A 36yo G4P2 female was transferred at 30 weeks gestation from another hospital due to severe fetal growth restriction. She had known Type 1 diabetes of 3 years duration. Pre-pregnancy she was taking a multi-dose insulin regime but swapped to an insulin pump in the first trimester to optimize her diabetes control.  

Her past obstetric history revealed a miscarriage (<10/40) in 2011. In 2012, she delivered a liveborn male born at 40 weeks gestation by vaginal delivery (birthweight 3046g). In 2020, she delivered a liveborn male born at 29 weeks gestation by Caesarean section for severe IUGR (birthweight 495g, placental weight 194g). Placental histopathology was consistent with chronic histiocytic intervillositis (CHI). The neonate had severe prematurity-related morbidity and presumed metabolic bone disease.

In the current pregnancy, the early antenatal course was unremarkable. She was commenced on aspirin for preeclampsia prophylaxis and hydroxyurea given the prior CHI. Glycemic control was acceptable with time in range (TIR) 58-78%. At 25 weeks gestation, EFW and AC were both <1^st centile and serial growth scans revealed persistent severe fetal growth restriction. At 30 weeks gestation, ALP was 1220U/L with a predominant placental isoform of ALP. The ALP peaked at 1672U/L prior to delivery.

At 36 weeks gestation, she presented with PROM and delivered an 1890g female infant. Within 5 days post-partum, the ALP was 721U/L. Placental histopathology is pending.

Learning points:

CHI is a rare placental lesion defined by infiltration of the intervillous space with maternal CD68+ histocytes, often accompanied by massive peri-villous fibrin deposition,¹ leading to poor perinatal outcomes including severe growth restriction (66%) and fetal death (27%)². CHI is more common in women with autoimmune diseases, especially SLE. This case is the first reported case of CHI in a person with T1D.

The immunological basis of CHI is poorly understood. Some studies suggest CHI results from the absence of the Th1 to Th2 immune response shift observed in normal pregnancy². Other studies suggest a first pregnancy causes broad sensitization to HLA antigens. In subsequent pregnancies, the binding of alloantibodies to paternal HLAs induces activation of the classical complement pathway in trophoblastic villi. This process fulfills the diagnosis of antibody-mediated placental rejection³.

Therapeutic strategies include aspirin and immunosuppression (hydroxyurea, prednisolone, hydroxychloroquine, adalimumab, tacrolimus, IVIG), plasmapheresis, and gestational surrogacy^2,4. CHI affects 80% of subsequent pregnancies but 20% of pregnancies are unaffected underscoring the need to better understand the autoimmune nature of this condition⁵.