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Observational Study
. 2025 Mar 20;51(1):85.
doi: 10.1186/s13052-025-01938-4.

Activin-A urine levels correlate with radiological patterns in preterm infants complicated by intraventricular hemorrhage

Giuseppe Lapergola  1 , Giorgia Gasparroni  1 , Alessandro Graziosi  1 , Darek Gruzfeld  2 , Bashir Moataza  3 , Hanna Aboulgar  3 , Hala Mufeed  3 , Iman Iskander  3 , Giovanni Livolti  4 , Fabio Galvano  4 , Gabriella Levantini  1 , Ebe D'Adamo  1 , Adele Patrizia Primavera  1 , Elisabetta Barbante  1 , Rita Salomone  1 , Claudia D'Egidio  1 , Chiara Strozzi  5 , Antonio Maconi  6 , Danilo A W Gavilanes  7 , Ali Saber Abdelhameed  8 , Diego Gazzolo  9
Affiliations
Observational Study

Activin-A urine levels correlate with radiological patterns in preterm infants complicated by intraventricular hemorrhage

Giuseppe Lapergola et al. Ital J Pediatr. .

Abstract

Background: To validate the role of Activin A in the early diagnosis and prognosis of preterm newborns at risk for intraventricular hemorrhage and neurological sequelae by means of cerebral ultrasound and magnetic resonance imaging (MRI), currently considered standard of care procedures.

Methods: We conducted an observational case-control study in 46 preterm newborns, 23 with intraventricular hemorrhage (IVH group) and 23 controls matched for gestational age. Standard clinical, laboratory, cerebral ultrasound monitoring procedures and Activin A urine measurement were performed at four time-points (first void, 24, 48, 96 h) after birth. Cerebral MRI was performed at 40-42 weeks of corrected gestational age.

Results: Elevated (P < 0.001, for all) Activin A levels were observed in the IVH group at all monitoring time-point. Activin A correlated (P < 0.05, for all) with intraventricular hemorrhage grade on cerebral ultrasound. At the cut-off of 0.08 pg/mL Activin A at 48-h achieved the best sensitivity, specificity, positive/negative predictive values as early predictor of an abnormal MRI pattern (area under the curve: 0.93).

Conclusions: The present data showing a correlation among Activin A, cerebral ultrasound and MRI provide further support to Activin A inclusion in clinical daily management of cases at risk for intraventricular hemorrhage and adverse neurological outcome.

Keywords: Activin A; Cerebral ultrasound; Intraventricular hemorrhage; Magnetic resonance imaging; Preterm infants.

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Conflict of interest statement

Declarations. Ethical approval and consent to participate: Research involving human subjects complied with all relevant national regulations, institutional policies and is in accordance with the tenets of the Helsinki Declaration (as revised in 2013). The Local Ethic Committees of the Cooperative Multitask against Brain Injury of Neonates (CoMBINe) International Network approved the study protocol. Consent for publication: Informed consent was obtained from all individuals included in this study. Competing interests: The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart describing the recruitment of preterm infants complicated or not by intraventricular hemorrhage (IVH), diagnosed by cerebral ultrasound scanning (CUS), and abnormal magnetic resonance imaging (MRI) patterns
Fig. 2
Fig. 2
Activin A urine levels (pg/mL) recorded at the pre-determined monitoring time-points at first void (T0), 24 (T1), 48 (T2), 72 (T3) and 96 h (T4) from birth, in preterm newborns complicated or not (non-IVH) by intraventricular hemorrhage (IVH). AcA was significantly (P < 0.05, for all) higher in the IVH group at T0-T4. Values are expressed as median and interquartile ranges
Fig. 3
Fig. 3
Receiver operating characteristic curve (ROC) of AcA urine levels measured at first void (T0), 24 (T1), 48 (T2), 72 (T3) and 96 h (T4) from birth, in preterm newborns complicated or not by intraventricular hemorrhage for the early prediction for abnormal magnetic resonance imaging pattern. At T2 AcA, at the cut-off of 0.08 pg/mL, achieved the best sensitivity (CI 5–95%: 74, 52–90), specificity (CI 5–95%: 100, 85–100), positive (CI 5–95%: 100) and negative predictive value (CI 5–95%: 79, 66–88) as best predictor of abnormal magnetic resonance imaging pattern (area under the ROC curve: CI 5–95%: 0.93, 0.82–0.99). *P < 0.05 T2 vs. T0
See this image and copyright information in PMC

References

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