General obstetrics: The kinetics of routine antenatal prophylactic intramuscular injections of polyclonal anti‐D immunoglobulin

Abstract

Objective To observe the pharmacokinetics of intramuscular anti-D immunoglobulin (IgG) given for routine antenatal prophylaxis.Design Prospective observational study.Setting Maternity unit and antenatal serology laboratory in a district teaching hospital.Population Forty-five rhesus-D-negative pregnant women not sensitised to RhD. Results For the 43 women in whom serial data were collected, there were no detectable differences between pregnancies with an RhD-positive (26) or -negative (17) fetus. Maximum IgG concentrations were detected two to five days following the first anti-D IgG injection and ranged between 0 and 28 ng/mL. Only 30% of women still undelivered at 40 weeks of gestation had detectable IgG at 2 ng/mL or greater. There was a significant relationship between higher maximum values and low maternal surface body area (R 2 = 0.204, P = 0.002), but this did not influence duration of persistent IgG.Conclusion Using previously published data, 70% women are not adequately protected with anti-D IgG 12 weeks after the first prophylactic injection. Despite this, previous clinical results suggest that the antenatal prophylaxis schedule used provides adequate protection and that the recommendation for the lowest concentration of protective anti-D IgG antibody levels currently in use is probably overestimated.Please cite this paper as: MacKenzie I, Roseman F, Findlay J, Thompson K, Jackson E, Scott J, Reed M. The Kinetics of routine antenatal prophylactic intramuscular injections of polyclonal anti-D immunoglobulin.

Risk factors for RhD immunisation despite antenatal and postnatal anti‐D prophylaxis

“…The postmaturity risk factor might be explained by insufficient levels of preventive anti‐D Ig, after a single gift of 1000 iu (200 μg) in week 30 of pregnancy, in addition to the obvious immunogenic effect of prolonged exposure to fetal cells. Several studies showed undetectable levels of anti‐D Ig more than 12 weeks after administration, even when 300 μg of anti‐D Ig was administered in a single gift; 29 therefore, anti‐D Ig levels may drop too low if a pregnancy exceeds 42 weeks 30–32 …”

RhOD immune globulin products for prevention of alloimmunization during pregnancy

“…24 Based on assumptions of circulating maternal plasma volume and extravascular fluid, this dose would yield a circulating plasma concentration of 2.4 ng/mL. 25,26 This minimum concentration is based on the average circulating blood volume in pregnant women and therefore does not account for inherent interpatient variability; nevertheless, 25 mg of RhIG per milliliter of D-positive RBCs is the clinical rule of thumb for RhIG dosing. Pharmacodynamic analyses of the clearance of RBCs against a constant dose of RhIG have shown that clearance is nonlinear across a range of RBC volumes, indicating that the standard RhIG:RBC ratio (25 mg to 1 mL) is not appropriate in all situations.…”

Risk Factors for RhD Immunisation Despite Antenatal and Postnatal Anti-D Prophylaxis

“…Several studies showed undetectable levels of anti-D Ig more than 12 weeks after administration, even when 300 lg of anti-D Ig was administered in a single gift; 29 therefore, anti-D Ig levels may drop too low if a pregnancy exceeds 42 weeks. [30][31][32] RBC transfusion is a less obvious factor contributing to RhD immunisation. Most likely, the RhD-negative RBCs have been given in all cases, as false-negative typing of donors is extremely rare.…”