Placental Malperfusion Is Associated With Adverse Outcomes in Congenital Heart Disease and With Genetic Variants in Placental Developmental Pathways

doi:10.1016/j.jacc.2025.07.069

Congenital heart diseaseCase-control study

Placental Malperfusion Is Associated With Adverse Outcomes in Congenital Heart Disease and With Genetic Variants in Placental Developmental Pathways

J Am Coll CardiolPublished 11 Nov 2025

Retrospective case-control study

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Authors' conclusion

PMP is associated with impaired fetal growth, longer hospitalization, and possibly increased mortality in CHD. CHD fetuses with PMP harbor deleterious de novo variants in several key placental and cardiac developmental pathways, which may represent important mechanisms underlying PMP in CHD.

Study context

Population: Fetuses with congenital heart disease (CHD)Placental malperfusion (PMP) in 51%
Participants: 299 fetuses

Comparison: CHD fetuses with PMP vs without PMP
Outcome: Adverse outcomes and genomic variation in vascular or placental developmental pathways

Main finding

As reported in the abstract

Outcomes in nonsyndromic fetuses

PMP

2,986 g

Birth weight · Length 48 cm · Head circumference 33 cm · Index hospitalization 21 days · Mortality 12.3% · n = 122

No PMP

3,330 g

Birth weight · Length 48.9 cm · Head circumference 34 cm · Index hospitalization 15 days · Mortality 5.6% · n = 124

PMP vs No PMPEstimate (95% CI)P value

mortality, univariable

unadjusted HR 1.5(1.03–2.17)

P = 0.03

mortality, multivariable

adjusted HR 1.44(0.995–2.09)

P = 0.054

Observational data: associations, not effects.

Further findings

Outcomes in syndromic subjects (subgroup)

No significant differences in syndromic subjects

Genomic variants

Proportion with ≥1 angiogenesis pathway or de novo variant similar with and without PMP, not associated with outcomes
Fetuses with PMP: distinct enrichment in de novo variants in Notch signaling and extracellular matrix regulation/epithelial-to-mesenchymal transition genes

Original publication

Placental Malperfusion Is Associated With Adverse Outcomes in Congenital Heart Disease and With Genetic Variants in Placental Developmental Pathways. J Am Coll Cardiol. Published 11 November 2025. doi:10.1016/j.jacc.2025.07.069

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Summarised from the published abstract; every number is checked against it