Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-30 (of 46 Records) |
Query Trace: Carmichael H[original query] |
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Analysis of social determinants of health and individual factors found in health equity frameworks: Applications to injury research
Carmichael AE , Lennon NH , Qualters JR . J Safety Res 2023 87 508-518 Introduction: This research evaluated existing health equity frameworks as they relate to social determinants of health (SDOHs) and individual factors that may impact injury outcomes and identify gaps in coverage using the Healthy People (HP) 2030 key domains. Methods: The study used a list of health equity frameworks sourced from previous literature. SDOHs and individual factors from each framework were identified and categorized into the Healthy People 2030 domains. Five injury topic areas were used as examples for how SDOHs and individual factors can be compared to injury topic-specific health disparities to identify health equity frameworks to apply to injury research. Results: The study identified 59 SDOHs and individual factors from the list of 33 health equity frameworks. The number of SDOHs and individual factors identified varied by Healthy People 2030 domain: Neighborhood and Built Environment contained 16 (27.1%) SDOHs and individual actors, Social and Community Context contained 22 (37.3%), Economic Stability contained 10 (16.9%), Healthcare Access and Quality contained 10 (16.9%), and Education Access and Quality contained one (1.7%). Twenty-three (39.0%) SDOHs/individual factors related to traumatic brain injury, thirteen (22.0%) related to motor vehicle crashes and suicide, 11 (18.6%) related to drowning and older adult falls. Eight frameworks (24.2%) covered all HP 2030 key domains and may be applicable to injury topics. Conclusions: Incorporating health equity into research is critical. Health equity frameworks can provide a way to systematically incorporate health equity into research. The findings from this study may be useful to health equity research by providing a resource to injury and other public health fields. Practical Applications: Health equity frameworks are a practical tool to guide injury research, translation, evaluation, and program implementation. The findings from this study can be used to guide the application of health equity frameworks in injury research for specific topic areas. © 2023 |
Is gastroschisis associated with county-level socio-environmental quality during pregnancy?
Krajewski AK , Patel A , Gray CL , Messer LC , Keeler CY , Langlois PH , Reefhuis J , Gilboa SM , Werler MM , Shaw GM , Carmichael SL , Nembhard WN , Insaf TZ , Feldkamp ML , Conway KM , Lobdell DT , Desrosiers TA . Birth Defects Res 2023 115 (18) 1758-1769 BACKGROUND: Gastroschisis prevalence more than doubled between 1995 and 2012. While there are individual-level risk factors (e.g., young maternal age, low body mass index), the impact of environmental exposures is not well understood. METHODS: We used the U.S. Environmental Protection Agency's Environmental Quality Index (EQI) as a county-level estimate of cumulative environmental exposures for five domains (air, water, land, sociodemographic, and built) and overall from 2006 to 2010. Adjusted odds ratios (aOR) and 95% confidence interval (CI) were estimated from logistic regression models between EQI tertiles (better environmental quality (reference); mid; poorer) and gastroschisis in the National Birth Defects Prevention Study from births delivered between 2006 and 2011. Our analysis included 594 cases with gastroschisis and 4105 infants without a birth defect (controls). RESULTS: Overall EQI was modestly associated with gastroschisis (aOR [95% CI]: 1.29 [0.98, 1.71]) for maternal residence in counties with poorer environmental quality, compared to the reference (better environmental quality). Within domain-specific indices, only the sociodemographic domain (aOR: 1.51 [0.99, 2.29]) was modestly associated with gastroschisis, when comparing poorer to better environmental quality. CONCLUSIONS: Future work could elucidate pathway(s) by which components of the sociodemographic domain or possibly related psychosocial factors like chronic stress potentially contribute to risk of gastroschisis. |
Neighborhood deprivation and neural tube defects
Pruitt Evans S , Ailes EC , Kramer MR , Shumate CJ , Reefhuis J , Insaf TZ , Yazdy MM , Carmichael SL , Romitti PA , Feldkamp ML , Neo DT , Nembhard WN , Shaw GM , Palmi E , Gilboa SM . Epidemiology 2023 34 (6) 774-785 BACKGROUND: Individual measures of socioeconomic status (SES) have been associated with an increased risk of neural tube defects (NTDs); however, the association between neighborhood SES and NTD risk is unknown. Using data from the National Birth Defects Prevention Study (NBDPS) from 1997 to 2011, we investigated the association between measures of census tract SES and NTD risk. METHODS: The study population included 10,028 controls and 1829 NTD cases. We linked maternal addresses to census tract SES measures and used these measures to calculate the neighborhood deprivation index. We used generalized estimating equations to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) estimating the impact of quartiles of census tract deprivation on NTDs adjusting for maternal race-ethnicity, maternal education, and maternal age at delivery. RESULTS: Quartiles of higher neighborhood deprivation were associated with NTDs when compared with the least deprived quartile (Q2: aOR = 1.2; 95% CI = 1.0, 1.4; Q3: aOR = 1.3, 95% CI = 1.1, 1.5; Q4 (highest): aOR = 1.2; 95% CI = 1.0, 1.4). Results for spina bifida were similar; however, estimates for anencephaly and encephalocele were attenuated. Associations differed by maternal race-ethnicity. CONCLUSIONS: Our findings suggest that residing in a census tract with more socioeconomic deprivation is associated with an increased risk for NTDs, specifically spina bifida. |
Are individual-level risk factors for gastroschisis modified by neighborhood-level socioeconomic factors
Neo DT , Martin CL , Carmichael SL , Gucsavas-Calikoglu M , Conway KM , Evans SP , Feldkamp ML , Gilboa SM , Insaf TZ , Musfee FI , Shaw GM , Shumate C , Werler MM , Olshan AF , Desrosiers TA . Birth Defects Res 2023 115 (15) 1438-1449 BACKGROUND: Two strong risk factors for gastroschisis are young maternal age (<20 years) and low/normal pre-pregnancy body mass index (BMI), yet the reasons remain unknown. We explored whether neighborhood-level socioeconomic position (nSEP) during pregnancy modified these associations. METHODS: We analyzed data from 1269 gastroschisis cases and 10,217 controls in the National Birth Defects Prevention Study (1997-2011). To characterize nSEP, we applied the neighborhood deprivation index and used generalized estimating equations to calculate odds ratios and relative excess risk due to interaction. RESULTS: Elevated odds of gastroschisis were consistently associated with young maternal age and low/normal BMI, regardless of nSEP. High-deprivation neighborhoods modified the association with young maternal age. Infants of young mothers in high-deprivation areas had lower odds of gastroschisis (adjusted odds ratio [aOR]: 3.1, 95% confidence interval [CI]: 2.6, 3.8) than young mothers in low-deprivation areas (aOR: 6.6; 95% CI: 4.6, 9.4). Mothers of low/normal BMI had approximately twice the odds of having an infant with gastroschisis compared to mothers with overweight/obese BMI, regardless of nSEP (aOR range: 1.5-2.3). CONCLUSION: Our findings suggest nSEP modified the association between gastroschisis and maternal age, but not BMI. Further research could clarify whether the modification is due to unidentified biologic and/or non-biologic factors. |
Neighborhood-level socioeconomic position during early pregnancy and risk of gastroschisis
Neo DT , Desrosiers TA , Martin CL , Carmichael SL , Gucsavas-Calikoglu M , Conway KM , Evans SP , Feldkamp ML , Gilboa SM , Insaf TZ , Musfee FI , Shaw GM , Shumate CJ , Werler MM , Olshan AF . Epidemiology 2023 34 (4) 576-588 BACKGROUND: Neighborhood-level socioeconomic position has been shown to influence birth outcomes, including selected birth defects. This study examines the understudied association between neighborhood-level socioeconomic position during early pregnancy and risk of gastroschisis, an abdominal birth defect of increasing prevalence. METHODS: We conducted a case-control study of 1,269 gastroschisis cases and 10,217 controls using data from the National Birth Defects Prevention Study (1997 - 2011). To characterize neighborhood-level socioeconomic position, we conducted principal component analysis to construct two indices - Neighborhood Deprivation Index (NDI) and Neighborhood Socioeconomic Position Index (nSEPI). We created neighborhood-level indices using census socioeconomic indicators corresponding to census tracts associated with addresses where mothers lived the longest during the periconceptional period. We used generalized estimating equations to estimate odds ratios (ORs) and 95% confidence intervals (CIs), with multiple imputation for missing data and adjustment for maternal race-ethnicity, household income, education, birth year, and duration of residence. RESULTS: Mothers residing in moderate (NDI Tertile 2 aOR: 1.2; 95% CI: 1.0, 1.5 and nSEPI Tertile 2 aOR: 1.2; 95% CI: 1.0, 1.5) or low socioeconomic neighborhoods (NDI Tertile 3 aOR: 1.3; 95% CI: 1.01, 1.6 and nSEPI Tertile 3 aOR: 1.3, 95% CI: 1.1, 1.6) were more likely to deliver an infant with gastroschisis compared with mothers residing in high socioeconomic neighborhoods. CONCLUSIONS: Our findings suggest that lower neighborhood-level socioeconomic position during early pregnancy is associated with elevated odds of gastroschisis. Additional epidemiologic studies may aid in confirming this finding and evaluating potential mechanisms linking neighborhood-level socioeconomic factors and gastroschisis. |
Exome-wide assessment of isolated biliary atresia: A report from the National Birth Defects Prevention Study using child-parent trios and a case-control design to identify novel rare variants.
Sok P , Sabo A , Almli LM , Jenkins MM , Nembhard WN , Agopian AJ , Bamshad MJ , Blue EE , Brody LC , Brown AL , Browne ML , Canfield MA , Carmichael SL , Chong JX , Dugan-Perez S , Feldkamp ML , Finnell RH , Gibbs RA , Kay DM , Lei Y , Meng Q , Moore CA , Mullikin JC , Muzny D , Olshan AF , Pangilinan F , Reefhuis J , Romitti PA , Schraw JM , Shaw GM , Werler MM , Harpavat S , Lupo PJ . Am J Med Genet A 2023 191 (6) 1546-1556 The etiology of biliary atresia (BA) is unknown, but recent studies suggest a role for rare protein-altering variants (PAVs). Exome sequencing data from the National Birth Defects Prevention Study on 54 child-parent trios, one child-mother duo, and 1513 parents of children with other birth defects were analyzed. Most (91%) cases were isolated BA. We performed (1) a trio-based analysis to identify rare de novo, homozygous, and compound heterozygous PAVs and (2) a case-control analysis using a sequence kernel-based association test to identify genes enriched with rare PAVs. While we replicated previous findings on PKD1L1, our results do not suggest that recurrent de novo PAVs play important roles in BA susceptibility. In fact, our finding in NOTCH2, a disease gene associated with Alagille syndrome, highlights the difficulty in BA diagnosis. Notably, IFRD2 has been implicated in other gastrointestinal conditions and warrants additional study. Overall, our findings strengthen the hypothesis that the etiology of BA is complex. |
Assessing associations between residential proximity to greenspace and birth defects in the National Birth Defects Prevention Study
Weber KA , Yang W , Carmichael SL , Collins RT2nd , Luben TJ , Desrosiers TA , Insaf TZ , Le MT , Evans SP , Romitti PA , Yazdy MM , Nembhard WN , Shaw GM . Environ Res 2022 216 114760 BACKGROUND: Residential proximity to greenspace is associated with various health outcomes. OBJECTIVES: We estimated associations between maternal residential proximity to greenspace (based on an index of vegetation) and selected structural birth defects, including effect modification by neighborhood-level factors. METHODS: Data were from the National Birth Defects Prevention Study (1997-2011) and included 19,065 infants with at least one eligible birth defect (cases) and 8925 without birth defects (controls) from eight Centers throughout the United States. Maternal participants reported their addresses throughout pregnancy. Each address was systematically geocoded and residences around conception were linked to greenspace, US Census, and US Department of Agriculture data. Greenspace was estimated using the normalized difference vegetation index (NDVI); average maximum NDVI was estimated within 100m and 500m concentric buffers surrounding geocoded addresses to estimate residential NDVI. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals comparing those in the highest and lowest quartiles of residential NDVI and stratifying by rural/urban residence and neighborhood median income. RESULTS: After multivariable adjustment, for the 500m buffer, inverse associations were observed for tetralogy of Fallot, secundum atrial septal defects, anencephaly, anotia/microtia, cleft lipcleft palate, transverse limb deficiency, and omphalocele, (aORs: 0.54-0.86). Results were similar for 100m buffer analyses and similar patterns were observed for other defects, though results were not significant. Significant heterogeneity was observed after stratification by rural/urban for hypoplastic left heart, coarctation of the aorta, and cleft palate, with inverse associations only among participants residing in rural areas. Stratification by median income showed heterogeneity for atrioventricular and secundum atrial septal defects, anencephaly, and anorectal atresia, with inverse associations only among participants residing in a high-income neighborhood (aORs: 0.45-0.81). DISCUSSION: Our results suggest that perinatal residential proximity to more greenspace may contribute to a reduced risk of certain birth defects, especially among those living in rural or high-income neighborhoods. |
Incidence of COVID-19 Among Persons Experiencing Homelessness in the US From January 2020 to November 2021.
Meehan AA , Thomas I , Horter L , Schoonveld M , Carmichael AE , Kashani M , Valencia D , Mosites E . JAMA Netw Open 2022 5 (8) e2227248 IMPORTANCE: A lack of timely and high-quality data is an ongoing challenge for public health responses to COVID-19 among people experiencing homelessness (PEH). Little is known about the total number of cases of COVID-19 among PEH. OBJECTIVE: To estimate the number of COVID-19 cases among PEH and compare the incidence rate among PEH with that in the general population. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from a survey distributed by the Centers for Disease Control and Prevention to all US state, district, and territorial health departments that requested aggregated COVID-19 data among PEH from January 1, 2020, to September 30, 2021. Jurisdictions were encouraged to share the survey with local health departments. MAIN OUTCOMES AND MEASURES: The primary study outcome was the number of cases of COVID-19 identified among PEH. COVID-19 cases and incidence rates among PEH were compared with those in the general population in the same geographic areas. RESULTS: Participants included a population-based sample of all 64 US jurisdictional health departments. Overall, 25 states, districts, and territories completed the survey, among which 18 states (72.0%) and 27 localities reported COVID-19 data among PEH. A total of 26 349 cases of COVID-19 among PEH were reported at the state level and 20 487 at the local level. The annual incidence rate of COVID-19 among PEH at the state level was 567.9 per 10 000 person-years (95% CI, 560.5-575.4 per 10 000 person-years) compared with 715.0 per 10 000 person-years (95% CI, 714.5-715.5 per 10 000 person-years) in the general population. At the local level, the incidence rate of COVID-19 among PEH was 799.2 per 10 000 person-years (95% CI, 765.5-834.0 per 10 000 person-years) vs 812.5 per 10 000 person-years (95% CI, 810.7-814.3 per 10 000 person-years) in the general population. CONCLUSIONS AND RELEVANCE: These results provide an estimate of COVID-19 incidence rates among PEH in multiple US jurisdictions; however, a national estimate and the extent of under- or overestimation remain unknown. The findings suggest that opportunities exist for incorporating housing and homelessness status in infectious disease reporting to inform public health decision-making. |
Health equity guiding frameworks and indices in injury: A review of the literature
Lennon NH , Carmichael AE , Qualters JR . J Safety Res 2022 82 469-481 Background: In early 2021, CDC released the CORE Health Equity Strategy, which resolves to integrate a comprehensive health equity approach to the work of the Agency. One priority of the Injury Center's Division of Injury Prevention is to move health equity research in injury forward. The purpose of this research is to perform an initial exploration of health equity guiding frameworks and indices to better understand which of these has been applied to injury research topics. Methods: A PubMed and CINAHL search of meta-analysis and systematic review articles was conducted from January 1998 through April 2022. Articles of any type and additional frameworks/indices were also identified from staff knowledge of the literature. Books were also considered, where accessible. The following areas were reviewed for each resource: population addressed, guiding framework/index, other health equity variables, gaps identified, and whether the articles addressed an injury topic. Findings: The PubMed/CINAHL search produced 230 articles, and an additional 29 articles and 8 books were added from previous knowledge of the literature, resulting in a total of 267 resources for review. There were 60 frameworks/indices compiled that were relevant to health equity. Out of all the resources, three reported on an injury topic and used the PROGRESS-Plus framework, the WHO Social Determinants of Health Conceptual Framework, and a social-ecological framework. Conclusions: This study found there were many frameworks/indices for measuring health equity; however, there were few injury-related meta-analysis and systematic review articles. Some frameworks/indices may be more appropriate than others for measuring health equity in injury topic areas, depending on which social determinants of health (SDOHs) they address. Practical Applications: Measuring health equity in injury and other public health research areas can help build a foundation of evidence. Moving forward, injury researchers can consider the frameworks/indices identified through this study in their health equity injury research. © 2022 |
Public Health Lessons Learned in Responding to COVID-19 Among People Experiencing Homelessness in the United States.
Mosites E , Harrison B , Montgomery MP , Meehan AA , Leopold J , Barranco L , Schwerzler L , Carmichael AE , Clarke KEN , Butler JC . Public Health Rep 2022 137 (4) 333549221083643 Homelessness is a serious public health issue. The number of people experiencing homelessness (PEH) has been increasing since 2016; on a single night in January 2020, an estimated 580 000 people were experiencing homelessness in the United States, more than 225 000 of whom were unsheltered (ie, having a primary nighttime location that is not designated as a regular sleeping accommodation, such as on the streets or in abandoned buildings, vehicles, or encampments). 1 Compared with the general US population, PEH experience elevated rates of infectious and noninfectious disease and face 3 to 10 times higher mortality rates.2,3 In the United States, non-Hispanic Black people were 3.5 times more likely than non-Hispanic White people to experience homelessness. 4 American Indian/Alaska Native people also have disproportionately high rates of homelessness compared with non-Hispanic White people. 5 |
Non-fatal injury data: characteristics to consider for surveillance and research
Carmichael AE , Ballesteros MF , Qualters JR , Mack KA . Inj Prev 2022 28 (3) 262-268 BACKGROUND: All data systems used for non-fatal injury surveillance and research have strengths and limitations that influence their utility in understanding non-fatal injury burden. The objective of this paper was to compare characteristics of major data systems that capture non-fatal injuries in the USA. METHODS: By applying specific inclusion criteria (eg, non-fatal and non-occupational) to well-referenced injury data systems, we created a list of commonly used non-fatal injury data systems for this study. Data system characteristics were compiled for 2018: institutional support, years of data available, access, format, sample, sampling method, injury definition/coding, geographical representation, demographic variables, timeliness (lag) and further considerations for analysis. RESULTS: Eighteen data systems ultimately fit the inclusion criteria. Most data systems were supported by a federal institution, produced national estimates and were available starting in 1999 or earlier. Data source and injury case coding varied between the data systems. Redesigns of sampling frameworks and the use of International Classification of Diseases, 9th Revision, Clinical Modification/International Classification of Diseases, 10th Revision, Clinical Modification coding for some data systems can make longitudinal analyses complicated for injury surveillance and research. Few data systems could produce state-level estimates. CONCLUSION: Thoughtful consideration of strengths and limitations should be exercised when selecting a data system to answer injury-related research questions. Comparisons between estimates of various data systems should be interpreted with caution, given fundamental system differences in purpose and population capture. This research provides the scientific community with an updated starting point to assist in matching the data system to surveillance and research questions and can improve the efficiency and quality of injury analyses. |
COVID-19 Vaccine Acceptability Among Clients and Staff of Homeless Shelters in Detroit, Michigan, February 2021.
Meehan AA , Yeh M , Gardner A , DeFoe TL , Garcia A , Vander Kelen P , Montgomery MP , Tippins AE , Carmichael AE , Gibbs Chw R , Caidi H , Mosites E , Rehman N . Health Promot Pract 2021 23 (1) 15248399211049202 Understanding COVID-19 vaccine acceptability among clients and staff of homeless shelters can inform public health efforts focused on communicating with and educating this population about COVID-19 vaccines and thus improve vaccine uptake. The objective of this study was to assess COVID-19 vaccine acceptability and uptake among people in homeless shelters in Detroit, Michigan. A cross-sectional study was conducted from February 9 to 23, 2021. Seventeen homeless shelters were surveyed: seven male-only, three male/female, and seven women and family shelters. All clients and staff aged ≥18 years and able to complete a verbal survey in English or with a translator were eligible to participate; of the 168 individuals approached, 26 declined, leaving a total sample of 106 clients and 36 staff participating in the study. The median client and staff ages were 44 and 54 years, respectively. Most participants (>80%) identified as non-Hispanic Black or African American. Sixty-one (57.5%) clients and 27 (75.5%) staff had already received or planned to receive a COVID-19 vaccination. Twelve (11.3%) clients and four (11.1%) staff were unsure, and 33 (31.1%) clients and five (13.9%) staff did not plan to get vaccinated. Reasons for hesitancy were concerns over side effects (29 clients [64.4%] and seven staff [77.8%]) and unknown long-term health impacts (26 clients [57.8%] and six staff [66.7%]). More than half of the clients had already received or planned to receive the vaccine. Continuing efforts such as vaccine education for hesitant clients and staff and having accessible vaccine events for this population may improve acceptability and uptake. |
Maternal exposure to hydroxychloroquine and birth defects.
Howley MM , Werler MM , Fisher SC , Van Zutphen AR , Carmichael SL , Broussard CS , Heinke D , Ailes EC , Pruitt SM , Reefhuis J , Mitchell AA , Browne ML . Birth Defects Res 2021 113 (17) 1245-1256 BACKGROUND: Hydroxychloroquine is a treatment for rheumatic disease and considered safe during pregnancy. Interest in hydroxychloroquine has increased as it is being examined as a potential treatment and prophylaxis for coronavirus disease 2019. Data on the risks of specific birth defects associated with hydroxychloroquine use are sparse. METHODS: Using data from two case-control studies (National Birth Defects Prevention Study and Slone Epidemiology Center Birth Defects Study), we described women who reported hydroxychloroquine use in pregnancy and the presence of specific major birth defects in their offspring. Cases had at least one major birth defect and controls were live-born healthy infants. Women self-reported medication use information in the few months before pregnancy through delivery. RESULTS: In total, 0.06% (19/31,468) of case and 0.04% (5/11,614) of control mothers in National Birth Defects Prevention Study, and 0.04% (11/29,838) of case and 0.05% (7/12,868) of control mothers in Birth Defects Study reported hydroxychloroquine use. Hydroxychloroquine users had complicated medical histories and frequent medication use for a variety of conditions. The observed birth defects among women taking hydroxychloroquine were varied and included nine oral cleft cases; the elevated observed:expected ratios for specific oral cleft phenotypes and for oral clefts overall had 95% confidence intervals that included 1.0. CONCLUSION: While teratogens typically produce a specific pattern of birth defects, the observed birth defects among the hydroxychloroquine-exposed women did not present a clear pattern, suggesting no meaningful evidence for the risk of specific birth defects. The number of exposed cases is small; results should be interpreted cautiously. |
Drugs and Drug Classes Involved in Overdose Deaths Among Females, United States: 1999-2017
Carmichael AE , Schier JG , Mack KA . J Womens Health (Larchmt) 2021 31 (3) 425-430 Background: Drug overdose deaths among U.S. women have risen steadily from 1999 to 2017, especially among certain ages. Various studies report involvement of drugs and drug classes in overdose deaths. Less is known, however, regarding the combinations that are most often indicated on death certificates, particularly among females. Analyzing mutually, exclusive drug/drug class combinations listed on death certificates of females are the objective of this study. Materials and Methods: Mortality data for U.S. female residents were obtained from the 1999 to 2017 National Vital Statistics System (n = 260,782). Analyses included deaths with an underlying cause of death based on International Classification of Diseases, 10th Revision (ICD-10) codes for drug overdoses. The drug/drug class involved included individual 4-digit ICD-10 codes in the range T36.0-T50.9, including poisoning deaths due to all drugs, excluding alcohol. Years from 1999 to 2017 were grouped in six 3-year categories with the most recent year (2017) left separate for analysis. All drug overdose deaths were analyzed in mutually exclusive categories. Results: From 1999 to 2017, the top-listed drug/drug class overall and by year grouping was solely "other and unspecified drugs, medicaments and biological substances"; however, that listing dropped from 25.8% from the 1999 to 2001 period to 14.1% in 2017. Overall, the next most frequent single drug/drug class mentions were "natural and semisynthetic opioids" (20,951; 8.0%) and "cocaine" (10,882; 4.2%). Two of the top five drug/drug class combinations included benzodiazepines ("natural and semisynthetic opioids"/"benzodiazepines" and "methadone"/"benzodiazepines"). Conclusions: Analyzing trends in drugs and drug classes involved in female drug overdose deaths is a critical foundation for developing gender-responsive public health interventions. Reducing high-risk drug use by improving prescribing practices, preventing drug use initiation, and addressing use of multiple drugs can help prevent overdose deaths. |
Maternal exposure to disinfection by-products and risk of hypospadias in the National Birth Defects Prevention Study (2000-2005)
Zaganjor I , Luben TJ , Desrosiers TA , Keil AP , Engel LS , Michalski AM , Carmichael SL , Nembhard WN , Shaw GM , Reefhuis J , Yazdy MM , Langlois PH , Feldkamp ML , Romitti PA , Olshan AF , The National Birth Defects Prevention Study . Int J Environ Res Public Health 2020 17 (24) The purpose of this study was to estimate the association between 2nd and 3rd degree hypospadias and maternal exposure to disinfection by-products (DBPs) using data from a large case-control study in the United States. Concentration estimates for total trihalomethanes (TTHMs), the sum of the five most prevalent haloacetic acids (HAA5), and individual species of each were integrated with data on maternal behaviors related to water use from the National Birth Defects Prevention Study (NBDPS) to create three different exposure metrics: (1) household DBP concentrations; (2) estimates of DBP ingestion; (3) predicted uptake (i.e., internal dose) of trihalomethanes (THMs) via ingestion, showering, and bathing. The distribution of DBP exposure was categorized as follows: (Q1/referent) < 50%; (Q2) ≥ 50% to < 75%; and (Q3) ≥ 75%. Logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Generally, null associations were observed with increasing TTHM or HAA5 exposure. An increased risk was observed among women with household bromodichloromethane levels in the second quantile (aOR: 1.8; 95% CI: 1.2, 2.7); however, this association did not persist after the inclusion of individual-level water-use data. Findings from the present study do not support the hypothesis that maternal DBP exposures are related to the occurrence of hypospadias. |
Periconceptional stressors and social support and risk for adverse birth outcomes
Weber KA , Carmichael SL , Yang W , Tinker SC , Shaw GM . BMC Pregnancy Childbirth 2020 20 (1) 487 BACKGROUND: The prevalence of preterm birth and low birth weight has been increasing slightly in recent years. A few studies have suggested that psychosocial stress during pregnancy may increase risk for these adverse birth outcomes. To extend those observations, we analyzed various major life event stressors separately and cumulatively as potential risk factors for preterm birth and low birth weight using granular categories of each outcome in a large, population-based study. Additionally, we assessed if greater social support buffered any effects. METHODS: Data were from a nested prevalence study of 4395 women in the National Birth Defects Prevention Study who delivered live-born non-malformed infants (controls) between 2006 and 2011. Participants completed a standardized, computer-assisted interview between 6 weeks and 24 months after delivery that included questions on stress and social support from 3 months before pregnancy to the 3rd month of pregnancy. Cumulative stress and support indices were also calculated. Preterm birth was divided into "early preterm" (< 32 weeks), "late preterm" (32-36 weeks) and "term." Low birthweight was divided into "very low birth weight" (< 1500 g), "low birth weight" (1500-2499 g) and "normal birth weight" (≥2500 g). Relative risks and 95% confidence intervals (95% CI) were calculated using Poisson regression. RESULTS: For women reporting relationship difficulties, there was a suggestive risk of early preterm birth (RR: 1.9, 95%CI: 0.9-3.9) and very low birthweight (RR: 2.0, 95%CI: 0.9-4.4). For women reporting that they or someone close to them were victims of abuse, violence, or crime, there was an increased risk of low birthweight (RR: 1.8, 95%CI: 1.1-2.7) and late preterm birth (RR: 1.5, 95%CI: 1.0-2.2). There were no strong associations observed between social support questions and the various outcomes. CONCLUSIONS: Our results add some support to prior evidence that certain stressors may be associated with increase selected adverse birth outcomes risk. We did not find strong evidence that social support buffered the observed risks in our study. |
Risk of stillbirth for fetuses with specific birth defects
Heinke D , Nestoridi E , Hernandez-Diaz S , Williams PL , Rich-Edwards JW , Lin AE , Van Bennekom CM , Mitchell AA , Nembhard WN , Fretts RC , Roberts DJ , Duke CW , Carmichael SL , Yazdy MM . Obstet Gynecol 2019 135 (1) 133-140 OBJECTIVE: To estimate the risk of stillbirth (fetal death at 20 weeks of gestation or more) associated with specific birth defects. METHODS: We identified a population-based retrospective cohort of neonates and fetuses with selected major birth defects and without known or strongly suspected chromosomal or single-gene disorders from active birth defects surveillance programs in nine states. Abstracted medical records were reviewed by clinical geneticists to confirm and classify all birth defects and birth defect patterns. We estimated risks of stillbirth specific to birth defects among pregnancies overall and among those with isolated birth defects; potential bias owing to elective termination was quantified. RESULTS: Of 19,170 eligible neonates and fetuses with birth defects, 17,224 were liveborn, 852 stillborn, and 672 electively terminated. Overall, stillbirth risks ranged from 11 per 1,000 fetuses with bladder exstrophy (95% CI 0-57) to 490 per 1,000 fetuses with limb-body-wall complex (95% CI 368-623). Among those with isolated birth defects not affecting major vital organs, elevated risks (per 1,000 fetuses) were observed for cleft lip with cleft palate (10; 95% CI 7-15), transverse limb deficiencies (26; 95% CI 16-39), longitudinal limb deficiencies (11; 95% CI 3-28), and limb defects due to amniotic bands (110; 95% CI 68-171). Quantified bias analysis suggests that failure to account for terminations may lead to up to fourfold underestimation of the observed risks of stillbirth for sacral agenesis (13/1,000; 95% CI 2-47), isolated spina bifida (24/1,000; 95% CI 17-34), and holoprosencephaly (30/1,000; 95% CI 10-68). CONCLUSION: Birth defect-specific stillbirth risk was high compared with the U.S. stillbirth risk (6/1,000 fetuses), even for isolated cases of oral clefts and limb defects; elective termination may appreciably bias some estimates. These data can inform clinical care and counseling after prenatal diagnosis. |
Survival of infants with spina bifida and the role of maternal prepregnancy body mass index
Pace ND , Siega-Riz AM , Olshan AF , Chescheir NC , Cole SR , Desrosiers TA , Tinker SC , Hoyt AT , Canfield MA , Carmichael SL , Meyer RE . Birth Defects Res 2019 111 (16) 1205-1216 OBJECTIVE: To investigate first-year survival of infants born with spina bifida, and examine the association of maternal prepregnancy body mass index (BMI) with infant mortality. METHODS: This is a retrospective cohort study of 1,533 liveborn infants with nonsyndromic spina bifida with estimated dates of delivery from 1998 to 2011 whose mothers were eligible for the National Birth Defects Prevention Study (NBDPS). NBDPS data were linked to death records to conduct survival analyses. Kaplan-Meier survival functions estimated mortality risk over the first year of life. Cox proportional hazards models estimated hazard ratios (HRs) for maternal prepregnancy BMI categorized as underweight (<18.5), normal (18.5-24.9), overweight (25-29.9), and obese (>/=30). RESULTS: Infant mortality risk among infants with spina bifida was (4.4% [3.52, 5.60%]). Infants with multiple co-occurring defects, very preterm delivery, multiple gestation, high-level spina bifida lesions, or non-Hispanic Black mothers had an elevated risk of infant mortality. Maternal prepregnancy underweight and obesity were associated with higher infant mortality (15.7% [7.20, 32.30%] and 5.82% [3.60, 9.35%], respectively). Adjusted HR estimates showed underweight and obese mothers had greater hazard of infant mortality compared to normal weight mothers (HR: 4.5 [1.08, 16.72] and 2.6 [1.36, 8.02], respectively). CONCLUSION: The overall risk of infant mortality for infants born with spina bifida was lower than most previously reported estimates. Infants born with spina bifida to mothers who were underweight or obese prepregnancy were at higher risk of infant mortality. This study provides additional evidence of the importance of healthy maternal weight prior to pregnancy. |
Women's periconceptional diet and risk of biliary atresia in offspring
Carmichael SL , Ma C , Van Zutphen AR , Moore CA , Shaw GM . Birth Defects Res 2018 110 (12) 994-1000 INTRODUCTION: We examined the association of biliary atresia with maternal dietary intake, using National Birth Defects Prevention Study (NBDPS) data from 152 cases and 11,112 nonmalformed controls born 1997-2011. METHODS: NBDPS is a multisite, population-based case-control study. Exposure data were from maternal telephone interviews, which included a food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were generated from logistic regression models that included nutritional factors as continuous variables and were adjusted for energy intake only or energy intake plus covariates (maternal race-ethnicity, education, age, prepregnancy body mass index, vitamin/mineral supplement intake, conception during summer). Models included a quadratic term for the nutrient if p < 0.10. ORs reflect odds of having biliary atresia for nutrient values at the 75th compared to 25th percentile values of each nutrient, based on distributions among controls. RESULTS: ORs for which the 95% CI excluded 1.00 were energy-adjusted ORs for calcium (0.63), protein (0.65), riboflavin (0.71), and diet quality index (0.69), and fully adjusted ORs for calcium (0.68) and vitamin E (0.72). ORs that were fully adjusted for covariates tended to be closer to 1.0 than ORs adjusted only for energy intake. ORs for the other studied nutrients had 95% CIs that included 1.00. CONCLUSIONS: NBDPS is the first study to include detailed information on maternal dietary intake and risk of biliary atresia. Our results suggest reduced risks associated with some nutrients, which may provide etiologic clues but should be interpreted with caution given the small number of cases and novelty of the investigation. |
Maternal exposure to nitrogen dioxide, intake of methyl nutrients and congenital heart defects in offspring
Stingone JA , Luben TJ , Carmichael SL , Aylsworth AS , Botto LD , Correa A , Gilboa SM , Langlois PH , Nembhard WN , Richmond-Bryant J , Shaw GM , Olshan AF . Am J Epidemiol 2017 186 (6) 719-729 Nutrients that regulate methylation processes may modify susceptibility to the effects of air pollutants. Data from the National Birth Defects Prevention Study, 1997-2006, were used to estimate associations between maternal exposure to nitrogen dioxide (NO2), dietary intake of methyl nutrients and the odds of congenital heart defects in offspring. NO2 concentrations, a marker of traffic-related air pollution, averaged across post-conception weeks 2-8, were assigned to 6160 non-diabetic mothers of cases and controls using inverse distance-squared weighting of air monitors within 50 km of maternal residence. Intake of choline, folate, methionine, and vitamins B6 and B12 were assessed using a food frequency questionnaire. Hierarchical regression models, which accounted for similarities across defects, were constructed and relative excess risks due to interaction were calculated. Relative to women with the lowest NO2 exposure and high methionine intake, women with the highest NO2 exposure and lowest methionine intake had the greatest odds of offspring with a perimembranous ventricular septal defect (Odds Ratio: 3.23, 95% Confidence Interval, 1.74, 6.01; Relative Excess Risk due to Interaction: 2.15, 95% Confidence Interval, 0.39, 3.92). Considerable departure from additivity was not observed for other defects. These results provide modest evidence of interaction between nutrition and NO2 exposure during pregnancy. |
Maternal stressors and social support and risks of delivering babies with gastroschisis or hypospadias
Carmichael SL , Ma C , Tinker S , Shaw GM . Am J Epidemiol 2017 185 (12) 1-7 We examined the association of maternal stressful life events and social support with risks of gastroschisis and hypospadias, using data from the National Birth Defects Prevention Study, a population-based case-control study of US births taking place in 2006-2011. We examined maternal self-reports of 7 life events and 3 sources of social support during the periconceptional period among mothers of 593 gastroschisis cases, 1,142 male hypospadias cases, and 4,399 nonmalformed controls. Responses to the questions on stressful life events were summed to form an index (higher is worse), as were responses to questions on social support (higher is better). We used logistic regression to estimate adjusted odds ratios and 95% confidence intervals. The adjusted odds ratios for gastroschisis for a 4-point increase in the stress index were 3.5 (95% confidence interval (CI): 2.6, 4.8) among nonteenage mothers (age ≥20 years) and 1.0 (95% CI: 0.5, 1.7) among teenage mothers (age <20 years). The odds ratio for hypospadias (among all mothers) was 0.8 (95% CI: 0.7, 1.1). Adjusted odds ratios for a social support score of 3 (versus 0) in the 3 respective groups were 0.6 (95% CI: 0.4, 1.0), 1.0 (95% CI: 0.5, 2.3), and 0.6 (95% CI: 0.4, 0.9). Given the lack of prior research on these outcomes and stress, results should be interpreted with caution. |
Maternal autoimmune disease and birth defects in the National Birth Defects Prevention Study
Howley MM , Browne ML , Van Zutphen AR , Richardson SD , Blossom SJ , Broussard CS , Carmichael SL , Druschel CM . Birth Defects Res A Clin Mol Teratol 2016 106 (11) 950-962 BACKGROUND: Little is known about the association between maternal autoimmune disease or its treatment and the risk of birth defects. We examined these associations using data from the National Birth Defects Prevention Study, a multi-site, population-based, case-control study. METHODS: Analyses included 25,116 case and 9897 unaffected control infants with estimated delivery dates between 1997 and 2009. Information on autoimmune disease, medication use, and other pregnancy exposures was collected by means of telephone interview. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for birth defects with five or more exposed cases; crude ORs and exact 95% CIs were estimated for birth defects with three to four exposed cases. RESULTS: Autoimmune disease was reported by 373 mothers (279 case and 94 control mothers). The majority of birth defects evaluated were not associated with autoimmune disease; however, a statistically significant association between maternal autoimmune disease and encephalocele was observed (OR, 4.64; 95% CI, 1.95-11.04). Eighty-two mothers with autoimmune disease used an immune modifying/suppressing medication during pregnancy; this was associated with encephalocele (OR, 7.26; 95% CI, 1.37-24.61) and atrial septal defects (OR, 3.01; 95% CI, 1.16-7.80). CONCLUSION: Our findings suggest maternal autoimmune disease and treatment are not associated with the majority of birth defects, but may be associated with some defects, particularly encephalocele. Given the low prevalence of individual autoimmune diseases and the rare use of specific medications, we were unable to examine associations of specific autoimmune diseases and medications with birth defects. Other studies are needed to confirm these findings. |
Elevated body mass index and decreased diet quality among women and risk of birth defects in their offspring
Carmichael SL , Yang W , Gilboa S , Ailes E , Correa A , Botto LD , Feldkamp ML , Shaw GM . Birth Defects Res A Clin Mol Teratol 2015 106 (3) 164-71 BACKGROUND: We examined whether risks of 32 birth defects were higher than expected in the presence of overweight or obese body mass index (BMI) and low diet quality, based on estimating individual and joint effects of these factors and calculating relative excess risk due to interaction. METHODS: Analyses included mothers of 20,250 cases with birth defects and 8617 population-based controls without birth defects born from 1997 to 2009 and interviewed for the National Birth Defects Prevention Study. We used logistic regression to generate adjusted odds ratios (AORs) reflecting the combined effects of BMI and diet quality. We focused analyses on 16 birth defects (n = 11,868 cases, 8617 controls) for which initial results suggested an association with BMI or diet quality. RESULTS: Relative to the reference group (normal weight women with not low diet quality, i.e., >lowest quartile), AORs for low diet quality among normal weight women tended to be >1, and AORs for overweight and obese women tended to be stronger among women who had low diet quality than not low diet quality. For 9/16 birth defects, AORs for obese women who had low diet quality-the group we hypothesized to have highest risk-were higher than other stratum-specific AORs. Most relative excess risk due to interactions were positive but small (<0.5), with confidence intervals that included zero. CONCLUSION: These findings provide evidence for the hypothesis of highest birth defect risks among offspring to women who are obese and have low diet quality but insufficient evidence for an interaction of these factors in their contribution to risk. |
Next steps for birth defects research and prevention: the Birth Defects Study to Evaluate Pregnancy Exposures (BD-STEPS)
Tinker SC , Carmichael SL , Anderka M , Browne ML , Caspers Conway KM , Meyer RE , Nembhard WN , Olney RS , Reefhuis J . Birth Defects Res A Clin Mol Teratol 2015 103 (8) 733-40 BACKGROUND: The Birth Defects Study To Evaluate Pregnancy exposureS (BD-STEPS) is a population-based, multi-Center case-control study of modifiable risk factors for selected birth defects in the United States. BD-STEPS is the second major research effort of the Centers for Birth Defects Research and Prevention, which extends and expands the initial research effort, the National Birth Defects Prevention Study (NBDPS). METHODS: BD-STEPS focuses on 17 categories of structural birth defects selected based on severity, prevalence, consistent ascertainment, and previous findings that warrant additional research. Cases are identified through existing birth defects surveillance programs; controls are from vital records or birth hospital logs from the same catchment area. BD-STEPS uses a standardized computer-assisted telephone interview to collect information from case and control mothers on topics including demographics, health conditions, and medication use. Following the maternal interview, selected Centers request permission to sample residual newborn screening blood spots from state repositories for genetic analyses. New components planned for BD-STEPS include linkages with external datasets and use of online questionnaires to collect in-depth information on selected exposures. RESULTS: BD-STEPS extends NBDPS by continuing to collect data on many exposures that were assessed in NBDPS, allowing data from both studies to be combined and providing an unprecedented sample size to analyze rare exposures. BD-STEPS expands upon NBDPS by collecting more detailed information on existing exposures as well as new exposures. CONCLUSION: The goal of BD-STEPS is to provide women and healthcare providers with information they need to make decisions to promote the healthiest pregnancy possible. |
Craniosynostosis and risk factors related to thyroid dysfunction
Carmichael S , Ma C , Rasmussen S , Cunningham M , Browne M , Dosiou C , Lammer E , Shaw G . Am J Med Genet A 2015 167A (4) 701-7 Thyroid disease is a common problem among women of reproductive age but often goes undiagnosed. Maternal thyroid disease has been associated with increased risk of craniosynostosis. We hypothesized that known risk factors for thyroid disease would be associated with risk of craniosynostosis among women not diagnosed with thyroid disease. Analyses included mothers of 1,067 cases and 8,494 population-based controls who were interviewed for the National Birth Defects Prevention Study. We used multivariable logistic regression to estimate adjusted odds ratios (AOR) and 95% confidence intervals (CI). After excluding women with diagnosed thyroid disease, younger maternal age (AOR 0.7, 95% CI 0.6-0.9, for <25 years versus 25-29), black or other race-ethnicity (AOR 0.3, 95% CI 0.2-0.4 and AOR 0.6, 95% CI 0.4-0.8, respectively, relative to non-Hispanic whites), fertility medications or procedures (AOR 1.5, 95% CI 1.2-2.0), and alcohol consumption (AOR 0.8, 95% CI 0.7-0.9) were associated with risk of craniosynostosis, based on confidence intervals that excluded 1.0. These associations with craniosynostosis are consistent with the direction of their association with thyroid dysfunction (i.e., younger age, black race-ethnicity and alcohol consumption are associated with reduced risk and fertility problems are associated with increased risk of thyroid disease). This study thus provides support for the hypothesis that risk factors associated with thyroid dysfunction are also associated with risk of craniosynostosis. Improved understanding of the potential association between maternal thyroid function and craniosynostosis among offspring is important given that craniosynostosis carries significant morbidity and that thyroid disease is under-diagnosed and potentially modifiable. |
Differences in risk factors for second and third degree hypospadias in the National Birth Defects Prevention Study
Woud SG , Rooij IA , Gelder MM , Olney RS , Carmichael SL , Roeleveld N , Reefhuis J . Birth Defects Res A Clin Mol Teratol 2014 100 (9) 703-11 BACKGROUND: Hypospadias is a frequent birth defect with three phenotypic subtypes. With data from the National Birth Defects Prevention Study, a large, multi-state, population-based, case-control study, we compared risk factors for second and third degree hypospadias. METHODS: A wide variety of data on maternal and pregnancy-related risk factors for isolated second and third degree hypospadias was collected by means of computer-assisted telephone interviews to identify potential etiological differences between the two phenotypes. Logistic regression was used to calculate odds ratios including a random effect by study center. RESULTS: In total, 1547 second degree cases, 389 third degree cases, and 5183 male controls were included in our study. Third degree cases were more likely to have a non-Hispanic black or Asian/Pacific Islander mother, be delivered preterm, have a low birth weight, be small for gestational age, and be conceived with fertility treatments than second degree cases and controls. Associations with both second and third degree hypospadias were observed for maternal age, family history, parity, plurality, and hypertension during pregnancy. Risk estimates were generally higher for third degree hypospadias except for family history. CONCLUSION: Most risk factors were associated with both or neither phenotype. Therefore, it is likely that the underlying mechanism is at least partly similar for both phenotypes. However, some associations were different between second and third degree hypospadias, and went in opposite directions for second and third degree hypospadias for Asian/Pacific Islander mothers. Effect estimates for subtypes of hypospadias may be over- or underestimated in studies without stratification by phenotype. |
Corticosteroid use and risk of orofacial clefts
Skuladottir H , Wilcox AJ , Ma C , Lammer EJ , Rasmussen SA , Werler MM , Shaw GM , Carmichael SL . Birth Defects Res A Clin Mol Teratol 2014 100 (6) 499-506 BACKGROUND: Maternal use of corticosteroids during early pregnancy has been inconsistently associated with orofacial clefts in the offspring. A previous report from the National Birth Defect Prevention Study (NBDPS), using data from 1997 to 2002, found an association with cleft lip and palate (odds ratio, 1.7; 95% confidence interval [CI], 1.1-2.6), but not cleft palate only (odds ratio, 0.5, 95%CI, 0.2-1.3). From 2003 to 2009, the study population more than doubled in size, and our objective was to assess this association in the more recent data. METHODS: The NBDPS is an ongoing multi-state population-based case-control study of birth defects, with ascertainment of cases and controls born since 1997. We assessed the association of corticosteroids and orofacial clefts using data from 2372 cleft cases and 5922 controls born from 2003 to 2009. Maternal corticosteroid exposure was based on telephone interviews. RESULTS: The overall association of corticosteroids and cleft lip and palate in the new data was 1.0 (95% CI, 0.7-1.4). There was little evidence of associations between specific corticosteroid components or timing and clefts. CONCLUSION: In contrast to the 1997 to 2002 data from the NBDPS, the 2003 to 2009 data show no association between maternal corticosteroid use and cleft lip and palate in the offspring. |
Maternal stressors and social support as risks for delivering babies with structural birth defects
Carmichael SL , Ma C , Tinker S , Rasmussen SA , Shaw GM . Paediatr Perinat Epidemiol 2014 28 (4) 338-44 BACKGROUND: We examined the association of maternal stressful life events and social support with risks of birth defects using National Birth Defects Prevention Study data, a population-based case-control study. METHODS: We examined seven stressful life events and three social support questions applicable to the periconceptional period, among mothers of 552 cases with neural tube defects (NTDs), 413 cleft palate (CP), 797 cleft lip +/- cleft palate (CLP), 189 d-transposition of the great arteries (dTGA), 311 tetralogy of Fallot (TOF), and 2974 non-malformed controls. A stressful life events index equalled the sum of 'yes' responses to the seven questions. Social support questions were also summed to form an index. Data were analyzed using logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI), adjusted for maternal race-ethnicity, age, education, body mass index, smoking, drinking, and intake of vitamin supplements. RESULTS: Associations with the stress index tended to be higher with higher scores, but few 95% CIs excluded one. A four-point increase in the index was moderately associated with NTDs (OR 1.5, [95% CI 1.1, 2.0]) and CLP (OR 1.3, [95% CI 1.0, 1.7]). The social support index tended to be associated with reduced risk but most 95% CIs included one, with the exception of dTGA (OR for a score of 3 vs 0 was 0.5 [95% CI 0.3, 0.8]). CONCLUSIONS: Maternal periconceptional stressful life events, social support, and the two factors in combination were at most modestly, if at all, associated with risks of the studied birth defects. |
Quantification of 21 metabolites of methylnaphthalenes and polycyclic aromatic hydrocarbons in human urine
Li Z , Romanoff LC , Trinidad DA , Pittman EN , Hilton D , Hubbard K , Carmichael H , Parker J , Calafat AM , Sjodin A . Anal Bioanal Chem 2014 406 (13) 3119-29 Polycyclic aromatic hydrocarbons (PAHs) and their alkylated derivatives, such as methylnaphthalenes (MeNs), are harmful pollutants ubiquitously present in the environment. Exposure to PAHs has been linked to a variety of adverse health effects and outcomes, including cancer. Alkyl PAHs have been proposed as petrogenic source indicators because of their relatively high abundance in unburned petroleum products. We report a method to quantify 11 urinary methylnaphthols (Me-OHNs), metabolites of 1- and 2-methylnaphthalenes, and 10 monohydroxy PAH metabolites (OH-PAHs), using automated liquid-liquid extraction and isotope dilution gas chromatography tandem mass spectrometry (GC-MS/MS). After spiking urine (1 mL) with 13C-labeled internal standards, the conjugated target analytes were hydrolyzed enzymatically in the presence of ascorbic acid. Then, their free species were preconcentrated into 20 % toluene in pentane, derivatized and quantified by GC-MS/MS. The 11 Me-OHNs eluted as 6 distinct chromatographic peaks, each representing 1 - 3 isomers. Method detection limits were 1.0- 41 pg/mL and the coefficients of variation in quality control materials were 4.7 - 19 %. The method was used to analyze two National Institute of Standards and Technology's Standard Reference Materials(R) and samples from 30 smokers and 30 non-smokers. Geometric mean concentrations were on average 37 (Me-OHNs) and 9.0 (OH-PAHs) fold higher in smokers than in non-smokers. These findings support the usefulness of Me-OHNs as potential biomarkers of non-occupational exposure to MeNs and sources containing MeNs. |
Late detection of critical congenital heart disease among US infants: estimation of the potential impact of proposed universal screening using pulse oximetry
Peterson C , Ailes E , Riehle-Colarusso T , Oster ME , Olney RS , Cassell CH , Fixler DE , Carmichael SL , Shaw GM , Gilboa SM . JAMA Pediatr 2014 168 (4) 361-70 IMPORTANCE: Critical congenital heart disease (CCHD) was added to the Recommended Uniform Screening Panel for Newborns in the United States in 2011. Many states have recently adopted or are considering requirements for universal CCHD screening through pulse oximetry in birth hospitals. Limited previous research is directly applicable to the question of how many US infants with CCHD might be identified through screening. OBJECTIVES: To estimate the proportion of US infants with late detection of CCHD (>3 days after birth) based on existing clinical practice and to investigate factors associated with late detection. DESIGN, SETTING, AND PARTICIPANTS: Descriptive and multivariable analysis. Data were obtained from a multisite population-based study of birth defects in the United States, the National Birth Defects Prevention Study (NBDPS). We included all live-born infants with estimated dates of delivery from January 1, 1998, through December 31, 2007, and nonsyndromic, clinically verified CCHD conditions potentially detectable through screening via pulse oximetry. MAIN OUTCOMES AND MEASURES: The main outcome measure was the proportion of infants with late detection of CCHD through echocardiography or at autopsy under the assumption that universal screening at birth hospitals might reduce the number of such late diagnoses. Secondary outcome measures included prevalence ratios for associations between selected demographic and clinical factors and late detection of CCHD. RESULTS: Of 3746 live-born infants with nonsyndromic CCHD, late detection occurred in 1106 (29.5% [95% CI, 28.1%-31.0%]), including 6 (0.2%) (0.1%-0.4%) first receiving a diagnosis at autopsy more than 3 days after birth. Late detection varied by CCHD type from 9 of 120 infants (7.5% [95% CI, 3.5%-13.8%]) with pulmonary atresia to 497 of 801 (62.0% [58.7%-65.4%]) with coarctation of the aorta. In multivariable analysis, late detection varied significantly by CCHD type and study site, and infants with extracardiac defects were significantly less likely to have late detection of CCHD (adjusted prevalence ratio, 0.58 [95% CI, 0.49-0.69]). CONCLUSIONS AND RELEVANCE: We estimate that 29.5% of live-born infants with nonsyndromic CCHD in the NBDPS received a diagnosis more than 3 days after birth and therefore might have benefited from routine CCHD screening at birth hospitals. The number of infants in whom CCHD was detected through screening likely varies by several factors, including CCHD type. Additional population-based studies of screening in practice are needed. |
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