Very low birth weight: a problematic cohort for epidemiologic studies of very small or immature neonates.

Despite widespread acceptance of the concept of very low birth weight (VLBW), i.e., birth weight of less than or equal to 1,500 g, VLBW infants represent an extremely heterogeneous group of newborns, including those with very immature gestational age and those who are more mature but extremely growth retarded. To demonstrate how use of the VLBW rubric can lead to confounding bias that is not only large in magnitude but impossible to control satisfactorily, the authors divided 640 consecutive live neonates born in the Royal Victoria Hospital, Montreal, Canada, from 1978 to 1987 into two overlapping groups: a VLBW cohort (birth weight, 500-1500 g; n = 573) and a gestational age cohort (gestational age, 23-30 completed weeks; n = 466). Variation in growth status by gestational age was much more uniform in the 23- to 30-week cohort. Thus, although mean birth weight was similar in the 500- to 1,500-g and 23- to 30-week cohorts (1,055 vs. 1,064 g), the 500- to 1,500-g cohort was more mature (mean gestational age, 28.8 vs. 27.8 weeks; upper range, 39.7 vs. 30.9 weeks) and had twice the rate of intrauterine growth retardation (25.7 vs. 11.5%). These differences in maturity and growth resulted in a misleading protective effect of intrauterine growth retardation against in-hospital death in the 500- to 1,500-g cohort (crude odds ratio = 0.55 (95% confidence interval 0.36-0.83] and a greater discrepancy in maturity between cesarean- and vaginally delivered infants (3.1 vs. 1.5 weeks) in the 500- to 1,500-g vs. 23- to 30-week cohorts. These differences arise from inextricable confounding of growth status and maturity in the 500- to 1,500-g cohort, the most mature infants also being the most growth retarded. The removal of well-grown infants with birth weights of greater than 1,500 g from the VLBW cohort leads to a progressively distorted spectrum of growth with advancing gestational age and an artifactual blunting of the beneficial effects of increasing maturity. The authors suggest that whenever fetal growth is an important exposure, outcome, or confounding variable, epidemiologic studies of extremely small or immature newborns should be based on gestational age rather than the VLBW criterion.

Distribution of 99mTc-phosphate compounds in osteoarthritic femoral heads.

UNLABELLED: In a study of the distribution of 99mTc-polyphosphate and 99mTc-methylene diphosphonate in osteoarthritic femoral heads by macroautoradiography of samples obtained during replacement surgery, the bone-seeking agents were seen to accumulate in the weight-bearing, denuded areas, mainly in the cyst walls and at the osteochondral junctions in the osteophytes. The autoradiographic findings were substantiated by findings from impulse-counting of different zones in the femoral heads that were done on frozen sections. Morphological studies of sections adjacent to the cut surface used for autoradiography showed that the accumulations of the radionuclides were located in areas of new-bone formation, particularly enchondral ossification. This finding was confirmed by histochemical staining for alkaline phosphatase, a marker enzyme for bone mineralization. The over-all distribution of alkaline phosphatase activity in cells roughly paralleled the deposition of the bone-seeking agents. CLINICAL RELEVANCE: Scintigrams of osteoarthritic joints reflect primarily the rate of osteogenesis in subchondral bone and osteophytes. As the scan is positive even in very early stages in the development of the disease, a more detailed knowledge of the mechanism responsible for an increased uptake of 99mTc-phosphate compounds may, among other things, contribute to the elucidation of the pathogenesis.