Characterization of pregnancy outcome of women with an offspring with inborn errors of metabolism: A population-based study

Tali Epstein Weiss, Offer Erez, Itai Hazan, Amit Shira Babiev, Orna Staretz Chacham

    Research output: Contribution to journalArticlepeer-review


    Introduction: Inborn errors of metabolism (IEM) are scarce, and their diagnosis is often made after birth. This has led to the perception that most fetuses affected by these disorders do not become clinically apparent during pregnancy. Our aim was to determine the obstetrical characteristics of women with an offspring affected by IEM. Methods: This population-based retrospective cohort study included all women who delivered at the Soroka University Medical Center (SUMC) from 1988 to 2017 who met the inclusion criteria. Mothers who had an offspring with IEM were included in the study group, and those who had offsprings without IEM comprised the comparison group. Results: A total of 388,813 pregnancies were included in the study, and 184 of them were complicated by a fetus with IEM. The number of Bedouin women was higher in the IEM-affected infant group than in the comparison group (90.8% vs. 53.3%, p < 0.001); women who had a fetus with IEM had a higher rate of polyhydramnios (7.1% vs. 3.2%, p = 0.005), HELLP syndrome (3.3% vs. 1.1%, p = 0.014), and preterm birth (20.7% vs. 10.1%, p < 0.001); neonates with IEM had lower mean birth weight (p < 0.001), lower Apgar scores at 1′ and 5′ minutes (p < 0.001), and a higher rate of fetal growth restriction (FGR) (p < 0.001), postpartum death <28 days (p < 0.001), and neonatal death (p < 0.001) than those in the comparison group. Pregnancies with IEM fetuses were independently associated with preterm birth (OR 2.00; CI 1.4–3), polyhydramnios (OR 2.08; CI 1.17–3.71), and FGR (OR 2.24; CI 1.2–4.19). Each family of metabolic diseases is independently associated with specific pregnancy complications (i.e., mitochondrial diseases are associated with HELLP syndrome (OR 5.6; CI 1.8–17), and lysosomal storage disease are associated with nonimmune hydrops fetalis (OR 26.4; CI 3.39–206). Conclusion: This study reports for the first time, an independent association of IEM with specific complications of pregnancy. This observation has clinical implications, as the identification of specific pregnancy complications in a population at risk for IEM can assist in the prenatal diagnosis of an affected fetus.

    Original languageEnglish
    Article number1030361
    JournalFrontiers in Genetics
    StatePublished - 9 Nov 2022


    • HELLP syndrome
    • fetal growth restriction
    • inborn errors of metabolism
    • neonatal death
    • nonimmune hydrops fetalis
    • polyhydramnios
    • pregnancy characteristics
    • preterm birth

    ASJC Scopus subject areas

    • Genetics(clinical)
    • Genetics
    • Molecular Medicine


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