Understanding Intrauterine Retinol Transfer

Melissa Thoene, PhD, RD, assistant professor in the Division of Neonatology, is the corresponding author of an article recently published by the journal Biomedicines.1 Co-authors from UNMC include Ann Anderson-Berry, MD, PhD; Corrine Hanson, PhD, RD; Haley Haskett, MD; Maranda Thompson, and Matthew Van Ormer. The paper reports recent research to understand intrauterine transfer of retinol (vitamin A) from mothers to their infants. Dr. Thoene took time to respond to the following questions about the study for the CHRI Research Bulletin.

Q: How great is the importance of intrauterine retinol transfer between mother and baby?

A: Intrauterine retinol transfer has important implications for appropriate growth and fetal development. Prolonged retinol deficiency contributes to weakened immunity, blindness and slower growth. Comparatively, retinol excess can be teratogenic and cause fetal malformations, so modulation of intrauterine retinol transfer is critical.

Q: One of the surprising issues addressed in your study is that about half of pregnant women in the US have insufficient or deficient levels of retinol at childbirth. Do we know why this is the case?

A: Vitamin A deficiency has not previously been considered a prevalent problem in the U.S. population due to our high gross domestic product. However, our results endorse that a “moderate” public health problem (≥10% to <20% of the population) exists within a delivering Midwest population, per definitions by the World Health Organization.

Potential causes of deficiency include mothers with food insecurity during pregnancy or mothers who do not regularly consume foods high in vitamin A or provitamin-A carotenoids. We did not assess changes in maternal retinol levels from start to end of pregnancy, so an alternative consideration is if mother’s status declines throughout gestation in attempt to preserve fetal levels.

Q: What cohort of mother-infant dyads was your team able to study, with respect to maternal retinol status and transfer?

A: We enrolled a diverse cohort of mother-infant dyads who delivered their infants at term (>37 weeks gestation). Of these, approximately 10% of mothers were retinol deficient and 38% retinol insufficient. We chose not to include dyads who delivered preterm since nutrient levels and intrauterine transfer rates may vary based on stage of placental development.

Q: What were the main research questions, and how did you set about answering them?

A: Vitamin A is a critical nutrient and our past research identified many mothers to have inadequate retinol levels, so we wanted to understand how this impacts newborn retinol levels. We were able to compare retinol levels in umbilical cord blood between maternal groups of retinol deficiency, insufficiency and adequacy and to also assess mother-to-infant transfer rate between groups.

Q: What were the most noteworthy discoveries emerging from the study?

A: Our research identified two noteworthy discoveries. First, we identified that intrauterine transfer rate is augmented in cases of maternal retinol deficiency or insufficiency. Consequently, infant retinol levels at birth were not significantly different between those born to retinol deficient, insufficient or adequate mothers. This tells us that intrauterine retinol transfer is highly regulated, but at the expense of maternal stores.

A second unique finding is that <2% of infants had retinol levels that met adult criteria for retinol adequacy, per the World Health Organization. This leads us to question if initially low newborn concentrations do not present similar adverse effects as those seen in older populations, indicating lower reference ranges may be tolerable in very early life.

Q: Are there plans to expand upon this work in the future?

A: Yes, we recently looked at retinol levels in breast milk from a small cohort of NICU moms and found that 44% of samples were retinol inadequate. We plan to collect more breast milk samples and analyze the nutrient content to assess relationships with NICU infant outcomes like growth or bronchopulmonary dysplasia. Ideal future studies would also provide nutrition interventions during pregnancy to enhance retinol levels at time of delivery and during lactation.

  1. Thoene M, Haskett H, Furtado J, Thompson M, Van Ormer M, Hanson C, Anderson-Berry A. Effect of Maternal Retinol Status at Time of Term Delivery on Retinol Placental Concentration, Intrauterine Transfer Rate, and Newborn Retinol Status. Biomedicines. 2020 Aug 31;8(9):E321.


by Matthew Sandbulte, CHRI Grant & Scientific Writer | October 1, 2020