Post-ligation cardiac syndrome after surgical versus transcatheter closure of patent ductus arteriosus in low body weight premature infants: a multicenter retrospective cohort study.

Transcatheter patent ductus arteriosus (PDA) closure is a safe and effective alternative to surgical ligation in low-body-weight infants. Post-ligation cardiac syndrome (PLCS) is defined as severe hemodynamic and respiratory collapse within 24 h of PDA closure, requiring initiation or an increase of an inotropic agent by > 20% of preligation dosing and an absolute increase of at least 20% in ventilation parameters compared with the preoperative value. Whilst PLCS is routinely observed after surgery, its incidence remains poorly described following transcatheter closure. This study aimed to compare the incidence of PLCS after surgical versus transcatheter closure of PDA in low-body-weight premature infants. Propensity scores were used to compare surgical (N = 78) and transcatheter (N = 76) groups of preterm infants who underwent PDA closure at a procedural weight less than 2000 g in two tertiary institutions between 2009 and 2021. The primary outcome was the incidence of PLCS. Secondary outcomes included overall mortality before discharge, risk factors for PLCS, and post-procedural complications. Procedural success was 100% in both groups. After matching, transcatheter group experienced no PLCS vs 15% in the surgical group (p = 0.012). Furthermore, overall mortality (2% vs 17%; p = 0.03) and major complications (2% vs 23%; p = 0.002) were higher in the surgical group. Surgery (100% vs 47%; p < 0.01), gestation age (25 ± 1 vs 26 ± 2 weeks, p < 0.05) and inotropic support before closure (90% vs 29%; p < 0.001) were associated with PLCS occurrence.          Conclusion: Transcatheter PDA closure may be equally effective but safer than surgical PDA closure in low-body-weight premature infants. What is Known: • Post-ligation cardiac syndrome is a serious and common complication of surgical closure of the ductus arteriosus in preterm infants. • Transcatheter closure of preterm ductus arteriosus is a safe and effective technique that is becoming more and more common worldwide. What is New: • Device closure is safer than surgical ligation for patent ductus arteriosus closure in preterm infants and may be the first-line non-pharmacological therapeutic option in this indication in experienced teams. • Our findings should encourage neonatologists and pediatric cardiologists to start and/or strengthen a durable interventional program for transcatheter PDA closure in premature infants.

Increasing the dose of ibuprofen with postnatal age to close a hemodynamically significant patent ductus arteriosus in very preterm infants.

Patent ductus arteriosus (PDA) is associated with neonatal morbidities in high-risk preterm infants. Early neonatal treatment by ibuprofen induces the ductus arteriosus (DA) closure in approximatively 60% of infants. Dose escalation of ibuprofen according to postnatal age has been suggested for improving the DA closure rate. The aim of this study was to assess the efficacy and tolerance of an increasing dose regimen of ibuprofen. This single-center retrospective cohort study involved infants hospitalized from 2014 to 2019 in our neonatal unit. Selection criteria were gestational age < 30 weeks, birth weight < 1000 g, and treatment by ibuprofen. Three dose levels were used and consisted of a daily intravenous injection of ibuprofen-tris-hydroxymethyl-aminomethane (ibuprofen-THAM) for three consecutive days: (i) 10 -5 -5 mg/kg before the 70th h of life (H70) (dose level 1), (ii) 14 -7 -7 mg/kg between H70 and H108 (dose level 2), (iii) 18 -9 -9 mg/kg after H108 (dose level 3). The ibuprofen-induced DA closure was compared between ibuprofen schedules, and the Cox proportional-hazard regression was performed to identify factors associated with the ibuprofen efficacy. Tolerance was assessed through renal function, acidosis, and platelet count. One hundred forty-three infants met the inclusion criteria. The ibuprofen-induced DA closure was observed in 67 infants (46.8%). One course of ibuprofen at dose level 1 was more efficient in closing the DA than other schedules (dose level 1, one course (n = 70): 71%, dose level 2 or 3, one course (n = 20): 45%, two-course schedules (n = 53): 15%, p < 0.0001). Independent factors associated with ibuprofen-induced DA closure were a complete antenatal schedule of steroids (p = 0.001), a lower CRIB II score (p = 0.009), and a lower and earlier exposure to ibuprofen (p < 0.0001 and p = 0.002). No severe side effects were observed. Neonatal mortality and morbidities were similar regardless of the infant's response to ibuprofen.  Conclusion: Increasing ibuprofen doses with postnatal age failed to reach an efficacy similar to earlier treatment. Although the infant response to ibuprofen was likely to depend on multiple factors, the optimal use of ibuprofen included its early initiation. What is Known: • Ibuprofen is the current first-line treatment for patent ductus arteriosus during the early neonatal period in very preterm infants. • However, the ibuprofen efficacy rapidly declined with postnatal age during the first week of life. A dose escalation of ibuprofen according to postnatal age has been suggested to improve the ibuprofen-induced ductus arteriosus closure. What is New: • The rapid drop of ibuprofen's ability to close hemodynamically significant patent ductus arteriosus persisted beyond the postnatal day 2 despite the dose adjustment arguing for an early initiation to optimize its efficacy. • The early selection of patients who will suffer from patent ductus arteriosus-related morbidities and who will positively respond to ibuprofen is an issue that could determine the future place of ibuprofen in the patent ductus arteriosus management.

Staphylococcus capitis isolated from bloodstream infections: a nationwide 3-month survey in 38 neonatal intensive care units.

To increase the knowledge about S. capitis in the neonatal setting, we conducted a nationwide 3-month survey in 38 neonatal intensive care units (NICUs) covering 56.6% of French NICU beds. We demonstrated 14.2% of S. capitis BSI (S.capBSI) among nosocomial BSIs. S.capBSI incidence rate was 0.59 per 1000 patient-days. A total of 55.0% of the S.capBSIs were late onset catheter-related BSIs. The S. capitis strains infected preterm babies (median gestational age 26 weeks, median birth weight 855 g). They were resistant to methicillin and aminoglycosides and belonged to the NRCS-A clone. Evolution was favorable in all but one case, following vancomycin treatment.

Systematic ultrasound examinations in neonates admitted to NICU: evolution of portal vein thrombosis.

OBJECTIVE: The aim of the study was to better describe incidence, risk factors, and the natural evolution of neonatal portal vein thrombosis (PVT). STUDY DESIGN: One hundred and twenty-three premature newborns or with birth weight <1.5 kg were prospectively included in a single center during a one-year period. Three systematic abdominal ultrasound examinations at day 3, day 10, and day 45 (and 1 year in case of persistent PVT) were performed. Clinical and biological data were recorded. RESULTS: Seventy neonates (57%) had three normal US examinations. Fifty-three neonates (43%) had a clinical and biological asymptomatic left PVT. No right or extrahepatic portal venous thrombosis was observed. Umbilical vascular catheter (UVC) was removed in case of PVT. No anticoagulation therapy was required. No risk factor was significantly associated with PVT. At 1 year of follow-up, five infants had persistent isolated left PVT (4%). CONCLUSION: A spontaneous favorable evolution of left PVT occurred in more than of 95%.

Late Surfactant Administration in Very Preterm Neonates With Prolonged Respiratory Distress and Pulmonary Outcome at 1 Year of Age: A Randomized Clinical Trial.

IMPORTANCE: Although immature neonate survival has improved, there is an increased risk of developing bronchopulmonary dysplasia, leading to significant respiratory morbidity. Measures to reduce bronchopulmonary dysplasia are not always effective or have important adverse effects. OBJECTIVE: To evaluate the effect of late surfactant administration in infants with prolonged respiratory distress on ventilation duration, respiratory outcome at 36 weeks' postmenstrual age, and at 1 year postnatal age. DESIGN, SETTING, AND PARTICIPANTS: Double-blind randomized clinical trial at 13 level III French perinatal centers. Participants included 118 neonates at less than 33 weeks' gestation who still required mechanical ventilation on day 14 (SD, 2) with fraction of inspired oxygen of more than 0.30. All survivors were eligible for follow-up. We performed an intent-to-treat analysis. INTERVENTIONS: Infants received 200 mg/kg of poractant alfa (surfactant) or air after randomization. At 1 year, after parents' interview, infants underwent physical examination by pediatricians not aware of the randomization. MAIN OUTCOMES AND MEASURES: The duration of ventilation was the primary outcome. The combined outcome of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age and respiratory morbidity at 1 year of age were the main secondary outcome measures. RESULTS: Of the 118 infants who participated in the study, 65 (55%) were male. Fraction of inspired oxygen requirements dropped after surfactant, but not air, for up to 24 hours after instillation (0.36 [0.11] vs 0.43 [0.18]; P < .005). Severe bronchopulmonary dysplasia/death rates at 36 weeks' postmenstrual age were similar (27.1% vs 35.6%; P = .32). Less surfactant-treated infants needed rehospitalization for respiratory problems after discharge (28.3% vs 51.1%; P = .03); 39.5% vs 50% needed respiratory physical therapy (P = .35). No difference was observed for weight (7.8 [1.2] kg vs 7.6 [1.1] kg), height (69 [5] cm vs 69 [3] cm), and head circumference (44.4 [1.7] cm vs 44.2 [1.7] cm) measured at follow-up, nor for neurodevelopment outcome. CONCLUSIONS AND RELEVANCE: Late surfactant administration did not alter the early course of bronchopulmonary dysplasia. However, surfactant-treated infants had reduced respiratory morbidity prior to 1 year of age. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01039285.

A Reproducible and Individualized Method to Predict Osmolality of Compounded Pediatric Parenteral Nutrition Solutions.

BACKGROUND: Osmolality is a well-known factor in complications associated with parenteral nutrition (PN). The osmolality of compounded pediatric PN solutions is often inappropriately approximated by theoretical osmolarity, which carries a major risk of underestimation, especially in highly concentrated solutions. Only a few studies have proposed equations to overcome this problem, and to date their accuracy in settings other than those of their development has not been assessed. We propose a reproducible method to develop a predictive model of osmolality adapted to local practice, and we compare its predictive performance to osmolarity calculation and other equations. METHODS: From measures performed on dilutions of basic components of PN solutions, a predictive model establishing the relationship between the quantitative and qualitative composition of a PN solution and its osmolality was developed. This model was validated in routine practice on daily compounded pediatric PN solutions, and its predictive performance was compared with osmolarity calculation, 2 previously published predictive equations, and multilinear regression. RESULTS: We measured the osmolality of 321 routinely produced PN solutions. The model predicted osmolality with a mean relative error of -0.28% (±2.75%). All the other ways to approximate osmolality were less precise and sometimes provided critically underestimated values (from -16.67% to -33.24%). CONCLUSIONS: Our model predicted osmolality accurately and may be used in routine practice in any setting once adapted to the local production practice. Approximations by osmolarity severely underestimate actual osmolality. Keeping osmolarity <800 mOsm/L seems sufficient to ensure that actual osmolality does not exceed 1000 mOsm/kg.

Effect of persistent patent ductus arteriosus on mortality and morbidity in very low-birthweight infants.

AIM: Because New Caledonia is geographically isolated from the nearest cardiac surgical centre, surgical closure of ductus arteriosus is not performed in very low-birthweight (VLBW) infants who have a persistent patent ductus in spite of having undergone treatment with ibuprofen. This study aimed at investigating the possible effect of persistent patent ductus in VLBW infants. METHODS: The study included 177 VLBW infants born at 25-31 weeks of gestation from January 2006 to May 2011. Mortality and major morbidities were compared between infants with a persistent patent ductus (n = 33) and those without it (n = 104). Statistical associations between potential neonatal risk factors and significant morbidities were identified using multivariate regression analyses. RESULTS: Rates of mortality and major morbidities, including the rate of bronchopulmonary dysplasia, necrotizing enterocolitis, intraventricular haemorrhage grades I-II and III-IV, periventricular leucomalacia, late-onset infections and failure of hearing screening, were insignificantly higher in VLBW infants with a persistent patent ductus than in those without it. CONCLUSION: This study adds further evidence that persistent patent ductus arteriosus has no significant effect on mortality and morbidity in VLBW infants born at ≥25 weeks' gestational age.

Impaired lung function after intubation and mechanical ventilation for surgical ligation of the ductus arteriosus in preterm infants.

OBJECTIVE: Significant patent ductus arteriosus (PDA) in the preterm infant has been associated with pulmonary edema and impaired gas exchange. Therefore, surgical ligature of the DA may be required. However, the effects of intubation and mechanical ventilation on the PDA-induced lung dysfunction presently are unknown. The aim of the study was to investigate whether intubation and mechanical ventilation alter pulmonary function in the preterm infant with significant PDA. DESIGN: A prospective study. SETTING: The neonatal intensive care unit and department of anesthesiology in a university hospital. PARTICIPANTS: Preterm infants <32 weeks' gestational age treated with nasal continuous positive airway pressure (NCPAP) and requiring mechanical ventilation for undergoing surgical DA ligature. INTERVENTIONS: Respiratory, Doppler echocardiographic parameters, and chest x-ray transparencies of the lungs were measured during NCPAP and 2 hours after intubation and starting mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Twenty preterm infants (gestational age = 27 ± 1 wk, birth weight = 950 ± 140 g) were included. Heart rate, O(2) need, PaCO(2), and plasma lactate concentrations were significantly higher after intubation. The mean oxygenation index increased from 1.5 ± 0.6 to 7.2 ± 3 (p < 0.05). The overall transparencies of the lungs decreased after intubation. DA diameter, shortening fraction of the left ventricle, left pulmonary artery blood flow velocities, and left atrium/aorta did not change. CONCLUSION: In preterm infants with significant PDA, intubation and mechanical ventilation before surgical DA ligation may increase the O(2) need and PaCO(2) and may promote lung edema formation. Mechanical ventilation-induced impairment in lung function is not associated with a change in pulmonary or systemic circulation or DA flow. Special care should be taken to prevent respiratory failure when intubation and mechanical ventilation are required for undergoing surgical DA ligation in the preterm infant.

A new technique for interrupted aortic arch repair: the Neville tube.

We have developed a new technique for interrupted aortic arch repair in which the pulmonary artery anterior wall is cut off and tailored so as to re-establish aortic continuity with an autologous tube. We are describing this method herein, with an 8-year follow-up of the first patient.

Hypotension in preterm infants with significant patent ductus arteriosus: effects of dopamine.

OBJECTIVE: To study the effects of dopamine on systemic arterial pressure (SAP) and systemic blood flow (SBF) (estimated with the superior vena cava [SVC] flow) in preterm infants with hypotension and patent ductus arteriosus (PDA). STUDY DESIGN: Clinical and echocardiographic variables were measured before and 2 hours after starting dopamine in premature infants <32 weeks gestational age with PDA and systemic hypotension. RESULTS: Seventeen premature infants were included (gestational age, 28+/-2 weeks; birth weight, 1030 +/- 400 g). A mean rate of 8 +/- 2 microg/kg/min of dopamine raised SAP from 30 +/- 3 to 41 +/- 5 mm Hg (P < .05), and the pulmonary artery pressures from 25 +/- 5 to 32 +/- 8 mm Hg (P < .05). The SVC flow increased by 30% (from 130 +/- 40 to 170 +/- 44 mL/kg/min; P < .05). The left ventricular output and the end-diastolic and mean left pulmonary artery blood flow velocities did not change despite the increase in pulmonary artery pressure. CONCLUSION: In preterm infants with hypotension and PDA, dopamine (<10 microg/kg/min) increases the systemic blood pressure and the systemic blood flow. Our results suggest that dopamine decreases left-to-right shunting across ductus arteriosus, caused by a rise in pulmonary vascular resistances.

Pulmonary circulatory effects of norepinephrine in newborn infants with persistent pulmonary hypertension.

OBJECTIVE: To evaluate the respiratory and the pulmonary circulatory effects of norepinephrine in newborn infants with persistent pulmonary hypertension (PPHN)-induced cardiac dysfunction. STUDY DESIGN: Inclusion criteria were: 1) Newborn infants >35 weeks gestational age; 2) PPHN treated with inhaled nitric oxide; and 3) symptoms of circulatory failure despite adequate fluid resuscitation. Lung function and pulmonary hemodynamic variables assessed with Doppler echocardiography were recorded prospectively before and after starting norepinephrine. RESULTS: Eighteen newborns were included (gestational age: 37 +/- 3 weeks; birth weight: 2800 +/- 700 g). After starting norepinephrine, systemic pressure and left ventricular output increased respectively from 33 +/- 4 mm Hg to 49 +/- 4 mm Hg and from 172 +/- 79 mL/kg/min to 209+/-90 mL/kg/min (P < .05). Although the mechanical ventilatory variables have not been changed, the post-ductal transcutaneous arterial oxygen saturation increased from 89% +/- 1% to 95% +/- 4%, whereas the oxygen need decreased from 51% +/- 24% to 41% +/- 20% (P < .05). The pulmonary/systemic pressure ratio decreased from 0.98 +/- 0.1 to 0.87 +/- 0.1 (P < .05). Mean left pulmonary artery blood flow velocity increased by 20% (P < .05). CONCLUSION: Norepinephrine may improve lung function in newborn infants with PPHN through a decrease in pulmonary/systemic artery pressure ratio and improved cardiac performance.