While prenatal Fe supplementation prevents maternal Fe deficiency and anaemia, it is uncertain whether it improves infant health outcomes, at least when taken by Fe-replete women. Inflammation as ...well as physiological changes complicates the assessment of Fe status during pregnancy. In the present study, we measured the concentrations of serum ferritin and soluble transferrin receptors (sTfR), Hb and the acute-phase proteins C-reactive protein (CRP) and α1-antichymotrypsin (ACT) in a cross-sectional study among 738 pregnant women attending antenatal care in Guinea-Bissau, West Africa. Multiple linear regression analysis was used to identify the predictors of Fe status markers. The mean gestational age was 23 (sd 7) weeks. Serum ferritin values were lower with progressing gestation, from 27% lower during weeks 16-20 of gestation up to 59% lower after 29 weeks of gestation compared with early pregnancy. Using cut-off values for Fe deficiency as established in non-pregnant individuals, 52% of the women had sTfR levels >2·3 mg/l, while only 25% had serum ferritin levels 2·3 mg/l decreased to 47% after adjustment for elevated serum CRP and ACT levels. On the contrary, the proportion of serum ferritin < 12 μg/l increased to 33% after adjustment for ACT and CRP. The high proportion of elevated serum sTfR calls for pregnancy-specific cut-offs since increased erythropoiesis is expected in response to increased plasma volume of pregnancy. The present study further underlines the need to adjust for inflammation when serum sTfR and serum ferritin are used to assess Fe status in pregnancy.
Biomarkers of iron status are affected by inflammation. In order to interpret them in individuals with inflammation, the use of correction factors (CFs) has been proposed.
The objective of this study ...was to investigate the use of regression models as an alternative to the CF approach.
Morbidity data were collected during clinical examinations with morbidity recalls in a cross-sectional study in children aged 6-23 mo with moderate acute malnutrition. C-reactive protein (CRP), α
-acid glycoprotein (AGP), serum ferritin (SF), and soluble transferrin receptor (sTfR) were measured in serum. Generalized additive, quadratic, and linear models were used to model the relation between SF and sTfR as outcomes and CRP and AGP as categorical variables (model 1; equivalent to the CF approach), CRP and AGP as continuous variables (model 2), or CRP and AGP as continuous variables and morbidity covariates (model 3) as predictors. The predictive performance of the models was compared with the use of 10-fold crossvalidation and quantified with the use of root mean square errors (RMSEs). SF and sTfR were adjusted with the use of regression coefficients from linear models.
Crossvalidation revealed no advantage to using generalized additive or quadratic models over linear models in terms of the RMSE. Linear model 3 performed better than models 2 and 1. Furthermore, we found no difference in CFs for adjusting SF and those from a previous meta-analysis. Adjustment of SF and sTfR with the use of the best-performing model led to a 17% point increase and <1% point decrease, respectively, in estimated prevalence of iron deficiency.
Regression analysis is an alternative to adjust SF and may be preferable in research settings, because it can take morbidity and severity of inflammation into account. In clinical settings, the CF approach may be more practical. There is no benefit from adjusting sTfR. This trial was registered at www.controlled-trials.com as ISRCTN42569496.
Accelerated growth in early childhood is an established risk factor for later obesity and cardiometabolic disease, but the relative importance of fat mass (FM) and fat-free mass (FFM) accretion is ...not well understood. We aimed to study how FM and FFM at birth and their accretion during infancy were associated with body composition and cardiometabolic risk markers at 5 years.
Healthy children born at term were enrolled in the Infant Anthropometry and Body Composition (iABC) birth cohort between December 2008 and October 2012 at Jimma University Specialized Hospital in the city of Jimma, Ethiopia. FM and FFM were assessed using air displacement plethysmography a median of 6 times between birth and 6 months of age. In 507 children, we estimated individual FM and FFM at birth and their accretion over 0-3 and 3-6 months of age using linear-spline mixed-effects modelling. We analysed associations of FM and FFM at birth and their accretion in infancy with height, waist circumference, FM, FFM, and cardiometabolic risk markers at 5 years using multiple linear regression analysis. A total of 340 children were studied at the 5-year follow-up (mean age: 60.0 months; girls: 50.3%; mean wealth index: 45.5 out of 100; breastfeeding status at 4.5 to 6 months post-partum: 12.5% exclusive, 21.4% almost exclusive, 60.6% predominant, 5.5% partial/none). Higher FM accretion in infancy was associated with higher FM and waist circumference at 5 years. For instance, 100-g/month higher FM accretion in the periods 0-3 and 3-6 months was associated with 339 g (95% CI: 243-435 g, p < 0.001) and 367 g (95% CI: 250-484 g, p < 0.001) greater FM at 5 years, respectively. Higher FM at birth and FM accretion from 0 to 3 months were associated with higher FFM and cholesterol concentrations at 5 years. Associations for cholesterol were strongest for low-density lipoprotein (LDL)-cholesterol, and remained significant after adjusting for current FM. A 100-g higher FM at birth and 100-g/month higher FM accretion from 0 to 3 months were associated with 0.16 mmol/l (95% CI: 0.05-0.26 mmol/l, p = 0.005) and 0.06 mmol/l (95% CI: 0.01-0.12 mmol/l, p = 0.016) higher LDL-cholesterol at 5 years, respectively. Higher FFM at birth and FFM accretion in infancy were associated with higher FM, FFM, waist circumference, and height at 5 years. For instance, 100-g/month higher FFM accretion in the periods 0-3 and 3-6 months was associated with 1,002 g (95% CI: 815-1,189 g, p < 0.001) and 624 g (95% CI: 419-829 g, p < 0.001) greater FFM at 5 years, respectively. We found no associations of FM and FFM growth with any of the other studied cardiometabolic markers including glucose, HbA1c, insulin, C-peptide, HOMA-IR, triglycerides, and blood pressure. Non-attendance at the 5-year follow-up visit was the main limitation of this study, which may have introduced selection bias and limited the power of the regression analyses.
FM accretion in early life was positively associated with markers of adiposity and lipid metabolism, but not with blood pressure and cardiometabolic markers related to glucose homeostasis. FFM accretion was primarily related to linear growth and FFM at 5 years.
Vitamin A deficiencies in pregnancy may impair the health of the mother and the growth, development, and later health of her offspring. However, the understanding of the variability of micronutrient ...status markers during pregnancy is limited. We measured serum retinol and β-carotene and the acute phase proteins C-reactive protein (CRP) and α(1)-antichymotrypsin (ACT) in 738 pregnant women in a cross-sectional study in Guinea-Bissau, West Africa. Gestational age ranged from 7 to 42 wk (mean ± SD = 23 ± 7 wk). The serum retinol concentration was 1.03 ± 0.33 μmol/L (mean ± SD) whereas serum β-carotene was 1.40 (0.85, 2.13) μmol/L median (25, 75 percentile). Vitamin A deficiency (serum retinol <0.70 μmol/L) was observed in 13.8% of individuals. Serum CRP was elevated (>3 mg/L) in 51.6% of individuals and ACT (>0.3 g/L) in 66.3%. Gestational age >20 wk (β = -0.11; P < 0.001) as well as elevated serum CRP (β = -0.16; P < 0.001) and ACT (β = -0.80; P = 0.004) were associated with lower serum retinol. Based on this large cross-sectional study, we suggest that serum retinol and its conventional cutoff may be underestimating the vitamin A status in late pregnancy and in populations with high prevalence of infections. However, prospective cohort studies measuring the serum concentration of retinol during and after pregnancy and inflammation are needed to describe the physiological behavior of serum retinol and thereby to improve the assessment of vitamin A status.
Both impaired and accelerated postnatal growth have been associated with adult risks of obesity and cardiometabolic diseases, like type 2 diabetes and cardiovascular disease. However, the timing of ...the onset of cardiometabolic changes and the specific growth trajectories linking early growth with later disease risks are not well understood.
The aim of this study was to identify distinct trajectories of BMI growth from 0 to 5 y and examine their associations with body composition and markers of cardiometabolic risk at age 5 y.
In a prospective birth cohort study of 453 healthy and term Ethiopian children with BMIs assessed a median of 9 times during follow-up, we identified subgroups of distinct BMI trajectories in early childhood using latent class trajectory modeling. Associations of the identified growth trajectories with cardiometabolic markers and body composition at 5 y were analyzed using multiple linear regression analyses in 4 adjustment models for each outcome.
We identified 4 heterogeneous BMI growth trajectories: stable low BMI (19.2%), normal BMI (48.8%), rapid catch-up to high BMI (17.9%), and slow catch-up to high BMI (14.1%). Compared with the normal BMI trajectory, children in the rapid catch-up to high BMI trajectory had higher triglycerides (TGs) (range of β-coefficients in Models 1–4: 19–21%), C-peptides (23–25%), fat masses (0.48–0.60 kg), and fat-free masses (0.50–0.77 kg) across the 4 adjustment models. Children in the stable low BMI trajectory had lower LDL cholesterol concentrations (0.14–0.17 mmol/L), HDL cholesterol concentrations (0.05–0.09 mmol/L), fat masses (0.60–0.64 kg), and fat-free masses (0.35–0.49 kg), but higher TGs (11–13%).
The development of obesity and cardiometabolic risks may be established already in early childhood; thus, our data provide a further basis for timely interventions targeted at young children from low-income countries with unfavorable growth patterns. The birth cohort was registered at ISRCTN as ISRCTN46718296.
Improving the quality of people's diets represents a major challenge for developing countries, particularly in Sahelian African countries. Foods from trees, shrubs, and palms are present in many ...meals and may improve dietary quality, especially for rural communities but, as their contributions have rarely been quantified, investigating the link between the intake of tree foods and the nutritional composition of diet is important. This study assesses the contribution of tree and palm foods to dietary intake in three rural communities in Senegal, using three household food consumption surveys to quantify the dietary intake of meals. The consumption of tree and palm foods in meals was frequent, mentioned by 93-99% of the families depending on the time of year. Products of 11 tree and palm species were used in meals, with Adansonia digitata (baobab) leaves the most frequently mentioned. The energy contribution of tree and palm foods was low, but their contribution of certain micronutrients was high, with 56% of the daily household food consumption of vitamin A, 45% of vitamin C, 17% of vitamin B6 and 21% of iron (Fe). Products from 18 tree and palm species were consumed as snacks or beverages between meals, and consumption was frequent in February and June, but rare in October. We discuss the possibilities of improving nutrition in rural communities from an increased use of trees and palms.
(1) Background: Breastfeeding (BF) has been shown to lower the risk of overweight and cardiometabolic disease later in life. However, evidence from low-income settings remains sparse. We examined the ...associations of BF status at 6 months with anthropometry, body composition (BC), and cardiometabolic markers at 5 years in Ethiopian children. (2) Methods: Mother–child pairs from the iABC birth cohort were categorised into four BF groups at 6 months: 1. “Exclusive”, 2. “Almost exclusive”, 3. “Predominantly” and 4. “Partial or none”. The associations of BF status with anthropometry, BC, and cardiometabolic markers at 5 years were examined using multiple linear regression analyses in three adjustment models. (3) Results: A total of 306 mother–child pairs were included. Compared with “Exclusive”, the nonexclusive BF practices were associated with a lower BMI, blood pressure, and HDL-cholesterol at 5 years. Compared with “Exclusive”, “Predominantly” and “Almost exclusive” had shorter stature of −1.7 cm (−3.3, −0.2) and −1.2 cm (−2.9, 0.5) and a lower fat-free mass index of −0.36 kg/m2 (−0.71, −0.005) and −0.38 kg/m2 (−0.76, 0.007), respectively, but a similar fat mass index. Compared with “Exclusive”, “Predominantly” had higher insulin of 53% (2.01, 130.49), “Almost exclusive” had lower total and LDL-cholesterol, and “Partial or none” had a lower fat mass index. (5) Conclusions: Our data suggest that children exclusively breastfed at 6 months of age are overall larger at 5 years, with greater stature, higher fat-free mass but similar fat mass, higher HDL-cholesterol and blood pressure, and lower insulin concentrations compared with predominantly breastfed children. Long-term studies of the associations between BF and metabolic health are needed to inform policies.
Severe acute malnutrition has two main clinical manifestations, i.e., oedematous and non-oedematous. However, factors associated with oedema are not well established.
Children 0.5-14 years of age ...with SAM (MUAC < 11.0 cm or weight-for-height < 70 % of median and/or nutritional oedema) admitted to the nutrition unit were included. Information on infections before and during admission was collected together with anthropometry. Predictors of oedema was analysed separately for younger (< 60 months) and older children (≥ 60 months).
351 children were recruited (median age: 36 months (interquartile range 24 to 60); 43.3% females). Oedema was detected in 61.1%. The prevalence of oedema increased with age, peaked at 37-59 months (75%) and declined thereafter. Infection was more common in the younger group (33% vs. 8.9%, p < 0.001) and in this group children with oedema had less infections (25.2% vs. 45.1%, p = 0.001). In the older group the prevalence of infections was not different between oedematous and non-oedematous children (5.5% v. 14.3%, p = 0.17). In the younger group oedema was less common in children with TB (OR = 0.20, 95% CI: 0.06, 0.70) or diarrhea (OR = 0.40, 95% CI: 0.21, 0.73).
The proportion of oedema in SAM peaked at three to five years of age and a considerable proportion was above 5 years. Furthermore, the prevalence of infection seemed to be lower among children with oedema. Further studies are needed to better understand the role of infection-immunity interaction.
Glomerular filtration rate estimating equations using serum creatinine are not validated in most African settings. We compared serum creatinine and estimated glomerular filtration rate (eGFR) in HIV ...positive and negative adults and assessed the performance of eGFR equations ((Cockcroft and Gault (CG), Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)) compared to 24-hour creatinine clearance in HIV positive adults.
Data were collected on demographic, anthropometric, body composition, clinical parameters and serum creatinine in HIV positive and negative adults. 24-hour urine was collected from some of the HIV positive adults who volunteered. Bias was calculated as mean difference between 24-hr creatinine clearance and eGFR (eGFR- 24 hour creatinine clearance) and the accuracy of each eGFR equation was calculated as the percentage of estimates within 30% of creatinine clearance.
A total of 340 HIV positive and 100 HIV negative adults were included in this study. Creatinine clearance was determined for 46 of HIV positive adults. Serum creatinine increased with increasing age, weight, height, body surface area, fat free mass and grip strength in both HIV positive and negative adults (P<0.05). No difference was observed in eGFR between HIV positive and HIV negative adults. For all eGFR equations, the correlation between eGFR and 24-hr creatinine clearance was 0.45-0.53 and the accuracy within 30% of 24-hr creatinine clearance was 24-46%. Removing ethnic coefficient reduced the bias and improved accuracy of the CKD-EPI and the MDRD estimates.
Ethiopian HIV positive adults in the present study had good kidney function at the initiation of antiretroviral treatment. However, all eGFR equations overestimated 24-hr creatinine clearance in the study population. Creatinine based eGFR equations that accounts for low muscle mass and body surface area are needed.
Limited data are available on the effect of antiretroviral treatment (ART) or Tenofovir disoproxil fumarate (TDF) on renal function in Ethiopians. We aimed to assess factors associated with renal ...function changes during the first year of ART with special focus on TDF. HIV positive persons who were greater than or equai to 18 years of age and eligible for ART initiation were recruited. Creatinine measurement to estimate glomerular filtration rate (eGFR) and spot urine analyses were performed at baseline and after 3, 6 and 12 months of ART. Univariate and multivariate linear regression and univariate logistic regression were used to determine factors associated with eGFR as continuous and categorical variable respectively. A linear mixed model was used to assess 12 month eGFR difference in TDF and non-TDF based regimen. Of 340 ART-naïve HIV patients with baseline renal function tests, 82.3% (279/339) were initiated on a TDF based ART regimen. All patients were on non-nucleoside reverse transcriptase inhibitors (NNRTI) based ART regimen. The median (IQR) change in eGFR with 12 months of ART was 0.8 (- 11.1; 10.0) ml/min/1.73m.sup.2. About 41 and 26.9% of HIV patients had a drop of greater than 3 and 10 mL/min/1.73 m.sup.2 in eGFR at 12 month, respectively. However, none of the HIV patients declined to < 60 ml/min/1.73m.sup.2 within 12 months. Moreover, none of the HIV patients had persistent proteinuria or glycosuria. Older HIV patients especially age > 45 years and those with unsuppressed viral load at 6 month of ART had a significantly lower eGFR at 12 months of ART initiation. However, there was no difference in 12 month eGFR between HIV patients initiated on TDF based regimen and non-TDF based regimen. Renal function remained stable with no difference between HIV patients treated with TDF or non-TDF NNRTI based ART regimen over 12 months. However, older HIV patients and those with unsuppressed viral load deserve special focus on renal monitoring. Data on long-term safety of TDF (> 1 year) is still warranted in this population.
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