Philip L. Glick

Diaphragmatic hernia in the fetus: Prenatal diagnosis and outcome in 94 cases

Most babies born with congenital diaphragmatic hernia (CDH) die after birth. The natural course of CDH in the human fetus is not known. We found 94 cases of fetal CDH in the records of surgeons and obstetricians surveyed in the United States and Canada. We found the following: (1) prenatal diagnosis of CDH is accurate and current techniques can detect lethal nonpulmonary anomalies and prevent diagnostic errors; (2) despite optimal conventional therapy, most fetuses with detectable CDH will die in the neonatal period (80% mortality); (3) polyhydramnios is both a common prenatal marker for CDH (present in 76% of fetuses) and a predictor for poor clinical outcome (only 11% survived); (4) fetal CDH is a dynamic process--nonsurvivors have larger defects and may have more viscera displaced into the chest at an earlier stage of development. Surgical intervention before birth may be necessary to improve survival of the fetus with CDH and polyhydramnios.

Fetal cystic adenomatoid malformation: Prenatal diagnosis and natural history

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.

Comparison of fetal, newborn, and adult wound healing by histologic, enzyme-histochemical, and hydroxyproline determinations***

We compared simultaneous healing processes in fetal, newborn, and maternal rabbits using a miniaturized wound cylinder of expanded Gore-Tex tubing. The tubing was placed subcutaneously in fetal and maternal rabbits on day 23 of pregnancy (term = 31 to 32 days), and in 7-day-old newborn rabbits. At specific intervals, the tubing was removed and analyzed for hydroxyproline accumulation, histology, and cellular enzyme-histochemistry. Granulation tissue ingrowth and accumulation of hydroxyproline were each inversely related to age (fetus greater than newborn greater than maternal). The fetus showed an impressive infiltration of macrophages by day 4, fibroblasts by day 7, and a conspicuous lack of neutrophils in all specimens. Newborns and mothers had few cells until day 7, when a mixture of macrophages, neutrophils, and some fibroblasts appeared. We conclude that the fetus heals wounds rapidly by both mesenchymal cell proliferation and collagen deposition, and that these processes are more rapid in fetuses than in newborn or adult animals despite relative fetal hypoxemia.

Pathophysiology of congenital diaphragmatic hernia II: The fetal lamb CDH model is surfactant deficient

The high mortality for congenital diaphragmatic hernia (CDH) has been attributed to a combination of pulmonary hypoplasia and pulmonary hypertension. We hypothesize that a surfactant deficiency may in part be contributing to the pathophysiology of CDH. This study documents the functional, quantitative, and qualitative aspects of the surfactant status of the alveolar air-liquid interface and the type II pneumocyte in the fetal lamb CDH model. Ten lamb fetuses (gestational age, 80 days) had a CDH created via a left thoracotomy and then were allowed to continue in utero development until term. Three litter mates and three nonoperated time-dated fetuses served as controls. At term, pressure-volume curves were performed to measure pulmonary compliance and total lung capacity. Alveolar lavage was then performed to measure the quantitative and the qualitative aspects of pulmonary surfactant. Finally, isolation of type II pneumocytes allowed quantification of phospholipid synthesis. When compared with controls (N = 6), the CDH lambs (N = 5) had significantly smaller lungs (P = .009), decreased total lung capacity (P less than .001) and compliance (P less than .001), reduced total lavaged phospholipids (P = .006), and decreased percent phosphatidylcholine (P = .02). CDH lambs also had increased total lavaged proteins (P = .05) and higher minimum dynamic surface tension (P less than .001). A surfactant deficiency may be contributing to the pathophysiology of CDH. Surfactant replacement therapy in premature infants has been shown to improve lung compliance, decrease morbidity, and improve survival. Exogenous surfactant may also benefit infants with CDH.

Experimental pulmonary hypoplasia and oligohydramnios: Relative contributions of lung fluid and fetal breathing movements***

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.

Correction of congenital hydronephrosis in utero III. Early mid-trimester ureteral obstruction produces renal dysplasia

Is the renal dysplasia (RD) commonly seen in babies with urinary tract obstruction a developmental consequence of the obstruction or is it an associated embryologic malformation? We produced complete unilateral ureteral obstruction in six 58- to 66-day old lamb fetuses by clipping a silastic ring on the ureter. Three fetuses survived to term. All obstructed kidneys were not only grossly hydronephrotic but dysplastic by histologic criteria; ie, parenchymal disorganization, primitive epithelial structures, and marked fibrosis. The contralateral unobstructed control kidneys were normal. The changes were similar to those seen in the human neonate with obstruction and RD, suggesting that in this model RD was caused by obstruction to the flow of urine early in fetal development.

Correction of congenital diaphragmatic hernia in utero IV. An early gestational fetal lamb model for pulmonary vascular morphometric analysis

Infants born with congenital diaphragmatic hernia (CDH) often have specific pathologic abnormalities of the pulmonary microcirculation that result in high pulmonary vascular resistance and extrapulmonary right-to-left shunting after birth. In an attempt to make an animal model with similar vascular changes, we created CDH in fetal lambs at 60 to 63 days gestation, repaired some at 100 to 113 days gestation, and subsequently performed morphometric analysis of the pulmonary vasculature. Creation of CDH at this early gestational age resulted in a high fetal mortality rate. In the unrepaired CDH lambs, the pulmonary vascular abnormalities were more severe in the left lung. Similar to human CDH, diaphragmatic hernia in the fetal lamb resulted in a decrease in the total size of the pulmonary vascular bed, a decrease in the number of vessels per unit area lung, and increased muscularization of the arterial tree. Fetal surgical repair of CDH restored the pulmonary arterial bed towards normal.

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.

Pathophysiology of congenital diaphragmatic hernia III: Exogenous surfactant therapy for the high-risk neonate with CDH

Exogenous surfactant therapy (EST) in surfactant-deficient premature infants has been shown to improve lung compliance, decrease morbidity, and improve survival. Reports have demonstrated that newborns with congenital diaphragmatic hernia (CDH) have lung compliance, pressure-volume curves, and hyaline membrane formation resembling those changes seen in surfactant deficient premature newborns. We hypothesize that EST may also benefit infants with CDH. All high risk cases of prenatally diagnosed CDH at Childrens Hospital of Buffalo from November 1988 to February 1991 were prospectively evaluated for EST. In those families who chose to participate, the surfactant preparation, Infasurf (100 mg/kg), was instilled into the newborns lungs prior to the first breath. The remainder of the perinatal, neonatal, and surgical care was performed in a routine manner. Three high-risk prenatally diagnosed newborns with left CDH were treated with EST. All showed signs of decreased pulmonary compliance, but could still be adequately oxygenated and ventilated. Surgical correction was performed after stabilization and all required patch closures. Two of the three infants suffered no life-threatening episodes of pulmonary hypertension and all survived. These infants had many known indicators for poor outcome in CDH with an expected survival of less than 20%. We believe that EST in these neonates with CDH contributed to their survival with minimum morbidity. These results suggest that surfactant replacement for the high-risk neonate with CDH warrants further consideration and a randomized clinical trial is being planned.

PEDIATRIC HERNIAS AND HYDROCELES

Hernias and hydroceles are common conditions of infancy and childhood, and inguinal hernia repair is one of the most frequently performed pediatric surgical operations. As a result of improved neonatal intensive care, more and more premature babies are being delivered, and consequently the incidence of neonatal inguinal hernia is increasing. The most important aspect of the management of neonatal inguinal hernias relate to its risk on incarceration, and emphasis is placed on this point. This article covers the embryology, incidence, clinical presentation, and treatment of groin hernias and hydroceles, as well as dealing with abdominal wall hernias other than umbilical hernias. This article places special emphasis on when a patient with a hernia or hydrocele should be referred to a pediatric surgeon.