Corticosteroids for Hellp Syndrome – an Incursion in Suspicious Science

Background In 1980’s, several case reports emerged implying that administration of corticosteroids for fetal maturation in pregnancies complicated by HELLP syndrome may be followed by improvement in clinical and laboratory markers. It has been hypothesized that the underlying mechanism for such observations resides in the antiinflammatory and immunosuppressive effects of corticosteroids. Preeclampsia is characterized by endothelial dysfunction as part of an inappropriate maternal systemic inflammatory response. The inflammatory response is stimulated in turn by placental hypoxia resulting from poor placentation at an early gestational age. The degree of inappropriate inflammatory activation seems to be greater in earlier cases of preeclampsia, which will bear the greatest maternal and perinatal risks. In addition to inflammation, immune mechanisms may also play an important role in preeclampsia. HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome is a type of severe preeclampsia, featuring specific manifestations of endothelial dysfunction, with variable degrees of hepatic damage, microangiopathic hemolytic anemia, and thrombocytopenia. Its presence is associated with increased maternal morbidity and mortality. Immediate delivery is required to reverse the ominous course of this condition, with the resulting iatrogenic prematurity contributing to a very high rate of perinatal morbidity and mortality. The long-acting fluorinated corticosteroids used for fetal maturation, dexamethasone (DXM) or betamethasone (BTM), have an antiinflammatory activity 25 to 30 times more potent than that of cortisol. As the underlying molecular mechanisms, it is known that corticosteroids decrease the gene transcription of various cytokines: interleukins-1 to 6, interleukin-8, interleukins-11 to 13, interferon gamma, and tumor necrosis factor alpha. Moreover, corticosteroids upregulate gene transcription of lipocortin-I, an antiinflammatory protein and interleukin-1 receptor antagonist. Corticosteroids can also diminish tissue edema by decrease of blood vessel diameter and permeability, and a stabilizing effect of corticosteroids on endothelial cells has been reported. In addition, corticosteroids inhibit the infiltration of inflammatory leukocytes and platelet aggregation. One can see that, at least theoretically, corticosteroids have the ability to modify the proinflammatory features of severe preeclampsia.