Low Birthweight, Pre-Term
Conditions
Keywords
Infant Health, Low and Middle Income Countries [LMIC], Maternal Health, Infant Feeding, Low Birthweight
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.
Interventions
None listed
Sponsors
Study design
Eligibility
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Length-for-Age Z-score | At 6 month of age | A Child's length-for-age z-score at 6 months of age. Length-for-age z-scores (LAZ) are based on World Health Organization (WHO) child growth standards for term infants and INTERGROWTH-21st standards were used for preterm infants. A LAZ Z-score of 0 represents the population mean and scores below 0 represent a worse outcome. Further, Z-scores less than -2.0 indicates stunting in the infant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Diarrheal Disease | 6 month postpartum | Maternal Report of Ever having Diarrheal Disease from weeks 1 to 6 months of age |
Other
| Measure | Time frame | Description |
|---|---|---|
| Weight-for-age Z-score | At 6 month of age | Child's weight-for-age z-score. Weight-for-age (WAZ) z-scores at 6 months of age were based on WHO growth standards for term infants and INTERGROWTH- 21st standards, for preterm infants. A Z-score of 0 represents the population mean, and Z-scores below 0 represent a worse outcome. Further, WAZ Z-scores less than -2 indicates an infant who is underweight. |
| Percentage of Infants Malnourished at 6 Months | 6 months of age | Infants who were stunted and/or wasted and/or underweight according to WHO Growth Standards at 6 months of age. A Z-score of 0 represents the population mean, and Z-scores below 0 represent a worse outcome Infants who have Z-score (weight for age; length for age; or weight for length) less than -2 are considered malnourished. |
| Percentage of Infants Malnourished at 12 Months | 12 months of age | Infants who were stunted and/or wasted and/or underweight according to WHO Growth Standards at 12 months of age. A Z-score of 0 represents the population mean, and Z-scores below 0 represent a worse outcome Infants who have Z-score (weight for age; length for age; or weight for length) less than -2 are considered malnourished. |
Countries
India, Malawi, Tanzania
Participant flow
Pre-assignment details
The LIFE study did not involve an intervention. Enrollment of the prospective cohort was of mother-infant dyads; we have reported baseline data of the respective individuals. Outcome measurement is at the infant level. Similarly, for the in-facility observation cohort, we have reported baseline characteristics of individuals (mothers and infants); however, the outcomes are focused on infants. Thus, we have reported outcomes at that level.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 2,184 |
| In-facility Observations Moderately low birthweight (1500 to \< 2500g) infants and their mothers were enrolled during their admission to the postnatal ward or neonatal intensive care unit. | 290 |
| Total | 2,474 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 41 | 0 | 0 | 0 |
| Overall Study | Infant died, so mother withdrawn | 34 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 72 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 112 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Prospective Cohort Study - Quantitative | In-facility Observations |
|---|---|---|---|
| Age, Continuous | 25.8 Years STANDARD_DEVIATION 5.4 | 25.4 Years STANDARD_DEVIATION 5.3 | 26.5 Years STANDARD_DEVIATION 6.1 |
| Maternal Education Primary or less | 564 Participants | 501 Participants | 63 Participants |
| Maternal Education Secondary or more | 648 Participants | 569 Participants | 79 Participants |
| Race/Ethnicity, Customized African Infants | 683 Participants | 608 Participants | 75 Participants |
| Race/Ethnicity, Customized African Mothers | 643 Participants | 573 Participants | 70 Participants |
| Race/Ethnicity, Customized South Asian Infants | 579 Participants | 506 Participants | 73 Participants |
| Race/Ethnicity, Customized South Asian Mothers | 569 Participants | 497 Participants | 72 Participants |
| Region of Enrollment India Infants | 579 Participants | 506 Participants | 73 Participants |
| Region of Enrollment India Mothers | 569 Participants | 497 Participants | 72 Participants |
| Region of Enrollment Malawi Infants | 335 Participants | 300 Participants | 35 Participants |
| Region of Enrollment Malawi Mothers | 308 Participants | 273 Participants | 35 Participants |
| Region of Enrollment Tanzania Infants | 348 Participants | 308 Participants | 40 Participants |
| Region of Enrollment Tanzania Mothers | 335 Participants | 300 Participants | 35 Participants |
| Sex: Female, Male Infant Sex Female | 693 Participants | 608 Participants | 85 Participants |
| Sex: Female, Male Infant Sex Male | 569 Participants | 506 Participants | 63 Participants |
| Sex: Female, Male Mothers sex Female | 1212 Participants | 1070 Participants | 142 Participants |
| Sex: Female, Male Mothers sex Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 37 / 1,114 | 4 / 1,070 | 3 / 142 |
| other Total, other adverse events | 0 / 1,114 | 0 / 1,070 | 0 / 142 |
| serious Total, serious adverse events | 172 / 1,114 | 22 / 1,070 | 8 / 142 |
Outcome results
Length-for-Age Z-score
A Child's length-for-age z-score at 12 months of age. A Child's length-for-age z-score at 12 months of age. Length-for-age (LAZ) z-scores were based on World Health Organization (WHO) growth standards for term infants and preterm infants; we corrected for gestational age (GA) for preterm infants. A LAZ z-score of 0 represents the population mean and scores below 0 represent a worse outcome. Further, Z-scores less than -2.0 indicates an infant who is underweight.
Time frame: At 12 month of age
Population: Low birth weight infants; This outcome was only collected on the quantitative prospective cohort population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prospective Cohort Study - Quantitative | Length-for-Age Z-score | -1.58 Z-score | Standard Deviation 1.21 |
Length-for-Age Z-score
A Child's length-for-age z-score at 6 months of age. Length-for-age z-scores (LAZ) are based on World Health Organization (WHO) child growth standards for term infants and INTERGROWTH-21st standards were used for preterm infants. A LAZ Z-score of 0 represents the population mean and scores below 0 represent a worse outcome. Further, Z-scores less than -2.0 indicates stunting in the infant.
Time frame: At 6 month of age
Population: Low birth weight infants. This outcome was only collected on the quantitative prospective cohort population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prospective Cohort Study - Quantitative | Length-for-Age Z-score | -1.43 Z-score | Standard Deviation 1.28 |
Incidence of Diarrheal Disease
Maternal Report of Ever having Diarrheal Disease from weeks 1 to 6 months of age
Time frame: 6 month postpartum
Population: Low Birth Weight Infants; This outcome was only collected on the quantitative prospective cohort population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prospective Cohort Study - Quantitative | Incidence of Diarrheal Disease | 130 Participants |
Percentage of Infants Malnourished at 12 Months
Infants who were stunted and/or wasted and/or underweight according to WHO Growth Standards at 12 months of age. A Z-score of 0 represents the population mean, and Z-scores below 0 represent a worse outcome Infants who have Z-score (weight for age; length for age; or weight for length) less than -2 are considered malnourished.
Time frame: 12 months of age
Population: Low birth weight infants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prospective Cohort Study - Quantitative | Percentage of Infants Malnourished at 12 Months | 518 Participants |
Percentage of Infants Malnourished at 6 Months
Infants who were stunted and/or wasted and/or underweight according to WHO Growth Standards at 6 months of age. A Z-score of 0 represents the population mean, and Z-scores below 0 represent a worse outcome Infants who have Z-score (weight for age; length for age; or weight for length) less than -2 are considered malnourished.
Time frame: 6 months of age
Population: Low birth weight infants; This outcome was only collected on the quantitative prospective cohort population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prospective Cohort Study - Quantitative | Percentage of Infants Malnourished at 6 Months | 373 Participants |
Weight-for-age Z-score
Child's weight-for-age z-score. Child's weight-for-age z-score. Weight-for-age (WAZ) z-scores at 12 months were based on WHO growth standards for term infants and preterm infants. A Z-score of 0 represents the population mean, and Z-scores below 0 represent a worse outcome. Further, WAZ Z-scores less than -2 indicates an infant who is underweight.
Time frame: At 12 month of age
Population: Low Birth Weight Infants; This outcome was only collected on the quantitative prospective cohort population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prospective Cohort Study - Quantitative | Weight-for-age Z-score | -1.28 Z-score | Standard Deviation 1.12 |
Weight-for-age Z-score
Child's weight-for-age z-score. Weight-for-age (WAZ) z-scores at 6 months of age were based on WHO growth standards for term infants and INTERGROWTH- 21st standards, for preterm infants. A Z-score of 0 represents the population mean, and Z-scores below 0 represent a worse outcome. Further, WAZ Z-scores less than -2 indicates an infant who is underweight.
Time frame: At 6 month of age
Population: Low Birth Weight Infants; This outcome was only collected on the quantitative prospective cohort population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prospective Cohort Study - Quantitative | Weight-for-age Z-score | -1.23 Z-score | Standard Deviation 1.2 |