Placental inflammatory cytokines mRNA expression and preschool children's cognitive performance: a birth cohort study in China.

BACKGROUND: The immunologic milieu at the maternal-fetal interface has profound effects on propelling the development of the fetal brain. However, accessible epidemiological studies concerning the association between placental inflammatory cytokines and the intellectual development of offspring in humans are limited. Therefore, we explored the possible link between mRNA expression of inflammatory cytokines in placenta and preschoolers' cognitive performance. METHODS: Study subjects were obtained from the Ma'anshan birth cohort (MABC). Placental samples were collected after delivery, and real-time quantitative polymerase chain reaction (RT-qPCR) was utilized to measure the mRNA expression levels of IL-8, IL-1ß, IL-6, TNF-α, CRP, IFN-γ, IL-10, and IL-4. Children's intellectual development was assessed at preschool age by using the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV). Multiple linear regression and restricted cubic spline models were used for statistical analysis. RESULTS: A total of 1665 pairs of mother and child were included in the analysis. After adjusting for confounders and after correction for multiple comparisons, we observed that mRNA expression of IL-8 (ß = - 0.53; 95% CI, - 0.92 to - 0.15), IL-6 (ß = - 0.58; 95% CI, - 0.97 to - 0.19), TNF-α (ß = - 0.37; 95% CI, - 0.71 to - 0.02), and IFN-γ (ß = - 0.31; 95% CI, - 0.61 to - 0.03) in the placenta was negatively associated with preschoolers' full scale intelligence quotient (FSIQ). Both higher IL-8 and IL-6 were associated with lower children's low fluid reasoning index (FRI), and higher IFN-γ was associated with lower children's working memory index (WMI). After further adjusting for confounders and children's age at cognitive testing, the integrated index of six pro-inflammatory cytokines (index 2) was found to be significantly and negatively correlated with both the FSIQ and each sub-dimension (verbal comprehension index (VCI), visual spatial index (VSI), FRI, WMI, processing speed index (PSI)). Sex-stratified analyses showed that the association of IL-8, IFN-γ, and index 2 with children's cognitive development was mainly concentrated in boys. CONCLUSIONS: Evidence of an association between low cognitive performance and high expression of placental inflammatory cytokines (IL-8, IL-6, TNF-α, and IFN-γ) was found, highlighting the potential importance of intrauterine placental immune status in dissecting offspring cognitive development.

Association of maternal thyroid peroxidase antibody during pregnancy with placental morphology and inflammatory and oxidative stress responses.

Background: Studies suggest that thyroid peroxidase antibody (TPOAb) positivity exposure during pregnancy may contribute to changes in placental morphology and pathophysiology. However, little is known about the association of maternal TPOAb during pregnancy with placental morphology and cytokines. This study focuses on the effect of repeated measurements of maternal TPOAb during pregnancy on the placental morphology and cytokines. Methods: Based on Ma'anshan Birth Cohort (MABC) in China, maternal TPOAb levels were retrospectively detected in the first, second and third trimesters. Placental tissues were collected 30 minutes after childbirth, placental morphological indicators were obtained by immediate measurement and formula calculation, and cytokine mRNA expression was detected by real-time quantitative polymerase chain reaction (RT-qPCR) afterward. Generalized linear models and linear mixed models were analyzed for the relationships of maternal TPOAb in the first, second and third trimesters with placental indicators. Results: Totally 2274 maternal-fetal pairs were included in the analysis of maternal TPOAb levels and placental morphology, and 2122 pairs were included in that of maternal TPOAb levels and placental cytokines. Maternal TPOAb levels in early pregnancy were negatively associated with placental length, thickness, volume, weight and disc eccentricity, while positively correlated with placental IL-6, TNF-α, CRP, CD68, MCP-1, IL-10, HO-1, HIF-1α and GRP78. In mid-pregnancy, maternal TPOAb levels were negatively correlated with placental length, width and area. In late pregnancy, maternal TPOAb levels were negatively correlated with placental length, area, volume and weight. Repeated measures analysis showed that maternal TPOAb positivity tended to increase placental TNF-α, CD68 and MCP-1 while decreasing placental length, width and area than TPOAb negativity. Repeated measures analysis showed that maternal TPOAb levels were positively correlated with placental IL-6, TNF-α, CD68, MCP-1, IL-10, HO-1, HIF-1α and GRP78, while negatively correlated with placental length, area, volume, weight, and disc eccentricity. Conclusion: There may be trimester-specific associations between maternal TPOAb levels and placental morphology and inflammatory and oxidative stress responses. The effect of maternal TPOAb levels on placental morphology is present throughout pregnancy. Early pregnancy may be the critical period for the association between maternal TPOAb levels and placental inflammatory and oxidative stress responses.

Effect of anti-tumor necrosis factor α treatment on radiographic progression in patient with ankylosing spondylitis: A systematic review and meta-analysis.

BACKGROUND: Efficacy of anti-tumor necrosis factor (anti-TNF)α treatment in patient with active ankylosing spondylitis (AS) had been proved by many clinical studies. Inflammation and new bone formation in spine were two pivotal aspects in AS. TNF α inhibitor could eliminate inflammation including clinical and laboratory inflammatory manifestation. Paradoxical results whether TNF α antagonist could delay radiographic progression in AS were often been reported simultaneously. OBJECTIVES: To review the literature about the effect of TNF α inhibitor on radiographic progression and disease activity in patient with AS. METHODS: We conducted a comprehensive search including Medline, EMBASE and the Cochrane Library from 1 January 2000 to 15 August 2017. Two reviewers independently supplemented with hand searching for the reference lists of inclusion. All trials focusing on radiographic progression or disease activity in patients with AS treated with anti-TNF α agents. Primary outcomes were modified Stokes AS Spinal Score (mSASSS), as well as Bath AS disease activity index (BASDAI) and Bath AS functional index (BASFI). Two reviewers independently selected studies and analyzed data. Methodological quality was assessed using the Newcastle-Ottawa scale (NOS). We pooled effects recorded on different scales as Standardized mean differences (SMDs) with 95% confidence intervals (CIs) using random-effects models. RESULTS: We included 14 studies of low to moderate risk of bias with 3,186 patients, compared with control group, there was no effect of mSASSS changes (SMD = -0.12, 95% CI: -1.17-0.93, p value = .82, I2 = 95%) and follow-up (SMD = 0.03, 95% CI: 0.21-0.26, p value = .82, I2 = 36%) estimation in anti-TNF α group. However anti-TNF α agent treatment led to remarkable improvements on both Bath AS disease activity index (BASDAI) (SMD = 1.06, 95% CI: 0.22-1.89, p value = .01, I2 = 96%) and Bath AS functional index (BASFI) (SMD = 0.93, 95% CI: 0.24-1.92, p value = .01, I2 = 97%) scores at 12 weeks. CONCLUSION: Our meta-analysis found no significant effect on delaying radiographic progression in AS treated with TNF α inhibitor, although TNF α inhibitor could do improve significantly disease activity and physical function in AS.