Abstract
Spontaneous preterm birth before 37 weeks of completed gestation is responsible for the majority of baby deaths and long-term disability worldwide. Researchers still do not fully understand why some women give birth prematurely nor how to accurately predict who is most at risk, and thus how to prevent it from occurring. Our preliminary work in this field discovered that in a small group of women who had previously had premature babies, the concentrations of innate immune system proteins (called cathelicidin and elafin) measured in the vaginal mucus during early pregnancy, were higher in women who developed a short cervix (a precursor to many preterm births), and those who birthed premature babies. This research project was designed to evaluate, in a larger study, whether these proteins were indeed associated with premature birth, and how they are influenced by demographic characteristics of the mother (e.g., ethnicity) and the local bacterial composition of the vagina. This could provide both insight into the contribution of the mother’s cervicovaginal immune system to the disease process of preterm birth, and potentially markers which could identify women at high-risk of premature birthI measured the concentration of immune system proteins elafin and cathelicidin, and a related enzyme human neutrophil elastase in the cervicovaginal fluid collected from 619 women, including women at both high and low risk of premature birth, assessed them for the presence of bacterial vaginosis, a change in the natural balance of bacteria in the vagina.
Cathelicidin and human neutrophil elastase were raised in the vaginal mucus of high-risk women who birthed babies spontaneously before 37 weeks of gestation. Elafin concentrations were mildly raised in women who delivered early. Elafin was influenced by gestation, body mass index and smoking status. Innate immune proteins were influenced by ethnicity; Black women had higher concentrations of elafin and cathelicidin, yet low elafin was associated with cervical shortening in Black women, whereas high elafin was associated with cervical shortening and premature birth in White women. Women with bacterial vaginosis had lower elafin but higher cathelicidin. High cathelicidin was associated with high concentrations of fetal fibronectin, an established protein predictor of preterm birth. Given that it can be measured earlier than fetal fibronectin, it may be of value in earlier prediction of premature birth.
In conclusion, I have demonstrated that changes in the innate immune system early in pregnancy may contribute to some premature births, and that there are distinctive patterns of expression according to ethnicity. We suggest that this may range from a failure of an immune response to infection or inflammation (low concentrations of elafin), leading to preterm birth (which may be related to bacterial imbalance including bacterial vaginosis), to an excessive immune response (high elafin and/or cathelicidin) which may also result in premature birth. This requires further investigation to fully understand these mechanisms, as well as to further evaluate the potential for cathelicidin to be used as a predictive test for preterm birth.
| Date of Award | 1 Nov 2021 |
|---|---|
| Original language | English |
| Awarding Institution |
|
| Supervisor | Rachel Tribe (Supervisor) & Andrew Shennan (Supervisor) |