{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T15:32:44Z","timestamp":1786548764206,"version":"build-2736575974"},"reference-count":49,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,7,21]],"date-time":"2021-07-21T00:00:00Z","timestamp":1626825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Prenatal Diagnosis"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>To investigate whether second trimester maternal serum screening (2TMSS) biomarkers are associated with cerebral palsy (CP) and identify CP characteristics associated with abnormal biomarker levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>In this retrospective case\u2013control data linkage study, we linked mothers of 129 singleton CP cases from a population register to their 2TMSS records and selected 10 singleton pregnancy controls per case (<jats:italic>n<\/jats:italic>\u00a0=\u00a01290). We compared mean and abnormal levels of alpha\u2010fetoprotein (AFP), beta subunit of human chorionic gonadotrophin (<jats:italic>\u03b2<\/jats:italic>\u2010hCG), unconjugated estriol (uE3), and inhibin between cases and controls and within CP subgroups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to control pregnancies, CP pregnancies had higher mean levels of AFP (1.10 vs. 1.01 multiple of the population median [MoM], <jats:italic>p<\/jats:italic>\u00a0=\u00a00.01) and inhibin (1.10 vs. 0.98 MoM, <jats:italic>p<\/jats:italic>\u00a0\u2264\u00a00.01). CP pregnancies were 2.5 times more likely to be associated with high levels of AFP (OR 2.52 [95% confidence interval [CI] 1.30, 4.65]; <jats:italic>p\u00a0&lt;\u00a0<\/jats:italic>0.01) and 2.6 times for inhibin (OR 2.63 [95% CI 1.37, 4.77]; <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.01), and 6.8 times when AFP and inhibin were both elevated (OR 6.75 [95% CI 2.41, 18.94]; <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.01). In CP cases, high AFP and high inhibin levels were associated with preterm birth and low birthweight.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Abnormal second\u2010trimester biomarker levels suggest abnormal placentation plays a role in the causal pathway of some CP cases.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pd.6011","type":"journal-article","created":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T18:37:10Z","timestamp":1626460630000},"page":"1101-1110","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Second trimester maternal serum biomarkers and the risk of cerebral palsy"],"prefix":"10.1002","volume":"41","author":[{"given":"Monique","family":"Peris","sequence":"first","affiliation":[{"name":"Neurodisability and Rehabilitation Murdoch Children's Research Institute  Melbourne Australia"},{"name":"Department of Paediatrics University of Melbourne  Melbourne Australia"},{"name":"Neurodevelopment and Disability Royal Children's Hospital  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan M.","family":"Reid","sequence":"additional","affiliation":[{"name":"Neurodisability and Rehabilitation Murdoch Children's Research Institute  Melbourne Australia"},{"name":"Department of Paediatrics University of Melbourne  Melbourne Australia"},{"name":"Neurodevelopment and Disability Royal Children's Hospital  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Dobie","sequence":"additional","affiliation":[{"name":"Victorian Clinical Genetics Services  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo","family":"Bonacquisto","sequence":"additional","affiliation":[{"name":"Victorian Clinical Genetics Services  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisy A.","family":"Shepherd","sequence":"additional","affiliation":[{"name":"Neurodisability and Rehabilitation Murdoch Children's Research Institute  Melbourne Australia"},{"name":"Department of Paediatrics University of Melbourne  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7191-8511","authenticated-orcid":false,"given":"David J.","family":"Amor","sequence":"additional","affiliation":[{"name":"Neurodisability and Rehabilitation Murdoch Children's Research Institute  Melbourne Australia"},{"name":"Department of Paediatrics University of Melbourne  Melbourne Australia"},{"name":"Neurodevelopment and Disability Royal Children's Hospital  Melbourne Australia"},{"name":"Victorian Clinical Genetics Services  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,7,21]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"8","article-title":"A report: the definition and classification of cerebral palsy April 2006","volume":"109","author":"Rosenbaum P","year":"2007","journal-title":"Dev Med Child Neurol Suppl"},{"key":"e_1_2_8_3_1","volume-title":"Report of the Australian Cerebral Palsy Register Birth Years 1995\u20102012","author":"Australian Cerebral Palsy Register Group","year":"2018"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ogc.2017.02.004"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/153537020422900602"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-374984-0.00039-5"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18102037"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7827-8-102"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.15761\/CRT.1000109"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmh057"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-018-0043-6"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3109\/01443615.2015.1036400"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0232634"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod57.6.1490"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2003.08.008"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.12262"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1258\/096914106776179782"},{"key":"e_1_2_8_18_1","first-page":"1323","article-title":"Maternal serum\u2010alpha\u2010fetoprotein measurement in antenatal screening for anencephaly and spina bifida in early pregnancy. Report of U.K. collaborative study on alpha\u2010fetoprotein in relation to neural\u2010tube defects","volume":"1","author":"Wald NJ","year":"1977","journal-title":"Lancet"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm3020504"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.13166"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12884-020-2789-2"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.AOG.0000172419.37410.eb"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.4370"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2009.04.017"},{"key":"e_1_2_8_25_1","article-title":"Association of high maternal blood alpha\u2010fetoprotein level with risk of delivering small for gestational age: a meta\u2010analysis","author":"Goto E","year":"2020","journal-title":"Pediatr Res"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.1970151109"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0029-7844(96)00310-9"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1701-2163(15)30331-5"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)92471-X"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1053\/plac.2002.0816"},{"key":"e_1_2_8_31_1","first-page":"1","article-title":"Alpha\u2010fetoprotein (AFP) and inflammation: is AFP an acute and\/or chronic phase reactant?","volume":"3","author":"Mizejewski GJ","year":"2015","journal-title":"J Hematol Thromboembol Dis"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/jog.14085"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2020.09.026"},{"key":"e_1_2_8_34_1","first-page":"309","article-title":"Endothelial dysfunction. An important mediator in the pathophysiology of hypertension during pre\u2010eclampsia","volume":"64","author":"Lamarca B","year":"2012","journal-title":"Minerva Ginecol"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ogc.2019.10.008"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.2009.03415.x"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2007.07.001"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.2007.00252.x"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00268-002-6746-1"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2393-8-33"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.3109\/14767058.2015.1075503"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0029-7844(97)00677-7"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1159\/000495614"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.01027"},{"key":"e_1_2_8_45_1","first-page":"27","article-title":"Indication of prenatal diagnosis in pregnancies complicated by undetectable second\u2010trimester maternal serum estriol levels","volume":"2","author":"Minsart A\u2010F","year":"2008","journal-title":"J Prenat Med"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12884-019-2266-y"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/1471-0528.13495"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2011.01.018"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.2350\/06-12-0203.1"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.14732"}],"container-title":["Prenatal Diagnosis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pd.6011","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pd.6011","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pd.6011","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T08:39:20Z","timestamp":1693298360000},"score":1,"resource":{"primary":{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/10.1002\/pd.6011"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,21]]},"references-count":49,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2021,8]]}},"alternative-id":["10.1002\/pd.6011"],"URL":"https:\/\/doi.org\/10.1002\/pd.6011","archive":["Portico"],"relation":{},"ISSN":["0197-3851","1097-0223"],"issn-type":[{"value":"0197-3851","type":"print"},{"value":"1097-0223","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,21]]},"assertion":[{"value":"2021-03-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}