{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T02:51:34Z","timestamp":1790736694000,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T00:00:00Z","timestamp":1743984000000},"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: The importance and etiology of meconium-stained amniotic fluid (MSAF) in preterm pregnancies are still poorly understood. Among other factors, intrauterine inflammation is proposed to be a pathophysiological change associated with MSAF. To study the extent of intrauterine inflammation, histological evaluation represents the \u201cgold standard\u201d of diagnostics. Objectives: To investigate the concomitant occurrence of MSAF and histological chorioamnionitis (HCA) and fetal inflammatory response (FIR). To investigate the incidence of short-term neonatal outcomes in preterm infants born from MSAF. Materials and methods: We conducted a single-center retrospective study in a tertiary neonatal intensive care unit between 2020 and 2022. 237 preterm infants born \u2264 32 weeks or with \u22641500 g birthweight were investigated. The group of infants born from MSAF was compared to the group of infants born from clear amniotic fluid (CAF). The variables measured were the following: HCA, FIR, maternal and fetal vascular malformations (MVM, FVM), maternal clinical and laboratory signs of chorioamnionitis (CA), early neonatal outcomes, neonatal white blood cell count (WBC) in the first day of life, and neonatal c-reactive protein (CRP) level on the second day of life. Histological evaluation of the placenta and the umbilical cord was based on the recommendation of the 2014 Amsterdam Placental Workshop Group Consensus Statement (APWGCS). Results: Out of 237 preterm infants (mean gestational age: 28.6 (95% CI: 28.2; 28.9) weeks, mean birth weight: 1165 (95% CI: 1110; 1218) grams), 22 were born from MSAF. There was no difference between the perinatal characteristics of the two groups. A higher incidence of HCA (54.5% vs. 32.6%; p: &lt;0.001), a higher incidence of stage 3 HCA (45.4% vs. 9.3%), a higher incidence of FIR (50% vs. 16.7%; p: &lt;0.001), and a higher incidence of stage 3 FIR (18.2% vs. 1.9%) were found in the MSAF group in comparison with the CAF group. A higher incidence of elevated (&gt;30 mg\/L) maternal CRP level (36.8% vs. 15.3%; p: 0.02) and elevated (&gt;15 mg\/L) neonatal CRP level (31.8% vs. 14.4%; p: 0.03) was detected in the MSAF group. Among neonatal complications, severe (Stage III\/IV) intraventricular hemorrhage (IVH) had a higher incidence in the MSAF group (22.2% vs. 5.1%; p: 0.005). Conclusion: MSAF in preterm pregnancies is associated with a severe maternal and fetal inflammatory response in the placenta and the umbilical cord. MSAF is also accompanied by elevated systemic inflammatory parameters and a higher incidence of severe neonatal IVH as well.<\/jats:p>","DOI":"10.3390\/children12040477","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T05:59:00Z","timestamp":1744091940000},"page":"477","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Association of Meconium-Stained Amniotic Fluid and Histological Chorioamnionitis with Fetal Inflammatory Response in Preterm Deliveries"],"prefix":"10.3390","volume":"12","author":[{"given":"D\u00f3ra Csenge","family":"Balogh","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Semmelweis University, H-1088 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8883-7603","authenticated-orcid":false,"given":"Kinga","family":"Kov\u00e1cs","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Semmelweis University, H-1088 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0964-988X","authenticated-orcid":false,"given":"\u0150zike Zsuzsanna","family":"Kov\u00e1cs","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Semmelweis University, H-1088 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eszter","family":"Reg\u0151s","sequence":"additional","affiliation":[{"name":"Department of Pathology and Experimental Cancer Research, Semmelweis University, H-1088 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0519-8170","authenticated-orcid":false,"given":"Attila","family":"Fintha","sequence":"additional","affiliation":[{"name":"Department of Pathology and Experimental Cancer Research, Semmelweis University, H-1088 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9671-2903","authenticated-orcid":false,"given":"\u00c1gnes","family":"Harmath","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Semmelweis University, H-1088 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3317-5619","authenticated-orcid":false,"given":"Mikl\u00f3s","family":"Szab\u00f3","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Pediatric Center Semmelweis University, 53-54 Bokay Janos St 1083, H-1088 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1kos","family":"Gasparics","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Semmelweis University, H-1088 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8533-6341","authenticated-orcid":false,"given":"P\u00e9ter","family":"Varga","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Semmelweis University, H-1088 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"104953","DOI":"10.1016\/j.earlhumdev.2020.104953","article-title":"The effect of meconium thickness level on neonatal outcome","volume":"142","author":"Gluck","year":"2020","journal-title":"Early Hum. Dev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1080\/08998280.2009.11928491","article-title":"Prevention of meconium aspiration syndrome: An update and the Baylor experience","volume":"22","author":"Whitfield","year":"2009","journal-title":"Bayl. Univ. Med. Cent. Proc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1097\/01.ogx.0000149659.89530.c2","article-title":"Meconium passage in utero: Mechanisms, consequences, and management","volume":"60","author":"Ahanya","year":"2005","journal-title":"Obs. Gynecol. Surv."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Cohen, G., Shilony, A., Amrami, R.B., Biron-Shental, T., Kovo, M., and Schreiber, H. (2025). The combined impact of meconium stained amniotic fluid and small for gestational age on delivery outcomes. Arch. Gynecol. Obs.","DOI":"10.1007\/s00404-025-07995-8"},{"key":"ref_5","first-page":"174","article-title":"Significance of meconium-stained amniotic fluid in the preterm population","volume":"21","author":"Scott","year":"2001","journal-title":"J. Perinatol. Off. J. Calif. Perinat. Assoc."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Monfredini, C., Cavallin, F., Villani, P.E., Paterlini, G., Allais, B., and Trevisanuto, D. (2021). Meconium Aspiration Syndrome: A Narrative Review. Children, 8.","DOI":"10.3390\/children8030230"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Dani, C., Ciarcia, M., Barone, V., Di Tommaso, M., Mecacci, F., Pasquini, L., and Pratesi, S. (2023). Neonatal Outcomes of Term Infants Born with Meconium-Stained Amniotic Fluid. Children, 10.","DOI":"10.3390\/children10050780"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1097\/AOG.0b013e3182117a26","article-title":"Maternal and fetal characteristics associated with meconium-stained amniotic fluid","volume":"117","author":"Balchin","year":"2011","journal-title":"Obstet. Gynecol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S1158","DOI":"10.1016\/j.ajog.2022.11.1283","article-title":"Meconium-stained amniotic fluid","volume":"228","author":"Gallo","year":"2023","journal-title":"Am. J. Obs. Gynecol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"F328","DOI":"10.1136\/adc.2002.021949","article-title":"Preterm meconium staining of the amniotic fluid: Associated findings and risk of adverse clinical outcome","volume":"89","author":"Tybulewicz","year":"2004","journal-title":"Arch. Dis. Childhood. Fetal Neonatal Ed."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4102","DOI":"10.1080\/14767058.2019.1597045","article-title":"Meconium-stained amniotic fluid as a risk factor for necrotizing enterocolitis in very low-birth weight preterm infants: A retrospective cohort study","volume":"33","author":"Chen","year":"2020","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/S0029-7844(97)00308-6","article-title":"Meconium-stained amniotic fluid and risk for cerebral palsy in preterm infants","volume":"90","author":"Spinillo","year":"1997","journal-title":"Obstet. Gynecol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/0002-9378(91)90529-Z","article-title":"Meconium-stained amniotic fluid: A risk factor for microbial invasion of the amniotic cavity","volume":"164","author":"Romero","year":"1991","journal-title":"Am. J. Obs. Gynecol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/BF02389637","article-title":"Listeria monocytogenes. The role of transabdominal amniocentesis in febrile patients with preterm labor","volume":"252","author":"Mazor","year":"1992","journal-title":"Arch. Gynecol. Obs."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1097\/00005792-200207000-00002","article-title":"Listeriosis during pregnancy: A case series and review of 222 cases","volume":"81","author":"Mylonakis","year":"2002","journal-title":"Medicine"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.1080\/14767058.2016.1236246","article-title":"Preterm meconium-stained amniotic fluid is an ominous sign for the development of chorioamnionitis and for in utero cord compression","volume":"30","author":"Nir","year":"2017","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_17","first-page":"537","article-title":"Meconium-stained amniotic fluid and neonatal morbidity in near-term and term deliveries with acute histologic chorioamnionitis and\/or funisitis","volume":"21","author":"Rao","year":"2001","journal-title":"J. Perinatol. Off. J. Calif. Perinat. Assoc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1007\/s00404-020-05541-2","article-title":"The effect of meconium-stained amniotic fluid on perinatal outcome in pregnancies complicated by preterm premature rupture of membranes","volume":"301","author":"Wertheimer","year":"2020","journal-title":"Arch. Gynecol. Obs."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"698","DOI":"10.5858\/arpa.2015-0225-CC","article-title":"Sampling and Definitions of Placental Lesions: Amsterdam Placental Workshop Group Consensus Statement","volume":"140","author":"Khong","year":"2016","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1038\/s41379-021-00747-4","article-title":"Four major patterns of placental injury: A stepwise guide for understanding and implementing the 2016 Amsterdam consensus","volume":"34","author":"Redline","year":"2021","journal-title":"Mod. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Fenton, T.R., and Kim, J.H. (2013). A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr., 13.","DOI":"10.1186\/1471-2431-13-59"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0301-2115(98)00141-9","article-title":"Meconium stained amniotic fluid in preterm delivery is an independent risk factor for perinatal complications","volume":"81","author":"Mazor","year":"1998","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.ejogrb.2020.12.052","article-title":"Early Preterm meconium stained amniotic fluid is an independent risk factor for peripartum maternal bacteremia","volume":"258","author":"Attali","year":"2021","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/infdis\/145.1.1","article-title":"Quantitative bacteriology of amniotic fluid from women with clinical intraamniotic infection at term","volume":"145","author":"Gibbs","year":"1982","journal-title":"J. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1097\/AOG.0000000000001246","article-title":"Evaluation and Management of Women and Newborns With a Maternal Diagnosis of Chorioamnionitis: Summary of a Workshop","volume":"127","author":"Higgins","year":"2016","journal-title":"Obstet. Gynecol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1159\/000514898","article-title":"Interleukin-6 in Amniotic Fluid: A Reliable Marker for Adverse Outcomes in Women in Preterm Labor and Intact Membranes","volume":"48","year":"2021","journal-title":"Fetal Diagn. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1080\/14767058.2019.1618822","article-title":"Should the diagnostic criteria for suspected clinical chorioamnionitis be changed?","volume":"34","author":"Sung","year":"2021","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1136\/jcp.2008.055244","article-title":"The placenta in preterm birth","volume":"61","year":"2008","journal-title":"J. Clin. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"538","DOI":"10.3109\/00016349309058159","article-title":"Meconium stained amniotic fluid is associated with maternal infectious morbidity in pre term delivery","volume":"72","author":"Markovitch","year":"1993","journal-title":"Acta Obs. Gynecol. Scand."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1016\/j.placenta.2015.10.021","article-title":"Histological severity of fetal inflammation is useful in predicting neonatal outcome","volume":"36","author":"Yamada","year":"2015","journal-title":"Placenta"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/s13643-020-01389-4","article-title":"Maternal inflammatory markers for chorioamnionitis in preterm prelabour rupture of membranes: A systematic review and meta-analysis of diagnostic test accuracy studies","volume":"9","author":"Etyang","year":"2020","journal-title":"Syst. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Eichberger, J., Resch, E., and Resch, B. (2022). Diagnosis of Neonatal Sepsis: The Role of Inflammatory Markers. Front. Pediatr., 10.","DOI":"10.3389\/fped.2022.840288"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.pedneo.2017.09.001","article-title":"Intrauterine inflammation, infection, or both (Triple I): A new concept for chorioamnionitis","volume":"59","author":"Peng","year":"2018","journal-title":"Pediatr. Neonatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1542\/peds.2010-0935","article-title":"Interpreting complete blood counts soon after birth in newborns at risk for sepsis","volume":"126","author":"Newman","year":"2010","journal-title":"Pediatrics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/s41390-021-01633-0","article-title":"Chorioamnionitis and neonatal outcomes","volume":"91","author":"Jain","year":"2022","journal-title":"Pediatr. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1159\/000320170","article-title":"Chorioamnionitis: Important risk factor or innocent bystander for neonatal outcome?","volume":"99","author":"Thomas","year":"2011","journal-title":"Neonatology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"101146","DOI":"10.1016\/j.siny.2020.101146","article-title":"The fetal inflammatory response syndrome: The origins of a concept, pathophysiology, diagnosis, and obstetrical implications","volume":"25","author":"Jung","year":"2020","journal-title":"Semin. Fetal Neonatal Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"366.e1","DOI":"10.1016\/j.ajog.2015.10.009","article-title":"Meconium aspiration syndrome: A role for fetal systemic inflammation","volume":"214","author":"Lee","year":"2016","journal-title":"Am. J. Obs. Gynecol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.ejogrb.2018.11.024","article-title":"Intentional early delivery versus expectant management for preterm premature rupture of membranes at 28\u201332 weeks\u2019 gestation: A multicentre randomized controlled trial (MICADO STUDY)","volume":"233","author":"Pasquier","year":"2019","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1097\/OGX.0000000000001024","article-title":"Management of Preterm Premature Rupture of Membranes in the Late Preterm Period","volume":"77","author":"Freeman","year":"2022","journal-title":"Obs. Gynecol. Surv."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"498","DOI":"10.5603\/GP.a2021.0038","article-title":"Early planned labor induction vs expectant management in late preterm pre-labor rupture of membranes: Maternal and neonatal outcomes","volume":"92","author":"Sgayer","year":"2021","journal-title":"Ginekol. Pol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.placenta.2020.10.002","article-title":"Placental histology of acute versus continuous meconium exposure\u2014Association with obstetric and neonatal outcomes","volume":"103","author":"Tamayev","year":"2021","journal-title":"Placenta"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.placenta.2011.10.007","article-title":"Immunohistochemical detection of meconium in the fetal membrane, placenta and umbilical cord","volume":"33","author":"Furuta","year":"2012","journal-title":"Placenta"}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/12\/4\/477\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:11:42Z","timestamp":1760029902000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/12\/4\/477"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,7]]},"references-count":43,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["children12040477"],"URL":"https:\/\/doi.org\/10.3390\/children12040477","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,7]]}}}