The interplay between prenatal liver growth and lung development in congenital diaphragmatic hernia

Abstract

ObjectiveLiver 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.MethodsClinical 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.ResultsData 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.ConclusionRight-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.

Review of the Evaluation of Pulmonary Hypoplasia as an Important Determinant of Clinical Outcomes in Infants with Congenital Diaphragmatic Hernia

“…While o/e LHR and liver herniation are the most commonly used markers for prediction of lungs hypoplasia and qualification criteria for the FETO procedure, it seems that more research is focused on further improving those methods [ 8 ]. Both velocity of intrathoracic liver growth and quantification of liver herniation show a lot of promise; however, more research is needed to optimize the method and introduce it effectively into clinical practice [ 36 , 37 , 47 ]. The aforementioned markers are used not only to assess initial risk of pulmonary hypertension but also to monitor the defect and its severity.…”

“…Nonetheless, this remains a less commonly used method, as the percentage of herniation is subject to measurement inconsistencies. Similarly, Ott et al examined the relations between herniated liver volume and lung development dependent on the side of herniation in their research [ 37 ]. They showed that liver growth inside the thoracic cavity adversely affects lung development.…”