Metabolism of Neonatal Vitamin A Supplementation: A Systematic Review

Abstract

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.

Evidence to Underpin Vitamin A Requirements and Upper Limits in Children Aged 0 to 48 Months: A Scoping Review

“…Studies assessing the relationship between vitamin A intake and a marker of vitamin A status (Excel sheet 2B Intake Status) and between status and health, growth, or development outcomes (Excel sheet 2C Status Outcome) may in combination support the data directly assessing intake and outcomes. For Intake Status studies, we included three systematic reviews published since early 2013 [ 24 , 25 , 26 ], which were data-extracted and assessed for risk of bias (plus two older systematic reviews), 31 recent trials, of which 12 appeared particularly recent and relevant [ 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ] (and 80 older trials). Alongside these we noted 12 recent cohort or case–control studies, 15 earlier studies, nine recent cross-sectional studies, 25 older studies, and nine non-systematic reviews.…”

“…The most relevant studies appear on the Excel sheet 2B Intake Status. There are three relevant systematic reviews [ 24 , 25 , 26 ], plus a set of trials assessing effects of supplementation on serum retinol and beta-carotene. Many isotopic studies (shown in Table 2 ) also assessed intake status relationships.…”

“…However, we discuss them together as there is a great deal of overlap (Excel sheet 3 Factorial). The most relevant systematic review (“Metabolism of Neonatal Vitamin A Supplementation” [ 24 ]) focused on the first 28 days of life. The authors of that review searched systematically between August 2013 and 5 Jan 2020, with a supplemental Medline search extending to January 2020.…”

“…Six recent systematic reviews reported adverse effects of vitamin A supplementation or overload [ 3 , 5 , 24 , 52 , 119 , 120 ], and a useful older systematic review collated case reports on toxicity due to retinol or retinyl esters in foods or supplements [ 121 ]. Two recent isotopic studies provided data on hypervitaminosis A [ 90 , 122 ], and 13 recent trials reported adverse effects of vitamin A supplementation [ 37 , 38 , 57 , 65 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 ].…”

The importance of vitamin a in the nutrition

“…Most carotenoids are found in red and orange fruits and vegetables, such as broccoli, carrots, spinach and sweet potatoes (4). since 2011, vitamin A supplementation is no longer recommended for breastfeeding mothers, as a public health intervention, due to the lack of evidence that it prevents morbidity and mortality in mothers and infants (6). Vitamin A is commonly found in these products in two forms, as palmityl or retinyl acetate.…”