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A prospective cohort study was conducted including 187 preterm neonates of\u2009\u2264\u200934\u00a0weeks of gestational age. Genotype frequencies of rs4963506, rs12270961, and rs3741240 CC16 polymorphisms were detected, comparing the CC16 polymorphisms between neonates with versus without RDS, and with versus without BPD. Serum CC16 was measured, when available, on the first and fourteenth postnatal days. A significant association of increased risk of RDS was detected for the homozygous GG rs4963506 variant (OR 3.03, 95%CI 1.36\u20136.75, <jats:italic>p<\/jats:italic>\u2009=\u20090.021), and the homozygous GG rs12270961 variant (OR 2.88, 95%CI 1.31\u20136.28, <jats:italic>p<\/jats:italic>\u2009=\u20090.024), but not for the homozygous GG rs3741240 variant, after adjusting for gestational age, mode of delivery, and antenatal administration of steroids. The homozygous GG rs4963506 variant was also associated with higher serum levels of CC16 compared to the GA\/AA rs4963506 variants, on the first postnatal day. No associations between BPD and the genotype frequencies of any polymorphisms were detected. <jats:italic>Conclusion<\/jats:italic>:\u00a0In preterm neonates, the homozygous GG rs4963506 and rs12270961 variants were both substantially associated with a higher risk of RDS. Further studies are warranted to validate our findings and explore the potential role of CC16 polymorphism detection in neonates at risk of respiratory morbidities.\n<jats:table-wrap>\n              <jats:table>\n                <jats:tbody>\n                  <jats:tr>\n                    <jats:td align=\"left\" colspan=\"2\">\n                      <jats:bold>What is Known:<\/jats:bold>\u2219 Serum club cell secretory protein (CC16) reflects the lung\u2019s developmental maturation and healing mechanisms for tissue damage.\u2219 The CC16 polymorphisms have been inconsistently associated with lung function in children.\u2219 No evidence exists regarding the association between CC16 polymorphisms and respiratory morbidity in neonates.<\/jats:td>\n                  <\/jats:tr>\n                  <jats:tr>\n                    <jats:td align=\"left\" colspan=\"2\">\n                      <jats:bold>What is new:<\/jats:bold>\u2219 Homozygous GG rs4963506 and GG rs12270961variants were associated with increased risk of respiratory distress in neonates.\u2219 Homozygous GG rs4963506 variant was also associated with higher serum levels of CC16 on the first postnatal day.\u2219 No associations between BPD and the genotype frequencies of any polymorphisms were detected.<\/jats:td>\n                  <\/jats:tr>\n                <\/jats:tbody>\n              <\/jats:table>\n            <\/jats:table-wrap>\n          <\/jats:p>","DOI":"10.1007\/s00431-025-06169-7","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T15:19:54Z","timestamp":1747322394000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Club cell secretory protein (CC16) polymorphisms in preterm neonates with respiratory distress syndrome and bronchopulmonary dysplasia"],"prefix":"10.1007","volume":"184","author":[{"given":"Dimitrios","family":"Rallis","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petros","family":"Bozidis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianthi","family":"Sotiropoulou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgia","family":"Ragia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Baltogianni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niki","family":"Dermitzaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleni","family":"Maragoudaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vangelis G.","family":"Manolopoulos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konstantina","family":"Gartzonika","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katerina","family":"Antoniou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasileios","family":"Giapros","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,5,15]]},"reference":[{"key":"6169_CR1","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1046\/j.1365-2222.2000.00760.x","volume":"30","author":"F Broeckaert","year":"2000","unstructured":"Broeckaert F, Bernard A (2000) Clara cell secretory protein (CC16): characteristics and perspectives as lung peripheral biomarker. 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