Hemolytic Disease of the Fetus and Newborn and Perinatal Testing
Rh immune globulin
A 300 microgram dose (about 1500 IU) neutralizes roughly 15 mL of D-positive red cells, about 30 mL of whole blood. Give antenatally at 28 weeks and postpartum within 72 hours to D-negative, antibody-negative mothers of D-positive infants; also after abortion, ectopic pregnancy, amniocentesis, chorionic villus sampling, trauma, and antepartum bleeding. Fetomaternal hemorrhage is quantified by Kleihauer-Betke (fetal cells resist acid elution) or flow cytometry; the dose is the volume of fetal red cells divided by 30, rounded up, plus one additional vial for large bleeds. Weak D types 1, 2, and 3 do not require RhIG; partial D, such as DVI, does. RhIG can produce a weakly positive DAT.
Predicting severity
ABO HDFN affects group O mothers with IgG anti-A or anti-B, is usually mild, may show a negative DAT, and features spherocytes. Rh and other IgG-mediated disease worsens with each subsequent pregnancy; anti-K can cause severe disease at low titer because K suppresses erythroid progenitors. A titer of 16 (some laboratories use 32) is the critical value for anti-D, after which middle cerebral artery peak systolic velocity above 1.5 multiples of the median is the standard noninvasive test for fetal anemia, superseding the Liley delta OD 450 method. Severe anemia is treated with intrauterine transfusion.
Postnatal evaluation
Cord blood testing includes ABO/Rh, DAT, hemoglobin or hematocrit, and bilirubin, followed by bilirubin nomograms, phototherapy, selected IVIG, and exchange transfusion when indicated.
Traps
Giving RhIG to a D-positive mother is an error; verify weak D status. IgM antibodies such as anti-Lea, anti-Leb, anti-I, anti-P1, and anti-M do not cause HDFN. A previously affected infant predicts severity better than titer alone.
Rule of thumb: any IgG red cell antibody in a pregnant woman warrants paternal antigen typing and serial maternal monitoring.