Water, energy and early postnatal growth in preterm infants.

Non-invasive methods, including stable isotope techniques, indirect calorimetry, nutritional balance and skinfold thickness, have given a new insight into early postnatal growth in neonates. Neonates and premature infants in particular, create an unusual opportunity to study the fluid and metabolic adaptation to extrauterine life because their physical environment can be controlled, fluid and energy balance can be measured and the link between metabolism and the energetics of their postnatal growth can be assessed accurately. Thus the postnatal time course of total body water, heat production, energy cost of growth and composition of weight gain have been quantified in a series of "healthy" low-birth-weight premature infants. These results show that total body water is remarkably stable between postnatal days 3-21. Energy expenditure and heat production rates increase postnatally from mean values of 40 kcal/kg/day during the first week to 60 kcal/kg/day in the third week. An apparent energy balance deficit of 180 kcal/kg can be ascribed to premature delivery. The cost of protein metabolism is the highest energy demanding process related to growth. The fact that nitrogen balance becomes positive within 72 h after birth places the newborn in a transitional situation of dissociated balance between energy and protein metabolism during early postnatal growth: skinfold thickness, dry body mass and fat decrease, while there is a gain in protein and increase in supine length. This particular situation ends during the second postnatal week and soon thereafter the rate of weight gain matches statural growth. The goals of the following review are to summarize data on total body water and energy metabolism in premature infants and to discuss how they correlate with physiological aspects of early postnatal growth.

Historical background of changes in FDA policy on the study and evaluation of drugs in women.

The Food and Drug Administration (FDA) has recently made two important changes in its policy for the study and evaluation of drugs in women: (1) sex-specific analyses of the safety and efficacy of drugs will be required as part of all new drug applications, and (2) it will no longer be recommended that women of childbearing potential be restricted from participating in the earliest phases of drug trials. These changes have come about as a result of continuous efforts to individualize therapy, to improve upon the safety and efficacy of drugs, and to respond to important questions about whether the drug development process produces adequate information about the effects of drugs in women. In turn, these efforts are the outgrowth of a long history in the United States of changes in the clinical care for women, changes in the use of women as research subjects, changing attitudes about the balance between protection and risks for women in clinical trials, and national movements by women to focus on issues of their health care and to transform the male-oriented model of clinical research. The new FDA guidelines, published in July 1993, will provide guidance to researchers on accumulating valuable information on how drugs work in women and will help make it possible for physicians and other caregivers to consider the effects of gender on health and treatment.