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Abstract Background Rheumatoid arthritis (RA) is often preceded by symptomatic phases during which classification criteria are not fulfilled. The health burden of these “at-risk” stages is not well described. This study assessed health-related quality of life (HRQoL), function, fatigue and depression in newly presenting patients with clinically suspect arthralgia (CSA), unclassified arthritis (UA) or RA. Methods Cross-sectional analysis of baseline Patient-Reported Outcome Measures (PROMs) was conducted in patients from the Birmingham Early Arthritis Cohort. HRQoL, function, depression and fatigue at presentation were assessed using EQ-5D, HAQ-DI, PHQ-9 and FACIT-F. PROMs were compared across CSA, UA and RA and with population averages from the HSE with descriptive statistics. Multivariate linear regression assessed associations between PROMs and clinical and sociodemographic variables. Results Of 838 patients included in the analysis, 484 had RA, 200 had CSA and 154 had UA. Patients with RA reported worse outcomes for all PROMs than those with CSA or UA. However, “mean EQ-5D utilities were 0.65 (95%CI: 0.61 to 0.69) in CSA, 0.61 (0.56 to 0.66) in UA and 0.47 (0.44 to 0.50) in RA, which was lower than in general and older (≥ 65 years) background populations.” In patients with CSA or UA, HRQoL was comparable to chronic conditions such as heart failure, severe COPD or mild angina. Higher BMI and older age (≥ 60 years) predicted worse depression (PHQ-9: -2.47 (-3.85 to -1.09), P

The Deepwater Horizon oil spill triggered a complex cascade of microbial responses that reshaped the dynamics of heterotrophic carbon degradation and the turnover of dissolved organic carbon (DOC) in oil contaminated waters. Our results from 21-day laboratory incubations in rotating glass bottles (roller bottles) demonstrate that microbial dynamics and carbon flux in oil-contaminated surface water sampled near the spill site two weeks after the onset of the blowout were greatly affected by activities of microbes associated with macroscopic oil aggregates. Roller bottles with oil-amended water showed rapid formation of oil aggregates that were similar in size and appearance compared to oil aggregates observed in surface waters near the spill site. Oil aggregates that formed in roller bottles were densely colonized by heterotrophic bacteria, exhibiting high rates of enzymatic activity (lipase hydrolysis) indicative of oil degradation. Ambient waters surrounding aggregates also showed enhanced microbial activities not directly associated with primary oil-degradation (β-glucosidase; peptidase), as well as a twofold increase in DOC. Concurrent changes in fluorescence properties of colored dissolved organic matter (CDOM) suggest an increase in oil-derived, aromatic hydrocarbons in the DOC pool. Thus our data indicate that oil aggregates mediate, by two distinct mechanisms, the transfer of hydrocarbons to the deep sea: a microbially-derived flux of oil-derived DOC from sinking oil aggregates into the ambient water column, and rapid sedimentation of the oil aggregates themselves, serving as vehicles for oily particulate matter as well as oil aggregate-associated microbial communities.

BackgroundThe acute-phase increase in serum C-reactive protein (CRP) is used to diagnose and monitor infectious and inflammatory diseases. Little is known about the influence of genetics on acute-phase CRP, particularly in patients with chronic inflammation.Methods and findingsWe studied two independent sets of patients with chronic inflammation due to rheumatoid arthritis (total 695 patients). A tagSNP approach captured common variation at the CRP locus and the relationship between genotype and serum CRP was explored by linear modelling. Erythrocyte sedimentation rate (ESR) was incorporated as an independent marker of inflammation to adjust for the varying levels of inflammatory disease activity between patients. Common genetic variants at the CRP locus were associated with acute-phase serum CRP (for the most associated haplotype: p = 0.002, pConclusionsOur findings raise questions about the interpretation of acute-phase serum CRP. In particular, failure to take into account the potential for genetic effects may result in the inappropriate reassurance or suboptimal treatment of patients simply because they carry low-CRP-associated genetic variants. CRP is increasingly being incorporated into clinical algorithms to compare disease activity between patients and to predict future clinical events: our findings impact on the use of these algorithms. For example, where access to effective, but expensive, biological therapies in rheumatoid arthritis is rationed on the basis of a DAS28-CRP clinical activity score, then two patients with identical underlying disease severity could be given, or denied, treatment on the basis of CRP genotype alone. The accuracy and utility of these algorithms might be improved by using a genetically adjusted CRP measurement.

Objective: To develop risk prediction models for preterm birth among infants with orofacial clefts., Design: Data from the Texas Birth Defects Registry for infants with orofacial clefts born between 1999-2014 were used to develop preterm birth predictive models. Logistic regression was used to consider maternal and infant characteristics, and internal validation of the final model was performed using bootstrapping methods. The area under the curve (AUC) statistic was generated to assess model performance, and separate predictive models were built and validated for infants with cleft lip and cleft palate alone. Several secondary analyses were conducted among subgroups of interest., Setting: State-wide, population-based Registry data., Patients/participants: 6774 infants with orofacial clefts born in Texas between 1999-2014., Main Outcome Measure(s): Preterm birth among infants with orofacial clefts., Results: The final predictive model performed modestly, with an optimism-corrected AUC of 0.67 among all infants with orofacial clefts. The optimism-corrected models for cleft lip (with or without cleft palate) and cleft palate alone had similar predictive capability, with AUCs of 0.66 and 0.67, respectively. Secondary analyses had similar results, but the model among infants with delivery prior to 32 weeks demonstrated higher optimism-corrected predictive capability (AUC = 0.74)., Conclusions: This study provides a first step towards predicting preterm birth risk among infants with orofacial clefts. Identifying pregnancies affected by orofacial clefts at the highest risk for preterm birth may lead to new avenues for improving outcomes among these infants., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective:  The Apgar score is a clinical tool to assess newborn health at delivery and has shown utility in predicting neonatal mortality in the general population, but its predictive ability in neonates with birth defects remains unexplored. As such, we aimed to investigate the performance of the 5-minute Apgar score in predicting neonatal mortality among neonates with a spectrum of major birth defects., Study Design:  Data for neonates with birth defects born between 1999 and 2017 were obtained from the Texas Birth Defect Registry. We generated receiver operating characteristic curves and corresponding area under the curve (AUC) values for neonatal mortality (death within the first 28 days of life) by 5-minute Apgar score (<7 vs. ≥7) to measure discrimination capacity. We performed secondary analyses to determine the predictive ability of the Apgar score: (1) among infants with an isolated birth defect and (2) separately in preterm and term neonates., Results:  Low Apgar score yielded substantial predictive ability for neonatal mortality, with 25 out of 26 AUC values > 0.70 across a spectrum of defect categories. High predictive ability was consistent among neonates with isolated defects, and preterm and term neonates., Conclusion:  The Apgar score is likely useful for predicting neonatal mortality among most neonates with birth defects. Despite small sample sizes limiting some secondary analyses, the findings emphasize the potential continued use of the Apgar score as a rapid clinical assessment tool for newborns with birth defects. Continued research may refine the Apgar score's application in this important population, both in clinical practice and population health research., Key Points: · Predictive models suggest the 5-minute Apgar score (<7) is predictive of neonatal mortality.. · Consistent results were observed across spectrum of birth defect categories.. · Secondary analyses (e.g., preterm infants) yielded similarly consistent results.., Competing Interests: None declared., (Thieme. All rights reserved.)

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.)

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 System automatically coded occupations, with manual 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., Competing Interests: Conflicts of interest: None declared., (Copyright © 2024 American College of Occupational and Environmental Medicine.)

Introduction: Traditional strategies for grouping congenital heart defects (CHDs) using birth defect registry data do not adequately address differences in expected clinical consequences between different combinations of CHDs. We report a lesion-specific classification system for birth defect registry-based outcome studies., Methods: For Core Cardiac Lesion Outcome Classifications (C-CLOC) groups, common CHDs expected to have reasonable clinical homogeneity were defined. Criteria based on combinations of Centers for Disease and Control-modified British Pediatric Association (BPA) codes were defined for each C-CLOC group. To demonstrate proof of concept and retention of reasonable case counts within C-CLOC groups, Texas Birth Defect Registry data (1999-2017 deliveries) were used to compare case counts and neonatal mortality between traditional vs. C-CLOC classification approaches., Results: C-CLOC defined 59 CHD groups among 62,262 infants with CHDs. Classifying cases into the single, mutually exclusive C-CLOC group reflecting the highest complexity CHD present reduced case counts among lower complexity lesions (e.g., 86.5% of cases with a common atrium BPA code were reclassified to a higher complexity group for a co-occurring CHD). As expected, C-CLOC groups had retained larger sample sizes (i.e., representing presumably better-powered analytic groups) compared to cases with only one CHD code and no occurring CHDs., Discussion: This new CHD classification system for investigators using birth defect registry data, C-CLOC, is expected to balance clinical outcome homogeneity in analytic groups while maintaining sufficiently large case counts within categories, thus improving power for CHD-specific outcome association comparisons. Future outcome studies utilizing C-CLOC-based classifications are planned., (© 2024 Wiley Periodicals LLC.)

Choanal atresia and stenosis are common causes of congenital nasal obstruction, but their epidemiology is poorly understood. Compared to bilateral choanal atresia/stenosis, unilateral choanal atresia/stenosis is generally diagnosed later and might be under-ascertained in birth defect registries. Data from the population-based Texas Birth Defects Registry and Texas vital records, 1999-2018, were used to assess the prevalence of choanal atresia/stenosis. Poisson regression models were used to evaluate associations with infant and maternal characteristics in two analytic groups: isolated choanal atresia/stenosis (n = 286) and isolated, bilateral choanal atresia/stenosis (n = 105). The overall prevalence of choanal atresia/stenosis was 0.92/10,000, and the prevalence of isolated choanal atresia/stenosis was 0.37/10,000 livebirths. Variables associated with choanal atresia/stenosis in one or both analytic groups included infant sex, pregnancy plurality, maternal race/ethnicity, maternal age, and maternal residence on the Texas-Mexico border. In general, adjusted prevalence ratios estimated from the two analytic groups were in the same direction but tended to be stronger in the analyses restricted to isolated, bilateral defects. Epidemiologic studies of isolated choanal atresia/stenosis should consider focusing on cases with bilateral defects, and prioritizing analyses of environmental, social, and structural factors that could account for the association with maternal residence on the Texas-Mexico border., (© 2024 Wiley Periodicals LLC.)

Background: Birth defects are a leading cause of neonatal, infant, and childhood mortality, but recent population-based survival estimates for a spectrum in the U.S. are lacking., Methods: Using the statewide Texas Birth Defects Registry (1999-2017 births) and vital records linkage to ascertain deaths, we conducted Kaplan-Meier analyses to estimate survival probabilities at 1, 7, and 28 days, and 1, 5, and 10 years. We evaluated survival in the full cohort of infants with any major defect and for 30 specific conditions. One-year survival analyses were stratified by gestational age, birth year, and case classification., Findings: Among 246,394 live-born infants with any major defect, the estimated survival probabilities were 98.9% at 1 day, 95.0% at 1 year, and 93.9% at 10 years. Ten-year survival varied by condition, ranging from 36.9% for holoprosencephaly to 99.3% for pyloric stenosis. One-year survival was associated with increasing gestational age (e.g., increasing from 46.9% at <28 weeks to 95.8% at ≥37 weeks for spina bifida). One-year survival increased in more recent birth years for several defect categories (e.g., increasing from 86.0% among 1999-2004 births to 93.1% among 2014-2017 births for unilateral renal agenesis/dysgenesis) and was higher among infants with an isolated defect versus those with multiple defects., Interpretation: This study describes short- and long-term survival outcomes from one of the largest population-based birth defect registries in the world and highlights improved survival over time for several conditions. Our results may lend insight into future healthcare initiatives aimed at reducing mortality in this population., Funding: This study was funded in part by a Centers for Disease Control and Prevention (CDC) birth defects surveillance cooperative agreement with the Texas Department of State Health Services and Health Resources and Services Administration (HRSA) Block Grant funds., Competing Interests: The authors have no conflicts of interest to disclose., (© 2023 The Authors.)

Many infants with anotia or microtia (A/M) have co-occurring birth defects, although few receive syndromic diagnoses in the perinatal period. Evaluation of co-occurring birth defects in children with A/M could identify patterns indicative of undiagnosed/unrecognized syndromes. We obtained information on co-occurring birth defects among infants with A/M for delivery years 1999-2014 from the Texas Birth Defects Registry. We calculated observed-to-expected ratios (OER) to identify birth defect combinations that occurred more often than expected by chance. We excluded children diagnosed with genetic or chromosomal syndromes from analyses. Birth defects and syndromes/associations diagnosed ≤1 year of age were considered. We identified 1310 infants with non-syndromic A/M, of whom 38% (N = 492) were diagnosed with co-occurring major defects. Top combinations included: hydrocephalus, ventricular septal defect, and spinal anomalies (OER 58.4); microphthalmia and anomalies of the aorta (OER 55.4); and cleft lip with or without cleft palate and rib or sternum anomalies (OER 32.8). Some combinations observed in our study may represent undiagnosed/atypical presentations of known A/M associations or syndromes, or novel syndromes yet to be described in the literature. Careful evaluation of infants with multiple birth defects including A/M is warranted to identify individuals with potential genetic or chromosomal syndromes., (© 2022 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.)

Background: Few risk factors have been identified for nonsyndromic anotia/microtia (A/M)., Methods: We obtained data on cases and a reference population of all livebirths in Texas for 1999-2014 from the Texas Birth Defects Registry (TBDR) and Texas vital records. We estimated prevalence ratios (PRs) and 95% confidence intervals (CIs) for A/M (any, isolated, nonisolated, unilateral, and bilateral) using Poisson regression. We evaluated trends in prevalence rates using Joinpoint regression., Results: We identified 1,322 cases, of whom 982 (74.3%) had isolated and 1,175 (88.9%) had unilateral A/M. Prevalence was increased among males (PR: 1.3, 95% CI: 1.2-1.4), offspring of women with less than high school education (PR: 1.3, 95% CI: 1.1-1.5), diabetes (PR: 2.0, 95% CI: 1.6-2.4), or age 30-39 versus 20-29 years (PR: 1.2, 95% CI: 1.0-1.3). The prevalence was decreased among offspring of non-Hispanic Black versus White women (PR: 0.6, 95% CI: 0.4-0.8) but increased among offspring of Hispanic women (PR: 2.9, 95% CI: 2.5-3.4) and non-Hispanic women of other races (PR: 1.7, 95% CI: 1.3-2.3). We observed similar results among cases with isolated and unilateral A/M. Sex disparities were not evident for nonisolated or bilateral phenotypes, nor did birth prevalence differ between offspring of non-Hispanic Black and non-Hispanic White women. Maternal diabetes was more strongly associated with nonisolated (PR: 4.5, 95% CI: 3.2-6.4) and bilateral A/M (PR: 5.0, 95% CI: 3.3-7.7). Crude prevalence rates increased throughout the study period (annual percent change: 1.82)., Conclusion: We identified differences in the prevalence of nonsyndromic A/M by maternal race/ethnicity, education, and age, which may be indicators of unidentified social/environmental risk factors., (© 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.)

Importance: Hypospadias is a common birth defect of the male urinary tract that may be isolated or may co-occur with other structural malformations, including congenital heart defects (CHDs). The risk for co-occurring CHDs among boys with hypospadias remains unknown, which limits screening and genetic testing strategies., Objective: To characterize the risk of major CHDs among boys born with hypospadias., Design, Setting, and Participants: This retrospective cohort study used data from population-based birth defect surveillance programs on all male infants born in 11 US states from January 1, 1995, to December 31, 2014. Statistical analysis was performed from September 2, 2020, to March 25, 2022., Exposure: Hypospadias., Main Outcomes and Measures: Demographic and diagnostic data were obtained from 2 active state-based birth defect surveillance programs for primary analyses, the Texas Birth Defects Registry and the Arkansas Reproductive Health Monitoring System, with validation among 9 additional states in the National Birth Defects Prevention Network (NBDPN). Birth defect diagnoses were identified using the British Pediatric Association coding for hypospadias (exposure) and major CHDs (primary outcomes). Maternal covariates and birth year were also abstracted from the vital records. Poisson regression was used to estimate adjusted prevalence ratios and 95% CIs for major CHDs within Texas and Arkansas and combined using inverse variance-weighted meta-analysis. Findings were validated using the NBDPN., Results: Among 3.7 million pregnancies in Texas and Arkansas, 1485 boys had hypospadias and a co-occurring CHD. Boys with hypospadias were 5.8 times (95% CI, 5.5-6.1) more likely to have a co-occurring CHD compared with boys without hypospadias. Associations were observed for every specific CHD analyzed among boys with hypospadias, occurred outside of chromosomal anomalies, and were validated in the NBDPN. An estimated 7.024% (95% CI, 7.020%-7.028%) of boys with hypospadias in Texas and 5.503% (95% CI, 5.495%-5.511%) of boys with hypospadias in Arkansas have a co-occurring CHD. In addition, hypospadias severity and maternal race and ethnicity were independently associated with the likelihood for hypospadias to co-occur with a CHD; boys in Texas with third-degree (ie, more severe) hypospadias were 2.7 times (95% CI, 2.2-3.4) more likely than boys with first-degree hypospadias to have a co-occurring CHD, with consistent estimates in Arkansas (odds ratio, 2.7; 95% CI, 1.4-5.3), and boys with hypospadias born to Hispanic mothers in Texas were 1.5 times (95% CI, 1.3-1.8) more likely to have a co-occurring CHD than boys with hypospadias born to non-Hispanic White mothers., Conclusions and Relevance: In this cohort study, boys with hypospadias had a higher prevalence of CHDs than boys without hypospadias. These findings support the need for consideration of additional CHD screening programs for boys born with hypospadias.

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.

Background: The population-level landscape of co-occurring birth defects among infants without a syndromic diagnosis is not well understood., Methods: We analyzed data from 40,771 infants with two or more major birth defects in the Texas Birth Defects Registry (TBDR; 1999-2014). We calculated adjusted observed-to-expected (O/E) ratios for all two, three, four, and five-way combinations of 138 major defects., Results: Among 530 patterns with the highest adjusted O/E ratios (top 5% of 10,595 patterns), 66% included only defects co-occurring within one organ system and 28% were suggestive of known patterns (e.g., midline developmental defects). Of the remaining patterns, the combination of defects with the highest O/E ratio (193.8) encompassed the diaphragm, spine, spleen, and heart defects. Fourteen patterns involved heart and spine defects with or without rib defects. Ten additional patterns primarily involved two hallmark components of VACTERL association (specifically, vertebral defects, anal atresia, cardiac defects, renal, or limb defects, but not tracheoesophageal fistula)., Conclusions: Our analyses provide a description of the birth defect co-occurrence patterns in a multi-ethnic, population-based sample, and revealed several patterns of interest. This work complements prior work that has suggested etiologic connections between select defects (e.g., diaphragmatic hernia and heart and spleen anomalies; heart and spine defects)., Impact: In this large-scale, population-based study of birth defect co-occurrence patterns, we found several birth defect combinations of potential interest that warrant further investigation: congenital diaphragmatic hernia, heart, spine, and spleen defects and scimitar syndrome with vertebral defects. The majority of patterns of co-occurring defects observed more frequently than expected involved multiple defects within the same system and combinations suggestive of known associations. Nearly all of the top patterns (beyond the same system and those suggestive of known associations) involved organ systems that are components of the VACTERL association, with heart, spine, and rib defect patterns being the most common., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

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., (© 2022 Wiley Periodicals LLC.)

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

Few population-based studies have analyzed patterns of co-occurring birth defects among those with trisomy 13. We evaluated the frequency of all possible combinations of any one, two, three, or four additional co-occurring birth defects among 736 individuals with trisomy 13 using data from the Texas Birth Defects Registry for deliveries during 1999-2014. We calculated the observed-to-expected ratio for each combination, adjusting for the known tendency for birth defects to cluster non-specifically. To address potential ascertainment differences among live births and non-live births, we repeated analyses specifically among live births. The combination of defects with the largest observed-to-expected ratio was microcephalus, reduction deformities of brain (e.g., holoprosencephaly), anomalies of nose, and polydactyly. As expected, most of the highest 30 observed-to-expected ratios involved combinations with documented features of trisomy 13, including defects of the scalp (e.g., aplasia cutis) and heart. Results were similar among sensitivity analyses restricted to live births. Our findings may help further delineate the phenotypic spectrum for trisomy 13 and may inform future research related to improving screening and counseling for the condition., (© 2021 Wiley Periodicals LLC.)

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.)

Background: Maternal hypertension has been associated with congenital heart defect occurrence in several studies. We assessed whether maternal genotypes associated with this condition were also associated with congenital heart defect occurrence., Methods: We used data from the National Birth Defects Prevention Study to identify non-Hispanic white (NHW) and Hispanic women with (cases) and without (controls) a pregnancy in which a select simple, isolated heart defect was present between 1999 and 2011. We genotyped 29 hypertension-related single nucleotide polymorphisms (SNPs). We conducted logistic regression analyses separately by race/ethnicity to assess the relationship between the presence of any congenital heart defect and each SNP and an overall blood pressure genetic risk score (GRS). All analyses were then repeated to assess 4 separate congenital heart defect subtypes., Results: Four hypertension-related variants were associated with congenital heart defects among NHW women (N = 1,568 with affected pregnancies). For example, 1 intronic variant in ARHGAP2, rs633185, was associated with conotruncal defects (odds ratio [OR]: 1.3, 95% confidence interval [CI]: 1.1-1.6). Additionally, 2 variants were associated with congenital heart defects among Hispanic women (N = 489 with affected pregnancies). The GRS had a significant association with septal defects (OR: 2.1, 95% CI: 1.2-3.5) among NHW women., Conclusions: We replicated a previously reported association between rs633185 and conotruncal defects. Although additional hypertension-related SNPs were also associated with congenital heart defects, more work is needed to better understand the relationship between genetic risk for maternal hypertension and congenital heart defects occurrence., (© American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

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: We sought to investigate associations between maternal/infant characteristics and isolated craniosynostosis as well as its subtypes sagittal, metopic, and coronal synostosis, and assess trends in the prevalence of these conditions., Methods: We identified cases in the Texas Birth Defects Registry from 1999 to 2014. We used Poisson regression to identify associations between maternal/infant characteristics and craniosynostosis. We used joinpoint regression and unadjusted Poisson regression to evaluate temporal trends. Finally, we computed adjusted Poisson models to evaluate whether temporal trends were evident after accounting for changes in the population distributions of maternal/infant characteristics over time., Results: Relative to all live births in the general population, cases were more frequently male or preterm. Mothers of cases were more frequently non-Hispanic white and more frequently obese. Non-Hispanic black or Hispanic maternal race/ethnicity was associated with a lower prevalence of all craniosynostosis subtypes. Previous live births were associated with sagittal synostosis; residence on the U.S.-Mexico border was associated with sagittal and coronal synostosis. The prevalence of any isolated craniosynostosis increased (average annual percent change estimated from joinpoint regression [AAPC]: 2.9%), as did the prevalences of sagittal (AAPC: 3.3%) and metopic synostosis (AAPC: 5.4%). In crude Poisson models, the same temporal trends were observed, however these were attenuated after adjusting for maternal/infant characteristics., Conclusions: Prevalence of isolated craniosynostosis increased from 1999 to 2014. The largest AAPC was observed for metopic synostosis. Changes in the population distribution of associated maternal/infant characteristics may explain these trends., (© 2020 Wiley Periodicals LLC.)

Gastroschisis and omphalocele are the two most common abdominal wall birth defects, and epidemiologic characteristics and frequency of occurrence as part of a syndromic condition suggest distinct etiologies between the two defects. We assessed complex patterns of defect co-occurrence with these defects separately using the Texas Birth Defects Registry. We used co-occurring defect analysis (CODA) to compute adjusted observed-to-expected (O/E) ratios for all observed birth defect patterns. There were 2,998 non-syndromic (i.e., no documented syndrome diagnosis identified) cases with gastroschisis and 789 (26%) of these had additional co-occurring defects. There were 720 non-syndromic cases with omphalocele, and 404 (56%) had additional co-occurring defects. Among the top 30 adjusted O/E ratios for gastroschisis, most of the co-occurring defects were related to the gastrointestinal system, though cardiovascular and kidney anomalies were also present. Several of the top 30 combinations co-occurring with omphalocele appeared suggestive of OEIS (omphalocele, exstrophy of cloaca, imperforate anus, spinal defects) complex. After the exclusion of additional cases with features suggestive of OEIS in a post-hoc sensitivity analysis, the top combinations involving defects associated with OEIS (e.g., spina bifida) were no longer present. The remaining top combinations involving omphalocele included cardiovascular, gastrointestinal, and urogenital defects. In summary, we identified complex patterns of defects that co-occurred more frequently than expected with gastroschisis and omphalocele using a novel software platform. Better understanding differences in the patterns between gastroschisis and omphalocele could lead to additional etiologic insights., (© 2020 Wiley Periodicals LLC.)

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: It is hypothesized that cesarean delivery may reduce mortality among infants with spina bifida (e.g., by reducing trauma to the open lesion); however, few studies have assessed this relationship., Methods: We used the Texas Birth Defects Registry to identify neonates with spina bifida born between 1999 and 2014. The mode of delivery (main exposure) was abstracted from each subject's birth certificate. The vital status (main outcome) was determined based on the presence or absence of a death certificate. When a death certificate was present, survival time was calculated by subtracting the date of birth from the date of death. We then conducted multivariable Cox proportional hazards regression to estimate the adjusted hazard ratio between cesarean delivery and death prior to 29 days. We adjusted for maternal race/ethnicity, maternal education, gestational age/birthweight, and breech presentation. This analysis was repeated for death prior to 365 days., Results: We analyzed 1,983 nonsyndromic, liveborn neonates with spina bifida, and 68% of these neonates were delivered by cesarean. After adjusting for potential confounders, the adjusted hazard ratio [aHR] for death prior to 29 days was 0.77 (95% confidence interval [CI] 0.49, 1.21) and the aHR for death prior to 365 days was 0.93 (95% CI 0.63, 1.38) comparing infants delivered by cesarean to those delivered vaginally., Conclusions: Despite a lack of strong prior epidemiologic evidence, cesarean rates for neonates with spina bifida were high. Further investigations of the relationship between mode of delivery and infant outcomes, including mortality, complications, and long-term prognosis, are warranted., (© 2019 Wiley Periodicals, Inc.)

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: 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: We examined the association between the maternal genotype for celiac disease-associated variants and risk of neural tube defects (NTDs)., Methods: We conducted a case-control study, using data from the National Birth Defects Prevention Study. We evaluated 667 cases (women with an offspring with NTD) and 743 controls (women with an offspring without a birth defect). We classified women as having low, intermediate, or high risk of celiac disease based on human leukocyte antigen (HLA) variants. We used logistic regression to assess the relationship between HLA celiac risk group (low, intermediate, high) and risk of NTDs. Fifteen non-HLA variants (identified from genome-wide association studies of celiac disease) were individually evaluated and modeled additively., Results: There was no association between HLA celiac risk group and NTDs (intermediate vs. low risk: aOR, 1.0; 95% CI, 0.8-1.3; high vs. low risk: aOR, 0.8; 95% CI, 0.5-1.3). Of the fifteen non-HLA variants, we observed five significant associations after accounting for multiple comparisons. Three negative associations were observed with rs10903122, rs13314993, rs13151961 (aOR range: 0.69-0.81), and two positive associations were observed with rs13003464 and rs11221332 (aOR range: 1.27-1.73)., Conclusion: If confirmed, our results suggest that the maternal variants related to celiac disease may be involved in the risk of NTDs., (© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

Background: Mode of delivery is hypothesised to influence clinical outcomes among neonates with gastroschisis. Results from previous studies of neonatal mortality have been mixed; however, most studies have been small, clinical cohorts and have not adjusted for potential confounders., Objectives: To evaluate whether caesarean delivery is associated with mortality among neonates with gastroschisis., Methods: We studied liveborn, nonsyndromic neonates with gastroschisis delivered during 1999-2014 using data from the Texas Birth Defect Registry. Using multivariable Cox proportional hazards regression, we separately assessed the relationship between caesarean and death during two different time periods, prior to 29 days (<29 days) and prior to 365 days (<365 days) after delivery, adjusting for potential confounders. We also updated a recent meta-analysis on this relationship, combining our estimates with those from the literature., Results: Among 2925 neonates with gastroschisis, 63% were delivered by caesarean. No associations were observed between caesarean delivery and death <29 days (adjusted hazard ratio [aHR] 1.00, 95% confidence interval [CI] 0.63, 1.61) or <365 days after delivery (aHR 0.99, 95% CI 0.70, 1.41). The results were similar among those with additional malformations and among those without additional malformations. When we combined our estimate with prior estimates from the literature, results were similar (combined risk ratio [RR] 1.00, 95% CI 0.84, 1.19)., Conclusions: Although caesarean rates among neonates with gastroschisis were high, our results suggest that mode of delivery is not associated with mortality among these individuals. However, data on morbidity outcomes (eg intestinal damage, infection) were not available in this study., (© 2019 John Wiley & Sons Ltd.)

Background: Maternal prepregnancy body mass index (BMI) is associated with several infant outcomes, but it is unclear whether these associations reflect causal relationships. We conducted a study of interpregnancy change in BMI (IPC-BMI) to improve understanding of the associations between BMI and large for gestational age (LGA), small for gestational age (SGA), and preterm birth (PTB)., Methods: Birth certificate data from 2481 linked sibling pairs (Texas, 2005-2012) were used to estimate IPC-BMI and evaluate its association with LGA, SGA, and PTB in the younger sibling of the pair. Multivariable logistic regression was used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) using data from the full sample and within strata defined by prepregnancy BMI for the older sibling., Results: On average, women gained 1.1 BMI units between pregnancies. In the full sample, interpregnancy BMI decreases were associated with reduced odds of LGA and increased odds of SGA and PTB (IPC-BMI < -1 versus 0 to < 1: LGA aOR 0.7, 95% CI 0.4, 1.1; SGA aOR 1.6, 95% CI 1.0, 2.7; PTB aOR 1.9, 95% CI 1.3, 2.8). In stratified analyses, similar associations were observed in some, but not all, strata. Findings for interpregnancy BMI increases were less consistent, with little evidence for associations between these outcomes and the most extreme IPC-BMI increases., Conclusions: There is growing evidence that interpregnancy BMI decreases are associated with LGA, SGA, and PTB. However, taken as a whole, the literature provides insufficient evidence to establish causal links between maternal BMI and these outcomes.

Background: The risk of neural tube defect (NTD)-affected pregnancies is reduced with adequate folic acid intake during early pregnancy. However, NTDs have been observed among offspring of women with adequate folic acid intake. Some of these women are possibly not absorbing enough folic acid. Because lactase deficiency can lead to poor nutrient absorption, we hypothesized that lactase-deficient women will be at increased risk of having offspring with NTDs., Objective: We examined the association between maternal rs4988235 (a lactase deficiency genetic marker) and NTDs in offspring., Methods: We conducted a case-control study using data from the National Birth Defects Prevention Study, United States, 1997-2009, restricting to non-Hispanic white (NHW) and Hispanic women. Cases were women with an offspring with an NTD (n = 378 NHW, 207 Hispanic), and controls were women with an offspring without a birth defect (n = 461 NHW, 165 Hispanic). Analyses were conducted separately by race/ethnicity, using logistic regression. Women with the CC genotype were categorized as being lactase deficient. To assess potential effect modification, analyses were stratified by lactose intake, folic acid supplementation, dietary folate, and diet quality., Results: Among NHW women, the odds of being lactase deficient were greater among cases compared with controls (OR: 1.37; 95% CI: 1.02, 1.82). Among Hispanic women, the odds of being lactase deficient were significantly lower among cases compared with controls (OR: 0.50, 95% CI: 0.33, 0.77). The association differed when stratified by lactose intake in NHW women (higher odds among women who consumed ≥12 g lactose/1000 kcal) and by dietary folate in Hispanic women (opposite direction of associations). The association did not differ when stratified by folic acid supplementation or diet quality., Conclusions: Our findings suggest that maternal lactase deficiency is associated with NTDs in offspring. However, we observed opposite directions of effect by race/ethnicity that could not be definitively explained., (© 2019 American Society for Nutrition.)

Objective: To evaluate the relationships between maternal fish consumption and pregnancy outcomes in a large, population-based sample of women in the USA., Design: We collected average fish consumption prior to pregnancy using a modified version of the semi-quantitative Willett FFQ. We estimated adjusted OR (aOR) and 95 % CI for associations between different levels of fish consumption and preterm birth (&lt;37 weeks), early preterm birth (&lt;32 and &lt;35 weeks) and small-for-gestational-age infants (SGA; &lt;10th percentile)., Setting: The National Birth Defects Prevention Study (NBDPS)., Subjects: Control mother-infant pairs with estimated delivery dates between 1997 and 2011 (n 10 919)., Results: No significant associations were observed between fish consumption and preterm birth or early preterm birth (aOR = 0·7-1·0 and 0·7-0·9, respectively). The odds of having an SGA infant were elevated (aOR = 2·1; 95 % CI 1·2, 3·4) among women with daily fish consumption compared with women consuming fish less than once per month. No associations were observed between other levels of fish consumption and SGA (aOR = 0·8-1·0)., Conclusions: High intake of fish was associated with twofold higher odds of having an SGA infant, while moderate fish consumption prior to pregnancy was not associated with preterm or SGA. Our study, like many other studies in this area, lacked information regarding preparation methods and the specific types of fish consumed. Future studies should incorporate information on nutrient and contaminant contents, preparation methods and biomarkers to assess these relationships.

Background: Bariatric procedures are on the rise. The risk of birth defects in pregnancies following such procedures may be increased (eg, due to nutrient deficiencies) or decreased (eg, due to decreased maternal body mass index, BMI)., Methods: We conducted a systematic literature review of the association between bariatric surgery and birth defects using Ovid MEDLINE and PubMed (1946-2017). Information was abstracted on study design, exposures, outcomes, covariates and estimates of association., Results: Fifteen studies met our inclusion criteria: 14 evaluated the outcome of any birth defect, and one evaluated neural tube defects. Estimates of association between bariatric surgery and birth defects were available for nine studies and ranged from 0.6 to 1.9 (all 95% confidence intervals included 1.0). When studies were stratified by surgery type, there was no obvious pattern of association. When stratified by the approach used to account for BMI, positive associations were observed in studies that did not account for maternal prepregnancy BMI or used women with normal BMI as the reference group (range: 1.3-1.9). Estimates from studies that either matched or adjusted for prepregnancy BMI were closer to the null (range: 1.1-1.2) and studies that compared to morbidly obese women reported protective associations (range: 0.6-0.7)., Conclusions: Studies of the association between bariatric surgery and birth defects vary with respect to the surgical procedures included, birth defects ascertainment methods and approaches used to account for maternal BMI. Consequently, it is not possible to draw a conclusion regarding the association between bariatric surgery and birth defects. Additional studies are warranted., (© 2018 John Wiley & Sons Ltd.)