Effects of low oxygen saturation limits on the ductus arteriosus in extremely low birth weight infants

The mechanisms involved in the natural closure of the ductus arteriosus (DA) are complex: although the balance between vasoconstrictive and vasodilatory factors in utero favors patency of the DA, several factors lead ultimately to constriction and final closure of the DA after birth. Among these, changes in oxygen tension play a key role. In fact, the postpartum increase in blood oxygen tension initiates a sequence of events leading to ductal constriction. Following constriction of the DA, hypoxia within the vessel wall determines a permanent ductal closure. Of note, this process is developmentally regulated and is attenuated and prolonged in ELBW infants.
The optimal arterial oxygen saturation minimizing potential oxygen toxicity in infants born preterm is still unknown. In some centers, lower oxygen saturation limits are implemented for ELBW neonates to decrease the incidence of severe retinopathy of prematurity (ROP). However, the effect of lowering the oxygen saturation target range on the incidence of PDA has not been evaluated systematically in this patient population.
An American group has recently conducted a retrospective study to compare the incidence of early hemodynamically significant patent DA (hsPDA) and the need for surgical ligation in ELBW infants before and after implementation of lower oxygen saturation limits.
In total, 263 ELBW infants treated 4 years before (target oxygen saturation 89 to 94%) and after implementation of the use of lower oxygen saturation limits (target oxygen saturation 83 to 89%) were considered. More infants in the second period were exposed to indomethacin than those managed in the first period. Infants with a birth weight of 1000 to 1500 g were managed with the same oxygen saturation target range (89 to 94%) during both periods, and were considered as controls.
Results showed an increase in the incidence of hsPDA (63.2 vs 74.8%, p=0.043), without an increase in the need for surgical ligation (24.2 vs 29.9%) after implementation of the lower oxygen saturation target range policy. Statistical analysis indicated an increase in the odds of having an hsPDA [odds ratio (OR)=1.77, 95% confidence interval (CI): 1.03- 3.06), p=0.04] but not in the need for ductal ligation. The incidence of severe ROP (50.7 vs 15.7%; p<0.0001) and the need for laser ablation (33.8% vs 8.7%; p<0.0001) were also significantly reduced in infants managed with the lower oxygen saturation target. No change in the incidence of hsPDA or ductal ligation was observed in the control group.
In conclusion, a lower saturation limit reduced the incidence of severe ROP and the need of laser ablation; on the other hand, it increased the incidence of early hsPDA. However, final closure rate and the incidence of surgical ligation of the ductus arteriosus were not affected. The implications of the higher rate of indomethacin exposure of ELBW infants on short- and long-term outcomes remains unclear and needs to be considered when weighing the benefits and risks of targeting a lower oxygen saturation range.

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