Interesting Case Conference: Intrauterine Transfusion Daniel Long, M.D. February 22, 2019

Case Details 31 year old pregnant female (G4T3003) at 26 wks EGA The patient’s 3rd child required neonatal transfusion and photherapy for hemolytic of the newborn 2/28/13 (9 wks EGA) Anti-D titer: 1:16, anti-C titer: 1:2 (OSH) 5/20/13 (20 wks EGA) Anti-D titer: 1:32, anti-C titer: 1:1 (OSH) 7/4/13 (26 wks EGA) Anti-D titer: 1:128, anti-C titer: 1:1 (VUMC) Ultrasound: active fetus, MCA PSV: 1.76 MoM Fetal monitoring: reassuring

Fetal Monitoring: MCA Velocity Source: Duckler D, et al. Am J Obstet Gynecol. 2003;188:1310-4.

Fetal Monitoring: Amniocentesis Source: Queenan JT, et al. Am J Obstet Gynecol. 1993;168:1370-6.

Fetal Monitoring Source: Oepkes D, et al. N Engl J Med. 2006;355:156-64.

Treatment Algorithm Source: Moise KJ. Semin Hematol. 2005 Jul;42(3):169-78.

Intrauterine Transfusion Type O Rh negative RBCs CMV antibody negative Fresh (enhanced 2-3 DPG level) In the UK: no more than 5 days old Irradiated Leukodepletion Washed and packed (Hct 75-85%)

Intrauterine Transfusion

Risks of IUT Perinatal death: 1.6% Emergency cesarean delivery: 2.0% Infection: 0.3% Premature rupture of membranes: 0.1% Inadvertent arterial puncture: 3% Bradycardia or tachycardia: 5% 57% of cases with perinatal death or emergent delivery Long-term morbidity Cerebral palsy: 2.8%, developmental delay: 3.9%, hearing loss: 2.3% Immunomodulatory effect? Sources: van Kamp IL, et al. Am J Obstet Gynecol. 2005;192:171-7. Moise, KJ, et al. Alloimmune disorders in pregnancy. Anaemia, thrombocytopenia and neutropenia in the fetus and newborn, Hadley, A, Soothill, P (Eds), Cambridge Press, Cambridge, 2002.

Iron Overload Source: Rath MEA. Vox Sang. 2013 Jun 27.

Transfused Volume Goal Hct 40-50% (consistent with the normal fetus) Giannina G, et al. Fetal Diagn Ther. 1998;13:94-7. Fetal weight (g) x 0.02 = amount required to increase the fetal Hct by 10% Mandelbrot L, et al. Fetal Ther. 1988;3(1-2):60-6. Fetoplacental volume (mL) x goal change in Hct / donor unit Hct Fetoplacental volume = 1.046 + fetal weight (g) x 0.14

7/5/13 Intrauterine Transfusion Estimated fetal weight: 940 g (37%ile) Pre-transfusion fetal Hgb: 4.1 g/dL (Hct 12%) Amniotic bilirubin scan: 0.198 OD

Fetal Monitoring: Amniocentesis Source: Queenan JT, et al. Am J Obstet Gynecol. 1993;168:1370-6.

7/5/13 Intrauterine Transfusion Estimated fetal weight: 940 g (37%ile) Pre-transfusion fetal Hgb: 4.1 g/dL (Hct 12%) Amniotic bilirubin scan: 0.198 OD Transfusion requirement (goal Hct 45%) Giannina estimate: 62 mL / 33% change Mandlebrot estimate: 55 mL / 33% change 58/60/68 mL of PRBCs were transfused Post-transfusion fetal Hgb: 7.5 g/dL (Hct 23%)

Case Details 7/4, 7/5/13 (26 wks EGA) 7/15, 7/18/13 (28 wks EGA) Anti-D titer: 1:128 , anti-C titer: 1:1 MCA PSV: 1.76 MoM IUT: ~60 mL transfused 7/15, 7/18/13 (28 wks EGA) Anti-D titer: 1:1024, anti-C titer: 1:2 MCA PSV: 1.9 MoM

7/18/13 Intrauterine Transfusion Estimated fetal weight: 1013 g (56%ile) Pre-transfusion fetal Hct: 27% Transfusion requirement (goal Hct 45%) Giannina estimate: 36 mL / 18% change Mandlebrot estimate: 32 mL / 18% change 37 mL of PRBCs were transfused Post-transfusion fetal(?) Hct: 35%

Case Details 7/4, 7/5/13 (26 wks EGA) 7/15, 7/18/13 (28 wks EGA) Anti-D titer: 1:128 , anti-C titer: 1:1 MCA PSV: 1.76 MoM IUT: ~60 mL transfused 7/15, 7/18/13 (28 wks EGA) Anti-D titer: 1:1024, anti-C titer: 1:2 MCA PSV: 1.9 MoM 7/23/13 (29 wks EGA) Non-reassuring fetal status, ↓ movements C-section performed

Case Resolution Baby girl L was delivered at 29.3 wks APGARS 4/6/6 Initial labs: Hgb 3.5 g/dL, TBil 5.5 mg/dL, DAT negative Patient is currently stable on room air 4 additional PRBC transfusions to date Most recent labs: Hgb 9.5 g/dL, TBil 5.3 mg/dL, retic 0.3%

Efficacy of IVIG? Sources: Kirplani, A. Gynecol Obstet Invest. 2007;63(3):176-80. Matsuda, H. J Perinatol. 2011 Apr;31(4):289-92.