Association of plasma cortisol and chronic lung disease in preterm infants.

BACKGROUND: It has been suggested that preterm infants may have developmental immaturity of the hypothalamic-pituitary-adrenal axis, and that decreased cortisol response to stress increases risk of chronic lung disease (CLD) secondary to inflammatory lung injury. METHODS: To investigate the relationship between endogenous corticosteroid and CLD, we measured plasma cortisol during the first 28 days of life in a subset of neonates in the North American Thyrotropin-Releasing Hormone (TRH) Collaborative Trial. Analyses were performed on 314 infants, 24 to 32 weeks' gestation, whose mothers received 1 or 2 courses of antenatal corticosteroids plus TRH or placebo. RESULTS: Mean cortisol was 3.1 microg/dL (range: 0.1-17.9) at birth, reached maximal levels at 24 hours (19.4 microg/dL, range: 0.8-124.6), and decreased to 5.9 microg/dL (range: 0.2-24.7) at 14 to 28 days of age; levels during the first week were not associated with gestational age. The Clinical Risk Index for Babies (CRIB), a neonatal assessment tool that is correlated with risk of mortality, was positively associated with cortisol level on days 1 and 3 through 7. TRH versus placebo treatment did not influence cortisol levels at any time point. To examine the relationship between cortisol and adverse outcome of death or CLD at 36 weeks' postmenstrual age (CLD36), logistic regression models adjusting for known contributing clinical factors (gestational age and CRIB score) were fit. There was a statistically borderline negative association between median cortisol level at 3 to 7 days and CLD36. After adjusting for gestational age and CRIB score, the predicted probability of CLD36 was only minimally influenced by the cortisol concentration. CONCLUSION: In preterm infants, basal plasma cortisol concentration during the first week is a weak predictor for CLD36. Possible benefits as well as risks of supplemental, low-dose cortisol treatment of high-risk preterm infants remain to be determined.

Effect of single versus multiple courses of antenatal corticosteroids on maternal and neonatal outcome.

OBJECTIVE: Treatment of pregnant mothers with a single course of antenatal corticosteroids significantly reduces neonatal mortality and morbidity. Multiple weekly courses are often given. However, the safety and efficacy of repeated courses of antenatal corticosteroids have not been adequately studied. STUDY DESIGN: A retrospective study was performed for 609 mothers and their 713 infants who were treated with 1 to 12 courses of antenatal corticosteroids. Data for 369 singleton preterm infants born at < or =34 weeks' gestation, 210 multiple gestations, and 134 infants delivered at > or =35 weeks' gestation were analyzed separately. RESULTS: The incidence of respiratory distress syndrome was 45% for single-course and 35% for multiple-course groups (P =.005; odds ratio, 0.44; 95% confidence interval, 0.25-0.79). The multiple-course group also had significantly less patent ductus arteriosus (20% vs 13%; P =.016). Incidence of death before discharge and other neonatal morbidities were similar. The multiple-course group had a reduction of 0.46 +/- 0.19 cm in head circumference at birth (P =.013) when adjusted for gestational age and preeclampsia. The 2 groups had similar birth weights. Infants born at > or =35 weeks' gestation, multiple-gestation infants, and infants who were born >7 days after the last corticosteroid dose had similar outcomes, regardless of the number of courses they received. Mothers treated with multiple courses compared with a single course had a significantly higher incidence of postpartum endometritis (P =.013), even though they had a lower incidence of prolonged rupture of membranes (24% vs 33%, P =.06) and similar cesarean delivery rates. CONCLUSION: Exposure to multiple courses of antenatal corticosteroids compared with a single course resulted in a significant reduction in the incidence of respiratory distress syndrome in singleton preterm infants delivered within a week of the last corticosteroid dose. This was associated with a reduction in birth head circumference and an increased incidence of maternal endometritis. Whether the potential benefits of repeated therapy clearly outweigh the risks will ultimately be determined in randomized prospective controlled trials.

Risk factors for low bone mineral density in children and young adults with Crohn's disease.

OBJECTIVE: Low bone mineral density (BMD) is a recognized complication of Crohn's disease (CD). The aim of this study was to identify the risk factors for low BMD in pediatric patients with CD. STUDY DESIGN: One hundred nineteen subjects with CD ranging in age from 5 to 25 years were enrolled. BMD of the lumbar spine was measured by dual-energy x-ray absorptiometry. Growth parameters were assessed by examination. Disease-specific variables and use of selected medications were determined by chart review. RESULTS: Powerful risk factors for low BMD z-score included hypoalbuminemia, exposure to nasogastric tube feeds, total parenteral nutrition, 6-mercaptopurine, and corticosteroids. Corticosteroid dosing at a level >7.5 mg/d, 5000 mg lifetime cumulative dose, or >12 months of lifetime exposure were significant risk factors for low BMD z-score. Weaker but significant associations with low BMD z-scores included measures of disease severity such as pediatric Crohn's disease activity index, hospital admissions, and length of hospital stay. Site and duration of disease were not predictive. CONCLUSIONS: The presence of several clinically available factors was predictive of poor bone mineral status in this sample of subjects with CD. Hypoalbuminemia, corticosteroid exposure, nasogastric tube feeds, total parenteral nutrition, and 6-mercaptopurine were the most powerful risk factors for low bone mineral status.

Results of the 1988-1989 Patterns of Care Study process survey for Hodgkin's disease.

PURPOSE: To document national standards of care for patients receiving radiotherapy as part of curative treatment for Hodgkin's disease. MATERIALS AND METHODS: A national survey was conducted of 61 institutions treating 275 patients with Stages I-III Hodgkin's disease and representing six facility type strata. Pretreatment evaluation, radiotherapy treatment parameters, and use of combined modality therapy were assessed. RESULTS: Ann Arbor stage for the 275 patients was as follows: IA, 69 (25%); IB, 7 (3%); IIA, 123 (45%); IIB, 36 (13%); IIIA 23 (8%), IIIB, 14 (5%); unknown, 3 (1%). Pretreatment evaluation included complete blood count for 93%, sedimentation rate in 29%, chest CT in 88%, abdominal CT scan in 87%, and bone marrow biopsy in 81%. Lymphangiograms were obtained in 50% of cases; laparotomy was performed in 46%. The yield of positive findings in the spleen at laparotomy was 6.5 % overall. Facility differences with respect to staging were seen only for the use of gallium scans, which were more commonly used in academic centers (44% vs. 15-23% elsewhere, p<0.001). Radiotherapy was delivered with a linear accelerator in 94% of cases. Treatment simulation was performed for 94% and individualized blocks constructed for 95% overall; however, freestanding facilities had a lower rate of performance of these procedures (78% vs. 98-99% for simulation and 88% vs. 96-99% for customized blocking, p<0.001). The mean supradiaphragmatic dose was 36.74 Gy and the mean subdiaphragmatic dose was 33.81 Gy. Planned combined modality therapy was given in 36% of patients. The use of combined modality therapy by stage was as follows: IA, 11%; IB, 43%; IIA, 30%; IIB, 68%; IIIA, 57%; IIIB, 100%. Chemotherapy was completed prior to radiation in 80% of cases and generally consisted of ABVD (32%), an alternating regimen (25%), or MOPP (22%). Among Stage I/II patients, use of chemotherapy was associated with reduced radiation doses (mean supradiaphragmatic dose 34.53 Gy vs. 38.43 Gy and mean subdiaphragmatic dose 31.27 Gy vs. 34.51 Gy), and reduced volumes of treatment (87% vs. 28% treated to one side of the diaphragm only). Laparotomy was not associated with decreased supra- or subdiaphragmatic radiation doses or decreased volumes of treatment. CONCLUSIONS: With the exception of gallium scans, pretreatment evaluation is relatively uniform across facility strata. Increased understanding of prognostic factors in Hodgkin's disease and greater use of planned combined modality therapy for higher risk patients appears to have contributed to a decreased use of and low yield of positive findings for laparotomy. Laparotomy was not associated with reduced radiation volumes or doses. Freestanding radiation facilities had a lower rate than other facility types for the performance of treatment simulation and customized patient blocking.

Experiences with 6-mercaptopurine and azathioprine therapy in pediatric patients with severe ulcerative colitis.

BACKGROUND: The effectiveness of 6-mercaptopurine combined with azathioprine in treating severe ulcerative colitis has been shown in several adult studies. Reported pediatric experiences are rare. The purpose of this study was to investigate the safety and the potential efficacy of 6-mercaptopurine and azathioprine in the treatment of active ulcerative colitis in a pediatric population. METHODS: The medical records of patients with active ulcerative colitis who were under observation at The Children's Hospital of Philadelphia and its satellite clinics from January 1984 through December 1997 were retrospectively reviewed. Patients were included who had received a diagnosis of ulcerative colitis, who met no criteria for Crohn's colitis, and who had received treatment with 6-mercaptopurine and azathioprine. They were then analyzed for the development of side effects, the indication to use 6-mercaptopurine and azathioprine, and the ability to discontinue corticosteroid use in those patients taking 5-acetylsalicylic acid products who were corticosteroid-dependent or whose disease was refractory to treatment. Excluded from the corticosteroid analyses were patients who underwent surgery for their disease and patients treated with 5-acetylsalicylic acid only. Statistical analysis was performed by the Kaplan-Meier survival curve and paired Student's t-test. RESULTS: In a review of 200 medical records of patients with active ulcerative colitis, 20 patients met the criteria. The patients' average age at the initiation of treatment with 6-mercaptopurine and azathioprine was 13.8 years. Sixteen patients (80%) were corticosteroid dependent and 3 (15%) had ulcerative colitis refractory to corticosteroid treatment. One patient had severe colitis treated with 5-acetylsalicylic acid only. Discontinuation of corticosteroid was accomplished in 12 (75%) of 16 patients. The median time to discontinuation of corticosteroid after initiation of 6-mercaptopurine and azathioprine therapy was 8.4 months. Eight patients (67%), observed from 3 months to 65 months, have continued without corticosteroid therapy. Side effects included pancreatitis and shingles that resulted in discontinuation of 5-acetylsalicylic acid, leukopenia corrected by withholding 6-mercaptopurine, and self-resolved hepatitis. CONCLUSIONS: The data support the safety of 6-mercaptopurine and azathioprine use in the treatment of pediatric patients with ulcerative colitis; side effects were minimal and reversible. Eighteen (90%) of 20 patients tolerated the therapy well. The results also show that 12 (75%) of 16 pediatric patients with ulcerative colitis will benefit from the use of 6-mercaptopurine and azathioprine after initial discontinuation of corticosteroid therapy. Although 6-mercaptopurine and azathioprine may not prevent further relapses, medical management of these flares may be less intense and may not require long-term corticosteroid use. Prospective clinical trials in pediatric patients are necessary to delineate further the role of 6-mercaptopurine and azathioprine in pediatric ulcerative colitis.