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Introduction <p>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.</p> Method <p>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).</p> Results <p>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.</p> Conclusion <p>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.</p>

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Prenatal and Maternal Contributors to Disease Severity in Congenital Heart Disease

  • 期刊论文

  • 发表日期：

    2026年2月20日

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  • Masahiro Nishide,
  • Desiree C. K. Hilton,
  • Gary F. Sholler,
  • David S. Winlaw,
  • Sally L. Dunwoodie,
  • Natasha Nassar,
  • Samantha J. Lain,
  • Gillian M. Blue

摘要

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.