Antenatal maternal antidepressants drugs treatment affects S100B levels in maternal-fetal biological fluids in a dose dependent manner.

BACKGROUND: The increased use of antidepressant treatment during pregnancy occurred without firm evidence on safety/efficacy. The present study investigated the correlation among S100B and paroxetine blood levels with the occurrence of short-term post-natal neurological abnormalities. METHODS: We conducted a cross-sectional study in 50 pregnant women using paroxetine because of depression and in 150 controls. Standard laboratory parameters and S100B were measured at seven monitoring time-points (maternal blood: T1, 16-20 wks; T2, 27-30 wks; T3, 35-40 wks; T4, at delivery; amniotic fluid, T5; venous and arterial cord blood, T6-T7). Paroxetine levels were measured at T1-T6. Neurological outcome was set at 7th day from birth. RESULTS: Higher S100B concentrations at T1-T7 were found in the paroxetine-treated group. S100B correlated with paroxetine blood levels. The paroxetine/S100B ratio cut-off of 1.31 at T2 achieved sensitivity 100%, specificity 96.5% and positive/negative predictive values 87.5-100, respectively, as a single marker to predict adverse neonatal neurological outcome. CONCLUSIONS: The present study offers additional support to the usefulness of longitudinal S100B and drug level monitoring in depressed pregnant women and in the early detection of cases at risk for short-term neurological abnormalities. Results open the way at further investigations correlating antidepressant drugs and neurobiomarkers in the maternal bloodstream.

Antenatal Maternal Antidepressants Drugs Affect S100B Concentrations in Fetal-Maternal Biological Fluids.

INTRODUCTION: Antidepressant treatment during pregnancy is speedily increasing in developed countries and this phenomenon has occurred without firm evidence on safety and/or efficacy. AIMS: The present study investigated from mid-trimester of pregnancy up to 24 hours after birth the pattern of a brain damage marker, namely S100B, in maternal fetal and neonatal biological fluids of pregnant women and their newborns antenatally treated by antidepressant drugs such as selective serotonin re-uptake inhibitors (SSRI). METHODS: we conducted an observational study on 75 pregnant women treated in the mid -third trimester by antidepressant drugs and 231 healthy pregnancies. S100B concentrations were measured at 7 predetermined monitoring time-points before, during and after treatment in maternal, fetal and neonatal biological fluids and correlated with neurological follow-up at 7 days from birth. RESULTS: In SSRI group S100B concentrations were significantly higher in SSRI than controls (P<0.001, for all) in maternal blood, in amniotic fluid, in arterial and venous cord blood and at 24-h from birth. Highest (P<0.05) S100B levels were found in SSRI infants showing major neurological symptoms at 7-d follow-up. CONCLUSION: The present data on increased S100B levels in maternal, fetal and neonatal biological fluids suggest that SSRI administration although beneficial to the mother, presents some risks for the infant.

Next generation biomarkers for brain injury.

In perinatal medicine, there is an emerging interest on the potential usefulness of non-invasive brain biochemical monitoring in infants at risk for brain injury. To date, several biomarkers such as neuro-proteins, calcium binding proteins, oxidative stress markers, vasoactive agents, inflammatory mediators, have been investigated. Results showed that hypoxia insult, under different conditions, triggers a biochemical pathophysiological cascade of events leading to brain damage. In this setting, increased biomarkers concentrations in different biological fluids have been found to correlate with the occurrence of brain damage at short-long term both in preterm and term fetuses/newborns. However, before inclusion of any biomarker in guidelines, USA and European institutions have recently stated a panel of criteria that have to be fulfilled. Therefore, the present review offers an overview of the main biomarkers currently studied in perinatal medicine and their progresses according to institutions' criteria.

Antenatal maternal antidepressants drugs affect Activin A concentrations in maternal blood, in amniotic fluid and in fetal cord blood.

OBJECTIVE: The use of antidepressant drugs during pregnancy is rapidly increasing both in Europe and in the USA, with controversial data regarding side-effects on fetus and newborn. We investigated, in pregnant women and in fetal biological fluids whether the concentrations of a brain protein, Activin A, changed in association with the use of selective serotonin re-uptake inhibitors (SSRI). METHODS: We conducted a case control study in 24 women treated with SSRIs, matched with 24 healthy pregnancies as controls. Maternal blood (during labor, T1), fetal blood (venous (T2) and arterial [T3] umbilical cord blood) and amniotic fluid (T4) were drawn for standard laboratory assessment and for Activin A measurement. RESULTS: Activin A concentrations in maternal and fetal biological fluids were significantly higher in SSRI users than in the control groups(P < 0.05, for all). CONCLUSIONS: Activin A in maternal and fetal biological fluids is increased after SSRI administration in the third trimester of pregnancy. The present findings open up a new cue for further studies aimed at investigating protein's key role in central nervous system protection/damage in pregnant women using these drugs.

Italia-Netherland PhD Program: the I.O. PhD Research Program.

In the framework of long-term scientific collaboration among the founder members coming from Holland and Italy there was a growing consensus to activate a philosophical doctorate (PhD) program, involving young Italian researchers in the field of perinatal medicine, neonatology and pediatrics. The aims were to promote excellence in research, offering to young Italian physicians the opportunity to maturate an International research experience leading to PhD degree, and to promote human and technological improvement energies in perinatal, neonatal and pediatrics research. Thus, an official collaboration among the Dutch Universities from Maastricht and Utrecht and the Italian Children's Hospital from Alessandria, has been activated on March 1st 2010, finalized to the PhD program. The experimental phase included the selection of projects and relative candidates after an interview-selection focusing on their scientific attitudes and the availability on their research projects. Candidates' selection started on May 2010 and on September 29th ten projects and candidates have been approved by the scientific commission. Research topics included: perinatal asphyxia, aging and the origin of adulthood neurodegenerative disease, neuroprotective strategies, biochemical pulmonology, intrauterine growth retardation and perinatal teratology. To date, all projects have been approved by local Ethics Committee from the University/Hospital of origin of the candidates. Five manuscripts have been published and/or submitted to international Journals regarding pneumology, perinatal asphyxia and teratology, whilst about 60-70% of data regarding clinical studies have already been collected.

S100B protein and near infrared spectroscopy in preterm and term newborns.

Cerebral monitoring constitutes an emerging issue in perinatal medicine. Near Infrared Spectroscopy (NIRS) monitors brain oxygenation status in sick infants although data in healthy infants are lacking. The present study investigates whether NIRS parameters change according to gestational age and correlate with S100B protein. We recruited 64 healthy newborns (weeks' gestation: 30-42 wks) in which we performed in the first 6-hours after birth routine clinical, radiological and laboratory variables, cerebral oxygen saturation (rSO2), fractional cerebral tissue oxygen extraction (FTOE) values and S100B urine assessment. rSO2 and FTOE correlated (R=-0.73; R=0.51; P less than 0.01, for both) with gestational age. Highest rSO2 and the lowest FTOE peaks (P less than 0.001) were found at 30-33 wks. From 34 wks onwards, rSO2 progressively decreased and FTOE increased reaching their lower dip/peak (P less than 0.001) at 38-39 weeks. A significant correlation between S100B and NIRS parameters (rSO2: r=0.77; FTOE: r=-0.69; P less than 0.01) has been found. The present study shows that NIRS parameters and S100B protein correlation may be of help in brain function monitoring.