{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T11:35:23Z","timestamp":1768563323004,"version":"3.49.0"},"reference-count":53,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T00:00:00Z","timestamp":1664323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Academy of Finland","award":["284859"],"award-info":[{"award-number":["284859"]}]},{"name":"Academy of Finland","award":["312670"],"award-info":[{"award-number":["312670"]}]},{"name":"Academy of Finland","award":["1324596"],"award-info":[{"award-number":["1324596"]}]},{"name":"Banting Postdoctoral Fellowship","award":["284859"],"award-info":[{"award-number":["284859"]}]},{"name":"Banting Postdoctoral Fellowship","award":["312670"],"award-info":[{"award-number":["312670"]}]},{"name":"Banting Postdoctoral Fellowship","award":["1324596"],"award-info":[{"award-number":["1324596"]}]},{"name":"Academy of Finland, University of Helsinki Funds","award":["284859"],"award-info":[{"award-number":["284859"]}]},{"name":"Academy of Finland, University of Helsinki Funds","award":["312670"],"award-info":[{"award-number":["312670"]}]},{"name":"Academy of Finland, University of Helsinki Funds","award":["1324596"],"award-info":[{"award-number":["1324596"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Several studies have shown that children from pregnancies with estimated first-trimester risk based on fetal nuchal translucency thickness and abnormal maternal serum pregnancy protein and hormone levels maintain a higher likelihood of adverse outcomes, even if initial testing for known genetic conditions is negative. We used the Finnish InTraUterine cohort (ITU), which is a comprehensively characterized perinatal cohort consisting of 943 mothers and their babies followed throughout pregnancy and 18 months postnatally, including mothers shortlisted for prenatal genetic testing but cleared for major aneuploidies (cases: n = 544, 57.7%) and control pregnancies (n = 399, 42.3%). Using genome-wide genotyping and RNA sequencing of first-trimester and term placental tissue, combined with medical information from registry data and maternal self-report data, we investigated potential negative medical outcomes and genetic susceptibility to disease and their correlates in placenta gene expression. Case mothers did not present with higher levels of depression, perceived stress, or anxiety during pregnancy. Case children were significantly diagnosed more often with congenital malformations of the circulatory system (4.12 (95% CI [1.22\u201313.93]) higher hazard) and presented with significantly more copy number duplications as compared to controls (burden analysis, based on all copy number variants (CNVs) with at most 10% frequency, 823 called duplications in 297 cases versus 626 called duplications in 277 controls, p = 0.01). Fifteen genes showed differential gene expression (FDR &lt; 0.1) in association with congenital malformations in first-trimester but not term placenta. These were significantly enriched for genes associated with placental dysfunction. In spite of normal routine follow-up prenatal testing results in early pregnancy, case children presented with an increased likelihood of negative outcomes, which should prompt vigilance in follow-up during pregnancy and after birth.<\/jats:p>","DOI":"10.3390\/ijms231911448","type":"journal-article","created":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T22:53:19Z","timestamp":1664405599000},"page":"11448","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Genome-Wide Copy Number Variant and High-Throughput Transcriptomics Analyses of Placental Tissues Underscore Persisting Child Susceptibility in At-Risk Pregnancies Cleared in Standard Genetic Testing"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7381-904X","authenticated-orcid":false,"given":"Darina","family":"Czamara","sequence":"first","affiliation":[{"name":"Department of Translational Research in Psychiatry, Max-Planck-Institute of Psychiatry, 80804 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7799-5531","authenticated-orcid":false,"given":"Cristiana","family":"Cruceanu","sequence":"additional","affiliation":[{"name":"Department of Translational Research in Psychiatry, Max-Planck-Institute of Psychiatry, 80804 Munich, Germany"},{"name":"Department of Physiology and Pharmacology, Karolinska Institutet, 171 77 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5244-5525","authenticated-orcid":false,"given":"Marius","family":"Lahti-Pulkkinen","sequence":"additional","affiliation":[{"name":"Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland"},{"name":"Finnish Institute for Health and Welfare, 00271 Helsinki, Finland"},{"name":"Centre for Cardiovascular Science, Queen\u2019s Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda","family":"Dieckmann","sequence":"additional","affiliation":[{"name":"Department of Translational Research in Psychiatry, Max-Planck-Institute of Psychiatry, 80804 Munich, Germany"},{"name":"International Max Planck Research School for Translational Psychiatry, 80804 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maik","family":"K\u00f6del","sequence":"additional","affiliation":[{"name":"Department of Translational Research in Psychiatry, Max-Planck-Institute of Psychiatry, 80804 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susann","family":"Sauer","sequence":"additional","affiliation":[{"name":"Department of Translational Research in Psychiatry, Max-Planck-Institute of Psychiatry, 80804 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monika","family":"Rex-Haffner","sequence":"additional","affiliation":[{"name":"Department of Translational Research in Psychiatry, Max-Planck-Institute of Psychiatry, 80804 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Sammallahti","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Helsinki University Hospital and University of Helsinki, 00014 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eero","family":"Kajantie","sequence":"additional","affiliation":[{"name":"Finnish Institute for Health and Welfare, 00271 Helsinki, Finland"},{"name":"Children\u2019s Hospital, Helsinki University Hospital and University of Helsinki, 00014 Helsinki, Finland"},{"name":"Faculty of Medicine, PEDEGO Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, 90014 Oulu, Finland"},{"name":"Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannele","family":"Laivuori","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland, HiLIFE, University of Helsinki, 00014 Helsinki, Finland"},{"name":"Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, 00014 Helsinki, Finland"},{"name":"Department of Obstetrics and Gynecology, Tampere University Hospital and Faculty of Medicine and Health Technology, Center for Child, Adolescent and Maternal Health Research, Tampere University, 33520 Tampere, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jari","family":"Lahti","sequence":"additional","affiliation":[{"name":"Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katri","family":"R\u00e4ikk\u00f6nen","sequence":"additional","affiliation":[{"name":"Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabeth B.","family":"Binder","sequence":"additional","affiliation":[{"name":"Department of Translational Research in Psychiatry, Max-Planck-Institute of Psychiatry, 80804 Munich, Germany"},{"name":"Department of Psychiatry and Behavioral Sciences, School of Medicine, Emory University, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.ogc.2017.02.004","article-title":"Prenatal Diagnosis: Screening and Diagnostic 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