Prevention of recurrent pregnancy loss due to chronic histiocytic intervillositis (CHI): experience with an anti-transplant rejection regimen.

No Thumbnail Available

All Authors

Cornish, E.F.
Whitten, S.M.
Simpson, N.A.B.
Bonney, E.
Cowan, S.
Peregrine, E.
Donnelly, J.
Kent, E.
Magee, C.
Berlet, T.

LTHT Author

Simpson, Nigel
Bonney, Elizabeth

LTHT Department

Women's Services
Obstetrics & Gynaecology
Obstetrics

Non Medic

Publication Date

2023

Item Type

Conference Abstract

Language

Subject

ADULT , BIRTH RATE , BIRTH WEIGHT , CASE REPORTS , CHILD , WOMEN , FOETUS , GESTATIONAL AGE , GRAFT REJECTION , HISTOLOGY , IMMUNOHISTOCHEMISTRY , IMMUNOSUPPRESSIVE AGENTS , INCIDENCE , FOETAL DEVELOPMENT , LIVE BIRTH , DRUG DOSAGE CALCULATIONS , INFANT, NEWBORN , INFANT DEATH , PILOT PROJECTS , PREGNANCY , PRIMARY PREVENTION , RECURRENT PREGNANCY LOSS , RECURRENCE , RETROSPECTIVE STUDIES , PREGNANCY LOSS , STILLBIRTH , THROMBOSIS , PREDNISOLONE , TACROLIMUS

Subject Headings

Abstract

Introduction: Chronic histiocytic intervillositis (CHI) affects 1:600 pregnancies and is associated with high rates of miscarriage, severe fetal growth restriction and stillbirth. Diagnosed through placental histology, CHI is characterised by excessive accumulation of maternal macrophages in the intervillous space. Women who have had >=2 CHI pregnancies almost always have recurrent disease. The cause of CHI is unclear. However, affected women have a high incidence of auto-/alloimmune disease and placental immunohistochemistry shows similarities with rejected solid organ allografts. These observations suggest that CHI is driven by abnormalities in maternal immune tolerance of the placenta. Evidence for clinical benefit of maternal immunosuppression to prevent recurrent CHI has thus far been limited to case reports and small retrospective series, with wide variation in drug choice, dose and timing of initiation. We present our experience of an anti-transplant rejection regimen for prevention of recurrent CHI. Method(s): Pilot study of tacrolimus, azathioprine and low-dose prednisolone, combined with thromboprophylaxis, in women with a history of recurrent pregnancy loss due to CHI. Result(s): 17 pregnancies in 12 women were treated with the antirejection regimen. Prior to use of the regimen, these women had a total of 36 pregnancies. Only 6/36 (17%) ended in live birth. There was one neonatal death, meaning only 5/36 (14%) pregnancies resulted in a surviving child. The anti-rejection regimen led to a significant improvement in the rate of live birth, from 6/36 (17%) to 12/17 (71%) (p < 0.001). There was also a significant increase in median gestational age at delivery (31.9 vs. 34.3 weeks), birthweight (782 g vs. 2068 g) and birthweight centile (0.9 vs. 34.6) in the treatment group. CHI recurred in 6/17 (35%) placentas, from which 3/6 (50%) neonates survived. Conclusion(s): An anti-rejection regimen of tacrolimus, azathioprine and prednisolone significantly increases the live birth rate in women with recurrent pregnancy loss due to CHI.

Journal

Obstetric Medicine