Introduction:

sFlt-1 (soluble fms-like tyrosine kinase-1)/PlGF (placental growth factor) ratio and soluble endoglin (sEng) are angiogenic factors used for early detection of preeclampsia (PE), a hypertensive, placenta-derived pregnancy disorder. PE is often associated with placental dysfunction and fetal growth restriction. A severe complication in PE is preterm birth, which often leads to immature and impaired fetal lung development. Bronchopulmonary dysplasia (BPD) and Respiratory Distress Syndrome (RDS) are the most common lung diseases in premature born infants.

There are controverse studies about the association of anti-angiogenic molecules in maternal blood before birth and lung development pathology in premature born infants.

Materials and Methods:

A retrospective cohort with N = 51 pregnant women, which delivered preterm at the University Hospital in Essen from 2015 until 2022 are included in this study.

The control group consisting of spontaneous preterm births (sPTB) (N = 30 (58.8%)) were compared to the PE group (N = 21 (41.2%)). All of them gave birth < 30 gestational weeks (Group PE M = 185,5 (SD = 13.06) gestational days post menstruationem; group sPTB M =184(SD = 11.89) days gestational days post menstruationem). BPD, but also RDS and invasive lung treatment (intubation, hydrocortisone therapy, infant flow need and O₂ need) in the preterm infant starting immediately after birth, are correlated with the serum level of sFlt-1/PlGF and with a further biomarker for PE, sEndoglin (sENG) measured by ELISA techniques.

Statistical differences are determined by Mann-Whitney-U Test, Chi Square Test. Correlation analyses are done by Spearman Rho and Eta.

Results:

Comparing the two groups, there is a significant (p < .001) association of developing severe BPD and serum level in the mother before birth of both sFlt-1/PlGF-Ratio (Group PE M = 2116,26, SD = 1589,22; group sPTB M = 47,56, SD = 89,23) and sEng (Group PE M = 339,29, SD = 128,23; group sPTB M = 167,24, SD = 19,01). When considering only the severe BPD there is a high correlation between high sFlt-1/PlGF-Ratio, sEng and BPD (η = 0.5, ρ = .574).

This is also shown in infants with RDS, severe RDS (group PE N = 16 (77,3 %), group sPTB N = 14 (44,8 %)) is more correlated to high maternal serum level of sFlt-1/PlGF-Ratio (Group PE M = 2078,86, SD = 415,01; group sPTB M =69,17, SD = 41,46), whereas mild RDS is more associated with low serum levels of the biomarker (Group PE M =2002,10, SD = 371,44; group sPTB M = 96,23, SD = 54,77).

Also invasive lung treatment, specifically intubation and hydrocortisone therapy are correlated with the sFlt-1/PlGF-Ratio serum level (χ ²= .537).

We did not find sex-specific differences in our cohort.

Conclusion:

There is a statistically significant association between high blood level of sFlt-1/PlGF-Ratio and sEng in the mother and development of severe BPD and RDS in premature infants. Also a higher necessity for more invasive lung treatment in premature infants can be associated with higher sFlt-1/PlGF-Ratio or sEng.

The lung outcome of the preterm born infants could therefore be improved by therapeutical plasma exchange during pregnancy as a treatment option to eliminate the anti-angiogenic molecules to prolong pregnancy. This should be evaluated in furthers studies.