Fluid management of the prematurely born infant must reconcile the need to “grow the infant,” while too much fluid may increase morbidity including patent ductus arteriosus (PDA), necrotizing enterocolitis (NEC), and bronchopulmonary dysplasia (BPD); too little fluid may exacerbate electrolyte and metabolic disturbances, even acute renal failure. The sick, prematurely born infant’s fluid management is particularly complex for a number of reasons. Prematurely born infants have a high trans-epidermal water loss due to their skin immaturity and a large surface area to weight ratio; trans-epidermal water loss can be compounded if infants are nursed naked under a radiant warmer. In all infants, shortly after birth, there is a contraction of the extracellular compartment due to the loss of interstitial fluid, which is associated with postnatal weight loss (Modi et al. 2000). The timing of the diuresis/natriuresis, however, is related to the fall in the pulmonary vascular resistance, which may be variable in sick, prematurely born infants. Prematurely born infants have immature renal function, and in addition, respiratory water loss is influenced by the level of humidification of the inspired gases in ventilated infants. They may also be exposed to therapies that affect their fluid balance. For example, the majority of mothers of prematurely born infants will have been given antenatal corticosteroids in an attempt to improve lung immaturity, and antenatal corticosteroids may enhance fetal epithelial cell maturation and improve skin barrier function (Omar et al. 1999; Dimitriou et al. 2005). This results in lower insensible water loss and a higher urine output (Dimitriou et al. 2005). In this section, assessments of fluid balance are reviewed and the evidence for the type and magnitude of fluid given to prematurely born infants is discussed.

Fluid intake should be carefully recorded on an hourly basis, including all crystalloid and colloid input, plus medications and “flush” volumes. Urine output needs also to be accurately determined. One method is to collect urine output on open nappies, and for extremely low birth weight infants, cotton wool balls are placed on the nappy (Kavvadia et al. 2000a). As soon as the infant voids, the nappy or cotton wool ball should be weighed; otherwise, the volume may be underestimated due to losses from evaporation. An alternative method is to use a urine bag and aspirate urine with a fine catheter from the bag as soon as the urine is voided (Hartnoll et al. 2000). It is important, if the infant appears to be oliguric, to check that the bladder is not palpable. The magnitude of fluid input should be reduced if the infant develops acute renal failure defined as for any 24-h period a creatinine level greater than 132 μmol/l and urine output less than 1.0 ml/kg/h, except one day when a urine output of less than 0.5 ml/kg/h may indicate acute renal failure. Urine osmolality should also be measured; a level of between 200 and 400 mOsm/kg suggests a satisfactory fluid intake. Immature infants, however, have a limited ability to concentrate their urine and may pass urine of low osmolality while becoming dehydrated; hence, it is important to concurrently check the infant’s weight. Infants should be weighed on a daily basis, which is greatly facilitated by use of “bed” scales which remain inside the incubator and the infants are nursed upon them; hence, minimal handling is required to assess the weight.

Electrolytes and creatinine should be measured at least on a daily basis and more frequently if the infant is developing or has developed renal failure. Creatinine is derived from phosphocreatine in muscle and excreted in urine and is used as an index of the glomerular filtration rate (GFR). The serum level at birth reflects the maternal concentration. Creatinine clearance and the GFR increase with increasing postnatal age in premature infants (Gallini et al. 2000). Serum creatinine falls in the first week after birth as the maternally derived creatinine is excreted; therefore, failure to see the expected decline or a rise in the creatinine level indicates a reduced GFR.

Sodium supplementation should be delayed until the onset of postnatal extracellular volume contraction, which is indicated by marked weight loss (Modi et al. 2000). Prematurely born infants have a limited capacity to excrete a sodium load (Robillard et al. 1992), and in a randomized trial which included 25–30-week gestation infants, early (4 mmol/kg/day from the second day) compared to delayed (when weight loss of 6 % of birth weight had been achieved) supplementation was associated with delayed loss of body water (Hartnoll et al. 2000). In addition, by the end of the first week, 35 % of the babies in the delayed group but only 8.7 % of the early intake group no longer required supplementary oxygen (Hartnoll et al. 2000).

Colloid infusions should be used sparingly in sick, preterm infants, not least as there may be a safer, cheaper, and an at least equally effective alternative (Greenough 1998). In a randomized trial, isotonic saline and albumin were equally as effective in reducing the hematocrit in polycythemic infants (packed cell volume greater than 65 %) (Wong et al. 1997). Colloid infusions should not be used as first-line treatment for hypotension as several studies have demonstrated it is the volume infused rather than the protein load which is more efficacious in treating hypotension (Greenough 1998). In addition, in a randomized trial, isotonic saline was equally as effective as a similar volume of colloid in treating hypotension (So et al. 1997). Indeed, results highlight crystalloid may be more appropriate to treat hypovolemic hypotension, as the infants given albumin had significantly higher weight gain in the first 48 h, suggesting they suffered fluid retention (So et al. 1997). Albumin should not be given as part of the initial resuscitation process, as low Apgar scores may indicate myocardial depression in which case volume load is contraindicated. Asphyxia also results in increased capillary permeability and protein leak into the lung could impair resuscitation (Jobe et al. 1985). Furthermore, we have demonstrated that the amount of colloid infused in the perinatal period significantly correlated with the duration of oxygen dependency (Kavvadia et al. 2000a) and abnormal perinatal lung function (Marks et al. 1978). Colloid was prescribed to hypotensive infants (Kavvadia et al. 2000a) and thus it might be that the adverse outcomes were related to the severity of the underlying illness rather than colloid infusion per se. An alternative explanation, however, is that when colloid is given to infants with increased vascular permeability, it leaks into the lungs, worsening respiratory function (Marks et al. 1978) and necessitating higher levels of respiratory support, and hence could predispose to BPD. There are also no data to support the use of albumin infusion to “treat” low serum albumin levels. Two randomized, but small trials have been performed with no differences in mortality or morbidity (Jardine et al. 2010). In one of the studies (Greenough et al. 1993), albumin infusion was associated with a significant increase in the albumin level and a reduction in weight, but no significant changes in the peak inflating pressures.

Excessive fluid input increases the likelihood of PDA and BPD development. In a retrospective analysis of data from 1,382 ELBW infants of birth weight between 401 and 1,080 g, multivariate logistic regression demonstrated that higher fluid in the infant and less weight loss during the first 10 days were significantly related to death or BPD (Oh et al. 2005). Yet administration of diuretics to infants with RDS results in no long-term benefits and only transient improvements in lung function (Brion and Soll 2011). An alternative approach has been to use fluid restriction to try and prevent morbidity and mortality in prematurely born infants. There has been a number of randomized trials comparing restricted versus liberal water intake. Meta-analysis of five such studies (Bell and Acarregui 2008) demonstrated that restricted water intake increased postnatal weight loss and significantly reduced the risks of PDA and necrotizing enterocolitis (NEC), but not BPD and intracranial hemorrhage (ICH). In only one of the studies, however, were antenatal steroids and postnatal surfactant given routinely (Kavvadia et al. 2000a). That study (Kavvadia et al. 2000a) demonstrated no statistically significant differences in PDA, ICH, NEC, or BPD, but significantly more (43 % versus 19 %) of the liberal versus restricted group received postnatal corticosteroids, as it was considered they were at high risk of developing BPD. Importantly, there were no statistically significant differences in the incidence of acute renal failure (Kavvadia et al. 2000a) or electrolyte or metabolic disturbances (Kavvadia et al. 2000b). Those results (Kavvadia et al. 2000a, b) support the conclusion in the Cochrane review (Bell and Acarregui 2008) that the most prudent prescription for water intake of prematurely born infants is careful restriction of water intake so that physiological needs are met without allowing significant dehydration. Whether fluid restriction is beneficial in specific situations remains to be appropriately tested. One of three Cochrane reviews at the protocol stage has now been reported and demonstrated no eligible trials.