Folic acid supplementation for pregnant women and those planning pregnancy: 2015 update

During the last decade critical new information has been published pertaining to folic acid supplementation in the prevention of neural tube defects (NTDs) and other folic acid-sensitive congenital malformations. These new data have important implications for women, their families, and health care professionals. We performed a review looking for the optimal dosage of folic acid that should be given to women of reproductive age who are planning or not avoiding conception to propose updated guidelines and thus help health care providers and patients. In addition to fortification of dietary staples with folic acid, women of reproductive age should supplement before conception with 0.4-1.0 mg of folic acid daily as part of their multivitamins. In the United States all enriched rice is also fortified with folic acid at 0.7 mg per pound of raw rice. However, this is not the case in many countries, and it has been estimated that only 1% of industrially milled rice is fortified with folic acid. In countries where rice is the main staple (eg, China), this does not allow effective folate fortification. Whereas the incidence of NTDs is around 1/1000 in the United States, it is 3- to 5-fold higher in Northern China and 3-fold higher in India. A recent population-based US study estimated that the reduction in NTD rates by folic acid is more modest than previously predicted. The potential of NTD prevention by folic acid is underutilized due to low adherence with folic acid supplementation, and calls for revising the policy of supplementation have been raised. We identified groups of women of reproductive age who may benefit from higher daily doses of folic acid, and this should be considered in current practice. These include women who have had previous pregnancies with NTDs, those who did not plan their pregnancy and hence did not supplement, and women with low intake or impaired adherence to daily folic acid supplementation. In addition, women with known genetic variations in the folate metabolic cycle, those exposed to medications with antifolate effects, smokers, diabetics, and the obese may benefit from higher doses of folic acid daily during the first trimester

Description of 3,180 courses of chelation with dimercaptosuccinic acid in children ≤ 5 y with severe lead poisoning in Zamfara, Northern Nigeria: a retrospective analysis of programme data.

BACKGROUND: In 2010, Médecins Sans Frontières (MSF) discovered extensive lead poisoning impacting several thousand children in rural northern Nigeria. An estimated 400 fatalities had occurred over 3 mo. The US Centers for Disease Control and Prevention (CDC) confirmed widespread contamination from lead-rich ore being processed for gold, and environmental management was begun. MSF commenced a medical management programme that included treatment with the oral chelating agent 2,3-dimercaptosuccinic acid (DMSA, succimer). Here we describe and evaluate the changes in venous blood lead level (VBLL) associated with DMSA treatment in the largest cohort of children ≤ 5 y of age with severe paediatric lead intoxication reported to date to our knowledge. METHODS AND FINDINGS: In a retrospective analysis of programme data, we describe change in VBLL after DMSA treatment courses in a cohort of 1,156 children ≤ 5 y of age who underwent between one and 15 courses of chelation treatment. Courses of DMSA of 19 or 28 d duration administered to children with VBLL ≥ 45 µg/dl were included. Impact of DMSA was calculated as end-course VBLL as a percentage of pre-course VBLL (ECP). Mixed model regression with nested random effects was used to evaluate the relative associations of covariates with ECP. Of 3,180 treatment courses administered, 36% and 6% of courses commenced with VBLL ≥ 80 µg/dl and ≥ 120 µg/dl, respectively. Overall mean ECP was 74.5% (95% CI 69.7%-79.7%); among 159 inpatient courses, ECP was 47.7% (95% CI 39.7%-57.3%). ECP after 19-d courses (n = 2,262) was lower in older children, first-ever courses, courses with a longer interval since a previous course, courses with more directly observed doses, and courses with higher pre-course VBLLs. Low haemoglobin was associated with higher ECP. Twenty children aged ≤ 5 y who commenced chelation died during the period studied, with lead poisoning a primary factor in six deaths. Monitoring of alanine transaminase (ALT), creatinine, and full blood count revealed moderate ALT elevation in <2.5% of courses. No clinically severe adverse drug effects were observed, and no laboratory findings required discontinuation of treatment. Limitations include that this was a retrospective analysis of clinical data, and unmeasured variables related to environmental exposures could not be accounted for. CONCLUSIONS: Oral DMSA was a pharmacodynamically effective chelating agent for the treatment of severe childhood lead poisoning in a resource-limited setting. Re-exposure to lead, despite efforts to remediate the environment, and non-adherence may have influenced the impact of outpatient treatment. Please see later in the article for the Editors' Summary

Averting the foul taste of pediatric medicines improves adherence and can be lifesaving - Pheburane® (sodium phenylbutyrate)

Background: Children’s aversions to poor and mostly bitter tastes and their inability to swallow tablets and capsules are major challenges in pediatric medicine. Sodium phenylbutyrate (NaPB) is a lifesaving waste nitrogen, alternative to urea nitrogen, for individuals suffering from urea cycle disorders. A major issue in the use of NaPB is its highly foul taste, which often leads to children being unable to consume it, resulting in ineffective treatment, or alternatively, necessitating the application of the drug through a nasogastric tube or gastrostomy. Methods: This study reviews the published data on a novel formulation of NaPB, Pheburane® granules, which begin to release their NaPB after a lag time of ~10 seconds followed by a slow release over several minutes. Results: The taste-masked granule formulation of NaPB dramatically improves the acceptability of the drug by children and appears in initial studies to be both safe and effective. Conclusion: While more studies are needed to substantiate and enrich these initial trials, the available data provide a telling example where masking the drug taste of medicine for children can sometimes be the difference between life and death

Exploratory Spatial Data Analysis of Congenital Malformations (CM) in Israel, 2000–2006

Congenital Malformations (CM) impose a heavy burden on families and society. Identification of spatial patterns of CM is useful for understanding the epidemiology of this public health issue. In Israel, about 1,000,000 births and 25,000 CM cases at 37 groups were geocoded during 2000–2006. These were geo-analyzed using global-Moran’s-I statistics. Eight groups demonstrated geospatial heterogeneity and were further analyzed at both the census tract (Local Indicator of Spatial Association (LISA) and hot spot analyses) and street levels (spatial scan statistics with two population threshold sizes). The positional definition of results is further discussed in relevance to possible exposure to teratogenic sources in the region. Limitations of data and methods used are presented as well

Green spaces and adverse pregnancy outcomes

Objective: The objective of this study was to evaluate the associations between proximity to green spaces and surrounding greenness and pregnancy outcomes, such as birth weight, low birth weight (LBW), very LBW (VLBW), gestational age, preterm deliveries (PTD) and very PTD (VPTD). Methods: This study was based on 39 132 singleton live births from a registry birth cohort in Tel Aviv, Israel, during 2000–2006. Surrounding greenness was defined as the average of satellite-based Normalised Difference Vegetation Index (NDVI) in 250 m buffers and proximity to major green spaces was defined as residence within a buffer of 300 m from boundaries of a major green space (5000 m2), based on data constructed from OpenStreetMap. Linear regression (for birth weight and gestational age) and logistic regressions models (for LBW, VLBW, PTD and VPTD) were used with adjustment for relevant covariates. Results: An increase in 1 interquartile range greenness was associated with a statistically significant increase in birth weight (19.2 g 95% CI 13.3 to 25.1) and decreased risk of LBW (OR 0.84, 95% CI 0.78 to 0.90). Results for VLBW were in the same direction but were not statistically significant. In general, no associations were found for gestational age, PTD and VPTD. The findings were consistent with different buffer and green space sizes and stronger associations were observed among those of lower socioeconomic status. Conclusions: This study confirms the results of a few previous studies demonstrating an association between maternal proximity to green spaces and birth weight. Further investigation is needed into the associations with VLBW and VPTD, which has never been studied before

Flow chart of children commencing chelation in period analysed, with inclusion and exclusion in analysis and death outcomes.

<p>Lead was attributed as the primary cause of death where there was a high (>100 µg/dl) VBLL within 10 d before death, where there was no other obvious cause, and where lead toxicity could not be excluded as a cause. Lead was attributed as a contributory cause where a serious comorbidity was present (measles, bronchopneumonia, malaria, septicaemia, or severe malnutrition) but with a recent VBLL> 90 µg/dl. Deaths were categorized as “no clear role of lead” where there was another obvious cause (e.g., fell into an open well, anaemic heart failure, or measles) and no recent VBLL> 65 µg/dl. Reasons for not including in the study cohort were not finishing the chelation course (through defaulting or death before end of course) or no VBLL recorded at end of course. *All died during first treatment course. †Two died during first treatment course.</p