OBJECTIVE: Naturally occurring insulin autoantibodies [IAA] intrinsic to the fetal immune repertoire or transplacentally acquired, may influence insulin bioavailability and its function as a growth factor. We hypothesize that IAA play a role in determining fetal growth.STUDY DESIGN: 42 paired umbilical cord (CB) and maternal serum (MB) samples were collected at delivery from normal pregnancies with ultrasound determined fetal macrosomia (EFW >90%). All were singleton deliveries at ≥36 wks, had normal diabetic screening and no fetal anomaly or other antepartum complications. CB and MB were assayed for glucose, insulin (radioimmune inhibition assay) and IAA (radio binding assay) levels. 1642(38%) patients delivered normal weight neonates [control] and2642 (62%) delivered macrosomic neonates, birthweight >90% [macro].RESULTS: The groups were similar for maternal demographics, EGA @ delivery, prepregnancy weight, pregnancy weight gain, 1 hour post-glucola, family history of DM and birthweight of previous largest baby. BWt in macro was significantly higher than for controls [4,437 ± 418 vs 3,729 ± 176 p<.0001]. CB glucose, insulin and IAA levels and MB glucose, insulin and IAA levels were comparable in both groups. CB IAA levels were significantly higher than maternal IAA in both the macro and control groups [5.4 ± 3.2 vs 1.8±1.7 p<.0001 & 6.5 ± 3.5 vs 1.9±2.1 p<.0001].POSITIVE CORRELATIONS:CONCLUSIONS: Individual differences in IAA capacity and avidity may determine which fetuses will become macrosomic. IAA presence may indirectly affect the correlations & explain the differences observed between the macro and control groups particularly relating to CB insulinemia and birthweight.