Cardiac Ion Channels Associated with Unexplained Stillbirth – An Immunohistochemical Study

Introduction
Despite the use of post-mortem investigations, approximately 20% of
stillbirths remain unexplained. Cardiac ion channelopathies have been
identified as a cause of death in Sudden Infant Death Syndrome (SIDS)
and could be associated with unexplained stillbirths. This study aimed to
understand if the expression or localisation of cardiac ion channels
associated with channelopathies were altered in cases of unexplained
stillbirths.
Materials and Methods
A case control study was conducted using formalin-fixed cardiac tissue
from 20 cases of unexplained stillbirth and a control group of 20 cases of
stillbirths from intrapartum hypoxia. 4μm tissue sections were stained
using Haematoxylin and Eosin, Masson’s Trichrome (MT) and Elastic van
Gieson (EVG). Immunohistochemistry (IHC) was performed using
antibodies against CACNA1G, KCNJ2, KCNQ1, KCNH2 and KCNE1. The
cardiac conduction system in samples stained with MT and EVG could not
be identified. Therefore, the levels of immunoperoxidase staining were
quantified using QuPath software.
Results
The nuclear-cytoplasmic ratio of sections stained with haematoxylin and
eosin was higher for the hypoxia group (Hypoxia median 0.13 vs. 0.04
unexplained, p< 0.001). CACNA1G (Unexplained median 0.26 vs.
Hypoxia 0.30, p=0.009) and KCNJ2 (Unexplained median 0.35 vs.
Hypoxia 0.41, p=0.001) had lower staining intensity in the unexplained
stillbirth group. There were no statistically significant differences in the
staining intensity of KCNQ1, KCNH2 and KCNE1.
Discussion
Two ion channels associated with channelopathies demonstrated lower
levels of expression in cases of unexplained stillbirth. Further genetic
studies using human tissue should be performed to understand the
association between channelopathies and otherwise unexplained
stillbirths.