Caution on COX inhibitor use in preterm infants

Feb 5 2013

By medwireNews Reporters

Very-low-birthweight preterm infants with thrombocytopenia treated with cyclooxygenase (COX) inhibitors are at an increased risk for intracerebral hemorrhage, particularly if they have decreased platelet levels, research shows.

Although COX inhibitors are frequently used to treat patent ductus arteriosus (PDA), a common complication related to gestational age of preterm birth, "any benefits of this therapy should be carefully balanced against this potential hazard," say Ursula Kiechl-Kohlendorfer (Innsbruck Medical University, Austria) and colleagues.

To assess the risk for cerebral bleeding in preterm infants with thrombocytopenia and COX inhibitor treatment, "a blood cell count should be obtained after the first day of life," they advise.

In their study, published in the Journal of Pediatrics, the researchers analyzed prospectively collected data from infants born at a gestational age of less than 32 weeks and with a birthweight of 1500 g or lower. In these preterm infants, the frequency of PDA ranges from 50% to more than 80% and, if left untreated, is associated with an increased risk for morbidity and death.

Given the risks, several management strategies have been developed to induce closure of the PDA, including treatment with the COX inhibitors indomethacin and ibuprofen.

In the present analysis of 325 infants, 149 (45.9%) were treated with a COX inhibitor. Of the 325 infants, 65 (20%) had an intraventricular hemorrhage (IVH).

For infants with a platelet count of at least 100 x 10⁹/L, treatment of PDA with a COX inhibitor was not associated with an increased risk for IVH. By contrast, for those with moderately decreased platelets (50-99 x 10⁹/L), COX inhibition amplified the risk for bleeding on days 2 to 7 more than 50-fold compared with infants with a platelet count of at least 100 x 10⁹/L who received no treatment.

"The association remained significant when only patients with severe IVH were analyzed and also when patients with early- and late-onset sepsis were excluded from the analysis," write the researchers.

Their findings "indicate that a decreased platelet count potentiates the risk for bleeding in the presence of COX inhibitors," conclude Kiechl-Kohlendorfer and colleagues.

They add that the lack of association between COX inhibitor treatment and IVH in the absence of moderate thrombocytopenia should be interpreted cautiously, as the study was not powered to detect associations of moderate strength.

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