Vitamin A Supplementation and Breast Milk Vitamin A Levels in Mothers of Preterm Infants

Vitamin A (VA) is an essential micronutrient involved in normal vision, immune function, epithelial integrity, growth, and lung development. Adequate vitamin A status is particularly important during early infancy, a period characterized by rapid growth and organ development. Preterm infants are at increased risk of vitamin A deficiency because they are born before substantial fetal accumulation of vitamin A stores occurs during the third trimester of pregnancy. As a result, many preterm infants begin life with limited vitamin A reserves and depend largely on external sources of nutrition to meet their vitamin A requirements.

Human milk is an important source of vitamin A for infants. However, breast milk vitamin A concentrations vary substantially among lactating mothers and may be influenced by maternal nutritional status and dietary intake. Because preterm infants are especially vulnerable to vitamin A deficiency and its associated complications, including impaired growth, increased susceptibility to infection, and adverse pulmonary outcomes such as bronchopulmonary dysplasia (BPD), interventions that increase vitamin A concentrations in breast milk may provide a practical strategy to improve nutrient delivery to this high-risk population.

Previous studies have evaluated maternal vitamin A supplementation in various populations, but limited information is available regarding the effects of daily standardized-dose vitamin A supplementation in mothers of extremely preterm infants. Furthermore, little is known about the feasibility of implementing such supplementation programs in mothers whose infants require prolonged neonatal intensive care hospitalization.

The primary objective of this pilot study is to evaluate the effect of daily maternal vitamin A supplementation on breast milk vitamin A concentrations during the first four months postpartum in mothers of infants born at less than 29 weeks' gestation. Participants will receive a commercially available oral multivitamin containing 1,300 mcg retinol activity equivalents (RAE) of vitamin A daily for four months after delivery. Breast milk samples will be collected longitudinally to evaluate changes in vitamin A concentrations over time.

A secondary objective is to assess the feasibility of conducting a larger clinical trial of maternal vitamin A supplementation in this population. Feasibility measures will include recruitment rates, participant retention, adherence to supplementation, safety and tolerability, and the practicality of study procedures. Recruitment and retention data will help determine whether mothers of very preterm infants can be successfully enrolled and followed for four months postpartum. Adherence will be assessed through participant self-report and pill counts. Study personnel will evaluate the feasibility of blood collection, breast milk sampling, scheduling of study visits, and completion of data collection procedures within the planned study timeline and available resources.

An additional objective is to determine the relationship between maternal serum retinol concentrations and breast milk vitamin A concentrations during the supplementation period. Maternal serum vitamin A levels and breast milk vitamin A concentrations will be measured at predefined time points to evaluate whether changes in maternal vitamin A status are associated with corresponding changes in breast milk vitamin A content.

This study is designed as a prospective, single-arm interventional pilot study. Approximately 20 lactating mothers of infants born before 29 weeks' gestation will be enrolled. Maternal serum vitamin A concentrations will be measured at baseline, 2 months, and 4 months postpartum. Breast milk vitamin A concentrations will be measured at approximately 2 weeks, 2 months, and 4 months postpartum. Demographic and clinical information will be collected through medical record review and participant surveys. Additional data regarding maternal health, breastfeeding practices, adherence to supplementation, and infant clinical outcomes will be collected throughout the study period.

Participant safety will be monitored throughout the study. The vitamin A dose used in this study is consistent with the Recommended Dietary Allowance (RDA) for lactating women and remains below the established tolerable upper intake level. Maternal serum vitamin A concentrations will be monitored during follow-up visits. Participants will be assessed for symptoms potentially associated with vitamin A excess, including headache, nausea, dizziness, skin changes, and other adverse events. If elevated serum vitamin A levels or symptoms suggestive of hypervitaminosis A occur, supplementation will be discontinued and appropriate clinical evaluation will be performed. Additional laboratory testing, including liver function testing, may be obtained when clinically indicated. Infants will not undergo research blood sampling but will continue to receive routine clinical monitoring as part of standard neonatal intensive care.

Because this is a pilot study, the primary emphasis is on feasibility, safety, adherence, and estimation of effect size rather than formal hypothesis testing. The information obtained will provide important preliminary data regarding the potential effectiveness of maternal vitamin A supplementation in increasing breast milk vitamin A concentrations and will inform the design, implementation, and sample size calculations of future adequately powered clinical trials. The results may contribute to the development of nutritional strategies aimed at improving vitamin A delivery to preterm infants through human milk and ultimately improving health outcomes in this vulnerable population.

Inclusion criteria

• Mothers aged 18 to 45 years Delivered an infant born at less than 29 weeks' gestation Intending to provide breast milk for at least 4 months postpartum Willing and able to swallow oral tablets Willing to comply with study procedures, including blood draws and breast milk collection at scheduled time points Able to provide written informed consent

Exclusion criteria

• Age less than 18 or greater than 45 years Contraindications to breastfeeding or inability to provide breast milk Known liver disease or conditions affecting vitamin A metabolism (e.g., chronic liver disease, known hypervitaminosis A) Baseline elevated vitamin A levels above the normal reference range Multiple gestation pregnancy (if you intend to exclude this-remove if not required) Known substance use disorder that may interfere with adherence or safety Infants with major congenital anomalies or known syndromic conditions Maternal refusal or inability to provide informed consent Planned discontinuation of breastfeeding within 4 months postpartum