival rates were 100% for the mothers and 80% for the fetuses. One fetus died in utero after an overdose of a sedative to the mother, and another was stillborn. Postmortem examination revealed no intracranial or systemic abnormalities in either case, and the cause of death was attributed to drug overdose and a naturally occurring stillbirth, respectively. Newborns were maintained either with their mothers or in a nursery, where they were observed and evaluated for 3 weeks. Weight, crown-rump length, and occipitofrontal head circumference were measured. General patterns of behavior and neurological assessments were recorded weekly. The eight surviving neonates were normal with respect to all parameters evaluated. Several principles of fetal intracranial surgery are emphasized as important: uterine relaxation by prostaglandin inhibition; low-dose halothane anesthesia supplemented by nitrous oxide in oxygen; perioperative ultrasonography and intraoperative transillumination of the uterus for placental localization; lower uterine segment opening; controlled exposure of the fetal cranium; minimization of amniotic fluid loss; enhancement of fetal anesthesia by injection of a local anesthetic agent at the fetal operative site; and multilayered watertight closure.