Metabolism of Neonatal Vitamin A Supplementation: A Systematic Review

A systematic review was conducted to summarize the absorption, transport, storage, and metabolism of oral neonatal vitamin A supplementation (NVAS). This review focused specifically on the neonatal period (first 28 d of life for humans) to inform guidance by WHO on recommendations related to NVAS. A systematic search of international and regional databases was conducted. Inclusion criteria were human or animal studies that gave oral vitamin A as a single or limited number of doses to apparently healthy neonates. Studies evaluating fortification or food-based approaches, dosing with retinoic acid, or studies of neonatal models of disease were excluded. The search retrieved 8847 unique records. After screening by title and abstract, 88 were screened using the full text, and 35 records met inclusion criteria: 13 human and 22 animal studies. Studies indicate that high-dose NVAS is absorbed well by neonates, typically mirroring fat absorption. Doses were primarily stored in the liver and transiently increased in the lung, kidney, spleen, adrenal glands, brain, skin, and adipose tissue, generally with a dose-response. Serum retinol and retinyl esters also transiently increased following NVAS. Although minimal acute adverse effects are noted, there is a lack of data supporting NVAS for improving organ maturation or sustained delivery to target organs. Research gaps include the physiological effects of the short-term increase of vitamin A concentrations in extrahepatic tissues, or whether there are unknown adverse effects over time.