Lindsey M. Locks

The prevalence of anemia and iron deficiency is more common in breastfed infants than their mothers in Bhaktapur, Nepal

Background/Objectives:Iron deficiency anemia is a widespread public health problem, particularly in low- and middle-income countries. Maternal iron status around and during pregnancy may influence infant iron status. We examined multiple biomarkers to determine the prevalence of iron deficiency and anemia among breastfed infants and explored its relationship with maternal and infant characteristics in Bhaktapur, Nepal.Subjects/Methods:In a cross-sectional survey, we randomly selected 500 mother–infant pairs from Bhaktapur municipality. Blood was analyzed for hemoglobin, ferritin, total iron-binding capacity, transferrin receptors and C-reactive protein.Results:The altitude-adjusted prevalence of anemia was 49% among infants 2–6-month-old (hemaglobin (Hb) <10.8 g/dl) and 72% among infants 7–12-month-old (Hb <11.3 g/dl). Iron deficiency anemia, defined as anemia and serum ferritin <20 or <12 μg/l, affected 9 and 26% of infants of these same age groups. Twenty percent of mothers had anemia (Hb <12.3 g/dl), but only one-fifth was explained by depletion of iron stores. Significant predictors of infant iron status and anemia were infant age, sex and duration of exclusive breastfeeding and maternal ferritin concentrations.Conclusions:Our findings suggest that iron supplementation in pregnancy is likely to have resulted in a low prevalence of postpartum anemia. The higher prevalence of anemia and iron deficiency among breastfed infants compared with their mothers suggests calls for intervention targeting newborns and infants.

Iron deficiency is uncommon among lactating women in urban Nepal, despite a high risk of inadequate dietary iron intake

The main objective of the present study was to examine the association between dietary Fe intake and dietary predictors of Fe status and Hb concentration among lactating women in Bhaktapur, Nepal. We included 500 randomly selected lactating women in a cross-sectional survey. Dietary information was obtained through three interactive 24 h recall interviews including personal recipes. Concentrations of Hb and plasma ferritin and soluble transferrin receptors were measured. The daily median Fe intake from food was 17·5 mg, and 70% of the women were found to be at the risk of inadequate dietary Fe intake. Approximately 90% of the women had taken Fe supplements in pregnancy. The prevalence of anaemia was 20% (Hb levels < 123 g/l) and that of Fe deficiency was 5% (plasma ferritin levels < 15 μg/l). In multiple regression analyses, there was a weak positive association between dietary Fe intake and body Fe (β 0·03, 95% CI 0·014, 0·045). Among the women with children aged < 6 months, but not those with older infants, intake of Fe supplements in pregnancy for at least 6 months was positively associated with body Fe (P for interaction < 0·01). Due to a relatively high dietary intake of non-haem Fe combined with low bioavailability, a high proportion of the women in the present study were at the risk of inadequate intake of Fe. The low prevalence of anaemia and Fe deficiency may be explained by the majority of the women consuming Fe supplements in pregnancy.

Effect of zinc and multivitamin supplementation on the growth of Tanzanian children aged 6–84 wk: a randomized, placebo-controlled, double-blind trial

BACKGROUND Poor child growth increases risks of mortality and morbidity. Micronutrient supplements have the potential to improve child growth. OBJECTIVE We assessed the effect of daily zinc, multivitamin (vitamins C, E, and B-complex), and zinc and multivitamin (Zn+MV) supplementation on growth in infants in Tanzania. DESIGN In this randomized, 2 × 2 factorial, double-blind trial, 2400 infants were randomly assigned to receive zinc, multivitamins, Zn+MVs, or a placebo at 6 wk of age and were followed up for 18 mo with monthly growth measurements. Mixed-effects models with restricted cubic splines for the mean change in anthropometric z scores were fit for each group. Likelihood ratio tests were used to compare the effect of supplements on growth trajectories. Cox proportional hazards models were used to compare incidences of stunting, wasting, and underweight. RESULTS Children in all groups experienced growth faltering. At 19 mo of age, prevalences of stunting, wasting, and underweight were 19.8%, 6.0%, and 10.8%, respectively. Changes in weight-for-age z scores (WAZs) and weight-for-height z scores (WHZs) were significantly different across the 4 groups (P < 0.001 for both). The mean ± SE decline in the WAZ from baseline to the end of follow-up in the Zn+MV group was significantly less than in the placebo group (-0.36 ± 0.04 compared with -0.50 ± 0.04; P = 0.020), whereas the decline in the WHZ was significantly greater in the zinc-only group than in the placebo group (-0.57 ± 0.07 compared with -0.35 ± 0.07; P = 0.021). Supplements did not have a significant effect on mean change in the height-for-age z score or on rates of stunting, wasting, or underweight. CONCLUSIONS Although there were small but significant improvements in the WAZ in the Zn+MV group, daily zinc supplementation alone, multivitamin supplementation alone, and the combined Zn+MV did not reduce the incidences of underweight, stunting, or wasting in Tanzanian infants. Alternative approaches to prevent growth faltering should be pursued. This trial was registered at clinicaltrials.gov as NCT00421668.

High Burden of Morbidity and Mortality but Not Growth Failure in Infants Exposed to but Uninfected with Human Immunodeficiency Virus in Tanzania.

Objective To compare health and growth outcomes in children infected with HIV, children exposed to but uninfected with HIV, and children unexposed to HIV. Study design Our cohort included 3554 Tanzanian children enrolled in 2 trials of micronutrient supplementation. Among infants born to mothers infected with HIV, 264 were infected with HIV and 2088 were exposed to but uninfected at 6 weeks of age. An additional 1202 infants were unexposed to HIV. Infants were followed until 18 months of age, death, or loss to follow‐up. Morbidity and growth were assessed at monthly nurse visits. Results Compared with unexposed infants, hazard ratios (95% CI) for all‐cause mortality in infants infected with HIV and infants who were exposed to but uninfected with HIV were 28.99 (14.83‐56.66) and 2.79 (1.41‐5.53), respectively, after adjusting for demographic and nutritional covariates. Compared with infants unexposed to HIV, infants infected with HIV also had a significantly greater risk of all measured morbidities, while infants who were exposed to but uninfected with HIV were significantly more likely to suffer from cough, fever, unscheduled outpatient visits, and hospitalizations. Infants infected with HIV also were more likely to experience stunting, wasting, and underweight at baseline and during follow‐up. Infants exposed to but uninfected with HIV were more likely to be underweight at baseline (adjusted relative risk, 2.05; 95% CI, 1.45‐2.89), but on average, experienced slower declines in height‐for‐age z‐score, weight‐for‐age z‐score, and weight‐for‐height z‐score as well as a lower rate of stunting over follow‐up, compared with unexposed infants. Conclusion In addition to preventing and treating HIV infection in infants, prevention‐of‐mother‐to‐child‐transmission of HIV and child health services should also target children exposed to but uninfected with HIV to improve health outcomes in this vulnerable population. Trial registration Clinicaltrials.gov: NCT00197730 and NCT00421668.

The Impact of Integrated Infant and Young Child Feeding and Micronutrient Powder Intervention on Feeding Practices and Anemia in Children Aged 6–23 Months in Madagascar

This study assesses the impact of an integrated infant and young child feeding (IYCF) and micronutrient powder (MNP) intervention on children’s risk of anemia and IYCF practices in Madagascar. Quantitative baseline and endline surveys were conducted in representative households with children 6–23 months from two districts, where an 18-month IYCF-MNP intervention was implemented. Relative risks comparing children’s risk of anemia and maternal IYCF knowledge and practices at baseline versus endline, and also at endline among MNP-users versus non-users were estimated using log-binomial regression models. 372 and 475 children aged 6–23 months were assessed at baseline and endline respectively. Prevalence of anemia fell from 75.3% to 64.9% from baseline to endline (p = 0.002); the reduction in the risk of anemia remained significant in models adjusting for sociodemographic characteristics (ARR (95% CI): 0.86 (0.78, 0.95), p = 0.003). In endline assessments, 229 out of 474 (48.3%) of children had consumed MNPs. MNP-users had a lower risk of anemia (ARR (95% CI): 0.86 (0.74, 0.99), p = 0.04) than non-users, after controlling for child’s dietary diversity and morbidity, maternal counseling by community-health-workers, and sociodemographic characteristics. Mothers interviewed at endline also had greater nutrition knowledge and were more likely to feed their children ≥4 food groups (ARR (95% CI): 2.92 (2.24, 3.80), p < 0.001), and the minimum acceptable diet (ARR (95% CI): 2.88 (2.17, 3.82), p < 0.001) than mothers interviewed at baseline. Integration of MNP into IYCF interventions is a viable strategy for improving children’s consumption of micronutrients and reducing risk of anemia. The addition of MNP does not negatively impact, and may improve, IYCF practices.

Delayed Breastfeeding Initiation Is Associated with Infant Morbidity

Objective To assess the relationship between breastfeeding initiation time and postneonatal mortality, morbidity, and growth through 24 months in a cohort of Tanzanian infants. Study design We included 4203 infants from 2 trials of micronutrient supplementation. We used Cox proportional hazards models or general estimating equations to estimate relative risks. Results A total of 13% of infants initiated breastfeeding >1 hour after birth (n = 536). There was no association between breastfeeding initiation time and risk of all‐cause or cause‐specific mortality, nor infant growth failure, from 6 weeks to 2 years of age. However, delayed breastfeeding was associated with an increased risk of several common infectious morbidities in early infancy, including upper respiratory infection symptoms and vomiting. Compared with those who initiated breastfeeding within the first hour of birth, delayed breastfeeding initiation was associated with an 11% increased risk of cough (relative risk 1.11, 95% CI 1.02–1.21) and a 48% increased risk of difficulty breathing (relative risk 1.48, 95% CI 1.09–2.01) during the first 6 months. Delayed initiation was associated with a greater risk of difficulty breathing from 6 to 12 months of age, but it was not associated with risk of any other morbidity during this time, nor any morbidity between 12 and 24 months. Conclusion Delayed breastfeeding initiation is associated with an increased risk of infant morbidity during the first 6 months of life. Early breastfeeding initiation, along with exclusive and prolonged breastfeeding, should be prioritized and promoted in efforts to improve child health.

The effect of daily zinc and/or multivitamin supplements on early childhood development in Tanzania: results from a randomized controlled trial.

Abstract Impaired childhood development has lifelong consequences for educational attainment and wage‐earning potential. Micronutrient supplements have the potential to improve development. The objective of this study was to determine the effect of daily zinc and/or multivitamin (vitamins C, E and B‐complex) supplements on development among Tanzanian infants. In this randomized, 2 × 2 factorial, double‐blind trial, 2400 infants were randomized to zinc (Zn), multivitamins (MV), zinc and multivitamins (Zn + MV) or placebo at 6 weeks of age. At approximately 15 months, a sub‐sample of 247 children underwent developmental assessment using the cognitive, language (receptive and expressive) and motor (fine and gross) scales of the Bayley Scales of Infant and Toddler Development Third Edition (BSID‐III). Mean BSID‐III scores were compared using univariate and multivariate linear regression models adjusted for childs sex, post‐conceptual age and test administrator. Logistic regressions were used to assess odds of low developmental scores. We did not detect a significant difference in mean BSID‐III scores in any of the five domains in univariate or multivariate models comparing each of the four treatment groups. We also did not detect a significant difference in mean BSID‐III scores when comparing children who received zinc supplements versus those who did not, or in comparisons of children who received multivitamin supplements versus those who did not. There was no significant difference in odds of a low BSID‐III score in any of the five domains in treatment arms either. Because neither daily zinc nor multivitamin (vitamins B‐complex, C and E) supplementation led to improvements in any of the developmental domains assessed using the BSID‐III, we recommend pursuing alternative interventions to promote early childhood development in vulnerable populations.

Biomarkers of Systemic Inflammation and Growth in Early Infancy are Associated with Stunting in Young Tanzanian Children

Stunting can afflict up to one-third of children in resource-constrained countries. We hypothesized that low-grade systemic inflammation (defined as elevations in serum C-reactive protein or alpha-1-acid glycoprotein) in infancy suppresses the growth hormone–insulin-like growth factor (IGF) axis and is associated with subsequent stunting. Blood samples of 590 children from periurban Dar es Salaam, Tanzania, were obtained at 6 weeks and 6 months of age as part of a randomized controlled trial. Primary outcomes were stunting, underweight, and wasting (defined as length-for-age, weight-for-age and weight-for-length z-scores < −2) between randomization and endline (18 months after randomization). Cox proportional hazards models were constructed to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of time to first stunting, underweight, and wasting as outcomes, with measures of systemic inflammation, insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) as exposures, adjusting for numerous demographic and clinical variables. The incidences of subsequent stunting, underweight, and wasting were 26%, 20%, and 18%, respectively. In multivariate analyses, systemic inflammation at 6 weeks of age was significantly associated with stunting (HR: 2.14, 95% CI: 1.23, 3.72; p = 0.002). Children with higher levels of IGF-1 at 6 weeks were less likely to become stunted (HR: 0.58, 95% CI: 0.37, 0.93; p for trend = 0.019); a similar trend was noted in children with higher levels of IGF-1 at 6 months of age (HR: 0.50, 95% CI: 0.22, 1.12; p for trend = 0.07). Systemic inflammation occurs as early as 6 weeks of age and is associated with the risk of future stunting among Tanzanian children.

Infant Nutritional Status and Markers of Environmental Enteric Dysfunction are Associated with Midchildhood Anthropometry and Blood Pressure in Tanzania

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 lengthfor‐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.