Study Reveals Link Between Intra-Amniotic Infection and Fetal Cardiac Complications in Preterm Births

The study revealed that fetuses with preterm prelabor rupture of membranes or preterm labor showed signs of subclinical dysfunction and cardiac remodeling, which was more evident in those exposed to intra-amniotic infection and/or inflammation.

The findings published in the American Journal of Obstetrics and Gynecology support that the cardiovascular effects observed in adults and children born preterm have, at least in part, a prenatal origin.

Preterm birth, defined as delivery before 37 weeks of gestation, poses substantial risks to both maternal and fetal health. Among the myriad complications that arise from preterm birth, cardiovascular issues in the newborn have been a growing concern. Previous studies have linked intra-amniotic infection or inflammation with adverse outcomes such as neurodevelopmental impairment and respiratory distress syndrome in preterm infants. However, the specific impact on fetal cardiac health has remained relatively unexplored until now.

To fill the knowledge gap, Teresa Cobo, University of Barcelona, Barcelona, Spain, and colleagues evaluated fetal cardiac morphology and function in fetuses of mothers admitted for preterm labor or PPROM and the association of these changes with the presence of intra-amniotic infection and/or inflammation.

For this purpose, the researchers performed fetal echocardiography and amniocentesis at admission in singleton pregnant women with preterm labor and/or PPROM between 24.0 and 34.0 weeks gestation with (intra-amniotic infection and/or inflammation group, n=41) and without intra-amniotic infection and/or inflammation (non–intra-amniotic infection and/or inflammation, n=54). Controls (n=48) included outpatient pregnant women without preterm labor or preterm prelabor rupture of membranes.

Intra-amniotic infection was defined by a positive 16S ribosomal RNA gene or positive amniotic fluid culture. Intra-amniotic inflammation was defined by using the amniotic fluid interleukin-6 cutoff levels previously reported by the group being >1.43 ng/mL in preterm prelabor rupture of membranes and >13.4 ng/mL in preterm labor.

Fetal cardiac function and morphology were evaluated using echocardiography, and troponin-I and N-terminal pro-brain natriuretic peptide concentrations were measured in amniotic fluid from women with preterm labor or PPROM and compared with 20 amniotic fluid Biobank samples obtained for reasons other than preterm labor or PPROM or cardiac pathology.

The data was adjusted for the estimated fetal weight below the 10th percentile for preterm prelabor rupture of membranes at admission and also for gestational age at amniocentesis when amniotic fluid biomarkers were compared.

The study revealed the following findings:

• From 2018 to 2021, 143 fetuses were included; 95 fetuses were from mothers admitted with a diagnosis of preterm labor or preterm prelabor rupture of membranes, and among those, 41 were in the intra-amniotic infection and/or inflammation group and 54 were in the non–intra-amniotic infection and/or inflammation group. 48 fetuses were included in the control group.
• Fetuses with preterm labor and/or preterm prelabor rupture of membranes had signs of subclinical cardiac concentric hypertrophy (median left wall thickness of 0.93 in the intra-amniotic infection and/or inflammation group; 0.79 in the non–intra-amniotic infection and/or inflammation group; and 0.69 in controls) and diastolic dysfunction (tricuspid A duration 0.23 seconds, 0.24, and 0.21).
• Systolic function was similar among groups.
• Higher values of amniotic fluid troponin I (1413 pg/mL, 1190, and 841) and N-terminal pro-brain natriuretic peptide were detected (35.0%, 17%, and 0%) in fetuses with preterm labor or PPROM when compared with the control group.
• The highest N-terminal pro-brain natriuretic peptide concentrations were found in the intra-amniotic infection and/or inflammation group.

"The study provides evidence that fetuses with spontaneous PTL or PPROM have echocardiographic and biomarker signs of subclinical cardiac dysfunction and remodeling, supporting a prenatal origin of cardiovascular programming described in children and adults born prematurely," the researchers wrote.

Reference:

Murillo, C., Rueda, C., Larroya, M., Boada, D., Grau, L., Ponce, J., Herranz, A., Gómez, O., Ferrero, S., Andreu-Fernández, V., Gratacós, E., Crispi, F., Palacio, M., & Cobo, T. (2024). Intra-amniotic infection and/or inflammation is associated with fetal cardiac concentric hypertrophy and diastolic dysfunction in preterm labor and preterm prelabor rupture of membranes. American Journal of Obstetrics and Gynecology, 230(6), 665.e1-665.e30. https://doi.org/10.1016/j.ajog.2023.10.017