Intravenous Immune Globulin in Neonatal ABO Isoimmunization: Factors Associated with Clinical Efficacy

Abstract

Objective: Intravenous immune globulin (IVIG) reduces jaundice in many but not all cases of neonatal isoimmunization. We sought to elucidate the type of infant most likely to benefit from IVIG administration by attempting to define pretreatment parameters associated with both clinical symptomatology and therapeutic responsiveness to IVIG. Methods: Term, healthy Coombs-positive infants were studied prospectively. IVIG was administered if, despite phototherapy, serum bilirubin reached ≥ 222 μmol/l (13 mg/dl) at ≤ 24 h of age and/or ≥ 274 μmol/l (16 mg/dl) at > 24 h of age. Clinical data including serial serum total bilirubin levels, rate of bilirubin rise on day 1 of life, serial corrected carboxyhemoglobin levels (a sensitive indicator of hemolysis) and total hemoglobin (tHb) levels were collected. Results: Infants were classified as IVIG responders (n = 18), those in whom total serum bilirubin levels either remained stable or decreased following IVIG administration; IVIG nonresponders (n = 5), those who developed a total serum bilirubin of ≥ 2 mg/dl greater than pre-IVIG bilirubin levels within the first 24 h after IVIG administration, or nontreated, those not meeting IVIG treatment criteria (n = 13). Four of the five nonresponders proceeded to require exchange transfusion vs. none of the others (p < 0.001). Four of the five nonresponders had a pretreatment rate of bilirubin rise of > 1 mg/dl/h as compared with only 1 of 18 responders and none of the nontreated (p < 0.001). Pretreatment tHb levels were also different (13.2 ± 1.3 vs. 15.5 ± 2.3 vs. 17.7 ± 2.4 g/dl for nonresponders vs. responders vs. nontreated infants, respectively; p < 0.005). The highest pretreatment COHbc levels were seen in the nonresponders (1.8 ± 0.7 vs. 1.4 ± 0.3 vs. 0.9 ± 0.3% tHb, respectively). Conclusions: Our 3 groups represent a spectrum of hemolysis, ranging from severe to moderate to mild. This spectrum appears to relate not only to the severity of hemolysis, but also to the therapeutic responsiveness to IVIG. We speculate that some or all of the factors identified can be used prospectively to predict the subsequent clinical course of ABO-incompatible infants and to facilitate optimal management.

Single versus multiple dose intravenous immunoglobulin in combination with LED phototherapy in the treatment of ABO hemolytic disease in neonates

“…Kaura et al [12] studied 30 neonates with Rh or ABO blood incompatibility and used single dose IVIG (500 mg/kg) in 15 neonates and showed that it reduces the need for exchange transfusion. Hammerman et al [13] evaluated 36 ABO blood group incompatible newborns whose direct Coombs tests were positive and used IVIG in addition to phototherapy in 23 patients, five of them did not respond to the treatment and four of them received exchange transfusion. Alpay et al [14] showed that IVIG therapy in newborns with ABO or Rh hemolytic diseases reduces hemolysis, serum bilirubin levels and the need for exchange transfusion.…”

Maternal IgG anti‐A and anti‐B titres predict outcome in ABO‐incompatibility in the neonate

“…Earlier studies have demonstrated that some neonates with ABO‐incompatibility fail to respond to IVIG‐treatment (30), and multiple doses of IVIG may reduce the duration of phototherapy and the need for EXT (21). However, these studies did not measure maternal IgG anti‐A and ‐B titre levels.…”

Neonatal bilirubin production, reflected by carboxyhaemoglobin concentrations, in Down's syndrome

“…Therefore, accurately determined COHb values, corrected for inspired CO, offer a reliable index of the rate of haem catabolism, and by inference, bilirubin production. For comparison, we have provided COHbc values for other haemolytic conditions, taken from neonates studied in the same nursery as the current study: G-6-PD deficient neonates who developed hyperbilirubinaemia had a mean third day COHbc value of 0.80 ± 0.19%,16 while direct Coombs’ test positive ABO isoimmunised neonates ranged from 0.9 + 0.3% in the milder cases, to 1.8 ± 0.7% in the more severe cases 17…”