A study published online first in the Journal of Pediatrics questions a common practice, the practice of fluid restricting babies who have a patent ductus arteriosus.
De Buyst J, Rakza T, Pennaforte T, Johansson AB, Storme L: Hemodynamic Effects of Fluid Restriction in Preterm Infants with Significant Patent Ductus Arteriosus. J Pediatr 2012(0).
Julie De Buyst studied 18 very preterm babies before and 24 hours after a major reduction in their fluid intakes, from between 140 and 160 mL/kg/d to between 100 and 120 mL/kg/d.
Although this practice is frequent it is something I have never really been able to understand. We know that renal physiology in preterm babies is limited in many ways, but after the first couple of days, during which GFR is rapidly increasing, there is little limitation in the ability to excrete a water load. So giving more fluids has no real effect on total body water, it just increases urine output. Although the ability to concentrate the urine is more limited, with maximal concentrations far less than those seen in older children, administration of fluids within the range down to 100 mL/kg/d generally leads to no change in total body water, it just decreases urine output, leading to a more concentrated urine. How this is supposed to affect PDA patency or the hemodynamic effects of a PDA I do not understand. If we restrict a baby from 160 to 100 mL/kg/d then every hour they receive 2.5 mL/kg less fluid, and make 2.5 mL/kg less urine. Unless they are severely enough restricted to go beyond the renal concentrating ability, and become truly dehydrated, there will be no effect on circulating blood volume. The same arguments can be made for fluid restriction in BPD, and the lack of any likely effect on pulmonary function, more of which later.
So not surprisingly Julie De Buyst and her collaborators found no effect of fluid restriction on any of the ductal measurements, they did show a decrease in SVC flow, which I have difficulty understanding, it certainly is not likely to be a beneficial change; but there were several comparisons made, so perhaps it is a type 1 error.
To go back to the history of why people started fluid restricting babies with a PDA we probably need to return to studies done in the mid to late 1970’s.
There are a few small or modestly sized studies examining how much fluid we should give to preterm infants in the first few days of life. On first look there seems to be some evidence that giving less fluid might reduce the occurrence of a PDA (which is not the same thing as helping to manage it once it has occurred!) If the studies are examined carefully, however, the administration of sodium was also different between groups in several of the studies. Also the diagnosis of a PDA was often made clinically in some of the earlier studies, which we now know is very inaccurate.
Sodium administration, and sodium restriction have more effect on total body water than how much water is given, because babies have more limitations in their ability to excrete (or retain) sodium than water. In fact this is true throughout life, so adults with congestive heart failure are not told to restrict their water intake, but may be counselled to restrict their sodium intake. So, for example, the study of Tammela (Tammela OK, Koivisto ME. Fluid restriction for preventing bronchopulmonary dysplasia? Reduced fluid intake during the first weeks of life improves the outcome of low-birth-weight infants. Acta Paediatr. 1992;81(3):207-12. Epub 1992/03/01.) was a study of fluid restriction in 100 low birth weight babies (<1750g), but there was a standard concentration of sodium in the fluids (3 mmol/100mL for the fluid restricted group and for most of the high fluid group, but 4 mmol/kg for the infants in the high fluid group who were <1000g), so when fluids were restricted so was sodium. They showed more BPD and death in the high fluid/high sodium group, and more PDA 9/50 compared to 5/50.
In the study of fluid restriction by Jack Lorenz and others (Lorenz JM, Kleinman LI, Kotagal UR, Reller MD: Water balance in very low-birth-weight infants: Relationship to water and sodium intake and effect on outcome. J Pediatr 1982, 101(3):423-432. http://www.sciencedirect.com/science/article/pii/S0022347682800784) babies were given no sodium on day one, but then the high fluid group also received more sodium than the low fluid group. In this study 88 babies 750 to 1500 grams were enrolled; the high fluid/high sodium group had slightly more PDA, and slightly more BPD.
On the other hand Vasiliki Kavvadia (Kavvadia V, Greenough A, Dimitriou G, Hooper R: Randomised trial of fluid restriction in ventilated very low birthweight infants. Arch Dis Child Fetal Neonatal Ed 2000, 83(2):F91-96.) randomized 168 VLBW infants to high or low fluid regimes, and gave no sodium to either group in the first 24 hours, and individualized the sodium intakes thereafter. They showed no difference in mortality or BPD. On the other hand the group that got more free water made more urine; see physiology works!
The study by Ed Bell (Bell EF, Warburton D, Stonestreet BS, Oh W: Effect of fluid administration on the development of symptomatic patent ductus arteriosus and congestive heart failure in premature infants. N Engl J Med 1980, 302(11):598-604.) randomized 170 babies between 750 and 2000 g birth weight to high and low fluid intakes starting at 72 hours of age. The paper doesn’t clearly describe how the sodium was managed. This is the only one that really showed a difference in PDA, but it seems that many of the diagnoses were clinical, which we know is not very sensitive, nor specific.
The other side of the evidence are the studies comparing different sodium intakes without changing fluid intakes. There are 2 (Costarino AT, Jr., Gruskay JA, Corcoran L, Polin RA, Baumgart S: Sodium restriction versus daily maintenance replacement in very low birth weight premature neonates: a randomized, blind therapeutic trial. J Pediatr 1992, 120(1):99-106. http://www.sciencedirect.com/science/article/pii/S0022347605806110 and Hartnoll G, Betremieux P, Modi N: Randomised controlled trial of postnatal sodium supplementation on oxygen dependency and body weight in 25-30 week gestational age infants. Arch Dis Child Fetal Neonatal Ed 2000, 82(1):F19.)
Both of these show adverse effects of giving more sodium earlier in life. The earlier sodium supplementation groups had more BPD in both studies, and more PDA, but not statistically significant. The Costarino study was tiny (17 babies) and the Hartnoll study was small (44 babies), nevertheless the differences in resolution of lung disease were significant. The high sodium babies lost less weight, even though fluid intakes were the same.
To get back to my point, it seems, from my evaluation of the evidence, that restricting sodium intake in the first few days of life leads to greater weight loss, a lower incidence of PDA and less BPD; but restricting fluids without changing sodium administration does nothing to PDA, or indeed to any other outcome.
The implications of this are as follows, during the first 3 days of life, babies need little or no exogenous sodium. They should be managed with as little sodium as possible, but the total volume of fluids is relatively unimportant, especially after ths first 24 hours during which renal blood flow, urine output, and glomerular filtration increase rapidly.
When a PDA becomes evident, several days later, there is no evidence whatsoever to support fluid restriction. This is a practice without physiologic rationale, without clinical studies to support it, and is potentially harmful. Effective renal solute load is increased by decreasing free water. If macro and micro nutrients are also restricted then the risks of undernutrition, undermineralization etc. are serious. In Ed Bell’s article from 1980, the calorie administration in the restricted group were substantially less than the non-restricted group (and both were far below what we would consider acceptable today). So babies with a PDA should NOT be fluid restricted.