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Objective To evaluate the 10-year economic burden experienced by mothers of children with major congenital anomalies in Denmark.Design Population-based matched retrospective cohort study.Setting Denmark, 1 January 2007 to 31 December 2017.Participants All women who gave birth to a singleton child with a major congenital anomaly during the study period (n=12 513). A comparison cohort of mothers with singleton births of children without major congenital anomalies was included, matched 1:10 by maternal age, parity and delivery year (n=125 008).Main outcome measures Societal costs associated with mothers of children with major congenital anomalies. Costs were quantified as direct healthcare costs (primary care, outpatient, inpatient, psychiatric services and prescriptions) and indirect costs (productivity losses estimated using the human capital approach, including income, labour market contributions, supplementary pensions and fringe benefits).Results Direct costs peaked in the delivery year with a mean attributable cost of more than €1731 (95% CI €1634 to €1824). Indirect costs increased over time, reaching a peak of €2251 (95% CI €978 to €3442) at 9 years after delivery. Over a median follow-up of 6.3 years, attributable indirect costs were two and a half times higher than direct costs. Total societal costs associated with the 12 513 mothers of children with major congenital anomalies in our cohort were estimated at €152 million (95% CI €92 million to €219 million).Conclusions Mothers of children with major congenital anomalies experienced substantial and persistent economic burdens, with indirect costs increasing over time and exceeding direct healthcare costs. These findings highlight the need for targeted public health and policy initiatives to support affected families and address long-term societal costs.