Combined oral prednisolone and heparin versus heparin: the effect on peripheral NK cells and clinical outcome in patients with unexplained recurrent miscarriage. A double-blind placebo randomized controlled trial

Abstract

PurposeTo evaluate the efficacy of the use of oral Prednisolone and heparin versus the use of heparin alone in treatment of patients with unexplained recurrent miscarriage.MethodologyThe study was a double-blind placebo randomized control trial conducted on 160 patients with unexplained recurrent miscarriage. Patients recruited were randomized into two groups. The first group received oral Prednisolone in addition to low dose aspirin and heparin, while the other group received a placebo in addition to low dose aspirin and heparin. A peripheral venous blood sample was taken from all included patients before starting treatment and collected in heparinized tubes. Natural Killer (NK) cells were checked in each sample and then re-checked in another sample at 20 weeks of gestation.ResultsWe found that in the prednisolone group, 70.3 % of women had successful outcome (defined as an ongoing pregnancy beyond 20 weeks gestation), while 29.7 % miscarried before this gestation. On the contrary, among women in the placebo group, 9.2 % had successful outcome while 90.8 % miscarried before 20 weeks, which was statistically significant. On the other hand, we found that there were no significant paired differences between initial serum levels of the NK cells markers CD16 and CD56 and their levels at 20 weeks gestation in both groups.ConclusionThe addition of prednisolone to heparin and low dose aspirin might be beneficial in patients with unexplained recurrent miscarriage, and this effect might be due to a suppressive effect of steroids on the peripheral CD16 NK cells concentration.

Innate Immune System at the Maternal–Fetal Interface: Mechanisms of Disease and Targets of Therapy in Pregnancy Syndromes

“…121 Authors suggested a suppressive effect of steroids on the peripheral NK cells concentration in women with unexplained RM. 122 However, a study published by Tang et al on the use of prednisolone in patients with high levels of uterine NK (uNK) cells suggested that live birth rate among the prednisolone group was 60% and among the placebo group it was 40% with a risk ratio of 1.5, and hence non-significant. 123 The discrepancy between these data may be due to the sample size and the beginning of treatment.…”

“…123 The discrepancy between these data may be due to the sample size and the beginning of treatment. 122 The role of the low dose aspirin (LDA) in treatment strategies of obstetrical syndromes has been investigated. 124,125 Acetylsalicylic acid has non-platelet-mediated effects that contribute to its efficacy in the primary and secondary prevention of cardiovascular events.…”

Recurrent pregnancy loss: current perspectives

“…Prednisolone effectively reduces the number of uterine NK cells in women with RPL and is the most widely used in this patient population 126. Some studies showed an improvement in LBR when prednisolone was combined with aspirin or LMWH,127,128 whereas others showed no effect 41. Moreover, the safety of corticosteroid treatment in the first trimester is still under scrutiny, with some studies showing an increased risk of prematurity, as well as maternal hypertension and diabetes 41,129.…”

A comparison of effectiveness among frequent treatments of recurrent spontaneous abortion: A Bayesian network meta‐analysis

“…For the 85 remaining articles, the full texts were examined carefully on the bases of both inclusion and exclusion criteria, and 36 studies were excluded due to unavailable data, lack of intervention group, or small sample size. Finally, results from 49 literatures were selected for further analysis . The process is displayed in a flowchart in Figure .…”