Observational study of birth outcomes in children with inborn errors of metabolism

We examined the birth outcomes of children with inborn errors of metabolism detected at birth or later in life.

We carried out a retrospective cohort study of 1733 children with inborn errors of metabolism and 1,033,693 unaffected children born in Canada between 2006 and 2019. Primary outcomes included preterm birth, low birth weight, congenital anomalies, and other neonatal complications. We estimated adjusted risk ratios (RR) and 95% confidence intervals (CI) for the association of inborn errors of metabolism with each outcome.

Children with inborn errors of metabolism had 2.51 times the risk of preterm birth (95% CI 2.27-2.77) and 3.08 times the risk of low birth weight (95% CI 2.77-3.42) compared with unaffected children. Disorders of mineral and lipoprotein metabolism were more strongly associated with adverse birth outcomes. Inborn errors of metabolism were associated with congenital anomalies (RR 2.62; 95% CI 2.36-2.90), particularly abdominal wall defects (RR 8.35; 95% CI 5.18-13.44). Associations were present for errors of metabolism diagnosed both at birth and later in life.

Children with inborn errors of metabolism, whether detected at birth or later, are at high risk of adverse birth outcomes and congenital anomalies.

Inborn errors of metabolism may affect fetal development, but the association with adverse birth outcomes is not well characterized. This study indicates that children with inborn errors of metabolism are at risk of preterm birth, neonatal jaundice, congenital anomalies, and a range of other adverse birth outcomes. Mothers of children with inborn errors of metabolism are at risk of preeclampsia and cesarean delivery. Adverse birth outcomes may be a first sign of inborn errors of metabolism that merit increased screening.