Search

Gastroschisis and omphalocele are the two most common abdominal wall birth defects, and epidemiologic characteristics and frequency of occurrence as part of a syndromic condition suggest distinct etiologies between the two defects. We assessed complex patterns of defect co-occurrence with these defects separately using the Texas Birth Defects Registry. We used co-occurring defect analysis (CODA) to compute adjusted observed-to-expected (O/E) ratios for all observed birth defect patterns. There were 2,998 non-syndromic (i.e., no documented syndrome diagnosis identified) cases with gastroschisis and 789 (26%) of these had additional co-occurring defects. There were 720 non-syndromic cases with omphalocele, and 404 (56%) had additional co-occurring defects. Among the top 30 adjusted O/E ratios for gastroschisis, most of the co-occurring defects were related to the gastrointestinal system, though cardiovascular and kidney anomalies were also present. Several of the top 30 combinations co-occurring with omphalocele appeared suggestive of OEIS (omphalocele, exstrophy of cloaca, imperforate anus, spinal defects) complex. After the exclusion of additional cases with features suggestive of OEIS in a post-hoc sensitivity analysis, the top combinations involving defects associated with OEIS (e.g., spina bifida) were no longer present. The remaining top combinations involving omphalocele included cardiovascular, gastrointestinal, and urogenital defects. In summary, we identified complex patterns of defects that co-occurred more frequently than expected with gastroschisis and omphalocele using a novel software platform. Better understanding differences in the patterns between gastroschisis and omphalocele could lead to additional etiologic insights.

BACKGROUND Maternal hypertension has been associated with congenital heart defect occurrence in several studies. We assessed whether maternal genotypes associated with this condition were also associated with congenital heart defect occurrence. METHODS We used data from the National Birth Defects Prevention Study to identify non-Hispanic white (NHW) and Hispanic women with (cases) and without (controls) a pregnancy in which a select simple, isolated heart defect was present between 1999 and 2011. We genotyped 29 hypertension-related single nucleotide polymorphisms (SNPs). We conducted logistic regression analyses separately by race/ethnicity to assess the relationship between the presence of any congenital heart defect and each SNP and an overall blood pressure genetic risk score (GRS). All analyses were then repeated to assess 4 separate congenital heart defect subtypes. RESULTS Four hypertension-related variants were associated with congenital heart defects among NHW women (N = 1,568 with affected pregnancies). For example, 1 intronic variant in ARHGAP2, rs633185, was associated with conotruncal defects (odds ratio [OR]: 1.3, 95% confidence interval [CI]: 1.1–1.6). Additionally, 2 variants were associated with congenital heart defects among Hispanic women (N = 489 with affected pregnancies). The GRS had a significant association with septal defects (OR: 2.1, 95% CI: 1.2–3.5) among NHW women. CONCLUSIONS We replicated a previously reported association between rs633185 and conotruncal defects. Although additional hypertension-related SNPs were also associated with congenital heart defects, more work is needed to better understand the relationship between genetic risk for maternal hypertension and congenital heart defects occurrence.

Purpose Maternal body mass index (BMI) is inversely associated with gastroschisis, but a causal relationship has not been established. As data demonstrating that a change in exposure status is related to a change in the frequency of the outcome can add to the evidence for causality, we conducted a case-control study of change in maternal BMI, assessed using interpregnancy change in BMI (IPC-BMI), and gastroschisis. Methods Data for 258 gastroschisis cases and 2,561 controls were obtained from the Texas Birth Defects Registry and vital records (2006-2012). Logistic regression was used to estimate the adjusted association between IPC-BMI and gastroschisis. Results The continuous IPC-BMI variable was inversely associated with gastroschisis (adjusted odds ratio [aOR]=0.90, 95% confidence interval [CI]: 0.86-0.95). When assessed as a six-level categorical variable, with weight stable women as the referent, the odds of gastroschisis were higher following a BMI decrease of >1 unit (aOR=1.37, 95% CI: 0.91-2.06) and lower after a BMI increase of > 3 units (aOR=0.62, 95% CI: 0.42-0.94) Conclusions Our findings suggest that maternal change in BMI is associated with gastroschisis and, thus, add to the epidemiological evidence that can be used to inform our understanding of the relationship between BMI and gastroschisis.

To estimate the proportion of neonatal mortality risk attributable to preterm delivery among neonates with birth defects.Using a statewide cohort of live born infants from the Texas Birth Defects Registry (1999-2014 deliveries), we estimated the population attributable fraction and 95% CI of neonatal mortality (death28 days) attributable to prematurity (birth at37 weeks vs ≥37 weeks) for 31 specific birth defects. To better understand the overall population burden, analyses were repeated for all birth defects combined.Our analyses included 169 148 neonates with birth defects, of which 40 872 (24.2%) were delivered preterm. The estimated proportion of neonatal mortality attributable to prematurity varied by birth defect, ranging from 12.5% (95% CI: 8.7-16.1) for hypoplastic left heart syndrome to 71.9% (95% CI: 41.1-86.6) for anotia or microtia. Overall, the proportion was 51.7% (95% CI: 49.4-54.0) for all birth defects combined.A large proportion of deaths among neonates with birth defects are attributable to preterm delivery. Our results highlight differences in this burden across common birth defects. Our findings may be helpful for prioritizing future work focused on better understanding the etiology of prematurity among neonates with birth defects and the mechanisms by which prematurity contributes to neonatal mortality in this population.

The study of n-dimensional fuzzy logic contributes to overcome the insufficiency of traditional FL in modeling imperfect and imprecise information coming from different experts. Based on representability, we extend results from fuzzy connectives to n-dimensional approach. This research on n-dimensional fuzzy implications (n-DI) pass through the next steps: (i) analytical studies; (ii) algebraic aspects; (iii) n-dimensional approach of fuzzy implication classes represented by fuzzy connectives as (S, N)-implications and QL-implications; (iv) studies of n-dimensional R-implications (n-DRI); (v) constructive method obtaining n-DRI based on n-dimensional aggregation operators and (vi) an introductory study considering an n-DI in modeling approximate reasoning.

This paper aims to study the Atanassov's correlation coefficient (A-CC) between two of Atanassov's intuitionistic fuzzy sets (A-IFS), obtained as images of intuitionistic fuzzy modal operators. The composition of modal operators are investigated, verifying under which conditions an A-CC preserves the main properties related to conjugate and complement operations performed on A-IFS. In addition, a simulation based on the proposal methodology using operators described above is applied to a medical diagnosis analysis.

Background It is hypothesized that cesarean delivery may reduce mortality among infants with spina bifida (e.g., by reducing trauma to the open lesion); however, few studies have assessed this relationship. Methods We used the Texas Birth Defects Registry to identify neonates with spina bifida born between 1999 and 2014. The mode of delivery (main exposure) was abstracted from each subject's birth certificate. The vital status (main outcome) was determined based on the presence or absence of a death certificate. When a death certificate was present, survival time was calculated by subtracting the date of birth from the date of death. We then conducted multivariable Cox proportional hazards regression to estimate the adjusted hazard ratio between cesarean delivery and death prior to 29 days. We adjusted for maternal race/ethnicity, maternal education, gestational age/birthweight, and breech presentation. This analysis was repeated for death prior to 365 days. Results We analyzed 1,983 nonsyndromic, liveborn neonates with spina bifida, and 68% of these neonates were delivered by cesarean. After adjusting for potential confounders, the adjusted hazard ratio [aHR] for death prior to 29 days was 0.77 (95% confidence interval [CI] 0.49, 1.21) and the aHR for death prior to 365 days was 0.93 (95% CI 0.63, 1.38) comparing infants delivered by cesarean to those delivered vaginally. Conclusions Despite a lack of strong prior epidemiologic evidence, cesarean rates for neonates with spina bifida were high. Further investigations of the relationship between mode of delivery and infant outcomes, including mortality, complications, and long-term prognosis, are warranted.

O presente artigo teve por objetivo compreender como um grupo de professoras de inglês que atuam na escola pública reconhecem o ensino da língua inglesa nesse espaço, em particular, observamos os sentidos elaborados pelas docentes acerca do lugar da língua inglesa na escola pública e da justificativa para ensinar o idioma nesse espaço. Para tanto, realizamos uma análise enunciativo-discursiva de seus discursos, com aporte na dialogia de Bakhtin. Depreendemos das análises que a disciplina se configura como supérflua no espaço escolar e também não é reconhecida pelas professoras como um conhecimento emancipador para os alunos da escola pública, ensejando a premência de uma discussão mais ampla acerca da docência em língua inglesa no âmbito da formação desses professores.

This article examines the centrality of uranium-enrichment centrifuges to the Brazilian nuclear program, arguing that these machines enabled the emergence of a technopolitical regime that i...

Objective: To investigate 2- to 5-way patterns of defects co-occurring with orofacial clefts using data from a population-based registry. Design: We used data from the Texas Birth Defects Registry for deliveries between 1999 and 2014 to Texas residents, including 1884 cases with cleft palate (CP) and 5289 cases with cleft lip with or without cleft palate (CL±P) without a known syndrome. We identified patterns of defects co-occurring with CP and with CL±P observed more frequently than would be expected if these defects occurred independently. We calculated adjusted observed-to-expected ( O/ E) ratios to account for the known tendency of birth defects to cluster nonspecifically. Results: Among infants without a syndrome, 23% with CP and 21% with CL±P had at least 1 additional congenital anomaly. Several combinations of defects were observed much more often than expected. For example, the combination of CL±P, congenital hydrocephaly, anophthalmia, and other nose anomalies had an O/ E ratio of 605. For both CP and CL±P, co-occurrence patterns with the highest O/ E ratios involved craniofacial and brain abnormalities, and many included the skeletal, cardiovascular, and renal systems. Conclusions: The patterns of defects we observed co-occurring with clefts more often than expected may help improve our understanding of the relationships between multiple defects. Further work to better understand some of the top defect combinations could reveal new phenotypic subgroups and increase our knowledge of the developmental mechanisms that underlie the respective defects.

Few population-based studies have analyzed patterns of co-occurring birth defects among those with trisomy 13. We evaluated the frequency of all possible combinations of any one, two, three, or four additional co-occurring birth defects among 736 individuals with trisomy 13 using data from the Texas Birth Defects Registry for deliveries during 1999-2014. We calculated the observed-to-expected ratio for each combination, adjusting for the known tendency for birth defects to cluster non-specifically. To address potential ascertainment differences among live births and non-live births, we repeated analyses specifically among live births. The combination of defects with the largest observed-to-expected ratio was microcephalus, reduction deformities of brain (e.g., holoprosencephaly), anomalies of nose, and polydactyly. As expected, most of the highest 30 observed-to-expected ratios involved combinations with documented features of trisomy 13, including defects of the scalp (e.g., aplasia cutis) and heart. Results were similar among sensitivity analyses restricted to live births. Our findings may help further delineate the phenotypic spectrum for trisomy 13 and may inform future research related to improving screening and counseling for the condition.

Supplemental Material, sj-docx-1-cpc-10.1177_10556656211010060 for Birth Defect Co-Occurrence Patterns Among Infants With Cleft Lip and/or Palate by Maria Luisa Navarro Sanchez, Renata H. Benjamin, Laura E. Mitchell, Peter H. Langlois, Mark A. Canfield, Michael D. Swartz, Angela E. Scheuerle, Daryl A. Scott, Hope Northrup, Christian P. Schaaf, Joseph W. Ray, Scott D. McLean, Han Chen, Philip J. Lupo and A.J. Agopian in The Cleft Palate-Craniofacial Journal

PURPOSE: Infants with anophthalmia or microphthalmia frequently have co-occurring birth defects. Nonetheless, there have been few investigations of birth defects patterns among these children. Such studies may identify novel multiple malformation syndromes, which could inform future research into the developmental processes that lead to anophthalmia/microphthalmia and assist physicians in determining whether further testing is appropriate. METHODS: This study includes cases with anophthalmia/microphthalmia identified by the Texas Birth Defects Registry from 1999–2014 without clinical or chromosomal diagnoses of recognized syndromes. We calculated adjusted observed-to-expected ratios for two- through five-way birth defect combinations involving anophthalmia/microphthalmia to estimate whether these combinations co-occur more often than would be expected if they were independent. We report combinations observed in ≥5 cases. RESULTS: We identified 653 eligible cases with anophthalmia/microphthalmia (514 [79%] with co-occurring birth defects), and 111 birth defect combinations, of which 44 were two-way combinations, 61 were three-way combinations, six were four-way combinations and none were five-way combinations. Combinations with the largest observed-to-expected ratios were those involving central nervous system (CNS) defects, head/neck defects, and orofacial clefts. We also observed multiple combinations involving cardiovascular and musculoskeletal defects. CONCLUSION: Consistent with previous reports, we observed that a large proportion of children diagnosed with anophthalmia/microphthalmia have co-occurring birth defects. While some of these defects may be part of a sequence involving anophthalmia/microphthalmia (e.g., CNS defects), other combinations could point to as yet undescribed susceptibility patterns (e.g., musculoskeletal defects). Data from population-based birth defects registries may be useful for accelerating the discovery of previously uncharacterized malformation syndromes.

Background We sought to investigate associations between maternal/infant characteristics and isolated craniosynostosis as well as its subtypes sagittal, metopic, and coronal synostosis, and assess trends in the prevalence of these conditions. Methods We identified cases in the Texas Birth Defects Registry from 1999 to 2014. We used Poisson regression to identify associations between maternal/infant characteristics and craniosynostosis. We used joinpoint regression and unadjusted Poisson regression to evaluate temporal trends. Finally, we computed adjusted Poisson models to evaluate whether temporal trends were evident after accounting for changes in the population distributions of maternal/infant characteristics over time. Results Relative to all live births in the general population, cases were more frequently male or preterm. Mothers of cases were more frequently non-Hispanic white and more frequently obese. Non-Hispanic black or Hispanic maternal race/ethnicity was associated with a lower prevalence of all craniosynostosis subtypes. Previous live births were associated with sagittal synostosis; residence on the U.S.-Mexico border was associated with sagittal and coronal synostosis. The prevalence of any isolated craniosynostosis increased (average annual percent change estimated from joinpoint regression [AAPC]: 2.9%), as did the prevalences of sagittal (AAPC: 3.3%) and metopic synostosis (AAPC: 5.4%). In crude Poisson models, the same temporal trends were observed, however these were attenuated after adjusting for maternal/infant characteristics. Conclusions Prevalence of isolated craniosynostosis increased from 1999 to 2014. The largest AAPC was observed for metopic synostosis. Changes in the population distribution of associated maternal/infant characteristics may explain these trends.

This study identifies and analyzes strategic risks experienced by the Badan Pengelola Jaminan Sosial (BPJS) Kesehatan. This health insurance program has a deficit due to the number of claims exceeding income and there is no detection system for the number of claims that are not appropriate. This research is explanatory by using the IFE-EFE Matrix as a basis for identifying and mitigating the strategic risk of BPJS Kesehatan. The Analysis results shows the need for more accurate and transparent calculations, intense socialization, pricing of tariff should be adjusted to the ability of the people, as well as a fraud detection system by BPJS Kesehatan. Keyword s : Strategic Risk; IFE and EFE Matrix; BPJS Kesehatan, UCS Thailand

Background Bariatric procedures are on the rise. The risk of birth defects in pregnancies following such procedures may be increased (eg, due to nutrient deficiencies) or decreased (eg, due to decreased maternal body mass index, BMI). Methods We conducted a systematic literature review of the association between bariatric surgery and birth defects using Ovid MEDLINE and PubMed (1946-2017). Information was abstracted on study design, exposures, outcomes, covariates and estimates of association. Results Fifteen studies met our inclusion criteria: 14 evaluated the outcome of any birth defect, and one evaluated neural tube defects. Estimates of association between bariatric surgery and birth defects were available for nine studies and ranged from 0.6 to 1.9 (all 95% confidence intervals included 1.0). When studies were stratified by surgery type, there was no obvious pattern of association. When stratified by the approach used to account for BMI, positive associations were observed in studies that did not account for maternal prepregnancy BMI or used women with normal BMI as the reference group (range: 1.3-1.9). Estimates from studies that either matched or adjusted for prepregnancy BMI were closer to the null (range: 1.1-1.2) and studies that compared to morbidly obese women reported protective associations (range: 0.6-0.7). Conclusions Studies of the association between bariatric surgery and birth defects vary with respect to the surgical procedures included, birth defects ascertainment methods and approaches used to account for maternal BMI. Consequently, it is not possible to draw a conclusion regarding the association between bariatric surgery and birth defects. Additional studies are warranted.

Background Suboptimal folate intake, a risk factor for birth defects, is common even in areas with folate fortification. A polymorphism in methylenetetrahydrofolate dehydrogenase 1 (MTHFD1), R653Q (MTHFD1 c.1958 G > A), has also been associated with increased birth defect risk, likely through reduced purine synthesis. Objective We aimed to determine if the interaction of MTHFD1 synthetase deficiency and low folate intake increases developmental abnormalities in a mouse model for MTHFD1 R653Q. Methods Female Mthfd1S+/+ and Mthfd1S+/- mice were fed control or low-folate diets (2 and 0.3 mg folic acid/kg diet, respectively) before mating and during pregnancy. Embryos and placentas were examined for anomalies at embryonic day 10.5. Maternal 1-carbon metabolites were measured in plasma and liver. Results Delays and defects doubled in litters of Mthfd1S+/- females fed low-folate diets compared to wild-type females fed either diet, or Mthfd1S+/- females fed control diets [P values (defects): diet 0.003, maternal genotype 0.012, diet × maternal genotype 0.014]. These adverse outcomes were associated with placental dysmorphology. Intrauterine growth restriction was increased by embryonic Mthfd1S+/- genotype, folate deficiency, and interaction of maternal Mthfd1S+/- genotype with folate deficiency (P values: embryonic genotype 0.045, diet 0.0081, diet × maternal genotype 0.0019). Despite a 50% increase in methylenetetrahydrofolate reductase expression in low-folate maternal liver (P diet = 0.0007), methyltetrahydrofolate concentration decreased 70% (P diet