Improved newborn screening and advances in critical care have increased survival to adulthood for people with inherited metabolic disorders (IMDs), creating a growing population of reproductive-age women with IMDs. Because these conditions are rare, guidance on pregnancy management remains limited and is often driven by case reports and expert opinion. This single-center retrospective report aimed to evaluate pregnancy outcomes and the metabolic management strategies applied to women with genetically confirmed IMDs who had initiated treatment prior to conception and subsequently gave birth.
The study was retrospective and conducted at a single tertiary metabolic center. Inclusion criteria were female patients aged 15–49 years with genetically confirmed IMDs who had started treatment before conception and delivered an infant. The flow of participant screening, exclusions, and final cohort selection is presented in the study’s participant flowchart (Figure 1).
Seven pregnancies in six women met inclusion criteria. The median maternal age at conception was 29.0 years, and the median gestational age at birth was 38.4 weeks. Diagnoses represented among the cohort included glutaric aciduria type I, tyrosinemia type II, gyrate atrophy, Gaucher disease, and 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGCLD).
The report details individualized, disease-specific strategies applied during pregnancy and the peripartum period.
For two patients with glutaric aciduria type I, individualized peripartum management protocols were successfully implemented. Longitudinal biochemical monitoring and dietary modulation were components of these protocols (see Figures 3A and 3B).
In the patient with Gaucher disease, enzyme replacement therapy was continued throughout pregnancy without reported complications, indicating that continuation of treatment was feasible in this case.
Dietary management and amino acid supplementation were used in at least one case of tyrosinemia type II, where natural protein intake, a tyrosine- and phenylalanine-free amino acid mixture, and plasma tyrosine concentrations were followed across preconception, trimesters and postpartum (Figure 2).
For the patient with HMGCLD, intensive metabolic monitoring encompassed frequent measurements of blood pH, plasma ammonia and blood glucose, with serial acylcarnitine profiles tracked during pregnancy and the peripartum period (Figure 4).
The authors emphasize tailored, multidisciplinary plans that integrate metabolic, nutritional, obstetric and critical care considerations for each diagnostic category.
Serial biochemical markers and dietary intake were used to guide management across diagnoses. Reported laboratory measures included:
Dietary tracking included natural protein intake (g/kg/day), supplement intake (for example, tyrosine- and phenylalanine-free amino acid mixtures) and total caloric intake. Figures in the report display longitudinal dietary intake alongside biochemical results, illustrating how nutritional adjustments were correlated with metabolic parameters during the course of pregnancy and postpartum follow-up.
Overall, the cohort experienced mostly successful pregnancies, but notable adverse events occurred:
A previously unreported congenital heart defect was detected in the infant of a mother with tyrosinemia type II; the publication reports the detection but does not provide further detail on the defect’s classification or outcome beyond its identification.
One patient with HMGCLD demonstrated peripartum metabolic instability in her first pregnancy yet delivered a healthy infant. However, following a subsequent miscarriage, the same patient experienced fatal metabolic decompensation. The report highlights this fatal outcome as a severe maternal complication linked to metabolic instability; additional clinical details and contributory factors are not reported beyond what is summarized.
Two glutaric aciduria type I patients were managed successfully through individualized peripartum protocols, and the Gaucher disease patient continued enzyme replacement therapy through pregnancy without complications.
These outcomes illustrate heterogeneity in pregnancy risk across IMD diagnoses and individual patient courses.
The manuscript includes several figures that document monitoring strategies and individual patient courses:
Figure 1: Flowchart of participant screening, exclusions and final cohort selection.
Figure 2: For the patient with tyrosinemia type II, stacked bars show daily protein intake from natural sources and TYR mixture (g/kg/day) across preconception, trimesters and postpartum, while a red line traces plasma tyrosine concentrations (μmol/L) over the same intervals.
Figure 3: Longitudinal biochemical profiles and dietary intake in two glutaric aciduria type I patients. Panels present serial plasma C5DC, C0 and lysine values from preconception through pregnancy and postpartum, together with dietary protein intake (g/kg/day) and total caloric intake (kcal/day).
Figure 4: Metabolic monitoring in the HMGCLD patient. Panel A charts blood pH, plasma ammonia and blood glucose across pregnancy, the peripartum period and postpartum follow-up, demonstrating transient hyperammonemia with mild acidemia and hypoglycemia in the peripartum window that improved postpartum. Panel B presents serial measurements of C5OH, C6DC and C0 during pregnancy and postpartum.
These figures illustrate the central role of longitudinal biochemical and dietary surveillance for guiding peripartum decision-making in IMD patients.
This single-center series demonstrates that pregnancies in women with varied inherited metabolic disorders can result in successful live births under disease-specific, multidisciplinary management. Nonetheless, the cohort also experienced severe maternal complications, a fetal structural anomaly, and a fatal maternal metabolic decompensation following a miscarriage in one case. These findings underscore the limited evidence base for pregnancy management in IMDs and the need for structured adult care pathways, standardized monitoring protocols and disease-specific pregnancy strategies as more individuals with IMDs reach reproductive age.
The authors call for expanded, systematic reporting and development of guidance to improve evidence-based care for this growing patient population. The publication declares no conflicts of interest.