Jorge Rosenthal

Describing the Prevalence of Neural Tube Defects Worldwide: A Systematic Literature Review

Background Folate-sensitive neural tube defects (NTDs) are an important, preventable cause of morbidity and mortality worldwide. There is a need to describe the current global burden of NTDs and identify gaps in available NTD data. Methods and Findings We conducted a systematic review and searched multiple databases for NTD prevalence estimates and abstracted data from peer-reviewed literature, birth defects surveillance registries, and reports published between January 1990 and July 2014 that had greater than 5,000 births and were not solely based on mortality data. We classified countries according to World Health Organization (WHO) regions and World Bank income classifications. The initial search yielded 11,614 results; after systematic review we identified 160 full text manuscripts and reports that met the inclusion criteria. Data came from 75 countries. Coverage by WHO region varied in completeness (i.e., % of countries reporting) as follows: African (17%), Eastern Mediterranean (57%), European (49%), Americas (43%), South-East Asian (36%), and Western Pacific (33%). The reported NTD prevalence ranges and medians for each region were: African (5.2–75.4; 11.7 per 10,000 births), Eastern Mediterranean (2.1–124.1; 21.9 per 10,000 births), European (1.3–35.9; 9.0 per 10,000 births), Americas (3.3–27.9; 11.5 per 10,000 births), South-East Asian (1.9–66.2; 15.8 per 10,000 births), and Western Pacific (0.3–199.4; 6.9 per 10,000 births). The presence of a registry or surveillance system for NTDs increased with country income level: low income (0%), lower-middle income (25%), upper-middle income (70%), and high income (91%). Conclusions Many WHO member states (120/194) did not have any data on NTD prevalence. Where data are collected, prevalence estimates vary widely. These findings highlight the need for greater NTD surveillance efforts, especially in lower-income countries. NTDs are an important public health problem that can be prevented with folic acid supplementation and fortification of staple foods.

Factors Associated with Underimmunization at 3 Months of Age in Four Medically Underserved Areas

Objective. Risk factors for underimmunization at 3 months of age are not well described. This study examines coverage rates and factors associated with underimmunization at 3 months of age in four medically underserved areas. Methods. During 1997–1998, cross-sectional household surveys using a two-stage cluster sample design were conducted in four federally designated Health Professional Shortage Areas. Respondents were parents or caregivers of children ages 12–35 months: 847 from northern Manhattan, 843 from Detroit, 771 from San Diego, and 1,091 from rural Colorado. A child was considered up-to-date (UTD) with vaccinations at 3 months of age if documentation of receipt of diphtheria-tetanus-pertussis, polio, haemophilus influenzae type B, and hepatitis B vaccines was obtained from a provider or a hand-held vaccination card, or both. Results. Household response rates ranged from 79% to 88% across sites. Vaccination coverage levels at 3 months of age varied across sites: 82.4% in northern Manhattan, 70.5% in Detroit, 82.3% in San Diego, and 75.8% in rural Colorado. Among children who were not UTD, the majority (65.7% to 71.5% per site) had missed vaccines due to missed opportunities. Factors associated with not being UTD varied by site and included having public or no insurance, ⩾2 children living in the household, and the adult respondent being unmarried. At all sites, vaccination coverage among WIC enrollees was higher than coverage among children eligible for but not enrolled in WIC, but the association between UTD status and WIC enrollment was statistically significant for only one site and marginally significant for two other sites. Conclusions. Missed opportunities were a significant barrier to vaccinations, even at this early age. Practice-based strategies to reduce missed opportunities and prenatal WIC enrollment should be focused especially toward those at highest risk of underimmunization.

Assessing the association between the methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism and blood folate concentrations: a systematic review and meta-analysis of trials and observational studies

BACKGROUND The methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism is a risk factor for neural tube defects. The T allele produces an enzyme with reduced folate-processing capacity, which has been associated with lower blood folate concentrations. OBJECTIVE We assessed the association between MTHFR C677T genotypes and blood folate concentrations among healthy women aged 12-49 y. DESIGN We conducted a systematic review of the literature published from January 1992 to March 2014 to identify trials and observational studies that reported serum, plasma, or red blood cell (RBC) folate concentrations and MTHFR C677T genotype. We conducted a meta-analysis for estimates of percentage differences in blood folate concentrations between genotypes. RESULTS Forty studies met the inclusion criteria. Of the 6 studies that used the microbiologic assay (MA) to measure serum or plasma (S/P) and RBC folate concentrations, the percentage difference between genotypes showed a clear pattern of CC > CT > TT. The percentage difference was greatest for CC > TT [S/P: 13%; 95% credible interval (CrI): 7%, 18%; RBC: 16%; 95% CrI: 12%, 20%] followed by CC > CT (S/P: 7%; 95% CrI: 1%, 12%; RBC: 8%; 95% CrI: 4%, 12%) and CT > TT (S/P: 6%; 95% CrI: 1%, 11%; RBC: 9%; 95% CrI: 5%, 13%). S/P folate concentrations measured by using protein-binding assays (PBAs) also showed this pattern but to a greater extent (e.g., CC > TT: 20%; 95% CrI: 17%, 22%). In contrast, RBC folate concentrations measured by using PBAs did not show the same pattern and are presented in the Supplemental Material only. CONCLUSIONS Meta-analysis results (limited to the MA, the recommended population assessment method) indicated a consistent percentage difference in S/P and RBC folate concentrations across MTHFR C677T genotypes. Lower blood folate concentrations associated with this polymorphism could have implications for a population-level risk of neural tube defects.

Assessing immunization performance of private practitioners in Maine: impact of the assessment, feedback, incentives, and exchange strategy.

Introduction. A provider-based vaccination strategy that has strong supportive evidence of efficacy at raising immunization coverage level is known as Assessment, Feedback, Incentives, and Exchange. The Maine Immunization Program, and the Maine Chapter of the American Academy of Pediatrics collaborated on the implementation and evaluation of this strategy among private providers. Methods. Between November 1994 and June 1996, the Maine Immunization Program conducted baseline immunization assessments of all private practices administering childhood vaccines to children 24 to 35 months of age. Coverage level assessments were conducted using the Clinic Assessment Software Application. Follow-up assessments were among the largest practices, delivering 80% of all vaccines. Results. Of the 231 practices, 58 were pediatric and 149 were family practices. The median up-to-date vaccination coverages among all providers for 3 doses of diphtheria-tetanus-pertussis vaccine and 2 doses of oral polio vaccine, and 4 doses of diphtheria-tetanus-pertussis vaccine, 3 doses of oral polio vaccine, and 1 dose of measles-mumps-rubella vaccine at age 12 and 24 months were 90% and 78%, respectively, and did not vary by number of providers in a practice or by specialty. Urban practices had higher coverage than rural practices at 12 months (92% vs 88%). The median up-to-date coverage for 4 doses of diphtheria-tetanus-pertussis vaccine, 3 doses of oral polio vaccine, and 1 dose of measles-mumps-rubella vaccine at 24 months of age improved significantly among those practices assessed 1 year later (from 78% at baseline to 87% at the second assessment). On average, the assessments required 2½ person-days of effort. Conclusions. We document the feasibility and impact of a public/private partnership to improve immunization delivery on a statewide basis. Implications. Other states should consider using public/private partnerships to conduct private practice assessments. More cost-effective methods of assessing immunization coverage levels in private practices are needed.

Neural tube defects in Latin America and the impact of fortification: A literature review

OBJECTIVE Data on the prevalence of birth defects and neural tube defects (NTD) in Latin America are limited. The present review summarizes NTD prevalence and time trends in Latin American countries and compares pre- and post-fortification periods to assess the impact of folic acid fortification in these countries. DESIGN We carried out a literature review of studies and institutional reports published between 1990 and 2010 that contained information on NTD prevalence in Latin America. RESULTS NTD prevalence in Latin American countries varied from 0·2 to 9·6 per 1000 live births and was influenced by methods of ascertainment. Time trends from Bogota, Costa Rica, Dominican Republic, Guatemala City, Mexico and Puerto Rico showed average annual declines of 2·5 % to 21·8 %. Pre- and post-fortification comparisons were available for Argentina, Brazil, Chile, Costa Rica, Puerto Rico and Mexico. The aggregate percentage decline in NTD prevalence ranged from 33 % to 59 %. CONCLUSIONS The present publication is the first to review data on time trends and the impact of folic acid fortification on NTD prevalence in Latin America. Reported NTD prevalence varied markedly by geographic region and in some areas of Latin America was among the lowest in the world, while in other areas it was among the highest. For countries with available information, time trends showed significant declines in NTD prevalence and these declines were greater in countries where folic acid fortification of staples reached the majority of the population at risk, such as Chile and Costa Rica.

Fragmentation of immunization history among providers and parents of children in selected underserved areas

OBJECTIVE We assessed fragmentation of childrens immunization history among providers and parents of children aged 12 to 35 months in four selected underserved areas. STUDY DESIGN Area probability cluster sample surveys were conducted in 1997-1998 in northern Manhattan, San Diego, Detroit, and rural Colorado. Surveys consisted of face-to-face interviews with parents followed by record checks with all named immunization providers. We used Advisory Committee on Immunization Practices recommendations to determine up-to-date (UTD) status with vaccinations. The UTD status for each child was determined in four ways: (1) according to the parent-held immunization records, (2) according to the records of the childs most recent provider, (3) according to the records of the childs second most recent provider, and (4) according to provider and parent-reconciled information. RESULTS In all four areas, the majority of records of the most recent provider agreed with the reconciled information. However, in all areas, the percentage of children UTD according to provider- and parent-reconciled information was higher than the percentage of children UTD according to information from only the childs most recent provider or from only parent-held immunization records. Across all sites, the percentage of children UTD with the DTP/DTaP vaccine was 2% to 9% lower, according to the most recent providers information than according to reconciled information. Similar results were seen for other vaccines. The most recent provider not having complete immunization history was significantly associated with not being UTD in New York and having received unnecessary immunizations in San Diego and Detroit. CONCLUSION For most children, although the records of the most recent provider give accurate data for clinical decision making, the immunization histories of some children in these underserved areas are fragmented between providers and parents. This can limit the providers ability to vaccinate children appropriately.

Do Laws Bring Children in Child Care Centers Up to Date for Immunizations

BACKGROUND Pennsylvania state law requires licensed child care centers (CCCs) to document that each enrolled child is up to date (UTD) for routine immunizations within 60 days of enrollment. This study evaluates the laws impact on immunization coverage among children aged <or=59 months who attend CCCs in Philadelphia. METHODS Out of Philadelphias 440 commercial CCCs, 75 were randomly selected. Of these, 9 had closed, 3 did not accept children aged <or=59 months, and 3 refused assessment. For the remaining 60 CCCs, vaccination dates were abstracted from CCC records for all enrolled children <or=59 months. For children not UTD for all vaccines according to CCC records, additional data were sought from Philadelphias immunization registry, health care providers, and parents. RESULTS Records of 2847 children were assessed. According to CCC records, information from the immunization registry, vaccination providers, and parents, 71% of children aged 0-18 months, 77% of children 19-35 months, and 84% of children 36-59 months were UTD for their age for diphtheria, tetanus toxoids, and pertussis vaccine; polio; Haemophilus influenzae type b; and measles, mumps, and rubella vaccines. No significant increase in immunization coverage levels was found between the date children enrolled in a CCC and 60 days later. CONCLUSIONS Up to one quarter of children <5 years of age enrolled in Philadelphias CCCs are not UTD for immunizations, with children 0-18 months of age being most behind in their immunizations. Furthermore, many children do not receive vaccines within 60 days of enrollment. These low coverage levels combined with the potential exposures inherent in group care settings indicate that children in CCCs are at risk for contracting vaccine-preventable diseases.

African-American Children Are at Risk of a Measles Outbreak in an Inner-City Community of Chicago, 2000

BACKGROUND Since the measles resurgence of 1989-1991, which affected predominantly inner-city preschoolers, national vaccination rates have risen to record-high levels, but rates among inner-city, preschool-aged, African-American children lag behind national rates. The threat of measles importations from abroad exists and may be particularly important in large U.S. cities. To stop epidemic transmission, measles vaccination coverage should be at least 80%. OBJECTIVE To determine measles vaccination rates and predictors for having received a dose of measles-containing vaccine by age 19 to 35 months among children in an inner-city community of Chicago. METHODS We used a cross-sectional survey with probability proportional to size cluster sampling. Immunization histories from parent-held records and providers were combined to establish a complete vaccination history. RESULTS A total of 2545 households were contacted, and 170 included a resident child aged 12 to 35 months. Of these, 97% (N=165 children) agreed to participate. Immunization history from a parent or provider was not available for 20 children. Among children aged 19 to 35 months with available immunization histories, 74% received measles vaccine (n=100); of these, 84% received the vaccine as recommended at ages 12 to 15 months. However, when including children without immunization histories, measles coverage levels among children aged 19 to 35 months were 64% (n=114). Among children with records, predictors for receipt of measles vaccine by age 19 to 35 months were possessing a hand-held immunization card (odds ratio [OR]=16.8; 95% confidence interval [CI]=4.2-67.1); utilizing a public health department provider for a usual source of care (OR=8.9; 95% CI=1.6-47.2); and being up-to-date for vaccines at 3 months of age (OR=5.0; 95% CI=1.8-14.1). CONCLUSIONS Optimistically assuming that children without immunization histories are as well immunized as children with immunization histories, the measles vaccination rate among Englewoods children aged 19 to 35 months is too low to maintain immunity (74%). Measles coverage levels lagged behind coverage reported in a national survey in Chicago (86%) and the nation as a whole (92%). Efforts to raise and sustain coverage should be undertaken.

Assessing the Association between Natural Food Folate Intake and Blood Folate Concentrations: A Systematic Review and Bayesian Meta-Analysis of Trials and Observational Studies

Folate is found naturally in foods or as synthetic folic acid in dietary supplements and fortified foods. Adequate periconceptional folic acid intake can prevent neural tube defects. Folate intake impacts blood folate concentration; however, the dose-response between natural food folate and blood folate concentrations has not been well described. We estimated this association among healthy females. A systematic literature review identified studies (1 1992–3 2014) with both natural food folate intake alone and blood folate concentration among females aged 12–49 years. Bayesian methods were used to estimate regression model parameters describing the association between natural food folate intake and subsequent blood folate concentration. Seven controlled trials and 29 observational studies met the inclusion criteria. For the six studies using microbiologic assay (MA) included in the meta-analysis, we estimate that a 6% (95% Credible Interval (CrI): 4%, 9%) increase in red blood cell (RBC) folate concentration and a 7% (95% CrI: 1%, 12%) increase in serum/plasma folate concentration can occur for every 10% increase in natural food folate intake. Using modeled results, we estimate that a natural food folate intake of ≥450 μg dietary folate equivalents (DFE)/day could achieve the lower bound of an RBC folate concentration (~1050 nmol/L) associated with the lowest risk of a neural tube defect. Natural food folate intake affects blood folate concentration and adequate intakes could help women achieve a RBC folate concentration associated with a risk of 6 neural tube defects/10,000 live births.

Postpartum women in the Honduran health system: folic acid knowledge, attitudes, and practices

OBJECTIVES This study had two purposes: first, to determine the knowledge, attitudes, and practices related to folic acid and birth defects among a convenience sample of postpartum Honduran women; and second, to identify food consumption patterns in this population and determine high-consumption staples for potential folic acid fortification. METHODS Convenience sampling methodology was used to recruit potential study participants. Participants for this study were 2 619 postpartum Honduran women who had had a normal, in-hospital delivery in one of 16 public hospitals located throughout the country or the two social security hospitals that provide services to the Honduran working class population. Over a 10-month period, in-depth, face-to-face oral interviews, supervised by the research coordinator and staff, were conducted in-hospital prior to discharge. RESULTS The majority of the women were between 16 and 29 years of age. Approximately half of the respondents (46.4%) had heard of folic acid and over one-third (37.6%) knew that it was a vitamin related to preventing birth defects. Birth defects were most often attributed to drug and alcohol use (20.6%) and lack of vitamin intake (18.1%), but 23.0% related defects to mystical, mythical, or religious causes. Aside from red beans, oranges, and natural fruit juices, folate-rich foods are not widely consumed by this population. The highest consumption frequency of staple foods with the potential to be fortified with folic acid were rice, white flour, corn flour, and pasta. CONCLUSIONS Results from this study provide potential avenues for food fortification, as well as underscore the need for further education about the role of folic acid in the prevention of neural tube defects. Results highlight that standardized health education for Honduran women of reproductive age is needed if folic acid consumption through fortification and supplementation is to be successful and sustainable.