{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T06:39:13Z","timestamp":1770359953200,"version":"3.49.0"},"reference-count":23,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Maternal serum screening remains widely implemented for prenatal aneuploidy assessment despite increased uptake of cell-free DNA testing. Evidence suggests that fetal sex may influence placental endocrine function and maternal serum biomarker levels; however, available studies are inconsistent and often limited by sample size or incomplete adjustment for maternal factors. Objective: The aim of this study was to determine whether fetal sex independently modifies first- and second-trimester maternal serum marker Multiple of the Median (MoM) values and whether sex-related biochemical variation affects trisomy-21 screen-positive classification. Methods: A retrospective cohort was identified from institutional screening records (10,384 screened pregnancies), of which 5040 first-trimester and 1476 second-trimester cases had complete biochemical data. First-trimester PAPP-A and free \u03b2-hCG, as well as second-trimester AFP, uE3, and free \u03b2-hCG, were measured. Implausible MoM values (&lt;0.10 or &gt;5.00) were excluded. Multivariable linear and logistic regression models adjusted for maternal age, maternal weight, gestational age at sampling, and parity assessed independent associations. Results: Pregnancies with female fetuses showed significantly higher MoM values for first-trimester PAPP-A and free \u03b2-hCG as well as second-trimester AFP and uE3. The magnitude of these differences was small, and no significant differences were observed in trisomy-21 screen-positive rates between fetal sex groups. Conclusions: Fetal sex independently influences several maternal serum markers across both trimesters but does not result in clinically meaningful differences in trisomy-21 screening outcomes under current algorithms. Any potential relevance of fetal sex for risk interpretation should be regarded as hypothesis-generating and requires outcome-validated investigation before clinical application.<\/jats:p>","DOI":"10.3390\/jcm15031276","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T15:24:19Z","timestamp":1770305059000},"page":"1276","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sex-Specific Variation in Maternal Serum Screening Markers Across the First and Second Trimesters: Evidence from 10,384 Screened Pregnancies"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2375-6253","authenticated-orcid":false,"given":"Mehmet","family":"\u00c7opuro\u011flu","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Kayseri City Hospital, Kayseri 38030, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3467-3783","authenticated-orcid":false,"given":"H\u00fcseyin","family":"Aksoy","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Kayseri City Hospital, Kayseri 38030, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2987-9795","authenticated-orcid":false,"given":"Mehmet","family":"Genco","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Kayseri City Hospital, Kayseri 38030, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1777-7380","authenticated-orcid":false,"given":"Merve","family":"Genco","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Kayseri State Hospital, Kayseri 38030, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3242-025X","authenticated-orcid":false,"given":"Cemal","family":"\u00dcnl\u00fc","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Special Clinic, Kayseri 38050, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1002\/pd.6298","article-title":"A systematic review and meta-analysis of cell-free DNA testing for detection of fetal sex chromosome aneuploidy","volume":"43","author":"Shear","year":"2023","journal-title":"Prenat. 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