Clinical trial NCT04002908: Low-birthweight Infant Feeding Exploration
Official title: Low-birthweight Infant Feeding Exploration
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Low Birthweight
Pre-Term
Keywords: Infant Health
Low and Middle Income Countries [LMIC]
Maternal Health
Infant Feeding
Low Birthweight
Lead sponsor: Harvard School of Public Health (HSPH)
Sponsor class: OTHER
Collaborators: name: Bill and Melinda Gates Foundation
name: Emory University
name: Boston Children's Hospital
name: Brigham and Women's Hospital
name: PATH
name: University of North Carolina, Chapel Hill
name: Jawaharlal Nehru Medical College
name: Muhimbili University of Health and Allied Sciences
name: University of North Carolina
name: Ariadne Labs
First posted: 2019-07-01
Enrollment: 3188
Sex: ALL
Minimum age (years): 16
Maximum age (years): 59
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Mothers and their LBW babies who are either born in the study health facilities or arrive within 72 hours of birth and meet eligibility criteria

Brief summary: Globally, 15% of all babies, amounting to 20 million infants each year, are born low birthweight (LBW), defined less than 2500 grams (5.5 lbs). Compared to normal weight infants, LBW infants are at higher risk of morbidity, mortality, and poor growth (Risnes et al 2011; Larroque et al 2001; WHO 2006). The main causes of LBW are preterm birth, intrauterine growth restriction (IUGR), or their combination. Unfortunately, there is a paucity of information around feeding practices and optimal feeding strategies for this population, particularly for LBW infants who struggle with breastfeeding or growth. This study hopes to address these gaps.

Detailed description: The Low-birthweight Infant Feeding Exploration (LIFE)(original grant 0-6 months of age) and the 6- month extension (6-12 months of age) will fill a critical data gap in the field of newborn care regarding vulnerability and feeding of LBW infants. The investigators aim to establish the background information required to set up and test the most efficient and feasible infant feeding strategies for LBW infants: first to support breastfeeding, and then to support infants who are nutritionally at risk in the first 6 month of life in low and middle income countries (LMIC). The investigators will explore all three infant feeding options currently included in the WHO guidelines for LBW infants (WHO 2011), namely mother's own milk (MOM), donor human milk (DHM), and breast milk substitute or formula (BMS), in that order. This work will provide much-needed evidence to inform infant feeding guidelines.

In addition, this 6-month extension will allow for a more comprehensive exploration and understanding of feeding options for LBW infants from 6 to 12 months of age, accounting for timing of introduction of complementary liquids and foods, changes in feeding types, growth and health outcomes over the entire infancy period. This will contribute significantly and allow for high quality data to describe the burden of disease across sites. Specifically, we will be able to describe the following for LBW infants:

* Growth trajectories from 0 to 12 months of age
* Patterns and timing of complementary feeding and continued breastfeeding/breastmilk consumption
* Common infant morbidities and timing of mortality
* Maternal demographics, well-being and environmental factors affecting infant feeding and growth

The overall study goal is to understand feeding options for LBW infants in LMIC settings, including current feeding practices, health outcomes, and potential interventions. The study will take place in four study sites located in three countries: Tanzania, Malawi, and India. Each study site will encompass 2 to 5 individual study facilities. The three study objectives under the goal include:

1. Understand the current practices and standard of care (SOC) for feeding LBW infants
2. Define and document the key outcomes (including growth, morbidity, and lack of success on MOM) for LBW infants under current practices
3. Assess the acceptability and feasibility of a system-level IYCF intervention and the proposed infant feeding options for LBW infants

The investigators will also use the results of this work to design ways to support exclusive breastfeeding (including strategies for feeding with MOM), and to support other options, when mother's own milk (MOM) is unavailable or infants are nutritionally at risk. To do this, the investigators will engage in discussion and consensus-building activities among study staff and key stakeholders, using the collected study data to inform feasible, acceptable Infant and Young Child Feeding (IYCF) strategies for LBW infants that include specific options for those who are nutritionally at risk. The strategies will be tailored to the country as much as possible. A primary product for this later stage will be a white paper documenting key findings from the research and proposing feeding strategies for LBW infants in study sites.

Eligibility criteria: Inclusion Criteria:

* Infant birthweight between 1500 and \<2500g (according to chart and then verified by study staff).
* Residence within catchment area of facility.
* Mother's consent obtained for herself and infant.
* Newborns must be enrolled within 72 hours of birth.
* Women (mothers) who are of age of majority in their respective countries.

Exclusion Criteria:

* Mother does not meet the local age of majority.
* Infant very low birthweight \<1500g.
* Infant has congenital abnormality that interferes with feeding, which includes: Cleft lip or palate; Hydrocephalus; Gastrointestinal tract anomalies including gastroschisis, omphalocele, or anal atresia; Neural tube defects; Congenital cardiac defects; Suspected Trisomy 21; Suspected TORCH infection such as congenital rubella, cytomegalovirus (CMV), toxoplasmosis, or syphilis.
* Critical or severe illness jeopardizing early survival, specifically, investigators will exclude infants with severe encephalopathy as determined by modified Sarnat criteria.
* If the Infant dies before enrollment can occur.
* Infant has a twin or triplet that has died.
* Plans to leave the study area before end of data collection.
* Infants must be enrolled in the prospective study within 72 hours of birth. If the infant is older than 72 hours at the time of screening, s/he will be ineligible for the study.
* Maternal death: The study will exclude cases of maternal death that occur during labor and delivery (or at any time before the consenting process would begin for this study).
* Maternal deaths will count as an exclusion criterion for the prospective cohort if they occur before enrollment. In the event that a mother dies at any time after enrollment the infant will still be retained in the cohort.

  6-Month Extension Study Criteria:

Inclusion criteria for the mother/infant pair are:

* Currently enrolled in the LIFE study and fulfills all original inclusion criteria.
* Mother's or surrogate consent obtained for herself and infant for another 6 months of follow up.

Exclusion criteria for the mother/infant pair are:

• Not previously enrolled in the LIFE study in addition to all original exclusion criteria.

Primary outcomes:
measure: Length-for-Age Z-score
timeFrame: At 6 month of age
measure: Length-for-Age Z-score
timeFrame: At 12 month of age
Secondary outcomes:
measure: Incidence of Diarrheal Disease
timeFrame: 6 month postpartum
Other outcomes:
measure: Weight-for-age Z-score
timeFrame: At 6 month of age
measure: Percentage of Infants Malnourished at 6 Months
timeFrame: 6 months of age
measure: Percentage of Infants Malnourished at 12 Months
timeFrame: 12 months of age
measure: Weight-for-age Z-score
timeFrame: At 12 month of age
Locations:
city: Belgaum
country: India
facility: Jawaharlal Nehru Medical College
city: Lilongwe
country: Malawi
facility: UNC Project Malawi (UNCPM)
city: Dar Es Salaam
country: Tanzania
facility: Muhas/ Hsph
Study officials:
affiliation: Ariadne Labs
name: Katherine Semrau, PhD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vesel L, Spigel L, Behera JN, Bellad RM, Das L, Dhaded S, Goudar SS, Guruprasad G, Misra S, Panda S, Shamanur LG, Vernekar SS, Hoffman IF, Mvalo T, Phiri M, Saidi F, Kisenge R, Manji K, Salim N, Somji S, Sudfeld CR, Adair L, Caruso BA, Duggan C, Israel-Ballard K, Lee AC, Martin SL, Mansen KL, North K, Young M, Benotti E, Marx Delaney M, Fishman E, Fleming K, Henrich N, Miller K, Subramanian L, Tuller DE, Semrau KE. Mixed-methods, descriptive and observational cohort study examining feeding and growth patterns among low birthweight infants in India, Malawi and Tanzania: the LIFE study protocol. BMJ Open. 2021 Dec 2;11(12):e048216. doi: 10.1136/bmjopen-2020-048216.