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.

Omega-3 fatty acid supply in pregnancy for risk reduction of preterm and early preterm birth.

This clinical practice guideline on the supply of the omega-3 docosahexaenoic acid and eicosapentaenoic acid in pregnant women for risk reduction of preterm birth and early preterm birth was developed with support from several medical-scientific organizations, and is based on a review of the available strong evidence from randomized clinical trials and a formal consensus process. We concluded the following. Women of childbearing age should obtain a supply of at least 250 mg/d of docosahexaenoic+eicosapentaenoic acid from diet or supplements, and in pregnancy an additional intake of ≥100 to 200 mg/d of docosahexaenoic acid. Pregnant women with a low docosahexaenoic acid intake and/or low docosahexaenoic acid blood levels have an increased risk of preterm birth and early preterm birth. Thus, they should receive a supply of approximately 600 to 1000 mg/d of docosahexaenoic+eicosapentaenoic acid, or docosahexaenoic acid alone, given that this dosage showed significant reduction of preterm birth and early preterm birth in randomized controlled trials. This additional supply should preferably begin in the second trimester of pregnancy (not later than approximately 20 weeks' gestation) and continue until approximately 37 weeks' gestation or until childbirth if before 37 weeks' gestation. Identification of women with inadequate omega-3 supply is achievable by a set of standardized questions on intake. Docosahexaenoic acid measurement from blood is another option to identify women with low status, but further standardization of laboratory methods and appropriate cutoff values is needed. Information on how to achieve an appropriate intake of docosahexaenoic acid or docosahexaenoic+eicosapentaenoic acid for women of childbearing age and pregnant women should be provided to women and their partners.

Iron and n-3 fatty acid depletion, alone and in combination, during early development provoke neurochemical changes, anhedonia, anxiety and social dysfunction in rats.

Objectives: Both iron and omega-3 (n-3) fatty acids (FA) play important roles in the development and functioning of the brain. We investigated the effects of n-3 FA and iron deficiencies, alone and in combination, during early development on behaviour and brain monoamines in rats. Methods: Using a 2-factorial design, female Wistar rats were randomly allocated to one of four diet groups: Control, n-3 FA deficient (n-3 FAD), iron deficient (ID), or n-3 FAD + ID. Females received these diets throughout mating, pregnancy and lactation. Offspring (n = 24/group; male:female = 1:1) continued on the same diet until post-natal day 42-45, and underwent a sucrose preference test (SPT), novel object recognition test, elevated plus maze (EPM) and social interaction test (SIT). Results: ID offspring consumed less sucrose in the SPT and spent more time in closed arms and less time in open arms of the EPM than non-ID offspring. In female offspring only, ID and n-3 FAD reduced time approaching and together in the SIT, with an additive effect of ID and n-3 FAD for even less time approaching and spent together in the n-3 FAD + ID group compared to controls. ID offspring had higher striatal dopamine and norepinephrine and lower frontal cortex dopamine concentrations. N-3 FAD and ID affected frontal cortex serotonin concentrations in a sex-specific manner. Conclusions: Our results suggest that ID and n-3 FAD during early development provoke anhedonia, anxiety and social dysfunction in rats, with potential additive and attenuating effects when combined. These effects may in part be attributed to disturbances in brain neurochemistry and may be sex-specific.

A Cross-Sectional Study of the Associations between Biomarkers of Vitamin D, Iron Status, and Hemoglobin in South African Women of Reproductive Age: the Healthy Life Trajectories Initiative, South Africa.

Background: Vitamin D deficiency and anemia impact the health of women of reproductive age. Evidence suggests an inverse relationship between serum vitamin D (25-hydroxyvitamin D [25(OH)D]) and anemia/iron deficiency, but less is known about these associations in women of reproductive age, in particular in a setting with a combined burden of micronutrient deficiency, food insecurity, and obesity. Objective: We aimed to assess the associations between 25(OH)D and biomarkers of iron and anemia in a cohort of women of reproductive age from Soweto, South Africa. The prevalence of vitamin D deficiency was also assessed. Methods: In this cross-sectional substudy of the Healthy Life Trajectories Initiative (HeLTI) South Africa pilot trial, 25(OH)D, iron markers (ferritin and soluble transferrin receptor [sTFR]), and altitude-adjusted hemoglobin (Hb) were measured in 493 women aged 18 to 25 years. Associations between iron deficiency/anemia and vitamin D status were evaluated using multivariable logistic regression, adjusting for confounders including fat mass index (FMI). Structural equation modeling (SEM) was performed to evaluate direct and indirect pathways between 25(OH)D, iron and anemia markers, and covariates. Results: Of 493 participants, 136 (27.6%) had vitamin D insufficiency (25(OH)D ≥12-20 ng/mL), whereas 28 (5.6%) had vitamin D deficiency (<12 ng/mL). Anemia and iron deficiency were not significantly associated with vitamin D category (25(OH)D<20 ng/mL compared with ≥20 ng/mL) in multivariable logistic regression analyses. In SEM, log-transformed 25(OH)D was not significantly associated with Hb, ferritin, or sTFR, but it was significantly associated with season of data collection, hormonal contraceptive use, and FMI (total effects: B = 0.17, 95% CI: 0.104, 0.236, P < 0.001; B: 0.10, 95% CI: 0.041, 0.154, P < 0.001; B: -0.01, 95%CI: -0.016, -0.003, P = 0.003, respectively). Conclusion: No significant association between vitamin D (25(OH)D), anemia (Hb), and iron markers was found. The inverse relationship between FMI and vitamin D status emphasizes the overlap between adiposity and micronutrient deficiencies in young South African women, exacerbating their risk of disease development.

Association between maternal postpartum depressive symptoms, socioeconomic factors, and birth outcomes with infant growth in South Africa.

This study aimed to investigate the association between maternal postpartum depressive symptoms, household demographic, socioeconomic, and infant characteristics with infant physical growth, and how these factors correlate to determine latent factors. This study was based on the baseline data of a 6-month randomised controlled trial aimed at providing an egg a day to infants aged 6 to 9-months from a low socioeconomic community in South Africa. Information collected on household demographic, socioeconomic, and infant characteristics was by face-to-face structured interviews, and trained assessors took anthropometric measurements. The Edinburgh Postnatal Depression Scale (EPDS) was used to assess maternal postpartum depressive symptoms. The analysis was based on 428 mother-infant pairs. Total EPDS score and its subscales score were not associated with stunting or underweight risk. However, a three- to four-fold increased risk of stunting and underweight, respectively was observed for premature birth. Low birthweight was associated with an estimated six-fold increased risk of underweight and stunting. Being female was associated with about 50% reduced risk of stunting and underweight. In conclusion, more robust studies are needed to substantiate these findings, with more awareness creation on the consequences of LBW and prematurity on the physical growth of infants from resource-limited settings.

Determinants of anaemia among women of reproductive age in South Africa: A Healthy Life Trajectories Initiative (HeLTI).

Anaemia continues to be a persistent concern among South African women of reproductive age (WRA), yet population specific information on its determinants remains sparse. We used baseline data from the Healthy Lives Trajectory Initiative a randomised trial (n = 480) to quantify factors associated with anaemia in Soweto, South Africa aged 18-25 years. We used multivariable logistic regression to describe associations with anaemia and used structural equation modelling to assess a theoretical model, which tested three categories socioeconomic status (household asset score, education level), nutritional factors (food security, leafy green vegetable and chicken and beef consumption, iron status and vitamin A status) and biodemographic factors (parity, age at start of menarche, HIV status, contraception use, anthropometry, and inflammation status). The multiple logistic regression showed that ID (OR: 2.62, 95% CI: 1.72, 3.98), iron deficiency erythropoiesis (IDE) (OR: 1.62, 95% CI: 1.07, 2.46), and elevated CRP (OR: 1.69, 95% CI: 1.04, 2.76), increased the odds of being anaemic. SEM analysis revealed Hb was directly and positively associated with adjusted ferritin (0.0031 per mg/dL; p≤0.001), and CRP (0.015 per mg/dL; p≤0.05), and directly and negatively associated with soluble transferrin receptor sTfR (-0.042 per mg/dL; p≤0.001). While contraception use had both a direct (0.34; p≤0.05) and indirect (0.11; p≤0.01) positive association with Hb. Additionally, chicken and beef consumption had a positive indirect association with Hb concentrations (0.15; p≤0.05) through adjusted ferritin. Iron deficiency was the main anaemia risk factor in this low resource setting. However, anaemia of inflammation is present. Therefore, we suggest that in our setting, WRA anaemia control programs that include interventions to reduce ID and inflammation should be tested.

Higher n-3 polyunsaturated fatty acid status during early pregnancy is associated with lower risk for depression at 12 months postpartum: The NuPED study.

Perinatal depression can negatively affect the health of the mother and her offspring. N-3 polyunsaturated fatty acids (PUFA) may play a role in the aetiology of depression. Therefore, we investigated the association of n-3 PUFA status during early pregnancy with perinatal depression among women living in urban Johannesburg, South Africa. For this prospective analysis, we analysed red blood cell (RBC) total phospholipid fatty acid (FA) composition (% of total FA) of 242 pregnant women at <18 weeks' gestation. We used the Edinburgh Postnatal Depression Scale (EPDS) to identify women at risk for depression (EPDS score ≥9) at <18, 22 and 36 weeks' gestation, and at 6 and 12 months postpartum. RBC EPA status was negatively (ß=-0.22, p<0.05), and the AA/EPA ratio positively (ß=0.24, p<0.05) associated with EPDS scores at 12 months postpartum. Higher RBC DHA and n-3 index were further associated with lower odds (OR=0.56 [95% CI: 0.32-0.91]; OR=0.63 [95% CI: 0.39-0.94]), while higher n-6/n-3 PUFA and AA/EPA ratios early in pregnancy were associated with higher odds for depression at 12 months postpartum ((OR=2.34 [95% CI: 1.12-4.97]; OR=1.02 [95% CI: 1.00-1.05]). Our results suggest that women with a higher RBC n-3 PUFA status during early pregnancy may be at lower risk for depression at 12 months postpartum.

Retail Cost and Energy Adjusted Cost Are Associated with Dietary Diversity and Nutrient Adequacy for Diets of 6-24 Months Children.

Poor nutrition during the first two years of life has long term consequences, but resource-poor households often do not have the means to access nutrient-dense and diverse diets. Pooled data of 24-h dietary recalls (n = 3336) and 2019 retail food prices were analyzed to determine associations of retail cost and energy cost (per 100 kcal) with diet quality indicators for diets of 6-24-month-old South African children who were breastfed (BF-diet) and not breastfed (NBF-diet) during the 24-h recall period. Compared to the BF-diet, retail cost for the NBF-diet was three times higher for age 6-11 months, and double for age 12-17 months. Higher retail cost and energy cost were both associated with higher mean adequacy ratios and dietary diversity scores for BF and NBF diets, except energy cost for the NBF-diet for age 6-11 months. Overall, inclusion of flesh foods, vitamin A-rich fruits and vegetables, and other fruit and vegetables increased from the lowest to the highest retail cost tertile. The higher cost of more nutritious diets highlights the importance of the affordability of diets in interventions aimed at improving diet quality. Possible strategies include: identifying the most-affordable foods within each food group, focusing on foods that provide multiple key micronutrients, and the inclusion of locally available indigenous foods.

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.

Animal-source foods as a suitable complementary food for improved physical growth in 6 to 24-month-old children in low- and middle-income countries: a systematic review and meta-analysis of randomised controlled trials.

Although animal-source foods are suitable complementary food for child growth in low- and middle-income countries (LMICs), their efficacy is still under discussion. This systematic review and meta-analysis was done to investigate the suitability of animal-source foods intake on child physical growth in LMICs. A systematic literature search was done using electronic databases and scanning the reference list of included studies, previous meta-analysis and systematic reviews. Paper selection was based on the PICO (ST) criteria. Papers were selected if based on 6 to 24-month-old children, if they were randomised controlled trials evaluating the effect of complementary animal-based food supplementation of any natural origin, if reporting at least a measure of body size and published after 2000. The PRISMA guidelines for reporting systematic review was followed in the paper selection. Fourteen papers were included in the systematic review and eight were considered for the meta-analysis. Animal-based food supplementation resulted in a higher length-for-age LAZ and weight-for-age (WAZ) Z-scores compared with the control group with random effect size of 0·15 (95 % CI 0·02, 0·27) and 0·20 (95 % CI 0·03, 0·36), respectively. Results were confirmed after influence analyses, and publication bias resulted as negligible. An increased effect on LAZ and WAZ was observed when the food supplementation was based on egg with effect size of 0·31 (95 % CI = -0·03, 0·64) and 0·36 (95 % CI = -0·03, 0·75), respectively. Animal-source foods are a suitable complementary food to improve growth in 6 to 24-month-old children in LMICs.

Barriers and facilitators of micronutrient supplementation among non-pregnant women of reproductive age in Johannesburg, South Africa.

The prevalence of anaemia among South African women of reproductive age (WRA) remains high at 39%. Multiple micronutrient supplementation (MMS) may be an effective strategy in the prevention and management of anaemia. Our aim was to understand facilitators and barriers to preconception MMS adherence and to explore perceptions and beliefs of MMS in the prevention and treatment of anaemia among non-pregnant WRA. This qualitative study was embedded in a preconception MMS intervention trial of WRA and was conducted in two phases. Phase one assessed the barriers and facilitators of MMS adherence. Individual interviews were conducted with the community health workers (n = 7) administering MMS, and with non-pregnant WRA (n = 25) participating in the trial. Phase two included four focus groups with participating WRA (n = 26), which further explored participants' perceptions and beliefs of MMS provision and adherence, and strategies to improve adherence. The reported facilitators to supplementation were family support, interaction with the community health workers, easy access to MMS, and experienced benefits of MMS. Barriers to preconception supplementation included the lack of family support, the link of supplements to antenatal care, and the perceived lack of benefits of MMS. Participants reported negative associations of supplements with medication, individual and societal stigma around medication and challenges around the supplementation schedule. For successful preconception MMS interventions, young women, their families, and communities need to be convinced of the value of supplementation. Public health interventions utilising preconception supplementation will require specialised training for health care providers, targeted counselling materials and community household support.

n-3 long-chain PUFA promote antibacterial and inflammation-resolving effects in Mycobacterium tuberculosis-infected C3HeB/FeJ mice, dependent on fatty acid status.

Non-resolving inflammation is characteristic of tuberculosis (TB). Given their inflammation-resolving properties, n-3 long-chain PUFA (n-3 LCPUFA) may support TB treatment. This research aimed to investigate the effects of n-3 LCPUFA on clinical and inflammatory outcomes of Mycobacterium tuberculosis-infected C3HeB/FeJ mice with either normal or low n-3 PUFA status before infection. Using a two-by-two design, uninfected mice were conditioned on either an n-3 PUFA-sufficient (n-3FAS) or -deficient (n-3FAD) diet for 6 weeks. One week post-infection, mice were randomised to either n-3 LCPUFA supplemented (n-3FAS/n-3+ and n-3FAD/n-3+) or continued on n-3FAS or n-3FAD diets for 3 weeks. Mice were euthanised and fatty acid status, lung bacterial load and pathology, cytokine, lipid mediator and immune cell phenotype analysed. n-3 LCPUFA supplementation in n-3FAS mice lowered lung bacterial loads (P = 0·003), T cells (P = 0·019), CD4+ T cells (P = 0·014) and interferon (IFN)-γ (P < 0·001) and promoted a pro-resolving lung lipid mediator profile. Compared with n-3FAS mice, the n-3FAD group had lower bacterial loads (P = 0·037), significantly higher immune cell recruitment and a more pro-inflammatory lipid mediator profile, however, significantly lower lung IFN-γ, IL-1α, IL-1ß and IL-17, and supplementation in the n-3FAD group provided no beneficial effect on lung bacterial load or inflammation. Our study provides the first evidence that n-3 LCPUFA supplementation has antibacterial and inflammation-resolving benefits in TB when provided 1 week after infection in the context of a sufficient n-3 PUFA status, whilst a low n-3 PUFA status may promote better bacterial control and lower lung inflammation not benefiting from n-3 LCPUFA supplementation.

Iodine status of pregnant women living in urban Johannesburg, South Africa.

Adequate intake of iodine is important during pregnancy because of its essential role in foetal growth and neurodevelopment. Data on iodine status of South African pregnant women are scarce, and the salt reduction policy implemented in 2016 may decrease iodine intake of South Africans. This cross-sectional study assessed the iodine status of pregnant women residing in urban Johannesburg, South Africa. A total of 250 pregnant women were enrolled into the 'Nutrition during Pregnancy and Early Development' (NuPED) study and 312 pregnant women into the 'Assessment of dried blood spot thyroglobulin in pregnant women to redefine the range of median urinary iodine concentration that indicates adequate iodine intake, South Africa' (STRIPE-SA) study and were included in this analysis. Urinary iodine concentration (UIC) was analysed in a spot urine sample. Thyroglobulin (Tg) was measured in serum, and thyroid-stimulating hormone (TSH) and total thyroxine (tT4) were measured in dried blood spots. The median [interquartile range (IQR)] UIC of pregnant women was 144 (84-234) µg/L. Women in the first (n = 99), second (n = 262) and third (n = 174) trimester had a median UIC of 133 (81-316), 145 (84-236) and 156 (89-245) µg/L, respectively (p = 0.419). Median TSH, tT4 and Tg were 2.7 (2.3-3.2) mU/L, 202 (163-236) nmol/L and 9.2 (5.4-17.9) µg/L, respectively. Based on the median UIC, pregnant women residing in urban Johannesburg may be borderline iodine deficient. These findings highlight the need for ongoing monitoring of iodine status among vulnerable pregnant women, especially considering the recently introduced salt reduction policy in South Africa.

Maternal postpartum depression in relation to child undernutrition in low- and middle-income countries: a systematic review and meta-analysis.

Perinatal (antenatal and postpartum) depression is increasingly becoming a global public health problem. Studies have shown that the presence of depression during the perinatal period impact on a mother's ability to adequately provide nutritional care for herself and her infants and young children. This may thus negatively influence the nutritional status of these vulnerable children resulting in poor growth, such as stunting which is currently a public health problem in low- and middle-income countries (LMICs). The aim of this systematic review and meta-analysis was to determine the association between maternal postpartum depression and child growth in LMICs. Electronic databases were systematically reviewed by screening abstracts, titles, full text and additional data sources of eligible papers. Articles were eligible for inclusion if based on children aged 0 to 59 months, if reporting maternal postpartum depression as an exposure, if based on observational studies evaluating the relation between maternal postpartum depression and child growth, if reporting at least one physical growth indicator such as stunting as an outcome, and if published after 2000. Article selection was based on the PRISMA guidelines for reporting systematic reviews. Twelve articles were included in the quantitative synthesis (12 for stunting, 8 for underweight and 2 for wasting). Maternal postpartum depression was observed to be associated with an increased risk of child stunting (1.87 (95% CI: 1.52, 2.30; I2 = 41.6%, p = 0.064)) and underweight (1.81 (95% Cl: 1.25, 2.62; I2 = 70.7%, p = 0.001)). These results were confirmed after influence analyses, with publication bias being negligible.      Conclusion: Maternal depression is a risk factor for poor child growth in LMICs. This study contributes to the knowledge on this topic and calls on policymakers to improve on its understanding, screening and treatment to alleviate the potential negative impact on child growth. What is Known: • Maternal postpartum depression is currently a public health relevance in low- and middle-income countries (LMICs). • Maternal postpartum depression is a risk factor for poor nutritional status in children from LMICs. What is New: • Maternal postpartum depression is associated with an 80 to 90% increased risk of childhood stunting and underweight in LMICs. • The association between risk of childhood stunting and underweight with maternal postpartum depression is slightly influenced by geographical area, rural or urban location, by factors such as study design, study quality and sample size.

Adjunct n-3 Long-Chain Polyunsaturated Fatty Acid Treatment in Tuberculosis Reduces Inflammation and Improves Anemia of Infection More in C3HeB/FeJ Mice With Low n-3 Fatty Acid Status Than Sufficient n-3 Fatty Acid Status.

Populations at risk for tuberculosis (TB) may have a low n-3 polyunsaturated fatty acid (PUFA) status. Our research previously showed that post-infection supplementation of n-3 long-chain PUFA (LCPUFA) in TB without TB medication was beneficial in n-3 PUFA sufficient but not in low-status C3HeB/FeJ mice. In this study, we investigated the effect of n-3 LCPUFA adjunct to TB medication in TB mice with a low compared to a sufficient n-3 PUFA status. Mice were conditioned on an n-3 PUFA-deficient (n-3FAD) or n-3 PUFA-sufficient (n-3FAS) diet for 6 weeks before TB infection. Post-infection at 2 weeks, both groups were switched to an n-3 LCPUFA [eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA)] supplemented diet and euthanized at 4- and 14- days post-treatment. Iron and anemia status, bacterial loads, lung pathology, lung cytokines/chemokines, and lung lipid mediators were measured. Following 14 days of treatment, hemoglobin (Hb) was higher in the n-3FAD than the untreated n-3FAS group (p = 0.022), whereas the n-3FAS (drug) treated control and n-3FAS groups were not. Pro-inflammatory lung cytokines; interleukin-6 (IL-6) (p = 0.011), IL-1α (p = 0.039), MCP1 (p = 0.003), MIP1- α (p = 0.043), and RANTES (p = 0.034); were lower, and the anti-inflammatory cytokine IL-4 (p = 0.002) and growth factor GMCSF (p = 0.007) were higher in the n-3FAD compared with the n-3FAS mice after 14 days. These results suggest that n-3 LCPUFA therapy in TB-infected mice, in combination with TB medication, may improve anemia of infection more in low n-3 fatty acid status than sufficient status mice. Furthermore, the low n-3 fatty acid status TB mice supplemented with n-3 LCPUFA showed comparatively lower cytokine-mediated inflammation despite presenting with lower pro-resolving lipid mediators.

Characterization of Genetic Variants in the SLC5A5 Gene and Associations With Breast Milk Iodine Concentration in Lactating Women of African Descent: The NUPED Study.

Background: The sodium iodide symporter is responsible for the transfer of iodine into breast milk and is encoded for by the SLC5A5 gene. The role of genetic variants in the SLC5A5 gene locus in relation to the transfer of iodine from plasma into breast milk in healthy lactating individuals has, to our knowledge, not been explored. Objective: To identify and characterize possible genetic variants of the SLC5A5 gene in women of African descent living in urban South Africa, and to study associations with breast milk iodine concentrations (BMIC) in lactating women. Methods: This study is affiliated to the Nutrition during Pregnancy and Early Development (NuPED) cohort study (n = 250 enrolled pregnant women). In a randomly selected sub-sample of 32 women, the SLC5A5 gene was sequenced to identify known and novel variants. Of the identified variants, genotyping of selected variants was performed in all pregnant women who gave consent for genetic analyses (n = 246), to determine the frequency of the variants in the study sample. Urinary iodine concentration (UIC) in spot urine samples and BMIC were measured to determine iodine status. Associations of SLC5A5 genetic variants with BMIC were studied in lactating women (n = 55). Results: We identified 27 variants from sequencing of gene exomes and 10 variants were selected for further study. There was a significant difference in BMIC between the genotypes of the rs775249401 variant (P = 0.042), with the homozygous GG group having lower BMIC [86.8 (54.9-167.9) µg/L] compared to the (A) allele carriers rs775249401(AG+AA) [143.9 (122.4-169.3) µg/L] (P = 0.042). Of the rs775249401(GG), 49% had UIC <100 µg/L and 61% had BMIC <100 µg/L. On the other hand, 60% of the rs775249401(AG+AA) carriers had UIC <100 µg/L, and none had a BMIC <100 µg/L. Conclusion: Our results suggest that A-allele carriers of rs775249401(AG+AA) are likely to have higher iodine transfer into breast milk compared to the homozygous GG counterparts. Thus, genetic variations in the SLC5A5 gene may play an important role in the transfer of iodine from plasma into breast milk and may partially explain inter-individual variability in BMIC.

Beneficial effect of long-chain n-3 polyunsaturated fatty acid supplementation on tuberculosis in mice.

Intakes of the omega-3 essential fatty acids (n-3 EFAs) are low in the general adult population, with high n-6/n-3 polyunsaturated fatty acid (PUFA) ratios and the accompanying suboptimal n-3 PUFA status. Eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) have antibacterial and inflammation-resolving effects in tuberculosis (TB). However, whether switching to a diet with optimum n-3 EFA intake after the infection has comparable benefits has not been investigated. We aimed to compare the effects of a diet with sufficient n-3 EFA content in an acceptable n-6/n-3 PUFA ratio for rodents ((n-3)eFAS group) with those on the same diet supplemented with EPA and DHA (EPA/DHA group) in Mycobacterium tuberculosis (Mtb)-infected C3HeB/FeJ mice with a low n-3 PUFA status. Mice were conditioned on an n-3 PUFA-deficient diet with a high n-6/n-3 PUFA ratio for 6 weeks before Mtb infection and randomized to either (n-3)eFAS or EPA/DHA diets 1 week post-infection for 3 weeks. At endpoint, EPA and DHA compositions were higher and arachidonic acid, osbond acid, and total n-6 LCPUFAs lower in all lipid pools measured in the EPA/DHA group (all P < 0.001). Percentage body weight gain was higher (P = 0.017) and lung bacterial load lower (P < 0.001) in the EPA/DHA group. Additionally, the EPA/DHA group had a more pro-resolving lung lipid mediator profile and lower lung in IL-1α and IL-1ß concentrations (P = 0.023, P = 0.049). Inverse correlations were found between the lung and peripheral blood mononuclear cell EPA and DHA and selected pro-inflammatory cytokines. These are the first findings that indicate that EPA/DHA supplementation provides benefits superior to a diet with sufficient n-3 EFAs concerning bacterial killing, weight gain and lung inflammation resolution in Mtb-infected mice with a low n-3 PUFA status. Therefore, EPA and DHA may be worth considering as adjunct TB treatment.

Longer-Term Omega-3 LCPUFA More Effective Adjunct Therapy for Tuberculosis Than Ibuprofen in a C3HeB/FeJ Tuberculosis Mouse Model.

Advancement in the understanding of inflammation regulation during tuberculosis (TB) treatment has led to novel therapeutic approaches being proposed. The use of immune mediators like anti-inflammatory and pro-resolving molecules for such, merits attention. Drug repurposing is a widely used strategy that seeks to identify new targets to treat or manage diseases. The widely explored nonsteroidal anti-inflammatory drug (NSAID) ibuprofen and a more recently explored pharmaconutrition therapy using omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs), have the potential to modulate the immune system and are thus considered potential repurposed drugs in this context. These approaches may be beneficial as supportive therapy to the already existing treatment regimen to improve clinical outcomes. Here, we applied adjunct ibuprofen and n-3 LCPUFA therapy, respectively, with standard anti-TB treatment, in a C3HeB/FeJ murine model of TB. Bacterial loads, lung pathology, lung cytokines/chemokines and lung lipid mediators were measured as outcomes. Lung bacterial load on day 14 post-treatment (PT) was lower in the n-3 LCPUFA, compared to the ibuprofen group (p = 0.039), but was higher in the ibuprofen group than the treated control group (p = 0.0315). Treated control and ibuprofen groups had more free alveolar space initially as compared to the n-3 LCPUFA group (4 days PT, p= 0.0114 and p= 0.002, respectively); however, significantly more alveolar space was present in the n-3 LCPUFA group as compared to the ibuprofen group by end of treatment (14 days PT, p = 0.035). Interleukin 6 (IL-6) was lower in the ibuprofen group as compared to the treated control, EPA/DHA and untreated control groups at 4 days PT (p = 0.019, p = 0.019 and p = 0.002, respectively). Importantly, pro-resolving EPA derived 9-HEPE, 11-HEPE, 12-HEPE and 18-HEPE lipid mediators (LMs) were significantly higher in the EPA/DHA group as compared to the ibuprofen and treated control groups. This suggests that n-3 LCPUFAs do improve pro-resolving and anti-inflammatory properties in TB, and it may be safe and effective to co-administer as adjunct therapy with standard TB treatment, particularly longer-term. Also, our results show host benefits upon short-term co-administration of ibuprofen, but not throughout the entire TB treatment course.

A Priori and a Posteriori Dietary Patterns among Pregnant Women in Johannesburg, South Africa: The NuPED Study.

Dietary pattern analyses allow assessment of the diet as a whole. Limited studies include both a priori and a posteriori dietary pattern analyses. This study aimed to explore the diet of pregnant women in urban South Africa through both a priori and a posteriori dietary pattern analyses and associated maternal and household factors. Dietary data were collected during early pregnancy using a quantified food frequency questionnaire from 250 pregnant women enrolled in the Nutrition During Pregnancy and Early Development (NuPED) cohort. A priori dietary patterns were determined using the Diet Quality Index-International (DQI-I), and a posteriori nutrient patterns using exploratory factor analysis. Based on the DQI-I, the study population followed a borderline low-quality diet. Three a posteriori nutrient patterns were identified: Pattern 1 "plant protein, iron, thiamine, and folic acid"; pattern 2 "animal protein, copper, vitamin A, and vitamin B12"; pattern 3 "fatty acids and sodium". Pattern 1 was associated with higher dietary quality (p < 0.001), lower maternal educational level (p = 0.03) and socioeconomic status (p < 0.001). Pattern 3 was significantly associated with lower dietary quality. The low dietary quality among pregnant women residing in urban South Africa should be addressed to ensure optimal maternal and offspring health outcomes.