Iliana Bersani

Chorioamnionitis - the good or the evil for neonatal outcome?

Chorioamnionitis represents a major risk factor for preterm birth and contributes to prematurity-associated morbidity and mortality. Comparison of studies addressing neonatal outcome after exposure to either histological or clinical chorioamnionitis is hampered by the great heterogeneity regarding study cohorts and disease definitions which were applied. Moreover, the impact of exposure to inflammation in utero on neonatal outcome has become less evident with major advances in perinatal and neonatal care. Histologic chorioamnionitis evidently is associated with a reduction of incidence and severity of respiratory distress syndrome. Short-term maturational effects on the lungs of ventilated extremely premature infants are, however, accompanied by a greater susceptibility of the lung, eventually contributing to an increased risk of bronchopulmonary dysplasia. Chorioamnionitis has been shown associated with increased rate of early-onset sepsis but, according to recent data, histological chorioamnionitis might be protective against late-onset sepsis. Inconsistent data exist concerning the true role of chorioamnionitis in the development of brain lesions such as cystic periventricular leukomalacia, diffuse white matter disease, and intraventricular hemorrhage. However, an association with the development of cerebral palsy has been reported.

Surfactant proteins A and D in pulmonary diseases of preterm infants

Immaturity of the pulmonary and immune systems represents an important risk factor for increased morbidity and mortality in neonates. Surfactant protein (SP)-A and SP-D, linking molecules between these two systems, are critical for lung homeostasis as they regulate surfactant metabolism and host immunodefense activities in innate and adaptive immunity. Preterm neonates with respiratory distress syndrome showed lower concentrations of SP-A and SP-D, and the administration of exogenous surfactant was found to strengthen the secretion of SPs. Low levels of SP-A and SP-D also correlated with a higher risk of infection and development of bronchopulmonary dysplasia. Moreover, SP-A- and SP-D-enriched surfactant formulations were more resistant to the inhibitory action of the plasmatic proteins in animal models. Based on these assumptions, new-generation surfactants, enriched with SP-A and/or SP-D, may enhance the function of immune system and lungs in neonates, potentially improving the clinical outcome.

Synergistic Effect of Caffeine and Glucocorticoids on Expression of Surfactant Protein B (SP-B) mRNA

Administration of glucocorticoids and caffeine is a common therapeutic intervention in the neonatal period, but possible interactions between these substances are still unclear. The present study investigated the effect of caffeine and different glucocorticoids on expression of surfactant protein (SP)-B, crucial for the physiological function of pulmonary surfactant. We measured expression levels of SP-B, various SP-B transcription factors including erythroblastic leukemia viral oncogene homolog 4 (ErbB4) and thyroid transcription factor-1 (TTF-1), as well as the glucocorticoid receptor (GR) after administering different doses of glucocorticoids, caffeine, cAMP, or the phosphodiesterase-4 inhibitor rolipram in the human airway epithelial cell line NCI-H441. Administration of dexamethasone (1 µM) or caffeine (5 mM) stimulated SP-B mRNA expression with a maximal of 38.8±11.1-fold and 5.2±1.4-fold increase, respectively. Synergistic induction was achieved after co-administration of dexamethasone (1 mM) in combination with caffeine (10 mM) (206±59.7-fold increase, p<0.0001) or cAMP (1 mM) (213±111-fold increase, p = 0.0108). SP-B mRNA was synergistically induced also by administration of caffeine with hydrocortisone (87.9±39.0), prednisolone (154±66.8), and betamethasone (123±6.4). Rolipram also induced SP-B mRNA (64.9±21.0-fold increase). We detected a higher expression of ErbB4 and GR mRNA (7.0- and 1.7-fold increase, respectively), whereas TTF-1, Jun B, c-Jun, SP1, SP3, and HNF-3α mRNA expression was predominantly unchanged. In accordance with mRNA data, mature SP-B was induced significantly by dexamethasone with caffeine (13.8±9.0-fold increase, p = 0.0134). We found a synergistic upregulation of SP-B mRNA expression induced by co-administration of various glucocorticoids and caffeine, achieved by accumulation of intracellular cAMP. This effect was mediated by a caffeine-dependent phosphodiesterase inhibition and by upregulation of both ErbB4 and the GR. These results suggested that caffeine is able to induce the expression of SP-transcription factors and affects the signaling pathways of glucocorticoids, amplifying their effects. Co-administration of caffeine and corticosteroids may therefore be of benefit in surfactant homeostasis.

Neonatal emergencies associated with cardiac rhabdomyomas: an 8-year experience.

During the foetal-neonatal period, rhabdomyomas represent the majority of cardiac tumours and are closely associated with tuberous sclerosis. Cardiac rhabdomyomas may be completely asymptomatic and are incidentally discovered during an echocardiogram, or may cause cardiac dysfunctions requiring medical and/or surgical intervention. During foetal life and the early neonatal period, life-threatening conditions, mostly due to arrhythmias, cardiac failure or obstruction, do occur on rare occasions. We reviewed the medical records of all cases of cardiac rhabdomyomas diagnosed prenatally or postnatally over an 8-year period. The present study reviews 7 cases of life-threatening conditions. Arrhythmic episodes were described in 5 patients, and blood flow obstruction was reported in 2 cases. Antiarrhythmic agents successfully controlled the clinical and electrophysiological conditions. Obstructive conditions were associated with poor outcomes. In conclusion, when prenatal diagnosis of rhabdomyoma is made, appropriate planning at delivery for the management of potential haemodynamic complications may prevent adverse neonatal outcomes. The clinical outcome is more influenced by obstructive rather than by dysrhythmic complications. Appropriate antiarrhythmic treatment is of primary importance. In all cases discovered through prenatal and/or neonatal life-threatening conditions, an accurate follow-up should always be performed to anticipate the development of tuberous sclerosis.

The potential role of high or low birthweight as risk factor for adult schizophrenia

Abstract Objective: Obstetric complications may be an important factor in the development of schizophrenia. The aim of this study is to evaluate the role of these complications in the development of schizophrenia in adult life, with particular attention to the potential role of birth weight. Method: We carried out a case-control study, comprising schizophrenics and patients with diseases of the schizophrenia spectrum as cases, and their healthy male brothers as controls. Obstetric complications were assessed using the “Midwife Protocol” of Parnas et al. Results: The main result was that birth weight may be a risk factor for schizophrenia, as indicated by odds ratio analysis. The confidence intervals are very wide and, without compromising the clinical significance of the results, they give a limited indication of the real entity of the risk. Conclusions: The results contribute to understanding of the role played by a single complications.

Maternal-neonatal vitamin K deficiency secondary to maternal biliopancreatic diversion

Bariatric surgery has become a common therapeutic approach for severe obesity, in case of unsuccessful behavioural and/or medical interventions. During the past years, the number of obese women who underwent bariatric surgery in childbearing age has progressively increased. We report a case of vitamin K deficiency, due to maternal biliopancreatic diversion, resulting in a symptomatic clinical presentation in the mother and in a hypocoagulable state in her neonate.

Correlation analysis between echocardiographic flow pattern and N-terminal-pro-brain natriuretic peptide for early targeted treatment of patent ductus arteriosus

Abstract Objective: Echocardiographic flow patterns of patent ductus arteriosus (PDA) are useful to predict the development of hemodynamically significant ductus in premature infants. N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations seem to be useful to detect PDA. We investigated how NT-proBNP levels change on the basis of different flow patterns during the first day of life, and whether NT-proBNP might represent a reliable decision tool in PDA management. Methods: Neonates with gestational age <32 weeks were assessed prospectively, using paired Doppler-echocardiographic evaluation and NT-proBNP values, at T0 (6–24 h of life), and daily until ductal closure. Results: At T0, NT-proBNP concentrations of 41 neonates correlated to the kind of pattern (p = 0.018) with the highest values in neonates with pulsatile or growing patterns. A value <9854 pg/ml identified neonates with spontaneous closure (sensitivity 71.8%, specificity 100%). Overall, 32 infants needed treatment. Pre-treatment NT-proBNP values increased compared to those at T0, significantly in neonates with growing pattern at T0 (p = 0.001). After treatment, NT-proBNP concentrations decreased compared to pre-treatment values (p = 0.0024), more markedly in the responders than in the non-responders (p = 0.042). Conclusions: NT-proBNP concentrations at T0 show a good agreement with different flow patterns and represent a useful tool to identify neonates at risk of developing hemodynamically significant PDA.

Antifungal lock therapy with combined 70% ethanol and micafungin in a critically ill infant.

So-called lock therapy, consisting of high concentrations of antimicrobials instilled into the lumen of the catheter, has been suggested avoid central venous catheter removal during fungal infection. We report a baby who developed catheter-related candidemia. Systemic antifungal treatment did not resolve the candidemia. Lock therapy with 0.3 mL of ethanol 70% and micafungin sodium 5 mg/L was added to the therapy, and blood cultures became sterile.

Use of Early Biomarkers in Neonatal Brain Damage and Sepsis: State of the Art and Future Perspectives

The identification of early noninvasive biochemical markers of disease is a crucial issue of the current scientific research, particularly during the first period of life, since it could provide useful and precocious diagnostic information when clinical and radiological signs are still silent. The ideal biomarker should be practical and sensitive in the precocious identification of at risk patients. An earlier diagnosis may lead to a larger therapeutic window and improve neonatal outcome. Brain damage and sepsis are common causes of severe morbidity with poor outcome and mortality during the perinatal period. A large number of potential biomarkers, including neuroproteins, calcium binding proteins, enzymes, oxidative stress markers, vasoactive agents, and inflammatory mediators, have been so far investigated. The aim of the present review was to provide a brief overview of some of the more commonly investigated biomarkers used in case of neonatal brain damage and sepsis.

Excess in the spring and deficit in the autumn in birth rates of male schizophrenic patients in Italy: Potential role of perinatal risk factors

Objective. The aim of this study was to evaluate whether there were different seasonal variations of births in an Italian population of patients with schizophrenia, with other psychotic disorders, and with personality disorders than in the general population. Methods. Birth dates of 1270 patients admitted to one university psychiatric unit in Rome between 1990 and 2003, with a diagnosis of schizophrenia, other psychotic disorder (OPD) and personality disorder/cluster A (PD) were analyzed according to seasonal variation. Results. A significant excess of births in spring (with a peak in May) and a deficit in autumn (with a trough in October) was found in the sample of male schizophrenics (n = 506). No statistically significant variations were found in either the sample of female schizophrenics (n = 88) or in the combined sample with OPD and PD (n = 676). Conclusions. The findings serve to strengthen the existing hypotheses that schizophrenia is related to environmental factors acting on the development of the central nervous system intrauterinely.