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In this large-scale study, we sought to validate previously-reported associations and test new hypotheses using statistical analysis of two very large datasets incorporating electronic medical records (EMRs). One of the datasets represents over half (\u223c 150 million) of the US population for over 8 years (IBM Watson Health MarketScan insurance claims) while another covers the entire Swedish population (\u223c 9 million) for over 30 years (the Swedish National Patient Register). After testing more than 100 hypotheses, we showed that neither dataset supported models in which the SRB changed seasonally or in response to variations in ambient temperature. However, increased levels of a diverse array of air and water pollutants, were associated with lower SRBs, including increased levels of industrial and agricultural activity, which served as proxies for water pollution. Moreover, some exogenous factors generally considered to be environmental toxins turned out to induce higher SRBs. Finally, we identified new factors with signals for either higher or lower SRBs. In all cases, the effect sizes were modest but highly statistically significant owing to the large sizes of the two datasets. We suggest that while it was unlikely that the associations have arisen from sex-specific selection mechanisms, they are still useful for the purpose of public health surveillance if they can be corroborated by empirical evidences.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1009586","type":"journal-article","created":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T13:45:36Z","timestamp":1638452736000},"page":"e1009586","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":19,"title":["Observable variations in human sex ratio at birth"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7171-0443","authenticated-orcid":true,"given":"Yanan","family":"Long","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4602-4388","authenticated-orcid":true,"given":"Qi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrik","family":"Larsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6959-7405","authenticated-orcid":true,"given":"Andrey","family":"Rzhetsky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,12,2]]},"reference":[{"issue":"3","key":"pcbi.1009586.ref001","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1093\/humrep\/deh662","article-title":"The epigenetic environment: secondary sex ratio depends on differential survival in embryogenesis","volume":"20","author":"CE Boklage","year":"2005","journal-title":"Human Reproduction"},{"issue":"16","key":"pcbi.1009586.ref002","doi-asserted-by":"crossref","first-page":"E2102","DOI":"10.1073\/pnas.1416546112","article-title":"The human sex ratio from conception to birth","volume":"112","author":"SH Orzack","year":"2015","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"pcbi.1009586.ref003","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.ssmph.2018.05.010","article-title":"Selection in utero and population health: theory and typology of research","volume":"5","author":"TA Bruckner","year":"2018","journal-title":"SSM-population health"},{"issue":"3","key":"pcbi.1009586.ref004","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1530\/REP-10-0137","article-title":"Can mammalian mothers influence the sex of their offspring peri-conceptually?","volume":"140","author":"VJ Grant","year":"2010","journal-title":"Reproduction"},{"key":"pcbi.1009586.ref005","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.jtbi.2013.06.023","article-title":"Evolution and the variation of mammalian sex ratios at birth: reflections on Trivers and Willard (1973)","volume":"334","author":"WH James","year":"2013","journal-title":"Journal of theoretical biology"},{"issue":"1","key":"pcbi.1009586.ref006","doi-asserted-by":"crossref","first-page":"7109","DOI":"10.3402\/ehtj.v4i0.7109","article-title":"Can environmental or occupational hazards alter the sex ratio at birth? 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