Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-30 (of 45 Records) |
Query Trace: Lupo D[original query] |
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Incidence and survival of pediatric and adult hepatocellular carcinoma, United States, 2001-2020
Arnett A , Siegel DA , Dai S , Thompson TD , Foster J , di Pierro EJ , Momin B , Lupo PJ , Heczey A . medRxiv 2024 IMPORTANCE: Hepatocellular carcinoma accounts for approximately 80% of liver neoplasms. Globally, hepatocellular carcinoma ranks as the third most lethal cancer, with the number of deaths expected to further increase by 2040. In adults, disparities in incidence and survival are well described while pediatric epidemiology is not well characterized. OBJECTIVE: To describe incidence and survival for pediatric (ages 0-19 years) hepatocellular carcinoma cases and compare these measures to adults (ages ≥20 years) diagnosed with hepatocellular carcinoma. We evaluated demographic factors and clinical characteristics that influence incidence and outcomes. DESIGN: Population-based cohort study. SETTING: Incidence data from the US Cancer Statistics database from 2003 to 2020 and 5-year relative survival from the National Program of Cancer Registries from 2001 to 2019, covering 97% and 83% of the US population, respectively. PARTICIPANTS: 355,349 US Cancer Statistics and 257,406 the National Program of Cancer Registries patients were identified using ICD-O-3 C22.0 and 8170-5 codes. MAIN OUTCOMES AND MEASURES: Incidence annual percent change (APC) and average APC (AAPC) using joinpoint regression. Five-year relative survival. All-cause survival estimated using multivariate Cox modeling. Corresponding 95% confidence intervals (CI) were calculated. RESULTS: Incidence rate per 100,000 persons was 0.056 (95%CI:0.052-0.060) for pediatric cases and 7.793 (7.767-7.819) for adults. Incidence was stable in the pediatric population (0.3 AAPC, -1.1-1.7). In contrast, after periods of increase, incidence declined in adults after 2015 (-1.5 APC). Relative survival increased over time for both pediatric and adult ages and was higher for children and adolescents (46.4%, 95%CI:42.4-50.3) than adults (20.7%, 95%CI:20.5-20.9) overall and when stratified by stage. Regression modeling showed that non-Hispanic Black race and ethnicity was associated with higher risk of death in children and adolescents (1.48, 95%CI:1.07-2.05) and adults (1.11, 95%CI:1.09-1.12) compared to non-Hispanic white race and ethnicity. CONCLUSIONS AND RELEVANCE: Between 2003 and 2020 in the United States, pediatric incidence was stable while incidence in adults began to decline after 2015. Survival was higher across all stages for children and adolescents compared to adults. Non-Hispanic Black race and ethnicity showed a higher risk of death for both age groups. Further studies could explore the factors that influence these outcome disparities. |
A comprehensive analysis of neuroblastoma incidence, survival, and racial and ethnic disparities from 2001 to 2019
Campbell K , Siegel DA , Umaretiya PJ , Dai S , Heczey A , Lupo PJ , Schraw JM , Thompson TD , Scheurer ME , Foster JH . Pediatr Blood Cancer 2023 71 (1) e30732 BACKGROUND: We characterize the incidence and 5-year survival of children and adolescents with neuroblastoma stratified by demographic and clinical factors based on the comprehensive data from United States Cancer Statistics (USCS) and the National Program of Cancer Registries (NPCR). METHODS: We analyzed the incidence of neuroblastoma from USCS (2003-2019) and survival data from NPCR (2001-2018) for patients less than 20 years old. Incidence trends were calculated by average annual percent change (AAPC) using joinpoint regression. Differences in relative survival were estimated comparing non-overlapping confidence intervals (CI). RESULTS: We identified 11,543 primary neuroblastoma cases in USCS. Age-adjusted incidence was 8.3 per million persons [95% CI: 8.2, 8.5], with an AAPC of 0.4% [95% CI: -0.1, 0.9]. Five-year relative survival from the NPCR dataset (n = 10,676) was 79.7% [95% CI: 78.9, 80.5]. Patients aged less than 1 year had the highest 5-year relative survival (92.5%). Five-year relative survival was higher for non-Hispanic White patients (80.7%) or Hispanic patients (80.8%) compared to non-Hispanic Black patients (72.6%). CONCLUSION: Neuroblastoma incidence was stable during 2003-2019. Differences in relative survival exist by sex, age, race/ethnicity, and stage; patients who were male, older, non-Hispanic Black, or with distant disease had worse survival. Future studies could seek to assess the upstream factors driving disparities in survival, and evaluate interventions to address inequities and improve survival across all groups. |
Scientific impact of the National Birth Defects Prevention Network multistate collaborative publications
Bascom JT , Stephens SB , Lupo PJ , Canfield MA , Kirby RS , Nestoridi E , Salemi JL , Mai CT , Nembhard WN , Forestieri NE , Romitti PA , St Louis AM , Agopian AJ . Birth Defects Res 2023 BACKGROUND: Given the lack of a national, population-based birth defects surveillance program in the United States, the National Birth Defects Prevention Network (NBDPN) has facilitated important studies on surveillance, research, and prevention of major birth defects. We sought to summarize NBDPN peer-reviewed publications and their impact. METHODS: We obtained and reviewed a curated list of 49 NBDPN multistate collaborative publications during 2000-2022, as of December 31, 2022. Each publication was reviewed and classified by type (e.g., risk factor association analysis). Key characteristics of study populations and analytic approaches used, along with publication impact (e.g., number of citations), were tabulated. RESULTS: NBDPN publications focused on prevalence estimates (N = 17), surveillance methods (N = 11), risk factor associations (N = 10), mortality and other outcomes among affected individuals (N = 6), and descriptive epidemiology of various birth defects (N = 5). The most cited publications were those that reported on prevalence estimates for a spectrum of defects and those that assessed changes in neural tube defects (NTD) prevalence following mandatory folic acid fortification in the United States. CONCLUSIONS: Results from multistate NBDPN publications have provided critical information not available through other sources, including US prevalence estimates of major birth defects, folic acid fortification and NTD prevention, and improved understanding of defect trends and surveillance efforts. Until a national birth defects surveillance program is established in the United States, NBDPN collaborative publications remain an important resource for investigating birth defects and informing decisions related to health services planning of secondary disabilities prevention and care. |
Counts, incidence rates, and trends of pediatric cancer in the United States, 2003-2019
Siegel DA , King JB , Lupo PJ , Durbin EB , Tai E , Mills K , Van Dyne E , Buchanan Lunsford N , Henley SJ , Wilson RJ . J Natl Cancer Inst 2023 115 (11) 1337-1354 BACKGROUND: Cancer is a leading cause of death by disease among children and adolescents in the United States. This study updates cancer incidence rates and trends using the most recent and comprehensive US cancer registry data available. METHODS: We used data from US Cancer Statistics to evaluate counts, age-adjusted incidence rates, and trends among children and adolescents aged <20 years diagnosed with malignant tumors during 2003-2019. We calculated average annual percent change and annual percent change (APC) using joinpoint regression. Rates and trends were stratified by demographic and geographic characteristics and by cancer type. RESULTS: With 248,749 cases reported during 2003-2019, the overall cancer incidence rate was 178.3 per 1 million; incidence rates were highest for leukemia (46.6), central nervous system (CNS) neoplasms (30.8), and lymphoma (27.3). Rates were highest for males, children aged 0-4 years, Non-Hispanic White children and adolescents, those in the Northeast census region, top 25% of counties by economic status, and metropolitan counties with population ≥1 million. While the overall incidence rate of pediatric cancer increased 0.5% per year on average during 2003-2019, the rate increased during 2003-2016 (APC = 1.1%) and then decreased during 2016-2019 (APC = -2.1%). During 2003-2019, rates of leukemia, lymphoma, hepatic tumors, bone tumors, and thyroid carcinomas increased, while melanoma rates decreased. CNS neoplasms rates increased until 2017 and then decreased. Other cancer types remained stable. CONCLUSIONS: Incidence of pediatric cancer increased overall, although increases were limited to certain cancer types. These findings may guide future public health and research priorities. |
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. |
Prevalence and descriptive epidemiology of Turner syndrome in the United States, 2000-2017: A report from the National Birth Defects Prevention Network.
Martin-Giacalone BA , Lin AE , Rasmussen SA , Kirby RS , Nestoridi E , Liberman RF , Agopian AJ , Carey JC , Cragan JD , Forestieri N , Leedom V , Boyce A , Nembhard WN , Piccardi M , Sandidge T , Shan X , Shumate CJ , Stallings EB , Stevenson R , Lupo PJ . Am J Med Genet A 2023 191 (5) 1339-1349 The lack of United States population-based data on Turner syndrome limits assessments of prevalence and associated characteristics for this sex chromosome abnormality. Therefore, we collated 2000-2017 data from seven birth defects surveillance programs within the National Birth Defects Prevention Network. We estimated the prevalence of karyotype-confirmed Turner syndrome diagnosed within the first year of life. We also calculated the proportion of cases with commonly ascertained birth defects, assessed associations with maternal and infant characteristics using prevalence ratios (PR) with 95% confidence intervals (CI), and estimated survival probability. The prevalence of Turner syndrome of any pregnancy outcome was 3.2 per 10,000 female live births (95% CI = 3.0-3.3, program range: 1.0-10.4), and 1.9 for live birth and stillbirth (≥20 weeks gestation) cases (95% CI = 1.8-2.1, program range: 0.2-3.9). Prevalence was lowest among cases born to non-Hispanic Black women compared to non-Hispanic White women (PR = 0.5, 95% CI = 0.4-0.6). Coarctation of the aorta was the most common defect (11.6% of cases), and across the cohort, individuals without hypoplastic left heart had a five-year survival probability of 94.6%. The findings from this population-based study may inform surveillance practices, prenatal counseling, and diagnosis. We also identified racial and ethnic disparities in prevalence, an observation that warrants further investigation. |
Pharmacology of boosted and unboosted integrase strand transfer inhibitors for two-dose event-driven HIV prevention regimens among men
Haaland RE , Fountain J , Martin A , Dinh C , Holder A , Edwards TE , Lupo LD , Hall L , Conway-Washington C , Massud I , García-Lerma JG , Kelley CF , Heneine WM . J Antimicrob Chemother 2023 78 (2) 497-503 BACKGROUND: Event-driven HIV prevention strategies are a priority for users who do not require daily pre-exposure prophylaxis (PrEP). Regimens containing integrase strand transfer inhibitors (INSTIs) are under evaluation as alternatives to daily PrEP. To better understand INSTI distribution and inform dosing selection we compared the pharmacology of two-dose boosted elvitegravir and unboosted bictegravir regimens in MSM. MATERIALS AND METHODS: Blood, rectal and penile secretions and rectal biopsies were collected from 63 HIV-negative MSM aged 18-49 years. Specimens were collected up to 96 h after two oral doses of tenofovir alafenamide and emtricitabine with elvitegravir boosted by cobicistat or unboosted bictegravir given 24 h apart. Antiretroviral drugs were measured by LC-MS. RESULTS: Mean bictegravir plasma concentrations remained above the 95% protein-adjusted effective concentration 96 h after dosing [273 (95% CI: 164-456) ng/mL] whereas elvitegravir plasma concentrations became undetectable 48 h after the second dose. Bictegravir and elvitegravir reached rectal tissues within 2 h after the first dose, and elvitegravir tissue concentrations [1.07 (0.38-13.51) ng/mg] were greater than bictegravir concentrations [0.27 (0.15-0.70) ng/mg]. Both INSTIs became undetectable in tissues within 96 h. Elvitegravir and bictegravir were not consistently detected in penile secretions. CONCLUSIONS: Whereas bictegravir plasma concentrations persist at least 4 days after a two-oral-dose HIV prophylaxis regimen, elvitegravir accumulates in mucosal tissues. Differing elvitegravir and bictegravir distribution may result in variable mucosal and systemic antiviral activity and can inform dosing strategies for event-driven HIV prevention. |
Pediatric rhabdomyosarcoma incidence and survival in the United States: An assessment of 5656 cases, 2001-2017
McEvoy MT , Siegel DA , Dai S , Okcu MF , Zobeck M , Venkatramani R , Lupo PJ . Cancer Med 2022 12 (3) 3644-3656 BACKGROUND: While rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents, past epidemiology studies of this malignancy used data that covered <30% of the US population. Therefore, we evaluated RMS incidence using data from U.S. Cancer Statistics (USCS) and survival trends using the National Program of Cancer Registries (NPCR), which covers 100% and 94% of the U.S. population, respectively. METHODS: Incidence and survival were assessed for pediatric patients diagnosed with RMS during 2003-2017 and 2001-2016, respectively. Both demographic and clinical variables were evaluated. Age-adjusted incidence rates, average annual percent change (AAPC), and 5-year relative survival (RS) were calculated, all with corresponding 95% confidence intervals (CIs). Cox regression models were used to evaluate the impact of demographic and clinical variables on survival. RESULTS: We identified 5656 primary RMS cases in USCS during 2003-2017. The age-adjusted incidence rate was 4.58 per 1 million (95% CI: 4.46-4.70) with an AAPC of 0.3% (95% CI: -0.7 to 1.2%). In NPCR, 5-year RS for all cases was 68.0% (95% CI: 66.6-69.3%). In multivariable analyses, non-Hispanic (NH) Black cases had worse survival compared with NH White cases (hazard ratio [HR] = 1.16, 95% CI: 1.01-1.33). CONCLUSION: The incidence and survival rates were stable in the largest and most comprehensive population-based analysis for pediatric RMS cases in the U.S. Additionally, we observed a survival disparity among NH Black cases. Findings from this study could inform interventions to address disparities, risk stratification strategies, and clinical trial design. |
Self-medication and ILI etiologies among individuals presenting at pharmacies with influenza-like illness: Guatemala City, 2018 influenza season
Ramay BM , Jara J , Moreno MP , Lupo P , Serrano C , Alvis JP , Arriola CS , Veguilla V , Kaydos-Daniels SC . BMC Public Health 2022 22 (1) 1541 OBJECTIVES: We aimed to characterize the proportion of clients presenting to community pharmacies with influenza-like illness (ILI) and the severity of their illness; the proportion with detectable influenza A, influenza B, and other pathogens (i.e., parainfluenza I, II, and III, adenovirus, respiratory syncytial virus, human metapneumovirus); and to describe their self-medication practices. METHODS: A cross-sectional study was conducted in six pharmacies in Guatemala City. Study personnel collected nasopharyngeal and oropharyngeal swabs from participants who met the ILI case definition and who were self-medicating for the current episode. Participants were tested for influenza A and B and other pathogens using real-time RT-PCR. Participants' ILI-associated self-medication practices were documented using a questionnaire. RESULTS: Of all patients entering the pharmacy during peak hours who responded to a screening survey (n = 18,016) 6% (n = 1029) self-reported ILI symptoms, of which 45% (n = 470/1029) met the study case definition of ILI. Thirty-one percent (148/470) met inclusion criteria, of which 87% (130/148) accepted participation and were enrolled in the study. Among 130 participants, nearly half tested positive for viral infection (n = 55, 42.3%) and belonged to groups at low risk for complications from influenza. The prevalence of influenza A was 29% (n = 35). Thirteen percent of the study population (n = 17) tested positive for a respiratory virus other than influenza. Sixty-four percent of participants (n = 83) reported interest in receiving influenza vaccination if it were to become available in the pharmacy. Medications purchased included symptom-relieving multi-ingredient cold medications (n = 43/100, 43%), nonsteroidal anti-inflammatory drugs (n = 23, 23%), and antibiotics (n = 16, 16%). Antibiotic use was essentially equal among antibiotic users regardless of viral status. The broad-spectrum antibiotics ceftriaxone and azithromycin were the most common antibiotics purchased. CONCLUSIONS: During a typical influenza season, a relatively low proportion of all pharmacy visitors were experiencing influenza symptoms. A high proportion of clients presenting to pharmacies with ILI tested positive for a respiratory virus. Programs that guide appropriate use of antibiotics in this population are needed and become increasingly important during pandemics caused by respiratory viral pathogens. |
Incidence and 5-year survival of children and adolescents with hepatoblastoma in the United States
Kahla JA , Siegel DA , Dai S , Lupo PJ , Foster JH , Scheurer ME , Heczey AA . Pediatr Blood Cancer 2022 69 (10) e29763 OBJECTIVE: Hepatoblastoma (HB) is the most common pediatric primary malignant liver tumor, its incidence has been increasing worldwide, but recent changes in incidence and outcomes with high population coverage are not well characterized. METHODS: We defined the incidence of HB diagnosed during 2003-2017 from United States Cancer Statistics (USCS) database, and survival during 2001-2016 from the National Program of Cancer Registries (NPCR). Data were stratified by sex, race/ethnicity, age, tumor stage, county population, and diagnosis year. Incidence trends were assessed by calculating average annual percent change (AAPC) using Joinpoint regression. Differences in overall 5-year survival were estimated using Cox regression analysis. RESULTS: 2178 HB cases with an annual incidence rate of 1.76 per million persons were identified and incidence increased over time (AAPC = 2.2, 95% confidence interval [CI], 0.9-3.6). The 5-year relative survival was 76.9% (95% CI: 74.9-78.8) and the risk of death was lower for cases diagnosed after 2009 (hazard ratio [HR] = 0.77, 95% CI: 0.63-0.94), higher for ages 3-7 years and 8-19 years compared to 0-2 years (HR = 1.38, 95% CI: 1.10-1.76 and 1.83, 95% CI: 1.31-2.70, respectively), for distant compared to locoregional stage (HR = 2.77, 95% CI: 2.27-3.36), and for non-Hispanic Black compared to non-Hispanic White cases (HR = 1.39, 95% CI: 1.02-1.84). CONCLUSIONS: HB incidence increased, and survival improved over the study period. Disparities in survival exist by age, race or ethnicity, and stage. Further studies could identify factors affecting increases in HB cases, inform future interventions, and address disparities in outcomes. |
Prevalence of critical congenital heart defects and select co-occurring congenital anomalies, 2014-2018: A U.S. population-based study
Stallings EB , Isenburg JL , Aggarwal D , Lupo PJ , Oster ME , Shephard H , Liberman RF , Kirby RS , Nestoridi E , Hansen B , Shan X , Navarro Sanchez ML , Boyce A , Heinke D . Birth Defects Res 2022 114 (2) 45-56 BACKGROUND: Critical congenital heart defects (CCHDs) are one of the most common types of birth defects and can lead to significant morbidity and mortality along with surgical or catheter interventions within the first year of life. This report updates previously published estimates of CCHD prevalence with the latest population-based surveillance data from 19 birth defect surveillance programs. METHODS: The U.S. population-based surveillance programs submitted data on identified cases of 12 CCHDs and co-occurring cardiovascular and chromosomal birth defects from 2014 to 2018. We estimated prevalence by program type and maternal and infant characteristics. Among nine programs with active case ascertainment that collect more than live births, we estimated the percentage of co-occurring cardiovascular and chromosomal birth defects for the 12 CCHDs. RESULTS: We identified 18,587 cases of CCHD among all participating programs. Overall CCHD prevalence was 19.6 per 10,000 live births among all 19 programs and 20.2 per 10,000 live births among active programs. Among maternal racial/ethnic groups, infants/fetuses born to American Indian/Alaska Native mothers showed the highest overall prevalence for all CCHDs (28.3 per 10,000) along with eight of the 12 individual CCHDs. Among 7,726 infants/fetuses with CCHD from active case ascertainment programs, 15.8% had at least one co-occurring chromosomal birth defect. CONCLUSION: Our study provides prevalence estimates for CCHDs by maternal and infant characteristics along with co-occurrence with cardiovascular and chromosomal birth defects among infants/fetuses with CCHD using one of the largest and most recent cohorts since the implementation of widespread CCHD screening. These data can provide a basis for future research to better understand risk factors for these defects. |
Co-occurrence of congenital anomalies by maternal race/ethnicity among infants and fetuses with Down syndrome, 2013-2017: A U.S. population-based analysis.
Stallings EB , Isenburg JL , Heinke D , Sherman SL , Kirby RS , Lupo PJ . Birth Defects Res 2021 114 (2) 57-61 BACKGROUND: Individuals with Down syndrome (DS) have a higher prevalence of additional congenital anomalies, especially cardiovascular defects, compared to the general population. Several reports have indicated that the prevalence of DS among live births varies by race and ethnicity within the United States. We aim to examine variations in co-occurring congenital anomalies by maternal race/ethnicity among infants and fetuses diagnosed with DS born during 2013-2017. METHODS: State birth defect surveillance systems (N = 12) submitted data on infants and fetuses diagnosed with DS born during 2013-2017. We calculated the prevalence of co-occurring major and minor congenital anomalies, by organ system, and four selected cardiovascular birth defects, all stratified by maternal race/ethnicity. RESULTS: Among 5,836 cases of DS, 79.7% had one or more co-occurring congenital anomalies. There was a higher percentage of co-occurring congenital anomalies among infants and fetuses born to Hispanic mothers. The lowest percentage of co-occurring congenital anomalies, including three out of the four individual cardiovascular conditions examined, was among infants/fetuses born to non-Hispanic American Indian/Alaska Native mothers. CONCLUSIONS: We describe differences in DS co-occurrence with additional congenital anomalies among maternal racial/ethnic groups. These data may help focus future research on differences among racial/ethnic groups in the diagnosis and reporting of co-occurring congenital anomalies in infants/fetuses diagnosed with DS. |
Antiretroviral drug exposure in urethral and glans surface sampling of the penis
Haaland RE , Fountain J , Dinh C , Lupo LD , Martin A , Conway-Washington C , Hall L , Kelley CF , Garcia-Lerma JG , Heneine W . J Antimicrob Chemother 2021 76 (9) 2368-2374 BACKGROUND: HIV exposure to penile tissues provides a risk of acquisition among men, yet studies evaluating penile antiretroviral (ARV) drug distribution have been lacking. We measured ARVs on urethral and glans surface swabs collected following a dose of tenofovir alafenamide, emtricitabine, elvitegravir, darunavir and cobicistat. METHODS: Thirty-five HIV-negative male participants provided urethral swabs, glans swabs, rectal swabs, blood and urine up to 96 h following a single dose of tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat and darunavir. ARVs were measured by liquid chromatography-mass spectrometry with a lower limit of detection (LOD) of 1 ng/swab for swabs and 10 ng/mL for plasma and urine. Concentrations are reported as median and range. RESULTS: Urethral swab emtricitabine and darunavir concentrations peaked at 4 h for emtricitabine (36 ng/swab; 3-307 ng/swab) and 8 h for darunavir (25 ng/swab; 2-52 ng/swab). Glans swab emtricitabine and darunavir concentrations peaked 24 h after dosing (emtricitabine 14 ng/swab, <LOD-328 ng/swab; darunavir 6 ng/swab, <LOD-149 ng/swab). Estimated peak urethral secretion emtricitabine and darunavir concentrations are between 10 and 20 μg/mL, similar to rectal secretions, 4-fold greater than in plasma, but 2-fold lower than in urine. Tenofovir and elvitegravir were detected on less than 20% of urethral or glans swabs collected within 24 h of dosing. CONCLUSIONS: We document ARV dosing in the urethra and on the glans surface with high drug concentrations noted for emtricitabine and darunavir and lower tenofovir and elvitegravir concentrations. Data suggest a potential protective role of urethral emtricitabine or darunavir against penile HIV acquisition. |
Evaluation of antiretroviral drug concentrations in minimally invasive specimens for potential development of point of care drug assays
Haaland R , Martin A , Mengesha M , Dinh C , Fountain J , Lupo LD , Hall L , Conway-Washington C , Kelley C . AIDS Res Hum Retroviruses 2021 37 (10) 744-747 Point of care (POC) tests for antiretroviral drugs (ARVs) could help improve individual adherence. This study sought to define the utility of urine, blood, and buccal swabs as minimally invasive specimens amenable to development of POC tests for ARVs. Urine, dried blood spots (DBS) and buccal swabs were collected from 35 HIV-negative men between 2 and 96 hours following a single dose of tenofovir alafenamide (TAF)/emtricitabine (FTC)/elvitegravir (EVG)/cobicistat and darunavir (DRV). ARV concentrations were measured by high performance liquid chromatography-mass spectrometry. High concentrations of FTC, DRV and TFV were detectable in urine at least 24 hours after dosing. FTC, DRV and EVG remained detectable in DBS at least 24 hours post dose. FTC and DRV were detectable on buccal swabs up to 2- and 24-hours post dose, respectively. TFV was not detectable in DBS or buccal swabs collected between 2 and 96 hours after dosing. Variable distribution of ARVs in minimally invasive specimens highlights the challenge of developing POC assays for recent ARV exposure. |
Prevalence of structural birth defects among infants with Down syndrome, 2013-2017: A US population-based study
Heinke D , Isenburg JL , Stallings EB , Short TD , Le M , Fisher S , Shan X , Kirby RS , Nguyen HH , Nestoridi E , Nembhard WN , Romitti PA , Salemi JL , Lupo PJ . Birth Defects Res 2020 113 (2) 189-202 BACKGROUND: Down syndrome is the most common chromosomal disorder at birth and is often accompanied by structural birth defects. Current data on major structural defects in this population are limited. METHODS: States and territorial population-based surveillance programs submitted data on identified cases of Down syndrome and identified structural birth defects during 2013-2017. We estimated prevalence by program type and maternal and infant characteristics. Among programs with active case ascertainment, we estimated the prevalence of birth defects by organ system and for specific defects by maternal age (<35, ≥35) and infant sex. RESULTS: We identified 13,376 cases of Down syndrome. Prevalence among all programs was 12.7 per 10,000 live births. Among these children, 75% had at least one reported co-occurring birth defect diagnosis code. Among 6,210 cases identified by active programs, 66% had a cardiovascular defect with septal defects being the most common: atrial (32.5%), ventricular (20.6%), and atrioventricular (17.4%). Defect prevalence differed by infant sex more frequently than by maternal age. For example, atrioventricular septal defects were more common in female children (20.1% vs. 15.1%) while limb deficiencies were more prevalent in male children (0.4% vs. 0.1%). CONCLUSIONS: Our study provides updated prevalence estimates for structural defects, including rare defects, among children with Down syndrome using one of the largest and most recent cohorts to date. These data may aid clinical care and surveillance. |
Maternal occupational exposure to polycyclic aromatic hydrocarbons and the risk of isolated congenital heart defects among offspring
Patel J , Nembhard WN , Politis MD , Rocheleau CM , Langlois PH , Shaw GM , Romitti PA , Gilboa SM , Desrosiers TA , Insaf T , Lupo PJ . Environ Res 2020 186 109550 BACKGROUND: Although there is evidence in experimental model systems that exposure to polycyclic aromatic hydrocarbons (PAHs) is linked with congenital heart defects (CHDs), few studies have examined the association in humans. We conducted a case-control study to examine the association between maternal exposure to PAHs and CHDs in offspring using data from the National Birth Defects Prevention Study (NBDPS) (1997-2011). METHODS: We obtained detailed information on maternal occupation during the month before to three months after conception. Expert raters, masked to case-control status, assessed job descriptions to assign categorical levels of exposure. Categories were quantitatively mapped to estimate cumulative exposure to PAHs, incorporating exposure intensity, frequency, work duration, and work hours. Quartiles were generated for cumulative maternal exposure to PAHs. Crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using unconditional logistic regression for quartiles of PAH exposure and six CHD groupings (e.g. conotruncal) and specific subtypes (e.g. tetralogy of Fallot [ToF]). Final models were adjusted for maternal age, race/ethnicity, education, smoking, anticonvulsant use, folic acid supplementation, and study center. RESULTS: There were 4,775 case and 7,734 control infants eligible for the study. The prevalence of occupational exposure to PAHs was 10.2% among both case and control mothers. In adjusted analysis, compared to mothers with no occupational PAH exposure, those in the highest quartile of exposure were more likely to have offspring in the conotruncal heart defects group (OR 1.41; 95% CI 1.00-2.00), and with ToF (OR 1.83; 95% CI 1.21-2.78). CONCLUSIONS: Women in the highest quartile of estimated cumulative occupational PAH exposure during early pregnancy were more likely to have offspring with conotruncal heart defects, specifically ToF, compared to women with no occupational PAH exposure. Other comparisons between PAHs and other CHDs subgroups did not show any statistically precise associations. |
Impact of etonogestrel implant use on T-cell and cytokine profiles in the female genital tract and blood
Haddad LB , Swaims-Kohlmeier A , Mehta CC , Haaland RE , Brown NL , Sheth AN , Chien H , Titanji K , Achilles SL , Lupo D , Hart CE , Ofotokun I . PLoS One 2020 15 (3) e0230473 BACKGROUND: While prior epidemiologic studies have suggested that injectable progestin-based contraceptive depot medroxyprogesterone acetate (DMPA) use may increase a woman's risk of acquiring HIV, recent data have suggested that DMPA users may be at a similar risk for HIV acquisition as users of the copper intrauterine device and levonorgestrel implant. Use of the etonogestrel Implant (Eng-Implant) is increasing but there are currently no studies evaluating its effect on HIV acquisition risk. OBJECTIVE: Evaluate the potential effect of the Eng-Implant use on HIV acquisition risk by analyzing HIV target cells and cytokine profiles in the lower genital tract and blood of adult premenopausal HIV-negative women using the Eng-Implant. METHODS: We prospectively obtained paired cervicovaginal lavage (CVL) and blood samples at 4 study visits over 16 weeks from women between ages 18-45, with normal menses (22-35 day intervals), HIV uninfected with no recent hormonal contraceptive or copper intrauterine device (IUD) use, no clinical signs of a sexually transmitted infection at enrollment and who were medically eligible to initiate Eng-Implant. Participants attended pre-Eng-Implant study visits (week -2, week 0) with the Eng-Implant inserted at the end of the week 0 study visit and returned for study visits at weeks 12 and 14. Genital tract leukocytes (enriched from CVL) and peripheral blood mononuclear cells (PBMC) from the study visits were evaluated for markers of activation (CD38, HLA-DR), retention (CD103) and trafficking (CCR7) on HIV target cells (CCR5+CD4+ T cells) using multicolor flow cytometry. Cytokines and chemokines in the CVL supernatant and blood plasma were measured in a Luminex assay. We estimated and compared study endpoints among the samples collected before and after contraception initiation with repeated-measures analyses using linear mixed models. RESULTS: Fifteen of 18 women who received an Eng-Implant completed all 4 study visits. The percentage of CD4+ T cells in CVL was not increased after implant placement but the percentage of CD4+ T cells expressing the HIV co-receptor CCR5 did increase after implant placement (p = 0.02). In addition, the percentage of central memory CD4+ T-cells (CCR7+) in CVL increased after implant placement (p = 0.004). The percentage of CVL CD4+, CCR5+ HIV target cells expressing activation markers after implant placement was either reduced (HLA-DR+, p = 0.01) or unchanged (CD38+, p = 0.45). Most CVL cytokine and chemokine concentrations were not significantly different after implant placement except for a higher level of the soluble lymphocyte activation marker (sCD40L; p = 0.04) and lower levels of IL12p70 (p = 0.02) and G-CSF (p<0.001). In systemic blood, none of the changes noted in CVL after implant placement occurred except for decreases in the percentage CD4 T-cells expressing HLA-DR+ T cells (p = 0.006) and G-CSF (p = 0.02). CONCLUSIONS: Eng-Implant use was associated with a moderate increase in the availability of HIV target cells in the genital tract, however the percentage of these cells that were activated did not increase and there were minimal shifts in the overall immune environment. Given the mixed nature of these findings, it is unclear if these implant-induced changes alter HIV risk. |
Genome-wide association studies of structural birth defects: A review and commentary.
Lupo PJ , Mitchell LE , Jenkins MM . Birth Defects Res 2019 111 (18) 1329-1342 BACKGROUND: While there is strong evidence that genetic risk factors play an important role in the etiologies of structural birth defects, compared to other diseases, there have been relatively few genome-wide association studies (GWAS) of these conditions. We reviewed the current landscape of GWAS conducted for birth defects, noting novel insights, and future directions. METHODS: This article reviews the literature with regard to GWAS of structural birth defects. Key defects included in this review include oral clefts, congenital heart defects (CHDs), biliary atresia, pyloric stenosis, hypospadias, craniosynostosis, and clubfoot. Additionally, other issues related to GWAS are considered, including the assessment of polygenic risk scores and issues related to genetic ancestry, as well as utilizing genome-wide single nucleotide polymorphism array data to evaluate gene-environment interactions and Mendelian randomization. RESULTS: For some birth defects, including oral clefts and CHDs, several novel susceptibility loci have been identified and replicated through GWAS, including 8q24 for oral clefts, DGKK for hypospadias, and 4p16 for CHDs. Relatively common birth defects for which there are currently no published GWAS include neural tube defects, anotia/microtia, anophthalmia/microphthalmia, gastroschisis, and omphalocele. CONCLUSIONS: Overall, GWAS have been successful in identifying several novel susceptibility genes and genomic regions for structural birth defects. These findings have provided new insights into the etiologies of these phenotypes. However, GWAS have been underutilized for understanding the genetic etiologies of several birth defects. |
Population-based birth defects data in the United States, 2012-2016: A focus on abdominal wall defects
Stallings EB , Isenburg JL , Short TD , Heinke D , Kirby RS , Romitti PA , Canfield MA , O'Leary LA , Liberman RF , Forestieri NE , Nembhard WN , Sandidge T , Nestoridi E , Salemi JL , Nance AE , Duckett K , Ramirez GM , Shan X , Shi J , Lupo PJ . Birth Defects Res 2019 111 (18) 1436-1447 BACKGROUND/OBJECTIVES: In this report, the National Birth Defects Prevention Network (NBDPN) examines and compares gastroschisis and omphalocele for a recent 5-year birth cohort using data from 30 population-based birth defect surveillance programs in the United States. METHODS: As a special call for data for the 2019 NBDPN Annual Report, state programs reported expanded data on gastroschisis and omphalocele for birth years 2012-2016. We estimated the overall prevalence (per 10,000 live births) and 95% confidence intervals (CI) for each defect as well as by maternal race/ethnicity, maternal age, infant sex, and case ascertainment methodology utilized by the program (active vs. passive). We also compared distribution of cases by maternal and infant factors and presence/absence of other birth defects. RESULTS: The overall prevalence estimates (per 10,000 live births) were 4.3 (95% CI: 4.1-4.4) for gastroschisis and 2.1 (95% CI: 2.0-2.2) for omphalocele. Gastroschisis was more frequent among young mothers (<25 years) and omphalocele more common among older mothers (>40 years). Mothers of infants with gastroschisis were more likely to be underweight/normal weight prior to pregnancy and mothers of infants with omphalocele more likely to be overweight/obese. Omphalocele was twice as likely as gastroschisis to co-occur with other birth defects. CONCLUSIONS: This report highlights important differences between gastroschisis and omphalocele. These differences indicate the importance of distinguishing between these defects in epidemiologic assessments. The report also provides additional data on co-occurrence of gastroschisis and omphalocele with other birth defects. This information can provide a basis for future research to better understand these defects. |
National population-based estimates for major birth defects, 2010-2014
Mai CT , Isenburg JL , Canfield MA , Meyer RE , Correa A , Alverson CJ , Lupo PJ , Riehle-Colarusso T , Cho SJ , Aggarwal D , Kirby RS . Birth Defects Res 2019 111 (18) 1420-1435 BACKGROUND: Using the National Birth Defects Prevention Network (NBDPN) annual data report, U.S. national prevalence estimates for major birth defects are developed based on birth cohort 2010-2014. METHODS: Data from 39 U.S. population-based birth defects surveillance programs (16 active case-finding, 10 passive case-finding with case confirmation, and 13 passive without case confirmation) were used to calculate pooled prevalence estimates for major defects by case-finding approach. Fourteen active case-finding programs including at least live birth and stillbirth pregnancy outcomes monitoring approximately one million births annually were used to develop national prevalence estimates, adjusted for maternal race/ethnicity (for all conditions examined) and maternal age (trisomies and gastroschisis). These calculations used a similar methodology to the previous estimates to examine changes over time. RESULTS: The adjusted national birth prevalence estimates per 10,000 live births ranged from 0.62 for interrupted aortic arch to 16.87 for clubfoot, and 19.93 for the 12 critical congenital heart defects combined. While the birth prevalence of most birth defects studied remained relatively stable over 15 years, an increasing prevalence was observed for gastroschisis and Down syndrome. Additionally, the prevalence for atrioventricular septal defect, tetralogy of Fallot, omphalocele, and trisomy 18 increased in this period compared to the previous periods. Active case-finding programs generally had higher prevalence rates for most defects examined, most notably for anencephaly, anophthalmia/microphthalmia, trisomy 13, and trisomy 18. CONCLUSION: National estimates of birth defects prevalence provide data for monitoring trends and understanding the impact of these conditions. Increasing prevalence rates observed for selected conditions warrant further examination. |
Urine emtricitabine and tenofovir concentrations provide markers of recent antiretroviral drug exposure among HIV-negative men who have sex with men
Haaland RE , Martin A , Livermont T , Fountain J , Dinh C , Holder A , Lupo LD , Hall L , Conway-Washington C , Kelley CF . J Acquir Immune Defic Syndr 2019 82 (3) 252-256 BACKGROUND: Urine provides a minimally invasive specimen that may allow for development of rapid tests to detect antiretroviral drugs (ARVs) and provide opportunities to improve individual adherence. This study sought to determine if urine could provide a biomarker of adherence for currently approved PrEP and HIV treatment regimens. METHODS: Urine and blood were collected from 34 HIV-negative men who have sex with men aged 18-49 years enrolled in a clinical trial comparing 2 ARV regimens. Specimens were collected 4 and 24 hours after a single oral dose of tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) (n=10) or tenofovir alafenamide (TAF)/FTC/cobicistat (COBI)/elvitegravir (EVG) (n=8), or after 4 and 10 days of daily oral TDF/FTC (n=9) or TAF/FTC/COBI/EVG (n=7). Tenofovir (TFV), FTC, and EVG were measured by high performance liquid chromatography-mass spectrometry. RESULTS: Median urine FTC concentrations at 4 and 24 hours were similar between men receiving TDF/FTC (4 hours 147 microg/mL; 24 hours 10 microg/mL) and men receiving TAF/FTC/COBI/EVG (4 hours 333 microg/mL, p=0.173; 24 hours 13 microg/mL, p=0.681). Median urine TFV concentrations were lower among men receiving TAF/FTC/COBI/EVG (4 hours 1.2 microg/mL; 24 hours 0.8 microg/mL) compared to men receiving TDF/FTC (4 hours 17 microg/mL, p<0.001; 24 hours 7 microg/mL, p=0.001). Urine TFV concentrations remained reduced among men receiving TAF/FTC/COBI/EVG compared to men receiving TDF/FTC following daily dosing. EVG was not consistently measureable in urine. CONCLUSION: High urine FTC and TFV concentrations could provide an indication of adherence to daily oral dosing with TDF or TAF-based regimens used for treatment and prevention. |
Exome sequencing of family trios from the National Birth Defects Prevention Study: Tapping into a rich resource of genetic and environmental data.
Jenkins MM , Almli LM , Pangilinan F , Chong JX , Blue EE , Shapira SK , White J , McGoldrick D , Smith JD , Mullikin JC , Bean CJ , Nembhard WN , Lou XY , Shaw GM , Romitti PA , Keppler-Noreuil K , Yazdy MM , Kay DM , Carter TC , Olshan AF , Moore KJ , Nascone-Yoder N , Finnell RH , Lupo PJ , Feldkamp ML , Nickerson DA , Bamshad MJ , Brody LC , Reefhuis J . Birth Defects Res 2019 111 (20) 1618-1632 BACKGROUND: The National Birth Defects Prevention Study (NBDPS) is a multisite, population-based, case-control study of genetic and nongenetic risk factors for major structural birth defects. Eligible women had a pregnancy affected by a birth defect or a liveborn child without a birth defect between 1997 and 2011. They were invited to complete a telephone interview to collect pregnancy exposure data and were mailed buccal cell collection kits to collect specimens from themselves, their child (if living), and their child's father. Over 23,000 families representing more than 30 major structural birth defects provided DNA specimens. METHODS: To evaluate their utility for exome sequencing (ES), specimens from 20 children with colonic atresia were studied. Evaluations were conducted on specimens collected using cytobrushes stored and transported in open versus closed packaging, on native genomic DNA (gDNA) versus whole genome amplified (WGA) products and on a library preparation protocol adapted to low amounts of DNA. RESULTS: The DNA extracted from brushes in open packaging yielded higher quality sequence data than DNA from brushes in closed packaging. Quality metrics of sequenced gDNA were consistently higher than metrics from corresponding WGA products and were consistently high when using a low input protocol. CONCLUSIONS: This proof-of-principle study established conditions under which ES can be applied to NBDPS specimens. Successful sequencing of exomes from well-characterized NBDPS families indicated that this unique collection can be used to investigate the roles of genetic variation and gene-environment interaction effects in birth defect etiologies, providing a valuable resource for birth defect researchers. |
Population-based birth defects data in the United States, 2011-2015: A focus on eye and ear defects
Stallings EB , Isenburg JL , Mai CT , Liberman RF , Moore CA , Canfield MA , Salemi JL , Kirby RS , Short TD , Nembhard WN , Forestieri NE , Heinke D , Alverson CJ , Romitti PA , Huynh MP , Denson LE , Judson EM , Lupo PJ . Birth Defects Res 2018 110 (19) 1478-1486 BACKGROUND/OBJECTIVES: In this data brief, we examine major eye and ear anomalies (anophthalmia/microphthalmia, anotia/microtia, and congenital cataract) for a recent 5-year birth cohort using data from 30 population-based birth defects surveillance programs in the United States. METHODS: As a special call for data for the 2018 NBDPN Annual Report, state programs reported expanded data on eye/ear anomalies for birth years 2011-2015. We calculated the combined overall prevalence (per 10,000 live births) and 95% confidence intervals (CI), for the three anomalies as well as by maternal age, maternal race/ethnicity, infant sex, laterality, presence/absence of other major birth defects, and case ascertainment methodology utilized by the program (active vs. passive). RESULTS: The overall prevalence estimate (per 10,000 live births) was 1.5 (95% CI: 1.4-1.5) for anophthalmia/microphthalmia, 1.5 (95% CI: 1.4-1.6) for congenital cataract, and 1.8 (95% CI: 1.7-1.8) for anotia/microtia. Congenital cataract prevalence varied little by maternal race/ethnicity, infant sex, or case ascertainment methodology; prevalence differences were more apparent across strata for anophthalmia/microphthalmia and anotia/microtia. Prevalence among active vs. passive ascertainment programs was 50% higher for anophthalmia/microphthalmia (1.9 vs. 1.2) and two-fold higher for anotia/microtia (2.6 vs. 1.2). Anophthalmia/microphthalmia was more likely than other conditions to co-occur with other birth defects. All conditions were more frequent among older mothers (40+ years). CONCLUSIONS: This data brief provides recent prevalence estimates for anophthalmia/microphthalmia, congenital cataract, and anotia/microtia that address a data gap by examining pooled data from 30 population-based surveillance systems, covering a five-year birth cohort of about 12.4 million births. |
Status of population-based birth defects surveillance programs before and after the Zika public health response in the United States
Anderka M , Mai CT , Judson EM , Langlois PH , Lupo PJ , Hauser K , Salemi JL , Correia J , Canfield MA , Kirby RS . Birth Defects Res 2018 110 (19) 1388-1394 BACKGROUND: The 2016 Zika public health response in the United States highlighted the need for birth defect surveillance (BDS) programs to collect population-based data on birth defects potentially related to Zika as rapidly as possible through enhanced case ascertainment and reporting. The National Birth Defects Prevention Network (NBDPN) assessed BDS program activities in the United States before and after the Zika response. METHODS: The NBDPN surveyed 54 BDS programs regarding activities before and after the Zika response, lessons learned, and programmatic needs. Follow-up emails were sent and phone calls were held for programs with incomplete or no response to the online survey. Survey data were cleaned and tallied, and responses to open-ended questions were placed into best-fit categories. RESULTS: A 100% response rate was achieved. Of the 54 programs surveyed, 42 reported participation in the Zika public health response that included BDS activities. Programs faced challenges in expanding their surveillance effort given the response requirements but reported mitigating factors such as establishing and enhancing partnerships and program experience with surveillance and clinical activities. Beyond funding, reported program needs included training, surveillance tools/resources, and availability of clinical experts. CONCLUSIONS: Existing BDS programs with experience implementing active case-finding and case verification were able to adapt their surveillance efforts rapidly to collect and report data necessary for the Zika response. Program sustainability for BDS remains challenging; thus, continued support, training, and resource development are important to ensure that the infrastructure built during the Zika response is available for the next public health response. |
Population-based birth defects data in the United States, 2010-2014: A focus on gastrointestinal defects
Lupo PJ , Isenburg JL , Salemi JL , Mai CT , Liberman RF , Canfield MA , Copeland G , Haight S , Harpavat S , Hoyt AT , Moore CA , Nembhard WN , Nguyen HN , Rutkowski RE , Steele A , Alverson CJ , Stallings EB , Kirby RS . Birth Defects Res 2017 109 (18) 1504-1514 BACKGROUND: Gastrointestinal defects are a phenotypically and etiologically diverse group of malformations. Despite their combined prevalence and clinical impact, little is known about the epidemiology of these birth defects. Therefore, the objective of the 2017 National Birth Defects Prevention Network (NBDPN) data brief was to better describe the occurrence of gastrointestinal defects. METHODS: As part of the 2017 NBDPN annual report, 28 state programs provided additional data on gastrointestinal defects for the period 2010-2014. Counts and prevalence estimates (per 10,000 live births) were calculated overall and by demographic characteristics for (1) biliary atresia; (2) esophageal atresia/tracheoesophageal fistula; (3) rectal and large intestinal atresia/stenosis; and (4) small intestinal atresia/stenosis. Additionally, we explored the frequency of these malformations co-occurring with other structural birth defects. RESULTS: Pooling data from all participating registries, the prevalence estimates were: 0.7 per 10,000 live births for biliary atresia (713 cases); 2.3 per 10,000 live births for esophageal atresia/tracheoesophageal fistula (2,472 cases); 4.2 per 10,000 live births for rectal and large intestinal atresia/stenosis (4,334 cases); and 3.4 per 10,000 live births for small intestinal atresia/stenosis (3,388 cases). Findings related to co-occurring birth defects were especially notable for esophageal atresia/tracheoesophageal fistula, rectal and large intestinal atresia/stenosis, and small intestinal atresia/stenosis, where the median percentage of non-isolated cases was 53.9%, 45.5%, and 50.6%, respectively. CONCLUSIONS: These population-based prevalence estimates confirm some previous studies, and provide a foundation for future epidemiologic studies of gastrointestinal defects. Exploring the genetic and environmental determinants of these malformations may yield new clues into their etiologies. |
Estimated maternal pesticide exposure from drinking water and heart defects in offspring
Kim J , Swartz MD , Langlois PH , Romitti PA , Weyer P , Mitchell LE , Luben TJ , Ramakrishnan A , Malik S , Lupo PJ , Feldkamp ML , Meyer RE , Winston JJ , Reefhuis J , Blossom SJ , Bell E , Agopian AJ . Int J Environ Res Public Health 2017 14 (8) Our objective was to examine the relationship between estimated maternal exposure to pesticides in public drinking water and the risk of congenital heart defects (CHD). We used mixed-effects logistic regression to analyze data from 18,291 nonsyndromic cases with heart defects from the Texas Birth Defects Registry and 4414 randomly-selected controls delivered in Texas from 1999 through 2005. Water district-level pesticide exposure was estimated by linking each maternal residential address to the corresponding public water supply district's measured atrazine levels. We repeated analyses among independent subjects from the National Birth Defects Prevention Study (NBDPS) (1620 nonsyndromic cases with heart defects and 1335 controls delivered from 1999 through 2005). No positive associations were observed between high versus low atrazine level and eight CHD subtypes or all included heart defects combined. These findings should be interpreted with caution, in light of potential misclassification and relatively large proportions of subjects with missing atrazine data. Thus, more consistent and complete monitoring and reporting of drinking water contaminants will aid in better understanding the relationships between pesticide water contaminants and birth defects. |
Maternal exposure to ozone and PM2.5 and the prevalence of orofacial clefts in four U.S. states
Zhou Y , Gilboa SM , Herdt ML , Lupo PJ , Flanders WD , Liu Y , Shin M , Canfield MA , Kirby RS . Environ Res 2016 153 35-40 BACKGROUND: While there is some evidence that maternal exposure to ambient air pollution is associated with orofacial clefts in offspring, the epidemiologic studies have been largely equivocal. We evaluated whether maternal exposure to elevated county-level ambient fine particulate matter with aerodynamic diameter ≤2.5microm (PM2.5) and ozone during early gestation was associated with a higher prevalence of orofacial clefts. METHODS: Birth data consisting of 4.7 million births from 2001 to 2007 were obtained from National Birth Defects Prevention Network for four states - Arizona, Florida, New York (excluding New York City), and Texas. The air pollution exposure assessment for gestational weeks 5-10 was based on county-level average concentrations of PM2.5 and ozone data generated using a Bayesian fusion model available through CDC's Environmental Public Health Tracking Network. Two outcomes were analyzed separately: cleft lip with or without cleft palate, cleft palate alone. In logistic regression analyses, we adjusted for factors that were suspected confounders or modifiers of the association between the prevalence of orofacial clefts and air pollution, i.e., infant sex, race-ethnicity, maternal education, smoking status during pregnancy, whether this was mother's first baby, maternal age. RESULTS: Each 10microg/m3 increase in PM2.5 concentration was significantly associated with cleft palate alone (OR =1.43, 95% CI: 1.11-1.86). There was no significant association between PM2.5 concentration and cleft lip with or without cleft palate. No associations were observed between ozone exposure and the two outcomes of orofacial clefts. CONCLUSIONS: Our study suggests that PM2.5 significantly increased the risk of cleft palate alone, but did not change the incidence of cleft lip with or without palate. Ozone levels did not correlate with incidence of orofacial clefts. |
Paternal and joint parental occupational pesticide exposure and spina bifida in the National Birth Defects Prevention Study, 1997 to 2002
Pettigrew SM , Bell EM , Van Zutphen AR , Rocheleau CM , Shaw GM , Romitti PA , Olshan A , Lupo PJ , Soim A , Makelarski JA , Michalski AM , Sanderson W . Birth Defects Res A Clin Mol Teratol 2016 106 (11) 963-971 BACKGROUND: Because of persistent concerns over the association between pesticides and spina bifida, we examined the role of paternal and combined parental occupational pesticide exposures in spina bifida in offspring using data from a large population-based study of birth defects. METHODS: Occupational information from fathers of 291 spina bifida cases and 2745 unaffected live born control infants with estimated dates of delivery from 1997 to 2002 were collected by means of maternal report. Two expert industrial hygienists estimated exposure intensity and frequency to insecticides, herbicides, and fungicides. Multivariable logistic regression models were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for exposure to any pesticide and to any class of pesticide (yes/no; and by median), and exposure to combinations of pesticides (yes/no) and risk of spina bifida. Adjusted odds ratios were also estimated by parent exposed to pesticides (neither, mother only, father only, both parents). RESULTS: Joint parental occupational pesticide exposure was positively associated with spina bifida (aOR, 1.5; 95% CI, 0.9-2.4) when compared with infants with neither maternal nor paternal exposures; a similar association was not observed when only one parent was exposed. There was a suggested positive association between combined paternal insecticide and fungicide exposures and spina bifida (aOR, 1.5; 95% CI, 0.8-2.8), however, nearly all other aORs were close to unity. CONCLUSION: Overall, there was little evidence paternal occupational pesticide exposure was associated with spina bifida. However, the small numbers make it difficult to precisely evaluate the role of pesticide classes, individually and in combination. |
Population-based microcephaly surveillance in the United States, 2009 to 2013: An analysis of potential sources of variation
Cragan JD , Isenburg JL , Parker SE , Alverson CJ , Meyer RE , Stallings EB , Kirby RS , Lupo PJ , Liu JS , Seagroves A , Ethen MK , Cho SJ , Evans M , Liberman RF , Fornoff J , Browne ML , Rutkowski RE , Nance AE , Anderka M , Fox DJ , Steele A , Copeland G , Romitti PA , Mai CT . Birth Defects Res A Clin Mol Teratol 2016 106 (11) 972-982 BACKGROUND: Congenital microcephaly has been linked to maternal Zika virus infection. However, ascertaining infants diagnosed with microcephaly can be challenging. METHODS: Thirty birth defects surveillance programs provided data on infants diagnosed with microcephaly born 2009 to 2013. The pooled prevalence of microcephaly per 10,000 live births was estimated overall and by maternal/infant characteristics. Variation in prevalence was examined across case finding methods. Nine programs provided data on head circumference and conditions potentially contributing to microcephaly. RESULTS: The pooled prevalence of microcephaly was 8.7 per 10,000 live births. Median prevalence (per 10,000 live births) was similar among programs using active (6.7) and passive (6.6) methods; the interdecile range of prevalence estimates was wider among programs using passive methods for all race/ethnicity categories except Hispanic. Prevalence (per 10,000 live births) was lowest among non-Hispanic Whites (6.5) and highest among non-Hispanic Blacks and Hispanics (11.2 and 11.9, respectively); estimates followed a U-shaped distribution by maternal age with the highest prevalence among mothers <20 years (11.5) and ≥40 years (13.2). For gestational age and birth weight, the highest prevalence was among infants <32 weeks gestation and infants <1500 gm. Case definitions varied; 41.8% of cases had an HC ≥ the 10th percentile for sex and gestational age. CONCLUSION: Differences in methods, population distribution of maternal/infant characteristics, and case definitions for microcephaly can contribute to the wide range of observed prevalence estimates across individual birth defects surveillance programs. Addressing these factors in the setting of Zika virus infection can improve the quality of prevalence estimates. |
Role of maternal occupational physical activity and psychosocial stressors on adverse birth outcomes
Lee LJ , Symanski E , Lupo PJ , Tinker SC , Razzaghi H , Chan W , Hoyt AT , Canfield MA . Occup Environ Med 2016 74 (3) 192-199. Objectives We examined the association of an array of estimated maternal occupational physical activities and psychosocial stressors during pregnancy with odds for preterm birth (PTB) and small-for-gestational age (SGA). Methods Data for infants born without major birth defects delivered from 1997 to 2009 whose mothers reported working at least 1 month during pregnancy were obtained from the National Birth Defects Prevention Study. We linked occupational codes to the US Department of Labor's Occupational Information Network, which provides estimates of exposure for multiple domains of physical activity and psychosocial stressors by occupational categories. We conducted factor analysis using principal components extraction with 17 occupational activities and calculated factor scores. ORs for PTB and SGA across quartiles of factor scores in each trimester were computed using logistic regression. Results Factor analysis grouped occupational domains into 4 groups based on factor loadings. These groups were 'occupational physical activity', 'interpersonal stressor', 'automated work' and 'job responsibility'. High levels of 'occupational physical activity' were significantly associated with SGA (adjusted OR (AOR) for highest quartile compared with lowest quartile of factor score: 1.36; 95% CIs 1.02 to 1.82; p for trend=0.001) and were also positively associated with PTB (AOR: 1.24; 95% CI 0.93 to 1.64; p for trend=0.01). No clear results were observed across domains of psychosocial stressors. Conclusions Our findings expand understanding of associations between occupational physical activity and psychosocial stressors and PTB and SGA and suggest that additional research is needed to further examine these relationships. |
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