Habitat loss and forest fragmentation are often linked to increased pathogen transmission, but the extent to which habitat isolation and landscape connectivity affect disease dynamics through movement of disease vectors and reservoir hosts has not been well examined. Tick-borne diseases are the most prevalent vector-borne diseases in the United States and on the West Coast, Ixodes pacificus is one of the most epidemiologically important vectors. We investigated the impacts of habitat fragmentation on pathogens transmitted by I. pacificus and sought to disentangle the effects of wildlife communities and landscape metrics predictive of pathogen diversity, prevalence and distribution. We collected pathogen data for four co-occurring bacteria transmitted by I. pacificus and measured wildlife parameters. We also used spatial data and cost-distance analysis integrating expert opinions to assess landscape metrics of habitat fragmentation. We found that landscape metrics were significant predictors of tick density and pathogen prevalence. However, wildlife variables were essential when predicting the prevalence and distribution of pathogens reliant on wildlife reservoir hosts for maintenance. We found that landscape structure was an informative predictor of tick-borne pathogen richness in an urban matrix. Our work highlights the implications of large-scale land management on human disease risk.

BACKGROUND: HIV drug resistance (HIVDR) can reduce the effectiveness of antiretroviral (ARV) drugs in preventing morbidity and mortality, limit options for treatment, and prevention. Our study aimed to assess HIV-1 subtypes and HIVDR among key populations in HIV Sentinel Surveillance Plus Behavior (HSS+) in 2018 and 2020. METHODS: One-stage venue-based cluster sampling was used to recruit participants at hotspots identified for Men who have sex with men (MSM) in 7 provinces and SEM females and female sex worker (FSW) in 13 provinces. Participants completed a standard questionnaire about risk and preventive behaviors, and ART history, and provided intravenous blood for HIV testing. HIVDR testing was conducted on HIV-positive samples with VL >1,000 copies/ml. RESULTS: A total of 185/435 (42.5%) HIV-positive samples had viral load ≥1,000 copies/ml, of which 130/136 from MSM and 26/49 from FSW, were successfully sequenced. Six HIV-1 subtypes were detected (CRF01_AE, A, CRF07/08_BC, B, C, CRF25_cpx), with CRF01_AE (82.7%, 129/156) the most common. Drug resistance mutations were detected in 16.7% of participants overall (26/156), in 15.4% (20/130) of MSM, and in 23.1% (6/26) of FSW. Mutations associated with resistance to NNRTI were the most frequently detected (73.1%, 19/26). The high level of resistance was presented in NNRTI and NRTI classes. There are 10 major resistance mutations detected with NRTI (M184VI-25.0%, K65KR-50.0%, Y115F-25%), NNRTI (K103N-21.1%, E138A-10.5%, V106M-5.3%, K101E-5.3%, G190A-5.3%) PI (L33F-40.0%, M46L-20.0%). CONCLUSIONS: Vietnam's HSS+ system identified an emerging strain of HIV-1 and mutations associated with resistance to multiple drug classes among MSM and FSW.

Background: The U.S. Public Health Service and the Institute of Medicine recommend that all women capable of becoming pregnant consume 400 μg of folic acid daily to help prevent neural tube defects (NTDs). Hispanic women are at higher risk of having babies with NTDs than non-Hispanic White women. This study assessed multivitamin (MV) use, a main source of folic acid, among Hispanic women of reproductive age using a survey of solely U.S. Hispanic adults. Materials and Methods: MV use was assessed as part of Porter Novelli's Estilos survey, fielded annually through the largest online U.S. Hispanic panel, Offerwise's QueOpinas. During the study period of 2013-2022, 9,999 surveys were completed; selection was weighted to match the U.S. Census American Community Survey proportions. Log-binomial regression models were applied to estimate MV use trends by age groups, acculturation levels, and pregnancy intention. Results: Among 3,700 Hispanic women of reproductive age, overall no MV use increased from 39.3% in 2013 to 54.7% in 2022 (p for trend <0.0001), especially among Hispanic women aged 18-34 years and those classified as acculturated. Among women planning to get pregnant, daily MV use was 31.1% in 2013 compared with 18.7% in 2020-2022 (p = 0.04). Conclusions: Given the increase in no MV use among Hispanic women of reproductive age, targeted interventions may help reach at-risk groups for NTDs prevention.

BACKGROUND: Birth defects affect 1 in 33 infants in the United States and are a leading cause of infant mortality. Birth defects surveillance is crucial for informing public health action. The Massachusetts Birth Defects Monitoring Program (MBDMP) began collecting other pregnancy losses (OPLs) in 2011, including miscarriages (<20 weeks gestation) or elective terminations (any gestational age), in addition to live births and stillbirths (≥20 weeks gestation). We describe programmatic changes for adding OPLs and their impact on prevalence estimates. METHODS: Using population-based, statewide, data from the MBDMP (2012-2020), we assessed prevalence per 10,000 live births and 95% confidence intervals (CIs) with and without OPLs overall and for specific birth defects by time period, maternal age, and race/ethnicity. RESULTS: Including OPLs required amending a state statute and promulgating regulations, new data sources, and additional data processing, cleaning, and verification. Overall prevalence with OPLs increased from 257.4 (95% CI: 253.5-261.4) to 333.9 (95% CI: 329.4-338.4) per 10,000; increases were observed in all time periods, age, and race/ethnicity groups. After including OPLs, the prevalence increased for neural tube defects [3.2 (2.7-3.6) to 8.3 (7.6-9.0)], and trisomies 13 [0.5 (0.3-0.7) to 4.1 (3.6-4.6)], 18 [1.5 (1.2-1.9) to 8.2 (7.5-8.9)], and 21 [12.3 (11.4-13.2) to 28.9 (27.6-30.2)]. Cardiovascular defects increased slightly, while prevalence of eye/ear, respiratory, and gastrointestinal defects remained similar. CONCLUSIONS: Adding OPLs required substantial programmatic efforts and resulted in more complete case ascertainment, particularly for certain birth defects. More complete case ascertainment will allow for improved research, screening, and resource allocation.

Delays in illness recognition, healthcare seeking, and in the provision of appropriate clinical care are common in resource-limited settings. Our objective was to determine the frequency of delays in the "Three Delays-in-Healthcare", and factors associated with delays, among deceased infants and children in seven countries with high childhood mortality. We conducted a retrospective, descriptive study using data from verbal autopsies and medical records for infants and children aged 1-59 months who died between December 2016 and February 2022 in six sites in sub-Saharan Africa and one in South Asia (Bangladesh) and were enrolled in Child Health and Mortality Prevention Surveillance (CHAMPS). Delays in 1) illness recognition in the home/decision to seek care, 2) transportation to healthcare facilities, and 3) the receipt of clinical care in healthcare facilities were categorized according to the "Three Delays-in-Healthcare". Comparisons in factors associated with delays were made using Chi-square testing. Information was available for 1,326 deaths among infants and under 5 children. The majority had at least one identified delay (n = 854, 64%). Waiting >72 hours after illness recognition to seek health care (n = 422, 32%) was the most common delay. Challenges in obtaining transportation occurred infrequently when seeking care (n = 51, 4%). In healthcare facilities, prescribed medications were sometimes unavailable (n = 102, 8%). Deceased children aged 12-59 months experienced more delay than infants aged 1-11 months (68% vs. 61%, P = 0.018). Delays in seeking clinical care were common among deceased infants and children. Additional study to assess the frequency of delays in seeking clinical care and its provision among children who survive is warranted.

BACKGROUND: Diarrheal diseases continue to contribute significantly to morbidity and mortality in infants and young children in developing countries. There is an urgent need to better understand the contributions of novel, potentially uncultured, diarrheal pathogens to severe diarrheal disease, as well as distortions in normal gut microbiota composition that might facilitate severe disease. RESULTS: We use high throughput 16S rRNA gene sequencing to compare fecal microbiota composition in children under five years of age who have been diagnosed with moderate to severe diarrhea (MSD) with the microbiota from diarrhea-free controls. Our study includes 992 children from four low-income countries in West and East Africa, and Southeast Asia. Known pathogens, as well as bacteria currently not considered as important diarrhea-causing pathogens, are positively associated with MSD, and these include Escherichia/Shigella, and Granulicatella species, and Streptococcus mitis/pneumoniae groups. In both cases and controls, there tend to be distinct negative correlations between facultative anaerobic lineages and obligate anaerobic lineages. Overall genus-level microbiota composition exhibit a shift in controls from low to high levels of Prevotella and in MSD cases from high to low levels of Escherichia/Shigella in younger versus older children; however, there was significant variation among many genera by both site and age. CONCLUSIONS: Our findings expand the current understanding of microbiota-associated diarrhea pathogenicity in young children from developing countries. Our findings are necessarily based on correlative analyses and must be further validated through epidemiological and molecular techniques.

Rotavirus (RV), norovirus (NoV), sapovirus (SaV), and human astrovirus (HAstV) are the most common viral causes of gastroenteritis in children worldwide. From 2016 to 2021, we conducted a cross-sectional descriptive study to determine the prevalence of these viruses in hospitalized children under five years old in Nam Dinh and Thua Thien Hue provinces in Vietnam during the pilot introduction of the RV vaccine, Rotavin-M1 (POLYVAC, Hanoi, Vietnam). We randomly selected 2317/6718 (34%) acute diarrheal samples from children <5 years of age enrolled at seven sentinel hospitals from December 2016 to May 2021; this period included one year surveillance pre-vaccination from December 2016 to November 2017. An ELISA kit (Premier Rotaclone(®), Meridian Bioscience, Inc., Cincinnati, OH, USA) was used to detect RV, and two multiplex real-time RT-PCR assays were used for the detection of NoV, SaV and HAstV. The prevalence of RV (single infection) was reduced from 41.6% to 22.7% (p < 0.0001) between pre- and post-vaccination periods, while the single NoV infection prevalence more than doubled from 8.8% to 21.8% (p < 0.0001). The SaV and HAstV prevalences slightly increased from 1.9% to 3.4% (p = 0.03) and 2.1% to 3.3% (p = 0.09), respectively, during the same period. Viral co-infections decreased from 7.2% to 6.0% (p = 0.24), mainly due to a reduction in RV infection. Among the genotypeable samples, NoV GII.4, SaV GI.1, and HAstV-1 were the dominant types, representing 57.3%, 32.1%, and 55.0% among the individual viral groups, respectively. As the prevalence of RV decreases following the national RV vaccine introduction in Vietnam, other viral pathogens account for a larger proportion of the remaining diarrhea burden and require continuing close monitoring.

BACKGROUND: Limited diagnostic capabilities, resources and health worker skills have deterred the advancement of birth defects surveillance systems in most low- and middle-income countries (LMICs). Empowering health workers to identify and diagnose major external birth defects (BDs) is crucial to establishing effective hospital-based BD surveillance. Makerere University-Johns Hopkins University (MU-JHU) Research Collaboration BD Surveillance System consists of three diagnostic levels: (1) surveillance midwives, (2) MU-JHU clinical team, and (3) U.S. Centers for Disease Control and Prevention (CDC) birth defects subject matter experts (SMEs) who provide confirmatory diagnosis. The diagnostic concordance of major external BDs by surveillance midwives or MU-JHU clinical team with CDC birth defects SMEs were estimated. METHODS: Study staff went through a series of trainings, including birth defects identification and confirmation, before surveillance activities were implemented. To assess the diagnostic concordance, we analyzed surveillance data from 2015 to 2021 for major external BDs: anencephaly, iniencephaly, encephalocele, spina bifida, craniorachischisis, microcephaly, anophthalmia/microphthalmia, anotia/microtia, cleft palate alone, cleft lip alone, cleft lip with cleft palate, imperforate anus, hypospadias, talipes equinovarus, limb reduction, gastroschisis, and omphalocele. Positive predictive value (PPV) as the proportion of BDs diagnosed by surveillance midwives or MU-JHU clinical team that were confirmed by CDC birth defects SMEs was computed. PPVs between 2015 and 2018 and 2019-2021 were compared to assess the accuracy of case diagnosis over time. RESULTS: Of the 204,332 infants examined during 2015-2021, 870 infants had a BD. Among the 1,245 BDs identified, 1,232 (99.0%) were confirmed by CDC birth defects SMEs. For surveillance midwives, PPV for 7 of 17 BDs was > 80%. For the MU-JHU clinical team, PPV for 13 of 17 BDs was > 80%. Among surveillance midwives, PPV improved significantly from 2015 to 2018 to 2019-2021, for microcephaly (+ 50.0%), cleft lip with cleft palate (+ 17.0%), imperforate anus (+ 30.0%), and talipes equinovarus (+ 10.8%). Improvements in PPV were also observed among MU-JHU clinical team; however, none were significant. CONCLUSION: The diagnostic accuracy of the midwives and clinical team increased, highlighting that BD surveillance, by front-line health care workers (midwives) in LMICs is possible when midwives receive comprehensive training, technical support, funding and continuous professional development.

Background Influenza viruses pose significant disease burdens through annual seasonal outbreaks and unpredictable pandemics. Existing influenza surveillance programs have relied heavily on reporting of medically attended influenza (MAI). Continuously monitoring cause-specific school absenteeism may identify local acceleration of seasonal influenza activity. The Oregon Child Absenteeism Due to Respiratory Disease Study (ORCHARDS; Oregon, WI) implements daily school-based monitoring of influenza-like illness–specific student absenteeism (a-ILI) in pre-kindergarten through grade 12 schools and assesses this approach for early detection of accelerated influenza and other respiratory pathogen transmission in schools and surrounding communities.Methods Starting in September 2014, ORCHARDS combined automated reporting of daily absenteeism within 6 schools and home visits to school children with acute respiratory infections (ARI). Demographic, epidemiological, and symptom data are collected along with respiratory specimens. Specimens are tested for influenza and other respiratory viruses. Household members can opt into a supplementary household transmission study. Community comparisons are possible using a pre-existing, long-standing, and highly effective influenza surveillance program, based on MAI at 5 primary care clinics in the same geographical area.Results Over the first 5 years, a-ILI occurred on 6,634 (0.20%) of 3,260,461 student school days. Viral pathogens were detected in 64.5% of the 1,728 children with ARI who received a home visit. Influenza was the most commonly detected virus, noted in 23.3% of ill students. Influenza (p&lt;0.001) and adenovirus (P=0.004) were significantly associated with a-ILI.Conclusion ORCHARDS uses a community-based design to detect influenza trends over multiple seasons and to evaluate the utility of absenteeism for early detection of accelerated influenza and other respiratory pathogen transmission in schools and surrounding communities. Initial findings suggest the study design is succeeding in collecting appropriate data to achieve study objectives.Competing Interest StatementDr. Jonathan Temte has received financial and material support from Quidel Corporation. Dr. John Tamerius and Quidel Corporation have generously supplied RIDT analyzers and tests.Funding StatementDr. John Tamerius and Quidel Corporation have generously supplied RIDT analyzers and tests. This study has been supported by CDC through the cooperative agreement # 5U01CK000542-02-00. The findings and conclusions in this study are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:All components of this proposed study were reviewed and approved by the Human Subjects Committees of the Education Research IRB - Social and Behavioral Sciences IRB (initial approval on September 4, 2013) and the University of Wisconsin Health Sciences-IRB (initial approval on December 5, 2013, with additional approvals as the protocol expanded and modified). The study is in full compliance with the Health Insurance Portability and Accountability Act of 1996 (HIPAA), FERPA, and all other federally mandated human subjects regulations. The US Office of Management and Budget has approved all forms used in this study.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a s atement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesThe datasets generated and/or analyzed during the current study are not publicly available because the study is ongoing, but may be available from the corresponding author on reasonable request.4k4-year-old pre-kindergartena-Iabsenteeism due to illnessa-ILIabsenteeism due to influenza-like illnessa-TOTall-cause absenteeismARIacute respiratory infectionCDCCenters for Disease Control and PreventionCoVcoefficient of variationFERPAFamily Educational Rights and Privacy ActFluinfluenzaFDAFood and Drug AdministrationHIPPAHealth Insurance Portability and Accountability ActILIinfluenza-like illnessITinformation technologyIRBinstitutional review boardMAImedically attended influenzaNPnasopharyngealORCHARDSOregon Child Absenteeism Due to Respiratory Disease StudyOSDOregon School DistrictOPoropharyngealPCRpolymerase chain reactionRIDTrapid influenza diagnostic testRedCapResearch Electronic Data CaptureRPPrespiratory pathogen panelR/Erhinovirus/enterovirusRPhuman RNAse PSISschool information systemW-IISPWisconsin Influenza Incidence Surveillance ProjectWIRWisconsin Immunization RegistryWSLHWisconsin State Laboratory of HygieneVTMviral transport medium

Background Schools are primary venues of influenza amplification with secondary spread to communities. We assessed K-12 student absenteeism monitoring as a means for early detection of influenza activity in the community.Materials and Methods Between September 2014 and March 2020, we conducted a prospective observational study of all-cause (a-TOT), illness-associated (a-I), and influenza-like illness–associated (a-ILI) absenteeism within the Oregon School District (OSD), Dane County, Wisconsin. Absenteeism was reported through the electronic student information system. Students were visited at home where pharyngeal specimens were collected for influenza RT-PCR testing. Surveillance of medically-attended laboratory-confirmed influenza (MAI) occurred in five primary care clinics in and adjoining OSD. Poisson general additive log linear regression models of daily counts of absenteeism and MAI were compared using correlation analysis.Findings Influenza was detected in 723 of 2,378 visited students, and in 1,327 of 4,903 MAI patients. Over six influenza seasons, a-ILI was significantly correlated with MAI in the community (r = 0.57; 95% CI: 0.53—0.63) with a one-day lead time and a-I was significantly correlated with MAI in the community (r = 0.49; 0.44-0.54) with a 10-day lead time, while a-TOT performed poorly (r = 0.27; 0.21—0.33), following MAI by six days.Discussion Surveillance using cause-specific absenteeism was feasible and performed well over a study period marked by diverse presentations of seasonal influenza. Monitoring a-I and a-ILI can provide early warning of seasonal influenza in time for community mitigation efforts.Competing Interest StatementDr. Jonathan Temte has received financial and material support from Quidel Corporation. Dr. John Tamerius and Quidel Corporation have generously supplied RIDT analyzers and tests.Funding StatementThis study has been supported by CDC through the cooperative agreement # 5U01CK000542-02-00. The findings and conclusions in this study are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:All components of this proposed study were reviewed and approved by the Human Subjects Committees of the Education and Social/Behavioral Sciences IRB (initial approval on September 4, 2013) and the University of Wisconsin Health Sciences-IRB (initial approval on December 5, 2013, with additional approvals as the protocol expanded and modified). The study is in full compliance with the Health Insurance Portability and Accountability Act of 1996 (HIPAA), FERPA, and all other federally mandated human subjects regulations. The US Office of Management and Budget has approved all forms used in this study.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesThe datasets generated and/or analyzed during the current study are not publicly available because the study is ongoing, but may be available from the corresponding author on reasonable request.

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.

World Birth Defects Day (WorldBDDay), observed annually on March 3, was launched in 2015 to advocate for public health surveillance, research, and prevention of birth defects, along with improved care and treatment for affected individuals. Following its fifth observance in 2019, we assessed WorldBDDay by analyzing: (a) engagement and content of over 2000 WorldBDDay posts on Facebook, Twitter, and Instagram; (b) interview responses from 9 WorldBDDay charter (founding) organizations on their perceptions of strengths and areas for improvement for WorldBDDay; (c) survey responses from 61 WorldBDDay 2019 partner (participating) organizations on their WorldBDDay 2019 activities; and (d) post-2019 social media engagement. Most social media posts (60%) occurred from organizations using Twitter (80% vs. 14% for Instagram and 6% for Facebook), although posts from individuals had higher levels of engagement (e.g., likes and comments). The highest engagement occurred for posts focused on general awareness, prevention, or events. Charter organizations reported the need for existing and new partner engagement, including a designated WorldBDDay contact for regular communication and coordination of activities and prepared prevention-focused messaging. Partner organizations reported using the WorldBDDay toolkit, especially key messages and social media tips, and suggested expanding the toolkit with relevant resources. Post-2019 Twitter engagement was lower than 2019 WorldBDDay (peak event) but showed similar reach to WorldBDDay events prior to 2019. Our assessment identified WorldBDDay health observance events as an important tool to support knowledge dissemination and global community engagement around birth defects. Moving forward, engagement with more individuals and organizations may improve the reach of WorldBDDay.

Background: Half of diarrhea hospitalizations in children aged <5 years in Vietnam are due to rotavirus. Following introduction of a locally developed and licensed oral rotavirus vaccine, Rotavin-M1, into the routine immunization program in two Vietnamese provinces, Nam Dinh and TT Hue, we describe changes in rotavirus positivity among children hospitalized for diarrhea and calculate vaccine effectiveness against moderate-to-severe rotavirus hospitalizations. Methods: Active rotavirus surveillance among children <5 years began in December 2016 at sentinel hospitals in districts where rotavirus vaccine was introduced in December 2017. To estimate reductions in rotavirus detection, we calculated risk ratios comparing rotavirus positivity pre- and post-vaccine introduction. We used a test-negative case–control design to calculate vaccine effectiveness. Findings: From December 2016 to May 2021, 7228 children <5 years hospitalized for diarrhea were enrolled. Following introduction, Rotavin-M1 coverage was 77% (1066/1377) in Nam Dinh and 42% (203/489) in TT Hue. In Nam Dinh, rotavirus positivity among children <5 years significantly declined by 40.6% (95% CI: 34.8%–45.8%) during the three-year post-vaccine introduction period. In TT Hue, no change in rotavirus positivity was observed. Among children aged 6–23 months, a 2-dose series of Rotavin-M1 was 57% (95% CI: 39%–70%) effective against moderate-to-severe rotavirus hospitalizations. Interpretation: Higher vaccination coverage in Nam Dinh than TT Hue likely contributed to substantial declines in rotavirus positivity observed in Nam Dinh following rotavirus vaccine introduction. Robust vaccine effectiveness was observed through the second year of life. National rotavirus vaccine introduction with high coverage may have substantial impact on reducing rotavirus disease burden in Vietnam. Funding: Bill and Melinda Gates Foundation. © 2023

following which a substantial decline in neural tube defects at birth occurred. Studies also have suggested that lesion levels in cases of spina bifida are directly affected by folic acid fortification. Locations of such lesions contribute to outcome and prognosis of the condition. When compared with sacral and lower lumbar lesions, the greatest risks of disability and mortality are associated with cervical, thoracic, and high lumbar lesions. Individuals with thoracic or high lumbar lesions require a wheelchair and orthosis in adulthood for ambulation 70% to 99% of the time. As lesion levels therefore determine function and overall quality of life, assessment of whether folic acid fortification significantly impacts lesion levels is important. This study aimed to examine patterns of lesion levels in spina bifida following mandatory folic acid fortification in the United States. | | A call was issued by the National Birth Defects Prevention Network for State Birth Defects Programs' spina bifida lesion data before and after fortification mandate. To be eligible, programs needed to provide verbatim medical record text descriptions of spina bifida diagnoses. The 6 participating programs were from the states of Arizona, California (covering 8 counties), Oklahoma, South Carolina, Utah, and metropolitan Atlanta (Georgia). Birth years examined included the prefortification years of 1992–1996 and the postfortification period of 1999–2016. Central processing and analysis occurred as each program provided case-level data (deidentified) based on the exclusion/inclusion criteria to the Centers for Disease Control and Prevention. Medical and record text description of the spina bifida diagnosis and codes were the basis of case information, using the International Classification of Diseases, Ninth Edition, Clinical Modification or the Centers for Disease Control and Prevention and Prevention/British Pediatric Association coding system. Types of spina bifida included in the study were spinal rachischisis, myelomeningocele/meningomyelocele, meningocele, and spina bifida not otherwise specified. Cases excluded were cranial lesions, lipomyelomeningocele/lipomeningomyelocele, dysraphism related to split cord malformations, and spina bifida occulta. | | Lesion-level information was provided based on the highest lesion using nonradiographic clinical assessment. Classification of severe upper-level lesions included cervical or thoracic lesion-level cases, whereas lower-level lesions included cases with lumbar or sacral. The study defined open lesion as leaking spinal fluid or membrane covered only, whereas closed lesions were defined as having intact-skin covering and lacking fluid leakage. Spina bifida cases were considered isolated when no other anomalies related to the primary cause of abnormal neural tube closure were present (nor were secondary to the neurologic complications caused by it). Examining associations between fortification period and the outcomes (lesion level and spina bifida) occurred using the generalized estimating approach to logistic (case severity analyses) and log-linear (PR analyses) regression, which accounted for clustering of cases by state. | | From a total of 7,816,062 live births, 2593 cases of spina bifida met the case inclusion criteria. Overall, 573 cases were included in the prefortification period (birth prevalence of 4.07 per 10,000 live births), and 2020 cases were included in the postfortification period (birth prevalence of 3.15 per 10,000 live births). Overall, 80.2% of cases resulted in live births, and most cases of spina bifida involved lower-level lesions (81.3%). Most lesions were lumbar, and the proportions prefortification and postfortification were 61.4% and 72.0%, respectively, with a higher proportion of lumbar lesions seen in the postfortification period. The odds of upper-level to lower-level lesions decreased by 70% after fortification. The spina bifida live birth prevalence decreased significantly and remained consistently low throughout the early, mid, and recent postfortification periods. The study found a 72% decrease overall in prevalence of severe, upper-level lesions following mandatory folic acid fortification in the United States. | | The limitations of the study include the shortcomings of relying on diagnostic codes, the difficulty of coding lesion level using the International Classification of Diseases, Ninth Edition, Clinical Modification coding scheme, the lack of recorded functional outcome for children in medical records (indirect indicators of severity), the lack of preconception and prenatal folic acid data, and the possible variation of case ascertainment within programs contributing studies. A major study strength is its potential to address additional important questions regarding epidemiology and spina bifida. The classification of spinal defects is complex, and this study adds to the limited distribution data that exist for prefortification and postfortification subtypes. | | The study concluded that the overall prevalence of severe upper-level lesions in spina bifida cases experienced a steep reduction following mandatory folic acid fortification institution within the United States, whereas no change in the prevalence of less severe lower-level lesions took place. Additional examinations are warranted to better understand the magnitude and mechanism of spina bifida severity in relation to folic acid intake.

OBJECTIVES: To examine the potential for bias in the estimate of under-5 mortality due to birth defects recently produced by the WHO and the Maternal and Child Epidemiology Estimation research group. DESIGN: Systematic analysis. METHODS: We examined the estimated number of under-5 deaths due to birth defects, the birth defect specific under-5 mortality rate, and the per cent of under-5 mortality due to birth defects, by geographic region, national income and under-5 mortality rate for three age groups from 2000 to 2019. RESULTS: The under-5 deaths per 1000 live births from birth defects fell from 3.4 (95% uncertainty interval (UI) 3.1-3.8) in 2000 to 2.9 (UI 2.6-3.3) in 2019. The per cent of all under-5 mortality attributable to birth defects increased from 4.6% (UI 4.1%-5.1%) in 2000 to 7.6% (UI 6.9%-8.6%) in 2019. There is significant variability in mortality due to birth defects by national income level. In 2019, the under-5 mortality rate due to birth defects was less in high-income countries than in low-income and middle-income countries, 1.3 (UI 1.2-1.3) and 3.0 (UI 2.8-3.4) per 1000 live births, respectively. These mortality rates correspond to 27.7% (UI 26.6%-28.8%) of all under-5 mortality in high-income countries being due to birth defects, and 7.4% (UI 6.7%-8.2%) in low-income and middle-income countries. CONCLUSIONS: While the under-5 mortality due to birth defects is declining, the per cent of under-5 mortality attributable to birth defects has increased, with significant variability across regions globally. The estimates in low-income and middle-income countries are likely underestimated due to the nature of the WHO estimates, which are based in part on verbal autopsy studies and should be taken as a minimum estimate. Given these limitations, comprehensive and systematic estimates of the mortality burden due to birth defects are needed to estimate the actual burden.

As authorities braced for the arrival of the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), infrastructure investments and government directives prompted action in central Viet Nam to establish capacity for genomic surveillance sequencing. From 17 November 2021 to 7 January 2022, the Pasteur Institute in Nha Trang sequenced 162 specimens from 98 150 confirmed SARS-CoV-2 cases in the region collected from 8 November to 31 December 2021. Of these, all 127 domestic cases were identified as the B.1.617.2 (Delta) variant, whereas 92% (32/35) of imported cases were identified as the B.1.1.529 (Omicron) variant, all among international flight passengers. Patients were successfully isolated, enabling health-care workers to prepare for additional cases. Most (78%) of the 32 Omicron cases were fully vaccinated, suggesting continued importance of public health and social measures to control the spread of new variants.

For three decades, the US Public Health Service has recommended that all persons capable of becoming pregnant consume 400 μg/day of folic acid (FA) to prevent neural tube defects (NTDs). The neural tube forms by 28 days after conception. Fortification can be an effective NTD prevention strategy in populations with limited access to folic acid foods and/or supplements. This review describes the status of mandatory FA fortification among countries that fortify (n = 71) and the research describing the impact of those programs on NTD rates (up to 78% reduction), blood folate concentrations [red blood cell folate concentrations increased ∼1.47-fold (95% CI, 1.27, 1.70) following fortification], and other health outcomes. Across settings, high-quality studies such as those with randomized exposures (e.g., randomized controlled trials, Mendelian randomization studies) are needed to elucidate interactions of FA with vitamin B(12) as well as expanded biomarker testing.

OBJECTIVE: To assess whether the severity of cases of spina bifida changed after mandatory folic acid fortification in the United States. STUDY DESIGN: Six active population-based birth defects programs provided data on cases of spina bifida for 1992-1996 (pre-fortification) and 1999-2016 (post-fortification); programs contributed varying years of data. Case information included both medical record verbatim text description of the spina bifida diagnosis and spina bifida codes (International Classification of Diseases, Clinical Modification, or a modified birth defects surveillance coding system). Comparing pre- with post-fortification periods, adjusted odds ratios (aOR) for case severity [upper-level (cervical, thoracic) to lower-level (lumbar, sacral) lesion cases] and prevalence ratios (PR) were estimated. RESULTS: A total of 2,593 cases of spina bifida (7,816,062 live births) met inclusion criteria, with 573 and 2,020 cases from the pre- and post-fortification periods respectively. Case severity decreased 70% (aOR: 0.30; 95% confidence interval [CI] 0.26, 0.35) between the fortification periods. The decrease was most pronounced for non-Hispanic white mothers. Overall spina bifida prevalence declined 23% (PR=0.77, 95% CI=0.71, 0.85), with similar reduction seen across early, mid, and recent post-fortification periods. A statistically significant decrease in upper-level lesions occurred in the post-fortification compared with pre-fortification periods (PR=0.28, 95% CI=0.22, 0.34), while prevalence of lower-level lesions remained relatively similar (PR: 0.94, 95% CI: 0.84, 1.05). CONCLUSIONS: Severity of cases of spina bifida decreased after mandatory folic acid fortification in the United States. Further examination is warranted to understand better the potential effect of folic acid on spina bifida severity.

BACKGROUND: Schools are primary venues of influenza amplification with secondary spread to communities. We assessed K-12 student absenteeism monitoring as a means for early detection of influenza activity in the community. MATERIALS AND METHODS: Between September 2014 and March 2020, we conducted a prospective observational study of all-cause (a-TOT), illness-associated (a-I), and influenza-like illness-associated (a-ILI) absenteeism within the Oregon School District (OSD), Dane County, Wisconsin. Absenteeism was reported through the electronic student information system. Students were visited at home where pharyngeal specimens were collected for influenza RT-PCR testing. Surveillance of medically-attended laboratory-confirmed influenza (MAI) occurred in five primary care clinics in and adjoining the OSD. Poisson general additive log linear regression models of daily counts of absenteeism and MAI were compared using correlation analysis. FINDINGS: Influenza was detected in 723 of 2,378 visited students, and in 1,327 of 4,903 MAI patients. Over six influenza seasons, a-ILI was significantly correlated with MAI in the community (r = 0.57; 95% CI: 0.53-0.63) with a one-day lead time and a-I was significantly correlated with MAI in the community (r = 0.49; 0.44-0.54) with a 10-day lead time, while a-TOT performed poorly (r = 0.27; 0.21-0.33), following MAI by six days. DISCUSSION: Surveillance using cause-specific absenteeism was feasible and performed well over a study period marked by diverse presentations of seasonal influenza. Monitoring a-I and a-ILI can provide early warning of seasonal influenza in time for community mitigation efforts.

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To examine the effects of folic acid supplementation, at various doses, on malaria susceptibility (risk of infection) and severity among people living in areas with various degrees of malaria endemicity. We will examine the interaction between folic acid supplements and antifolate antimalarial drugs. Specifically, we will aim to answer the following. Among uninfected people living in malaria endemic areas, who are taking or not taking antifolate antimalarials for malaria prophylaxis, does taking a folic acid-containing supplement increase susceptibility to or severity of malaria infection? Among people with malaria infection who are being treated with antifolate antimalarials, does folic acid supplementation increase the risk of treatment failure?. Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

BACKGROUND: Expanding access to and use of medication for opioid use disorder (MOUD) is a key component of overdose prevention. An important barrier to the uptake of MOUD is exposure to inaccurate and potentially harmful health misinformation on social media or web-based forums where individuals commonly seek information. There is a significant need to devise computational techniques to describe the prevalence of web-based health misinformation related to MOUD to facilitate mitigation efforts. OBJECTIVE: By adopting a multidisciplinary, mixed methods strategy, this paper aims to present machine learning and natural language analysis approaches to identify the characteristics and prevalence of web-based misinformation related to MOUD to inform future prevention, treatment, and response efforts. METHODS: The team harnessed public social media posts and comments in the English language from Twitter (6,365,245 posts), YouTube (99,386 posts), Reddit (13,483,419 posts), and Drugs-Forum (5549 posts). Leveraging public health expert annotations on a sample of 2400 of these social media posts that were found to be semantically most similar to a variety of prevailing opioid use disorder-related myths based on representational learning, the team developed a supervised machine learning classifier. This classifier identified whether a post's language promoted one of the leading myths challenging addiction treatment: that the use of agonist therapy for MOUD is simply replacing one drug with another. Platform-level prevalence was calculated thereafter by machine labeling all unannotated posts with the classifier and noting the proportion of myth-indicative posts over all posts. RESULTS: Our results demonstrate promise in identifying social media postings that center on treatment myths about opioid use disorder with an accuracy of 91% and an area under the curve of 0.9, including how these discussions vary across platforms in terms of prevalence and linguistic characteristics, with the lowest prevalence on web-based health communities such as Reddit and Drugs-Forum and the highest on Twitter. Specifically, the prevalence of the stated MOUD myth ranged from 0.4% on web-based health communities to 0.9% on Twitter. CONCLUSIONS: This work provides one of the first large-scale assessments of a key MOUD-related myth across multiple social media platforms and highlights the feasibility and importance of ongoing assessment of health misinformation related to addiction treatment.

BACKGROUND: Influenza viruses pose significant disease burdens through seasonal outbreaks and unpredictable pandemics. Existing surveillance programs rely heavily on reporting of medically attended influenza (MAI). Continuously monitoring cause-specific school absenteeism may identify local acceleration of seasonal influenza activity. The Oregon Child Absenteeism Due to Respiratory Disease Study (ORCHARDS; Oregon, WI) implements daily school-based monitoring of influenza-like illness-specific student absenteeism (a-ILI) in kindergarten through Grade 12 schools and assesses this approach for early detection of accelerated influenza and other respiratory pathogen transmission in schools and surrounding communities. METHODS: Starting in September 2014, ORCHARDS combines automated reporting of daily absenteeism within six schools and home visits to school children with acute respiratory infection (ARI). Demographic, epidemiological, and symptom data are collected along with respiratory specimens. Specimens are tested for influenza and other respiratory viruses. Household members can opt into a supplementary household transmission study. Community comparisons are possible using a pre-existing and highly effective influenza surveillance program, based on MAI at five family medicine clinics in the same geographical area. RESULTS: Over the first 5 years, a-ILI occurred on 6634 (0.20%) of 3,260,461 student school days. Viral pathogens were detected in 64.5% of 1728 children with ARI who received a home visit. Influenza was the most commonly detected virus, noted in 23.3% of ill students. CONCLUSION: ORCHARDS uses a community-based design to detect influenza trends over multiple seasons and to evaluate the utility of absenteeism for early detection of accelerated influenza and other respiratory pathogen transmission in schools and surrounding communities.

Influenza burden estimates are essential to informing prevention and control policies. To complement recent influenza vaccine production capacity in Vietnam, we used acute respiratory infection (ARI) hospitalization data, severe acute respiratory infection (SARI) surveillance data, and provincial population data from 4 provinces representing Vietnam's major regions during 2014-2016 to calculate provincial and national influenza-associated ARI and SARI hospitalization rates. We determined the proportion of ARI admissions meeting the World Health Organization SARI case definition through medical record review. The mean influenza-associated hospitalization rates per 100,000 population were 218 (95% uncertainty interval [UI] 197-238) for ARI and 134 (95% UI 119-149) for SARI. Influenza-associated SARI hospitalization rates per 100,000 population were highest among children <5 years of age (1,123; 95% UI 946-1,301) and adults >65 years of age (207; 95% UI 186-227), underscoring the need for prevention and control measures, such as vaccination, in these at-risk populations.

The drivers and patterns of zoonotic virus emergence in the human population are poorly understood. The mosquito Aedes aegypti is a major arbovirus vector native to Africa that invaded most of the world's tropical belt over the past four centuries, after the evolution of a "domestic" form that specialized in biting humans and breeding in water storage containers. Here, we show that human specialization and subsequent spread of A. aegypti out of Africa were accompanied by an increase in its intrinsic ability to acquire and transmit the emerging human pathogen Zika virus. Thus, the recent evolution and global expansion of A. aegypti promoted arbovirus emergence not solely through increased vector-host contact but also as a result of enhanced vector susceptibility.

INTRODUCTION: Birth defects are common, costly, and contribute substantially to infant mortality. The South Carolina Birth Defects Program (SCBDP) employs active population-based surveillance to monitor major birth defects statewide. We evaluated SCBDP's system attributes using published CDC guidelines. METHODS: To determine timeliness, completeness, and accuracy of birth defects information, we examined SCBDP's reports, program and education materials, advisory group meeting minutes, and strategic plan. We also met with program staff and stakeholders (n = 10) to discuss program goals and data utilization. We calculated the percentage of birth defects cases found 6 months after a birth cohort year for 2016-2018. RESULTS: SCBDP identifies 900-1,200 birth defects cases for a birth population of approximately 55,000 live births annually through active case reviews. SCBDP uses trained medical staff to abstract detailed information from maternal and infant medical records; SCBDP also has established auto-linkage with state vital statistics to capture demographic and birth data. SCBDP is timely and captures 97.1% (range 96.7-97.6%) of birth defects cases within 6 months after the birth cohort year closes. Active case identification using medical records as the primary data source improves quality assurance and completeness, while prepopulating demographic information improves timeliness. CONCLUSIONS: Given that birth defects significantly contribute to infant morbidity and mortality, monitoring these conditions is important to understand their impact on communities and to drive public health actions. SCBDP active surveillance and rigorous data quality practices provide the program with timely, complete, and accurate birth defects data.

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.

RATIONALE & OBJECTIVE: Contaminated water and other fluids are increasingly recognized to be associated with health care-associated infections. We investigated an outbreak of Gram-negative bloodstream infections at 3 outpatient hemodialysis facilities. STUDY DESIGN: Matched case-control investigations. SETTING & PARTICIPANTS: Patients who received hemodialysis at Facility A, B, or C from July 2015 to November 2016. EXPOSURES: Infection control practices, sources of water, dialyzer reuse, injection medication handling, dialysis circuit priming, water and dialysate test findings, environmental reservoirs such as wall boxes, vascular access care practices, pulsed-field gel electrophoresis, and whole-genome sequencing of bacterial isolates. OUTCOMES: Cases were defined by a positive blood culture for any Gram-negative bacteria drawn July 1, 2015 to November 30, 2016 from a patient who had received hemodialysis at Facility A, B, or C. ANALYTICAL APPROACH: Exposures in cases and controls were compared using matched univariate conditional logistic regression. RESULTS: 58 cases of Gram-negative bloodstream infection occurred; 48 (83%) required hospitalization. The predominant organisms were Serratia marcescens (n=21) and Pseudomonas aeruginosa (n=12). Compared with controls, cases had higher odds of using a central venous catheter for dialysis (matched odds ratio, 54.32; lower bound of the 95% CI, 12.19). Facility staff reported pooling and regurgitation of waste fluid at recessed wall boxes that house connections for dialysate components and the effluent drain within dialysis treatment stations. Environmental samples yielded S marcescens and P aeruginosa from wall boxes. S marcescens isolated from wall boxes and case-patients from the same facilities were closely related by pulsed-field gel electrophoresis and whole-genome sequencing. We identified opportunities for health care workers' hands to contaminate central venous catheters with contaminated fluid from the wall boxes. LIMITATIONS: Limited patient isolates for testing, on-site investigation occurred after peak of infections. CONCLUSIONS: This large outbreak was linked to wall boxes, a previously undescribed source of contaminated fluid and biofilms in the immediate patient care environment.

OBJECTIVES: We investigated differences in prevalence of major birth defects by maternal nativity within racial/ethnic groups for 27 major birth defects. METHODS: Data from 11 population-based birth defects surveillance systems in the United States including almost 13 million live births (approximately a third of U.S. births) during 1999-2007 were pooled. We calculated prevalence estimates for each birth defect for five racial/ethnic groups. Using Poisson regression, crude and adjusted prevalence ratios (aPRs) were also calculated using births to US-born mothers as the referent group in each racial/ethnic group. RESULTS: Approximately 20% of case mothers and 26% of all mothers were foreign-born. Elevated aPRs for infants with foreign-born mothers were found for spina bifida and trisomy 13, 18, and 21, while lower prevalence patterns were found for pyloric stenosis, gastroschisis, and hypospadias. CONCLUSIONS: This study demonstrates that birth defects prevalence varies by nativity within race/ethnic groups, with elevated prevalence ratios for some specific conditions and lower prevalence for others. More detailed analyses focusing on a broader range of maternal behaviors and characteristics are required to fully understand the implications of our findings.

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.

BACKGROUND: Higher prevalence of selected birth defects has been reported among American Indian/Alaska Native (AI/AN) newborns. We examine whether known risk factors for birth defects explain the higher prevalence observed for selected birth defects among this population. METHODS: Data from 12 population-based birth defects surveillance systems, covering a birth population of 11 million from 1999 to 2007, were used to examine prevalence of birth defects that have previously been reported to have elevated prevalence among AI/ANs. Prevalence ratios (PRs) were calculated for non-Hispanic AI/ANs and any AI/ANs (regardless of Hispanic ethnicity), adjusting for maternal age, education, diabetes, and smoking, as well as type of case-finding ascertainment surveillance system. RESULTS: After adjustment, the birth prevalence of two of seven birth defects remained significantly elevated among AI/ANs compared to non-Hispanic whites (NHWs): anotia/microtia was almost threefold higher, and cleft lip +/- cleft palate was almost 70% higher compared to NHWs. Excluding AI/AN subjects who were also Hispanic had only a negligible impact on adjusted PRs. CONCLUSIONS: Additional covariates accounted for some of the elevated birth defect prevalences among AI/ANs compared to NHWs. Exclusion of Hispanic ethnicity from the AI/AN category had little impact on birth defects prevalences in AI/ANs. NHWs serve as a viable comparison group for analysis. Birth defects among AI/ANs require additional scrutiny to identify modifiable risk and protective factors.