Second trimester maternal serum biomarkers and the risk of cerebral palsy

Aims 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. Method In this retrospective case–control data linkage study, we linked mothers of 129 singleton...

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Veröffentlicht in:Prenatal diagnosis 2021-08, Vol.41 (9), p.1101-1110
Hauptverfasser: Peris, Monique, Reid, Susan M., Dobie, Stephen, Bonacquisto, Leo, Shepherd, Daisy A., Amor, David J.
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container_issue 9
container_start_page 1101
container_title Prenatal diagnosis
container_volume 41
creator Peris, Monique
Reid, Susan M.
Dobie, Stephen
Bonacquisto, Leo
Shepherd, Daisy A.
Amor, David J.
description Aims 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. Method In this retrospective case–control 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 (n = 1290). We compared mean and abnormal levels of alpha‐fetoprotein (AFP), beta subunit of human chorionic gonadotrophin (β‐hCG), unconjugated estriol (uE3), and inhibin between cases and controls and within CP subgroups. Results Compared to control pregnancies, CP pregnancies had higher mean levels of AFP (1.10 vs. 1.01 multiple of the population median [MoM], p = 0.01) and inhibin (1.10 vs. 0.98 MoM, p ≤ 0.01). 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]; p 
doi_str_mv 10.1002/pd.6011
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Method In this retrospective case–control 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 (n = 1290). We compared mean and abnormal levels of alpha‐fetoprotein (AFP), beta subunit of human chorionic gonadotrophin (β‐hCG), unconjugated estriol (uE3), and inhibin between cases and controls and within CP subgroups. Results Compared to control pregnancies, CP pregnancies had higher mean levels of AFP (1.10 vs. 1.01 multiple of the population median [MoM], p = 0.01) and inhibin (1.10 vs. 0.98 MoM, p ≤ 0.01). 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]; p &lt; 0.01) and 2.6 times for inhibin (OR 2.63 [95% CI 1.37, 4.77]; p &lt; 0.01), and 6.8 times when AFP and inhibin were both elevated (OR 6.75 [95% CI 2.41, 18.94]; p &lt; 0.01). In CP cases, high AFP and high inhibin levels were associated with preterm birth and low birthweight. Interpretation Abnormal second‐trimester biomarker levels suggest abnormal placentation plays a role in the causal pathway of some CP cases. Key points What is already known about this topic? Abnormal second‐trimester levels of biomarkers in maternal serum are associated with later cerebral palsy (CP). Early pregnancy factors have potential importance in causal pathways to CP. What does this study add? Causal pathways involving placental dysfunction and genetic syndromes may be implicated.</description><identifier>ISSN: 0197-3851</identifier><identifier>EISSN: 1097-0223</identifier><identifier>DOI: 10.1002/pd.6011</identifier><identifier>PMID: 34270813</identifier><language>eng</language><publisher>HOBOKEN: Wiley</publisher><subject><![CDATA[Adult ; Analysis of Variance ; Biomarkers ; Biomarkers - analysis ; Biomarkers - blood ; Birth weight ; Case-Control Studies ; Cerebral palsy ; Cerebral Palsy - diagnosis ; Cerebral Palsy - epidemiology ; Cerebral Palsy - genetics ; Confidence intervals ; Control data (computers) ; Female ; Genetics & Heredity ; Humans ; Inhibin ; Life Sciences & Biomedicine ; Mothers - statistics & numerical data ; Obstetrics & Gynecology ; Paralysis ; Pituitary (anterior) ; Pregnancy ; Pregnancy Trimester, Second - blood ; Pregnancy Trimester, Second - genetics ; Premature birth ; Prenatal Diagnosis - methods ; Prenatal Diagnosis - standards ; Prenatal Diagnosis - statistics & numerical data ; Retrospective Studies ; Science & Technology ; Subgroups ; Victoria - epidemiology]]></subject><ispartof>Prenatal diagnosis, 2021-08, Vol.41 (9), p.1101-1110</ispartof><rights>2021 John Wiley &amp; Sons Ltd.</rights><rights>2021 John Wiley &amp; Sons Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>2</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000675075400001</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c3781-c3ed1f7570fea9d1eb9975e47666427f1875f3632b997d5819029249011ed1933</citedby><cites>FETCH-LOGICAL-c3781-c3ed1f7570fea9d1eb9975e47666427f1875f3632b997d5819029249011ed1933</cites><orcidid>0000-0001-7191-8511 ; 0000-0001-8540-0473</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpd.6011$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpd.6011$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,27929,27930,39263,45579,45580</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34270813$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Peris, Monique</creatorcontrib><creatorcontrib>Reid, Susan M.</creatorcontrib><creatorcontrib>Dobie, Stephen</creatorcontrib><creatorcontrib>Bonacquisto, Leo</creatorcontrib><creatorcontrib>Shepherd, Daisy A.</creatorcontrib><creatorcontrib>Amor, David J.</creatorcontrib><title>Second trimester maternal serum biomarkers and the risk of cerebral palsy</title><title>Prenatal diagnosis</title><addtitle>PRENATAL DIAG</addtitle><addtitle>Prenat Diagn</addtitle><description>Aims 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. Method In this retrospective case–control 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 (n = 1290). We compared mean and abnormal levels of alpha‐fetoprotein (AFP), beta subunit of human chorionic gonadotrophin (β‐hCG), unconjugated estriol (uE3), and inhibin between cases and controls and within CP subgroups. Results Compared to control pregnancies, CP pregnancies had higher mean levels of AFP (1.10 vs. 1.01 multiple of the population median [MoM], p = 0.01) and inhibin (1.10 vs. 0.98 MoM, p ≤ 0.01). 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]; p &lt; 0.01) and 2.6 times for inhibin (OR 2.63 [95% CI 1.37, 4.77]; p &lt; 0.01), and 6.8 times when AFP and inhibin were both elevated (OR 6.75 [95% CI 2.41, 18.94]; p &lt; 0.01). 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Method In this retrospective case–control 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 (n = 1290). We compared mean and abnormal levels of alpha‐fetoprotein (AFP), beta subunit of human chorionic gonadotrophin (β‐hCG), unconjugated estriol (uE3), and inhibin between cases and controls and within CP subgroups. Results Compared to control pregnancies, CP pregnancies had higher mean levels of AFP (1.10 vs. 1.01 multiple of the population median [MoM], p = 0.01) and inhibin (1.10 vs. 0.98 MoM, p ≤ 0.01). 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]; p &lt; 0.01) and 2.6 times for inhibin (OR 2.63 [95% CI 1.37, 4.77]; p &lt; 0.01), and 6.8 times when AFP and inhibin were both elevated (OR 6.75 [95% CI 2.41, 18.94]; p &lt; 0.01). In CP cases, high AFP and high inhibin levels were associated with preterm birth and low birthweight. Interpretation Abnormal second‐trimester biomarker levels suggest abnormal placentation plays a role in the causal pathway of some CP cases. Key points What is already known about this topic? Abnormal second‐trimester levels of biomarkers in maternal serum are associated with later cerebral palsy (CP). Early pregnancy factors have potential importance in causal pathways to CP. What does this study add? Causal pathways involving placental dysfunction and genetic syndromes may be implicated.</abstract><cop>HOBOKEN</cop><pub>Wiley</pub><pmid>34270813</pmid><doi>10.1002/pd.6011</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-7191-8511</orcidid><orcidid>https://orcid.org/0000-0001-8540-0473</orcidid><oa>free_for_read</oa></addata></record>
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subjects Adult
Analysis of Variance
Biomarkers
Biomarkers - analysis
Biomarkers - blood
Birth weight
Case-Control Studies
Cerebral palsy
Cerebral Palsy - diagnosis
Cerebral Palsy - epidemiology
Cerebral Palsy - genetics
Confidence intervals
Control data (computers)
Female
Genetics & Heredity
Humans
Inhibin
Life Sciences & Biomedicine
Mothers - statistics & numerical data
Obstetrics & Gynecology
Paralysis
Pituitary (anterior)
Pregnancy
Pregnancy Trimester, Second - blood
Pregnancy Trimester, Second - genetics
Premature birth
Prenatal Diagnosis - methods
Prenatal Diagnosis - standards
Prenatal Diagnosis - statistics & numerical data
Retrospective Studies
Science & Technology
Subgroups
Victoria - epidemiology
title Second trimester maternal serum biomarkers and the risk of cerebral palsy
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