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We also investigated the role of metabolomic signatures in the associations of maternal risk factors such as parity and gestational weight gain with adverse birthweight outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Ninety-six pregnant women and their newborns from the MADRES prospective cohort were studied. Maternal serum at third trimester and newborn cord blood were assayed for untargeted metabolomics using mass-spectrometry. Metabolome-wide association analysis was conducted to assess maternal and newborn metabolomic features association with birth weight Z-score, followed by network analysis of maternal and newborn metabolomics. Lastly, the contribution of maternal and newborn metabolomics to associations between maternal risk factors and newborn birthweight was assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Maternal gestational weight gain and parity were positively associated with newborn birthweight. Maternal glucose and branched-chain amino acid metabolism pathways and newborn\u2019s fatty acid, glucose metabolism and C21-steroid hormone biosynthesis were significantly enriched with high birth weight Z-score. Dysregulation in these pathways linked maternal factors such as gestational weight gain and parity with high birth weight Z-score.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings indicate that altered maternal sugar and energy metabolism, newborn sugar and amino acid metabolism, and newborn C21-steroid hormone biosynthesis were associated with high birth weight. Dysregulated metabolism in pregnant women and newborn may contribute to the pathophysiological mechanisms linking maternal excessive gestational weight gain and multiparity with high birth weight.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41366-025-01775-9","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T04:43:21Z","timestamp":1744865001000},"page":"1345-1353","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Dysregulated maternal and newborn fatty acid, sugar and amino acid metabolism associated with high birth weight"],"prefix":"10.1038","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1360-0166","authenticated-orcid":false,"given":"Chenyu","family":"Qiu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8246-0542","authenticated-orcid":false,"given":"Jiawen","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roya","family":"Gheissari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anika","family":"Kapai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2941-7833","authenticated-orcid":false,"given":"David V.","family":"Conti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2090-0677","authenticated-orcid":false,"given":"Dean P.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0029-5641","authenticated-orcid":false,"given":"Theresa M.","family":"Bastain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6082-4066","authenticated-orcid":false,"given":"Carrie V.","family":"Breton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanghua","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,17]]},"reference":[{"key":"1775_CR1","doi-asserted-by":"publisher","first-page":"3246","DOI":"10.1161\/01.CIR.94.12.3246","volume":"94","author":"GC Curhan","year":"1996","unstructured":"Curhan GC, Willett WC, Rimm EB, Spiegelman D, Ascherio AL, Stampfer MJ. 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All authors were involved in writing the paper and had final approval of the submitted and published versions.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"All methods were performed in accordance with the relevant guidelines and regulations, as approved by the University of Southern California\u2019s Institutional Review Board (IRB).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"The study protocol was approved by the University of Southern California\u2019s Institutional Review Board (IRB). Written informed consent and HIPAA authorization to access medical records of pregnant women and their newborns were obtained at study entry and signed by the women before their enrollment.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent statement"}}]}}