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Introduction: As many as 250 million children under the age of 5 may not be reaching their full developmental potential partly due to poor nutrition during pregnancy and the first 2 years of life. Micronutrients, including vitamin B12, are important for the development of brain structure and function; however, the timing, duration and severity of deficiencies may alter the impact on functional development outcomes. Consequently, to fully explore the effect of vitamin B12 on cognitive function, it is crucial to measure neurodevelopment at different ages, in different populations and with vitamin B12 supplementation at different times during the critical periods of neurodevelopment. Methods and analysis In this project, we follow up children from four recently completed randomised placebo-controlled trials of oral vitamin B12 supplementation, two in India and two in Tanzania, to explore the long-term effects on neurodevelopmental outcomes and growth. All the included trials provided at least two recommended dietary allowances of oral vitamin B12 daily for at least 6 months. Vitamin B12 was supplemented either during pregnancy, early infancy or early childhood. Primary outcomes are neurodevelopmental status, cognitive function and growth later in childhood. We apply validated and culturally appropriate instruments to identify relevant developmental outcomes. All statistical analyses will be done according to intention-to-treat principles. The project provides an excellent opportunity to examine the effect of vitamin B12 supplementation in different periods during early life and measure the outcomes later in childhood. Ethics and dissemination The study has received ethical approvals from all relevant authorities in Norway, USA, Tanzania and India and complies fully with ethical principles for medical research. Results will be presented at national and international research and policy meetings and published in peer-reviewed scientific journals, preferably open access. Trial registration number NCT00641862 (Bangalore); NCT00717730, updated CTRI/2016/11/007494 (Delhi); NCT00197548 and NCT00421668 (Dar es Salaam).

Background: Environmental Enteric Dysfunction (EED) in children from low-income countries has been linked to linear growth declines. There is a critical need to identify sensitive and early EED biomarkers. Objective: Determine whether levels of antibodies against bacterial components flagellin (flic) and lipopolysaccharide (LPS) predict poor growth. Design/Methods In a prospective birth cohort of 380 children in rural Pakistan blood and stool samples were obtained at ages 6 and 9 months. Linear mixed effects models were used to examine longitudinal associations between quartiles of anti-flic and anti-LPS antibodies and changes in LAZ, WAZ and WLZ scores. Spearman’s correlations were measured between anti-flic and anti-LPS immunoglobulins with measures of systemic/enteric inflammation and intestinal regeneration. Results: Anti-LPS IgA correlated significantly with CRP, AGP and Reg1 serum at 6mo and with MPO at 9mo. In multivariate analysis at 6mo of age, higher anti-LPS IgA levels predicted greater declines in LAZ scores over subsequent 18mo (comparing highest to lowest quartile, β (SE) change in LAZ score/year = -0.313 (0.125), p-value = 0.013). Anti-flic Ig A in the two highest quartiles measured at 9mo of age had declines in LAZ of -0.269 (0.126), p = 0.033; and -0.306 (0.129), p = 0.018 respectively, during the subsequent 18mo of life, compared to those in the lowest quartile of anti-flic IgA. Conclusions and relevance Elevated anti-flic IgA and anti-LPS IgA antibodies at 6 and 9mo, predict declines in linear growth. Systemic and enteric inflammation correlated with anti-LPS IgA provides mechanistic considerations for potential future interventions.

(1) Background: The effects of zinc supplementation on child growth, and prior reviews of these studies, have shown mixed results. We aim to systematically review and meta-analyze randomized controlled trials evaluating effects of preventive zinc supplementation for 3 months or longer during pregnancy or in children up to age 5 years on pregnancy outcomes and child growth; (2) Methods: We searched PubMed, EMBASE, Cochrane Library, Web of Science, and trial registries for eligible trials up to October 10, 2017. Inclusion selection and data extractions were performed independently and in duplicate. Study quality was evaluated by the Cochrane Risk of Bias tool. Findings were pooled using random effects meta-analysis, with heterogeneity assessed by I2 and τ2 statistic, stratified analyses, and meta-regression, and publication bias by Egger’s and Begg’s tests; (3) Results: Seventy-eight trials with 34,352 unique participants were identified, including 24 during pregnancy and 54 in infancy/childhood. Maternal zinc supplementation did not significantly increase birth weight (weighted mean difference (WMD) = 0.08 kg, 95%CI: −0.05, 0.22) or decrease the risk of low birth weight (RR = 0.76, 95%CI: 0.52–1.11). Zinc supplementation after birth increased height (WMD = 0.23 cm, 95%CI: 0.09–0.38), weight (WMD = 0.14 kg, 95%CI: 0.07–0.21), and weight-for-age Z-score (WMD = 0.04, 95%CI: 0.001–0.087), but not height-for-age Z-score (WMD = 0.02, 95%CI: −0.01–0.06) or weight-for-height Z score (WMD = 0.02, 95%CI: −0.03–0.06). Child age at zinc supplementation appeared to modify the effects on height (P-interaction = 0.002) and HAZ (P-interaction = 0.06), with larger effects of supplementation starting at age ≥2 years (WMD for height = 1.37 cm, 95%CI: 0.50–2.25; WMD for HAZ = 0.12, 95%CI: 0.05–0.19). No significant effects of supplementation were found on the risk of stunting, underweight or wasting; (4) Conclusion: Although the possibility of publication bias and small study effect could not be excluded, the current meta-analysis indicates that zinc supplementation in infants and early childhood, but not pregnancy, increases specific growth outcomes, with evidence for a potentially stronger effect after 2 years of age. These findings inform recommendation and policy development for zinc supplementation to improve growth among young children.

Background: Vitamin D has significant immunomodulatory effects on both adaptive and innate immune responses. Observational studies indicate that adults infected with HIV with low vitamin D status may be at increased risk of mortality, pulmonary tuberculosis, and HIV disease progression. Growing observational evidence also suggests that low vitamin D status in pregnancy may increase the risk of adverse birth and infant health outcomes. As a result, antiretroviral therapy (ART) adjunct vitamin D3 supplementation may improve the health of HIV-infected pregnant women and their children. Methods/design The Trial of Vitamins-5 (ToV5) is an individually randomized, double-blind, placebo-controlled trial of maternal vitamin D3 (cholecalciferol) supplementation conducted among 2300 HIV-infected pregnant women receiving triple-drug ART under Option B+ in Dar es Salaam, Tanzania. HIV-infected pregnant women of 12–27 weeks gestation are randomized to either: 1) 3000 IU vitamin D3 taken daily from randomization in pregnancy until trial discharge at 12 months postpartum; or 2) a matching placebo regimen. Maternal participants are followed-up at monthly clinic visits during pregnancy, at delivery, and then with their children at monthly postpartum clinic visits. The primary efficacy outcomes of the trial are: 1) maternal HIV disease progression or death; 2) risk of small-for-gestational age (SGA) births; and 3) risk of infant stunting at 1 year of age. The primary safety outcome of the trial is incident maternal hypercalcemia. Secondary outcomes include a range of clinical and biological maternal and child health outcomes. Discussion The ToV5 will provide causal evidence on the effect of vitamin D3 supplementation on HIV progression and death, SGA births, and infant stunting at 1 year of age. The results of the trial are likely generalizable to HIV-infected pregnant women and their children in similar resource-limited settings utilizing the Option B+ approach. Trial registration ClinicalTrials.gov identifier: NCT02305927. Registered on 29 October 2014. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2157-3) contains supplementary material, which is available to authorized users.

Objective: To assess whether growth and biomarkers of environmental enteric dysfunction in infancy are related to health outcomes in midchildhood in Tanzania. Study design Children who participated in 2 randomized trials of micronutrient supplements in infancy were followed up in midchildhood (4.6-9.8 years of age). Anthropometry was measured at age 6 and 52 weeks in both trials, and blood samples were available from children at 6 weeks and 6 months from 1 trial. Linear regression was used for height-for-age z-score, body mass index-for-age z-score, and weight for age z-score, and blood pressure analyses; log-binomial models were used to estimate risk of overweight, obesity, and stunting in midchildhood. Results: One hundred thirteen children were followed-up. Length-for-age z-score at 6 weeks and delta length-for-age z-score from 6 to 52 weeks were associated independently and positively with height-for-age z-score and inversely associated with stunting in midchildhood. Delta weight-for-length and weight-for-age z-score were also positively associated with midchildhood height-for-age z-score. The 6-week and delta weight-for-length z-scores were associated independently and positively with midchildhood body mass index-for-age z-score and overweight, as was the 6-week and delta weight-for-age z-score. Delta length-for-age z-score was also associated with an increased risk of overweight in midchildhood. Body mass index-for-age z-score in midchildhood was associated positively with systolic blood pressure. Serum anti-flagellin IgA concentration at 6 weeks was also associated with increased blood pressure in midchildhood. Conclusions: Anthropometry at 6 weeks and growth in infancy independently predict size in midchildhood, while anti-flagellin IgA, a biomarker of environmental enteric dysfunction, in early infancy is associated with increased blood pressure in midchildhood. Interventions in early life should focus on optimizing linear growth while minimizing excess weight gain and environmental enteric dysfunction. Trial registration ClinicalTrials.gov: NCT00197730 and NCT00421668.

BACKGROUND Zinc supplementation adversely affects iron status in animal and adult human studies but few, trials have included young infants. OBJECTIVE To determine the effects of zinc and multivitamin supplementation on infant hematologic and iron status. METHODS In a double-blind RCT, Tanzanian infants were randomized to daily, oral zinc (Zn), multivitamins (MV), Zn and MV, or placebo treatment arms at age 6 wk. Hemoglobin concentration (Hb) and red blood cell indices were measured at baseline and at 6, 12, and 18 mo of age. Plasma samples from 589 infants were examined for iron deficiency (ID) at 6 mo. RESULTS In logistic regression models, Zn treatment was associated with greater odds of ID (OR 1.8 [95% CI 1.0–3.3]), and MV treatment was associated with lower odds (OR 0.49 [95% CI 0.3–0.9]). In Cox models, MV were associated with a 28% reduction in risk of severe anemia (HR=0.72 [95% Cl 0.56–0.94]) and a 26% reduction in risk of severe microcytic anemia (HR=0.74 [0.56–0.96]) through 18 months. No effects of Zn on risk of anemia were seen. Infants treated with MV alone had higher mean Hb (9.9 g/dL [95% CI 9.7–10.1]) than those given placebo (9.6 g/dL [9.4–9.8]) or Zn alone (9.6 g/dL [9.4–9.7]). CONCLUSIONS MV treatment improved iron status in infancy, whereas Zn worsened iron status but without an associated increase in risk for anemia. Infants in long-term zinc supplementation programs at risk for ID may benefit from screening and/or the addition of a multivitamin supplement.

Background: Menopausal hormone therapy (MHT) use has been consistently associated with a decreased risk of colorectal cancer (CRC) in women. Our aim was to use a genome-wide gene–environment interaction analysis to identify genetic modifiers of CRC risk associated with use of MHT. Methods: We included 10 835 postmenopausal women (5419 cases and 5416 controls) from 10 studies. We evaluated use of any MHT, oestrogen-only (E-only) and combined oestrogen–progestogen (E+P) hormone preparations. To test for multiplicative interactions, we applied the empirical Bayes (EB) test as well as the Wald test in conventional case–control logistic regression as primary tests. The Cocktail test was used as secondary test. Results: The EB test identified a significant interaction between rs964293 at 20q13.2/CYP24A1 and E+P (interaction OR (95% CIs)=0.61 (0.52–0.72), P=4.8 × 10−9). The secondary analysis also identified this interaction (Cocktail test OR=0.64 (0.52–0.78), P=1.2 × 10−5 (alpha threshold=3.1 × 10−4). The ORs for association between E+P and CRC risk by rs964293 genotype were as follows: C/C, 0.96 (0.61–1.50); A/C, 0.61 (0.39–0.95) and A/A, 0.40 (0.22–0.73), respectively. Conclusions: Our results indicate that rs964293 modifies the association between E+P and CRC risk. The variant is located near CYP24A1, which encodes an enzyme involved in vitamin D metabolism. This novel finding offers additional insight into downstream pathways of CRC etiopathogenesis.

Genome-wide association studies (GWAS) have identified many genetic susceptibility loci for colorectal cancer (CRC). However, variants in these loci explain only a small proportion of familial aggregation, and there are likely additional variants that are associated with CRC susceptibility. Genome-wide studies of gene-environment interactions may identify variants that are not detected in GWAS of marginal gene effects. To study this, we conducted a genome-wide analysis for interaction between genetic variants and alcohol consumption and cigarette smoking using data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Interactions were tested using logistic regression. We identified interaction between CRC risk and alcohol consumption and variants in the 9q22.32/HIATL1 (Pinteraction = 1.76×10−8; permuted p-value 3.51x10-8) region. Compared to non-/occasional drinking light to moderate alcohol consumption was associated with a lower risk of colorectal cancer among individuals with rs9409565 CT genotype (OR, 0.82 [95% CI, 0.74–0.91]; P = 2.1×10−4) and TT genotypes (OR,0.62 [95% CI, 0.51–0.75]; P = 1.3×10−6) but not associated among those with the CC genotype (p = 0.059). No genome-wide statistically significant interactions were observed for smoking. If replicated our suggestive finding of a genome-wide significant interaction between genetic variants and alcohol consumption might contribute to understanding colorectal cancer etiology and identifying subpopulations with differential susceptibility to the effect of alcohol on CRC risk.

Extracellular vesicles (EVs) have emerged as a promising biomarker platform for glioblastoma patients. However, the optimal method for quantitative assessment of EVs in clinical bio-fluid remains a point of contention. Multiple high-resolution platforms for quantitative EV analysis have emerged, including methods grounded in diffraction measurement of Brownian motion (NTA), tunable resistive pulse sensing (TRPS), vesicle flow cytometry (VFC), and transmission electron microscopy (TEM). Here we compared quantitative EV assessment using cerebrospinal fluids derived from glioblastoma patients using these methods. For EVs <150 nm in diameter, NTA detected more EVs than TRPS in three of the four samples tested. VFC particle counts are consistently 2–3 fold lower than NTA and TRPS, suggesting contribution of protein aggregates or other non-lipid particles to particle count by these platforms. While TEM yield meaningful data in terms of the morphology, its particle count are consistently two orders of magnitude lower relative to counts generated by NTA and TRPS. For larger particles (>150 nm in diameter), NTA consistently detected lower number of EVs relative to TRPS. These results unveil the strength and pitfalls of each quantitative method alone for assessing EVs derived from clinical cerebrospinal fluids and suggest that thoughtful synthesis of multi-platform quantitation will be required to guide meaningful clinical investigations.

Critical to the design and assessment of interventions for enteropathy and its developmental consequences in children living in impoverished conditions are non-invasive biomarkers that can detect intestinal damage and predict its effects on growth and development. We therefore assessed fecal, urinary and systemic biomarkers of enteropathy and growth predictors in 375 6–26 month-old children with varying degrees of malnutrition (stunting or wasting) in Northeast Brazil. 301 of these children returned for followup anthropometry after 2-6m. Biomarkers that correlated with stunting included plasma IgA anti-LPS and anti-FliC, zonulin (if >12m old), and intestinal FABP (I-FABP, suggesting prior barrier disruption); and with citrulline, tryptophan and with lower serum amyloid A (SAA) (suggesting impaired defenses). In contrast, subsequent growth was predicted in those with higher fecal MPO or A1AT and also by higher L/M, plasma LPS, I-FABP and SAA (showing intestinal barrier disruption and inflammation). Better growth was predicted in girls with higher plasma citrulline and in boys with higher plasma tryptophan. Interactions were also seen with fecal MPO and neopterin in predicting subsequent growth impairment. Biomarkers clustered into markers of 1) functional intestinal barrier disruption and translocation, 2) structural intestinal barrier disruption and inflammation and 3) systemic inflammation. Principle components pathway analyses also showed that L/M with %L, I-FABP and MPO associate with impaired growth, while also (like MPO) associating with a systemic inflammation cluster of kynurenine, LBP, sCD14, SAA and K/T. Systemic evidence of LPS translocation associated with stunting, while markers of barrier disruption or repair (A1AT and Reg1 with low zonulin) associated with fecal MPO and neopterin. We conclude that key noninvasive biomarkers of intestinal barrier disruption, LPS translocation and of intestinal and systemic inflammation can help elucidate how we recognize, understand, and assess effective interventions for enteropathy and its growth and developmental consequences in children in impoverished settings.

Genome-wide association studies (GWAS) have identified many common single nucleotide polymorphisms (SNPs) associated with colorectal cancer risk. These SNPs may tag correlated variants with biological importance. Fine-mapping around GWAS loci can facilitate detection of functional candidates and additional independent risk variants. We analyzed 11,900 cases and 14,311 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. To fine-map genomic regions containing all known common risk variants, we imputed high-density genetic data from the 1000 Genomes Project. We tested single-variant associations with colorectal tumor risk for all variants spanning genomic regions 250-kb upstream or downstream of 31 GWAS-identified SNPs (index SNPs). We queried the University of California, Santa Cruz Genome Browser to examine evidence for biological function. Index SNPs did not show the strongest association signals with colorectal tumor risk in their respective genomic regions. Bioinformatics analysis of SNPs showing smaller P-values in each region revealed 21 functional candidates in 12 loci (5q31.1, 8q24, 11q13.4, 11q23, 12p13.32, 12q24.21, 14q22.2, 15q13, 18q21, 19q13.1, 20p12.3, and 20q13.33). We did not observe evidence of additional independent association signals in GWAS-identified regions. Our results support the utility of integrating data from comprehensive fine-mapping with expanding publicly available genomic databases to help clarify GWAS associations and identify functional candidates that warrant more onerous laboratory follow-up. Such efforts may aid the eventual discovery of disease-causing variant(s).

Background: Several regions of the genome show pleiotropic associations with multiple cancers. We sought to evaluate whether 181 single-nucleotide polymorphisms previously associated with various cancers in genome-wide association studies were also associated with melanoma risk. Methods: We evaluated 2,131 melanoma cases and 20,353 controls from three studies in the Population Architecture using Genomics and Epidemiology (PAGE) study (EAGLE-BioVU, MEC, WHI) and two collaborating studies (HPFS, NHS). Overall and sex-stratified analyses were performed across studies. Results: We observed statistically significant associations with melanoma for two lung cancer SNPs in the TERT-CLPTM1L locus (Bonferroni-corrected p<2.8x10-4), replicating known pleiotropic effects at this locus. In sex-stratified analyses, we also observed a potential male-specific association between prostate cancer risk variant rs12418451 and melanoma risk (OR=1.22, p=8.0x10-4). No other variants in our study were associated with melanoma after multiple comparisons adjustment (p>2.8e-4). Conclusions: We provide confirmatory evidence of pleiotropic associations with melanoma for two SNPs previously associated with lung cancer, and provide suggestive evidence for a male-specific association with melanoma for prostate cancer variant rs12418451. This SNP is located near TPCN2, an ion transport gene containing SNPs which have been previously associated with hair pigmentation but not melanoma risk. Previous evidence provides biological plausibility for this association, and suggests a complex interplay between ion transport, pigmentation, and melanoma risk that may vary by sex. If confirmed, these pleiotropic relationships may help elucidate shared molecular pathways between cancers and related phenotypes.

Background: The nutrition and epidemiologic transition has been associated with an increasing incidence of preterm birth in developing countries, but data from large observational studies in China have been limited. Our study was to describe the trends and factors associated with the incidence of preterm birth and infant mortality due to prematurity in Hubei Province, China. Methods: We conducted a population-based survey through the Maternal and Child Health Care Network in Hubei Province from January 2001 to December 2012. We used data from 16 monitoring sites to examine the trend and risk factors for premature birth as well as infant mortality associated with prematurity. Results: A total of 818,481 live births were documented, including 76,923 preterm infants (94 preterm infants per 1,000 live births) and 2,248 deaths due to prematurity (2.75 preterm deaths per 1,000 live births). From 2001 to 2012, the incidence of preterm birth increased from 56.7 to 105.2 per 1,000 live births (P for trend < 0.05), while the infant mortality rate due to prematurity declined from 95.0 to 13.4 per 1,000 live births (P for trend < 0.05). Older maternal age, lower maternal education, use of assisted reproductive technology (ART), higher income, residence in urban areas, and infant male sex were independently associated with a higher incidence of preterm birth (all p values < 0.05). Shorter gestation, lower birth weight, and lower income were associated with a higher mortality rate, while use of newborn emergency transport services (NETS) was associated with a lower preterm mortality rate (all p values < 0.05). Conclusion: An increasing incidence of preterm birth and a parallel reduction in infant mortality due to prematurity were observed in Hubei Province from 2001 to 2012. Our results provide important information for areas of improvements in reducing incidence and mortality of premature birth. Electronic supplementary material The online version of this article (doi:10.1186/s12884-015-0767-x) contains supplementary material, which is available to authorized users.

Designed in collaboration with 23andMe and Pathway Genomics, the Impact of Personal Genomics (PGen) Study serves as a model for academic-industry partnership and provides a longitudinal dataset for studying psychosocial, behavioral, and health outcomes related to direct-to-consumer personal genomic testing (PGT). Web-based surveys administered at three time points, and linked to individual-level PGT results, provide data on 1,464 PGT customers, of which 71% completed each follow-up survey and 64% completed all three surveys. The cohort includes 15.7% individuals of non-white ethnicity, and encompasses a range of income, education, and health levels. Over 90% of participants agreed to re-contact for future research. Electronic supplementary material The online version of this article (doi:10.1186/s13073-014-0096-0) contains supplementary material, which is available to authorized users.

Introduction: HIV and malaria infections occur in the same individuals, particularly in sub-Saharan Africa. We examined whether daily multivitamin supplementation (vitamins B complex, C, and E) or vitamin A supplementation altered malaria incidence in HIV-infected women of reproductive age. Methods: HIV-infected pregnant Tanzanian women recruited into the study were randomly assigned to daily multivitamins (B complex, C, and E), vitamin A alone, both multivitamins and vitamin A, or placebo. Women received malaria prophylaxis during pregnancy and were followed monthly during the prenatal and postpartum periods. Malaria was defined in 2 ways: presumptive diagnosis based on a physician's or nurse's clinical judgment, which in many cases led to laboratory investigations, and periodic examination of blood smears for malaria parasites. Results: Multivitamin supplementation compared with no multivitamins significantly lowered women's risk of presumptively diagnosed clinical malaria (relative risk: 0.78, 95% confidence interval: 0.67 to 0.92), although multivitamins increased their risk of any malaria parasitemia (relative risk: 1.24, 95% confidence interval: 1.02 to 1.50). Vitamin A supplementation did not change malaria incidence during the study. Conclusions: Multivitamin supplements have been previously shown to reduce HIV disease progression among HIV-infected women, and consistent with that, these supplements protected against development of symptomatic malaria. The clinical significance of increased risk of malaria parasitemia among supplemented women deserves further research, however. Preventive measures for malaria are warranted as part of an integrated approach to the care of HIV-infected individuals exposed to malaria.

Dietary factors, including meat, fruits, vegetables and fiber, are associated with colorectal cancer; however, there is limited information as to whether these dietary factors interact with genetic variants to modify risk of colorectal cancer. We tested interactions between these dietary factors and approximately 2.7 million genetic variants for colorectal cancer risk among 9,287 cases and 9,117 controls from ten studies. We used logistic regression to investigate multiplicative gene-diet interactions, as well as our recently developed Cocktail method that involves a screening step based on marginal associations and gene-diet correlations and a testing step for multiplicative interactions, while correcting for multiple testing using weighted hypothesis testing. Per quartile increment in the intake of red and processed meat were associated with statistically significant increased risks of colorectal cancer and vegetable, fruit and fiber intake with lower risks. From the case-control analysis, we detected a significant interaction between rs4143094 (10p14/near GATA3) and processed meat consumption (OR = 1.17; p = 8.7E-09), which was consistently observed across studies (p heterogeneity = 0.78). The risk of colorectal cancer associated with processed meat was increased among individuals with the rs4143094-TG and -TT genotypes (OR = 1.20 and OR = 1.39, respectively) and null among those with the GG genotype (OR = 1.03). Our results identify a novel gene-diet interaction with processed meat for colorectal cancer, highlighting that diet may modify the effect of genetic variants on disease risk, which may have important implications for prevention.

Background: India has a wide range of nutrition and health problems which require professionals with appropriate skills, knowledge and trans-disciplinary collaborative abilities to influence policy making at the national and global level. Methods: The Bangalore Boston Nutrition Collaborative (BBNC) was established as collaboration between St. John’s Research Institute (SJRI), Harvard School of Public Health and Tufts University, with a focus on nutrition research and training. The goals of the BBNC were to conduct an interdisciplinary course, develop web-based courses and identify promising Indian students and junior faculty for graduate training in Boston. Results: From 2010, an annual two-week short course in nutrition research methods was conducted on the SJRI campus taught by international faculty from Indian and US universities. More than 100 students applied yearly for approximately 30 positions. The course had didactic lectures in the morning and practical hands-on sessions in the afternoon. Student rating of the course was excellent and consistent across the years. The ratings on the design and conduct of the course significantly improved (p <0.001) from 2010 to 2012. Through open-ended questions, students reported the main strengths of the course to be the excellent faculty and practical “hands-on” sessions. A web based learning system TYRO, was developed, which can be used for distance learning. Four faculty members/graduate students from SJRI have visited Boston for collaborative research efforts. Conclusion: The BBNC has become a well-established capacity building and research training program for young professionals in nutrition and global health. Efforts are ongoing to secure long term funding to sustain and expand this collaboration to deliver high quality nutrition and global health education enabled by information and communication technologies.

Immunization and nutritional interventions are mainstays of child health programs in sub-Saharan Africa, yet few published data exist on their interactions. HIV-exposed (but uninfected) infants enrolled in a randomized placebo-controlled trial of multivitamin supplements (vitamins B complex, C, and E) conducted in Tanzania were sampled for an assessment of measles IgG quantity and avidity at 15 to 18 months. Infants were vaccinated between 8.5 and 12 months of age, and all mothers received high-dose multivitamins as the standard of care. Of 201 HIV-exposed infants who were enrolled, 138 (68.7%) were seropositive for measles. There were no effects of infant multivitamin supplementation on measles seroconversion proportions, IgG concentrations, or IgG avidity (P > 0.05). The measles seroconversion proportion was greater for HIV-exposed infants vaccinated at 10 to 11 months of age than for those vaccinated at 8.5 to 10 months (P = 0.032) and greater for infants whose mothers had a CD4 T-cell count of <200 cells/μl than for infants whose mothers had a CD4 T-cell count of >350 cells/μl (P = 0.039). Stunted infants had a significantly decreased IgG quantity compared to nonstunted infants (P = 0.012). As for measles avidity, HIV-exposed infants vaccinated at 10 to 11 months had increased antibody avidity compared to those vaccinated at 8.5 to 10 months (P = 0.031). Maternal CD4 T-cell counts of <200 cells/μl were associated with decreased avidity compared to counts of >350 cells/μl (P = 0.047), as were lower infant height-for-age z-scores (P = 0.016). Supplementation with multivitamins containing B complex, C, and E does not appear to improve measles vaccine responses for HIV-exposed infants. Studies are needed to better characterize the impact of maternal HIV disease severity on the immune system development of HIV-exposed infants and the effect of malnutrition interventions on vaccine responses. (This study has been registered at ClinicalTrials.gov under registration no. NCT00197730.)

Objective To describe the burden of pediatric tuberculosis (TB) in a human immunodeficiency virus (HIV)-infected population and explore the demographic and clinical factors associated with the occurrence of pediatric TB. Design Longitudinal analysis of a cohort of HIV-infected children. Methods The endpoint of the study was clinically diagnosed TB. Cox proportional hazard regression was used to explore the predictors of incident TB among HIV-infected children under age 15 years after enrollment into the HIV program. Results The cohort comprised of 5040 children [median age: 5 years, interquartile range (IQR): 1–9 years]. During a median follow-up of 0.8 (IQR: 0.1–2.5) years, 376 out of 5040 children met the case definition for TB. The overall incidence of TB was 5.2/100 person-years. In multivariate analyses, older age at enrollment [relative risk (RR): 1.7, 95%, confidence interval (CI): 1.5–1.8], severe wasting (RR: 1.8, 95% CI: 1.3 –2.5), severe immune-suppression (RR: 2.6, 95% CI: 1.8–3.8), anemia (RR: 1.4, 95% CI: 1.0–1.9) and World Health Organization (WHO) stage IV (RR: 4.5, 95% CI: 2.4–8.5) were all independently associated with a higher risk of TB. In addition, the use of antiretroviral drugs for more than 180 days reduced the risk of TB by 70% (RR: 0.3, 95% CI: 0.2–0.4). Conclusions ART use is strongly associated with a reduced risk of tuberculosis among HIV-infected children, and should therefore be included in HIV care and treatment programs. Trials of interventions designed to improve the nutritional and hematologic status of these children should also be performed.

BACKGROUND: We assembled a prospective cohort of 3144 children less than 15 years of age initiating antiretroviral therapy (ART) in Dar es Salaam, Tanzania. METHODS: The relationships of nutritional status and other baseline characteristics in relation to mortality were examined using Cox proportional hazards model. RESULTS: Compared with children with weight for age (WAZ) > -1, those with WAZ ≤ -2 to < -3 had a nearly double risk of death (relative risk [RR], 1.85; 95% confidence interval [CI], 1.10-3.11), and among those with WAZ ≤ -3, the risk more than tripled (RR, 3.36; 95% CI, 2.12-5.32). Other baseline risk factors for overall mortality included severe anemia (P < .001), severe immune suppression (P = .02), history of tuberculosis (P = .01), opportunistic infections (P < .001), living in the poorest district (P < .001), and advanced World Health Organization stage (P = .003). CONCLUSIONS: To sustain the obtained benefit of ART in this setting, interventions to improve nutritional status may be used as an adjunct to ART.

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 <80fL), 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.

Objective: Investigate the effects of 12 months of dietary weight loss and/or aerobic exercise on leukocyte telomere length in postmenopausal women. Design and Methods 439 overweight or obese women (50–75 y) were randomized to: i) dietary weight loss (N=118); ii) aerobic exercise (N=117), iii) diet + exercise (N=117), or iv) control (N=87). The diet intervention was a group-based program with a 10% weight loss goal. The exercise intervention was 45 mins/day, 5 days/week of moderate-to-vigorous aerobic activity. Fasting blood samples were taken at baseline and 12 months. DNA was extracted from isolated leukocytes and telomere length was measured by quantitative-polymerase chain reaction (qPCR). Mean changes were compared between groups (intent-to-treat) using generalized estimating equations. Results: Baseline telomere length was inversely associated with age (r=−0.12 p<0.01) and positively associated with maximal oxygen uptake (r=0.11, p=0.03), but not with BMI or %body fat. Change in telomere length was inversely correlated with baseline telomere length (r=−0.47, p<0.0001). No significant difference in leukocyte telomere length was detected in any intervention group compared to controls, nor was the magnitude of weight loss associated with telomere length at 12 months. Conclusions: Twelve-months of dietary weight loss and exercise did not change telomere length in postmenopausal women.

Background: Bone mineral density (BMD) increases progressively during childhood and adolescence and is affected by various genetic and environmental factors. The aim of this study was to establish reference values for lumbar BMD in healthy Chinese infants and young children and investigate its influencing factors. Methods and Findings: Healthy children aged 0 to 3 years who underwent regular physical examinations at the Child Health Care Clinic of Hubei Maternal and Child Health Hospital (N = 11,898) were recruited for this study. We also chose 379 preterm infants aged 0 to 1 years to preliminarily explore the development of BMD in this special population. BMD (g/cm2) measurements of the lumbar spine (L2–L4) were carried out with dual-energy X-ray absorptiometry and a questionnaire was administered to full-term children's parents to gather information on various nutritional and lifestyle factors as well as mothers' nutritional supplement use during pregnancy. Lumbar BMD significantly increased with age among both boys and girls (p<0.05), with fastest growth observed during the first postnatal year. There was no significant difference in lumbar BMD between boys and girls of similar age (p>0.05), either among healthy reference children or preterm infants. However, BMD values in preterm infants were significantly lower than those in term infants 3 to 8 months old (p<0.05) after adjustment for gestational age. Multivariable linear regression analysis indicated significant positive associations between lumbar BMD of healthy children and the child's age and current weight, mother's weight gain during pregnancy, birth weight, children's outdoor activity duration and children's physical activity duration. Conclusion: Our study provides reference values of lumbar BMD for healthy Chinese children aged 0 to 3 years and identifies several influencing factors.

Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and women of African ancestry, and followed up the most significant associations in an additional 32,268 individuals of African ancestry. We identified one novel locus at 5q33 (GALNT10, rs7708584, p=3.4×10−11) and another at 7p15 when combined with data from the Giant consortium (MIR148A/NFE2L3, rs10261878, p=1.2×10−10). We also found suggestive evidence of an association at a third locus at 6q16 in the African ancestry sample (KLHL32, rs974417, p=6.9×10−8). Thirty-two of the 36 previously established BMI variants displayed directionally consistent effect estimates in our GWAS (binomial p=9.7×10−7), of which five reached genome-wide significance. These findings provide strong support for shared BMI loci across populations as well as for the utility of studying ancestrally diverse populations.

Introduction: Anaemia is prevalent among children born to HIV-positive women, and it is associated with adverse effects on cognitive and motor development, growth, and increased risks of morbidity and mortality. Objective: To examine the effect of daily multivitamin supplementation on haematologic status and mother-to-child transmission (MTCT) of HIV through breastfeeding. Methods: A total of 2387 infants born to HIV-positive women from Dar es Salaam, Tanzania were enrolled in a randomized, double-blind, placebo-controlled trial, and provided a daily oral supplement of multivitamins (vitamin B complex, C and E) or placebo at age 6 weeks for 24 months. Among them, 2008 infants provided blood samples and had haemoglobin concentrations measured at baseline and during a follow-up period. Anaemia was defined as haemoglobin concentrations<11 g/dL and severe anaemia<8.5 g/dL. Results: Haemoglobin concentrations among children in the treatment group were significantly higher than those in the placebo group at 12 (9.77 vs. 9.64 g/dL, p=0.03), 18 (9.76 vs. 9.57 g/dL, p=0.004), and 24 months (9.93 vs. 9.75 g/dL, p=0.02) of follow-up. Compared to those in the placebo group, children in the treatment group had a 12% lower risk of anaemia (hazard ratio (HR): 0.88; 95% CI: 0.79–0.99; p=0.03). The treatment was associated with a 28% reduced risk of severe anaemia among children born to women without anaemia (HR: 0.72; 95% CI: 0.56–0.92; p=0.008), but not among those born to women with anaemia (HR: 1.10; 95% CI: 0.79–1.54; p=0.57; p for interaction=0.007). One thousand seven hundred fifty three infants who tested HIV-negative at baseline and had HIV testing during follow-up were included in the analysis for MTCT of HIV. No association was found between multivitamin supplements and MTCT of HIV. Conclusions: Multivitamin supplements improve haematologic status among children born to HIV-positive women. Further trials focusing on anaemia among HIV-exposed children are warranted in the context of antiretroviral therapy.

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 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 including vitamin D) in Tanzania. Information on child morbidities, anemia and hypochromic microcytosis, and anthropometry was recorded through monthly clinic visits. Generalized estimated 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 (RR: 1.11; 95% 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 underweight (weight-for-age z-score <-2; RR: 1.33; 95% CI: 1.03-1.71). Conclusions Maternal vitamin D status may be an important risk factor for respiratory infections, and ensuring optimal growth in HIV-exposed children.

Prenatal iron supplementation may improve pregnancy outcomes and decrease the risk of child mortality. However, little is known about the importance of postnatal maternal iron status for child health and survival, particularly in the context of HIV infection. We examined the association of maternal anemia 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 anemia 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 anemia and hypochromic microcytosis were associated with greater risk of child mortality (HR for severe anemia=2.58, 95% 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 anemia was not significantly associated with greater risk of child HIV infection (HR for severe anemia=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 anemia:-93, 95% CI: -204-17, P trend=0.02). The potential child health risks associated with maternal anemia and iron deficiency may not be limited to the prenatal period. Efforts to reduce maternal anemia and iron deficiency during pregnancy may need to be expanded to include the postpartum period.

Background: Children born to HIV-infected women are susceptible to undernutrition, but modifiable risk factors and the time course of the development of undernutrition have not been well characterized. Objective: To identify maternal, socioeconomic, and child characteristics that are associated with stunting, wasting, and underweight among Tanzanian children born to HIV-infected mothers, followed from 6 weeks for 24 months. Methods: Maternal and socioeconomic characteristics were recorded during pregnancy, data pertaining to the infant’s birth were collected immediately after delivery, morbidity histories and anthropometric measurements were performed monthly. Multivariate Cox proportional hazards methods were used to assess the association between potential predictors and the time to first episode of stunting, wasting, and underweight. Results: 2387 infants (54.0% male) were enrolled and followed for a median duration of 21.2 months. The respective prevalence of prematurity (<37 weeks) and low birthweight (<2500g) was 15.2% and 7.0%; 11.3% of infants were HIV-positive at 6 weeks. Median time to first episode of stunting, wasting, and underweight was 8.7, 7.2, and 7.0 months, respectively. Low maternal education, few household possessions, low infant birthweight, child HIV infection and male sex were all independent predictors of stunting, wasting, and underweight. In addition, preterm infants were more likely to become wasted and underweight, whereas those with a low Apgar score at birth were more likely to become stunted. Conclusion: Interventions to improve maternal education and nutritional status, reduce mother-to-child transmission of HIV, and increase birth weight may lower the risk of undernutrition among children born to HIV-infected women.

Genome-wide association studies (GWAS) have successfully identified a number of single-nucleotide polymorphisms (SNPs) associated with colorectal cancer (CRC) risk. However, these susceptibility loci known today explain only a small fraction of the genetic risk. Gene-gene interaction (GxG) is considered to be one source of the missing heritability. To address this, we performed a genome-wide search for pair-wise GxG associated with CRC risk using 8,380 cases and 10,558 controls in the discovery phase and 2,527 cases and 2,658 controls in the replication phase. We developed a simple, but powerful method for testing interaction, which we term the Average Risk Due to Interaction (ARDI). With this method, we conducted a genome-wide search to identify SNPs showing evidence for GxG with previously identified CRC susceptibility loci from 14 independent regions. We also conducted a genome-wide search for GxG using the marginal association screening and examining interaction among SNPs that pass the screening threshold (p<\(10^{−4}\)). For the known locus rs10795668 (10p14), we found an interacting SNP rs367615 (5q21) with replication p = 0.01 and combined p = 4.19×\(10^{−8}\). Among the top marginal SNPs after LD pruning (n = 163), we identified an interaction between rs1571218 (20p12.3) and rs10879357 (12q21.1) (nominal combined p = 2.51×\(10^{−6}\); Bonferroni adjusted p = 0.03). Our study represents the first comprehensive search for GxG in CRC, and our results may provide new insight into the genetic etiology of CRC.

Meta-analyses of European populations has successfully identified genetic variants in over 100 loci associated with lipid levels, but our knowledge in other ethnicities remains limited. To address this, we performed dense genotyping of ∼2,000 candidate genes in 7,657 African Americans, 1,315 Hispanics and 841 East Asians, using the IBC array, a custom ∼50,000 SNP genotyping array. Meta-analyses confirmed 16 lipid loci previously established in European populations at genome-wide significance level, and found multiple independent association signals within these lipid loci. Initial discovery and in silico follow-up in 7,000 additional African American samples, confirmed two novel loci: rs5030359 within ICAM1 is associated with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) \((p = 8.8×10^{−7} and p = 1.5×10^{−6}\) respectively) and a nonsense mutation rs3211938 within CD36 is associated with high-density lipoprotein cholesterol (HDL-C) levels \((p = 13.5×10^{−12})\). The rs3211938-G allele, which is nearly absent in European and Asian populations, has been previously found to be associated with CD36 deficiency and shows a signature of selection in Africans and African Americans. Finally, we have evaluated the effect of SNPs established in European populations on lipid levels in multi-ethnic populations and show that most known lipid association signals span across ethnicities. However, differences between populations, especially differences in allele frequency, can be leveraged to identify novel signals, as shown by the discovery of ICAM1 and CD36 in the current report.

Bone mineral density (BMD) is the most important predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and East Asian ancestry. We tested the top-associated BMD markers for replication in 50,933 independent subjects and for risk of low-trauma fracture in 31,016 cases and 102,444 controls. We identified 56 loci (32 novel)associated with BMD atgenome-wide significant level (P<5×10−8). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal-stem-cell differentiation, endochondral ossification and the Wnt signalling pathways. However, we also discovered loci containing genes not known to play a role in bone biology. Fourteen BMD loci were also associated with fracture risk (P<5×10−4, Bonferroni corrected), of which six reached P<5×10−8 including: 18p11.21 (C18orf19), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.

Background: Experimental data suggest a role for iron in the course of tuberculosis (TB) infection, but there is limited evidence on the potential effects of iron deficiency or iron overload on the progression of TB disease in humans. The aim of the present analysis was to examine the association of iron status with the risk of TB progression and death. Methodology/Principal Findings: We analyzed plasma samples and data collected as part a randomized micronutrient supplementation trial (not including iron) among HIV-infected and HIV-uninfected TB patients in Dar es Salaam, Tanzania. We prospectively related baseline plasma ferritin concentrations from 705 subjects (362 HIV-infected and 343 HIV-uninfected) to the risk of treatment failure at one month after initiation, TB recurrence and death using binomial and Cox regression analyses. Overall, low (plasma ferritin<30 \(\mu\)g/L) and high (plasma ferritin>150 \(\mu\)g/L for women and>200 \(\mu\)g/L for men) iron status were seen in 9% and 48% of patients, respectively. Compared with normal levels, low plasma ferritin predicted an independent increased risk of treatment failure overall (adjusted RR = 1.95, 95% CI: 1.07 to 3.52) and of TB recurrence among HIV-infected patients (adjusted RR = 4.21, 95% CI: 1.22 to 14.55). High plasma ferritin, independent of C-reactive protein concentrations, was associated with an increased risk of overall mortality (adjusted RR = 3.02, 95% CI: 1.95 to 4.67). Conclusions/Significance: Both iron deficiency and overload exist in TB patients and may contribute to disease progression and poor clinical outcomes. Strategies to maintain normal iron status in TB patients could be helpful to reduce TB morbidity and mortality.

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.

Objective We examined the relationships between exclusive breast-feeding and the risks of respiratory, diarrhoea and nutritional morbidities during the first 2 years of life among children born to women infected with HIV-1. Design We prospectively determined the incidence of respiratory illnesses, diarrhoea, fever, hospitalizations, outpatient visits and nutritional morbidities. Generalized estimating equations were used to estimate the relative risks for morbidity episodes and Cox proportional hazards models to estimate the incidence rate ratios of nutritional morbidities. Setting Dar es Salaam, Tanzania. Subjects The sample consisted of 666 children born to HIV-infected women. Results The 666 children were followed for 2 years. Exclusive breast-feeding was associated with lower risk for cough (rate ratio (RR) = 0·49, 95 % CI 0·41, 0·60, P < 0·0001), cough and fever (RR = 0·44, 95 % CI 0·32, 0·60, P < 0·0001) and cough and difficulty breathing or refusal to feed (RR = 0·31, 95 % CI 0·18, 0·55, P < 0·0001). Exclusive breast-feeding was also associated with lower risk of acute diarrhoea, watery diarrhoea, dysentery, fever and outpatient visits during the first 6 months of life, but showed no effect at 6–24 months of life. Exclusive breast-feeding did not significantly reduce the risks of nutritional morbidities during the first 2 years of life. Conclusions Exclusive breast-feeding is strongly associated with reductions in the risk of respiratory and diarrhoea morbidities during the first 6 months of life among children born to HIV-infected women.

This paper examines predictors of breastfeeding cessation among a cohort of human immunodeficiency virus (HIV)-infected women. This was a prospective follow-up study of HIV-infected women who participated in a randomized micronutrient supplementation trial conducted in Dar es Salaam, Tanzania. 795 HIV-infected Tanzanian women with singleton newborns were utilized from the cohort for this analysis. The proportion of women breastfeeding declined from 95% at 12 months to 11% at 24 months. The multivariate analysis showed breastfeeding cessation was significantly associated with increasing calendar year of delivery from 1995 to 1997 [risk ratio (RR), 1.36; 95% confidence interval (CI) 1.13–1.63], having a new pregnancy (RR 1.33; 95% CI 1.10–1.61), overweight [body mass index (BMI) ≥25 kg m−2; RR 1.37; 95% CI 1.07–1.75], underweight (BMI <18.5 kg m−2; RR 1.29; 95% CI 1.00–1.65), introduction of cow’s milk at infant’s age of 4 months (RR 1.30; 95% CI 1.04–1.63). Material and social support was associated with decreased likelihood of cessation (RR 0.83; 95% CI 0.68–1.02). Demographic, health and nutritional factors among women and infants are associated with decisions by HIV-infected women to cease breastfeeding. The impact of breastfeeding counselling programs for HIV-infected African women should consider individual maternal, social and health contexts.

HIV infection can contribute to disturbances in both linear growth and weight gain in early childhood, with disturbances often apparent as early as 3 mo of age. There is little evidence for a difference in the early growth of HIV-exposed but uninfected children compared to healthy controls. Owing to the close association of growth with immune function and clinical progression, an understanding of growth patterns may be an important tool to ensure the provision of appropriate care to HIV-infected and exposed children. Timely growth monitoring may be used to improve the clinical course and quality of life of these children.