Malnutrition PregnancyUZBCS-2NCT07195006
Early Life Malnutrition, Environmental Enteric Dysfunction and Microbiome Trajectories
An observational study of Malnutrition Pregnancy and Malnutrition in Children, run by University of Zimbabwe at 1 site in Zimbabwe.
Trial summary
Malnutrition in women of reproductive age remains a public health concern in Sub-Saharan Africa (SSA). Malnutrition during pregnancy affects foetal growth with a tendency of the exposed infants to also develop it. Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Malnutrition Pregnancy, Malnutrition in Children, Malnutrition (Calorie)
- What is being tested?
- Malnutrition in pregnancy as exposure and Poor WASH living conditions as exposure
- How many people
- 368 participants
- Where
- 1 siteZimbabwe
- Study dates
- 27 Jan 2025to 31 Dec 2032
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Study population: Pregnant women at least 20 weeks gestational age seeking antenatal care services at any of the two primary health care centres, Kuwadzana and Hopely.
Who may be able to join
- MUAC ≤23 cm in pregnancy
- ≥18 years' old
- At least 20 weeks' gestational age
- Height ≥150 cm
- Planning to be staying in the study area for the next 3 years
- Willing to participate and comply with all study requirements and procedures.
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- Any pregnant woman meeting the above eligible criteria regardless of HIV status who meet the above inclusion criteria will be invited to participate in the study
- Age, HIV status, gestational age at enrolment, and area residence matched normo-nourished peers with MUAC ≥25 - ≤35 cm
- Haemoglobin level of ≥11g/dL
- ≥18 years' old
- At least 20 weeks' gestational age
- Height ≥150 cm
- Planning to stay in the study area for the next 3 years
Who cannot join
- Acute or chronic conditions in mothers interfering with the study according to the judgment of the investigator (HIV infection is not an exclusion criterion)
- Presence of severe mental health disorders interfering with study procedures according to the judgment of the investigator.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Zimbabwe1 site, 1 recruiting
- Recruiting
University of Zimbabwe
Harare
Kerina Duri, PhD, +2634791631, kerina.duri@gmail.com
Benjamin Misselwitz, MD
About this study
Official title: Early Life Diarrhoea Episode(s), Malnutrition, Environmental Enteric Dysfunction and Microbiome Trajectories From Birth Until 3 Years of Life ; The University of Zimbabwe Birth Cohort Study-2 (UZBCS-2)
Malnutrition in women of reproductive age remains a public health concern in Sub-Saharan Africa (SSA). Malnutrition during pregnancy affects foetal growth with a tendency of the exposed infants to also develop it. The interaction of the mother with the infant shapes the seeding and the trajectory of the infant intestinal microbiota which is crucial for development of a healthy immune system Malnutrition has been associated with intestinal inflammation, intestinal leakage and reduced calorie absorption. Early life malnutrition and environmental enteric dysfunction (EED) immunopathology remains poorly described in the context of mother-infant dyads. This is essential as malnutrition, poor water, sanitation and hygiene (WASH), including the presence of infectious diseases limit the developmental potential of the exposed infants in SSA, including Zimbabwe. In addition, maternal stress and poor mental health may also affect standard hygiene practices, including how a mother cares for her baby, potentially aggravating EED and the risk of the infant being malnourished.
Primary outcomes
Read more
- Infant malnutrition and recovery.
- Gut dysfunction (gut inflammation, leaky gut, malabsorption, dysbiosis)
- Diarrhea episodes, defined as any episode of acute diarrhoea (≥3 passages of loose stool within 24 hours as reported by the mother) occurring before the next study visit.
Definition of malnutrition outcomes to be assessed in babies born to malnourished women, is a mid- upper arm circumference (MUAC) <23cm;
- MUAC for age: Malnourished defined as those below -2 standard (SD) of the World Health Organisation (WHO) reference
- Weight-for-age: Underweight defined as those below -2SD WHO reference
- Weight-for-height: Wasted defined as those below -2SD WHO reference
- Height-for-age: Stunted defined as those below -2SD WHO reference
- Z-scores (as they are i.e. a continuous variable, taking age of infants into account)
- A composite variable, any of malnourished, underweight, wasted or stunted.
Read the detailed description
Background Malnutrition, poor hygiene, lack of access to clean water, infectious diseases, and low access to medicine limit life expectancy and developmental potential of infants in Sub-Saharan Africa (SSA) including Zimbabwe. These conditions severely affect infant growth and neurodevelopment, especially within the first 1000 days of life, and the affected infants might never reach their full development potential in life. The interaction of the mother with the infant shapes the trajectory of the intestinal microbiota and the development of its immune system is considered crucial for a healthy development, yet the therapeutic success remains limited. Malnutrition is a subacute or chronic condition related to insufficient consumption or absorption of nutrients. Malnutrition leads to changes in body composition and diminished functions, exemplified by anthropometric measures of the infant below 2 standard deviations compared to an age-matched control population. Underweight is defined by a low weight-for-age Z-score, wasted by a low weight-for-height Z-score, stunted by a low height-for-age Z-score and malnourished refers to a low mid-upper arm circumference (MUAC) for age. In a systematic review in SSA, risk factors for malnutrition were low maternal education, short birth intervals of <18 months, being first or second in birth order, male sex, lack of safe drinking water, and economic instability. On the other hand, antenatal health education could reduce the risk for malnutrition. Malnutrition is associated with detrimental infant outcomes including reduced physical growth, lower intellectual quotient, behavioral problems, and deficient social skills.
Poor water, sanitation and hygiene (WASH) affects approximately one third of the world's population. For instance, in Africa, approximately 70% of water systems are frequently non-functional and people walk long distances to collect water. On the other hand, in SSA, sewage systems are frequently inefficient with sewage bursts or lacking altogether. Lack of efficient WASH practices has been associated with intestinal infections and malnutrition in infants in SSA. The effects of WASH and malnutrition on infant development are at least partially mediated by the intestinal microbiota and the disruption of interaction networks of intestinal bacteria. From birth throughout life, human microbiome profile is constantly changing either temporarily or permanently due to diet, exposure to microbes, or medications. In birth cohorts from Bangladesh and other continents, an "ecogroup" of bacterial taxa showed consistent co-variation. Variations in this ecogroup concisely reflected microbiota development and the level of microbiota perturbation in infants with severe and moderate acute malnutrition. A causal role of the microbiota is also suggested by animal experiments. Intestinal microbiota transplantation from malnourished infants to germ-free mice resulted in a malnourished phenotype and this phenotype could even be reproduced with two isolated strains (Ruminococcus gnavus and Clostridium symbiosome). Finally, microbiota-directed complementary food corrected the intestinal microbiota of malnourished infants to a composition similar to age-matched controls, and showed superior effects in correcting growth compared to ready-to-use supplementary food.
The trajectory of the development of the intestinal microbiota is closely linked to the maturation of the infant intestinal immune system. A critical "window of opportunity" exists from birth until the end of weaning (~18 months of age), during which environmental influences can prime the immune system. In mice, a decrease in maternal epidermal growth factor intake causes the intestinal barrier to open, resulting in increased antigen passage and a vigorous immune response. This "weaning reaction" is characterized by high expression of interferon-γ (IFN-γ) and tumor necrosis factor in the intestine. Inhibition of this weaning reaction by antibiotics usage results in increased susceptibility to inflammatory conditions such as inflammatory bowel diseases (IBD) and allergies. However, how priming of the intestinal immune system is effected by environmental challenges such as infections, poor hygiene and nutrition remains unknown.
The intestinal microbiota has manifold bidirectional interactions with the host immune system. For example, Th17 cells, induced by the intestinal microbiota are a crucial line of defence against external bacteria. Further, short chain fatty acids (SCFA), and aryl hydrocarbon receptor (Ahr) agonists are microbiota products with beneficial immunomodulatory effects. Any interaction of the intestinal immune system with the microbiota should be regarded as an effort to maintain the intestinal barrier ensuring absorption of nutrients while excluding bacteria from the system and maintaining the integrity of the host.
WASH, malnutrition and associated microbiota changes lead to changes in intestinal physiology including inflammation, leakage and reduced calory absorption, which can be assessed in infants. Faecal calprotectin (FC) is an established diagnostic marker for intestinal inflammation. In the first year of life, FC values are much higher than in adulthood (277 mg/kg, vs. <50 in adults), likely related to an immature infant immune system as well as the gut microbiota. FC values decrease during the first 1.5 years of life. Variable results have been observed between 1-4 years, with possibly higher measurements in healthy infants in developing countries (Uganda).
Malnutrition has also been associated with intestinal leakage and leaky gut syndrome. Intestinal leakage leads to the loss of small and large molecules including albumin and antibodies from the systemic circulation into the gut lumen, associated with loss of calories and reduced calory absorption in the intestine. On the other hand, permeability of the intestinal wall for bacteria, bacterial toxins and/ or pathogen associated molecular patterns is increased, leading to intestinal inflammation. Intestinal leakage can be non-invasively assessed with the lactulose rhamnose permeability test.
Intestinal calory absorption can be non-invasively assessed. Bomb calorimetry can be used to measure the residual chemical energy organic material. To this end, the material will be saturated with oxygen in a sealed container and ignited, leading to the conversion of organic material to carbon dioxide, water and gaseous nitrogen. The method assesses enthalpy changes upon conversion of the organic material such as food or stool into simple gaseous molecules. Upon assessment of total energy intake with detailed food questionnaires and quantification of the residual energy in stool the total absorption capacity for energy, carbohydrates, proteins and fat has been estimated to be 89.4%, 92.5%, 86.9% and 87.3%, respectively in healthy adults.
Malnutrition is a complex condition and is also related to oral health. In African countries, inflammatory oral diseases (e.g. periodontal diseases, acute necrotising gingivitis, noma) can aggravate malnutrition due to reduced calory absorption. On the other hand, malnourishment and related conditions can also manifest as oral pathologies. Poor oral health such as missing teeth or dental caries and periodontal disease lead to diminished ability to chew or swallow certain food, leading to poorer nutritional status.
Finally, the health of the infant cannot be separated from the well-being of the mother. Mothers in low-resource settings face stress, anxiety and depression and challenges to female empowerment which might negatively impact on mother child bonding.
The current project attempts to do a comprehensive analysis of malnutrition in infants from high-density areas in Harare, Zimbabwe considering the infant microbiota, immune system, intestinal function as well as all surrounding factors affecting the health of the mother and the infant.
Rationale Gut microbiome characterization remains inadequately described in resource limited settings. In this project, investigators will recruit and follow pregnant women at high risk for subsequent malnutrition of the infant. Investigators will study development of the intestinal microbiota as well as the infant immune system, intestinal inflammation, leakage and calory extraction. This longitudinal study with comprehensive analysis of bio-samples will provide insights to move from correlation to causality. This work will inform future mechanistic studies and downstream translational work such as the development of next-generation probiotics and prebiotics.
Main hypothesis Environmental and microbiota factors result in intestinal dysfunction leading to malnutrition and suboptimal infant growth and development.
- Conditions
- Malnutrition Pregnancy, Malnutrition in Children, Malnutrition (Calorie), Environmental Enteric Dysfunction, Gut Dysbiosis, Gut Permeability, Gut Inflammation
- Being tested
- Malnutrition in pregnancy as exposure, Poor WASH living conditions as exposure
- Keywords
- diarrhoeal episodes, short chain fatty acids receptor agonists, intestinal inflammation, leakage and calory extraction, toxins in drinking water and food, macro- and micronutrient composition of breast milk, human anti-Gal antibodies, mitochondria health and nutrient uptake, endothelial dysfunction and oxidative stress, hormonal mediated molecular signalling mechanisms, interaction of epigenetics & socioeconomic factors, microbiota, pathobionts and oral microbiota, metagenomics, undernutrition and intestinal infections, infant mortality, morbidity within 1st 1000 days of life, low mid upper arm circumference, sleep adequacy in maternal mental health, chronic inflammation
- Medical subject headings
- Child Nutrition Disorders, Malnutrition, Dysentery, Infant Death
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Malnutrition in pregnancy as exposureOther
MUAC ≤23 cm in pregnancy at least 20 weeks gestational age
Poor WASH living conditions as exposureOther
Poor water (source, quality, access, reliability), sanitation (toilet type, cleanliness, number of people using toilet) and personal (hand wash practices) and household hygiene (dumpster availability and emptying frequency) index scores.
WASH Index score ranges; 1.Basic services (76-100%), 2.Semi-basic services (51-75%) 3.Poor services (26-50%) 4.No services (0-25%)
| Study group | Role | What they receive |
|---|---|---|
| Group 1; Malnourished pregnant women, improved WASH living conditions | Malnourished, improved WASH: Pregnant women (≥20 weeks) with MUAC ≤23 cm, residing in improved WASH area (Kuwadzana research site, Harare) Receives: Other: Malnutrition in pregnancy as exposure | |
| Group 2; Normo-nourished pregnant women, improved WASH living conditions | Normo-nourished women, improved WASH living conditions: Pregnant women (≥20 weeks) with MUAC 25-35 cm and Hb ≥11 g/dL, residing in improved WASH area (Kuwadzana research site, Harare) | |
| Group 3; Malnourished pregnant women, poor WASH living conditions | Malnourished women, poor WASH: Pregnant women (≥20 weeks) with MUAC ≤23 cm, residing in poor WASH area (Hopley research site, Harare) Receives: Other: Malnutrition in pregnancy as exposure; Other: Poor WASH living conditions as exposure | |
| Group 4; Normo-nourished pregnant women, poor WASH living conditions | Normo-nourished women, poor WASH: Pregnant women (≥20 weeks) with MUAC 25-35 cm and Hb ≥11 g/dL, residing in poor WASH area (Hopley research site, Harare) Receives: Other: Poor WASH living conditions as exposure |
What is being measured
The primary outcome is the main question the study is designed to answer.
Alpha diversity of maternal gut microbiota
Alpha diversity of maternal stool microbiota will be assessed by shotgun metagenomic sequencing, and calculated using the Shannon index. This measure reflects within-sample diversity and evenness of microbial communities.
Unit of Measure: Shannon index (unitless; typical range 1-6)
Measured: Third trimester of pregnancy, week(s) 1, 6, 14, 24, 48, 96, 144 after delivery
Beta diversity of maternal gut microbiota
Beta diversity of maternal stool microbiota will be assessed by shotgun metagenomic sequencing and calculated using Bray-Curtis dissimilarity. This measure reflects between-sample differences in community composition.
Unit of Measure: % variance explained
Measured: Third trimester of pregnancy, week(s) 1, 6, 14, 24, 48, 96, 144 after delivery
Alpha diversity of human breast milk microbiota
Alpha diversity of maternal breast milk microbiota will be assessed by shotgun metagenomic sequencing, and calculated using the Shannon index. This measure reflects within-sample diversity and evenness of microbial communities.
Unit of Measure: Shannon index (unitless; typical range 1-6)
Measured: Week(s) 1, 6, 14, 24, 48, 96, 144 after delivery/ until weaning
Beta diversity of human breast milk microbiota
Beta diversity of breast milk microbiota will be assessed by shotgun metagenomic sequencing, and calculated using Bray-Curtis dissimilarity. This measure reflects between-sample differences in community composition. Unit of Measure: % variance explained.
Measured: Week(s) 1, 6, 14, 24, 48, 96, 144 after delivery/ until weaning
Protein content of breast milk
Breast milk samples will be analyzed by photo-spectrometric protein assays, such as the BSA assay.
Comparison of milk of mothers of infants with and without clinical signs of malnutrition (defined by WHO growth standards: WLZ or LAZ < -2), 100 infants per group.
Unit of Measure: g/100mL
Measured: Maternal breast milk samples collected at week(s) 1, 6, 14, 24, 48 post birth.
Fat content of breast milk
Breast milk samples will be analyzed by creamatocrit test. Comparison of milk of mothers of infants with and without clinical signs of malnutrition (defined by WHO growth standards: WLZ or LAZ < -2), 100 infants per group.
Unit of Measure: mL/100mL
Measured: Maternal breast milk samples collected at week(s) 1, 6, 14, 24, 48 post birth.
Lactose content of breast milk
Breast milk samples will be analyzed by high-performance liquid chromatography (HPLC) Comparison of milk of mothers of infants with and without clinical signs of malnutrition (defined by WHO growth standards: WLZ or LAZ < -2), 100 infants per group.
Unit of Measure: g/100mL
Measured: Maternal breast milk samples collected at week(s) 1, 6, 14, 24, 48 post birth.
Micronutrient content of breast milk
Breast milk micronutrients (vitamins A, D, B12, folate; trace elements such as iron, zinc, selenium) assessment using ELISA, and colorimetric assays. Comparison of milk of mothers of infants with and without clinical signs of malnutrition (defined by WHO growth standards: WLZ or LAZ < -2), 100 infants per group.
Vit A: µg/L• Vit D: ng/mL• Folate: ng/mL• Vitamin B12: pg/mL• Iron, zinc, selenium;µg/L.
Measured: Maternal breast milk samples collected at week(s) 1, 6, 14, 24, 48 post birth.
Metabolic composition of breast milk Assessing whether compositional differences in maternal milk are associated with infant intestinal development potential
Breast milk samples will be analyzed by untargeted mass spectrometry. Comparison of milk of mothers of infants with and without clinical signs of malnutrition (defined by WHO growth standards: WLZ or LAZ < -2), 100 infants per group.
Unit of Measure: relative counts of ionized metabolites (mass-to-charge ratio, m/z)
Measured: Maternal breast milk samples collected at week(s) 1, 6, 14, 24, 48 post birth.
Impact of breast milk on infant intestinal organoid barrier function
Primary infant-derived 2D intestinal epithelial organoids will be generated from patient biopsies and treated with diluted breast milk samples to assess epithelial cell proliferation, barrier maturation, and differentiation. Transepithelial electrical resistance (TEER) will be measured as a read-out of intestinal barrier. Comparison of milk of mothers of infants with and without clinical signs of malnutrition (defined by WHO growth standards: WLZ or LAZ < -2), 100 infants per group.
Unit of Measure: TEER: ohms·cm²
Measured: Maternal breast milk samples collected at week(s) 1, 6, 14, 24 post birth.
Impact of breast milk on infant intestinal organoid morphology
Primary infant-derived 3D intestinal epithelial organoids will be generated from patient biopsies and treated with diluted breast milk samples for several days. Microscopy will be used to determine the organoid morphology: organoid-to-spheroid ratio. Comparison of milk of mothers of infants with and without clinical signs of malnutrition (defined by WHO growth standards: WLZ or LAZ < -2), 100 infants per group.
Organoid morphology: villus-crypt architecture scores
Unit of Measure: qualitative/semi-quantitative
Measured: Maternal breast milk samples collected at week(s) 1, 6, 14, 24 post birth.
Impact of breast milk on infant intestinal organoid size
Primary infant-derived 3D intestinal epithelial organoids will be generated from patient biopsies and treated with diluted breast milk samples for several days. Microscopy will be used to determine the organoid size. Comparison of milk of mothers of infants with and without clinical signs of malnutrition (defined by WHO growth standards: WLZ or LAZ < -2), 100 infants per group.
Unit of Measure: µm
Measured: Maternal breast milk samples collected at week(s) 1, 6, 14, 24 post birth.
Impact of breast milk on infant intestinal organoid gene expression
Primary infant-derived 2D intestinal epithelial organoids will be generated from patient biopsies and treated with diluted breast milk samples for 24 hours. RNA will be isolated and used for reverse transcription quantitative polymerase chain reaction (RT-qPCR). Comparison of milk of mothers of infants with and without clinical signs of malnutrition (defined by WHO growth standards: WLZ or LAZ < -2), 100 infants per group.
Expression of tight junction proteins (e.g., ZO-1, occludin): relative fluorescence intensity
Unit of Measure: relative expression of gene of interest in relation to housekeeping gene (2^(-delta CT))
Unit of Measure: TEER: ohms·cm²
Measured: Maternal breast milk samples collected at week(s) 1, 6, 14, 24 post birth.
Alpha diversity of infant gut microbiota
Alpha diversity of infant stool microbiota will be assessed by shotgun metagenomic sequencing, and calculated using the Shannon index. This measure reflects within-sample diversity and evenness of microbial communities.
Unit of Measure: Shannon index (unitless; typical range 1-6)
Measured: Week(s) 1, 6, 14, 24, 48, 96, 144 of age
Beta diversity of infant gut microbiota
Beta diversity of infant stool microbiota will be assessed by shotgun metagenomic sequencing and calculated using Bray-Curtis dissimilarity. This measure reflects between-sample differences in community composition.
Unit of Measure: % variance explained.
Measured: Week(s) 1, 6, 14, 24, 48, 96, 144 of age
Relative abundance of dominant bacterial taxa and microbial metabolic pathways
Relative abundance of dominant bacterial taxa in maternal and infant stool, including breast milk, and of microbial metabolic pathways (KEGG modules) in infant stool, will be determined using MetaPhlAn3 and HUMAnN3.
Unit of Measure: % of total sequences assigned.
Relative abundance (%) of dominant bacterial taxa in maternal and infant stool
Relative abundance (%) of microbial metabolic pathways (KEGG) in infant stool.
Measured: Maternal stool: third trimester, birth, 6, 12, and 24 months postpartum • Breast milk: birth, 6, and 12 months postpartum • Infant stool: birth, 6, 12, and 24 months old.
Maternal serum immunoglobulin concentrations
Total IgG, IgA, and IgM will be quantified in maternal serum using ELISA/Luminex assays as biomarkers of systemic and mucosal barrier function.
Unit of Measure: mg/mL
Measured: From pregnancy and once every year for 3 years
Maternal levels of serum proteins
Albumin, prealbumin, and total protein will be measured in maternal serum using ELISA/Luminex assays to assess intestinal barrier integrity and nutritional status.
Unit of Measure: g/dL
Measured: From pregnancy and once every year for 3 years
Maternal levels of serum inflammatory markers
Myeloperoxidase, neopterin, soluble CD14, soluble CD163 and C-reactive protein will be quantified using ELISA/Luminex assays in maternal serum as biomarkers of intestinal and systemic inflammation.
Unit of measurement: µg or ng/mL
Measured: Once in pregnancy, and once every year for 3 years.
Maternal biomarkers of epithelial and microbial translocation
Intestinal fatty-acid binding protein (I-FABP) and endotoxin core antibodies (EndoCAb) will be measured using ELISA/Luminex assays in maternal serum as biomarkers of epithelial barrier disruption and microbial translocation.
Unit of Measure: pg/mL (I-FABP) and EU/mL (EndoCAb).
Measured: Once in pregnancy, and once every year for 3 years.
Maternal Iron and anabolism-related biomarkers
Soluble transferrin receptor (sTfR), hepcidin, and insulin-like growth factor 1 (IGF-1) will be measured in maternal serum as biomarkers of iron status and systemic growth regulation.
Unit of Measure: ng/mL
Measured: Mother from pregnancy and once every year for 3 years
Maternal serum biochemical indicators
Urea, creatinine, and liver enzyme alkaline phosphatase will be measured in maternal serum to assess renal and hepatic function.
Unit of Measure: mg/dL (urea, creatinine) and U/L (alkaline phosphatase)
Measured: Once in pregnancy, and once every year for 3 years after delivery.
Timing of infant malnutrition and oral health status
The objective is to assess the relationship between the timing of malnutrition in the infant and the development of oral health issues:
- Dental caries
- Oral infections and other oral manifestations,
- Enamel dysplasia) in children from 6 months to 2 years of age.
The standardized oral health assessment tool will be used to describe the following;
- Dmft index (decayed, missing, filled teeth) for dental caries
- Visual examination for enamel dysplasia
- Oral infections including other oral manifestations
Oral thrush (fungal) Herpetic gingivostomatitis (herpes simplex virus) Tooth abscess (bacterial) Gangrenous disease noma (bacterial) Apthous stomatitis Eruption cysts around teething teeth
Measured: From 6 months after delivery or birth and once a year for 2 years
Correlation between Oral Health of mother and that of the child
The objective is to evaluate the correlation between the oral health status of mothers and their children, including the presence of dental caries, oral infections, and periodontal disease.
Measurement Tool: Standardized oral health assessment tools will be used to define the following
- DMFT index (Decayed, Missing, Filled Teeth) for mothers
- dmft index for children
- Plaque Index (PI) and Gingival Index (GI) for both mothers and children
Oral health issues:
- Dental caries
- Oral infections and other oral manifestations,
- Enamel dysplasia) in children from 6 months to 2 years of age.
- Plaque/Gingival index score; Total number of surfaces with plaque/gingivitisis divided by total number of observed surfaces.
Measured: From 6 months after delivery or birth and once a year for 2 years
Maternal socio-demographic and the development of infant malnutrition and gut dysfunction and mortality
Determine the correlation between maternal socio-demographic, including household characteristics in pregnancy at least 20 weeks gestational age assessed using a questionnaire administered by a research nurse and,
- adverse pregnancy outcomes (low birth weight, pre-maturity birth < 37 weeks gestational age at birth
- development of infant malnutrition from birth, weeks 6, 24, 24 48, 96 and 144 of age
- Gut dysbiosis as in objective 1 above
Comparing infants born of women in the 4 groups, malnourished versus normo-nourished in pregnancy at least 20 weeks gestational age by poor versus relatively better WASH living conditions Definition of malnutrition outcomes to be assessed
- MUAC for age: Malnourished defined as those below -2SD WHO reference
- Weight-for-age: Underweight defined as those below -2SD WHO reference
- Weight-for-height: Wasted defined as those below -2SD WHO reference
- Height-for-age: Stunted defined as those below -2SD WHO reference
Measured: Mothers; from pregnancy and every 6 months until 3 years after deliveryInfants; from birth and every 6 months until 3 years old
Maternal stress assessment using Cohen Perceived Stress Scale (CPSS)
The CPSS tool measures the perception of stress in individuals and how unpredictable, uncontrollable, and overloaded mothers find their lives. It consists of 10 items with mothers rating their feelings and thoughts during the last month.
Each item is scored 0 to 4:
0: Never
- Almost never
- Sometimes
- Fairly often
- Very often Total Score
The total score is calculated by summing the scores of all items, yielding a range from 0 to 40:
Low Stress:
Scores between 0-13. Indicates low levels of perceived stress.
Moderate Stress:
Scores between 14-26. Suggests moderate levels of perceived stress.
High Stress:
Scores between 27-40. Indicates high levels of perceived stress.
All the 300 mothers will be assessed.
Measured: In pregnancy , weeks 6 and 24 months after delivery
Maternal stress measurement using Edinburgh Post Partum Depression Scale (EPDS)
EPDS screening tool will be used to identify mothers who may be experiencing postpartum depression. It consists of 10 multiple-choice questions, each focusing on the presence or absence symptoms experienced in the past week.
Scoring Each item on the EPDS is scored from 0 to 3, with higher scores indicating more severe symptoms. The total score can range from 0 to 30.
Categorization of Scores 0-9: Low risk of postpartum depression. Indicates minimal or no depressive symptoms.
10-12: Moderate risk of postpartum depression. Suggests the need for further evaluation and possibly monitoring.
13-30: High risk of postpartum depression. Indicates significant depressive symptoms and suggests the need for further assessment and intervention.
All the 300 mothers will be assessed.
Measured: weeks 6 and 24 weeks and 48 weeks after delivery
Maternal sleeping disorders as indicator of stress using Pittsburgh Sleep Quality Index (PSQI)
The PSQI has 7 components:
- Subjective Sleep Quality: Self-rated sleep quality.
- Sleep latency: Time taken to fall asleep.
- Sleep Duration: Total hours of sleep per night.
- Habitual Sleep Efficiency: Ratio of actual sleep time to time spent in bed.
- Frequency of problems that disrupt sleep.
- Use of sleeping medications to aid sleep.
- Daytime Dysfunction: Impact of sleepiness or fatigue on daily activities. Scoring Each component is scored from 0 to 3, with higher scores indicating worse sleep quality.
Total score ranges from 0 to 21. Interpretation 0-5: Good sleep quality 6-10: Moderate sleep problems 11-21: Severe sleep problems This assessment helps in identifying mothers who may require further evaluation or intervention for sleep-related issues.
All the 300 mothers will be assessed.
Measured: In pregnancy, weeks 6 and 24 months after delivery
Sleeping disorders assessment using Epworth Sleepiness Scale (ESS)
Maternal sleeping disorders will be screened using The ESS tool that measures daytime sleepiness and assesses mothers' propensity to fall asleep in different situations. It consists of eight scenarios where Mothers rate their likelihood of dozing off on a scale from 0 to 3.
Each of the eight items is scored as follows:
0: Would never doze
- Slight chance of dozing
- Moderate chance of dozing
- High chance of dozing
All the eight scenarios are summed to give a total score ranging from 0 to 24.
Interpretation 0-10: Normal daytime sleepiness 11-12: Mild excessive daytime sleepiness 13-15: Moderate excessive daytime sleepiness 16-24: Severe excessive daytime sleepiness
This tool helps identifying mothers who may have sleep disorders or excessive daytime sleepiness that could impact their daily functioning, including caring for their babies.
All the 300 mothers will be assessed.
Measured: In pregnancy, weeks 6 and 24 months after delivery
Maternal assessment of life stressful events
The Life Stressful Events Questionnaire tool will be used to assess the impact of stressful life events (frequencies and severity) on the mothers.
Categories of stressful events:
Personal events:
- Death of a loved one
- Divorce or separation
- Serious illness or injury
- Job loss
- Family Events:
- Family member illness
- Marital problems
- Birth of a child
- Changes in family structure
Social Events:
- Moving to a new location
- Change in social status
- Major life transitions (e.g retirement)
Economic Events:
- Financial difficulties
- Significant changes in income or employment status
Environmental Events:
- Natural disasters
- Major accidents
Higher scores or frequency of reported stressful events are typically associated with increased levels of stress and potential negative health outcomes. Tool helps identify individuals who may benefit from further support or intervention based on their stress levels.
Measured: In pregnancy, weeks 6 and 24 months after delivery
Maternal sleep quality measurements
Sleep quality will be measured as
- Total sleep duration (time in hours from sleep onset to final waking)
- Sleep onset latency (time in minutes from bedtime to the first 20-minute period of sleep)
- Sleep efficiency (ratio of total sleep duration to total time spent in bed (hours)
Classification into 3 groups by duration of sleeping;
-Short sleep duration: Generally defined as less than 6 hours per night. Associated with increased risks for health issues, including fatigue, cognitive impairment, and mood disorders.
-Adequate sleep duration: Defined as 7-9 hours per night. Considered optimal for good health, cognitive function, and overall well-being.
-Long sleep duration: Defined as more than 9 hours per night.
Should also be considered together with other factors such as sleep efficiency, sleep disturbances etc for a more comprehensive assessment.
All the 300 mothers will be assessed.
Measured: In pregnancy, weeks 6 and 24 months after delivery
Maternal empowerment status using SWPER tool
The empowerment status of women may influence how they care for their infants, ultimately affecting infant mortality and morbidity.
Domains to be assessed;
- Social independence
- Decision making in house hold matters
- Attitude towards violence
A total of 14 items in the above SWPER 3 domains will be assessed.
Standard cut points to categorize scores into low, medium, and high levels of empowerment will be used and correlated with infant health.
All the 300 mothers will be assessed.
Measured: In pregnancy, weeks 6 and 24 months after delivery
Women's marital satisfaction status using Kansas tool
Marital satisfaction status of women may influence how they care for their infants, ultimately affecting infant mortality and morbidity.
The main question; 'How satisfied are you with your marriage?' Two more related questions are also asked.
The responses to all the 3 questions are a seven-point Likert scale (1 = 'Extremely dissatisfied'; 2 = 'Very dissatisfied'; 3 = 'Somewhat dissatisfied'; 4 = 'Mixed'; 5 = 'Somewhat satisfied'; 6 = 'Very satisfied'; 7 = 'Extremely satisfied').
Score will range from 3 to 21, with a higher score indicating greater marital satisfaction and will be correlated with infant health.
All the 300 mothers will be assessed.
Measured: In pregnancy, weeks 6 and 24 months after delivery
Concentrations of infant gut intestinal inflammation
Infant stool will be quantified using ELISA or multiplex immunoassay for the following platforms:
- Fecal calprotectin (intestinal inflammation)
Comparison between infants born to mothers with different nutritional statuses (MUAC ≤23 cm vs. 25-35 cm) and exposed to either improved or poor WASH environments during pregnancy. These comparisons aim to characterize the biological signatures of environmental enteric dysfunction (EED), dysbiosis, and malnutrition, in the 4 groups.
Unit of mesurement: Fecal calprotectin: µg/g stool•
Measured: Stool samples at 12, 24, and 36 months of age
Concentrations of infant intestinal permeability
Infant stool will be quantified using ELISA or multiplex immunoassay for the faecal α1-antitrypsin and albumin. Biomarker concentrations will be compared between infants born to mothers with different nutritional statuses (MUAC ≤23 cm vs. 25-35 cm) and exposed to either improved or poor WASH environments during pregnancy. These comparisons aim to characterize the biological signatures of environmental enteric dysfunction (EED), dysbiosis, and malnutrition, in the 4 groups.
Unit of measurements:
Fecal α1-antitrypsin, albumin: mg/dL or µg/g.
Measured: Stool samples at 12, 24, and 36 months of age •
Infant fecal pH and fecal fat content
Infant stool will be assessed for biomarkers of malabsorption and digestive efficiency. The van de Kamer test and/or non extractive method of nuclear magnetic resonance or infrared spectroscopy will be used measure fat in dried stool samples. A nitrazine paper strip will be used to measure pH of the stool samples Comparison between infants born to mothers with different nutritional statuses (MUAC ≤23 cm vs. 25-35 cm) and exposed to either improved or poor WASH environments during pregnancy. These comparisons aim to characterize the biological signatures of environmental enteric dysfunction (EED), dysbiosis, and malnutrition, in the 4 groups.
Units of measurement; Fecal pH: pH units (1-7 scale)
Fecal fat: % of stool mass.
Measured: Stool samples at 12, 24, and 36 months of age •
Infant systemic endotoxemia from gut leakage
Infant serum lipopolysaccharide (LPS) will be measured using ELISA or multiplex immunoassay. Biomarker concentrations will be compared between infants born to mothers with different nutritional statuses (MUAC ≤23 cm vs. 25-35 cm) and exposed to either improved or poor WASH environments during pregnancy. These comparisons aim to characterize the biological signatures of environmental enteric dysfunction (EED), dysbiosis, and malnutrition, in the 4 groups.
Unit of measurement; Serum LPS: ng/mL
Measured: Stool samples at 12, 24, and 36 months of age •
Percentages of circulating T and B lymphocyte subsets and natural killer
PBMCs will be isolated from peripheral blood samples of infants at 6, 12, 24, and 36 months of age. Multicolor flow cytometry will be used to quantify the percentages of :
- CD4⁺ and CD8⁺ T lymphocytes
- Regulatory T cells (CD4⁺CD25⁺FOXP3⁺)
- CD19⁺ B cells
- CD56⁺ natural killer (NK) cells Comparisons will be stratified by maternal nutritional status (MUAC ≤23 cm vs. MUAC 25-35 cm) and household water, sanitation, and hygiene (WASH) exposure (better vs. poor WASH conditions).
Arm/Group title: Children will be assigned to 4 groups defined by maternal nutritional status (MUAC ≤23 cm vs. 25-35 cm) and household WASH conditions (improved vs. poor) at the time of pregnancy.
Overall number of participants: 300 children
Measured: Infant blood samples collected at 12, 24, and 36 months of age. Expected measures/ Unit of measures: Percentage (%) of total PBMCs per cell subset (e.g., % CD4⁺ T cells, % CD56⁺ NK cells)
Metabolic dysregulation and vaccine immune responses in infants presenting with malnutrition
Investigators hypothesise that there is presence of metabolic dysregulation in malnourished infants further exacerbating this condition.
Peripheral blood mononuclear cells of malnourished babies, including their matched normo-nourished counterparts will analysed using flow cytometry to characterise natural killer (NK) cells important in early life immunity and measure fatty acid uptake (BODIPY FL C16), glucose uptake and mitochondrial mass [MitoTracker Green (MTG)]. Granzyme B and perforin levels will be correlated with mean fluorescence intensity (MFI) MTG of NKG2A+/-CD56 dim and bright NK cells.
All malnourished babies and theirs controls will be assessed, these results will be correlated with humoural standard EPI vaccine immune responses (titres).
Measured: weeks 48, 96 and 144 old.
Short and long term relationship between presence and frequency of early life diarrhea episodes and infant malnutrition, neurodevelopment and mental health
The prevalence and incidence of diarrhea, including recovery cycles will be determined in infants born of malnourished /normonourished women in pregnancy living relatively better/poor WASH conditions. Diarrhea episodes will be defined as any episode of acute diarrhoea (≥3 passages of loose stool for 24 hours as reported by the mother) occurring before the next study visit In stool samples we will assess intestinal pathogens (viruses, parasites, bacterial pathogens).
Plating of stool samples on McConkey agars and Enterobacteria will be further characterized using standard and advanced microbiology tools including full-length sequencing if possible.
Intestinal helminthes ova will be assessed using Kato Katz smear of 41.7mg stool and calculate the number of egg count per 1gram stool.
Measured: From birth and followed up to 3 years of age
Intestinal leakage of severely malnourished babies
In all severely malnourished 50% of matched infants without malnutrition, a lactulose/ rhamnose permeability test will be done.
Weight-for-length/height below -3 standard deviations from the median with bilateral pitting edema and mid-upper arm circumference (MUAC) measurement below 110 mm in children aged 12-36, according to the World Health Organization definition of severe malnourished.
Following drinking the sweet solution the urine will be periodically collected by the Study Gastroenterologist, and samples will stored appropriately. Mass spectrometry assessments of urine will be done in Switzerland.
Measured: From 1 years old up until 3 years of age
Intestinal calory extraction in severely malnourished babies
In a subset of randomly chosen infants (20 with malnutrition and 20 matched infants without malnutrition), total calory extraction will be assessed longitudinally. Following consuming a specified diet, where the weight of the food will be accurately measured mothers will collect total infant stool for 24 hours on two subsequent days, using specific diapers.
Analysis of remaining calories in infant stool samples will be done in Bern, Switzerland where a bomb calorimetry is available.
Measured: Weeks 48, 96 and 144 old regardless of whether or not the babies recover from malnutrition.
Colonisation patterns of Clostridioides difficile in Zimbabwe and Switzerland maternal-infant dyads
To compare the differential impact of infant intestinal Clostridioides difficile colonization in Zimbabwe and Switzerland maternal-infant dyads.
Measured: From birth and followed up every 6 months up until 3 years of age
Intestinal inflammation assessment via endoscopy
All infants with severe malnutrition and 50% randomly selected infants with moderate malnutrition will be offered endoscopy. Gastroscopy/rectosigmoidoscopy with general anesthesia will be done by the study Gastroenterologist. During endoscopy, biopsies will be acquired for histopathological assessment by the histopathologist, as well as assessment of inflammation and the intestinal microbiota.
Measured: Any affected babies from one year of age
Secondary outcomes (7)
Concentrations of anti-Gal natural antibodies and memory B cell frequencies in infant blood and stool across early life
Anti-Gal natural antibody levels and memory B cell responses will be characterized in infant serum, stool, and peripheral blood mononuclear cells (PBMCs) over the first three years of life. Anti-Gal IgG, IgA, and IgM concentrations will be quantified using ELISA in both serum and stool. Additionally, memory B cells specific for the α-Gal epitope will be identified and quantified by B cell ELISpot and/or flow cytometry with α-gal-conjugated tetramers or labeled glycoconjugates.
This outcome will assess the ontogeny and maturation of the anti-Gal antibody response and its relationship with microbial colonization, nutritional status, and WASH exposure. Functional immune memory will be evaluated in the context of microbial antigen exposure and early-life health outcomes.
Arm/Group title: Children will be assigned to one of the four groups defined by maternal nutritional status (MUAC ≤23 cm vs. 25-35 cm) and household WASH conditions (improved vs. poor) at the time of pregnancy.
Measured: Infant blood, serum, and stool samples at 3, 6, 12, 24, and 36 months of age.• Serum anti-Gal IgG, IgA, IgM: µg/mL• Stool anti-Gal IgA, IgM: µg/g• Memory B cell frequency specific to α-gal: % of total B cells or spot-forming units (SFU) per 10⁶ PBMCs
Serum concentrations of anti-Gal antibodies
Concentrations of anti-Gal IgG, IgA, and IgM will be quantified in infant serum using ELISA to characterize the ontogeny of the anti-Gal response and its relationship with microbial colonization, nutritional status, and WASH exposure. These measurements will provide insight into the systemic development of natural antibody repertoires across early life.
Unit of Measure: µg/mL
Measured: Infant serum samples at 3, 6, 12, 24, and 36 months of age.
Stool concentrations of anti-Gal antibodies
Concentrations of anti-Gal IgA and IgM will be quantified in infant stool using ELISA to assess mucosal anti-Gal antibody responses. These data will reveal how gut-associated natural antibodies develop in relation to early microbial colonization and nutritional status.
Unit of Measure: µg/g
Measured: Infant serum samples at 3, 6, 12, 24, and 36 months of age.
Frequency of anti-Gal-specific memory B cells
Frequencies of memory B cells specific to the α-Gal epitope will be quantified in infant PBMCs using B cell ELISpot and/or flow cytometry with α-Gal-conjugated tetramers or labeled glycoconjugates. This measure captures the functional development of immune memory directed against microbial glycans in early life.
Unit of Measure: % of total B cells or spot-forming units (SFU) per 10⁶ PBMCs
Measured: Infant PBMCs at 12, 24, and 36 months of age.
Correlation of neonate mortality/morbidity and the presence of group B streptococcus (GBS)
Maternal under-nutrition is generally associated low birth weight which at least in murine models increases the shedding of GBS faecal load. PCR on neonate stool samples using relevant primers. Comparison GBS shedding in neonates born to malnourished women in pregnancy vs those born to their normo-nourished peers Unit of measurement: Copies GBS/gram of stool
Measured: Neonates from pregnancy up to 6 weeks of age
Levels of environmental toxins, agrochemicals, microplastics, antibiotics, antiretrovirals in drinking water and soils (heavy metals)
To determine the levels of environmental toxins, agrochemicals, microplastics, antibiotics, antiretrovirals in drinking water and soils (heavy metals) and mycotoxins in foods (fermented cow milk), their impact on infants' health and development
Measured: 5 years (1.5 years of recruitment plus about 3 years of follow up after birth.
Maternal breast milk including including urinary versus fermented cow milk aflatoxin levels
Aflatoxin B1 (AFB1) and fumonisin B1 (FB1) are toxic secondary products of fungi that frequently contaminate staple crops in resource-limited settings. Urinary aflatoxin M1 (AFM1) and FB1, biomarkers of AFB1 and FB1 exposure, respectively, will be quantified in random antenatal urine via ELISA/Luminex and correlated with adverse birth outcomes and infant growth.
AFB1and ochratoxin A will be tested in breastmilk around delivery and once a year for 2 years/ until weaning in all the 300 women, 4 groups. Unit of measurements ng/mL.
Aflatoxin levels will also be determined in fermented cow milk sampled during the same period.
Measured: From pregnancy and 24 months after delivery (post-lactation)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2025
- Study start27 Jan 2025
- Primary completion31 Dec 2029 (estimated)
- Study completion31 Dec 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (32)Papers the sponsor has linked to this study.
- Other trials for Malnutrition PregnancyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 368 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Zimbabwe
- Sponsor type
- University, hospital or other
- Collaborators
- University of Bern, Insel Gruppe AG, University Hospital Bern, LMU Klinikum
- Responsible party
- Sponsor
- Investigators
- Kerina Duri, Phd, Principal investigator, University of ZimbabweExnevia Gomo, PhD, Study director, University of Zimbabwe
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07195006
- Sponsor's protocol ID
- MRCZ/A/3256
- Other IDs
- JREC/451/2024
- Acronym
- UZBCS-2
- Status last verified
- Sep 2025
- First submitted
- 18 Jul 2025
- Last updated
- 26 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be anonymised prior to release for data sharing. All original data will be stored locally in the Immunology Unit for at least 10 years on appropriate electronic devices with approval for data sharing between the collaborating Institutions. All databases will be password-protected and accessible to authorised personnel only. Data users will be required to acknowledge the source of data and to ensure that the regulatory requirements of the MRCZ and other ethics regulators reviewing the projects are met. The PI through the data manager will be responsible for the overall quality and integrity of the data. Published data will be made available to other researchers upon request and verification. Additional use of data beyond thus study will be guided by the original approved study protocols and the signed participant informed consent.
Publications
Agyepong IA, Sewankambo N, Binagwaho A, Coll-Seck AM, Corrah T, Ezeh A, Fekadu A, Kilonzo N, Lamptey P, Masiye F, Mayosi B, Mboup S, Muyembe JJ, Pate M, Sidibe M, Simons B, Tlou S, Gheorghe A, Legido-Quigley H, McManus J, Ng E, O'Leary M, Enoch J, Kassebaum N, Piot P. The path to longer and healthier lives for all Africans by 2030: the Lancet Commission on the future of health in sub-Saharan Africa. Lancet. 2017 Dec 23;390(10114):2803-2859. doi: 10.1016/S0140-6736(17)31509-X. Epub 2017 Sep 13. No abstract available.
PubMed 28917958Alderman H, Behrman JR, Glewwe P, Fernald L, Walker S. Evidence of Impact of Interventions on Growth and Development during Early and Middle Childhood. In: Bundy DAP, Silva ND, Horton S, Jamison DT, Patton GC, editors. Child and Adolescent Health and Development. 3rd edition. Washington (DC): The International Bank for Reconstruction and Development / The World Bank; 2017 Nov 20. Chapter 7. Available from http://www.ncbi.nlm.nih.gov/books/NBK525234/
PubMed 30212122Perkins JM, Kim R, Krishna A, McGovern M, Aguayo VM, Subramanian SV. Understanding the association between stunting and child development in low- and middle-income countries: Next steps for research and intervention. Soc Sci Med. 2017 Nov;193:101-109. doi: 10.1016/j.socscimed.2017.09.039. Epub 2017 Sep 22.
PubMed 29028557Smith MI, Yatsunenko T, Manary MJ, Trehan I, Mkakosya R, Cheng J, Kau AL, Rich SS, Concannon P, Mychaleckyj JC, Liu J, Houpt E, Li JV, Holmes E, Nicholson J, Knights D, Ursell LK, Knight R, Gordon JI. Gut microbiomes of Malawian twin pairs discordant for kwashiorkor. Science. 2013 Feb 1;339(6119):548-54. doi: 10.1126/science.1229000. Epub 2013 Jan 30.
PubMed 23363771Kau AL, Planer JD, Liu J, Rao S, Yatsunenko T, Trehan I, Manary MJ, Liu TC, Stappenbeck TS, Maleta KM, Ashorn P, Dewey KG, Houpt ER, Hsieh CS, Gordon JI. Functional characterization of IgA-targeted bacterial taxa from undernourished Malawian children that produce diet-dependent enteropathy. Sci Transl Med. 2015 Feb 25;7(276):276ra24. doi: 10.1126/scitranslmed.aaa4877.
PubMed 25717097Gehrig JL, Venkatesh S, Chang HW, Hibberd MC, Kung VL, Cheng J, Chen RY, Subramanian S, Cowardin CA, Meier MF, O'Donnell D, Talcott M, Spears LD, Semenkovich CF, Henrissat B, Giannone RJ, Hettich RL, Ilkayeva O, Muehlbauer M, Newgard CB, Sawyer C, Head RD, Rodionov DA, Arzamasov AA, Leyn SA, Osterman AL, Hossain MI, Islam M, Choudhury N, Sarker SA, Huq S, Mahmud I, Mostafa I, Mahfuz M, Barratt MJ, Ahmed T, Gordon JI. Effects of microbiota-directed foods in gnotobiotic animals and undernourished children. Science. 2019 Jul 12;365(6449):eaau4732. doi: 10.1126/science.aau4732.
PubMed 31296738Keats EC, Das JK, Salam RA, Lassi ZS, Imdad A, Black RE, Bhutta ZA. Effective interventions to address maternal and child malnutrition: an update of the evidence. Lancet Child Adolesc Health. 2021 May;5(5):367-384. doi: 10.1016/S2352-4642(20)30274-1. Epub 2021 Mar 7.
PubMed 33691083Humphrey JH, Mbuya MNN, Ntozini R, Moulton LH, Stoltzfus RJ, Tavengwa NV, Mutasa K, Majo F, Mutasa B, Mangwadu G, Chasokela CM, Chigumira A, Chasekwa B, Smith LE, Tielsch JM, Jones AD, Manges AR, Maluccio JA, Prendergast AJ; Sanitation Hygiene Infant Nutrition Efficacy (SHINE) Trial Team. Independent and combined effects of improved water, sanitation, and hygiene, and improved complementary feeding, on child stunting and anaemia in rural Zimbabwe: a cluster-randomised trial. Lancet Glob Health. 2019 Jan;7(1):e132-e147. doi: 10.1016/S2214-109X(18)30374-7.
PubMed 30554749Simwanza NR, Kalungwe M, Karonga T, Mtambo CMM, Ekpenyong MS, Nyashanu M. Exploring the risk factors of child malnutrition in Sub-Sahara Africa: A scoping review. Nutr Health. 2023 Mar;29(1):61-69. doi: 10.1177/02601060221090699. Epub 2022 Apr 4.
PubMed 35369816Grantham-McGregor S. A review of studies of the effect of severe malnutrition on mental development. J Nutr. 1995 Aug;125(8 Suppl):2233S-2238S. doi: 10.1093/jn/125.suppl_8.2233S.
PubMed 7542705Omidakhsh N, von Ehrenstein OS. Improved Water, Sanitation and Utilization of Maternal and Child Health Services in South Asia-An Analysis of Demographic Health Surveys. Int J Environ Res Public Health. 2021 Jul 19;18(14):7667. doi: 10.3390/ijerph18147667.
PubMed 34300122Valcourt N, Javernick-Will A, Walters J, Linden K. System Approaches to Water, Sanitation, and Hygiene: A Systematic Literature Review. Int J Environ Res Public Health. 2020 Jan 21;17(3):702. doi: 10.3390/ijerph17030702.
PubMed 31973179McDade TW. Early environments and the ecology of inflammation. Proc Natl Acad Sci U S A. 2012 Oct 16;109 Suppl 2(Suppl 2):17281-8. doi: 10.1073/pnas.1202244109. Epub 2012 Oct 8.
PubMed 23045646Guerrant RL, DeBoer MD, Moore SR, Scharf RJ, Lima AA. The impoverished gut--a triple burden of diarrhoea, stunting and chronic disease. Nat Rev Gastroenterol Hepatol. 2013 Apr;10(4):220-9. doi: 10.1038/nrgastro.2012.239. Epub 2012 Dec 11.
PubMed 23229327Raman AS, Gehrig JL, Venkatesh S, Chang HW, Hibberd MC, Subramanian S, Kang G, Bessong PO, Lima AAM, Kosek MN, Petri WA Jr, Rodionov DA, Arzamasov AA, Leyn SA, Osterman AL, Huq S, Mostafa I, Islam M, Mahfuz M, Haque R, Ahmed T, Barratt MJ, Gordon JI. A sparse covarying unit that describes healthy and impaired human gut microbiota development. Science. 2019 Jul 12;365(6449):eaau4735. doi: 10.1126/science.aau4735.
PubMed 31296739
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Life Diarrhoea Episode(s), Malnutrition, Environmental Enteric Dysfunction and Microbiome Trajectories From Birth Until 3 Years of Life ; The University of Zimbabwe Birth Cohort Study-2 (UZBCS-2)
- ClinicalTrials.gov ID
- NCT07195006
- Acronym / sponsor ID
- UZBCS-2 / MRCZ/A/3256
- Conditions
- Malnutrition Pregnancy, Malnutrition in Children, Malnutrition (Calorie), Environmental Enteric Dysfunction, Gut Dysbiosis, Gut Permeability, Gut Inflammation
- Keywords
- diarrhoeal episodes, short chain fatty acids receptor agonists, intestinal inflammation, leakage and calory extraction, toxins in drinking water and food, macro- and micronutrient composition of breast milk, human anti-Gal antibodies, mitochondria health and nutrient uptake, endothelial dysfunction and oxidative stress
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 368 participants (estimated)
- Lead sponsor
- University of ZimbabweUniversity, hospital or other
- Collaborators
- University of Bern, Insel Gruppe AG, University Hospital Bern, LMU Klinikum
- Study start
- 27 Jan 2025 (actual)
- Primary completion
- 31 Dec 2029 (estimated)
- Study completion
- 31 Dec 2032 (estimated)
- First posted
- 26 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Malnutrition in women of reproductive age remains a public health concern in Sub-Saharan Africa (SSA). Malnutrition during pregnancy affects foetal growth with a tendency of the exposed infants to also develop it. The interaction of the mother with the infant shapes the seeding and the trajectory of the infant intestinal microbiota which is crucial for development of a healthy immune system Malnutrition has been associated with intestinal inflammation, intestinal leakage and reduced calorie absorption. Early life malnutrition and environmental enteric dysfunction (EED) immunopathology remains poorly described in the context of mother-infant dyads. This is essential as malnutrition, poor water, sanitation and hygiene (WASH), including the presence of infectious diseases limit the developmental potential of the exposed infants in SSA, including Zimbabwe. In addition, maternal stress and poor mental health may also affect standard hygiene practices, including how a mother cares for her baby, potentially aggravating EED and the risk of the infant being malnourished.
Primary outcomes
- Infant malnutrition and recovery.
- Gut dysfunction (gut inflammation, leaky gut, malabsorption, dysbiosis)
- Diarrhea episodes, defined as any episode of acute diarrhoea (≥3 passages of loose stool within 24 hours as reported by the mother) occurring before the next study visit.
Definition of malnutrition outcomes to be assessed in babies born to malnourished women, is a mid- upper arm circumference (MUAC) <23cm;
- MUAC for age: Malnourished defined as those below -2 standard (SD) of the World Health Organisation (WHO) reference
- Weight-for-age: Underweight defined as those below -2SD WHO reference
- Weight-for-height: Wasted defined as those below -2SD WHO reference
- Height-for-age: Stunted defined as those below -2SD WHO reference
- Z-scores (as they are i.e. a continuous variable, taking age of infants into account)
- A composite variable, any of malnourished, underweight, wasted or stunted.
Detailed description
Background Malnutrition, poor hygiene, lack of access to clean water, infectious diseases, and low access to medicine limit life expectancy and developmental potential of infants in Sub-Saharan Africa (SSA) including Zimbabwe. These conditions severely affect infant growth and neurodevelopment, especially within the first 1000 days of life, and the affected infants might never reach their full development potential in life. The interaction of the mother with the infant shapes the trajectory of the intestinal microbiota and the development of its immune system is considered crucial for a healthy development, yet the therapeutic success remains limited. Malnutrition is a subacute or chronic condition related to insufficient consumption or absorption of nutrients. Malnutrition leads to changes in body composition and diminished functions, exemplified by anthropometric measures of the infant below 2 standard deviations compared to an age-matched control population. Underweight is defined by a low weight-for-age Z-score, wasted by a low weight-for-height Z-score, stunted by a low height-for-age Z-score and malnourished refers to a low mid-upper arm circumference (MUAC) for age. In a systematic review in SSA, risk factors for malnutrition were low maternal education, short birth intervals of <18 months, being first or second in birth order, male sex, lack of safe drinking water, and economic instability. On the other hand, antenatal health education could reduce the risk for malnutrition. Malnutrition is associated with detrimental infant outcomes including reduced physical growth, lower intellectual quotient, behavioral problems, and deficient social skills.
Poor water, sanitation and hygiene (WASH) affects approximately one third of the world's population. For instance, in Africa, approximately 70% of water systems are frequently non-functional and people walk long distances to collect water. On the other hand, in SSA, sewage systems are frequently inefficient with sewage bursts or lacking altogether. Lack of efficient WASH practices has been associated with intestinal infections and malnutrition in infants in SSA. The effects of WASH and malnutrition on infant development are at least partially mediated by the intestinal microbiota and the disruption of interaction networks of intestinal bacteria. From birth throughout life, human microbiome profile is constantly changing either temporarily or permanently due to diet, exposure to microbes, or medications. In birth cohorts from Bangladesh and other continents, an "ecogroup" of bacterial taxa showed consistent co-variation. Variations in this ecogroup concisely reflected microbiota development and the level of microbiota perturbation in infants with severe and moderate acute malnutrition. A causal role of the microbiota is also suggested by animal experiments. Intestinal microbiota transplantation from malnourished infants to germ-free mice resulted in a malnourished phenotype and this phenotype could even be reproduced with two isolated strains (Ruminococcus gnavus and Clostridium symbiosome). Finally, microbiota-directed complementary food corrected the intestinal microbiota of malnourished infants to a composition similar to age-matched controls, and showed superior effects in correcting growth compared to ready-to-use supplementary food.
The trajectory of the development of the intestinal microbiota is closely linked to the maturation of the infant intestinal immune system. A critical "window of opportunity" exists from birth until the end of weaning (~18 months of age), during which environmental influences can prime the immune system. In mice, a decrease in maternal epidermal growth factor intake causes the intestinal barrier to open, resulting in increased antigen passage and a vigorous immune response. This "weaning reaction" is characterized by high expression of interferon-γ (IFN-γ) and tumor necrosis factor in the intestine. Inhibition of this weaning reaction by antibiotics usage results in increased susceptibility to inflammatory conditions such as inflammatory bowel diseases (IBD) and allergies. However, how priming of the intestinal immune system is effected by environmental challenges such as infections, poor hygiene and nutrition remains unknown.
The intestinal microbiota has manifold bidirectional interactions with the host immune system. For example, Th17 cells, induced by the intestinal microbiota are a crucial line of defence against external bacteria. Further, short chain fatty acids (SCFA), and aryl hydrocarbon receptor (Ahr) agonists are microbiota products with beneficial immunomodulatory effects. Any interaction of the intestinal immune system with the microbiota should be regarded as an effort to maintain the intestinal barrier ensuring absorption of nutrients while excluding bacteria from the system and maintaining the integrity of the host.
WASH, malnutrition and associated microbiota changes lead to changes in intestinal physiology including inflammation, leakage and reduced calory absorption, which can be assessed in infants. Faecal calprotectin (FC) is an established diagnostic marker for intestinal inflammation. In the first year of life, FC values are much higher than in adulthood (277 mg/kg, vs. <50 in adults), likely related to an immature infant immune system as well as the gut microbiota. FC values decrease during the first 1.5 years of life. Variable results have been observed between 1-4 years, with possibly higher measurements in healthy infants in developing countries (Uganda).
Malnutrition has also been associated with intestinal leakage and leaky gut syndrome. Intestinal leakage leads to the loss of small and large molecules including albumin and antibodies from the systemic circulation into the gut lumen, associated with loss of calories and reduced calory absorption in the intestine. On the other hand, permeability of the intestinal wall for bacteria, bacterial toxins and/ or pathogen associated molecular patterns is increased, leading to intestinal inflammation. Intestinal leakage can be non-invasively assessed with the lactulose rhamnose permeability test.
Intestinal calory absorption can be non-invasively assessed. Bomb calorimetry can be used to measure the residual chemical energy organic material. To this end, the material will be saturated with oxygen in a sealed container and ignited, leading to the conversion of organic material to carbon dioxide, water and gaseous nitrogen. The method assesses enthalpy changes upon conversion of the organic material such as food or stool into simple gaseous molecules. Upon assessment of total energy intake with detailed food questionnaires and quantification of the residual energy in stool the total absorption capacity for energy, carbohydrates, proteins and fat has been estimated to be 89.4%, 92.5%, 86.9% and 87.3%, respectively in healthy adults.
Malnutrition is a complex condition and is also related to oral health. In African countries, inflammatory oral diseases (e.g. periodontal diseases, acute necrotising gingivitis, noma) can aggravate malnutrition due to reduced calory absorption. On the other hand, malnourishment and related conditions can also manifest as oral pathologies. Poor oral health such as missing teeth or dental caries and periodontal disease lead to diminished ability to chew or swallow certain food, leading to poorer nutritional status.
Finally, the health of the infant cannot be separated from the well-being of the mother. Mothers in low-resource settings face stress, anxiety and depression and challenges to female empowerment which might negatively impact on mother child bonding.
The current project attempts to do a comprehensive analysis of malnutrition in infants from high-density areas in Harare, Zimbabwe considering the infant microbiota, immune system, intestinal function as well as all surrounding factors affecting the health of the mother and the infant.
Rationale Gut microbiome characterization remains inadequately described in resource limited settings. In this project, investigators will recruit and follow pregnant women at high risk for subsequent malnutrition of the infant. Investigators will study development of the intestinal microbiota as well as the infant immune system, intestinal inflammation, leakage and calory extraction. This longitudinal study with comprehensive analysis of bio-samples will provide insights to move from correlation to causality. This work will inform future mechanistic studies and downstream translational work such as the development of next-generation probiotics and prebiotics.
Main hypothesis Environmental and microbiota factors result in intestinal dysfunction leading to malnutrition and suboptimal infant growth and development.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group 1; Malnourished pregnant women, improved WASH living conditions | – | Other: Malnutrition in pregnancy as exposureMalnourished, improved WASH: Pregnant women (≥20 weeks) with MUAC ≤23 cm, residing in improved WASH area (Kuwadzana research site, Harare) |
| Group 2; Normo-nourished pregnant women, improved WASH living conditions | – | –Normo-nourished women, improved WASH living conditions: Pregnant women (≥20 weeks) with MUAC 25-35 cm and Hb ≥11 g/dL, residing in improved WASH area (Kuwadzana research site, Harare) |
| Group 3; Malnourished pregnant women, poor WASH living conditions | – | Other: Malnutrition in pregnancy as exposure, Other: Poor WASH living conditions as exposureMalnourished women, poor WASH: Pregnant women (≥20 weeks) with MUAC ≤23 cm, residing in poor WASH area (Hopley research site, Harare) |
| Group 4; Normo-nourished pregnant women, poor WASH living conditions | – | Other: Poor WASH living conditions as exposureNormo-nourished women, poor WASH: Pregnant women (≥20 weeks) with MUAC 25-35 cm and Hb ≥11 g/dL, residing in poor WASH area (Hopley research site, Harare) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Pregnant women at least 20 weeks gestational age seeking antenatal care services at any of the two primary health care centres, Kuwadzana and Hopely.
Key inclusion criteria (13 listed)
- MUAC ≤23 cm in pregnancy
- ≥18 years' old
- At least 20 weeks' gestational age
- Height ≥150 cm
- Planning to be staying in the study area for the next 3 years
Key exclusion criteria (2 listed)
- Acute or chronic conditions in mothers interfering with the study according to the judgment of the investigator (HIV infection is not an exclusion criterion)
- Presence of severe mental health disorders interfering with study procedures according to the judgment of the investigator.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Malnutrition in pregnancy as exposureMUAC ≤23 cm in pregnancy at least 20 weeks gestational age | Other | Group 1; Malnourished pregnant women, improved WASH living conditions, Group 3; Malnourished pregnant women, poor WASH living conditions |
| Poor WASH living conditions as exposurePoor water (source, quality, access, reliability), sanitation (toilet type, cleanliness, number of people using toilet) and personal (hand wash practices) and household hygiene (dumpster availability and emptying frequency) index scores. WASH Index score ranges; 1.Basic services (76-100%), 2.Semi-basic services (51-75%) 3.Poor services (26-50%) 4.No services (0-25%) | Other | Group 3; Malnourished pregnant women, poor WASH living conditions, Group 4; Normo-nourished pregnant women, poor WASH living conditions |
Primary outcome
Alpha diversity of maternal gut microbiota
Time frame: Third trimester of pregnancy, week(s) 1, 6, 14, 24, 48, 96, 144 after delivery
Alpha diversity of maternal stool microbiota will be assessed by shotgun metagenomic sequencing, and calculated using the Shannon index. This measure reflects within-sample diversity and evenness of microbial communities. Unit of Measure: Shannon index (unitless; typical range 1-6)
Beta diversity of maternal gut microbiota
Time frame: Third trimester of pregnancy, week(s) 1, 6, 14, 24, 48, 96, 144 after delivery
Beta diversity of maternal stool microbiota will be assessed by shotgun metagenomic sequencing and calculated using Bray-Curtis dissimilarity. This measure reflects between-sample differences in community composition. Unit of Measure: % variance explained
Alpha diversity of human breast milk microbiota
Time frame: Week(s) 1, 6, 14, 24, 48, 96, 144 after delivery/ until weaning
Alpha diversity of maternal breast milk microbiota will be assessed by shotgun metagenomic sequencing, and calculated using the Shannon index. This measure reflects within-sample diversity and evenness of microbial communities. Unit of Measure: Shannon index (unitless; typical range 1-6)
Beta diversity of human breast milk microbiota
Time frame: Week(s) 1, 6, 14, 24, 48, 96, 144 after delivery/ until weaning
Beta diversity of breast milk microbiota will be assessed by shotgun metagenomic sequencing, and calculated using Bray-Curtis dissimilarity. This measure reflects between-sample differences in community composition. Unit of Measure: % variance explained.
Protein content of breast milk
Time frame: Maternal breast milk samples collected at week(s) 1, 6, 14, 24, 48 post birth.
Breast milk samples will be analyzed by photo-spectrometric protein assays, such as the BSA assay. Comparison of milk of mothers of infants with and without clinical signs of malnutrition (defined by WHO growth standards: WLZ or LAZ < -2), 100 infants per group. Unit of Measure: g/100mL
Fat content of breast milk
Time frame: Maternal breast milk samples collected at week(s) 1, 6, 14, 24, 48 post birth.
Breast milk samples will be analyzed by creamatocrit test. Comparison of milk of mothers of infants with and without clinical signs of malnutrition (defined by WHO growth standards: WLZ or LAZ < -2), 100 infants per group. Unit of Measure: mL/100mL
Lactose content of breast milk
Time frame: Maternal breast milk samples collected at week(s) 1, 6, 14, 24, 48 post birth.
Breast milk samples will be analyzed by high-performance liquid chromatography (HPLC) Comparison of milk of mothers of infants with and without clinical signs of malnutrition (defined by WHO growth standards: WLZ or LAZ < -2), 100 infants per group. Unit of Measure: g/100mL
Micronutrient content of breast milk
Time frame: Maternal breast milk samples collected at week(s) 1, 6, 14, 24, 48 post birth.
Breast milk micronutrients (vitamins A, D, B12, folate; trace elements such as iron, zinc, selenium) assessment using ELISA, and colorimetric assays. Comparison of milk of mothers of infants with and without clinical signs of malnutrition (defined by WHO growth standards: WLZ or LAZ < -2), 100 infants per group. Vit A: µg/L• Vit D: ng/mL• Folate: ng/mL• Vitamin B12: pg/mL• Iron, zinc, selenium;µg/L.
Metabolic composition of breast milk Assessing whether compositional differences in maternal milk are associated with infant intestinal development potential
Time frame: Maternal breast milk samples collected at week(s) 1, 6, 14, 24, 48 post birth.
Breast milk samples will be analyzed by untargeted mass spectrometry. Comparison of milk of mothers of infants with and without clinical signs of malnutrition (defined by WHO growth standards: WLZ or LAZ < -2), 100 infants per group. Unit of Measure: relative counts of ionized metabolites (mass-to-charge ratio, m/z)
Impact of breast milk on infant intestinal organoid barrier function
Time frame: Maternal breast milk samples collected at week(s) 1, 6, 14, 24 post birth.
Primary infant-derived 2D intestinal epithelial organoids will be generated from patient biopsies and treated with diluted breast milk samples to assess epithelial cell proliferation, barrier maturation, and differentiation. Transepithelial electrical resistance (TEER) will be measured as a read-out of intestinal barrier. Comparison of milk of mothers of infants with and without clinical signs of malnutrition (defined by WHO growth standards: WLZ or LAZ < -2), 100 infants per group. Unit of Measure: TEER: ohms·cm²
Impact of breast milk on infant intestinal organoid morphology
Time frame: Maternal breast milk samples collected at week(s) 1, 6, 14, 24 post birth.
Primary infant-derived 3D intestinal epithelial organoids will be generated from patient biopsies and treated with diluted breast milk samples for several days. Microscopy will be used to determine the organoid morphology: organoid-to-spheroid ratio. Comparison of milk of mothers of infants with and without clinical signs of malnutrition (defined by WHO growth standards: WLZ or LAZ < -2), 100 infants per group. Organoid morphology: villus-crypt architecture scores Unit of Measure: qualitative/semi-quantitative
Impact of breast milk on infant intestinal organoid size
Time frame: Maternal breast milk samples collected at week(s) 1, 6, 14, 24 post birth.
Primary infant-derived 3D intestinal epithelial organoids will be generated from patient biopsies and treated with diluted breast milk samples for several days. Microscopy will be used to determine the organoid size. Comparison of milk of mothers of infants with and without clinical signs of malnutrition (defined by WHO growth standards: WLZ or LAZ < -2), 100 infants per group. Unit of Measure: µm
Impact of breast milk on infant intestinal organoid gene expression
Time frame: Maternal breast milk samples collected at week(s) 1, 6, 14, 24 post birth.
Primary infant-derived 2D intestinal epithelial organoids will be generated from patient biopsies and treated with diluted breast milk samples for 24 hours. RNA will be isolated and used for reverse transcription quantitative polymerase chain reaction (RT-qPCR). Comparison of milk of mothers of infants with and without clinical signs of malnutrition (defined by WHO growth standards: WLZ or LAZ < -2), 100 infants per group. Expression of tight junction proteins (e.g., ZO-1, occludin): relative fluorescence intensity Unit of Measure: relative expression of gene of interest in relation to housekeeping gene (2^(-delta CT)) Unit of Measure: TEER: ohms·cm²
Alpha diversity of infant gut microbiota
Time frame: Week(s) 1, 6, 14, 24, 48, 96, 144 of age
Alpha diversity of infant stool microbiota will be assessed by shotgun metagenomic sequencing, and calculated using the Shannon index. This measure reflects within-sample diversity and evenness of microbial communities. Unit of Measure: Shannon index (unitless; typical range 1-6)
Beta diversity of infant gut microbiota
Time frame: Week(s) 1, 6, 14, 24, 48, 96, 144 of age
Beta diversity of infant stool microbiota will be assessed by shotgun metagenomic sequencing and calculated using Bray-Curtis dissimilarity. This measure reflects between-sample differences in community composition. Unit of Measure: % variance explained.
Relative abundance of dominant bacterial taxa and microbial metabolic pathways
Time frame: Maternal stool: third trimester, birth, 6, 12, and 24 months postpartum • Breast milk: birth, 6, and 12 months postpartum • Infant stool: birth, 6, 12, and 24 months old.
Relative abundance of dominant bacterial taxa in maternal and infant stool, including breast milk, and of microbial metabolic pathways (KEGG modules) in infant stool, will be determined using MetaPhlAn3 and HUMAnN3. Unit of Measure: % of total sequences assigned. Relative abundance (%) of dominant bacterial taxa in maternal and infant stool Relative abundance (%) of microbial metabolic pathways (KEGG) in infant stool.
Maternal serum immunoglobulin concentrations
Time frame: From pregnancy and once every year for 3 years
Total IgG, IgA, and IgM will be quantified in maternal serum using ELISA/Luminex assays as biomarkers of systemic and mucosal barrier function. Unit of Measure: mg/mL
Maternal levels of serum proteins
Time frame: From pregnancy and once every year for 3 years
Albumin, prealbumin, and total protein will be measured in maternal serum using ELISA/Luminex assays to assess intestinal barrier integrity and nutritional status. Unit of Measure: g/dL
Maternal levels of serum inflammatory markers
Time frame: Once in pregnancy, and once every year for 3 years.
Myeloperoxidase, neopterin, soluble CD14, soluble CD163 and C-reactive protein will be quantified using ELISA/Luminex assays in maternal serum as biomarkers of intestinal and systemic inflammation. Unit of measurement: µg or ng/mL
Maternal biomarkers of epithelial and microbial translocation
Time frame: Once in pregnancy, and once every year for 3 years.
Intestinal fatty-acid binding protein (I-FABP) and endotoxin core antibodies (EndoCAb) will be measured using ELISA/Luminex assays in maternal serum as biomarkers of epithelial barrier disruption and microbial translocation. Unit of Measure: pg/mL (I-FABP) and EU/mL (EndoCAb).
Maternal Iron and anabolism-related biomarkers
Time frame: Mother from pregnancy and once every year for 3 years
Soluble transferrin receptor (sTfR), hepcidin, and insulin-like growth factor 1 (IGF-1) will be measured in maternal serum as biomarkers of iron status and systemic growth regulation. Unit of Measure: ng/mL
Maternal serum biochemical indicators
Time frame: Once in pregnancy, and once every year for 3 years after delivery.
Urea, creatinine, and liver enzyme alkaline phosphatase will be measured in maternal serum to assess renal and hepatic function. Unit of Measure: mg/dL (urea, creatinine) and U/L (alkaline phosphatase)
Timing of infant malnutrition and oral health status
Time frame: From 6 months after delivery or birth and once a year for 2 years
The objective is to assess the relationship between the timing of malnutrition in the infant and the development of oral health issues: * Dental caries * Oral infections and other oral manifestations, * Enamel dysplasia) in children from 6 months to 2 years of age. The standardized oral health assessment tool will be used to describe the following; * Dmft index (decayed, missing, filled teeth) for dental caries * Visual examination for enamel dysplasia * Oral infections including other oral manifestations Oral thrush (fungal) Herpetic gingivostomatitis (herpes simplex virus) Tooth abscess (bacterial) Gangrenous disease noma (bacterial) Apthous stomatitis Eruption cysts around teething teeth
Correlation between Oral Health of mother and that of the child
Time frame: From 6 months after delivery or birth and once a year for 2 years
The objective is to evaluate the correlation between the oral health status of mothers and their children, including the presence of dental caries, oral infections, and periodontal disease. Measurement Tool: Standardized oral health assessment tools will be used to define the following * DMFT index (Decayed, Missing, Filled Teeth) for mothers * dmft index for children * Plaque Index (PI) and Gingival Index (GI) for both mothers and children Oral health issues: * Dental caries * Oral infections and other oral manifestations, * Enamel dysplasia) in children from 6 months to 2 years of age. * Plaque/Gingival index score; Total number of surfaces with plaque/gingivitisis divided by total number of observed surfaces.
Maternal socio-demographic and the development of infant malnutrition and gut dysfunction and mortality
Time frame: Mothers; from pregnancy and every 6 months until 3 years after deliveryInfants; from birth and every 6 months until 3 years old
Determine the correlation between maternal socio-demographic, including household characteristics in pregnancy at least 20 weeks gestational age assessed using a questionnaire administered by a research nurse and, 1. adverse pregnancy outcomes (low birth weight, pre-maturity birth < 37 weeks gestational age at birth 2. development of infant malnutrition from birth, weeks 6, 24, 24 48, 96 and 144 of age 3. Gut dysbiosis as in objective 1 above Comparing infants born of women in the 4 groups, malnourished versus normo-nourished in pregnancy at least 20 weeks gestational age by poor versus relatively better WASH living conditions Definition of malnutrition outcomes to be assessed * MUAC for age: Malnourished defined as those below -2SD WHO reference * Weight-for-age: Underweight defined as those below -2SD WHO reference * Weight-for-height: Wasted defined as those below -2SD WHO reference * Height-for-age: Stunted defined as those below -2SD WHO reference
Maternal stress assessment using Cohen Perceived Stress Scale (CPSS)
Time frame: In pregnancy , weeks 6 and 24 months after delivery
The CPSS tool measures the perception of stress in individuals and how unpredictable, uncontrollable, and overloaded mothers find their lives. It consists of 10 items with mothers rating their feelings and thoughts during the last month. Each item is scored 0 to 4: 0: Never 1. Almost never 2. Sometimes 3. Fairly often 4. Very often Total Score The total score is calculated by summing the scores of all items, yielding a range from 0 to 40: Low Stress: Scores between 0-13. Indicates low levels of perceived stress. Moderate Stress: Scores between 14-26. Suggests moderate levels of perceived stress. High Stress: Scores between 27-40. Indicates high levels of perceived stress. All the 300 mothers will be assessed.
Maternal stress measurement using Edinburgh Post Partum Depression Scale (EPDS)
Time frame: weeks 6 and 24 weeks and 48 weeks after delivery
EPDS screening tool will be used to identify mothers who may be experiencing postpartum depression. It consists of 10 multiple-choice questions, each focusing on the presence or absence symptoms experienced in the past week. Scoring Each item on the EPDS is scored from 0 to 3, with higher scores indicating more severe symptoms. The total score can range from 0 to 30. Categorization of Scores 0-9: Low risk of postpartum depression. Indicates minimal or no depressive symptoms. 10-12: Moderate risk of postpartum depression. Suggests the need for further evaluation and possibly monitoring. 13-30: High risk of postpartum depression. Indicates significant depressive symptoms and suggests the need for further assessment and intervention. All the 300 mothers will be assessed.
Maternal sleeping disorders as indicator of stress using Pittsburgh Sleep Quality Index (PSQI)
Time frame: In pregnancy, weeks 6 and 24 months after delivery
The PSQI has 7 components: * Subjective Sleep Quality: Self-rated sleep quality. * Sleep latency: Time taken to fall asleep. * Sleep Duration: Total hours of sleep per night. * Habitual Sleep Efficiency: Ratio of actual sleep time to time spent in bed. * Frequency of problems that disrupt sleep. * Use of sleeping medications to aid sleep. * Daytime Dysfunction: Impact of sleepiness or fatigue on daily activities. Scoring Each component is scored from 0 to 3, with higher scores indicating worse sleep quality. Total score ranges from 0 to 21. Interpretation 0-5: Good sleep quality 6-10: Moderate sleep problems 11-21: Severe sleep problems This assessment helps in identifying mothers who may require further evaluation or intervention for sleep-related issues. All the 300 mothers will be assessed.
Sleeping disorders assessment using Epworth Sleepiness Scale (ESS)
Time frame: In pregnancy, weeks 6 and 24 months after delivery
Maternal sleeping disorders will be screened using The ESS tool that measures daytime sleepiness and assesses mothers' propensity to fall asleep in different situations. It consists of eight scenarios where Mothers rate their likelihood of dozing off on a scale from 0 to 3. Each of the eight items is scored as follows: 0: Would never doze 1. Slight chance of dozing 2. Moderate chance of dozing 3. High chance of dozing All the eight scenarios are summed to give a total score ranging from 0 to 24. Interpretation 0-10: Normal daytime sleepiness 11-12: Mild excessive daytime sleepiness 13-15: Moderate excessive daytime sleepiness 16-24: Severe excessive daytime sleepiness This tool helps identifying mothers who may have sleep disorders or excessive daytime sleepiness that could impact their daily functioning, including caring for their babies. All the 300 mothers will be assessed.
Maternal assessment of life stressful events
Time frame: In pregnancy, weeks 6 and 24 months after delivery
The Life Stressful Events Questionnaire tool will be used to assess the impact of stressful life events (frequencies and severity) on the mothers. Categories of stressful events: Personal events: * Death of a loved one * Divorce or separation * Serious illness or injury * Job loss * Family Events: * Family member illness * Marital problems * Birth of a child * Changes in family structure Social Events: * Moving to a new location * Change in social status * Major life transitions (e.g retirement) Economic Events: * Financial difficulties * Significant changes in income or employment status Environmental Events: * Natural disasters * Major accidents Higher scores or frequency of reported stressful events are typically associated with increased levels of stress and potential negative health outcomes. Tool helps identify individuals who may benefit from further support or intervention based on their stress levels.
Maternal sleep quality measurements
Time frame: In pregnancy, weeks 6 and 24 months after delivery
Sleep quality will be measured as * Total sleep duration (time in hours from sleep onset to final waking) * Sleep onset latency (time in minutes from bedtime to the first 20-minute period of sleep) * Sleep efficiency (ratio of total sleep duration to total time spent in bed (hours) Classification into 3 groups by duration of sleeping; -Short sleep duration: Generally defined as less than 6 hours per night. Associated with increased risks for health issues, including fatigue, cognitive impairment, and mood disorders. -Adequate sleep duration: Defined as 7-9 hours per night. Considered optimal for good health, cognitive function, and overall well-being. -Long sleep duration: Defined as more than 9 hours per night. Should also be considered together with other factors such as sleep efficiency, sleep disturbances etc for a more comprehensive assessment. All the 300 mothers will be assessed.
Maternal empowerment status using SWPER tool
Time frame: In pregnancy, weeks 6 and 24 months after delivery
The empowerment status of women may influence how they care for their infants, ultimately affecting infant mortality and morbidity. Domains to be assessed; * Social independence * Decision making in house hold matters * Attitude towards violence A total of 14 items in the above SWPER 3 domains will be assessed. Standard cut points to categorize scores into low, medium, and high levels of empowerment will be used and correlated with infant health. All the 300 mothers will be assessed.
Women's marital satisfaction status using Kansas tool
Time frame: In pregnancy, weeks 6 and 24 months after delivery
Marital satisfaction status of women may influence how they care for their infants, ultimately affecting infant mortality and morbidity. The main question; 'How satisfied are you with your marriage?' Two more related questions are also asked. The responses to all the 3 questions are a seven-point Likert scale (1 = 'Extremely dissatisfied'; 2 = 'Very dissatisfied'; 3 = 'Somewhat dissatisfied'; 4 = 'Mixed'; 5 = 'Somewhat satisfied'; 6 = 'Very satisfied'; 7 = 'Extremely satisfied'). Score will range from 3 to 21, with a higher score indicating greater marital satisfaction and will be correlated with infant health. All the 300 mothers will be assessed.
Concentrations of infant gut intestinal inflammation
Time frame: Stool samples at 12, 24, and 36 months of age
Infant stool will be quantified using ELISA or multiplex immunoassay for the following platforms: * Fecal calprotectin (intestinal inflammation) Comparison between infants born to mothers with different nutritional statuses (MUAC ≤23 cm vs. 25-35 cm) and exposed to either improved or poor WASH environments during pregnancy. These comparisons aim to characterize the biological signatures of environmental enteric dysfunction (EED), dysbiosis, and malnutrition, in the 4 groups. Unit of mesurement: Fecal calprotectin: µg/g stool•
Concentrations of infant intestinal permeability
Time frame: Stool samples at 12, 24, and 36 months of age •
Infant stool will be quantified using ELISA or multiplex immunoassay for the faecal α1-antitrypsin and albumin. Biomarker concentrations will be compared between infants born to mothers with different nutritional statuses (MUAC ≤23 cm vs. 25-35 cm) and exposed to either improved or poor WASH environments during pregnancy. These comparisons aim to characterize the biological signatures of environmental enteric dysfunction (EED), dysbiosis, and malnutrition, in the 4 groups. Unit of measurements: Fecal α1-antitrypsin, albumin: mg/dL or µg/g.
Infant fecal pH and fecal fat content
Time frame: Stool samples at 12, 24, and 36 months of age •
Infant stool will be assessed for biomarkers of malabsorption and digestive efficiency. The van de Kamer test and/or non extractive method of nuclear magnetic resonance or infrared spectroscopy will be used measure fat in dried stool samples. A nitrazine paper strip will be used to measure pH of the stool samples Comparison between infants born to mothers with different nutritional statuses (MUAC ≤23 cm vs. 25-35 cm) and exposed to either improved or poor WASH environments during pregnancy. These comparisons aim to characterize the biological signatures of environmental enteric dysfunction (EED), dysbiosis, and malnutrition, in the 4 groups. Units of measurement; Fecal pH: pH units (1-7 scale) Fecal fat: % of stool mass.
Infant systemic endotoxemia from gut leakage
Time frame: Stool samples at 12, 24, and 36 months of age •
Infant serum lipopolysaccharide (LPS) will be measured using ELISA or multiplex immunoassay. Biomarker concentrations will be compared between infants born to mothers with different nutritional statuses (MUAC ≤23 cm vs. 25-35 cm) and exposed to either improved or poor WASH environments during pregnancy. These comparisons aim to characterize the biological signatures of environmental enteric dysfunction (EED), dysbiosis, and malnutrition, in the 4 groups. Unit of measurement; Serum LPS: ng/mL
Percentages of circulating T and B lymphocyte subsets and natural killer
Time frame: Infant blood samples collected at 12, 24, and 36 months of age. Expected measures/ Unit of measures: Percentage (%) of total PBMCs per cell subset (e.g., % CD4⁺ T cells, % CD56⁺ NK cells)
PBMCs will be isolated from peripheral blood samples of infants at 6, 12, 24, and 36 months of age. Multicolor flow cytometry will be used to quantify the percentages of : * CD4⁺ and CD8⁺ T lymphocytes * Regulatory T cells (CD4⁺CD25⁺FOXP3⁺) * CD19⁺ B cells * CD56⁺ natural killer (NK) cells Comparisons will be stratified by maternal nutritional status (MUAC ≤23 cm vs. MUAC 25-35 cm) and household water, sanitation, and hygiene (WASH) exposure (better vs. poor WASH conditions). Arm/Group title: Children will be assigned to 4 groups defined by maternal nutritional status (MUAC ≤23 cm vs. 25-35 cm) and household WASH conditions (improved vs. poor) at the time of pregnancy. Overall number of participants: 300 children
Metabolic dysregulation and vaccine immune responses in infants presenting with malnutrition
Time frame: weeks 48, 96 and 144 old.
Investigators hypothesise that there is presence of metabolic dysregulation in malnourished infants further exacerbating this condition. Peripheral blood mononuclear cells of malnourished babies, including their matched normo-nourished counterparts will analysed using flow cytometry to characterise natural killer (NK) cells important in early life immunity and measure fatty acid uptake (BODIPY FL C16), glucose uptake and mitochondrial mass [MitoTracker Green (MTG)]. Granzyme B and perforin levels will be correlated with mean fluorescence intensity (MFI) MTG of NKG2A+/-CD56 dim and bright NK cells. All malnourished babies and theirs controls will be assessed, these results will be correlated with humoural standard EPI vaccine immune responses (titres).
Short and long term relationship between presence and frequency of early life diarrhea episodes and infant malnutrition, neurodevelopment and mental health
Time frame: From birth and followed up to 3 years of age
The prevalence and incidence of diarrhea, including recovery cycles will be determined in infants born of malnourished /normonourished women in pregnancy living relatively better/poor WASH conditions. Diarrhea episodes will be defined as any episode of acute diarrhoea (≥3 passages of loose stool for 24 hours as reported by the mother) occurring before the next study visit In stool samples we will assess intestinal pathogens (viruses, parasites, bacterial pathogens). Plating of stool samples on McConkey agars and Enterobacteria will be further characterized using standard and advanced microbiology tools including full-length sequencing if possible. Intestinal helminthes ova will be assessed using Kato Katz smear of 41.7mg stool and calculate the number of egg count per 1gram stool.
Intestinal leakage of severely malnourished babies
Time frame: From 1 years old up until 3 years of age
In all severely malnourished 50% of matched infants without malnutrition, a lactulose/ rhamnose permeability test will be done. Weight-for-length/height below -3 standard deviations from the median with bilateral pitting edema and mid-upper arm circumference (MUAC) measurement below 110 mm in children aged 12-36, according to the World Health Organization definition of severe malnourished. Following drinking the sweet solution the urine will be periodically collected by the Study Gastroenterologist, and samples will stored appropriately. Mass spectrometry assessments of urine will be done in Switzerland.
Intestinal calory extraction in severely malnourished babies
Time frame: Weeks 48, 96 and 144 old regardless of whether or not the babies recover from malnutrition.
In a subset of randomly chosen infants (20 with malnutrition and 20 matched infants without malnutrition), total calory extraction will be assessed longitudinally. Following consuming a specified diet, where the weight of the food will be accurately measured mothers will collect total infant stool for 24 hours on two subsequent days, using specific diapers. Analysis of remaining calories in infant stool samples will be done in Bern, Switzerland where a bomb calorimetry is available.
Colonisation patterns of Clostridioides difficile in Zimbabwe and Switzerland maternal-infant dyads
Time frame: From birth and followed up every 6 months up until 3 years of age
To compare the differential impact of infant intestinal Clostridioides difficile colonization in Zimbabwe and Switzerland maternal-infant dyads.
Intestinal inflammation assessment via endoscopy
Time frame: Any affected babies from one year of age
All infants with severe malnutrition and 50% randomly selected infants with moderate malnutrition will be offered endoscopy. Gastroscopy/rectosigmoidoscopy with general anesthesia will be done by the study Gastroenterologist. During endoscopy, biopsies will be acquired for histopathological assessment by the histopathologist, as well as assessment of inflammation and the intestinal microbiota.
7 secondary outcomes
Concentrations of anti-Gal natural antibodies and memory B cell frequencies in infant blood and stool across early life
Time frame: Infant blood, serum, and stool samples at 3, 6, 12, 24, and 36 months of age.• Serum anti-Gal IgG, IgA, IgM: µg/mL• Stool anti-Gal IgA, IgM: µg/g• Memory B cell frequency specific to α-gal: % of total B cells or spot-forming units (SFU) per 10⁶ PBMCs
Serum concentrations of anti-Gal antibodies
Time frame: Infant serum samples at 3, 6, 12, 24, and 36 months of age.
Stool concentrations of anti-Gal antibodies
Time frame: Infant serum samples at 3, 6, 12, 24, and 36 months of age.
Frequency of anti-Gal-specific memory B cells
Time frame: Infant PBMCs at 12, 24, and 36 months of age.
Correlation of neonate mortality/morbidity and the presence of group B streptococcus (GBS)
Time frame: Neonates from pregnancy up to 6 weeks of age
Levels of environmental toxins, agrochemicals, microplastics, antibiotics, antiretrovirals in drinking water and soils (heavy metals)
Time frame: 5 years (1.5 years of recruitment plus about 3 years of follow up after birth.
Maternal breast milk including including urinary versus fermented cow milk aflatoxin levels
Time frame: From pregnancy and 24 months after delivery (post-lactation)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2025.
- Background: PubMed 28917958Agyepong IA, Sewankambo N, Binagwaho A, Coll-Seck AM, Corrah T, Ezeh A, Fekadu A, Kilonzo N, Lamptey P, Masiye F, Mayosi B, Mboup S, Muyembe JJ, Pate M, Sidibe M, Simons B, Tlou S, Gheorghe A, Legido-Quigley H, McManus J, Ng E, O'Leary M, Enoch J, Kassebaum N, Piot P. The path to longer and healthier lives for all Africans by 2030: the Lancet Commission on the future of health in sub-Saharan Africa. Lancet. 2017 Dec 23;390(10114):2803-2859. doi: 10.1016/S0140-6736(17)31509-X. Epub 2017 Sep 13. No abstract available.
- Background: PubMed 30212122Alderman H, Behrman JR, Glewwe P, Fernald L, Walker S. Evidence of Impact of Interventions on Growth and Development during Early and Middle Childhood. In: Bundy DAP, Silva ND, Horton S, Jamison DT, Patton GC, editors. Child and Adolescent Health and Development. 3rd edition. Washington (DC): The International Bank for Reconstruction and Development / The World Bank; 2017 Nov 20. Chapter 7. Available from http://www.ncbi.nlm.nih.gov/books/NBK525234/
- Background: PubMed 29028557Perkins JM, Kim R, Krishna A, McGovern M, Aguayo VM, Subramanian SV. Understanding the association between stunting and child development in low- and middle-income countries: Next steps for research and intervention. Soc Sci Med. 2017 Nov;193:101-109. doi: 10.1016/j.socscimed.2017.09.039. Epub 2017 Sep 22.
- Background: PubMed 23363771Smith MI, Yatsunenko T, Manary MJ, Trehan I, Mkakosya R, Cheng J, Kau AL, Rich SS, Concannon P, Mychaleckyj JC, Liu J, Houpt E, Li JV, Holmes E, Nicholson J, Knights D, Ursell LK, Knight R, Gordon JI. Gut microbiomes of Malawian twin pairs discordant for kwashiorkor. Science. 2013 Feb 1;339(6119):548-54. doi: 10.1126/science.1229000. Epub 2013 Jan 30.
- Background: PubMed 25717097Kau AL, Planer JD, Liu J, Rao S, Yatsunenko T, Trehan I, Manary MJ, Liu TC, Stappenbeck TS, Maleta KM, Ashorn P, Dewey KG, Houpt ER, Hsieh CS, Gordon JI. Functional characterization of IgA-targeted bacterial taxa from undernourished Malawian children that produce diet-dependent enteropathy. Sci Transl Med. 2015 Feb 25;7(276):276ra24. doi: 10.1126/scitranslmed.aaa4877.
- Background: PubMed 31296738Gehrig JL, Venkatesh S, Chang HW, Hibberd MC, Kung VL, Cheng J, Chen RY, Subramanian S, Cowardin CA, Meier MF, O'Donnell D, Talcott M, Spears LD, Semenkovich CF, Henrissat B, Giannone RJ, Hettich RL, Ilkayeva O, Muehlbauer M, Newgard CB, Sawyer C, Head RD, Rodionov DA, Arzamasov AA, Leyn SA, Osterman AL, Hossain MI, Islam M, Choudhury N, Sarker SA, Huq S, Mahmud I, Mostafa I, Mahfuz M, Barratt MJ, Ahmed T, Gordon JI. Effects of microbiota-directed foods in gnotobiotic animals and undernourished children. Science. 2019 Jul 12;365(6449):eaau4732. doi: 10.1126/science.aau4732.
- Background: PubMed 33691083Keats EC, Das JK, Salam RA, Lassi ZS, Imdad A, Black RE, Bhutta ZA. Effective interventions to address maternal and child malnutrition: an update of the evidence. Lancet Child Adolesc Health. 2021 May;5(5):367-384. doi: 10.1016/S2352-4642(20)30274-1. Epub 2021 Mar 7.
- Background: PubMed 30554749Humphrey JH, Mbuya MNN, Ntozini R, Moulton LH, Stoltzfus RJ, Tavengwa NV, Mutasa K, Majo F, Mutasa B, Mangwadu G, Chasokela CM, Chigumira A, Chasekwa B, Smith LE, Tielsch JM, Jones AD, Manges AR, Maluccio JA, Prendergast AJ; Sanitation Hygiene Infant Nutrition Efficacy (SHINE) Trial Team. Independent and combined effects of improved water, sanitation, and hygiene, and improved complementary feeding, on child stunting and anaemia in rural Zimbabwe: a cluster-randomised trial. Lancet Glob Health. 2019 Jan;7(1):e132-e147. doi: 10.1016/S2214-109X(18)30374-7.
- Background: PubMed 35369816Simwanza NR, Kalungwe M, Karonga T, Mtambo CMM, Ekpenyong MS, Nyashanu M. Exploring the risk factors of child malnutrition in Sub-Sahara Africa: A scoping review. Nutr Health. 2023 Mar;29(1):61-69. doi: 10.1177/02601060221090699. Epub 2022 Apr 4.
- Background: PubMed 7542705Grantham-McGregor S. A review of studies of the effect of severe malnutrition on mental development. J Nutr. 1995 Aug;125(8 Suppl):2233S-2238S. doi: 10.1093/jn/125.suppl_8.2233S.
- Background: PubMed 34300122Omidakhsh N, von Ehrenstein OS. Improved Water, Sanitation and Utilization of Maternal and Child Health Services in South Asia-An Analysis of Demographic Health Surveys. Int J Environ Res Public Health. 2021 Jul 19;18(14):7667. doi: 10.3390/ijerph18147667.
- Background: PubMed 31973179Valcourt N, Javernick-Will A, Walters J, Linden K. System Approaches to Water, Sanitation, and Hygiene: A Systematic Literature Review. Int J Environ Res Public Health. 2020 Jan 21;17(3):702. doi: 10.3390/ijerph17030702.
- Individual participant dataSharing planned: Yes. Data will be anonymised prior to release for data sharing. All original data will be stored locally in the Immunology Unit for at least 10 years on appropriate electronic devices with approval for data sharing between the collaborating Institutions. All databases will be password-protected and accessible to authorised personnel only. Data users will be required to acknowledge the source of data and to ensure that the regulatory requirements of the MRCZ and other ethics regulators reviewing the projects are met. The PI through the data manager will be responsible for the overall quality and integrity of the data. Published data will be made available to other researchers upon request and verification. Additional use of data beyond thus study will be guided by the original approved study protocols and the signed participant informed consent.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Kerina Duri, Phd principal investigator
University of Zimbabwe
Exnevia Gomo, PhD study director
University of Zimbabwe
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Malnutrition Pregnancy and Malnutrition in Children, run by University of Zimbabwe at 1 site in Zimbabwe.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 26 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Zimbabwe. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kerina Duri, PhD (+2634791631 ext. 2428, kerina.duri@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Alpha diversity of maternal gut microbiota (time frame: Third trimester of pregnancy, week(s) 1, 6, 14, 24, 48, 96, 144 after delivery). The study lists 44 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07195006, which also lists 32 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Sep 2025.