Table 2.
Definitions of vitamin A deficiency, by sample type and device.
| Blood (whole, serum, plasma)a | |||
|---|---|---|---|
| Biomarker | Typeb | Device (studies using) | Deficiency or insufficiency definitions usedc |
| Retinol |
Status | iCheck Fluoro (BioAnalyt)d (Boateng et al., 2018, Elom et al., 2015, Ghaffari et al., 2019, Raila et al., 2017, Schweigert et al., 2011a, Bechir et al., 2012, Crump et al., 2017, Schweigert et al., 2011b, Whang et al., 2012, Zambo et al., 2012) Spectrophotometer model 450 (Sequoia-Turner) (Marinovic et al., 1997) CRAFTI (Craft Technologies) (Chaimongkol et al., 2011) |
Severe/clinical deficiency: ≤0.35 µmol/L (10 µg/dL) (WHO, 2011) Low/subclinical deficiency: ≤0.70 µmol/L (20 µg/dL) (WHO, 2011) Insufficiency: ≤1.05 µmol/L (30 µg/dL) (de Pee and Dary, 2002) |
| RBP | Status | Custom REI (Hix et al., 2004) EE-µPAD (Lee et al., 2016) Tidbit (Lu and Erickson, 2017, Lu et al., 2017) ± HYPER filtration (Lu et al., 2018) Custom Ag-Ab reaction (Ciaiolo et al., 2015) |
Deficiency: ≤0.70 µmol/L (Hix et al., 2004) Deficiency: <16.3 µg/mLe (Lee et al., 2016) Deficiency: <14.7 µg/mL (correlated with retinol ≤ 0.70 µmol/L) (Lu et al., 2017) Not defined (Ciaiolo et al., 2015) |
| Beta-carotene | Not defined (indicator of recent dietary intake) | iCheck Carotene (BioAnalyt)f (Ghaffari et al., 2019, Hye et al., 2020, Klein et al., 2013, Livingston et al., 2020, Meinke et al., 2016, Raila et al., 2012, Madureira et al., 2020) |
Humans: No official cut-off defined (von Lintig, 2020) Cattle (Klein et al., 2013, De Ondarza and al., 2009, Schweigert and Immig, 2007): Deficient: 0.6–1.5 mg/L or < 1.5 mg/L Marginal: ≥1.5 mg/L to < 3.5 mg/L Optimal: ≥3.5 mg/L |
| Milk | |||
| Biomarker | Typeb | Device | Deficiency or insufficiency definitions usedc |
| Retinol | Status, exposure | iCheck Fluoro (BioAnalyt)d (Jans et al., 2018, Abebe et al., 2019, Engle-Stone et al., 2014, Schweigert et al., 2011a, Schweigert et al., 2011b, Bechir et al., 2012, Crump et al., 2017) |
Humans: Inadequate: <1.05 µmol/L (Blaner, 2020) or milk fat < 8 µg/g (Blaner, 2020) Cattle: not defined |
| Beta carotene | Not defined (indicator of recent dietary intake) | iCheck Carotene (BioAnalyt)d (no studies) |
Humans: not defined Cattle: not defined |
| Eyes | |||
| Biomarker | Typeb | Device (studies using) | Deficiency or insufficiency definitions usedc |
| Visual score/threshold | Function | Scotopic sensitivity hand-held illuminator (LKC Technologies, Inc.) (Congdon et al., 1995, Sanchez et al., 1997, Reilly et al., 2006) EmTech A meter V.01g (Mehta, 2018) Portable visual adaptometer (Wald, 1941, Steven and Wald, 1941) Scotopic Sensitivity Tester-1TM (SST-1) (Peters et al., 2000) |
Abnormal: ≥stimulus #10 (Congdon et al., 1995) ≥-3.76 log cd/m2 h (Congdon et al., 1995) Highly abnormal: ≥stimulus #11 ≥-3.39 log cd/m2 (Congdon et al., 1995) A decrease of ≥ 0.3 log units after administration of vitamin A supplementation (Wald, 1941, Steven and Wald, 1941) |
| Dark adaptation: pupillary score/responsiveness [lowest light intensity that stimulated percentage relative change in pupil diameter (Labrique et al., 2015)] | Function | Scotopic sensitivity hand-held illuminator (LKC Technologies, Inc.) (Congdon et al., 1995, Sanchez et al., 1997, Peters et al., 2000) Portable field dark adaptometer (PFDA) or digital pupillometer (Labrique et al., 2015, Palmer et al., 2015, Palmer et al., 2016) |
Normal: ≥-1.24 log cd/m2 (Congdon and West, 2002) Abnormal: ≥stimulus #9 (Congdon et al., 1995) ≥-0.575 log cd/m2 (Congdon et al., 1995) i.e.,≥20% (Labrique et al., 2015) ≥-1.11 log cd/m2 (Congdon et al., 2000) ≥-0.9 log cd/m2 (Palmer et al., 2016) ≥15% relative change in diameter (Labrique et al., 2015) ≥10% contraction in pupil size (Palmer et al., 2016) Threshold: ≥15 cd/m2 (Khan et al., 2019) |
| Pupillary dynamics [i.e., response time: absolute value of difference in frame numbers from pre- to post-stimulus divided by number of frames per second (Labrique et al., 2015)] | Function | Portable field dark adaptometer (PFDA) or digital pupillometer (Labrique et al., 2015, Palmer et al., 2015, Palmer et al., 2016) | No official cut-off defined |
| Rod function [dark-adapted rod full-field electro-retinogram responses (Peters et al., 2000)] | Function | Scotopic Sensitivity Tester-1TM (SST-1) (Peters et al., 2000) | No official cut-off defined |
| Ocular morbidities |
Function | Mobile eye unit (comprised of vision drum, trial box, retinoscope, slit-lamp bio-microscope, applanation tonometer, non-mydriatic fundus camera) (Agrawal and Sahu, 2020) Heine HSL-100 biomicroscope equipped with portable slit lamp (Melo et al., 2004) |
Night blindness, conjunctival xerosis with Bitot’s spots (X1B), keratomalacia (X3B), ocular lesions (Agrawal and Sahu, 2020) (stages as designated by World Health Organization grading system (World Health, 2014) Ocular lesions (Melo et al., 2004) |
Notes:Ag-Ab, antigen–antibody; EE-µPAD, electronics enabled microfluidic paper-based analytical device; HYPER, High-yield paper-based quantitative blood separation system; RBP, retinol-binding protein; REI, rapid enzyme immunoassay.
h cd/m2 is the SI unit of luminance (Congdon et al., 2000).
a
Adapted from reference (Tanumihardjo et al., 2016).
b
Whereas serum or plasma is required to measure circulating vitamin A, some devices can use whole blood as the sample input.
c
Defined by global standards (e.g., World Health Organization) or by study authors.
d
An earlier version of this device is referenced as iCheck Ret 435–1 (Bechir et al., 2012).
e
Correlated with retinol ≤ 0.70 µmol/L, when sandwich ELISA is used for RBP measurement (Erhardt et al., 2004).
f
An earlier version of this device is referenced as iCheck Ret 515–2 (Bechir et al., 2012).
g
Device also referenced as “dark adaptometer” (Banerjee, 2019) or “In-Direct method and system for Vitamin A deficiency detection” (Mehta, 2019b, Mehta, 2019a, Mehta and Mehta, 2018).