{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T12:53:17Z","timestamp":1774529597419,"version":"3.50.1"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the association between maternal analgesic exposure in late pregnancy and fetal ductal and pulmonary hemodynamics using serial echocardiographic assessment, and to explore potential differences between metamizole and acetaminophen.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this prospective cohort study, 67 third\u2010trimester pregnancies were evaluated: 47 exposed to analgesics (27 metamizole and 20 acetaminophen) and 20 unexposed controls. Two standardized fetal echocardiograms were performed: during exposure (T1) and after a 5\u20137\u2009day drug\u2010free interval (T2). Ductal Doppler parameters, including systolic velocity, diastolic velocity, and pulsatility index (PI), were used to define ductal constriction based on established criteria (PI &lt;\u20091.9 and\/or increased velocities). Right\u2010heart and pulmonary hemodynamic parameters, including mean pulmonary artery pressure (MPAP) and acceleration time\/ejection time ratio (AT\/ET), were also assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In the primary pooled analysis, ductal constriction occurred in 38.3% (18\/47) of exposed fetuses and in 0% (0\/20) of controls (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.00065). When stratified by exposure, constriction was observed in 52% (14\/27) of metamizole\u2010exposed fetuses and in 20% (4\/20) of acetaminophen\u2010exposed fetuses. In multivariable analysis, metamizole use (OR 2.05; 95% CI 1.28\u20133.28), exposure within 48\u2009h (OR 1.96; 95% CI 1.12\u20133.44), and dose &gt;\u20091\u2009g (OR 2.64; 95% CI 1.31\u20135.32) were independently associated with ductal constriction. Within the metamizole group, higher doses were associated with a greater proportion of constriction, although subgroup size limited statistical precision. After metamizole withdrawal, PI increased significantly (1.86\u2009\u00b1\u20090.43 to 2.28\u2009\u00b1\u20090.41;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), accompanied by reductions in systolic and diastolic velocities (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). In the acetaminophen group, mild and reversible constriction was observed, with modest PI improvement at T2 (2.20\u2009\u00b1\u20090.44 to 2.40\u2009\u00b1\u20090.29;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.040) and no major velocity changes. Neither exposure significantly altered MPAP or AT\/ET.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Maternal exposure to analgesics in late pregnancy was associated with fetal ductal constriction compared with unexposed controls. The association was stronger for metamizole and consistent with a dose\u2010related pattern. Acetaminophen was associated with mild, reversible ductal involvement in a subset of fetuses. Reversibility after drug withdrawal supports a functional, prostaglandin\u2010mediated mechanism. These findings have important implications for maternal analgesic use in late gestation and highlight the value of Doppler surveillance following exposure to prostaglandin\u2010modulating agents.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bdr2.70039","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T23:30:29Z","timestamp":1773012629000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Maternal Analgesic Exposure and Fetal Ductal Constriction: A Prospective Cohort Study in Late Pregnancy"],"prefix":"10.1002","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4296-3708","authenticated-orcid":false,"given":"Isaura Elaine Gon\u00e7alves Moreira","family":"Rocha","sequence":"first","affiliation":[{"name":"Federal University of Pernambuco (UFPE)  Recife Brazil"},{"name":"Federal University of Cariri (UFCA)  Barbalha Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3596-8022","authenticated-orcid":false,"given":"Andresa Carvalho","family":"Nobre","sequence":"additional","affiliation":[{"name":"Federal University of Cariri (UFCA)  Barbalha Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz Gon\u00e7alves","family":"Rocha","sequence":"additional","affiliation":[{"name":"Federal University of Cariri (UFCA)  Barbalha Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9583-2915","authenticated-orcid":false,"given":"Paulo Henrique Benevides","family":"Siqueira","sequence":"additional","affiliation":[{"name":"Federal University of Cariri (UFCA)  Barbalha Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9434-2930","authenticated-orcid":false,"given":"Estelita Lima","family":"C\u00e2ndido","sequence":"additional","affiliation":[{"name":"Federal University of Cariri (UFCA)  Barbalha Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9899-1612","authenticated-orcid":false,"given":"Simone Cristina Soares","family":"Brand\u00e3o","sequence":"additional","affiliation":[{"name":"Federal University of Pernambuco (UFPE)  Recife Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228\u2010021\u201003191\u20100"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.1377"},{"key":"e_1_2_9_4_1","volume-title":"ACOG Response to Consensus Statement on Paracetamol Use During Pregnancy","author":"American College of Obstetricians and Gynecologists","year":"2021"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1157\/13123300"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2017\u20104021"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/bcp.70101"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.118.084541"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228\u2010024\u201003769\u20104"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002\u20109149(87)91189\u20101"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00404\u2010008\u20100707\u20103"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/1471\u20100528.15872"},{"key":"e_1_2_9_13_1","volume-title":"Metamizole Article\u201031 Referral: Annex III. 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