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. 2022 Dec 2;23(23):15178.
doi: 10.3390/ijms232315178.

Associations between Maternal Risk Factors and Intrinsic Placental and Fetal Brain Functional Properties in Congenital Heart Disease

Vidya Rajagopalan  1   2 , Vanessa Schmithorst  3   4 , Alexander El-Ali  5 , William Reynolds  6 , Vincent Lee  5 , Julia Wallace  5 , Jacqueline Weinberg  7 , Jennifer Johnson  7 , Jodie Votava-Smith  2   8 , Jennifer Adibi  9 , Ashok Panigrahy  3   4   5
Affiliations

Associations between Maternal Risk Factors and Intrinsic Placental and Fetal Brain Functional Properties in Congenital Heart Disease

Vidya Rajagopalan et al. Int J Mol Sci. .

Abstract

The relationship between maternal risk factors (MRFs) (particularly pre-gravid obesity, diabetes, and hypertension) and congenital heart disease (CHD) to placental and fetal brain outcomes is poorly understood. Here, we tested the hypothesis that MRF and CHD would be associated with reduced intrinsic placental and fetal brain function using a novel non-invasive technique. Pregnant participants with and without MRF and fetal CHD were prospectively recruited and underwent feto-placental MRI. Using intrinsic properties of blood oxygen level dependent imaging (BOLD) we quantified spatiotemporal variance of placenta and fetal brain. MRFs and CHD were correlated with functional characteristics of the placenta and fetal brain. Co-morbid MRF (hypertension, diabetes, and obesity) reduced spatiotemporal functional variance of placenta and fetal brain (p < 0.05). CHD predicted reduced fetal brain temporal variance compared to non-CHD (p < 0.05). The presence of both MRF and CHD was associated with reduced intrinsic pBOLD temporal variance (p = 0.047). There were no significant interactions of MRFs and CHD status on either temporal or spatial variance of intrinsic brain BOLD. MRF and CHD reduced functional characteristic of placenta and brain in fetuses. MRF modification and management during pregnancy may have the potential to not only provide additional risk stratification but may also improve neurodevelopmental outcomes.

Keywords: fetal brain resting BOLD signal; maternal diabetes; maternal hypertension; placenta.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Pipeline for calculation of intrinsic spatial-temporal variance of placental and fetal brain BOLD signal: Schematics showing the computation of: (A) temporal variance (TV) and; (B) spatial variance (SV) of intrinsic BOLD signal in the whole placental structure. A similar method was used to compute these metrics in the whole fetal brain structure.
Figure 2
Figure 2
Spatiotemporal characteristics of intrinsic pBOLD in CHD and non-CHD cases: (A) Histogram characteristics of pBOLD temporal variance between CHD and non-CHD groups: while the distribution of pBOLD temporal variance between the two group is not different (K-S test, p value = 0.182), the pBOLD temporal variance is reduced in the CHD group compared to non-CHDs, corrected for gestational age and; (B) Regression plot showing significant interaction of CHD status on the relationship between gestational age and pBOLD spatial variance (p = 0.004).
Figure 3
Figure 3
Spatiotemporal characteristics of intrinsic fetal brain BOLD in CHD and non-CHDs: (A) Distribution of brain BOLD temporal variance is significantly different between CHD and non-CHD groups, with CHD cases showing a smaller change from unity mean (denoted by red arrow or the width of the base of the curve) indicating reduced temporal variance of the whole fetal brain compared to the non-CHD cases (p = 0.001). (B) Regression plots show no significant difference in brain spatial variance with age between CHD and non-CHD groups.
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