TABLE 5.
Infant immune system biomarkers measured across the retained studies (N = 40)
| Infant immune biomarker | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Study authors | Final N | IL‐6 | IL‐8 | TNF‐α | IL‐1β | CRP | IL‐10 | MCP‐1 | IL‐4 | RANTES | VEGF | MIP‐1β | IFN‐γ | MPO | IP‐10 | IL‐2 | IL‐12p70 | IL‐6R | SAA | MCP‐4 | MMP‐9 |
| Jiang et al. (2017) | 422 | C–L↓M–E– | C–L↓M–E– | C–L↓M–E– | C↓L↓M–E↓ | C↓L↓M↓E↓ | C–L↓M–E– | ||||||||||||||
| Jiang et al. (2014) | 127 | C↓L↓M↓ | C↑L↑M↓ | C↑L↑M↓ | C↑L↓M↓ | C↑L↑M↑ | |||||||||||||||
| Ahearne et al. (2017) | 33 | C–L–M– | |||||||||||||||||||
| Dietrick et al. (2020) | 185 | C↓M↓L↓ | C↓M↓L↓ | C↓M↓L↓ | C↓M↑L↓ | ||||||||||||||||
| Camargos et al. (2017) | 50 | C↑M– | C–M– | C–M↓ | C–M– | ||||||||||||||||
| Chalak et al. (2014) | 27 | S↓ | S↓ | S↓ | S↓ | S↓ | |||||||||||||||
| Lee et al. (2021) | 94 | C–L–M–A–S– | C↕L↕M↕A↕S↕ | C↓L↓M↓A↓S↕ | C↓L↓M↓A↓S↓ | C↓L↓M↓A↓S↓ | |||||||||||||||
| Etheredge et al. (2018) | 107 | C↑M↓L↑ | |||||||||||||||||||
| Benavides et al. (2022) | 71 | C– | C↓ | C– | |||||||||||||||||
| Nist, Shoben, et al. (2020) a | 62 | C↓M– | C↓M– | C–M↓ | C–M– | C–M– | C–M– | ||||||||||||||
| Carlo et al. (2011) | 755 | C↑M↓ | C↑M↑ | C↑M↑ | C↑M↑ | C↓M↑ | |||||||||||||||
| Varner et al. (2014) | 615 | C↑M↑ | C↓M↓ | C↑M↑ | |||||||||||||||||
| Silveira & Procianoy (2011) | 62 | C↓M↓ | C↓M↓ | C↓M↓ | C↓M↓ | C↓M↓ | |||||||||||||||
| Díllí et al. (2013) | 40 | C↓M– | C↓M– | ||||||||||||||||||
| Lodha et al. (2010) | 40 | C–M– | C–M– | C–M– | |||||||||||||||||
| Leviton et al. (2013) | 805 | C↓ | C↓ | C↓ | C↓ | C↓ | C↓ | C↓ | C↓ | C↓ | C↓ | C↓ | C↓ | C↓ | C↓ | ||||||
| Leviton et al. (2016) | 750 | C↓ | C↓ | C↓ | C↕ | C↓ | C↑ | ||||||||||||||
| O'Shea et al. (2012) | 939 | C↓M↓ | C↓M↓ | C↓ M↓ | C↕ M↓ | C↓ M↓ | C↑M↕ | C↑M↕ | C↑M↕ | C↓M↕ | C↕ M↓ | C↕M↕ | C↓M↓ | C↕M↕ | |||||||
| O'Shea et al. (2013) | 800 | C↓ | C↓ | C↓ | C↓ | C↓ | C↓ | C↓ | C↓ | C↓ | C↓ | C↓ | C↓ | C↓ | C↓ | ||||||
| O'Shea et al. (2014) | 600 | C↓E↕ | C↓E↕ | C↓E↕ | C↓E↕ | C↓E↕ | C↓E↕ | C↓E↕ | C↓E↕ | C↓E↑ | C↓E↕ | C↓E↕ | C↓E↕ | C↓E↓ | C↓E↕ | ||||||
| Voltas et al. (2017) | 51 | C↓L↓M↓E↓ | C↓L↓M↓E↓ | C↓L↓M↓E↓ | |||||||||||||||||
| Ghassabian et al. (2018) | 3038 | S– | S– | S– | S– | S↑ | S– | ||||||||||||||
| Rodriguez‐Trujillo et al. (2019) | 98 | S↓ | |||||||||||||||||||
| Xie et al (2019) | 260 | C↓ | |||||||||||||||||||
| Krakowiak et al. (2017) | 303 | C–A–L– | C–A–L– | C–A–L– | C–A–L↑ | C–A–L– | C–A–L– | L↓ | C–A–L– | C–A–L– | C–A–L– | C–A–L– | C–A–L– | ||||||||
| Jensen et al. (2019) | 122 | C↓L↓M↓ | |||||||||||||||||||
| Ashwood et al. (2011) | 223 | C–A– | C↓A↓ | C–A– | C–A– | C–A– | C–A– | C–A– | C–A– | ||||||||||||
| Liu & Feng (2010) | 52 | S↓ | S↓ | S↓ | |||||||||||||||||
| Blok et al. (2011) | 105 | S– | S– | S– | |||||||||||||||||
| Kinjo et al. (2011) | 29 | C↓L–M– | C↓L↓M↓ | C–L–M– | C↓L–M↓ | C–L–M– | C–L–M– | C–L–M– | |||||||||||||
| Kyriklaki et al. (2019) b | 642 | C↑M↑ | C↓M↓ | C↓M↓ | C↕M↓ | C↑M↑ | |||||||||||||||
| Nist, Pickler, et al. (2020) | 68 | C–L–M– | C↑L–M– | C–L–M– | C–L–M– | C–L–M– | C–L–M– | C–L–M– | |||||||||||||
| Magalhaes et al. (2017) | 40 | M↑ | M↑ | M↑ | M↕ | M↓ | M↓ | M↓ | M↑ | M↓ | |||||||||||
| Von Ehrenstein et al. (2012) | 369 | C↓ | C↕ | C↕ | C↕ | C↓ | |||||||||||||||
| Sorokin et al. (2014) | 465 | C–M– | C–M– | C–M– | |||||||||||||||||
| Rose et al. (2016) | 92 | C↓M↓L↓ | |||||||||||||||||||
| Van Den Berg et al. (2016) | 79 | C– | C– | C– | C↓M– | C– M– | C –M↓ | C– M↓ | C– M↓ | ||||||||||||
| Sevenoaks et al. (2021) | 267 | C↓L↓M↓ | C↓L↓M↓ | C↓L↓M↓ | C↓L↓M↓ | C↓L↓M↓ | C↓L↓M↓ | C↓L↓M↓ | C↓L↓M↓ | C↓L↓M↓ | |||||||||||
| Sweetman et al. (2021) | 94 | C↓M↓L↓ | |||||||||||||||||||
| Abraham et al. (2021) | 47 | ||||||||||||||||||||
Note: Only biomarkers that were examined in five or more studies are reported in this table. A complete list of all biomarkers examined across these studies is provided in the Supporting Information. Biomarkers not included in this table but measured in these studies are noted here. Biomarkers investigated in four studies are GMCSF, ICAM‐1, MIP‐1α, TNF‐R1, TNF‐R2, I‐TAC, VCAM‐1, E‐SEL, MMP‐1, VEGF‐R1, VEGF‐R2, and IGFBP‐1. Biomarkers investigated in three studies are IL‐16, ICAM‐3, IL‐5, IL‐1α, and IL‐13. Biomarkers investigated in two studies are MIG, TNF‐β, IL‐17, Eotaxin, TARC, sVCAM‐1, sICAM‐1, and IL‐7. Biomarkers investigated in only one study are sTNFR1, sTNFR2, IL‐1, IL‐1‐RA, GCSF, CD64, CXCL9, CXCL10, IL‐17A, Adiponectin, s‐IgA, IL‐12, FGF, IL‐1ra, 6Ckine, CTACK, IL‐20, MCP‐2, MIP‐1d, SDF‐1, Cathepsin D, PDGF‐AA, PAI‐1, NCAM, CD26E, Eotaxin‐3, bFGF, MDC, sFlt‐1 , VEGF‐C, PIGF, IL‐15, VEGF‐D, TIE‐1, IL‐17α , and NGAL. Associations depicted in red denote at least one statistically significant association between biomarker and neurodevelopmental outcome reported by study authors. C, cognitive development; L, language/communication development; M, motor development; A, adaptive behavior; E, social–emotional development; S, neurodevelopmental outcome composed of several domains. ↓ = associated with poorer neurodevelopmental outcome. ↑ = associated with better neurodevelopmental outcome. ↕ = mixed (positive and negative) association with better outcome across specific domains of subtypes neurodevelopmental outcome (e.g., vocabulary produced, or vocabulary understood as subtypes of language/communication development), timing of the biosample (e.g., sampled at multiple points in time), or source of biosample (e.g., blood and cerebrospinal fluid). – = direction and/or significance of association with neurodevelopmental outcome not reported.
Study examined latent “inflammatory” or “anti‐inflammatory” profiles, with specific biomarkers identified as items driven by the latent construct.
Study also examined a ratio of inflammatory to anti‐inflammatory biomarkers.