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Few studies investigated the effect of fetal sex on proinflammatory biomarkers during pregnancy and whether maternal race could impact this association. We aimed to examine whether fetal sex could, independently of maternal race\/ethnicity and the condition of pregnancy (normal vs. complicated), impact inflammatory markers (C\u2010reactive protein [CRP] and interleukin\u20108 [IL\u20108] levels) in early and late pregnancy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods of study<\/jats:title><jats:p>This study was a cohort analysis using prospectively collected data from pregnant women who participated in the Vitamin Antenatal Asthma Reduction Trial (VDAART, <jats:italic>N<\/jats:italic>\u00a0=\u00a0816). Maternal serum CRP and IL\u20108 levels were measured in early and late pregnancy (10\u201318 and 32\u201338\u00a0weeks of gestation, respectively). Five hundred and twenty\u2010eight out of 816 pregnant women who participated in the trial had available CRP and IL\u20108 measurements at both study time points. We examined the association of fetal sex with early and late CRP and IL\u20108 levels and their paired sample difference. We further investigated whether maternal race\/ethnicity, pregnancy complications (i.e., preeclampsia and gestational diabetes), and early pregnancy body mass index (BMI) could affect the association between these two biomarkers and fetal sex adjusting for potential confounders. For this purpose, we used generalized linear and logistic regression models on log\u2010normalized early and late CRP and IL\u20108 levels as well as their split at median to form high and low groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Women pregnant with male fetuses (266\/528\u00a0=\u00a056.5%) had higher CRP levels in early to mid\u2010pregnancy (<jats:italic>\u03b2<\/jats:italic>\u00a0=\u00a0.18: 95% confidence interval [CI]: CI\u00a0=\u00a00.03\u20130.32; <jats:italic>p<\/jats:italic>\u00a0=\u00a0.02). Twenty\u2010seven percent (143\/528) of the study subjects were Hispanic. Hispanic African American [AA] women and women of races other than White and AA had higher levels of CRP at early to mid\u2010pregnancy compared with White women (<jats:italic>\u03b2<\/jats:italic>\u00a0=\u00a0.57; 95% CI: 0.17\u20130.97; <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.01 and <jats:italic>\u03b2<\/jats:italic>\u00a0=\u00a0.27; 95% CI: 0.05\u20130.48; <jats:italic>p<\/jats:italic>\u00a0=\u00a0.02, respectively). IL\u20108 levels were not associated with fetal sex in early and late pregnancy (<jats:italic>p<\/jats:italic>\u2019s\u00a0&gt;\u00a0.05). Other factors such as gestational diabetes and early pregnancy BMI were associated with higher CRP levels and higher CRP and IL\u20108 levels, respectively. Dichotomizing log\u2010normalized cytokine levels at the median in a sensitivity analysis, women with male fetuses had lower odds of high (above\u2010median) IL\u20108 levels at early pregnancy. Also, women with races other than AA and White carrying male fetuses had higher odds of having high (above\u2010median) late\u2010pregnancy CRP and early\u2010pregnancy IL\u20108 levels (adjusted odds ratio [aOR]\u00a0=\u00a03.80, 95% CI: 0.24\u20131.23; <jats:italic>p<\/jats:italic>\u00a0=\u00a0.02 and aOR\u00a0=\u00a03.57; 95% CI: 0.23\u20131.03; <jats:italic>p<\/jats:italic>\u00a0=\u00a0.02, respectively). Of the pregnancy complications, women with gestational diabetes mellitus had a higher paired difference of early and late pregnancy CRP levels (<jats:italic>\u03b2<\/jats:italic>\u00a0=\u00a0.38; 95% CI: 0.09\u20130.68; <jats:italic>p<\/jats:italic>\u00a0=\u00a0.01), but no difference in IL\u20108 levels (<jats:italic>p<\/jats:italic>\u2019s\u00a0&gt;\u00a0.05). No associations between the inflammatory markers and preeclampsia were found.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Fetal sex is associated with CRP in early pregnancy and an association with IL\u20108 in early pregnancy is implied. Our study further indicates that maternal race\/ethnicity could be a contributing factor in the relationship between fetal sex and inflammatory responses during pregnancy. However, the specificity and level of the contribution might vary by type of cytokine, pregnancy stage, and other confounding factors such as BMI that may impact these associations.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.13746","type":"journal-article","created":{"date-parts":[[2023,7,7]],"date-time":"2023-07-07T05:03:53Z","timestamp":1688706233000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The relationship of fetal sex and maternal race and ethnicity with early and late pregnancy C\u2010reactive protein and interleukin\u20108"],"prefix":"10.1111","volume":"90","author":[{"given":"Anjali","family":"Jha","sequence":"first","affiliation":[{"name":"Channing Division of Network Medicine Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noah","family":"Baumann","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iskander","family":"Shadid","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Clinical Pharmacy and Toxicology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jhill","family":"Shah","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"},{"name":"Division of Pediatric Pulmonary Medicine Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yih\u2010Chieh S.","family":"Chen","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"},{"name":"Division of Allergy and Clinical Immunology Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen A.","family":"Lee\u2010Sarwar","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"},{"name":"Division of Allergy and Clinical Immunology Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert S.","family":"Zeiger","sequence":"additional","affiliation":[{"name":"Department of Clinical Science Kaiser Permanente Bernard J. 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