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BACKGROUND: Emerging evidence suggests newborn screening analytes may yield insights into the etiologies of birth defects, yet no effort has evaluated associations between a range of newborn screening analytes and birth defects. METHODS: This population-based study pooled statewide data on birth defects, birth certificates, and newborn screening analytes from Texas occurring between January 1, 2007 and December 31, 2009. Associations between a panel of thirty-six newborn screening analytes, collected by the statewide Texas Newborn Screening Program, and the presence of a birth defect, defined as at least one of 39 birth defects diagnoses recorded by the Texas Birth Defects Registry, were assessed using regression analysis. FINDINGS: Of the 27,643 births identified, 20,205 had at least one of the 39 birth defects of interest (cases) as identified by the Texas Birth Defects Registry, while 7,438 did not have a birth defect (controls). Among 1,404 analyte-birth defect associations evaluated, 377 were significant in replication analysis. Analytes most consistently associated with birth defects included the phenylalanine/tyrosine ratio (N = 29 birth defects), tyrosine (N = 28 birth defects), and thyroxine (N = 25 birth defects). Birth defects most frequently associated with a range of analytes included gastroschisis (N = 29 analytes), several cardiovascular defects (N = 26 analytes), and spina bifida (N = 23 analytes). CONCLUSIONS: Several significant and novel associations were observed between newborn screening analytes and birth defects. While some findings could be consequences of the defects themselves or to the care provided to infants with these defects, these findings could help to elucidate mechanisms underlying the etiology of some birth defects.
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Anomalías Congénitas , Tamizaje Neonatal , Humanos , Recién Nacido , Tamizaje Neonatal/métodos , Anomalías Congénitas/epidemiología , Anomalías Congénitas/diagnóstico , Texas/epidemiología , Femenino , Sistema de Registros , MasculinoRESUMEN
Epidemiologic studies of birth defects often conduct separate analyses for cases that have isolated defects (e.g., spina bifida only) and cases that have multiple defects (e.g., spina bifida and a congenital heart defect). However, in some instances, cases with additional defects (e.g., spina bifida and clubfoot) may be more appropriately considered as isolated because the co-occurring defect (clubfoot) is believed to be developmentally related to the defect of interest. Determining which combinations should be considered isolated can be challenging and potentially resource intensive for registries. Thus, we developed automated classification procedures for differentiating between isolated versus multiple defects, while accounting for developmentally related defects, and applied the approach to data from the Texas Birth Defects Registry (1999-2018 deliveries). Among 235,544 nonsyndromic cases in Texas, 89% of cases were classified as having isolated defects, with proportions ranging from 25% to 92% across 43 specific defects analyzed. A large proportion of isolated cases with spina bifida (44%), lower limb reduction defects (44%), and holoprosencephaly (32%) had developmentally related defects. Overall, our findings strongly support the need to account for isolated versus multiple defects in risk factor association analyses and to account for developmentally related defects when doing so, which has implications for interpreting prior studies.
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BACKGROUND: To characterize neurodevelopmental abnormalities in children up to 36 months of age with congenital Zika virus exposure. METHODS: From the U.S. Zika Pregnancy and Infant Registry, a national surveillance system to monitor pregnancies with laboratory evidence of Zika virus infection, pregnancy outcomes and presence of Zika associated birth defects (ZBD) were reported among infants with available information. Neurologic sequelae and developmental delay were reported among children with ≥1 follow-up exam after 14 days of age or with ≥1 visit with development reported, respectively. RESULTS: Among 2248 infants, 10.1% were born preterm, and 10.5% were small-for-gestational age. Overall, 122 (5.4%) had any ZBD; 91.8% of infants had brain abnormalities or microcephaly, 23.0% had eye abnormalities, and 14.8% had both. Of 1881 children ≥1 follow-up exam reported, neurologic sequelae were more common among children with ZBD (44.6%) vs. without ZBD (1.5%). Of children with ≥1 visit with development reported, 46.8% (51/109) of children with ZBD and 7.4% (129/1739) of children without ZBD had confirmed or possible developmental delay. CONCLUSION: Understanding the prevalence of developmental delays and healthcare needs of children with congenital Zika virus exposure can inform health systems and planning to ensure services are available for affected families. IMPACT: We characterize pregnancy and infant outcomes and describe neurodevelopmental abnormalities up to 36 months of age by presence of Zika associated birth defects (ZBD). Neurologic sequelae and developmental delays were common among children with ZBD. Children with ZBD had increased frequency of neurologic sequelae and developmental delay compared to children without ZBD. Longitudinal follow-up of infants with Zika virus exposure in utero is important to characterize neurodevelopmental delay not apparent in early infancy, but logistically challenging in surveillance models.
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Microcefalia , Trastornos del Neurodesarrollo , Complicaciones Infecciosas del Embarazo , Infección por el Virus Zika , Virus Zika , Lactante , Recién Nacido , Embarazo , Niño , Femenino , Humanos , Preescolar , Infección por el Virus Zika/complicaciones , Infección por el Virus Zika/epidemiología , Infección por el Virus Zika/congénito , Complicaciones Infecciosas del Embarazo/epidemiología , Microcefalia/epidemiología , Trastornos del Neurodesarrollo/complicacionesRESUMEN
BACKGROUND: Gastroschisis prevalence more than doubled between 1995 and 2012. While there are individual-level risk factors (e.g., young maternal age, low body mass index), the impact of environmental exposures is not well understood. METHODS: We used the U.S. Environmental Protection Agency's Environmental Quality Index (EQI) as a county-level estimate of cumulative environmental exposures for five domains (air, water, land, sociodemographic, and built) and overall from 2006 to 2010. Adjusted odds ratios (aOR) and 95% confidence interval (CI) were estimated from logistic regression models between EQI tertiles (better environmental quality (reference); mid; poorer) and gastroschisis in the National Birth Defects Prevention Study from births delivered between 2006 and 2011. Our analysis included 594 cases with gastroschisis and 4105 infants without a birth defect (controls). RESULTS: Overall EQI was modestly associated with gastroschisis (aOR [95% CI]: 1.29 [0.98, 1.71]) for maternal residence in counties with poorer environmental quality, compared to the reference (better environmental quality). Within domain-specific indices, only the sociodemographic domain (aOR: 1.51 [0.99, 2.29]) was modestly associated with gastroschisis, when comparing poorer to better environmental quality. CONCLUSIONS: Future work could elucidate pathway(s) by which components of the sociodemographic domain or possibly related psychosocial factors like chronic stress potentially contribute to risk of gastroschisis.
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Gastrosquisis , Embarazo , Lactante , Femenino , Humanos , Gastrosquisis/epidemiología , Gastrosquisis/etiología , Exposición a Riesgos Ambientales/efectos adversos , Edad Materna , Prevalencia , Oportunidad RelativaRESUMEN
BACKGROUND: Studies have reported increased rates of birth defects among children with germ cell tumors (GCTs). However, few studies have evaluated associations by sex, type of defect, or tumor characteristics. METHODS: Birth defect-GCT associations were evaluated among pediatric patients (N = 552) with GCTs enrolled in the Germ Cell Tumor Epidemiology Study and population-based controls (N = 6380) without cancer from the Genetic Overlap Between Anomalies and Cancer in Kids Study. The odds ratio (OR) and 95% confidence interval (CI) of GCTs according to birth defects status were estimated by using unconditional logistic regression. All defects were considered collectively and by genetic and chromosomal syndromes and nonsyndromic defects. Stratification was by sex, tumor histology (yolk sac tumor, teratoma, germinoma, and mixed/other), and location (gonadal, extragonadal, and intracranial). RESULTS: Birth defects and syndromic defects were more common among GCT cases than controls (6.9% vs. 4.0% and 2.7% vs. 0.2%, respectively; both p < .001). In multivariable models, GCT risk was increased among children with birth defects (OR, 1.7; 95% CI, 1.3-2.4) and syndromic defects (OR, 10.4; 95% CI, 4.9-22.1). When stratified by tumor characteristics, birth defects were associated with yolk sac tumors (OR, 2.7; 95% CI, 1.3-5.0) and mixed/other histologies (OR, 2.1; 95% CI, 1.2-3.5) and both gonadal tumors (OR, 1.7; 95% CI, 1.0-2.7) and extragonadal tumors (OR, 3.8; 95% CI, 2.1-6.5). Nonsyndromic defects specifically were not associated with GCTs. In sex-stratified analyses, associations were observed among males but not females. CONCLUSIONS: These data suggest that males with syndromic birth defects are at an increased risk of pediatric GCTs, whereas males with nonsyndromic defects and females are not at an increased risk. PLAIN LANGUAGE SUMMARY: We investigated whether birth defects (such as congenital heart disease or Down syndrome) are linked to childhood germ cell tumors (GCTs), cancers that mainly develop in the ovaries or testes. We studied different types of birth defects (defects that were caused by chromosome changes such as Down syndrome or Klinefelter syndrome and defects that were not) and different types of GCTs. Only chromosome changes such as Down syndrome or Klinefelter syndrome were linked to GCTs. Our study suggests that most children with birth defects are not at an increased risk of GCTs because most birth defects are not caused by chromosome changes.
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Síndrome de Down , Síndrome de Klinefelter , Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Masculino , Niño , Humanos , Adolescente , Neoplasias de Células Germinales y Embrionarias/epidemiología , Neoplasias de Células Germinales y Embrionarias/genética , Neoplasias Testiculares/epidemiología , Neoplasias Testiculares/genéticaRESUMEN
BACKGROUND: Building on findings that linked higher levels of sunspot (SS) activity with a range of health and adverse birth outcomes, we sought to understand how SS activity over a 17-year time period may be correlated with the occurrence of birth defects. METHODS: Data from the Texas Birth Defects Registry, vital events from the Texas Center for Health Statistics, and mean monthly numbers of sunspots from the National Oceanic and Atmospheric Administration were utilized. Poisson regression was used to calculate crude/adjusted prevalence ratios (cPRs/aPRs) and 95% confidence intervals for three quartiles (Q) of increasing SS activity (compared to a referent of low activity) and 44 birth defects (31 non-cardiac; 13 cardiac) with estimated dates of conception from 1998 to 2016. RESULTS: We found moderately protective aPRs (range: 0.60-0.89) in a little over half of the case groups examined in our quartiles of higher SS activity (19 non-cardiac; 6 cardiac), after adjusting for maternal age, race/ethnicity, and education. Particularly protective aPRs in the highest SS quartiles (Q3-4) were noted for: anophthalmia, cataract, gastroschisis, trisomy 18, ventricular septal defects, atrial septal defects, and pulmonary valve atresia or stenosis. Conversely, modestly elevated aPRs were noted for two defect groups (agenesis, aplasia, and hypoplasia of the lung and microcephaly [Q2-3]). Following an additional adjustment of year of conception, results remained similar although many of the estimates were attenuated. CONCLUSION: The seemingly protective associations between increasing SS activity may be an artifact of increasing spontaneous abortions that occur following conception during these periods of heightened SS activity.
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Gastrosquisis , Malformaciones del Sistema Nervioso , Embarazo , Femenino , Humanos , Texas/epidemiología , Actividad Solar , Gastrosquisis/epidemiología , Edad MaternaRESUMEN
In this exploratory analysis, we assessed whether nutrition modified the association between prenatal exposure to tobacco and childhood cognition/behavior among 366 Colorado-based mothers and their offspring (born ≥ 37 weeks with birthweights ≥ 2500 g). Interaction by folate (≥ 1074 µg/day) and breastfeeding (≥ 5 months) was assessed by including a product term with cotinine (≥ limit of detection [LOD]) in regression models for NIH Toolbox and Child Behavior Checklist T-scores. Main effects were observed between cotinine ≥ LOD and inhibitory control (- 3.2; 95% CI: - 6.8, 0.3), folate < 1074 µg/day and anxious/depressed symptoms (1.1; 95% CI: 0.1, 2.1), and breastfeeding < 5 months and receptive language (- 4.3; 95% CI: - 8.5, - 0.02), though these findings would not survive Bonferroni correction. Breastfeeding modified the tobacco-behavior associations. Sleep (3.8; 95% CI: 0.5, 7.1; interaction p-value = 0.02), depressive (4.6; 95% CI: 1.0, 8.2; interaction p-value = 0.01) and total problems (5.8; 95% CI: - 0.7, 12.4; interaction p-value = 0.09) were observed among tobacco-exposed offspring who breastfed > 5 months, but not for shorter durations. Our findings support the need for smoking cessation campaigns throughout pregnancy and throughout the postpartum period breastfeeding to reduce neurobehavioral risks in the offspring.
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To describe the current epidemiology of nonsyndromic cleft palate alone (CP) and cleft lip with or without cleft palate (CL ± P) in Texas and examine differences in the characteristics of infants with CP and CL ± P based on the presence/absence of additional defects.We used data from the Texas Birth Defects Registry, a statewide active birth defect surveillance system, from 1815 cases with CP and 5066 with CL ± P, without a syndrome diagnosis (1999-2014 deliveries). All live births in Texas were used for comparison. Poisson regression was used to calculate crude and adjusted prevalence ratios (aPR) for each characteristic, separately for each cleft subphenotype.The prevalence of CL ± P and CP in our study was estimated as 8.3 and 3.0 per 10â 000 live births, respectively. After adjusting for several characteristics, several factors were associated with CL ± P, CP, or both, including infant sex and maternal race/ethnicity, age, smoking, and diabetes. There were several differences between infants with isolated versus nonisolated clefts. For example, maternal prepregnancy diabetes was associated with an increased prevalence of CL ± P (aPR 7.91, 95% confidence interval [CI]: 5.53, 11.30) and CP (aPR 3.24, 95% CI: 1.43, 7.36), but only when additional defects were present.Findings from this study provide a contemporary description of the distribution of orofacial clefts in Texas accounting for differences between isolated and nonisolated clefts. They may contribute to increasing our understanding of the etiology of CP and CL ± P.
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Labio Leporino , Fisura del Paladar , Lactante , Humanos , Labio Leporino/epidemiología , Fisura del Paladar/epidemiología , Texas/epidemiología , Estudios Retrospectivos , PrevalenciaRESUMEN
Structural birth defects that occur in infants with syndromes may be etiologically distinct from those that occur in infants in whom there is not a recognized pattern of malformations; however, population-based registries often lack the resources to classify syndromic status via case reviews. We developed criteria to systematically identify infants with suspected syndromes, grouped by syndrome type and level of effort required for syndrome classification (e.g., text search). We applied this algorithm to the Texas Birth Defects Registry (TBDR) to describe the proportion of infants with syndromes delivered during 1999-2014. We also developed a bias analysis tool to estimate the potential percent bias resulting from including infants with syndromes in studies of risk factors. Among 207,880 cases with birth defects in the TBDR, 15% had suspected syndromes and 85% were assumed to be nonsyndromic, with a range across defect types from 28.5% (atrioventricular septal defects) to 98.9% (pyloric stenosis). Across hypothetical scenarios varying expected parameters (e.g., nonsyndromic proportion), the inclusion of syndromic cases in analyses resulted in up to 50.0% bias in prevalence ratios. In summary, we present a framework for identifying infants with syndromic conditions; implementation might harmonize syndromic classification across registries and reduce bias in association estimates.
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Anomalías Congénitas , Defectos de los Tabiques Cardíacos , Lactante , Humanos , Síndrome , Prevalencia , Sistema de Registros , Texas/epidemiología , Anomalías Congénitas/diagnóstico , Anomalías Congénitas/epidemiología , Anomalías Congénitas/genéticaRESUMEN
INTRODUCTION: Arsenic crosses the placenta and accumulates in fetal tissues. In the United States, diet is the predominant route of arsenic exposure, but epidemiologic data are sparse regarding this exposure and development of birth defects. Using data from a large case-control study, we explored associations between maternal dietary arsenic exposure and congenital heart defects (CHDs), the most prevalent birth defects. METHODS: We used maternal self-reported dietary assessments and arsenic concentration estimates in food items to estimate average daily exposure to dietary arsenic during the year before pregnancy for mothers of 10,446 unaffected control children and 6,483 case children diagnosed with CHDs. Using tertiles of dietary exposure to total arsenic (all species) and inorganic arsenic, we applied logistic regression analysis to estimate associations for middle and high tertiles, compared with the low tertile. RESULTS: Positive associations (odds ratio [OR] ≥ 1.2) for total arsenic were observed in both tertiles for perimembranous ventricular septal defect (VSD) and high tertile only for double outlet right ventricle-transposition of the great arteries (DORV-TGA), partial anomalous pulmonary venous return (PAPVR), and tricuspid atresia. Positive associations were also observed in both tertiles (tricuspid atresia) and high tertile only (DORV-TGA, conoventricular VSD, PAPVR, and pulmonary atresia) for inorganic arsenic. Most remaining associations were near or below unity. DISCUSSION: Exploration of maternal dietary exposure to total and inorganic arsenic and CHDs produced few positive associations but was limited by available food item concentrations. Future research requires expanded collection of dietary data, improved estimates of concentrations, and consideration of nondietary sources of arsenic exposure.
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Arsénico , Arsenicales , Ventrículo Derecho con Doble Salida , Transposición de los Grandes Vasos , Atresia Tricúspide , Embarazo , Femenino , Niño , Humanos , Estados Unidos/epidemiología , Arsénico/toxicidad , Estudios de Casos y Controles , MadresRESUMEN
INTRODUCTION: Because the etiology and outcomes of birth defects may differ by the presence vs. absence of co-occurring anomalies, epidemiologic studies often attempt to classify cases into isolated versus non-isolated groupings. This report describes a computer algorithm for such classification and presents results using data from the Texas Birth Defects Registry (TBDR). METHODS: Each of the 1,041 birth defects coded by the TBDR was classified as chromosomal, syndromic, minor, or "needs review" by a group of three clinical geneticists. A SAS program applied those classifications to each birth defect in a case (child/fetus), and then hierarchically combined them to obtain one summary classification for each case, adding isolated and multiple defect categories. The program was applied to 136,121 cases delivered in 2012-2017. RESULTS: Of total cases, 49% were classified by the platform as isolated (having only one major birth defect). This varied widely by birth defect; of those examined, the highest proportion classified as isolated was found in pyloric stenosis (87.6%), whereas several cardiovascular malformations had low proportions, including tricuspid valve atresia/stenosis (2.3%). DISCUSSION: This is one of the first and largest attempts to identify the proportion of isolated cases across a broad spectrum of birth defects, which can inform future epidemiologic and genomic studies of these phenotypes. Our approach is designed for easy modification for use with any birth defects coding system and category definitions, allowing scalability for different studies or birth defects registries, which often do not have resources for individual clinical review of all case records.
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Manejo de Datos , Estenosis Hipertrófica del Piloro , Humanos , Sistema de Registros , Texas , AlgoritmosRESUMEN
BACKGROUND: Fetal exposure to tobacco increases the risk for many adverse birth outcomes, but whether diet mitigates these risks has yet to be explored. Here, we examined whether maternal folate intake (from foods and supplements) during pregnancy modified the association between prenatal exposure to tobacco and with preterm delivery, small-for-gestational age (SGA) births, or neonatal adiposity. METHODS: Mother-child pairs (n = 701) from Healthy Start were included in this analysis. Urinary cotinine was measured at ~ 27 weeks gestation. Diet was assessed using repeated 24-h dietary recalls. Neonatal adiposity (fat mass percentage) was measured via air displacement plethysmography. Interaction was assessed by including a product term between cotinine (< / ≥ limit of detection [LOD]) and folate (< / ≥ 25th percentile [1077 µg/day]) in separate logistic or linear regression models, adjusting for maternal age, race, ethnicity, education, pre-pregnancy body mass index, and infant sex. RESULTS: Approximately 26% of women had detectable levels of cotinine. Folate intake was significantly lower among women with cotinine ≥ LOD as compared to those with cotinine < LOD (1293 µg/day vs. 1418 µg/day; p = 0.01). Folate modified the association between fetal exposure to tobacco with neonatal adiposity (p for interaction = 0.07) and SGA (p for interaction = 0.07). Among those with lower folate intake, fetal exposure to tobacco was associated with lower neonatal adiposity (mean difference: -2.09%; 95% CI: -3.44, -0.74) and increased SGA risk (OR: 4.99; 95% CI: 1.55, 16.14). Conversely, among those with higher folate intake, there was no difference in neonatal adiposity (mean difference: -0.17%; 95% CI: -1.13, 0.79) or SGA risk (OR: 1.15; 95% CI: 0.57, 2.31). CONCLUSIONS: Increased folate intake during pregnancy (from foods and/or supplements) may mitigate the risk of fetal growth restriction among those who are unable to quit smoking or cannot avoid secondhand smoke during pregnancy.
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BACKGROUND: Maternal exposure to weather-related extreme heat events (EHEs) has been associated with congenital heart defects (CHDs) in offspring. Certain medications may affect an individual's physiologic responses to EHEs. We evaluated whether thermoregulation-related medications modified associations between maternal EHE exposure and CHDs. METHODS: We linked geocoded residence data from the U.S. National Birth Defects Prevention Study, a population-based case-control study, to summertime EHE exposures. An EHE was defined using the 90th percentile of daily maximum temperature (EHE90) for each of six climate regions during postconceptional weeks 3-8. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for associations between EHE90 and the risk of CHDs were estimated by strata of maternal thermoregulation-related medication use and climate region. Interaction effects were evaluated on multiplicative and additive scales. RESULTS: Over 45% of participants reported thermoregulation-related medication use during the critical period of cardiogenesis. Overall, these medications did not significantly modify the association between EHEs and CHDs. Still, medications that alter central thermoregulation increased aORs (95% CI) of EHE90 from 0.73 (0.41, 1.30) among non-users to 5.09 (1.20, 21.67) among users in the Southwest region, U.S. This effect modification was statistically significant on the multiplicative (P = 0.03) and additive scales, with an interaction contrast ratio (95% CI) of 1.64 (0.26, 3.02). CONCLUSION: No significant interaction was found for the maternal use of thermoregulation-related medications with EHEs on CHDs in general, while medications altering central thermoregulation significantly modified the association between EHEs and CHDs in Southwest U.S. This finding deserves further research.
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Cardiopatías Congénitas , Calor , Estudios de Casos y Controles , Femenino , Cardiopatías Congénitas/epidemiología , Humanos , Exposición Materna , Factores de RiesgoRESUMEN
During the Centers for Disease Control and Prevention's Zika Virus Response, birth defects surveillance programs adapted to monitor birth defects potentially related to Zika virus (ZIKV) infection during pregnancy. Pregnancy outcomes occurring during January 2016 to June 2017 in 22 U.S. states and territories were used to estimate the prevalence of those brain and eye defects potentially related to ZIKV. Jurisdictions were divided into three groups: areas with widespread ZIKV transmission, areas with limited local ZIKV transmission, and areas without local ZIKV transmission. Prevalence estimates for selected brain and eye defects and microcephaly per 10,000 live births were estimated. Prevalence ratios (PRs) and 95% confidence intervals (CIs) were estimated using Poisson regression for areas with widespread and limited ZIKV transmission compared with areas without local ZIKV transmission. Defects with significantly higher prevalence in areas of widespread transmission were pooled, and PRs were calculated by quarter, comparing subsequent quarters to the first quarter (January-March 2016). Nine defects had significantly higher prevalence in areas of widespread transmission. The highest PRs were seen in intracranial calcifications (PR = 12.6, 95% CI [7.4, 21.3]), chorioretinal abnormalities (12.5 [7.1, 22.3]), brainstem abnormalities (9.3 [4.7, 18.4]), and cerebral/cortical atrophy (6.7 [4.2, 10.8]). The PR of the nine pooled defects was significantly higher in three quarters in areas with widespread transmission. The largest difference in prevalence was observed for defects consistently reported in infants with congenital ZIKV infection. Birth defects surveillance programs could consider monitoring a subset of birth defects potentially related to ZIKV in pregnancy.
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Anomalías Congénitas , Anomalías del Ojo , Complicaciones Infecciosas del Embarazo , Infección por el Virus Zika , Virus Zika , Encéfalo/anomalías , Encéfalo/virología , Anomalías Congénitas/epidemiología , Anomalías Congénitas/virología , Anomalías del Ojo/epidemiología , Anomalías del Ojo/virología , Femenino , Humanos , Lactante , Microcefalia , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Prevalencia , Infección por el Virus Zika/complicaciones , Infección por el Virus Zika/congénito , Infección por el Virus Zika/epidemiologíaRESUMEN
OBJECTIVES: To explore associations between maternal pre-pregnancy exposure to arsenic in diet and non-cardiac birth defects. DESIGN: This is a population-based, case-control study using maternal responses to a dietary assessment and published arsenic concentration estimates in food items to calculate average daily total and inorganic arsenic exposure during the year before pregnancy. Assigning tertiles of total and inorganic arsenic exposure, logistic regression analysis was used to estimate OR for middle and high tertiles, compared to the low tertile. SETTING: US National Birth Defects Prevention Study, 1997-2011. PARTICIPANTS: Mothers of 10 446 children without birth defects and 14 408 children diagnosed with a non-cardiac birth defect. RESULTS: Maternal exposure to total dietary arsenic in the middle and high tertiles was associated with a threefold increase in cloacal exstrophy, with weak positive associations (1·2-1·5) observed either in both tertiles (intercalary limb deficiency) or the high tertile only (encephalocele, glaucoma/anterior chamber defects and bladder exstrophy). Maternal exposure to inorganic arsenic showed mostly weak, positive associations in both tertiles (colonic atresia/stenosis, oesophageal atresia, bilateral renal agenesis/hypoplasia, hypospadias, cloacal exstrophy and gastroschisis), or the high (glaucoma/anterior chamber defects, choanal atresia and intestinal atresia stenosis) or middle (encephalocele, intercalary limb deficiency and transverse limb deficiency) tertiles only. The remaining associations estimated were near the null or inverse. CONCLUSIONS: This exploration of arsenic in diet and non-cardiac birth defects produced several positive, but mostly weak associations. Limitations in exposure assessment may have resulted in exposure misclassification. Continued research with improved exposure assessment is recommended to identify if these associations are true signals or chance findings.
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In population research, exposure to environmental contaminants is often indirectly assessed by linking residence to geocoded databases of environmental exposures. We explored the potential for misclassification of residence-based environmental exposure as a result of not accounting for the workplace environments of employed pregnant women using data from a National Birth Defects Prevention Study (NBDPS) analysis of drinking water haloacetic acids and hypospadias. Methods: The original analysis used NBDPS data from women with haloacetic acid exposure information in eight states who delivered an infant with second- or third-degree hypospadias (cases) or a male infant without a birth defect (controls) between 2000 and 2005. In this bias analysis, we used a uniform distribution to randomly select 11%-14% of employed women that were assumed to change municipal water systems between home and work and imputed new contaminant exposures for tap water beverages consumed at work among the selected women using resampled values from the control population. Multivariable logistic regression was used to estimate the association between hypospadias and haloacetic acid ingestion with the same covariates and exposure cut-points as the original study. We repeated this process across 10,000 iterations and then completed a sensitivity analysis of an additional 10,000 iterations where we expanded the uniform distribution (i.e., 0%, 28%). Results: In both simulations, the average results of the 10,000 iterations were nearly identical to those of the initial study. Conclusions: Our results suggest that household estimates may be sufficient proxies for worksite exposures to haloacetic acids in tap water.
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OBJECTIVE: To identify key epidemiologic factors relevant to fetal development that are associated with biliary atresia. STUDY DESIGN: This population-based registry study examined infants born in Texas between 1999 and 2014. Epidemiologic data relevant to fetal development were compared between cases of biliary atresia identified in the Texas Birth Defects Registry (n = 305) vs all live births (n = 4 689 920), and Poisson regression was used to calculate prevalence ratios (PRs) and 95% CIs. RESULTS: The prevalence of biliary atresia over the study period was 0.65 per 10 000 live births. Biliary atresia was positively associated with female sex (adjusted PR, 1.68; 95% CI, 1.33-2.12), delivery before 32-37 weeks of gestation (adjusted PR, 1.64; 95% CI, 1.18-2.29), delivery before 32 weeks of gestation (adjusted PR, 3.85; 95% CI, 2.38-6.22), and non-Hispanic Black vs non-Hispanic White maternal race/ethnicity (adjusted PR, 1.54, 95% CI, 1.06-2.24), while biliary atresia was inversely associated with season of conception in the fall relative to spring (adjusted PR, 0.62; 95% CI, 0.45-0.86). In addition, biliary atresia was associated with maternal diabetes (adjusted PR, 2.34; 95% CI, 1.57-3.48), with a stronger association with pregestational diabetes compared with gestational diabetes. In subgroup analyses, these associations were present in isolated biliary atresia cases that do not have any additional birth defects. CONCLUSIONS: Biliary atresia is associated with multiple factors related to fetal development, including pregestational maternal diabetes, female sex, and preterm birth. These associations also were observed in isolated cases of biliary atresia without other malformations or laterality defects. Our results are consistent with early life events influencing the pathogenesis of biliary atresia, and support further studies investigating in utero events to better understand etiology and time of onset.
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Atresia Biliar , Diabetes Gestacional , Nacimiento Prematuro , Atresia Biliar/epidemiología , Femenino , Humanos , Lactante , Recién Nacido , Nacimiento Vivo , Embarazo , PrevalenciaRESUMEN
BACKGROUND: Trisomy 21 (T21) is common, with affected infants having an increased risk of infant mortality (5.9-7.1%). Maternal smoking is associated with infant mortality in the general population, and we evaluated if similar associations were present among infants with T21. METHODS: We identified infants with T21 from the Texas Birth Defects Registry, and maternal smoking and infant vital status were obtained from linked birth and death certificate data, respectively. Cox proportional hazards regression models were used to calculate hazard ratios between maternal smoking and death between 0 to ≤ 364 days, 28-364 days, and 0-27 days. RESULTS: We found a significant association between maternal smoking and death between 0 to ≤ 364 (unadjusted HR 1.72, 95% CI 1.07, 2.77), which was no longer statistically significant after adjustment for covariates (adjusted HR 1.55, 95% CI 0.94, 2.56). A similar pattern was observed for death between 28-364 days (adjusted HR: 1.68, 95% CI 0.93, 3.03), whereas the association for 0-27 days (adjusted HR: 1.30, 95% CI 0.51, 3.29) was not statistically significant before and after adjustment. CONCLUSIONS: The observed magnitudes of associations were similar to previous estimates among the general population. Further work considering the role of other maternal and infant risk factors and social determinants of health is necessary to better understand the observed results.
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Síndrome de Down , Humanos , Lactante , Mortalidad Infantil , Modelos de Riesgos Proporcionales , Factores de Riesgo , Fumar/efectos adversosRESUMEN
Zika virus infection during pregnancy can cause serious birth defects of the brain and eyes, including intracranial calcifications, cerebral or cortical atrophy, chorioretinal abnormalities, and optic nerve abnormalities (1,2). The frequency of these Zika-associated brain and eye defects, based on data from the U.S. Zika Pregnancy and Infant Registry (USZPIR), has been previously reported in aggregate (3,4). This report describes the frequency of individual Zika-associated brain and eye defects among infants from pregnancies with laboratory evidence of confirmed or possible Zika virus infection. Among 6,799 live-born infants in USZPIR born during December 1, 2015-March 31, 2018, 4.6% had any Zika-associated birth defect; in a subgroup of pregnancies with a positive nucleic acid amplification test (NAAT) for Zika virus infection, the percentage was 6.1% of live-born infants. The brain and eye defects most frequently reported included microcephaly, corpus callosum abnormalities, intracranial calcification, abnormal cortical gyral patterns, ventriculomegaly, cerebral or cortical atrophy, chorioretinal abnormalities, and optic nerve abnormalities. Among infants with any Zika-associated birth defect, one third had more than one defect reported. Certain brain and eye defects in an infant might prompt suspicion of prenatal Zika virus infection. These findings can help target surveillance efforts to the most common brain and eye defects associated with Zika virus infection during pregnancy should a Zika virus outbreak reemerge, and might provide a signal to the reemergence of Zika virus, particularly in geographic regions without ongoing comprehensive Zika virus surveillance.
Asunto(s)
Encéfalo/anomalías , Anomalías Congénitas/virología , Anomalías del Ojo/virología , Complicaciones Infecciosas del Embarazo , Infección por el Virus Zika/complicaciones , Anomalías Congénitas/epidemiología , Anomalías del Ojo/epidemiología , Femenino , Humanos , Recién Nacido , Nacimiento Vivo/epidemiología , Vigilancia de la Población , Embarazo , Sistema de Registros , Estados Unidos/epidemiologíaRESUMEN
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.