0031-3998/04/5503-0528 PEDIATRIC RESEARCH Vol. 55, No. 3, 2004 Copyright © 2004 International Pediatric Research Foundation, Inc. Printed in U.S.A. Latin American Society for Paediatric Research (LASPR) Selected Abstracts from the XLI Annual Meeting October 2003 – Marbella, Chile President: Fernando Pizarro (Chile) President Elect: Jose´ Tantalean (Peru´) General Secretary: Luis Guimarey (Argentina) 1 3 IMPACT OF FOLIC ACID FORTIFICATION OF WHEAT FLOUR ON THE CHARACTERIZATION OF THE HANTAVIRUS INFECTION IN CHILE: IN- INCIDENCE OF NEURAL TUBE DEFECTS IN CHILE. CUBATION PERIOD, CLINICAL PRESENTATION AND VIRAL LOAD IN Hertrampf E, Cortes F, Mellado C, Erickson D. Instituto de Nutricio´n y Tecnologı´a de los Alimentos, BODY FLUIDS IN PATIENTS WITH HANTA CARDIOPULMONARY SYN- INTA. Universidad de Chile y Centers for Disease Control and Prevention, Atlanta, USA. DROME (HCPS) Introduction. With the objective of preventing neural tube defects (NTD), the fortification of wheat Vial P, Ferre´s M, Belmar E, Castillo C, Tapia M, Donoso S, Ortega C, Noriega M, Aldunate R, Ferrer flour with folic acid (FA), in a concentration of 220ug per 100g of flour, was established as a national P, Hjelle B, Mertz G. Universidad del Desarrollo, Universidad Cato´lica de Chile, Ministerio de Salud, policy in Chile in the year 2000. During this intervention, it was shown in 605 women of childbearing Santiago, Chile y University of New Mexico, USA. age, that the average concentration plasma folate increased four-fold from baseline to post-fortification. HCPS is an endemic disease in Chile. By July 2003, 312 cases have been reported. Most cases With the consumption of fortified flour, the average consumption of FA increased by 427ug/day. (Ͼ70%) have occupational or peridomestic exposure to rodents, the reservoir of the Andes virus. Objective. To evaluate the impact of folic acid fortification on the frequency of NTD in infants born Twenty –five percent of cases are acquired by recreational exposure, with well defined periods of risk, in Santiago. allowing to calculate the time between exposure and disease. Twenty -one patients with known period Subjects and methods. A system was established to monitor the occurrence of NTD (anencephaly, of recreational exposure were enrolled to calculate the incubation period (IP) of HCPS. The IP ranged encephalocele, and spina bifida) which included all live and still-births with a birth weight greater than between 8 to 43 days. In 11 cases the exposure period was less than 3 days, allowing to calculate the 500g of the public maternity wards in Santiago between 1999 and 2000 (120,566 births pre- IP more precisely as between 10 to 35 days (mean 18). The prodromic phase, characterized by fever, fortification) and from 2001 to 2002 (117,704 births post-fortification). One trained neonatologist or myalgia, headache, transient skin rash, conjunctivitis, nausea, abdominal pain, and diarrhea, lasted nurse from each hospital was responsible for recording appropriate data upon the birth of each child. between 3 to 10 days (mean 6). HCPS clinical presentation included abnormal chest X ray (bilateral These data were recorded in a birth registry book and were revised monthly by the geneticist then infiltrates) (21/21, 100 %), O2 requirement (20/21, 95%), pleural effusion (11/21, 52 %), respiratory confirmed through random checks every three months. failure and mechanical ventilation (16/ 21, 76%), lung’s hemorrhage (3/15, 20%); hypotension and Results. The rate of NTD decreased from 17.2/10,000 births pre-fortification to 10/10,000 births shock (15/21,72%), refractory shock (6/21, 29%), extreme bradycardia/CP arrest (5/21, 24%), 2 post-fortification, a reduction of 42% (odds ratio 0.58, 95% confidence interval 0.47 to 0.73.) The patients were connected to ECMO. Overall case-fatality ratio was 19% (4/21). HCPS patients exhibited Ͻ incidences of anencephaly and spina bifida were significantly reduced by 41% and 47% (p 0.000001) an unusually high incidence of renal and coagulation involvement: azotemia (15/21, 75%), oliguric Ͼ respectively and the incidence of encephalocele by 26% (p 0.05). The rate of still-births mortality renal failure/ dialysis (5/21, 24%), proteinuria/ microscopic hematuria (100%), diabetes insipidus Ͻ presented a significant post-fortification reduction from 76.4 to 61.8/10,000 births (p 0.0001), and (1/20, 5%); and trombocytopenia (21/21, 100%), petechiae (11/21, 53 %), bleeding (9/21, 43%) ϭ there were no significant changes in the rate of multiple births (8.43 and 8.89/1,000 births; p 0.22.) (excluding hematuria), and altered coagulation tests (17/21, 81%). In a cohort study of 66 patients, Conclusion: The fortification of wheat flour with folic acid is feasible at the population level in (including some of the previously reported), plasma viremia was prospectively analyzed in 56, (days Chile and is highly effective in the prevention of NTD over a dramatically short time period. 1, 2, 3, 4, 5, 14, 28). Thirty -three (58%) patients had detectable viral load(VL) (in-house quantitative Supported by March of Dimes, Centers for Disease Control and Prevention, PAHO/WHO, Chilean RT-PCR, Roche Light Cycler) at the time of admission with a progressive decline during the first 5 Ministry pf Health. days of hospitalization. Urine (VL) was positive in 16/56 (28%) cases. VL in tracheal fluids were analyzed in 17 cases, 11 (65%) were positive with a significantly higher VL than plasma and urine. Cell associated virus was detected by RT-PCR as far as 28 days after admission. This study contributes to the epidemiologic, clinical and pathogenesis characterization of HCPS. ICIDR, Grant NIAID, NIH n° AI 45452. 2 4 DEVELOPMENT OF CEREBRAL APOPTOSIS AND PRENATAL UNDERNU- HYPERGLYCEMIA AND MORTALITY IN CRITICALLY ILL PATIENTS TRITION IN RATS: PRELIMINARY RESULTS Tantalea´n J, Leo´n R, Santos A, Sa´nchez E, Ramı´rez A. Tantalea´n J, Leo´n R, Santos A, Sa´nchez E, Fustin˜ana C, Fedriani G, Vranic F. Departamento de Pediatrı´a. Divisio´n Neonatologı´a. IIBME. Ramı´rez A. Instituto Especializado de Salud del Nin˜o, Lima, Peru´ Hospital Italiano, Buenos Aires, Argentina. Hyperglicemia in Intensive Care Units (ICU) has been considered innocuous. Recent studies in Apoptosis or programmed cell death plays an important role in cellular differentiation and devel- adults show evidence of a relationship between hyperglycemia and mortality. opment. The interaction between IUGR and apoptosis has not been studied in prenatal nutritional Objective: To determine if hyperglycemia is associated with mortality in critically ill children in restriction models. The existence of critical periods in cerebral development and previous studies that ICU. show neuronal damage in association with IUGR, lead us to raise the hypothesis that the reduction of Material and Methods: All patients admitted to our ICU from December 2001 to June 2003 were neuronal population in starved rats is secondary to apoptosis in the developing brain. registered as prospective subjects. A data base was created to include glycemia value upon admission, Objective: The purpose of this study was to analyze if prenatal induced undernutrition in rats could PRISM score (risk of mortality), length of stay in ICU, sex, age and mortality. Glycemia values produce apoptosis in the rat hippocampus. between 60-120 mg/dL were considered in the control group and all values Ͼ120 mg/dL were Methods: Pregnant Wistar rats were included in the study and randomly assigned to two groups, considered hyperglycemic. Only deaths that occurred during the ICU stay were included in mortality. with 6 animals each one. The Control Group was fed ad libitum with a standard diet and the Study Chi square (withYates correction) was to associate glycemia and mortality, OR to measure the risk of Group received 30 % of the intake from day 1 after pregnancy to day 23. The fetuses were delivered death and z-score to compare mortality percentages. Differences in PRISM score were detected with by cesarean section, weighted and decapitated. The puppies’ brains were extracted. Apoptosis was ANOVA and the Tukey test. assessed by TUNEL method (apopDETEK Cell Death Assay System®). The counting of positive Results: Five hundred and twelve patients were registered During the study period. Sixty eight nuclei was performed in 10 camps with 20x objective. The apoptotic activity (TUNEL-positive) was subjects without an initial glycemia value and 4 who remained hospitalized in the ICU were considered high (ϩϩ) with 10 cells, moderate (ϩ) 5-10 and mild below 5 cells positives. eliminated, leaving 440 cases for analysis, 253 males and 187 females. Average age was 45.8 mo Results: 14 rats were included (2 non pregnant) and 89 puppies were obtained. Control Group nϭ47 (0.02-192), median stay was 5.8 days and average PRISM was 13.7 (0-49). Global mortality was 20% and Study Group nϭ42. The Control Group had significant higher food intake, daily weight increase (88). Average glycemia was 148.9 in survivors vs. 189.9 in non-survivors (pϭ0.006). There were 257 and final mother weight. Significant differences were found in fetal birth weight (5.11Ϯ1.15 vs patients in the Hyperglycemia group (57.9%) and 152 cases in the control group. We found an 2.82Ϯ0.61 g, pϽ0.001). Apoptotic activity in the hippocampus was assessed in 8 samples of the Study association between glycemia and mortality (pϭ0.001, chi square with Yates correctionϭ10.703, Group and in 7 of the Control Group, high apoptotic activity ( 7/8 ) was found in the Study Group and ORϭ2.782, IC 1.5-5.1). Mortality was higher in children with glycemia Ͼ120 mg/dL than in the only slight activity ( 2/7) in the Control Group (pϭ0.0406). control group (23.3% vs 9.9%, pϭ0.001).