{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T23:11:07Z","timestamp":1778195467733,"version":"3.51.4"},"posted":{"date-parts":[[2026,5,5]]},"group-title":"Public and Global Health","reference-count":61,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP), an antifolate drug with antimalarial and antibiotic activity, reproducibly improves birthweight across sub-Saharan Africa and the Western Pacific. This clinical protection is independent of SP\u2019s original malaria indication: it is not diminished by widespread antimalarial resistance or reduced transmission, and SP outperforms more potent non-antibiotic antimalarials (e.g., dihydroartemisinin-piperaquine, DP) for fetal growth. The biological mechanism is unexplained. We previously showed that gestational weight gain (GWG) is a significant component of this mechanism and mediates two-thirds of SP\u2019s overall birthweight benefit (\n                  <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03009526\">NCT03009526<\/jats:ext-link>\n                  ). In the first longitudinal characterization of antifolate antibiotic effects on the pregnant gut microbiome, we show that \u223c45% of SP\u2019s GWG advantage over DP is explained by gut microbial changes consistent with its pharmacology. Microbiome-mediated GWG coincided with 126g higher birthweight in SP but not DP recipients (95%CI 22.6-229.3g; p=0.019). Relative to DP, SP suppressed gastrointestinal pathobionts and enriched anaerobic commensals with recognized roles in mucosal immunity and host metabolism, a microbiome-sparing pattern distinct from conventional antibiotic-associated dysbiosis.\n                <\/jats:p>","DOI":"10.64898\/2026.05.03.26352319","type":"posted-content","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T22:25:26Z","timestamp":1778019926000},"source":"Crossref","is-referenced-by-count":0,"title":["Beyond malaria prevention: sulfadoxine-pyrimethamine treatment in pregnancy selectively remodels the maternal gut microbiome to increase gestational weight gain and improve birthweight"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9219-6570","authenticated-orcid":false,"given":"Andreea","family":"Waltmann","sequence":"first","affiliation":[{"name":"Institute for Global Health and Infectious Diseases, School of Medicine, University of North Carolina, Chapel Hill, NC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sydney M.","family":"Puerto-Meredith","sequence":"additional","affiliation":[{"name":"Undergraduate Biology Program, University of North Carolina, Chapel Hill, NC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jobiba","family":"Chinkhumba","sequence":"additional","affiliation":[{"name":"National Malaria Control Program, Lilongwe, Malawi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enala","family":"Mzembe","sequence":"additional","affiliation":[{"name":"National Malaria Control Program, Lilongwe, Malawi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Kayange","sequence":"additional","affiliation":[{"name":"Malaria Alert Centre (MAC), University of Malawi College of Medicine, Blantyre, Malawi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian","family":"Carroll","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9817-5877","authenticated-orcid":false,"given":"Jeffrey","family":"Roach","sequence":"additional","affiliation":[{"name":"Research Computing, University of North Carolina, Chapel Hill, NC, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Don P.","family":"Mathanga","sequence":"additional","affiliation":[{"name":"National Malaria Control Program, Lilongwe, Malawi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6769-7322","authenticated-orcid":false,"given":"Julie R.","family":"Gutman","sequence":"additional","affiliation":[{"name":"Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, GA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0591-0850","authenticated-orcid":false,"given":"Jonathan J.","family":"Juliano","sequence":"additional","affiliation":[{"name":"Institute for Global Health and Infectious Diseases, School of Medicine, University of North Carolina, Chapel Hill, NC, USA"},{"name":"Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026050716000913000_2026.05.03.26352319v1.1","doi-asserted-by":"crossref","unstructured":"Grey, K. et al. 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