Birth Defects Research最新文献

{"title":"Reply to Correspondence on “Comparison of Perceived Adverse Events After COVID-19 Vaccination Between Pregnant and NonPregnant Women Using Two Cohort Studies in The Netherlands”","authors":"Petra J. Woestenberg, Florence van Hunsel, Veronique Y. F. Maas","doi":"10.1002/bdr2.2511","DOIUrl":"https://doi.org/10.1002/bdr2.2511","url":null,"abstract":"","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 7","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted Re-Sequencing of Neural Tube Defects Patients and Families Identifies Rare Variants in Genes Candidate From Animal Models","authors":"Ferruccio Romano,&nbsp;Patrizia De Marco,&nbsp;Marzia Ognibene,&nbsp;Michele Iacomino,&nbsp;Marco Di Duca,&nbsp;Irene Schiavetti,&nbsp;Marcello Scala,&nbsp;Marco Pavanello,&nbsp;Gianluca Piatelli,&nbsp;Valeria Capra","doi":"10.1002/bdr2.2507","DOIUrl":"https://doi.org/10.1002/bdr2.2507","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background/Objectives</h3>\u0000 \u0000 <p>Neural tube defects (NTDs) are congenital malformations arising when the neural tube (NT), precursor of the brain and spine, fails to properly close during neurulation. Etiology is multifactorial, with environmental and genetic factors variably contributing on a case-by-case basis. Molecular genetic studies of murine NTD genes have been precious in the identification of predisposing NTD genes in humans, highlighting the peculiar role of the planar cell polarity (PCP) pathway in a fraction of human NTD patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Seventy-eight patients with NTD treated at a pediatric tertiary care center were selected for genetic analysis. A custom next-generation sequencing (NGS) panel of 29 genes encoding for components of the core PCP pathway or for family members and paralogs of proteins (including SHROOM and GRHL) underlying NTDs in well-known animal models was used to re-sequence patients with NTD. A gene-burden analysis was also performed to assess potential enrichment of rare damaging variants in the NTD cohort compared to ethnically matched controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Thirty-nine of 78 individuals (50%) presented with at least one putatively damaging rare variant, most of which (87%) were missense substitutions. Rare variants of <i>GRHL1</i> and <i>WNT5A</i>, and among gene families <i>GRHL</i> and <i>SHROOM</i>, were significantly enriched in the patients' cohort compared to controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study supports the involvement of human orthologues of mouse genes in human NTD phenotypes. Further re-sequencing or, even better, whole-exome sequencing of a large group of cases will give the clues for a better understanding of NTD etiology, ameliorating the clinical management of patients and their families.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 7","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Prenatal Exposure to Traffic-Related Air Pollution and Orofacial Clefts Among Newborns in New York State, Excluding New York City (2000–2019)","authors":"Douglas Done,&nbsp;Michele Herdt,&nbsp;Tabassum Z. Insaf,&nbsp;Beth Feingold,&nbsp;Akiko Hosler","doi":"10.1002/bdr2.2503","DOIUrl":"https://doi.org/10.1002/bdr2.2503","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Prenatal exposure to tobacco smoke is strongly associated with the development of orofacial clefts. Traffic-related air pollution (TRAP) has many of the same toxic combustion byproducts as burning tobacco, such as benzene and PM_2.5, and may therefore act through similar pathways to cause harm to developing fetuses. Since concentrations of TRAP are highest close to the roadway, they can be assessed using distance-weighted traffic density (DWTD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A case–control study of birthing parent–newborn pairs was conducted among children born between January 1, 2000, and December 31, 2019, to people residing in New York State (NYS), excluding New York City. Cases of cleft lip alone, cleft palate alone, and cleft lip with cleft palate were identified from the NYS Birth Defects Registry. Orofacial clefts were also analyzed as an aggregated group. Controls without diagnosed major birth defects were randomly selected from hospital discharge records. DWTD measured in vehicles per day (VPD) was calculated from NYS Department of Transportation traffic data. A multivariate logistic regression model, adjusted for the birthing parent's age, race, ethnicity, and census tract-level disadvantage, was constructed to evaluate the association between orofacial clefts and DWTD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There was a statistically significant adjusted odds ratio (aOR) comparing the DWTD ≥ 500 VPD group to the DWTD reference group (&lt; 500 VPD) found only among orofacial clefts as an aggregate group (aOR = 1.13 [1.04–1.22]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The current study, covering 20 years of case collection, generally supports the DWTD's potential risk for orofacial clefts. Larger observational studies are warranted to further investigate associations between DWTD and individual categories of orofacial clefts.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 7","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Teratogenic Effects of Serotonin Receptor 2B Disruption on the Migration and Cardiac Derivatives of the Cardiac Neural Crest","authors":"Brian K. Wells,&nbsp;Gwyneth K. Garramone,&nbsp;Amira Mahomed,&nbsp;Max Ezin","doi":"10.1002/bdr2.2506","DOIUrl":"https://doi.org/10.1002/bdr2.2506","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cardiac neural crest cells (cNCCs) are critical for heart development, and their disruption can result in congenital heart defects. Serotonin (5-HT) signaling, specifically via 5-HT2B and 5-HT2C receptors, regulates diverse physiological processes, including neural crest migration. This study investigates how modulation of 5-HT2B and 5-HT2C receptor activity impacts cNCC migration and the development of their derivatives, with relevance to serotonergic drug safety during pregnancy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Chicken embryos at HH8 were treated with 50 μL of 20 μM 1-Methylpsilocin (1-MP), an inverse agonist of 5-HT2B and agonist of 5-HT2C, and collected at HH14 to assess cNCC migration. Embryos were pre-treated with SB242084, a selective 5-HT2C antagonist, to isolate receptor-specific contributions before 1-MP application. Phenotypic outcomes were assessed at HH32 and HH36 for structural heart defects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>1-MP disrupted cNCC migration at HH14, evidenced by abnormal shortening of the circumpharyngeal neural crest (CirNCC) stream. Pre-treatment with SB242084 did not rescue the phenotype, implicating 5-HT2B as the primary driver, though potential contributions from 5-HT2C cannot be excluded. At HH32, 1-MP-treated embryos displayed gaps in the aorticopulmonary septum. By HH36, interventricular septal defects and delayed development further supported the role of 5-HT2B in cNCC migration and differentiation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings reveal that 5-HT2B receptor activity is critical for cNCC migration and heart development. They underscore the potential teratogenic risks of serotonergic drugs targeting 5-HT2B/5-HT2C receptors during pregnancy, with implications for drug safety and heart morphogenesis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 7","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bdr2.2506","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain Weight Effect of Ambrisentan in Juvenile Rat Toxicity Studies Associated With Breathing Sounds, Apnea, and Sustained Hypoxemia","authors":"Susan B. Laffan,&nbsp;Kohrs Loren,&nbsp;Kambara Takahito,&nbsp;Turner Sandra","doi":"10.1002/bdr2.2504","DOIUrl":"https://doi.org/10.1002/bdr2.2504","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Ambrisentan is a selective endothelin-1 receptor antagonist marketed for pulmonary arterial hypertension (PAH) in adults, adolescents, and children above 8 years old.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>A juvenile toxicity study conducted to support clinical studies in patients under 8 years old dosed rats from postnatal days 7 to 62. In subsequent investigative studies, respiratory function was assessed by ventilatory parameters and arterial blood gases, along with other endpoints.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Noisy breathing occurred, and brain weight was lower (4%, <i>p</i> &lt; 0.05) without histologic changes at the highest dose (20 mg/kg/day). Respiratory sounds described as clicking noises seemingly synchronous with the breathing cycle were sustained. Hypoxemia and hypercapnia associated with apneic times occurred, suggesting an intermittent physical airway blockade.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>It's postulated that the brain weight decrease was mediated by sustained hypoxemia during a period of rapid brain growth. Improper interaction of rat laryngeal tissues, in close apposition during early postnatal stages, may constitute a sensitive period. Clinical relevance is unknown; palatal/laryngeal maturation timing in healthy children supports up to ~2 years as the period for any potential risk. However, for children with PAH, chronic hypoxemia and/or concomitant conditions associated with developmental delay could hypothetically extend the sensitive age period for potential risk through the third year of life.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 7","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144606511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “How Does Maternal Lipopolysaccharide Exposure Impact Prenatal Testicular Development in Rats, and Could α-Tocopherol Provide a Protective Effect? A Histological, Immunohistochemical and Biochemical Study”","authors":"","doi":"10.1002/bdr2.2502","DOIUrl":"https://doi.org/10.1002/bdr2.2502","url":null,"abstract":"<p>Fareed, S. A., H. E.-S. Mostafa, Y. M. Saleh, Y. I. Magdi, and I. M. M. Ammar. 2025. “How Does Maternal Lipopolysaccharide Exposure Impact Prenatal Testicular Development in Rats, and Could α-Tocopherol Provide a Protective Effect? A Histological, Immunohistochemical and Biochemical Study.” <i>Birth Defects Research</i> 117: e2469. https://doi.org/10.1002/bdr2.2469.</p><p>In the originally published article, the following sentence in the Abstract is incorrect:</p><p>“Forty pregnant female rats were divided into four groups. Group I (control) included a negative control receiving normal saline and a positive control receiving 30 mg/kg of α-tocopherol intraperitoneally from the 3rd to 18th gestational day.”</p><p>The correct sentence is:</p><p>“Forty pregnant female rats were divided into three groups. Group I (control) was divided into two subgroups: Group Ia (negative control; receiving normal saline) and Group Ib (positive control; receiving 30 mg/kg of α-tocopherol intraperitoneally from the 3rd to 18th gestational day).”</p><p>In the Animals and Experimental Procedures section of the Materials and Methods section the following sentences are incorrect. They are presented below with the correct sentences.</p><p>Incorrect: “The pregnant rats were divided into four groups (10 pregnant rats for each) as follows…”</p><p>Correct: “The pregnant rats were divided into three groups as follows…”</p><p>Incorrect: “Group I (Control groups): Divided into two subgroups as follows (<i>n</i> = 5)…”</p><p>Correct: “Group I (Control groups): Divided into two subgroups as follows (<i>n</i> = 10 for each subgroup):”</p><p>“<i>Group II</i> (<i>LPS group</i>)” was omitted from the following sentence: “Group II (LPS group, <i>n</i> = 10 rats)…”</p><p>“Group III (α-T + LPS, protected group)” was omitted from the following sentence: “Group III (α-T + LPS, protected group, <i>n</i> = 10 rats)…”</p><p>We apologize for these errors.</p>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 7","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bdr2.2502","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144606561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microarray Application in Newborns With Multiple Congenital Anomalies: Genotype–Phenotype Correlation","authors":"Ramazan Keçeci,&nbsp;Hayriye Nermin Keçeci,&nbsp;Müşerref Başdemirci","doi":"10.1002/bdr2.2509","DOIUrl":"https://doi.org/10.1002/bdr2.2509","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Microarray is considered the first step in the diagnostic test in patients with multiple congenital anomalies (MCA). This technique can detect small copy number variations (CNVs) in DNA and help to understand the genetic causes in newborns.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials &amp; Methods</h3>\u0000 \u0000 <p>The present study investigated a group of 63 newborns with MCA during the study period. Microarray analysis was performed on newborns with MCA after excluding those with examination results suggesting a recognizable numerical chromosome anomaly and a history of teratogenicity. The observed CNVs were examined in databases, pathogenicity evaluation was performed, and the variations were compared with the results reported in the patient database.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 11 of 50 patients (22%) included in the study had 13 CNVs. Variations in the literature were observed in nine of the previously described cases, while the other four CNVs were described for the first time. Among the detected CNVs, nine were pathogenic, one was likely pathogenic, and three were of uncertain clinical significance (VOUS). The variation in four patients was de novo, two were paternally inherited, and one was maternally inherited. All 11 patients with CNVs had congenital heart defects, 9 had craniofacial dysmorphism, 8 had extremity anomalies, 4 had hydronephrosis, 3 had cleft lip and/or palate, 2 had proximal hypospadias, and other rare congenital anomalies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Microarray application in newborns with MCA is of great importance in terms of clinical guidance and genetic counseling. With the increase in relevant studies, the interpretation of previously unidentified CNVs with clinical results will contribute to patient management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 7","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144606562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to Food Fortification Ineffective in Preventing Neural Tube Defects in India due to Regulation Promoting Inadequate Levels of Folic Acid and Vitamin B12","authors":"","doi":"10.1002/bdr2.2510","DOIUrl":"https://doi.org/10.1002/bdr2.2510","url":null,"abstract":"<p>Kancherla, V., P. Bhalla, S. K. Dutta, R. Mehta, R. M. Vora, and S. Karmarkar. 2025. “Food Fortification Ineffective in Preventing Neural Tube Defects in India due to Regulation Promoting Inadequate Levels of Folic Acid and Vitamin B12.” <i>Birth Defects Research</i> 117, no. 7: e2498. https://doi.org/10.1002/bdr2.2498.</p><p>In the originally published article, an incorrect unit of measurement was given in Section 1. The corrected unit is given below. This has been corrected in the online version of the article.</p><p>Incorrect</p><p>The 2020 RDA proposed for vitamin B12 ranges between 1.2 and 2.5 mg for non-pregnant women, children, and men (FSSAI 2021).</p><p>Correct</p><p>The 2020 RDA proposed for vitamin B12 ranges between 1.2 and 2.5 mcg for non-pregnant women, children, and men (FSSAI 2021).</p><p>We apologize for this error.</p>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 7","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bdr2.2510","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144606556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional Annotation of De Novo Variants Found Near GWAS Loci Associated With Cleft Lip With or Without Cleft Palate","authors":"Sarah W. Curtis,&nbsp;Laura E. Cook,&nbsp;Kitt Paraiso,&nbsp;Axel Visel,&nbsp;Justin L. Cotney,&nbsp;Jeffrey C. Murray,&nbsp;Terri H. Beaty,&nbsp;Mary L. Marazita,&nbsp;Jenna C. Carlson,&nbsp;Elizabeth J. Leslie-Clarkson","doi":"10.1002/bdr2.2499","DOIUrl":"https://doi.org/10.1002/bdr2.2499","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Orofacial clefts (OFCs) are the most common craniofacial birth defects, affecting 1 in 700 births, and have a strong genetic basis with a high recurrence risk within families.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>While many of the previous studies have associated common, noncoding genetic loci with OFCs, previous studies on de novo variants (DNVs) in OFC cases have focused on coding variants that could have a functional impact on protein structure, and the contribution of noncoding DNVs to the formation of OFCs has largely been ignored and is not well understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We reanalyzed an existing dataset of DNVs from 1409 trios with OFCs that had undergone targeted sequencing of known OFC-associated loci. We then annotated these DNVs with information from datasets of predicted epigenetic function during human craniofacial development.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 66 DNVs called in the targeted regions in this study, 17 (25.7%) were within a predicted enhancer or promoter region. Two DNVs fell within the same enhancer region (hs1617), which is more than expected by chance (<i>p</i> = 0.0017). The sequence changes caused by these hs1617 DNVs are predicted to create binding sites not seen in the reference sequence for transcription factors PAX6 and ZBTB7A and to disrupt binding sites for STAT1 and STAT3.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>The hs1617 enhancer region is within the same topologically associated domain as <i>HHAT</i>, <i>SERTAD4</i>, and <i>IRF6</i>, all of which are involved in craniofacial development. All three genes are highly expressed in human neural crest cells. Knockout mice for <i>Hhat</i> and <i>Irf6</i> have abnormal embryonic development including a cleft palate, and variants in and around <i>IRF6</i> are associated with nonsyndromic and syndromic forms of OFCs in humans.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Taken together, this suggests that noncoding DNVs contribute to the genetic architecture of OFCs, with an excess of DNVs in OFC trios in enhancer regions near known OFC-associated genes. Overall, this adds to our understanding of the genetic mechanisms that underlie OFC formation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 7","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144581771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prenatal Exposure to Methamphetamine and Its Association With Birth Outcomes: A Meta-Analysis","authors":"Nima Rastegar-Pouyani,&nbsp;Fatemeh Fakhari,&nbsp;Armineh Rezagholi Lalani,&nbsp;Emad Jafarzadeh,&nbsp;Reza Zafari,&nbsp;Nader Rahimi,&nbsp;Ahmad Habibian Sezavar,&nbsp;Seyed Nasser Ostad","doi":"10.1002/bdr2.2488","DOIUrl":"https://doi.org/10.1002/bdr2.2488","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>The growing prevalence of methamphetamine abuse has been regarded as a matter of great concern due to its damaging impact on public health worldwide. Our study aimed to perform a systematic review of the literature with meta-analysis to evaluate the association between prenatal methamphetamine exposure, Preterm Birth (PTB) Low Birth Weight (LBW), and being Small for Gestational Age (SGA). Later on, we investigated the association between prenatal methamphetamine use and the aforementioned birth defects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a systematic search of English-language articles in Web of Science, Scopus, and PubMed from inception to December 24, 2021, identifying 1223 observational studies. After removing duplicates, 911 articles remained for title and abstract screening, of which 868 were excluded. Following a full-text review of 43 studies, 35 were excluded due to insufficient data, leaving eight studies for meta-analysis. Data were analyzed using Stata 15.0, with Odds Ratio (OR) (95% Confidence Intervals (CI)) as effect sizes. Subgroup analysis was performed by sample type (urine, meconium, and …), and heterogeneity was assessed using the Chi-square test (<i>I</i>² more than 50% was considered heterogenic), applying fixed- or random-effects models accordingly. Publication bias was evaluated via Egger's test and funnel plots, and sensitivity analysis was conducted to assess result robustness.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Prenatal exposure to methamphetamine was found to be associated with PTB (OR 2.64; 95% CI 1.89–3.70), LBW (OR 2.83; 95% CI 1.09–7.38), and SGA (OR 1.44; 95% CI 1.04–1.99).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our meta-analysis shows a substantial association between prenatal exposure to methamphetamine and PTB, LBW, and being SGA.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 7","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}