{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:15:29Z","timestamp":1784556929792,"version":"3.55.0"},"reference-count":44,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:00:00Z","timestamp":1784332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background: Inflammatory mechanisms may contribute to persistent ductal patency in preterm infants with hemodynamically significant patent ductus arteriosus (hsPDA). This study evaluated early postnatal temporal patterns of complete blood count (CBC)-derived inflammatory indices in relation to ductal status and pharmacologic treatment response. Methods: This retrospective single-center study included preterm infants born at &lt;34 weeks\u2019 gestation who received pharmacologic treatment for hsPDA. Hematologic parameters and CBC-derived inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), pan-immune inflammation value (PIV), and immature granulocyte (IG) parameters, were assessed on postnatal days 1, 3, and 7. Results: The final cohort included 71 preterm infants with hsPDA. Over the first postnatal week, NLR and PLR peaked on day 3, MLR remained elevated, and PIV increased toward day 7. SII and SIRI showed significant temporal variation, whereas IG parameters did not. Among longitudinal changes, only \u0394PIV, calculated as day 3 minus day 7 values, differed by treatment response, with a greater increase in PIV observed among non-responders. \u0394PIV yielded limited discrimination for non-response (AUC = 0.646; sensitivity, 92%; specificity, 37%; cut-off, \u2264110.4). Birth weight and gestational age were positively correlated with several hematologic parameters and inflammatory indices, whereas ductal status showed inverse associations with IG% on day 1 and with monocyte count and MLR on day 3. After adjustment for maturational factors and treatment type, the \u0394PIV\u2013response association was attenuated, without improved discrimination. Conclusions: CBC-derived inflammatory indices demonstrated distinct early postnatal patterns in infants with hsPDA. \u0394PIV may serve as a hypothesis-generating longitudinal marker of treatment response rather than a stand-alone predictor and warrants further validation.<\/jats:p>","DOI":"10.3390\/children13070945","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:18:31Z","timestamp":1784553511000},"page":"945","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inflammatory Indices in Preterm Infants with Hemodynamically Significant Patent Ductus Arteriosus: Early Postnatal Patterns and Treatment Response"],"prefix":"10.3390","volume":"13","author":[{"given":"Demet","family":"T\u00fcrkeli","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, Recep Tayyip Erdogan University, 53200 Rize, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4562-3829","authenticated-orcid":false,"given":"Ilkay","family":"Er","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology, Faculty of Medicine, Recep Tayyip Erdogan University, 53200 Rize, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8422-4113","authenticated-orcid":false,"given":"Hikmet","family":"K\u0131ztan\u0131r","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Cardiology, Faculty of Medicine, Recep Tayyip Erdogan University, 53200 Rize, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8321-4829","authenticated-orcid":false,"given":"Medeni","family":"Arpa","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine, Recep Tayyip Erdogan University, 53200 Rize, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,18]]},"reference":[{"key":"ref_1","first-page":"247","article-title":"Mechanisms regulating the ductus arteriosus","volume":"42","author":"Clyman","year":"2018","journal-title":"Semin. Perinatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e20153730","DOI":"10.1542\/peds.2015-3730","article-title":"Patent ductus arteriosus in preterm infants","volume":"137","author":"Benitz","year":"2016","journal-title":"Pediatrics"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Hung, Y.C., Yeh, J.L., and Hsu, J.H. (2018). Molecular Mechanisms for Regulating Postnatal Ductus Arteriosus Closure. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19071861"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.1007\/s00431-023-04882-9","article-title":"Identifying two distinct subphenotypes of patent ductus arteriosus in preterm infants using machine learning","volume":"182","author":"Matsushita","year":"2023","journal-title":"Eur. J. Pediatr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1080\/15513815.2019.1686786","article-title":"Utility of the Platelet-to-Lymphocyte Ratio in Diagnosing and Predicting Treatment Success in Preterm Neonates with Patent Ductus Arteriosus","volume":"40","author":"Karabulut","year":"2021","journal-title":"Fetal Pediatr. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Wei, Y.J., Hsu, R., Lin, Y.C., Wong, T.W., Kan, C.D., and Wang, J.N. (2022). The Association of Patent Ductus Arteriosus with Inflammation: A Narrative Review of the Role of Inflammatory Biomarkers and Treatment Strategy in Premature Infants. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232213877"},{"key":"ref_7","first-page":"e20240211","article-title":"Systemic Inflammatory Indices as New Biomarkers for Hemodynamically Significant Ductus Arteriosus","volume":"121","author":"Cakir","year":"2024","journal-title":"Arq. Bras. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1161\/CIRCRESAHA.117.310795","article-title":"Circulating Platelets as Mediators of Immunity, Inflammation, and Thrombosis","volume":"122","author":"Koupenova","year":"2018","journal-title":"Circ. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e14834","DOI":"10.1097\/MD.0000000000014834","article-title":"Prognostic significance of blood inflammatory biomarkers NLR, PLR, and LMR in cancer-A protocol for systematic review and meta-analysis","volume":"98","author":"Kumarasamy","year":"2019","journal-title":"Medicine"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"8","DOI":"10.4103\/tjem.tjem_198_23","article-title":"Unraveling the clinical significance and prognostic value of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune-inflammation index, systemic inflammation response index, and delta neutrophil index: An extensive literature review","volume":"24","author":"Islam","year":"2024","journal-title":"Turk. J. Emerg. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2623","DOI":"10.2147\/JIR.S454117","article-title":"Correlations Between Acute Coronary Syndrome and Novel Inflammatory Markers (Systemic Immune-Inflammation Index, Systemic Inflammation Response Index, and Aggregate Index of Systemic Inflammation) in Patients with and without Diabetes or Prediabetes","volume":"17","author":"Tuzimek","year":"2024","journal-title":"J. Inflamm. Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Mangoni, A.A., and Zinellu, A. (2023). Systemic inflammation index, disease severity, and mortality in patients with COVID-19: A systematic review and meta-analysis. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1212998"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1309\/LT30BV9UJJV9CFHQ","article-title":"Immature granulocyte measurement using the Sysmex XE-2100. Relationship to infection and sepsis","volume":"120","author":"Kickler","year":"2003","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"225","DOI":"10.24293\/ijcpml.v28i3.1961","article-title":"Correlation of immature granulocytes and C-reactive protein with blood culture in neonatal-SIRS at Gambiran Hospital","volume":"28","author":"Widyaningsih","year":"2022","journal-title":"Indones. J. Clin. Pathol. Med. Lab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.jaapos.2015.04.008","article-title":"Serum Neutrophil-to-lymphocyte Ratio in Retinopathy of Prematurity","volume":"19","author":"Kurtul","year":"2015","journal-title":"J. Am. Assoc. Pediatr. Ophthalmol. Strabismus"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1097\/MPH.0000000000001059","article-title":"The Value of Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio for Detecting Early-onset Neonatal Sepsis","volume":"40","author":"Can","year":"2018","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3026","DOI":"10.1080\/14767058.2018.1455182","article-title":"Does Neutrophil\/ lymphocyte Ratio have Good Diagnostic Value in Neonatal Necrotizing Colitis?","volume":"32","author":"Yang","year":"2019","journal-title":"J. Matern. Fetal. Neonatal. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.clineuro.2019.03.012","article-title":"Peripheral Blood Neutrophil-to-lymphocyte Ratio in Preterm Infants with Intraventricular Hemorrhage","volume":"180","author":"Stein","year":"2019","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1515\/jpm-2019-0016","article-title":"The Value of Neutrophil-to-lymphocyte Ratio (NLR) and Platelet-to-lymphocyte Ratio (PLR) Parameters in Analysis with Fetal Malnutrition Neonates","volume":"47","author":"Can","year":"2019","journal-title":"J. Perinat. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"fmab100","DOI":"10.1093\/tropej\/fmab100","article-title":"Simple Hematological Markers in Predicting the Severity of Transient Tachypnea of Newborn: New Wine in Old Bottles","volume":"67","author":"Bolat","year":"2021","journal-title":"J. Trop. Pediatr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.arbres.2023.01.003","article-title":"Role of Systemic Inflammatory Indices in the Prediction of Moderate to Severe Bronchopulmonary Dysplasia in Preterm Infants","volume":"59","author":"Cakir","year":"2023","journal-title":"Arch. Bronconeumol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Aslan, M.T., G\u00fcney Varal, I., Tun\u00e7, G., Bagc\u0131, O., and \u00d6ren, A. (2025). Systemic Inflammatory Indices in Transient Tachypnea of the Newborn: A Retrospective Case\u2013Control Study. Children, 12.","DOI":"10.3390\/children12060727"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1177\/21501351211064143","article-title":"Neutrophil-Lymphocyte Ratio in Congenital Heart Surgery: What Is Known and What Is New?","volume":"13","author":"Manuel","year":"2022","journal-title":"World J. Pediatr. Congenit. Heart Surg."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Yin, X., Xin, M., Ding, S., Gao, F., Wu, F., Wang, J., Chen, J., Jiang, L., Wu, X., and Wang, X. (2021). Predictive role of perioperative neutrophil to lymphocyte ratio in pediatric congenital heart disease associated with pulmonary arterial hypertension. BMC Surg., 21.","DOI":"10.1186\/s12893-020-01009-x"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Moosmann, J., Schroeder, C., Cesnjevar, R., Rottermann, K., Weigelt, A., and Dittrich, S. (2021). Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratio in Univentricular Patients From Birth to Follow-Up After Fontan-Predicting Lymphatic Abnormalities. Front. Pediatr., 9.","DOI":"10.3389\/fped.2021.740951"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Li, M., Nie, Y., and Yang, Z. (2024). The association between systemic immune-inflammation index (SII) and early nosocomial infections after cardiopulmonary bypass surgery in children with congenital heart disease. BMC Cardiovasc. Disord., 24.","DOI":"10.1186\/s12872-024-04378-w"},{"key":"ref_27","first-page":"S76","article-title":"Turkish Neonatal Society guideline on the management of patent ductus arteriosus in preterm infants","volume":"53","author":"Uras","year":"2018","journal-title":"Turk. Pediatri Ars."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e2025071425","DOI":"10.1542\/peds.2025-071425","article-title":"Patent Ductus Arteriosus in Preterm Infants","volume":"155","author":"Ambalavanan","year":"2025","journal-title":"Pediatrics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1016\/0002-9378(91)90707-X","article-title":"Progress in pathogenesis and management of clinical intraamniotic infection","volume":"164","author":"Gibbs","year":"1991","journal-title":"Am. J. Obs. Gynecol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1007\/s00431-020-03822-1","article-title":"Comparison of the Effect of Continuous and Standard Intermittent Bolus Paracetamol Infusion on Patent Ductus Arteriosus","volume":"180","author":"Cakir","year":"2021","journal-title":"Eur. J. Pediatr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/mrdd.10008","article-title":"Intrauterine infection and prematurity","volume":"8","author":"Chaiworapongsa","year":"2002","journal-title":"Ment. Retard. Dev. Disabil. Res. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/S0022-3476(96)70356-6","article-title":"Influence of infection on patent ductus arteriosus and chronic lung disease in premature infants weighing 1000 grams or less","volume":"128","author":"Gonzalez","year":"1996","journal-title":"J. Pediatr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/s00281-020-00803-2","article-title":"Preterm birth and sustained inflammation: Consequences for the neonate","volume":"42","author":"Humberg","year":"2020","journal-title":"Semin. Immunopathol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Pietrasanta, C., Pugni, L., Merlo, D., Acaia, B., Consonni, D., Ronchi, A., Ossola, M.W., Ghirardi, B., Bottino, I., and Cribi\u00f9, F.M. (2019). Impact of different stages of intrauterine inflammation on outcome of preterm neonates: Gestational age-dependent and -independent effect. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0211484"},{"key":"ref_35","first-page":"28","article-title":"Placenta, Secret Witness of Infant Morbidities: The Relationship Between Placental Histology and Outcome of the Premature Infant","volume":"35","author":"Yildiz","year":"2019","journal-title":"Turk. Patoloji Derg."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.pedneo.2020.03.016","article-title":"Perinatal risk factors of symptomatic preterm patent ductus arteriosus and secondary ligation","volume":"61","author":"Lee","year":"2020","journal-title":"Pediatr. Neonatol."},{"key":"ref_37","first-page":"491","article-title":"Association between neutrophil\/lymphocyte ratio with ductus arteriosus patency in preterm newborns","volume":"118","author":"Temel","year":"2017","journal-title":"Bratisl. Lek. Listy"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1111\/apa.12563","article-title":"Adult and child automated immature granulocyte norms are inappropriate for evaluating early-onset sepsis in newborns","volume":"103","author":"Wiland","year":"2014","journal-title":"Acta Paediatr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1515\/cclm-2011-0656","article-title":"The predictive value of immature granulocyte count and immature myeloid information in the diagnosis of neonatal sepsis","volume":"50","author":"Cimenti","year":"2012","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1007\/s00431-025-06544-4","article-title":"Complete blood count reference intervals for extremely preterm neonates","volume":"184","author":"Wolfsberger","year":"2025","journal-title":"Eur. J. Pediatr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/0006-2952(84)90228-4","article-title":"Effects of non-steroidal anti-inflammatory agents on human neutrophil functions in vitro and in vivo","volume":"33","author":"Kaplan","year":"1984","journal-title":"Biochem. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1097\/00000542-200510000-00009","article-title":"Dose-dependent inhibition of platelet function by acetaminophen in healthy volunteers","volume":"103","author":"Munsterhjelm","year":"2005","journal-title":"Anesthesiology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1002\/rth2.12283","article-title":"Not all (N)SAID and done: Effects of nonsteroidal anti-inflammatory drugs and paracetamol intake on platelets","volume":"4","author":"Driver","year":"2019","journal-title":"Res. Pract. Thromb. Haemost."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1159\/000345337","article-title":"Intravenous paracetamol treatment in the management of patent ductus arteriosus in extremely low birth weight infants","volume":"103","author":"Oncel","year":"2013","journal-title":"Neonatology"}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/13\/7\/945\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:25:55Z","timestamp":1784553955000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/13\/7\/945"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,18]]},"references-count":44,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["children13070945"],"URL":"https:\/\/doi.org\/10.3390\/children13070945","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,18]]}}}