Maternal dietary diversity and dietary quality scores in relation to adverse birth outcomes in Tanzanian women.

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.

Effect of multivitamin supplements on weight gain during pregnancy among HIV-negative women in Tanzania.

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.

Macronutrient and sociodemographic determinants of gestational weight gain among HIV-negative women in Tanzania.

BACKGROUND: The effect of dietary macronutrient composition on the rate of gestational weight gain among women in sub-Saharan Africa is unclear. OBJECTIVE: To examine the effect of macronutrient intake on the rate of gestational weight gain among HIV-negative women in Tanzania. METHODS: The weights of 8,428 women were measured monthly from 12 weeks of gestation to term. Prenatal dietary intake was estimated as the cumulative average of multiple 24-hour dietary recalls. The association between energy intake and percentage of energy from carbohydrate, protein, and total fat and rate of weight gain (grams per month) was estimated from generalized estimating equation models. Macronutrient effects were adjusted for total energy using the nutrient density model and maternal age, maternal height, maternal mid-upper-arm circumference, parity, marital status, maternal occupation, maternal education, household wealth, season, and treatment regimen assignment. Body mass index (BMI) was considered as a confounder and a potential modifier of the effect of macronutrient intake on gestational weight gain. RESULTS: A 6 g/month increase in rate of weight gain was associated with every 100-kcal increment in daily total energy intake (95% CI, 1 to 12; p = .03). Analyses substituting 5% of energy from fat by protein showed that weight gain would decrease by 72 g/month (95% CI, 6 to 140; p = .03); substituting 5% of energy from carbohydrate by protein decreased gain by 70 g/month (95% CI, 15 to 124; p = .01). Baseline BMI did not modify these associations. CONCLUSIONS: Further research on the effects of macronutrient composition on gestational weight gain is needed to inform the design of supplementation programs for women in developing countries.

Maternal vitamin D status and child morbidity, anemia, and growth in human immunodeficiency virus-exposed children in Tanzania.

BACKGROUND: Vitamin D may help prevent adverse pediatric outcomes, including infectious diseases and growth failure, based on its role in immune and metabolic functions. We examined the association of maternal vitamin D status and pediatric health outcomes in children born to human immunodeficiency virus (HIV)-infected women. METHODS: Vitamin D status was determined in 884 HIV-infected pregnant women at 12 to 27 weeks of gestation in a trial of vitamin supplementation (not excluding vitamin D) in Tanzania. Information on child morbidities, anemia and hypochromic microcytosis, and anthropometry was recorded through monthly clinic visits. Generalized estimating equations and Cox proportional hazards models were used to assess the relationships of outcomes with maternal vitamin D status. RESULTS: A total of 39% of women had low vitamin D levels (<32 ng/mL). Children born to women with low vitamin D status were 1.11 times more likely to report cough during follow-up (relative risk [RR], 1.11; 95% confidence interval [CI], 1.02-1.21). No significant associations were noted for other respiratory symptoms, diarrhea, or anemia outcomes. Low maternal vitamin D status was associated with significantly increased risk of stunting (height-for-age z score, <-2; RR, 1.29; 95% CI, 1.05-1.59) and being underweight (weight-for-age z score, <-2; RR, 1.33; 95% CI, 1.03-1.71). CONCLUSIONS: Maternal vitamin D status may be important for preventing respiratory infections and ensuring optimal growth in HIV-exposed children.

Post-natal anaemia and iron deficiency in HIV-infected women and the health and survival of their children.

Prenatal iron supplementation may improve pregnancy outcomes and decrease the risk of child mortality. However, little is known about the importance of post-natal maternal iron status for child health and survival, particularly in the context of HIV infection. We examined the association of maternal anaemia and hypochromic microcytosis, an erythrocyte morphology consistent with iron deficiency, with child health and survival in the first two to five years of life. Repeated measures of maternal anaemia and hypochromic microcytosis from 840 HIV-positive women enrolled in a clinical trial of vitamin supplementation were prospectively related to child mortality, HIV infection and CD4 T-cell count. Median duration of follow-up for the endpoints of child mortality, HIV infection and CD4 cell count was 58, 17 and 23 months, respectively. Maternal anaemia and hypochromic microcytosis were associated with greater risk of child mortality [hazard ratio (HR) for severe anaemia = 2.58, 95% confidence interval (CI): 1.66-4.01, P trend < 0.0001; HR for severe hypochromic microcytosis = 2.36, 95% CI: 1.27-4.38, P trend = 0.001]. Maternal anaemia was not significantly associated with greater risk of child HIV infection (HR for severe anaemia = 1.46, 95% CI: 0.91, 2.33, P trend = 0.08) but predicted lower CD4 T-cell counts among HIV-uninfected children (difference in CD4 T-cell count/µL for severe anaemia: -93, 95% CI: -204-17, P trend = 0.02). The potential child health risks associated with maternal anaemia and iron deficiency may not be limited to the prenatal period. Efforts to reduce maternal anaemia and iron deficiency during pregnancy may need to be expanded to include the post-partum period.

Predictors of anaemia and iron deficiency in HIV-infected pregnant women in Tanzania: a potential role for vitamin D and parasitic infections.

OBJECTIVE: Anaemia is common during pregnancy, and prenatal Fe supplementation is the standard of care. However, the persistence of anaemia despite Fe supplementation, particularly in HIV infection, suggests that its aetiology may be more complex and warrants further investigation. The present study was conducted to examine predictors of incident haematological outcomes in HIV-infected pregnant women in Tanzania. DESIGN: Prospective cohort study. Cox proportional hazards and binomial regression models were used to identify predictors of incident haematological outcomes: anaemia (Hb < 110 g/l), severe anaemia (Hb < 85 g/l) and hypochromic microcytosis, during the follow-up period. SETTING: Antenatal clinics in Dar es Salaam, Tanzania. SUBJECTS: Participants were 904 HIV-infected pregnant women enrolled in a randomized trial of vitamins (1995-1997). RESULTS: Malaria, pathogenic protozoan and hookworm infections at baseline were associated with a two-fold increase in the risk of anaemia and hypochromic microcytosis during follow-up. Higher baseline erythrocyte sedimentation rate and CD8 T-cell concentrations, and lower Hb concentrations and CD4 T-cell counts, were independent predictors of incident anaemia and Fe deficiency. Low baseline vitamin D (<32 ng/ml) concentrations predicted a 1.4 and 2.3 times greater risk of severe anaemia and hypochromic microcytosis, respectively, during the follow-up period. CONCLUSIONS: Parasitic infections, vitamin D insufficiency, low CD4 T-cell count and high erythrocyte sedimentation rate were the main predictors of anaemia and Fe deficiency in pregnancy and the postpartum period in this population. A comprehensive approach to prevent and manage anaemia, including micronutrient supplementation and infectious disease control, is warranted in HIV-infected women in resource-limited settings - particularly during the pre- and postpartum periods.

Vitamin D status and its association with morbidity including wasting and opportunistic illnesses in HIV-infected women in Tanzania.

Vitamin D has a potential role in preventing HIV-related complications, based on its extensive involvement in immune and metabolic function, including preventing osteoporosis and premature cardiovascular disease. However, this association has not been examined in large studies or in resource-limited settings. Vitamin D levels were assessed in 884 HIV-infected pregnant women at enrollment in a trial of multivitamin supplementation (excluding vitamin D) in Tanzania. Information on HIV related complications was recorded during follow-up (median, 70 months). Proportional hazards models and generalized estimating equations were used to assess the relationship of vitamin D status with these outcomes. Women with low vitamin D status (serum 25-hydroxyvitamin D<32 ng/mL) had 43% higher risk of reaching a body mass index (BMI) less than 18 kg/m(2) during the first 2 years of follow-up, compared to women with adequate vitamin D levels (hazard ratio [HR]: 1.43; 95% confidence intervals: [1.03-1.99]). The relationship between continuous vitamin D levels and risk of BMI less than 18 kg/m(2) during follow-up was inverse and linear (p=0.03). Women with low vitamin D levels had significantly higher incidence of acute upper respiratory infections (HR: 1.27 [1.04-1.54]) and thrush (HR: 2.74 [1.29-5.83]) diagnosed during the first 2 years of follow-up. Low vitamin D status was a significant risk factor for wasting and HIV-related complications such as thrush during follow-up in this prospective cohort in Tanzania. If these protective associations are confirmed in randomized trials, vitamin D supplementation could represent a simple and inexpensive method to improve health and quality of life of HIV-infected patients, particularly in resource-limited settings.

Malaria parasitemia and CD4 T cell count, viral load, and adverse HIV outcomes among HIV-infected pregnant women in Tanzania.

We examined the cross-sectional relationships between malaria parasitemia and CD4 T cell count and viral load among human immunodeficiency virus (HIV)-infected pregnant women. We then followed women to investigate whether or not baseline parasitemia predicted CD4 T cell counts or viral loads > 90 days post-baseline or predicted time to HIV disease stage 3 or 4 or acquired immune deficiency syndrome (AIDS)-related death (ARD). Parasitemia level was nonlinearly associated with viral load at baseline and among measurements taken > 90 days post-baseline; women with low baseline parasitemia, versus none, had higher viral loads at both time points. Any baseline parasitemia predicted an increased rate of ARD among women with baseline CD4 T cell counts > or = 500 cells/microL (ratio rate [RR] = 2.6; 95% confidence interval [CI] = 1.1-6.0; P test for heterogeneity = 0.05). Further study is warranted to determine whether or not parasitemia is especially detrimental to individuals with lower levels of immunosuppression or chronic low parasitemia.

Vitamin D status of HIV-infected women and its association with HIV disease progression, anemia, and mortality.

BACKGROUND: Vitamin D has a potential role in slowing HIV disease progression and preventing mortality based on its extensive involvement in the immune system; however, this relationship has not been examined in large studies or in resource-limited settings. METHODOLOGY/PRINCIPAL FINDINGS: Vitamin D levels were assessed in 884 HIV-infected pregnant women at enrollment in a trial of multivitamin supplementation (not including vitamin D) in Tanzania. Women were followed up for a median of 69.5 months, and information on hemoglobin levels, HIV disease progression, and mortality was recorded. Proportional hazard models and generalized estimating equations were used to assess the relationship of these outcomes with vitamin D status. CONCLUSIONS/SIGNIFICANCE: Low vitamin D status (serum 25-hydroxyvitamin D<32 ng/mL) was significantly associated with progression to WHO HIV disease stage III or greater in multivariate models (incidence rate ratio [RR]: 1.25; 95% confidence intervals [CI]: 1.05, 1.50). No significant relationship was observed between vitamin D status and T-cell counts during follow-up. Women with low vitamin D status had 46% higher risk of developing severe anemia during follow-up, compared to women with adequate vitamin D levels (RR: 1.46; 95% CI: 1.09, 1.96). Women in the highest vitamin D quintile had a 42% lower risk of all-cause mortality, compared to the lowest quintile (RR: 0.58; 95% CI: 0.40, 0.84). Vitamin D status had a protective association with HIV disease progression, all-cause mortality, and development of anemia during follow-up in HIV-infected women. If confirmed in randomized trials, vitamin D supplementation could represent a simple and inexpensive method to prolonging the time to initiation of antiretroviral therapy in HIV-infected patients, particularly in resource-limited settings.

Vitamin A and vitamin B-12 concentrations in relation to mortality and morbidity among children born to HIV-infected women.

Vitamin A supplementation starting at 6 months of age is an important child survival intervention; however, not much is known about the association between vitamin A status before 6 months and mortality among children born to HIV-infected women. Plasma concentrations of vitamins A and B-12 were available at 6 weeks of age (n = 576 and 529, respectively) for children born to HIV-infected women and they were followed up for morbidity and survival status until 24 months after birth. Children in the highest quartile of vitamin A had a 49% lower risk of death by 24 months of age compared to the lowest quartile (HR: 0.51, 95% CI: 0.29-0.90; P-value for trend = 0.01). Higher vitamin A levels were protective in the sub-groups of HIV-infected and un-infected children but this was statistically significant only in the HIV-uninfected subgroup. Higher vitamin A concentrations in plasma are protective against mortality in children born to HIV-infected women.

Predictors and consequences of anaemia among antiretroviral-naïve HIV-infected and HIV-uninfected children in Tanzania.

OBJECTIVE: Predictors and consequences of childhood anaemia in settings with high HIV prevalence are not well known. The aims of the present study were to identify maternal and child predictors of anaemia among children born to HIV-infected women and to study the association between childhood anaemia and mortality. DESIGN: Prospective cohort study. Maternal characteristics during pregnancy and Hb measurements at 3-month intervals from birth were available for children. Information was also collected on malaria and HIV infection in the children, who were followed up for survival status until 24 months after birth. SETTING: Dar es Salaam, Tanzania. SUBJECTS: The study sample consisted of 829 children born to HIV-positive women. RESULTS: Advanced maternal clinical HIV disease (relative risk (RR) for stage > or =2 v. stage 1: 1.31, 95 % CI 1.14, 1.51) and low CD4 cell counts during pregnancy (RR for <350 cells/mm3 v. > or =350 cells/mm3: 1.58, 95 % CI 1.05, 2.37) were associated with increased risk of anaemia among children. Birth weight <2500 g, preterm birth (<34 weeks), malaria parasitaemia and HIV infection in the children also increased the risk of anaemia. Fe-deficiency anaemia in children was an independent predictor of mortality in the first two years of life (hazard ratio 1.99, 95 % CI 1.06, 3.72). CONCLUSIONS: Comprehensive care including highly active antiretroviral therapy to eligible HIV-infected women during pregnancy could reduce the burden of anaemia in children. Programmes for the prevention of mother-to-child transmission of HIV and antimalarial treatment to children could improve child survival in settings with high HIV prevalence.

Perinatal outcomes, including mother-to-child transmission of HIV, and child mortality and their association with maternal vitamin D status in Tanzania.

BACKGROUND: Vitamin D is a strong immunomodulator and may protect against adverse pregnancy outcomes, mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV), and child mortality. METHODS: A total of 884 HIV-infected pregnant women who were participating in a vitamin supplementation trial in Tanzania were monitored to assess pregnancy outcomes and child mortality. The association of these outcomes with maternal vitamin D status at enrollment was examined in an observational analysis. RESULTS: No association was observed between maternal vitamin D status and adverse pregnancy outcomes, including low birth weight and preterm birth. In multivariate models, a low maternal vitamin D level (<32 ng/mL) was associated with a 50% higher risk (95% confidence interval [CI], 2%-120%) of MTCT of HIV at 6 weeks, a 2-fold higher risk of MTCT of HIV through breast-feeding among children who were HIV uninfected at 6 weeks (95% CI, 1.08-3.82), and a 46% higher overall risk of HIV infection (95% CI, 11%-91%). Children born to women with a low vitamin D level had a 61% higher risk of dying during follow-up (95% CI, 25%-107%). CONCLUSIONS: If found to be efficacious in randomized trials, vitamin D supplementation could prove to be an inexpensive method of reducing the burden of HIV infection and death among children, particularly in resource-limited settings.

Placental malaria and mother-to-child transmission of human immunodeficiency virus-1.

There are few studies of the association between placental malaria (PM) and mother-to-child transmission (MTCT) of human immunodeficiency virus-1 (HIV-1), and the results of published studies are inconsistent. To determine the association between PM and MTCT of HIV-1, we performed a secondary analysis of data from a clinical trial of antibiotics to reduce chorioamnionitis. Data regarding 1,662 HIV-1-infected women with live born singleton and first-born twin infants with information regarding PM and infant HIV-1 infection status at birth were analyzed. At the time of the study, women did not have access to antiretroviral drugs for treatment of acquired immunodeficiency syndrome but had received nevirapine prophylaxis to reduce the risk of MTCT of HIV-1. Placental malaria was not associated with the infant HIV-1 infection status at birth (P = 0.67). Adjustment for maternal plasma viral load and CD4+ cell count did not change these results (odds ratio = 1.06, 95% confidence interval = 0.51-2.20, P = 0.87). Placental malaria was more likely to be related to HIV-1 infection at birth among women with low viral load at baseline (P for interaction = 0.08). In conclusion, PM was not associated with infant HIV-1 infection status at birth. The interaction of maternal plasma viral load, PM, and MTCT of HIV-1 warrants further studies.

Predictors of stillbirth among HIV-infected Tanzanian women.

OBJECTIVE: To determine maternal risk factors for stillbirth among pregnant HIV-infected women in sub-Saharan Africa. DESIGN: Prospective cohort study nested within a micronutrient trial. At enrollment, maternal sociodemographic, obstetric, immunologic, clinical, and nutritional variables were measured. Women were followed through monthly clinic visits until delivery. Multivariate predictors of stillbirth were identified in Poisson regression models. SETTING: Antenatal clinic in a tertiary care hospital in urban Dar es Salaam, Tanzania. POPULATION: N=1,078 women enrolled between 12 and 27 weeks of gestation. MAIN OUTCOME MEASURES: Stillbirth (delivery of dead baby > or = 28 weeks' gestation), fresh stillbirth, and macerated stillbirth. RESULTS: Among 1,017 singleton pregnancies, there were 49 stillbirths, yielding a stillbirth risk of 50.0 per 1,000 deliveries (95% Confidence Interval(CI) = 37.2, 65.6). Of stillbirths with known type, 53.7% were fresh and 46.3% macerated. In multivariate analyses, baseline measures of late (> or = 21 weeks' gestation) study entry (Relative Risk (RR) = 2.13, 95% CI = 1.17, 3.87), CD3 count > or = 1,179 cells/ml (RR = 2.15, 95% CI = 1.16, 4.01), stillbirth history (RR = 3.53, 95% CI = 1.30, 9.59), primiparity (RR = 3.65, 95% CI = 1.83, 7.29), and syphilis infection (RR = 2.06, 95% CI = 1.09, 3.88) predicted increased stillbirth risk. Late study entry, illiteracy, stillbirth history, primiparity, CD3 count > or = 1,179 cells/ml, gonorrhea infection, and previous hospitalization predicted increased risk of fresh stillbirth, while living alone and syphilis infection predicted increased risk of macerated stillbirth. CONCLUSIONS: Applying antenatal screening and preventive tools for the socioeconomic, obstetric, immunologic, and clinical risk factors identified may assist in reducing the high incidence of stillbirth among HIV-infected women in urban sub-Saharan Africa.

Patterns and predictors of CD4 T-cell counts among children born to HIV-infected women in Tanzania.

We assessed age-specific CD4 T-cell counts and their determinants among Tanzanian children born to HIV-infected mothers to address a major research gap. A total of 474 HIV-uninfected and 69 HIV-infected children were followed until age of 12 months. Maternal predictors were measured during pregnancy and child predictors at birth and throughout the follow up. Child CD4 T-cell counts were evaluated at the age of 3 months and subsequent 3-month intervals; they decreased linearly among HIV-infected (beta = -8 cells per week; 95% CI -12 to -4; P = 0.0003) and increased linearly among HIV-uninfected children (beta = 4 cells/week; 95% CI 2-7; P = 0.0008). Decreased child counts were predicted by low child anthropometry, maternal HIV stage > or =2, and maternal mid-upper arm circumference <27 cm among HIV-infected children; and by weight-for-height <-2 z-score, maternal HIV stage > or =2, maternal erythrocyte sedimentation rate <81 mm/h and maternal haemoglobin <8.5 g/dl among HIV-uninfected children. The maternal and child predictors described may serve as intervention targets among HIV-exposed children.

Randomized, double-blind, placebo-controlled trial of selenium supplements among HIV-infected pregnant women in Tanzania: effects on maternal and child outcomes.

BACKGROUND: In observational studies, adequate selenium status has been associated with better pregnancy outcomes and slowed HIV disease progression. OBJECTIVE: We investigated the effects of daily selenium supplements on CD4 cell counts, viral load, pregnancy outcomes, and maternal and infant mortality among 913 HIV-infected pregnant women. DESIGN: In this randomized, double-blind, placebo-controlled trial, eligible women between 12 and 27 wk of gestation were given daily selenium (200 mug as selenomethionine) or placebo as supplements from recruitment until 6 mo after delivery. All women received prenatal iron, folic acid, and multivitamin supplements irrespective of experimental assignment. RESULTS: The selenium regimen had no significant effect on maternal CD4 cell counts or viral load. Selenium was marginally associated with a reduced risk of low birth weight [relative risk (RR) = 0.71; 95% CI: 0.49, 1.05; P = 0.09] and increased risk of fetal death (RR = 1.58; 95% CI = 0.95, 2.63; P = 0.08), but had no effect on risk of prematurity or small-for-gestational age birth. The regimen had no significant effect on maternal mortality (RR = 1.02; 95% CI = 0.51, 2.04; P = 0.96). There was no significant effect on neonatal or overall child mortality, but selenium reduced the risk of child mortality after 6 wk (RR = 0.43; 95% CI = 0.19, 0.99; P = 0.048). CONCLUSION: Among HIV-infected women from Dar es Salaam, Tanzania, selenium supplements given during and after pregnancy did not improve HIV disease progression or pregnancy outcomes, but may improve child survival. This trial was registered at clinicaltrials.gov as NCT00197561.

Maternal disease stage and child undernutrition in relation to mortality among children born to HIV-infected women in Tanzania.

OBJECTIVE: To examine whether maternal HIV disease stage during pregnancy and child malnutrition are associated with child mortality. DESIGN: Prospective cohort study in Tanzania. METHODS: Indicators of disease stage were assessed for 939 HIV-infected women during pregnancy and at delivery, and children's anthropometric status was obtained at scheduled monthly clinic visits after delivery. Children were followed up for survival status until 24 months after birth. RESULTS: Advanced maternal HIV disease during pregnancy (CD4 count <350 vs. >or=350 cells/mm) was associated with increased risk of child mortality through 24 months of age (hazard ratio [HR] = 1.74, 95% confidence interval [CI]: 1.32 to 2.30). CD4 count <350 cells/mm was also associated with an increased risk of death among children who remained HIV-negative during follow-up (HR = 2.00, 95% CI: 1.36 to 2.94). Low maternal hemoglobin concentration and child undernutrition were related to an increased risk of mortality in this cohort of children. CONCLUSIONS: Low maternal CD4 cell count during pregnancy is related to increased risk of mortality in children born to HIV-infected women. Care and treatment for HIV disease, including highly active antiretroviral therapy to pregnant women, could improve child survival. Prevention and treatment of undernutrition in children remain critical interventions in settings with high HIV prevalence.

Iron status is an important cause of anemia in HIV-infected Tanzanian women but is not related to accelerated HIV disease progression.

In HIV-infected populations from developing countries, it is unclear what proportion of anemia is attributable to iron deficiency (ID) and whether high body iron stores worsen HIV disease progression. We therefore evaluated these research questions in 584 HIV-infected Tanzanian women. Hemoglobin (Hb), serum ferritin (SF), serum transferrin receptor (sTfR), and C-reactive protein (CRP) concentrations were evaluated between 13 and 43 wk after women gave birth. ID was defined as SF or sTfR outside normal ranges, and ID anemia (IDA) as ID plus low Hb. In multivariate Cox regression models, the association between SF and HIV disease progression was assessed. Participants received iron + folate supplements during pregnancy. Hb (r = -0.159; P = 0.0001), SF (r = 0.355; P < 0.0001), and sTfR/log SF index (r = -0.119; P = 0.004) were related to CRP, whereas sTfR (r = 0.029; P = 0.48) was not. Prevalence estimates were 39.7% for ID and 23.6% for IDA. ID was associated with 48.9% of anemia cases. Categories of SF were not significantly associated with HIV-related mortality or progression to stage 4. Nevertheless, SF > 150.0 microg/L was related to a nonsignificantly elevated risk of progression to stage 4 (rate ratio = 1.78; 95% CI = 0.68-4.64; P = 0.24) compared with SF < 12.0 microg/L. In HIV-infected, parous women from sub-Saharan Africa, ID is of moderately high prevalence and is an important underlying cause of anemia. High storage iron does not appear to be related to HIV disease progression in this population, but more research on the role of iron during HIV disease is needed.

C-reactive protein independently predicts HIV-related outcomes among women and children in a resource-poor setting.

OBJECTIVE: To evaluate C-reactive protein (CRP) as a predictor of HIV-related outcomes among women and children in a resource-poor setting. DESIGN: We measured serum CRP concentration among 606 HIV-infected women, all of whom were not taking highly-active antiretroviral therapy, 3 to 11 months after they gave birth, and assessed relationships of CRP to HIV-related endpoints, including maternal disease progression, mother-to-child transmission of HIV, and maternal and child mortality. METHODS: We used Cox proportional hazards and regression models adjusted for age, sociodemographic characteristics, anthropometric measurements, hemoglobin, CD4 cell count, HIV viral load, and, for child outcomes, breastfeeding status. RESULTS: Ninety-four women had a high CRP concentration (> 10 mg/l). During the follow-up, 56 women progressed to WHO stage 4 and 188 died, and a high maternal CRP concentration was associated with a 2.26-fold [95% confidence interval (CI), 1.64-3.12] greater risk of progression to stage 4 or death. Among children, 174 acquired HIV and 116 died by age 2 years, and a high maternal CRP concentration was associated with a 3.03-fold (95% CI, 1.85-4.96) greater risk of child mortality. In multivariate analyses among adults, a high maternal CRP concentration was associated with a 1.55-fold (95% CI, 1.08-2.23) greater risk of progression to stage 4 or death. A maternal CRP concentration was not significantly associated with mother-to-child transmission of HIV. CONCLUSIONS: A high maternal CRP concentration independently predicts HIV disease progression, maternal mortality, and child mortality in a resource-poor setting. C-reactive protein may be an important and inexpensive prognostic indicator for HIV-infected women and their children.

Multivitamin supplementation improves hematologic status in HIV-infected women and their children in Tanzania.

BACKGROUND: Anemia is a frequent complication among HIV-infected persons and is associated with faster disease progression and mortality. OBJECTIVE: We examined the effect of multivitamin supplementation on hemoglobin concentrations and the risk of anemia among HIV-infected pregnant women and their children. DESIGN: HIV-1-infected pregnant women (n = 1078) from Dar es Salaam, Tanzania, were enrolled in a double-blind trial and provided daily supplements of preformed vitamin A and beta-carotene, multivitamins (vitamins B, C, and E), preformed vitamin A and beta-carotene + multivitamins, or placebo. All women received iron and folate supplements only during pregnancy according to local standard of care. The median follow-up time for hemoglobin measurement for mothers was 57.3 mo [interquartile range (IQR): 28.6-66.8] and for children it was 28.0 mo (IQR: 5.3-41.7). RESULTS: During the whole period, hemoglobin concentrations among women who received multivitamins were 0.33 g/dL higher than among women who did not receive multivitamins (P=0.07). Compared with placebo, multivitamin supplementation resulted in a hemoglobin increase of 0.59 g/dL during the first 2 y after enrollment (P=0.0002). Compared with placebo, the children born to mothers who received multivitamins had a reduced risk of anemia. In this group, the risk of macrocytic anemia was 63% lower than in the placebo group (relative risk: 0.37: 95% CI: 0.18, 0.79; P=0.01). CONCLUSION: Multivitamin supplementation provided during pregnancy and in the postpartum period resulted in significant improvements in hematologic status among HIV-infected women and their children, which provides further support for the value of multivitamin supplementation in HIV-infected adults.