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Objective: To compare maternal demographics based on occupation coding status and evaluate potential bias by excluding manually coded occupations. Methods: This case-control study assessed cases with clefts obtained from the Texas Birth Defects Registry. The NIOSH Industry and Occupation Computerized Coding Systemautomatically coded occupations, withmanual coding for unclassified cases. Maternal demographics were tabulated by occupation coding status (manual vs. automatic). Logistic regression examined associations between major occupation groups and clefts. Results: Automatic coding covered over 90% of all mothers. Building, grounds cleaning, and maintenance occupations, and office and administrative support occupations were significantly associated with cleft lip with or without cleft palate, even after excluding manually coded occupations. Conclusion: We found consistent associations before and after excluding manually coded data for most comparisons, suggesting that machine learning can facilitate occupation-related birth defects research. [ABSTRACT FROM AUTHOR]

Background: Coloboma is a rare congenital malformation in which part of the tissue that makes up the eye is missing and may cause visual impairment or blindness. Little is known about the epidemiology of this condition. Therefore, we obtained data from the Texas Birth Defects Registry on children identified with coloboma for the period 1999-2014., Methods: Using information on all live births from the same period, prevalence ratios (PRs) for selected demographic and clinical factors were used to estimate associations using Poisson regression among cases with coloboma. Coloboma cases were divided into subgroups to explore patterns of co-occurring defects and syndromes. All variables significant in unadjusted models (p < 0.05) were included in multivariable models to evaluate adjusted PRs (aPRs)., Results: We identified 1587 cases with coloboma, of whom 934 (58.8%) were nonsyndromic, and 474 (29.9%) were isolated. When considering all identified cases, factors associated with significant differences in prevalence included plurality (multiple vs. singleton aPR = 1.4, 95% CI: 1.1-1.8); maternal education (college or greater vs. less than high school aPR = 0.7, 95% CI: 0.6-0.9); maternal race/ethnicity (Hispanic vs. non-Hispanic White aPR = 0.9, 95% CI: 0.8-1.0); and maternal diabetes (yes vs. no aPR = 1.3, 95% CI: 1.0-1.6). There was a notable increase in the birth prevalence of coloboma during the study period (p-for-trend < 0.001). Effect estimates were similar across the different subgroups., Conclusion: In our large population, we identified several factors associated with the prevalence of coloboma. These findings may help define subgroups of women more likely to have children affected by coloboma, which could inform improved screening efforts., (© 2024 Wiley Periodicals LLC.)

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., (© 2024 Wiley Periodicals LLC.)

Study Question: What is the association between ART conception and treatment parameters and the risk of birth defects?Summary Answer: Compared to naturally conceived singleton infants, the risk of a major nonchromosomal defect among ART singletons conceived with autologous oocytes and fresh embryos without use of ICSI was increased by 18%, with increases of 42% and 30% for use of ICSI with and without male factor diagnosis, respectively.What Is Known Already: Prior studies have indicated that infertility and ART are associated with an increased risk of birth defects but have been limited by small sample size and inadequate statistical power, failure to differentiate results by plurality, differences in birth defect definitions and methods of ascertainment, lack of information on ART treatment parameters or study periods spanning decades resulting in a substantial historical bias as ART techniques have improved.Study Design, Size, Duration: This was a population-based cohort study linking ART cycles reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) from 1 January 2004 to 31 December 2015 that resulted in live births from 1 September 2004 to 31 December 2016 in Massachusetts and North Carolina and from 1 September 2004 to 31 December 2015 for Texas and New York: these were large and ethnically diverse States, with birth defect registries utilizing the same case definitions and data collected, and with high numbers of ART births annually. A 10:1 sample of non-ART births were chosen within the same time period as the ART birth. Naturally conceived ART siblings were identified through the mother's information. Non-ART children were classified as being born to women who conceived with ovulation induction (OI)/IUI when there was an indication of infertility treatment on the birth certificate, but the woman did not link to the SART CORS; all others were classified as being naturally conceived.Participants/materials, Setting, Methods: The study population included 135 051 ART children (78 362 singletons and 56 689 twins), 23 647 naturally conceived ART siblings (22 301 singletons and 1346 twins) and 9396 children born to women treated with OI/IUI (6597 singletons and 2799 twins) and 1 067 922 naturally conceived children (1 037 757 singletons and 30 165 twins). All study children were linked to their respective State birth defect registries to identify major defects diagnosed within the first year of life. We classified children with major defects as either chromosomal (i.e. presence of a chromosomal defect with or without any other major defect) or nonchromosomal (i.e. presence of a major defect but having no chromosomal defect), or all major defects (chromosomal and nonchromosomal). Logistic regression models were used to generate adjusted odds ratios (AORs) and 95% CI to evaluate the risk of birth defects due to conception with ART (using autologous oocytes and fresh embryos), and with and without the use of ICSI in the absence or presence of male factor infertility, with naturally conceived children as the reference. Analyses within the ART group were stratified by combinations of oocyte source (autologous, donor) and embryo state (fresh, thawed), with births from autologous oocytes and fresh embryos as the reference. Analyses limited to fresh embryos were stratified by oocyte source (autologous, donor) and the use of ICSI. Triplets and higher-order multiples were excluded.Main Results and the Role Of Chance: A total of 21 998 singleton children (1.9%) and 3037 twin children (3.3%) had a major birth defect. Compared to naturally conceived children, ART singletons (conceived from autologous oocytes, fresh embryos without the use of ICSI) had increased risks of a major nonchromosomal birth defect (AOR 1.18, 95% 1.05, 1.32), cardiovascular defects (AOR 1.20, 95% CI 1.03, 1.40), and any birth defect (AOR 1.18, 95% CI 1.09, 1.27). Compared to naturally conceived children, ART singletons conceived (from autologous oocytes, fresh embryos) with the use of ICSI, the risks were increased for a major nonchromosomal birth defect (AOR 1.30, 95% CI 1.16, 1.45 without male factor diagnosis; AOR 1.42, 95% CI 1.28, 1.57 with male factor diagnosis); blastogenesis defects (AOR 1.49, 95% CI 1.08, 2.05 without male factor; AOR 1.56, 95% CI 1.17, 2.08 with male factor); cardiovascular defects (AOR 1.28, 95% CI 1.10,1.48 without male factor; AOR 1.45, 95% CI 1.27, 1.66 with male factor); in addition, the risk for musculoskeletal defects was increased (AOR 1.34, 95% CI 1.01, 1.78 without male factor) and the risk for genitourinary defects in male infants was increased (AOR 1.33, 95% CI 1.08, 1.65 with male factor). Comparisons within ART singleton births conceived from autologous oocytes and fresh embryos indicated that the use of ICSI was associated with increased risks of a major nonchromosomal birth defect (AOR 1.18, 95% CI 1.03, 1.35), blastogenesis defects (AOR 1.65, 95% CI 1.08, 2.51), gastrointestinal defects (AOR 2.21, 95% CI 1.28, 3.82) and any defect (AOR 1.11, 95% CI 1.01, 1.22). Compared to naturally conceived children, ART singleton siblings had increased risks of musculoskeletal defects (AOR 1.32, 95% CI 1.04, 1.67) and any defect (AOR 1.15, 95% CI 1.08, 1.23). ART twins (conceived with autologous oocytes, fresh embryos, without ICSI) were at increased risk of chromosomal defects (AOR 1.89, 95% CI 1.10, 3.24) and ART twin siblings were at increased risk of any defect (AOR 1.26, 95% CI 1.01, 1.57). The 18% increased risk of a major nonchromosomal birth defect in singleton infants conceived with ART without ICSI (∼36% of ART births), the 30% increased risk with ICSI without male factor (∼33% of ART births), and the 42% increased risk with ICSI and male factor (∼31% of ART births) translates into an estimated excess of 386 major birth defects among the 68 908 singleton children born by ART in 2017.Limitations, Reasons For Caution: In the SART CORS database, it was not possible to differentiate method of embryo freezing (slow freezing vs vitrification), and data on ICSI was only available in the fresh embryo ART group. In the OI/IUI group, it was not possible to differentiate type of non-ART treatment utilized, and in both the ART and OI/IUI groups, data were unavailable on duration of infertility.Wider Implications Of the Findings: The use of ART is associated with increased risks of a major nonchromosomal birth defect, cardiovascular defect and any defect in singleton children, and chromosomal defects in twins; the use of ICSI further increases this risk, the most with male factor infertility. These findings support the judicious use of ICSI only when medically indicated. The relative contribution of ART treatment parameters versus the biology of the subfertile couple to this increased risk remains unclear and warrants further study.Study Funding/competing Interest(s): This project was supported by grant R01 HD084377 from the National Institute of Child Health and Human Development. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Child Health and Human Development, or the National Institutes of Health, nor any of the State Departments of Health which contributed data. E.W. is a contract vendor for SART; all other authors report no conflicts.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Background: Congenital hydrocephaly, an abnormal accumulation of fluid within the ventricular spaces at birth, can cause disability or death if untreated. Limited information is available about survival of infants born with hydrocephaly in Texas. Therefore, the purpose of the study was to calculate survival estimates among infants born with hydrocephaly without spina bifida in Texas., Methods: A cohort of live-born infants delivered during 1999-2017 with congenital hydrocephaly without spina bifida was identified from the Texas Birth Defects Registry. Deaths within 1 year of delivery were identified using vital and medical records. One-year infant survival estimates were generated for multiple descriptive characteristics using the Kaplan-Meier method. Crude hazard ratios (HRs) for one-year survival among infants with congenital hydrocephaly by maternal and infant characteristics and adjusted HRs for maternal race and ethnicity were estimated using Cox proportional hazard models., Results: Among 5709 infants born with congenital hydrocephaly without spina bifida, 4681 (82%) survived the first year. The following characteristics were associated with infant survival: maternal race and ethnicity, clinical classification (e.g., chromosomal or syndromic), preterm birth, birth weight, birth year, and maternal education. In the multivariable Cox proportional hazards model, differences in survival were observed by maternal race and ethnicity after adjustment for other maternal and infant characteristics. Infants of non-Hispanic Black (HR: 1.28, 95% CI: 1.04-1.58) and Hispanic (HR: 1.31, 95% CI: 1.12-1.54) women had increased risk for mortality, compared with infants of non-Hispanic White women., Conclusions: This study showed infant survival among a Texas cohort differed by maternal race and ethnicity, clinical classification, gestational age, birth weight, birth year, and maternal education in infants with congenital hydrocephaly without spina bifida. Findings confirm that mortality continues to be common among infants with hydrocephaly without spina bifida. Additional research is needed to identify other risk factors of mortality risk., (Published 2023. This article is a U.S. Government work and is in the public domain in the USA.)

Background: Few studies of congenital anomalies provide prevalence estimates stratified by maternal race/ethnicity. We sought to determine whether the prevalence of a broad spectrum of anomalies varies among offspring of women from different race/ethnic groups., Methods: We obtained information on cases with anomalies from the population-based Texas Birth Defects Registry, and denominator data on livebirths among Texas residents during 1999-2018 from the Texas Center for Health Statistics. We estimated the prevalence ratio (PR) and 95% confidence interval (CI) of N = 145 anomalies among offspring of Hispanic and non-Hispanic Black relative to non-Hispanic White women using Poisson regression, adjusting for maternal age, education, body mass index, and previous livebirths. We performed a two-stage analysis with a Bonferroni-adjusted p < 1.7 × 10 -4 in the initial screening phase to identify anomalies with statistically significant variation., Results: There were 7,698,768 livebirths and 1,187,385 anomalies diagnosed in 368,393 cases. The prevalence of any monitored congenital anomaly was similar among offspring of non-Hispanic White (referent), non-Hispanic Black (PR 0.98, CI 0.96-1.00), and Hispanic (PR 0.95, CI 0.93-0.96) women. We observed statistically significant racial/ethnic variation for 42 anomalies. Marked differences were observed when comparing offspring of non-Hispanic Black to non-Hispanic White women with respect to polydactyly (PR 4.38, CI 4.07-4.72), pyloric stenosis (PR 0.34, CI 0.29-0.40), and aortic valve atresia/stenosis (PR 0.51, CI 0.36-0.72)., Conclusions: Birth prevalence of many major congenital anomalies varies by maternal race and ethnicity. While the reasons for these differences are likely multifactorial, a thorough understanding of racial and ethnic disparities is useful to stimulate etiologic research., (© 2023 Wiley Periodicals LLC.)

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., (© 2023 Wiley Periodicals LLC.)

Objective: To estimate the proportion of neonatal mortality risk attributable to preterm delivery among neonates with birth defects., Study Design: 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 (death <28 days) attributable to prematurity (birth at <37 weeks vs ≥37 weeks) for 31 specific birth defects. To better understand the overall population burden, analyses were repeated for all birth defects combined., Results: 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., Conclusions: 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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., (© 2022 Wiley Periodicals LLC.)

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., (© 2022 Wiley Periodicals LLC.)

Background: Timely referral to services for children born with birth defects can improve health outcomes. Birth defects surveillance registries may be a valuable data source for connecting children to health and social service programs., Methods: Population-based, state-wide data from the Texas Birth Defects Registry (TBDR) at the Texas Department of State Health Services (DSHS) were used to connect children 9-18 months old, born with select birth defects with DSHS social workers. The social workers reviewed developmental milestones and referred children and their families to various health and social service programs. We tabulated the proportions of children meeting milestones and referral characteristics by referral program type and type of birth defect., Results: Social workers reached 67% (909/1,362) of identified families. Over half of children (54%, 488/909) were not meeting the developmental milestones for their age. Social workers provided over 3,000 program referrals, including referring 21% (194/909) of children to Early Childhood Intervention (ECI) and 28% (257/909) to case management., Conclusion: Our results illustrate a method of leveraging a birth defects surveillance system for referral services. Given the large number of referrals made, our findings suggest that birth defects registries can be a valuable source of data for referring children to programs., (© 2022 Wiley Periodicals LLC.)

Background: Birth defects are major contributors to healthcare resource use, disability, and mortality, particularly during the perinatal period. As the nation's public insurance program for low-income individuals, Medicaid funds a large proportion of healthcare costs associated with birth defects. Here, we explore birth defect-related factors associated with Medicaid participation in the first year of life., Methods: Infants born with birth defects between 2010 and 2014 were linked from the Texas Birth Defects Registry to the state's Medicaid claims database. Variation in Medicaid participation was examined by individual birth defect and by birth defect characteristics. The associations between covariates and Medicaid participation are described using percentages and adjusted prevalence ratios (APR)., Results: Of the 107,968 infants included in this study, 55,172 (51.1%) participated in Medicaid. Medicaid participation ranged from 12.1% for anencephaly to 77.8% for total anomalous pulmonary venous connection. An indicator of defect severity was associated with an increased likelihood of participation (APR = 1.22, 95% CI: 1.20-1.23). Medicaid participation was 60.8% for individuals with multiple major defects, compared with 45.4% for those without (APR = 1.24, 95% CI: 1.22-1.25). Among individual birth defects, Medicaid participation was almost universally higher for those co-occurring with other major defects., Conclusions: We detected large variations in Medicaid participation by individual birth defect. Infants participating in Medicaid tended to have more severe defects and were more likely to have multiple major defects. Medicaid claims databases can serve as valuable sources of data for surveillance efforts and observational studies, but care should be taken when generalizing findings., (© 2022 Wiley Periodicals LLC.)

Birth defects may influence the risk of childhood cancer development through a variety of mechanisms. The rarity of both birth defects and childhood cancers makes it challenging to study these associations, particularly for the very rare instances of each. To address this limitation, the authors conducted a record linkage-based cohort study among Texas children born between 1996 and 2005. Birth defects in the cohort were identified through the Texas Birth Defects Registry, and children who developed cancer were identified by using record linkage with Texas Cancer Registry data. Over 3 million birth records were included; 115,686 subjects had birth defects, and there were 2,351 cancer cases. Overall, children with a birth defect had a 3-fold increased risk of developing cancer (incidence rate ratio (IRR) = 3.05, 95% confidence interval (CI): 2.65, 3.50), with germ cell tumors (IRR = 5.19, 95% CI: 2.67, 9.41), retinoblastomas (IRR = 2.34, 95% CI: 1.21, 4.16), soft-tissue sarcomas (IRR = 2.12, 95% CI: 1.09, 3.79), and leukemias (IRR = 1.39, 95% CI: 1.09, 1.75) having statistically significant elevated point estimates. All birth defect groups except for musculoskeletal had increased cancer incidence. Untangling the strong relation between birth defects and childhood cancers could lead to a better understanding of the genetic and environmental factors that affect both conditions. [ABSTRACT FROM PUBLISHER]

Lowered maternal weight gain and reduction in early pregnancy have been associated with risk of neural tube defects (NTDs) in offspring. We examined the association of self-reported maternal dieting behaviors on the occurrence of NTDs. We conducted a population based case-control study among Mexican-American women who were residents of the 14 Texas counties bordering Mexico. Case women had an NTD-affected pregnancy identified at birth or prenatally and had deliveries during the years 1995-2000. Control women were those who delivered live born infants without an apparent congenital malformation, randomly selected and frequency-matched to cases by year and facility. One hundred eighty-four case women and 225 control women were asked in person about the use of nutritional supplements, dieting to lose weight, and type of weight reduction supplements used during the 3 months before conception. Women who reported being on a diet to lose weight during the 3 months before conception had an NTD odds ratio (OR) of 1.9 (95% confidence interval (CI) = 1.1, 3.3) compared with those not reporting being on a diet. Neither consuming vitamin drinks (OR = 1.2) nor using diet pills (OR = 1.6) during the 3 months before conception had ORs that were different from the null, when compared to women not reporting those behaviors. The risk effect for dieting did not differ markedly among normal or underweight (OR = 2.0, 95% CI = 0.7, 5.6), overweight (OR = 1.9, 95% CI = 0.7, 5.0), or obese women (OR = 1.5, 95% CI = 0.6, 4.0). No effect was seen among dieting women who were consuming at least 1.0 mg/day of folate (OR = 1.1, CI = 0.3, 4.5). Maternal dieting prior to conception may increase the risk of NTDs in offspring. [ABSTRACT FROM AUTHOR]

BACKGROUND: Previous studies have reported positive associations between maternal exposure to air pollutants and several adverse birth outcomes. However, there have been no studies assessing the association between environmental levels of hazardous air pollutants, such as benzene, and neural tube defects (NTDs), a common and serious group of congenital malformations. OBJECTIVE: Our goal was to conduct a case-control study assessing the association between ambient air levels of benzene, toluene, ethylbenzene, and xylene (BTEX) and the prevalence of NTDs among offspring. METHODS: The Texas Birth Defects Registry provided data on NTD cases (spina bifida and anencephaly) delivered between 1999 and 2004. The control group was a random sample of unaffected live births, frequency matched to cases on year of birth. Census tract-level estimates of annual BTEX levels were obtained from the U.S. Environmental Protection Agency 1999 Assessment System for Population Exposure Nationwide. Restricted cubic splines were used in mixed-effects logistic regression models to determine associations between each pollutant and NTD phenotype. RESULTS: Mothers living in census tracts with the highest benzene levels were more likely to have offspring with spina bifida than were women living in census tracts with the lowest levels (odds ratio = 2.30; 95% confidence interval, 1.22-4.33). No significant associations were observed between anencephaly and benzene or between any of the NTD phenotypes and toluene, ethylbenzene, or xylene. CONCLUSION: In the first study to assess the relationship between environmental levels of BTEX and NTDs, we found an association between benzene and spina bifida. Our results contribute to the growing body of evidence regarding air pollutant exposure and adverse birth outcomes. [ABSTRACT FROM AUTHOR]

Purpose: (1) Determine if there is an association between 3 conotruncal heart birth defects and urban/rural residence of mother. (2) Compare results using different methods of measuring urban/rural status. Methods: Data were taken from the Texas Birth Defects Registry, 1999-2003. Poisson regression was used to compare crude and adjusted birth prevalence. Findings: Based on residences of births in Texas, the values for urban influence code (UIC), rural urban continuum code (RUCC), and rural urban commuting area (RUCA) were highly correlated with each other and, less highly, to percentage of land in crops. For tetralogy of Fallot, the most rural category consistently showed the highest prevalence ratio for all measures. The adjusted prevalence ratio for highest percentage cropland was 1.73 [95% CI, 1.14-2.51] using natural breaks and 1.42 [95% CI, 1.07-1.86] using quartiles. The trend with cropland percentage was significant ( P < .03), whether crude or adjusted. The crude trend was also significant using RUCC. Neither truncus arteriosus nor transposition of the great arteries exhibited consistent associations with urban or rural residence. Conclusions: The urban/rural measures were generally correlated with each other; as a broad measure, RUCA has advantages for many health studies. Tetralogy of Fallot was most prevalent in rural areas; that pattern was strongest using percentage of land in crops. [ABSTRACT FROM AUTHOR]

Abstract: Objective. : Neural tube defects (NTDs) affect about seven of every 10,000 deliveries in Texas. To reduce the risk for NTDs, women are encouraged to supplement with 400 mcg folic acid daily during their reproductive years. This study examines folic acid awareness, knowledge, and supplementation practices among women of childbearing age (WCBA), including residents of Texas–Mexico border as well as women of Hispanic origin/ethnicity, populations that have NTD rates up to three times higher than the national average. Methods. : We conducted a statewide multistage sample telephone survey among Texas women of childbearing age in 2001. In total 1,196 women age 18 to 44 were interviewed. Results. : About 78% of WCBA knew about folic acid, 28% knew that folic acid prevents birth defects, and 25% knew to take folic acid before pregnancy. The prevalence of daily folic acid supplementation among all women of childbearing age was 33%. Education was the strongest predictor of folic acid awareness followed by race/ethnicity and age. Significant predictors of daily folic acid supplementation were education and ethnicity. Conclusions. : Our findings suggest the need for more emphases on strategies to improve the level of folic acid supplementation among low educated women, and race ethnic minority populations. [Copyright &y& Elsevier]

Background: The etiologies of major birth defects are still unclear and few spatial analyses have been conducted in the United States. Spatial analyses of individual-level data can help elucidate environmental and social risk factors., Methods: We used generalized additive models to analyze 52,955 cases of neural tube defects, congenital heart defects (CHDs), gastroschisis, and orofacial cleft defects, and sampled from 642,399 controls born between 1999 and 2011 in Texas. The effect of geographic location was measured using a bivariable smooth term of geocoded birth address within a logistic regression framework. We calculated and mapped odds ratios (ORs) and 95% confidence intervals (CIs) for birth defects subtypes across Texas, and adjusted for maternal characteristics, environmental indicators, and community-level covariates. We also performed time-stratified spatiotemporal analyses for more prevalent birth defects., Results: Location was significantly associated with crude odds of all birth defects except hypoplastic left heart syndrome. After adjusting for maternal characteristics, environmental indicators, and community-level factors, ORs in many geographic areas were no longer statistically significant for most defects, especially CHDs. However, areas of significant and insignificant elevated risk remained for defects in all groups in North and South Texas, with ORs for ventricular septal defects increasing over time. Low risk of birth defects was often present in the northern part of East Texas., Conclusion: Significant spatial patterns of birth defects were identified and varied depending on adjustment of different categories of covariates. Further investigation of areas with increased risks may aid in our understanding of birth defects., (© 2021 Wiley Periodicals LLC.)

Unconventional natural gas developments (UNGD) may release air and water pollutants into the environment, potentially increasing the risk of birth defects. We conducted a case-control study evaluating 52,955 cases with birth defects and 642,399 controls born between 1999 and 2011 to investigate the relationship between UNGD exposure and the risk of gastroschisis, congenital heart defects (CHD), neural tube defects (NTDs), and orofacial clefts in Texas. We calculated UNGD densities (number of UNGDs per area) within 1, 3, and 7.5 km of maternal address at birth and categorized exposure by density tertiles. For CHD subtypes with large case numbers, we also performed time-stratified analyses to examine temporal trends. We calculated adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the association with UNGD exposure, accounting for maternal characteristics and neighborhood factors. We also included a bivariable smooth of geocoded maternal location in an additive model to account for unmeasured spatially varying risk factors. Positive associations were observed between the highest tertile of UNGD density within 1 km of maternal address and risk of anencephaly (aOR: 2.44, 95% CI: 1.55, 3.86), spina bifida (aOR: 2.09, 95% CI: 1.47, 2.99), gastroschisis among older mothers (aOR: 3.19, 95% CI: 1.77, 5.73), aortic valve stenosis (aOR: 1.90, 95% CI: 1.33, 2.71), hypoplastic left heart syndrome (aOR: 2.00, 95% CI: 1.39, 2.86), and pulmonary valve atresia or stenosis (aOR: 1.36, 95% CI: 1.10, 1.66). For CHD subtypes, results did not differ substantially by distance from maternal address or when residual confounding was considered, except for atrial septal defects. We did not observe associations with orofacial clefts. Our results suggest that UNGDs were associated with some CHDs and possibly NTDs. In addition, we identified temporal trends and observed presence of spatial residual confounding for some CHDs. • Unconventional natural gas development (UNGD) density assessed at 1, 3, and 7.5 km. • Living near UNGDs increased the risk of some neural tube defects and gastroschisis. • Risk of congenital heart defects (CHD) did not differ by UNGD distance. • Increased risk for ventricular septal defects and atrial septal defects over time. [ABSTRACT FROM AUTHOR]

Purpose: Our objective was to comprehensively evaluate the risk of a broad range of birth defects among offspring of women with diabetes, overall and stratified by pregestational versus gestational diagnosis, using the phenome-wide association (PheWAS) methodology.Methods: We performed a registry linkage study of all live births (>6,500,000) and birth defects cases (>290,000) in Texas, 1999-2015. We ascertained diabetes from birth and fetal death certificates. We calculated prevalence rate ratios (PRR) for phenotypes with ≥10 cases among exposed offspring (n = 130).Results: Diabetes was associated with the prevalence of any defect (PRR 1.40, 95% confidence interval [CI] 1.38-1.42), multiple defects (PRR 1.86, 95% CI 1.81-1.91), and 60 specific phenotypes, including novel (hypospadias, mitral stenosis) and previously reported phenotypes (renal a-/dysgenesis, spinal anomalies). Pregestational diabetes was a stronger risk factor for any defect (PRR 2.00, 95% CI 1.93-2.07), multiple defects (PRR 3.27, 95% CI 3.11-3.44), and the 60 specific phenotypes evaluated. Gestational diabetes was associated with any defect (PRR 1.21, 95% CI 1.19-1.23) and 47 specific birth defects phenotypes, although associations were weaker than for pregestational diabetes.Conclusions: The PheWAS is an efficient way to identify risk factors for disease using population-based registry data. Pregestational diabetes is associated with a broader range of phenotypes than previously reported. Because diabetes is diagnosed in 1% of women prior to pregnancy and 6%-9% during pregnancy, our results highlight a significant public health concern. [ABSTRACT FROM AUTHOR]

Myelomeningocele (MMC) and congenital heart disease (CHD) are independent risk factors for increased morbidity and mortality in the newborn period and each can require significant operations shortly after birth. Few studies have examined the impact of these combined lesions. We sought to examine the incidence of CHD in patients with MMC, and to evaluate length of stay (LOS), hospital charges, and mortality. Using the Texas Inpatient Public Use Data File, ~ 6.9 million newborn records between 1/1999 and 12/2016 were examined. Hospitalizations were classified as MMC without CHD (n = 3054), CHD without MMC (n = 72,266), and MMC with CHD (n = 171). The birth prevalence of CHD with MMC was 0.3/10,000 live hospital births, with 5% of patients with MMC having CHD, and 0.2% of those with CHD having MMC. There was increased LOS in patients with both MMC and CHD (median 15 days, IQR 5-31), compared to CHD without MMC (median 6 days, IQR 2-20) and MMC without CHD (median 8 days, IQR 1-14) and higher total hospital charges (median $95,007, IQR $26,731-$222,660) compared to CHD without MMC (median $27,726, $6463-$118,370) and MMC without CHD (median $40,066, IQR $5744-$97,490). Mortality was significantly higher in patients with MMC and CHD (22.2% compared to 3.1% in MMC without CHD and 4.1% in CHD without MMC). Significance remained when limiting for patients without genetic conditions or additional major birth defects. MMC with CHD in the newborn compared to either CHD or MMC alone is associated with longer LOS, higher charges, and increased mortality.

Background: The proportion of deaths attributed to various causes has not been quantified among infants with birth defects. We sought to describe the causes of neonatal and postneonatal death among infants in the Texas Birth Defects Registry., Methods: We calculated frequencies and percentages for both underlying causes and all causes (underlying or contributing) of neonatal (0-27 days) and postneonatal (28-364 days) death listed on death certificates among infants born alive with birth defects and delivered in Texas during 1999-2013 (n = 8,389 deaths). Analyses were repeated separately for infants with isolated, multiple, and syndromic defects., Results: After birth defects, the most frequently listed causes of neonatal death were preterm/low birth weight (10%), circulatory system diseases (8%), and sepsis (5%). The leading postneonatal causes of death beyond birth defects were circulatory system diseases (32%), sepsis (11%), and renal failure (7%)., Conclusions: Improved understanding of the causes of mortality among infants with birth defects may help identify priorities for postnatal care. Our results suggest that potentially modifiable causes of death (e.g., circulatory system diseases, sepsis) contribute substantially to mortality in this population. Prioritizing continued improvements in prevention, diagnosis, and management of preventable conditions may reduce mortality among infants born with birth defects., (© 2021 Wiley Periodicals LLC.)

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., Competing Interests: Conflict of interest None., (Copyright © 2020 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background: Causes of most birth defects are largely unknown. Genetics, maternal factors (e.g., age, smoking) and environmental exposures have all been linked to some birth defects, including neural tube, oral cleft, limb reduction, and gastroschisis; however, the contribution of cumulative exposures across several environmental domains in association with these defects is not well understood., Methods: The Environmental Quality Index (EQI) and its domains (air, water, land, sociodemographic, built) were used to estimate county-level cumulative environmental exposures from 2006-2010 and matched to birth defects identified from Texas Birth Defects Registry and live birth records from births in years 2007-2010 (N = 1,610,709). Poisson regression models estimated prevalence ratios (PR) and 95% confidence intervals (CI) for associations between 10 birth defects and the EQI., Results: We observed some positive associations between worst environmental quality and neural tube, anencephaly, spina bifida, oral cleft, cleft palate, cleft lip with and without cleft palate, and gastroschisis [PR range: 1.12-1.55], but near null associations with limb reduction defects. Among domain specific results, we observed the strongest positive associations with the sociodemographic domain across birth defects but varied positive associations among the air and water domains, and negative or null associations with the land and built domains. Overall, few exposure-response patterns were evident., Conclusions: Our results highlight the complexities of cumulative, simultaneous environmental exposures in the prevalence rates of 10 selected birth defects. We were able to explore the impact of overall and domain specific environmental quality on birth defects and identify potential domain specific drivers of these associations., (© 2020 Wiley Periodicals LLC.)

Birth defects prevalence may vary seasonally, but previous studies have focused on a few commonly occurring phenotypes. We performed a phenome-wide association study (PheWAS) in order to evaluate the associations between season of conception and a broad range of birth defects. Date of conception was estimated for all livebirths and birth defect cases in Texas from 1999-2015 using data from vital records, provided by the Texas Department of State Health Services Center for Health Statistics. Birth defects diagnoses were obtained from the Texas Birth Defects Registry, a statewide, active surveillance system. We estimated prevalence ratios (PRs) for phenotypes with ≥50 cases according to conception in spring (March-May), summer (June-August) or fall (September-November) relative to winter (December-February), using Poisson regression. Season of conception was associated with 5% of birth defects studied in models adjusted for maternal age, education, race/ethnicity, and number of previous livebirths. Specifically, summer conception was associated with any monitored birth defect (PR 1.03, 95% CI 1.02-1.04) and five specific phenotypes, most notably Hirschsprung disease (PR 1.46, 95% CI 1.22-1.75). These findings suggest that seasonally variable exposures influence the development of several birth defects and may assist in identifying novel environmental risk factors.

Objective: To examine state-wide population trends in preterm delivery of children with critical congenital heart disease (CHD) over an 18-year period. We hypothesized that, coincident with early advancements in prenatal diagnosis, preterm delivery initially increased compared with the general population, and more recently has decreased., Study Design: Data from the Texas Public Use Data File 1999-2016 was used to evaluate annual percent preterm delivery (<37 weeks) in critical CHD (diagnoses requiring intervention at <1 year of age). We first evaluated for pattern change over time using joinpoint segmented regression. Trends in preterm delivery were then compared with all Texas livebirths. We then compared trends examining sociodemographic covariates including race/ethnicity, sex, and neighborhood poverty levels., Results: Of 7146 births with critical CHD, 1339 (18.7%) were delivered preterm. The rate of preterm birth increased from 1999 to 2004 (a mean increase of 1.69% per year) then decreased between 2005 and 2016 (a mean decrease of -0.41% per year). This represented a faster increase and then a similar decrease to that noted in the general population. Although the greatest proportion of preterm births occurred in newborns of Hispanic ethnicity and non-Hispanic black race, newborns with higher neighborhood poverty level had the most rapidly increasing rate of preterm delivery in the first era, and only a plateau rather than decrease in the latter era., Conclusions: Rates of preterm birth for newborns with critical CHD in Texas first were increasing rapidly, then have been decreasing since 2005., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: In this paper, we aimed to investigate the potential impacts of a fire accident in a fertilizer warehouse on chromosomal anomalies, including Trisomy 21 (T21) and Trisomy (T18) among pregnancies in Brazos County, Texas. We conducted an observational study in Brazos County, TX, with all patients of T18 and T21 cases in the live births in Brazos County between 2005-2014. The prevalence of T18 and T21 before, during, and after the accident in Brazos County were calculated and compared. The Standardized Morbidity Ratio (SMR) was applied to compare the prevalence of T18 and T21 in Brazos County to the statewide prevalence in Texas after adjusting for maternal race and age. Compared with statewide risk, the risk of T18 during the impacted years in Brazos county was found to be significantly higher (SMR = 5.0, 95% Confidence Interval(CI): 2.19-9.89), while there was no significant difference before (SMR = 0.77, 0.13-2.54) and after the accident (SMR = 0.71, 0.12-2.36). However, the prevalence of T21 during the impacted years was not significantly different from those before or after the accident. This study conclusively suggests that this fertilizer fire may be related to the increased prevalence of T18 in Brazos County, though the findings warrant further investigation.

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 2561 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 greater than 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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Few 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., Methods: We 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., Results: We 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., Conclusions: CODA 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)., (© 2019 Wiley Periodicals, Inc.)

Background: There is considerable variability in the prevalence of birth defects among racial/ethnic groups. This study estimated birth defect prevalence among the less studied non-Hispanic (NH) Asian/Pacific Islander (PI) and American Indian/Alaska Native (AI/AN) populations in Texas relative to NH Whites., Methods: Data were obtained from the Texas Birth Defect Registry from 1999 to 2015 for deliveries to Texas-resident women who were NH White, NH Asian/PI, or AI/AN. This covers a live birth population of 2.6 million. Prevalence ratios and 95% confidence intervals (95% CIs) were calculated for NH Asian/PIs and AI/ANs (relative to NH Whites) for 44 birth defects using Poisson regression adjusting for maternal age., Results: After adjustment there were 33 statistically significant prevalence ratios (aPRs). Among NH Asian/PIs, 23 defects had a lower aPR (0.38-0.86) and three defects had a higher aPR (1.19-2.50). AI/ANs had one defect with a significantly lower aPR (0.64) and six with a higher aPR (1.36-4.63)., Conclusions: Non-Hispanic Asian/PIs generally have a lower prevalence ratio for many birth defects while AI/ANs have a higher prevalence ratio compared to NH Whites. These findings update the limited literature on this topic and warrant additional research to identify the true associations across a range of birth defects among these understudied racial/ethnic groups., (© 2019 Wiley Periodicals, Inc.)

Background: Epidemiologic studies have consistently identified an association between spina bifida and maternal body mass index (BMI). Whether this reflects a causal relationship is unknown. If this association does reflect a causal relationship, the risk of spina bifida should change with changes in maternal BMI. We evaluated the association between spina bifida and maternal change in BMI, assessed using interpregnancy change in BMI (IPC-BMI)., Methods: We used data from the Texas Birth Defects Registry and statewide vital records for 248 spina bifida cases and 2,562 controls (2006-2012) to conduct a case-control study. We used logistic regression to estimate the association between IPC-BMI and spina bifida, with adjustment for potential confounders., Results: When assessed as a continuous variable, IPC-BMI was associated with spina bifida, with a 5% increase in the odds of spina bifida per unit (approximately 6 pounds) increase in BMI (adjusted odds ratios [aOR] = 1.05, 95% CI: 1.02, 1.09). When assessed as a categorical variable, with weight stable women as the referent, the odds of spina bifida were lower in women with any BMI decrease (aOR = 0.73, 95% CI: 0.50, 1.08) and higher in women with an increase of ≥1 BMI units (aOR = 1.17, 95% CI: 0.85, 1.62)., Conclusions: Our findings provide suggestive, although not conclusive, evidence that maternal prepregnancy change in BMI, assessed using IPC-BMI, is associated with spina bifida in the later pregnancy. Additional studies aimed at confirming this association and further strengthening the evidence for a causal relationship between spina bifida and maternal BMI are needed., (© 2019 Wiley Periodicals, Inc.)

Background: This is the first study to utilize the index of concentration at the extremes (ICE) to examine risk factors for spina bifida in Texas. The ICE is a useful measure for providing the degree to which residents in a certain area are concentrated into groups at the extremes of disadvantage and privilege. We introduce two novel ICE measures (language and nativity), and three existing ICE measures (race/ethnicity, income, and education), which we applied specifically to Texas residents., Methods: We used multivariable mixed-model Poisson regression analyses to estimate spina bifida birth prevalence and prevalence ratios among singleton live births in Texas, 1999-2014, for each of our ICE measures. Maternal census tract at delivery was included in the models as a random effect. Analyses were stratified by maternal race/ethnicity (Hispanics and non-Hispanic whites). Live births served as denominators for each category., Results: Among non-Hispanic white women, those in the most disadvantaged versus the advantaged census tract quintile had adjusted relative risk between 1.6 and 8.5 for having a baby affected by spina bifida. However, Hispanic women in the most disadvantaged versus advantaged census tract quintile for four ICE measures had a 33% to 87% lower risk of having an affected pregnancy., Conclusions: Findings suggest spina bifida risk is associated with neighborhood disadvantage or advantage, and that relationship seems to vary by race-ethnicity. The varied associations between ICE measures and spina bifida by race/ethnicity highlights the importance of using targeted interventions in the prevention of spina bifida., (© 2018 Wiley Periodicals, Inc.)

Objective: Assess temporal trends in congenital microcephaly., Methods: We used Texas inpatient discharge diagnoses between 2000 and 2015, restricting to newborns. Between 2000 and 2003, the maximum number of fields for recording diagnostic codes was eight, and between 2004 and 2015 it was 24. Microcephaly was classified into four subgroups based on co-occurring diagnoses: A (Known Causes), B (Other Birth Defects), C (Preterm Birth or Fetal Growth Restriction) and D (Isolated Cases)., Results: We identified 2,301 cases of microcephaly or 4.0 cases per 10,000 live births. There was an increase in the prevalence of microcephaly in 2012-2015 compared with 2000-2003, odds ratio = 1.85 (95% CI 1.64-2.10) Significant temporal increases in microcephaly were observed within each of the four microcephaly subgroups and significant temporal increases were also observed for eight other neonatal diagnoses during the same time period. When we restricted our analysis to cases with microcephaly identified using only the eight diagnostic codes available throughout the entire study period, the temporal trend for microcephaly was diminished or absent., Conclusions: It remains uncertain whether the observed increases in microcephaly and other neonatal diagnoses are real or an artifact of the change in the number of fields. However, since it is unlikely that there would be a simultaneous increase in microcephaly and eight other neonatal diagnoses, it is likely that some or all of the temporal increases in neonatal diagnoses are artifactual., (© 2019 Wiley Periodicals, Inc.)

Anophthalmia and microphthalmia are a set of rare, yet severe, birth defects considered to be part of a spectrum of developmental ocular malformations ranging from smaller than average to completely absent eyes. Despite their clinical significance, little is known about the etiologies of these conditions. The goal of this study was to expand our understanding of the epidemiology of anophthalmia and microphthalmia. Data for this population-based assessment were obtained from the Texas Birth Defects Registry (TBDR) and Center for Health Statistics for the period 1999-2009. Descriptive analyses and estimates of birth prevalence and prevalence ratios (PR) were determined for this defect. There were 1,262 definite anophthalmia and microphthalmia patients identified in the TBDR, with an overall combined prevalence of 3.0 per 10,000 live births. More than half (55.7%) of the patients had at least one chromosome abnormality or syndrome. In addition, 92.4% of nonsyndromic patients (i.e., have no recorded chromosome abnormalities or syndromes) had at least one additional birth defect. After adjustment for multiple factors, the prevalence of nonsyndromic anophthalmia and microphthalmia was higher among mothers who had ≥2 previous fetal deaths (PR = 1.43, 95% confidence interval [CI]: 1.03-1.97) and among mothers with any reported diabetes (PR = 2.08, 95% CI: 1.49-2.90). Our results confirm that children with anophthalmia and microphthalmia frequently have genetic syndromes or are born with other major birth defects. Our findings add to the limited body of literature on anophthalmia and microphthalmia as well as help define subgroups of women who are more likely to have children with this malformation., (© 2018 Wiley Periodicals, Inc.)

Background: The current study is the first to examine the association of a broad range of sociodemographic factors with conditions thought to arise most of the time by de novo mutation., Methods: Data were taken from 1999 to 2009 from the Texas Birth Defects Registry (TBDR), a statewide active surveillance program. We used Poisson regression to generate crude and adjusted measures of association; the latter included models with all variables and with a parsimonious subset of variables., Results: There were 1694 cases with any of the phenotypes in the panel, 1100 cases in a subpanel with ≥90% of cases thought to arise de novo, 523 with chromosomal deletion disorders, and 243 with imprinting disorders. In the most parsimonious models, there was an increasing time trend in all groups except imprinting (p ≤ 0.01). Plurality (twins, triplets, etc.) was associated with greater risk of all groups except chromosomal deletions (p ≤ 0.01). Parental age showed strong trends with all groups; paternal age was most important for the total and imprinting groups (p ≤ 0.0001), and maternal age for the others (p ≤ 0.04). De novo mutation phenotypes were more prevalent among offspring of fathers who are non-Hispanic White compared with some other race/ethnic groups., Conclusion: This study suggests that birth defects arising by new mutation may be more prevalent among offspring of older parents and in plural births. The increasing time pattern and race/ethnic pattern may be related to greater use of or access to genetic tests. This approach to mutation epidemiology seems feasible for birth defects registries to consider., (© 2015 Wiley Periodicals, Inc.)

Background: Previous studies observed that first birth is associated with an increased risk of some categories of birth defects. However, multiple statistical tests were conducted and it was unclear which of these associations would be replicated in a larger study. We used a large database to assess the association between maternal parity and 65 birth defects including birth defects that have not been previously studied., Methods: Using data from the Texas Birth Defects Registry for years 1999-2009, the risk of a birth defect occurring in a first, third, or fourth or higher birth was compared to the risk of a birth defect occurring in a second birth., Results: Women having their first birth had significantly increased odds of having an infant with 24 of 65 categories of birth defects when compared to women having their second birth. We also observed associations between first birth and an increased risk of five birth defects not previously reported (small penis, preaxial polydactyly, anomalies of the thoracic vertebrae, anomalies of the lumbar vertebrae, and sacroccygeal anomalies). Women having their third or fourth or higher birth had significantly increased odds of giving birth to infants with five of 65 birth defects when compared to second births., Conclusions: Our observations regarding the categories of birth defects that were associated with first births were highly consistent with observations from two previous studies. Research into biological, behavioral, and environmental factors that may increase the risk of specific birth defects among first births is needed to further explore these associations., (© 2015 Wiley Periodicals, Inc.)

This paper tests whether the strength of the "spring spike" in birth defects is related to agricultural production and urban location using Texas Birth Defects Registry data for the period 1996-2007. We find evidence of a spike in birth defects among children conceived in the spring and summer, but it is more pronounced in urban non-agricultural counties than in other types of counties. Furthermore, the spike lasts longer in urban non-agricultural counties as compared to other types of counties., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Low maternal intake of dietary choline and betaine (a choline derivative) has recently been investigated as a possible risk factor for neural tube defects (NTDs)., Methods: This case-control study examined the NTD risk associated with choline and betaine in 409 Mexican-American women who gave birth during 1995 to 2000 in the 14-county border region of Texas., Results: Using data from the food frequency questionnaire and the lowest quartiles of intake as the reference categories, a protective association was suggested between higher intakes of choline and betaine and NTD risk although the 95% confidence intervals for all risk estimates included 1.0. For choline intake in the second, third, and fourth quartiles, adjusted odds ratios were 1.2, 0.80, and 0.89, respectively. Betaine appeared more protective with odds ratios of 0.62, 0.73, and 0.61, respectively, for the second, third, and fourth quartiles of intake., Conclusion: Study findings suggest that dietary betaine may help to prevent NTDs., (© 2014 Wiley Periodicals, Inc.)

Background: Case reports and series have suggested an association between injury during pregnancy and several nervous system and nervous system-related adverse fetal/neonatal outcomes. This study's purpose is to further determine if there is an association between injury during pregnancy and nervous system birth defects in infancy., Methods: Through a case-control study, the association between injury during pregnancy and nervous system birth defects was tested using the Texas Birth Defects Registry (1999-2003). Semiautomated probabilistic bias analysis was used to correct for systematic error from misclassification of injury during pregnancy., Results: Of the 59,750 infants eligible for this study, 4144 (6.94%) were diagnosed with a nervous system birth defect and 315 (0.53%) of the infants' mothers were injured during pregnancy. Among these 315 women, 25 (7.94%) delivered an infant with a subsequent nervous system birth defect. The adjusted odds ratio for the association between injury during pregnancy and nervous system birth defects among all study infants was 1.00; 95% confidence interval, 0.63-1.56 and 2.44; 95% confidence interval, 1.08-5.53 among breech presentation infants. Probabilistic bias analysis supported these findings., Conclusion: No association between injury during pregnancy and nervous system birth defects was identified. Further exploration into the association among breech presentation infants is warranted., (Copyright © 2013 Wiley Periodicals, Inc.)