Retrospective Discussion of Neonatal Mortality (1990–2010) in Common Chimpanzees (Pan troglodytes) with Consideration of Maternal-Fetal Incompatibility of Blood Groups
Although great apes often serve as physiologic model species for humans, advances in human medicine can also be translated to their great ape counterparts. A pertinent example of this is blood group determination. Non-human primates have served both as the source of discovery, as in the Rh-factor discovered in Rhesus macaques (Macaca mulatta), and as recipient of human technology for blood group determination.6 Blood groups refer to erythrocyte (RBC) membrane proteins that serve as antigens that can stimulate antibody production in an immunologically naïve recipient of a blood transfusion. Specifically in gestation, exposure to blood antigens between fetal and maternal circulation occurs via the hemochorial placenta and sensitization may result.3,6
“Maternal-fetal incompatibility” (MFI) is defined as any of several manifestations that occur when an offspring’s blood is alloimmunized due to antibodies present in the dam’s blood, and includes erythroblastosis fetalis, congenital anemia, icterus gravis neonatorum and hydrops fetalis. For MFI to occur, the fetus must possess a blood-antigen that is absent in the dam. Often times the first pregnancy is the initial exposure and does not result in any clinical manifestation of MFI. However, effects may be observed when the offspring ingests maternal lacteal antibodies or during subsequent gestations exposed to the pre-existing antibodies.
These antibodies cause the destruction of antigen presenting RBCs.3 Clinical manifestations in affected offspring include marked increase in extramedullary hematopoesis (EMHP) of spleen and liver to combat the anemia secondary to erythrocyte destruction. Exposure of developing organs to extreme EMHP concentrations will result in reduced fetal albumin production and hypoproteinemic sequelae of hydrops, edema, ascites and bicavitary effusion. During gestation, fetal hyperbilirubinemia is not noted, even with marked RBC destruction, as the maternal liver often corrects for the icterus during gestation. Postpartum, however, the neonate no longer has the benefit of its dam’s reserve hepatic capacity, so neonatal hyperbilirubinemia develops quickly.1,3,8
Sensitization from prior pregnancies is the most common situation associated with MFI in humans. However, antepartum hemorrhage, spontaneous abortions, ectopic pregnancies, abdominal trauma during pregnancy, and blood mistransfusions can similarly produce alloimmunization. Clinical procedures of amniocentesis, chorionic villous sampling or induced abortions may also expose fetal to maternal circulations and cause alloimmunization. Twinning and chimeric gestations in non-human primates have been hypothesized as yet another predisposing factor for MFI.3,8
Since the discovery of Rh-factor, MFI in humans has been prevented by commercially prepared Rho(D) immunoglobulin (RhoGAM) that is administered to prevent alloimmunization. Prenatal parental testing for blood group is performed to establish risk of MFI. This preventive screening and administration of RhoGAM coupled with intravascular fetal transfusions has changed the emphasis from treatment to prevention of MFI, so human infants born with clinical signs for MFI are increasingly rare.3
In primate populations carefully managed for reproduction, neonatal loss due to preventable conditions is of great importance. MFI has been documented in a chimpanzee (Pan troglodytes)8 and an orangutan (Pongo sp.)1,5 secondary to non-uniform blood types. Infant death occurred due to erythroblastosis fetalis and marked hyperbilirubinemia due to severe hemolytic anemia. With completion of a recent study that evaluated great ape blood groups, investigation into potential MFI and reproductive loss is now possible. Focusing on chimpanzees of managed USA and European zoos and in situ managed populations (n=233), primary blood groups of A and O were identified, with A predominant in the population. Blood group O occurred in different frequencies in each population, especially by animal origin (zoo-born versus wild-origin).2 Although blood group O in humans indicates a non-reactive state without antibodies present, it remains possible that blood group O in chimpanzees was simply non-reactive to human monoclonal antibody technology but could be reactive intra-specifically.
For this retrospective discussion, analysis of the Chimpanzee Species Survival Plan population’s postmortem data identified 45 deceased neonates up to 5 months of age as candidates for MFI investigation. Available dam and sire blood groups, family tree assessment in context of reproductive history of the dam and sire, and available necropsy reports (n=35) were reviewed to identify possible MFI cases. Although conclusive determination of MFI was not made, parental and sibling blood group assessment in some family lines suggested potential risk. Clinical awareness of this diagnosis during pregnancy in great apes can prepare veterinarians to manage cases prophylactically or by treatment postpartum.
The authors would like to thank Jessica Lovstad and Kathy Wagner for their informational support and Eldon Biologicals for support of the blood group project materials.
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