Female rats consuming an iron and omega-3 fatty acid deficient diet preconception require combined iron and omega-3 fatty acid supplementation for the prevention of bone impairments in offspring.

We previously showed in rats that pre- and postnatal deficiencies in iron and omega-3 (n-3) fatty acids can impair bone development, with additive and potentially irreversible effects when combined. This study aimed to investigate, in female rats consuming a combined iron and n-3 fatty acid deficient (ID + n-3 FAD) diet preconception, whether supplementation with iron and docosahexaenoic/eicosapentaenoic acid (DHA/EPA), alone and in combination, can prevent bone impairments in offspring. Using a 2 × 2 factorial design, female Wistar rats consuming an ID + n-3 FAD diet preconception were randomised to receive an: 1) iron supplemented (Fe + n-3 FAD), 2) DHA/EPA supplemented (ID + DHA/EPA), 3) Fe + DHA/EPA, or 4) ID + n-3 FAD diet from gestational day 10 throughout pregnancy and lactation. Post-weaning, offspring (n = 24/group; male:female = 1:1) remained on the respective experimental diets for three weeks until postnatal day 42-45. Offspring born to female rats consuming a control diet preconception and an Fe+DHA/EPA diet throughout pregnancy and lactation served as non-deficient reference group (Control+Fe+DHA/EPA). Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry and bone strength using three-point bending tests. Only offspring in the Fe+DHA/EPA group had significantly higher spine and femur BMD, and higher femur stiffness than offspring in the ID + n-3 FAD group, and had similar spine BMD and femur stiffness as the Control + Fe + DHA/EPA group. Offspring in the Fe + DHA/EPA group further had significantly higher femur strength (ultimate load) than the other experimental groups, and a similar femur strength as the Control + Fe + DHA/EPA group. This study shows that only combined iron and DHA/EPA supplementation can prevent bone impairments in offspring of female rats consuming an iron and n-3 FA deficient diet preconception.

Effects of egg as an early complementary food on growth of 6- to 9-month-old infants: a randomised controlled trial.

OBJECTIVE: To assess the effect of daily egg consumption for six months on linear growth (primary outcome), weight-for-age, weight-for-length, mid-upper arm circumference-for-age, head circumference-for-age Z-scores, gross motor milestones development, anaemia and iron status (secondary outcomes) in a low socioeconomic community. PARTICIPANTS: Infants aged 6 to 9 months living in the peri-urban Jouberton area, in the Matlosana Municipality, South Africa. DESIGN: A randomised controlled trial with a parallel design was implemented. Eligible infants were randomly allocated to the intervention (n 250) receiving one egg/day and the control group (n 250) receiving no intervention. The participants were visited weekly to monitor morbidity and gross motor development, with information on adherence collected for the intervention group. Trained assessors took anthropometric measurements, and a blood sample was collected to assess anaemia and iron status. There was blinding of the anthropometric assessors to the groups during measurements and the statistician during the analysis. RESULTS: Baseline prevalence of stunting, underweight, wasting, overweight and anaemia was 23·8 %, 9·8 %, 1·2 %, 13·8 % and 29·2 %, respectively, and did not differ between groups. Overall, 230 and 216 participants in the intervention and control groups completed the study, respectively. There was no intervention effect on length-for-age, weight-for-age, weight-for-length Z-scores, gross motor milestone development, anaemia and iron status. CONCLUSIONS: Daily egg intake did not affect linear growth, underweight, wasting, motor milestones development, anaemia and iron status. Other interventions are necessary to understand the effect of animal-source food intake on children's growth and development. This trial was registered at https://clinicaltrials.gov/ (NCT05168085).

Potential of Egg as Complementary Food to Improve Nutrient Intake and Dietary Diversity.

The original aim was to determine the effect of egg consumption on infant growth in a low socioeconomic community in South Africa in a randomized controlled trial. Enrolment was, however, prematurely stopped due to COVID-19 lockdown regulations. The resultant small sample (egg group n = 70; control group n = 85) was followed up to assess the feasibility of egg consumption for eight months in terms of dietary intake, egg usage and perceived effects of lockdown on child feeding. Egg consumption remained low in the control group, <10% consumed egg ≥4 days/week at the follow-up points. In the egg group, egg was frequently consumed at midpoint (daily 87.1%, 4−6 days 8.1%) and endpoint (daily 53.1%, 4−6 days 21.9%). At endpoint, dietary intake of cholesterol and vitamin D was higher, and intake of niacin and vitamin B6 lower in the egg group compared to the control group. Dietary diversity was low, 36.2% of the egg group and 18.9% of the control group (p < 0.05) achieved minimum dietary diversity at endpoint. No babies developed egg allergy or sensitization, and adjusted regression analysis showed that frequency of egg intake was not related with the incidence or duration of allergy-related symptoms. This study showed that frequent egg consumption can contribute safely to complementary food for babies, especially in low- and middle-income countries.

Effect of small-quantity lipid-based nutrient supplements on growth, psychomotor development, iron status, and morbidity among 6- to 12-mo-old infants in South Africa: a randomized controlled trial.

Background: Evidence on the effect of small-quantity lipid-based nutrient supplements (SQ-LNSs) on early child growth and development is mixed. Objective: This study assessed the effect of daily consumption of 2 different SQ-LNS formulations on linear growth (primary outcome), psychomotor development, iron status (secondary outcomes), and morbidity in infants from age 6 to 12 mo within the context of a maize-based complementary diet. Methods: Infants (n = 750) were randomly assigned to receive SQ-LNS, SQ-LNS-plus, or no supplement. Both SQ-LNS products contained micronutrients and essential fatty acids. SQ-LNS-plus contained, in addition, docosahexaenoic acid, arachidonic acid (important for brain and eye development), lysine (limiting amino acid in maize), phytase (enhances iron absorption), and other nutrients. Infants' weight and length were measured bimonthly. At age 6 and 12 mo, psychomotor development using the Kilifi Developmental Inventory and South African Parent Rating Scale and hemoglobin, plasma ferritin, C-reactive protein, and α1-acid glycoprotein were assessed. WHO Motor Milestone outcomes, adherence, and morbidity were monitored weekly through home visits. Primary analysis was by intention-to-treat, comparing each SQ-LNS group with the control. Results: SQ-LNS-plus had a positive effect on length-for-age zscore at age 8 mo (mean difference: 0.11; 95% CI: 0.01, 0.22; P = 0.032) and 10 mo (0.16; 95% CI: 0.04, 0.27; P = 0.008) but not at 12 mo (0.09; 95% CI: -0.02, 0.21; P = 0.115), locomotor development score (2.05; 95% CI: 0.72, 3.38; P = 0.003), and Parent Rating Score (1.10; 95% CI: 0.14, 2.07; P = 0.025), but no effect for weight-for-age zscore. Both SQ-LNS (P = 0.027) and SQ-LNS-plus (P = 0.005) improved hemoglobin concentration and reduced the risk of anemia, iron deficiency, and iron-deficiency anemia. Both SQ-LNS products reduced longitudinal prevalence of fever, coughing, and wheezing but increased incidence and longitudinal prevalence of diarrhea, vomiting, and rash/sores. Conclusions: Point-of-use fortification with SQ-LNS-plus showed an early transient effect on linear growth and improved locomotor development. Both SQ-LNS products had positive impacts on anemia and iron status. This trial was registered at clinicaltrials.gov as NCT01845610.

The prevalence and factors associated with stunting among infants aged 6 months in a peri-urban South African community.

OBJECTIVE: To determine the prevalence and factors associated with stunting in 6-month-old South African infants. DESIGN: This cross-sectional study was part of the baseline of a randomized controlled trial. Weight-for-length, length-for-age and weight-for-age Z-scores were based on the WHO classification. Blood samples were analysed for Hb, plasma ferritin and soluble transferrin receptor (sTfR). Socio-economic, breast-feeding and complementary feeding practices were assessed by questionnaire. Setting/Subjects Infants aged 6 months (n 750) from a peri-urban area of Matlosana Municipality, North West Province of South Africa. RESULTS: Stunting, underweight, wasting and overweight affected 28·5, 11·1, 1·7 and 10·1 % of infants, respectively. Exclusive breast-feeding to 6 months of age was reported in 5·9 % of the infants. Multivariable binary logistic regression showed that birth weight (OR=0·12; 95 % CI 0·07, 0·21, P8·3 mg/l) concentrations. CONCLUSIONS: The association between stunting and lower birth weight, shorter maternal height and male sex reflects possibly the intergenerational origins of stunting. Therefore, interventions that focus on improving preconceptual and maternal nutritional status, combined with strategies to promote appropriate infant feeding practices, may be an important strategy to prevent stunting in vulnerable settings.

Lipid-based nutrient supplements and linear growth in children under 2 years: a review.

The prevalence of stunting remains high in low- and middle-income countries despite adoption of comprehensive nutrition interventions, particularly in low-income countries. In the present paper, we review current evidence on the acceptability and efficacy of small-quantity lipid-based nutrient supplements (SQ-LNS) on preventing stunting in children under 2 years, discuss the factors that affect their efficacy, highlight the implications of the current findings at pragmatic level and identify research priorities. Although the present paper is not a generic systematic review, we used a systematic approach to select relevant literature. The review showed that there is growing interest in the potential benefits of using SQ-LNS to prevent growth faltering. Acceptability studies showed that SQ-LNS are generally well accepted. However, results on the efficacy of SQ-LNS on improving linear growth or preventing growth faltering in infants and young children are still inconclusive. Factors that may affect efficacy include the duration of the trial, composition and dosage of SQ-LNS given, and baseline demographics and nutritional status of research participants. Future research should focus on controlled and long-term follow-up trials to obtain more conclusive results. In the long term, there will be need for studies to investigate how provision of SQ-LNS can be integrated with existing strategies to prevent stunting in low- and middle-income settings.

Differential ferritin interpretation methods that adjust for inflammation yield discrepant iron deficiency prevalence.

We reassessed the iron deficiency (ID) prevalence in a South African trial that formed part of the International Research on Infant Supplementation study by comparing four methods that account for the high prevalence of acute (28.6%) and chronic (41.8%) inflammation observed in the study. Serum ferritin (SF) was measured as marker of iron status in 192 apparently healthy, 4-13-month-old infants. Alpha-1 glycoprotein and C-reactive protein concentrations were determined to indicate chronic and acute inflammation, respectively. The ID prevalence was obtained by four methods that adjust for inflammation: (1) excluding infants with inflammation; (2) using a higher cut-off (SF < 30 µg L(-1) ); (3) using different cut-offs for infants with vs. without inflammation (SF < 30 µg L(-1) vs. SF < 12 µg L(-1) ); and (4) adjusting SF concentrations with correction factors (CFs) were compared with a reference method (SF < 12 µg L(-1) ) not accounting for inflammation. Using the higher SF cut-off method resulted in the highest ID prevalence (52.1%), followed by using two different cut-offs (31.8%), using CFs (21.9%) and excluding subjects with inflammation (17.6%). The CF method showed the best agreement with the reference method. Disregarding inflammation resulted in a significantly lower ID prevalence (17.2%). ID anaemia (IDA) prevalence ranged from 13.2% to 24.5%, with the lowest prevalence (12.0%) for the reference method. Our analysis highlights the challenge of assessing ID and IDA using only SF as marker of iron status in the presence of inflammation. We demonstrate the importance of measuring inflammation markers to account for their elevating effect on SF.

Effects of a multi-micronutrient-fortified beverage, with and without sugar, on growth and cognition in South African schoolchildren: a randomised, double-blind, controlled intervention.

Little is known about the effects of combined micronutrient and sugar consumption on growth and cognition. In the present study, we investigated the effects of micronutrients and sugar, alone and in combination, in a beverage on growth and cognition in schoolchildren. In a 2 × 2 factorial design, children (n 414, 6-11 years) were randomly allocated to consume beverages containing (1) micronutrients with sugar, (2) micronutrients with a non-nutritive sweetener, (3) no micronutrients with sugar or (4) no micronutrients with a non-nutritive sweetener for 8.5 months. Growth was assessed and cognition was tested using the Kaufman Assessment Battery for Children version II (KABC-II) subtests and the Hopkins Verbal Learning Test (HVLT). Micronutrients decreased the OR for Fe deficiency at the endpoint (OR 0.19; 95% CI 0.07, 0.53). Micronutrients increased KABC Atlantis (intervention effect: 0.76; 95% CI 0.10, 1.42) and HVLT Discrimination Index (1.00; 95% CI 0.01, 2.00) scores. Sugar increased KABC Atlantis (0.71; 95% CI 0.05, 1.37) and Rover (0.72; 95% CI 0.08, 1.35) scores and HVLT Recall 3 (0.94; 95% CI 0.15, 1.72). Significant micronutrient × sugar interaction effects on the Atlantis, Number recall, Rover and Discrimination Index scores indicated that micronutrients and sugar in combination attenuated the beneficial effects of micronutrients or sugar alone. Micronutrients or sugar alone had a lowering effect on weight-for-age z-scores relative to controls (micronutrients - 0.08; 95% CI - 0.15, - 0.01; sugar - 0.07; 95% CI - 0.14, - 0.002), but in combination, this effect was attenuated. The beverages with micronutrients or added sugar alone had a beneficial effect on cognition, which was attenuated when provided in combination.

Positive association between dietary iron intake and iron status in HIV-infected children in Johannesburg, South Africa.

Anemia is a common complication of pediatric HIV infection and is associated with suboptimal cognitive performance and growth failure. Routine iron supplementation is not provided to South African HIV-infected children. We hypothesized that dietary iron intake without supplementation is sufficient to protect against iron deficiency (ID) in HIV-infected children receiving highly active antiretroviral therapy. In this prospective study, the difference between dietary intakes of iron-deficient children (soluble transferrin receptor >9.4 mg/L) and iron-sufficient children after 18 months on highly active antiretroviral therapy was examined. The association between iron intake and hemoglobin (Hb) concentration was also assessed. Longitudinal data collected for 18 months from 58 HIV-infected African children were assessed by generalized estimation equations, with adjustment for demographic information, dietary intakes, growth parameters, and CD4%. After adjustment for covariates, the longitudinal association between dietary iron intake and Hb concentration remained significant. This association shows that for every 1-mg increase in iron intake per day, Hb increases by 1.1 g/L (P < .001). Mean Hb increased significantly after 18 months of follow-up (106 ± 14 to 129 ± 14 g/L, P < .01), but soluble transferrin receptor also increased (7.7 ± 2.7 to 8.9 ± 3.0 mg/L, P < .01). The incidence of ID increased from 15.2% at baseline to 37.2% after 18 months. Children with animal protein intakes greater than >20 g/d had significantly lower odds for ID at 18 months than did children with lower intakes (odds ratio, 0.40; 95% confidence interval, 0.21-0.77). Dietary iron intake was insufficient to protect against ID, pointing to a need for low-dose iron supplementation for iron-deficient HIV-infected children and interventions to increase the consumption of animal protein.