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Beneficial or Harmful Effect of Antipaternal Human Leukocyte Antibodies on Pregnancy Outcome? A Systematic Review and Meta-Analysis



Eileen E.L.O. Lashley, Department of Obstetrics, Leiden University Medical Centre, PO Box 9600 (location code: P3-24), 2300 RC Leiden, The Netherlands.




During pregnancy, antibodies are induced that target the paternal human leukocyte antigens of the semi-allogeneic fetus. The level and presence of these antibodies have been reported increased as well as decreased for a variety of pregnancy complications; the clinical relevance and consequences of these antibodies are not very clear. Therefore, the objective of this review is to determine whether the presence of antipaternal antibodies influences pregnancy outcome.


We performed a systematic search of studies that described the effect of antipaternal antibodies on pregnancy complications. The primary outcome was the risk ratio for HLA class I and class II antibodies on pregnancy complications. Furthermore, we calculated the risk for first- and third-trimester complications.


The seventeen studies that were selected for meta-analysis showed high level of statistical and clinical heterogeneity. In the meta-analysis, we found no significant effect of HLA class I or class II antibodies on pregnancy outcome.


No consistent conclusions can be drawn from the meta-analysis. Discrepancies in the meta-analysis are the result of different screening techniques, varying time points of screening, and use of incorrect control groups. Furthermore, more detailed analyses of the characteristics and specificity of the antibodies involved are essential.