Preeclampsia and Its Impact on Human Milk Activin A Concentration.

BACKGROUND: It is known that preeclampsia affects lactogenesis. However, data on the effects of this pathology on human milk neurobiomarker composition are not available. The aim of this study is to investigate the effects of this gestational pathology on activin A levels, a neurobiomarker known to play an important role in the development and protection of the central nervous system. METHODS: The women recruited were divided in two different study groups: preeclamptic or normotensive women. All the human milk samples were collected using the same procedure. Activin A was quantified using an Enzyme-linked immunosorbent assay (ELISA) test. To investigate the effect of preeclampsia on the activin A concentration in the three lactation phases, a mixed linear model with a unistructural covariance structure, with the mother as the random effect, and fixed effects were performed. RESULTS: Activin A was detected in all samples. There were no significant differences between preeclamptic and normotensive women. The only significant effect is related to the lactation phase: the difference between colostrum and mature milk (p < 0.01) was significant. In conclusion, these results allow us to affirm that breast milk's beneficial properties are maintained even if preeclampsia occurs.

S100B protein, cerebral ultrasound and magnetic resonance imaging patterns in brain injured preterm infants.

OBJECTIVES: The early detection of preterm infants (PI) at risk for intraventricular hemorrhage (IVH) and neurological sequelae still constitutes an unsolved issue. We aimed at validating the role of S100B protein in the early diagnosis and prognosis of IVH in PI by means of cerebral ultrasound (CUS) and magnetic resonance imaging (MRI) today considered standard of care procedures. METHODS: We conducted an observational case-control study in 216 PI of whom 36 with IVH and 180 controls. Standard clinical, laboratory, radiological monitoring procedures and S100B 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) S100B levels were observed in the IVH group at all monitoring time-point particularly at first void when standard monitoring procedures were still silent or unavailable. S100B measured at first void correlated (p<0.001) with the grade of hemorrhage by means of CUS and with the site and extension of neurological lesion (p<0.001, for all) as assessed by MRI. CONCLUSIONS: The present results showing a correlation among S100B and CUS and MRI offer additional support to the inclusion of the protein in clinical daily management of cases at risk for IVH and adverse neurological outcome. The findings open the way to further investigations in PI aimed at validating new neurobiomarkers by means of S100B.

Glutathione Blood Concentrations: A Biomarker of Oxidative Damage Protection during Cardiopulmonary Bypass in Children.

BACKGROUND: Pediatric open-heart surgery with cardiopulmonary bypass (CPB) still remains a risky interventional procedure at high mortality/morbidity. To date, there are no clinical, laboratory, and/or monitoring parameters providing useful information on perioperative stress. We therefore investigated whether blood concentrations of glutathione (GSH), a powerful endogenous antioxidant, changed in the perioperative period. METHODS: We conducted an observational study in 35 congenital heart disease (CHD) children in whom perioperative standard laboratory and monitoring parameters and GSH blood levels were assessed at five monitoring time points. RESULTS: GSH showed a pattern characterized by a progressive increase from pre-surgery up to 24 h after surgery, reaching its highest peak at the end of CPB. GSH measured at the end of CPB correlated with CPB duration, cross-clamping, arterial oxygen partial pressure, and with body core temperature. CONCLUSIONS: The increase in GSH levels in the perioperative period suggests a compensatory mechanism to oxidative damage during surgical procedure. Caution is needed in controlling different CPB phases, especially systemic reoxygenation in a population that is per se more prone to oxidative stress/damage. The findings may point the way to detecting the optimal temperature and oxygenation target by biomarker monitoring.

Effects of Sustained Inflation or Positive Pressure Ventilation on the Release of Adrenomedullin in Preterm Infants with Respiratory Failure at Birth.

OBJECTIVE: Delivery room (DR) management may play an important role in the development and prevention of lung injury. Therefore, in a cohort of low birth weight infants (LBW), we investigated the effects of two different lung recruitment maneuvers, such as positive pressure ventilation (PPV) and sustained inflation (SI) on adrenomedullin (AM), a well-established lung-specific vasoactive agent. STUDY DESIGN: This is a prospective case-control randomized study in 44 LBW infants spontaneously breathing with respiratory failure at birth requiring respiratory support. LBW were randomized to receive PPV (n = 22) or SI (n = 22) support. AM was measured from blood in samples collected at birth from arterial artery (BLT0) and at 1-hour (BLT1) and at 24-hour (BLT2) from peripheral venous site. AM assessment in urine samples was performed at 1-hour (URT1) and at 24-hour (URT2). RESULTS: No significant differences in AM (p > 0.05) blood (T0-T2) and urine (T1, T2) levels were observed between groups. CONCLUSION: The present data, showing the absence of any differences in AM blood and urine levels, suggest that PPV and SI are both feasible and equally effective DR maneuvers. The findings open the way to further studies evaluating the effects of PPV and SI on short-/long-term respiratory outcome through biomarkers assessment.

Monitoring the effectiveness of hypothermia in perinatal asphyxia infants by urinary S100B levels.

Background Perinatal asphyxia is a major cause of mortality and morbidity in neonates: The aim of the present study was to investigate, by means of longitudinal assessment of urinary S100B, the effectiveness of hypothermia, in infants complicated by perinatal asphyxia and hypoxic-ischemic encephalopathy. Methods We performed a retrospective case-control study in 108 asphyxiated infants, admitted to nine tertiary departments for neonatal intensive care from January 2004 to July 2017, of whom 54 underwent hypothermia treatment and 54 did not. The concentrations of S100B protein in urine were measured using an immunoluminometric assay at first urination and 4, 8, 12, 16, 20, 24, 48, 72, 96, 108 and 120 h after birth. The results were correlated with the achievement of S100B levels within normal ranges at 72 h from hypothermia treatment. Routine laboratory parameters, longitudinal cerebral function monitoring, cerebral ultrasound and neurologic patterns were assessed according to standard protocols. Results Higher S100B concentrations were found in hypothermia-treated infants in both moderate (up to 12 h) and severe (up to 24 h) hypoxic-ischemic encephalopathy. S100B levels returned to normal ranges starting from 20 h of hypothermia treatment in moderate and from 36 h in severe hypoxic-ischemic encephalopathy. Conclusions The present results offer additional support to the usefulness of longitudinal neuro-biomarkers monitoring in asphyxiated infants treated by hypothermia. The pattern of S100B concentrations during hypothermia supports the need for further investigations aimed at reconsidering the time-window for patient recruitment and treatment, and the optimal duration of the cooling and rewarming phases of the hypothermia procedure.

Lutein levels in arterial cord blood correlate with neuroprotein activin A in healthy preterm and term newborns: A trophic role for lutein?

BACKGROUND: Lutein (LT) is a naturally occurring xanthophyll carotenoid most predominant in the central nervous system (CNS), but its neurotrophic role is still debated. We therefore investigated whether cord blood concentrations correlated with a well-established neurobiomarker, namely activin A. METHODS: We conducted a prospective study on the distribution of LT and activin A in arterial cord blood of healthy preterm (n=50) and term (n=82) newborns according to weeks of gestational age (wGA) and gender. RESULTS: LT and activin A showed a pattern of concentration characterized by higher levels (P<0.01, for all) at 33-36 wGA followed by a progressive decrease (P<0.01, for all) from 37 onwards with a dip at term. Both LT and activin A were gender-dependent with significantly (P<0.01, for all) higher levels in all recruited females and after sub-grouping for preterm and term births. LT (R=0.33; P<0.001) correlated with wGA at sampling. There were significant positive correlations between lutein and activin A in male (R=0.93; P<0.001) and female (R=0.89; P<0.001) groups. CONCLUSIONS: The present data showing a correlation between LT and activin A support the notion of a neurotrophic role gender-dependent for LT and open the way to further investigations correlating LT with well-established biochemical markers of CNS development/damage.

The development of lung biochemical monitoring can play a key role in the early prediction of bronchopulmonary dysplasia.

AIM: Despite advances in perinatal management, there is a flat trend in incidences of respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) in preterm infants. The main feature of BPD development in preterm infants is an imbalance between increased exposure to free radicals and inadequate antioxidant defences. We investigated the associations between BPD and lipid hydro-peroxide (LOOH) and glutathione (GSH) concentrations in bronchoalveolar lavage fluid (BALF). METHODS: In this prospective study, BALF samples were collected from 44 preterm infants with RDS and oxidative stress markers were measured in 11 with BPD and 33 controls without BPD. RESULTS: LOOH levels were significantly higher (p < 0.01) in the BPD group (median 16.35; 25th-75th centile 13.75-17.05 nmol/mL) than in the no BPD group (median 13.18; 25th-75th centile 12.92-13.63 nmol/mL). Conversely, GSH levels were significantly lower in the BPD group (p < 0.01) (median 11.52; 25th-75th centile 6.95-13.85 µmol/mg) than the no BPD group (median: 18.69; 25th-75th centile: 13.89-23.64 µmol/mg). Multiple regression analysis showed significant correlations between BPD and mechanical ventilation time (p < 0.01) and LOOH levels (p < 0.05). CONCLUSION: Early LOOH level increases in preterm infants developing BPD suggest that lung biochemical monitoring of sick infants might be possible and BPD could be predicted early by evaluating biomarkers.