{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T10:15:55Z","timestamp":1778062555852,"version":"3.51.4"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Res"],"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Advances in genomic technologies, particularly massively parallel sequencing of cell-free fetal DNA, have transformed prenatal screening and created opportunities for fetal therapies. First-tier screening for trisomy 21 (T21) now enables early identification of affected fetuses, raising the possibility of prenatal intervention. Down syndrome (DS) is increasingly recognized not only as a neurodevelopmental condition but also as an interferon-driven disorder of immune dysregulation. Preclinical studies using human cellular models and trisomic mice demonstrated abnormalities in oxidative stress and inflammatory pathways. Connectivity Map\u2013guided identification of apigenin, a naturally occurring flavonoid, showed partial normalization of gene expression, reduced neuroinflammation, and improved hippocampal-dependent learning in a mouse model, supporting the concept that atypical fetal brain development in T21 may be modifiable. Parallel human studies have confirmed chronic hypercytokinemia and autoimmunity in DS, and postnatal treatment with JAK inhibitors has shown early clinical benefit. A similar therapeutic paradigm is emerging for cystic fibrosis, where noninvasive prenatal testing detects CFTR variants and highly effective CFTR modulators are increasingly used during pregnancy. Early reports suggest that in utero exposure may ameliorate fetal complications such as meconium ileus. Together, these advances support a framework in which selected genetic disorders may be treatable beginning in fetal life.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Impact<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Advances in engineering and computational science, coupled with new biological and genomic knowledge, have led to novel prenatal opportunities to improve child health and treat disease.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41390-026-05044-x","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T09:45:27Z","timestamp":1778060727000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Opportunities for antenatal medical treatment of genetic conditions: the earlier, the better"],"prefix":"10.1038","author":[{"given":"Diana W.","family":"Bianchi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"key":"5044_CR1","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1056\/NEJMra1705345","volume":"379","author":"DW Bianchi","year":"2018","unstructured":"Bianchi, D. W. & Chiu, R. W. K. Sequencing of circulating cell-free DNA during pregnancy. N. Engl. J. Med. 379, 464\u2013473 (2018).","journal-title":"N. Engl. J. Med."},{"key":"5044_CR2","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1111\/ajo.13638","volume":"63","author":"L Hui","year":"2023","unstructured":"Hui, L. & Halliday, J. A decade of non-invasive prenatal screening in Australia: National impact on prenatal screening and diagnostic testing. Aust. NZ J. Obstet. Gynaecol. 63, 264\u2013267 (2023).","journal-title":"Aust. NZ J. Obstet. Gynaecol."},{"key":"5044_CR3","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1093\/cercor\/bhz094","volume":"30","author":"T Tarui","year":"2020","unstructured":"Tarui, T. et al. Quantitative MRI analyses of regional brain growth in living fetuses with Down syndrome. Cereb. Cortex 30, 382\u2013390 (2020).","journal-title":"Cereb. 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Analysis of genotype effects and inter-individual variability in iPSC-derived trisomy 21 neural progenitor cells. Hum. Mol. Genet. 34, 85\u2013100 (2025).","journal-title":"Hum. Mol. Genet."},{"key":"5044_CR7","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.cels.2017.11.001","volume":"6","author":"AB Keenan","year":"2018","unstructured":"Keenan, A. B. et al. The library of integrated network-based cellular signatures NIH program: system-level cataloging of human cells response to perturbations. Cell Syst. 6, 13\u201324 (2018).","journal-title":"Cell Syst."},{"key":"5044_CR8","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1016\/j.ajhg.2020.10.001","volume":"107","author":"F Guedj","year":"2020","unstructured":"Guedj, F. et al. Apigenin as a candidate prenatal treatment for trisomy 21: effects in human amniocytes and the Ts1Cje mouse model. Am. J. Hum. Genet. 107, 911\u2013931 (2020).","journal-title":"Am. J. Hum. 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Trends Biotechnol. 43, 732\u2013733 (2025).","journal-title":"Trends Biotechnol."},{"key":"5044_CR12","first-page":"e16144","volume":"13","author":"A Zaher","year":"2021","unstructured":"Zaher, A., ElSaygh, J., Elsori, D., ElSaygh, H. & Sanni, A. A review of trikafta: triple cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy. Cureus 13, e16144 (2021).","journal-title":"Cureus"},{"key":"5044_CR13","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1016\/j.jcf.2025.07.015","volume":"24","author":"S Szentpetery","year":"2025","unstructured":"Szentpetery, S. et al. Prenatal mOdulator treatment to PrEvent CF complicaTions (PROTECT) workshop report. J. Cyst. Fibros. 24, 1058\u20131066 (2025).","journal-title":"J. Cyst. Fibros."},{"key":"5044_CR14","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1016\/j.jcf.2024.11.011","volume":"24","author":"A Metcalf","year":"2025","unstructured":"Metcalf, A. et al. Outcomes of prenatal use of elexacaftor\/tezacaftor\/ivcaftor in carrier mothers to treat meconium ileus in fetuses with cystic fibrosis. J. Cyst. Fibros. 24, 466\u2013468 (2025).","journal-title":"J. Cyst. Fibros."},{"key":"5044_CR15","doi-asserted-by":"publisher","first-page":"e001289","DOI":"10.1136\/bmjresp-2022-001289","volume":"9","author":"R Jain","year":"2022","unstructured":"Jain, R. et al. Prospectively evaluating maternal and fetal outcomes in the era of CFTR modulators: the MAYFLOWERS observational clinical trial study design. BMJ Open Resp. Res. 9, e001289 (2022).","journal-title":"BMJ Open Resp. 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