Pre-eclampsia is associated with increased neurodevelopmental disorders in children with congenital heart disease

Camilla Omann; Camilla Nyboe; Rasmus Kristensen; Andreas Ernst; Cecilia Høst Ramlau-Hansen; Charlotte Rask; Ann Tabor; J William Gaynor; Vibeke E Hjortdal

doi:10.1093/ehjopen/oeac027

Pre-eclampsia is associated with increased neurodevelopmental disorders in children with congenital heart disease

Eur Heart J Open. 2022 Apr 21;2(3):oeac027. doi: 10.1093/ehjopen/oeac027. eCollection 2022 May.

Authors

Camilla Omann^{1

2}, Camilla Nyboe^{1

2}, Rasmus Kristensen³, Andreas Ernst⁴, Cecilia Høst Ramlau-Hansen⁴, Charlotte Rask^{5

5}, Ann Tabor⁶, J William Gaynor⁷, Vibeke E Hjortdal³

Affiliations

¹ Department of Cardiothoracic & Vascular Surgery, Aarhus University Hospital, Aarhus, Denmark.
² Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
³ Department of Cardiothoracic Surgery, Copenhagen University Hospital, Copenhagen, Denmark.
⁴ Department of Public Health, Research Unit for Epidemiology, Aarhus University, Aarhus, Denmark.
⁵ Department of Child and Adolescent Psychiatry, Aarhus University Hospital, Aarhus, Denmark.
⁶ Center of Fetal Medicine, Department of Obstetrics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
⁷ Division of Cardiothoracic Surgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Abstract

Aims: Our primary aim was to examine whether exposure to pre-eclampsia increases the risk of neurodevelopmental disorders in children born with congenital heart disease (CHD). Our secondary aim was to evaluate whether CHD and pre-eclampsia may act in synergy and potentiate this risk.

Method and results: Using population-based registries, we included all Danish children born with CHD between 1994 and 2017. Non-singletons and children born with a syndrome were excluded. Neurodevelopmental disorders including attention-deficit/hyperactivity disorder, autism spectrum disorders, and tic disorders were identified with the use of the 10th edition of International Classification of Disease (ICD-10) codes DF80-DF98. Using Cox proportional hazard regression, we estimated the risk of neurodevelopmental disorders in children with CHD exposed to pre-eclampsia compared with those with CHD not exposed to pre-eclampsia. The population consisted of 11 449 children born with CHD. Children exposed to pre-eclampsia had an increased risk of neurodevelopmental disorders, hazard ratio: 1.84 (95% confidence interval: 1.39-2.42). Furthermore, a comparison cohort of 113 713 children with no CHD diagnoses were included. Using cumulative incidence analyses with death as competing risk, we compared the risk of neurodevelopmental disorders if exposed to pre-eclampsia among children with CHD and children without CHD. Exposure to pre-eclampsia drastically increased the cumulative incidence of neurodevelopmental disorders in children born with CHD.

Conclusion: Exposure to pre-eclampsia is associated with increased risk of neurodevelopmental disorders in children born with CHD. CHD and pre-eclampsia may act in synergy and potentiate this effect. Clinicians should therefore be especially attentive to neurodevelopmental problems in this vulnerable subgroup.

Keywords: Congenial heart disease; Foetus; Neurodevelopment; Pre-eclampsia; Psychiatry.