Alterations in Endogenous Progesterone Metabolism Associated with Spontaneous Very Preterm Delivery

A peer-reviewed study from Nixxi, just published in Human Reproduction Open, demonstrates that measurement of two different steroid hormones in the blood of women early in pregnancy may be predictive for an increased risk for delivery prior to 32 weeks, which is classified as a very preterm delivery. Very preterm deliveries are associated with higher rates of complications, greater likelihood of long-term care needs, and greater costs to the healthcare system. The study is publicly accessible at: https://academic.oup.com/hropen/article/2020/2/hoaa007/5816056

Preterm birth is common and is an important source of long-term handicaps and mortality for newborns. Currently, there are limited tools available to identify which pregnant women will deliver prematurely. Identification of women at risk for preterm delivery is important to facilitate targeted treatment or enhanced care to decrease the likelihood of having a premature baby. Reviewing a woman’s obstetric history is the primary means by which providers have to screen an individual woman for risk of preterm delivery, as a prior spontaneous preterm delivery is an important risk factor. Despite this, the vast majority of preterm deliveries occur in women without a history of preterm birth.

Spontaneous preterm birth is increasingly being recognized to represent a common end pathway for a number of different disease phenotypes that include infection, inflammation, premature rupture of the membranes, uterine over distension, cervical insufficiency, placental dysfunction and genetic predisposition. In addition to these phenotypes, longitudinal changes in the maternal-fetal hypothalamic-pituitary-adrenal axis also likely contribute to a significant proportion of the disease burden of spontaneous preterm birth.

Nixxi’s new study demonstrates that differential production of steroid metabolites is associated with very preterm birth. The identified biomarkers may hint at a pathophysiologic mechanism and changes in the maternal-fetal dyad that result in preterm delivery. The early identification of abnormal changes in HPA metabolites may allow for targeted interventions that reverse the aberrant steroid metabolic profile to a more favorable one, thereby decreasing the risk for early delivery.