Patterns of co-occurring birth defects among infants with hypospadias.
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ABSTRACT: Introduction
Hypospadias, one of the most common male genital birth defects, occurs in 1 out of every 200 male births in the United States and is increasing in prevalence globally.Objective
This study aimed to characterize the combinations of birth defects that co-occur with hypospadias more often than expected by chance, while accounting for the complex clustering patterns of congenital defects.Study design
We analyzed cases with hypospadias and at least one additional co-occurring defect from the Texas Birth Defect Registry born between 1999 and 2014. For each combination, we calculated adjusted observed-to-expected (O/E) ratios, using Co-Occurring Defect Analysis (CODA).Results
Among 16,442 cases with hypospadias and without known syndromes, 2,084 (12.7%) had at least one additional defect. Many of the birth defect combinations within the highest adjusted O/E ratios included cardiac, musculoskeletal, and additional urogenital defects. For example, a top combination with an adjusted O/E of 139.0 included renal agenesis and dysgenesis, reduction defects of the upper limb, and other anomalies of upper limb (including shoulder girdle). High adjusted O/E ratios were also observed in combinations that included defects outside of the urogenital developmental field. For instance, the combination with the highest O/E ratio included buphthalmos, and congenital cataract and lens anomalies (adjusted O/E ratio: 192.9). Similar results were obtained when we restricted our analyses to cases with second- or third-degree hypospadias.Discussion
Many combinations in the top results were expected (e.g., multiple urogenital defects); however, some combinations with seemingly unrelated patterns of defects may suggest the presence of some etiologic mechanisms yet to be identified.Conclusion
In summary, this study described patterns of co-occurring defect combinations with hypospadias that can inform further study and may provide insights for screening and diagnostic practices.
SUBMITTER: Ludorf KL
PROVIDER: S-EPMC7935759 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe population-level landscape of co-occurring birth defects among infants without a syndromic diagnosis is not well understood.MethodsWe analyzed data from 40,771 infants with two or more major birth defects in the Texas Birth Defects Registry (TBDR; 1999-2014). We calculated adjusted observed-to-expected (O/E) ratios for all two, three, four, and five-way combinations of 138 major defects.ResultsAmong 530 patterns with the highest adjusted O/E ratios (top 5% of 10,595 patterns), 66% included only defects co-occurring within one organ system and 28% were suggestive of known patterns (e.g., midline developmental defects). Of the remaining patterns, the combination of defects with the highest O/E ratio (193.8) encompassed the diaphragm, spine, spleen, and heart defects. Fourteen patterns involved heart and spine defects with or without rib defects. Ten additional patterns primarily involved two hallmark components of VACTERL association (specifically, vertebral defects, anal atresia, cardiac defects, renal, or limb defects, but not tracheoesophageal fistula).ConclusionsOur analyses provide a description of the birth defect co-occurrence patterns in a multi-ethnic, population-based sample, and revealed several patterns of interest. This work complements prior work that has suggested etiologic connections between select defects (e.g., diaphragmatic hernia and heart and spleen anomalies; heart and spine defects).ImpactIn this large-scale, population-based study of birth defect co-occurrence patterns, we found several birth defect combinations of potential interest that warrant further investigation: congenital diaphragmatic hernia, heart, spine, and spleen defects and scimitar syndrome with vertebral defects. The majority of patterns of co-occurring defects observed more frequently than expected involved multiple defects within the same system and combinations suggestive of known associations. Nearly all of the top patterns (beyond the same system and those suggestive of known associations) involved organ systems that are components of the VACTERL association, with heart, spine, and rib defect patterns being the most common.
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Project description:BACKGROUND:Zika virus (ZIKV) was first isolated in Uganda in 1947. In Brazil, the first reported case of ZIKV infection was in May 2015. Additionally, dengue (DENV) is endemic and there has been a recent outbreak of chikungunya (CHIKV). Since the clinical manifestations of different arboviral infections (AI) can be similar, definitive diagnosis requires laboratory testing. OBJECTIVES:To determine the prevalence of ZIKV, DENV, and CHIKV infections in a Brazilian cohort of HIV-infected pregnant women, to assess clinical/immunological characteristics and pregnancy outcomes of women with evidence of recent AI. STUDY DESIGN:Laboratory diagnosis of ZIKV, DENV and CHIKV infections utilized serological assays, RT-PCR and PRNT. The tests were performed at the first visit, 34-36 weeks of gestation and at any time if a woman had symptoms suggestive of AI. Mann-Whitney tests were used for comparison of medians, Chi-square or Fisher's to compare proportions; p< 0.05 was considered statistically significant. Poisson regression was used to analyze risk factors for central nervous system (CNS) malformations in the infant according to maternal symptomatology. RESULTS:Of 219 HIV-infected pregnant women enrolled, 92% were DENV IgG+; 47(22%) had laboratory evidence of recent AI. Of these, 34 (72%) were ZIKV+, nine (19%) CHIKV+, and two (4%) DENV+. Symptoms consistent with AI were observed in 23 (10%) women, of whom 10 (43%) were ZIKV+, eight (35%) CHIKV+. No CNS abnormalities were observed among infants of DENV+ or CHIKV+ women; four infants with CNS abnormalities were born to ZIKV+ women (three symptomatic). Infants born to ZIKV+ women had a higher risk of CNS malformations if the mother was symptomatic (RR = 7.20), albeit not statistically significant (p = 0.066). CONCLUSIONS:Among HIV-infected pregnant women with laboratory evidence of a recent AI, 72% were ZIKV-infected. In this cohort, CNS malformations occurred among infants born to both symptomatic and asymptomatic pregnant women with Zika infection.
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Project description:BackgroundFew studies have systematically evaluated birth defect co-occurrence patterns, perhaps, in part, due to the lack of software designed to implement large-scale, complex analytic methods.MethodsWe created an R-based platform, "co-occurring defect analysis" (CODA), designed to implement analyses of birth defect co-occurrence patterns in birth defect registries. CODA uses an established algorithm for calculating the observed-to-expected ratio of a given birth defect combination, accounting for the known tendency of birth defects to co-occur nonspecifically. To demonstrate CODA's feasibility, we evaluated the computational time needed to assess 2- to 5-way combinations of major birth defects in the Texas Birth Defects Registry (TBDR) (1999-2014). We report on two examples of pairwise patterns, defects co-occurring with trisomy 21 or with non-syndromic spina bifida, to demonstrate proof-of-concept.ResultsWe evaluated combinations of 175 major birth defects among 206,784 infants in the TBDR. CODA performed efficiently in the data set, analyzing 1.5 million 5-way combinations in 18 hr. As anticipated, we identified large observed-to-expected ratios for the birth defects that co-occur with trisomy 21 or spina bifida.ConclusionsCODA is available for application to birth defect data sets and can be used to better understand co-occurrence patterns. Co-occurrence patterns elucidated by using CODA may be helpful for identifying new birth defect associations and may provide etiological insights regarding potentially shared pathogenic mechanisms. CODA may also have wider applications, such as assessing patterns of additional types of co-occurrence patterns in other large data sets (e.g., medical records).
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Project description:The purpose of this study was to estimate the association between 2nd and 3rd degree hypospadias and maternal exposure to disinfection by-products (DBPs) using data from a large case-control study in the United States. Concentration estimates for total trihalomethanes (TTHMs), the sum of the five most prevalent haloacetic acids (HAA5), and individual species of each were integrated with data on maternal behaviors related to water use from the National Birth Defects Prevention Study (NBDPS) to create three different exposure metrics: (1) household DBP concentrations; (2) estimates of DBP ingestion; (3) predicted uptake (i.e., internal dose) of trihalomethanes (THMs) via ingestion, showering, and bathing. The distribution of DBP exposure was categorized as follows: (Q1/referent) < 50%; (Q2) ? 50% to < 75%; and (Q3) ? 75%. Logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Generally, null associations were observed with increasing TTHM or HAA5 exposure. An increased risk was observed among women with household bromodichloromethane levels in the second quantile (aOR: 1.8; 95% CI: 1.2, 2.7); however, this association did not persist after the inclusion of individual-level water-use data. Findings from the present study do not support the hypothesis that maternal DBP exposures are related to the occurrence of hypospadias.
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Project description:BackgroundThe aims of this study were to identify common patterns of comorbidities observed in people living with HIV (PLWH), using a data-driven approach, and evaluate associations between patterns identified.MethodsA wide range of comorbidities were assessed in PLWH participating in 2 independent cohorts (POPPY: UK/Ireland; AGEhIV: Netherlands). The presence/absence of each comorbidity was determined using a mix of self-reported medical history, concomitant medications, health care resource use, and laboratory parameters. Principal component analysis (PCA) based on Somers' D statistic was applied to identify patterns of comorbidities.ResultsPCA identified 6 patterns among the 1073 POPPY PLWH (85.2% male; median age [interquartile range {IQR}], 52 [47-59] years): cardiovascular diseases (CVDs), sexually transmitted diseases (STDs), mental health problems, cancers, metabolic disorders, chest/other infections. The CVDs pattern was positively associated with cancer (r = .32), metabolic disorder (r = .38), mental health (r = .16), and chest/other infection (r = .17) patterns (all P < .001). The mental health pattern was correlated with all the other patterns (in particular cancers: r = .20; chest/other infections: r = .27; both P < .001). In the 598 AGEhIV PLWH (87.6% male; median age [IQR], 53 [48-59] years), 6 patterns were identified: CVDs, chest/liver, HIV/AIDS events, mental health/neurological problems, STDs, and general health. The general health pattern was correlated with all the other patterns (in particular CVDs: r = .14; chest/liver: r = .15; HIV/AIDS events: r = .31; all P < .001), except STDs (r = -.02; P = .64).ConclusionsComorbidities in PLWH tend to occur in nonrandom patterns, reflecting known pathological mechanisms and shared risk factors, but also suggesting potential previously unknown mechanisms. Their identification may assist in adequately addressing the pathophysiology of increasingly prevalent multimorbidity in PLWH.
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Project description: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.
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Project description:To understand the forces driving differentiation and diversification in wild bacterial populations, we must be able to delineate and track ecologically relevant units through space and time. Mapping metagenomic sequences to reference genomes derived from the same environment can reveal genetic heterogeneity within populations, and in some cases, be used to identify boundaries between genetically similar, but ecologically distinct, populations. Here we examine population-level heterogeneity within abundant and ubiquitous freshwater bacterial groups such as the acI Actinobacteria and LD12 Alphaproteobacteria (the freshwater sister clade to the marine SAR11) using 33 single-cell genomes and a 5-year metagenomic time series. The single-cell genomes grouped into 15 monophyletic clusters (termed "tribes") that share at least 97.9% 16S rRNA identity. Distinct populations were identified within most tribes based on the patterns of metagenomic read recruitments to single-cell genomes representing these tribes. Genetically distinct populations within tribes of the acI Actinobacterial lineage living in the same lake had different seasonal abundance patterns, suggesting these populations were also ecologically distinct. In contrast, sympatric LD12 populations were less genetically differentiated. This suggests that within one lake, some freshwater lineages harbor genetically discrete (but still closely related) and ecologically distinct populations, while other lineages are composed of less differentiated populations with overlapping niches. Our results point at an interplay of evolutionary and ecological forces acting on these communities that can be observed in real time.
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Project description:BackgroundEsophageal atresia (EA) affects around 2.3-2.6 per 10,000 births world-wide. Infants born with this condition require surgical correction soon after birth. Most survival studies of infants with EA are locally or regionally based. We aimed to describe survival across multiple world regions.MethodsWe included infants diagnosed with EA between 1980 and 2015 from 24 birth defects surveillance programs that are members of the International Clearinghouse for Birth Defects Surveillance and Research. We calculated survival as the proportion of liveborn infants alive at 1 month, 1- and 5-years, among all infants with EA, those with isolated EA, those with EA and additional anomalies or EA and a chromosomal anomaly or genetic syndrome. We also investigated trends in survival over the decades, 1980s-2010s.ResultsWe included 6,466 liveborn infants with EA. Survival was 89.4% (95% CI 88.1-90.5) at 1-month, 84.5% (95% CI 83.0-85.9) at 1-year and 82.7% (95% CI 81.2-84.2) at 5-years. One-month survival for infants with isolated EA (97.1%) was higher than for infants with additional anomalies (89.7%) or infants with chromosomal or genetic syndrome diagnoses (57.3%) with little change at 1- and 5-years. Survival at 1 month improved from the 1980s to the 2010s, by 6.5% for infants with isolated EA and by 21.5% for infants with EA and additional anomalies.ConclusionsAlmost all infants with isolated EA survived to 5 years. Mortality was higher for infants with EA and an additional anomaly, including chromosomal or genetic syndromes. Survival improved from the 1980s, particularly for those with additional anomalies.
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