**12. Prevention of Pregnancy Complications**

To date, interventions to prevent late-onset pregnancy complications have been largely unsuccessful. There is currently no effective intervention to prevent GDM, FGR, or stillbirth. Efforts to prevent PTB have been similarly disappointing. Despite initial enthusiasm regarding the use of 17α-hydroxyprogesterone caproate (17P) supplementation to prevent PTB in patients at high risk due to one or more prior unexplained spontaneous PTBs based on a single clinical trial [142], follow-up studies have failed to show significant benefit [143]. If there exist a subset of women who do benefit from 17P supplementation—and it is not clear that there is—the mode of action is most likely through a direct anti-inflammatory effect of progesterone on the decidua rather than by supporting suboptimal circulating progesterone concentrations [111,144]. A plausible explanation for the extent of this failure is to be found in the current model, which posits that the foundation for adverse pregnancy events is laid down before pregnancy with abnormalities in endometrial decidualization. Once the pregnancy is established, it is too late to intervene effectively.

The one possible exception to our inability to prevent late pregnancy complications is low-dose aspirin prophylaxis to prevent preeclampsia in patients at high risk [145]. Aspirin is a nonselective inhibitor of COX enzyme, which suppresses the production of the primary pro-inflammatory mediators (PGF2α and PGE2) in the maternal decidua, thereby promoting immune tolerance and facilitating trophoblast invasion. However, it needs to be given early in pregnancy around the time of the second wave of trophoblast invasion and the protective effect is limited.
