{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T12:08:04Z","timestamp":1784290084828,"version":"3.55.0"},"reference-count":13,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pregnancy"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Polyhydramnios, megalencephaly, and symptomatic epilepsy (PMSE) syndrome is a rare autosomal recessive mTORopathy caused by biallelic STE20\u2010related kinase adaptor alpha (\n                      <jats:italic>STRADA<\/jats:italic>\n                      ) loss\u2010of\u2010function variants. Animal models demonstrate that in utero mechanistic target of rapamycin (mTOR) inhibition can prevent cortical dyslamination, suggesting a prenatal therapeutic window.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A gravida 3 para 2 patient presented at 32+2\u00a0weeks with medication\u2010refractory preterm labor and severe polyhydramnios. Fetal magnetic resonance imaging (MRI) demonstrated macrocephaly and an enlarged cavum septum pellucidum (CSP). Amniocentesis with microarray revealed homozygosity across the\n                      <jats:italic>STRADA<\/jats:italic>\n                      locus; sequencing confirmed the founder\n                      <jats:italic>STRADA<\/jats:italic>\n                      exons 9\u201313 deletion. After counseling, maternal sirolimus therapy was initiated at 35+6\u00a0weeks using a 20\u00a0mg loading regimen followed by 6\u20138\u00a0mg\/day maintenance dosing. Serial ultrasound monitored fetal biometry and CSP size. Delivery occurred at 39+1\u00a0weeks. Pediatric follow\u2010up was extended nearly 5 years.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Maternal sirolimus was well tolerated. Amniotic fluid index (AFI) declined from 36.1 to 26.2\u00a0cm, head circumference normalized from the 89th to 35th percentile, and CSP diameter decreased from 14.0 to 12.3\u00a0mm. A term vaginal delivery produced a 3554\u00a0g infant with normocephaly. Cord blood sirolimus level (3.9 mcg\/L) approximated maternal level (3.4 mcg\/L). Postnatally, sirolimus was continued from day of life 7. The first seizure occurred at 4.5 months, coincident with subtherapeutic trough levels; seizure control was achieved thereafter. At nearly 5 years, the child shows adequate growth but severe global developmental delay typical of PMSE.<\/jats:p>\n                    <jats:p>This case demonstrates the feasibility and pharmacokinetic effectiveness of maternal sirolimus during late gestation, with no identified maternal or fetal adverse consequences in this first case of third\u2010trimester prenatal mTOR inhibition in confirmed PMSE.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pmf2.70297","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T04:01:31Z","timestamp":1777521691000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antenatal diagnosis and maternal sirolimus treatment of polyhydramnios, megalencephaly, and symptomatic epilepsy (PMSE) syndrome"],"prefix":"10.1002","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1230-4752","authenticated-orcid":false,"given":"Christian","family":"Macedonia","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Michigan College of Pharmacy  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent J.","family":"Carson","sequence":"additional","affiliation":[{"name":"Clinic For Special Children  Lancaster Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Holmes","family":"Morton","sequence":"additional","affiliation":[{"name":"The Central Pennsylvania Clinic  Bellville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin J.","family":"Blakemore","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark I.","family":"Evans","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter B.","family":"Crino","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Maryland  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI41592"},{"key":"e_1_2_12_3_1","unstructured":"Clinic for Special Children Registry Data (unpublished);2019."},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2016.81"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1800352"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2021.09.014"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.tp.0000252683.74584.29"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.50.4.515"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003081-196606000-00016"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/1740774514546574"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25956"},{"key":"e_1_2_12_12_1","volume-title":"Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease","author":"National Research Council (US) Committee on A Framework for Developing a New Taxonomy of Disease","year":"2011"},{"key":"e_1_2_12_13_1","unstructured":"Defense Advanced Research Projects Agency.2011.Biochronicity. Technical Report DARPA\u2010BAA\u201011\u201066."},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature23884"}],"container-title":["Pregnancy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pmf2.70297","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pmf2.70297","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pmf2.70297","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T11:51:21Z","timestamp":1784289081000},"score":1,"resource":{"primary":{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/10.1002\/pmf2.70297"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,29]]},"references-count":13,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/pmf2.70297"],"URL":"https:\/\/doi.org\/10.1002\/pmf2.70297","archive":["Portico"],"relation":{},"ISSN":["2997-9684","2997-9684"],"issn-type":[{"value":"2997-9684","type":"print"},{"value":"2997-9684","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,29]]},"assertion":[{"value":"2025-11-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70297"}}