Birth Defects Research最新文献

{"title":"Differential Associations of Maternal Factors With Anotia and Microtia Laterality in a North American Case–Control Study","authors":"Molly N. Hoffman,&nbsp;Sharon M. Casey,&nbsp;Martha M. Werler,&nbsp;Samantha E. Parker","doi":"10.1002/bdr2.70123","DOIUrl":"10.1002/bdr2.70123","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Congenital underdevelopment of one or both ears (microtia/anotia) is the most common component of craniofacial microsomia (CFM). Although the right side is more commonly affected, social determinants of laterality remain understudied.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using a multicenter North American case–control study of CFM (1996–2002), we evaluated associations between maternal periconceptional cigarette smoking, pregnancy intention, timing of pregnancy recognition, education, and prepregnancy body mass index with microtia/anotia, overall and by laterality. Cases were 137 children &lt; 36 months with microtia/anotia identified at craniofacial centers; up to 4 controls per case (<i>n</i> = 678) were matched on residence, age at ascertainment, and calendar time. Exposures were ascertained from maternal interviews. We performed conditional logistic regression adjusted for maternal age and education to estimate odds ratios (ORs) and 95% CIs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 137 cases, 51 (37%) were left-sided, 61 (45%) right-sided, 11 (8%) bilateral, and 14 (10%) unknown. Point estimates for smoking, later pregnancy recognition, lower education, and obesity were elevated overall, though confidence intervals were wide. Left-sided ORs were smoking 2.16 (95% CI: 0.88–5.30); unplanned pregnancy 1.36 (95% CI: 0.67–2.78); pregnancy recognition &gt; 9 weeks after last menstrual period (vs. &lt; 5 weeks) 3.64 (95% CI: 0.95–14.03); &lt; 12 years of education (vs. ≥ 16 years) 5.24 (95% CI: 1.47–18.68); and obesity (vs. normal weight) 1.65 (95% CI: 0.58–4.63). Corresponding right-sided ORs were 1.28, 1.00, 1.63, 2.11, and 1.24.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Several maternal factors were modestly associated with microtia/anotia, with consistently larger estimates for left- than right-sided anomalies. These findings provide limited evidence that the etiology of microtia/anotia may differ by laterality and warrant confirmation in larger studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 10","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191106","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":"Ameliorative Potential of Green and Red Cabbage Extracts Against Teratogenic and Hepatotoxic Effects of Dimenhydrinate in Chick Embryo","authors":"Naila Kanwal,&nbsp;Iram Inayat,&nbsp;Muhammad Ali Kanwal,&nbsp;Syeda Nadia Ahmad,&nbsp;Aima Iram Batool,&nbsp;Khawaja Raees Ahmad,&nbsp;Asma Younis,&nbsp;Saira Siddique,&nbsp;Rabiyah Ali","doi":"10.1002/bdr2.70120","DOIUrl":"10.1002/bdr2.70120","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Dimenhydrinate (DH) is the first generation medicine used as antiemetic. It is neurotoxic in rat and chick embryos. Both green cabbage (GCbg) and red cabbage (RCbg) have many health benefits and red cabbage is also full of anthocyanins and may minimize oxidative stress in chick embryo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Material and Method</h3>\u0000 \u0000 <p>The study was designed to check the teratogenic impacts of dimenhydrinate and curative abilities of green and red cabbage extracts against dimenhydrinate in chick embryo through morphometry, histopathology and micrometry. Fertilized eggs were divided into six groups (<i>n</i> = 50): (1) control (Cnt), injected with 0.02 mL distilled water (2) GCbg, injected with 0.02 mL green cabbage extract (3) RCbg, injected with 0.02 mL red cabbage extract (4) DH, injected with 0.02 mL dimenhydrinate (5) DH + GCbg, injected with 0.01 mL dimenhydrinate and 0.01 mL green cabbage extract (6) DH + RCbg, injected with 0.01 mL dimenhydrinate and 0.01 mL red cabbage extract. All groups were administered on the zero day of incubation, and recovery was made on the 14th day.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The embryos of DH exposed group indicated significant decrease in embryonic body weight (7.71 ± 2.82 g) and liver weight (0.03 ± 0.02 g) as compared to control group (15.58 ± 0.75 g; 0.35 ± 0.01 g). The prominent morphometric malformations were amelia, phocomelia, microcephaly and microtia. The hepato-histopathologic signs include decreased hepatocytes, irregular hepatocyte cords and sinusoidal space and de-shaping central veins.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Concusion</h3>\u0000 \u0000 <p>This study indicated that dimenhydrinate is teratogenic in chick embryo and both cabbages have ability to decrease birth defects and red cabbage indicated more positive potential compared to green cabbage.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 10","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164737","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":"Effects of Vitamin B12, Folic Acid, and L-Carnitine on Congenital Malformations Induced by Vitamin A Hypervitaminosis","authors":"İlayda Açık,&nbsp;Alpaslan Gökçimen,&nbsp;Nur Sevim Kalkan","doi":"10.1002/bdr2.70118","DOIUrl":"10.1002/bdr2.70118","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Excessive intake of exogenous vitamin A during pregnancy has been associated with congenital malformations. This experimental study aimed to evaluate whether vitamin B12, folic acid, and L-carnitine exert a protective or contributory effect on malformations induced by hypervitaminosis A.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Thirty-five healthy adult female Wistar albino rats and seven male rats were used. Pregnant rats received vitamin A alone or in combination with vitamin B12, folic acid, or L-carnitine for 21 consecutive days (GD 0–21). At the end of gestation, neonates were evaluated for gross congenital malformations. Brain, liver, and eye tissues were excised and processed for histopathological and morphometric analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No gross external malformations were observed in any group; however, significant growth restriction and multi-organ histopathological alterations were detected in the offspring. Histological examination revealed interstitial edema in brain tissue and retinal detachment in the eye. Hepatic alterations included sinusoidal dilatation, hyperchromatic nuclei, necrotic cells, and cytoplasmic degenerative changes; these lesions remained mild. Somatic and organ morphometry showed that vitamin B12 supplementation partially alleviated retinoid-induced somatic growth retardation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Although maternal hypervitaminosis A did not cause overt external malformations under the tested regimen, it induced multi-organ histopathological damage and severe fetal growth restriction. Adjuvant supplementation, particularly with vitamin B12, demonstrated modulatory effects against retinoid-induced developmental suppression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 10","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104142","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":"The Fetal Effects of Chorionic Villus Sampling","authors":"Lewis B. Holmes,&nbsp;Caroline M. Golden,&nbsp;Joan M. Stoler,&nbsp;Stephen E. Gellis,&nbsp;Hamzeh Nasri,&nbsp;Anne-Therese Hunt","doi":"10.1002/bdr2.70106","DOIUrl":"https://doi.org/10.1002/bdr2.70106","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Physical examinations have been essential in the delineation of the spectrum of teratogenic effects of teratogens, such as valproate, isotretinoin and thalidomide, as well as chorionic villus sampling (CVS). CVS became an alternative to amniocentesis in the 1980s, because results were provided earlier in pregnancy. In 1991, a dramatic report of 5 CVS-exposed infants, out of 289 exposed, with severe limb and craniofacial defects raised the question of a significant risk, particularly when the procedure was carried out before 70 days of gestation. Some epidemiologic studies using data from birth defects registries showed an increase in the number of CVS-exposed infants with limb reduction defects and others did not. However, case reports of physical examination findings showed a wider range of abnormalities, including hypoplasia of two or three fingers or toes in CVS-exposed children as well as terminal transverse limb defects with nubbins. In addition, hemangiomas were found to be a common non-limb malformation in CVS-exposed children.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Presented here are the findings from a case-control study of 38 CVS-exposed and 41 unexposed, matched children.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results and Conclusions</h3>\u0000 \u0000 <p>The physical examinations identified a spectrum of abnormalities from terminal transverse limb defects with nubbins to hypoplastic, shortened or stiff fingers and toes with small or absent nails.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 10","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149068595","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":"Developmental Toxicity Study for the Antimalarial Drug Combination Cabamiquine-Pyronaridine Using a Translational Approach","authors":"Wookyung Kim,&nbsp;Geum-Sil Cho,&nbsp;Andreas Gado,&nbsp;Tobias Hyun Ho Baeurle,&nbsp;Habib Karimi,&nbsp;Filippo Venezia,&nbsp;Claude Oeuvray,&nbsp;Thomas Spangenberg,&nbsp;Sebastian G. Wicha,&nbsp;Claudia Demarta-Gatsi","doi":"10.1002/bdr2.70105","DOIUrl":"10.1002/bdr2.70105","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The safety of pharmacological treatments during pregnancy is a significant concern, as many medications lack comprehensive reproductive safety data. This creates gaps in therapeutic options for pregnant women, particularly malaria, which poses serious risks to maternal and fetal health. Additionally, there is an urgent need to develop combination therapies for which reproductive safety data are currently unavailable, further complicating treatment options for this vulnerable population. The combination of cabamiquine and pyronaridine emerges as a promising solution; however, since no reproductive safety data exist for this combination, comprehensive evaluations are essential to ensure maternal and fetal well-being.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Materials and Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The cabamiquine–pyronaridine combination was evaluated using an in vivo embryo-fetal development (EFD) toxicity study in rats and a Zebrafish Embryo Developmental Toxicity Assay (ZEDTA), following regulatory frameworks. Zebrafish developmental toxicity data were further integrated using pharmacokinetic and toxicokinetic modeling to assess safety margins and predict potential toxicity at anticipated clinical study doses and exposures.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Combined administration of cabamiquine and pyronaridine showed no significant impact on prenatal outcomes. Both compounds exhibited dose-proportional increases in maternal systemic exposure, with no fetal mortality or adverse findings. No adverse effects on embryo-fetal development were observed at the previously defined monotherapy NOAEL doses, indicating the absence of adverse drug–drug interactions. Safety assessments at higher doses in the ZEDTA revealed no toxicity effects at ongoing clinical study doses. Pharmacokinetics and toxicokinetics modeling do not suggest the potential of cabamiquine and pyronaridine to cause toxicity at the forecast clinical study doses and anticipated exposures.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Discussion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The combined findings from the rat EFD study, ZEDTA, and model-based pharmacokinetic and toxicokinetic analyses consistently demonstrated the absence of developmental toxicity and adverse drug-drug interactions across multiple complementary approaches. These data provide confidence that the combination is unlikely to pose developmental safety concerns at clinically relevant exposures.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 ","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 10","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079709","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":"Epidemiology of Neural Tube Defects in Puerto Rico in the Era of Folic Acid Fortification: Population-Based Surveillance, Pregnancy Outcomes, and Lesion Patterns (2015–2024)","authors":"Derick Rodríguez-Reyes,&nbsp;Hiram E. Luigi-Martinez,&nbsp;Joseph Salem-Hernández,&nbsp;Gustavo E. Ronda-Rodríguez,&nbsp;Samuel Fernández","doi":"10.1002/bdr2.70110","DOIUrl":"10.1002/bdr2.70110","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neural tube defects (NTDs) remain clinically important congenital conditions, but contemporary Puerto Rico–specific epidemiological data in the current folic acid fortification era are limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To describe the epidemiology of NTDs in Puerto Rico from 2015 through 2024, characterize pregnancy outcomes and lesion patterns, evaluate temporal trends, and compare contemporary metrics with prior Puerto Rico reports using directly comparable denominators.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Retrospective population-based cross-sectional surveillance study of NTD-affected pregnancies in Puerto Rico, 2015–2024. Case data were obtained from the Puerto Rico NTD surveillance dataset; annual live-birth denominators were obtained from the Puerto Rico Department of Health. Surveillance-based rates per 10,000 live births were calculated with exact Poisson 95% confidence intervals. Temporal trends were evaluated with negative binomial regression. The study was conducted under local institutional and public health data policies as a secondary analysis of de-identified data; institutional review board review was not required.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 194 NTD-affected pregnancies and 220,138 live births, the overall surveillance-based rate was 8.8 per 10,000 live births (95% CI 7.6, 10.1). No significant temporal trend was identified (rate ratio 1.01, 95% CI 0.81, 1.26). The live-born NTD rate was 3.7 per 10,000 live births (95% CI 3.0, 4.6). Spina bifida (88; 45.4%) and anencephaly (79; 40.7%) predominated. Termination occurred in 54 of 79 (68.4%) anencephaly pregnancies compared with 23 of 88 (26.1%) spina bifida pregnancies. Lumbosacral lesions were the most common spina bifida level (39; 44.3%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The contemporary live-born NTD rate in Puerto Rico is lower than the pre-fortification era estimate, reflecting the influence of prenatal diagnosis and termination. The overall surveillance-based rate remains similar to the earlier post-fortification estimate, with no significant recent decline, supporting the need for strengthened territory-specific surveillance and earlier, coordinated folate-centred prevention strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 9","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015566","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":"Compound Heterozygous Mutations in FGA Cause Congenital Afibrinogenemia: A Case Report and Literature Review","authors":"Liangliang Liu,&nbsp;Desheng Yuan,&nbsp;Huaxing Zhao,&nbsp;Bacui Yu","doi":"10.1002/bdr2.70109","DOIUrl":"10.1002/bdr2.70109","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Congenital afibrinogenemia is an extremely rare autosomal recessive bleeding disorder with an estimated incidence of one in one million, caused by mutations in the fibrinogen-encoding genes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We report a genetically confirmed case of FGA-related congenital afibrinogenemia in a 9-year-old female child. Comprehensive coagulation analysis revealed undetectable fibrinogen activity (FIB:C, &lt; 0.2 g/L) as measured by the Clauss assay, along with significantly prolonged prothrombin time, activated partial thromboplastin time, and thrombin time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Next-generation sequencing targeting coagulation-related genes identified compound heterozygous mutations in FGA (NM_000508): a paternal nonsense mutation c.502C&gt;T (p.Arg168Ter) in Exon 4 and a maternal frameshift mutation c.668delT (p.Leu223ArgfsX2) in Exon 5. These pathogenic variants were further confirmed by Sanger sequencing in the proband and her parents, which demonstrated that the proband carried the two FGA variants in a compound heterozygous state, with paternal inheritance of c.502C&gt;T and maternal inheritance of c.668delT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This case expands the genotype–phenotype correlation database for fibrinogen disorders and underscores the necessity of molecular diagnosis for congenital coagulation defects.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 9","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148987938","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":"Accuracy of Preliminary Birth Defect Surveillance in Utah: A Validation Study Supporting Timely Family Referrals","authors":"Aubree Boyce,&nbsp;Stephanie Pocius","doi":"10.1002/bdr2.70119","DOIUrl":"https://doi.org/10.1002/bdr2.70119","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Public health surveillance is critical for understanding disease burden, yet rigorous case confirmation often introduces significant latency. The Utah Birth Defect Network (UBDN) utilizes a multistage active surveillance process that, while highly accurate, is a long and labor-intensive process. This delay creates a barrier to timely family referrals for early intervention services. This study evaluates whether preliminary surveillance data is sufficiently accurate to initiate public health actions before final clinician confirmation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective analysis of 27 monitored birth defects for delivery years 2018–2025. Positive predictive values (PPVs) were calculated for cases identified during initial medical record review by nonclinical staff compared with the “gold standard” of final clinician-led confirmation. Analysis was performed using SAS version 9.4, with 95% confidence intervals calculated via the Wilson score method.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 1245 unique potential cases, the overall mean PPV was 68% (range: 8%–95%). Accuracy was highest for musculoskeletal defects (95%) and chromosomal anomalies (92%), with gastroschisis (95%), limb deficiencies (93%), and Trisomy 21 (92%) showing high stability. Cardiovascular defects demonstrated lower categorical accuracy (78%), with complex conditions like single ventricle (8%) showing the greatest diagnostic discordance. However, we observed categorical stability, as 77% of reclassified cardiovascular cases remained within the same body system.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Preliminary surveillance reviews demonstrate high diagnostic stability for the majority of monitored conditions. These findings validate the use of preliminary data to trigger early family-centered referrals, significantly reducing the latency between case confirmation and intervention without compromising the integrity of formal reporting.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 9","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148994345","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":"Evaluating the Performance of Traditional Pharmacoepidemiologic and Machine Learning Models to Predict Pregnancies at Risk of Major Congenital Malformations","authors":"Gabra Nohmie,&nbsp;Marc Lanovaz,&nbsp;Odile Sheehy,&nbsp;Cristina Longo,&nbsp;Robert Platt,&nbsp;Audrey Durand,&nbsp;Christine Damase-Michel,&nbsp;Anick Bérard","doi":"10.1002/bdr2.70117","DOIUrl":"10.1002/bdr2.70117","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>With approximately 50% of pregnancies being unplanned, there is an unintended exposure to potential feto-toxic drugs that may cause major congenital malformations (MCM). This study aims to compare the predictive performance between traditional pharmacoepidemiologic (PE) and machine learning (ML) models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a cohort study within the Quebec Pregnancy Cohort, including all pregnancies covered by Quebec's prescription drug insurance program and their children from 01/1998 to 12/2015. Medication exposures, comorbidities, and women's characteristics 12 months before pregnancy and during the first trimester were considered. Robust Poisson models were used to obtain adjusted risk ratios (aRR) and 95% confidence intervals (CI) of predictors. Logistic regression, robust Poisson, K-Nearest Neighbors, Random Forest, XGBoost, Naïve bayes, Multilayer Perceptron, and Support Vector Machine were developed to predict pregnancies at risk of MCM. Sensitivity, specificity, PPV, NPV, accuracy, ROC-AUCs, PR-AUCs, and F1-score were used to evaluate the performance of predictive models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We analyzed 213,744 pregnancies, finding a 9.7% prevalence of MCM. Logistic regression had the highest discriminative power across models at predicting MCM, with a ROC-AUC of 53.3% and the highest sensitivity (41.5%) and F1-score (46.6%). KNN had the highest specificity (97.9%) but the lowest sensitivity (2.3%). Robust Poisson performed similarly to logistic regression, with the highest accuracy (52.3%). Robust Poisson performed slightly better than logistic regression at classifying organ-specific malformations. All models showed poor overall predictive performance. Results were robust across sensitivity analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>There is insufficient evidence for the superiority of ML over traditional pharmacoepidemiologic modeling in predicting MCM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 9","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13550799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905115","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":"Nicotine Exposure During Gestation: From Placental Dysfunction to Long-Term Neurobehavioral Outcomes","authors":"Harsh Dave,&nbsp;Shubham Maru,&nbsp;Kaid Johar SR","doi":"10.1002/bdr2.70115","DOIUrl":"10.1002/bdr2.70115","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Prenatal nicotine exposure (PNE) remains a significant public health concern due to persistent tobacco use, electronic nicotine delivery systems, and second-hand exposure during pregnancy. Epidemiological and experimental evidence has demonstrated that nicotine can readily cross the placenta, disrupt placental development, and interfere with tightly regulated processes of fetal organogenesis. These early perturbations are increasingly recognized as initiating a cascade of structural, functional, and molecular alterations that extend beyond gestation and influence health trajectories across the lifespan. However, existing studies are often compartmentalized by developmental stage, limiting mechanistic integration across prenatal, natal, postnatal, and later-life outcomes.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This review aims to (i) synthesize evidence from placental biology, developmental toxicology, neurobiology, and epigenetics to propose an integrated, life-course cascade model of PNE; (ii) delineate how nicotine-induced placental dysfunction and fetal hypoxia during prenatal development transition into structural, physiological, perinatal autonomic, and cardiorespiratory vulnerability, contributing to adverse birth outcomes and increased risk of sudden infant death syndrome; and (iii) examine how early disruption of nicotinic acetylcholine receptor mediated signaling alters neuronal differentiation, synaptic maturation, neuroimmune interactions, and stress-response pathways, leading to persistent cognitive, behavioral, and psychiatric susceptibility in postnatal life and adulthood. Emerging evidence for epigenetic reprogramming, sex-specific vulnerability, and intergenerational transmission, including paternal contributions, is also evaluated.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Evidence synthesized across placental biology, developmental toxicology, neurobiology, and epigenetics supports a cascade in which nicotine-induced placental dysfunction and fetal hypoxia contribute to structural, physiological, perinatal autonomic, and cardiorespiratory vulnerability, adverse birth outcomes, and increased risk of sudden infant death syndrome. Early disruption of nicotinic acetylcholine receptor-mediated signaling is associated with alterations in neuronal differentiation, synaptic maturation, neuroimmune interactions, and stress-response pathways, contributing to persistent cognitive, behavioral, and psychiatric susceptibility in postnatal life and adulthood. Emerging evidence also supports roles for epigenetic reprogramming, sex-specific vulnerability, and intergenerational transmission, including paternal contributions.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 ","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 9","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886427","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}