Managing the Unusual Causes of Fetal Anemia

Fetal Diagn Ther. 2020;47(2):156-164. doi: 10.1159/000501554. Epub 2019 Sep 10.


Background: Rare causes of fetal anemia requiring intrauterine transfusion (IUT) are challenging for fetal medicine specialists.

Objectives: The aim of this study was to describe the perinatal patterns and prognosis in a consecutive series of fetuses transfused for fetal anemia of rare or unknown etiology, and to propose a protocol of investigation for fetal anemia of undetermined cause and for the management of subsequent pregnancies.

Method: We conducted a retrospective descriptive study on fetuses transfused for severe anemia of rare or unknown etiology managed in our national referral center (Centre National de Référence d'Hémobiologie Périnatale) and born between 2010 and 2017.

Results: During the study period, 584 IUT were performed in 253 fetuses. Among those IUT, 23 (3.9%) were performed for a rare or unknown cause of anemia in 13 fetuses (5.1% of transfused fetuses). The median gestational age at diagnosis was 26 weeks of gestation (WG; range 21-33). Hemoglobin levels ranged from 1.6 to 9.1 g/dL (0.18-0.83 multiples of median) before the first IUT. The fetuses received between 1 and 6 IUT (39% received at least 2 IUT). The definitive etiologies for central anemia were: congenital syphilis, neonatal poikilocytosis, type II congenital dyserythropoietic anemia (CDA), and neonatal hemochromatosis. There was 1 case with suspected type I CDA and 1 with suspected Diamond-Blackfan anemia. There was 1 case of peripheral anemia, secondary to cerebral hemorrhages of different ages, related to a variant of the COL4A1 gene. In 6 fetuses corresponding to 4 mothers, no precise diagnosis was found despite a complete workup. In our series, there were 8 live births, 4 terminations of pregnancy, and 1 intrauterine fetal death.

Conclusions: Fetal anemia of rare or unknown diagnosis represents 5% of all transfused fetuses in our cohort. Fetal and neonatal anemias can be recurrent in further pregnancies, with variable expressivity.

Keywords: Fetal anemia; Fetal blood sampling; Hydrops fetalis; Intrauterine transfusion; Rare cause of anemia.

MeSH terms

  • Abortion, Induced
  • Anemia / blood
  • Anemia / diagnosis
  • Anemia / etiology
  • Anemia / therapy*
  • Biomarkers / blood
  • Blood Transfusion, Intrauterine* / adverse effects
  • Female
  • Fetal Death / etiology
  • Fetal Diseases / blood
  • Fetal Diseases / diagnosis
  • Fetal Diseases / etiology
  • Fetal Diseases / therapy*
  • Fetal Hemoglobin / metabolism
  • Gestational Age
  • Humans
  • Live Birth
  • Pregnancy
  • Retrospective Studies
  • Risk Factors
  • Treatment Outcome


  • Biomarkers
  • Fetal Hemoglobin