Prophylactic cyclo-oxygenase inhibitor drugs for the prevention of morbidity and mortality in extremely preterm infants: a clinical practice guideline incorporating family values and preferences

Importance: Prophylactic cyclooxygenase inhibitors (COX-Is) such as indomethacin, ibuprofen and acetaminophen may prevent morbidity and mortality in extremely preterm infants (born ≤28 weeks’ gestation). However, there is controversy around which COX-I, if any, is the most effective and safest, which has resulted in considerable variability in clinical practice. Objective: To develop rigorous and transparent clinical practice guideline recommendations for the prophylactic use of COX-I drugs for the prevention of mortality and morbidity in extremely preterm infants. Methods: The GRADE (Grading of Recommendations Assessment, Development and Evaluation) Evidence-to-Decision framework for multiple comparisons was used to develop the guideline recommendations. A 12-member panel, including five experienced neonatal care providers, two methods experts, one pharmacist, two parents of former extremely preterm infants and two adults born extremely preterm, was convened. A rating of the most important clinical outcomes was established a priori. Evidence from a Cochrane network meta-analysis, and a cross-sectional mixed-methods study exploring family values and preferences were used as the primary sources of evidence. Recommendations: The panel recommended that prophylaxis with intravenous indomethacin may be considered in extremely preterm infants [conditional recommendation, moderate certainty in estimate of effects]. Shared decision making with parents was encouraged to evaluate their values and preferences prior to therapy. The panel recommended against routine use of ibuprofen prophylaxis in this gestational age group [conditional recommendation, low certainty in the estimate of effects]. The panel strongly recommended against use of prophylactic acetaminophen [strong recommendation, very low certainty in estimate of effects] until further research evidence is available.