Time to full enteral feeds in hospitalised preterm and very low birth weight infants in Nigeria and Kenya.

BACKGROUND: Preterm (born < 37 weeks' gestation) and very low birthweight (VLBW; <1.5kg) infants are at the greatest risk of morbidity and mortality within the first 28 days of life. Establishing full enteral feeds is a vital aspect of their clinical care. Evidence predominantly from high income countries shows that early and rapid advancement of feeds is safe and reduces length of hospital stay and adverse health outcomes. However, there are limited data on feeding practices and factors that influence the attainment of full enteral feeds among these vulnerable infants in sub-Saharan Africa. AIM: To identify factors that influence the time to full enteral feeds, defined as tolerance of 120ml/kg/day, in hospitalised preterm and VLBW infants in neonatal units in two sub-Saharan African countries. METHODS: Demographic and clinical variables were collected for newborns admitted to 7 neonatal units in Nigeria and Kenya over 6-months. Multiple linear regression analysis was conducted to identify factors independently associated with time to full enteral feeds. RESULTS: Of the 2280 newborn infants admitted, 484 were preterm and VLBW. Overall, 222/484 (45.8%) infants died with over half of the deaths (136/222; 61.7%) occurring before the first feed. The median (inter-quartile range) time to first feed was 46 (27, 72) hours of life and time to full enteral feeds (tFEF) was 8 (4.5,12) days with marked variation between neonatal units. Independent predictors of tFEF were time to first feed (unstandardised coefficient B 1.69; 95% CI 1.11 to 2.26; p value <0.001), gestational age (1.77; 0.72 to 2.81; <0.001), the occurrence of respiratory distress (-1.89; -3.50 to -0.79; <0.002) and necrotising enterocolitis (4.31; 1.00 to 7.62; <0.011). CONCLUSION: The use of standardised feeding guidelines may decrease variations in clinical practice, shorten tFEF and thereby improve preterm and VLBW outcomes.

Molecular surveillance reveals widespread colonisation by carbapenemase and extended spectrum beta-lactamase producing organisms in neonatal units in Kenya and Nigeria.

OBJECTIVES: Neonatal sepsis, a major cause of death amongst infants in sub-Saharan Africa, is often gut derived. Gut colonisation by Enterobacteriaceae producing extended spectrum beta-lactamase (ESBL) or carbapenemase enzymes can lead to antimicrobial-resistant (AMR) or untreatable infections. We sought to explore the rates of colonisation by ESBL or carbapenemase producers in two neonatal units (NNUs) in West and East Africa. METHODS: Stool and rectal swab samples were taken at multiple timepoints from newborns admitted to the NNUs at the University College Hospital, Ibadan, Nigeria and the Jaramogi Oginga Odinga Teaching and Referral Hospital, Kisumu, western Kenya. Samples were tested for ESBL and carbapenemase genes using a previously validated qPCR assay. Kaplan-Meier survival analysis was used to examine colonisation rates at both sites. RESULTS: In total 119 stool and rectal swab samples were taken from 42 infants admitted to the two NNUs. Colonisation with ESBL (37 infants, 89%) was more common than with carbapenemase producers (26, 62.4%; P = 0.093). Median survival time before colonisation with ESBL organisms was 7 days and with carbapenemase producers 16 days (P = 0.035). The majority of ESBL genes detected belonged to the CTX-M-1 (36/38; 95%), and CTX-M-9 (2/36; 5%) groups, and the most prevalent carbapenemase was blaNDM (27/29, 93%). CONCLUSIONS: Gut colonisation of neonates by AMR organisms was common and occurred rapidly in NNUs in Kenya and Nigeria. Active surveillance of colonisation will improve the understanding of AMR in these settings and guide infection control and antibiotic prescribing practice to improve clinical outcomes.

Enteral Feeding Practices for Very Preterm and Very Low Birth Weight Infants in Nigeria and Kenya.

Background: Optimizing nutrition in very preterm (28-32 weeks gestation) and very low birth weight (VLBW; 1,000 g to <1,500 g) infants has potential to improve their survival, growth, and long-term health outcomes. Aim: To assess feeding practices in Nigeria and Kenya for very preterm and VLBW newborn infants. Methods: This was a cross-sectional study where convenience sampling was used. A standard questionnaire was sent to doctors working in neonatal units in Nigeria and Kenya. Results: Of 50 respondents, 37 (74.0%) were from Nigeria and 13 (26.0%) from Kenya. All initiated enteral feeds with breastmilk, with 24 (48.0%) initiating within 24 h. Only 28 (56.0%) used written feeding guidelines. Starting volumes ranged between 10 and 80 ml/kg/day. Median volume advancement of feeds was 20 ml/kg/day (IQR 10-20) with infants reaching full feeds in 8 days (IQR 6-12). 26 (52.0%) of the units fed the infants 2 hourly. Breastmilk fortification was practiced in 7 (14.0%) units, while folate, iron, calcium, and phosphorus were prescribed in 42 (84.0%), 36 (72.0%), 22 (44.0%), 5 (10.0%) of these units, respectively. No unit had access to donor breastmilk, and only 18 (36.0%) had storage facilities for expressed breastmilk. Twelve (24.0%) used wet nurses whilst 30 (60.0%) used formula feeds. Conclusion: Feeding practices for very preterm and VLBW infants vary widely within Nigeria and Kenya, likely because of lack of locally generated evidence. High quality research that informs the feeding of these infants in the context of limited human resources, technology, and consumables, is urgently needed.

Prospective observational study of the challenges in diagnosing common neonatal conditions in Nigeria and Kenya.

OBJECTIVES: Accurate and timely diagnosis of common neonatal conditions is crucial for reducing neonatal deaths. In low/middle-income countries with limited resources, there is sparse information on how neonatal diagnoses are made. The aim of this study was to describe the diagnostic criteria used for common conditions in neonatal units (NNUs) in Nigeria and Kenya. DESIGN: Prospective observational study. Standard case report forms for suspected sepsis, respiratory disorders, birth asphyxia and abdominal conditions were co-developed by the Neonatal Nutrition Network (https://www.lstmed.ac.uk/nnu) collaborators. Clinicians completed forms for all admissions to their NNUs. Key data were displayed using heatmaps. SETTING: Five NNUs in Nigeria and two in Kenya comprising the Neonatal Nutrition Network. PARTICIPANTS: 2851 neonates, which included all neonates admitted to the seven NNUs over a 6-month period. RESULTS: 1230 (43.1%) neonates had suspected sepsis, 874 (30.6%) respiratory conditions, 587 (20.6%) birth asphyxia and 71 (2.5%) abdominal conditions. For all conditions and across all NNUs, clinical criteria were used consistently with sparse use of laboratory and radiological criteria. CONCLUSION: Our findings highlight the reliance on clinical criteria and extremely limited use of diagnostic technologies for common conditions in NNUs in sub-Saharan Africa. This has implications for the management of neonatal conditions which often have overlapping clinical features. Strategies for implementation of diagnostic pathways and investment in affordable and sustainable diagnostics are needed to improve care for these vulnerable infants.

Effectiveness of Training and Use of Novasil Binder in Mitigating Aflatoxins in Cow Milk Produced in Smallholder Farms in Urban and Periurban Areas of Kenya.

Aflatoxins, which commonly contaminate animal feeds and human food, present a major public health challenge in sub-Saharan Africa. After ingestion by cows, aflatoxin B1 is metabolized to aflatoxin M1 (AFM1), some of which is excreted in milk. This study involved smallholder dairy farms in urban and periurban areas of Nairobi and Kisumu, Kenya. The objective was to determine the effectiveness of training and providing farmers with aflatoxin binder (NovaSil®) on AFM1 contamination in raw milk. A baseline survey was undertaken and 30 farmers whose milk had AFM1 levels above 20 ppt were randomly selected for inclusion in the study. Of these, 20 farmers were part of the intervention, and were given training on the usage of the NovaSil® binder, while 10 served as a control group. All farmers were visited biweekly for three months for interviews and milk samples were collected to measure the AFM1 levels. The AFM1 levels were quantified by enzyme linked immunosorbent assay. The NovaSil® binder significantly reduced AFM1 concentrations in the raw milk produced by the farmers in the intervention group over the duration of the study (p < 0.01). The control farms were more likely to have milk with AFM1 levels exceeding the regulatory limit of 50 ppt compared to the intervention farms (p < 0.001) (odds ratio = 6.5). The farmers in the intervention group perceived that there was an improvement in milk yield, and in cow health and appetite. These farmers also felt that the milk they sold, as well as the one they used at home, was safer. In conclusion, the use of binders by dairy farmers can be effective in reducing AFM1 in milk. Further research is needed to understand their effectiveness, especially when used in smallholder settings.

Antenatal iron supplementation, FGF23, and bone metabolism in Kenyan women and their offspring: secondary analysis of a randomized controlled trial.

BACKGROUND: Fibroblast growth factor-23 (FGF23) regulates body phosphate homeostasis primarily by increasing phosphaturia. It also acts as a vitamin D-regulating hormone. Maternal iron deficiency is associated with perturbed expression and/or regulation of FGF23 and hence might be implicated in the pathogenesis of hypophosphatemia-driven rickets in their offspring. OBJECTIVES: We aimed to determine the effect of antenatal oral iron supplementation on FGF23 concentration and maternal and infant markers of bone-mineral regulation. METHODS: We performed a secondary analysis of a trial in which 470 rural Kenyan women with singleton pregnancies and hemoglobin concentrations ≥ 90 g/L were randomly allocated to daily, supervised supplementation with 60 mg elemental iron as ferrous fumarate or placebo from 13-23 weeks of gestation until 1 mo postpartum. As previously reported, iron supplementation improved iron status in mothers and neonates. For the present study, we reanalyzed all available plasma samples collected in mothers and neonates at birth, with primary outcomes being concentrations of FGF23, measured by 2 assays: 1 that detects intact hormone and C-terminal cleavage products (total-FGF23) and another that detects the intact hormone only (intact-FGF23). RESULTS: Analysis was performed on 433 women (n = 216, iron group; n = 217, placebo group) and 414 neonates (n = 207, iron group; n = 207, placebo group). Antenatal iron supplementation reduced geometric mean total-FGF23 concentrations in mothers and neonates by 62.6% (95% CI: 53.0%, 70.3%) and 15.2% (95% CI: -0.3%, 28.4%, P = 0.06), respectively. In addition, it increased geometric mean neonatal intact-FGF23 concentrations by 21.6% (95% CI: 1.2%, 46.1%), increased geometric mean maternal hepcidin concentrations by 136.4% (95% CI: 86.1%, 200.3%), and decreased mean maternal 25-hydroxyvitamin D concentrations by 6.1 nmol/L (95% CI: -11.0, -1.2 nmol/L). CONCLUSIONS: Analysis of this randomized trial confirms that iron supplementation can reverse elevated FGF23 production caused by iron deficiency in iron-deficient mothers and their neonates. Further investigations are warranted to assess to what extent iron supplementation can prevent FGF23-mediated hypophosphatemic rickets or osteomalacia.

Burden of disease and risk factors for mortality amongst hospitalized newborns in Nigeria and Kenya.

OBJECTIVE: To describe the patient population, priority diseases and outcomes in newborns admitted <48 hours old to neonatal units in both Kenya and Nigeria. STUDY DESIGN: In a network of seven secondary and tertiary level neonatal units in Nigeria and Kenya, we captured anonymised data on all admissions <48 hours of age over a 6-month period. RESULTS: 2280 newborns were admitted. Mean birthweight was 2.3 kg (SD 0.9); 57.0% (1214/2128) infants were low birthweight (LBW; <2.5kg) and 22.6% (480/2128) were very LBW (VLBW; <1.5 kg). Median gestation was 36 weeks (interquartile range 32, 39) and 21.6% (483/2236) infants were very preterm (gestation <32 weeks). The most common morbidities were jaundice (987/2262, 43.6%), suspected sepsis (955/2280, 41.9%), respiratory conditions (817/2280, 35.8%) and birth asphyxia (547/2280, 24.0%). 18.7% (423/2262) newborns died; mortality was very high amongst VLBW (222/472, 47%) and very preterm infants (197/483, 40.8%). Factors independently associated with mortality were gestation <28 weeks (adjusted odds ratio 11.58; 95% confidence interval 4.73-28.39), VLBW (6.92; 4.06-11.79), congenital anomaly (4.93; 2.42-10.05), abdominal condition (2.86; 1.40-5.83), birth asphyxia (2.44; 1.52-3.92), respiratory condition (1.46; 1.08-2.28) and maternal antibiotics within 24 hours before or after birth (1.91; 1.28-2.85). Mortality was reduced if mothers received a partial (0.51; 0.28-0.93) or full treatment course (0.44; 0.21-0.92) of dexamethasone before preterm delivery. CONCLUSION: Greater efforts are needed to address the very high burden of illnesses and mortality in hospitalized newborns in sub-Saharan Africa. Interventions need to address priority issues during pregnancy and delivery as well as in the newborn.

Effectiveness of zinc-fortified water on zinc intake, status and morbidity in Kenyan pre-school children: a randomised controlled trial.

OBJECTIVE: Zn deficiency and diarrhoea are prevalent and may coexist in children living in low-resource settings. Recently, a novel approach for delivering Zn via microbiologically treated, Zn-fortified water was shown to be effective in improving Zn status in West African schoolchildren. We assessed the effectiveness of Zn-fortified, microbiologically purified water delivered as a household intervention on Zn intake, status and morbidity in children aged 2-6 years from rural western Kenya. DESIGN: Randomised controlled trial. Intervention included households assigned to water treatment device with (ZFW) or without (FW) Zn delivery capability SETTING: Rural households in Kisumu, western Kenya. SUBJECTS: Children aged 2-6 years. RESULTS: The ZFW group had higher dietary Zn intake compared with the FW group. ZFW contributed 36 and 31 % of daily requirements for absorbable Zn in children aged 2-3 and 4-6 years, respectively, in the ZFW group. Consumption of Zn-fortified water resulted in lower prevalence of reported illness (risk ratio; 95 % CI) in the ZFW group compared with the FW group: for cold with runny nose (0·91; 0·83, 0·99; P=0·034) and abdominal pain (0·70; 0·56, 0·89; P=0·003) in the intention-to-treat analysis and for diarrhoea (0·72; 0·53, 0·96; P=0·025) in the per-protocol analysis. We did not detect an effect of treatment on plasma Zn concentration. CONCLUSIONS: Daily consumption of Zn-fortified, microbiologically treated water results in increased intake of absorbable dietary Zn and may help in preventing childhood infections in pre-school children in rural Africa.

Combining food-based dietary recommendations using Optifood with zinc-fortified water potentially improves nutrient adequacy among 4- to 6-year-old children in Kisumu West district, Kenya.

Children in developing countries often face multiple micronutrient deficiencies. Introduction of zinc-fortified water can increase zinc intake, but additional recommendations are required to address overall diet nutrient adequacy. We developed and tested food-based recommendations (FBRs) that included zinc-fortified water for children aged between 4 and 6 years from rural Kenya to achieve the best possible nutrient adequacy. Dietary intakes of 60 children aged 4-6 years, from Kisumu West district, Kenya, were assessed using a quantitative multipass 24-hr recall. Linear programming model parameters were derived, including a list of foods consumed, median serving sizes, and distribution of frequency of consumption. By using the Optifood linear programming tool, we developed FBRs for diets including zinc-fortified water. FBRs with nutrient levels achieving ≥70% recommended nutrient intake (RNI) of the World Health Organization/Food and Agriculture Organization of the United Nations RNI for most of the 12 considered nutrients were selected as the final recommendations for the children. With no FBRs and no zinc-fortified water, percent RNI coverage range was between 40% and 76% for zinc, improving to 66-101% after introduction of zinc-fortified water. The final set of FBRs achieved nutrient adequacy for all nutrients except for vitamin A (25% RNI) and folate (68% RNI). Introduction of zinc-fortified water combined with FBRs will likely improve the nutrient adequacy of diets consumed by children in Kenya but needs to be complemented with alternative interventions to ensure dietary adequacy.

Diagnostic utility of zinc protoporphyrin to detect iron deficiency in Kenyan preschool children: a community-based survey.

BACKGROUND: Zinc protoporphyrin (ZPP) has been used to screen and manage iron deficiency in individual children, but it has also been recommended to assess population iron status. The diagnostic utility of ZPP used in combination with haemoglobin concentration has not been evaluated in pre-school children. We aimed to a) identify factors associated with ZPP in children aged 12-36 months; b) assess the diagnostic performance and utility of ZPP, either alone or in combination with haemoglobin, to detect iron deficiency. METHODS: We used baseline data from 338 Kenyan children enrolled in a community-based randomised trial. To identify factors related to ZZP measured in whole blood or erythrocytes, we used bivariate and multiple linear regression analysis. To assess diagnostic performance, we excluded children with elevated plasma concentrations of C-reactive protein or α1-acid glycoprotein, and with Plasmodium infection, and we analysed receiver operating characteristics (ROC) curves, with iron deficiency defined as plasma ferritin concentration < 12 µg/L. We also developed models to assess the diagnostic utility of ZPP and haemoglobin concentration when used to screen for iron deficiency. RESULTS: Whole blood ZPP and erythrocyte ZPP were independently associated with haemoglobin concentration, Plasmodium infection and plasma concentrations of soluble transferrin receptor, ferritin, and C-reactive protein. In children without inflammation or Plasmodium infection, the prevalence of true iron deficiency was 32.1%, compared to prevalence of 97.5% and 95.1% when assessed by whole blood ZPP and erythrocyte ZPP with conventional cut-off points (70 µmol/mol and 40 µmol/mol haem, respectively). Addition of whole blood ZPP or erythrocyte ZPP to haemoglobin concentration increased the area-under-the-ROC-curve (84.0%, p = 0.003, and 84.2%, p = 0.001, respectively, versus 62.7%). A diagnostic rule (0.038689 [haemoglobin concentration, g/L] + 0.00694 [whole blood ZPP, µmol/mol haem] >5.93120) correctly ruled out iron deficiency in 37.4%-53.7% of children screened, depending on the true prevalence, with both specificity and negative predictive value ≥90%. CONCLUSIONS: In young children, whole blood ZPP and erythrocyte ZPP have added diagnostic value in detecting iron deficiency compared to haemoglobin concentration alone. A single diagnostic score based on haemoglobin concentration and whole blood ZPP can rule out iron deficiency in a substantial proportion of children screened. TRIAL REGISTRATION: ClinicalTrials.gov NCT02073149 (25 February 2014).

Daily home fortification with iron as ferrous fumarate versus NaFeEDTA: a randomised, placebo-controlled, non-inferiority trial in Kenyan children.

BACKGROUND: We aimed to show the non-inferiority of home fortification with a daily dose of 3 mg iron in the form of iron as ferric sodium ethylenediaminetetraacetate (NaFeEDTA) compared with 12.5 mg iron as encapsulated ferrous fumarate in Kenyan children aged 12-36 months. In addition, we updated a recent meta-analysis to assess the efficacy of home fortification with iron-containing powders, with a view to examining diversity in trial results. METHODS: We gave chemoprevention by dihydroartemisinin-piperaquine, albendazole and praziquantel to 338 afebrile children with haemoglobin concentration ≥70 g/L. We randomly allocated them to daily home fortification for 30 days with either placebo, 3 mg iron as NaFeEDTA or 12.5 mg iron as encapsulated ferrous fumarate. We assessed haemoglobin concentration (primary outcome), plasma iron markers, plasma inflammation markers and Plasmodium infection in samples collected at baseline and after 30 days of intervention. We conducted a meta-analysis of randomised controlled trials in pre-school children to assess the effect of home fortification with iron-containing powders on anaemia and haemoglobin concentration at end of intervention. RESULTS: A total of 315 children completed the 30-day intervention period. At baseline, 66.9% of children had inflammation (plasma C-reactive protein concentration >5 mg/L or plasma α 1-acid glycoprotein concentration >1.0 g/L); in those without inflammation, 42.5% were iron deficient. There was no evidence, either in per protocol analysis or intention-to-treat analysis, that home fortification with either of the iron interventions improved haemoglobin concentration, plasma ferritin concentration, plasma transferrin receptor concentration or erythrocyte zinc protoporphyrin-haem ratio. We also found no evidence of effect modification by iron status, anaemia status and inflammation status at baseline. In the meta-analysis, the effect on haemoglobin concentration was highly heterogeneous between trials (I 2: 84.1%; p value for test of heterogeneity: <0.0001). CONCLUSIONS: In this population, home fortification with either 3 mg iron as NaFeEDTA or 12.5 mg iron as encapsulated ferrous fumarate was insufficiently efficacious to assess non-inferiority of 3 mg iron as NaFeEDTA compared to 12.5 mg iron as encapsulated ferrous fumarate. Our finding of heterogeneity between trial results should stimulate subgroup analysis or meta-regression to identify population-specific factors that determine efficacy. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov ( NCT02073149 ) on 25 February 2014.

Effect of Daily Antenatal Iron Supplementation on Plasmodium Infection in Kenyan Women: A Randomized Clinical Trial.

IMPORTANCE: Anemia affects most pregnant African women and is predominantly due to iron deficiency, but antenatal iron supplementation has uncertain health benefits and can increase the malaria burden. OBJECTIVE: To measure the effect of antenatal iron supplementation on maternal Plasmodium infection risk, maternal iron status, and neonatal outcomes. DESIGN, SETTING, AND PARTICIPANTS: Randomized placebo-controlled trial conducted October 2011 through April 2013 in a malaria endemic area among 470 rural Kenyan women aged 15 to 45 years with singleton pregnancies, gestational age of 13 to 23 weeks, and hemoglobin concentration of 9 g/dL or greater. All women received 5.7 mg iron/day through flour fortification during intervention, and usual intermittent preventive treatment against malaria was given. INTERVENTIONS: Supervised daily supplementation with 60 mg of elemental iron (as ferrous fumarate, n = 237 women) or placebo (n = 233) from randomization until 1 month postpartum. MAIN OUTCOMES AND MEASURES: Primary outcome was maternal Plasmodium infection at birth. Predefined secondary outcomes were birth weight and gestational age at delivery, intrauterine growth, and maternal and infant iron status at 1 month after birth. RESULTS: Among the 470 participating women, 40 women (22 iron, 18 placebo) were lost to follow-up or excluded at birth; 12 mothers were lost to follow-up postpartum (5 iron, 7 placebo). At baseline, 190 of 318 women (59.7%) were iron-deficient. In intention-to-treat analysis, comparison of women who received iron vs placebo, respectively, yielded the following results at birth: Plasmodium infection risk: 50.9% vs 52.1% (crude difference, -1.2%, 95% CI, -11.8% to 9.5%; P = .83); birth weight: 3202 g vs 3053 g (crude difference, 150 g, 95% CI, 56 to 244; P = .002); birth-weight-for-gestational-age z score: 0.52 vs 0.31 (crude difference, 0.21, 95% CI, -0.11 to 0.52; P = .20); and at 1 month after birth: maternal hemoglobin concentration: 12.89 g/dL vs 11.99 g/dL (crude difference, 0.90 g/dL, 95% CI, 0.61 to 1.19; P < .001); geometric mean maternal plasma ferritin concentration: 32.1 µg/L vs 14.4 µg/L (crude difference, 123.4%, 95% CI, 85.5% to 169.1%; P < .001); geometric mean neonatal plasma ferritin concentration: 163.0 µg/L vs 138.7 µg/L (crude difference, 17.5%, 95% CI, 2.4% to 34.8%; P = .02). Serious adverse events were reported for 9 and 12 women who received iron and placebo, respectively. There was no evidence that intervention effects on Plasmodium infection risk were modified by intermittent preventive treatment use. CONCLUSIONS AND RELEVANCE: Among rural Kenyan women with singleton pregnancies, administration of daily iron supplementation, compared with administration of placebo, resulted in no significant differences in overall maternal Plasmodium infection risk. Iron supplementation led to increased birth weight. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01308112.

Diagnostic utility of zinc protoporphyrin to detect iron deficiency in Kenyan pregnant women.

BACKGROUND: Iron-deficient erythropoiesis results in excess formation of zinc protoporphyrin (ZPP), which can be measured instantly and at low assay cost using portable haematofluorometers. ZPP is used as a screening marker of iron deficiency in individual pregnant women and children, but also to assess population iron status in combination with haemoglobin concentration. We examined associations between ZPP and disorders that are common in Africa. In addition, we assessed the diagnostic utility of ZPP (measured in whole blood and erythrocytes), alone or in combination with haemoglobin concentration, in detecting iron deficiency (plasma ferritin concentration <15 µg/L). METHODS: Single blood samples were collected from a population sample of 470 rural Kenyan women with singleton pregnancies, gestational age 13 to 23 weeks, and haemoglobin concentration ≥90 g/L. We used linear regression analysis to assess associations between ZPP and iron markers (including anaemia), factors known or suspected to be associated with iron status, inflammation markers (plasma concentrations of C-reactive protein and α 1-acid glycoprotein), infections (Plasmodium infection, HIV infection), and other disorders (α(+)-thalassaemia, plasma concentrations of total bilirubin, and lactate dehydrogenase). Subsequently, in those without inflammation, Plasmodium infection, or HIV infection, we used logistic discriminant analysis and examined receiver operating characteristics curves with corresponding area-under-the-curve to assess diagnostic performance of ZPP, alone and in combination with haemoglobin concentration. RESULTS: Individually, whole blood ZPP, erythrocyte ZPP, and erythrocyte protoporphyrin had limited ability to discriminate between women with and without iron deficiency. Combining each of these markers with haemoglobin concentration had no additional diagnostic value. Conventional cut off points for whole blood ZPP (>70 µmol/mol haem) resulted in gross overestimates of the prevalence of iron deficiency. CONCLUSIONS: Erythrocyte ZPP has limited value to rule out iron deficiency when used for screening in conditions with a low prevalence (e.g., 10%). ZPP is of unreliable diagnostic utility when discriminating between pregnant women with and without iron deficiency. Based on these findings, guidelines on the use of ZPP to assess iron status in individuals or populations of pregnant women need review. TRIAL REGISTRATION: NCT01308112 (2 March 2011).

Alpha+ -thalassemia protects against anemia associated with asymptomatic malaria: evidence from community-based surveys in Tanzania and Kenya.

BACKGROUND: In hospital-based studies, alpha(+)-thalassemia has been found to protect against severe, life-threatening falciparum malaria. alpha(+)-Thalassemia does not seem to prevent infection or high parasite densities but rather limits progression to severe disease--in particular, severe malarial anemia. We assessed to what extent alpha(+)-thalassemia influences the association between mild, asymptomatic Plasmodium falciparum infection and hemoglobin concentration. METHODS: The study was based on 2 community-based surveys conducted among afebrile children (0.5-8 years old; n=801) in Kenya and Tanzania. RESULTS: Among children without inflammation (whole-blood C-reactive protein concentration

Efficacy of iron-fortified whole maize flour on iron status of schoolchildren in Kenya: a randomised controlled trial.

BACKGROUND: Sodium iron edetic acid (NaFeEDTA) might be a more bioavailable source of iron than electrolytic iron, when added to maize flour. We aimed to assess the effect, on children's iron status, of consumption of whole maize flour fortified with iron as NaFeEDTA or electrolytic iron. METHODS: 516 children, aged 3-8 years, from four schools in Marafa, Kenya, were randomly assigned to four groups. All were given the same amount of porridge five times a week. The porridge for one group was made from unfortified whole maize flour; for the other three groups it was fortified with either high-dose NaFeEDTA (56 mg/kg), low-dose NaFeEDTA (28 mg/kg), or electrolytic iron (56 mg/kg). Concentrations of haemoglobin, plasma ferritin, and transferrin receptor were analysed in samples taken at baseline and at the end of the 5-month intervention. The primary outcome was iron-deficiency anaemia. We analysed data on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT00386074. FINDINGS: The prevalence of iron-deficiency anaemia in children given unfortified flour was 10%. Compared with placebo, the prevalence of iron-deficiency anaemia in children given flour fortified with high-dose NaFeEDTA, low-dose NaFeEDTA, and electrolytic iron changed by -89% (95% CI -97% to -49%), -48% (-77% to 20%), and 59% (-18% to 209%), respectively. Consumption of high-dose NaFeEDTA improved all measured iron-status indicators. Low-dose NaFeEDTA decreased the prevalence of iron deficiency but did not noticeably change the prevalence of anaemia. Electrolytic iron did not improve any of these iron-status indicators. Children who were iron-deficient at baseline benefited more from high-dose and low-dose NaFeEDTA than those with sufficient iron at baseline. INTERPRETATION: Consumption of whole maize flour fortified with NaFeEDTA caused modest, dose-dependent improvements in children's iron status. Fortification with electrolytic iron did not improve their iron status. Therefore, in high-phytate flours, NaFeEDTA is more suitable than electrolytic iron for supplementation of iron in the diet.