Stefania Vedovato

Neurodevelopmental outcome in preterm histological chorioamnionitis

The role of histological chorioamnionitis in neonatal neurological outcome is not yet fully understood. The present study aimed to assess the neurodevelopmental outcome of preterm babies born after pregnancy complicated by histological chorioamnionitis. Clinical data were prospectively collected for consecutive premature neonates born before 32 weeks of gestation, admitted to Neonatal Intensive Care Unit of Padua University from January 1998 to December 2001. Placental histology was performed. Outcome at 18 months of corrected age was evaluated by a standardized postal parental questionnaire. Among 104 placentas examined, 41 (39.4%) were diagnosed with histological chorioamnionitis. Reply to the postal questionnaire was available from 76.1% of the families. The relative risk of disability in vision, hearing, speech and motor development was higher in the histological chorioamnionitis than in the non-histological chorioamnionitis group, with statistical significance in speech delay (relative risk 2.37; 95% confidence interval: 1.33-4.22) and hearing loss (relative risk 2.76; 95% confidence interval:1.64-4,64). To our knowledge this is the first report suggesting preterm histological chorioamnionitis as a possible risk factor for hearing loss and speech delay.

Histological Inflammatory Responses in the Placenta and Early Neonatal Brain Injury

We investigated the relationship between the severity of histological inflammatory responses in the placenta, chorionic plate, and umbilical cord in conjunction with the intraventricular hemorrhage (IVH) risk in premature infants. Clinical data were prospectively collected for 287 consecutive premature neonates born before 32 completed weeks of gestation and admitted to the level III neonatal intensive care unit of the Department of Pediatrics at Padua University from January 1999 to December 2004. Placental histology for histological chorioamnionitis (HCA) was graded and scored according to Redline and others. The diagnosis of IVH (grades I–IV) was graded according to Volpes classification. Among the placentas of the 287 preterm examined infants, 68 (23.6%) were diagnosed with acute HCA. Overall incidence of IVH was 11.8%. Of 68 preterm neonates with HCA, 11 developed IVH (16.1%). Maternal HCA at the higher grades and stages increased the risk of IVH: 7 (64%) of the 11 preterm infants with maternal HCA grade 3 developed IVH (RR; 95% CI 2.05; 1.1–3.6) and 8 (73%) of the 11 preterm neonates with stage 3 developed IVH (RR; 95% CI 1.59; 1.0–2.5). Conversely, fetal inflammation was not associated with an increased risk of IVH. In conclusion, the IVH risk in preterm infants at less than 32 gestation weeks is significantly associated with severe grade and stage maternal HCA inflammatory scores.

Preterm premature rupture of membranes, chorioamnion inflammatory scores and neonatal respiratory outcome

Objective  To evaluate whether histological chorioamnionitis (HCA), in the setting of preterm premature rupture of membranes (PPROM), affects infant respiratory outcome.

Neonatal pneumothorax: comparison between neonatal transfers and inborn infants.

Abstract Objective: To assess the differences in clinical characteristics, management and outcome between the neonatal transfers and inborn neonates with pneumothorax. Methods: The records of 36 neonatal transfers (Group A) and 25 inborn (Group B) neonates with symptomatic pneumothorax were retrospectively analyzed. Results: In Group A, gestational age (36±2 vs. 31±4 weeks; P<0.01), birth weight (2720±537 vs. 1736±1028 g; P<0.01), exclusive oxygen-therapy before the event (47% vs. 20%; P<0.05) and tube thoracostomy (78% vs. 44%; P<0.05) were significantly higher than in Group B. The need of resuscitation at birth (19% vs. 44%; P<0.05), conventional mechanical ventilation (20% vs. 56%; P<0.05), presence of associated major congenital malformations (0% vs. 20%; P<0.01), length of hospital stay (9±6 vs. 32±32 days; P=0.01) and mortality (0% vs. 16%; P=0.01) were significantly lower in Group A than in Group B. Conclusions: Neonatal transfers and inborn neonates with pneumothorax have different clinical characteristics and outcome. This information could be useful for all persons involved in the interhospital care of perinatal patients.

Effects of Ibuprofen and Indomethacin on Urinary Antidiuretic Hormone Excretion in Preterm Infants Treated for Patent Ductus Arteriosus

Objective: To compare the effects of intravenous ibuprofen and indomethacin for treatment of patent ductus arteriosus (PDA) on urinary antidiuretic hormone (ADH) excretion, as a cause of oliguria. Study Design: Forty-four respiratory distress syndrome prematures (≤34 weeks’ gestation) with PDA received either ibuprofen (n = 22) in an initial dose of 10 mg/kg followed by two doses of 5 mg/kg each after 24 and 48 h or three doses at 12-hour intervals of indomethacin (n = 24), 0.2 mg/kg, both infused continuously over a period of 15 min. Urinary ADH excretion, diuresis, serum creatinine, urinary sodium, fractional excretion of sodium, and urinary osmolality were measured before and after treatment. Results: Indomethacin treatment caused a significant decrease in urinary ADH excretion (21.8 ± 20.8 vs. 13.8 ± 12.9 pg/ml; p < 0.05), along with a significant reduction in urinary sodium (92.1 ± 36.1 vs. 64.8 ± 35.6; p < 0.05), fractional excretion of sodium (68.5 ± 37.1 vs. 45.6 ± 37.1; p < 0.05), and urinary osmolality (276.2 ± 103.9 vs. 226.4 ± 60.3; p < 0.05). Ibuprofen treatment did not modify urinary ADH excretion and caused a statistically insignificant decrease in urinary sodium and in fractional excretion of sodium. Conclusions: Compared with ibuprofen, indomethacin caused a significant reduction in urinary ADH excretion and a significant decrease in urinary sodium and osmolality.

Fetal placental inflammation is associated with poor neonatal growth of preterm infants: a case-control study

Abstract Objective: To determine whether there is an association between histological chorioamnionitis (HCA) and postnatal growth of preterm infants in the neonatal period. Method: This case–control study is part of a larger prospective histological study on placentas performed in all deliveries prior to 32 weeks of gestation. Eligible cases involved all placentas with a diagnosis of HCA. Control subjects were those without HCA, matched 1:1 with case subjects according to gestational age (±1 week). Placental inflammatory status and serial weight gain were analyzed for all infants during the first four postnatal weeks. Based on placental inflammation extension, HCA was defined as maternal HCA (MHCA) or fetal HCA (FHCA). Results: Of the 320 mother–infant pairs, 71 (22.1%) presented with HCA (27 MHCA and 44 FHCA). Decreases in weight gain at 21 and 28 days were associated with the presence of FHCA (β coefficient ± SE = −4.40 ± 2.21, p = 0.05 and −6.92 ± 2.96, p = 0.02, respectively), whereas no significant differences were found between MHCA and no-HCA groups. FHCA and MHCA were not identified as risk factors of weekly weight gain, after adjusting for possible confounders (maternal ethnicity, parity, smoking during pregnancy, infant gender, IUGR status, SGA status, antenatal steroids, total fluid intake, late-onset sepsis, BPD). Conclusions: We found an association between fetal placental inflammation and poor neonatal growth but we were not able to identify a specific week wherein weight gain could be mostly affected. Placental findings may be used to identify preterm infants at risk of postnatal growth failure.

Sensorineural hearing loss in very low birth weight infants with histological chorioamnionitis

Abstract Objective: Histological chorioamnionitis (HCAM) has been associated with inflammatory diseases of preterm infants. Recently we have observed that it increased the risk of speech delay and hearing loss. So the aim of this study was to evaluate the relationship between sensorineural hearing loss (SNHL) of VLBW infants and HCAM. Methods: We performed an observational study on VLBW infants admitted to the NICU of Padua. Each patient with HCAM was matched with one control without HCAM. All infants underwent hearing screening before discharge by means of automated transient–evoked otoacustic emissions and automated auditory brainstem responses, which were repeated at 3 and 6 months of age with tympanometry measurement. Incidence of SNHL at 6 months of age was compared in the 2 groups and risk factors for hearing loss were studied. Results: Two of 77 (2.6%) newborns with HCAM e 6/73 (8.2%) without it presented SNHL at 6 months of corrected age (p = 0.16). Multivariable logistic regression analysis identified surgical ligation of patent ductus arteriosus (PDA) as independent predictors of SNHL (OR: 5.75, 95% CI 1.34–24.84, p = 0.02), whereas the effect of HCAM on SNHL was only near to statistical significance level. Conclusions: Surgical ligation of PDA is associated with an increased risk of SNHL in VLBW infants, regardless of HCAM.

Leukemoid Reaction and Bronchopulmonary Dysplasia: A Primary Inflammatory Mechanism?

To the Editor .— We read with great interest “Outcome of Extremely Low Birth Weight Infants With Leukemoid Reaction” by Hsiao and Omar.1 Their objective was to examine the effect of leukemoid reaction (LR) in morbidity, mortality, and long-term developmental outcome in extremely low birth weight (ELBW) infants. The study showed that LR in ELBW infants is associated with a higher incidence of bronchopulmonary dysplasia (BPD), compared with no-LR infants. Although hypothesized in their discussion, the study by Hsiao and Omar did not investigate if …

Relationship between the neonatal white blood cell count and histologic chorioamnionitis in preterm newborns

Objective: The aim was to examine the relationship between neonatal white blood cell (WBC) count and the diagnosis of histologic chorioamnionitis (HCA). Design: We measured WBC, a widely used marker of inflammation, to evaluate whether the values at birth were associated with HCA. Setting: NICU, Department of Pediatrics of Padua University, Padua, Italy. Subjects: WBC count was evaluated in 71 preterm neonates (<32 weeks of gestation) with HCA and in a control group without HCA on day 1, 3, and 6 after delivery. Logistic regression analysis and diagnostic accuracy analysis were used to assess the association between WBC counts and HCA. Main results: WBC levels were significantly higher in infants with HCA than in those without HCA (Median IQR, WBC (x109/l): day 1, 13.2 (6.2–21.8) vs 8.1 (6–11.4), p < 0.001; day 3, 17.4 (11.4–26.9) vs 6.3 (5.2–8.3), p < 0.001; day 6, 18.4 (11.1–31) vs 6.5 (4.4–9), p < 0.0001). The neonatal WBC count on the third day of life was the most sensitive parameter associated with HCA (sensitivity: 0.80; specificity: 0.88). The cut-off value based on the ROC curve was 10 (x109/l). Conclusions: WBC count in the third day of life is strongly associated with HCA.

Pharmacological closure of patent ductus arteriosus: effects on pulse pressure and on endothelin-1 and vasopressin excretion.

Widened pulse pressure is a classic sign of significant left-to-right shunting patent ductus arteriosus (PDA), but little evidence supports this statement in the early life of premature infants with respiratory distress syndrome (RDS) needing nonsteroidal anti-inflammatory drugs (NSAIDs), the pharmacological treatment for PDA. Pulse pressure and urinary endothelin-1 (ET-1) and arginine vasopressin (AVP) vasoactive factors involved in the transitional circulation were measured before and after the NSAIDs treatment of 46 RDS premature infants receiving either ibuprofen (n = 22) or indomethacin (n = 24), with 28 responders and 18 nonresponders to the first NSAIDs course. We found that following pharmacological PDA closure, systolic and diastolic blood pressure significantly increased, maintaining a stable pulse pressure. However, when pharmacological closure failed, the trend (nonsignificant) was for a more consistent increase in systolic than in diastolic blood pressure, which determined a statistically significant widening pulse pressure. In addition, urinary ET-1 excretion rates decreased significantly after PDA closure, whereas persistent more aggressive pharmacological therapy failed. Urinary AVP excretion rates decreased insignificantly after therapy, uninfluenced by the efficacy of the drugs. We concluded that widened pulse pressure is a clinical sign of failed PDA pharmacological closure in RDS premature infants. ET-1 levels remain elevated when NSAIDs fail to interrupt left-to-right PDA shunting that complicates recovery from RDS.