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OBJECTIVE: The determinants of anemia during both pregnancy and postpartum recovery remain incompletely understood in sub-Saharan African women. SUBJECTS/METHODS: In a prospective cohort study among pregnant women, we assessed dietary, biochemical, anthropometric, infectious and sociodemographic factors at baseline. In multivariate Cox proportional hazards models, we examined predictors of incident anemia (hemoglobin < 11 g/dl) and iron deficiency anemia (anemia plus mean corpuscular volume < 80 fL), and recovery from anemia and iron deficiency anemia through 18 months postpartum at antenatal clinics in Dar es Salaam, Tanzania between 2001 and 2005. A total of 2364 non-anemic pregnant women and 4884 anemic women were enrolled between 12 and 27 weeks of gestation. RESULTS: In total, 292 women developed anemia during the postpartum period and 165 developed iron deficiency anemia, whereas 2982 recovered from baseline anemia and 2044 from iron deficiency anemia. Risk factors for postpartum anemia were delivery complications (RR 1.6, 95% confidence interval (CI) 1.13, 2.22) and low postpartum CD4 cell count (RR 1.73, 95% CI 0.96, 3.17). Iron/folate supplementation during pregnancy had a protective relationship with the incidence of iron deficiency anemia. Absence of delivery complications, education status and iron/folate supplementation were positively associated with time to recovery from iron deficiency. CONCLUSION: Maternal nutritional status during pregnancy, prenatal iron/folate supplementation, perinatal care, and prevention and management of infections, such as malaria, are modifiable risk factors for the occurrence of, and recovery from, anemia. European Journal of Clinical Nutrition (2013) 67, 708-717; doi:10.1038/ejcn.2013.71; published online 24 April 2013 Keywords: anemia; postpartum; iron deficiency; pregnancy, INTRODUCTION The World Health Organization estimates that 55.8% of pregnant women in Africa are anemic. (1) In addition, 41% of women of childbearing age in Africa are anemic. (2,3) It [...]

Pregnant women attending a prenatal clinic can be tested for HIV to estimate the impact of HIV infection on the entire population. In the town of Bukoba, Tanzania, the percentage of pregnant women infected with HIV dropped from 22% in 1990 to 14% in 1996. This mirrored a drop in the infection rate among the town's women.

Abstract Background Youth have been reported to be at a higher risk of acquiring STIs with significant adverse health and social consequences. Knowledge on the prevailing risky practices is an essential tool to guide preventive strategies. Methods Youth aged between 18 and 25 years attending an STI clinic were recruited. Social, sexual and demographic characteristics were elicited using a structured standard questionnaire. Blood samples were tested for syphilis and HIV infections. Urethral, high vaginal and cervical swabs were screened for common STI agents. Results A total of 304 youth were studied with mean age of 21.5 and 20.3 years for males and females respectively. 63.5% of youth were seeking STI care. The mean age of coitache was 16.4 and 16.2 years for males and females respectively. The first sexual partner was significantly older in females compared to male youth (23.0 vs 16.8 years) (p < 0.01). 93.2% of male youth reported more than one sexual lifetime partner compared to 63.0% of the females. Only 50% of males compared to 43% of females had ever used a condom and fewer than 8.3% of female youth used other contraceptive methods. 27.1% of pregnancies were unplanned and 60% of abortions were induced. 42.0% of female youth had received gifts/money for sexual favours. The HIV prevalence was 15.3% and 7.5% for females and males respectively. The prevalence of other STIs was relatively low. Among male youth, use of alcohol or illicit drugs was associated with increased risk of HIV infection. However, the age of sexual initiation, number of sexual partners or the age of the first sexual partner were not associated with increased risk of being HIV infected. Conclusion Most female youth seen at the STI clinic had their first sexual intercourse with older males. Youth were engaging in high risk unprotected sexual practices which were predisposing them to STIs and unplanned pregnancies. There is a great need to establish more youth-friendly reproductive health clinics, encourage consistent and correct use of condoms, delay in sexual debut and avoid older sexual partners in females.

Data on slow progression following HIV-1 infection in Africa are sparse. From a study on the natural history of HIV-1 infection in Dar es Salaam, Tanzania, an analysis of immunological and clinical data from 237 HIV-1 seropositive individuals was performed. Annual CD4 cell determinations were carried out by flow cytometry. None was on antiretroviral treatment. CD4+ cell slopes were obtained by fitting a linear regression model. A study population of 50 individuals with >3 CD4 cell determinations and followed for >5 y had a mean follow-up of 72.7 months, and mean 5.7 CD4+ cell determinations. With a criterion of maintaining a CD4 cell count >or=500 cells/ml, 8 of the 50 (16.0%) were long-term non-progressors (LTNP). With a definition of maintaining a CD4+ cell slope

OBJECTIVE: To determine the prevalence trends of HIV-1 infection among pregnant women seen between 1995 and 2003 at public antenatal clinics (ANC) in the city of Dar es Salaam. DESIGN AND SETTINGS: Cross-sectional studies among pregnant women at selected antenatal clinics who were offered HIV testing as part of research and service programmes to prevent vertical transmission of HIV infection and improve pregnancy outcomes. SUBJECTS AND METHODS: Consenting women gave blood for HIV antibody testing using a sequential ELISA protocol. Sociodemographic information was collected using structured interviews. RESULTS: In total, 62% of women attending the antenatal clinics gave informed consent for HIV testing and 51,076 had final confirmed results available for this analysis. Women below 20 years of age had the lowest HIV seroprevalence. The HIV-1 prevalence declined from 14.2% in 1995 to 10.6% in 2003. CONCLUSION: There is a definite substantial decline in prevalence of HIV-1 infection among pregnant women in Dar es Salaam following ongoing interventions, which have been carried out in Tanzania. There is a need to further strengthen these interventions. [ABSTRACT FROM AUTHOR]

Background: Prematurity and low birth weight are associated with high perinatal and infant mortality, especially in developing countries. Maternal micronutrient deficiencies may contribute to these adverse outcomes.Methods: In a double-blind trial in Dar es Salaam, Tanzania, we randomly assigned 8468 pregnant women (gestational age of fetus, 12 to 27 weeks) who were negative for human immunodeficiency virus infection to receive daily multivitamins (including multiples of the recommended dietary allowance) or placebo. All the women received prenatal supplemental iron and folic acid. The primary outcomes were low birth weight (<2500 g), prematurity, and fetal death.Results: The incidence of low birth weight was 7.8% among the infants in the multivitamin group and 9.4% among those in the placebo group (relative risk, 0.82; 95% confidence interval [CI], 0.70 to 0.95; P=0.01). The mean difference in birth weight between the groups was modest (67 g, P<0.001). The rates of prematurity were 16.9% in the multivitamin group and 16.7% in the placebo group (relative risk, 1.01; 95% CI, 0.91 to 1.11; P=0.87), and the rates of fetal death were 4.3% and 5.0%, respectively (relative risk, 0.87; 95% CI, 0.72 to 1.05; P=0.15). Supplementation reduced both the risk of a birth size that was small for gestational age (<10th percentile; 10.7% in the multivitamin group vs. 13.6% in the placebo group; relative risk, 0.77; 95% CI, 0.68 to 0.87; P<0.001) and the risk of maternal anemia (hemoglobin level, <11 g per deciliter; relative risk, 0.88; 95% CI, 0.80 to 0.97; P=0.01), although the difference in the mean hemoglobin levels between the groups was small (0.2 g per deciliter, P<0.001).Conclusions: Multivitamin supplementation reduced the incidence of low birth weight and small-for-gestational-age births but had no significant effects on prematurity or fetal death. Multivitamins should be considered for all pregnant women in developing countries. (ClinicalTrials.gov number, NCT00197548 [ClinicalTrials.gov].). [ABSTRACT FROM AUTHOR]

Background: Gestational weight gain (GWG) is a modifiable factor associated with maternal and child health outcomes, but the relationship between diet quality and GWG has not been evaluated using metrics validated for low-income and middle-income countries (LMICs)., Objective: This study aimed to investigate relationships between diet quality, socioeconomic characteristics, and GWG adequacy using the novel Global Diet Quality Score (GDQS), the first diet quality indicator validated for use across LMIC., Methods: Weights of pregnant women enrolled between 12 and 27 wk of gestation ( N = 7577) were recorded in Dar es Salaam, Tanzania, from 2001 to 2005 during a prenatal micronutrient supplementation trial. GWG adequacy was the ratio of measured GWG to Institute of Medicine-recommended GWG, categorized into severely inadequate (<70%), inadequate (70 to <90%), adequate (90 to <125%), or excessive (≥125%). Dietary data were collected using 24-h recalls. Multinomial logit models were used to estimate relationships between GDQS tercile, macronutrient intake, nutritional status, and socioeconomic characteristics and GWG., Results: GDQS scores in the second [relative risk (RR): 0.82; 95% confidence interval (CI): 0.70, 0.97] tercile were associated with lower risk of inadequate weight gain than those in the first tercile. Increased protein intake was associated with higher risk of severely inadequate GWG (RR: 1.06; 95% CI: 1.02, 1.09). Nutritional status and socioeconomic factors were associated with GWG: underweight prepregnancy BMI (in kg/m 2 ) with a higher risk of severely inadequate GWG (RR: 1.49; 95% CI: 1.12, 1.99), overweight or obese BMI with a higher risk of excessive GWG (RR: 6.80; 95% CI: 5.34, 8.66), and a higher education (RR: 0.61; 95% CI: 0.42, 0.89), wealth (RR: 0.68; 95% CI: 0.48, 0.80), and height (RR: 0.96; 95% CI: 0.95, 0.98) with a lower risk of severely inadequate GWG., Conclusions: Dietary indicators showed few associations with GWG. However, stronger relationships were revealed between GWG, nutritional status, and several socioeconomic factors.This trial was registered at clinicaltrials.gov as NCT00197548., (© 2023 The Author(s).)

Background: Maternal micronutrient status is critical for child growth and nutrition. It is unclear whether maternal multiple micronutrient supplementation (MMS) during pregnancy and lactation improves child growth and prevents child morbidity., Methods: This study aimed to determine the effects of prenatal and postnatal maternal MMS on child growth and morbidity. In this double-blind, randomized-controlled trial, 8428 HIV-negative pregnant women were enrolled from Dar es Salaam, Tanzania, between 2001 and 2004. From pregnancy (12-27 weeks of gestation) through to 6 weeks postpartum, participants were randomized to receive daily oral MMS or placebo. All women received daily iron and folic acid during pregnancy. From 6 weeks postpartum through to 18 months postpartum, 3100 women were re-randomized to MMS or placebo. Child-growth measures, haemoglobin concentrations and infectious morbidities were assessed longitudinally from birth to ≤18 months., Results: Prenatal MMS led to modest increases in weight-for-age z-scores (mean difference: 0.050; 95% confidence interval: 0.002, 0.099; p = 0.04) and length-for-age z-score (mean difference: 0.062; 95% confidence interval: 0.013, 0.111; p = 0.01) during the first 6 months of life but not thereafter. Prenatal or postnatal MMS did not have benefits for other child outcomes., Conclusions: Whereas maternal MMS is a proven strategy to prevent adverse birth outcomes, other approaches may also need to be considered to curb the high burdens of child morbidity and growth faltering., (© The Author(s) 2021; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: The prevalence of adverse birth outcomes is highest in resource-limited settings such as sub-Saharan Africa. Maternal consumption of diets with adequate nutrients during pregnancy may protect against these adverse outcomes., Objectives: The objective was to determine the association between maternal dietary consumption of animal source foods (ASFs) and the risk of adverse birth outcomes among HIV-negative pregnant women in Tanzania., Methods: Using dietary intake data from 7564 HIV-negative pregnant women, we used Poisson regression with the empirical variance (generalized estimating equation) to estimate the RR of adverse birth outcomes-preterm birth, very preterm birth, small for gestational age (SGA), low birth weight (LBW), stillbirth, and neonatal death-for higher and lower frequency of ASF intake., Results: Median daily dietary intake of animal protein was 17 g (IQR: 1-48 g). Higher frequency of ASF protein intake was associated with lower risk of neonatal death (quartile 4 compared with quartile 1; RR: 0.59; 95% CI: 0.38, 0.90; P-trend = 0.01). Higher fish intake was associated with lower risk of very preterm birth (high tertile compared with low; RR: 0.76; 95% CI: 0.58, 0.99; P-trend = 0.02). Any meat intake was protective of preterm birth (RR: 0.73; 95% CI: 0.65, 0.82; P < 0.001), very preterm birth (P < 0.001), LBW (P < 0.001), and neonatal death (P = 0.01) but was associated with increased risk of SGA (RR:1.19; 95% CI: 1.01, 1.36; P = 0.04). Any egg intake was protective of very preterm birth (RR: 0.50; 95% CI: 0.31, 0.83; P = 0.01) as compared with no egg intake. Finally, any dairy intake was associated with lower risk of preterm birth (RR: 0.82; 95% CI: 0.68, 0.98; P = 0.03) and very preterm birth (RR: 0.53; 95% CI: 0.34, 0.84; P = 0.01)., Conclusions: Higher frequency of dietary intake of ASF is associated with lower risk of adverse birth outcomes in urban Tanzania. Promoting prenatal dietary intake of ASF may improve birth outcomes in this region and similar resource-limited settings., (Copyright © 2022 American Society for Nutrition.)

Background: Gestational weight gain (GWG) is a modifiable risk factor associated with adverse birth outcomes. Studies have shown that the provision of multiple micronutrient supplements to pregnant women reduces the risk of low birth weight. However, the effect of multiple micronutrient supplements on GWG has been understudied., Objectives: We examined the effect of daily supplementation of pregnant women with multivitamins on GWG in relation to the GWG recommendation by the Institute of Medicine (IOM)., Methods: Pregnant women with gestational age between 12 and 27 wk were randomly assigned to receive daily multivitamins or placebo until delivery. Weight was measured at enrollment and every follow-up visit. Percentage adequacy of GWG was calculated as actual GWG divided by the recommended GWG according to the IOM recommendation. Binary outcomes included severely inadequate (<70%), inadequate (<90%), and excessive GWG (≥125%). The analysis included 7573 women with singleton pregnancies. Multiple linear regression models were used to examine the association between multivitamin supplementation and percentage adequacy of GWG, and log-binomial models were used for binary outcomes., Results: The mean percentage adequacy of GWG was 96.7% in the multivitamin arm and 94.4% in the placebo arm, with a mean difference of 2.3% (95% CI: 0.3%, 4.2%; P = 0.022). Compared with women in the placebo arm, those who received multivitamins had a lower risk of severely inadequate GWG (RR: 0.90; 95% CI: 0.83, 0.97; P = 0.008) and inadequate GWG (RR: 0.95; 95% CI: 0.91, 0.99; P = 0.018). No significant difference was found in excessive GWG., Conclusions: Multivitamin supplementation increased GWG and reduced the risk of severely inadequate and inadequate GWG among pregnant women in Tanzania. Together with previously reported beneficial effects of the supplements on birth outcomes in low- and middle-income countries, our findings support scaling up the use of prenatal supplements that include multivitamins in addition to iron and folic acid.This trial was registered at clinicaltrials.gov as NCT00197548., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: The first 6 mo of life are critical for subsequent risk of undernutrition and mortality. The predictive abilities of attained weight at the end of each month and monthly weight velocity for undernutrition and mortality need to be compared., Objectives: This study aimed to examine the predictive abilities of different weight metrics during the first 6 mo of life in predicting undernutrition and mortality., Methods: This study used a cohort of infants in Tanzania. Weight and length were measured monthly from birth to 18 mo of age. Three weight metrics during the first 6 mo of life were considered as predictors, including attained weight-for-age z score (WAZ) at the end of each month, monthly change in WAZ, and monthly weight velocity z score (WVZ). Logistic models were used with undernutrition (at 6 or 12 mo) and mortality (over the first 18 mo) as outcomes. AUC values were compared across metrics., Results: For predicting wasting at 6 mo, WVZ (AUC: 0.80) had a greater predictive ability than attained WAZ (AUC: 0.76) and change in WAZ (AUC: 0.71) during the second month of life. After 2 mo, attained WAZ (AUC: 0.81-0.89) had greater predictive abilities than WVZ (AUC: 0.71-0.77) and change in WAZ (AUC: 0.65-0.67). For predicting stunting at 6 mo, attained WAZ (AUC: 0.75-0.79) had consistently greater predictive abilities than WVZ (AUC: 0.56-0.66) and change in WAZ (AUC: 0.50-0.57). The weight metrics had similar abilities in predicting mortality, with the AUC rarely reaching >0.65., Conclusions: Attained weight at the end of each month had greater abilities than monthly weight velocity in the same month in predicting undernutrition. Attained weight remains a useful indicator for identifying infants at greater risk of undernutrition., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Introduction: Gestational weight gain (GWG) is associated with fetal and newborn health; however, data from sub-Saharan Africa are limited., Methods: We used data from a prenatal micronutrient supplementation trial among a cohort of human immunodeficiency virus-negative pregnant women in Dar es Salaam, Tanzania to estimate the relationships between GWG and neonatal outcomes. GWG adequacy was defined as the ratio of the total observed weight gain over the recommended weight gain based on the Institute of Medicine body mass index-specific guidelines. Neonatal outcomes assessed were stillbirth, perinatal death, preterm birth, low birthweight, macrosomia, small-for-gestational age (SGA), large-for-gestational age (LGA), stunting at birth, and microcephaly. Modified Poisson regressions with robust standard error were used to estimate the relative risk of newborn outcomes as a function of GWG adequacy., Results: Of 7,561 women included in this study, 51% had severely inadequate (<70%) or inadequate GWG (70 to <90%), 31% had adequate GWG (90 to <125%), and 18% had excessive GWG (≥125%). Compared to adequate GWG, severely inadequate GWG was associated with a higher risk of low birthweight, SGA, stunting at birth, and microcephaly, whereas excessive GWG was associated with a higher risk of LGA and macrosomia., Conclusion: Interventions to support optimal GWG are needed and may contribute to preventing adverse neonatal outcomes., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Background: Gestational weight gain (GWG) has critical implications for maternal and child health. Inflammation and angiogenesis are implicated in various aspects of maternal metabolism that may play a role in gestational weight gain. The associations of inflammatory, angiogenic, and metabolic pathways with GWG are yet to be elucidated. This study evaluated associations between a panel of inflammatory, angiogenic, and metabolic proteins measured in mid-pregnancy and gestational weight gain., Methods: Pregnant women were enrolled from Dar es Salaam, Tanzania, between 2001 and 2004. The participants were enrolled at mid-pregnancy (12 to 27 weeks of gestation) and followed up until delivery. This analysis focused on a cohort of 1002 women who were primigravid, had singleton live births, had longitudinal measures of gestational weight, and whose mid-pregnancy plasma samples underwent analysis for 18 proteins., Results: Higher plasma concentrations of leptin (mean difference in GWG percent adequacy comparing highest with lowest quartiles: 10.24; 95% CI 3.31, 17.16; p-trend = 0.003) and chitinase-3-like protein-1 (CH3L1) (mean difference in GWG percent adequacy comparing highest with lowest quartiles: 7.02; 95% CI 0.31, 13.72; p-trend = 0.007) were associated with greater GWG in a dose-response pattern. Higher leptin concentrations were associated with a lower risk of inadequate GWG (risk ratio comparing highest with lowest quartiles: 0.77; 95% CI 0.65, 0.91; p-trend = 0.001) and a higher risk of excessive GWG (risk ratio comparing highest with lowest quartiles: 1.57; 95% CI 1.03, 2.39; p-trend = 0.03). Higher CH3L1 concentrations were associated with a higher risk of excessive GWG (p-trend = 0.007). The associations of leptin and CH3L1 with inadequate GWG were stronger during the second than the third trimester. The other 16 proteins examined were not significantly associated with GWG., Conclusions: Mid-pregnancy plasma leptin concentrations may be associated with GWG and have clinical predictive utility in identifying women at a higher risk of inadequate or excessive gestational weight gain., (© 2021. The Author(s).)

Objectives: To investigate the association between gestational age, birthweight, and birthweight adjusted for gestational age, with domains of neurocognitive development and behavioral problems in adolescents in Tanzania., Study Design: Data from a long-term follow-up of adolescents aged 11-15 years born to women previously enrolled in a randomized controlled trial of prenatal multiple micronutrient supplementation in Dar es Salaam, Tanzania, were used. A battery of neurodevelopmental tests were administered to measure adolescent general intelligence, executive function, and behavioral problems. The INTERGROWTH-21 st newborn anthropometric standards were used to derive birthweight for gestational age z-scores. We assessed the shape of relationships using restricted cubic splines and estimated the associations of gestational age, birthweight, and birthweight for gestational age z-score with adolescent development using multivariable linear regressions., Results: Among adolescents studied (n = 421), higher gestational age (per week), birthweight (per 100 grams), and birthweight for gestational age z-score (per SD) were linearly associated with higher intelligence score (adjusted standardized mean difference, 0.05 SD [95% CI, 0.01-0.09], 0.04 SD [95% CI, 0.02-0.06], and 0.09 SD [95% CI, 0.01-0.17], respectively). Birthweight and birthweight for gestational age z-score, but not gestational age, were also associated with improved executive function. Low birthweight (<2500 g) was associated with lower intelligence and executive function scores. Associations between birthweight and executive function were stronger among adolescents born to women with higher education., Conclusions: The duration of gestation and birthweight were positively associated with adolescent neurodevelopment in Tanzania. These findings suggest that interventions to improve birth outcomes may also benefit adolescent cognitive function., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Preterm birth (PTB), small for gestational age (SGA), and low birth weight (LBW) are risk factors for morbidity and mortality among infants. High-quality maternal diets during pregnancy may protect against these adverse birth outcomes., Objectives: The aim of this study was to prospectively examine the association of maternal dietary diversity and quality during pregnancy with birth outcomes among women in Dar es Salaam, Tanzania., Methods: We analyzed data from 7553 HIV-negative pregnant women enrolled in a multivitamin trial at 12-27 weeks of gestation. Dietary intake was assessed using 24-h dietary recalls. Dietary diversity scores (DDS; range: 0-10) were computed as the number of food groups consumed by women, using FAO's Minimum Dietary Diversity for Women index. The Prime Diet Quality Score (PDQS; range: 0-42) assessed maternal diet quality based on consumption of 21 healthy and unhealthy food groups. Log binomial regression methods were used to assess associations of DDS and PDQS with PTB, SGA, LBW, and fetal loss., Results: In the previous 24 h, 99.9% of all women had consumed cereal and staples, 57.9% meats, 4.7% eggs, and 0.5% nuts and seeds. Median DDS was 3.0 (IQR: 2.5-3.5). For the PDQS, all women consumed ≥4 servings/wk of green leafy vegetables and refined grains. Higher DDS was associated with lower risk of SGA (RR highest compared with lowest quintile: 0.74; 95% CI: 0.62, 0.89). Higher PDQS was associated with lower risk of PTB (RR highest compared with lowest quintile: 0.55; 95% CI: 0.46, 0.66), LBW (RR: 0.53; 95% CI: 0.40, 0.70), and fetal loss (RR: 0.53; 95% CI, 0.34, 0.82)., Conclusions: PDQS was inversely associated with PTB, LBW, and fetal loss, and DDS was inversely associated with SGA. These findings suggest that in addition to dietary diversity, diet quality should be considered as important in understanding dietary risk factors for poor birth outcomes.This trial was registered at clinicaltrials.gov as NCT00197548., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Background: Maternal micronutrient supplementation in pregnancy (MMS) has been shown to improve birth weight among infants in low- and middle-income countries. Recent evidence suggests that the survival benefits of MMS are greater for female infants compared to male infants, but the mechanisms leading to differential effects remain unclear., Objective: The objective of this study was to examine the potential mechanisms through which MMS acts on infant mortality among Tanzanian infants., Methods: We used data collected from pregnant women and newborns in a randomized, double-blind, placebo-controlled trial of MMS conducted in Tanzania to examine mediators of the effect of MMS on 6-wk infant mortality (NCT00197548). Causal mediation analyses with the counterfactual approach were conducted to assess the contributions of MMS on survival via their effects on birth weight, gestational age, weight-for-gestational age, and the joint effect of gestational age and weight-for-gestational age. The weighting method allowed for interaction between gestational age and weight-for-gestational age., Results: Among 7486 newborns, the effect of MMS on 6-wk survival was fully mediated (100%) through the joint effect of gestational age and weight-for-gestational age. MMS was also found to have a significant natural indirect effect through increased birth weight (P-value < 0.001) that explained 75% of the total effect on 6-wk mortality. When analyses were stratified by sex, changes in gestational age and weight-for-gestational age fully mediated the mortality effect among female infants (n = 3570), but these mediators only explained 34% of the effect among males (n = 3833)., Conclusions: The potential sex-specific effects of MMS on mortality may be a result of differences in mechanisms related to birth outcomes. In the context of the Tanzanian trial, the observed effect of MMS on 6-wk mortality for female infants was entirely mediated by increased gestation duration and improved intrauterine growth, while these mechanisms did not appear to be major contributors among male infants., (Copyright © American Society for Nutrition 2019.)

Background: Without an effective vaccine, as was the case early in the 2014-2016 Ebola Outbreak in West Africa, disease control depends entirely on interrupting transmission through early disease detection and prompt patient isolation. Lateral Flow Immunoassays (LFI) are a potential supplement to centralized reference laboratory testing for the early diagnosis of Ebola Virus Disease (EVD). The goal of this study was to assess the performance of commercially available simple and rapid antigen detection LFIs, submitted for review to the WHO via the Emergency Use Assessment and Listing procedure. The study was performed in an Ebola Treatment Centre laboratory involved in EVD testing in Sierra Leone. In light of the current Ebola outbreak in May 2018 in the Democratic Republic of Congo, which highlights the lack of clarity in the global health community about appropriate Ebola diagnostics, our findings are increasingly critical., Methods: A cross-sectional study was conducted to assess comparative performance of four LFIs for detecting EVD. LFIs were assessed against the same 328 plasma samples and 100 whole EDTA blood samples, using the altona RealStar Filovirus Screen real-time RT-PCR as the bench mark assay. The performance of the Public Health England (PHE) in-house Zaire ebolavirus-specific real time RT-PCR Trombley assay was concurrently assessed. Statistical analysis using generalized estimating equations was conducted to compare LFI performance., Findings: Sensitivity and specificity varied between the LFIs, with specificity found to be significantly higher for whole EDTA blood samples compared to plasma samples in at least 2 LFIs (P≤0.003). Using the altona RT-PCR assay as the bench mark, sensitivities on plasma samples ranged from 79.53% (101/127, 95% CI: 71.46-86.17%) for the DEDIATEST EBOLA (SD Biosensor) to 98.43% (125/127, 95% CI: 94.43-99.81%) for the One step Ebola test (Intec). Specificities ranged from 80.20% (158/197, 95% CI: 74.07-88.60%) for plasma samples using the ReEBOV Antigen test Kit (Corgenix) to 100.00% (98/98, 95% CI: 96.31-100.00%) for whole blood samples using the DEDIATEST EBOLA (SD Biosensor) and SD Ebola Zaire Ag (SD Biosensor). Results also showed the Trombley RT-PCR assay had a lower limit of detection than the altona assay, with some LFIs having higher sensitivity than the altona assay when the Trombley assay was the bench mark., Interpretation: All of the tested EVD LFIs may be considered suitable for use in an outbreak situation (i.e. rule out testing in communities), although they had variable performance characteristics, with none possessing both high sensitivity and specificity. The non-commercial Trombley Zaire ebolavirus RT-PCR assay warrants further investigation, as it appeared more sensitive than the current gold standard, the altona Filovirus Screen RT-PCR assay., Competing Interests: Dr. Gatton reports personal fees from Foundation for Innovative New Diagnostics, during the conduct of the study. Ms Wonderly, Dr Jones, Mr Barber, Dr Killip, Mr Hudson, Ms Carter, Dr Perkins and Dr Boehme are employees of FIND. Drs Brooks, Simpson, Semper, Urassa and Chua have no competing interests to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: CD4 T-cell counts are still widely used to assess treatment eligibility and follow-up of HIV-infected patients. The World Health Organization (WHO) prequalification of in vitro diagnostics requested a manufacturer independent laboratory evaluation of the analytical performance at the Institute of Tropical Medicine (ITM) Antwerp, Belgium, of the Muse Auto CD4/CD4% system (Millipore), a new small capillary-flow cytometer dedicated to count absolute CD4-T cells and percentages in venous blood samples from HIV-infected patients., Methods: Two hundred and fifty (250) patients were recruited from the HIV outpatient clinic at ITM. Accuracy and precision of CD4 T cell counting on fresh EDTA anticoagulated venous blood samples were assessed in the laboratory on a Muse Auto CD4/CD4% system. Extensive precision analyses were performed both on fresh blood and on normal and low stabilized whole blood controls. Accuracy ((bias) was assessed by comparing results from Muse CD4/CD4% to the reference (single-platform FACSCalibur). Clinical misclassification was measured at 500, 350, 200 and 100 cells/μL thresholds., Results: Intra-assay precision was < 5%, and inter-assay was < 9%. CD4 T cell counts measured on Muse Auto CD4/CD4% System and on the reference instrument resulted in regression slopes of 0.97 for absolute counts and 1.03 for CD4 T cell percentages and a correlation coefficient of 0.99 for both. The average absolute bias as compared to the reference was negligible (4 cells/μL or 0.5%). The absolute average bias on CD4 T cell percentages was < 1%. Clinical misclassification at different CD4 T cell thresholds was small resulting in sensitivities and specificities equal or >90% at all thresholds except at 100 cells/μL (sensitivity = 87%). All samples could be analyzed as there was no repetitive rejection errors recorded., Conclusions: The Muse Auto CD4/CD4% System performed very well on fresh venous blood samples and met all WHO acceptance criteria for analytical performance of CD4 technologies., Competing Interests: The authors have declared that no competing interests exist.

Background: Sexually transmitted infections, such as HIV and syphilis, are one of the major health care problems worldwide, especially in low- and middle income countries. HIV screening programmes have been widely used for many years. The introduction of rapid point-of-care tests (RDTs) that can detect both HIV and syphilis, using one single blood specimen, would be a promising tool to integrate the detection of syphilis into HIV programmes and so improve the accessibility of syphilis testing and treatment., Methods: As part of the World Health Organization pre-qualification of in vitro diagnostics assessment, the laboratory performance of four dual HIV-Syphilis rapid diagnostic tests (SD Bioline HIV/Syphilis Duo, DPP HIV-Syphilis Assay, Multiplo Rapid TP/HIV Antibody Test and Insti Multiplex HIV-1/HIV-2/Syphilis Antibody Test) was assessed using a well characterized multiregional panel of stored sera specimens., Results: In total 400 specimens were tested with each assay, resulting in excellent sensitivities and specificities for HIV, ranging from 99.5 to 100% and from 93.5 to 99.5%, respectively. Results obtained for the Treponema pallidum antibodies were lower, with the lowest sensitivity of 73.5% for Multiplo and the highest of 87% for SD Bioline. Specificities ranged from 99.0 to 100%., Conclusion: Although these results suggest that the tests could further improve in accuracy in detection of treponemal antibodies, their introduction into screening programmes to increase the accessibility of HIV/Syphilis diagnosis and treatment for difficult to reach populations in the world is promising.

Background: The ability of individuals to use HIV self-tests correctly is debated. To inform the 2016 WHO recommendation on HIV self-testing, we assessed the reliability and performance of HIV rapid diagnostic tests when used by self-testers., Methods: In this systematic review and meta-analysis, we searched PubMed, PopLine, and Embase, conference abstracts, and additional grey literature between Jan 1, 1995, and April 30, 2016, for observational and experimental studies reporting on HIV self-testing performance. We excluded studies evaluating home specimen collection because patients did not interpret their own test results. We extracted data independently, using standardised extraction forms. Outcomes of interest were agreement between self-testers and health-care workers, sensitivity, and specificity. We calculated κ to establish the level of agreement and pooled κ estimates using a random-effects model, by approach (directly assisted or unassisted) and type of specimen (blood or oral fluid). We examined heterogeneity with the I 2 statistic., Findings: 25 studies met inclusion criteria (22 to 5662 participants). Quality assessment with QUADAS-2 showed studies had low risk of bias and incomplete reporting in accordance with the STARD checklist. Raw proportion of agreement ranged from 85·4% to 100%, and reported κ ranged from fair (κ 0·277, p<0·001) to almost perfect (κ 0·99, n=25). Pooled κ suggested almost perfect agreement for both types of approaches (directly assisted 0·98, 95% CI 0·96-0·99 and unassisted 0·97, 0·96-0·98; I 2 =34·5%, 0-97·8). Excluding two outliers, sensitivity and specificity was higher for blood-based rapid diagnostic tests (4/16) compared with oral fluid rapid diagnostic tests (13/16). The most common error that affected test performance was incorrect specimen collection (oral swab or finger prick). Study limitations included the use of different reference standards and no disaggregation of results by individuals taking antiretrovirals., Interpretation: Self-testers can reliably and accurately do HIV rapid diagnostic tests, as compared with trained health-care workers. Errors in performance might be reduced through the improvement of rapid diagnostic tests for self-testing, particularly to make sample collection easier and to simplify instructions for use., Funding: The Bill & Melinda Gates Foundation and Unitaid., (© 2018. World Health Oranization. Licensee Elseviere. This is an Open Access article published under the CC BY 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

Objectives: To evaluate the risk of newborn and infant mortality associated with preterm, small for gestational age (SGA), and low birth weight (LBW) stratified by maternal HIV status and the location of birth., Study Design: We created a prospective cohort by pooling 5 individually randomized trials. We used Cox proportional hazard models to estimate the risk of mortality for SGA defined using the recently published Intergrowth standard, preterm, LBW, and gestational age and size for gestational age categories (preterm- appropriate for gestational age [AGA], term-SGA, and preterm-SGA). Effect modification by maternal HIV status and place of residence was assessed using the likelihood ratio test., Results: Of the 31 988 infants, 15.3% were preterm, 16.6% were SGA, and 7.3% were LBW. The proportion of preterm and SGA births was higher among the HIV-infected cohort than in the uninfected cohort. Compared with term-AGA groups, infants born both preterm and SGA had a greater risk of neonatal mortality (hazard ratio [HR] 5.43, 95% CI 2.01-14.63) than preterm-AGA infants (HR 2.40, 95% CI 1.89-3.05) and term-SGA infants (HR 2.56, 95% CI 1.96-3.34). Maternal HIV infection modified the risk of infant mortality associated with being born preterm or LBW, with a higher relative risk among those born to HIV-uninfected women. Rural residence significantly modified the risk of neonatal mortality associated with being LBW (P for interaction = .005)., Conclusions: Preterm and SGA newborns had an increased risk of mortality during the first year of life. Interventions targeting these conditions, especially in HIV-exposed and rural populations, should be integrated into existing maternal and child health programs., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Micronutrient deficiencies are common among women in low-income and middle-income countries. Data from randomised trials suggest that maternal multiple micronutrient supplementation decreases the risk of low birthweight and potentially improves other infant health outcomes. However, heterogeneity across studies suggests influence from effect modifiers. We aimed to identify individual-level modifiers of the effect of multiple micronutrient supplements on stillbirth, birth outcomes, and infant mortality in low-income and middle-income countries., Methods: This two-stage meta-analysis of individual patient included data from 17 randomised controlled trials done in 14 low-income and middle-income countries, which compared multiple micronutrient supplements containing iron-folic acid versus iron-folic acid alone in 112 953 pregnant women. We generated study-specific estimates and pooled subgroup estimates using fixed-effects models and assessed heterogeneity between subgroups with the χ 2 test for heterogeneity. We did sensitivity analyses using random-effects models, stratifying by iron-folic acid dose, and exploring individual study effect., Findings: Multiple micronutrient supplements containing iron-folic acid provided significantly greater reductions in neonatal mortality for female neonates compared with male neonates than did iron-folic acid supplementation alone (RR 0·85, 95% CI 0·75-0·96 vs 1·06, 0·95-1·17; p value for interaction 0·007). Multiple micronutrient supplements resulted in greater reductions in low birthweight (RR 0·81, 95% CI 0·74-0·89; p value for interaction 0·049), small-for-gestational-age births (0·92, 0·87-0·97; p=0·03), and 6-month mortality (0·71, 0·60-0·86; p=0·04) in anaemic pregnant women (haemoglobin <110g/L) as compared with non-anaemic pregnant women. Multiple micronutrient supplements also had a greater effect on preterm births among underweight pregnant women (BMI <18·5 kg/m 2 ; RR 0·84, 95% CI 0·78-0·91; p=0·01). Initiation of multiple micronutrient supplements before 20 weeks gestation provided greater reductions in preterm birth (RR 0·89, 95% CI 0·85-0·93; p=0·03). Generally, the survival and birth outcome effects of multiple micronutrient supplementation were greater with high adherence (≥95%) to supplementation. Multiple micronutrient supplements did not significantly increase the risk of stillbirth or neonatal, 6-month, or infant mortality, neither overall or in any of the 26 examined subgroups., Interpretation: Antenatal multiple micronutrient supplements improved survival for female neonates and provided greater birth-outcome benefits for infants born to undernourished and anaemic pregnant women. Early initiation in pregnancy and high adherence to multiple micronutrient supplements also provided greater overall benefits. Studies should now aim to elucidate the mechanisms accounting for differences in the effect of antenatal multiple micronutrient supplements on infant health by maternal nutrition status and sex., Funding: None., (Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: The spread of Extended Spectrum β-lactamases (ESBLs) among Enterobacteriaceae and other Gram-Negative pathogens in the community and hospitals represents a major challenge to combat infections. We conducted a study to assess the prevalence and genetic makeup of ESBL-type resistance in bacterial isolates causing community- and hospital-acquired urinary tract infections., Methods: A total of 172 isolates of Enterobacteriaceae were collected in Dar es Salaam, Tanzania, from patients who met criteria of community and hospital-acquired urinary tract infections. We used E-test ESBL strips to test for ESBL-phenotype and PCR and sequencing for detection of ESBL genes., Results: Overall 23.8% (41/172) of all isolates were ESBL-producers. ESBL-producers were more frequently isolated from hospital-acquired infections (32%, 27/84 than from community-acquired infections (16%, 14/88, p < 0.05). ESBL-producers showed high rate of resistance to ciprofloxacin (85.5%), doxycycline (90.2%), gentamicin (80.5%), nalidixic acid (84.5%), and trimethoprim-sulfamethoxazole (85.4%). Furthermore, 95% of ESBL-producers were multi-drug resistant compared to 69% of non-ESBL-producers (p < 0.05). The distribution of ESBL genes were as follows: 29/32 (90.6%) bla CTX-M-15 , two bla SHV-12 , and one had both bla CTX-M-15 and bla SHV-12 . Of 29 isolates carrying bla CTX-M-15 , 69% (20/29) and 31% (9/29) were hospital and community, respectively. Bla SHV-12 genotypes were only detected in hospital-acquired infections., Conclusion: bla CTX-M-15 is a predominant gene conferring ESBL-production in Enterobacteriaceae causing both hospital- and community-acquired infections in Tanzania.

Background: CD4 T-cell counts are widely used to assess treatment eligibility and to follow-up HIV-infected patients. The World Health Organization prequalification of in vitro diagnostics program conducted a performance evaluation of the FACSPresto (BD Biosciences), a new point-of-care instrument to measure absolute CD4-T cell (CD4) counts and percentages in venous and capillary blood samples from HIV-infected patients., Methods: Patients were recruited in Belgium (200 patients) and in Tanzania (247 patients). Venous blood samples were analyzed in two nearby reference laboratories. In addition, nurses/technicians collected a capillary blood sample by finger prick directly into a FACSPresto CD4 cartridge. Assay precision was assessed on fresh blood and on external quality control samples. Trueness (bias) was assessed by comparing results from FACSPresto with the reference (single-platform FACSCalibur). Clinical misclassification was measured at 200, 350 and 500 cells/μL thresholds., Results: Intra-assay precision was < 6%, and inter-assay < 8%. CD4 results from FACSPresto and reference method resulted in regression slopes of 0.99-1.11 using either venous or capillary blood. Correlation was better for venous than for capillary blood (minimum 0.97 vs 0.93 respectively). Capillary blood resulted in a larger bias than venous blood, with 24 and 83 cells/μL for absolute CD4 counts on capillary blood in Antwerp and Dar es Salaam respectively, vs 12 and 41 cells/μL on venous blood. Bias on CD4% was < 1% on both venous and capillary blood, and was proportionally better than for absolute CD4 counts. Clinical misclassification was in line with the average overestimation, showing a very good specificity, but sensitivity around 70-90%. The rejection rate was 11% on first reading, leading to 6% of all samples without final result after a second reading., Conclusions: The FACSPresto performed very well on venous blood samples, and well on capillary blood samples., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Placental vascular development, and ultimately placental weight, is essential to healthy fetal development. Here, we examined placental weight in a cohort of Tanzanian women in association with angiogenic proteins known to regulate placental vascular development and perinatal outcomes., Methods: A total of n = 6579 women with recorded placental weight were included in this study. The relative risk of adverse perinatal outcomes (Apgar score, death, asphyxia, respiratory distress, seizures, pneumonia and sepsis) was compared between placental weight in the bottom and top 10th percentiles. We quantified angiogenic mediators (Ang-1, Ang-2, VEGF, PGF and sFlt-1) in plasma samples (n = 901) collected between 12 to 27 weeks of pregnancy using ELISA and assessed the relative risk of placental weight in the bottom and top 10th percentiles by protein levels in quartiles., Results: Women with Ang-2 levels in the highest quartile had an increased relative risk of placental weight in the bottom 10th percentile (RR = 1.45 (1.10, 1.91), p = 0.01). Women with VEGF-A (RR = 0.73 (0.56, 0.96), p = 0.05) and PGF (RR = 0.58 (0.44, 0.72), p = 0.002) in the highest quartile had a reduced relative risk of placental weight in the bottom 10th percentile. Low placental weight (in bottom 10th percentile) was associated with an increased relative risk of Apgar score of <7 at 1 minute (RR = 2.31 (1.70, 3.13), p = 0.001), at 5 minutes (RR = 3.53 (2.34, 5.33), p = 0.001), neonatal death (RR = 5.02 (3.61, 7.00), p = 0.001), respiratory distress (RR = 4.80(1.71, 13.45), p = 0.001), and seizures (RR = 4.18 (1.16, 15.02), p = 0.03)., Discussion: The association between low placental weight and risk of adverse perinatal outcomes in this cohort suggests that placental weight could serve as a useful indicator, providing additional insight into high-risk pregnancies and identifying neonates that may require additional monitoring and follow-up., Competing Interests: The authors have declared that no competing interests exist.

Research Question: Preterm birth (PTB) is the leading cause of perinatal mortality worldwide, with the greatest burden occurring in resource-constrained settings. Based on the hypothesis that altered placental angiogenesis and inflammation early in pregnancy lead to PTB, we examined whether levels of inflammatory and angiogenic mediators, measured early in pregnancy, were predictive of spontaneous PTB (sPTB)., Study Design: Plasma samples were collected from a prospective cohort of primigravid Tanzanian women between 12-27 weeks gestation. A panel of 18 markers was screened on a training cohort of 426 women. Markers associated with sPTB in the training cohort were repeated in a test cohort of 628 women. All markers were measured by ELISA., Findings: In both the training and test cohorts plasma levels of IL-18BP, sICAM-1, sEndoglin and CHI3L1 were elevated and Leptin was lower at enrollment in women who subsequently experienced sPTB. In multivariate analysis women with plasma levels of CHI3L1, C5a, sICAM-1, AngptL3, sEndgolin, sFlt-1 and IL-18BP in the highest quartile had an increased risk of sPTB compared with those in the lowest quartile. Women with Leptin and Ang2 in the highest quartile had a reduced risk of sPTB compared with women in the lowest quartile., Implications: Levels of angiogenic and inflammatory mediators measured at mid-pregnancy were associated with subsequent sPTB. These findings provide insight into mechanisms underlying sPTB and suggest biomarkers that may have clinical utility in risk-stratifying pregnancies.

Multivitamin supplementation has been shown to reduce the risk of low birthweight. This effect could be mediated through gestational weight gain. However, the effect of multivitamin supplementation on weight gain during pregnancy has not been fully studied. The objective of this study was to examine the effects of multivitamins on pregnancy weight gain. We enrolled 8468 HIV-negative women from Dar es Salaam, Tanzania, in a randomised, placebo-controlled trial of multivitamins on birth outcomes. Women were randomly assigned to receive either a daily oral dose of multivitamin tablets or a placebo and were weighed every 4 weeks from enrolment until the last visit before delivery. Intent-to-treat analyses were carried out to examine the effects of multivitamins on pregnancy weight gain. Multivariate linear and binomial regression models with the log-link function were used to examine the association of weight gain during pregnancy to birthweight. The overall total weight gain was 253 g (SE: 69, P: 0.0003) more, while the overall 4 weekly weight gain was 59 g greater (SE: 18, P: 0.005) among women who received multivitamins compared to placebo. Women in the lowest quartile of gestational weight gain had babies with an average birthweight of 3030 g (SD: 524), while women in the highest quartile had babies weighing 3246 g (SD: 486), on average. Prenatal multivitamin supplements increased gestational weight gain, which was a significant predictor of birthweight., (© 2012 Blackwell Publishing Ltd.)