Related Experiment Video
Updated: Dec 17, 2025

A Pipeline to Characterize Structural Heart Defects in the Fetal Mouse
Published on: December 16, 2022
Frontal lobe growth is impaired in fetuses with congenital heart disease
D Paladini1, A Finarelli1, G Donarini1
1Fetal Medicine and Surgery Unit, Istituto G. Gaslini, Genoa, Italy.
Insights
Fetuses with congenital heart disease (CHD) show smaller frontal brain areas and a reduced frontal-to-occipital-frontal diameter ratio compared to healthy fetuses. This brain development difference is observed across all CHD types.
Area of Science:
- Fetal Medicine
- Pediatric Cardiology
- Neurodevelopmental Pediatrics
Background:
- Congenital heart disease (CHD) affects fetal development.
- The impact of CHD on fetal brain structure, specifically frontal lobe development, requires further investigation.
Purpose of the Study:
- To compare frontal brain areas in fetuses with CHD versus normal controls.
- To analyze frontal brain area differences among various CHD subtypes based on hemodynamic impact.
Main Methods:
- Retrospective cross-sectional study of 421 normal and 101 CHD fetuses (20-39 weeks gestation).
- Measurement of frontal lobe anteroposterior diameter (FAPD) and occipitofrontal diameter (OFD) using transventricular axial view.
- Calculation of FAPD/OFD ratio and comparison between groups, with adjustments for gestational age.
Main Results:
- Fetuses with CHD exhibited a shorter FAPD and a significantly smaller FAPD/OFD ratio compared to normal fetuses (P < 0.0001).
- These differences were evident from 20 weeks gestation and increased after 30 weeks.
- No significant differences in the FAPD/OFD ratio were found among different CHD categories.
Conclusions:
- Fetuses with CHD demonstrate reduced frontal brain area growth compared to controls.
- Impaired frontal lobe development in CHD appears independent of the specific hemodynamic impact of the defect.
Objectives:
The primary objective of this study was to assess whether fetuses with congenital heart disease (CHD) have smaller frontal brain areas compared with normal controls. The secondary objective was to evaluate whether there are any differences in frontal brain area between cases with different types of CHD, grouped according to their impact on hemodynamics.
Methods:
This was a retrospective cross-sectional study, including 421 normal fetuses and 101 fetuses with isolated CHD evaluated between 20 and 39 gestational weeks at our fetal medicine and surgery unit in the period January 2016-December 2019. The study group was subdivided, according to the CHD hemodynamics, as follows: (1) hypoplastic left heart syndrome and other forms of functionally univentricular heart defect; (2) transposition of the great arteries; (3) conotruncal defects and other CHDs with large shunts; (4) right ventricular outflow tract obstruction, without a hypoplastic right ventricle; (5) left outflow tract obstruction; (6) others. The transventricular axial view of the fetal head was used as the reference view, on which the frontal lobe anteroposterior diameter (FAPD) and the occipitofrontal diameter (OFD) were measured, assuming the former to be representative of the area of the frontal lobes. The FAPD/OFD ratio was then calculated as FAPD/OFD × 100. These two variables (FAPD and FAPD/OFD ratio) were then evaluated and compared between the study and control groups. Adjustment for gestational age, both via multiple linear regression and by using a-posteriori matching based on the propensity score, was employed.
Results:
In normal fetuses, FAPD showed a linear positive correlation with gestational age. In fetuses with CHD, the FAPD was shorter than in normal fetuses from the 20th gestational week onwards, with the difference increasing after 30 gestational weeks. FAPD/OFD ratio was significantly smaller in fetuses with CHD than in normal fetuses (P < 0.0001) at all gestational ages, with no apparent differences among the various CHD categories, all of which had smaller FAPD/OFD ratio compared with controls.
Conclusions:
Fetuses with CHD have a shorter FAPD and a smaller FAPD/OFD ratio compared with normal fetuses. This impaired growth of the frontal area of the brain seems to occur in all types of CHD, regardless of their impact on hemodynamics. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Related Concept Videos
Development of the Heart
As the embryo undergoes lateral folding, these paired tubes approach each other, merging into a single primitive heart...
Teratogenicity
Fetal Circulation
Two umbilical arteries transport blood from the fetus to the placenta. At the placenta, the blood absorbs oxygen and nutrients while simultaneously eliminating waste products. This oxygen-enriched and nutrient-rich blood then returns to the fetus through one...
Neurulation

