National and regional population attributable fractions for anemia risk factors (iron, folate, and vitamin B12) in Belize: potential impact of fortification / Fracciones atribuibles poblacionales nacionales y regionales de factores de riesgo de anemia (hierro, folato y vitamina B12) en Belice: posible impacto del enriquecimiento de los alimentos con suplementos / Frações atribuíveis populacionais nacionais e regionais de fatores de risco para anemia (ferro, ácido fólico e vitamina B12) em Belize: potencial impacto da fortificação

[ABSTRACT]. Objective. To estimate the national and regional population attributable fraction (PAF) and potential number of preventable anemia cases for three nutritional risk factors (iron, red blood cell folate [RBCF], and vitamin B12 deficiencies) among women of childbearing age in Belize. Methods. A national probability-based household and micronutrient survey capturing sociodemographic and health information was conducted among 937 nonpregnant Belizean women aged 15–49 years. Blood samples were collected to determine hemoglobin, ferritin, alpha-1-glycoprotein (AGP), RBCF, and vitamin B12 status. All analyses used sample weights and design variables to reflect a complex sample survey. Logistic regression was used to determine adjusted prevalence risk (aPR) ratios, which were then used to estimate national and regional PAF for anemia. Results. The overall prevalence of anemia (hemoglobin <12 g/dL) was 21.2% (95% CI [18.7, 25.3]). The prevalence of anemia was significantly greater among women with iron deficiency (59.5%, 95% CI [48.7, 69.5]) compared to women without iron deficiency (15.2%, 95% CI [12.2, 18.3]; aPR 3.9, 95% CI [2.9, 5.1]). The three nutritional deficiencies examined contributed to 34.6% (95% CI [22.1, 47.1]) of the anemia cases. If all these nutritional deficiencies could be eliminated, then an estimated 5 953 (95% CI [3 807, 8 114]) anemia cases could be prevented. Conclusions. This study suggests that among women of child-bearing age in Belize, anemia cases might be reduced by a third if three modifiable nutritional risk factors (iron, RBCF, and vitamin B12 deficiencies) could be eliminated. Fortification is one potential strategy to improve nutritional status and reduce the burden of anemia in this population.

[RESUMEN]. Objetivo. Calcular la fracción atribuible poblacional a nivel nacional y regional y el número de casos de anemia que podrían prevenirse para tres factores de riesgo nutricional (deficiencia de hierro, folato eritrocitario y vitamina B12) en las mujeres en edad reproductiva en Belice. Metodología. Se llevó a cabo una encuesta probabilística nacional sobre características de los hogares y micronutrientes en la que se recopiló información sociodemográfica y de salud de 937 mujeres beliceñas no embarazadas de entre 15 y 49 años. Se extrajeron muestras de sangre para determinar los niveles de hemoglobina, ferritina, alfa–1–glucoproteína, folato eritrocitario y vitamina B12. En todos los análisis se emplearon ponderaciones muestrales y variables calculadas para tener en cuenta que se trataba de una encuesta con una muestra compleja. Se estimaron mediante regresión logística las razones de riesgos de prevalencia ajustados, que posteriormente se utilizaron para calcular la fracción atribuible poblacional con respecto a la anemia a nivel nacional y regional. Resultados. La prevalencia global de la anemia (hemoglobina <12 g/dl) fue del 21,2% (IC del 95%: 18,7– 25,3). La prevalencia de la anemia fue significativamente mayor en las mujeres con ferropenia (59,5%, IC del 95%: 48,7–69,5) que en las que no tenían ferropenia (15,2%, IC del 95%: 12,2, 18,3); razón de riesgos de prevalencia ajustados = 3.9, IC del 95%; 2,9–5,1). Las tres deficiencias nutricionales examinadas explicaban al 34,6% (IC del 95%: 22,1–47,1) de los casos de anemia. Se estima que si pudieran eliminarse todas estas deficiencias nutricionales, se prevendrían unos 5953 (IC del 95%: 3807–8114) casos de anemia. Conclusiones. Los resultados de este estudio sugieren que los casos de anemia en las mujeres en edad reproductiva de Belice podrían reducirse en un tercio si se pudieran eliminar tres factores de riesgo nutricionales modificables (deficiencias de hierro, folato eritrocitario y vitamina B12). Una posible estrategia para mejorar el estado nutricional y reducir la carga de la anemia en este grupo poblacional es en el enriquecimiento de los alimentos con suplementos.

[RESUMO]. Objetivo. Estimar a fração atribuível populacional (FAP) nacional e regional e o potencial número de casos preveníveis de anemia para três fatores de risco nutricionais (deficiência de ferro, ácido fólico eritrocitário e vitamina B12) entre mulheres em idade fértil em Belize. Métodos. Realizou-se um inquérito probabilístico domiciliar nacional sobre micronutrientes, que coletou informações sociodemográficas e de saúde de 937 mulheres belizenhas não grávidas com idade entre 15 e 49 anos. Coletaram-se amostras de sangue para dosagem de hemoglobina, ferritina, alfa-1-glicoproteína (AGP), ácido fólico eritrocitário e vitamina B12. Todas as análises usaram variáveis de delineamento e ponderações amostrais para refletir um inquérito amostral complexo. Aplicou-se regressão logística para determinar razões ajustadas de risco de prevalência (RPa), que foram usadas para estimar a FAP nacional e regional para anemia. Resultados. A prevalência geral de anemia (hemoglobina <12 g/dL) foi de 21,2% (IC 95% [18,7–25,3]). A prevalência de anemia foi significativamente maior em mulheres com deficiência de ferro (59,5%, IC 95% [48,7–69,5]) que em mulheres sem deficiência de ferro (15,2%, IC 95% [12,2–18,3]); RPa 3,9, IC 95% [2,9– 5,1]). As três deficiências nutricionais analisadas contribuíram para 34,6% (IC 95% [22,1–47,1]) dos casos de anemia. Caso se eliminassem todas essas deficiências nutricionais, seria possível evitar cerca de 5.953 (IC 95% [3.807–8.114]) casos de anemia. Conclusões. Este estudo sugere que, nas mulheres belizenhas em idade fértil, os casos de anemia poderiam ser reduzidos em um terço caso fosse possível eliminar três fatores de risco nutricionais modificáveis (deficiência de ferro, ácido fólico eritrocitário e vitamina B12). A fortificação é uma possível estratégia para melhorar o estado nutricional e reduzir a carga de anemia nessa população.

Forecasting species' responses to climate change using space-for-time substitution.

To anticipate species' responses to climate change, ecologists have largely relied on the space-for-time-substitution (SFTS) approach. However, the hypothesis and its underlying assumptions have been poorly tested. Here, we detail how the efficacy of using the SFTS approach to predict future locations will depend on species' traits, the ecological context, and whether the species is declining or introduced. We argue that the SFTS approach will be least predictive in the contexts where we most need it to be: forecasting the expansion of the range of introduced species and the recovery of threatened species. We highlight how evaluating the underlying assumptions, along with improved methods, will rapidly advance our understanding of the applicability of the SFTS approach, particularly in the context of modelling the distribution of species.

Update on the impact of voluntary folic acid fortification of corn masa flour on red blood cell folate concentrations-National Health and Nutrition Examination Survey, 2011-March 2020.

BACKGROUND: Folic acid is a micronutrient that is effective at preventing neural tube defects (NTDs). In 2016, the FDA authorized the voluntary fortification of corn masa flour (CMF) with folic acid to reduce disparities in NTDs among infants of women who do not regularly consume other fortified cereal grains, in particular Hispanic women of reproductive age (WRA). METHODS: We analyzed data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to March 2020 assessing the impact of voluntary fortification of CMF on the folate status of Hispanic WRA. We analyzed folic acid usual intake and red blood cell (RBC) folate concentrations among non-pregnant, non-lactating Hispanic WRA, comparing pre-fortification (2011-2016) to post-fortification (2017-March 2020) data. RBC folate concentrations were used to create model-based estimation of NTD rates. RESULTS: The proportion of Hispanic WRA with folic acid usual intakes <400 µg/d did not change (2011-2016: 86.1% [95% Confidence Interval, CI: 83.7-88.5]; 2017-March 2020: 87.8% [95% CI: 84.8-90.7]; p = .38) nor did the proportion of Hispanic WRA with RBC folate below optimal concentrations (<748 nmol/L, 2011-2016: 16.0% [95% CI: 13.7-18.2]; 2017-March 2020: 18.1% [95% CI: 12.1-24.0]; p = 0.49). Model-based estimates of NTD rates suggest further improvements in the folate status of Hispanic WRA might prevent an additional 157 (95% Uncertainty Interval: 0, 288) NTDs/year. CONCLUSIONS: Voluntary fortification of CMF with folic acid has yet to have a significant impact on the folate status of WRA. Continued monitoring and further research into factors such as fortified product availability, community knowledge, and awareness of folic acid benefits would inform and improve future public health interventions.

Folate and vitamin B12 status and predicted neural tube defects risk among nonpregnant women of reproductive age from the Malawi National Micronutrient Survey, 2015-2016.

BACKGROUND: Maternal folate and vitamin B12 deficiency can lead to serious adverse pregnancy outcomes. There are no nationally representative estimates on folate and vitamin B12 status among women of reproductive age (WRA) in Malawi. OBJECTIVE: We assessed folate and vitamin B12 status among nonpregnant WRA in Malawi and predicted the risk of folate-sensitive neural tube defects (NTDs) were they to become pregnant. METHODS: Using data from the cross-sectional, nationally representative 2015-2016 Malawi Micronutrient Survey, we calculated the proportion of folate and vitamin B12 deficiency and insufficiency by demographic characteristics among 778 nonpregnant WRA (15-49 years). We predicted NTD prevalence using red blood cell (RBC) folate distributions and a published Bayesian model of the association between RBC folate and NTD risk. Analyses accounted for complex survey design. RESULTS: Among WRA, 8.5% (95% CI: 6.2, 11.6) and 13.3% (10.0, 17.4) had serum (<7 nmol/L) and RBC folate (<305 nmol/L) deficiency, respectively. The proportion of vitamin B12 deficiency (<148 pmol/L) and insufficiency (≤221 pmol/L) was 11.8% (8.6, 16.0) and 40.6% (34.1, 47.4), respectively. RBC folate insufficiency (<748 nmol/L, defined as the concentration associated with the threshold for elevated NTD risk: >8 cases per 10,000 births) was widespread: 81.4% (75.0, 86.4). The predicted NTD risk nationally was 24.7 cases per 10,000 live births. RBC folate insufficiency and higher predicted NTD risk were more common among WRA living in urban areas or with higher education. CONCLUSIONS: These findings highlight the importance of nutritional and NTD surveillance in Malawi and the opportunity for improving folate and vitamin B12 nutrition among Malawian WRA.

Vitamin B12 supplementation during pregnancy for maternal and child health outcomes.

BACKGROUND: Vitamin B12 deficiency is a major public health problem worldwide, with the highest burden in elderly people, pregnant women, and young children. Due to its role in DNA synthesis and methylation, folate metabolism, and erythropoiesis, vitamin B12 supplementation during pregnancy may confer longer-term benefits to maternal and child health outcomes. OBJECTIVES: To evaluate the benefits and harms of oral vitamin B12 supplementation during pregnancy on maternal and child health outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP) on 2 June 2023, and reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials (RCTs), quasi-RCTs, or cluster-RCTs evaluating the effects of oral vitamin B12 supplementation compared to placebo or no vitamin B12 supplementation during pregnancy. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Four review authors independently assessed trial eligibility. Two review authors independently extracted data from included studies and conducted checks for accuracy. Three review authors independently assessed the risk of bias of the included studies using the Cochrane RoB 1 tool. We used GRADE to evaluate the certainty of evidence for primary outcomes. MAIN RESULTS: The review included five trials with 984 pregnant women. All trials were conducted in low- and middle-income countries, including India, Bangladesh, South Africa, and Croatia. At enrolment, 26% to 51% of pregnant women had vitamin B12 deficiency (less than 150 pmol/L), and the prevalence of anaemia (haemoglobin less than 11.0 g/dL) ranged from 30% to 46%. The dosage of vitamin B12 supplementation varied from 5 µg/day to 250 µg/day, with administration beginning at 8 to 28 weeks' gestation through to delivery or three months' postpartum, and the duration of supplementation ranged from 8 to 16 weeks to 32 to 38 weeks. Three trials, involving 609 pregnant women, contributed data for meta-analyses of the effects of vitamin B12 supplementation compared to placebo or no vitamin B12 supplementation. Maternal anaemia: there may be little to no difference for maternal anaemia by intervention group, but the evidence is very uncertain (70.9% versus 65.0%; risk ratio (RR) 1.08, 95% confidence interval (CI) 0.93 to 1.26; 2 trials, 284 women; very low-certainty evidence). Maternal vitamin B12 status: vitamin B12 supplementation during pregnancy may reduce the risk of maternal vitamin B12 deficiency compared to placebo or no vitamin B12 supplementation, but the evidence is very uncertain (25.9% versus 67.9%; RR 0.38, 95% CI 0.28 to 0.51; 2 trials, 272 women; very low-certainty evidence). Women who received vitamin B12 supplements during pregnancy may have higher total vitamin B12 concentrations compared to placebo or no vitamin B12 supplementation (mean difference (MD) 60.89 pmol/L, 95% CI 40.86 to 80.92; 3 trials, 412 women). However, there was substantial heterogeneity (I2 = 85%). Adverse pregnancy outcomes: the evidence is uncertain about the effect on adverse pregnancy outcomes, including preterm birth (RR 0.97, 95% CI 0.55 to 1.74; 2 trials, 340 women; low-certainty evidence), and low birthweight (RR 1.50, 95% CI 0.93 to 2.43; 2 trials, 344 women; low-certainty evidence). Two trials reported data on spontaneous abortion (or miscarriage); however, the trials did not report quantitative data for meta-analysis and there was no clear definition of spontaneous abortion in the study reports. No trials evaluated the effects of vitamin B12 supplementation during pregnancy on neural tube defects. Infant vitamin B12 status: children born to women who received vitamin B12 supplementation had higher total vitamin B12 concentrations compared to placebo or no vitamin B12 supplementation (MD 71.89 pmol/L, 95% CI 20.23 to 123.54; 2 trials, 144 children). Child cognitive outcomes: three ancillary analyses of one trial reported child cognitive outcomes; however, data were not reported in a format that could be included in quantitative meta-analyses. In one study, maternal vitamin B12 supplementation did not improve neurodevelopment status (e.g. cognitive, language (receptive and expressive), motor (fine and gross), social-emotional, or adaptive (conceptual, social, practical) domains) in children compared to placebo (9 months, Bayley Scales of Infant and Toddler Development Third Edition (BSID-III); 1 trial; low-certainty evidence) or neurophysiological outcomes (72 months, event-related potential measures; 1 trial; low-certainty evidence), though children born to women who received vitamin B12 supplementation had improved expressive language domain compared to placebo (30 months, BSID-III; 1 trial; low-certainty evidence). AUTHORS' CONCLUSIONS: Oral vitamin B12 supplementation during pregnancy may reduce the risk of maternal vitamin B12 deficiency and may improve maternal vitamin B12 concentrations during pregnancy or postpartum compared to placebo or no vitamin B12 supplementation, but the evidence is very uncertain. The effects of vitamin B12 supplementation on other primary outcomes assessed in this review were not reported, or were not reported in a format for inclusion in quantitative analyses. Vitamin B12 supplementation during pregnancy may improve maternal and infant vitamin B12 status, but the potential impact on longer-term clinical and functional maternal and child health outcomes has not yet been established.

Regional habitat suitability for aquatic and terrestrial invasive plant species may expand or contract with climate change.

The threat of invasive species to biodiversity and ecosystem structure is exacerbated by the increasingly concerning outlook of predicted climate change and other human influences. Developing preventative management strategies for invasive plant species before they establish is crucial for effective management. To examine how climate change may impact habitat suitability, we modeled the current and future habitat suitability of two terrestrial species, Geranium lucidum and Pilosella officinarum, and two aquatic species, Butomus umbellatus and Pontederia crassipes, that are relatively new invasive plant species regionally, and are currently spreading in the Pacific Northwest (PNW, North America), an area of unique natural areas, vibrant economic activity, and increasing human population. Using North American presence records, downscaled climate variables, and human influence data, we developed an ensemble model of six algorithms to predict the potential habitat suitability under current conditions and projected climate scenarios RCP 4.5, 7.0, and 8.5 for 2050 and 2080. One terrestrial species (P. officinarum) showed declining habitat suitability in future climate scenarios (contracted distribution), while the other terrestrial species (G. lucidum) showed increased suitability over much of the region (expanded distribution overall). The two aquatic species were predicted to have only moderately increased suitability, suggesting aquatic plant species may be less impacted by climate change. Our research provides a template for regional-scale modelling of invasive species of concern, thus assisting local land managers and practitioners to inform current and future management strategies and to prioritize limited available resources for species with expanding ranges. Supplementary Information: The online version contains supplementary material available at 10.1007/s10530-023-03139-8.

Strengthening capacity of health workers to diagnose birth defects in Ugandan hospitals from 2015 to 2021.

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.

Effect of a Peer Health Coaching Intervention on Clinical Outcomes Among US Veterans With Cardiovascular Risks: The Vet-COACH Randomized Clinical Trial.

Importance: Although cardiovascular disease (CVD) is the leading cause of death in the US, CVD risk factors remain suboptimally controlled. Objective: To test the effectiveness of a home-visit, peer health coaching intervention to improve health outcomes for veterans with multiple CVD risks. Design, Setting, and Participants: This 2-group, unblinded randomized clinical trial, called Vet-COACH (Veteran Peer Coaches Optimizing and Advancing Cardiac Health), used a novel geographic-based method to recruit a racially diverse population of veterans with low income. These veterans were enrolled at the Seattle or American Lake Veterans Health Affairs primary care clinics in Washington state. Veterans with a diagnosis of hypertension with at least 1 blood pressure reading of 150/90 mm Hg or higher in the past year, and 1 other CVD risk factor (current smoker, overweight or obesity, and/or hyperlipidemia), who resided in Census tracts with the highest prevalence of hypertension were eligible to participate. Participants were randomized to the intervention group (n = 134) or control group (n = 130). An intention-to-treat analysis was performed from May 2017 to October 2021. Intervention: Participants in the intervention group received peer health coaching for 12 months with mandatory and optional educational materials, an automatic blood pressure monitor, a scale, a pill organizer, and healthy nutrition tools. Participants in the control group received usual care plus educational materials. Main Outcomes and Measures: The primary outcome was a change in systolic blood pressure (SBP) from baseline to 12-month follow-up. Secondary outcomes included change in health-related quality of life (HRQOL; measured using the 12-item Short Form survey's Mental Component Summary and Physical Component Summary scores), Framingham Risk Score, and overall CVD risk and health care use (hospitalizations, emergency department visits, and outpatient visits). Results: The 264 participants who were randomized (mean [SD] age of 60.6 [9.7] years) were predominantly male (229 [87%]) and 73 (28%) were Black individuals and 103 (44%) reported low annual income (<$40 000 per year). Seven peer health coaches were recruited. No difference was found in change in SBP between the intervention and control groups (-3.32 [95% CI, -6.88 to 0.23] mm Hg vs -0.40 [95% CI, -4.20 to 3.39] mm Hg; adjusted difference in differences, -2.05 [95% CI, -7.00 to 2.55] mm Hg; P = .40). Participants in the intervention vs control group reported greater improvements in mental HRQOL scores (2.19 [95% CI, 0.26-4.12] points vs -1.01 [95% CI, -2.91 to 0.88] points; adjusted difference in differences, 3.64 [95% CI, 0.66-6.63] points; P = .02). No difference was found in physical HRQOL scores, Framingham Risk Scores, and overall CVD risk or health care use. Conclusions and Relevance: This trial found that, although the peer health coaching program did not significantly decrease SBP, participants who received the intervention reported better mental HRQOL compared with the control group. The results suggest that a peer-support model that is integrated into primary care can create opportunities for well-being improvements beyond blood pressure control. Trial Registration: ClinicalTrials.gov Identifier: NCT02697422.

A Randomized Trial of Quadruple-Fortified Salt for Anemia and Birth Defects Prevention in Southern India: Protocol Design and Methods.

Background: Women of reproductive age are at an increased risk of anemia and micronutrient deficiencies. Evidence supports the role of periconceptional nutrition in the development of neural tube defects (NTDs) and other pregnancy complications. Vitamin B12 deficiency is a risk factor for NTDs and may modify folate biomarkers that predict NTD risk at the population level. There is an interest in mandatory fortification with vitamin B12 and folic acid for anemia and birth defect prevention. However, there are limited population-representative data needed to inform policy and guidelines. Objectives: This randomized trial will be conducted to evaluate the efficacy of quadruple-fortified salt (QFS; iron, iodine, folic acid, vitamin B12) in 1,000 households in Southern India. Methods: Women 18 to 49 y who are not pregnant or lactating and reside within the catchment area of our community-based research site in Southern India will be screened and invited to participate in the trial. After informed consent, women and their households will be randomized to receive one of the following 4 interventions: 1) double-fortified salt (DFS; iron, iodine), 2) DFS + folic acid (iron, iodine, folic acid), 3) DFS + vitamin B12 (iron, iodine, vitamin B12), or 4) DFS + folic acid and vitamin B12 (QFS; iron, iodine, folic acid, vitamin B12) for 12 mo. Structured interviews will be conducted by trained nurse enumerators to collect sociodemographic, anthropometric, dietary, health, and reproductive history data. Biological samples will be collected at baseline, midpoint, and endpoint. Whole blood will be analyzed for hemoglobin using Coulter Counter. Total vitamin B12 will be measured by chemiluminescence; red blood cell folate and serum folate will be evaluated using the World Health Organization-recommended microbiologic assay. Conclusions: The results of this randomized trial will help to evaluate the efficacy of QFS to prevent anemia and micronutrient deficiencies. Clinical trial registration numbers: NCT03853304 and Clinical Trial Registry of India REF/2019/03/024479. Registration number: NCT03853304 and REF/2019/03/024479.

Estimating the serum folate concentration that corresponds to the red blood cell folate concentration threshold associated with optimal neural tube defects prevention: A population-based biomarker survey in Southern India.

BACKGROUND: RBC folate concentrations are monitored at the population level, with a recommended threshold for optimal neural tube defect (NTD) prevention. A corresponding threshold for serum folate has not been established. OBJECTIVES: This study aimed to estimate the serum folate insufficiency threshold corresponding to the RBC folate threshold for NTD prevention and examine how this threshold is modified by vitamin B12 status. METHODS: Participants were women (15-40 y; not pregnant or lactating; n = 977) from a population-based biomarker survey in Southern India. RBC folate and serum folate were measured via microbiologic assay. RBC folate deficiency (<305 nmol/L) and insufficiency (<748 nmol/L), serum vitamin B12 deficiency (<148 pmol/L) and vitamin B12 insufficiency (<221 pmol/L), elevated plasma MMA (>0.26 µmol/L), elevated plasma homocysteine (>10.0 µmol/L), and elevated HbA1c (≥6.5%) were evaluated. Bayesian linear models were used to estimate unadjusted and adjusted thresholds. RESULTS: Compared with adequate vitamin B12 status, the estimated serum folate threshold was higher in participants with serum vitamin B12 deficiency (72.5 vs. 28.1 nmol/L) or vitamin B12 insufficiency (48.7 vs. 24.3 nmol/L) and elevated MMA (55.6 vs. 25.9 nmol/L). The threshold was lower in participants with elevated HbA1c (HbA1c ≥6.5% vs. <6.5%; 21.0 vs. 40.5 nmol/L). CONCLUSIONS: The estimated serum folate threshold for optimal NTD prevention was similar to previous reports (24.3 vs. 25.6 nmol/L) among participants with sufficient vitamin B12 status. However, this threshold was more than 2-fold higher in participants with vitamin B12 deficiency and substantially higher across all indicators of insufficient vitamin B12 status (<221 pmol/L, elevated MMA, combined B12, impaired vitamin B12 status), and lower in participants with elevated HbA1c. Findings suggest a serum folate threshold for NTD prevention may be possible in some settings; however, it may not be appropriate in populations with high prevalence of vitamin B12 insufficiency. Am J Clin Nutr 2023;xx:xx-xx. This trial was registered at https://clinicaltrials.gov as NCT04048330.

Experimental evolution of dispersal: Unifying theory, experiments and natural systems.

Dispersal is a central life history trait that affects the ecological and evolutionary dynamics of populations and communities. The recent use of experimental evolution for the study of dispersal is a promising avenue for demonstrating valuable proofs of concept, bringing insight into alternative dispersal strategies and trade-offs, and testing the repeatability of evolutionary outcomes. Practical constraints restrict experimental evolution studies of dispersal to a set of typically small, short-lived organisms reared in artificial laboratory conditions. Here, we argue that despite these restrictions, inferences from these studies can reinforce links between theoretical predictions and empirical observations and advance our understanding of the eco-evolutionary consequences of dispersal. We illustrate how applying an integrative framework of theory, experimental evolution and natural systems can improve our understanding of dispersal evolution under more complex and realistic biological scenarios, such as the role of biotic interactions and complex dispersal syndromes.

Systematic estimates of the global, regional and national under-5 mortality burden attributable to birth defects in 2000-2019: a summary of findings from the 2020 WHO estimates.

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.

Comparison of Anemia Screening Methods Using Paired Venous Samples in Women of Reproductive Age in Southern India.

BACKGROUND: Anemia is an important public health problem, and accurate estimates may inform policy and programs. Although hemoglobin (Hb) assessment of venous blood via automated hematology analyzers (AHAs) is recommended, most population-based surveys estimate anemia prevalence based on analysis of capillary blood via portable hemoglobinometers. OBJECTIVES: We aimed to evaluate screening methods for hemoglobin and anemia assessment using paired venous samples. METHODS: Participants were women 15-40 y who were not pregnant or lactating. Paired venous whole blood samples (n = 896) were analyzed for hemoglobin (Hb) via portable hemoglobinometer (HemoCue 301) and Coulter Counter AHA. Anemia and severe anemia were defined as Hb <12.0g/dL and <8.0 g/dL, respectively. Bland-Altman methods were used to assess the level of agreement for Hb results (mean difference, SD of differences, limits of agreement). Diagnostic accuracy parameters (sensitivity, specificity, positive predictive value, negative predictive value, accuracy) were calculated to evaluate HemoCue performance compared to the AHA reference, overall and by sociodemographic, nutritional, and metabolic characteristics. RESULTS: The estimated anemia prevalence was significantly lower via HemoCue vs. AHA (36.3% compared with 41.6%; P value < 0.0001). The HemoCue had 84.4% accuracy for anemia screening and 98.8% for severe anemia, compared to the AHA reference. The HemoCue had 74.8% sensitivity and 91.2% specificity, compared to AHA. HemoCue sensitivity was higher in women with iron deficiency [serum ferritin (SF) <15.0 µg/L: 81.6% compared with SF ≥15.0 µg/L: 41.3%], and lower in women with metabolic risk factors, including overweight [BMI ≥25.0 kg/m2: 63.9% vs. BMI <25.0 kg/m2: 78.8%], or elevated CRP (>1.0 mg/L: 67.2% vs. ≤1.0 mg/L: 82.9%), trunk fat (>35%: 62.7% vs. ≤35%: 80.1%), or whole-body fat (>35%: 63.9% vs. ≤35%: 80.3%). CONCLUSIONS: Findings suggest that women with anemia may be incorrectly identified as not anemic via portable hemoglobinometer, and anemia prevalence may be underestimated at the population level.This study was registered at clinicaltrials.gov as NCT04048330.

Folic Acid and the Prevention of Birth Defects: 30 Years of Opportunity and Controversies.

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 B12 as well as expanded biomarker testing.

Outcomes in pediatric patients with documented delays between ileocolic intussusception diagnosis and therapeutic enema attempt: evaluation of reduction efficacy and complication rate.

BACKGROUND: Ileocolic intussusception is considered a pediatric emergency, with concerns for risk of significant morbidity in children with a prolonged intussusception state. Emergent therapy is standard of care, as prior studies have shown poor outcomes in patients with long delays (> 24 h) before intervention. Various factors can result in shorter delays, and there are limited studies evaluating outcomes in these patients. This study aimed to determine if there were differences in reduction success rates associated with short in-hospital time delays. OBJECTIVE: This study is to determine enema success rate and morbidity in patients with documented time delays between intussusception diagnosis and therapeutic enema. MATERIALS AND METHODS: A retrospective evaluation of pediatric patients with intussusception at a single children's hospital between 2007 and 2019 was performed. Patient's records were reviewed for time of symptom onset, radiologic diagnosis, and attempted enema. Ultrasounds and radiographs were reviewed for bowel obstruction, free peritoneal fluid, trapped fluid around the intussusceptum, and absent bowel wall perfusion. Patients were evaluated for efficacy of reduction attempt, requirement for surgical reduction, and complications including bowel resection and bowel perforation. RESULTS: There were 175 cases of ileocolic intussusception requiring enema reduction. Successful reduction occurred in 72.2% (13/18) of cases performed within 1 h of diagnosis; 74.3% (78/105) between 1 and3 h; 73.2% (30/41) between 3 and 6 h; and 81.2% (9/11) with greater than 6 h. Need for bowel resection was not associated with short delays between diagnosis and reduction attempts (p = .07). CONCLUSIONS: There was no difference in intussusception reduction efficacy or complication rate in patients with increasing time between imaging diagnosis of ileocolic intussusception and reduction attempt, including delay intervals up to 8 h.

Evaluation of real-world referential and probabilistic patient matching to advance patient identification strategy.

OBJECTIVE: This study sought both to support evidence-based patient identity policy development by illustrating an approach for formally evaluating operational matching methods, and also to characterize the performance of both referential and probabilistic patient matching algorithms using real-world demographic data. MATERIALS AND METHODS: We assessed matching accuracy for referential and probabilistic matching algorithms using a manually reviewed 30 000 record gold standard reference dataset derived from a large health information exchange containing over 47 million patient registrations. We applied referential and probabilistic algorithms to this dataset and compared the outputs to the gold standard. We computed performance metrics including sensitivity (recall), positive predictive value (precision), and F-score for each algorithm. RESULTS: The probabilistic algorithm exhibited sensitivity, positive predictive value (PPV), and F-score of .6366, 0.9995, and 0.7778, respectively. The referential algorithm exhibited corresponding sensitivity, PPV, and F-score values of 0.9351, 0.9996, and 0.9663, respectively. Treating discordant and limited-data records as nonmatches increased referential match sensitivity to 0.9578. Compared to the more traditional probabilistic approach, referential matching exhibits greater accuracy. CONCLUSIONS: Referential patient matching, an increasingly popular method among health IT vendors, demonstrated notably greater accuracy than a more traditional probabilistic approach without the adaptation of the algorithm to the data that the traditional probabilistic approach usually requires. Health IT policymakers, including the Office of the National Coordinator for Health Information Technology (ONC), should explore strategies to expand the evidence base for real-world matching system performance, given the need for an evidence-based patient identity strategy.

Iron status and inflammation in women of reproductive age: A population-based biomarker survey and clinical study.

BACKGROUND: Women of reproductive age (WRA) are at increased risk for anemia and iron deficiency. However, there is limited population-level data in India, which could help inform evidence-based recommendations and policy. AIMS: To conduct a population-based biomarker survey of anemia, iron deficiency, and inflammation in WRA in Southern India. METHODS: Participants were WRA (15-40 y) who were not pregnant or lactating. Blood samples (n = 979) were collected and analyzed for hemoglobin (Hb), serum ferritin (SF), soluble transferrin receptor (sTfR), C-reactive protein (CRP), and alpha-1 acid glycoprotein (AGP). Anemia and severe anemia were defined as Hb < 12.0 and < 8.0 g/dL. Serum ferritin was adjusted for inflammation using BRINDA methods. Iron deficiency was defined as SF <15.0 µg/L, iron insufficiency was defined as SF < 20.0 and < 25.0 µg/L, and iron deficiency anemia was defined as Hb < 12.0 g/dL and SF < 15.0 µg/L. Inflammation was defined as CRP > 5.0 mg/L or AGP > 1.0 g/L. Restricted cubic spline regression models were also used to determine if alternative SF thresholds should be used t to classify iron deficiency. RESULTS: A total of 41.5% of WRA had anemia, and 3.0% had severe anemia. Findings from spline analyses suggested a SF cut-off of < 15.0 µg/L, consistent with conventional cut-offs for iron deficiency. 46.3% of WRA had SF < 15.0 µg/L (BRINDA-adjusted: 61.5%), 55.0% had SF < 20.0 µg/L (72.7%), 61.8% had SF < 25.0 µg/L (81.0%), and 30.0% had IDA (34.5%). 17.3% of WRA had CRP > 5.0 mg/L and 22.2% had AGP > 1.0 g/L. The prevalence of ID (rural vs. urban: 49.1% vs. 34.9%; p = 0.0004), iron insufficiency (57.8% vs. 43.8%; p = 0.0005), and IDA (31.8% vs. 22.4%; p = 0.01) were significantly higher in rural areas, although CRP levels were lower and there were no differences in elevated CRP or AGP. CONCLUSIONS: The burden of anemia and iron deficiency in this population was substantial, and increased after adjusting for inflammation, suggesting potential to benefit from screening and interventions. REGISTRATION NUMBER: NCT04048330.

Anemia and Vitamin B-12 and Folate Status in Women of Reproductive Age in Southern India: Estimating Population-Based Risk of Neural Tube Defects.

BACKGROUND: Women of reproductive age (WRA) are a high-risk population for anemia and micronutrient deficiencies. However, there are few representative population-level data from India, which could help inform evidence-based recommendations and policy. OBJECTIVE: To conduct a population-based biomarker survey of anemia and vitamin B-12 and folate status in WRA as part of a periconceptional surveillance program in southern India. METHODS: Participants were WRA (15-40 y) who were not pregnant or lactating. Whole blood (n = 979) was analyzed for hemoglobin via a Coulter counter (Coulter HMX). Plasma, serum, and RBCs were processed and stored at -80°C or less until batch analysis. Vitamin B-12 concentrations were measured via chemiluminescence; RBC and serum folate concentrations were evaluated via microbiological assay. Anemia and severe anemia were defined as hemoglobin <12.0 g/dL and <8.0 g/dL, respectively. Vitamin B-12 deficiency and insufficiency were defined as total vitamin B-12 <148 pmol/L and <221 pmol/L, respectively. Folate deficiency and insufficiency were defined as RBC folate <305 nmol/L and <748 nmol/L. A previously developed Bayesian model was used to predict neural tube defect (NTD) prevalence per 10,000 births. RESULTS: A total of 41.5% of WRA had anemia and 3.0% had severe anemia. A total of 48.3% of WRA had vitamin B-12 deficiency and 74.3% had vitamin B-12 insufficiency. The prevalence of RBC folate deficiency was 7.6%, and 79.3% of WRA had RBC folate <748 nmol/L, the threshold for optimal NTD prevention. Predicted NTD prevalence per 10,000 births based on RBC folate concentrations was 20.6 (95% uncertainty interval: 16.5-25.5). CONCLUSIONS: The substantial burden of anemia, vitamin B-12 deficiency, and RBC folate insufficiency in WRA in this setting suggests an opportunity for anemia and birth defects prevention. Findings will directly inform the development of a randomized trial for anemia and birth defects prevention in southern India.This study was registered at clinicaltrials.gov as NCT04048330.

Impact of Voluntary Folic Acid Fortification of Corn Masa Flour on RBC Folate Concentrations in the U.S. (NHANES 2011-2018).

Surveillance data have highlighted continued disparities in neural tube defects (NTDs) by race-ethnicity in the United States. Starting in 2016, the Food and Drug Administration (FDA) authorized voluntary folic acid fortification of corn masa flour to reduce the risk of neural tube defects (NTDs) among infants of Hispanic women of reproductive age. To assess the impact of voluntary corn masa fortification, cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 for Hispanic women of reproductive age with available red blood cell (RBC) folate concentrations were analyzed, with additional analyses conducted among Hispanic women whose sole source of folic acid intake was fortified foods (enriched cereal grain products (ECGP) only), excluding ready-to-eat cereals and supplements. RBC folate concentration (adjusted geometric mean) among Hispanic women of reproductive age did not differ between 2011-2016 and 2017-2018, though RBC folate concentration increased significantly among lesser acculturated Hispanic women consuming ECGP only. Concentrations of RBC folate for those born outside the U.S and residing in the U.S <15 years increased from 894 nmol/L (95% CI: 844-946) in 2011-2016 to 1018 nmol/L (95% CI: 982-1162; p < 0.001) in 2017-2018. Primarily Spanish-speaking Hispanic women of reproductive age who only consumed ECGP saw an increase from 941 nmol/L (95% CI: 895-990) in 2011-2016 to 1034 nmol/L (95% CI: 966-1107; p = 0.03) in 2017-2018. By subpopulation, we observed no significant changes in the proportion at risk of NTDs (<748 nmol/L) and no changes in the model-based estimated NTD rates following voluntary corn masa fortification. This analysis suggests that there is a remaining risk among Hispanics for folate sensitive NTDs, though continued monitoring of folate status in future NHANES data cycles will help inform the long-term efficacy of voluntary fortification of corn masa flour.