Congenital abdominal aortic aneurysm causing renovascular hypertension, cardiomyopathy, and death in a 19-day-old neonate.

A full-term baby girl who was sent home day of life 2 was admitted to the hospital on day of life 7 for respiratory distress and poor feeding. The child was found to be hypertensive and in heart failure. Further workup led to the diagnosis of a suprarenal abdominal aortic aneurysm, but the infant had deteriorated clinically with heart failure, modest renal failure, renovascular hypertension, and no operative cure. The child died on day of life 20. Early diagnosis and prompt surgical resection are essential to managing this rare and lethal condition.

All angiogenesis is not the same: Distinct patterns of response to antiangiogenic therapy in experimental neuroblastoma and Wilms tumor.

BACKGROUND/PURPOSE: Neuroblastoma and Wilms tumor exhibit different patterns of metastasis, invasion, and therapeutic response. Vascular endothelial growth factor (VEGF) is an angiogenic factor expressed in both tumors. The authors hypothesized that because the clinical behavior of these tumors differs, the response to anti-VEGF therapy would be distinct, and tumor vascular architectures would reflect this distinction. METHODS: Xenografts were induced by intrarenal injection of cultured cells in athymic mice. After 1 week, anti-VEGF antibody or vehicle were administered for 5 weeks before sacrifice. Additional animals were maintained for 3 weeks after termination of antibody injections to assess rebound growth of tumors. Fluorescein angiography was performed in selected animals. RESULTS: Neuroblastoma control and treated tumor weights were not significantly different (1.48 g v 0.77 g, P =.34). By comparison, as previously reported, antibody-treated Wilms tumors were growth inhibited. Angiograms of treated (but not control) neuroblastomas displayed novel rounded structures at vessel branches, which the authors term terminal vascular bodies (TVBs). Wilms tumor vessels displayed no such alteration. CONCLUSIONS: Neuroblastoma xenografts are less effectively suppressed by anti-VEGF antibody than Wilms tumors. Neuroblastoma vascular architecture displays a novel alteration during antibody administration, which attenuates when antibody is withdrawn. These studies suggest that angiogenesis is differently regulated in experimental neuroblastoma and Wilms tumor.

Suppression of primary tumor growth in a mouse model of human neuroblastoma.

BACKGROUND/PURPOSE: Neuroblastoma is the most common tumor of the abdomen in children. Consistently effective treatments are lacking for aggressive disease. The authors previously reported that therapy with anti-vascular endothelial growth factor (VEGF) antibodies suppresses both growth and metastasis in an experimental model of Wilms' tumor. The authors hypothesized that, in a parallel model of neuroblastoma, anti-VEGF treatment would inhibit (1) growth and (2) metastasis. METHODS: Primary tumors were established in the kidneys of nude mice. In cohort 1 (n = 42), mice were killed at 3 time-points, and tissues were evaluated histologically. Tumors were assayed for VEGF. In cohort 2 (n = 28), anti-VEGF antibody or vehicle was administered. Tumor weights and the incidence of metastases in the 2 groups were compared. VEGF deposition was evaluated by immunohistochemistry. RESULTS: Mice displayed large tumors with liver and lung metastases. VEGF levels in tumors increased over time. Antibody-treated animals displayed significantly smaller tumors, but incidence and size of metastases were unaffected. VEGF was localized to tumor stroma immunohistochemically, with no difference in pattern observed in control and antibody-treated tumors. CONCLUSIONS: Anti-VEGF antibodies inhibit primary tumor growth in experimental neuroblastoma, but not metastasis. This may contrast with the effect of the same antibody in a parallel model of Wilms' tumor.

Anti-VEGF antibody suppresses primary tumor growth and metastasis in an experimental model of Wilms' tumor.

BACKGROUND/PURPOSE: Vascular endothelial growth factor (VEGF) has been shown previously to correlate with tumor growth and metastasis in an experimental model of anaplastic Wilms' tumor. The authors hypothesized that treatment with anti-VEGF antibodies would suppress both primary tumor growth and metastasis in this model. METHODS: Tumors were induced in the right kidneys of nude mice by the injection of cultured Wilms' tumor cells. After 1 week, anti-VEGF treatment was begun with injection of either vehicle or an anti-VEGF antibody intraperitoneally. Mice were killed after 4.5 weeks of treatment and tumor weights and the incidence of metastases evaluated. RESULTS: Anti-VEGF treatment resulted in a greater than 95% reduction in tumor weight (P < .0001). Anti-VEGF treatment also abolished the establishment of lung metastases (40% in control animals, P < .003). Cessation of treatment resulted in rebound tumor growth. CONCLUSION: Anti-VEGF therapy can suppress both primary tumor growth and the establishment of metastases in experimental anaplastic Wilms' tumor.

ECMO in the newborn.

Since the first use in neonates in 1974, extracorporeal membrane oxygenation (ECMO) has been a life-saving technology for newborns with respiratory and cardiac failure. ECMO has been used to treat a variety of cardio-respiratory problems, including meconium aspiration syndrome (MAS), persistent pulmonary hypertension of the neonate (PPHN), congenital diaphragmatic hernia (CDH), sepsis, and cardiac anomalies. For this group of high-mortality neonates, ECMO has produced a survival of 76% in all newborns treated. This review article will examine the current selection criteria for ECMO, the clinical management of neonates on ECMO and discuss the long-term outcome of neonates treated with ECMO.

Pathological angiogenesis in a murine model of human Wilms' tumor.

BACKGROUND/PURPOSE: Pathological vascular architecture is a feature of neoangiogenic processes such as diseases of the retina and tumor growth. The authors hypothesized that experimental human Wilms' tumors would display a vascular architecture similar to retinal diseases that are driven by vascular endothelial growth factor (VEGF). METHODS: Human Wilms' tumors were established in the right kidneys of nude mice. After 4.5 weeks of tumor growth, fluorescein angiograms were performed before death. Representative sections of tumors and contralateral, control kidneys were evaluated by fluorescent microscopy. RESULTS: Fluorescein angiograms demonstrated a characteristic pathological architecture. Vascular tortuosity, capillary tufting, and hemorrhage were noted. These features were not present in normal kidneys. CONCLUSIONS: Vascular architecture of Wilms' tumor displays the specific features previously described in diseases of the retina, which have been shown to be driven by VEGF, suggesting that neoangiogenesis in this model is also VEGF driven.

Metastasis correlates with production of vascular endothelial growth factor in a murine model of human Wilms' tumor.

BACKGROUND/PURPOSE: The growth and spread of solid tumors are critically dependent on the induction of angiogenesis. We hypothesized that vascular endothelial growth factor (VEGF) would be detected in Wilms' tumors, and that both growth and metastasis would parallel VEGF levels in a murine model. METHODS: Primary tumors were established in the right kidneys of nude mice (n = 21). Mice were killed at 3, 4.5, or 6 weeks. Tumor-bearing and control kidneys were subjected to enzyme-linked immunosorbent assay (ELISA) for VEGF. Representative sections were assessed by histology and immunohistochemistry. Lungs were examined for metastases. Clinical specimens of Wilms' tumor (n = 12) also were assayed for VEGF. RESULTS: The authors detected VEGF by ELISA with increasing frequency, and in increasing quantity, as experimental Wilms' tumors were grown over time. Immunohistochemistry demonstrated accumulation of VEGF in areas of viable tumor. Lung metastases occurred in 8 of 10 animals with VEGF-positive tumors, but in only 3 of 11 animals with VEGF-negative tumors, an association that was statistically significant. VEGF was found in 10 of 12 clinical Wilms' tumor specimens tested. CONCLUSIONS: VEGF is present in both clinical and experimental Wilms' tumors. In a murine model, absolute VEGF levels increase as primary tumors grow, and VEGF production is significantly associated with tumor metastasis.

Immature teratomas in children: pathologic considerations: a report from the combined Pediatric Oncology Group/Children's Cancer Group.

Pediatric germ cell tumors (n = 135) with a major component of immature teratoma (IT) registered on Pediatric Oncology Group/Children's Cancer Group treatment protocols from 1990 to 1995 were reviewed. Sixty cases were pure IT with no malignant component and 75 were mixed tumors with a major component of IT. Foci of yolk sac tumor (YST) were present in all 75 mixed tumors; additional malignant components were present in 15. The IT component was as follows: 47% grade 3, 29% grade 2, 24% grade 1. There were no significant correlations between tumor grade and patient age by specific subsets or overall (all p > 0.10). Significant correlations were detected between stage and the presence of foci of YST (p = 0.0145) and grade and the presence of foci of YST (p < 0.001). Serum alpha-fetoprotein concentrations were elevated at diagnosis in 96% of ovarian tumors with foci of YST and were mildly elevated (< 60 ng/dL) in only 16% of tumors without YST. Overall 2- to 6-year survival rate was 96% and was related to the presence of YST. Central pathologic review revealed aspects of morphologic diagnosis that were most frequently misinterpreted by contributing pathologists. These included the classification of differentiating tissues as immature and the failure to recognize two well-differentiated patterns of YST (the hepatoid pattern resembling fetal liver and the well-differentiated glandular pattern resembling fetal lung or intestine). Such foci were often overlooked. The authors conclude that the presence of microscopic foci of YST, rather than the grade of IT, per se, is the only valid predictor of recurrence in pediatric IT at any site.

Pressure- versus volume-cycled ventilation in liquid-ventilated neonatal piglet lungs.

BACKGROUND/PURPOSE: If the goal of partial liquid ventilation (PLV) with perfluorocarbons in the management of respiratory failure is to improve dynamic lung compliance (Cdyn) and pulmonary vascular resistance (PVR) while sustaining O2 delivery, the optimal ventilatory management is unclear. The authors asked if volume-cycled or pressure-limited ventilation had different effects on PVR, cardiac index (CI), and Cdyn in uninjured and injured neonatal piglet lungs. METHODS: Anesthetized piglets (6 to 8 kg) were ventilated after tracheostomy. Cdyn was measured by in-line Fleisch pneumotach/PC data acquisition terminal. Thermodilution instrumentation allowed determination of both CI and PVR. Volume-control or pressure-limited ventilation was established in uninjured or injured (surfactant deficiency induced by saline lavage at 18 mL/kg) animals. After a stable 30-minute baseline, animals were assigned randomly to one of four groups: group I (n = 9), uninjured animals plus volume-cycled ventilation (intermittent mandatory ventilation [IMV], 10 bpm; tidal volume [TV], 15 mL/kg, positive end-expiratory pressure [PEEP], 5 cm H2O; FIO2, 1.0; and PLV for 150 minutes); group II (n = 9), uninjured animals plus pressure-limited ventilation (IMV, 10 bpm; peak inspiratory pressure (PIP), 25 cm H2O, PEEP, 5 cm H2O, FIO2, 1.0; and PLV for 150 minutes); group III (n = 7), injured animals plus volume-cycled ventilation (IMV, 10 bpm; TV, 15 mL/kg; PEEP, 5 cm H2O; FIO2, 1.0 for 30 minutes, followed by saline injury for group IV (n = 7), injured animals plus pressure-limited ventilation (IMV, 10 bpm; PIP, 25 cm H2O; PEEP, 5 cm H2O; FIO2, 1.0 for 30 minutes, followed by saline injury, and PLV rescue). Comparison within and between groups was accomplished by repeated measures analysis of variance (ANOVA) with Tukey correction. RESULTS: There was no significant difference between volume-cycled or pressure-limited ventilation in healthy lungs; however, in the setting of lung injury, dynamic compliance was 1.44 +/- 0.15 after 180 minutes in the volume-cycled group and 0.91 +/- 0.10 in the pressure-limited group after the same interval (mL/cm H2O x kg +/- SEM). Similarly, PVR was 100 +/- 6 in the volume-cycled group and 145 +/- 12 in the pressure-limited group after 180 minutes of lung injury (mm Hg/L/kg x min +/- SEM). Cardiac index declined significantly in all groups independent of ventilatory mode. CONCLUSIONS: These results suggest that in the setting of lung injury, Cdyn and PVR improved significantly when volume-cycled, compared with pressure-limited ventilation was used. Although no difference existed between ventilatory modes in healthy lungs, pressure-limited ventilation, when combined with PLV in injured lungs, had adverse effects on lung compliance and pulmonary vascular resistance. Volume-cycled ventilation may optimize the ability of perfluorocarbon to recruit collapsed or atelectatic lung regions.

Congenital diaphragmatic hernia survival and use of extracorporeal life support at selected level III nurseries with multimodality support.

BACKGROUND: Congenital diaphragmatic hernia (CDH) has been cited to have a mortality rate of 50%. There have been multiple studies at individual institutions demonstrating potential benefits from various strategies including extracorporeal life support (ECLS), delayed repair, and lower levels of ventilator support. There has been no multicenter survey of institutions offering these modalities to describe the current use of ECLS and survival of these infants. In addition, the relationship between the number of patients with CDH managed at an individual institution and outcome has not been evaluated. METHODS: We queried 16 level III neonatal intensive care centers on the use of ECLS and survival of infants with CDH who were treated during 2 consecutive years (1993 to 1995). Data are presented as mean +/- SEM, median, and range. RESULTS: Data were collected on 411 patients. Of these, 71% +/- 8% were outborn and 8% +/- 3% were considered nonviable. Overall survival of CDH infants was 69% +/- 4% (range, 39% to 95%). The survival rate of infants on ECLS was 55% +/- 4%, whereas survival of infants not requiring ECLS was significantly increased at 81% +/- 5% (p = 0.005). The mean rate of ECLS use was 46% +/- 2%. There was no correlation between the number of cases per year at an individual institution and overall survival, ECLS survival, or ECLS use (r = 0.341, 0.305, and 0.287, respectively). There was also no correlation between case volume at an individual institution and ECLS survival (r = 0.271). CONCLUSIONS: The current survival rate and rate of ECLS use in infants with CDH at level III neonatal intensive care units in the United States are 69% +/- 4% and 46% +/- 2%, respectively. There is no correlation between the yearly individual center experience with managing CDH and rate of ECLS use or outcome.

Evaluation and management of pediatric solid ovarian tumors.

Solid ovarian tumors are uncommon in the pediatric population, but when they occur, they are a major source of anxiety for the patient and her family. The pediatric surgeon will be relied on to diagnose these tumors because they usually present as abdominal pain with a mass. The diagnostic evaluation consists of a carefully obtained history and physical examination, ultrasound examination, serum assay for tumor markers, and further radiographic evaluation as indicated. Two thirds of malignant tumors in children are germ cell tumors, and most of these are dysgerminomas or endodermal sinus tumors. A multimodal, team-oriented approach to therapy is crucial. Reproductive organ-sparing surgery with salpingo-oophorectomy, ascites sampling, nodule biopsy, omentectomy, and contralateral ovarian biopsy as indicated, may be curative for stage I tumors; more advanced or highly aggressive tumors should be treated with cytoreduction surgery and will require platinum-based chemotherapy. Postinduction surgery is indicated for progressive or recurrent disease. One third of tumors are physiologically active stromal tumors that often become apparent because of hormonal effects. Epithelial tumors, common in the adult, are uncommon in children and are of mild to moderate malignant potential. Other miscellaneous tumors and benign lesions are less common.

Incidence and outcome of primary Epstein-Barr virus infection and lymphoproliferative disease in pediatric heart transplant recipients.

BACKGROUND: The objective of this study was to assess the relationship between Epstein-Barr virus (EBV) infection and posttransplantation lymphoproliferative disease (PTLD) in pediatric heart transplant recipients. EBV is implicated in the development of PTLD. However, the relationship between primary EBV infection and PTLD is not well understood. METHODS: Serial EBV titers were determined prospectively in 50 children before and after heart transplantation. Results were correlated with the development of PTLD. The clinical presentation, management, and outcome of PTLD were characterized. RESULTS: Before transplantation, EBV titers were positive in 19 and negative in 31 patients. After transplantation, all EBV-positive patients remained positive; 1 developed PTLD. Among EBV-negative patients, 12 of 31 remained negative; none developed PTLD. Nineteen patients demonstrated serologic evidence of primary EBV infection after heart transplantation; 12 developed PTLD. Mean follow-up after heart transplantation was 3.3 years (range 0.4 to 8.4 years). Mean time from heart transplantation to histologic confirmation of PTLD was 29 months (range 3 to 72 months). Survival with PTLD was 92%. CONCLUSIONS: Twelve of 13 pediatric heart transplant recipients who developed PTLD had evidence of primary EBV infection. Serial monitoring of EBV titers may lead to earlier identification and improved treatment of PTLD.

What do survivors of congenital diaphragmatic hernia look like when they grow up?

An important consequence of the extracorporeal membrane oxygenation (ECMO) era is a renewed interest by pediatric surgeons in the infant with congenital diaphragmatic hernia (CDH). As increasing numbers of the infants survive, previously unappreciated aspects of the problem are being unmasked, provoking important questions as to their etiology. Importantly, as these children grow and develop, we must ask ourselves if their various problems are specific to CDH or are they consequences of our treatment strategies. This article considers pulmonary, cardiac, gastrointestinal, and neurocognitive markers of outcome.

Endogenous nitric oxide and pulmonary vascular tone in the neonate.

PURPOSE: In newborns, inhaled nitric oxide (NO) has been shown to ameliorate increased pulmonary vascular resistance (PVR) precipitated by hypoxia. The role of endogenous NO production in this response is not clear. The contribution of endogenous NO to resting PVR in normoxic newborns also has not been well studied. The authors used an isolated, in situ, neonatal piglet lung-perfusion model, devoid of systemic detractors in which endogenous NO could be selectively inhibited, to determine whether (1) endogenous NO plays a role in the maintenance of PVR with normoxia, (2) endogenous NO plays a role in the response to hypoxia, and (c) inhaled NO can reverse changes induced by inhibition of endogenous NO. METHODS: Sixteen neonatal piglets underwent occlusive tracheostomy and pressure-cycled ventilation. After heparinization and ligation of the ductus arteriosus, left atrial and pulmonary arterial cannulation were performed, without ischemia, via a median sternotomy. The aorta was ligated, and lung perfusion was set at 80 mL/kg/min via an extracorporeal membrane oxygenation circuit. Hematocrit (40% to 45%), pH (7.37 to 7.44), Pco2 (35 to 40 mm Hg), and peak inspiratory pressures (20 mm Hg) were constant. Pulmonary artery pressure (PPA), left atrial pressure (PLA), and circuit flow (QPA) were recorded continuously. PVR calculated as follows: PVR[(dynes x seconds x cm(-5)) x 1,000] = [(PPA-PLA/(QPA x 1,000/60)] x 1,332. The experimental animals were ventilated with normoxic gas (FIO2, 0.21), followed by hypoxic gas (FIO2, 0.07), returned to normoxia, and then divided into two groups of eight animals each. One group remained normoxemic (FIO2, 0.21; SPA02, 100%) while the other group was made hypoxemic by ventilation with hypoxic gas (FIO2, 0.07; SPA02, 50%). Endogenous NO was suppressed with L-arginine-N-omega methyl ester (L-NAME) at 40 mg/kg in both groups. Inhaled NO was given at 40 ppm in both groups. Analysis of variance for repeated measures was used to test for statistical significance. RESULTS: Baseline normoxic PVR (3,403 +/- 1,169) was increased significantly by hypoxia (6,524 +/- 1,018, P < .01) and was fully resorted to baseline by normoxia (3,497 +/- 1,079; P = NS). In normoxic animals, inhibition of endogenous NO production by L-NAME increased PVR to levels similar to those seen during hypoxic stress (6,345 +/- 1,441, P < .01). Replacement of endogenous NO by inhaled NO reversed PVR to normoxic baseline values (3,986 +/- 1,363, P = NS). In hypoxic animals, inhibition of endogenous NO production by L-NAME also increased PVR from hypoxic baseline (9,655 +/- 1,642, P < .01). Replacement of endogenous NO by inhaled NO reversed PVR to hypoxic baseline (6,450 +/- 1,796, P = NS). CONCLUSION: In this piglet model, endogenous NO is important in the regulation of pulmonary vascular tone during both normoxia and hypoxia. Inhaled NO completely reversed the elevations in PVR caused by inhibition of endogenous NO and may normalize PVR in diseases in which the production of endogenous NO is compromised.

Preoperative cardiorespiratory trends in infants with congenital diaphragmatic hernia.

The objective of this study was to determine the cardiovascular and pulmonary adaptations of infants with congenital diaphragmatic hernia (CDH) from birth until delayed surgery through the use of continuous monitoring. Continuous cardiovascular (HR, heart rate variability [HR-SD], BP, blood pressure variability [BP-SD], and oxygen saturation) and ventilatory (minute volume, airway pressure, and effective compliance) measurements were made on-line, using a computerized whole-body plethysmograph-incubator (Vital-trends, VT1000), in nine ventilated infants with CDH. Data collection commenced at birth and continued until surgery. Minute mean values for each variable were recorded. Hourly means were computed from the minute means, averaged across infants each hour over the first 50 hours of life, and regressed against postnatal age. Results showed a significant increase in BP (P < .01), BP-SD (P < .05), HR-SD (P < .04), and pH (P < .02) versus postnatal age, and a decrease in PaCO2 (P < .04), FIO2 (P < .001), Alveolar-arterial oxygen gradient (P < .003), and oxygenation index (P < .002). Infants with CDH show cardiopulmonary trends over the first 2 days of life that are qualitatively similar to those of normal newborn infants. Deviation from these idealized patterns may identify an infant who is not responding satisfactorily to the given therapy and who may require alternative treatment modalities.

Congenital diaphragmatic hernia: survival treated with very delayed surgery, spontaneous respiration, and no chest tube.

This report suggests that stabilization of the intrauterine to extrauterine transitional circulation combined with a respiratory care strategy that avoids pulmonary overdistension, takes advantage of inherent biological cardiorespiratory mechanics, and very delayed surgery for congenital diaphragmatic hernia results in improved survival and decreases the need for extracorporeal membrane oxygenation (ECMO). This retrospective review of a 10-year experience in which the respiratory care strategy, ECMO availability, and technique of surgical repair remained essentially constant describes the evolution of this method of management of congenital diaphragmatic hernia.

Neurocognitive outcome for neonates treated with extracorporeal membrane oxygenation: are infants with congenital diaphragmatic hernia different?

The neurocognitive outcome for infants with congenital diaphragmatic hernia treated with extracorporeal membrane oxygenation (ECMO) is compared with that of neonates treated with ECMO for other diagnoses. The mean age at the time of the latest assessment (for the 51 survivors with adequate follow-up) was 31 months. The neurological outcomes did not differ significantly. However, the cognitive outcome for infants with congenital diaphragmatic hernia was significantly poorer than for those without it. This was particularly true if the infant with congenital diaphragmatic hernia was a boy and his mother had limited formal education.

Cholelithiasis in pediatric cardiac transplant patients on cyclosporine.

From June 1984 to June 1993, symptomatic chlolethiasis was observed in six (6.7%) of 90 cases of pediatric heart or heart-lung transplants at the author's institution. The incidence of cholelithiasis for all children under 16 years of age is estimated to be less than 1%. Previously, information on cholelithiasis in pediatric transplant patients on cyclosporine therapy had been limited. Studies concerning the incidence of gallstones in adult kidney and cardiac transplant patients have shown that there is an increase associated with cyclosporine, possibly related to elevated levels and hepatoxicity. Five patients underwent uneventful cholecystectomy. There was only one death, which occurred after emergency cholecysostomy tube placement for biliary sepsis. If indicated, biliary tract surgery can be performed safely in cardiac transplant patients. The authors report on their experience with symptomatic cholelithiasis in pediatric cardiac transplant patients and review the current literature on the hepatotoxic effects of cyclosporine.

Midgut malfixation in patients with congenital diaphragmatic hernia: what is the risk of midgut volvulus?

Twenty-four patients with repaired diaphragmatic hernia had upper gastrointestinal series to assess the rotation and fixation of the bowel. A spectrum of rotational abnormalities was present in almost all patients, although those with repaired right-sided hernias demonstrated a more obvious anomaly of rotation than those with repaired left-sided hernias. No patient developed a midgut volvulus despite the presence of malfixation. Postoperative adhesions likely limit the occurrence of volvulus.

Fetal breathing characteristics and postnatal outcome in cases of congenital diaphragmatic hernia.

OBJECTIVE: Our purpose was to determine characteristics of fetal breathing activity by recording fetal nasal fluid flow velocity in cases of congenital diaphragmatic hernia. STUDY DESIGN: Fetal breathing-related nasal fluid flow was studied in 47 patients at 34 to 41 weeks of gestation, 16 cases of antenatally diagnosed congenital diaphragmatic hernia and 31 cases of uncomplicated pregnancy. The examination was performed by ultrasonography combined with color-flow and spectral Doppler analysis. An average of 25 breath cycles from each case was determined for each of the following timing parameters: breath-to-breath interval, time of inspiration, time of expiration, and ratio of time of inspiration and time of expiration. RESULTS: In all cases with uncomplicated pregnancy fetal breathing-related nasal fluid flow was seen at the level of the nose, and the timing components of this flow were determined as control values. In two cases with diaphragmatic hernia no perinasal flow was demonstrated, although fetal breathing movements observed as chest wall movements were present. The other 14 cases with congenital diaphragmatic hernia who demonstrated perinasal flow had the following postnatal outcome: one stillbirth, five neonatal deaths (group I), and eight survived and were discharged (group II). The study revealed that the time of expiration (in milliseconds) in group II (493.2 +/- 34.3 SEM) was significantly (p = 0.0030) shorter than in group I (653.4 +/- 38.4) and in cases of uncomplicated pregnancy (633.6 +/- 18.5). The value of the time of inspiration/time of expiration ratio in group II was approximately 15% higher than in group I and approximately 30% higher than in cases of uncomplicated pregnancies. CONCLUSIONS: Observation of fetal breathing-related nasal fluid flow velocity in cases of antenatally diagnosed congenital diaphragmatic hernia provides a rationale for the hypothesis that time of expiration and the time of inspiration/time of expiration ratio may be useful in the prediction of postnatal outcome. We speculate that the changes in the group of survivors may represent a compensatory phenomenon by causing intermittent changes in the volume of fluid within the lungs.