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Human milk (HM) contains a wide array of peptide hormones including leptin and adiponectin, which are involved in the regulation of infant growth and development. These essential hormones might play an important role in the regulation of metabolic reprogramming of the new-born infant. The protective activity of HM is thought to be due to the presence of bioactive molecules that are dynamic in response to maternal conditions and can positively modulate energy metabolism and inflammatory responses in infants and mothers. Hormones such as leptin, adiponectin, ghrelin, insulin, resistin, obestatin and apelin have been recently identified in HM.
Author | Year | Sample Size (n) | Sample Type | Sampling | Time of the Day (h) | Time Postpartum |
Preparation | Method | Intra, Inter Assay (%CV) |
LOD (ng/mL) |
R (%) | Concentration (ng/mL) |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Houseknecht et al. [11] | 1997 | 14 | - | 12 h fast | 08:00 | - | SM and Wm | RIA | 3.0, 12.6 | 0.3 | SM: 90 WM: 82 |
WM, 10.1 ± 2.6; SM, 1.5 ± 0.87 |
Uçar et al. [12] | 2000 | 18 | C, M | pre- and post-feed | 9:00–12:00 | 3–120 d | SM | RIA | - | 0.5 | - | (0.8–15) (range) |
Lönnerdal and Havel [13] | 2000 | - | M | - | - | 2–4 mo | SM and WM | RIA | - | - | - | WM, 32.7 ± 14.1 SM, 0.2 ± 0.1 |
Resto et al. [14] | 2001 | 29 | M | - | - | 1–4 wk | M, added pancreatic lipase, NaHCO3 |
RIA | - | - | - | 5.28 (24.79) |
Uysal et al. [15] | 2002 | 50 | M | 2 h after last feed | 8:00–10:00 | 1,2, 3 mo | SM | RIA | <6, - | 0.1 | - | Non-Ob, 0.37 ± 0.4 Ob, 0.27 ± 0.2 |
Bielicki et al. [16] | 2004 | 33 | C, M | 1–3 h after breakfast | - | 2–3, 4–5 d 4–6 wk |
WM | RIA | <10, 9.7 | 0.25 | 97 | Preterm, 0.63 ± 0.18 Term, 1.34 ± 0.14 |
Dundar et al. [17] | 2005 | 47 | M | pre-feed | 10:00–11:00 | 15 d, 1, 2, 3 mo | WM | RIA | 6.2, - | 0.5 | 83 ± 4 | 15 d, AGA, 18.4 ± 2; LGA, 28.5 ± 4.4; SGA, 13.4 ± 2.2 |
Ilcol et al. [18] | 2006 | 160 | C, M | pre-feed, 3 h after breakfast | morning | 2, 8, 25 d | WM | IRMA | <5, 7 | 0.1 | - | 2 d, 3.35 ± 0.25; 8 d, 2.65 ± 0.21; 25 d, 1.63 ± 0.18 |
Bronsky et al. [19] | 2006 | 59 | C | collected on EDTA and aprotinin | after 7:00 | 1–2 d | SM | ELISA | 7.6, 9.1 | 0.05 | - | 0.50 (0.05) mean (SEM) |
Miralles et al. [20] | 2006 | 28 | M | post-feed | morning | 1, 3, 6, 9 mo | WM | ELISA | - | 0.008 | 103.1 ± 1.4 | 1 mo, 0.156 ± 0.039 |
Weyermann et al. [8] | 2006 | 766 | M | pre-feed | - | 6 wk, 6 mo |
SM | ELISA | <7 | - | - | 12.8 ± 10.1 |
Weyermann et al. [21] | 2007 | 767 | M | - | - | 6 wk | SM | ELISA | <7, - | - | - | 0.175 (0–4.1) median (range) |
Aydin et al. [22] | 2008 | 31 | C, M | pre-feed, collected on aprotinin | 9:00 | 2, 25 d | SM | ELISA | - | - | - | C, 2.01 ± 0.34; M, 2.04 ± 0.67 |
Savino et al. [23] | 2010 | 36 | - | - | - | <6 mo | SM | RIA | <5, 8 | 0.04 | - | 0.51 (0.34) |
Bronsky et al. [24] | 2011 | 72 | C, M | collected on EDTA + protease inhibitor | - | 1 d; 1, 3, 6, 12 mo | SM | ELISA | 6, 9 | 0.5 | - | 1 d, 0.3 ± 0.04; 1 mo, 0.2 ± 0.03; 3 mo, 0.1 ± 0.01; 6 mo, 0.1 ± 0.02; 12 mo, 0.2 ± 0.04 |
Schuster et al. [25] | 2011 | 23 | C, M | - | - | 1, 2, 3, 4 wk 2, 3, 4, 5, 6 mo |
SM | RIA | - | 0.01 | 70.2 ± 8.7 | 1 wk, 0.21 ± 0.19 6 mo, 0.18 ± 0.15 |
Eilers et al. [26] | 2011 | 77 | C, M | fasting 2 h prior sampling | 16:00–20:00 | 3 d, 28 d | SM | RIA | 5, 6 | - | ~94 | Preterm, 3 d, 0.7 ± 0.79; 28 d, 0.5 ± 0.4; Term, 3 d, 0.65 ± 0.67; 28 d, 0.5 ± 0.4 |
Fields and Demerath [27] | 2012 | 19 | M | complete breast expression |
8:00–10:00 | ~1 mo | SM | - | - | - | - | 0.95 ± 0.73 |
Savino et al. [28] | 2012 | 23 | - | - | - | <6 mo | SM | ELISA | <5, 6.8 | 6 | - | 2.34 (5.73) |
Schueler et al. [29] | 2013 | 13 | M | overnight fast, pre- and post-feed |
7:00–10:00 | 29–38 d. | SM | RIA | 9.4, - | - | - | pre, 0.9 ± 0.7 post, 1.0 ± 0.8 |
Chang et al. [30] | 2013 | - | - | - | - | 3–4 mo | SM | ELISA | <5, 6 | 0.5 | - | - |
Ojeda et al. [31] | 2013 | - | - | - | - | 2 mo | - | ECIs, & ELISA | + | ECIs, 2.6 ± 0.1 ELISA, 2.9 ± 0.5 |
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Kon et al. [32] | 2014 | 103 | M | - | Morning | 1, 2, 3 mo | SM | ELISA | 3.7, - | 0.42 | - | LWG, 1 mo, 1.63 (0.27); 3 mo, 1.35 (0.31); NWG, 1 mo, 1.55 (0.17); 2 mo, 1.83 (0.23); 3 mo, 3.29 (0.70) HWG,1 mo: 1.53 (0.29); 2 mo, 2.20 (0.28); 3 mo, 3.57 (1.37) mean (SEM) |
Brunner et al. [33] | 2014 | 6 wk, 152 6 mo, 120 |
M | overnight fast | Morning | 6 wk, 6 mo |
SM | RIA | - | - | - | 6 wk, 0.11 (0.19); 6 mo, 0.09 (0.18) |
Khodabakhshi et al. [34] | 2015 | Ob, 40 NW, 40 |
M | overnight fast, 2 h after last breast feed | 8:00–10:00 | 2–5 mo | SM | ELISA | - | - | - | NW, 1.81 (1.65–1.94) Ob, 1.78 (1.67–1.94) |
Cannon et al. [35] | 2015 | 19 | M | pre- and post-feed | 24 h milk collection | 3–21 wk | SM | RIA | -, 9.9 | 0.017 | 98.4 ± 6.8 | pre, 0.43 ± 0.10, post, 0.42 ± 0.11 |
Quinn et al. [36] | 2015 | 113 | mid-feed sampling | 6:00–10:00 | 10 d–36 mo | SM | ELISA | - | - | - | 0.3 ± 0.29 | |
Andreas et al. [37] | 2016 | 120 | - | 1 h fast prior sampling, pre- and post-feed, on protease inhibitors | 10:00–13:00 | 1 wk, 3 mo |
SM | Multiplex assay |
3, - | 3.1 | - | 1 wk, pre 541.7 (161.2); post 614.4 (172.1) 3 mo, pre 684.8 (117.4); post 464.3 (125.1) mean (SEM) |
Gridneva et al. [38] | 2016 | 27 | M | pre- and post-feed | 09:30–11:30 | 2–5 mo | SM and WM | ELISA | -, <7.2 | - | 97.7 ± 9.7 | WM, 0.51 ± 0.18 [0.23–1.10] SM, 0.28 ± 0.12 [0.20–0.84] |
Kugananthan et al. [39] | 2016 | 61 | M | pre- and post-feed | 11:00 | 2, 5, 9, 12 mo | SM and WM | ELISA | <5, 7.2 | - | 97.7 ± 9.7 | WM, 2 mo, 0.50 ± 0.16; 5 mo, 0.48 ± 0.16; 9 mo, 0.56 ± 0.11; 12 mo, 0.54 ± 0.14 SM, 2 mo, 0.32 ± 0.16; 5 mo, 0.26 ± 0.07; 9 mo, 0.22 ± 0.03; 12 mo, 0.21 ± 0.02 |
De Luca et al. [40] | 2016 | 100 | M | over-feed | 9:00–11:00 | 1 mo | SM | RIA | <10, - | 0.5 | + | Non-Ob, 2.5 [2.1–3.0] Ob, 4.8 [4.1–5.6] mean (95% CI) |
Savino et al. [41] | 2016 | 58 | - | collected on protease inhibitor |
7:00–9:00 | - | SM | RIA | - | 0.04 | - | 0.89 (1.32) |
Fields et al. [42] | 2017 | 37 | M | complete breast expression |
8:00–10:00 | 1, 6 mo | SM | - | - | - | - | 1 mo (n = 37), 0.589 (0.353–1.45) 6 mo (n = 30), 0.426 (0.145–940) |
Meyer et al. [43] | 2017 | 147 | M | overnight fast | - | 6 wk, 4 mo | - | RIA | - | - | - | - |
Quinn and Childs [44] | 2017 | 116 | - | mid-feed | 6:00–10:00 | - | SM | ELISA | 17.8, - | - | - | 0.27 ± 0.25 |
Nunes et al. [45] | 2017 | 69 | C, M | - | - | 1, 2, 30 d | SM | ELISA | - | - | - | SGA, M, 0.377 (0.36–0.41) GDM, M, 0.460 (0.45–0.70) CTL, M, 0.715 (0.48–0.9) |
Cannon et al. [46] | 2017 | 20 | - | pre- and post-feed | 24 h milk collection | 6–32 wk | SM | ELISA | -, 9.9 | 0.017 | 98.4 ± 6.8 | 0.51 ± 0.16 (0.42–1.15) |
Kugananthan et al. [9] | 2017 | 59 | M | pre- and post-feed | 9:30–11:30 | 2, 5, 9, 12 mo | SM and WM | ELISA | -, <7.2 | 0.05 | SM, 96.3 ± 1.2 WM, 97.1 ± 9.1 |
WM, 0.53 ± 0.19 (0.20–2.24) 2 mo, 0.55 ± 0.29; 5 mo, 050 ± 0.17; 9 mo, 0.53 ± 0.15; 12 mo, 0.54 ± 0.13 SM, 0.28 ± 0.12 (0.19–1.46) 2 mo, 0.34 ± 0.21; 5 mo, 0.27 ± 0.07; 9 mo, 0.26 ± 0.09; 12 mo, 0.26 ± 0.08 |
Gridneva et al. [47] | 2018 | 20 | M | pre- and post-fed | 24 h milk collection | 2, 5, 9, 12 mo | SM and WM | ELISA | -, <7.2 | 0.05 | 97.1 ± 9.1 | WM, 2 mo, 0.50 ± 0.18; 5 mo, 0.49 ± 0.17; 9 mo, 0.56 ± 0.11; 12 mo, 0.50 ± 0.11 SM, 2 mo, 0.34 ± 0.20; 5 mo, 0.26 ± 0.08; 9 mo, 0.21 ± 0.02; 12 mo, 0.21 ± 0.03 |
Chan et al. [48] | 2018 | 430 | M | pooled 24 h milk collection |
24 h milk collection | 4 mo | SM | ELISA | - | 0.137 | _ | 349 (186–689) |
Yu et al. [49] | 2018 | 96 | C, M | pre- and post-feed for mature milk | 3 d, 8:00–9:00 42, 90 d, 14:00–16:00 |
3, 42, 90 d |
SM | ELISA | <7.4, 9.3 | - | - | GDM (n = 48), 3 d, 1.28 (0.87–2.63); Healthy (n = 48), 3 d, 1.49 (0.56–3.25) |
Sadr Dadres et al. [50] | 2019 | 135 | M | 2 h after feeding | 10:00–12:00 | 1, 3 mo | SM | ELISA | <6, 6 | 0.008 | 90–94 | 1 mo, 0.640 ± 0.606 3 mo, 0.484 ± 0.672 |
Zamanillo et al. [51] | 2019 | 59 | M | - | 9:00–14:00 | 30, 60, 90 d | WM | ELISA | - | - | - | 1 mo, 0.376 ± 0.353; 2 mo, 0.341 ± 0.314; 3 mo, 0.346 ± 0.333 |
Logan et al. [52] | 2019 | SPATZ, 1090 UBCS, 1006 |
M | 1 h after last feed | 9:00–12:00 | 6 wk, 6 mo |
SM | ELISA | <7.0, - | - | - | SPATZ, 6 wk, 266.5 (152.0–498.0); UBCS, 6 wk, 175.0 (79.8–350.0) |
Larrosa Haro et al. [53] | 2019 | 131 | M | pre- and post-feed | - | 8, 16 wk | SM | ELISA | - | 0.01 | - | 8 wk, pre, 0.316 (0.50); post, 0.317 (0.57); 16 wk, pre, 0.447 (0.48); post, 0.411 (0.64) |
Logan et al. [54] | 2019 | 694 | M | 1 h after last feed | 9:00–12:00 | 6 wk, 6 mo, 12 mo |
SM | ELISA | -, 5.8 | - | - | 6 wk (n = 668), 388.8 ± 398.1; 6 mo (n = 445), 269.6 ± 305.3; 12 mo (n = 69), 320.4 ± 345.2 |
Kocaadam et al. [55] | 2019 | 65 | M | pre-feed, ~2 h fast prior, ~2 h after last feed, on EDTA and aprotinin | 8:00–11:00 | 15–30 d | SM | ELISA | - | - | - | preterm, (n = 31), 2.0 (2.5) term, (n = 34), 0.0 (2.3) |
Schneider-Worthington et al. [56] | 2020 | 25 | M | - | - | 1 mo | SM | ELISA | 4.48, 13.56 | - | - | 0.47 (0.94) |
Dal Bello et al. [57] | 2020 | - | - | - | - | - | - | nano-HPLC-HRMS | - | 27 | - | 6.70 |
Galante et al. [58] | 2020 | 501 | - | pre-feed | 10:00–24:00 | 2–3 mo | SM | ELISA | 4, 8 | - | - | 0.116 ± 0.112, ng/mg (raw values corrected per mg of protein per mL) |
Joung et al. [59] | 2021 | 50 | C, M | post-feed, 24 h pooled | - | 7, 14, 21 and 28 d | WM | ELISA | 10 | 0.01 | - | - |