An hypothetical external validation of the ARRIVE trial in a European academic hospital.

BACKGROUND: Recent evidence supports elective induction of labor at 39 weeks in low-risk pregnancies to improve maternal and perinatal outcomes. This evidence includes the ARRIVE trial (A Randomized Trial of Induction Versus Expectant Management). However, concerns have been raised on the external validity of the ARRIVE trial, especially with regard to the demographic and clinical characteristics of the pregnant women recruited. OBJECTIVE: This study compared the outcomes in a cohort of consecutive pregnant women, who fulfilled the criteria of the ARRIVE trial and were managed expectantly in an Italian referral academic hospital, with those reported in the expectant and induction arms of the ARRIVE trial. STUDY DESIGN: This was a retrospective single-center study. Consecutive low-risk nulliparous women who fulfilled the ARRIVE trial criteria were evaluated for eligibility at 36-38 weeks of gestation. Those who neither developed complications nor delivered spontaneously before 39 weeks were eligible for this comparative analysis. Maternal and fetal growth and wellbeing were screened and monitored from 36 to 38 weeks of gestation. RESULTS: A total of 1696 patients met the established criteria at recruitment. Of these, 343 spontaneously delivered in <39 weeks, 82 delivered because of maternal indication, and 37 for fetal indication. A total of 1234 pregnant women were eligible for comparison with the elective induction and the expectant management groups of the ARRIVE trial. The socioeconomic status was significantly better, maternal age was significantly higher, and body mass index was significantly lower in our cohort. Cesarean section rate in our cohort was lower than that of the expectant group of the ARRIVE trial (18.7 vs. 22.2%; p = 0.02) and similar to that of the elective induction group (18.7 vs. 18.6%). A new diagnosis of hypertensive disorders during expectant management was noted in 1.6% in our cohort vs. 14.1% in the ARRIVE arm. Among the different obstetric outcomes, only the prevalence of postpartum hemorrhage was not significantly lower in our cohort. The primary perinatal composite outcome was significantly better in our cohort than in both arms of the ARRIVE trial (2.1 vs. 5.4% in the expectant group and 4.3% in the induction group). We did not record cases with an Apgar score ≤ 3 or hypoxic-ischemic encephalopathy. CONCLUSION: In our cohort, expectant management in low-risk pregnancies with late preterm screening of feto-maternal well-being seemed to achieve better maternal and perinatal outcomes than a universal policy of induction at 39 weeks. The results of the ARRIVE trial should be carefully evaluated in different demographic and clinical settings and cannot be extended to the general population.

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.

Minimally invasive fetal surgery for myelomeningocele: preliminary report from a single center.

OBJECTIVE: Recent trials have shown the safety and benefits of fetoscopic treatment of myelomeningocele (MMC). The authors' aim was to report their preliminary results of prenatal fetoscopic treatment of MMC using a biocellulose patch, focusing on neurological outcomes, fetal and maternal complications, neonatal CSF leakage, postnatal hydrocephalus, and radiological outcomes. METHODS: Preoperative assessment included clinical examination, ultrasound imaging, and MRI of the fetus. Patients underwent purely fetoscopic in utero MMC repair, followed by postoperative in utero and postnatal MRI. All participants received multidisciplinary follow-up. RESULTS: Five pregnant women carrying fetuses affected by MMC signed informed consent for the fetoscopic treatment of the defect. The mean MMC size was 30.4 mm (range 19-49 mm). Defect locations were L1 (2 cases), L5 (2 cases), and L4 (1 case). Hindbrain herniation and ventriculomegaly were documented in all cases. The mean gestational age at surgery was 28.2 weeks (range 27.8-28.8 weeks). Fetoscopic repair was performed in all cases. The mean gestational age at delivery was 33.9 weeks (range 29.3-37.4 weeks). After surgery, reversal of hindbrain herniation was documented in all cases. Three newborns developed signs of hydrocephalus requiring CSF diversion. Neurological outcomes in terms of motor level were favorable in all cases, but a premature newborn died due to CSF infection and sepsis. CONCLUSIONS: The authors' preliminary results suggest that fetoscopic treatment of MMC is feasible, reproducible, and safe for mothers and their babies. Neurological outcomes were favorable and similar to those in the available literature. As known, prematurity was the greatest complication.

Multidisciplinary management of congenital giant head and neck masses: Our experience and review of the literature.

BACKGROUND: Large fetal head and neck (HN) masses can be life-threatening at birth and postnatally owing to airway obstruction. The two most frequent congenital masses that may obstruct the airway are lymphatic malformation (LM) and teratoma. The aim of this paper was to evaluate the results of our experience in the management of giant congenital HN masses and to conduct a literature review. METHODS: The study involved a consecutive series of 13 newborns (7 females) affected by giant HN masses. Prenatal diagnosis was achieved by means of ultrasound (US) and fetal magnetic resonance imaging (MRI). Delivery was performed by means of EXIT procedure in case of radiological evidence of airway obstruction. In the postnatal period all feasible therapeutic options (surgery, sclerotherapy, medical therapy) were discussed and adopted by a multidisciplinary team. Twelve patients underwent surgery and one received Rapamycin for one month, with consequent surgical resection owing to increasing size of the mass. RESULTS: The histopathological diagnosis was LM in 11 cases and teratoma in 2 cases. Airway obstruction was solved in 11 cases; 2 LM patients required a tracheotomy because of persistent airway obstruction. Major complications were flap necrosis (one patient) and facial nerve palsy (2 cases). Recurrence occurred in 5 patients. CONCLUSIONS: The management of congenital HN masses is always challenging and necessarily requires an interdisciplinary approach. Current therapeutic options include surgery, sclerotherapy, medical therapy or a combination of them. When they are large enough to obstruct the airway, a patient-centered approach should guide timing and modality of treatment. LEVEL OF EVIDENCE: IV.

Tracheal Diameter and Respiratory Outcome in Infants with Congenital Diaphragmatic Hernia Treated by Fetal Endoscopic Tracheal Occlusion.

AIM: To evaluate tracheal diameters and their clinical impact in patients with congenital diaphragmatic hernia (CDH) after fetal endoscopic tracheal occlusion (FETO). METHODS: Patients born with CDH between January 2012 and August 2016 were divided into two groups: noFETO and FETO. Tracheal diameters at three levels (T1, carina, and maximum tracheal dilation) on chest X-ray at 1, 3, 6, 12, 24, and 36 months of follow-up, requirements of invasive and noninvasive respiratory support, the incidence of respiratory infections, and results of pulmonary function tests (PFT) were compared. RESULTS: A total of 71 patients with CDH were born in the study period, and there were 34/41 survivors in the no-FETO group (82.9%) and 13/30 in the FETO group (43.3%). The maximum tracheal diameter was significantly greater in the FETO group at all ages. No differences were observed in the diameters at T1 and the carina, in the requirements of invasive and noninvasive respiratory support, and in the incidence respiratory infections. At the PFT (6-12 months), the FETO group presented higher respiratory rates (46.1 ± 6.2 vs. 36.5 ± 10.6, p = 0.02). No differences in PFT results were found between the groups after the 1st year of life. CONCLUSIONS: The FETO procedure leads to persistent tracheomegaly. However, the tracheomegaly does not seem to have a significant clinical impact.

Is the new, noninvasive, continuous cardiorespiratory monitoring reliable during neonatal ECMO?

BACKGROUND: Advances in cardiorespiratory monitoring have made the extracorporeal membrane oxygenation (ECMO) technique safer for the patient. Noninvasive, continuous tools are available, although data on their applications in the neonatal ECMO setting are lacking. OBJECTIVE: We retrospectively described the neonatal clinical application of this continuous, noninvasive ECMO monitor and compared the analyzed parameters from those derived from blood gas analysis. MATERIALS AND METHODS: We performed 897 h of cardiorespiratory monitoring during neonatal venoarterial-ECMO (VA-ECMO) for four patients affected by (cardio-) respiratory failure, to compare the reliability of a noninvasive, continuous monitoring Spectrum M4® (M4) (Spectrum Medical, Gloucester, England) to an invasive, intermittent co-monitoring with blood gas analyzer (Radiometer Medical ApS, Brønshøj, Denmark). RESULTS: A range of 117 pairs (time-matched BGA-derived vs. M4-derived parameters) was retrospectively analyzed. T-test, linear regression and Bland-Altman analysis for hemoglobin, hematocrit, venous oxygen saturation, oxygen delivery, oxygen consumption, oxygen extraction ratio, oxygen partial pressure, and carbon dioxide partial pressure showed a strong relationship between the two monitors for all parameters analyzed (p < 0.0001). CONCLUSIONS: Continuous, noninvasive cardiorespiratory monitoring appears to be feasible and reliable, although its accuracy needs to be verified in a more extensive cohort.

Start a Neonatal Extracorporeal Membrane Oxygenation Program: A Multistep Team Training.

Background: Extracorporeal membrane oxygenation (ECMO) is a complex life-saving support for acute cardio-respiratory failure, unresponsive to medical treatment. Emergency events on ECMO are rare but require immediate and proficient management. Multidisciplinary ECMO team members need to acquire and maintain over time cognitive, technical and behavioral skills, to safely face life-threatening clinical scenarios. Methods: A multistep educational program was delivered in a 4-year period to 32 ECMO team members, based on guidelines from the Extracorporeal Life Support Organization. A first traditional module was provided through didactic lectures, hands-on water drills, and laboratory animal training. The second phase consisted of a multi-edition high-fidelity simulation-based training on a modified neonatal mannequin (SimNewB®). In each session, participants were called to face, in small groups, ten critical scenarios, followed by debriefing time. Trainees underwent a pre-test for baseline competency assessment. Once completed the full training program, a post-test was administered. Pre- and post-test scores were compared. Trainees rated the educational program through survey questionnaires. Results: 28 trainees (87.5%) completed the full educational program. ECMO staff skills improved from a median pre-test score of 7.5/18 (IQR = 6-11) to 14/18 (IQR = 14-16) at post-test (P < 0.001, Wilcoxon rank test). All trainees highly rated the educational program and its impact on their practice. They reported high-fidelity simulations to be beneficial to novice learners as it increased self-confidence in ECMO-emergencies (according to 100% of surveyed), theoretical knowledge (61.5%) and team-work/communicative skills (58%). Conclusions: The multistep ECMO team training increased staff' knowledge, technical skills, teamwork, and self-confidence, allowing the successful development of a neonatal respiratory ECMO program. Conventional training was perceived as relevant in the early phase of the program development, while the active learning emerged to be more beneficial to master ECMO knowledge, specific skills, and team performance.

Fetal Doppler changes 1 week after endoscopic equatorial laser for twin-to-twin transfusion syndrome: A longitudinal study.

OBJECTIVE: To investigate sequential Doppler changes in donors and recipients before and 1 week after endoscopic laser for twin-to-twin transfusion syndrome (TTTS) and to examine factors that may be associated with such changes. METHODS: In TTTS pregnancies undergoing laser treatment, we examined fetal Doppler changes before and 1 week postintervention. Intrauterine death rates and preoperative factors were analyzed in relation to Doppler changes. RESULTS: Among 129 (85.4%) donors surviving at 1 week after laser, there was normalization of umbilical artery flow in 26 (72.2%) of 36 cases with preoperative abnormal Dopplers. In the remaining 10 (27.8%) fetuses, abnormal findings persisted. The rate of later intrauterine death was significantly higher in the latter group (6 of 10, 60.0%) compared with fetuses in which Doppler findings normalized (4 of 26, 15.4%; P < .05), with no difference in the rate of severe donor growth restriction between the 2 groups (80.0% vs 65.4%, respectively; P = .688). CONCLUSIONS: In about 70% of TTTS donors with preoperative abnormal umbilical artery Doppler, there was normalization 1 week after endoscopic laser. The incidence of fetal growth restriction was not significantly different in donors with persistence of Doppler abnormalities compared with those with normalized findings.

The use of sirolimus in the treatment of giant cystic lymphangioma: Four case reports and update of medical therapy.

RATIONALE: Lymphatic malformations (LMs) are rare and benign anomalies resulting from the defective embryological development of the primordial lymphatic structures. Due to their permeative growth throughout all tissue layers, treatment is often challenging. Small asymptomatic lesions can be conservatively managed, while symptomatic lesions require active management. Surgery has been historically considered the treatment of choice, but today less invasive therapeutic options are preferred (sclerotherapy, laser therapy, oral medications). However, there are not uniform therapeutic protocols. Sirolimus is an oral medication that has been reported to be effective in the recent literature. Here we present the case of 4 newborns with giant multicystic lymphangioma treated with oral sirolimus after surgical resection had failed. PATIENT CONCERNS: At birth the LMs were clinically appreciated as giant masses involving different organs and structures. DIAGNOSES: All patients had a prenatal diagnosis of giant multicystic lymphangioma confirmed at histological and cytological analysis. INTERVENTIONS: Patients were treated with oral sirolimus after unsuccessful surgical resection. OUTCOMES: In all patients, sirolimus determined an overall reduction of the mass and a global involution from the macro- to the microcystic composition. Sirolimus was safe and poor disadvantages had been observed. The main and isolated adverse effect at laboratory analysis was progressive dyslipidemia, with increasing levels of total cholesterol and triglycerides. LESSONS: To date, our experience with sirolimus in the management of LMs is favorable. We recommend the use of sirolimus after unsuccessful surgical excision have been tried or when the surgical approach is not feasible. A multidisciplinary follow-up is needed to monitor disease evolution.

Fetoscopic Endoluminal Tracheal Occlusion in Fetuses with Severe Diaphragmatic Hernia: A Three-Year Single-Center Experience.

OBJECTIVE: To report on our experience in the prenatal treatment of severe congenital diaphragmatic hernia (CDH) by fetoscopic endoluminal tracheal occlusion (FETO). METHODS: Between 2012 and 2014, FETO was performed at our center in 21 cases of CDH considered to be severe based on sonographic measurement of observed/expected lung-to-head ratio (O/E LHR) and side of the defect. We reported pre- and postoperative ultrasound findings, procedure-related complications, pregnancy outcome and survival at 1-3 years of age. RESULTS: The median gestational age (GA) at balloon insertion was 28.1 weeks (range 26.0-31.1) and the median GA at delivery 34.7 weeks (range 31.6-39.0); delivery before 32 and 34 weeks occurred in 2 (9.5%) and 7 (33.3%) cases, respectively. Postnatal survival at 1-3 years of age in the 17 cases with isolated unilateral CDH was 47.1%. The percentage difference between pre-balloon removal O/E LHR and pre-FETO O/E LHR was significantly higher in survivors compared to neonates who died (40.8 vs. 21.2%, respectively; p < 0.05). CONCLUSIONS: In this study, FETO was associated with an infant survival of 47% in cases with isolated unilateral severe CDH. The post-FETO increase in O/E LHR was higher in fetuses that survived compared to those who died.

Delivery room management of extremely low birth weight infants in Italy: comparison between academic and non-academic birth centres.

OBJECTIVE: International Guidelines provide a standardised approach to newborn resuscitation in the DR and, in their most recent versions, recommendations dedicated to management of ELBWI were progressively increased. It is expected that introduction in clinical practice and dissemination of the most recent evidence should be more consistent in academic than in non-academic hospitals. The aim of the study was to compare adherence to the International Guidelines and consistency of practice in delivery room management of extremely low birth weight infants between academic and non-academic institutions. METHODS: A questionnaire was sent to the directors of all Italian level III centres between April and August 2012. RESULTS: There was a 92% (n = 98/107) response rate. Apart from polyethylene wrapping to optimise thermal control, perinatal management approach was comparable between academic and non-academic centres. CONCLUSIONS: There were minor differences in management of extremely low birth weight infants between Italian academic and non-academic institutions, apart from thermal management. Although there was a good, overall adherence to the International Guidelines for Neonatal Resuscitation, temperature management was not in accordance with official recommendations and every effort has to be done to improve this aspect.

Oxygen administration at birth in preterm infants: a retrospective analysis.

OBJECTIVE: The aim of the study was to retrospectively investigate the association between initial oxygen concentration in delivery room and short-term outcomes in preterm infants. METHODS: Data from infants needing neonatal resuscitation, born at our department between January 2008 and December 2011, were analyzed. Patients were divided into three groups based on gestational age: between 32 and 36 weeks, between 31 and 28 weeks, and below 28 weeks. RESULTS: The administration of each additional unit of oxygen up to 50% showed an association with a 5% increased need for mechanical ventilation (MV) in the neonatal intensive care unit in infants between 32 and 36 weeks [adjusted odds ratio 1.1, 95% confidence interval (CI) 1.04-1.1] and infants between 28 and 31 weeks (adjusted odds ratio 1.12, 95% CI 1.08-1.44). On the contrary, in infants below 28 weeks, increasing initial concentration of supplementary oxygen did not show any association with MV. CONCLUSIONS: Initial oxygen concentration seems to be associated with increased MV in the NICU. Our observations further stress the need for randomized controlled studies in order to obtain definitive recommendations for the optimal initial oxygen concentration during neonatal resuscitation of preterm infants.

Delivery room management of ELBW infants in Italy.

In this article we evaluated the consistency of practice and the adherence to the International Guidelines in early delivery room management of ELBW infants in Italy. A polyethylene bag/wrap was used by 54 centres (55.1%). In Northern regions, one centre (2.5%) reported to use oxygen concentrations >40% to initiate positive pressure ventilation in ELBW infants. These proportions were higher in the Central (14.3%) and Southern (16.2%) areas. A T-piece device for positive pressure ventilation was widely used (77/97, 79.4%). A median of 13% (IQR: 5%-30%) of ELBW infants received chest compressions at birth in Italy. Forty-seven out of 98 (47.9%) centres declared to administer prophylactic surfactant in delivery room. Although there were geographic differences in the country, our results showed a good general adherence to the International Guidelines for Neonatal Resuscitation.

Changes over time in delivery room management of extremely low birth weight infants in Italy.

AIM: To identify changes in practice between two historical periods (2002 vs. 2011) in early delivery room (DR) management of ELBWI in Italian tertiary centres. METHODS: A questionnaire was sent to the directors of all Italian level III centres between April and August 2012. The same questionnaire was used in a national survey conducted in 2002. Among the participating centres, those that filled the questionnaire in both study periods were selected for inclusion in this study. RESULTS: There was an 88% (n=76/86) and 92% (n=98/107) response rate in the 2 surveys, respectively. The two groups overlapped for 64 centres. During the study period, the use of polyethylene bags/wraps increased from 4.7% to 59.4% of the centres. The units using 100% oxygen concentrations to initiate resuscitation of ELBWI decreased from 56.2% to 6.2%. The approach to respiratory management was changed for the majority of the examined issues: positive pressure ventilation (PPV) administered through a T-piece resuscitator (from 14.0% to 85.9%); use of PEEP during PPV (from 35.9% to 95.3%); use of CPAP (from 43.1% to 86.2%). From 2002 to 2011, the percentages of ELBWI intubated in DR decreased in favor of those managed with N-CPAP; ELBWI receiving chest compressions and medications at birth were clinically comparable. CONCLUSIONS: During the two study periods, the approach to the ELBWI at birth significantly changed. More attention was devoted to temperature control, use of oxygen, and less-invasive respiratory support. Nevertheless, some relevant interventions were not uniformly followed by the surveyed centres.

Delivery room management of extremely low birthweight infants shows marked geographical variations in Italy.

AIM: To evaluate any geographical variations in practice and adherence to international guidelines for early delivery room management of extremely low birthweight (ELBW) infants in the North, Centre and South of Italy. METHODS: A questionnaire was sent to all 107 directors of Italian level III centres between April and August 2012. RESULTS: There was a 92% (n = 98) response rate. A polyethylene bag/wrap was used by 54 centres (55.1%), with the highest rate in Northern Italy (77.5%) and the lowest rate in Southern (37.7%) areas. In Northern regions, one centre (2.5%) said it used oxygen concentrations >40% to initiate positive pressure ventilation in ELBW infants. These proportions were higher in the Central (14.3%) and Southern (16.2%) areas. A T-piece device for positive pressure ventilation was more frequently available in the Northern (95%) units than in those in the Central (66.7%) and Southern (69.4%) regions. A median of 13% (IQR: 5%-30%) of ELBW infants received chest compressions at birth in Italy: 5%, 18% and 22% in Northern, Central and Southern units, respectively. CONCLUSION: In Italy, delivery room management of ELBW infants showed marked geographical variations. Implementation of national training programmes could increase adherence to the guidelines and reduce such discordance.

Oxygen administration for the resuscitation of term and preterm infants.

Oxygen has been widely used in neonatal resuscitation for about 300 years. In October 2010, the International Liaison Committee on Neonatal Resuscitation released new guidelines. Based on experimental studies and randomized clinical trials, the recommendations on evaluation and monitoring of oxygenation status and oxygen supplementation in the delivery room were revised in detail. They include: inaccuracy of oxygenation clinical assessment (colour), mandatory use of pulse oximeter, specific saturation targets and oxygen concentrations during positive pressure ventilation in preterm and term infants. In this review, we describe oxygen management in the delivery room in terms of clinical assessment, monitoring, treatment and the gap of knowledge.

Nasal continuous positive airway pressure with heliox in preterm infants with respiratory distress syndrome.

OBJECTIVE: To assess the therapeutic effects of breathing a low-density helium and oxygen mixture (heliox, 80% helium and 20% oxygen) in premature infants with respiratory distress syndrome (RDS) treated with nasal continuous positive airway pressure (NCPAP). METHODS: Infants born between 28 and 32 weeks of gestational age with radiologic findings and clinical symptoms of RDS and requiring respiratory support with NCPAP within the first hour of life were included. These infants were randomly assigned to receive either standard medical air (control group) or a 4:1 helium and oxygen mixture (heliox group) during the first 12 hours of enrollment, followed by medical air until NCPAP was no longer needed. RESULTS: From February 2008 to September 2010, 51 newborn infants were randomly assigned to two groups, 24 in the control group and 27 in the heliox group. NCPAP with heliox significantly decreased the risk of mechanical ventilation in comparison with NCPAP with medical air (14.8% vs 45.8%). CONCLUSIONS: Heliox increases the effectiveness of NCPAP in the treatment of RDS in premature infants.