Bernard J. Brabin

Delayed cord clamping and haemoglobin levels in infancy: a randomised controlled trial in term babies.

Objectivesu2002 This study was carried out to assess whether delaying umbilical cord clamping is effective in improving the haematological status of term infants living in a malaria‐endemic area, and whether this is associated with complications in infants and mothers.

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

BACKGROUNDnThe combined dose response effects of pregnancy cigarette smoke exposure on childhood overweight, obesity and short stature have not been reported.nnnMETHODnA 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.nnnRESULTSnOf 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% (Pu2009=u20090.001), 15.6% (Pu2009<u20090.001) and 5.5% (Pu2009=u20090.001), respectively. Mean height for age z-scores was lower among heavy maternal (Pu2009<u20090.001) and paternal smokers (Pu2009<u20090.01) compared to non-smokers. Childhood overweight, obesity or short stature were all associated with heavy maternal smoking during pregnancy (all Pu2009<u20090.001). Mean body mass index (BMI) z-scores were higher in boys of mothers who smoked (Pu2009=u20090.043). 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.nnnCONCLUSIONnA dose-response association was observed between pregnancy smoking exposure, short stature and obesity.

Iron Status Predicts Malaria Risk in Malawian Preschool Children

Introduction Iron deficiency is highly prevalent in pre-school children in developing countries and an important health problem in sub-Saharan Africa. A debate exists on the possible protective effect of iron deficiency against malaria and other infections; yet consensus is lacking due to limited data. Recent studies have focused on the risks of iron supplementation but the effect of an individuals iron status on malaria risk remains unclear. Studies of iron status in areas with a high burden of infections often are exposed to bias. The aim of this study was to assess the predictive value of baseline iron status for malaria risk explicitly taking potential biases into account. Methods and materials We prospectively assessed the relationship between baseline iron deficiency (serum ferritin <30 µg/L) and malaria risk in a cohort of 727 Malawian preschool children during a year of follow-up. Data were analyzed using marginal structural Cox regression models and confounders were selected using causal graph theory. Sensitivity of results to bias resulting from misclassification of iron status by concurrent inflammation and to bias from unmeasured confounding were assessed using modern causal inference methods. Results and Conclusions The overall incidence of malaria parasitemia and clinical malaria was 1.9 (95% CI 1.8–2.0) and 0.7 (95% CI 0.6–0.8) events per person-year, respectively. Children with iron deficiency at baseline had a lower incidence of malaria parasitemia and clinical malaria during a year of follow-up; adjusted hazard ratios 0.55 (95%-CI:0.41–0.74) and 0.49 (95%-CI:0.33–0.73), respectively. Our results suggest that iron deficiency protects against malaria parasitemia and clinical malaria in young children. Therefore the clinical importance of treating iron deficiency in a pre-school child should be weighed carefully against potential harms. In malaria endemic areas treatment of iron deficiency in children requires sustained prevention of malaria.

ABO Blood Group Phenotypes and Plasmodium falciparum Malaria: Unlocking a Pivotal Mechanism

Host susceptibility to Plasmodium falciparum infection is central for improved understanding of malaria in human populations. Red blood cell (RBC) polymorphisms have been proposed as factors associated with malaria infection or its severity, although no systematic appraisal of ABO phenotypes and malaria risk has been undertaken. This analysis summarises epidemiological, clinical and immunological evidence on the nature of ABO histo-blood antigens and their interaction with malaria in terms of population genetics, infection risk, severe malaria and placental malaria. In non-pregnant subjects, a meta-analysis showed no conclusive evidence associating ABO phenotypes with risk of uncomplicated malaria. There was stronger evidence that ABO phenotype modulates severity of P. falciparum malaria, with group A associated with severe disease and blood group O with milder disease. Among pregnant subjects, group O was associated with increased risk of placental malaria in primigravidae and reduced risk in multigravidae. The biological basis for ABO-related susceptibility to malaria is reviewed. Several mechanisms relate to these associations including affinity for Anopheles gambiae; shared ABO antigens with P. falciparum; impairment of merozoite penetration of RBCs; and cytoadherence, endothelial activation and rosetting. ABO phenotypic associations with malaria are related to its pathogenesis and improved understanding of these interactions is required for understanding the glycobiology of malaria infection.

Real-time PCR Demonstrates Ancylostoma duodenale Is a Key Factor in the Etiology of Severe Anemia and Iron Deficiency in Malawian Pre-school Children

Background Hookworm infections are an important cause of (severe) anemia and iron deficiency in children in the tropics. Type of hookworm species (Ancylostoma duodenale or Necator americanus) and infection load are considered associated with disease burden, although these parameters are rarely assessed due to limitations of currently used diagnostic methods. Using multiplex real-time PCR, we evaluated hookworm species-specific prevalence, infection load and their contribution towards severe anemia and iron deficiency in pre-school children in Malawi. Methodology and Findings A. duodenale and N. americanus DNA loads were determined in 830 fecal samples of pre-school children participating in a case control study investigating severe anemia. Using multiplex real-time PCR, hookworm infections were found in 34.1% of the severely anemic cases and in 27.0% of the non-severely anemic controls (p<0.05) whereas a 5.6% hookworm prevalence was detected by microscopy. Prevalence of A. duodenale and N. americanus was 26.1% and 4.9% respectively. Moderate and high load A. duodenale infections were positively associated with severe anemia (adjusted odds ratio: 2.49 (95%CI 1.16–5.33) and 9.04 (95%CI 2.52–32.47) respectively). Iron deficiency (assessed through bone marrow examination) was positively associated with intensity of A. duodenale infection (adjusted odds ratio: 3.63 (95%CI 1.18–11.20); 16.98 (95%CI 3.88–74.35) and 44.91 (95%CI 5.23–385.77) for low, moderate and high load respectively). Conclusions/Significance This is the first report assessing the association of hookworm load and species differentiation with severe anemia and bone marrow iron deficiency. By revealing a much higher than expected prevalence of A. duodenale and its significant and load-dependent association with severe anemia and iron deficiency in pre-school children in Malawi, we demonstrated the need for quantitative and species-specific screening of hookworm infections. Multiplex real-time PCR is a powerful diagnostic tool for public health research to combat (severe) anemia and iron deficiency in children living in resource poor settings.

ABO phenotypes and malaria related outcomes in mothers and babies in The Gambia: a role for histo-blood groups in placental malaria?

BackgroundHost susceptibility to P.falciparum is critical for understanding malaria in pregnancy, its consequences for the mother and baby, and for improving malaria control in pregnant women. Yet host genetic factors which could influence placental malaria risk are little studied and there are no reports of the role of blood group polymorphisms on pregnancy outcomes in malaria endemic areas.This study analyses the association between ABO blood group phenotypes in relation to placental malaria pathology.MethodsA total of 198 mother/child pairs delivering in Banjul and the Kombo-St Mary District (The Gambia) were analysed. ABO blood group was measured by agglutination. Placental malaria parasites wee enumerated and the presence of malaria pigment noted. Birth anthropometry was recorded and placental weight. Maternal and infant haemoglobin was measured.Results89 (45%) subjects were primiparae and 110 (55%)multiparae. The ABO phenotype distribution was 38(A), 52(B), 6(AB) and 102(O). Placental histo-pathology showed active placental malaria in 74 (37%), past infection in 42 (21%) and no infection in 82 cases (41%). In primiparae blood group O was associated with a higher risk of active infection (OR = 2.99; 95% CI = 1.24–7.25), and a lower risk of past infection (OR = 0.31, 0.10–1.01, p < 0.05). In multiparae the O phenotype was associated with reduced prevalence of active or past placental infection (OR = 0.45; 95% CI 0.21–0.98). The mean feto-placental weight ratio was significantly higher in multiparae with group O women compared to non-O phenotypes (5.74 vs 5.36; p = 0.04). Among primiparae with active placental infection, mean birth weight was higher in children of mothers with the O phenotype (p = 0.04).ConclusionThese results indicate that blood group O was significantly associated with increased placental malaria infection in primiparae and reduced risk of infection in multiparae. This parity related susceptibility was not present with other ABO phenotypes. Cell surface glycans, such as ABO and related antigens have special relevance in reproductive biology and could modulate specific cell interactions as those associated with the pathogenesis of placental malaria.

Comparative efficacy of chloroquine and sulphadoxine – pyrimethamine in pregnant women and children: a meta‐analysis

Objectiveu2002 To compare the efficacy of chloroquine and sulphadoxine–pyremethamine against Plasmodium falciparum infection in pregnant women and in children from the same endemic areas of Africa, with the aim of determining the level of correspondence in efficacy determinations in these two risk groups.

A case-control study of CYP1A1, GSTT1 and GSTM1 gene polymorphisms, pregnancy smoking and fetal growth restriction.

OBJECTIVESnTo determine the role of maternal CYP1A1, GSTT1, and GSTM1 metabolic gene polymorphisms in modulating the association between pregnancy smoking exposure and fetal growth restriction.nnnSTUDY DESIGNnA 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.nnnRESULTSnAlmost 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).nnnCONCLUSIONSnRisk 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.

Community-based distribution of sulfadoxine-pyrimethamine for intermittent preventive treatment of malaria during pregnancy improved coverage but reduced antenatal attendance in southern Malawi

Objectiveu2002 To evaluate the impact of a 2‐year programme for community‐based delivery of sulfadoxine‐pyremethamine (SP) on intermittent preventive treatment during pregnancy coverage, antenatal clinic attendance and pregnancy outcome.

Pregnancy smoking and birth outcomes.

This review summarizes the epidemiology and consequences of maternal smoking in pregnancy, with emphasis on the adverse effects on birth outcomes. In developed countries, approximately 15%, and in developing countries, approximately 8% of women smoke cigarettes, and adolescents and women from lower socioeconomic groups are more likely than other women to smoke while pregnant. Maternal smoking during pregnancy is the largest modifiable risk factor for intrauterine growth restriction. A meta-analysis of recent studies showed that the pooled estimate for reduction of mean birthweight was 174 g (95% confidence limits 132–220 g). Other studies confirm a weaker association between maternal smoking and preterm birth. The population attributable risk of low birthweight due to maternal smoking in the UK is estimated to be 29–39%. Tobacco smoke toxins damage the placenta and may lead to placental abruption, abortion or placenta praevia. Infants of mothers who smoke in pregnancy are at an increased risk of respiratory complications including asthma, obesity and, possibly, behavioral disorders. These effects may be dose-related, as there is good evidence that mean birthweight decrements are greater with increased numbers of cigarettes smoked during pregnancy. Cotinine is a useful indicator of tobacco smoke exposure in pregnant women and higher levels in body fluids have been related to lower birthweights. Maternal genetic polymorphisms of the cytochrome P (CYP)450 and glutathione-S-transferase (GST) subfamilies of metabolic genes influence the magnitude of the effect of nicotine exposure on birth outcomes through their influence on nicotine metabolism. Greatly increased risk of cigarette smoke-induced diseases, including low birthweight, has been found in individuals with susceptible genotypes. Interventions to control maternal smoking are also considered.