Maternal and Child Supplementation with Lipid-Based Nutrient Supplements, but Not Child Supplementation Alone, Decreases Self-Reported Household Food Insecurity in Some Settings.

Background: It is unknown whether self-reported measures of household food insecurity change in response to food-based nutrient supplementation.Objective: We assessed the impacts of providing lipid-based nutrient supplements (LNSs) to women during pregnancy and postpartum and/or to their children on self-reported household food insecurity in Malawi [DOSE and DYAD trial in Malawi (DYAD-M)], Ghana [DYAD trial in Ghana (DYAD-G)], and Bangladesh [Rang-Din Nutrition Study (RDNS) trial].Methods: Longitudinal household food-insecurity data were collected during 3 individually randomized trials and 1 cluster-randomized trial testing the efficacy or effectiveness of LNSs (generally 118 kcal/d). Seasonally adjusted Household Food Insecurity Access Scale (HFIAS) scores were constructed for 1127 DOSE households, 732 DYAD-M households, 1109 DYAD-G households, and 3671 RDNS households. The impact of providing LNSs to women during pregnancy and the first 6 mo postpartum and/or to their children from 6 to 18-24 mo on seasonally adjusted HFIAS scores was assessed by using negative binomial models (DOSE, DYAD-M, and DYAD-G trials) and mixed-effect negative binomial models (RDNS trial).Results: In the DOSE and DYAD-G trials, seasonally adjusted HFIAS scores were not different between the LNS and non-LNS groups. In the DYAD-M trial, the average household food-insecurity scores were 14% lower (P = 0.01) in LNS households than in non-LNS households. In the RDNS trial, compared with non-LNS households, food-insecurity scores were 17% lower (P = 0.02) during pregnancy and the first 6 mo postpartum and 15% lower (P = 0.02) at 6-24 mo postpartum in LNS households.Conclusions: The daily provision of LNSs to mothers and their children throughout much of the "first 1000 d" may improve household food security in some settings, which could be viewed as an additional benefit that may accrue in households should policy makers choose to invest in LNSs to promote child growth and development. These trials were registered at clinicaltrials.gov as NCT00945698 (DOSE) NCT01239693 (DYAD-M), NCT00970866 (DYAD-G) and NCT01715038 (RDNS).

Lipid-based nutrient supplementation in the first 1000 d improves child growth in Bangladesh: a cluster-randomized effectiveness trial.

Background: Stunting in linear growth occurs mainly during the first 1000 d, from conception through 24 mo of age. Despite the recognition of this critical period, there have been few evaluations of the growth impact of interventions that cover most of this window.Objective: We evaluated home fortification approaches for preventing maternal and child undernutrition within a community-based health program. We hypothesized that small-quantity lipid-based nutrient supplements (LNSs) provided to women during pregnancy and the first 6 mo postpartum, LNSs provided to their offspring from 6 to 24 mo of age, or both would result in greater child length-for-age z score (LAZ) at 24 mo than iron and folic acid (IFA) provided to women during pregnancy and postpartum plus micronutrient powder (MNP) or no supplementation for their offspring from 6 to 24 mo.Design: We conducted a cluster-randomized effectiveness trial with 4 arms: 1) women and children both received LNSs (LNS-LNS group), 2) women received IFA and children received LNSs (IFA-LNS group), 3) women received IFA and children received MNP (IFA-MNP group), and 4) women received IFA and children received no supplements (IFA-Control group). We enrolled 4011 women at ≤20 wk of gestation within 64 clusters, each comprising the supervision area of a community health worker. Analyses were primarily performed by using ANCOVA F tests and Tukey-Kramer-corrected pairwise comparisons.Results: At 24 mo, the LNS-LNS group had significantly higher LAZ (+0.13 compared with the IFA-MNP group) and head circumference (+0.15 z score compared with the IFA-Control group); these outcomes did not differ between the other groups. Stunting prevalence (LAZ <-2) was lower in the LNS-LNS group at 18 mo than in the IFA-MNP group (OR: 0.70; 95% CI: 0.53, 0.92), but the difference diminished by 24 mo (OR: 0.81; 95% CI: 0.63, 1.04).Conclusion: Home fortification with small-quantity LNSs, but not MNP, during the first 1000 d improved child linear growth and head size in rural Bangladesh. This trial was registered at clinicaltrials.gov as NCT01715038.

Low-dose oral interferon modulates expression of inflammatory and autoimmune genes in cattle.

While the safety and efficacy profiles of orally administered bovine interferon (IFN) alpha have been documented, the mechanism(s) that result in clinical benefits remain elusive. One approach to delineating the molecular pathways of IFN efficacy is through the use of gene expression profiling technologies. In this proof-of-concept study, different (0, 50, 200 and 800 units) oral doses of natural bovine IFN (type I) were tested in cattle to determine if oral IFN altered the expression of genes that may be pivotal to the development of systemic resistance to viral infections such as foot-and-mouth disease (FMD). Oral IFN was administered twice: Time 0 and 8h later. Blood was collected at 0, 8 and 24h after the first IFN administration, and DNA isolated from peripheral blood mononuclear cells (PBMCs) was employed in quantitative polymerase chain reaction (qPCR) microarray assays. Within 8h, 50 and 200 units of oral IFN induced significant (P<0.05) changes in expression of 41 of 92 tested autoimmune and inflammatory response-associated genes. These data suggest that orally administered IFN is a viable approach for providing short-term antiviral immunity to livestock exposed to viruses such as FMD virus (FMDV) until such a time that an effective vaccine can be produced and distributed to producers.

Lipid-based nutrient supplements for pregnant women reduce newborn stunting in a cluster-randomized controlled effectiveness trial in Bangladesh.

BACKGROUND: Maternal undernutrition and newborn stunting [birth length-for-age z score (LAZ) <-2] are common in Bangladesh. OBJECTIVE: The objective was to evaluate the effect of lipid-based nutrient supplements for pregnant and lactating women (LNS-PLs) on birth outcomes. DESIGN: We conducted a cluster-randomized effectiveness trial (the Rang-Din Nutrition Study) within a community health program in rural Bangladesh. We enrolled 4011 pregnant women at ≤20 gestational weeks; 48 clusters received iron and folic acid (IFA; 60 mg Fe + 400 µg folic acid) and 16 clusters received LNS-PLs (20 g/d, 118 kcal) containing essential fatty acids and 22 vitamins and minerals. Both of the supplements were intended for daily consumption until delivery. Primary outcomes were birth weight and length. RESULTS: Infants in the LNS-PL group had higher birth weights (2629 ± 408 compared with 2588 ± 413 g; P = 0.007), weight-for-age z scores (-1.48 ± 1.01 compared with -1.59 ± 1.02; P = 0.006), head-circumference-for-age z scores (HCZs; -1.26 ± 1.08 compared with -1.34 ± 1.12; P = 0.028), and body mass index z scores (-1.57 ± 1.05 compared with -1.66 ± 1.03; P = 0.005) than those in the IFA group; in adjusted models, the differences in length (47.6 ± 0.07 compared with 47.4 ± 0.04 cm; P = 0.043) and LAZ (-1.15 ± 0.04 compared with -1.24 ± 0.02; P = 0.035) were also significant. LNS-PLs reduced the risk of newborn stunting (18.7% compared with 22.6%; RR: 0.83; 95% CI: 0.71, 0.97) and small head size (HCZ <-2) (20.7% compared with 24.9%; RR: 0.85; 95% CI: 0.73, 0.98). The effects of LNS-PL on newborn stunting were greatest in infants born before a 10-wk interruption in LNS-PL distribution (n = 1301; 15.7% compared with 23.6%; adjusted RR: 0.69; 95% CI: 0.53, 0.89) and in infants born to women ≤24 y of age or with household food insecurity. CONCLUSION: Prenatal lipid-based nutrient supplements can improve birth outcomes in Bangladeshi women, especially those at higher risk of fetal growth restriction. This trial was registered at clinicaltrials.gov as NCT01715038.

Low-dose oral interferon alpha as prophylaxis against viral respiratory illness: a double-blind, parallel controlled trial during an influenza pandemic year.

BACKGROUND AND OBJECTIVE: Interferon alpha (IFNα) is a known antiviral agent. A double-blind, placebo-controlled clinical trial was conducted investigating the use of low-dose oral interferon alpha for preventing acute viral respiratory illnesses. METHODS: Two hundred healthy adults aged 18-75 years were enrolled and completed weekly health data questionnaires to monitor for symptoms and impact of respiratory illness. Serum samples were tested for antibodies against influenza and other common respiratory viruses. RESULTS: Low-dose oral IFNα prophylaxis did not reduce the incidence or impact of acute respiratory illness (ARI) or the impact of illness on daily activities. Post hoc analysis of participant subgroups, however, identified significant reductions in the incidence of ARI reported by males, those aged 50 years or more and those who received the 2009 seasonal influenza vaccine. Interferon alpha prophylaxis had a significant impact on the reporting of moderate-to-severe feverishness by the study population. Seropositive participants in the IFN group were more likely to report asymptomatic or mild symptoms compared with those in the placebo group who were more likely to report stronger symptoms. CONCLUSIONS: Low-dose oral IFNα prophylaxis was not effective in limiting the overall incidence of ARI in our study population. However, there was evidence that prophylaxis reduced the severity of symptoms and had a beneficial effect in some subpopulations, including those who received the 2009 seasonal trivalent influenza vaccination.

Oromucosal Administration of Interferon to Humans.

The prevailing dogma is that, to be systemically effective, interferon-alpha (IFNα) must be administered in sufficiently high doses to yield functional blood concentrations. Such an approach to IFNa therapy has proven effective in some instances, but high-dose parenteral IFNα therapy has the disadvantage of causing significant adverse events. Mounting evidence suggests that IFNα delivered into the oral cavity in low doses interacts with the oral mucosa in a unique manner to induce systemic host defense mechanisms without IFNα actually entering the circulation, thus reducing the potential for toxic side effects. A better understanding of the applications and potential benefits of this treatment modality are under active investigation. This paper provides a review of the relevant literature on the clinical use of the oromucosal route of administration of interferon, with an emphasis on the treatment of influenza.

Protection from lethal influenza virus challenge by oral type 1 interferon.

The persistence of highly pathogenic avian influenza within wild bird populations has forged interest in control measures to limit a possible human pandemic. We therefore investigated the efficacy of low dose oral administration of IFN-alpha as a potential therapy against influenza infection in a murine model. We have identified an optimal low oral dose of IFN-alpha that when delivered daily as prophylactic therapy protects C57BL/6J mice from a lethal challenge with mouse adapted human influenza virus A/PR/8/34 (H1N1). These results provide strong support for the application of low dose type 1 IFN pretreatment to human influenza control.

A third study on the use of orally administered anhydrous crystalline maltose for relief of dry mouth in primary Sjögren's syndrome.

OBJECTIVES: To examine the safety and efficacy of anhydrous crystalline maltose for treatment of dry mouth and other symptoms of dryness in patients with primary Sjögren's syndrome. DESIGN: Anhydrous crystalline maltose was delivered orally as a 200-mg lozenge given three times daily over a 24-week period to a total of 100 subjects. All participants had prominent complaints of persistent dry mouth associated with primary Sjögren's syndrome. Patients were examined at baseline and every 6 weeks of treatment. SETTINGS: Patients were seen in outpatient clinics at a total of 27 sites within the United States. OUTCOME MEASURES: Unstimulated whole saliva output, a measure of basal salivary gland function, was determined at each visit. Symptoms associated with oral and ocular dryness were assessed at the same time with the use of 100-mm visual analogue scales. Safety was assessed by physical examination and laboratory studies. RESULTS: During this clinical trial, a majority of evaluable subjects (39/76) demonstrated an increase in unstimulated whole saliva output, and the treatment exhibited an excellent safety profile. The anhydrous crystalline maltose treatment led to significant improvement in several subjective measures of oral and ocular comfort. CONCLUSIONS: In this study, anhydrous crystalline maltose lozenges administered three times daily for 24 weeks improved salivary output and decreased complaints of dry mouth and eyes in patients with primary Sjögren's syndrome. Side-effects were minimal, and treatment was without significant adverse events. These results are similar to the benefits observed in two prior studies reported by the authors. This safe and simple intervention appears to provide clinical benefit to primary Sjögren's syndrome patients with distressing dry mouth symptoms.