The maternal and fetal inflammatory response in normal pregnancy and fetal growth restriction : an ultrasound, flow-cytometry and immunoassay study

• Main Author: Mullins, Edward William Samuel
• Format: Dissertation
• Language: English
• Published: Imperial College London 2015
• DOI: 10.25560/25517

The fetal vascular phenotype in fetal growth restriction (FGR) is significantly altered, with affected fetuses appearing to have relatively more dilated vessels with increased proportional blood flow to the head and neck arteries. This concurs with the concept of 'brain sparing' in FGR, but sets it in the context of a globally altered fetal circulatory system. The data presented in this thesis suggest that there are subtle alterations in the maternal antenatal inflammatory cytokine and chemokine profile in FGR. In FGR cord blood there appears to be a mixed inflammatory picture. Cord blood monocytes from FGR samples demonstrate priming towards anti-inflammatory profile with increased levels of IL-10 whilst in blood samples from neonates on day 1 of life there is evidence of a more pro-inflammatory set of cytokines. Subsequent to this, there is a persistent increase in IL-8 in samples from FGR infants collected at 6 weeks of age. The marked difference from cord blood to day 1 cytokines suggests a response of the FGR infant to delivery and their post-natal environment. Maternal blood samples at delivery from pregnancies with FGR show decreased pro-inflammatory chemokines and IL-10. In addition, maternal antenatal IL-2 and MIP1α correlate positively and MMP-9 negatively with fetal vessel diameter (per kg) after correction for gestation and pre-eclampsia. Although maternal post-natal samples show few significant differences, there is positive correlation of IL-17 and negative correlation of sIL-6ra with the severity of FGR in cord blood. This suggests that chronic inflammation mediated by IL-17 and altered IL-6 signaling are possibly associated with the processes which impair fetal growth. The overall findings indicate that FGR fetuses and infants have a syndrome of vascular and inflammatory perturbation which could be factors influencing the short and long-term sequelae of these individuals.