Evaluating fetal pulmonary vascular development in congenital heart disease: a comparative study using the McGoon index and multiple parameters of fetal echocardiography

Introduction

In the fetuses studied, the time to peak velocity and the left-to-right flow ratio remained stable, yet peak aortic and pulmonary artery velocities and cardiac output decreased significantly [1]. In the 1980s, the McGoon index (MGI) and pulmonary artery index, also known as the Nakata index, emerged as pivotal tools for evaluating pulmonary vascular development in patients with congenital heart disease (CHD), MGI gained recognition as a comprehensive indicator for assessing the overall development of the pulmonary vascular bed [2], 3]. Clinically, both MGI and Nakata index serve as crucial surgical indicators for primary radical surgery in Tetralogy of Fallot syndrome (TOF), offering an important reference basis for preoperative evaluation, surgical selection, and postoperative intervention in TOF patients, closely impacting prognosis [4], 5]. Study has shown a high correlation between echocardiography and values measured by cardiovascular angiography, highlighting the accuracy of MGI in assessing pulmonary artery (PA) development and guiding surgical decisions [6]. Traditionally, MGI was primarily applied in the evaluation of adult or pediatric CHD. However, given that fetal hemodynamics and lung development differ from those after birth, recent years have seen an emerging interest in exploring the application of MGI in the fetal period.

The study by Guo Yong et al. [7] observed a significant linear positive correlation between the sum of RPA and LPA diameter (RPA + LPA) and fetal lung volume, suggesting that the two-dimensional ultrasound (US) measurement of RPA + LPA can, to some extent, reflect fetal lung development.In addition,it reported that the MGI of fetuses with moderate to severe pulmonary artery stenosis is significantly lower than that of normal fetuses and fetuses with mild PS [8].

Z-score refers to the standard deviation of the actual data compared with the average data, so the application of Z-score can more accurately evaluate the development of pulmonary arteries.In this study, we employed echocardiography to compare MGI and Z-scores in fetuses with different types of CHD under different pulmonary flow states. Our aim is to explore the application value of MGI combined with Z-score in fetuses with decreased pulmonary blood flow or pulmonary atresia, offering crucial insights for prenatal consultation and perinatal production planning in fetuses with CHD.

Materials and methods

Results

Impact of fetal DA flow on PA development

In the subset of 71 fetuses experiencing decreased pulmonary blood flow or pulmonary atresia, 33 exhibited reverse DA flow perfusion. Notably, this subgroup displayed lower values for PA, PA-Zs, LPA+RPA and MGI than the forward DA perfusion group. No significant difference was observed in AO and AO-Zs between these wo groups. The correlation between the direction of fetal DA blood perfusion and PA development in fetuses with decreased pulmonary blood flow or pulmonary atresia is detailed in Table 3. This correlation was also visualized in Figure 2 in the form of image. Moreover, the mean difference and the respective limits of agreement of each parameter in Bland-Altman plots are shown in Figure 3.

Figure 1:

Normal fetal McGoon index was measured by ultrasound. (A) Measurement of LPA and RPA; (B) measurements of DAO across the fetal diaphragm. LPA, left pulmonary artery; RPA, right pulmonary artery; DAO, descending aorta.

Table 3:

Relationship between the direction of fetal DA blood perfusion and PA development in Group B.

Group	The DA forward perfusion group (n=38)	The DA reverse perfusion group (n=33)
GA, week	25.50 ± 3.13	25.58 ± 3.24
CTR	0.28 ± 0.04	0.26 ± 0.46
AO, mm	5.00 ± 1.19	4.79 ± 0.93
AO-Zs	1.12 ± 2.33	0.61 ± 1.64
PA, mm	4.07 ± 1.02	3.44 ± 0.91a
PA-Zs	−2.25 ± 1.45	−3.22 ± 1.40a
PA/AO	0.84 ± 0.21	0.74 ± 0.24
LPA + RPA, mm	4.95 ± 1.32	4.35 ± 0.96a
MGI	1.23 ± 0.17	1.07 ± 0.16a
DA, mm	3.22 ± 0.84	2.87 ± 0.63

1. GA, gestational age; CTR, cardiothoracic ratio; AO, aortic outflow; AO-Zs, AO Z-scores; PA, pulmonary artery; PA-Zs, PA Z-scores; LPA, left PA; RPA, right PA; DAO, descending aorta; MGI, McGoon index. p<0.05 compared with the DA forward perfusion group.

Table 4:

ICC of different parameter measured by echocardiography in each group.

	LPA	RPA	DAO
	ICC	ICC	ICC
Group A (n=20)	0.956	0.966	0.977
Group B (n=20)	0.901	0.842	0.910
Group C (n=20)	0.980	0.904	0.965
Total (n=60)	0.957	0.961	0.973

1. LPA, left pulmonary artery; RPA, right pulmonary artery; DAO, descending aorta.

Figure 2:

Relationship between the direction of fetal DA blood perfusion and PA development in Group B.

Figure 3:

Bland-Altman plots of each parameters.

Discussion

The aim of this study was evaluating the value of McGoon index and multiple parameters measured by fetal echocardiography in assessing fetal pulmonary vascular development.

In our investigation involving 71 fetuses with decreased pulmonary blood flow or pulmonary atresia in Group B, we observed that their MGI, PA-Zs, and PA/AO ratios were significantly smaller than those in the normal group. Conversely, the study of 21 fetuses with reduced or detached aortic flow in Group C revealed significantly greater values for MGI, PA-Zs, and PA/AO ratios than those in the other two groups. These findings, in conjunction with previous studies on CHD fetuses [10], 11], suggest that fetal MGI serves as a valuable indicator for evaluating PA development during the prenatal period, which has great implications for the dynamic evaluation of cardiovascular development in advanced intrauterine CHD fetuses, guiding disease analysis and prognosis, and providing reasonable information for prenatal consultations. Subgroup analysis in Group B indicated that fetuses with backward DA flow had smaller values for PA, PA-Zs, LPA + RPA, and MGI than the forward DA perfusion group. This implies that reverse DA flow may signify more severe PS or pulmonary atresia, suggesting a more substantial impact on fetal pulmonary vascular development.

In this study, we established a mean MGI of 1.37 ± 0.21 for a large sample of normal mid-to-late pregnant fetuses. Our normal fetal sample size covered most of the GA range for fetal echocardiography and was categorized into four groups based on GA. We observed no significant differences in fetal MGI across different GAs, indicating that MGI does not change with GA. In normal developing fetuses, quantitative indicators reflecting cardiovascular development, such as PA and its branches and AO growth, and non-cardiovascular parameters reflecting fetal growth and development, including BPD, HC, FL, and AC, are clearly correlated with the increase in GA, which has been confirmed in several studies that applied Z-score [12], [13], [14], [15], [16]. Because MGI is the ratio of LPA + RPA inner diameter to DAO, which reflects the relative proportion of fetal PA and AO development, the results of MGI and Z-scores are consistent. In normal developing fetuses, MGI remains relatively stable within the normal range and does not exhibit variation with GA. This contrasts with Guo et al.’s findings [17] in a study of 110 normal fetuses and 54 fetuses with reduced pulmonary blood flow CHD, where CTR, FLV/EFW, and MGI showed significant differences between the two groups. The variation in results may be attributed to the broader spectrum of diseases included in our study than the more specific inclusion criteria of TOF, PA-VSD, and PA-IVVS in Guo et al.’s study [17].

Evaluation of pulmonary vascular development is crucial in the surgical context, especially for PS, as it strongly influences postoperative outcomes. Laban et al. [18] reported that compared to neonates with respiratory distress syndrome(RDS), healthy neonates had significantly higher FLVs (p<0.001).However, YEabdalla et al. [19] recommended that combining the mean FLV to the other parameters rather than using this measure alone.Clinical MGI assessment is a common practice in postnatal children and adults, providing an overview of pulmonary vascular bed growth in CHD patients. A low MGI often indicates lung hypoplasia and is associated with a poor prognosis [3], 13]. Higher incidences of surgical death and heart failure have been reported in patients with PA dysplasia [2]. MGI has also been studied in children with congenital diaphragmatic hernia (CDH). Several studies [5], 20], 21] have suggested that among various prognostic factors in children with CDH, the extent of lung development is crucial, and the severity of pulmonary hypoplasia is considered the main limiting factor for survival, whereas MGI is positively correlated with pulmonary vascular development, serving as a prognostic factor for survival.

From the follow-up in our study, we observed that patients with PS alone and MGI<1.2 had a favorable prognosis. Notably, one patient with MGI 0.96 did not undergo surgery throughout the follow-up period. Similarly, two patients with TOF and MGI<1.2 (MGI 1.17, 1.05) did not require surgical intervention and were generally in good condition. However, two deaths occurred due to TOF (MGI 1.20) and hypoplastic right heart syndrome (HRHS). This suggests that the cardiovascular structure and functional status of fetuses with severe PS can vary significantly postnatally, necessitating individualized treatment strategies based on each child’s PA development [10]. Despite the overall better prognosis in isolated PS, MGI may still decrease.

While MGI can be obtained through various methods such as cardiovascular angiography, CT, and echocardiography [22], the unique nature of the fetus places fetal echocardiography at the forefront of prenatal evaluation for cardiovascular structure and hemodynamics. Although MRI is utilized for the prenatal assessment of fetal brain and spine structures, its application in diagnosing fetal cardiovascular malformations is limited. The main challenges in fetal MGI measurement via echocardiography are obtaining clear images of the LPA, RPA, and DAO. This is dependent on the sonographer’s ability to obtain standardized sections, which, in our study, was carried out by highly experienced physicians. Quantitative measurements of LPA, RPA, and DAO inner diameters were averaged from at least three measurements, resulting in a very good within-group correlation coefficient for each parameter. This ensured the high repeatability and accuracy of MGI measurements in our study.

Our study has some limitations. First, the measurement of fetal MGI is challenging in early pregnancy and was, therefore, excluded from our study. With ongoing advancements in US technology, future studies may include more early pregnancies to explore the broader application of MGI throughout gestation. Additionally, this study follows a cross-sectional design, and no prenatal follow-up was conducted for the studied case group. Conducting multiple follow-ups for CHD fetuses throughout pregnancy could provide a more comprehensive understanding of MGI patterns and its utility during fetal development. Similarly, there is a lack of systematic follow-up on pulmonary vascular and pulmonary development in neonates and young children post-birth. A longitudinal systematic tracking of MGI changes both prenatally and postnatally would contribute to a more scientific assessment of pulmonary blood vessel development in fetuses, newborns, and young children under varying pulmonary blood flow conditions. This approach is crucial for analyzing fetal conditions, predicting prognosis, and informing prenatal consultations and postnatal treatments.

Conclusions

This study showed that MGI combined with various parameter Z-scores can reliably evaluates pulmonary blood flow in different CHD fetuses, offering insights into pulmonary blood vessel development. The presence of reverse DA flow suggests more severe PS or pulmonary atresia, as indicated by smaller values in PA, PA-Zs, LPA + RPA, and MGI. This type of CHD may exert a more significant impact on fetal pulmonary vascular development. Through the analysis of a large number of normal fetal MGIs from 18 weeks to 33+⁶ weeks, we observed that fetal MGI remains relatively constant during this GA range and does not change with increasing GA. Studies had demonstrated that a low MGI (≦1.25) was associated with a high mortality rate (80 %) and had important applications in the category of risk death [20]. These findings have potential clinical applications in prognostic prediction and early intervention treatment.