Newborns with congenital heart disease (CHD) and preterm newborns are at high risk for morbi-mortality. However, the extent to which CHD affects long-term outcomes, especially neurodevelopment, in preterm newborns remains unclear.

Retrospective case control matched study. Preterm infants (< 37 weeks of gestation) born with CHD between January 2013 and December 2022 included in the LIFT cohort and followed up at 24 months were matched 4:1 by gender, gestational age, year and place of birth and parental socio-professional status.

35 patients with significant CHD were matched with 132 preterm patients without CHD from the LIFT cohort. Severe to moderate neurodevelopmental impairment (NI) was more frequent for patients born preterm with CHD at 24 months of age (12/35 (34.29%) vs 16/132 (12.9%); P = 0.0073). Severe NI (14.29% vs 4%, P = 0.042) and physician reported motor or cognitive anomalies were also more common. Global ASQ and gross motor ASQ were lower in the CHD group. In an univariate model, unfavorable socio-economic level (OR 2.12, 95% CI [1.07, 4.18]), presence of CHD (OR 3.52, 95% CI [1.47, 8.43]) and duration of invasive ventilation (OR 1.08, 95% CI [1.02–1.15]) were associated with NI at 24 months in preterm infants. Duration of ventilation was associated with NI in multivariate analysis (OR 1.14, 95% CI [1.04, 1.24]).

Preterm infants with CHD are at higher risk of NI compared to a similar preterm population without CHD, especially regarding motor function. Unfavorable socio-professional level and longer invasive ventilation are associated with NI.