The 24-week fetus is composed of 90% total body water (TBW). Cell membranes separate intracellular water and extracellular water spaces. Sixty-five percent of TBW is in the extracellular (ECW) compartment and 25% is intracellular (ICW). As gestation proceeds towards term, TBW decreases to 74% of total body weight and the extracellular and intracellular volumes are 40% and 35%, respectively. Potassium (K+) is the major ion of the ICW and potassium's intracellular concentration is impaired by insufficient supplies of oxygen and energy. The major ion of ECW is sodium (Na+) and the major anion is chloride (Cl−).

The preterm infant is in a state of relative extracellular fluid volume with an excess of TBW compared with the full-term infant. VLBW infants are vulnerable to imbalances between intra- and extracellular compartments. The dilute urine and negative sodium balance the first few days after birth in the preterm infant is an appropriate adaptive response to extrauterine life. Therefore, the initial diuresis is physiologic, reflecting changes in interstitial fluid volume. This diuresis should be considered in the estimation of daily fluid needs. As a result, a gradual weight loss of 10–15% in a VLBW infant during the first week of life is expected without adversely affecting urine output, urine osmolality, or clinical status. Provision of large volumes of fluid to provide increased nutrition, for example, 160 to 180 mL/kg/d, does not prevent this weight loss and appears to increase the risk of the development of patent ductus arteriosus, intraventricular hemorrhage, bronchopulmonary dysplasia (BPD), and necrotizing enterocolitis (NEC).