{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T12:46:05Z","timestamp":1777898765898,"version":"3.51.4"},"reference-count":49,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"kinderherzen F\u00f6rdergemeinschaft Deutsche Kinderherzzentren e.V."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Congenital heart defects (CHDs) are associated with disruptions in one-carbon metabolism. In a family-based trio design, we investigated whether plasma concentrations of choline, betaine, and folate are associated with CHD severity. Methods: The study included 72 children with CHD, 69 of their mothers and 64 of the fathers. CHD clinical severity was classified according to the European network of population-based registries for the epidemiological surveillance of congenital anomalies (EUROCAT) system and the German PAN study (Prevalence of Congenital Heart Defects in Newborns). Concentrations of choline, betaine, and folates were quantified in plasma and urine samples from a subgroup of the participants. Results: The children [mean (SD) age 3.1 (3.2) years, 59.7% males] presented with varying CHD severities according to EUROCAT (62.5% severe and 37.5% mild) and PAN classifications (45.8% severe, 30.6% moderate and 23.6% mild). The means (SD) of plasma concentrations of choline were 14.0 (10.0) \u00b5mol\/L in the children, 9.5 (5.1) \u00b5mol\/L in the mothers and 10.3 (5.4) \u00b5mol\/L in the fathers. Plasma choline concentrations &lt; 10 \u00b5mol\/L were observed in 38 mothers (66.7%) and were associated with having a child with severe CHD [adjusted odds ratio (aOR) 3.7; 95% confidence intervals (95%CIs) = 1.1, 12.2] compared to mothers with choline \u2265 10 \u00b5mol\/L. Lowered plasma choline concentrations were detected in 27 fathers (62.8%) and were also associated with severe CHD (aOR 7.4; 95%CIs = 1.7, 31.5). Child concentrations of choline, betaine and folate and parents\u2019 concentrations of betaine and folate were not associated with disease severity. Conclusions: Lower plasma choline in the parents detectable several years after conception was related to having a child with severe CHD compared to families of children with higher plasma choline. Maternal and paternal choline metabolism may have a role in modulating CHD severity. Etiological studies aiming at the prevention of congenital anomalies should focus on maternal and paternal risk factors in the preconception and early pregnancy.<\/jats:p>","DOI":"10.3390\/nu18091455","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T09:33:17Z","timestamp":1777627997000},"page":"1455","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lowered Maternal and Paternal Plasma Concentrations of Choline Are Associated with the Severity of Congenital Heart Defects in the Offspring"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0064-7029","authenticated-orcid":false,"given":"Rima","family":"Obeid","sequence":"first","affiliation":[{"name":"Department of Clinical Chemistry and Laboratory Medicine, Saarland University Hospital, Kirrberg Street, Building 57, D-66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8460-8317","authenticated-orcid":false,"given":"Annabelle","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, Saarland University Hospital, Kirrberg Street, Building 9, D-66421 Homburg, Germany"},{"name":"Department of Pediatric Cardiology, Saarland University and University Hospital, Building 9, D-66424 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Celina","family":"L\u00f6hfelm","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Laboratory Medicine, Saarland University Hospital, Kirrberg Street, Building 57, D-66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00fcrgen","family":"Geisel","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Laboratory Medicine, Saarland University Hospital, Kirrberg Street, Building 57, D-66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hashim","family":"Abdul-Khaliq","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology, Saarland University and University Hospital, Building 9, D-66424 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1055\/s-0030-1254155","article-title":"Prevalence of congenital heart defects in newborns in Germany: Results of the first registration year of the PAN Study (July 2006 to June 2007)","volume":"222","author":"Lindinger","year":"2010","journal-title":"Klin. 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