{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:57:11Z","timestamp":1790575031625,"version":"4.1.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The fetal genome influences fetal growth; however, it is currently not used to customize fetal growth charts due to the need for invasive testing. Total cell-free-DNA (T-cfDNA) from maternal blood during pregnancy contains maternal-cfDNA and fetal-cfDNA. T-cfDNA offers the opportunity to non-invasively determine fetal single nucleotide polymorphisms (SNPs). This study aimed to determine the feasibility of genotyping fetal SNPs in pregnancy using parental genomic-DNA (gDNA) and maternal T-cfDNA, and computing fetal polygenic scores (PGS) as proxies for several health domains.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Parental and cord blood gDNA, and maternal T-cfDNA were collected. Genotyping was performed using Illumina Global Screening Array. Signal intensity parameters (SIPs) were extracted for genotyped SNPs. Fetal SNPs were predicted using corresponding paired parental SNPs when both parents were homozygous, and from maternal gDNA SIP confidence intervals otherwise. Six PGSs for phenotypes including birthweight-PGS were computed using predicted fetal SNPs. Predictions were verified against genotyped cord blood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The average fetal SNP prediction accuracy was 86.39% (95% CI: 85.94-86.84%). Improved performance was observed when computing PGSs with a greater number of SNPs; coefficient of variation ranged from 5.6-16.5%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Results suggested moderate predictive performance. Improvements in the accuracy of SNP prediction are needed before clinical implementation. This may be through advanced bioinformatics methods or genotyping methodology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1745404","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:44:28Z","timestamp":1790574268000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A bespoke non-invasive approach to predict fetal genotype in pregnancy"],"prefix":"10.3389","volume":"13","author":[{"given":"Carol A.","family":"Wang","sequence":"first","affiliation":[{"name":"School of Medicine and Public Health, University of Newcastle","place":["Newcastle, NSW, Australia"]},{"name":"Mothers' and Babies' Research Centre, Hunter Medical Research Institute","place":["Newcastle, NSW, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Riveros","sequence":"additional","affiliation":[{"name":"School of Medicine and Public Health, University of Newcastle","place":["Newcastle, NSW, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Attia","sequence":"additional","affiliation":[{"name":"School of Medicine and Public Health, University of Newcastle","place":["Newcastle, NSW, Australia"]},{"name":"Mothers' and Babies' Research Centre, Hunter Medical Research Institute","place":["Newcastle, NSW, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodney J.","family":"Scott","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy, University of Newcastle","place":["Newcastle, NSW, Australia"]},{"name":"Division of Molecular Medicine, Pathology North, John Hunter Hospital","place":["Newcastle, NSW, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig E.","family":"Pennell","sequence":"additional","affiliation":[{"name":"School of Medicine and Public Health, University of Newcastle","place":["Newcastle, NSW, Australia"]},{"name":"Mothers' and Babies' Research Centre, Hunter Medical Research Institute","place":["Newcastle, NSW, Australia"]},{"name":"Department of Maternity and Gynecology, John Hunter Hospital","place":["Newcastle, NSW, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e48","DOI":"10.1097\/AOG.0000000000004084","article-title":"Screening for fetal chromosomal abnormalities. ACOG practice bulletin No. 226","volume":"136","author":"Rose","year":"2020","journal-title":"Obs Gynecol"},{"key":"B2","year":"2021"},{"key":"B3","year":"2018"},{"key":"B4","year":"2023"},{"key":"B5","author":"Mackie","year":"2023"},{"key":"B6","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1002\/pd.4066","article-title":"Safe, accurate, prenatal diagnosis of thanatophoric dysplasia using ultrasound and free fetal DNA","volume":"33","author":"Chitty","year":"2013","journal-title":"Prenat Diagn"},{"key":"B7","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1038\/ejhg.2016.195","article-title":"Non-invasive prenatal diagnosis of spinal muscular atrophy by relative haplotype dosage","volume":"25","author":"Parks","year":"2017","journal-title":"Eur J Hum Genet"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1016\/j.jmoldx.2020.06.001","article-title":"Clinical service delivery of noninvasive prenatal diagnosis by relative haplotype dosage for single-gene disorders","volume":"22","author":"Young","year":"2020","journal-title":"J Mol Diagn"},{"key":"B9","volume-title":"Chorionic Villus Sampling","author":"Jones","year":"2023"},{"key":"B10","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1111\/j.1399-0004.1984.tb01079.x","article-title":"Parental determinants of birth weight","volume":"26","author":"Magnus","year":"1984","journal-title":"Clin Genet"},{"key":"B11","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1038\/nature19806","article-title":"Genome-wide associations for birth weight and correlations with adult disease","volume":"538","author":"Horikoshi","year":"2016","journal-title":"Nature"},{"key":"B12","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1111\/j.1399-0004.1984.tb00457.x","article-title":"Causes of variation in birth weight: a study of offspring of twins","volume":"25","author":"Magnus","year":"1984","journal-title":"Clin Genet"},{"key":"B13","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.1399-0004.1984.tb01061.x","article-title":"Further evidence for a significant effect of fetal genes on variation in birth weight","volume":"26","author":"Magnus","year":"1984","journal-title":"Clin Genet"},{"key":"B14","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1093\/aje\/kwk107","article-title":"Genetic and environmental influences on birth weight, birth length, head circumference, and gestational age by use of population-based parent-offspring data","volume":"165","author":"Lunde","year":"2007","journal-title":"Am J Epidemiol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1007\/s10519-014-9666-6","article-title":"Resolving the effects of maternal and offspring genotype on dyadic outcomes in genome wide complex trait analysis (\u201cM-GCTA\u201d)","volume":"44","author":"Eaves","year":"2014","journal-title":"Behav Genet"},{"key":"B16","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1038\/ng.2477","article-title":"New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism","volume":"45","author":"Horikoshi","year":"2013","journal-title":"Nat Genet"},{"key":"B17","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1038\/s41588-019-0403-1","article-title":"Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors","volume":"51","author":"Warrington","year":"2019","journal-title":"Nat Genet"},{"key":"B18","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1159\/000487618","article-title":"Perinatal origins of adult disease","volume":"113","author":"Simeoni","year":"2018","journal-title":"Neonatology"},{"key":"B19","doi-asserted-by":"publisher","first-page":"e10465","DOI":"10.1590\/1414-431x202010465","article-title":"Effects of FTO and PPARgamma variants on intrauterine growth restriction in a Brazilian birth cohort","volume":"54","author":"Barbieri","year":"2021","journal-title":"Braz J Med Biol Res"},{"key":"B20","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1080\/15513815.2020.1745970","article-title":"Association of insulin-like growth factor-II Apa1 and MspI polymorphisms with intrauterine growth restriction risk","volume":"40","author":"Karimi-Zarchi","year":"2021","journal-title":"Fetal Pediatr Pathol"},{"key":"B21","first-page":"6255","article-title":"Arguments for and against the whole-genome sequencing of newborns","volume":"15","author":"Szalai","year":"2023","journal-title":"Am J Transl Res"},{"key":"B22","doi-asserted-by":"publisher","first-page":"812781","DOI":"10.3389\/fped.2022.812781","article-title":"Factors affecting the fetal fraction in noninvasive prenatal screening: a review","volume":"10","author":"Deng","year":"2022","journal-title":"Front Pediatr"},{"key":"B23","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1002\/uog.12331","article-title":"Fetal fraction in maternal plasma cell-free DNA at 11\u201313 weeks\u2019 gestation: relation to maternal and fetal characteristics","volume":"41","author":"Ashoor","year":"2013","journal-title":"Ultrasound Obstet Gynecol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1097\/GIM.0b013e3182368a0e","article-title":"DNA sequencing of maternal plasma to detect down syndrome: an international clinical validation study","volume":"13","author":"Palomaki","year":"2011","journal-title":"Genet Med"},{"key":"B25","volume-title":"DNeasy Blood & Tissue Handbook","year":"2020"},{"key":"B26","volume-title":"QIAamp Circulating Nucleic Acid Handbook","year":"2019"},{"key":"B27","year":"2019"},{"key":"B28","year":"2022"},{"key":"B29","doi-asserted-by":"publisher","first-page":"giab008","DOI":"10.1093\/gigascience\/giab008","article-title":"Twelve years of SAMtools and BCFtools","volume":"10","author":"Danecek","year":"2021","journal-title":"Gigascience"},{"key":"B30","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: a tool set for whole-genome association and population-based linkage analyses","volume":"81","author":"Purcell","year":"2007","journal-title":"Am J Hum Genet"},{"key":"B31","volume-title":"R: A Language and Environment for Statistical Computing","year":"2019"},{"key":"B32","doi-asserted-by":"publisher","first-page":"2156","DOI":"10.1093\/bioinformatics\/btr330","article-title":"The variant call format and VCFtools","volume":"27","author":"Danecek","year":"2011","journal-title":"Bioinformatics"},{"key":"B33","year":"2006"},{"key":"B34","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1038\/s41593-018-0326-7","article-title":"Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions","volume":"22","author":"Howard","year":"2019","journal-title":"Nat Neurosci"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1807","DOI":"10.1038\/s41588-023-01520-w","article-title":"Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth","volume":"55","author":"Beaumont","year":"2023","journal-title":"Nat Genet"},{"key":"B36","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1038\/s41588-022-01285-8","article-title":"Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains","volume":"55","author":"Demontis","year":"2023","journal-title":"Nat Genet"},{"key":"B37","doi-asserted-by":"publisher","first-page":"3327","DOI":"10.1093\/hmg\/ddz161","article-title":"A trans-ancestral meta-analysis of genome-wide association studies reveals loci associated with childhood obesity","volume":"28","author":"Bradfield","year":"2019","journal-title":"Hum Mol Genet"},{"key":"B38","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1111\/j.1348-0421.2012.00439.x","article-title":"Development of new IL28B genotyping method using invader plus assay","volume":"56","author":"Kani","year":"2012","journal-title":"Microbiol Immunol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1066178","DOI":"10.3389\/fped.2023.1066178","article-title":"Maternal and fetal factors influencing fetal fraction: a retrospective analysis of 153,306 pregnant women undergoing noninvasive prenatal screening","volume":"11","author":"Deng","year":"2023","journal-title":"Front Pediatr"},{"key":"B40","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1002\/pd.4119","article-title":"Gestational age and maternal weight effects on fetal cell-free DNA in maternal plasma","volume":"33","author":"Wang","year":"2013","journal-title":"Prenat Diagn"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1745404\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:44:29Z","timestamp":1790574269000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1745404\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,28]]},"references-count":40,"alternative-id":["10.3389\/fmed.2026.1745404"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1745404","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,28]]},"article-number":"1745404"}}