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Human fetal bilirubin levels and fetal hemolytic disease

  • Author Footnotes
    a From the Fetal Diagnosis and Treatment Unit, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Iowa College of Medicine.
    Carl P. Weiner
    Correspondence
    Reprint requests: Carl P. Weiner, MD, Department of Obstetrics and Gynecology, University of Iowa College of Medicine, Iowa City, IA 52242.
    Footnotes
    a From the Fetal Diagnosis and Treatment Unit, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Iowa College of Medicine.
    Affiliations
    Iowa City, Iowa
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  • Author Footnotes
    a From the Fetal Diagnosis and Treatment Unit, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Iowa College of Medicine.
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      The development of secondary fetal anemia in association with maternal red blood cell alloimmunization requires hemolysis. In specimens obtained at the time of a clinically indicated cordocentesis, total and direct umbilical venous bilirubin was measured and the indirect umbilical venous bilirubin calculated in 43 antigen-positive and 30 control fetuses. Twenty—two (51%) of the antigen-positive fetuses had or subsequently developed severe anemia (hematocrit <30%). Umbilical venous total bilirubin (r = 0.47, p = 0.0008) and direct bilirubin (r = 0.520, p = 0.04) levels each rose with gestation. Indirect bilirubin did not vary significantly with gestation. Bilirubin was unrelated to hemoglobin. In contrast to the control fetuses, umbilical venous total bilirubin for antigen-positive fetuses was inversely related to hemoglobin (r = −0.57, p < 0.0001) independent of gestational age (r = 0.53, p < 0.0001) (multiple R of hemoglobin and gestational age for umbilical venous total bilirubin = 0.76, p < 0.0001 ). Eighteen of 22 (82%) fetuses in whom anemia developed had an umbilical venous total bilirubin ≥97.5 percentile compared with only eight of 21 (38%) fetuses in whom anemia did not develop (p = 0.009). In longitudinal study the umbilical venous total bilirubin frequently rose above normal weeks before the development of anemia. An umbilical venous total bilirubin >3 mg/dl represented the warning line. Fifteen of 16 (94%) fetuses in whom either severe antenatal anemia or significant postnatal hyperbilirubinemia developed had an umbilical venous total bilirubin >3 mg/dl. We conclude that the normal placental capacity for the transport of fetal bilirubin is exceeded in the face of enhanced fetal hemolysis. An elevated fetal bilirubin often precedes the development of antenatal anemia. The antigen-positive fetus with an elevated bilirubin is at high risk to develop anemia antenatally.

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