Factors associated with anemia among school-going adolescents aged 10-17 years in Zanzibar, Tanzania: a cross sectional study.

BACKGROUND: Anemia among adolescents (ages 10-19 years) is a leading cause of morbidity and mortality in low- and middle-income countries and carries long-term health and economic consequences. To address the issue, policymakers and programmers require evidence of the burden of anemia among adolescents in specific contexts, as well as an understanding of the factors associated with anemia in this population. METHODS: We conducted a cross-sectional survey as a baseline assessment to determine the prevalence and factors associated with anemia in secondary school students, as part of a cluster-randomized effectiveness trial testing different micronutrient supplementation strategies in addressing anemia among adolescents in Zanzibar. Between March 7th to 25th, 2022 the survey was conducted on 2,479 school-going adolescents aged 10-17 years from 42 schools on the island of Zanzibar, Tanzania. Hemoglobin concentration was measured along with the collection of socio-demographics, health, food frequency, and water, sanitation and hygiene data. RESULTS: Based on the World Health Organization cutoffs for anemia, 53.3% of the sample had anemia (mild, moderate, or severe). Using chi-square tests and logistic regressions, we determined that females had higher odds of anemia than males (Adjusted OR = 1.47; 95% CI: 1.24, 1.74), those in the highest wealth quintile had lower odds of anemia than those in the lowest wealth quintile (Adjusted OR = 0.7; CI: 0.54, 0.91), stunted adolescents had higher odds of anemia than non-stunted students (Adjusted OR = 1.38; 95% CI: 1.06,1.81), and those who used shared toilets had higher odds of moderate or severe anemia than those with private toilet access (Adjusted OR = 1.68; CI: 1.07, 2.64). CONCLUSIONS: The high prevalence of anemia in this sample indicates an urgent need to address anemia among adolescents in Zanzibar, and the factors associated with anemia point to the importance of water, sanitation, and hygiene interventions in addition to dietary and nutritional support. TRIAL REGISTRATION: NCT05104554, registered 03/11/2021.

Periconceptional Folic Acid Only Versus Multiple Micronutrients Containing Folic Acid and Association with Gestational Diabetes Mellitus - Beijing Municipality, China, 2017-2021.

What is already known about this topic?: Inconsistent results have been reported on the association between periconceptional folic acid only (FAO) or multiple micronutrients containing folic acid (MMFA) supplementation and the risk of gestational diabetes mellitus (GDM) in previous research. What is added by this report?: In a prospective cohort study conducted among pregnant women in Haidian District, Beijing Municipality, it was observed that those who took MMFA demonstrated a higher likelihood of developing GDM in comparison to those who consumed FAO periconceptionally. Interestingly, the increased risk for GDM in pregnant women supplemented with MMFA compared to FAO was primarily due to changes in fasting plasma glucose. What are the implications for public health practice?: It is highly recommended that women prioritize the use of FAO in order to yield potential benefits in the prevention of GDM.

Effects of iron supplementation on neural indices of habituation in Bangladeshi children.

BACKGROUND: Iron deficiency and anemia have been associated with poor cognition in children, yet the effects of iron supplementation on neurocognition remain unclear. OBJECTIVE: We aimed to examine the effects of supplementation with iron on neural indices of habituation using auditory event-related brain potentials (ERPs). METHODS: This substudy was nested within a 3-arm, double-blind, double-dummy, individual randomized trial in Bangladesh, in which 3300 8-mo-old children were randomly selected to receive 3 mo of daily iron syrup (12.5 mg iron), multiple micronutrient powders (MNPs) (including 12.5 mg iron), or placebo. Children were assessed after 3 mo of intervention (mo 3) and 9 mo thereafter (mo 12). The neurocognitive substudy comprised a randomly selected subset of children from the main trial. Brain activity elicited during an auditory roving oddball task was recorded using electroencephalography to provide an index of habituation. The differential response to a novel (deviant) compared with a repeated (standard) sound was examined. The primary outcome was the amplitude of the mismatch response (deviant minusstandard tone waveforms) at mo 3. Secondary outcomes included the deviant and standard tone-evoked amplitudes, N2 amplitude differences, and differences in mean amplitudes evoked by deviant tones presented in the second compared with first half of the oddball sequence at mo 3 and 12. RESULTS: Data were analyzed from 329 children at month 3 and 363 at mo 12. Analyses indicated no treatment effects of iron interventions compared with placebo on the amplitude of the mismatch response (iron syrup compared with placebo: mean difference (MD) = 0.07µV [95% CI: -1.22, 1.37]; MNPs compared with placebo: MD = 0.58µV [95% CI: -0.74, 1.90]) nor any secondary ERP outcomes at mo 3 or 12, despite improvements in hemoglobin and ferritin concentrations from iron syrup and MNPs in this nested substudy. CONCLUSION: In Bangladeshi children with >40% anemia prevalence, iron or MNP interventions alone are insufficient to improve neural indices of habituation. This trial was registered at the Australian New Zealand Clinical Trials Registry as ACTRN12617000660381.

Intervention Effect of a Soybean-Based Complementary Food Supplement on Anemic Infants in a Poor Rural Region in China: Evidence from Quasi-RCT.

The soybean-based Yingyang Bao complementary food supplement represents a special nutritional improvement method for anemic infants in many intervention projects across China, while its benefits lack rigorous evidence. Using a quasi-randomized controlled trial design, which adhered to randomization and control except for the blinding method, 248 anemic infants were divided randomly into an intervention group (128 cases received the Yingyang Bao intervention based on routine feeding) and a control group (120 cases only received routine feeding). Anthropometric indicators and 16 blood indicators were measured at baseline and 1 year after intervention. The levels of hemoglobin, 1,25-dihydroxy vitamin D, homocysteine, retinol, vitamin D3, and soluble transferrin receptor and the height-age-Z score and weight-age-Z score of the intervention group were significantly improved after the intervention (p < 0.05). The homocysteine level improvement appeared to be moderately negatively correlated with the cobalamin level improvement (p < 0.05). The improvements of five indicators were significant correlated with the intervention duration (p < 0.05), and the corresponding three significant regression equations could predict the intervention effect and the intervention duration to a certain extent. This quasi-randomized controlled trial provided more convincing evidence that Yingyang Bao can effectively improve three kinds of malnutrition compared to previous research which only adopted self before and after comparison.

Fortified Balanced Energy-Protein Supplementation, Maternal Anemia, and Gestational Weight Gain: A Randomized Controlled Efficacy Trial among Pregnant Women in Rural Burkina Faso.

BACKGROUND: Anemia and suboptimal gestational weight gain (GWG) are associated with adverse maternal and birth outcomes. Limited research indicates that balanced energy-protein (BEP) supplements reduce the incidence of inadequate GWG. OBJECTIVES: We assessed the efficacy of a micronutrient-fortified BEP supplement on the secondary outcomes of anemia, GWG, GWG rate, and GWG in relation to the Institute of Medicine (IOM)'s recommendations, as compared with an iron-folic acid (IFA) tablet. METHODS: We conducted a randomized controlled trial in Burkina Faso, among pregnant women (15-40 y old) enrolled at <21 weeks of gestation. Women received either BEP and IFA (intervention) or IFA (control). Hemoglobin (g/dL) concentrations were measured at baseline and the third antenatal care visit (ANC), whereas maternal weight was measured at baseline and all subsequent ∼7-weekly ANCs. GWG (kg) was calculated as a woman's last weight measurement (at ∼36 weeks of gestation) minus weight at enrollment, whereas GWG rate (kg/wk) was GWG divided by the time between the first and last weight measurements. GWG adequacy (%) was computed as GWG divided by the IOM's recommendation. Binary outcomes included severely inadequate, inadequate, and excessive GWG. Statistical analyses followed the intention-to-treat principle. Linear regression and probability models were fitted for the continuous and binary outcomes, respectively, adjusting for baseline measurements. RESULTS: Women in the BEP group tended to have higher, but nonsignificantly different, GWG (0.28 kg; 95% CI: -0.05, 0.58 kg; P = 0.099). Furthermore, there were no significant differences in prenatal anemia prevalence, GWG rate, GWG adequacy, or incidence of inadequate or excessive GWG. Findings were robust to model adjustments and complete case and per protocol analyses. CONCLUSIONS: This trial does not provide evidence that fortified BEP supplementation reduces maternal anemia or increases GWG, as compared with IFA. In conjunction with the small, but positive, effects of maternal BEP supplementation on birth outcomes, our findings warrant the investigation of additional biochemical and postnatal outcomes.This trial was registered at clinicaltrials.gov as NCT03533712.

Maternal Periconceptional Folic Acid Supplementation and Risk for Fetal Congenital Heart Defects.

OBJECTIVE: To determine the effects of maternal periconceptional supplementation with folic acid or multiple micronutrients containing folic acid on the prevention of fetal congenital heart defects (CHDs). STUDY DESIGN: Data were drawn from a Prenatal Health Care System and a Birth Defects Surveillance System in a district of Beijing, China. A total of 63 969 singleton births, live or stillborn, 308 CHDs among them, during 2013 to 2018 were included. Associations between different patterns of supplementation and risk for total CHDs or main types of CHDs were evaluated with risk ratios (RRs). RESULTS: For folic acid or multiple micronutrients containing folic acid users compared with nonusers, the adjusted RRs (ARRs) for total CHDs, critical CHD, and ventricular septal defect (VSD) were 0.60 (95% CI, 0.44-0.83), 0.41 (95% CI, 0.26-0.67), and 0.47 (95% CI, 0.30-0.74), respectively. When we compared multiple micronutrients containing folic acid users with folic acid users, the ARRs were 0.84 (95% CI, 0.66-1.09), 0.64 (95% CI, 0.41-1.00), and 0.94 (95% CI, 0.63-1.41) for total CHDs, critical CHD, and VSD, respectively. We also found that, compared with supplementation initiated after conception, supplementation initiated before conception was associated with a lower risk for CHDs: the ARRs were 0.68 (95% CI, 0.48-0.95) for total CHDs and 0.26 (95% CI, 0.10-0.71) for critical CHD, but 1.08 (95% CI, 0.63-1.83) for VSD. CONCLUSIONS: Maternal periconceptional supplementation with folic acid or multiple micronutrients containing folic acid seems to decrease the risk for CHDs, especially critical CHD, in offspring. Supplementation confers a greater protective effect when it is initiated before conception. We did not find any difference between folic acid and multiple micronutrients containing folic acid in terms of preventing CHDs.

Impact of scaling up prenatal nutrition interventions on human capital outcomes in low- and middle-income countries: a modeling analysis.

BACKGROUND: Prenatal nutrition interventions can lead to improved birth outcomes, which in turn are associated with better education and human capital outcomes later in life. OBJECTIVE: We estimated the impact of scaling up iron-folic acid (IFA), calcium, multiple micronutrient (MMS), and balanced energy protein (BEP) supplementation for pregnant women, on human capital outcomes in low- and middle-income countries (LMIC). METHODS: We used mathematical modeling with proportional reductions in adverse birth outcomes to estimate the potential gains in school years and lifetime income due to scaling up each prenatal nutrition intervention. Estimates of intervention effects on birth outcomes were derived from meta-analyses of randomized trials. Estimates of the associations between birth outcomes and schooling and lifetime income were derived from de novo meta-analyses of observational studies. RESULTS: Across 132 LMIC, scaling up prenatal nutrition interventions to 90% coverage was estimated to increase school years and lifetime income per birth cohort by: 2.28 million y (95% uncertainty intervals (UI): -0.44, 6.26) and $8.26 billion (95% UI: -1.60, 22.4) for IFA; 4.08 million y (95% UI: 0.12, 9.68) and $18.9 billion (95% UI: 0.59, 44.6) for calcium; 5.02 million y (95% UI: 1.07, 11.0) and $18.1 billion (95% UI: 3.88, 39.1) for MMS; and 0.53 million y (95% UI: -0.49, 1.70) and $1.34 billion (95% UI: -1.10, 3.10 billion) for BEP supplementation. South Asia and Sub-Saharan Africa tended to have the largest estimated regional gains in school years for scaling up each intervention due to the large population size and high burden of poor birth outcomes. Absolute income benefits for each intervention were estimated to be the largest in Latin America, where returns to education and incomes are higher relative to other regions. CONCLUSION: Increasing coverage of prenatal nutrition interventions in LMIC may lead to substantial gains in schooling and lifetime income. Decision makers should consider the potential long-term human capital returns of investments in maternal nutrition.

Maternal periconceptional folic acid supplements use and fetus risk for limb defects.

BACKGROUND: Associations between the periconceptional folic acid only (FAO) or multiple micronutrients containing folic acid (MMFA) supplementation and risk for limb defects are inconsistent. OBJECTIVE: To explore the association between periconceptional folic acid supplements use and risk for limb defects, including clubfoot, polydactyly, syndactyly, and limb deficiencies. METHODS: Data were derived from a cohort based on a pregnancy registry in a district of Beijing, China, from 2013 to 2018. Information on maternal periconceptional FAO and MMFA supplementation was collected via face-to-face interviews at first trimester. Pregnancy outcomes including limb defects were ascertained in livebirths, stillbirths, and elective pregnancy terminations and were recorded into the system. Propensity score methods were used to adjust for potential confounders. RESULTS: A total of 63 969 women with a singleton delivery were included. The overall prevalence of limb defects was 47.5 per 10 000 (n = 63 969) singleton deliveries. Decreased prevalence of limb defects was found among FAO/MMFA users compared with women who did not take supplements (nonusers) (46.1 vs. 61.9 per 10 000 births, adjusted risk ratio [RR] 0.80, 95% confidence interval [CI] 0.56, 1.12). Compared with nonusers (n = 6462, 10.2%), women who took either FAO (n = 26 567, 42.0%) or MMFA (n = 30 259, 47.8%) had a lower risk for total clubfoot (RR 0.40, 95% CI 0.20, 0.84), and for isolated clubfoot (RR 0.41, 95% CI 0.17, 0.97). For other limb defects except clubfoot, FAO supplementation did not appear to be associated with reduced risk, while MMFA supplementation group had 30%-50% reduced risks for other limb defects. A lower risk for limb defects or isolated limb defects was found with MMFA supplementation when FAO supplementation was used as a control. CONCLUSIONS: Maternal periconceptional supplements with either FAO or MMFA had inverse association with clubfoot in offspring, and MMFA was associated with lower risk for isolated limb defects compared with FAO.

Preconception micronutrient supplementation positively affects child intellectual functioning at 6 y of age: A randomized controlled trial in Vietnam.

BACKGROUND: Although there is growing evidence on the role of preconception nutrition for birth outcomes, very few studies have evaluated the long-term effects of nutrition interventions during the preconception period on offspring cognitive outcomes. OBJECTIVE: We evaluate the impact of preconception weekly multiple micronutrients (MMs) or iron and folic acid (IFA) supplementation compared with folic acid (FA) alone on offspring intellectual functioning at age 6-7 y. METHODS: We followed 1599 offspring born to women who participated in a double-blinded randomized controlled trial of preconception supplementation in Vietnam. Women received weekly supplements containing either 2800 µg FA only, 60 mg iron and 2800 µg FA, or MMs (15 micronutrients including IFA) from baseline until conception, followed by daily prenatal IFA supplements until delivery. We used the Wechsler Intelligence Scale for Children to measure full-scale IQ (FSIQ) and 4 related domains of intellectual functioning [Verbal Comprehension Index (VCI), Perceptual Reasoning Index (PRI), Working Memory Index (WMI), and Processing Speed Index (PSI) scores] at 6-7 y. Group comparisons were done using ANOVA tests for all children and the subgroup born to women who consumed the supplements ≥26 wk before conception (per-protocol analyses). RESULTS: The final sample with data at 6-7 y (n = 1321) was similar for baseline maternal and offspring birth characteristics and age at follow-up by treatment group. Compared with the offspring in the FA group, those in the MM group had higher FSIQ (ß = 1.7; 95% CI: 0.1, 3.3), WMI (ß = 1.7; 95% CI: 0.2, 3.2), and PSI (ß = 2.5; 95% CI: 0.9, 4.1). Similar findings were observed in the per-protocol analyses. There were no significant differences by treatment group for VCI and PRI. CONCLUSIONS: Preconception supplementation with MMs improved certain domains of intellectual functioning at age 6-7 y compared with FA. These findings suggest the potential for preconception micronutrient interventions to have long-term benefits for offspring cognition.

Consumption of multiple micronutrients or small-quantity lipid-based nutrient supplements containing iodine at the recommended dose during pregnancy, compared with iron and folic acid, does not affect women's urinary iodine concentration in rural Malawi: a secondary outcome analysis of the iLiNS DYAD trial.

OBJECTIVES: Inadequate iodine intake during pregnancy increases the risk of neonatal morbidity and mortality. We aimed to evaluate whether prenatal supplements containing iodine affect urinary iodine concentrations (UIC) of pregnant women in Malawi. DESIGN: A randomised controlled trial. Pregnant women (n 1391) were assigned to consume 60 mg/d Fe and 400 µg/d folic acid (IFA) or 18 vitamins and minerals including 250 µg/d iodine (MMN) or 20 g/d small-quantity lipid-based nutrient supplements (SQ-LNS) with similar nutrient contents as MMN group, plus macronutrients (LNS) until childbirth. In a sub-study (n 317), we evaluated group geometric mean urinary iodine concentration (UIC) (µg/L) at 36 weeks of gestation controlling for baseline UIC and compared median (baseline) and geometric mean (36 weeks) UIC with WHO cut-offs: UIC < 150, 150-249, 250-499 and ≥500 reflecting insufficient, adequate, above requirements and excessive iodine intakes, respectively. SETTING: Mangochi District, Malawi. PARTICIPANTS: Women ≤20 weeks pregnant. RESULTS: Groups had comparable background characteristics. At baseline, overall median (Q1, Q3) UIC (319 (167, 559)) suggested iodine intakes above requirements. At 36 weeks, the geometric mean (95 % CI) UIC of the IFA (197 (171, 226)), MMN (212 (185, 243)) and LNS (220 (192, 253)) groups did not differ (P = 0·53) and reflected adequate intakes. CONCLUSIONS: In this setting, provision of supplements containing iodine at the recommended dose to pregnant women with relatively high iodine intakes at baseline, presumably from iodised salt, has no impact on the women's UIC. Regular monitoring of the iodine status of pregnant women in such settings is advisable. Clinicaltrials.gov identifier: NCT01239693.

Provision of Lipid-Based Nutrient Supplements to Mothers During Pregnancy and 6 Months Postpartum and to Their Infants from 6 to 18 Months Promotes Infant Gut Microbiota Diversity at 18 Months of Age but Not Microbiota Maturation in a Rural Malawian Setting: Secondary Outcomes of a Randomized Trial.

BACKGROUND: Diet may alter the configuration of gut microbiota, but the impact of prenatal and postnatal nutritional interventions on infant gut microbiota has not been investigated. OBJECTIVE: We evaluated whether providing lipid-based nutrient supplements (LNSs) to mother-infant dyads promotes a more diverse and mature infant gut microbiota, compared to maternal supplementation with multiple micronutrients (MMN) or iron and folic acid (IFA). METHODS: We enrolled 869 pregnant women in a randomized trial in Malawi. There were 3 study groups, with women receiving 1 MMN capsule daily during pregnancy and 6 mo postpartum, or 1 LNS sachet (20 g) daily during pregnancy and 6 mo postpartum, or 1 IFA capsule daily (during pregnancy) then a placebo daily (postpartum). Infants in the LNS group received LNS from 6 to 18 mo; infants in the other groups did not receive supplements. The infants' fecal microbiota were characterized by PCR amplification and sequencing of the bacterial 16S rRNA gene (variable region 4). The primary outcomes were microbiota α diversity and maturation [as microbiota-for-age z score (MAZ)]. Specific associations of taxa with intervention were established with indicator species analysis (ISA). RESULTS: Primary outcomes did not differ between IFA and MMN groups, so these groups were combined (IFA + MMN). Mean ± SD α diversity was higher in the LNS group at 18 mo for Shannon index [3.01 ± 0.57 (LNS) compared with 2.91 ± 0.60 (IFA + MMN), P = 0.032] and Pielou's evenness index [0.61 ± 0.08 (LNS) compared with 0.60 ± 0.09 (IFA + MMN), P = 0.043]; no significant differences were observed at 1, 6, 12, or 30 mo. MAZ and ß diversity did not differ at any age. We found 10 and 3 operational taxonomic units (OTUs) positively associated with LNS and IFA + MMN, respectively; however, these associations became nonsignificant following false discovery rate correction at 10%. CONCLUSIONS: Prenatal and postnatal LNS intake promoted infant gut microbiota diversity at 18 mo, after 12 mo of child supplementation, but did not alter microbiota maturation. This trial was registered at clinicaltrials.gov as NCT01239693.

Effect of multi-pronged interventions in reducing low birth weight and maternal anaemia among pregnant women. A community-based interventions research in non-agrarian resource constrained setting of rural Pakistan.

OBJECTIVE: To investigate the effect on maternal and infant health of iron plus folate and multiple micronutrient supplements, along with deworming and health education session provided to pregnant women in rural, nonagrarian and food-insecure areas. METHODS: The quasi-experimental study was conducted in Tharparker and Umerkot districts, Sindh, Pakistan, in 2013-14, and comprised pregnant women in their earlier weeks of pregnancy. The enrolment and follow-up phase entailed 3 visits to each subject. Areas covered by lady health workers were designated as intervention areas, and those with non-LHW population were labelled as non-intervention areas. RESULTS: Of the 1204 subjects, 600(49.8%) were in the intervention group and 604(50.2%) were in the nonintervention group. By the end of the follow-up phase, significantly more women had increased number of meals in the intervention group compared to the non-intervention group (p<0.001). There was a significantly higher increase in mean haemoglobin levels and body mass index of women in the intervention arm after 3 and 6 months of interventions (p<0.05). Significantly higher mean birth weight was recorded in intervention areas compared to nonintervention areas (p<0.05). CONCLUSIONS: Community-based provision of multiple micronutrients to women along with deworming, health education and dietary counselling significantly reduced the prevalence of anaemia and reduced the incidence of low birth weight.

Acknowledging the gap: a systematic review of micronutrient supplementation in infants under six months of age.

Background: Micronutrient deficiencies remain common worldwide, but the consequences to growth and development in early infancy (under six months of age) are not fully understood. We present a systematic review of micronutrient interventions in term infants under six months of age, with a specific focus on iron supplementation. Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid) and Embase (Ovid) from January 1980 through December 2019. Interventions included iron or multiple micronutrients (MMNs). Results: Of 11,109 records identified, 33 publications from 24 trials were included (19 iron and five MMN supplementation trials). All but one trial (evaluating only morbidity and mortality) evaluated the effect of supplementation on biochemical outcomes, ten reported on growth, 15 on morbidity and/or mortality and six on neuro-behavioural development. Low- and middle- income countries made up 88% (22/25) of the total trial locations. Meta-analysis was not possible due to extensive heterogeneity in both exposure and outcome measures.  However, these trials indicated that infants less than six months of age benefit biochemically from early supplementation with iron, but the effect of additional nutrients or MMNs, along with the impacts on growth, morbidity and/or mortality, and neuro-behavioural outcomes remain unclear. Conclusions: Infants less than six months of age appear to benefit biochemically from micronutrient supplementation. However, well-powered randomised controlled trials are required to determine whether routine supplementation with iron or MMNs containing iron should commence before six months of life in exclusively breast-fed infants in low-resource settings.

Maternal Multiple Micronutrient Supplementation Stabilizes Mitochondrial DNA Copy Number in Pregnant Women in Lombok, Indonesia.

BACKGROUND: The Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT) in Lombok, Indonesia showed that maternal multiple micronutrients (MMN), as compared with iron and folic acid (IFA), reduced fetal loss, early infant mortality, and low birth weight. Mitochondria play a key role during pregnancy by providing maternal metabolic energy for fetal development, but the effects of maternal supplementation during pregnancy on mitochondria are not fully understood. OBJECTIVE: The aim of this study was to assess the impact of MMN supplementation on maternal mitochondrial DNA copy number (mtDNA-CN). METHODS: We used archived venous blood specimens from pregnant women enrolled in the SUMMIT study. SUMMIT was a cluster-randomized double-blind controlled trial in which midwives were randomly assigned to distribute MMN or IFA to pregnant women. In this study, we selected 108 sets of paired baseline and postsupplementation samples (MMN = 54 and IFA = 54). Maternal mtDNA-CN was determined by real-time quantitative polymerase chain reaction in baseline and postsupplementation specimens. The association between supplementation type and change in mtDNA-CN was performed using rank-based estimation for linear models. RESULTS: In both groups, maternal mtDNA-CN at postsupplementation was significantly elevated compared with baseline (P < 0.001). The regression revealed that the MMN group had lower postsupplementation mtDNA-CN than the IFA group (ß = -4.63, P = 0.003), especially for women with mtDNA-CN levels above the median at baseline (ß = -7.49, P = 0.007). This effect was rapid, and observed within 33 d of initiation of supplementation (ß = -7.39, P = 0.017). CONCLUSION: Maternal MMN supplementation rapidly stabilized mtDNA-CN in pregnant women who participated in SUMMIT, indicating improved mitochondrial efficiency. The data provide a mechanistic basis for the beneficial effects of MMN on fetal growth and survival, and support the transition from routine IFA to MMN supplementation.This trial was registered at www.isrctn.com as ISRCTN34151616.

The Impact of Preconceptional Multiple-Micronutrient Supplementation on Female Fertility.

In industrialized countries, fertility has declined in recent years to the lowest recorded levels. Identifying modifiable factors that influence human fertility, such as diet, is therefore of major clinical and public health relevance. Micronutrient status is a modifiable risk factor that may have an impact on female fertility, as essential vitamins and minerals have important roles in the physiological processes that are involved. Adequate levels are important for oocyte quality, maturation, fertilization, and implantation, whereas antioxidants are vital to reduce oxidative stress, a process known to impair fertility. In women who are diagnosed as infertile, lower than recommended levels of certain micronutrients have been reported. A similar scenario has been found in a proportion of women of childbearing age in general, some of whom may be struggling to conceive. Supplementation studies with multiple micronutrients are still scarce, but the literature suggests that supplementation before conception can help restore micronutrient status to recommended levels and reduce oxidative stress when antioxidants are included. Overall, supplementation has a small but beneficial effect on fertility in healthy and infertile women, including a shorter time to pregnancy and an increased chance of becoming pregnant. Nevertheless, many studies are small or observational, and adequately powered randomized controlled trials of supplementation with multiple micronutrients are necessary to confirm any definite effects on fertility. This review substantiates the potential benefits of micronutrient supplementation beyond the prevention of neural tube defects, the traditionally viewed value of prenatal vitamin use.

A feasibility study of multiple micronutrient supplement for home fortification of foods among Orang Asli children in Negeri Sembilan, Malaysia

@# Introduction: The prevalence of child undernutrition and micronutrient deficiencies are higher in the Orang Asli (OA) than the general Malaysian population. The World Health Organization recommends the use of multiple micronutrient supplement (MMS) that is a blend of micronutrients in powder form that can be sprinkled onto foods for home fortification to prevent undernutrition among children. This pilot study aimed to assess the feasibility of using MMS among OA children. Methods: A total of 25 OA children (14 boys and 11 girls) aged 6-31 months (mean±SD = 15.7±7.2 months) in Negeri Sembilan were given three sachets of MMS weekly for 5 weeks. Caregivers were instructed to add MMS to three types of food from the same food group per week varying with a different food group weekly. Written instruction for using MMS in simple language was given prior to the supplementation. Caregivers were interviewed for information on socio-demographics, compliance, acceptance, preference and adverse effect of MMS. Results: A high level of compliance was observed (85%). All caregivers reported that the instructions for use were easy to read. No noticeable changes to the foods mixed with MMS were observed and no adverse effects were reported. Conclusion: This study demonstrated feasibility of the use of MMS for future trials among OA children. The easy to read information that comes with the MMS, frequent monitoring of MMS use and support to caregivers were required to ensure compliance. Cultural feeding practices and financial constraints may limit the types of food that can be mixed with MMS.

Strategies for optimizing maternal nutrition to promote infant development.

BACKGROUND: The growing appreciation of the multi-faceted importance of optimal maternal nutrition to the health and development of the infant and young child is tempered by incompletely resolved strategies for combatting challenges. OBJECTIVE: To review the importance of maternal nutrition and strategies being employed to optimize outcomes. METHODS: Selected data from recent literature with special focus on rationale for and currently published results of maternal nutrition supplements, including lipid based nutrition supplements. RESULTS: 1) An impelling rationale for improving the maternal and in utero environment of low resource populations has emerged to achieve improved fetal and post-natal growth and development. 2) Based partly on population increases in adult height over one-two generations, much can be achieved by reducing poverty. 3) Maternal, newborn and infant characteristics associated with low resource environments include evidence of undernutrition, manifested by underweight and impaired linear growth. 4) Apart from broad public health and educational initiatives, to date, most specific efforts to improve fetal growth and development have included maternal nutrition interventions during gestation. 5) The relatively limited but real benefits of both iron/folic acid (IFA) and multiple micronutrient (MMN) maternal supplements during gestation have now been reasonably defined. 6) Recent investigations of a maternal lipid-based primarily micronutrient supplement (LNS) have not demonstrated a consistent benefit beyond MMN alone. 7) However, effects of both MMN and LNS appear to be enhanced by commencing early in gestation. CONCLUSIONS: Poor maternal nutritional status is one of a very few specific factors in the human that not only contributes to impaired fetal and early post-natal growth but for which maternal interventions have demonstrated improved in utero development, documented primarily by both improvements in low birth weights and by partial corrections of impaired birth length. A clearer definition of the benefits achievable by interventions specifically focused on correcting maternal nutrition deficits should not be limited to improvements in the quality of maternal nutrition supplements, but on the cumulative quantity and timing of interventions (also recognizing the heterogeneity between populations). Finally, in an ideal world these steps are only a prelude to improvements in the total environment in which optimal nutrition and other health determinants can be achieved.

Ghanaian parents' perceptions of pre and postnatal nutrient supplements and their effects.

Small-quantity lipid-based nutrient supplements (SQ-LNS) have been studied in efficacy and effectiveness trials, but little is known about how parents perceive the products and their effects. In a randomised trial in Ghana, efficacy of SQ-LNS provided to women during pregnancy and the first 6 months postpartum and to their children from 6 to 18 months of age was assessed by comparison with iron-folic acid (IFA) capsules and multiple micronutrient (MMN) capsules provided to women. In a follow-up study conducted when the index children from the original trial were between 4 and 6 years of age, we used survey-based methods to assess retrospective and current parental perceptions of nutrient supplements generally and of SQ-LNS and their effects compared with perceptions IFA and MMN capsules. Most parents perceived that the assigned supplements (SQ-LNS, IFA, or MMN) positively impacted the mother during pregnancy (approximately 89% of both mothers and fathers) and during lactation (84% of mothers and 86% of fathers). Almost all (≥90%) of mothers and fathers perceived that the assigned supplement positively impacted the index child and expected continued positive impacts on the child's health and human capital into the future. A smaller percentage of parents perceived negative impacts of the supplements (7%-17% of mothers and 4%-12% of fathers). Perceptions of positive impacts and of negative impacts did not differ by intervention group. The results suggest that similar populations would likely be receptive to programs to deliver SQ-LNS or micronutrient capsules.

The WHO recommendation of home fortification of foods with multiple-micronutrient powders in children under 2 years of age and its effectiveness on anaemia and weight: a pragmatic cluster-randomized controlled trial.

OBJECTIVE: To assess under real community settings the effectiveness of the WHO strategy of home fortification of foods (HFF) with multiple-micronutrient powders on Hb change, anaemia and weight in children. DESIGN: A pragmatic cluster-randomized controlled trial. SETTING: Forty villages in the Nioro Circle in Mali and 722 children aged 6-23 months were randomized to the intervention or control group. The intervention consisted of a daily dose of multiple-micronutrient powder for 3 months; in the control group, no supplement was given. In both groups, mothers received group education on child complementary feeding. Changes in weight, Hb concentration and anaemia were assessed as primary outcomes at baseline and 3 months. The HFF effect was determined using regression analyses and quantile regression with standard errors taking account of the cluster design. SUBJECTS: Children aged 6-23 months. RESULTS: Overall prevalence of anaemia in the sample was high: 90 %. HFF provided a modest but statistically significant Hb change v. no intervention (0·50 v. 0·09 g/dl, P=0·023). Prevalence of anaemia changed little: 91·3-85·8 % (P=0·04) in the intervention group v. 88·1-87·5 % % (P=0·86) in the control group. Proportion of severe anaemia was reduced by 84 % (from 9·8 to 1·6 %) in the intervention group, but increased in the control group (from 8·5 to 10·8 %). No effect was observed on weight. CONCLUSIONS: The WHO HFF strategy to fight anaemia showed a modest change on Hb concentration and significantly reduced the rate of severe anaemia.

Multi-micronutrient supplementation during pregnancy for prevention of maternal anaemia and adverse birth outcomes in a high-altitude area: a prospective cohort study in rural Tibet of China.

Anaemia during pregnancy, characterised by Hb <110 g/l, is a specific risk factor for adverse maternal and perinatal outcomes in developing countries. The objective of this study was to determine the effectiveness of daily antenatal supplementation with multiple micronutrients (MMN) compared with folic acid (FA) on the occurrence of anaemia among pregnant women and their infants' health in a high-altitude area. A prospective cohort study was carried out in two rural counties in Tibet from 2007 to 2012. A total of 1149 eligible pregnant women were allocated daily supplementation with FA in one county and MMN containing a recommended allowance of twenty-three vitamins and minerals in another county starting ≤24 weeks of gestation and continuing until delivery. Compared with the FA group, prenatal supplementation with MMN was significantly associated with reduced odds of anaemia in the third trimester. This was demonstrated in the primary outcome, with an adjusted OR (AOR) of 0·63; 95 % CI 0·45, 0·88 and P=0·007 and also reduced odds of preterm delivery (AOR: 0·31; 95 % CI 0·15, 0·61; P=0·001). There was no difference between MMN and FA groups in mean birth weight (adjusted mean difference: 36·78; 95 % CI -19·42, 92·98 g; P=0·200), whereas MMN supplementation significantly reduced the odds of low-birth weight (LBW) babies (AOR: 0·58; 95 % CI 0·36, 0·91; P=0·019). In conclusion, the antenatal MMN supplementation in rural Tibet is associated with a reduction of maternal anaemia in the third trimester, and may potentially decrease the risk of preterm delivery and LBW babies.