{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T09:18:53Z","timestamp":1787822333525,"version":"build-2784847793"},"reference-count":25,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T00:00:00Z","timestamp":1785628800000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2025\/02352\u20109"],"award-info":[{"award-number":["2025\/02352\u20109"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Nonsteroidal anti\u2010inflammatory drugs (NSAIDs) are widely used during pregnancy, yet information on their developmental safety during sensitive perinatal windows remains limited. This study evaluated the maternal and early developmental effects of paracetamol\/acetaminophen, aspirin, and nimesulide administered at therapeutically relevant doses during late gestation and lactation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Pregnant Wistar rats were treated daily by oral gavage with paracetamol\/acetaminophen (APAP; 126\u2009mg\/kg\/day), aspirin (ASA; 5.6\u2009mg\/kg\/day), or nimesulide (NIM; 11\u2009mg\/kg\/day) from gestational day 15 to postnatal day 22. Maternal clinical parameters, body weight, food and water intake, organ weights, hematological and biochemical markers, and maternal behavior were evaluated. In F1 offspring, early developmental indicators, anogenital distance, sexual maturation endpoints, reproductive organ weights, and hematological parameters were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Exposure to the evaluated NSAIDs produced little evidence of overt maternal toxicity. Maternal body weight, food and water intake, gestational length, and most organ weights remained unchanged. Mild hematological and biochemical alterations were observed, particularly in NIM\u2010treated dams. Maternal behavior was largely preserved, although APAP\u2010treated dams showed reduced latency to initiate pup grooming. In offspring, anogenital distance and female reproductive maturation were unaffected. Male offspring exposed to APAP showed earlier testicular descent, whereas ASA exposure was associated with increased seminal vesicle weight. These findings were isolated and were not associated with a consistent pattern of reproductive alterations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Perinatal exposure to therapeutically relevant doses of paracetamol\/acetaminophen, aspirin, and nimesulide produced little evidence of overt maternal or developmental toxicity during the evaluated period. Although a limited number of drug\u2010specific findings were identified, they were isolated and did not indicate a consistent pattern of reproductive toxicity. These results contribute to the preclinical safety assessment of NSAID exposure during pregnancy and lactation and support further studies to determine the functional relevance of these early observations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bdr2.70104","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T02:20:25Z","timestamp":1785723625000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Maternal and Early Developmental Effects of Perinatal Exposure to Therapeutically Relevant Doses of Common Nonsteroidal Anti\u2010Inflammatory Drugs in Rats"],"prefix":"10.1002","volume":"118","author":[{"given":"Sara Tawany Caetano","family":"dos Santos","sequence":"first","affiliation":[{"name":"Department of Cellular and Molecular Biology Institute of Biosciences of Botucatu, UNESP \u2013 Paulista State University  Botucatu S\u00e3o Paulo State 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Biosciences of Botucatu, UNESP \u2013 Paulista State University  Botucatu S\u00e3o Paulo State Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5466-6314","authenticated-orcid":false,"given":"Julia Vitoria Francisco","family":"de Aquino","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology Institute of Biosciences of Botucatu, UNESP \u2013 Paulista State University  Botucatu S\u00e3o Paulo State Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2558-9185","authenticated-orcid":false,"given":"Ot\u00e1vio Galassi","family":"Vitale","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology Institute of Biosciences of Botucatu, UNESP \u2013 Paulista State University  Botucatu S\u00e3o Paulo State Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4739-4102","authenticated-orcid":false,"given":"Livia Trippe","family":"Nagaoka","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology Institute of Biosciences of Botucatu, UNESP \u2013 Paulista State University  Botucatu S\u00e3o Paulo State Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8968-7416","authenticated-orcid":false,"given":"Julia","family":"Stein","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology Institute of Biosciences of Botucatu, UNESP \u2013 Paulista State University  Botucatu S\u00e3o Paulo State Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3281-6085","authenticated-orcid":false,"given":"Beatriz","family":"de Matos Manoel","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology Institute of Biosciences of Botucatu, UNESP \u2013 Paulista State University  Botucatu S\u00e3o Paulo State Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8754-4876","authenticated-orcid":false,"given":"B\u00e1rbara Campos","family":"Jorge","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology Institute of Biosciences of Botucatu, UNESP \u2013 Paulista State University  Botucatu S\u00e3o Paulo State Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2373-9399","authenticated-orcid":false,"given":"Arielle Cristina","family":"Arena","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology Institute of Biosciences of Botucatu, UNESP \u2013 Paulista State University  Botucatu S\u00e3o Paulo State 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