Non-invasively collected amniotic fluid as a source of possible biomarkers for premature rupture of membranes investigated by proteomic approach.

PURPOSE: Preterm delivery is one of the main causes of perinatal morbidity and mortality and it accounts for 75 % of perinatal mortality and more than half of the long-term morbidity. We applied a proteomic approach based on mass spectrometry (MS) for biomarkers discovery of preterm premature rupture of membranes (pPROM) by investigating amniotic fluid (AF) invasively and non-invasively collected. METHODS: Amniotic fluid was obtained from vagina of women with pPROM (group 1), PROM at term (group 2) and by genetic amniocentesis (group 3). Pre-fractionated AF proteome was analyzed through matrix assisted laser desorption ionization-time of flight (MALDI-TOF) MS. The characterization of proteins/peptides of interest was obtained by high performance liquid chromatography-electrospray tandem MS. RESULTS: Three peptides overexpressed in pPROM and able to discriminate the groups 1 and 2 were detected. One peptide was identified as the fragment Gly452LAVPDGPLGLPPKPro466 of the protein KIAA1522, expressed by fetal brain and liver. This peptide was overexpressed in a patient of the group 3, completely asymptomatic at the time of the amniocentesis, who later developed pPROM. CONCLUSION: Amniotic fluid invasively and non-invasively collected can be analyzed by MALDI-TOF MS to obtain proteomic profiles. Proteomic analysis identified a peptide with promising diagnostic capability for pPROM.

Antenatal variables associated with severe adverse neurodevelopmental outcome among neonates born at less than 32 weeks.

OBJECTIVE: To determine the association between antenatal factors and severe adverse neurodevelopmental outcome (ANDO) in preterm infants. STUDY DESIGN: Neurodevelopmental follow-up was performed in a cohort of babies born at <32.0 weeks' gestation with birth weight <1500 grams between 1999 and 2006. Logistic regression analysis was used to relate obstetric, perinatal and neonatal ultrasonographic predictors to severe ANDO, defined as cerebral palsy or neurodevelopmental impairment, including sensory damage and adjusted development quotient <70. RESULTS: 88.6% (195/220) of surviving babies underwent follow up for a median of 24 months (range 12-96); 45 of them (23%) had ANDO, which was severe in 28 (14.3%). Abnormal ultrasonographic findings (intraventricular hemorrhage grades 3 or 4, periventricular leukomalacia, or ventriculomegaly) were observed in 18 cases (9.2%) and they were significantly associated with severe ANDO (OR 11.8 95% CI 4.0-34.0). Only gestational age at delivery (OR 0.80 95% CI 0.66-0.97), but not intrauterine infection, was independently related to severe ANDO. Infants with severe ANDO born before 28 weeks presented lower umbilical artery pH (7.24±0.1 vs 7.31±0.06, p=0.005) and a significantly higher rate of cesarean delivery (85.7% vs 50%, OR 6 95%CI 1.3-26.3, p=0.03) compared with infants without severe ANDO. CONCLUSION: Gestational age at delivery and low umbilical artery pH at less than 28 weeks, but not intrauterine infection, are independent risk factors for severe ANDO in babies with birth weight <1500g.