Women First: Preconception Maternal Nutrition

Study Overview
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Brief Summary
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Multi-country three-arm, individually randomized, non-masked, controlled trial to ascertain the benefits of ensuring optimal maternal nutrition before conception and providing an evidence base for programmatic priority directed to minimizing the risk of malnutrition in all females of reproductive age.

Detailed Description
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The objective is to determine the benefits to the offspring of women in poor, food-insecure environments of commencing a daily comprehensive maternal nutrition supplement (with additional balanced calorie/protein supplement for underweight participants) ≥ 3 months prior to conception versus the benefits of commencing the same supplement at 12 weeks gestation and also to compare offspring outcomes with those of a control group which receives no supplement.

Official Title
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Women First: Preconception Maternal Nutrition

Conditions
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Maternal Malnutrition, Growth Failure, Mortality, Morbidity, Stunting

Intervention / Treatment
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* Dietary Supplement: Comprehensive Maternal Nutrition Intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 16-35 years of age; expectation to have first or further pregnancy without intent to utilize contraception Hb >8 g/dL Exclusion Criteria: Nulliparous women who do not agree to hospital delivery (equipped for caesarian section) or/and do not have ready access to such a facility.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: Preconception<br>Arm 1 will commence the comprehensive maternal nutrition intervention at 3-7 months postpartum. Delivery of the intervention will be monitored biweekly by collection of empty and unused sachets of the lipid-based supplement (LNS), maternal report, and casual observation of household behavior. Arm 1 participants will be weighed monthly and Body Mass Index (BMI) calculated. If BMI <20 an additional energy supplement will be provided. Menstrual history will be obtained at each visit and a urine pregnancy test will be performed if menses is delayed. | Dietary Supplement: Comprehensive Maternal Nutrition Intervention<br>* The nutrition intervention will be delivered before conception or at 12 weeks gestation and continued through delivery and compared with a control group. The supplement to be used is a multi-micronutrient (MMN) fortified lipid-based supplement composed of dried skimmed milk, soybean and peanut extract, sugar, maltodextrin stabilizers, and emulsifiers.<br>* Other names: LNS;|
| Experimental: Arm 2: Pregnancy<br>Participants in Arm 2 will commence the same comprehensive maternal nutrition intervention at 12 weeks gestation. | Dietary Supplement: Comprehensive Maternal Nutrition Intervention<br>* The nutrition intervention will be delivered before conception or at 12 weeks gestation and continued through delivery and compared with a control group. The supplement to be used is a multi-micronutrient (MMN) fortified lipid-based supplement composed of dried skimmed milk, soybean and peanut extract, sugar, maltodextrin stabilizers, and emulsifiers.<br>* Other names: LNS;|
| No Intervention: Arm 3: Control<br>Participants in Arm 3 will receive biweekly visits to monitor pregnancy status. No health advice will be given other than information about prenatal care, location of delivery, and breastfeeding education in the third trimester. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neonatal linear growth | Research assistants will obtain neonatal length measurement at <24 hours of age. | <24 hours of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length-for-age Z-scores | Research assistants will obtain infant anthropometry measurements, which include length, head circumference, triceps skin folds, Mid Upper Arm Circumference (MUAC), and weight, at age 0.5, 1, 3, 6, 12, 18 and 24 months of age. Length-for-age Z-scores will be compared for offspring of mothers randomized to the three intervention arms. | age 0.5, 1, 3, 6, 12, 18 and 24 months postnatal | 
| Estimate fetal growth | Ultrasound measurements will be undertaken at 12 weeks gestation with the goals of confirming gestational age and estimating fetal growth. | 12 weeks gestation | 
| Mean birth weight | As a dichotomous variable, the cutoff of 2500 g does not have the power of the continuum of birth length, but is included because of the long history of use in determining which newborns are severely underweight and this association with impaired neonatal and long-term prognosis. The design of this study will allow distinction between pre-term birth (PTB) and growth retardation of the term infant (mature IUGR). | at birth | 
| Incidence of low birth weight (LBW) infants | As a dichotomous variable, the cutoff of 2500 g does not have the power of the continuum of birth length, but is included because of the long history of use in determining which newborns are severely underweight and this association with impaired neonatal and long-term prognosis. The design of this study will allow distinction between pre-term birth (PTB) and growth retardation of the term infant (mature IUGR). | at birth | 
| Perinatal Mortality | The outcome is to determine, in poor food insecure communities if a daily comprehensive maternal nutrition supplement starting ≥ 3 months preconception and continuing throughout pregnancy will reduce the incidence of offspring perinatal mortality (including still births), compared with that for offspring of mothers who commence the same supplement starting at 12-16 weeks gestation. | From 20 weeks gestation through 1 month of age | 
| Incidence of severe neonatal and infant infectious disease | Outcome measure is number of acute visits / admissions to health center/hospital for severe infectious disease. This secondary outcome will provide insight into the importance of maternal and fetal nutrition in the early prenatal development of host-defense mechanisms and, through comparison with the prenatal and control Arms, on the importance of maternal nutrition throughout pregnancy. It is further intended to collect minor morbidity data. | birth to 6 months of age | 
| Epigenome (Maternal) | To compare longitudinal changes between groups in the maternal epigenome (including blood, buccal swabs, and possibly other readily obtainable samples) at baseline, 12 weeks pregnancy (prior to initiation of LNS in Arm 2), 34 weeks pregnancy, and at 3 months postpartum. Also will collect placental, fetal and cord blood epigenome at delivery by group and infant epigenome at 3 months with fingerstick blood and buccal swabs. | baseline, 12 and 34 weeks gestation, delivery, and 3 months postpartum (maternal); 2 weeks and 3 months of age (infant) | 
| Epigenome (Infant) | To compare longitudinal changes between groups in the maternal epigenome (including blood, buccal swabs, and possibly other readily obtainable samples) at baseline, 12 weeks pregnancy (prior to initiation of LNS in Arm 2), 34 weeks pregnancy, and at 3 months postpartum. Also will collect placental, fetal and cord blood epigenome at delivery by group and infant epigenome at 3 months with fingerstick blood and buccal swabs. | 2 weeks and 3 months of age | 
| Deep phenotyping of maternal metabolic and nutritional status | The outcome represents deep phenotyping by measuring in maternal tissues: hormones, metabolites, measures of inflammation, oxidant stress and immune function/status, and nutrient biomarkers as possible indices of fundamental metabolic alterations resulting from improved long-term maternal nutrition in food insecure populations. Longitudinal blood samples will be collected from maternal participants in Arms 1 and 2 at baseline, 12 weeks gestation (prior to initiation of LNS in Arm 2), 34 weeks gestation, delivery and 3 months postpartum. Samples will also be collected from participants in Arm 3 at 34 weeks gestation and at 3 months postpartum. | 12 and 34 weeks gestation, delivery, and 3 months postpartum | 
| Microbiome (maternal) | Based on potential long-term effects on maternal nutritional and metabolic state from preconception intervention, we hypothesize that the gut microbiota will differ between the two intervention arms at the three proposed time points. | 12 & 34 weeks gestation and delivery (maternal) | 
| Microbiome (infant) | Based on potential long-term effects on maternal nutritional and metabolic state from preconception intervention, we hypothesize that the gut microbiota will differ between the two intervention arms at the three proposed time points. | 14 days and 3 months of age (infant) | 
| Composition of breast milk | We hypothesize that improved maternal nutrition at the time of greatest plasticity in early pregnancy will favorably influence maternal metabolic and nutritional status throughout pregnancy and thus potentially the composition of breast milk in terms of hormonal content, immune factors, cytokines, and gut growth factors. | 14 days postpartum | 
| Neurodevelopment assessment | Offspring randomized to receive neurodevelopmental evaluation (BSID-III or InterNDA, 2:1 ratio) at 24 mo of age | 24 mo age | 
| Gestational weight gain (GWG) | Describe GWG and its associations with fetal growth and birth outcomes within each country by baseline maternal nutritional status (BMI) and the receipt of nutrition interventions. Evaluate how GWG might mediate the effects of maternal nutrition interventions. | Enrollment to delivery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LBW, preconception maternal nutrition, Length-for-age, maternal nutrition supplement, multi-micronutrient fortified lipid-based supplement, infant growth, low-resource settings