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Restricted versus liberal water intake for preventing morbidity and mortality in preterm infants

RHL Commentary by Warren JB and Schelonka RL

1. INTRODUCTION

Preterm delivery, defined as childbirth at less than 37 completed weeks of gestation, is a global problem. In 2005, nearly 10% of all births worldwide, a total of 12.9 million births, were preterm (1). In addition to increased risk of death, infants born preterm are at higher risk for other adverse outcomes such as patent ductus arteriosus (PDA), necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), and intracranial hemorrhage (2).

The prevention of morbidities associated with preterm birth could have worldwide implications. The majority of preterm births occur in developing countries and medically under-resourced regions. In 2005, for example, 10.9 million of the 12.9 million preterm births worldwide occurred in Africa and Asia (1). While the ultimate goal is to decrease rates of prematurity, until that happens, we must look for interventions that prevent adverse outcomes for infants born prematurely.

Without specialized care, many prematurely born infants will not survive. One aspect of the preterm infant’s care that is almost always completely regulated by the caregiver is water intake, as most preterm infants are generally not able to take orally the water and nutrients necessary for survival. This review (3) examines liberal versus restricted water intake in preterm newborns as related to common morbidities and death.

2. METHODS OF THE REVIEW

The Cochrane review team evaluating restricted versus liberal water intake for preventing morbidity and mortality in preterm infants searched English language databases as well as conference proceedings for related clinical trials. Randomized controlled trials (RCTs) involving infants who received water mainly or entirely intravenously were included. For inclusion in the review, the clinical trials had to include one or more of the following outcomes: excessive weight loss, dehydration, PDA, NEC, BPD, intracranial hemorrhage, and death.

3. RESULTS OF THE REVIEW

The comprehensive review of the literature yielded five RCTs comparing varying levels of water intake in preterm infants. There were a total of 582 infants included in the studies. Four of five studies focused on infants weighing less than 2000 g; the fifth study included mostly preterm infants whose mean weight was 2000 g. Each of the studies compared a group of preterm infants who received liberal water intake (the control group) with a group of preterm infants who received restricted water intake. Water intake was controlled beginning at birth for three studies, within 24 hours for one study, and within 72 hours for the remaining study. The studies differed in two main ways. First, the duration of controlled water intake varied from three to 30 days. Second, the amount of water given to the liberal and restricted water groups varied among studies. Liberal water intake ranged from 140–200 ml/kg/day, while restricted water intake ranged from 60–150 ml/kg/day.

Three studies (326 patients) examined the outcome of weight loss. When combined, there was a significantly greater weight loss in the restricted water intake group. There was an absolute percent difference in weight loss of 1.94% [95% confidence interval (CI): 0.82–3.07] between the two groups. Four of the studies (526 patients) considered the incidence of PDA. When examined together, the restricted water intake group had a significantly lower risk of PDA: risk ratio (RR) 0.52 [95% CI: 0.37–0.73 and number needed to treat (NNT) 7]. NEC was analysed in four studies (526 patients). In the restricted water intake group there was a significantly lower risk for NEC: risk ratio 0.43 (95% CI 0.21–0.87); NNT 20. When analysing other outcome measures, there was a trend towards increased risk for dehydration, a reduced risk for BPD, a reduced risk for intracranial hemorrhage, and reduced risk for death; none reached statistical significance.

4. DISCUSSION

4.1 Applicability of the results

Despite differences in study designs of the previous RCTs, especially regarding magnitude and duration of water restriction, when combined, the findings of reduced risk for PDA and NEC were robust. Although these trials were conducted in developed nations, there is no reason to believe that the results are not generalizable to medically under-resourced regions. In communities with sufficient medical resources to administer intravenous water and fluids to premature infants, therapeutic water restriction would be feasible.

Mortality rates of preterm infants are high in extremely under-resourced areas (4). A contributor to high mortality rates is dehydration due to the inability to give adequate water and nutrients to these infants. In these settings of limited medical resources, where facilities for administration of intravenous fluids are not available, managed fluid restriction would not be feasible.

In under-resourced regions, where intravenous fluids can be administered, morbidity and mortality of preterm infants comes not from the inability to provide fluid and nutrients, but from complications of prematurity. A precise estimate of PDA and NEC in preterm infants born in under-resourced settings is not known. If restricting water intake for preterm infants can be done safely in medically under-resourced areas, then this intervention could increase survival, as well as survival without morbidity, in preterm infants.

4.2 Implementing the Intervention

The most important aspect of implementing the practice of water restriction is education, since controlled fluid restriction is a change in practice and does not involve the use of novel therapeutics or equipment. Caregivers need to understand the goals of fluid restriction and be able to monitor closely for the side-effects of excessive weight loss and dehydration. In order to implement safely the practice of water restriction, local guidelines should be developed regarding the target volume of fluid per day given to preterm infants, the duration of the intervention, and how to manage infants who show signs of excessive weight loss or dehydration.

4.3 Implications for research

The evidence from available RCTs, when analysed in combination, is compelling and promising regarding improvement in two major morbidities associated with preterm delivery. Important questions remain, however. First, is there a subgroup of premature infants who would benefit most from water restriction? With increasing post-menstrual (gestational) age, the risk of PDA and NEC decreases in preterm infants. There is most likely a postmenstrual age when restriction of water, and concomitant nutrient restriction, is more harmful than beneficial. Second, how much water is too much, and how long should water be restricted? The studies to date had large differences in the magnitude and duration of fluid restriction, so a specific target daily water volume is not known. Further research is needed to define the optimal daily fluid intake, and for how long to restrict water in preterm infants in order to achieve the greatest reduction in PDA and NEC with the least weight loss, dehydration and nutrient deprivation. Finally, what are the long-term consequences of water restriction on learning and neurodevelopment? Because so little is known about the later effects of water restriction in the neonatal period, it is prudent to be cautious before widespread implementation of this therapeutic approach.

Acknowledgements: None

Sources of Support: None

References

• Beck S, Wojdyla D, Say L, Betran AP, Merialdi M, Requejo JH, et al. The worldwide incidence of preterm birth: a systematic review of maternal mortality and morbidity. Bulletin of the World Health Organization 2009;88:31-38; DOI: 10.2471/BLT.08.062554.
• Martin RJ, Fanaroff AA, Walsh MC (ed). Neonatal-perinatal medicine: diseases of the fetus and infant. Philadelphia, PA: Mosby Elsevier; 2006.
• Bell EF, Acarregui MJ. Restricted versus liberal water intake for preventing morbidity and mortality in preterm infants. Cochrane Database of Systematic Reviews 2008;Issue 1. Art. No.: DC000503; DOI: 10.1002/14651858.CD000503.pub2.
• WHO. The world health report 2005: make every mother and child count. Geneva: World Health Organization; 2005.

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This document should be cited as: Warren JB, Schelonka RL. Restricted versus liberal water intake for preventing morbidity and mortality in preterm infants (last revised: 1 March 2010). The WHO Reproductive Health Library; Geneva: World Health Organization.

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