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The interplay between prenatal liver growth and lung development in congenital diaphragmatic hernia
Katherine C Ott1, Michael Bi2, Federico Scorletti3
1Department of Surgery, Ann and Robert H. Lurie Children's Hospital, Chicago Institute for Fetal Health, Northwestern University Feinberg School of Medicine, Chicago, IL, United States.
Insights
Liver herniation in congenital diaphragmatic hernia (CDH) impacts liver and lung growth. Right-sided CDH shows more liver growth, and herniation disrupts the normal liver-lung growth correlation.
Area of Science:
- Fetal Medicine
- Developmental Biology
- Pediatric Surgery
Background:
- Congenital diaphragmatic hernia (CDH) is associated with liver herniation, which can worsen outcomes.
- Understanding the impact of liver herniation on fetal liver and lung development is crucial for improving CDH management.
- Previous studies lack detailed analysis of liver growth patterns in relation to herniation and lung development.
Purpose of the Study:
- To investigate how the nature of liver herniation in CDH affects fetal liver growth.
- To determine the relationship between liver growth, liver herniation, and lung development in fetuses with CDH.
- To compare liver growth patterns between different types of CDH (left-sided vs. right-sided, liver-up vs. liver-down).
Main Methods:
- Retrospective analysis of clinical data from prenatally diagnosed isolated CDH cases (2006-2021).
- Inclusion of cases with serial fetal MRI lung volumetry (mid- and late-gestation).
- Fractional liver volume and liver growth were indexed to estimated fetal weight and compared to lung growth.
Main Results:
- Right liver-up CDH (RLU) fetuses demonstrated greater overall and fractional liver growth compared to left liver-down (LLD) and left liver-up (LLU) CDH.
- Intra-thoracic liver growth was consistently slower than intra-abdominal liver growth in both right- and left-sided CDH.
- A positive correlation between liver and lung growth was observed when the liver was fully abdominal, but this correlation was lost with liver herniation.
Conclusions:
- Fetuses with right-sided CDH exhibit significantly greater liver growth than those with left-sided CDH.
- Liver herniation above the diaphragm disrupts the normally observed positive correlation between liver and lung growth.
- These findings highlight the complex interplay between liver positioning, growth, and lung development in CDH.
Objective:
Liver herniation is a known risk factor for increased severity in CDH and is associated with clinically significant pulmonary hypoplasia and pulmonary hypertension. Better studies are needed to understand the growth of the herniated liver compared to the liver that remains in the abdomen and how this liver growth then affects lung development. Serial hi-resolution fetal MRI enables characterization of liver growth throughout gestation and examination of macroscopic features that may regulate liver growth. Here, we hypothesized that the nature of liver herniation affects liver growth and, in turn, affects lung growth.
Methods:
Clinical data were retrospectively collected from consecutive cases of prenatally diagnosed isolated left-sided or right-sided CDH from June 2006 to August 2021. Only those cases with MRI lung volumetry for both mid-gestation and late-gestation time points were recruited for analysis. Cases with fetal chromosomal abnormalities and other major structural abnormalities were excluded. Fractional liver volume and liver growth was indexed to estimated fetal weight and compared to lung growth.
Results:
Data was collected from 28 fetuses with a left liver-down CDH (LLD), 37 left liver-up CDH (LLU) and 9 right liver-up CDH (RLU). Overall, RLU fetuses had greater overall and fractional (intra-thoracic vs. intra-abdominal) liver growth when compared to LLD and LLU fetuses. Additionally, intra-thoracic liver growth was consistently slower than intra-abdominal liver growth for either right- or left-sided CDH. When the liver was not herniated, a positive correlation was seen between liver growth and lung growth. However, when the liver was herniated above the diaphragm, this positive correlation was lost.
Conclusion:
Right-sided CDH fetuses exhibit greater liver growth compared to left-sided CDH. Liver herniation disrupts the normal positive correlation between liver and lung growth that is seen when the liver is entirely within the abdomen.
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