Nasal intermittent positive pressure ventilation during less invasive surfactant administration in preterm infants: An open-label randomized controlled study.

INTRODUCTION: Approximately half of very preterm infants with respiratory distress syndrome (RDS) fail treatment with nasal continuous positive airway pressure (NCPAP) and need mechanical ventilation (MV). OBJECTIVES: Our aim with this study was to evaluate if nasal intermittent positive pressure ventilation (NIPPV) during less invasive surfactant treatment (LISA) can improve respiratory outcome compared with NCPAP. MATERIALS AND METHODS: We carried out an open-label randomized controlled trial at tertiary neonatal intensive care units in which infants with RDS born at 25+0-31+6 weeks of gestation between December 1, 2020 and October 31, 2022 were supported with NCPAP before and after surfactant administration and received NIPPV or NCPAP during LISA. The primary endpoint was the need for a second dose of surfactant or MV in the first 72 h of life. Other endpoints were need and duration of invasive and noninvasive respiratory supports, changes in SpO2/FiO2 ratio after LISA, and adverse effect rate. RESULTS: We enrolled 101 infants in the NIPPV group and 99 in the NCPAP group. The unadjusted odds ratio for the composite primary outcome was 0.873 (95% confidence interval: 0.456-1.671; p = .681). We found that the SpO2/FiO2 ratio was transiently higher in the LISA plus NIPPV than in the LISA plus NCPAP group, while adverse effects of LISA had similar occurrence in the two arms. CONCLUSIONS: The application of NIPPV or NCPAP during LISA in very preterm infants supported with NCPAP before and after surfactant administration had similar effects on the short-term respiratory outcome and are both safe. Our study does not support the use of NIPPV during LISA.

Thermal management with and without servo-controlled system in preterm infants immediately after birth: a multicentre, randomised controlled study.

BACKGROUND: The thermal servo-controlled systems are routinely used in neonatal intensive care units (NICUs) to accurately manage patient temperature, but their role during the immediate postnatal phase has not been previously assessed. OBJECTIVE: To compare two modalities of thermal management (with and without the use of a servo-controlled system) immediately after birth. STUDY DESIGN AND SETTING: Multicentre, unblinded, randomised trial conducted 15 Italian tertiary hospitals. PARTICIPANTS: Infants with estimated birth weight <1500 g and/or gestational age <30+6 weeks. INTERVENTION: Thermal management with or without a thermal servo-controlled system during stabilisation in the delivery room. PRIMARY OUTCOME: Proportion of normothermia at NICU admission (axillary temperature 36.5°C-37.5°C). RESULTS: At NICU admission, normothermia was achieved in 89/225 neonates (39.6%) with the thermal servo-controlled system and 95/225 neonates (42.2%) without the thermal servo-controlled system (risk ratio 0.94, 95% CI 0.75 to 1.17). Thermal servo-controlled system was associated with increased mild hypothermia (36°C-36.4°C) (risk ratio 1.48, 95% CI 1.09 to 2.01). CONCLUSIONS: In very low birthweight infants, thermal management with the servo-controlled system conferred no advantage in maintaining normothermia at NICU admission, while it was associated with increased mild hypothermia. Thermal management of preterm infants immediately after birth remains a challenge. TRIAL REGISTRATION NUMBER: NCT03844204.

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

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.

Continuous renal replacement therapy in neonates and small infants: development and first-in-human use of a miniaturised machine (CARPEDIEM).

BACKGROUND: Peritoneal dialysis is the renal replacement therapy of choice for acute kidney injury in neonates, but in some cases is not feasible or effective. Continuous renal replacement therapy (CRRT) machines are used off label in infants smaller than 15 kg and are not designed specifically for small infants. We aimed to design and create a CRRT machine specifically for neonates and small infants. METHODS: We prospectively planned a 5-year project to conceive, design, and create a miniaturised Cardio-Renal Pediatric Dialysis Emergency Machine (CARPEDIEM), specifically for neonates and small infants. We created the new device and assessed it with in-vitro laboratory tests, completed its development to meet regulatory requirements, and obtained a licence for human use. Once approved, we used the machine to treat a critically ill neonate FINDINGS: The main characteristics of CARPEDIEM are the low priming volume of the circuit (less than 30 mL), miniaturised roller pumps, and accurate ultrafiltration control via calibrated scales with a precision of 1 g. In-vitro tests confirmed that both hardware and software met the specifications. We treated a 2·9 kg neonate with haemorrhagic shock, multiple organ dysfunction, and severe fluid overload for more than 400 h with the CARPEDIEM, using continuous venovenous haemofiltration, single-pass albumin dialysis, blood exchange, and plasma exchange. The patient's 65% fluid overload, raised creatinine and bilirubin concentrations, and severe acidosis were all managed safely and effectively. Despite the severity of the illness, organ function was restored and the neonate survived and was discharged from hospital with only mild renal insufficiency that did not require renal replacement therapy. INTERPRETATION: The CARPEDIEM CRRT machine can be used to provide various treatment modalities and support for multiple organ dysfunction in neonates and small infants. The CARPEDIEM could reduce the range of indications for peritoneal dialysis, widen the range of indications for CRRT, make the use of CRRT less traumatic, and expand its use as supportive therapy even when complete renal replacement therapy is not indicated. FUNDING: Associazione Amici del Rene di Vicenza.

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

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 (ß 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.

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 (x10(9)/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 (x10(9)/l). CONCLUSIONS: WBC count in the third day of life is strongly associated with HCA.

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.

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.

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 Volpe's 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.

Histological chorioamnionitis and neonatal leukemoid reaction in low-birth-weight infants.

We investigated whether histological chorioamnionitis (HCA) is a risk factor predisposing to leukemoid reaction (LR) and whether LR is associated with the preterm parturition syndrome and the systemic fetal inflammation response syndrome. A prospective histological study on placentas was performed in preterm infants (

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 (

Neonatal pneumothorax: comparison between neonatal transfers and inborn infants.

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.

Urinary ET-1, AVP and sodium in premature infants treated with indomethacin and ibuprofen for patent ductus arteriosus.

The relative potency and interrelationship between vasoactive and natriuretic mediators are thought to be important in the transition from fetal to neonatal life. The relationship between urinary vasoactive factors and sodium excretion has not been adequately addressed in premature infants receiving indomethacin and ibuprofen for therapy of patent ductus arteriosus. Excretion rates of AVP, ET-1 and sodium were measured in premature infants with RDS receiving indomethacin or ibuprofen. Forty-four RDS premature infants (<34-week 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 3 doses at 12-h intervals of indomethacin (n=24), 0.2 mg/kg, infused continuously over a period of 15 min. Urinary ET-1, AVP and sodium excretion were measured before and after treatment. Indomethacin treatment caused a significant decrease in urinary ET-1 and AVP excretion (UET-1/Ucr 0.14+/-0.01 vs. 0.10+/-0.05 fenton/mmol; P<0.05; 24.42+/-6.18 vs. 12.63+/-3.06 pg/mmol; P<0.05, respectively), along with a significant reduction in urinary sodium (92.1+/-36.1 vs. 64.8+/-35.6 mmol/l; P<0.01), fractional excretion of sodium (6.8+/-37.1 vs. 4.5+/-37.1%; P<0.01) and urinary osmolality (276.2+/-103.9 vs. 226.4+/-60.3 mOsmol/kg; P<0.05). Ibuprofen treatment caused a significant decrease in urinary AVP (UAVP/Ucr 24.5+/-3.4 vs. 16.3+/-2.04 pg/mmol; P<0.01), along with a significant decrease in urinary sodium (78.0+/-8.4 vs. 57.0+/-8.0 mmol/l; P<0.05) and in fractional excretion of sodium (7.5+/-1.3 vs. 3.9+/-3.0%; P<0.05), while it did not modify urinary ET-1 excretion. The association of renal ET-1 and AVP activity with sodium excretion in premature infants treated with indomethacin and ibuprofen supports the hypothesis that these factors may play a role in the physiologic changes in sodium excretion.

The influence of timing of elective cesarean section on neonatal resuscitation risk.

OBJECTIVE: Cesarean section has negative effects on the physiologic responses to birth, including the development of lung volumes, pulmonary vascular resistance, and biochemical responses. The objective of this study was to examine the association between the timing of delivery between 37 and 42 wks gestation and neonatal resuscitation risk in elective cesarean section. DESIGN: Observational, cohort study. SETTING: Maternity Department of Padua University, Italy. SUBJECTS: All pregnant women who delivered by elective cesarean section at term during a 3-yr period were identified from a perinatal database and compared retrospectively with pregnant women who delivered vaginally and matched for week of gestation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Comparative neonatal resuscitation risk (odds ratio, OR; confidence interval, CI) was analyzed. During this time, 1,284 (13%) elective cesarean section deliveries occurred at or after 37 wks of gestation. Forty-four (3.4%) newborns delivered by elective cesarean section and 18 (1.4%) newborns vaginally delivered needed positive pressure ventilation resuscitation by laryngeal mask airway or tracheal tube. Positive pressure ventilation resuscitation risk was significantly higher in the infant group delivered by elective cesarean section compared with vaginal delivery (OR, 2.05; CI, 1.25-5.67; p < .01) and involved both laryngeal mask airway and tracheal tube resuscitation maneuvers (OR, 2.77 CI, 1.26-5.8; p < .01 and OR, 2.9; CI, 1.02-7.81; p < .01, respectively). In the period of weeks 37(+0) to 38(+6), positive pressure ventilation resuscitation risk and single laryngeal mask airway and tracheal tube resuscitation maneuver risk were significantly greatly increased (OR, 4.25; CI, 1.46-16.12; p < .01; OR, 2.25; CI, 1.46-6.12; p < .01; and OR, 11.3; CI, 2.15-16.0; p < .01, respectively). After 38(+6) weeks, there was no significant difference in positive pressure ventilation resuscitation risk. CONCLUSIONS: Elective cesarean section at term, in an obstetric population without prenatally identified risk factors, remains associated with increased resuscitation risk with related implications for the neonate compared with vaginal delivery. A significant reduction in neonatal resuscitation risk would be obtained by waiting until week 39(+0) before performing elective cesarean section.