TABLE 1.
Included studies that examine the association between maternal immune system biomarkers and neurodevelopmental outcomes (N = 18)
| Author (year), country | Population context | Covariates | Study design | Final N (% male) | Biomarker(s) | Biosample age | Source | Source analytic method | Outcome measure (domains) | Age at outcome |
|---|---|---|---|---|---|---|---|---|---|---|
| Nazzari et al. (2019), Italy | Healthy | Gestational age, infant sex, maternal prepregnancy BMI, length of heel stick | Cohort | 104 (51.9%) | IL‐6; CRP; sAA | Late pregnancy | Maternal blood and saliva | Quantikine High Sensitivity ELISA kits (R&D Systems Europe); Expanded Range High Sensitivity Cortisol EIA Kit (Salimetrics); α‐Amylase Kinetic Enzyme Assay Kit (Salimetrics) | Behavior observation (regulation; emotional reactivity) | 48–72 h |
| Osborne et al. (2018), UK | Maternal MDD and controls | Maternal prepregnancy BMI | Cohort | 87 (not specified) | IL‐1β; IL‐2; IL‐6; IL‐8; IL‐10; TNF‐α; VEGF; EGF; MCP‐1 | Third trimester | Maternal blood | Sandwich chemiluminescent immunoassay | NBAS (automatic stability; regulation; orientation; motor skills) | 6 days |
| Yan et al. (2020), China | Healthy | Gestational age, birth weight, maternal age, education, spouses’ education, family income, parity, maternal prepregnancy BMI, gestational weight gain, delivery mode, infant sex. | Cohort | 1186 (52.1%) | TNF‐α; IL‐1β; IL‐6; IL‐10; MIP‐1β | Second trimester (16–18 weeks) | Maternal blood | MILLIPLEX MAP Human Cytokine/ChemokineMagnetic Bead Panel 96 Well Plate Assay (Millipore) | CDSC (cognition; language; gross motor skills; fine motor skills; social) | 1 month |
| Nazzari et al. (2020), Italy | Healthy | Gestational age, maternal emotional availability, maternal IQ, infant sex, maternal postnatal depression | Cohort | 104 (51%) | IL‐6; CRP | Mean (SD) = 34.76 (1.12) weeks | Maternal blood | Quantikine ELISA kits (R&D Systems) | BSID‐III (cognition) | 11.96 (1.85) weeks |
| Hunter et al. (2021), USA | Healthy | Maternal education, maternal postpartum depression, anxiety, and stress | Cohort | 127 (51%) | CRP; IL‐6; IL‐8; TNF‐α | 16 weeks | Maternal blood | Beckman‐Coulter high sensitivity assay; R&D Systems high sensitivity assay | IBQ‐R (surgency; negativity; regulation) | 3 months |
| Gustafsson et al. (2019), USA | High ADHD risk | Maternal third trimester depression and stress | Cohort | 68 (60%) | IL‐6; TNF‐α; MCP‐1 | Third trimester | Maternal blood | Enzyme‐linked immunosorbent assay | IBQ‐R + Still face paradigm observation (temperament; regulation) | 6 months |
| Gustafsson et al. (2018), USA | High ADHD risk | Maternal ADHD symptoms, maternal postnatal depression symptoms, infant age | Cohort | 68 (57%) | IL‐6; TNF‐α; MCP‐1; IL‐10 | Third trimester | Maternal blood | Enzyme‐linked immunosorbent assay (R&D Systems); Luminex polystyrene bead‐based multiplex immunoassays (R&D Systems) | IBQ‐R (negative affect; regulation) | 6.8 months (0.8) |
| Bodnar et al. (2018), Ukraine | Alcohol exposure in utero | Maternal marital status, BMI, socioeconomic status, smoking, parity, child sex, and study site | Cohort | 152 (40.9%–68.6%) | 40 cytokines/chemokines (see study for full list) | Second trimester (17–19 weeks) Third trimester (31–34 weeks) | Maternal blood | Meso Scale Discovery V‐PLEX Human Biomarker 40‐Plex kit | BSID‐II (cognition; language; psychomotorv ) | 6 and 12 months |
| Sowell et al. (2018), Ukraine | Alcohol exposed and controls | Maternal age, paternal age, maternal education, SES, prepregnancy BMI, parity, gravidity, MVM use, maternal smoking (cigarettes per day), study site, gestational week at blood draw, child sex, gestational age at birth, birth weight, and birth length | Cohort | 241 (56%) | IL‐1β; TNF‐α; IFN‐γ; GM‐CSF; IL‐2; IL‐4; IL‐6; IL‐8; IL‐10 | Second trimester (19 and 32 weeks) | Maternal blood | Human multiplexing bead immunoassay | BSID‐III (cognition; psychomotor) | 6 and 12 months |
| Freedman et al. (2019), USA | Infection and controls | Infant sex, maternal age, obesity, and depression, maternal age, maternal smoking | Cross‐sectional | 162 (not specified) | CRP; choline | 16 weeks | Maternal blood | Beckman–Coulter high sensitivity assay | IBQ‐R (surgency; negative emotionality; regulation) | 12 months |
| Rasmussen et al. (2019), USA | Healthy | Household income, prepregnancy BMI, obstetric risk, smoking during pregnancy, and infant sex | Cohort | 147 (55.8%) | IL‐6 |
Mean (SD) = 12.6 (2.8) weeks 20.4 (1.5) weeks 30.3 (1.3) weeks |
Maternal blood | Enzyme‐linked immunosorbent assay (eBioscience) | BSID‐III + MRI (cognition; socioemotional development) | 12 months |
| Spann et al. (2018), USA | Adolescent mothers | Sex, postmenstrual age, and scanner upgrade | Cohort | 72 (66.7%) | IL‐6; CRP | Third trimester (34–37 weeks) | Maternal blood | Enzyme‐linked immunosorbent assay; Cobras Integra 400 Plus (Roche Diagnostics) turbidimetric | BSID‐III (cognition) | 14 months |
| Irwin et al. (2019), Seychelles | Healthy | Child sex, maternal age, child age at assessment, number of parents living with child, socioeconomic status | Cohort | 1408 (52.1%) | IL‐1β; IL‐2; IFN‐γ; TNF‐α; IL‐4; IL‐6; IL‐5; IL‐10; CRP; MCP‐1; TARC; VEGF‐D; sFLT‐1 | Third trimester (28 weeks) | Maternal blood | Meso Scale Discovery multiplex assay | BSID‐II (cognition; psychomotor skills); CDI (expressive and receptive language); IBQ‐R (temperament) | 15–25 months |
| Rudolph et al. (2018), USA | Healthy | Not reported | Cohort | 84 (50%) | IL‐6 |
Mean = 12.7 weeks 20.5 weeks 30.4 weeks |
Maternal blood | Enzyme‐linked immunosorbent assay | IBQ + neuroimaging (negative emotionality; working memory) | 24 months |
| Graham et al. (2018), USA | Healthy | Gestational age at birth, age at scan | Cohort | 86 (59.3%) | IL‐6 | First, second, and third trimesters | Maternal blood | Enzyme‐linked immunosorbent assay | Behavioral observation—snack delay task (impulsivity) + neuroimaging | 24 months |
| Sevenoaks et al. (2021), South Africa | Maternal HIV compared to controls | Clinic, maternal smoking during pregnancy, maternal alcohol use during pregnancy, maternal socioeconomic status, maternal BMI at 6 weeks postpartum, infant birth weight, prematurity, infant sex and exclusive breastfeeding (yes/no), maternal HIV disease parameters adjusted for maternal CD4+ during pregnancy, maternal viral load during pregnancy, maternal ART regimen during pregnancy and initiation of ART (before or during pregnancy). | Cohort | 267 (28.8%–39%) | IFN‐γ; IL‐1β; IL‐2; IL‐4; IL‐5; IL‐6; IL‐7; IL‐8; IL‐10; IL‐12p70; IL‐13; TNF‐α; GM‐CSF; NGAL; MMP‐9 | 26 weeks gestation | Maternal blood | Multiplex bead assay; Enzyme‐linked immunosorbent assay | BSID‐III (cognition; language; motor skills) | 24–28 months |
| Monthe‐Dreze et al. (2019), USA | Healthy | Child sex, age at outcome | Cohort | 1246 (51.8%) | CRP | Second trimester | Maternal blood | Enzyme‐linked immunosorbent assay | WRAVMA (intelligence; visual‐motor skills) | 3.2 years |
| Rommel et al. (2020), USA | Healthy | Nutritional supplementation | Cohort | 512 (47.7%) | PGF2‐α | 32.6 weeks | Maternal urine | Gas chromatography; Mass spectrometry | BASC, SRS (Externalizing problems; Internalizing problems; Behavioral Symptoms Index; social problems) | 4–5 years |
Note: Studies are grouped based on age of first neurodevelopmental assessment.
Abbreviations: ADHD, attention deficit hyperactivity disorder; BASC, Behavior Assessment System for Children; BMI, Body Mass Index; BSID‐II, Bayley Scales of Infant Development—Second Edition; BSID‐III, Bayley Scales of Infant Development—Third Edition; B CDI, Communicative Development Inventory; CDSC, Child Developmental Scale of China; HIV, human immunodeficiency virus; IBQ‐R, Infant Behavior Questionnaire—Revised; MDD, Major Depressive Disorder; MRI, magnetic resonance imaging; NBAS, Neonatal Behavioral Assessment Scale; SRS, Social Responsiveness Scale; TD, typically developing; WRAVMA, Wide Range Assessment of Visual Motor Abilities.