Allocation of health care resources in the neonatal and perinatal area �CCPS Symposium 1996

There have been publically expressed concerns about the costs and allocation of neonatal and perinatal health care resources in Canada and elsewhere for the past 15 years. This paper reports information from a symposium held during the 1996 Canadian Paediatric Society (CPS) annual meeting sponsored by the CPS Section on Perinatal Medicine. Experts in perinatal epidemiology, health care economics, public policy and finance, and consumer perspectives on the outcomes of neonatal and perinatal intensive care explored the following questions: How should the need for health care resources in the neonatal and perinatal area be objectively determined? When there are competing needs between the maternal-newborn area and other areas, how should these be rationalized? What evidence should be used (or should be available) to support the present use of resources? What evidence should be available (or is needed) to change or introduce new uses of resources? The conclusions indicated that there are no generally accepted methods to determine the allocation of health care resources but that considerations need to include population characteristics, desired outcomes, achievable results, values, ethics, legalities, cost-benefit analyses and political objectives. Information from families and adolescents who required the use of high technology and/or high cost programs will contribute individual, family and societal values that complement cost-efficacy analyses.     

Diagnosis of perinatal TORCH infections

Collectively, TORCH infections create more neonatal morbidity than early-onset group B streptococcal sepsis. Fortunately, the incidence of maternal infection by CMV or toxoplasmosis is low (2-10 per 1,000 births). There have been tremendous advances in direct antigen testing and in the sensitivity and specificity of IgG and IgM testing. Consistently, research laboratories show more accurate results than in the past. Unfortunately, commercial laboratories are using older, single-kit testing. The relatively poor degree of reliability can lead to unnecessary obstetric intervention or elective termination. Any positive pathogen-specific IgM on maternal serum should have additional confirmatory testing in a reputable research laboratory before any intervention. Direct antigen testing or multiple testing would seem to be appropriate for confirmation. This may include amniocentesis of fetal blood sampling. The research on the newer tests is based of the evaluation of blood from seriously immunocompromised subjects. Extrapolations of test accuracy to similar tests on healthy, pregnant women and their fetuses are likely to be in error. The application of these accurate tests to the obstetric population is a critical research need.     

Brain damage after neonatal tetanus in a rural Kenyan hospital

OBJECTIVE: Neonatal tetanus (NNT) is an important cause of mortality in resource poor countries, particularly sub-Saharan Africa. There are no reports of the long-term outcome of children who survive NNT in African hospitals. DESIGN: In a retrospective study of children discharged from Kilifi District Hospital (KDH), Kenya with NNT, each child was linked with a comparative child (CC) in the community matched for age, sex and locality. PARTICIPANTS: A total of 123 patients were admitted with NNT between 1992 and 1996, of whom 68% died. Twenty-three (59%) of the 39 survivors were traced in the community, 10 had moved away, six had died. OUTCOME MEASURES: NNT survivors underwent a neurological and developmental examination and a questionnaire was administered to the parents about the behaviour of the child. A verbal autopsy was used to determine the cause of death in children who had died after discharge. RESULTS: The head circumference of NNT survivors was significantly smaller than that of CC (P=0.037); eight children had microcephaly compared with one CC (P=0.011). NNT survivors had more problems with hand-eye co-ordination tasks (P=0.035), a lower summated developmental score (P=0.023) and more mild neurological abnormalities (P=0.008) than CC. Parents of NNT survivors reported more behavioural problems (P=0.02) than parents of CC. CONCLUSIONS: Children who survive NNT have evidence of brain damage that manifests as microcephaly, mild neurological abnormalities, developmental impairment - particularly fine motor difficulties - and behaviour problems.     

Genome-wide loss of heterozygosity analysis of chemically induced rat hepatocellular carcinomas reveals elevated frequency of allelic imbalances on chromosomes 1, 6, 8, 11, 15, 17, and 20

Neoplastic development is a multistep process that involves the stochastic accumulation of heritable genetic alterations in proto-oncogenes, DNA repair genes, and tumor suppressor genes. Loss of heterozygosity (LOH) analysis has been used successfully to identify the genetic determinants of neoplastic development, including tumor suppressor genes, in several species and organs but not in the rat liver. We report the results of a sensitive genome-wide LOH analysis of rat hepatocellular carcinomas (HCCs). Heterozygous rats (Wistar-Furth x Fisher 344) were subjected to an Initiation-Promotion-Progression (IPP) protocol of hepatocarcinogenesis. Two weeks after initiation (by partial hepatectomy, 10 mg/kg diethylnitrosamine), the rats were placed on a diet containing 0.05% phenobarbital (PB). After 24 wk of PB promotion, the rats received either 100 or 1 50 mg/kg ethylnitrosourea. Hepatocellular tumors were resected after a total of 76wk of PB promotion. LOH analysis was completed on 26 HCCs by using 60 microsatellite markers covering all 20 rat autosomes and chromosome X. While 85% of the HCCs had one or more allelic imbalances, the average HCC had 3.3 allelic imbalances (range 0-9). A conditional hypothesis-testing method called the Hot-Cold model was used to determine the location of statistically significant elevations in the frequency of allelic imbalances. Elevated allelic imbalances were observed on chromosomes 1q, 6, 8, 11, 15, 17, and 20p. Together, these allelic imbalances suggest that the retinoblastoma and insulin-like growth factor genes as well as the resistance to chemical carcinogenesis (rcc) locus may be involved in HCC development in the rat but that LOH of the p53 gene is not. The elevated rate of allelic imbalances on chromosomes 8,11, and 17 may indicate the location of undiscovered tumor suppressor genes important to neoplastic development in rat liver. Microdissection-based LOH analysis of HCC revealed that contamination of non-neoplastic and nonhepatocellular tissue was not masking LOH in the whole-tumor analysis. There were no statistically significant differences in the frequency of allelic imbalances between HCC of any differentiation state (histological grade). To the degree that it does not reflect differences in etiological factors, the absence of allelic imbalances in chromosomal regions containing the p53 and mamose-6-phosphate/insulin-like growth factor II receptor tumor suppressor genes and the generally low frequency of allelic imbalances in these tumors, suggests that LOH and allelic imbalances play a less significant role in the molecular pathogenesis of HCC in rats than humans.