Association between fetal interleukin-1 receptor antagonist gene polymorphism and unexplained fetal death.
OBJECTIVE
In spite of extensive clinical examinations or autopsies, as many as 15% to 40% of stillbirths remain unexplained. A systemic fetal inflammatory response is an independent risk factor for severe neonatal morbidity, mediated by proinflammatory cytokines. As a major anti-inflammatory cytokine, interleukin-1 receptor antagonist (IL-1ra) plays a crucial role modulating the proinflammatory response. The gene coding for IL-1ra (IL1RN) is polymorphic. We hypothesized that fetal possession of a specific allele, IL-1RN*2, associated with increased proinflammatory responses, may increase susceptibility to intrauterine fetal death.


METHODS
Fetal kidney cells were obtained from paraffin blocks of 27 unexplained stillbirths. DNA was isolated and tested for IL-1RN genotypes by polymerase chain reaction. As a control group, DNA from 302 live births was also tested.


RESULTS
There was an enhanced rate of IL-1RN*2 homozygocity, 41%, among unexplained stillbirths compared with the control group, 8.6% (P < .001). Histologic analysis of fetal tissues demonstrated a predominant proinflammatory response in IL-1RN*2 homozygote fetuses. Extensive screening (microbiology, maternal serology, placenta histology) did not identify any specific trigger agent.


CONCLUSIONS
There is an association between unexplained stillbirth and fetal homozygous IL1RN*2 carriage.
Gerber
Stefan
S
Department of Obstetrics and Gynecology, Institute of Pathology, Lausanne, Switzerland. Stefan.Gerber@chuv.hospvd.ch
Vardhana
Santosh
S
Meagher-Villemure
Kathleen
K
Vial
Yvan
Y
Hohlfeld
P
P
Witkin
Steven S
SS
D000328:Adult; D005313:Fetal Death / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D011110:Polymorphism, Genetic; D012795:Sialoglycoproteins / Q000235:genetics*
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D012795:Sialoglycoproteins