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Brabin L.,University of Manchester | Brabin B.J.,Child and Reproductive Health Group | Brabin B.J.,Global Child Health Group | Gies S.,Institute of Tropical Medicine
Nutrition Reviews | Year: 2013

Infection is a major cause of neonatal death in developing countries. This review investigates whether host iron status affects the risk of maternal and/or neonatal infection, potentially contributing to neonatal death, and summarizes the iron acquisition mechanisms described for pathogens causing stillbirth, preterm birth, and congenital infection. In vitro evidence shows that iron availability influences the severity and chronicity of infections that cause these negative outcomes of pregnancy. In vivo evidence is lacking, as relevant studies of maternal iron supplementation have not assessed the effect of iron status on the risk of maternal and/or neonatal infection. Reducing iron-deficiency anemia among women is beneficial and should improve the iron stores of babies; moreover, there is evidence that iron status in young children predicts the risk of malaria and, possibly, the risk of invasive bacterial diseases. Caution with maternal iron supplementation is indicated in iron-replete women who may be at high risk of exposure to infection, although distinguishing between iron-replete and iron-deficient women is currently difficult in developing countries, where a point-of-care test is needed. Further research is indicated to investigate the risk of infection relative to iron status in mothers and babies in order to avoid iron intervention strategies that may result in detrimental birth outcomes in some groups of women. © 2013 International Life Sciences Institute.


Raiten D.J.,U.S. National Institutes of Health | Sakr Ashour F.A.,U.S. National Institutes of Health | Ross A.C.,Pennsylvania State University | Meydani S.N.,Tufts University | And 6 more authors.
Journal of Nutrition | Year: 2015

An increasing recognition has emerged of the complexities of the global health agenda-specifically, 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. EachWGwas 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. © 2015 American Society for Nutrition.


Koshy G.,Child and Reproductive Health Group | Delpisheh A.,Child and Reproductive Health Group | Brabin B.J.,Child and Reproductive Health Group | Brabin B.J.,Royal Liverpool Childrens Hospital | Brabin B.J.,University of Amsterdam
European Journal of Public Health | Year: 2011

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. © 2010 The Author.


Senga E.L.,University of Malawi | Koshy G.,Child and Reproductive Health Group | Brabin B.J.,Child and Reproductive Health Group | Brabin B.J.,University of Amsterdam
Malaria Journal | Year: 2012

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. © 2012 Senga et al.; licensee BioMed Central Ltd.


Kayentao K.,Child and Reproductive Health Group | Kayentao K.,University of Bamako | Garner P.,Child and Reproductive Health Group | Van Eijk A.M.,Child and Reproductive Health Group | And 8 more authors.
JAMA - Journal of the American Medical Association | Year: 2013

Importance: Intermittent preventive therapy with sulfadoxine-pyrimethamine to control malaria during pregnancy is used in 37 countries in sub-Saharan Africa, and 31 of those countries use the standard 2-dose regimen. However, 2 doses may not provide protection during the last 4 to 10 weeks of pregnancy, a pivotal period for fetal weight gain. Objective: To perform a systematic review and meta-analysis of trials to determine whether regimens containing 3 or more doses of sulfadoxine-pyrimethamine for intermittent preventive therapy during pregnancy are associated with a higher birth weight or lower risk of low birth weight (LBW) (<2500 g) than standard 2-dose regimens. Data Sources and Study Selection: ISI Web of Knowledge, EMBASE, SCOPUS, PubMed, LILACS, the Malaria in Pregnancy Library, Cochrane CENTRAL, and trial registries from their inception to December 2012, without language restriction. Eligible studies included randomized and quasi-randomized trials of intermittent preventive therapy during pregnancy with sulfadoxine-pyrimethamine monotherapy. Data Extraction: Data were independently abstracted by 2 investigators. Relative risk (RR), mean differences, and 95% CIs were calculated with random-effects models. Results: Of 241 screened studies, 7 trials of 6281 pregnancies were included. The median birth weight in the 2-dose group was 2870 g (range, 2722-3239 g) and on average 56 g higher (95% CI, 29-83 g; I2=0%) in the ≥3-dose group. Three or more doses were associated with fewer LBW births (RR, 0.80; 95% CI, 0.69-0.94; I2=0%), with a median LBW risk per 1000 women in the 2-dose group (assumed control group risk) of 167 per 1000 vs 134 per 1000 in the ≥3-dose group (absolute risk reduction, 33 per 1000 [95% CI, 10-52]; number needed to treat=31). The association was consistent across a wide range of sulfadoxine-pyrimethamine resistance (0% to 96% dihydropteroate-synthase K540E mutations). There was no evidence of small-study bias. The ≥3-dose group had less placental malaria (RR, 0.51; 95% CI, 0.38-0.68; I2=0%, in 6 trials, 63 vs 32 per 1000; absolute risk reduction, 31 per 1000 [95% CI, 20-39]). In primigravid plus secundigravid women, the risk of moderate to severe maternal anemia was lower in the ≥3-dose group (RR, 0.60; 95% CI, 0.36-0.99; I2=20%; in 6 trials, 36 vs 22 per 1000; absolute risk reduction, 14 per 1000 [95% CI, 0.4-23]). There were no differences in rates of serious adverse events. Conclusions and Relevance: Among pregnant women in sub-Saharan Africa, intermittent preventive therapy with 3 or more doses of sulfadoxine-pyrimethamine was associated with a higher birth weight and lower risk of LBW than the standard 2-dose regimens. These data provide support for the new WHO recommendations to provide at least 3 doses of intermittent preventive therapy during pregnancy at each scheduled antenatal care visit in the second and third trimester. ©2013 American Medical Association. All rights reserved.


Dellicour S.,Child and Reproductive Health Group | Tatem A.J.,Kenya Medical Research Institute | Tatem A.J.,University of Florida | Guerra C.A.,Kenya Medical Research Institute | And 5 more authors.
PLoS Medicine | Year: 2010

Background: Comprehensive and contemporary estimates of the number of pregnancies at risk of malaria are not currently available, particularly for endemic areas outside of Africa. We derived global estimates of the number of women who became pregnant in 2007 in areas with Plasmodium falciparum and P. vivax transmission. Methods and Findings: A recently published map of the global limits of P. falciparum transmission and an updated map of the limits of P. vivax transmission were combined with gridded population data and growth rates to estimate total populations at risk of malaria in 2007. Country-specific demographic data from the United Nations on age, sex, and total fertility rates were used to estimate the number of women of child-bearing age and the annual rate of live births. Subregional estimates of the number of induced abortions and country-specific stillbirths rates were obtained from recently published reviews. The number of miscarriages was estimated from the number of live births and corrected for induced abortion rates. The number of clinically recognised pregnancies at risk was then calculated as the sum of the number of live births, induced abortions, spontaneous miscarriages, and stillbirths among the population at risk in 2007. In 2007, 125.2 million pregnancies occurred in areas with P. falciparum and/or P. vivax transmission resulting in 82.6 million live births. This included 77.4, 30.3, 13.1, and 4.3 million pregnancies in the countries falling under the World Health Organization (WHO) regional offices for South-East-Asia (SEARO) and the Western-Pacific (WPRO) combined, Africa (AFRO), Europe and the Eastern Mediterranean (EURO/EMRO), and the Americas (AMRO), respectively. Of 85.3 million pregnancies in areas with P. falciparum transmission, 54.7 million occurred in areas with stable transmission and 30.6 million in areas with unstable transmission (clinical incidence <1 per 10,000 population/year); 92.9 million occurred in areas with P. vivax transmission, 53.0 million of which occurred in areas in which P. falciparum and P. vivax co-exist and 39.9 million in temperate regions with P. vivax transmission only. Conclusions: In 2007, 54.7 million pregnancies occurred in areas with stable P. falciparum malaria and a further 70.5 million in areas with exceptionally low malaria transmission or with P. vivax only. These represent the first contemporary estimates of the global distribution of the number of pregnancies at risk of P. falciparum and P. vivax malaria and provide a first step towards a more informed estimate of the geographical distribution of infection rates and the corresponding disease burden of malaria in pregnancy. © 2010 Dellicour et al.


Parry C.M.,Mahidol University | Wijedoru L.,Child and Reproductive Health Group | Arjyal A.,Kathmandu University | Baker S.,University of Oxford
Expert Review of Anti-Infective Therapy | Year: 2011

Enteric fever, an infection caused by Salmonella enterica serovar Typhi and serovar Paratyphi A, is common and endemic in many areas of the Asian and African continents. In endemic areas, diagnostic tests are needed to diagnose acute cases for clinical management, to detect convalescent and chronic fecal carriage and for contact tracing. A suitable test may also allow an assessment of disease burden in a community to determine the need for vaccination programs. Each specific role may warrant a dedicated test, utilizing different samples, targets and methods to serve their respective purpose. Current diagnostic methods are poor. Blood culture is insufficiently sensitive and technically demanding, and bone marrow culture, although more sensitive, is infrequently performed. Antibody- and antigen-detection tests lend themselves to point-of-care format but remain insufficiently sensitive and specific for this role. There are concerns about the sensitivity of nucleic acid amplification tests and they have not become widely adopted. However, new approaches using genomics, proteomics, transcriptomics, in vivo-induced antigen and immunoaffinity proteomics-based technologies are being employed to identify new antigens, gene targets and metabolic products that could be used as a basis for more effective diagnostic tests. If novel tests are to be credible and widely used they require rigorous evaluation in endemic areas in studies with appropriate selection of patients, adequate sample sizes and proper attention to a gold standard reference. Here, we discuss the range of methods currently used for diagnosing enteric fever in endemic locations and we suggest new technologies which may improve enteric fever diagnostics over the coming years. © 2011 Expert Reviews Ltd.


Davis J.L.,San Francisco General Hospital | Davis J.L.,University of California at San Francisco | Cattamanchi A.,San Francisco General Hospital | Cattamanchi A.,University of California at San Francisco | And 4 more authors.
The Lancet Infectious Diseases | Year: 2013

Background: Sputum smear microscopy is the most widely available diagnostic test for pulmonary tuberculosis in countries with a high burden of the disease. Improving its accuracy is crucial to achievement of case-detection targets established by the Millennium Development Goals. Unfortunately, many patients are unable to submit all of the specimens needed for examination or to return for treatment because standard sputum collection and reporting requires several clinic visits. To inform policy recommendations by a WHO-convened Expert Group, we aimed to assess the accuracy of sputum smear examination with strategies for obtaining sputum on 1 day compared with strategies for obtaining sputum over 2 days. Methods: We did a systematic review and meta-analysis of research articles comparing the accuracy of front-loaded or same-day microscopy and standard sputum smear microscopy for diagnosis of culture-confirmed pulmonary tuberculosis. We searched Medline, Embase, Biosis, and Web of Science for articles published between Jan 1, 2005, and Feb 14, 2012. Two investigators identified eligible articles and extracted data for individual study sites. We generated pooled summary estimates (95% CIs) for sensitivity and specificity by use of random-effects meta-analysis when four or more studies were available. Findings: We identified eight relevant studies from five articles enrolling 7771 patients with suspected tuberculosis in low-income countries. Compared with the standard approach of examination of two smears with Ziehl-Neelsen light microscopy over 2 days, examination of two smears taken on the same day had much the same sensitivity (64% [95% CI 60 to 69] for standard microscopy vs 63% [58 to 68] for same-day microscopy) and specificity (98% [97 to 99] vs 98% [97 to 99]). We noted similar results for studies employing light-emitting diode fluorescence microscopy and for studies examining three smears, whether they were compared with two-smear strategies or with one another. Interpretation: Same-day sputum smear microscopy is as accurate as standard smear microscopy. Data from tuberculosis programmes are needed to document the changes required in the health system to successfully implement the strategy and understand its effects. Funding: WHO and US National Institutes of Health. © 2013 Elsevier Ltd.


Van Eijk A.M.,Child and Reproductive Health Group | Van Eijk A.M.,University of Amsterdam | Hill J.,Child and Reproductive Health Group | Alegana V.A.,Kenya Medical Research Institute | And 6 more authors.
The Lancet Infectious Diseases | Year: 2011

Background: Insecticide-treated nets and intermittent preventive treatment with sulfadoxine-pyrimethamine are recommended for the control of malaria during pregnancy in endemic areas in Africa, but there has been no analysis of coverage data at a subnational level. We aimed to synthesise data from national surveys about these interventions, accounting for disparities in malaria risk within national borders. Methods: We extracted data for specific strategies for malaria control in pregnant women from national malaria policies from endemic countries in Africa. We identified the most recent national household cluster-sample surveys recording intermittent preventive treatment with sulfadoxine-pyrimethamine and use of insecticide-treated nets. We reconciled data to subnational administrative units to construct a model to estimate the number of pregnant women covered by a recommended intervention in 2007. Findings: 45 (96%) of 47 countries surveyed had a policy for distribution of insecticide-treated nets for pregnant women; estimated coverage in 2007 was 4·7 million (17%) of 27·7 million pregnancies at risk of malaria in 32 countries with data. 39 (83%) of 47 countries surveyed had an intermittent preventive treatment policy; in 2007, an estimated 6·4 million (25%) of 25·6 million pregnant women received at least one dose of treatment and 19·8 million (77%) visited an antenatal clinic (31 countries). Estimated coverage was lowest in areas of high-intensity transmission of malaria. Interpretation: Despite success in a few countries, coverage of insecticide-treated nets and intermittent preventive treatment in pregnant African women is inadequate; increased efforts towards scale-up are needed. Funding: The Malaria in Pregnancy Consortium and Wellcome Trust. © 2011 Elsevier Ltd.


Riedel C.,Ludwig Maximilians University of Munich | Schonberger K.,Ludwig Maximilians University of Munich | Yang S.,McGill University | Koshy G.,Child and Reproductive Health Group | And 5 more authors.
International Journal of Epidemiology | Year: 2014

Background: Some studies reported similar effect estimates for the impact of maternal smoking in pregnancy and paternal smoking on childhood obesity, whereas others suggested higher effects for maternal smoking. We performed a meta-analysis to compare the effect of in utero exposure to maternal smoking and that of paternal or household smoking exposure in utero or after birth with mutual adjustment. Methods: Meta-analysis of observational studies identified in MEDLINE, EMBASE and Web of Knowledge published in 1900-2013. Study inclusion criterion was assessment of the association of maternal smoking during pregnancy and paternal or household smoking (anyone living in the household who smokes) at any time with childhood overweight and obesity. The analyses were based on all studies with mutually adjusted effect estimates for maternal and paternal/household smoking applying a random-effects model. Results: Data for 109 838 mother/child pairs were reported in 12 studies. The pooled odds ratios (ORs) for overweight 1.33 [95% confidence interval (CI) 1.23;1.44] (n=6, I2=0.00%) and obesity 1.60 (95% CI 1.37;1.88) (n=4, I2=32.47%) for maternal smoking during pregnancy were higher than for paternal smoking: 1.07 (95% CI 1.00;1.16) (n=6, I2=41.34%) and 1.23 (95% CI 1.10;1.38) (n=4, I2=14.61%), respectively. Similar estimates with widely overlapping confidence limits were found for maternal smoking during pregnancy and childhood overweight and obesity: 1.35 (95% CI 1.20;1.51) (n=3,I2=0.00%) and 1.28 (95% CI 1.07;1.54) (n=3, I2=0.00%) compared with household smoking 1.22 (95% CI 1.06;1.39) (n=3, I2=72.14%) and 1.31 (95% CI 1.15;1.50)] (n=3, I2=0.00%). Conclusions: Higher effect estimates for maternal smoking in pregnancy compared with paternal smoking in mutually adjusted models may suggest a direct intrauterine effect. © The Author 2014; all rights reserved.

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