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Prenatal and Maternal Contributors to Disease Severity in Congenital Heart Disease
Masahiro Nishide1, Desiree C K Hilton1,2, Gary F Sholler1,2
1Sydney Medical School, The University of Sydney, Sydney, Australia.
Insights
Maternal diabetes and urinary tract infections are linked to complex congenital heart disease (CHD) severity. Identifying and treating these prenatal factors could aid in primary prevention strategies for complex CHD.
Area of Science:
- Cardiology
- Maternal-Fetal Medicine
- Genetics
Background:
- Congenital heart disease (CHD) arises from genetic and environmental interactions.
- Complex CHD may involve polygenic inheritance influenced by environmental factors.
- Understanding prenatal influences on CHD severity is crucial.
Purpose of the Study:
- To investigate the association between prenatal factors and maternal chronic health conditions with CHD severity.
- To identify specific maternal health conditions linked to complex CHD.
- To explore potential targets for primary prevention of complex CHD.
Main Methods:
- Utilized data linkage of the Kids Heart BioBank with perinatal and hospital admission records.
- Categorized CHD cases into complex (neonatal intervention) and other CHD groups.
- Compared prenatal factors and maternal chronic conditions (ICD-10-AM) between CHD severity groups and controls.
Main Results:
- Mothers of infants with complex CHD showed increased rates of pre-existing diabetes mellitus and urinary tract infections.
- Reduced rates of circulatory system disorders and preeclampsia/gestational hypertension were observed in mothers of infants with complex CHD.
- Associations remained significant after adjusting for confounding variables.
Conclusions:
- Prenatal factors and maternal chronic health conditions significantly influence CHD severity.
- Findings support the role of environmental 'stressors' in complex CHD presentation.
- Therapeutic interventions for modifiable maternal factors during pregnancy may offer primary prevention for complex CHD.
Introduction:
Most congenital heart disease (CHD) is due to a combination of genetic and environmental factors. Recent findings suggest a polygenic inheritance in more complex CHD, highlighting a role for environmental factors in final disease presentation. Using data linkage, this study investigated the association of prenatal factors and maternal chronic health conditions with CHD severity.
Method:
Patients from the Kids Heart BioBank (n = 2389) were linked to the NSW Perinatal Data Collection and the NSW Admitted Patient Data Collection containing prenatal and maternal health records. CHD cases were grouped into two categories according to disease severity: (i) complex CHD (comprising patients requiring neonatal intervention, n = 581) and (ii) other CHD (comprising patients requiring intervention after the neonatal period, n = 1808). Prenatal factors and chronic health conditions were coded using ICD-10-AM classification and compared across severity groups and healthy controls (n = 58,624).
Results:
Analyses identified a significant increase in preexisting diabetes mellitus (p = 0.003), and urinary tract infections (p = 0.01) in mothers of infants with complex CHD compared to other CHD. Conversely, circulatory system disorders and preeclampsia/gestational hypertension were reduced in mothers of infants with complex CHD compared to other CHD (p = 0.01 and p = 0.06, respectively). These risks remained after adjusting for confounding factors including socioeconomic status, smoking, age at pregnancy, gestational age and year of birth.
Conclusion:
These findings suggest an important role for prenatal factors and maternal chronic health conditions in CHD severity, in line with previous reports supporting polygenic inheritance in complex disease with contributions from environmental 'stressors' in the final disease presentation. Importantly, these findings hold promise for future primary prevention for complex CHD through therapeutic treatments of potentially modifiable factors in pregnancy.
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