Dietary aflatoxins exposure, environmental enteropathy, and their relation with childhood stunting.

Childhood stunting is a global phenomenon affecting more than 149 million children under the age of 5 worldwide. Exposure to aflatoxins (AFs) in utero, during breastfeeding, and consumption of contaminated food affect the gut microbiome, resulting in intestinal dysfunction and potentially contributing to stunting. This review explores the potential relationship between AF exposure, environmental enteropathy and childhood stunting. AFs bind to DNA, disrupt protein synthesis and elicit environmental enteropathy (EE). An EE alters the structure of intestinal epithelial cells, impairs nutrient uptake and leads to malabsorption. This article proposes possible intervention strategies for researchers and policymakers to reduce AF exposure, EE and childhood stunting, such as exposure reduction, the implementation of good agricultural practices, dietary diversification and improving environmental water sanitation and hygiene.

Development and validation of a simplified risk prediction model for preterm birth: a prospective cohort study in rural Ethiopia.

Preterm birth is one of the most common obstetric complications in low- and middle-income countries, where access to advanced diagnostic tests and imaging is limited. Therefore, we developed and validated a simplified risk prediction tool to predict preterm birth based on easily applicable and routinely collected characteristics of pregnant women in the primary care setting. We used a logistic regression model to develop a model based on the data collected from 481 pregnant women. Model accuracy was evaluated through discrimination (measured by the area under the Receiver Operating Characteristic curve; AUC) and calibration (via calibration graphs and the Hosmer-Lemeshow goodness of fit test). Internal validation was performed using a bootstrapping technique. A simplified risk score was developed, and the cut-off point was determined using the "Youden index" to classify pregnant women into high or low risk for preterm birth. The incidence of preterm birth was 19.5% (95% CI:16.2, 23.3) of pregnancies. The final prediction model incorporated mid-upper arm circumference, gravidity, history of abortion, antenatal care, comorbidity, intimate partner violence, and anemia as predictors of preeclampsia. The AUC of the model was 0.687 (95% CI: 0.62, 0.75). The calibration plot demonstrated a good calibration with a p-value of 0.713 for the Hosmer-Lemeshow goodness of fit test. The model can identify pregnant women at high risk of preterm birth. It is applicable in daily clinical practice and could contribute to the improvement of the health of women and newborns in primary care settings with limited resources. Healthcare providers in rural areas could use this prediction model to improve clinical decision-making and reduce obstetrics complications.

Neonatal mortality risk of vulnerable newborns by fine stratum of gestational age and birthweight for 230 679 live births in nine low- and middle-income countries, 2000-2017.

OBJECTIVE: To describe the mortality risks by fine strata of gestational age and birthweight among 230 679 live births in nine low- and middle-income countries (LMICs) from 2000 to 2017. DESIGN: Descriptive multi-country secondary data analysis. SETTING: Nine LMICs in sub-Saharan Africa, Southern and Eastern Asia, and Latin America. POPULATION: Liveborn infants from 15 population-based cohorts. METHODS: Subnational, population-based studies with high-quality birth outcome data were invited to join the Vulnerable Newborn Measurement Collaboration. All studies included birthweight, gestational age measured by ultrasound or last menstrual period, infant sex and neonatal survival. We defined adequate birthweight as 2500-3999 g (reference category), macrosomia as ≥4000 g, moderate low as 1500-2499 g and very low birthweight as <1500 g. We analysed fine strata classifications of preterm, term and post-term: ≥42+0 , 39+0 -41+6 (reference category), 37+0 -38+6 , 34+0 -36+6 ,34+0 -36+6 ,32+0 -33+6 , 30+0 -31+6 , 28+0 -29+6 and less than 28 weeks. MAIN OUTCOME MEASURES: Median and interquartile ranges by study for neonatal mortality rates (NMR) and relative risks (RR). We also performed meta-analysis for the relative mortality risks with 95% confidence intervals (CIs) by the fine categories, stratified by regional study setting (sub-Saharan Africa and Southern Asia) and study-level NMR (≤25 versus >25 neonatal deaths per 1000 live births). RESULTS: We found a dose-response relationship between lower gestational ages and birthweights with increasing neonatal mortality risks. The highest NMR and RR were among preterm babies born at <28 weeks (median NMR 359.2 per 1000 live births; RR 18.0, 95% CI 8.6-37.6) and very low birthweight (462.8 per 1000 live births; RR 43.4, 95% CI 29.5-63.9). We found no statistically significant neonatal mortality risk for macrosomia (RR 1.1, 95% CI 0.6-3.0) but a statistically significant risk for all preterm babies, post-term babies (RR 1.3, 95% CI 1.1-1.5) and babies born at 370 -386 weeks (RR 1.2, 95% CI 1.0-1.4). There were no statistically significant differences by region or underlying neonatal mortality. CONCLUSIONS: In addition to tracking vulnerable newborn types, monitoring finer categories of birthweight and gestational age will allow for better understanding of the predictors, interventions and health outcomes for vulnerable newborns. It is imperative that all newborns from live births and stillbirths have an accurate recorded weight and gestational age to track maternal and neonatal health and optimise prevention and care of vulnerable newborns.

A Multi-Omics and Human Biomonitoring Approach to Assessing the Effectiveness of Fortified Balanced Energy-Protein Supplementation on Maternal and Newborn Health in Burkina Faso: A Study Protocol.

Fortified balanced energy-protein (BEP) supplementation is a promising intervention for improving maternal health, birth outcomes and infant growth in low- and middle-income countries. This nested biospecimen sub-study aimed to evaluate the physiological effect of multi-micronutrient-fortified BEP supplementation on pregnant and lactating women and their infants. Pregnant women (15-40 years) received either fortified BEP and iron-folic acid (IFA) (intervention) or IFA only (control) throughout pregnancy. The same women were concurrently randomized to receive either a fortified BEP supplement during the first 6 months postpartum in combination with IFA for the first 6 weeks (i.e., intervention) or the postnatal standard of care, which comprised IFA alone for 6 weeks postpartum (i.e., control). Biological specimens were collected at different timepoints. Multi-omics profiles will be characterized to assess the mediating effect of BEP supplementation on the different trial arms and its effect on maternal health, as well as birth and infant growth outcomes. The mediating effect of the exposome in the relationship between BEP supplementation and maternal health, birth outcomes and infant growth were characterized via biomonitoring markers of air pollution, mycotoxins and environmental contaminants. The results will provide holistic insight into the granular physiological effects of prenatal and postnatal BEP supplementation.

Intrauterine growth pattern in Butajira HDSS, Southern Ethiopia: BUNMAP pregnancy cohort.

BACKGROUND: Abnormal fetal growth pattern during pregnancy including excessive fetal size and intrauterine growth restrictions are the major determinants for perinatal outcomes and postnatal growth. Ultrasonography is a useful tool in monitoring fetal growth for appropriate care and interventions. However, there are few longitudinal studies using serial ultrasonography in low and middle-income countries. Moreover, the reference charts used for fetal growth monitoring in low-income countries comes from high income countries with distinct population features. Therefore, the purpose of this study was to evaluate the intrauterine growth pattern of the fetus using serial ultrasonography. METHODS: We conducted a prospective community-based cohort study from March 2018 to December 2019. Pregnant women with gestational age of 24 weeks or below living in the Butajira HDSS were enrolled. We followed the pregnant women until delivery. Serial ultrasound measurements were taken, and fetal weight was estimated using the Hadlock algorithm based on biparietal diameter, head circumference, abdominal circumference, and femur length. The z-scores and percentiles of biometric measurements were calculated and compared to the INTERGROWTH-21st International Standards for Fetal Growth. RESULTS: We reviewed a total of 2055 ultrasound scans and 746 women who fulfill the inclusion criteria were involved". We found similar distribution patterns of biometric measurements and estimated fetal weight compared to the previous study done in Ethiopia, the WHO and INTERGROWTH-21st references. In our study, the 5th,50th and 95th percentiles of estimated fetal weight distribution have a similar pattern to the WHO and INTERGROWTH-21st charts. The 50th and 95th percentile had also a similar distribution pattern with the previous study conducted in Ethiopia. We found that 10% of the fetus were small for gestational age (below the 10th percentile) based on the Z-score of estimated fetal weight. CONCLUSION: Our study evaluated the fetal growth patterns in rural community of Ethiopia using serial ultrasound biometric measurements. We found similar IUG patterns to the WHO and INTERGROWTH-21st reference standards as well as the previous study conducted in Ethiopia.

Neonatal mortality risk of vulnerable newborns: A descriptive analysis of subnational, population-based birth cohorts for 238 203 live births in low- and middle-income settings from 2000 to 2017.

OBJECTIVE: We aimed to understand the mortality risks of vulnerable newborns (defined as preterm and/or born weighing smaller or larger compared to a standard population), in low- and middle-income countries (LMICs). DESIGN: Descriptive multi-country, secondary analysis of individual-level study data of babies born since 2000. SETTING: Sixteen subnational, population-based studies from nine LMICs in sub-Saharan Africa, Southern and Eastern Asia, and Latin America. POPULATION: Live birth neonates. METHODS: We categorically defined five vulnerable newborn types based on size (large- or appropriate- or small-for-gestational age [LGA, AGA, SGA]), and term (T) and preterm (PT): T + LGA, T + SGA, PT + LGA, PT + AGA, and PT + SGA, with T + AGA (reference). A 10-type definition included low birthweight (LBW) and non-LBW, and a four-type definition collapsed AGA/LGA into one category. We performed imputation for missing birthweights in 13 of the studies. MAIN OUTCOME MEASURES: Median and interquartile ranges by study for the prevalence, mortality rates and relative mortality risks for the four, six and ten type classification. RESULTS: There were 238 203 live births with known neonatal status. Four of the six types had higher mortality risk: T + SGA (median relative risk [RR] 2.6, interquartile range [IQR] 2.0-2.9), PT + LGA (median RR 7.3, IQR 2.3-10.4), PT + AGA (median RR 6.0, IQR 4.4-13.2) and PT + SGA (median RR 10.4, IQR 8.6-13.9). T + SGA, PT + LGA and PT + AGA babies who were LBW, had higher risk compared with non-LBW babies. CONCLUSIONS: Small and/or preterm babies in LIMCs have a considerably increased mortality risk compared with babies born at term and larger. This classification system may advance the understanding of the social determinants and biomedical risk factors along with improved treatment that is critical for newborn health.

Mycotoxins Exposure of Lactating Women and Its Relationship with Dietary and Pre/Post-Harvest Practices in Rural Ethiopia.

Mycotoxins can be transferred to breast milk during lactation. Hence, the presence of multiple mycotoxins (aflatoxins B1, B2, G1, G2, and M1, alpha and beta zearalanol, deoxynivalenol, fumonisins B1, B2, B3, and hydrolyzed B1, nivalenol, ochratoxin A, ochratoxin alpha, and zearalenone) in breast milk samples was assessed in our study. Furthermore, the relationship between total fumonisins and pre/post-harvest and the women's dietary practices was examined. Liquid chromatography coupled with tandem mass spectrometry was used to analyze the 16 mycotoxins. An adjusted censored regression model was fitted to identify predictors of mycotoxins, i.e., total fumonisins. We detected only fumonisin B2 (15% of the samples) and fumonisin B3 (9% of the samples) while fumonisin B1 and nivalenol were detected only in a single breast milk sample. No association between total fumonisins and pre/post-harvest and dietary practices was found (p < 0.05). The overall exposure to mycotoxins was low in the studied women, although fumonisins contamination was not negligible. Moreover, the recorded total fumonisins was not associated with any of the pre/post-harvest and dietary practices. Therefore, to better identify predictors of fumonisin contamination in breast milk, longitudinal studies with food samples in addition to breast milk samples and with larger sample sizes are needed for the future.

Chronic aflatoxin exposure during pregnancy is associated with lower fetal growth trajectories: a prospective cohort from the Butajira Nutrition, Mental Health, and Pregnancy (BUNMAP) Study in rural Ethiopia.

BACKGROUND: Aflatoxins are toxic secondary metabolites produced by Aspergillus fungi, which are ubiquitously present in the food supplies of low- and middle-income countries. Studies of maternal aflatoxin exposure and fetal outcomes are mainly focused on size at birth and the effect on intrauterine fetal growth has not been assessed. OBJECTIVES: In the present study, we examined the association between chronic aflatoxin exposure during pregnancy and fetal growth trajectories in a rural setting in Ethiopia. METHODS: In a prospective cohort study, we enrolled 492 pregnant females, with a singleton pregnancy and before 28 wk of gestation. Serum aflatoxin B1-lysine concentration was measured using LC-tandem MS. Three rounds of ultrasound measurements were conducted to estimate fetal weight at mean ± SD gestational age weeks of 19.1 ± 3.71, 28.5 ± 3.51, and 34.5 ± 2.44. Estimated fetal weight was expressed in centiles using the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) reference. We fitted a multivariable linear mixed-effects model to estimate the rate of fetal growth between aflatoxin-exposed (i.e., aflatoxin B1-lysine concentration above or equal to the limit of detection) and unexposed mothers in the study. RESULTS: Mothers had a mean ± SD age of 26.0 ± 4.58 y. The median (25th, 75th percentile) serum aflatoxin B1-lysine concentration was 12.6 (0.93, 96.9) pg/mg albumin, and aflatoxin exposure was observed in 86.6% of maternal blood samples. Eighty-five percent of the females enrolled provided at least 2 ultrasound measurements for analysis. On average, the aflatoxin-exposed group had a significantly lower change over time in fetal weight-for-gestational-age centile than the unexposed group (ß = -0.92; 95% CI: -1.77, -0.06 centiles/week; P = 0.037). CONCLUSIONS: Chronic maternal aflatoxin exposure is associated with lower fetal growth over time. Our findings emphasize the importance of nutrition-sensitive strategies to mitigate dietary aflatoxin exposure and adopting food safety measures in low-income settings, in particular during the fetal period of development.

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.

Multiple mycotoxin exposure during pregnancy and risks of adverse birth outcomes: a prospective cohort study in rural Ethiopia.

INTRODUCTION: Mycotoxin exposure during pregnancy has been associated with adverse birth outcomes in low- and middle-income countries. The evidence, however, is inconsistent and mainly limited to the assessment of a single mycotoxin. We assessed biomarkers of exposure to multiple mycotoxins during pregnancy and their associations with adverse birth outcomes in rural Ethiopia. METHODS: We analyzed data from 579 pregnant women between 8 and 24 weeks of completed gestation enrolled in a prospective cohort study. Serum mycotoxin concentrations were determined using liquid chromatography coupled with tandem mass spectrometry. Multivariable linear probability models, adjusted for potential confounding factors and multiple comparisons, were fitted to assess the associations between mycotoxin exposure and small for gestational age and preterm birth. We applied principal component analysis to reduce the dimensionality of biomarker data from several taxonomic mycotoxin groups. RESULTS: All pregnant women were co-exposed to at least five mycotoxins, and one pregnant woman was co-exposed to 27 mycotoxins. Fumonisins (FB), i.e., FB2, FB3, FB1, and tenuazonic acid were the most frequently identified mycotoxins in 98.8, 95.3, 93.3, and 81.4% of the samples respectively. Deoxynivalenol was detected in 38.7%, nivalenol in 50.1%, ochratoxin α in 67.9%, and zearalenone in 50.9% of the serum samples. After adjustment, we found no statistically significant (all P ≥ 0.05) associations between mycotoxin exposures and birth outcomes. CONCLUSIONS: Despite our study providing no evidence for relationships between mycotoxin biomarkers and adverse birth outcomes, our findings do indicate an extensive presence of multiple mycotoxin exposure among pregnant women. Public health policies and nutrition-sensitive interventions must ensure exposure to mycotoxins is reduced in rural Ethiopia.

Dietary mycotoxins exposure and child growth, immune system, morbidity, and mortality: a systematic literature review.

The aim of this study was to systematically review associations between dietary mycotoxins exposure and child growth and morbidity of children aged 5 years or younger. Peer-reviewed literature was searched in MEDLINE, EMBASE, COCHRANE, CINAHL, Web of Science, and PsycINFO. Experimental and observational studies were considered. The exposures were dietary mycotoxins during pregnancy, lactation and childhood, and mycotoxins concentrations in the diet, breast milk, urine, and blood. From a total of 4869 references, 86 full-text papers were extracted of which 50 were included in this review. The methodological quality and risk of bias were evaluated and quality of the collective evidence was assessed using GRADE. Uncertainty remains whether mycotoxins exposure affects child growth, immunity and mortality and the overall quality of the evidence is very low. Overall however, we cannot rule out a possible association between dietary mycotoxins, in particular, AF and FUM and child malnutrition. Our analyses were limited by the reporting quality, difference in findings, heterogeneity of outcomes, mycotoxins detection methods, and the observational nature of most studies. Robust study designs with adequate sample size, use of validated biomarkers of exposure and assessment of co-occurrence of mycotoxins and their synergistic effects are required to provide the further evidence regarding a potential effect of dietary mycotoxins exposure on child growth and immunity.

Pre-ART nutritional status and its association with mortality in adult patients enrolled on ART at Fiche Hospital in North Shoa, Oromia region, Ethiopia: a retrospective cohort study.

BACKGROUND: Human immunodeficiency virus (HIV) compromises the nutritional status of infected individuals and in turn, malnutrition worsens the effects of the infection itself by weakening the immune system consequently accelerating disease progression and death. However, few studies have examined the association between nutritional status at antiretroviral therapy (ART) initiation and early mortality. Therefore, this study assesses pre-ART nutritional status and other baseline characteristics and mortality among adult patients on ART at Fiche Hospital, Ethiopia. METHODS: A retrospective cohort study was conducted among 489 ART enrolled adult patients between August 01, 2006 and September 30, 2013 in Fiche Hospital. Study participants were selected by using systematic random sampling method. Actuarial table was used to estimate survival of patients after ART initiation and log rank test was used to compare the survival curves. Cox proportional-hazard regression was used to determine independent predictors of time to death. RESULTS: Most of the study subjects were females 254 (51.9%). A total of 489 patients were included in the analysis, of whom 87 died during a median study follow-up of 22 months. The estimated mortality among malnourished was 21, 28, 33, and 38% at 5, 10, 15, and 25 months respectively with mortality incidence density of 5.63 deaths per 100 person years. The independent predictors of mortality were: BMI <18.5 kg/m2 (AHR = 5.4 95% CI 3.03-9.58), baseline ambulatory functional status (AHR = 3.84; 95% CI 2.19-6.74), bedridden functional status (AHR = 4.78; 95% CI 2.14-10.65), WHO clinical stage III (AHR 2.21; 95% CI 1.16-4.21), WHO clinical stage IV (AHR 4.05; 95% CI 1.50-10.97) and CD4 count less than 200 cells/µl (AHR = 2.95; 95% CI 1.48-5.88), two and more opportunistic infections (AHR 2.30; 95% CI 1.11-4.75). CONCLUSIONS: Undernutrition at the time of ART initiation was associated with increased risk of death, particularly during the first 3 months after ART initiation. Interventions to promote earlier HIV diagnosis and treatment and integrating nutrition counseling at all stages of ART implementation may improve ART outcomes in this vulnerable population.