Low-birthweight Infant Feeding Exploration (LIFE)

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.

Study Overview

• Status: Completed
• Conditions: Low Birthweight; Pre-Term

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.

• Study Type: Observational
• Enrollment (Actual): 1126

Contacts and Locations

Study Locations

• India
  • Belgaum, India
    • Jawaharlal Nehru Medical College
• Malawi
  • Lilongwe, Malawi
    • UNC Project Malawi (UNCPM)
• Tanzania
  • Dar Es Salaam, Tanzania
    • Muhas/ Hsph

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 59 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort
In-facility Observations; Mothers and their LBW babies will be observed starting within 6 hours of birth until the baby is discharged from the health facility.
Prospective cohort study - Quantitative; Mothers and their low-birth weight babies will be enrolled 72 hours after birth and followed through 12 months postpartum. The prospective cohort survey (which includes anthropometric measurements and feeding observations) occurs at multiple time points over this 12-month period.
Prospective cohort study - Qualitative; Research specialists at each site will be speaking to key informants (includes doctors, nurses, midwives, community health workers (CHWs), Ministry of Health (MOH) officials, supply chain & milk bank experts) who are knowledgeable about breastfeeding policy, supply chain, or milk banks. Clinicians in study health facilities who work on labor and delivery, postnatal, newborn and neonatal ICU wards. They participate in In-depth interviews. Mothers, family members and health care workers of LBW babies, as well as community leaders (including religious leaders) who are knowledgeable about infant feeding in their communities will participate in focus group discussions. Focus group discussion will take up to 2 hours. In-depth interviews will take up to 1 hour. Mothers (6-month extension): Mothers chosen and consented for IDIs will include those currently enrolled in the prospective cohort. Additionally, their infants need to be between 9 and 12 months of age.
Retrospective Chart review; The retrospective chart review is a review of secondary data of mothers and their LBW babies who were born in the study health facilities prior to the start of the study.
Donor Human Milk Readiness Assessment; Key stakeholders in the area of newborn health who determine policy and procedures or who are directly involved with the provision of care. This includes clinicians, nurses, lactation/nutrition specialists, hospital leadership and/or Ministry of Health officials present in the study health facilities. This is a one-time data collection exercise in the form of either: (1) a largely qualitative facility readiness assessment tool with some qualitative questions for facility staff or (2) a facility tool observing the "flow of milk" along with key informant interviews in the study facilities. This could take anywhere from 1hr to a day depending on the tool administered, key informants involved and size of the study facility.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length-for-Age z-score	A Child's length-for-age z-score (cm) at 6 months of age	At 6 month of ag

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Infant Morbidity	Maternal Report of Diarrheal Disease, Pneumonia, Sepsis, Malaria, Necrotizing Entercolitis, Seizures, Hyperbilirubinemia	6 month postpartum;12 month postpartum

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight-for-age z-score	Child's weight-for-age z-score (kg)	At 6 month of age; at 12 month of age.
Percentage of children who are nutritionally at risk in first 12 months of life	Using a combination of traditional anthropometric measures we will define children who don't meet expected growth standards.	0-12 months of age.

Collaborators and Investigators

• Sponsor: Harvard School of Public Health (HSPH)
• Collaborators: Boston Children's Hospital; Emory University; Brigham and Women's Hospital; Bill and Melinda Gates Foundation; University of North Carolina, Chapel Hill; PATH; University of North Carolina; Jawaharlal Nehru Medical College; Muhimbili University of Health and Allied Sciences; Ariadne Labs
• Investigators: Principal Investigator: Katherine Semrau, PhD, MPH, Ariadne Labs

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2019
• Primary Completion (Actual): July 29, 2021
• Study Completion (Actual): July 29, 2021

Study Registration Dates

• First Submitted: June 27, 2019
• First Submitted That Met QC Criteria: June 27, 2019
• First Posted (Actual): July 1, 2019

Study Record Updates

• Last Update Posted (Actual): May 12, 2022
• Last Update Submitted That Met QC Criteria: May 11, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Maternal Health; Infant Health; Low and Middle Income Countries [LMIC]; Infant Feeding; Low Birthweight
• Additional Relevant MeSH Terms: Body Weight; Birth Weight
• Other Study ID Numbers: HSPH OPP1192260

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No