{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:14:32Z","timestamp":1788437672043,"version":"build-2803163510"},"reference-count":81,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Bialystok","award":["(B.SUB.25.539)"],"award-info":[{"award-number":["(B.SUB.25.539)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Spina Bifida (SB) and Congenital Diaphragmatic Hernia (CDH) are complex congenital anomalies that pose significant challenges in pediatric healthcare. This review synthesizes recent advancements in understanding the genetic, metabolic, and environmental factors contributing to these conditions, with the aim of integrating mechanistic insights into therapeutic innovations. In SB, key findings highlight the roles of KCND3, a critical regulator of spinal cord development, and VANGL2, essential for planar cell polarity and neural tube closure. MicroRNAs such as miR-765 and miR-142-3p are identified as key regulators of these genes, influencing neural development. Additionally, telomere shortening\u2014a marker of cellular senescence\u2014alongside disruptions in folate metabolism and maternal nutritional deficiencies, significantly increases the risk of SB. These findings underscore the crucial role of telomere integrity in maintaining neural tissue homeostasis during embryonic development. For CDH, genetic deletions, including those on chromosome 15q26, and chromosomal abnormalities have been shown to disrupt lung and vascular development, profoundly impacting neonatal outcomes. MicroRNAs miR-379-5p and miR-889-3p are implicated in targeting essential genes such as IGF1 and FGFR2, which play pivotal roles in pulmonary function. Promising emerging therapies, including degradable tracheal plugs and fibroblast growth factor-based treatments, offer potential strategies for mitigating pulmonary hypoplasia and improving clinical outcomes. This review underscores the intricate interplay of genetic, metabolic, and environmental pathways in SB and CDH, identifying critical molecular targets for diagnostics and therapeutic intervention. By integrating findings from genetic profiling, in vitro models, and clinical studies, it aims to inform future research directions and optimize patient outcomes through collaborative, multidisciplinary approaches.<\/jats:p>","DOI":"10.3390\/cells14141059","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T15:36:58Z","timestamp":1752161818000},"page":"1059","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Integrative Review of Molecular, Metabolic, and Environmental Factors in Spina Bifida and Congenital Diaphragmatic Hernia: Insights into Mechanisms and Emerging Therapeutics"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7403-6928","authenticated-orcid":false,"given":"Angelika","family":"Buczy\u0144ska","sequence":"first","affiliation":[{"name":"Clinical Research Centre, Medical University of Bia\u0142ystok, ul. M. Sk\u0142odowskiej-Curie 24a, 15-276 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0254-3095","authenticated-orcid":false,"given":"Iwona","family":"Sidorkiewicz","sequence":"additional","affiliation":[{"name":"Clinical Research Support Centre, Medical University of Bia\u0142ystok, ul. M. Waszyngtona 17, 15-276 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Przemys\u0142aw","family":"Kosi\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Perinatology and Gynecology, Medical University of Warsaw, 63A Zwirki i Wigury, 02-091 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4522-4978","authenticated-orcid":false,"given":"Adam Jacek","family":"Kr\u0119towski","sequence":"additional","affiliation":[{"name":"Clinical Research Centre, Medical University of Bia\u0142ystok, ul. M. Sk\u0142odowskiej-Curie 24a, 15-276 Bia\u0142ystok, Poland"},{"name":"Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bia\u0142ystok, ul. Sklodowskiej-Curie 24a, 15-276 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Zbucka-Kr\u0119towska","sequence":"additional","affiliation":[{"name":"Department of Gynecological Endocrinology and Adolescent Gynecology, Medical University of Bia\u0142ystok, ul. M. Sk\u0142odowskiej-Curie 24a, 15-276 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1016\/S0140-6736(04)17445-X","article-title":"Spina bifida","volume":"364","author":"Mitchell","year":"2004","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1186\/s40748-017-0045-1","article-title":"Congenital Diaphragmatic hernia\u2014A review","volume":"3","author":"Chandrasekharan","year":"2017","journal-title":"Matern. Health Neonatol. Perinatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1038\/s41390-023-02905-7","article-title":"The etiology of congenital diaphragmatic hernia: The retinoid hypothesis 20 years later","volume":"95","author":"Rivas","year":"2023","journal-title":"Pediatr. 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