Balanced Protein Energy Research Articles

A formative study of the sociocultural influences on dietary behaviours during pregnancy in rural Bangladesh.

Balanced energy protein supplementation (BEP) is recommended for contexts of high maternal undernutrition by the World Health Organization. Despite recent improvements in undernutrition, Bangladesh remains a context where BEP could help accelerate progress towards nutrition goals. In preparation for an effective trial testing a fortified BEP, a qualitative study was undertaken to better understand sociocultural factors influencing dietary behaviours in pregnancy. Married women of reproductive age (n = 23), their husbands (n = 6) and mothers-in-law (n = 6) were interviewed, and focus group discussions were conducted with women (n = 4). Women had a clear understanding of which nutritious foods are important to consume during pregnancy, including green leafy vegetables, dairy and other animal-source foods. Many explained affordability as a barrier to consuming those foods with the desired frequency. Women acquired information about diet and nutrition in pregnancy from community health workers as well as other women in the community. Most preferred to seek information from their own networks before formal health care providers. Women and husbands generally had positive views about micronutrient supplements, although some mothers-in-law were more hesitant. Some food taboos relating to the consumption of certain foods like duck and pigeon meat persist, mainly stemming from concerns for the unborn child. Opportunities exist to build on existing perceptions of healthy diets, potentially framing food or nutrient supplements as a beneficial 'add-on' to promote a healthy pregnancy. There is a scope to strengthen nutrition counselling, especially for the family members, to dispel myths and misconceptions and promote dietary and other support for pregnant women.

Perinatal intervention strategies providing food with micronutrients to pregnant and breastfeeding women in low‐ and middle‐income countries: A scoping review

AbstractIn resource‐constrained settings, pregnant and breastfeeding women and girls (PBW/G) are particularly vulnerable to undernutrition. Micronutrient‐fortified balanced energy protein (BEP) supplementation may be provided to boost maternal nutritional status and improve birth and infant outcomes. We conducted a scoping review of the published literature to determine the impact of BEP and other related nutrition interventions that provided fortified food or cash along with a minimum of 3 micronutrients on maternal, birth, and infant/child outcomes in low‐ and middle‐income countries. We conducted a PubMed search using pre‐defined keywords and controlled vocabulary search terms. All titles and abstracts were reviewed for eligibility by two independent reviewers, and data were extracted according to outcome type. We identified 149 eligible research articles that reported on a total of 21 trials and/or programme evaluations which assessed the health impact of one or more products (fortified lipid‐based nutrient supplement [LNS, n = 12], fortified blended flours [n = 5], milk‐based beverages [n = 2], and local food/snacks [n = 3]) that provided 118–750 kcal/day and varying levels of protein and micronutrients. Only one of these programme evaluations assessed the impact of the provision of cash and fortified food. Effects on maternal outcomes such as gestational weight gain and duration of gestation were promising but inconsistent. Birth outcomes were reported in 15 studies, and the effects on birthweight and birth length were generally positive. Seven studies demonstrated sustained benefits on infant and child growth out of the 15 studies that reported at least one of these outcomes, although data were sparse. Additional research is needed to investigate issues of dose, cost‐effectiveness, and incorporation into multi‐component interventions.

Examining Energy and Macronutrient Intake Substitution in Home-Based Diets Among Pregnant Women in a Balanced Energy-Protein (BEP) Supplementation Trial in Sarlahi, Nepal

Examining Energy and Macronutrient Intake Substitution in Home-Based Diets Among Pregnant Women in a Balanced Energy-Protein (BEP) Supplementation Trial in Sarlahi, Nepal

Effect of a Prenatal Balanced Energy-Protein (BEP) Supplement on Gestational Weight Gain in Rural Ethiopia

Effect of a Prenatal Balanced Energy-Protein (BEP) Supplement on Gestational Weight Gain in Rural Ethiopia

Maternal Fortified Balanced Energy-Protein Supplementation Increases Diversity of the Maternal Gut Microbiome and the Capacity of Carbohydrate Uptake in Infant Gut

Maternal Fortified Balanced Energy-Protein Supplementation Increases Diversity of the Maternal Gut Microbiome and the Capacity of Carbohydrate Uptake in Infant Gut

Effect of maternal postnatal balanced energy protein supplementation and infant azithromycin on infant growth outcomes: an open-label randomized controlled trial

BackgroundMaternal undernutrition is a direct risk factor for infant growth faltering. ObjectivesWe evaluated the effect of postnatal balanced energy protein (BEP) supplementation in lactating women and azithromycin (AZ) in infants on infant growth outcomes. MethodsA randomized controlled superiority trial of lactating mother–newborn dyads was conducted in Karachi, Pakistan. Mothers intending to breastfeed their newborns with mid-upper arm circumference of <23 cm and live infants between 0 and 6 d of life were randomly assigned to 1 of 3 arms in a 1:1:1 ratio. Lactating mothers in the control arm received standard-of-care counseling on exclusive breastfeeding, nutrition, infant immunization, and health promotion plus iron-folate supplementation until the infant was 6 mo old. In intervention arm 1, mothers additionally received two 75-g sachets of BEP per day. In intervention arm 2, along with the standard-of-care and BEP to the mother, the infant also received 1 dose of azithromycin (20 mg/kg) at the age of 42 d . The primary outcome was infant length velocity at 6 mo. The total sample size was 957 (319 in each arm). ResultsFrom 1 August, 2018 to 19 May, 2020, 319 lactating mother–newborn dyads were randomly assigned in each arm, and the last follow-up was completed on 20 November, 2020. The mean difference in length velocity (cm/mo) between BEP alone and control was 0.01 (95% confidence interval [CI]: −0.03, 0.06), BEP plus AZ and control was 0.08 (95% CI: 0.03, 0.13), and between BEP + AZ and BEP alone was 0.06 (95% CI: 0.01, 0.11). There were 1.46% (14/957) infant deaths in the trial, and 17.9% (171/957) nonfatal events (injectable treatment and/or hospitalizations) were recorded. ConclusionsPostnatal maternal BEP supplementation and infant AZ administration could modestly improve infant growth outcomes at 6 mo, suggesting potential benefits in simultaneously addressing maternal and infant undernutrition.This trial was registered at clinicaltrials.gov as NCT03564652.

Balanced Energy Protein Supplementation in Pregnancy: Adherence and Acceptability among Pregnant Women in Rural Ethiopia

BackgroundBalanced energy protein (BEP) supplementation in pregnant women in low-and middle-income countries may reduce the risk of stillbirth and low birth weight. ObjectivesThe objective of this study was to assess the adherence to and acceptability of a corn–soy blend (CSB) BEP product among pregnant women in rural Ethiopia. MethodsThis formative study was conducted from October to November 2018 among pregnant women in the rural Amhara region of Ethiopia prior to initiation of a clinical effectiveness study (ISRCTN: 15116516). We assessed adherence and acceptability of a micronutrient-fortified CSB BEP supplement among 40 pregnant women during a 4-wk utilization period. Acceptability was assessed using a 7-point Likert-style scale about the hedonic characteristics of the BEP product at 2 wk and 4 wk. Adherence was assessed by weekly monitoring and empty sachet counts for BEP consumption over 4 wk. ResultsAdherence to the BEP was, on average, 89% over the month-long pilot. The BEP product was rated favorably (mean Likert score >6 of 7) for the following domains: color, taste, odor, and likeability at mid and endpoints. Women found the product convenient to eat [mean (standard deviation [SD] = 5.9 (1.0))] and filling (mean (SD) = 6.1 (1.5) out of 7). Scores on acceptability and perception of the product remained stable throughout the duration of use. A majority of women (63%) reported consuming the BEP as a snack to supplement meals and splitting the serving over 2 or more sessions (68%). A quarter of respondents reported sharing the supplement with family members. ConclusionsAdherence and acceptability of the CSB BEP product were high among this population in rural Amhara, Ethiopia. This formative data was important to select the final product and shape the counseling and delivery of BEP in the parent study.

The effect of balanced energy-protein supplementation provided to lactating women on maternal and infant outcomes: study protocol for a prospectively planned individual patient data (IPD) meta-analysis

Abstract* Background The high prevalence of infant stunting and maternal undernutrition in low- and middle-income countries poses a significant public health threat. The World Health Organization recommends balanced energy-protein (BEP) supplementation to pregnant women from populations with a high prevalence of underweight (prepregnancy BMI &lt;18.5 kg/m2), leaving a notable gap in guidance for lactating women. Therefore, we established the Maternal BEP Studies Harmonization Initiative (BEP Initiative) to investigate the impact of BEP supplementation given to pregnant and/or lactating women on maternal and infant outcomes by synthesizing data from multiple clinical trials. This is a study protocol for our prospective individual participant data (IPD) meta-analysis on BEP lactation trials. Methods Data from four randomized controlled trials that include mother-infant dyads in India (n=816), Pakistan (n=957), Burkina Faso (n=800), and Nepal (n=726) will be pooled and analysed. Women were randomized to BEP (one trial had a third arm with maternal BEP plus infants receiving azithromycin) or control groups at baseline (during the first week) and received the intervention through six months postpartum. A one-stage IPD meta-analysis will be done using mixed-effects linear and log-binomial regression models to account for between-trial heterogeneity. The primary outcome of infant length-for-age z scores (LAZ) and secondary outcomes of maternal and infant indicators of nutritional status, all at six months of age, will be examined. Also, we will assess baseline characteristics as covariates and effect modifiers for the BEP to outcome relationship. Discussion This prospective IPD meta-analysis uses a one-stage IPD meta-analysis, which allows for higher statistical power to examine outcomes, more flexibility in defining variables, and can examine effect modifiers, which could inform which individuals or populations may benefit more from BEP given during lactation.

Perceived progress toward scale of 14 maternal, newborn, child health, and nutrition (MNCHN) assets at subnational level in Burkina Faso, Ethiopia, India, Kenya, and Nigeria.

Inequitable coverage of evidence-based MNCHN interventions is particularly pronounced in low and middle income countries where access and delivery of these interventions can vary dramatically at the subnational level. We conducted health system assessments in nine subnational geographies in five countries (Burkina Faso, Ethiopia, India, Kenya and Nigeria) to explore progress toward scale of 14 evidence-based MNCHN interventions (iron-folic acid, oxytocin, magnesium sulfate, misoprostol; 7.1% chlorhexidine for umbilical cord care, neonatal resuscitation, kangaroo mother care, community regimen for the treatment of possible severe bacterial infection; amoxicillin dispersible tablets, multiple micronutrient supplements, balanced energy protein supplementation, early and exclusive breastfeeding, feeding of small and sick newborns, and management of severe and moderate acute malnutrition in children less than five years old). Between March and October 2021, we conducted key informant interviews with a purposive sample of 275 healthcare providers and 94 district health management (DHMT) staff to better understand bottlenecks, facilitators and uptake of the interventions across varied subnational settings. Across all interventions and geographies, providers and DHMT staff perceived lack of robust HMIS data as the most significant barrier to scale followed by weak facility infrastructure. DHMT staff viewed limited budget allocation and training as a much larger barrier than healthcare providers, most likely given their purview as subnational managers. Healthcare providers were focused on supply chain and staffing, which affect workflows and service provision. Understanding provider and health facility management views of why interventions do or do not advance towards effective coverage can assist in creating enabling environments for the scale of best practices. These types of data are most helpful when collected at the subnational level, which allows for comparisons both within and between countries to show health disparities. Importantly, this strategic data collection can provide a starting point for improvement efforts to address existing health system gaps.

Assessing implementation outcomes for launching balanced energy protein supplementation: A formative study in rural Bangladesh.

Balanced energy protein (BEP) supplementation is an efficacious intervention in pregnancy for improving birthweight and is recommended by World Health Organization (WHO) in countries with high maternal undernutrition. Few countries have implemented BEP programmes due in part to high cost, lack of data on acceptability and feasibility, and complexity of delivery. We sought to address implementation gaps in BEP interventions through a formative study designed to understand implementation outcomes. We conducted 52 in-depth interviews and 8 focus-group discussions with married women of reproductive age, family members, health care providersand pharmacists in three unions of the Gaibandha district in rural Bangladesh. Interviews were translated and transcribed in English and analysed using an analytic framework for implementation science in nutrition. BEP was viewed as an acceptable and appropriate intervention to combat undernutrition in this setting. There was a lack of clarity on who should or could be responsible for providing/distributing BEP in a way convenient to mothers. Many participants preferred door-to-door delivery and thought this approach could address social and gender inequities, but providers mentioned already being overworked and worried about adding new tasks. Participants were concerned about the affordability of BEP and opportunity costs associated with travel to proposed distribution sites such as ANC or pharmacies. Women in these communities do not always have the agency to travel without supervision or make purchasing decisions. BEP supplementation is a complex intervention; future trials seek to assess ways to overcome these implementation challenges and inform a long-term systems-owned BEP intervention.

Acceptability of a balanced energy protein (BEP) supplement for pregnant women in Bangladesh.

Balanced energy protein (BEP) supplementation in pregnancy is recommended in the context of undernutrition for the reduction of small-for-gestational age neonates and stillbirths. To inform an effectiveness trial, we evaluated the acceptability of a packaged, ready-to-eat fortified BEP product among women of reproductive age and their health care providers (HCPs) in rural Bangladesh and explored the feasibility of adhering to daily supplementation. We implemented a formative study using focus groups discussions with women (n = 29) and HCPs (n = 17) to introduce the product and investigate components of acceptability. A "trials of improved practice" activity was conducted in subset of women (n = 16) to evaluate adherence to BEP over a 2-week period, followed by focus group discussions to identify challenges with adherence and strategies employed. Contributors to BEP acceptability included the product's sensory attributes, such as taste, smell and texture; the attractive packaging and informative labelling; and the perceived benefits of use. Participants also identified household and community level factors influencing the adoption of BEP, such as trust in the provider, cultural beliefs on supplement use in pregnancy, and family member tasting and approval. Over the 2-week period, women consumed over 80% of the supplements provided to them and identified strategies for adherence, including visual aids and reminders from family members or providers. HCPs recommended targeted communication messages for mothers-in-law to foster a supportive home environment. Findings informed changes to the BEP product to improve acceptability and shaped the content of communication messages to optimise adherence in a forthcoming effectiveness trial.

Supplementation with fortified balanced energy–protein during pregnancy and lactation and its effects on birth outcomes and infant growth in southern Nepal: protocol of a 2×2 factorial randomised trial

IntroductionMany women in low and middle-income countries enter pregnancy with low nutritional reserves with increased risk of fetal growth restriction and poor birth outcomes, including small-for-gestational-age (SGA) and preterm birth....

Effect of prenatal micronutrient-fortified balanced energy-protein supplementation on maternal and newborn body composition: A sub-study from the MISAME-III randomized controlled efficacy trial in rural Burkina Faso.

Micronutrient-fortified balanced energy-protein (BEP) supplements are promising interventions to prevent intrauterine growth retardation in low- and middle-income countries. On the other hand, one concern with blanket prenatal supplementation programs using energy-dense supplements is that they could lead to more maternal and/or infant overweight. However, evidence is lacking on the potential effect of BEP on maternal and offspring body composition. This study evaluates the effects of micronutrient-fortified BEP supplementation during pregnancy on body composition of mothers and their newborns in rural Burkina Faso. The MISAME-III study is an open label individually randomized controlled trial where pregnant women (n = 1,897) of gestational age <21 weeks received either a combination of micronutrient-fortified BEP and iron-folic acid (IFA) tablets (i.e., intervention) or IFA alone (i.e., control). The prenatal phase of the MISAME-III study was conducted between the first enrollment in October 2019 and the last delivery in August 2021. In a sub-study nested under the MISAME-III trial, we evaluated anthropometry and body composition in newborns who were born starting from 17 November 2020 (n: control = 368 and intervention = 352) and their mothers (n: control = 185 and intervention = 186). Primary study outcomes were newborn and maternal fat-free mass (FFMI) and fat-mass (FMI) indices. We used the deuterium dilution method to determine FFMI and FMI and %FFM and %FM of total body weight within 1 month postpartum. Our main analysis followed a modified intention-to-treat approach by analyzing all subjects with body composition data available. Univariable and multivariable linear regression models were fitted to compare the intervention and control arms, with adjusted models included baseline maternal age, height, arm fat index, hemoglobin concentration and primiparity, household size, wealth and food security indices, and newborn age (days). At study enrollment, the mean ± SD maternal age was 24.8 ± 6.13 years and body mass index (BMI) was 22.1 ± 3.02 kg/m2 with 7.05% of the mothers were underweight and 11.5% were overweight. Prenatal micronutrient-fortified BEP supplementation resulted in a significantly higher FFMI in mothers (MD (mean difference): 0.45; 95% CI (confidence interval): 0.05, 0.84; P = 0.026) and newborns (MD: 0.28; 95% CI: 0.06, 0.50; P = 0.012), whereas no statistically significant effects were found on FMI. The effect of micronutrient-fortified BEP on maternal FFMI was greater among mothers from food secure households and among those with a better nutritional status (BMI ≥21.0 kg/m2 or mid-upper arm circumference (MUAC) ≥23 cm). Key limitations of the study are the relatively high degree of missing data (approximately 18%), the lack of baseline maternal body composition values, and the lack of follow-up body composition measurements to evaluate any long-term effects. Micronutrient-fortified BEP supplementation during pregnancy can increase maternal and newborn FFMI, without significant effects on FMI. ClinicalTrials.gov with identifier NCT03533712.

P17-016-23 Implementation Research To Explore the Feasibility of a Balanced Energy Protein Supplementation Program in Bangladesh

P17-016-23 Implementation Research To Explore the Feasibility of a Balanced Energy Protein Supplementation Program in Bangladesh

OR05-07-23 The Effect of Balanced Energy-Protein Supplementation Provided to Lactating Women on Maternal and Infant Outcomes: A Prospectively Planned IPD Meta-Analysis

OR05-07-23 The Effect of Balanced Energy-Protein Supplementation Provided to Lactating Women on Maternal and Infant Outcomes: A Prospectively Planned IPD Meta-Analysis

Harmonization of maternal balanced energy-protein supplementation studies for individual participant data (IPD) meta-analyses – finding and creating similarities in variables and data collection

BackgroundPublic health and clinical recommendations are established from systematic reviews and retrospective meta-analyses combining effect sizes, traditionally, from aggregate data and more recently, using individual participant data (IPD) of published studies. However, trials often have outcomes and other meta-data that are not defined and collected in a standardized way, making meta-analysis problematic. IPD meta-analysis can only partially fix the limitations of traditional, retrospective, aggregate meta-analysis; prospective meta-analysis further reduces the problems.MethodsWe developed an initiative including seven clinical intervention studies of balanced energy-protein (BEP) supplementation during pregnancy and/or lactation that are being conducted (or recently concluded) in Burkina Faso, Ethiopia, India, Nepal, and Pakistan to test the effect of BEP on infant and maternal outcomes. These studies were commissioned after an expert consultation that designed recommendations for a BEP product for use among pregnant and lactating women in low- and middle-income countries. The initiative goal is to harmonize variables across studies to facilitate IPD meta-analyses on closely aligned data, commonly called prospective meta-analysis. Our objective here is to describe the process of harmonizing variable definitions and prioritizing research questions. A two-day workshop of investigators, content experts, and advisors was held in February 2020 and harmonization activities continued thereafter. Efforts included a range of activities from examining protocols and data collection plans to discussing best practices within field constraints. Prior to harmonization, there were many similar outcomes and variables across studies, such as newborn anthropometry, gestational age, and stillbirth, however, definitions and protocols differed. As well, some measurements were being conducted in several but not all studies, such as food insecurity. Through the harmonization process, we came to consensus on important shared variables, particularly outcomes, added new measurements, and improved protocols across studies.DiscussionWe have fostered extensive communication between investigators from different studies, and importantly, created a large set of harmonized variable definitions within a prospective meta-analysis framework. We expect this initiative will improve reporting within each study in addition to providing opportunities for a series of IPD meta-analyses.

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

ABSTRACTBackgroundAnemia 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.ObjectivesWe 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.MethodsWe 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.ResultsWomen 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.ConclusionsThis 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.

Seasonality and Day-to-Day Variability of Dietary Diversity: Longitudinal Study of Pregnant Women Enrolled in a Randomized Controlled Efficacy Trial in Rural Burkina Faso

BackgroundPanel data indicate that nonpregnant women’s dietary diversity fluctuates across climatic seasons in low- and middle-income countries. The natural day-to-day variability in food group consumption during gestation is unknown. ObjectivesA longitudinal study was conducted among pregnant women enrolled in the Micronutriments pour la Santé de la Mère et de l’Enfant study 3 randomized controlled efficacy trial [i.e., daily fortified balanced energy-protein supplement and an iron-folic acid (IFA) tablet compared with an IFA tablet only] to investigate the number of 24-hour recalls required to estimate usual prenatal food group (FG) diversity and the seasonality of pregnant women’s dietary diversity in Houndé, Burkina Faso. MethodsFG consumption was assessed twice weekly by qualitative, list-based, 24-hour recalls among 1757 pregnant women (892 control, 865 intervention). The number of days needed to estimate a woman’s usual prenatal 10-point FG diversity score was calculated using the within-subject coefficient of variation. Regression models, including truncated Fourier series, were fitted to assess seasonal variations in the FG diversity score and the probability of reaching Minimum Dietary Diversity for Women (MDD-W; i.e., ≥5 FGs). ResultsThe monthly mean FG scores (<5 FGs) and MDD-W prevalence (<45%) were low. Five list-based recalls allowed observed FG diversity to lie within 15% of the true mean in 90% of the estimations (mean ± SD, 40.4 ± 20.7 recalls per woman). Both the FG diversity score and prevalence achieving MDD-W showed responsiveness to seasonal variations, with peaks at the end of the dry season (i.e., April or May) and troughs in the rainy season (i.e., August). ConclusionsFive list-based recalls are sufficient to estimate usual FG diversity during gestation, although intra-annual seasonal patterns did modestly affect the FG diversity score and MDD-W prevalence. Thus, timing of repeated dietary surveys is critical to ensure nonbiased inferences of change and trends in Burkina Faso. This trial was registered at clinicaltrials.gov as NCT 03533712.

Prenatal fortified balanced energy-protein supplementation and birth outcomes in rural Burkina Faso: A randomized controlled efficacy trial

Providing balanced energy-protein (BEP) supplements is a promising intervention to improve birth outcomes in low- and middle-income countries (LMICs); however, evidence is limited. We aimed to assess the efficacy of fortified BEP supplementation during pregnancy to improve birth outcomes, as compared to iron-folic acid (IFA) tablets, the standard of care. We conducted an individually randomized controlled efficacy trial (MIcronutriments pour la SAnté de la Mère et de l'Enfant [MISAME]-III) in 6 health center catchment areas in rural Burkina Faso. Pregnant women, aged 15 to 40 years with gestational age (GA) <21 completed weeks, were randomly assigned to receive either fortified BEP supplements and IFA (intervention) or IFA (control). Supplements were provided during home visits, and intake was supervised on a daily basis by trained village-based project workers. The primary outcome was prevalence of small-for-gestational age (SGA) and secondary outcomes included large-for-gestational age (LGA), low birth weight (LBW), preterm birth (PTB), gestational duration, birth weight, birth length, Rohrer's ponderal index, head circumference, thoracic circumference, arm circumference, fetal loss, and stillbirth. Statistical analyses followed the intention-to-treat (ITT) principle. From October 2019 to December 2020, 1,897 pregnant women were randomized (960 control and 937 intervention). The last child was born in August 2021, and birth anthropometry was analyzed from 1,708 pregnancies (872 control and 836 intervention). A total of 22 women were lost to follow-up in the control group and 27 women in the intervention group. BEP supplementation led to a mean 3.1 percentage points (pp) reduction in SGA with a 95% confidence interval (CI) of -7.39 to 1.16 (P = 0.151), indicating a wide range of plausible true treatment efficacy. Adjusting for prognostic factors of SGA, and conducting complete cases (1,659/1,708, 97%) and per-protocol analysis among women with an observed BEP adherence ≥75% (1,481/1,708, 87%), did not change the results. The intervention significantly improved the duration of gestation (+0.20 weeks, 95% CI 0.05 to 0.36, P = 0.010), birth weight (50.1 g, 8.11 to 92.0, P = 0.019), birth length (0.20 cm, 0.01 to 0.40, P = 0.044), thoracic circumference (0.20 cm, 0.04 to 0.37, P = 0.016), arm circumference (0.86 mm, 0.11 to 1.62, P = 0.025), and decreased LBW prevalence (-3.95 pp, -6.83 to -1.06, P = 0.007) as secondary outcomes measures. No differences in serious adverse events [SAEs; fetal loss (21 control and 26 intervention) and stillbirth (16 control and 17 intervention)] between the study groups were found. Key limitations are the nonblinded administration of supplements and the lack of information on other prognostic factors (e.g., infection, inflammation, stress, and physical activity) to determine to which extent these might have influenced the effect on nutrient availability and birth outcomes. The MISAME-III trial did not provide evidence that fortified BEP supplementation is efficacious in reducing SGA prevalence. However, the intervention had a small positive effect on other birth outcomes. Additional maternal and biochemical outcomes need to be investigated to provide further evidence on the overall clinical relevance of BEP supplementation. ClinicalTrials.gov NCT03533712.

Preliminary report of the toxicity of Lippia junelliana (Lamiales: Verbenaceae) and Elionorus muticus (Poales: Poaceae) on Apis mellifera (Hymenoptera: Apidae)

Several phytochemicals, such as extracts and essential oils, are among the ecological alternatives that have been studied for the control of pathogens that affect humans, animals, and plants. Essential oils are aromatic oily liquids obtained from plant material and their use to control pathogens is widespread. However, they can have adverse effects when taken in high concentrations. The aim of this study was to evaluate the survival and palatability of a balanced-energy protein diet with the addition of two essential oils, Lippia junelliana (Mold.) Tronc. and Elionorus muticus (Spreng.) Kuntze, in newly hatched worker bees (Apis mellifera L.) during a period of 15 days. Consumption and number of live bees were measured daily for each treatment. For L. junelliana, our results showed a non-toxic trend in long-term survival trials (15 days) at low concentrations. In the case of E. muticus, a toxic effect with low survival was observed at all concentrations. Both essential oils showed good palatability, even at toxic levels. Our results allow us to propose the use of L. junelliana essential oil in field experiments of A. mellifera hives.