This week we're going to summarize all the tools we've discussed for alloimmunization and HDFN. We’re going to use case scenarios to walk through the individual diagnosis, management, surveillance, and treatment, followed by delivery and the neonatal course for each. Dr. Moise takes us through three different case scenarios - mild, moderate, and severe. See below for timestamps and some reference information!

2:57     Case 1 - 'Mild' Disease - First affected pregnancy with a low titer 

14:45   Case 2 – ‘Moderate’ Disease – Subsequent pregnancy with a moderate titer

32:47   Case 3 – ‘Severe’ Disease – Subsequent pregnancy with high titer or early need for IUTs

 

MCA MoM Score Calculators:

• Barcelona calculator: https://medicinafetalbarcelona.org/calc/
  • Select “Anemia” then “Cerebral Doppler”
• Perinatology: https://perinatology.com/calculators/MCA.htm

IUT Blood Volume Formulas

• IVT = volume of donor blood (78-80% hct) to raise the fetal hct 10 points = 0.02 x EFW (in grams)
• IPT = (GA (in weeks)) – 20 x 10

Bring the caffeine as we wrap up IUTs this week with our detailed step by step on the procedure itself. In this episode we talk about:

• The pre-operative process including consenting and lab studies
• Using the MCV value on a CBC to determine fetal vs. maternal sample (only works for the 1st IUT) 
• Fetal sample= 105-110
• Maternal sample = 80s-90s
• How much blood to order from the blood bank for a transfusion
• <24 weeks order 1/2 unit (split it - save the other half for the next IUT!) 
• 24-28 weeks order 1 unit
• 28-35 weeks order 2 units
• Fetal drug calculations
• Atropine = 0.02 mg/kg
• Fentanyl = 2 mcg/kg
• Vecuronium = 0.1 mg/kg
• Pre- & post-operative monitoring 
• Pre-op = 20 min strip of toco + FHR 
• Post-op = 2 hours continuous toco + FHR
• Patient positioning in the OR = left lateral tilt
• Patient comfort in the OR - aromatherapy kit, eye mask, spa music 
• How we warm up the blood in the OR, who checks it and what we check
• Brief sidebar on CMV - what it is, why we want CMV negative donor blood and what we do if we can't get CMV negative blood
• How to decide your needle type for the procedure
• 3-inch vs 6-inch length - depending on the depth measure on ultrasound
• Quincke tip vs. Whitacre tip
• Deciding gauge/size
• 22G (<22 weeks)
• 20G (>22 weeks)

• Role of a coulter and automated hemocytometer outside the OR
• Fetal labs to order at an IUT
  • At the 1st IUT
    • Initial Fetal Sample: CBC, ABO/Rh, (Fetal Antigen type), reticulocyte count, DAT
    • Final Fetal Sample: CBC, KB Stain +/- hemoglobin electrophoresis
  • On all subsequent IUTs for that pregnancy
    • Initial Fetal Sample: CBC, reticulocyte count
    • Final Fetal Sample: CBC, KB stain +/- hemoglobin electrophoresis
• Patient questions to ask your provider prior to having an IUT performed:
  • “How many IUT procedures do you perform in a year?”
  • “What are your outcomes?”
  • “Where/How did you get your training?”

Abbreviations:

• CBC = complete blood count
• MCV = mean corpuscular volume
• CMV = Cytomegalovirus
• KB Stain = Kleihauer-Betke Stain
• DAT = Direct Antiglobulin Test AKA Direct Coomb’s Test

Grab your coffee and eat your Wheaties wombmates! We’ve finally made it to our favorite topic – Intrauterine Transfusions! We love this topic so much we had to split it into two parts to cover everything we wanted to. This week we'll cover the background and leading up the procedure itself, then next week we'll go into more detail about the procedure itself. See the topic list below for part 1 and stay tuned next week for part 2!

• The 4 types of IUTs: intravascular (IVT), intraperitoneal (IPT), combined, and intracardiac
• When does a patient need an IUT?
• Timing of IUTs – when we start, the latest we’ll do them, and how often
• Common complications such as fetal bradycardia and options for treating it
• Donor blood preparation – extended maternal crossmatch, CMV negative, irradiated, leukocyte reduced, and washed
• How long the procedure lasts and where it takes place
• What type of anesthesia we use for Mom in IUTs (conscious sedation)
• Why we don’t use fetal Lasix (furosemide) for fetal hydrops in the setting of HDFN
• Formulas!
  • IVT = volume of donor blood (78-80% hct) to raise the fetal hct 10 points = 0.02 x EFW (in grams)
  • IPT = (GA (in weeks) – 20) x 10
  • Fetal vecuronium dose = EFW x 0.1 mg/kg
  • Fetal fentanyl dose = EFW x 2 mcg/kg
  • Fetal atropine dose = EFW x 0.02 mg/kg
• Abbreviations Key:
  • EFW = estimated fetal weight
  • GA = gestational age
  • IUT = intrauterine transfusion
  • IVT = intravascular transfusion
  • IPT = intraperitoneal transfusion
  • Hct = hematocrit
  • HDFN = hemolytic disease of the fetus & newborn
  • MCA = middle cerebral artery
  • MoM = multiples of the median

Breaking into our toolbox this week! Dr. Moise takes us through immune therapy options in the treatment and management of HDFN and alloimmunization.

This week we cover the following topics:

• Alloimmunized patients that qualify for immune therapy as management for HDFN
• Options available for immune therapy
  • Intravenous immunoglobulin (IVIG)
  • Plasmapheresis
• Timing, dosing, frequency, and administration of IVIG
• Common complications of IVIG
  • IgA deficiency
  • Headache
  • Fatigue
  • FDA Black Box Warning
• And our tricks for treating them!
  • Imitrex (sumatriptan) + Zofran (ondansetron)
  • Reglan (metoclopramide)
  • IVIG pre-meds and post-meds
  • IVIG rate adjustment

A brief little bonus episode of Erin's interview with Dr. Michael Harrison while at the 40th annual IFMSS conference in Los Cabos in early November 2022. 

Many consider Dr. Michael Harrison to be the Father of Fetal Surgery. He paved the way for many of the advancements we know today in fetal medicine and has continued his work as a professor of pediatric surgery and director emeritus of the Fetal Treatment Center at the University of California in San Francisco. Dr. Harrison was gracious enough to take some time to sit down and allow us to interview him - so please enjoy! 

*Please excuse our audio quality and the echo! 

This week we're going into a deep dive on MCA Doppler as Dr. Moise discusses the following: 

• The initial role & importance of ultrasound in pregnancy – determining crown rump length (CRL) to then calculate the estimated date of delivery (EDD)
• How MCA Doppler was first discovered – thanks to Dr. Gian Carlo Mari
• How viscosity and cardiac output are affected in an anemic fetus
• MCA Doppler peak systolic velocity (PSV) vs. multiples of the median (MoM)
• Factors that can affect an accurate MCA Doppler reading (here’s where the cop analogy comes in)
• Angle
• Fetal movement
• Software and ultrasound equipment
• Expertise and experience
• Rescue steroids (betamethasone)
• When to start MCA surveillance and how often
• Definition of fetal hydrops
• Using MCA Dopplers vs. empiric intervals for timing IUTs
• Other fetal conditions that utilize MCA Doppler to detect fetal anemia:
• Non-immune fetal hydrops
• Parvovirus
• TAPS in twins

MCA MoM Score Calculators:

• Barcelona calculator: https://medicinafetalbarcelona.org/calc/
  • Select “Anemia” then “Cerebral Doppler”
• Perinatology: https://perinatology.com/calculators/MCA.htm

Editorial by Dr. Kenneth Moise: “ Diagnosing Hemolytic Disease of the Fetus — Time to Put the Needles Away?”

DOI: 10.1056/NEJMe068071

Earlier this month we jetted off to Los Cabos, Mexico to attend the 40th annual the International Fetal Medicine and Surgery Society (IFMSS) conference. This is the first time the society has been able to meet since COVID-19 and with that came a lot of new research and exciting advancements in the field of fetal medicine.
Dr. Moise takes us through his top 11 topics from this jampacked conference. (Seriously. The detailed scientific program scheduled was 13 pages). See below for the episode timestamps and abstract details! 

 

8:44 – Fetal Enzyme Replacement: “A Fetal First: In Utero Enzyme Replacement Therapy in a Fetus with Infantile-Onset Pompe Disease”. Presented by Dr. Tippie MacKenzie from University of California, San Francisco.

 

13:28 – Stem Cell Therapy for Spina Bifida: “From the Barn to the Bedside: The Cure Trial Story”. Presented by Dr. Abd-Elrahman Hassan from University of California, Davis. “Safety Reports of First 3 CURE Trial Patients”. Presented by Dr. Su Yeon Lee from University of California, Davis.

 

16:42 – Artificial Placenta: “Toward Clinical Application: An Update on the Extra-Uterine Environment for Neonatal Developed (EXTEND)”. Presented by Dr. Alan Flake from Children’s Hospital of Philadelphia. 

 

22:41 – Robotic Fetoscopy: “Twin-Twin-Transfusion-Syndrome: Robotic Surgery Using Magnetic Navigation”. Presented by Dr. Ueli Moehrlen from University of Children’s Hospital Zurich.

 

25:49 – IUTs: “Natural Course of Hemolytic Disease of the Fetus and Newborn after Pregnancy with Intrauterine Transfusion”. Presented by Dr. Joanne Verweij from Leiden University Medical Center. 

 

27:50 – TAPS: “Low Risk for Co-Twin Death and Severe Cerebral Injury after Single Fetal Demise in Twin Anemia Polycythemia Sequence (TAPS)”. Presented by Dr. Enrico Lopriore from Leiden University Medical Center.

 

31:11 – Vasa Previa: “Fetoscopic Laser Ablation of Type 2 Vasa Previa”. Presented by Dr. Ramesha Papanna from University of Texas Health Science Center at Houston. 

 

35:30 – Heart Block: “Results from First 218 Anti-Ro/SSA Antibody Positive Pregnancies Enrolled in STOP BLOQ”. Presented by Dr. Lisa Howley from Midwest Fetal Care Center. 

 

38:56 – MMC Repair: “Open Maternal-Fetal Surgery for Myelomeningocele Closure: Outcomes from the fMMC Consortium Registry Sponsored by NAFTNet.” Presented by Dr. Julie Moldenhauer from Children’s Hospital of Philadelphia. 

 

41:58 – Amnioport: “Aggressive Management of Fetal Renal Failure" Lessions Learned from Single Institutional Experience". Presented by Dr. Timothy Crombleholm from Connecticut Children's Hospital.

 

43:49 – Trepostinil: “Prenatal Trepostinil Reduces Pulmonary Arterioles Media Thickness in Fetal Rabbits”. Presented by Dr. Felix De Bie from KU Leuven in Belgium. 

Financial Disclosure: Dr. Moise receives fees paid on his behalf to Dell Medical School - UT Austin for consultation with the genetics company BillionToOne, Inc. This week we're trekking on through more details about alloimmunization and HDFN in the setting of lab studies and specific testing. Dr. Moise discusses the timing intervals for maternal antibody screenings, defines a critical titer, and then we get into the juicy part.....who's the daddy?! We talk about the paternal zygosity as it applies to alloimmunization as well as cffDNA to find out baby's antigen status.

We're kicking off the holiday season early this year courtesy of the mneumonic 'DEcK' that stands for the major HDFN red blood cell antigens 'bad players' - D, big E, little c, and Kell. This week Dr. Moise talks about some of the more common red cell antigens and also the not so common. We wrap up our discussion on antigens using a dalmation analogy to help describe weak D.

Happy Halloween wombmates! Our special spooky gift to you is another segment of "Debunking Dramatizations". Dr. Moise is a diehard Game of Thrones fan and so naturally has closely followed the new House of the Dragon series on HBOMax. In this episode, Dr. Moise walks us through the series premiere episode, "The Heirs of the Dragon", in which Queen Aemma's attempts to delivery a male heir via Cesarean section. We talk about the history of anesthesia, Cesarean deliveries, and how delivery forceps were developed.