Successful Pregnancy and Childbirth Post Allogenic Islet Transplantation with Preservation of Graft Function and Insulin Independence

Presentation Number: SUN 640
Date of Presentation: April 2nd, 2017

Mohamed El-Shahawy*1, Jeannette Hacker-Stratton1, Donald Dafoe1, Alice Peng1, Behrouz Salehian1, Julie Ann Ressler1, Gabriel Danovitch2, Lydia K Lee3, Chris Orr1, Meirigeng Qi1, Kevin George Ferreri1, Yoko Mullen1, Ismail H. Al-Abdullah1 and Fouad R Kandeel1
1City of Hope, Duarte, CA, 2Ronald Reagan Medical Center and David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, 3David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA

Abstract

Background: Pregnancy post allo-islet transplantation is generally discouraged due to presumed risks to mother, fetus and graft. There is one published report of childbirth in an allogenic islet transplant recipient who required insulin during her 3rd trimester, but regained stable graft function post partum (1). Here we report the first known case of insulin-independent pregnancy and childbirth post allo-islet transplant.

Clinical Case: A 35 y/o Caucasian female with T1D since age 18 yrs, complicated by frequent hypoglycemia (5 episodes/wk) and diabetic eye disease, received 3 islet transplants in 2009. Pre transplant, C-peptide was undetectable and daily insulin use was 41 units/d (0.62 units/kg/d) with A1c of 7.3%.

Islets were isolated from deceased allogenic donors, cultured for <72 hrs and infused intraportally (total islet mass: 849,265 IEQ; 12,751 IEQ/kg). Immunosuppression consisted of basliximab/daclizumab, etanercept, tacrolimus and sirolimus, with intermittent MMF. Patient (pt) discontinued insulin after the 3rd islet infusion. She remained off insulin and hypoglycemia free, with A1c of 5.7% and stimulated c-peptide of 5.59 ng/ml at 5yrs.

At age 41 (insulin free 6yrs post transplant), pt conceived with ovarian stimulation and intrauterine insemination. Pre-conception, lisinopril was changed to nifedipine, sirolimus was discontinued and tacrolimus dose increased. Azothiaprine was added during the 1st trimester. Metabolic and immune studies were performed at 7, 15 and 25 wks of gestation and at 24 wks post partum.

Throughout pregnancy, 1st morning BG was 99 ± 14 mg/dl and A1c was maintained between 5.1-5.3% without insulin. Glyburide was started at 20 wks and maintained at a dose of 1.25 to 5 mg/d to achieve target fasting BG < 105 mg/dl. At 15 and 25 wks, plasma glucose (PG) 2-hrs post 75g OGTT was 149 mg/dl and 138 mg/dl, with peak c-peptide responses of 12.5 and 8.85 ng/ml; respectively. Blood pressure, renal function and diabetic eye disease were stable. At 36 wks, pt developed spontaneous contractions and vaginally delivered a healthy 6.0 lb baby girl without complication. The infant received 3 days of UV light therapy for hyperbilirubinemia, but was otherwise in good health.

24 wks post partum (7 yrs post transplant), pt remained off insulin with A1c of 5.5% and normal OGTT response (2-hr PG=149 mg/dl; peak c-peptide=8.46 ng/ml). No changes in auto or alloantibody status were observed.

Conclusion: This is the 1st reported case of successful pregnancy and childbirth post allo-islet transplantation with uninterrupted insulin independence. While pregnancy in T1D and immunosuppression remains high risk, this is further evidence that successful childbirth post islet transplant can be achieved without compromising graft function. Glycemic stability and freedom from hypoglycemia after islet transplant may be conducive to conception and normal childbirth.

 

Nothing to Disclose: ME, JH, DD, AP, BS, JAR, GD, LKL, CO, MQ, KGF, YM, IHA, FRK