Glucose‐6‐phosphate dehydrogenase deficiency as a cause for nonimmune hydrops fetalis and severe fetal anemia: A systematic review

Abstract

Abstract Background Glucose‐6‐phosphate dehydrogenase (G6PD) deficiency is an X‐linked recessive disorder that predisposes individuals to hemolysis due to an inborn error of metabolism. We performed a systematic literature review to evaluate G6PD deficiency as a possible etiology of nonimmune hydrops fetalis (NIHF) and severe fetal anemia. Methods PubMed, OVID Medline, Scopus, and clinicaltrials.gov were queried from inception until 31 April 2023 for all published cases of NIHF and severe fetal anemia caused by G6PD deficiency. Keywords included “fetal edema,” “hydrops fetalis,” “glucose 6 phosphate dehydrogenase deficiency,” and “fetal anemia.” Cases with workup presuming G6PD deficiency as an etiology for NIHF and severe fetal anemia were included. PRISMA guidelines were followed. Results Five cases of G6PD‐related NIHF and one case of severe fetal anemia were identified. Four fetuses (4/6, 66.7%) were male and two fetuses (2/6, 33.3%) were female. Mean gestational age at diagnosis of NIHF/anemia and delivery was 32.2 ± 4.9 and 35.7 ± 2.4 weeks, respectively. Four cases (66.7%) required a cordocentesis for fetal transfusion, and two cases (33.3%) received blood transfusions immediately following delivery. Among the four multigravida cases, two (50%) noted previous pregnancies complicated by neonatal anemia. When reported, the maternal cases included two G6PD deficiency carrier patients and two G6PD‐deficient patients. Exposures to substances known to cause G6PD deficiency‐related hemolysis occurred in 3/6 (50%) cases. Conclusion Six cases of NIHF/severe fetal anemia were associated with G6PD deficiency. While G6PD deficiency is an X‐linked recessive condition, female fetuses can be affected. Fetal G6PD deficiency testing can be considered if parental history indicates, particularly if the standard workup for NIHF is negative.

Keywords

• fetal anemia
• G6PD deficiency
• hydrops fetalis
• prenatal diagnosis