INTRODUCTION: Population risk for neural tube defects (NTDs) can be determined using red blood cell (RBC) folate. However, a paucity of biomarker and surveillance data among non-lactating, non-pregnant women of reproductive age (NPWRA) from Africa limits accurate assessment. Our study assessed folate and vitamin B12 status among non-lactating NPWRA and predicted population risk of NTDs in Tanzania. METHODS: A cross-sectional biomarker survey of non-lactating NPWRA (15-49 years) in the Morogoro region, Tanzania was conducted during June-October 2019. Questionnaire interview responses and non-fasting blood samples were collected. Folate was assessed using the CDC microbiologic assay kit and vitamin B12 was measured using an electrochemiluminescence immunoassay. Complex survey design analyses were conducted using SAS-callable SUDAAN (v11.0.1). RESULTS: Of the 761 participating non-lactating NPWRA, 294 (39.8%) had RBC folate insufficiency (<748 mol/L). The prevalence of RBC folate insufficiency was lower among non-lactating NPWRA living in urban than rural areas (PR: 0.72, 95% CI: 0.52-0.99) but did not differ by age or household wealth index. Vitamin B12 insufficiency was uncommon (< 221 pmol/L, 2.7%). The estimated NTD risk was 10.5 (95% uncertainty interval: 8.1-13.3) per 10,000 births. DISCUSSION: Elevated NTD risk was predicted in the Morogoro region of Tanzania, where ∼ 40% of non-lactating NPWRA had RBC folate insufficiency and < 3% had vitamin B12 insufficiency. The NTD risk is consistent with surveillance data for the area, limited folic acid fortification of staple foods, and low vitamin B12 insufficiency. Further studies are needed to better understand the context of these findings, especially the impact of micronutrient fortification in Tanzania.

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.

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.

BACKGROUND: Folate and vitamin B12 deficiencies in pregnant women are associated with increased risk for adverse maternal and infant health outcomes, including neural tube defects (NTDs). METHODS: A population-based cross-sectional survey was conducted in two rural areas in Ambala District, Haryana, India in 2017 to assess baseline folate and vitamin B12 status among women of reproductive age (WRA) and predict the prevalence of NTDs. We calculated the prevalence of folate and vitamin B12 deficiency and insufficiency by demographic characteristics among 775 non-pregnant, non-lactating WRA (18-49 years). Using red blood cell (RBC) folate distributions and an established Bayesian model, we predicted NTD prevalence. All analyses were conducted using SAS-callable SUDAAN Version 11.0.4 to account for complex survey design. RESULTS: Among WRA, 10.1% (95% CI: 7.9, 12.7) and 9.3% (95% CI: 7.4, 11.6) had serum (<7 nmol/L) and RBC folate (<305 nmol/L) deficiency, respectively. The prevalence of RBC folate insufficiency (<748 nmol/L) was 78.3% (95% CI: 75.0, 81.3) and the predicted NTD prevalence was 21.0 (95% uncertainly interval: 16.9, 25.9) per 10,000 live births. Prevalences of vitamin B12 deficiency (<200 pg/mL) and marginal deficiency (≥200 pg/mL and ≤300 pg/mL) were 57.7% (95% CI: 53.9, 61.4) and 23.5% (95% CI: 20.4, 26.9), respectively. CONCLUSIONS: The magnitude of folate insufficiency and vitamin B12 deficiency in this Northern Indian population is a substantial public health concern. The findings from the survey help establish the baseline against which results from future post-fortification surveys can be compared.

OBJECTIVES: Folate and vitamin B12 are important biomarkers of nutritional status of populations. This study aims to estimate folate and vitamin B12 usual intakes among US adults and examine folate and vitamin B12 biomarker status by intake source. METHODS: We analyzed data for U.S. adults (≥19 y) from National Health and Nutrition Examination Survey (NHANES) 2007-2018 (n=31,128), during which time voluntary corn masa flour fortification was started. Usual intake was estimated using National Cancer Institute (NCI) method. Folate intake included folate from natural foods and folic acid from four sources-enriched cereal grain products (ECGP), corn masa flour (CMF), ready-to-eat cereals (RTE), and folic acid containing supplements (SUP). Vitamin B12 is found in food and supplements. RESULTS: Median natural food folate intake (222 μg dietary folate equivalents (DFE)/d) was below the estimated average requirement (EAR) of 320 μg DFE/d. Proportions of those who consumed folic acid from ECGP/CMF only, ECGP/CMF+RTE, ECGP/CMF+SUP, and ECGP/CMF+RTE+SUP were 50%, 18%, 22%, and 10%, respectively. Median usual folic acid intakes (μg/d) were 236 (interquartile range: 152, 439) overall, and 134, 313, 496, 695 in the ECGP/CMF only, ECGP/CMF+RTE, ECGP/CMF+SUP, ECGP/CMF+RTE+SUP folic acid consumption groups, respectively. Overall, 2.0% (95% CI: 1.7%, 2.3%) of adults, all of whom used folic acid supplements, consumed greater than tolerable upper intake level (UL) of 1000 μg/d folic acid. Median usual vitamin B12 intake (μg/d) was 5.2 for vitamin B12 supplement non-users and 21.8 for users. Consumption of RTE and/or supplements with folic acid was associated with higher serum and RBC folate concentrations. Vitamin B12 supplement users had significantly higher serum vitamin B12 concentrations. CONCLUSIONS: Folic acid fortification plays a critical role in helping U.S. adults meet folate EAR. At current fortification levels, U.S. adults who do not consume supplements do not have usual folic acid intake exceeding the UL.

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. © 2023 The Author(s)

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.

BACKGROUND: Cognitive health is a public health concern among older adults. Dietary supplement (SUP) use is common and concerns have been raised about high folic acid intake among those with vitamin B-12 deficiency and exacerbation of poor cognitive performance (PCP). OBJECTIVES: We evaluated SUP use, usual folic acid intake, and blood folate and vitamin B-12 concentrations in relation to cognitive performance. METHODS: We used NHANES 2011-2014 data on adults aged ≥60 y (n = 2867) and estimated total usual folic acid intake from diet and supplements, vitamin B-12 intake from SUPs, blood folates, vitamin B-12 concentrations, vitamin B-12 insufficiency (≤258 pmol/L), high folate (serum folate ≥59 nmol/L or RBC folate ≥1609 nmol/L), and PCP (<34 on the Digit Symbol Substitution Test). We assessed folate distributions adjusted for multiple variables, including renal function. RESULTS: Compared with persons without PCP, adults with PCP were less likely to use supplements containing folic acid (mean ± SEE: 34.4% ± 2.4%) or vitamin B-12 (mean ± SEE: 47.5% ± 1.6%). Among vitamin B-12-insufficient adults, 18.0% ± 1.6% (mean ± SEE) reported taking a vitamin B-12 supplement. Among participants with high folate and insufficient vitamin B-12 concentrations, 34.3% ± 11.5% (mean ± SEE) reported taking vitamin B-12-containing supplements. Persons with high folate and normal vitamin B-12 concentrations had lower odds of PCP [aOR (adjusted odds ratio): 0.61; 95% CI: 0.45, 0.83] than persons with normal folate and vitamin B-12. Persons with high folate and normal methylmalonic acid (MMA) had lower odds of PCP (OR: 0.56; 95% CI: 0.40, 0.78) than those with normal folate and MMA concentrations. After adjustment for renal function, elevated risk of PCP was attenuated among persons with high folate and MMA. Concurrent high folate and insufficient vitamin B-12 concentrations were not associated with PCP. CONCLUSIONS: Differential associations between vitamin B-12 and MMA highlight the need to consider renal function in studies of high folate and low vitamin B-12 status. Consumption of vitamin B-12 supplements concurrent with low vitamin B-12 status may indicate vitamin B-12 malabsorption.

BACKGROUND: Current studies examining the effects of high concentrations of red blood cell (RBC) or serum folates assume that high folate concentrations are an indicator of high folic acid intakes, often ignoring the contributions of other homeostatic and biological processes, such as kidney function. OBJECTIVE: The current study examined the relative contributions of declining kidney function, as measured by the risk of chronic kidney disease (CKD), and usual total folic acid intake on the concentrations of RBC folate and serum folate (total as well as individual folate forms). DESIGN: Cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) collected in 2-year cycles were combined from 2011 to 2018. A total of 18,127 participants aged ≥16 years with available folate measures, kidney biomarker data (operationalized as a categorical CKD risk variable describing the risk of progression), and reliable dietary recall data were analyzed. RESULTS: RBC folate concentrations increased as CKD risk increased: low risk, 1089 (95% CI: 1069, 1110) nmol/L; moderate risk, 1189 (95% CI: 1158, 1220) nmol/L; high risk, 1488 (95% CI: 1419, 1561) nmol/L; and highest risk, 1443 (95% CI: 1302, 1598) nmol/L (p &lt; 0.0001). Similarly, serum total folate concentrations increased as CKD risk increased: low risk: 37.1 (95% CI: 26.3, 38.0) nmol/L; moderate risk: 40.2 (95% CI: 38.8, 41.7) nmol/L; high risk: 48.0 (95% CI: 44.3, 52.1) nmol/L; the highest Risk: 42.8 (95% CI: 37.8, 48.4) nmol/L (p &lt; 0.0001). The modeled usual intake of folic acid showed no difference among CKD risk groups, with a population median of 225 (interquartile range: 108-390) µg/day. CONCLUSION: Both RBC and serum folate concentrations increased with declining kidney function without increased folic acid intake. When analyzing associations between folate concentrations and disease outcomes, researchers may want to consider the confounding role of kidney function.

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: Neural tube defects (NTDs) encompass a variety of distinct types. We assessed if the preventive effect of folic acid (FA) varied by NTD type and infant sex. METHODS: We examined all pregnancies with NTD status confirmation from a pregnancy-monitoring system in selected locations in northern and southern regions of China between 1993 and 1996. Women who took 400 μg of FA daily during 42 days after last menstrual period were considered FA users. We analyzed NTD prevalence by FA use status, NTD type, geographic region, and infant sex. RESULTS: Among 626,042 pregnancies, 700 were affected by an NTD. Among FA nonusers, 65 pregnancies (8.8 per 10,000) in the north and 51 pregnancies (1.2 per 10,000) in the south were affected by one of the two rare NTDs, that is, craniorachischisis, iniencephaly. FA use prevented occurrence of these two rare NTDs and reduced the prevalence of spina bifida (SB) by 78% (from 17.9 to 3.9 per 10,000) in the north and 51% (from 2.4 to 1.2 per 10,000) in the south. Among FA users, SB prevalence, including SB with high lesion level, was significantly reduced in both geographic regions. FA use reduced prevalence of anencephaly and encephalocele by 85% and 50%, respectively in the north, while it did not reduce the prevalence of these two NTDs in the south. There was a greater reduction in NTD prevalence in female than in male infants and fetuses. CONCLUSIONS: This is the first study to show that FA prevents the entire spectrum of NTD types.

Food fortification has proven to be an effective approach for preventing micronutrient deficiencies in many settings. Factors that lead to successful fortification programs are well established. However, due to the multisectoral nature of fortification and the added complexities present in many settings, the barriers to success are not always evident and the strategies to address them are not always obvious. We developed a systematic process for identifying and addressing gaps in the implementation of a food fortification program. The framework is composed of 4 phases: (1) connect program theory of change to program implementation; (2) develop an implementation research agenda; (3) conduct implementation research; and (4) analyze findings and develop/disseminate recommendations for next steps. We detail steps in each phase to help guide teams through the process. To our knowledge, this is the first attempt to outline a systematic process for applying implementation science research to food fortification. The development of this framework is intended to promote implementation research in the field of food fortification, thus improving access to and effectiveness of this key public health intervention.

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: RBC folate (RBF) is an indicator of folate status and risk of neural-tube defects. It is calculated from whole blood folate (WBF), serum folate (SFOL), and hematocrit (Hct). SFOL and/or Hct are sometimes unavailable; hemoglobin (Hb) is generally available in surveys. OBJECTIVES: We assessed the ability of different RBF approximations to generate population data in women aged 12-49 y. METHODS: Using SFOL, RBF, Hct, Hb, and mean corpuscular Hb content (MCHC) from prefortification (1988-1994) and postfortification (1999-2006, 2007-2010) NHANES we applied 6 approaches: #1) assume SFOL = 0; #2) impute SFOL (population median); #3) impute Hct (population median); #4) estimate Hct (Hb/MCHC); #5) assume SFOL = 0 and estimate Hct; and #6) predict SFOL (from WBF) and estimate Hct. For each approach, we calculated the paired percentage difference to the "true" RBF and estimated various statistics. RESULTS: For 2007-2010 (unweighted data), the median relative difference from "true" RBF was lowest for approaches #2 (-0.74%), #4 (-0.96%), and #6 (-1.15%), intermediate for #3 (-3.36%), and highest for #5 (4.96%) and #1 (5.78%). The 95% agreement limits were smallest for approach #1 (2.33%, 13.0%) and largest for #3 (-20.8%, 11.3%). Approach #2 showed concentration-dependence (negative compared with positive differences at low compared with high RBF). Using weighted data, we found similar patterns across approaches for mean relative differences by demographic subgroup for all 3 time periods. CONCLUSIONS: We obtained the best agreement between estimated and "true" RBF when we predicted SFOL using a regression equation obtained from a subset of samples (approach #6). Alternatively, the consistent overestimation of RBF when assuming SFOL = 0 ( approximately 6%) could be addressed by adjusting the data (approach #5). Similar observations for pre- and postfortification periods suggest applicability to low and high folate status situations, but should be confirmed elsewhere. To estimate RBF, at least WBF and Hb are needed.

BACKGROUND: For women of reproductive age, a population-level red blood cell (RBC) folate concentration below the threshold 906 nmol/L or 400 ng/mL indicates folate insufficiency and suboptimal neural tube defect (NTD) prevention. A corresponding population plasma/serum folate concentration threshold for optimal NTD prevention has not been established. OBJECTIVE: The aim of this study was to examine the association between plasma and RBC folate concentrations and estimated a population plasma folate insufficiency threshold (pf-IT) corresponding to the RBC folate insufficiency threshold (RBCf-IT) of 906 nmol/L. METHODS: We analyzed data on women of reproductive age (n = 1673) who participated in a population-based, randomized folic acid supplementation trial in northern China. Of these women, 565 women with anemia and/or vitamin B-12 deficiency were ineligible for folic acid intervention (nonintervention group); the other 1108 received folic acid supplementation for 6 mo (intervention group). We developed a Bayesian linear model to estimate the pf-IT corresponding to RBCf-IT by time from supplementation initiation, folic acid dosage, methyltetrahydrofolate reductase (MTHFR) genotype, body mass index (BMI), vitamin B-12 status, or anemia status. RESULTS: Using plasma and RBC folate concentrations of the intervention group, the estimated median pf-IT was 25.5 nmol/L (95% credible interval: 24.6, 26.4). The median pf-ITs were similar between the baseline and postsupplementation samples (25.7 compared with 25.2 nmol/L) but differed moderately (+/-3-4 nmol/L) by MTHFR genotype and BMI. Using the full population-based baseline sample (intervention and nonintervention), the median pf-IT was higher for women with vitamin B-12 deficiency (34.6 nmol/L) and marginal deficiency (29.8 nmol/L) compared with the sufficient group (25.6 nmol/L). CONCLUSIONS: The relation between RBC and plasma folate concentrations was modified by BMI and genotype and substantially by low plasma vitamin B-12. This suggests that the threshold of 25.5 nmol/L for optimal NTD prevention may be appropriate in populations with similar characteristics, but it should not be used in vitamin B-12 insufficient populations. This trial was registered at clinicaltrials.gov as NCT00207558.

The threshold for population-level optimal red blood cell (RBC) folate concentration among women of reproductive age for the prevention of neural tube defects has been estimated at 906 nmol/L; however, the dose-response relationship between folic acid intake and blood folate concentrations is uncharacterized. To estimate the magnitude of blood folate concentration increase in response to specific dosages of folic acid under steady-state conditions (as could be achieved with food fortification), a systematic review of the literature and meta-analysis was conducted. Of the 14,002 records we identified, 533 were selected for full-text review, and data were extracted from 108 articles. The steady-state concentrations (homeostasis) of both serum/plasma and RBC folate concentrations were estimated using a Bayesian meta-analytic approach and one-compartment physiologically-based pharmacokinetic models. RBC folate concentrations increased 1.78 fold (95% credible interval (CI): 1.66, 1.93) from baseline to steady-state at 375(-)570 microg folic acid/day, and it took a median of 36 weeks of folic acid intake (95% CI: 27, 52) to achieve steady-state RBC folate concentrations. Based on regression analysis, we estimate that serum/plasma folate concentrations increased 11.6% (95% CI: 8.4, 14.9) for every 100 microg/day folic acid intake. These results will help programs plan and monitor folic acid fortification programs.

BACKGROUND: Women of reproductive age can consume 0.4 milligrams of folic acid daily to reduce the risk of a neural tube defect (NTD)-affected pregnancy. Multivitamins (MVs) are one source of folic acid. MATERIALS AND METHODS: Using HealthStyles survey data (n = 9268), we assessed change in prevalence of MV use during 2006-2016 among women by age (18-24, 25-34, and 35-44 years), race/ethnicity (non-Hispanic [NH] white, NH black, Hispanic), and pregnancy status (trying to get pregnant, not pregnant nor trying to get pregnant, and pregnant) using log-binomial regression. RESULTS: Daily MV consumption decreased overall from 32.7% to 23.6% during 2006-2016 for women aged 18-44 years (p for trend <0.001). Age-specific decreases were seen in women aged 25-34 years (2006: 34.1%; 2016: 23.7%; p < 0.001) and 35-44 years (2006: 37.3%; 2016: 27.1%; p < 0.001). Decreases in daily MV intake were found among NH whites (2006: 35.4%; 2016: 24.9%; p < 0.001) and Hispanics (2006: 30.6%; 2016: 22.1%; p < 0.001), but remained unchanged among NH blacks (2006: 23.7%; 2016: 21.8%; p = 0.87). Daily MV intake remained unchanged for women trying to get pregnant (2006: 40.2%; 2012: 38.3%; p = 0.19), decreased for women not pregnant nor trying to get pregnant (2006: 31.3%; 2012: 21.3%; p < 0.001), and fluctuated for pregnant women (2006: 53.8%; 2012: 71.0%; p = 0.21). Prevalence of no MV consumption increased significantly across all age and race/ethnicity groups. CONCLUSIONS: Overall MV intake decreased for the past decade and varied by age, race/ethnicity, and pregnancy status. Innovative messaging and targeted interventions for increasing folic acid intake are needed to reduce NTDs.

Children with heart conditions often use more health care services and specialized care than children without a heart condition (1); however, little is known about the number of U.S. children with heart conditions and their special health care needs. CDC used data from the 2016 National Survey of Children's Health (NSCH) to estimate the prevalence of heart conditions among U.S. children aged 0-17 years, which indicated that 1.3% had a current heart condition and 1.1% had a past heart condition (representing approximately 900,000 and 755,000 children, respectively). Sixty percent and 40% of children with current and past heart conditions, respectively, had one or more special health care needs, compared with 18.7% of children without a heart condition (adjusted prevalence ratios [aPRs] = 3.1 and 2.1, respectively). Functional limitations were 6.3 times more common in children with current heart conditions (30.7%) than in those without heart conditions (4.6%). Among children with current heart conditions, males, children with lower family income, and children living in other than a two-parent household had an increased prevalence of special health care needs. These findings highlight the importance of developmental surveillance and screening for children with heart conditions and might inform public health resource planning.

OBJECTIVES: This study assessed and compared the prevalence and severity of dental caries and the prevalence of periodontal disease among pregnant and nonpregnant women of reproductive age (15-44 years) using data from the National Health and Nutrition Examination Survey, NHANES (1999-2004). METHODS: Estimates were derived from a sample of 897 pregnant women and 3,971 nonpregnant women. Chi-square and two-sample t-tests were used to assess differences between groups stratified by age, race/ethnicity, education, and poverty. Bonferroni method was applied to adjust for multiple comparisons. RESULTS: In general, there were no statistically significant differences in the prevalence estimates of dental caries and periodontal disease between pregnant women and nonpregnant women. However, results showed significant differences when stratified by sociodemographic characteristics. For example, the prevalence of untreated dental caries among women aged 15-24 years was significantly higher in pregnant women than in nonpregnant women (41 percent versus 24 percent, P = 0.001). Regardless of their pregnancy status, racial/ethnic minorities or women with less education or lower family income had higher prevalence of untreated dental caries, severity of dental caries, and periodontal disease compared to the respective reference groups of non-Hispanic whites or women with more education or higher family income. CONCLUSION: Results of this study show few clinical differences in dental caries and periodontal disease between pregnant and nonpregnant women but persistent disparities by sociodemographic characteristics. In order to reduce oral health disparities in the United States, it is important to improve access to oral health care particularly among vulnerable groups. Integrating oral health into the overall health care could benefit and improve women's oral health outcomes.

In this issue of the American Journal of Preventive Medicine, Cui et al.1 examined the congenital anomaly (CA)–specific under-5 mortality rate in China from 1996 to 2013 and found a substantial reduction in this rate from 407.7 per 100,000 live births in 1996 to 217.4 per 100,000 live births in 2013. In addition, they also found that the proportion of total under-5 mortality due to CAs (also referred to as birth defects) was increasing but were unable to include CA-specific data on stillbirths and terminations of pregnancy. | The Millennium Development Goal (MDG)-4, established in 2000, aimed to reduce under-5 mortality rate by two thirds by 2015.2 Globally, the under-5 mortality rate has decreased by 53%, from an estimated rate of 90 deaths per 1,000 live births in 1990 to 43 deaths per 1,000 live births in 2015.2 However, the MDG-4 goal of a two-thirds reduction in under-5 mortality rate was not achieved despite great progress made during the past few decades.2 In January 2016, the MDGs were replaced by a new framework, the Sustainable Development Goals (SDGs), within which a new target to end preventable deaths of newborns and children under age 5 years was established with all countries aiming to reduce the neonatal mortality rate to 12 per 1,000 live births or fewer and the under-5 mortality rate to 25 per 1,000 live births or fewer by 2030.3 In order to achieve this SDG, a major cause of neonatal and under-5 mortality, birth defects, must be addressed. More global efforts need to be undertaken in the prevention of birth defects to realize a reduction in neonatal and under-5 mortality.

The Food and Drug Administration mandated that by 1998, all enriched cereal grain products (ECGP) be fortified with folic acid in order to prevent the occurrence of neural tube defects. The Institute of Medicine established the tolerable upper intake level (UL) for folic acid (1000 microg/day for adults) in 1998. We characterized U.S. adults with usual daily folic acid intake exceeding the UL. Using NHANES 2003-2010 data, we estimated the percentage of 18,321 non-pregnant adults with usual daily folic acid intake exceeding the UL, and among them, we calculated the weighted percentage by sex, age, race/ethnicity, sources of folic acid intake, supplement use and median usual daily folic acid intakes. Overall, 2.7% (standard error 0.6%) of participants had usual daily intake exceeding the UL for folic acid; 62.2% were women; 86.3% were non-Hispanic whites; and 98.5% took supplements containing folic acid. When stratified by sex and age groups among those with usual daily folic acid intake exceeding the UL, 20.8% were women aged 19-39 years. Those with usual daily intake exceeding the folic acid UL were more likely to be female, non-Hispanic white, supplement users or to have at least one chronic medical condition compared to those not exceeding the folic acid UL. Among those with usual daily folic acid intake exceeding the UL who also took supplements, 86.6% took on average >400 microg of folic acid/day from supplements. Everyone with usual daily folic acid intake exceeding the UL consumed folic acid from multiple sources. No one in our study population had usual daily folic acid intake exceeding the UL through consumption of mandatorily-fortified enriched cereal grain products alone. Voluntary consumption of supplements containing folic acid is the main factor associated with usual daily intake exceeding the folic acid UL.

INTRODUCTION: Oral diseases can be prevented or improved with regular dental visits. Our objective was to assess and compare national estimates on self-reported oral health conditions and dental visits among pregnant women and nonpregnant women of childbearing age by using data from the National Health and Nutrition Examination Survey (NHANES). METHODS: We analyzed self-reported oral health information on 897 pregnant women and 3,971 nonpregnant women of childbearing age (15-44 years) from NHANES 1999-2004. We used chi2 and 2-sample t tests to assess statistical differences between groups stratified by age, race/ethnicity, poverty, and education. We applied the Bonferroni adjustment for multiple comparisons. RESULTS: Our data show significant differences in self-reported oral health conditions and dental visits among women, regardless of pregnancy status, when stratified by selected sociodemographic characteristics. Significant differences were also found in self-reported oral health conditions and dental visits between pregnant and nonpregnant women, especially among young women, women from minority race/ethnicity groups, and women with less than high school education. CONCLUSION: We found disparities in self-reported oral health conditions and use of dental services among women regardless of pregnancy status. Results highlight the need to improve dental service use among US women of childbearing age, especially young pregnant women, those who are non-Hispanic black or Mexican American, and those with low family income or low education level. Prenatal visits could be used as an opportunity to encourage pregnant women to seek preventive dental care during pregnancy.

The findings described in this supplement can help improve collaboration among public health and other stakeholders who influence infant, child, and adolescent health (e.g., parents or guardians and their employers, health plans, health professionals, schools, child care facilities, community groups, and voluntary associations) to increase the use of selected clinical preventive services among U.S. infants, children, and adolescents. Increased use can substantially reduce illness and long-term disability and improve health and quality of life. This supplement underscores that the use of the clinical preventive services among U.S. infants, children, and adolescents is not optimal and is variable, ranging from <10% to approximately 85%, depending on the particular service. Use was particularly low for developmental screening and receipt of dental preventive services in young children, and for human papillomavirus (HPV) vaccination and tobacco cessation assistance, including counseling, in adolescents; however, opportunities exist to improve use of all of these services. Children and adolescents with no insurance and those with no usual source of health care (if available for analysis) were the groups least likely to have used the services. Use among the uninsured ranged from 1-39 percentage points below the general population averages, suggesting that improvements in insurance coverage that will result from the implementation of health-care reform are likely to increase use of these clinical preventive services. In 2012, a total of 4.9 million children (6.6% of children) were uninsured at the time of interview, and approximately 15% of eligible children in the United States are not enrolled in Medicaid and Children's Health Insurance Program (CHIP) programs. In addition, although opportunities exist for greater insurance coverage and for use of recommended clinical preventive services under the Patient Protection and Affordable Care Act of 2010 (P.L. 111-148), as amended by the Health Care and Education Reconciliation Act of 2010 (P.L. 111-152, together referred to as the Affordable Care Act [ACA]), a survey among the uninsured found a low level of awareness of the Health Insurance Marketplace (or Health Insurance Exchange) that can be used by families to acquire insurance or Medicaid coverage. The survey highlights the importance of focused efforts by governmental health agencies and other stakeholders to enroll uninsured children and adolescents in health plans. Also, although use of clinical preventive services in insured populations was greater than among the uninsured, use among the insured was generally <85%, and often much less. Therefore, having health insurance coverage alone might not be sufficient to optimize use of clinical preventive services, and additional measures to improve use probably will be necessary.

This supplement is the second of a series of periodic reports from a CDC initiative to monitor and report on the use of a set of selected clinical preventive services in the U.S. population in the context of recent national initiatives to improve access to and use of such services. Increasing the use of these services can result in substantial reductions in the burden of illness, death, and disability and lower treatment costs. This supplement focuses on services to improve the health of U.S. infants, children, and adolescents. The majority of clinical preventive services for infants, children, and adolescents are provided by the health-care sector. Public health agencies play important roles in increasing the use of these services by identifying and implementing policies that are effective in increasing use of the services and by collaborating with stakeholders to conduct programs to improve use. Recent health-reform initiatives, including efforts to increase the accessibility and affordability of preventive services, fund community prevention programs, and improve the use of health information technologies, offer opportunities to improve use of preventive services. This supplement, which follows a previous report on adult services, provides baseline information on the use of a set of selected clinical preventive services to improve the health of infants, children, and adolescents before implementation of these recent initiatives and discusses opportunities to increase the use of such services. This information can help public health practitioners, in collaboration with other stakeholders that have key roles in improving infant, child, and adolescent health (e.g., parents or guardians and their employers, health plans, health professionals, schools, child care facilities, community groups, and voluntary associations), understand the potential benefits of the recommended services, address the problem of underuse, and identify opportunities to apply effective strategies to improve use and foster accountability among stakeholders.

OBJECTIVE: To assess the knowledge, attitudes, and practices of infection control among staff in a residential care facility for children and young adults with neurologic and neurodevelopmental conditions. DESIGN: Self-administered survey. SETTING: Residential care facility (facility A). PARTICIPANTS: Facility A staff ([Formula: see text]). METHODS: We distributed a survey to staff at facility A. We classified staff with direct care responsibilities as clinical (ie, physicians, nurses, and therapists) or nonclinical (ie, habilitation assistants, volunteers, and teachers) and used chi(2) tests to measure differences between staff agreement to questions. RESULTS: Of 248 surveys distributed, 200 (81%) were completed; median respondent age was 36 years; 85% were female; and 151 were direct care staff (50 clinical, 101 nonclinical). Among direct care staff respondents, 86% agreed they could identify residents with respiratory symptoms, 70% stayed home from work when ill with respiratory infection, 64% agreed that facility administration encouraged them to stay home when ill with respiratory infection, and 72% reported that ill residents with respiratory infections were separated from well residents. Clinical and nonclinical staff differed in agreement about using waterless hand gel as a substitute for handwashing (96% vs 78%; [Formula: see text]) and whether handwashing was done after touching residents (92% vs 75%; [Formula: see text]). CONCLUSIONS: Respondents' knowledge, attitudes, and practices regarding infection control could be improved, especially among nonclinical staff. Facilities caring for children and young adults with neurologic and neurodevelopmental conditions should encourage adherence to infection control best practices among all staff having direct contact with residents.

We describe the efforts of the Maternal Health Team, which was formed to address the needs of pregnant and breastfeeding women during the Centers for Disease Control and Prevention's (CDC's) 2009 pandemic influenza A (2009 H1N1) emergency response. We examined the team's activities, constructed a timeline of key pandemic events, and analyzed the Maternal Health 2009 H1N1 inquiry database. During the pandemic response, 9 guidance documents that addressed the needs of pregnant and breastfeeding women and their providers were developed by the Maternal Health Team. The Team received 4661 maternal health-related inquiries that came primarily from the public (75.5%) and were vaccine related (69.3%). Peak inquiry volume coincided with peak hospitalizations (October-November 2009). The Maternal Health 2009 H1N1 inquiry database proved useful to identify information needs of the public and health care providers during the pandemic.

Pregnant women and their newborn infants are at increased risk for influenza-associated complications, based on data from seasonal influenza and influenza pandemics. The Centers for Disease Control and Prevention (CDC) developed public health recommendations for these populations in response to the 2009 H1N1 pandemic. A review of these recommendations and information that was collected during the pandemic is needed to prepare for future influenza seasons and pandemics. The CDC convened a meeting entitled "Pandemic Influenza Revisited: Special Considerations for Pregnant Women and Newborns" on August 12-13, 2010, to gain input from experts and key partners on 4 main topics: antiviral prophylaxis and therapy, vaccine use, intrapartum/newborn (including infection control) issues, and nonpharmaceutical interventions and health care planning. Challenges to communicating recommendations regarding influenza to pregnant women and their health care providers were also discussed. After careful consideration of the available information and individual expert input, the CDC updated its recommendations for these populations for future influenza seasons and pandemics.

BACKGROUND: US children consume folic acid from multiple sources. These sources may contribute differently to usual intakes above the age-specific tolerable upper intake level (UL) for folic acid and to folate and vitamin B-12 status. OBJECTIVE: We estimated usual daily folic acid intakes above the UL and adjusted serum and red blood cell folate, serum vitamin B-12, homocysteine, and methylmalonic acid (MMA) concentrations in US children by age group and by the following 3 major folic acid intake sources: enriched cereal-grain products (ECGP), ready-to-eat cereals (RTE), and supplements containing folic acid (SUP). DESIGN: We analyzed data in 4 groups of children aged 1-3, 4-8, 9-13, and 14-18 y from the National Health and Nutrition Examination Survey (NHANES), 2003-2006 (n = 7161). RESULTS: A total of 19-48% of children consumed folic acid from ECGP only. Intakes above the UL varied from 0-0.1% of children who consumed ECGP only to 15-78% of children who consumed ECGP+RTE+SUP. In children aged 1-8 y, 99-100% of those who consumed ≥200 mug folic acid/d from supplements exceeded their UL. Although <0.5% of children had folate deficiency or low vitamin B-12 status, the consumption of RTE or SUP with folic acid was associated with higher mean folate and vitamin B-12 concentrations and, in some older children, with lower homocysteine and MMA concentrations. CONCLUSIONS: Our data suggest that the majority of US children consume more than one source of folic acid. Postfortification, the consumption of RTE or SUP increases usual daily intakes and blood concentrations of folate and vitamin B-12.