Administering human IVIG or the HPA-1a–specific mAb 26.4 into pregnant females elevates the platelet count of pups born to APLDQ alloimmunized mothers. (A) Four WT BALB/c female mice that had been pre-immunized with APLDQ murine platelets were bred 5 successive times with APLDQ males. (B) In the first pregnancy, the female mice received no treatment, and as a result, all the pups born were severely thrombocytopenic (first column). On days 10.5 and 17.5 of the second pregnancy, all 4 females received 25 mg of human pharmaceutical-grade IVIG (∼1 g/kg) administrated via tail vein injection. As a result, the platelet counts of the resulting pups were normal to near normal. No additional drug was administered during the third pregnancy, resulting in thrombocytopenic pups and demonstrating that the beneficial effects of IVIG treatment do not persist for more than ∼2 months. For the fourth pregnancy, the effector-silent variant of the HPA-1a–specific mAb 26.4 was administered at 30 mg per female on days 10.5 and 17.5 of gestation, resulting in rescue of platelet counts in the pups of 3 of the 4 females. Similar to IVIG treatment, the beneficial effects of treatment with mAb 26.4 did not persist in subsequent pregnancy #5, even though it was <8 weeks after delivery of litter #4. (C-E) IVIG treatment suppressed the maternal immune response (C), decreased the corresponding anti-APLDQ antibody levels in pups (D), and increased litter sizes (E). Although mAb 26.4 improved neonatal platelet counts (B), it had no effect on maternal or neonatal anti-APLDQ antibody levels (not shown), as might be expected of a treatment whose mechanism of action differs from that of IVIG, which acts as a generalized immunosuppressive agent.