{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:22:39Z","timestamp":1784697759229,"version":"3.55.0"},"reference-count":34,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,18]],"date-time":"2025-05-18T00:00:00Z","timestamp":1747526400000},"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>This research aimed to assess the influence of prenatal and postnatal factors on the remodeling of the pulmonary microvasculature. Methods: The investigation analyzed 67 cases of preterm infants, whose lifespans ranged from 1 day to 149 days. After selecting the cases from the autopsy database, two lung tissue microarrays were created. Histological slides were stained using the hematoxylin and eosin technique to precisely capture the microscopic details. For the assessment of pulmonary microvascularization and the media layer of the vascular walls, an immunohistochemical analysis was performed utilizing CD34 and SMA markers. Results: Following the assessment of the quantity of capillaries positive for CD34, a negative correlation was identified between the average capillary count per alveolus and the duration of oxygen therapy. Preterm infants who developed pulmonary fibrosis exhibited an average reduction of 5.43 capillaries in comparison to other newborns. Preterm neonates born to mothers with preeclampsia exhibited an average reduction of 2.82 capillaries compared to those born to mothers unaffected by this pregnancy complication. A positive correlation was evident between increased thickness of the arteriolar media, lifespan, and the duration of oxygen therapy, as well as in those preterm infants who developed pulmonary fibrosis. Conclusions: Antenatal risk factors did not exert a significant impact on pulmonary vascular remodeling, whereas postnatal influences, particularly oxygen therapy, demonstrated a detrimental effect on the density of capillary structures within the alveolocapillary membrane. Premature neonates with increased thickness of the arteriolar media had a greater susceptibility to pulmonary hypertension.<\/jats:p>","DOI":"10.3390\/children12050650","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T04:48:18Z","timestamp":1747716498000},"page":"650","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Impact of Antenatal and Postnatal Factors on the Development of the Pulmonary Microvasculature in Preterm Infants"],"prefix":"10.3390","volume":"12","author":[{"given":"Raluca","family":"Chirculescu","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Department of Pathology, Filantropia Clinical Hospital, 011132 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruxandra Viorica","family":"St\u0103nculescu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul Cristian","family":"B\u0103l\u0103nescu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Department of Internal Medicine, Colentina Clinical Hospital, 020125 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gheorghe","family":"Peltecu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Department of Obstetrics and Gynecology, Ponderas Academic Hospital, 014142 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alvira, C.M. (2016). Aberrant Pulmonary Vascular Growth and Remodeling in Bronchopulmonary Dysplasia. Front. Med., 3.","DOI":"10.3389\/fmed.2016.00021"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1242\/dev.098186","article-title":"Lung development: Orchestrating the generation and regeneration of a complex organ","volume":"141","author":"Herriges","year":"2014","journal-title":"Development"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Lakshminrusimha, S. (2021). Neonatal and Postneonatal Pulmonary Hypertension. Children, 8.","DOI":"10.3390\/children8020131"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.clp.2016.04.001","article-title":"Fetal Physiology and the Transition to Extrauterine Life","volume":"43","author":"Morton","year":"2016","journal-title":"Clin. Perinatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s40748-015-0015-4","article-title":"Persistent pulmonary hypertension of the newborn","volume":"1","author":"Sharma","year":"2015","journal-title":"Matern. Health Neonatol. Perinatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s13052-016-0293-0","article-title":"The transition from intra to extra-uterine life in late preterm infant: A single-center study","volume":"42","author":"Pinna","year":"2016","journal-title":"Ital. J. Pediatr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1164\/rccm.201409-1594OC","article-title":"Early pulmonary vascular disease in preterm infants at risk for bronchopulmonary dysplasia","volume":"191","author":"Mourani","year":"2015","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1165\/rcmb.2013-0014TR","article-title":"Chronic lung disease in the preterm infant: Lessons learned from animal models","volume":"50","author":"Hilgendorff","year":"2014","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"El-Saie, A., and Binoy, S. (2020). Novel Strategies to Reduce Pulmonary Hypertension in Infants with Bronchopulmonary Dysplasia. Front. Pediatr., 8.","DOI":"10.3389\/fped.2020.00201"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Mi\u017e\u00edkov\u00e1, I., and Morty, R.E. (2015). The Extracellular Matrix in Bronchopulmonary Dysplasia: Target and Source. Front. Med., 2.","DOI":"10.3389\/fmed.2015.00091"},{"key":"ref_11","unstructured":"Sahni, M., and Mowes, A.K. (2025, March 29). Bronchopulmonary Dysplasia, StatPearls [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK53987."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Rivera, L., Siddaiah, R., Oji-Mmuo, C., Silveyra, G.R., and Silveyra, P. (2016). Biomarkers for Bronchopulmonary Dysplasia in the Preterm Infant. Front. Pediatr., 4.","DOI":"10.3389\/fped.2016.00033"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"L338","DOI":"10.1152\/ajplung.00094.2014","article-title":"Growth of alveoli during postnatal development in humans based on stereological estimation","volume":"307","author":"Herring","year":"2014","journal-title":"Am. J. Physiol.-Lung Cell. Mol. Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1159\/000381129","article-title":"Impaired pulmonary vascular development in bronchopulmonary dysplasia","volume":"107","author":"Baker","year":"2015","journal-title":"Neonatology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s00441-016-2545-0","article-title":"Development of the lung","volume":"367","author":"Schittny","year":"2017","journal-title":"Cell Tissue Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1164\/ajrccm.163.7.2011060","article-title":"Bronchopulmonary dysplasia","volume":"163","author":"Jobe","year":"2001","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1152\/japplphysiol.00708.2021","article-title":"Neonatal intermittent hypoxia persistently impairs lung vascular development and induces long-term lung mitochondrial DNA damage","volume":"133","author":"Damianos","year":"2022","journal-title":"J. Appl. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1164\/ajrccm.160.4.9810071","article-title":"Neonatal chronic lung disease in extremely immature baboons","volume":"160","author":"Coalson","year":"1999","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1164\/rccm.200608-1240OC","article-title":"Endoglin (CD105) up-regulation in pulmonary microvasculature of ventilated preterm infants","volume":"178","author":"Patel","year":"2008","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_20","unstructured":"Simon, L.V., Shah, M., and Bragg, B.N. (2025, March 29). APGAR Score, StatPearls [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470569\/."},{"key":"ref_21","first-page":"e63086","article-title":"Manual Construction of a Tissue Microarray using the Tape Method and a Handheld Microarrayer","volume":"184","author":"Wisner","year":"2022","journal-title":"J. Vis. Exp."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.tjem.2018.08.001","article-title":"User\u2019s guide to correlation coefficients","volume":"18","author":"Akoglu","year":"2018","journal-title":"Turk. J. Emerg. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1164\/ajrccm.164.10.2101140","article-title":"Disrupted pulmonary vasculature and decreased vascular endothelial growth factor, Flt-1, and TIE-2 in human infants dying with bronchopulmonary dysplasia","volume":"164","author":"Bhatt","year":"2001","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Matyas, M., Hasmasanu, M., Silaghi, C.N., Samasca, G., Lupan, I., Orsolya, K., and Zaharie, G. (2022). Early Preeclampsia Effect on Preterm Newborns Outcome. J. Clin. Med., 11.","DOI":"10.3390\/jcm11020452"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Wen, Y.H., Yang, H.I., Chou, H.C., Chen, C.Y., Hsieh, W.S., Tsou, K.I., Tsao, P.N., and Taiwan Premature Infant Developmental Collaborative Study Group (2019). Association of Maternal Preeclampsia with Neonatal Respiratory Distress Syndrome in Very-Low-Birth-Weight Infants. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-49561-8"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"265","DOI":"10.2147\/IJGM.S158184","article-title":"Evaluating the use of corticosteroids in preventing and treating bronchopulmonary dysplasia in preterm neonates","volume":"11","author":"Olaloko","year":"2018","journal-title":"Int. J. Gen. Med."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Collins, J.J.P., Tibboel, D., de Kleer, I.M., Reiss, I.K.M., and Rottier, R.J. (2017). The Future of Bronchopulmonary Dysplasia: Emerging Pathophysiological Concepts and Potential New Avenues of Treatment. Front. Med., 4.","DOI":"10.3389\/fmed.2017.00061"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Vitaliti, G., and Falsaperla, R. (2021). Chorioamnionitis, Inflammation and Neonatal Apnea: Effects on Preterm Neonatal Brainstem and on Peripheral Airways: Chorioamnionitis and Neonatal Respiratory Functions. Children, 8.","DOI":"10.3390\/children8100917"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Willems, M.G.M., Kemp, M.W., Fast, L.A., Wagemaker, N.M.M., Janssen, L.E.W., Newnham, J.P., Payne, M.S., Spiller, O.B., Kallapur, S.G., and Jobe, A.H. (2017). Pulmonary vascular changes in extremely preterm sheep after intra-amniotic exposure to Ureaplasma parvum and lipopolysaccharide. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0180114"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1007\/s00441-016-2539-y","article-title":"Pulmonary vascular remodeling in pulmonary hypertension","volume":"367","author":"Tuder","year":"2017","journal-title":"Cell Tissue Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Jia, Z., Wang, S., Yan, H., Cao, Y., Zhang, X., Wang, L., Zhang, Z., Lin, S., Wang, X., and Mao, J. (2023). Pulmonary Vascular Remodeling in Pulmonary Hypertension. J. Pers. Med., 13.","DOI":"10.3390\/jpm13020366"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Naumburg, E., and S\u00f6derstr\u00f6m, L. (2019). Increased risk of pulmonary hypertension following premature birth. BMC Pediatr., 19.","DOI":"10.1186\/s12887-019-1665-6"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Kumar, V.H.S. (2017). Diagnostic Approach to Pulmonary Hypertension in Premature Neonates. Children, 4.","DOI":"10.3390\/children4090075"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1089\/ped.2013.0323","article-title":"Pulmonary Hypertension in Preterm Infants with Bronchopulmonary Dysplasia","volume":"27","author":"Baker","year":"2014","journal-title":"Pediatr. Allergy Immunol. Pulmonol."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/12\/5\/650\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:34:49Z","timestamp":1760031289000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/12\/5\/650"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,18]]},"references-count":34,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["children12050650"],"URL":"https:\/\/doi.org\/10.3390\/children12050650","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,18]]}}}