Perspectives on the design and methodology of periconceptional nutrient supplementation trials.

Periconceptional supplementation could extend the period over which maternal and fetal nutrition is improved, but there are many challenges facing early-life intervention studies. Periconceptional trials differ from pregnancy supplementation trials, not only because of the very early or pre-gestational timing of nutrient exposure but also because they generate subsidiary information on participants who remain non-pregnant. The methodological challenges are more complex although, if well designed, they provide opportunities to evaluate concurrent hypotheses related to the health of non-pregnant women, especially nulliparous adolescents. This review examines the framework of published and ongoing randomised trial designs. Four cohorts typically arise from the periconceptional trial design--two of which are non-pregnant and two are pregnant--and this structure provides assessment options related to pre-pregnant, maternal, pregnancy and fetal outcomes. Conceptually the initial decision for single or micronutrient intervention is central--as is the choice of dosage and content--in order to establish a comparative framework across trials, improve standardisation, and facilitate interpretation of mechanistic hypotheses. Other trial features considered in the review include: measurement options for baseline and outcome assessments; adherence to long-term supplementation; sample size considerations in relation to duration of nutrient supplementation; cohort size for non-pregnant and pregnant cohorts as the latter is influenced by parity selection; integrating qualitative studies and data management issues. Emphasis is given to low resource settings where high infection rates and the possibility of nutrient-infection interactions may require appropriate safety monitoring. The focus is on pragmatic issues that may help investigators planning a periconceptional trial

Low birth weight and fetal anaemia as risk factors for infant morbidity in rural Malawi

Low birth weight (LBW) and fetal anaemia (FA) are common in malaria endemic areas. To investigate the incidence of infectious morbidity in infants in rural Malawi in relation to birth weight and fetal anaemia, a cohort of babies was followed for a year on the basis of LBW

The impact of endemic and epidemic malaria on the risk of stillbirth in two areas of Tanzania with different malaria transmission patterns

BACKGROUND: The impact of malaria on the risk of stillbirth is still under debate. The aim of the present analysis was to determine comparative changes in stillbirth prevalence between two areas of Tanzania with different malaria transmission patterns in order to estimate the malaria attributable component. METHODS: A retrospective analysis was completed of stillbirth differences between primigravidae and multigravidae in relation to malaria cases and transmission patterns for two different areas of Tanzania with a focus on the effects of the El Niño southern climatic oscillation (ENSO). One area, Kagera, experiences outbreaks of malaria, and the other area, Morogoro, is holoendemic. Delivery and malaria data were collected over a six year period from records of the two district hospitals in these locations. RESULTS: There was a significantly higher prevalence of low birthweight in primigravidae compared to multigravidae for both data sets. Low birthweight and stillbirth prevalence (17.5% and 4.8%) were significantly higher in Kilosa compared to Ndolage (11.9% and 2.4%). There was a significant difference in stillbirth prevalence between Ndolage and Kilosa between malaria seasons (2.4% and 5.6% respectively, p < 0.001) and during malaria seasons (1.9% and 5.9% respectively, p < 0.001). During ENSO there was no difference (4.1% and 4.9%, respectively). There was a significant difference in low birthweight prevalence between Ndolage and Kilosa between malaria seasons (14.4% and 23.0% respectively, p < 0.001) and in relation to malaria seasons (13.9% and 25.2% respectively, p < 0.001). During ENSO there was no difference (22.2% and 19.8%, respectively). Increased low birthweight risk occurred approximately five months following peak malaria prevalence, but stillbirth risk increased at the time of malaria peaks. CONCLUSION: Malaria exposure during pregnancy has a delayed effect on birthweight outcomes, but a more acute effect on stillbirth risk

Crystal structure of chlorido-methanol-(N-(2-(oxy)-3-methoxybenzylidene)pyridine-4-carbohydrazonato-κ3O,N,O′)-(4-methylphenyl)methyl-tin(IV), C23H24ClN3O4Sn

C23H24ClN3O4Sn, triclinic, P¯1 (no. 2), a=9.7536(2) Å, b=10.0755(2) Å, c=12.4215(3) Å, α=84.928(2)°, β=72.544(2)°, γ=74.382(2)°, V =1121.44(4) Å3, Z =2, Rgt(F)=0.021, wRref(F2)=0.054, T =100(2) K

子宮頸部及び内膜における aromatase の局在と周期性変化

Objectives: To determine the role of maternal CYP1A1, GSTT1, and GSTM1 metabolic gene polymorphisms in modulating the association between pregnancy smoking exposure and fetal growth restriction. Study design: A case-control study was conducted to investigate if the association of pregnancy smoking and birth outcome was modulated by maternal gene polymorphisms. A total of 90 mothers with an IUGR baby (cases) and 180 mothers without IUGR (controls) were enrolled. Results: Almost half of smokers who carried a CYP1A1 variant (51.3%), GSTT1 null (43.6%), or GSTM1 null genotypes (64.1%) delivered a baby with IUGR. Smokers with the variant CYP1A1 "aa" genotype had babies with lower mean birthweight than non-smokers with the same genotype (p = 0.004). An interaction test showed increased prevalence of IUGR in smokers with the CYP1A1 (Aa/aa) variant (adjusted OR, 1.9; 95% CI, 1.4-5.5, p = 0.01), or with the GSTT1 null (AOR, 1.5; 1.1-3.1, p = 0.001), or GSTM1 null genotypes (AOR, 1.5; 1.2-3.7, p = 0.001). Conclusions: Risk of fetal growth restriction in mothers who smoked during pregnancy was modulated by maternal metabolic gene polymorphisms. The genetic control of the conversion of toxic metabolites of tobacco smoke to less damaging substances is important for maternal and fetal health. (C) 2008 Elsevier Ireland Ltd. All rights reserved

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

New cut-off values for ferritin and soluble transferrin receptor for the assessment of iron deficiency in children in a high infection pressure area

Background: Due to the potential risk of iron supplementation in iron replete children, it is important to properly identify children who may require iron supplementation. However, assessment of the iron status has proven to be difficult, especially in children living in areas with high infection pressure (including malaria). Aims and Methods: Biochemical iron markers were compared to bone marrow iron findings in 381 Malawian children with severe anaemia. Results: Soluble transferrin receptor/log ferritin (TfR-F index), using a cut-off of 5.6, best predicted bone marrow iron stores deficiency (sensitivity 74%, specificity 73%, accuracy 73%). In order to improve the diagnostic accuracy of ferritin or sTfR as a stand-alone marker, the normal cut-off value needed to be increased by 810% and 83% respectively. Mean cell haemoglobin concentration (MCHC), using a cut-off of 32.1 g/dl, had a sensitivity of 67% and specificity of 64% for detecting iron stores deficiency. Conclusion: TfR-F index incorporated the high sensitivity of sTfR, a proxy for cellular iron need, and the high specificity of ferritin, a proxy for iron stores. In areas with a high infection pressure, the TfR-F index best predicted iron deficiency. However, in settings where diagnostic tests are limited, MCHC may be an acceptable alternative screening test