Growth Failure, Maternal Malnutrition, Morbidity, Mortality, Stunting
Conditions
Keywords
preconception maternal nutrition, LBW, Length-for-age, maternal nutrition supplement, multi-micronutrient fortified lipid-based supplement, infant growth, low-resource settings
Brief summary
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
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.
Interventions
DIETARY_SUPPLEMENTComprehensive Maternal Nutrition Intervention
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.
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Instituto de Nutricion de Centroamerica y Panama (INCAP)
Kinshasa School of Public Health
Jawaharlal Nehru Medical College
Aga Khan University
RTI International
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
16 Years to 35 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Neonatal linear growth | <24 hours of age | Research assistants will obtain neonatal length measurement at \<24 hours of age. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Estimate fetal growth | 12 weeks gestation | Ultrasound measurements will be undertaken at 12 weeks gestation with the goals of confirming gestational age and estimating fetal growth. |
| Mean birth weight | at birth | 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). |
| Incidence of low birth weight (LBW) infants | at birth | 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). |
| Perinatal Mortality | From 20 weeks gestation through 1 month of age | 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. |
| Incidence of severe neonatal and infant infectious disease | birth to 6 months of age | 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. |
| Epigenome (Maternal) | baseline, 12 and 34 weeks gestation, delivery, and 3 months postpartum (maternal); 2 weeks and 3 months of age (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. |
| Length-for-age Z-scores | age 0.5, 1, 3, 6, 12, 18 and 24 months postnatal | 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. |
| Deep phenotyping of maternal metabolic and nutritional status | 12 and 34 weeks gestation, delivery, and 3 months postpartum | 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. |
| Microbiome (maternal) | 12 & 34 weeks gestation and delivery (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. |
| Microbiome (infant) | 14 days and 3 months of age (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. |
| Composition of breast milk | 14 days postpartum | 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. |
| Neurodevelopment assessment | 24 mo age | Offspring randomized to receive neurodevelopmental evaluation (BSID-III or InterNDA, 2:1 ratio) at 24 mo of age |
| Gestational weight gain (GWG) | Enrollment to delivery | 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. |
| Epigenome (Infant) | 2 weeks and 3 months of age | 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. |
Countries
Democratic Republic of the Congo, Guatemala, India, Pakistan
Outcome results
None listed