Increased Plasma Concentrations of Activin A Predict Intraventricular Hemorrhage in Preterm Newborns

Abstract

Background: Intraventricular hemorrhage (IVH) is a major cause of neurologic disabilities in preterm newborns. We evaluated the use of plasma activin A concentrations to predict the development of perinatal IVH. Methods: We measured nucleated erythrocyte (NRBC) counts, plasma activin A, hypoxanthine (Hyp), and xanthine (Xan) in arterial blood samples obtained from 53 preterm infants during the first hour after birth. Cerebral ultrasound was performed within 48 h of birth and repeated at 5-or 6-day intervals until the age of 4 weeks. Results: Grade I or II IVH was detected during the first 10 days of life in 11 of 53 patients (21%). Activin A, Hyp, and Xan concentrations and NRBC counts were higher in preterm newborns who subsequently developed IVH than in those who did not (P <0.0001, except P ‫؍‬ 0.019 for Xan). Neonatal activin A was correlated (P <0.0001) with Hyp (r ‫؍‬ 0.95), Xan (r ‫؍‬ 0.90), and NRBC count (r ‫؍‬ 0.90) in newborns without later IVH and in those who developed IVH (Hyp, r ‫؍‬ 0.89, P ‫؍‬ 0.0002; Xan, r ‫؍‬ 0.95, P <0.0001; NRBC count, r ‫؍‬ 0.90, P ‫؍‬ 0.0002). At a cutoff of 0.8 g/L activin A, the sensitivity and specificity were 100% [11 of 11; 95% confidence interval (CI), 71%-100%] and 93% (39 of 42; 95% CI, 81%-98%), and positive and negative predictive values were 79% (95% CI, 61%-100%) and 0% (95% CI, 0%-2%), respectively. The area under the ROC curve was 0.98. Conclusions: Activin A concentrations at birth are increased in preterm newborns who later develop IVH

Activin-A exerts a crucial anti-inflammatory role in neonatal infections

“…Moreover, activin-A is increased in the cerebrospinal fluid during meningitis in animal models and adults (22,23). Serum levels of activin-A vary with certain studies reporting high levels (11,29) and other studies reporting similar levels, or even, reporting lower levels to our study (9,28,30,31). This discordance could be due to the differences in the experimental set up, including the age of the neonates studied, the disease context, the methodology employed, the time point of analysis, etc.…”

“…The diagnosis of suspected sepsis was established when at least three clinical signs and two laboratory findings of infection were present. Activin-A is increased during perinatal asphyxia/hypoxia and intraventricular hemorrhage (11)(12)(13)(14)29,38). In addition, maternal activin-A levels are associated with preeclampsia (39) and the use of antidepressants (30).…”

High Urinary Concentrations of Activin A in Asphyxiated Full-Term Newborns with Moderate or Severe Hypoxic Ischemic Encephalopathy

“…Activin A, a glycoprotein expressed in the central nervous system (3 ) shows increased concentrations after hypoxic-ischemic brain injury (4 ). An early increase in activin A has been found in newborns with perinatal hypoxia (5 ) and intraventricular hemorrhage (IVH) (6 ) and in infants developing HIE (7 ). We measured activin A in urine collected immediately after birth in AI patients and assessed the potential clinical usefulness of its measurement to predict the occurrence of HIE.…”

Perioperative Activin A Concentrations as a Predictive Marker of Neurologic Abnormalities in Children after Open Heart Surgery

“…(4,8 ), and shields striatal and midbrain neurons against neurotoxic damage (4,9 ). Activin A concentrations are highest in preterm newborns after perinatal hypoxia (10 ), in infants experiencing intraventricular hemorrhage (11 ), and in perinatal asphyxia (12 ). We investigated measurement of the low relative molecular mass form of activin A (M r ϭ 26 000) in blood as a method to monitor possible cerebral distress during CPB in children undergoing cardiac surgery for repair of congenital heart defects.…”

“…Activin A was measured by means of a specific 2-site enzyme immunoassay (Serotec) (11 ). The analytical detection limit of the activin A assay was Ͻ0.001 g/L, and intraassay and interassay CVs were 2.5% and 3.0%, respectively, for concentrations between 0.5 g/L and 4.5 g/L.…”