Biomedical subjects
Publications and source records attributed to M R Harrison.
Is gastroschisis embryologically distinct from omphalocele or simply a ruptured small omphalocele (hernia of the umbilical cord)? Serial sonographic imaging of a fetus with a small omphalocele at 27 weeks gestation has now provided the "missing link" in the pathogenesis of gastroschisis by documenting in utero rupture resulting in a gastroschisis.
To study the accuracy of prenatal diagnosis and define the natural history of fetal congenital diaphragmatic hernia (CDH), we reviewed experience with CDH at The University of California, San Francisco (UCSF) over the last three years. All nine babies born in our institution (inborns) and six of 11 babies referred from other hospitals after birth (outborns) died, an overall mortality of 75%. All had pulmonary hypoplasia. Forty percent had associated malformations or chromosomal abnormalities, a higher incidence than generally reported. Prenatal sonograms were available in all nine inborn cases. CDH was correctly diagnosed prospectively in only five, but could be recognized retrospectively in all nine cases using the sonographic criteria developed from the study. Polyhydramnios was present in all nine cases; in seven cases sonography was performed because the woman was large-for-dates clinically. There were no false positive interpretations, and when necessary the diagnosis was confirmed by amniography. All nine cases of CDH detected in utero died. Seven deteriorated so rapidly that surgical repair could not even be attempted. Two who had optimal care (maternal transport, immediate resuscitation and operation) died after repair despite maximal intensive care including vasodilator therapy. Despite the theoretical advantages of maternal transport to pediatric surgical specialty centers, a majority of fetuses with a prenatal diagnosis of CDH will die because their lungs are inadequate to support extra-uterine life even at term.
We studied the natural history and pathophysiology of congenital cystic adenomatoid malformation (CCAM) detected prenatally by ultrasound in twelve fetuses. Two types of fetal CCAM can be distinguished by gross anatomy, ultrasound findings, and prognosis. Microcystic lesions are usually associated with fetal hydrops and have a poor prognosis (five cases with one survivor). Antenatal diagnosis, maternal transport, and immediate thoracotomy after birth allowed the first reported survival of a newborn with a large microcystic CCAM. Macrocystic lesions are not usually associated with hydrops and have a favorable prognosis (five of seven survived). We conclude that fetuses with hydrops are at high risk for fetal or neonatal demise without intervention. Fetuses with CCAM but without hydrops have a good chance for survival with maternal transport, planned delivery, and immediate neonatal resuscitation and surgery.
This article is a summary of the prenatal and perinatal management of a variety of congenital lesions as practiced by the fetal treatment program at the University of California in San Francisco. Emphasis is placed on those lesions that are amenable to fetal intervention.
Fetus in fetu is an extremely uncommon cause of an abdominal mass in the neonate; fewer than 30 generally accepted cases are recorded in the literature. We report a case of intraabdominal fetus in fetu, with a unique location within an undescended left testicle. Chromosomal studies of cells from the fetus in fetu and the surviving infant revealed identical 46,XY karyotypes.
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Development of fetal animal models for congenital anomalies helps elucidate the pathophysiological consequences of the disease process as well as the efficiency of prenatal intervention in ameliorating the disease. The experimental work that supports the pathophysiological rationale for in-utero correction of diaphragmatic hernia and urinary tract obstruction is reviewed in this article.
Three neonates were born with marked abdominal muscular laxity from three different conditions (posterior urethral valves, nonimmune ascites, and intestinal duplication); two had fetal abdominal distention by ascites documented in utero by obstetric ultrasonographic examination. Another fetus, whose abdominal distention was relieved at 21 weeks' gestation by in utero decompression of urinary obstruction, was born with only mild abdominal changes, which suggests that the "prune belly" phenotype can resolve if distention is relieved early enough. These observations suggest that the abdominal laxity in prune belly syndrome is a simple deformation secondary to abdominal stretching and distention during fetal development and is not an intrinsic generalized mesodermal abnormality.
Preterm labor and late gestation fetal loss remain significant barriers to clinical fetal surgery. To investigate the response of the gravid uterus to anesthetic and tocolytic agents and surgical procedures, 27 chair-restrained pregnant rhesus monkeys from 123 to 152 days gestation (term 168 days) underwent implantation of electrodes to monitor uterine electromyographic (EMG) activity. Seven had electrodes placed at the time of hysterotomy for placement of intraamniotic pressure catheters, without disturbing the fetus; 12 at the time of hysterotomy for placement of fetal carotid and jugular catheters. Eight had electrodes placed as an initial procedure to study the uterine EMG response to one or more of the following procedures performed subsequently: amniocentesis, maternal laparotomy without uterine manipulations, hysterotomy without fetal surgery, and hysterotomy with fetal surgery. A total of 43 procedures was performed. Preterm labor and delivery were induced in 1 of 15 (6.7%) monkeys who underwent procedures with minimal uterine manipulation (electrode placement, amniocentesis, and maternal laparotomy), in 3 of 8 (38%) monkeys who had hysterotomies without fetal surgery, and in 11 of 20 (55%) monkeys who had hysterotomies with fetal manipulation. The difference between those undergoing minimal uterine manipulation and those undergoing hysterotomy (with and without fetal surgery; fetal loss in 14 of 28, 50%) is statistically significant (P = 0.01). In animals undergoing hysterotomy, frequent coordinated contractions (type I EMG pattern) emerged as the animal awoke. The uterine activity was inhibited by halothane anesthesia, but not by either preoperative indomethacin or postoperative ritodrine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Eleven fetuses with omphalocele and two with gastroschisis were diagnosed by prenatal ultrasonographic examination. Intact omphalocele was accurately distinguished from gastroschisis by detection of a membranous sac covering the herniated viscera, by liver protruding from the abdomen, and by the frequent association of major structural anomalies. Gastroschisis was characterized by the absence of these findings and the presence of bowel loops floating freely in the amniotic fluid. Nine of eleven fetuses with omphaloceles had other major malformations and did not survive. Two small omphaloceles and two gastroschises were correctly diagnosed as isolated defects, free from associated anomalies. All four underwent maternal transport and were successfully managed with good outcome. Prenatal ultrasonography allows rational decisions about perinatal management by distinguishing between omphalocele and gastroschisis and by screening for associated anatomic defects. Karyotype analysis should be a part of the prenatal workup. Most isolated defects can be followed and delivered normally near term. Accurate prenatal diagnosis allows maternal transport and in a few cases may alter the timing or mode of delivery.
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.
Inhibition of fetal breathing movements or increased loss of fetal lung fluid into the amniotic space have been suggested as two possible mechanisms causing pulmonary hypoplasia in the setting of oligohydramnios (OH). We examined the effect of OH produced by amniotic fluid shunting (AS) into the maternal abdominal cavity, ablation of fetal breathing by high cervical cord transection (CT), and CT and AS combined on fetal rabbit lungs at 24 days gestation. Lung growth at term (31 days) was measured by lung DNA content and wet lung weight. Compared to unoperated controls, newborns undergoing either AS alone or CT alone had much smaller lungs. When compared to CT alone, CT with AS resulted in a further significant decrease in lung growth. Thus, even when fetal breathing was eliminated by CT, AS caused further hypoplasia. If pulmonary hypoplasia in OH is related to increased loss of lung fluid, then tracheal ligation (TL) should prevent this process. TL combined with AS produced lungs with the same DNA content as controls, and thus the hypoplastic effects of OH were reversed by TL. Although fetal breathing is clearly important for lung growth, it appears that inhibition of fetal breathing is not the predominant etiology of oligohydramnios-related pulmonary hypoplasia. Fetal intrapulmonary fluid is formed by active transport across pulmonary epithelium, and may serve to distend potential airways and stimulate growth. These experiments suggest that lung hypoplasia associated with OH is related to loss of this internal stenting force.
Six infants with short-gut syndrome refractory to medical management underwent isoperistaltic colon interposition (length 11.7 +/- 3.1 cm.). The abdominal catastrophes that required extensive intestinal resection were: volvulus (3), necrotizing enterocolitis (2), and gastroschisis with intestinal atresia (1). No infant had another major congenital anomaly. The average trial of attempted medical therapy prior to colon interposition was 5.5 +/- 3.6 months. There was no perioperative mortality or morbidity associated with the colon interposition. Following the colon interposition, three infants were weaned from total parenteral nutrition (TPN) in 3 +/- 1 months and all survived. In contrast, three infants could not be withdrawn from TPN and they died secondary to complications of TPN (2 from sepsis and 1 from hepatic failure). Long-term survival was associated with a greater length of small bowel remaining after the initial resection (51 +/- 12 cm v 35 +/- 24 cm), colon interposition at a younger age (3 +/- 1 months v 8 +/- 3.5 months), and a shorter duration of medical management prior to colon interposition (2.8 +/- 0.8 months v 6.7 +/- 5.0 months). All survivors are now tolerating a regular diet and having one to four formed stools per day. Normal somatic growth and developmental milestones are being achieved. The follow-up period is from 24 to 84 months. Our experience with the colon interposition in the patient with short gut syndrome has led us to conclude that when a reasonable trial of medical management has failed, a colon interposition is a safe and effective adjuvant to treatment.
To study the effect of in utero ventricular decompression of hydrocephalus on brain development and prognosis, and to evaluate the function and possible complications of different shunt designs, we created fetal hydrocephalus in 28 fetal lambs and 17 fetal monkeys by injecting kaolin into the cisterna magna during the third trimester. One fetal lamb had indwelling intracranial subdural and amniotic cavity pressure catheters placed to study serial changes in the relationship of intracranial pressure (ICP) and amniotic fluid pressure (AFP) from the time of injection until term. Twenty hydrocephalic fetal lambs underwent ventricular decompression--ventriculoamniotic (V-A), N = 10; ventriculo-right atrial (V-RA), N = 9; and ventriculo-pleural (V-PL), N = 1--21 to 25 days after the kaolin was injected; seven hydrocephalic fetuses were left unshunted as controls (CON). Eight fetal monkeys underwent V-A decompression 14 to 21 days after kaolin injection; nine were left unshunted as controls. All animals were delivered by cesarean section near term, assessed for viability and their brains examined grossly and microscopically. After kaolin injection in the fetal lamb, ICP (r = 0.94) and ICP minus AFP (r = 0.93) rose in a linear fashion, while AFP showed no trend (r = 0.22). All unshunted newborn lambs and monkeys had split sutures, dilated ventricles, and thinned cortical mantle. Most shunted lambs showed anatomic improvement with decreased head circumference, overriding sutures, normal-sized ventricles, and improved survival. However, histopathology revealed marked white matter destruction. In contrast, most shunted monkeys showed little anatomic improvement. Both shunted and unshunted monkey brains showed a severe inflammatory ventriculitis. In both lambs and monkeys, shunting was associated with a variety of complications including subdural hematoma, subdural hygroma, shunt infection, shunt occlusion, and improper shunt tip placement. In this experimental model, in utero decompression of obstructive hydrocephalus improves overall survival, improves gross ventriculomegaly, does not improve histopathologic brain damage, and is associated with significant complications. The choice of the optimal shunt design and the effect on postnatal neurologic function requires further study. This work emphasizes the need for continuing research in an animal model prior to human application.
We studied 24 human fetuses with cerebral ventriculomegaly by serial obstetric ultrasound to define the natural history of fetal ventricular enlargement and to develop a management strategy. In 10 fetuses, ventriculomegaly was associated with other severe anomalies; nine of these families chose to terminate the pregnancy. In three other severely affected fetuses in whom ventriculomegaly was detected serendipitously late in gestation, routine obstetrical management was performed; none survived. Eleven fetuses had ventriculomegaly without associated severe anomalies. Ventriculomegaly remained stable or of moderate severity throughout gestation in nine, resolved gradually in one, and progressed in one who did not have signs of increased intracranial pressure at birth. All of these fetuses were viable; three patients required shunting in the neonatal period, and two others by 5 months of age. Although obstetric ultrasound usually can detect anomalies associated with fetal ventriculomegaly, three fetuses with isolated ventriculomegaly had midline brain malformations that could not be distinguished in utero from hydrocephalus, even in retrospect. Prenatal diagnosis improves perinatal management by allowing counseling, and selective pregnancy termination, or selection of the timing, mode, and place of delivery to optimize outcome. Most fetuses with ventriculomegaly do not require intervention before birth.
In an attempt to predict histologic fetal renal dysplasia among fetuses with obstructive uropathy, three antenatal sonographic features (presence of renal cortical cysts, echogenicity of renal parenchyma, and degree of hydronephrosis) were studied. Identification of renal cortical cysts in the kidneys of fetuses with obstructive uropathy enabled accurate prediction of renal dysplasia. Of 49 fetal kidneys with obstructive uropathy, all 15 kidneys with sonographically visible cortical cysts had severe but not necessarily lethal dysplasia (accuracy of positive prediction = 100%). Of 15 obstructed but nondysplastic fetal kidneys, none had sonographically visible cysts (specificity = 100%). The absence of fetal renal cysts on antenatal sonography, however, did not exclude the presence of dysplasia. Assessment of the echogenicity of renal parenchyma and the degree of hydronephrosis are of only limited value in predicting whether an obstructed fetal kidney will show histologic dysplasia.