{"doi":"10.1002/ppul.27312","title":"Prostaglandin E1 in neonatal pulmonary hypertension: Need for randomized trials based on physiology—Response","abstract":"We thank Dr. Mokha and Dr. Lakshminrusimha for adding their institution's experiences with PGE1 in the setting of persistent pulmonary hypertension of the newborn (PPHN). As we gain experience with this novel application of PGE1, it is important to share its efficacy and safety amongst the scientific community. We agree that standardization of the use of PGE1 for PPHN and multicenter randomized trials will only come as a result of these descriptive studies from specialized institutions. The cohort and approach described by Mokha are notably different from our published study, likely leading to differing conclusions. First, they describe use of PGE1 in a narrower group of infants who have iNO-resistant PPHN, which is a rarer phenotype that, by definition, responds differently to typical therapies (perhaps PGE1 included). Second, they initiate PGE1 later in the course as a third line agent when patients have established right ventricular (RV) failure. Our improved outcomes with PGE1 might highlight the importance, instead, of early initiation of PGE1, to achieve benefit of PGE1's multiple mechanisms of action, including off-loading the RV, inotropy, and providing direct pulmonary vasodilation. Our cohort had decreased RV function early in the course, exhibited by decreased fractional area change (FAC), and Isayama et al has similarly shown early decreased LV diastolic function and myocardial performance in the CDH population; thus, existing data suggests that waiting for RV failure may be too late to rescue these infants. Thirdly, adding PGE1 after all their patients are already on milrinone versus our patients with less than half on concurrent milrinone and PGE1, may contribute to the varying effects on hemodynamics as milrinone and PGE1 both can cause systemic vasodilation. Notably, Mokha's data does not include follow-up echocardiography that exhibit ductal status or direction of flow, so it is difficult to conclude that their data are not the result of no change in the degree of ductal restriction. Finally, their small sample size of only 10 patients and comparison to patients with congenital heart disease, who require PGE1 for an entirely different indication (to secure systemic or pulmonary perfusion, rather than to provide right ventricular off-loading to improve systemic perfusion as in PPHN) limits their conclusions with comparisons focused on changes in both oxygenation and hemodynamics. As their letter calls for, we need more robust studies that might compare early and later use of PGE1 and help identify the utility of PGE1 across the many different causes and phenotypes of PPHN. We appreciate the effort to initiate a dialogue that might lead to a comparison between different institutions' protocols for initiation and discontinuation of PGE1 in PPHN. We hope that further research in this area will continue to be shared, and ultimately improve our understanding and treatment of PPHN. Stephanie M. Tsoi: Writing—original draft; writing—review and editing. Roberta L. Keller: Supervision; writing—review and editing. The authors declare no conflict of interest.","journal":"Pediatric Pulmonology","year":2024,"id":504261,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9527,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":273910,"name":"Roberta L. Keller","orcid":"0000-0003-0743-8470","position":1,"is_corresponding":false},{"id":1131883,"name":"Stephanie M. Tsoi","orcid":"0000-0002-0115-5843","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:10:35.597333Z","pmid":"39360886","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}