Comparison of "IN-REC-SUR-E" and LISA in preterm neonates with respiratory distress syndrome: a randomized controlled trial (IN-REC-LISA trial).

BACKGROUND: Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. METHODS: In this study, 382 infants born at 24+0-27+6 weeks' gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks' postmenstrual age. The secondary outcomes are BPD at 36 weeks' postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). DISCUSSION: This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0-27+6 weeks' gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks' postmenstrual age of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

New perspective for pain control in neonates: a comparative effectiveness research.

OBJECTIVE: To compare sucrose 24% oral gel formulation to liquid formula and breastfeeding during a heel prick in neonates. STUDY DESIGN: In this comparative effectiveness research 195 neonates >36 weeks' gestation were randomised to three groups, receiving during heel stick: (i) breastfeeding, (ii) sucrose 24% liquid with non-nutritive sucking and (iii) sucrose 24% gel with non-nutritive sucking. The pain was assessed through the Neonatal Infant Pain Scale. RESULTS: All the methods analysed has shown to be effective in reducing pain. There was an increase in odds of pain following liquid sucrose compared to breastfeeding (OR = 1.60; 95% CI: 0.82-3.3; p = 0.17). A reduction of odds of pain was showed comparing sucrose to breastfeeding (OR = 0.78; 0.38-1.6; 0.48), and comparing sucrose gel to liquid formula (OR = 0.48; 0.23-0.96; p = 0.04). CONCLUSION: Sucrose 24% gel with non-nutritive sucking seems to be a valid alternative when breastfeeding is not possible. Further research is needed.

Timing of oral feeding changes in premature infants who underwent osteopathic manipulative treatment.

BACKGROUND: The delayed transition from gavage-to-nipple feeding is one of the most significant factors that may prolong hospital length of stay (LOS). Osteopathic manipulative treatment (OMT) has been demonstrated to be effective regarding LOS reduction, but no investigations have documented its clinical validity for attaining oral feeding. OBJECTIVES: To assess OMT utility regarding the timing of oral feeding in healthy preterm infants. DESIGN: Preliminary propensity score-matched retrospective cohort study. SETTING: Data were extrapolated from the neonatal intensive care unit (NICU) of Del Ponte Hospital in Varese, Italy, during the period between March 2012 and December 2013. INTERVENTIONS: Two propensity score-matched groups of healthy preterm infants aged 28+0 to 33+6 were compared, observing those supported with OMT until hospital discharge and control subjects. MAIN OUTCOME MEASURES: Days from birth to the attainment of oral feeding was the primary endpoint. Body weight, body length, head circumference and LOS were considered as secondary endpoints. RESULTS: Seventy premature infants were included in the study as the control group (n = 35; body weight (BW) = 1457.9 ± 316.2 g; gestational age (GA) = 31.5 ± 1.73 wk) and the osteopathic group (n = 35; BW = 1509.6 ± 250.8 g; GA = 31.8 ± 1.64 wk). The two groups had analogous characteristics at study entry. In this cohort, we observed a significant reduction in TOF (-5.00 days; p = 0.042) in the osteopathic group with a greater effect in very low birth weight infants. CONCLUSIONS: These data demonstrate the utility and potential efficacy of OMT for the attainment of oral feeding. Further adequately powered clinical trials are recommended.

Efficacy of lung volume optimization maneuver monitored by optoelectronic pletismography in the management of congenital diaphragmatic hernia.

Newborns affected by congenital diaphragmatic hernia (CDH) need cardio-respiratory stabilization before undergoing surgical repair. Open lung strategy is a well-established approach to optimize lung volume in preterm infants with Respiratory Distress Syndrome (RDS), using both High Frequency Oscillatory Ventilation (HFOV) and Conventional Mechanical Ventilation (CMV). We report a case of left CDH with severe lung hypoplasia, managed applying open lung strategy in HFOV (pre-surgery period) and in Assist-Control with Volume Guarantee (post-surgery period), guided by SpO2 changes, TcPO2 and TcPCO2 monitoring. Opto-electronic plethysmography was used to measure end-expiratory chest wall volume changes (ΔEEcw) related to lung volume variations occurring during pressure changes. OEP confirmed the efficacy of using SpO2 and transcutaneous gas monitoring during this recruitment maneuver.

Selective intrauterine growth restriction in monochorionic twins: changing patterns in umbilical artery Doppler flow and outcomes.

OBJECTIVES: To describe changes in umbilical artery (UA) Doppler flow in monochorionic diamniotic (MCDA) twins affected by selective intrauterine growth restriction (sIUGR), to correlate Doppler findings with pregnancy course and perinatal outcome, and to report postnatal follow-up. METHODS: This was a retrospective study of 140 MCDA twins with sIUGR. UA end-diastolic flow, defined as Doppler waveform pattern Type I (persistently positive), Type II (persistently absent or persistently reversed) or Type III (intermittently absent or intermittently reversed), was recorded at first examination and monitored weekly until double or single intrauterine fetal death (IUFD), bipolar cord coagulation or delivery. All neonates had an early neonatal brain scan, magnetic resonance imaging, when indicated, and neurological assessment during infancy. Rates (per 100 person-weeks) and hazard ratios (HR) of IUFD in the IUGR twin in each pregnancy were calculated considering UA Doppler pattern as a time-dependent variable. RESULTS: At first examination, there were 65 cases with UA Doppler waveform pattern Type I, 62 with Type II and 13 with Type III. Of the 65 Type-I cases, 48 (74%) remained stable, while 17 (26%) changed to either Type II absent (14%), Type II reversed (9%) or Type III (3%). Of 62 Type-II cases (47 with absent and 15 with reversed flow), 33 (53%) remained stable (18 with absent and all 15 with reversed flow). The 29 Type-II absent cases which changed became Type II reversed (24/47, 51%) or Type III (5/47, 11%). All 13 Type-III cases remained stable. Compared with Type I, the risk of IUFD (adjusted for estimated fetal weight discordance and amniotic fluid deepest vertical pocket) was highest when the pregnancy was or became Type II reversed (HR, 9.5; 95% CI, 2.7-32.7) or Type II absent (HR, 4.3; 95% CI, 1.3-14.3). Mild neurological impairment was more prevalent in the IUGR twin than in the large cotwin (7% vs 1%, P = 0.02). CONCLUSIONS: Risk stratification based on UA Doppler is useful for planning ultrasound surveillance. However, patterns can change over time, with important consequences for management and outcome. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Sustained inflation: Prophylactic or rescue maneuver?

Application of nasal continuous positive airway pressure (nCPAP) in the delivery room is a valid alternative to mechanical ventilation in the management of respiratory failure of preterm infants, with reduced occurrence of bronchopulmonary dysplasia and death. nCPAP at birth is still burdened by a high failure rate. Sustained inflation appears to be an intriguing approach to allow the respiratory transition at birth by clearing the lung fluid, thus obtaining an adequate functional residual capacity. This may enhance nCPAP success. Sustained inflation reduces the need for mechanical ventilation in the first 72 h of life, with no changes in the incidence of bronchopulmonary dysplasia and death. The efficacy of sustained inflation seems to be related to the presence of open glottis with active breathing of the infant. Further studies are needed to recommend the application of sustained inflation during delivery room management of preterm infants at risk of respiratory distress or with clinical signs of respiratory failure.

Non-surgically related causes of erectile dysfunction after bilateral nerve-sparing radical prostatectomy.

BACKGROUND: Erectile dysfunction (ED) represents one of the most common long-term side effects in prostate cancer (PCa) patients treated with bilateral nerve-sparing radical prostatectomy (BNSRP). The aim of our study was to assess the influence of non-surgically related causes of ED in patients treated with BNSRP. METHODS: Overall, 716 patients treated with BNSRP were retrospectively identified. All patients had complete data on erectile function (EF) assessed by the Index of Erectile Function-EF domain (IIEF-EF) and depressive status assessed by the Center for Epidemiologic Studies-Depression (CES-D) questionnaire. EF recovery was defined as an IIEF-EF of ⩾22. Kaplan-Meier analyses assessed the impact of preoperative IIEF-EF, depression and adjuvant radiotherapy (aRT) on the time to EF recovery. Multivariable Cox regression models were used to test the impact of aRT on EF recovery after accounting for depression and baseline IIEF-EF. RESULTS: Median follow-up was 48 months. Patients with a preoperative IIEF-EF of ⩾22 had substantially higher EF recovery rates compared with those with a lower IIEF-EF (P<0.001). Patients with a CES-D of <16 had significantly higher EF recovery rates compared to those with depression (60.8 vs 49.2%; P=0.03). Patients receiving postoperative aRT had lower rates of EF compared with their counterparts left untreated after surgery (40.7 vs 59.8%; P<0.001). These results were confirmed in multivariable analyses, where preoperative IIEF-EF (P<0.001), depression (P=0.04) and aRT (P=0.03) were confirmed as significant predictors of EF recovery. CONCLUSIONS: Preoperative functional status and depression should be considered when counseling PCa patients regarding the long-term side effects of BNSRP. Moreover, the administration of aRT has a detrimental effect on the probability of recovering EF after BNSRP. This should be taken into account when balancing the potential benefits and side effects of multimodal therapies in PCa patients.

LISA: Surfactant administration in spontaneous breathing. Which evidence from the literature?

Recent human and animal studies demonstrated that surfactant can be delivered intratracheally without traditional intubation and bagging, but using a fine catheter inserted into the trachea of spontaneously breathing preterm infants on CPAP. This strategy, known as LISA (less invasive surfactant administration) or MIST (minimal invasive surfactant therapy), seems to reduce failure of non-invasive respiratory approach. Avoiding mechanical ventilation and manual inflation it is possible to reduce lung injury due to baro-volutrauma. Moreover leaving the infants supported by N-CPAP during the maneuver, it is possible to reduce the risk of lung derecruitment. Further studies are needed to confirm the promising effects due to this strategy to deliver surfactant.

Cesarean section plus delayed cord clamping approach in the perinatal management of congenital high airway obstruction syndrome (CHAOS): a case report.

In this case, we describe a newborn with prenatal diagnosis of congenital high airway obstruction syndrome (CHAOS), successfully managed with a cesarean section with delayed cord clamping 180 seconds. In case of prenatal diagnosis of CHAOS, prompt airway intervention at delivery allows survival of this otherwise fatal condition. Ex utero intrapartum treatment (EXIT) is considered the elective procedure to secure the fetal airway before the baby is completely separated from the maternal circulation. In cases where the EXIT procedure is not possible for maternal reasons (Ballantyne's syndrome), delayed cord clamping may serve as an alternative method to manage CHAOS.

[Silymarin/galega administration in term and preterm mothers to sustain breast feeding: an observational study]. / La somministrazione di silimarina/galega per il sostegno dell'allatamento al sone: studio prospettico osservazionale in madri di neonati a termine e pretermine.

AIM: Breastfeeding is considered the most important source of nutrition both in the first year of life for term and preterm infants, because of its well-known positive effects on short and long-term outcome. Unfortunately not all the mothers can begin or maintain an adequate milk secretion. Premature delivery and prolonged length of stay in the hospital can influence maternal milk production due to maternal anxiety and/ or neonatal pathologies related to prematurity. A variety of herbal and pharmaceutical products have been recommended as galactogogues, substances that promote lactation. METHODS: In this observational study, the authors compared the effect on breast milk production of an oral maternal supplementation of two galactogogues (sylimarine and galega-Lutein latte®) in a term and preterm mothers group (preterm infants recovered in neonatal intensive care unit-NICU). RESULTS: The breast milk production significantly reduced at start in preterm mothers (N.=16) versus term mothers (N.=16) (P<0.08), after sylimarine and galega supplementation was the same in both groups within two months of life (P=NS). CONCLUSION: This galactogogues supplementation could be recommended to maintain an adequate lactation in premature mothers, especially when their infants are still recovered in the NICU.

Surfactant administration in spontaneous breathing with N-CPAP for RDS.

Surfactant administration in spontaneous breathing with N-CPAP seems to be a promising approach in the management of neonatal RDS. Both recent RCTs and single centre experience have shown feasibility and good respiratory outcomes with this approach even in extremely preterm infants with respiratory failure. The results of these studies seem to demonstrate that avoiding mechanical ventilation and manual inflation (therefore the risk of high positive pressure and inappropriate tidal volume) it is possible to reduce the risk of VILI and the evolution towards BPD. Further large clinical studies are needed to confirm this hypothesis.

Outcome of congenital diaphragmatic hernia: analysis of implicated factors.

AIM: Congenital diaphragmatic hernia remains a significant challenge for neonatologists and pediatric surgeons. Over the last years, new therapeutic approaches, as high-frequency oscillatory ventilation, inhaled nitric oxide, permissive hypercapnia, extracorporeal membrane oxygenation, have been used for the management of these newborns. We conducted a retrospective study of all infants who were managed for congenital diaphragmatic hernia in our NICU in order to identify possible clinical characteristics which were predictive for survival. METHODS: We reviewed a single institution's experience with 42 consecutive neonates with congenital diaphragmatic hernia admitted to our NICU from 1993 to 2009. RESULTS: Prenatal data and side of congenital diaphragmatic hernia were similar in survivors and no-survivors infants except for the lung-to-head ratio (LHR), which was higher and measured later in survivors than non-survivors. Multiple regression analysis showed that a gestational age ≥39 weeks, Apgar score at 5 min ≥7, FiO2<0.35, MAP<13 cmH2O, OI<10 and AaDO2 >282 before surgical repair, and the absence of persistent pulmonary hypoplasia were independent predictive factors of survival. CONCLUSION: Our study suggests that the outcome of newborns with congenital diaphragmatic hernia still depends on the severity of lung hypoplasia, despite the different respiratory and therapeutical approaches.

ELBW infants: to intubate or not to intubate in the delivery room?

Few years ago, elective tracheal intubation in the delivery room was considered as the routine approach in managing respiratory failure in extremely-low-birth-weight infants (ELBW), at least in terms of surfactant administration. Over recent years, the indications and principles of neonatal resuscitation of ELBW infants have been partially reviewed: many randomized clinical trials (RCT) have demonstrated that these infants do not die quickly without intubation in the delivery room, and many infants only need a little help in completing foetal-neonatal transition through the use of lung recruitment manoeuvres in the delivery room (e.g. sustained lung inflation, CPAP) and then only non-invasive ventilation support. Tracheal intubation and mechanical ventilation can be reserved solely for depressed or ELBW, although further RCTs are needed to provide additional information and to provide a conclusive response to the eternal debate as to whether intubation at birth can influence outcome for ELBW infants.

Fetal and maternal complications after selective fetoscopic laser surgery for twin-to-twin transfusion syndrome: a single-center experience.

OBJECTIVE: To report the incidence of fetal and maternal complications after selective fetoscopic laser surgery for twin-to-twin transfusion syndrome (TTTS). METHODS: A total of 150 cases of TTTS were treated from January 2004 to June 2009 (period 1, 2004-2006, 62 cases; period 2, 2007 to June 2009, 88 cases). Fetal complications (double and single intrauterine fetal death, recurrence of TTTS, twin anemia-polycythemia sequence (TAPS), reversal of TTTS, cerebral lesions in one twin) and maternal complications were recorded, and retrospectively analyzed. RESULTS: Nineteen (12.6%), 58 (38.7%), 61 (40.7%) and 12 cases (8.0%) were classified preoperatively as Quintero stage I, II, III and IV, respectively. The anterior placenta was described in 73 cases (48.6%). Double and single fetal death occurred overall in 7.3 and 36.0% of cases, respectively. The rate of recurrence was 11.3%, of TAPS 3.3%, and of reversal of TTTS 1.3%. Cerebral lesions were diagnosed in 3 donors (2.0%). Eighteen cases (12.0%) of fetal complications had a second procedure (6 repeat laser, 4 serial amnioreduction, 8 bipolar cord coagulation). Pregnancies undergoing a second procedure delivered at a median gestational age of 30.2 weeks compared to 32.1 weeks for those not repeating (p = 0.04). Perinatal survival of at least one twin improved from 66.1 to 79.5% (p = 0.06) in the two consecutive periods. For every 10 laser surgeries performed, there was an average improvement of 1.5% in the predicted percentage of survival of at least one twin (OR 1.09, 95% CI 1.00-1.19). Major maternal complications occurred in 9 cases (6.0%), 3 of which required admission to intensive care unit. CONCLUSIONS: Fetal complications are common after fetoscopic laser surgery. In this experience, an increasing number of procedures improved the performance of a new fetoscopic laser center.

Alveolar recruitment in the delivery room.

Most preterm babies with a gestational age less than 23-27 weeks need a respiratory support in the delivery room (DR); the aim of ventilation is to create and maintain a functional residual capacity (FRC); to facilitate gas exchange and to minimize acute lung injury. The application of a continuous positive airway pressure (CPAP) from the first breaths helps in obtaining a lung volume stabilization. Efficacy and safety of the application of a sustained lung inflation (SLI) at birth is still under careful evaluation. The prompt increase of the hearth rate and oxygen saturation in the preliminary studies at the moment available in the literature are signs of the good efficacy of the manoeuvre but the effects of the SLI on oxygenation and hemodynamics are undetermined. When preterm infants need respiratory assistance in the DR, respiratory function monitoring is desirable to apply adequate and gentle resuscitation manoeuvres. Clinical large trials taking place in the DR are needed but they are also extremely difficult to be designed and performed.

Deep medullary vein involvement in neonates with brain damage: an MR imaging study.

BACKGROUND AND PURPOSE: Different and specific MR imaging patterns of lesions involving WM are widely defined in neonatal encephalopathy. The aim of this study was to describe a novel MR imaging pattern of damage characterized by the abnormal prominence of DMVs in premature and full-term neonates. MATERIALS AND METHODS: Twenty-one (11 premature and 10 full-term) neonates with MR imaging evidence of linear radially oriented fan-shaped lesions in the periventricular WM and without dural venous thrombosis were enrolled in this retrospective study. A total of 37 MR imaging examinations were performed at ages ranging from day 0 to 24 months. RESULTS: According to the appearance of linear anomalies on T2-weighted images, we identified 2 main patterns: T2 hypointense lesions without WM cavitations and T2 hypointense lesions associated with linear cysts. The first pattern was found in 17 examinations performed between 0 and 44 days of life; the second pattern was found in another 14 examinations performed between 6 days and 4 months of life. Five examinations performed between 9 and 24 months of life showed a reduction in volume and hyperintense signal intensity of the periventricular WM on T2-weighted and FLAIR images. CONCLUSIONS: Subtle linear WM lesions with the same anatomic distribution of DMVs may be evident in premature and full-term neonates without signs of major venous thrombosis, both in the acute and subacute phases. Their appearance and evolution suggest that transient DMV engorgement/thrombosis may be responsible for WM damage that can lead to a PVL-like pattern.

Reclutamento alveolare in sala parto: la sustained lung inflation. (Alveolar recruitment in the delivery room: sustained lung inflation).

At birth the transition by the fetal situation to neonatal life occurs. The real mechanism of lung liquid reabsorption and lung aereation at birth, in the past attributed only to the epithelial sodium channel function, has recently been linked to the first important breaths too and to the following changes in transpulmonary pressure. If this quite easily happens in the term baby, the preterm infants and all the babies with poor respiratory effort may have a delayed achievement of an adequate functional residual capacity (FRC). Premature delivery is always associated to the failure of respiratory transition and preterm babies frequently need a respiratory support (e.g., N-CPAP). Actual recommendations do not consider to mimic the physiologic changes that usually happen to the term neonate at birth. The application at birth of the sustained lung inflation (SLI) (a peak pressure of 25-30 cm H2O for 10-20 seconds), with nasopharyngeal tube or an adequately sized mask and a Neo-puff device, followed by the application of a continuous adequate PEEP (e.g., 5 cmH2O) is effective in the achievement of the FRC in animal studies and in the reduction of the need of mechanical ventilation (MV) in preterm infants at risk for RDS. Large RCTs are needed to verify the real efficacy of SLI in the delivery room to prevent the need of mechanical ventilation and to improve respiratory outcomes of preterm infants at risk for RDS.

Height of the cerebellar vermis and gestational age at birth.

OBJECTIVES: The objective of this study was to construct reference ranges of the neonatal cerebellar vermis height with respect to the gestational age at birth. METHODS: This observational study assessed 434 neonates born at 25-42 weeks' gestation. The neonates were singleton and appropriate in size for gestational age, and did not exhibit any abnormalities or neonatal disease. Gestational age was based on the date of the last menstrual period and confirmed by ultrasound examination performed within the 12(th) week of pregnancy. Sonographic measurements of the height of the cerebellar vermis in the mid-sagittal plane were performed within 24 h of birth by the same neonatal sonographer. Reference ranges (5(th), 50(th) and 95(th) centiles) were estimated by a mean and SD model based on least-squares polynomial regression. RESULTS: Neonatal sonographic measurements were obtained in all cases. Mean (SD) maternal age was 30.2 (4.3) years. Mean cerebellar vermis height adjusted for gestational age did not differ between males and females, the mean adjusted difference being 0.012 (95% CI, - 0.009 to 0.033) cm. Mean cerebellar vermis height (cm) against gestational age (weeks) was suitably modeled by a linear-cubic polynomial as - 1.784 + 0.137 x GA - 0.000019 x GA(3) (SD = - 0.147 + 0.008 x GA), where GA = gestational age. CONCLUSIONS: Reference ranges for the height of the cerebellar vermis at birth with respect to gestational age at birth have been constructed in appropriate-for-gestational-age neonates.