{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T17:32:02Z","timestamp":1793381522074,"version":"4.5.0"},"reference-count":17,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Fetal Diagn Ther"],"abstract":"<jats:p>Introduction: We previously demonstrated elevated levels of secretory phospholipase A2 (sPLA2) and amylase in the amniotic fluid (AF) of a fetal rat retinoic acid (RA)-induced open spina bifida (OSB) model. Our objective was to determine whether these enzymes, as well as protease, were elevated in the AF of human fetuses with OSB. Methods: AF was collected at the time of diagnosis (early 21\u201322 weeks, n = 9) or during fetoscopic repair (late 26\u201327 weeks, n = 12). Controls (21\u201322 weeks, n = 3) were amniocentesis samples collected from advanced maternal age. Activity levels of amylase, protease, and sPLA2 in these samples were measured, and we compared enzymatic activity in the control versus early groups and the early versus late groups. Results: In comparison to the control group, the activities of amylase (p = 0.003), sPLA2 (p = 0.014), and protease (p = 0.012) were increased in the early OSB samples. No significant differences were seen in the activities of these enzymes between the early OSB and late OSB groups. Conclusion: Protease, amylase, and sPLA2 activity were increased in the AF of human OSB fetuses but did not appear to increase further during the late second trimester. These neurotoxic enzymes may contribute to the \u201csecond hit\u201d of OSB, the timing of which appears to be during the first half of the pregnancy. It is important to note that the assays used measure enzyme activity rather than absolute enzyme concentration, and findings should be interpreted accordingly. These findings, particularly the elevation of sPLA2, amylase, and protease activity in early second-trimester OSB samples relative to controls, are consistent with prior observations in the RA-induced rat model of OSB (J Matern Fetal Neonatal Med. 2015;29[18]:3003\u20133008 and J Matern Fetal Neonatal Med. 2022;35[1]:147\u2013154). This concordance between human and animal data lends support to the continued use of the RA rat model for investigating the enzymatic contributions to the \u201csecond hit\u201d of neural injury in OSB. Direct extrapolation should be made cautiously given differences in study design and species-specific developmental timing (see Discussion).<\/jats:p>","DOI":"10.1159\/fdt\/acuag015","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T18:24:37Z","timestamp":1789755877000},"page":"1-1","source":"Crossref","is-referenced-by-count":0,"title":["Protease, Amylase, and Secretory Phospholipase A2 Levels in Human Amniotic Fluid of Fetuses with Open Spina Bifida"],"prefix":"10.1159","author":[{"given":"Tess","family":"van Schoor","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew E.","family":"Thornton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Rodman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arlyn S.","family":"Llanes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramen H.","family":"Chmait","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan H.","family":"Grubbs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2026,10,15]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.3109\/14767058.2015.1112373"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1080\/14767058.2020.1713082"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1014379"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2021.05.044"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1053\/jpsu.2002.30872"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2022.909648"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4838(83)90126-7"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.3109\/14767058.2013.847918"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1136\/gut.45.3.317"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-006-9589-z"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2009.11.014"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1242\/dev.145904"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-0436.1986.tb00393.x"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2013.04.001"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1203\/01.PDR.0000180539.40399.93"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1080\/14767058.2025.2477770"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1002\/uog.27536"}],"container-title":["Fetal Diagnosis and Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/fdt\/acuag015","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T17:01:25Z","timestamp":1793379685000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/fdt\/acuag015"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,15]]},"references-count":17,"URL":"https:\/\/doi.org\/10.1159\/fdt\/acuag015","archive":["Portico"],"relation":{},"ISSN":["1015-3837","1421-9964"],"issn-type":[{"value":"1015-3837","type":"print"},{"value":"1421-9964","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,15]]}}}