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Background: Secundum atrial septal defect (ASD II), situated within the fossa ovalis, is the third most common congenital heart defect and even more common among preterm children. Spontaneous closure usually occurs during the first year of life. Most children with an ASD II remain asymptomatic during early childhood. Guidelines recommend ASD II closure in the presence of a significant left-to-right shunt. Percutaneous device closure, which is most commonly used, and surgery are both considered safe, with few major adverse events.

In Sweden, approximately 6% of all children are born preterm. The morbidity of preterm children includes increased risk of chronic pulmonary disease and altered cardiac morphology and function which remain into adulthood. Most studies on ASD II incidence and interventional and surgical risks following ASD II closure are based on otherwise healthy children. Preterm children are a special subset of patients with ASD II and the hypothesis in this thesis is that preterm birth may be associated with increased risks of ASD II diagnosis and adverse events following closure.

Aim: The overall aim of this thesis was to assess the incidence of ASD II, independent risk factors associated to ASD II diagnosis, and adverse events following ASD II interventional closure.

Methods: Paper I: A retrospective case-control study assessing associated risk factors for adverse events after percutaneous device closure among children with an interventional weight of less than 15 kg. Paper II: A cohort study assessing a preterm and a term cohort and time to first adverse event within one month or one year after ASD II closure, as well as number of events. Paper III: A retrospective case-control study assessing the association between major and minor adverse events after ASD II closure, and potential paediatric risk factors. Paper IV: A national registry-based retrospective incidence and case-control study calculating the incidence of ASD II diagnosis among term and preterm children and assessing potential maternal, neonatal, and paediatric risk factors for ASD II.

Results: Paper I: No independent risk factor was associated with adverse events after percutaneous device closure. However, major adverse events occurred in 11 (10%) of the children weighing less than 15 kg, compared with six (4%) children weighing over 15 kg (p = 0.04). Paper II: There was no difference between the preterm and term cohorts in time to first adverse event or in multiple adverse events within one month or within a year, neither in number of major events (p = 0.69) nor in number of minor events (p = 0.84). However, the preterm cohort was younger (2.1 versus 3.4 years, p < 0.01), lighter (11.6 versus 15.1 kg, p < 0.01), had a smaller ASD II size (12.0 versus 13.0 mm, p< 0.01), and a larger ASD II size to weight ratio (1.1 versus 0.8, p < 0.01) compared with the term cohort. Paper III: ASD II with significant clinical symptoms was associated with both minor OR = 2.18, (CI 95% 1.05–8.06) and major OR = 2.80 (CI 95% 1.23–6.37) adverse events following closure. Paper IV: The yearly overall incidence of ASD II was 150 per 100,000 live births. However, this incidence ranged from 449 to 1,737 per 100,000 live births, with higher incidence in preterm children. ASD II was associated with a presence of persistent ductus arteriosus; OR = 8.11 (CI 95% 2.80–16.69), female gender; OR = 1.39 (CI 95% 1.18–1.63), and being small for gestational age; OR = 1.86 (CI 95% 1.29–2.68). Being born preterm was also associated with ASD II diagnosis: born at 32–36 gestational weeks; OR = 3.21 (CI 95% 2.46–4.19), and born at < 32 gestational weeks; OR = 4.02 (CI 95% 2.80–7.12).

Conclusions: Preterm children have a high incidence of ASD II diagnosis, increasing with lower gestational age at birth, and is an independent risk factor for ASD II diagnosis. Few adverse events occurred among children following ASD II closure, and there were no neonatal or paediatric risk factors (including procedural body weight and gestational age) associated with adverse events. There was an association between clinical symptomatic ASD II and major adverse events. Despite younger procedural age, larger ASD II size to weight ratio and increased comorbidity, preterm children appeared to have similar risks of adverse events during the first year after ASD II closure when compared with term children.

Preterm children and children with symptomatic ASD II need careful management both prior to and after ASD II closure. A new, structured follow-up programme with assessment of indication and timing of treatment and closure should be considered for children born preterm.