Post-neonatal mortality, morbidity, and developmental outcome after ultrasound-dated preterm birth in rural Malawi: a community-based cohort study

Background

Preterm birth is considered to be associated with an estimated 27% of neonatal deaths, the majority in resource-poor countries where rates of prematurity are high. There is no information on medium term outcomes after accurately determined preterm birth in such settings.

Methods and Findings

This community-based stratified cohort study conducted between May–December 2006 in Southern Malawi followed up 840 post-neonatal infants born to mothers who had received antenatal antibiotic prophylaxis/placebo in an attempt to reduce rates of preterm birth (APPLe trial ISRCTN84023116). Gestational age at delivery was based on ultrasound measurement of fetal bi-parietal diameter in early-mid pregnancy. 247 infants born before 37 wk gestation and 593 term infants were assessed at 12, 18, or 24 months. We assessed survival (death), morbidity (reported by carer, admissions, out-patient attendance), growth (weight and height), and development (Ten Question Questionnaire [TQQ] and Malawi Developmental Assessment Tool [MDAT]). Preterm infants were at significantly greater risk of death (hazard ratio 1.79, 95% CI 1.09–2.95). Surviving preterm infants were more likely to be underweight (weight-for-age z score; p<0.001) or wasted (weight-for-length z score; p<0.01) with no effect of gestational age at delivery. Preterm infants more often screened positively for disability on the Ten Question Questionnaire (p = 0.002). They also had higher rates of developmental delay on the MDAT at 18 months (p = 0.009), with gestational age at delivery (p = 0.01) increasing this likelihood. Morbidity—visits to a health centre (93%) and admissions to hospital (22%)—was similar for both groups.

Conclusions

During the first 2 years of life, infants who are born preterm in resource poor countries, continue to be at a disadvantage in terms of mortality, growth, and development. In addition to interventions in the immediate neonatal period, a refocus on early childhood is needed to improve outcomes for infants born preterm in low-income settings. Please see later in the article for the Editors'' Summary     

Household vulnerability to food crisis and mortality in the drought-prone areas of northern Ethiopia

This study examines the association between a household's degree of vulnerability to food crisis and the incidence of deaths using primary survey data carried out to look at the demographic consequences of drought and famine in the drought-prone areas of northern Ethiopia. Retrospective data on the occurrences of deaths within a household were collected for the period 1984 to 1994. Consistent with previous studies, the findings confirm that mortality was clustered among the age groups 1-4 and 5-9 and varied considerably by famine and non-famine years. Enormous variation in incidence of deaths was also observed by region, ethnicity and religion. Most importantly, the analysis provides substantial evidence that the level of household vulnerability to food crisis is strongly related to the number of hunger-related deaths reported in a household.     

Bumblebee community homogenization after uphill shifts in montane areas of northern Spain

Widespread alterations in species distribution and abundance as a result of global environmental change include upwards and polewards shifts driven by local extinctions in the south or at lower elevations and colonizations of newly available habitat elements in the north or at higher elevations. Although cumulative changes on patterns of community composition are also expected, studies following a community-level approach are still scarce. Here, we estimate changes in abundance and distribution of bumblebee (Bombus spp.) species over two decades along an elevational gradient to test whether these changes entailed concomitant alterations on patterns of community composition. Bumblebee species showed an overall trend to shift uphill their upper- or lower-elevational boundaries, resulting in narrower elevational ranges from one period to another, coincident with a regional warming of ca. 0.9 °C. Changes in elevational ranges were, however, mainly related to retractions of the lower limit of species distribution, rather than to variations in their upper elevational limit. Species turnover was associated with colonization and extinction events and also with variability in the relative abundance of short-, medium- and long-tongued species along the elevational gradient. Extinctions were especially relevant at medium elevations, while only communities at higher elevations had a positive net outcome between colonization and extinction events. The combination of these effects resulted in the homogenization of bumblebee assemblages, especially between medium and upper elevations. The changes reported in our study strongly match with predictions of global change driving elevational shifts in species distribution and provide the first evidence of elevational changes in bumblebees at both species and community level.     

Quinolone therapy in the prevention of mortality after irradiation

The effect of oral therapy with three quinolones (ofloxacin, ciprofloxacin, and pefloxacin) in the prevention of postirradiation bacteremia and mortality was tested in B6D2F1 mice given 9.5 Gy 60Co gamma radiation. Only 8 of 60 (13%) untreated mice survived for 30 days, compared to 47 of 60 (78%) mice treated with ofloxacin, 44 of 60 (74%) mice treated with ciprofloxacin, and 42 of 60 (70%) mice treated with pefloxacin (P less than 0.05). The organisms recovered from the mice were Streptococcus spp. and Enterobacteriaceae. More Enterobacteriaceae were recovered from the livers of untreated animals than from the mice treated with the quinolones. However, no reduction in the number of Streptococcus spp. was noted in the animals given quinolones when compared to controls. This study shows that quinolones prolonged survival and decreased systemic spread of Enterobacteriaceae up to 30 days after exposure of mice to lethal irradiation.     

The effect of women's status on infant and child mortality in four rural areas of Bangladesh

In South Asia women are often the primary decision-makers regarding child health care, family health and nutrition. This paper examines the proposition that constraints on women's status adversely affect the survival of their children. Survey data are used to construct indices of women's household autonomy and authority, which are then linked to longitudinal data on survival of their children. Proportional hazard models indicate that enhanced autonomy significantly decreases post-neonatal mortality. Enhanced household authority significantly decreases child mortality. A simulation based on estimated effects of eliminating gender inequality suggests that achieving complete gender equality could reduce child mortality by nearly fifty per cent and post-neonatal mortality by one-third.     

Contrasting patterns of tree mortality in late‐successional Picea abies stands in two areas in northern Fennoscandia

Question: What are tree mortality rates and how and why do they vary in late‐successional Picea abies‐dominated forests? Do observed tree mortality patterns allow comparative assessment of models of long‐term stand development? Location: Northern boreal Fennoscandia. Methods: We measured stand structure in 10 stands in two different areas. We determined age distributions and constructed a chronology of tree deaths by cross‐dating the years of death of randomly sampled dead trees. Results: The stands in the two areas had contrasting tree age distributions, despite similar live tree structure. In one area, stands were relatively even‐aged and originated following a stand‐replacing fire 317 years earlier. The stands in the second area had an uneven age structure and virtually no signs of past fires, suggesting a very long period since the last major disturbance. The younger stands were characterized by a high mortality rate and inter‐annual variation, which we attributed to senescence of the relatively even‐aged stands approaching the maximum age of P. abies. In contrast, the tree mortality rates in the older stands were low and relatively stable. Conclusions: Patterns of tree mortality were, to a large extent, dependent on the time since the last stand‐replacing disturbance, suggesting that northern boreal P. abies stands eventually reach a shifting mosaic state maintained through small‐scale dynamics, but the time needed to reach this state appears to be lengthy; even 300 years after a forest fire stands showed changes in patterns of tree mortality that were related to the developmental stage of the stands.     

Disuse-induced deterioration of bone strength is not stopped after free remobilization in young adult rats

The effect of unilateral hindlimb immobilization and subsequent free remobilization on mechanical properties of femur was examined in young adult rats. Right hindlimb of 17 weeks old male rats was immobilized for 2 weeks. Rats were sacrificed either directly after immobilization (E0) or after 4 weeks of free remobilization (E4). Mechanical properties in three-point bending as well as dry mass (m_dry), geometry, apparent density (d_app), and mineralization of dry bone tissue were measured post mortem in right and left femora of experimental rats (E0, E4) and in right femora of age-matched controls (C0, C4). Differences between right femora of experimental and control animals and between right and left femora of experimental animals were analyzed. After immobilization only d_app in E0 was significantly lower than in C0. Side-to-side differences in E0 were present only in m_dry and d_app. Surprisingly, 4 weeks after remobilization the differences between experimental and control femora were more pronounced. Mineralization, d_app, maximum bending moment (M_max), yield bending moment (M_y) and stiffness of the right femur were lower in E4 than in age-matched C4. Side-to-side differences in remobilized rats (E4) were still significant for m_dry and d_app. Additionally, the medullary area was larger, and M_max, M_y, stiffness and work to failure were lower in the right femur than in the left. It is concluded, that the processes of bone deterioration initiated during immobilization do not cease immediately after resumption of normal mechanical loading.     

Association of age with mortality and virological and immunological response to antiretroviral therapy in rural South African adults

Objective

To assess whether treatment outcomes vary with age for adults receiving antiretroviral therapy (ART) in a large rural HIV treatment cohort.

Design

Retrospective cohort analysis using data from a public HIV Treatment & Care Programme.

Methods

Adults initiating ART 1^st August 2004 - 31^st October 2009 were stratified by age at initiation: young adults (16–24 years) mid-age adults (25–49 years) and older (≥50 years) adults. Kaplan-Meier survival analysis was used to estimate mortality rates and age and person-time stratified Cox regression to determine factors associated with mortality. Changes in CD4 cell counts were quantified using a piecewise linear model based on follow-up CD4 cell counts measured at six-monthly time points.

Results

8846 adults were included, 808 (9.1%) young adults; 7119 (80.5%) mid-age adults and 919 (10.4%) older adults, with 997 deaths over 14,778 person-years of follow-up. Adjusting for baseline characteristics, older adults had 32% excess mortality (p = 0.004) compared to those aged 25–49 years. Overall mortality rates (MR) per 100 person-years were 6.18 (95% CI 4.90–7.78); 6.55 (95% CI 6.11–7.02) and 8.69 (95% CI 7.34–10.28) for young, mid-age and older adults respectively. In the first year on ART, for older compared to both young and mid-aged adults, MR per 100 person-years were significantly higher; 0–3 months (MR: 27.1 vs 17.17 and 21.36) and 3–12 months (MR: 9.5 vs 4.02 and 6.02) respectively. CD4 count reconstitution was lower, despite better virological response in the older adults. There were no significant differences in MR after 1year of ART. Baseline markers of advanced disease were independently associated with very early mortality (0–3 months) whilst immunological and virological responses were associated with mortality after 12months.

Conclusions

Early ART initiation and improving clinical care of older adults are required to reduce high early mortality and enhance immunologic recovery, particularly in the initial phases of ART.     

A cluster randomised controlled trial of the community effectiveness of two interventions in rural Malawi to improve health care and to reduce maternal, newborn and infant mortality

Background

Paclitaxel-eluting stents decrease angiographic and clinical restenosis following percutaneous coronary intervention compared to bare metal stents. TAXUS Element is a third-generation paclitaxel-eluting stent which incorporates a novel, thinner-strut, platinum-enriched metal alloy platform. The stent is intended to have enhanced radiopacity and improved deliverability compared to other paclitaxel-eluting stents. The safety and efficacy of the TAXUS Element stent are being evaluated in the pivotal PERSEUS clinical trials.

Methods/Design

The PERSEUS trials include two parallel studies of the TAXUS Element stent in single, de novo coronary atherosclerotic lesions. The PERSEUS Workhorse study is a prospective, randomized (3:1), single-blind, non-inferiority trial in subjects with lesion length ≤28 mm and vessel diameter ≥2.75 mm to ≤4.0 mm which compares TAXUS Element to the TAXUS Express² paclitaxel-eluting stent system. The Workhorse study employs a novel Bayesian statistical approach that uses prior information to limit the number of study subjects exposed to the investigational device and thus provide a safer and more efficient analysis of the TAXUS Element stent. PERSEUS Small Vessel is a prospective, single-arm, superiority trial in subjects with lesion length ≤20 mm and vessel diameter ≥2.25 mm to <2.75 mm that compares TAXUS Element with a matched historical bare metal Express stent control.

Discussion

The TAXUS PERSEUS clinical trial program uses a novel statistical approach to evaluate whether design and metal alloy iterations in the TAXUS Element stent platform provide comparable safety and improved procedural performance compared to the previous generation Express stent. PERSEUS trial enrollment is complete and primary endpoint data are expected in 2010. PERSEUS Workhorse and Small Vessel are registered at http://www.clinicaltrials.gov, identification numbers NCT00484315 and NCT00489541.     

Benefits of using magnesium sulphate (MgSO4) for eclampsia management and maternal mortality reduction: lessons from Kano State in northern Nigeria

ABSTRACT: BACKGROUND: Despite clear emphasis through the Millennium Development Goals, the problem of high maternal mortality persists especially within low and middle income countries. Various studies report remarkably high maternal mortality rates in northern Nigeria, where maternal mortality rates exceed 1,000 deaths per 100,000 live births and eclampsia contributes approximately 40% of maternal deaths. Across Nigeria, diazepam is routinely used for the management of eclampsia. Prior to February 2008, diazepam was widely used for the management of eclampsia in Kano state (within northern Nigeria) with case fatality rate being over 20%. While magnesium sulphate (MgSO4) is recognized as the most effective drug for the management of eclampsia; this study aims to compare MgSO4 therapy with diazepam therapy in terms of case fatality rates and costs. FINDINGS: This retrospective study, including 1045 patients with eclampsia and pre-eclampsia during the years 2008 and 2009, reports a drop in case fatality rates from 20.9% (95% CI: 18.7, 23.2) to 2.3% (95% CI: 1.4, 3.2) among eclampsia patients following the MgSO4 intervention. The study observed no significant difference in the cost of using MgSO4 therapy compared to diazepam therapy. CONCLUSIONS: The study found a remarkable reduction in case fatality rate due to eclampsia in those who received MgSO4 therapy with minimal increase in costs when compared to diazepam therapy. Concerted efforts should be focused on properly introducing MgSO4 into emergency obstetric protocols especially within developing countries to reduce maternal mortality and also impact on health system performance.     

Temporal changes in free iron levels after brain ischemia Relevance to the timing of iron chelation therapy in stroke

Whereas iron chelators have been proposed as therapeutic agents in stroke, changes in free iron levels have never been explored after focal brain ischemia. Therefore, free and total iron levels in cortical tissue and free iron levels in plasma were measured before and after (1, 4 and 24h) photothrombotic occlusion of cortical vessels in rats. Brain ferritin expression and localization were also investigated before and after (24, 72 and 192 h) occlusion. The results showed that free iron remained below detectable levels in plasma and that the lesion exhibited high levels of free and total iron. As compared to contralateral values, free iron levels in ischemic core and penumbra increased (+50%) at 1h and returned to control values at 4h post-occlusion. In contrast, the increase in total iron levels (+20-30%) was long-lasting, but confined to the ischemic core. A time-dependent increase in the expression of both chains of ferritin was detected in regions that previously exhibited free iron accumulation. Finally, ischemic damage was reduced by the liposoluble iron chelator 2,2'-dipyridyl (20 mg/kg, i.p.) when injected 15 min or 1 h post-occlusion, yet not later (4 h). In conclusion, our results show that focal brain ischemia results in an early and transient elevation in free iron levels in the ischemic tissue and suggest that free iron excess does not originate in blood. They also highlight the importance of starting iron chelation therapy as soon as possible after stroke.     

Myogenic cells of regenerating adult chicken muscle can fuse into myotubes after a single cell division in vivo

Autoradiographic studies were carried out on regenerating muscles of adult chickens. Three different muscles of hens were injured, and tritiated thymidine (1 microCi/g) was injected at various times after injury to label replicating muscle precursors. Detailed comparisons of grain counts over premitotic nuclei in samples removed one hour after injection of tritiated thymidine, and of postmitotic myotube nuclei in samples removed 10 days after injury (when labeled precursors had fused to form myotubes), revealed how many times some labeled precursors had divided before fusing into myotubes. DNA synthesis in muscle precursors was initiated 30 h after injury. Grain counts of myotube nuclei indicated that many muscle precursors labeled at the onset of myogenic cell proliferation had divided only once, or twice, before fusing into myotubes. The relationship of these in vivo results to the cell lineage model of myogenesis is discussed.     

A microarray gene analysis of peripheral whole blood in normal adult male rats after long-term GH gene therapy

The main aims of this study were to determine the effects of GH gene abuse/misuse in normal animals and to discover genes that could be used as candidate biomarkers for the detection of GH gene therapy abuse/misuse in humans. We determined the global gene expression profile of peripheral whole blood from normal adult male rats after long-term GH gene therapy using CapitalBio 27 K Rat Genome Oligo Arrays. Sixty one genes were found to be differentially expressed in GH gene-treated rats 24 weeks after receiving GH gene therapy, at a two-fold higher or lower level compared to the empty vector group (p < 0.05). These genes were mainly associated with angiogenesis, oncogenesis, apoptosis, immune networks, signaling pathways, general metabolism, type I diabetes mellitus, carbon fixation, cell adhesion molecules, and cytokine-cytokine receptor interaction. The results imply that exogenous GH gene expression in normal subjects is likely to induce cellular changes in the metabolism, signal pathways and immunity. A real-time qRT-PCR analysis of a selection of the genes confirmed the microarray data. Eight differently expressed genes were selected as candidate biomarkers from among these 61 genes. These 8 showed five-fold higher or lower expression levels after the GH gene transduction (p < 0.05). They were then validated in real-time PCR experiments using 15 single-treated blood samples and 10 control blood samples. In summary, we detected the gene expression profiles of rat peripheral whole blood after long-term GH gene therapy and screened eight genes as candidate biomarkers based on the microarray data. This will contribute to an increased mechanistic understanding of the effects of chronic GH gene therapy abuse/misuse in normal subjects.     

洞庭湖青山垸退耕地不同水位土壤种子库特征

研究退耕地土壤种子库的组成特点和分布规律是评价受损湿地生态恢复效应的重要组成部分.本文以洞庭湖典型退田还湖区——青山垸为对象,研究了不同水位及湿地土壤(0～2、2～5和5～10 cm)种子库的大小、物种组成多样性及其与地上植被的关系.结果表明: 青山垸土壤种子库密度、丰富度指数以及地上植被与土壤种子库的相似性系数沿低-中-高水位梯度呈“V”型变化.常淹区种子库密度最高,为(36943±5207)粒·m^-2,偶淹区最低,为(18618±6977)粒·m^-2,洪淹区居中,为(30572±5329)粒·m^-2;地上植被与土壤种子库的相似性系数(Sorensen系数)为常淹区(0.76)>洪淹区(0.53)>偶淹区(0.41).种子库密度、物种多样性指数和物种丰富度指数沿土壤剖面呈递减趋势,但不同水位的递减幅度存在差异.种子库密度、物种丰富度以及地上植被与湿地种子库的相似性系数沿水位梯度呈规律性变化,与其所处的地理位置水文波动和植被的物种生活型组成等密切相关.     

Differences between single and paired heifers in residency in functional areas, length of travel path, and area used throughout days 1–6 after integration into a free stall dairy herd

The integration of heifers into free stall dairy herds is a frequent management procedure, but little systematic research has been conducted on its effect on cow behavior. Previous studies mainly focused on aggressive interactions, but it is also of interest how integration affects the spatial distribution of both the cows in the herd and the integrated heifers. In the present study we integrated a single and a pair of heifers on each of six Swiss working farms in a balanced order. Using an automatic tracking system, we recorded the positions of all the cows and of the integrated heifers at 1 min intervals for six continuous 24 h periods. From these data we calculated the proportion of time the animals spent in the activity area, at the feed rack and in the lying cubicles, their average path length and the area of the barn that they used. We then compared the behavior of the integrated heifers with that of the cows in the introductory weeks. We also compared the behavior of the cows recorded in the control weeks directly preceding the integration and in the introductory weeks. For evaluation we used linear mixed-effects models. Singly integrated heifers spent a higher proportion of time in the activity area (0.29 vs. 0.14; P < 0.001) and a lower proportion of time in the lying area (0.40 vs. 0.53; interaction with day, P = 0.011) than the cows, whereas the heifers of the pairs mainly spent a lower proportion of time in the feeding area than the cows (0.23 vs. 0.32; interaction with day, P = 0.044). Average path length was longer for the integrated heifers soon after introduction but approached the values of the cows later on (interaction with day, P = 0.012). The total barn area used by a given animal was largest in the cows and was reduced in heifers integrated singly or in pairs (cows: 341/373 m², pairs: 306 m², single heifer: 333 m²; P = 0.055). Cows were little influenced in their space use by the integration of a single or pair of heifers. In summary, the behavior of the singly integrated heifers differed more markedly from that of the cows than the behavior of the heifers introduced in pairs during the introductory week. We would therefore recommend integrating pairs rather than single heifers into herds of dehorned dairy cows to ease their integration.     

Loss of functional sperm entry into Xenopus eggs after activation correlates with a reduction in surface adhesivity

In Xenopus, the plasma membrane of the unactivated egg is receptive to sperm only in the animal hemisphere (R. Grey, M. Bastiani, D. Webb, and E. Schertel, 1982, Dev. Biol.89, 475–487). The reinsemination experiments of investment-free eggs reported in this paper demonstrate that functional sperm entry is lost after activation. Supernumerary sperm were excluded even though the fertilization envelope was absent and the membrane potential had returned to the level found in the unfertilized egg. Even when the electrical block to polyspermy was suppressed by 40 mM NaI (which reduces the membrane potential), polyspermy could be induced only if denuded eggs were initially inseminated in this medium. We estimate that the loss of functional sperm entry, independent of the electrical block, occurs during the first 10 min following fertilization. Sperm readily adhere to the surface of the animal hemisphere of unactivated eggs divested of their extracellular coats, but they do not adhere to the surface of activated eggs. Denuded eggs also adhere to each other, with the surface of the animal hemisphere of unactivated eggs exhibiting the greatest degree of adhesivity. We used electric field-induced fusion (EFIF), without prior dielectrophoresis, to quantify the regional and temporal adhesiveness of eggs. At electric field strengths greater than 8 V/cm, the probability of fusion during EFIF is highest with the animal hemisphere of unactivated eggs, moderate with both the vegetal hemisphere of unactivated eggs and the animal hemisphere of activated eggs, and lowest with the vegetal hemisphere of activated eggs. When pairs of eggs are constructed with different hemispheres in contact, the fusion characteristics of the pair are similar to the more adhesive member of the pair. The regional and temporal differences in the adhesiveness of the Xenopus egg surface correlate with its receptivity to sperm and could possibly account for the plasma membrane's activation-induced loss of functional sperm entry.     

Factors affecting the use of medicinal plants by migrants from rural areas of Brazilian Northeast after moving to a metropolitan region in Southeast of Brazil

Background

Ethnopharmacological studies about migrants reveal a dynamic process of knowledge and use of medicinal plants. In this study, we sought to elucidate quantitative and qualitatively the main factors influencing the use of medicinal plants by migrants from rural areas to an urban region in Brazil with traces of remnant natural vegetation.

Methods

Seven Northeastern individuals who migrated to the Southeastern Region of Brazil (Bororé Peninsula, in the city of São Paulo) were selected to participate in semi-structured interviews regarding the use of medicinal plants throughout their lives, and indicated an inhabitant in their hometown that would be able to accompany the field collections in each area. Socioeconomic, educational, family structure, and use of Western medicine data were provided during interviews with the individuals from their hometowns. Plant samples cited by the interviewees were collected both at the current place of residence and in their hometowns.

Results

The participants cited 131 plants and 315 recipes, being the main indications related to the gastrointestinal system, respiratory problems, and pain and inflammatory processes. We observed that most plant uses were maintained after migration. Higher percentages of maintenances and incorporations in plant uses occurred to exotic species, while replacements happen mainly to native plants. The introduction of new species into the migrants’ therapeutics occurred mainly by observations of organoleptic similarities between the substituted plant and the incorporated species, conversations with neighbors, and contact with the television and print media. In addition, the public health system allowed the interviewees access to prophylactic drugs, leading to the discontinuation of certain recipes used in endemic diseases.

Conclusion

Migrants were exposed to information about new plants and their uses, new diseases, and socioeconomic and cultural differences that impacted their use of medicinal plants. Although migration to a more developed city facilitated access to public health and education, on the other hand, it made access to fresh medicinal plants difficult, causing some medicinal plants to be replaced or ceased to be used.

     

Low proportions of folic acid deficiency after introduction of mandatory folic acid fortification in remote areas of northern Queensland,Australia: a secondary health data analysis

Abstract

Background: Australia implemented mandatory folic acid fortification of bread-making flour in 2009.

Objective: To assess the impact of folic acid fortification in remote vs. regional urban areas and Indigenous vs. non-Indigenous populations in northern Queensland.

Methods: Routinely collected data on folic acid measurements in remote areas and two regional urban centres in northern Queensland between 2004 and 2015 were analysed (n?=?13,929) dichotomously (folic deficient vs. non-deficient).

Results: Overall prevalence of folic acid deficiency was 3.2% (235/7282) in urban centres compared with 7.2% (480/6647) in remote areas (p?<?0.001), and 9.3% (393/4240) in the Indigenous population compared with 3.2% (273/8451) in the non-Indigenous population (p?<?0.001). Prevalence of folic acid deficiency dropped from 12.2% (n?=?481) in 2004–2008 to 1.5% (n?=?126) in 2010–2015 (p?<?0.001). This translates into a relative risk reduction (RRR) of 88%. RRR was 79% (7.2% vs. 1.5%) in urban centres, 91% (17.3% vs. 1.5%) in remote areas, 92% (20.5% vs. 1.6%) in the Indigenous population and 80% (7.4% vs. 1.5%) in the non-Indigenous population (p?<?0.001 for all).

Conclusions: Substantial declines of folic acid deficiency to low and comparable proportions in former high-risk populations indicate that mandatory folic acid fortification of flour has had a population-wide benefit in northern Queensland.