Risk of malaria in young children after periconceptional iron supplementation.

This study in Burkina Faso investigated whether offspring of young mothers who had received weekly periconceptional iron supplementation in a randomised controlled trial were at increased risk of malaria. A child safety survey was undertaken in the peak month of malaria transmission towards the end of the trial to assess child iron biomarkers, nutritional status, anaemia and malaria outcomes. Antenatal iron biomarkers, preterm birth, fetal growth restriction and placental pathology for malaria and chorioamnionitis were assessed. Data were available for 180 babies surviving to the time of the survey when their median age was 9 months. Prevalence of maternal iron deficiency in the last trimester based on low body iron stores was 16%. Prevalence of active placental malaria infection was 24.8%, past infection 59% and chorioamnionitis 55.6%. Babies of iron supplemented women had lower median gestational age. Four out of five children ≥ 6 months were iron deficient, and 98% were anaemic. At 4 months malaria prevalence was 45%. Child iron biomarkers, anaemia and malaria outcomes did not differ by trial arm. Factors associated with childhood parasitaemia were third trimester C-reactive protein level (OR 2.1; 95% CI 1.1-3.9), active placental malaria (OR 5.8; 1.0-32.5, P = 0.042) and child body iron stores (OR 1.13; 1.04-1.23, P = 0.002). Chorioamnionitis was associated with reduced risk of child parasitaemia (OR 0.4; 0.1-1.0, P = 0.038). Periconceptional iron supplementation of young women did not alter body iron stores of their children. Higher child body iron stores and placental malaria increased risk of childhood parasitaemia.

Inflammation and Nutritional Science for Programs/Policies and Interpretation of Research Evidence (INSPIRE).

An increasing recognition has emerged of the complexities of the global health agenda­specifically, the collision of infections and noncommunicable diseases and the dual burden of over- and undernutrition. Of particular practical concern are both 1) the need for a better understanding of the bidirectional relations between nutritional status and the development and function of the immune and inflammatory response and 2) the specific impact of the inflammatory response on the selection, use, and interpretation of nutrient biomarkers. The goal of the Inflammation and Nutritional Science for Programs/Policies and Interpretation of Research Evidence (INSPIRE) is to provide guidance for those users represented by the global food and nutrition enterprise. These include researchers (bench and clinical), clinicians providing care/treatment, those developing and evaluating programs/interventions at scale, and those responsible for generating evidence-based policy. The INSPIRE process included convening 5 thematic working groups (WGs) charged with developing summary reports around the following issues: 1) basic overview of the interactions between nutrition, immune function, and the inflammatory response; 2) examination of the evidence regarding the impact of nutrition on immune function and inflammation; 3) evaluation of the impact of inflammation and clinical conditions (acute and chronic) on nutrition; 4) examination of existing and potential new approaches to account for the impact of inflammation on biomarker interpretation and use; and 5) the presentation of new approaches to the study of these relations. Each WG was tasked with synthesizing a summary of the evidence for each of these topics and delineating the remaining gaps in our knowledge. This review consists of a summary of the INSPIRE workshop and the WG deliberations.

Clinical, nutritional and immunological characteristics of HIV-infected children in an area of high HIV prevalence.

OBJECTIVES: To evaluate the clinical, nutritional and neurodevelopment status of HIV-infected children in a high HIV prevalence area. METHODS: All HIV-infected children under 15 years of age attending an outpatient clinic of Mozambique between April and May 2010 were recruited. Clinical data were collected and physical examination was performed. RESULTS: In all, 140 children were recruited. The median age at HIV diagnosis was 2.1 years. Fifty-one percent of the children were classified in WHO clinical Stages 3 or 4. Median age of antiretroviral treatment commencement was 3.9 years. Overall, 68% were undernourished, mainly stunted. Forty-four percent failed to pass the national psychomotor developmental test. CONCLUSIONS: The pathways for early HIV diagnosis and start of antiretrovirals in children should be improved in Mozambique. Malnutrition, especially stunting, and developmental delay were highly prevalent. Further research focused on early diagnosis of neurocognitive disorders and on the indications of antiretroviral treatment commencement based on chronic malnutrition is required.

The interaction between malaria and human immunodeficiency virus infection in severely anaemic Malawian children: a prospective longitudinal study.

OBJECTIVE: Malaria and human immunodeficiency virus (HIV) infection are co-prevalent in sub-Saharan Africa and cause severe anaemia in children. Interactions between these infections occur in adults, although these are less clear in children. The aim of study was to determine their interaction in a cohort of severely anaemic children. METHODS: Severely anaemic Malawian children were enrolled, tested for HIV and malaria, transfused and followed for 18 months for malaria incidence. Antiretrovirals were not widely available in Malawi during the study period. RESULTS: Of 381 children (haemoglobin <5 g/dl), 357 consented for HIV testing, 12.6% were HIV-infected, and 59.5% had malaria parasitaemia. At enrolment, HIV-infected children had similar malaria parasitaemia prevalence (59.1% vs. 58.7%; P = 0.96) and parasite density (geometric mean [parasites/µl] 6903 vs. 12417; P = 0.18) as HIV-negative children. There were no differences in mean CD4%, or prevalence of severe immunosuppression, between those with and without malaria parasitaemia. Plasma viral load correlated negatively with log parasitaemia (r = -0.78; P = 0.01). During follow-up, HIV-infected children did not experience more frequent parasitaemias or symptomatic malaria episodes. Adjusted risk estimates (95% CI) for malaria parasitaemia in HIV-infected children at 6 and 18 months follow-up were 0.39 (0.13-1.14) and 0.40 (0.11-1.51), respectively. CONCLUSIONS: Severely anaemic HIV-infected children showed no increased susceptibility to asymptomatic or symptomatic malaria during or following their anaemic episode, although all experienced lower parasite prevalence during follow-up. This contrasts with data in adults and may relate to the malaria immunity of young children which is insufficiently developed to be impaired by HIV. The negative correlation between viral load and malaria parasitaemia remains unexplained.

Malaria's contribution to World War One - the unexpected adversary.

Malaria in the First World War was an unexpected adversary. In 1914, the scientific community had access to new knowledge on transmission of malaria parasites and their control, but the military were unprepared, and underestimated the nature, magnitude and dispersion of this enemy. In summarizing available information for allied and axis military forces, this review contextualizes the challenge posed by malaria, because although data exist across historical, medical and military documents, descriptions are fragmented, often addressing context specific issues. Military malaria surveillance statistics have, therefore, been summarized for all theatres of the War, where available. These indicated that at least 1.5 million solders were infected, with case fatality ranging from 0.2 -5.0%. As more countries became engaged in the War, the problem grew in size, leading to major epidemics in Macedonia, Palestine, Mesopotamia and Italy. Trans-continental passages of parasites and human reservoirs of infection created ideal circumstances for parasite evolution. Details of these epidemics are reviewed, including major epidemics in England and Italy, which developed following home troop evacuations, and disruption of malaria control activities in Italy. Elsewhere, in sub-Saharan Africa many casualties resulted from high malaria exposure combined with minimal control efforts for soldiers considered semi-immune. Prevention activities eventually started but were initially poorly organized and dependent on local enthusiasm and initiative. Nets had to be designed for field use and were fundamental for personal protection. Multiple prevention approaches adopted in different settings and their relative utility are described. Clinical treatment primarily depended on quinine, although efficacy was poor as relapsing Plasmodium vivax and recrudescent Plasmodium falciparum infections were not distinguished and managed appropriately. Reasons for this are discussed and the clinical trial data summarized, as are controversies that arose from attempts at quinine prophylaxis (quininization). In essence, the First World War was a vast experiment in political, demographic, and medical practice which exposed large gaps in knowledge of tropical medicine and unfortunately, of malaria. Research efforts eventually commenced late in the War to address important clinical questions which established a platform for more effective strategies, but in 1918 this relentless foe had outwitted and weakened both allied and axis powers.

Asthma in children in relation to pre-term birth and fetal growth restriction.

To assess the impact of parental asthma on risk of pre-term birth (PTB) and intrauterine growth restriction, and their subsequent association with childhood asthma. Three sequential cross-sectional surveys were conducted in 1993 (3,746), 1998 (1,964) and 2006 (1,074) in the same 15 schools among 5-11 year old children in Merseyside using the same respiratory health questionnaire completed by parents (sample size in brackets). Between 1993 and 2006, prevalence of PTB varied between 12.4 and 15.2 %, and of small for gestational age (SGA or growth restricted) babies between 2.1 and 4.6 %, and maternal asthma prevalence between 8.1 and 13.4 %. For the combined surveys mothers with asthma were more likely to have a PTB than non-asthmatic mothers (OR 1.39, 95 % CI 1.10-1.95, p < 0.001), and in the 2006 survey were more likely to have an SGA baby. 40.9 % of PTBs of asthmatic mothers developed doctor diagnosed asthma compared to 34.3 % for term babies (adjusted OR 1.65, 1.34-2.04, p < 0.001). The corresponding estimates for the symptom triad of cough, wheeze and breathlessness were 19.4 and 17.6 % (adjusted OR 1.78, 0.79-3.98). Conversely SGA babies were less likely to develop doctor diagnosed asthma (adjusted OR 0.49, 0.27-0.90, p < 0.021), or the symptom triad of cough, wheeze and breathlessness (adjusted OR 0.22, 0.05-0.97, p < 0.043), whether or not the mother was asthmatic. Maternal asthma is an independent risk factor for PTB which predisposes to childhood asthma. Intrauterine growth restriction was protective against childhood asthma.

Zinc erythrocyte protoporphyrin as marker of malaria risk in pregnancy - a retrospective cross-sectional and longitudinal study.

BACKGROUND: The effects of iron interventions and host iron status on infection risk have been a recurrent clinical concern, although there has been little research on this interaction in pregnant women. METHODS: Cross-sectional and longitudinal analyses were undertaken to determine the association of whole blood zinc erythrocyte protoporphyrin (ZPP) with malaria parasitaemia in pregnant women attending antenatal and delivery care at Montfort and Chikwawa Hospitals, Shire Valley, Malawi. Prevalence of antenatal, delivery and placental malaria was assessed in relation to maternal ZPP levels. The main outcome measures were prevalence of peripheral and placental Plasmodium falciparum parasitaemia and odds ratios of malaria risk. RESULTS: A total of 4,103 women were evaluated at first antenatal visit, of whom at delivery 1327 were screened for peripheral and 1285 for placental parasitaemia. Risk of malaria at delivery (peripheral or placental) was higher in primigravidae (p < 0.001), and lower (peripheral) with use of intermittent preventive anti-malarials during pregnancy (p < 0.001). HIV infection was associated with increased malaria parasitaemia (p < 0.02, peripheral or placental). Parasitaemia prevalence was lower in women with normal ZPP levels compared to those with raised concentrations at both first antenatal visit (all gravidae, p = 0.048, and at delivery (all gravidae, p < 0.001; primigravidae, p = 0.056). Between first antenatal visit and delivery women who transitioned from raised (at first antenatal visit) to normal ZPP values (at delivery) had lower peripheral parasitaemia prevalence at delivery compared to those who maintained normal ZPP values at both these visits (all gravidae: 0.70, 95%CI 0.4-1.1; primigravidae: 0.3, 0.1-0.8). In regression analysis this difference was lost with inclusion of HIV infection in the model. CONCLUSIONS: Raised ZPP concentrations in pregnancy were positively associated with P. falciparum parasitaemia and were probably secondary to malaria inflammation, rather than indicating an increased malaria risk with iron deficiency. It was not possible from ZPP measurements alone to determine whether iron deficiency or repletion alters malaria susceptibility in pregnancy.

The epidemiology of postpartum malaria: a systematic review.

Pregnant women are more susceptible to malaria than their non-pregnant counterparts. Less is known about the risk of malaria in the postpartum period. The epidemiology of postpartum malaria was systematically reviewed. Eleven articles fitted the inclusion criteria. Of the 10 studies that compared malaria data from the postpartum period with pregnancy data, nine studies suggested that the risk for malaria infection decreased after delivery. All three studies that compared postpartum data with non-pregnant non-postpartum women concluded that the risk did not return to pre-pregnancy levels immediately after delivery. The results of this review have to be carefully interpreted, as the majority of studies were not designed to study postpartum malaria, and there was large variability in study designs and reported outcomes. Current evidence suggests an effort should be made to detect and radically cure malaria during pregnancy so that women do not enter the postpartum period with residual parasites.

Parental compliance--an emerging problem in Liverpool community child health surveys 1991-2006.

BACKGROUND: Compliance is a critical issue for parental questionnaires in school based epidemiological surveys and high compliance is difficult to achieve. The objective of this study was to determine trends and factors associated with parental questionnaire compliance during respiratory health surveys of school children in Merseyside between 1991 and 2006. METHODS: Four cross-sectional respiratory health surveys employing a core questionnaire and methodology were conducted in 1991, 1993, 1998 and 2006 among 5-11 year old children in the same 10 schools in Bootle and 5 schools in Wallasey, Merseyside. Parental compliance fell sequentially in consecutive surveys. This analysis aimed to determine the association of questionnaire compliance with variation in response rates to specific questions across surveys, and the demographic profiles for parents of children attending participant schools. RESULTS: Parental questionnaire compliance was 92% (1872/2035) in 1991, 87.4% (3746/4288) in 1993, 78.1% (1964/2514) in 1998 and 30.3% (1074/3540) in 2006. The trend to lower compliance in later surveys was consistent across all surveyed schools. Townsend score estimations of socio-economic status did not differ between schools with high or low questionnaire compliance and were comparable across the four surveys with only small differences between responders and non-responders to specific core questions. Respiratory symptom questions were mostly well answered with fewer than 15% of non-responders across all surveys. There were significant differences between mean child age, maternal and paternal smoking prevalence, and maternal employment between the four surveys (all p < 0.01). Out-migration did not differ between surveys (p = 0.256) with three quarters of parents resident for at least 3 years in the survey areas. CONCLUSION: Methodological differences or changes in socio-economic status of respondents between surveys were unlikely to explain compliance differences. Changes in maternal employment patterns may have been contributory. This analysis demonstrates a major shift in community parental questionnaire compliance over a 15 year period to 2006. Parental questionnaire compliance must be factored into survey designs and methodologies.

Micronutrients and sickle cell disease, effects on growth, infection and vaso-occlusive crisis: a systematic review.

Patients with Sickle cell disease (SCD) exhibit signs of poor growth, increased susceptibility to infection and recurrent episodes of painful vaso-occlusive crises. Micronutrient deficiencies may increase susceptibility to these outcomes. We conducted a systematic review to assess the strength of evidence for improved outcomes related to micronutrient interventions. Six randomized-controlled trials of moderate quality met the inclusion criteria. Zinc supplementation was associated with improved growth and decreased incidence of infection and is a promising intervention in the management of SCD patients. Omega-3 fatty acid supplementation was associated with limited reduction in vaso occlusive crises. This review identifies key knowledge gaps, which are important research priorities for nutritional interventions.

Severe anemia in Malawian children.

BACKGROUND: Severe anemia is a major cause of sickness and death in African children, yet the causes of anemia in this population have been inadequately studied. METHODS: We conducted a case-control study of 381 preschool children with severe anemia (hemoglobin concentration, <5.0 g per deciliter) and 757 preschool children without severe anemia in urban and rural settings in Malawi. Causal factors previously associated with severe anemia were studied. The data were examined by multivariate analysis and structural equation modeling. RESULTS: Bacteremia (adjusted odds ratio, 5.3; 95% confidence interval [CI], 2.6 to 10.9), malaria (adjusted odds ratio, 2.3; 95% CI, 1.6 to 3.3), hookworm (adjusted odds ratio, 4.8; 95% CI, 2.0 to 11.8), human immunodeficiency virus infection (adjusted odds ratio, 2.0; 95% CI, 1.0 to 3.8), the G6PD(-202/-376) genetic disorder (adjusted odds ratio, 2.4; 95% CI, 1.3 to 4.4), vitamin A deficiency (adjusted odds ratio, 2.8; 95% CI, 1.3 to 5.8), and vitamin B12 deficiency (adjusted odds ratio, 2.2; 95% CI, 1.4 to 3.6) were associated with severe anemia. Folate deficiency, sickle cell disease, and laboratory signs of an abnormal inflammatory response were uncommon. Iron deficiency was not prevalent in case patients (adjusted odds ratio, 0.37; 95% CI, 0.22 to 0.60) and was negatively associated with bacteremia. Malaria was associated with severe anemia in the urban site (with seasonal transmission) but not in the rural site (where malaria was holoendemic). Seventy-six percent of hookworm infections were found in children under 2 years of age. CONCLUSIONS: There are multiple causes of severe anemia in Malawian preschool children, but folate and iron deficiencies are not prominent among them. Even in the presence of malaria parasites, additional or alternative causes of severe anemia should be considered.

Reduced risk for placental malaria in iron deficient women.

BACKGROUND: Nutritional iron deficiency may limit iron availability to the malaria parasite reducing infection risk, and/or impair host immunity thereby increasing this risk. In pregnant women, there is evidence of an adverse effect with iron supplementation, but the few reported studies are strongly confounded. METHODS: A case control study in pregnant Malawian women was undertaken in Chikhwawa southern Malawi in order to describe iron status in relation to placental malaria controlling for several confounding factors. Pregnancy characteristics were obtained and a blood sample at delivery. A full blood count was performed and serum ferritin and transferrin receptor quantified by enzyme-linked immunoassay. DNA analysis was used to identify genetic polymorphisms for ABO phenotype, hemoglobin HbS, and glucose -6 phosphate dehydrogenase deficiency. Placental tissue was obtained and malaria histology classified as active, past or no malaria infection. RESULTS: 112 cases with placental malaria were identified and 110 women with no evidence of placental infection. Iron deficiency was less frequent in women with placental Plasmodium falciparum infection. In those with acute, chronic or past placental infections the odds ratio for iron deficiency was 0.4, 95% CI 0.2-0.8, p = 0.01; for acute and chronic infections 0.4, 0.2-0.8, p = 0.006; for acute infection 0.3, 0.1-0.7, p = 0.001. The association was greater in multigravidae. CONCLUSION: Women with either acute, or acute and chronic placental malaria were less likely to have iron deficiency than women without placental malaria infection There is a priority to establish if reversing iron deficiency through iron supplementation programs either prior to or during pregnancy enhances malaria risk.

Dose response association of pregnancy cigarette smoke exposure, childhood stature, overweight and obesity.

BACKGROUND: The combined dose response effects of pregnancy cigarette smoke exposure on childhood overweight, obesity and short stature have not been reported. METHOD: A community based cross-sectional survey of 3038 children aged 5-11 years from 15 primary schools in Merseyside, UK. Self-completed parental questionnaires were used for family characteristics, socio-economic status and parental smoking practices. Children were measured for height and weight and z-scores calculated for parental smoking categories. RESULTS: Of 689 (34.0%) mothers who smoked during pregnancy 50.5% smoked ten or more cigarettes daily (heavy smokers). Children of maternal non-smokers had prevalence estimates for overweight, obesity and short stature of 25, 9.6 and 3.2%, respectively. Prevalence estimates were higher in children of mothers who were heavy smokers during pregnancy, 31.5% (P = 0.001), 15.6% (P < 0.001) and 5.5% (P = 0.001), respectively. Mean height for age z-scores was lower among heavy maternal (P < 0.001) and paternal smokers (P < 0.01) compared to non-smokers. Childhood overweight, obesity or short stature were all associated with heavy maternal smoking during pregnancy (all P < 0.001). Mean body mass index (BMI) z-scores were higher in boys of mothers who smoked (P = 0.043). The adjusted odds ratio for short stature in children of heavy maternal smokers was 2.76 (95% CI 1.21-6.33) and 4.28 (1.37-13.37) if both parents were heavy smokers. The adjusted OR for obesity in children of maternal smokers was 1.61(1.19-2.18). The population attributable risk for short stature was 8.8% (1.1-22.7) for heavy maternal smokers. CONCLUSION: A dose-response association was observed between pregnancy smoking exposure, short stature and obesity.

Trends in pregnancy outcomes in Malawian adolescents receiving antimalarial and hematinic supplements.

OBJECTIVE: To describe pregnancy outcomes of adolescent and adult primigravidae receiving antimalarials and hematinic supplementation and compare findings with a survey in this area a decade earlier. DESIGN: Cross-sectional surveys in intervention and control sites. SETTING: Community, antenatal and delivery facilities in Chikwawa, Malawi. A rural area with year round malaria transmission. METHODS: Data on antenatal attendance, uptake of intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP), birthweight, malaria, anaemia, for 2,152 primigravidae. OUTCOME MEASURES: Place of delivery, anaemia, malaria, birthweight. RESULTS: Fewer adolescent than adult primigravidae received >or=2 IPTp-SP doses (66 vs. 77.2%, p < 0.001), although more attended for two or more antenatal visits (92.0 vs. 76.7%, p < 0.001). Only 24.1% of adolescent primigravidae attended for hospital delivery. Women resident in intervention sites receiving IPTp-SP community distribution were more likely to choose a community delivery (p < 0.01), and have higher uptake of IPTp-SP (p = 0.036) than women not resident in these villages. Postnatal malaria prevalence was low and did not differ by age or place of delivery. Postnatal anaemia and low birthweight prevalence were higher in adolescents with community deliveries. Maternal anaemia and low birthweight prevalence were lower amongst adolescents in this study compared to estimates from the same population a decade previously. CONCLUSIONS: Adolescents had higher anaemia risk, lower IPTp-SP uptake than adults and under a quarter had a hospital delivery. Pregnancy outcomes improved compared to the survey a decade earlier. Monitoring and surveillance is required to reinforce to policy makers the need to improve adolescent coverage for available interventions.

Trends in prevalence of childhood and parental asthma in Merseyside, 1991-2006.

BACKGROUND: To determine changes in prevalence of parental and childhood asthma in Merseyside between 1991 and 2006. METHODS: Four standardized cross-sectional respiratory surveys using a parent-completed questionnaire were completed in 1991 (n = 1171), 1993 (n = 2368) 1998 (n = 1964) and in 2006 (n = 1074) among primary school children attending the same schools in lower socio-economic areas of Merseyside. Main outcome measures were prevalence of doctor diagnosed asthma (DDA) and the symptom triad of cough, wheeze and breathlessness (C+W+B+). RESULTS: Between 1991 and 1998 prevalence of DDA increased (P < 0.001), but in 2006 this decreased from 29.8 to 19.4% (P < 0.001). Prevalence of C+W+B+ increased from 7.8 to 8.0% by 1998, then decreased to 6.7% in 2006 (P = 0.39). Between 1998 and 2006, childhood hospital admissions for respiratory illness decreased from 11.3 to 9.7% (P = 0.23). During this period paternal asthma prevalence increased from 8.6 to 10.7% (P = 0.001) and maternal asthma from 11.2 to 13.4% (P = 0.09). CONCLUSIONS: An increase in the prevalence of DDA and asthmatic respiratory symptoms occurred in children prior to 1998, but this had decreased by 2006. Prevalence of parental asthma increased during the same period.

Parental smoking and increased likelihood of female births.

BACKGROUND: A recent decline in the male:female (M:F) sex ratio may relate to pregnancy cigarette smoke exposure. AIM: To assess trends and cigarette exposure dose-response effects on the sex ratio. SUBJECTS AND METHODS: A retrospective analysis was carried out of deliveries at the Liverpool Women's Hospital between 1998 and 2003, and of deliveries reported in community surveys from the same area in 1998 and 2006. RESULTS: For the hospital sample, the M:F sex ratio was 1.14 if no parent smoked, and 0.77 when both parents smoked during the mother's pregnancy (p < 0.001). Heavy maternal smokers (>10 cigarettes per day) were more likely to deliver a female baby than light smokers (p < 0.001). Smoking was associated with increased likelihood of female birth controlling for birth year, socio-economic status, alcohol exposure, maternal haemoglobin and body mass index (adjusted OR: 1.41, 95% CI 1.12-1.92, p < 0.001). In the community sample controlling for socio-economic status the ratios were 1.13 (95% CI 1.03-1.24, p = 0.015) in 1998 and 1.31 (95% CI 1.16-1.48, p < 0.001) in 2006. Secular trends showed decreasing ratios in hospital and community samples for both smokers and non-smokers. CONCLUSION: Pregnancy cigarette smoking increased the proportion of female births with evidence for a dose-response association.

Frequency of the MTHFR C677T polymorphism in Yemeni children with sickle cell disease.

The frequency of the methylenetetrahydrofolate reductase enzyme (MTHFR) C677T mutation was determined using polymerase chain reaction (PCR) and with measurement of plasma total homocysteine (tHcy), folate, vitamins B6, B12 and disease severity in 102 SS children from Yemen. The homozygous TT genotype for MTHFR C677T was present in 2% (2/102), and heterozygous CT in 10.8% (11/102), giving an allele frequency of 7.35%. The T allele was not associated with raised plasma tHcy or increased disease severity. The mean [+/-SD (standard deviation)] tHcy was 2.8 +/- 1.7 micromol/L, increased with age and was highest in children >10 years (3.6 +/- 2.5 vs. 2.5 +/- 1.2 micromol/L, p <0.05). Whole blood folate and plasma vitamin B12 levels were normal or elevated, and 4% had vitamin B6 deficiency. In Yemeni children with sickle cell disease the frequency of the MTHFR C677T mutation was not higher than expected in the general population and was not associated with disease severity.

Malaria early in the first pregnancy: Potential impact of iron status.

BACKGROUND & AIMS: Low iron stores may protect from malaria infection, therefore improving iron stores in early pregnancy in line with current recommendations could increase malaria susceptibility. To test this hypothesis we compared iron biomarkers and red cell indices in nulliparae and primigravidae who participated in a randomized controlled trial of long-term weekly iron supplementation. METHODS: Cross-sectional and longitudinal data analysis from a randomized controlled trial of long-term weekly iron supplementation in rural Burkina Faso. Malaria parasitaemia was monitored and biomarkers and red cell indices measured at study end-points: plasma ferritin, transferrin receptor (sTfR), zinc protoporphyrin, hepcidin, sTfR/log10 ferritin ratio, body iron, haemoglobin, red cell distribution width; mean corpuscular haemoglobin concentration/volume, and C-reactive protein. Correlation coefficients between biomarkers and red cell indices were determined. A regression correction approach based on ferritin was used to estimate iron body stores, allowing for inflammation. Body iron differences were compared between nulliparae and primigravidae, and the association determined of iron biomarkers and body iron stores with malaria. RESULTS: Iron and haematological indices of 972 nulliparae (mean age 16.5 years) and 314 primigravidae (median gestation 18 weeks) were available. Malaria prevalence was 54.0% in primigravidae and 41.8% in nulliparae (relative risk 1.28, 95% CI 1.13-1.45, P < 0.001), anaemia prevalence 69.7% and 43.4% (P < 0.001), and iron deficient erythropoiesis (low body iron) 8.0% and 11.7% (P = 0.088) respectively. Unlike other biomarkers the sTfR/log10 ferritin ratio showed no correlation with inflammation as measured by CRP. Most biomarkers indicated reduced iron deficiency in early pregnancy, with the exception of haemoglobin. Body iron increased by 0.6-1.2 mg/kg in early gestation, did not differ by malaria status in nulliparae, but was higher in primigravidae with malaria (6.5 mg/kg versus 5.0 mg/kg; relative risk 1.53, 95% CI 0.67-2.38, P < 0.001). CONCLUSION: In primigravidae, early pregnancy haemoglobin was not a good indicator of requirement for iron supplementation, which could be detrimental given the association of better iron status with increased malaria infection. TRIAL REGISTRATION: clinicaltrials.gov:NCT01210040. Until placed in a public repository, data relating to the current study can be requested from the corresponding author and will be made available following an end user data agreement and sponsor approval.

Monitoring and evaluation of malaria in pregnancy - developing a rational basis for control.

Monitoring and evaluation of malaria control in pregnancy is essential for assessing the efficacy and effectiveness of health interventions aimed at reducing the major burden of this disease on women living in endemic areas. Yet there is no currently integrated strategic approach on how this should be achieved. Malaria control in pregnancy is formulated in relation to epidemiological patterns of exposure. Current emphasis is on intermittent preventive treatment (IPTp) during pregnancy with sulphadoxine-pyrimethamine in higher transmission areas, combined with insecticide treated bed nets (ITNs) and case management. Emphasis in lower transmission areas is primarily on case management. This paper discusses a rational basis for monitoring and evaluation based on: assessments of therapeutic and prophylactic drug efficacy; proportional reductions in parasite prevalence; seasonal effects; rapid assessment methodologies; birthweight and/or anaemia nomograms; case-coverage methods; maternal mortality indices; operational and programmatic indicators; and safety and pharmacovigilance of antimalarials in pregnancy. These approaches should be incorporated more effectively within National Programmes in order to facilitate surveillance and improve identification of high-risk women. Systems for utilizing routinely collected data should be strengthened, with greater attention to safety and pharmacovigilance with the advent of artemisinin combination therapies, and prospects of inadvertent exposures to artemisinins in the first trimester. Integrating monitoring activities within malaria control, reproductive health and adolescent-friendly services will be critical for implementation. Large-scale operational research is required to further evaluate the validity of currently proposed indicators, and in order to clarify the breadth and scale of implementation to be deployed.

Prenatal alcohol exposure, CYP17 gene polymorphisms and fetal growth restriction.

OBJECTIVE: To determine the association of maternal CYP17 gene polymorphisms and prenatal alcohol consumption with intrauterine growth restriction (IUGR). STUDY DESIGN: A case-control study in singleton livebirths was conducted at the Liverpool Women's Hospital between 2004 and 2005. Cases (n=90) were mothers with an IUGR baby and controls (n=180) those with a normal birthweight infant. Maternal genomic DNA was extracted from buccal smears and PCR (RFLP) was used for genotyping. RESULTS: Amongst cases, the prevalence of the maternal CYP17 homozygous wild type "A1A1", heterozygous "A1A2" and homozygous "A2A2" variants was 36.7%, 47.7% and 15.6%, which did not differ significantly from their prevalence amongst controls (p=0.6). The proportion with prenatal alcohol exposure was significantly higher in cases than controls (45.6% versus 30.6%, p=0.01). Mean birthweight was significantly lower in mothers with the CYP17 A1A1 genotype compared to those with variant genotypes (A1A2/A2A2) in both the alcohol-exposed (p=0.03) and non-exposed groups (p=0.01). In all women regardless of genotype, IUGR risk increased in mothers exposed to alcohol during pregnancy (OR, 2.9, 95% CI; 1.8-4.2, p=0.01). There was a significant interaction between the CYP17 A1A1 genotype and prenatal alcohol consumption for fetal growth restriction (adjusted OR, 1.4, 95% CI; 1.1-1.9, p=0.04). CONCLUSION: The association between prenatal alcohol exposure and intrauterine fetal growth restriction was modulated by the maternal CYP17 A1A1 genotype.