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.

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.

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.

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.

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.

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.

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.

[Retropharingeal abscess in paediatrics]. / Absceso retrofaringeo en pediatría.

Retropharingeal abscess is a potentially lethal but infrequent infection of the retropharyngeal space, thanks to the use of antibiotics. Caused by a suppurative lymphadenitis secondary to a locoregional infection of the head and neck, it is the most frequent abscess in Paediatric age. It must be present in our differential diagnosis when facing a torpid development of head and neck infectious processes accompanied by adenitis. A cervical lateral X-Ray should be done without delay and in case of doubt, a CAT--scan is mandatory. We protocolise its diagnosis and treatment in order to avoid its serious complications.

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.

[Vaginal swab in pediatric age]. / II tampone vaginale in età pediatrica.

Vaginal secretion sampling in young patients. The aim of the study was to evaluate whether different instrumental tools (the classical cotton swab, the urethral cotton swab, the balloon shape cotton swab and cyto-brush) yield different sampling success in young patients presenting with suspected vulvovaginitis. The study was conducted in a randomised prospective way on 100 children with symptoms of vulvovaginal infection (age range: 4 months -8 years ) seen at the Clinic of Paediatric Gynaecology of the Department of Obstetric and Gynaecology, "V.Buzzi" Children's Hospital, Milano (Italy). Children's compliance and the number of samples which had to be discontinued, because of children's intolerance have allowed the evaluation of each tools. Each of these tools was tested on 25 young patients. The vaginal secretion sampling was not possible on 8 patients out of 25 with cyto-brush (32%), on 7 out of 25 with the balloon shape cotton swab (28%), on 4 out of 25 with the classical cotton swab (16%) and only 1 out of 25 with the urethral cotton swab (4%). In conclusion all the instruments tested allow sampling of vaginal secretion in young children, but the reaction and compliance of the patients has been best with the otologic cotton swab.

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.

Impact of targeted-volume ventilation on lung inflammatory response in preterm infants with respiratory distress syndrome (RDS).

Volutrauma and pulmonary inflammation are thought to be the most important predisposing factors of chronic lung disease (CLD), a major complication of prematurity. A new option in patient-triggered ventilation (PTV), the volume guarantee (VG), a volume-targeted ventilation, seems to be a promising approach in reducing the risk of CLD, by limiting lung inflammatory injury and volutrauma. Our aim was to evaluate lung inflammatory response in preterm infants with respiratory distress syndrome (RDS), mechanically ventilated with and without VG, as measured by proinflammatory cytokines (IL-6, IL-8, and TNF-alpha) in tracheobronchial aspirate (TA) fluid. Fifty-three preterm infants (GA = 25-32 weeks) with RDS were randomized at birth to be ventilated using pressure support ventilation (PSV) with VG (Vt = 5 ml/kg) (n = 30) and without VG (n = 23) (Draeger Babylog 8000 Plus, 5.n). IL-6, IL-8, and TNF-alpha were determined by ELISA in TA samples on days 1, 3, and 7 of life. We observed a significant difference (ANOVA) in IL-8 and IL-6 levels on day 3 between the two groups (P < 0.05), and an increasing significative trend in IL-8 values in PSV group (P < 0.05). Mechanical ventilation lasted longer in the PSV group (12.3 +/- 3 vs. 8.8 +/- 3 days) (P = no significance). In conclusion, these preliminary data suggest a role for volume-targeted ventilatory strategy in reducing acute inflammatory response in preterm infants with RDS. Further studies are required in order to define whether this ventilatory strategy prevents lung injury.

[HLA typing in a neonate with posttransfusional graft vs host disease (PT-GVHD)]. / Tipizzazione HLA in un neonato affetto da "graft versus host disease" post trasfusionale (PT-GVHD).

The authors report a case of post-transfusion-graft-versus-host disease (PT-GVHD) in a premature infant after parental blood donation. This disease seems to be due to the transfusion of immunocompetent T lymphocytes into an immunodeficient recipient or into an immunocompetent host who shares an HLA haplotype with HLA-homozygous blood donors (i.e. relatives or members of inbred populations) and who is therefore unable to reject the graft cells. The results of HLA typing of the patient and his family demonstrated that the infant was identical with his father for HLA class II antigens (DR, DQ) and, concerning HLA class I, he had in common the remaining paternal haplotype (A29, B44). Prevention of this disease, performed by gamma irradiation of blood components before transfusion, appears to be effective in most cases.

[Spontaneous regression of an adrenal mass detected in utero]. / Risoluzione spontanea di massa surrenalica diagnosticata in utero.

The case of a left adrenal mass detected by ultrasonography in a male fetus at the 37th week of gestation is presented. After an uneventful delivery at the 38th gw, the newborn was sonographically monitored, and during the follow-up clinical evaluations were performed, in order to make a differential diagnosis between an adrenal hemorrhage and a congenital neuroblastoma. VMA and HVA were within normal levels, and MIGB scan was negative. A MR of the the abdomen performed at the age of one month was suggestive for an adrenal hemorrhage in involution. We therefore decided to keep monitoring the mass by ultrasound, avoiding any surgical approach. The sonographic complete disappearance of the disease was documented at the end of the fourth month.

Correlations between volume delivery (VTHF) in course of high frequency oscillatory ventilation (HFOV) and severity of respiratory distress.

The treatment of severe respiratory distress in infants (e.g. respiratory distress syndrome--RDS, meconium aspiration syndrome--MAS and pulmonary haemorrage) with HFOV can cause sometimes a volume delivery (VTHF) exceeding the anatomical dead space, with the possibility of an increased risk of volutrauma, implicated in the pathogenesis of chronic lung disease (CLD). The authors examined the possible correlations between VTHF and the severity of respiratory distress in order to limit the risk of ventilator-induced lung injury (VILI). Thirty-five infants in HFOV because of respiratory distress were studied. The median VTHF registered was 2.25 ml/Kg (range: 1.3-3.4) with a significant correlation to some parameters espression of severity of the respiratory distress: arterial/Alveolar ratio (a/AO2) (r = 0.519), oxygen index (OI) (r = 0.512) and mean airway pressure (MAP) (r = 0.543).

[Lung injury and ventilatory strategies]. / Danno polmonare e strategie ventilatorie.

Premature lungs are highly susceptible to lung injury induced by chorioamionitis, mechanical ventilation or persistent exposure to high O2 concentrations. The Authors linger on the central role of atelectrauma and volutrauma (by inadequate tidal volume-Vt) in course of mechanical ventilation of preterm infants with RDS. In particular, they evaluate the efficacy and safety of the targeted volume ventilation with the option of the Volume Guarantee (VG). For this reason they present the results of randomized clinical trials in preterm infants (25-32 wks of gestational age) with severe RDS, in mechanical ventilation, without VG or with two different VG (Vt = 3 or 5 ml/Kg). Data collected demonstrate a significative difference (p < 0.05) in terms od reduction of mean airway pressure (PAW), peak inspiratory pressure (PIP) and cytokines production (IL6-IL8 and TNF alfa) in tracheal aspirate fluid in preterm infants in synchronized ventilation with VG set at 5 ml/Kg. These preliminary results seem to demonstrate the protective role of targeted volume ventilation with Vt = 5 ml/Kg (minimal volutrauma with less lung inflammatory response), but without significative reduction of chronic lung disease (CLD) in this group (probably due to multifactorial pathogenesis of CLD).