Milk Volume Outcomes Following Oral Nicotinamide Riboside Supplementation in Mothers of Extremely Preterm Infants

Nicotinamide Riboside and Milk Production in the NICU

This study aims to evaluate the feasibility and effects of nicotinamide riboside (NR) supplementation in lactating mothers of infants expected to be hospitalized in the neonatal intensive care unit (NICU) for at least four weeks.

An adequate supply of a mother's own milk plays a critical role in optimizing health outcomes for at-risk infants, such as preterm and medically or surgically complex term infants. Despite this, insufficient milk production disproportionately affects the mothers of these infants. In the United States, metoclopramide is the only drug approved by the FDA for off-label use as a galactagogue. Nicotinamide riboside (NR), a niacin precursor, has been shown in a murine model to support lean body composition in lactating dams while augmenting high-quality milk production and enhancing cognitive and physical development of pups. Human testing with NR has been limited to long-term safety and bioavailability measures. This study aims to assess the feasibility of NR supplementation in mothers whose infants are admitted to the NICU for at least 4 weeks.

To address this gap, this study will enroll a small cohort of mothers with infants, either born preterm (<32 weeks of gestation) or term infants with complex medical or surgical conditions, admitted to the NICU for at least four weeks.

This double-blinded, randomized, placebo-controlled pilot feasibility trial aims to investigate NR supplementation in mothers of infants who are hospitalized in the NICU for at least 4 weeks. The intervention period with maternal nicotinamide riboside supplementation/placebo and maternal milk, urine, and blood sampling will be 19 days, including an enrollment day.

We aim to establish the feasibility of conducting a supplementation study in mothers of hospitalized infants, with enrollment feasibility defined as enrolling ≥ 50% eligible mothers.

Secondary objectives include assessing feasibility metrics (supplement compliance, milk sample collection adherence, and withdrawal rates); protocol adherence; and the impact of nicotinamide riboside supplementation on milk volume, milk composition (including macro- and micronutrient composition, glycans, metabolites, lipidomics, and CCN3), and urinary metabolites. Remnant infant blood samples will be used to examine the relationship between infant feeding practices and neonatal insulin, glucose, and amino acid concentrations.

An optional component of the study is the collection of maternal blood to assess the impact of NR supplementation on the concentration of serum prolactin, AST, ALT, metabolites, and CCN3; plasma lipidomics; and whole blood concentration of NAD+ related precursors.

Inclusion criteria are required to be met before or at enrollment:

Mothers who are 18 years or older.

Infants delivered at 24-32 weeks OR infants (any GA) that researchers anticipate will be hospitalized in the NICU for at least 4 weeks, including, but not limited to, infants with a diagnosis of gastroschisis, a cardiac defect, intestinal atresia, etc.

Infants born at the UC Davis Medical Center or transferred to the UC Davis Medical Center NICU within the first 7 days of life.

Mothers who attempted initial milk expression within 12 hours of delivery.

Mothers who attempted milk expression at least 6 times every 24 hours from 72 hours after delivery to the Enrollment Visit.

Mothers who have delivered at least 96 hours (4 days) prior to the Enrollment Visit.

Mothers who have experienced a level "3" on the OMPQ before starting the collection of their first 24-hour pooled milk sample (study days 0-3).

Mothers who plan to feed their infants breast milk for at least 3 months.

Mothers who were pregnant with one infant.

Mothers willing to refrain from tandem feeding (directly breastfeeding) another child during the study period.

Mothers willing to refrain from enrolling themselves in another intervention trial during the study period.

Mothers willing to express, weigh, record, and collect 24-hour pooled milk

Mothers willing to remove nipple piercings during the study period.

Mothers willing to refrain from using pseudoephedrine (often found in Sudafed, Theraflu, Claritin-D, etc.) during the study period.

Mothers willing to express milk 6 times or more every 24 hours, including at least once during the night, and with no more than 5 hours between milk expression sessions, during the study period.

Mothers willing to refrain from consuming non-study supplements that contain nicotinamide-riboside (or similar derivatives, including NMN) during the study period.

Mothers willing to refrain from consuming galactagogues during the study period.