Implementation of less-invasive surfactant administration in a Canadian neonatal intensive care unit.

BACKGROUND: Less-invasive surfactant administration (LISA) is a recent technique used extensively in Europe but rarely used in North America. The aim of this study was to describe our experience following LISA implementation using poractant in a Canadian neonatal intensive care (NICU). METHODS: A retrospective analysis was conducted from June 2017 to April 2021 of LISA procedures in preterm infants. Data were collected on patient characteristics, outcomes following LISA, laryngoscopy, and adverse events. The primary outcome was the rate of successful LISA procedures. SETTING: Level IIIa academic NICU. RESULTS: LISA was successful in 93 of 101 infants (92%). Median gestational age was 30.9 weeks (interquartile range [IQR]: 29.4-33.0). All infants received atropine and fentanyl premedication. Eight LISA procedures were unsuccessful: five because of thoracic rigidity and three because of inability to expose the vocal cords. In the 93 successful procedures, a second dose of surfactant was needed for 15 of 93 infants (16.1%), either by repeated LISA (7/15; 7.5%) or by endotracheal intubation (8/15; 8.6%). In 63.4% of successful procedures, one laryngoscopy attempt was made. The median duration of laryngoscopy attempts was 60 s (IQR: 52-110). Two types of catheters were used: the multi-access catheter (MAC) or the Angiocath in 67% and 33% of procedures, respectively. One infant had bradycardia and 30.6% had profound desaturation of <75%. CONCLUSION: LISA with poractant alfa was implemented in a Canadian NICU with a high degree of procedural success. Fentanyl may lead to more adverse events with a risk of interrupting LISA and may not be the ideal agent for this procedure. These results may encourage wider dissemination of LISA in North America.

The Relationship between Antenatal Corticosteroid Administration-to-Delivery Intervals and Neonatal Respiratory Distress Syndrome and Respiratory Support.

Background: Administration of antenatal corticosteroids (ACSs) is an effective strategy for managing preterm infants, which improves neonatal respiratory distress syndrome (NRDS) and attenuates the risk of neonatal mortality. However, many preterm infants are not exposed to a complete course of ACS administration, and the effects of different ACS-to-delivery intervals on NRDS and respiratory support remain unclear. Therefore, this study explored the relationship between ACS-to-birth intervals and NRDS and respiratory support in preterm infants. Methods: In this retrospective cohort study, the preterm infants born between 240/7 and 316/7 wks of gestation were recruited from January 2015 to July 2021. All participants were categorised based on the time interval from the first ACS dose to delivery: <24 h, 1-2 d, 2-7 d, and >7 d. Multivariable logistic regression analysis examined the relationships between the ACS-to-birth interval and primary or secondary outcome while adjusting for potential confounders. Results: Of the 706 eligible neonates, 264, 83, 292, and 67 received ACS-to-delivery intervals of <24 h, 1-2 d, 2-7 d, and >7 d, respectively. After adjusting these confounding factors, the multivariable logistic analysis showed a significantly increased risk of NRDS (aOR: 1.8, 95% CI: 1.2-2.7), neonatal mortality (aOR: 2.8, 95% CI: 1.1-6.8), the need for surfactant use (aOR: 2.7, 95% CI: 1.7-4.4), endotracheal intubation in the delivery room (aOR: 1.9, 95% CI: 1.0-3.7), and mechanical ventilation (aOR: 1.9, 95% CI: 1.1-3.4) in the ACS-to-delivery interval of <24 h group when compared with the ACS-to-birth interval of 2-7 d group. Conclusions: Neonatal outcomes such as NRDS, neonatal mortality, the need for surfactant use, intubation in the delivery room, and the risk of mechanical ventilation are higher when the neonates are exposed to an ACS interval for less than 24 h before delivery.

Lipocalin-2 silencing suppresses inflammation and oxidative stress of acute respiratory distress syndrome by ferroptosis via inhibition of MAPK/ERK pathway in neonatal mice.

Neonatal acute respiratory distress syndrome (ARDS) has high morbidity and mortality rates worldwide, but there is a lack of pharmacologic treatment and clinical targeted therapies. In this study, we aimed to explore the effects of Lipocalin-2 (LCN2) on ferroptosis-mediated inflammation and oxidative stress in neonatal ARDS and the potential mechanism. In this study, we established an in vivo ARDS mouse model and an in vitro ARDS cell model by LPS (Lipopolysaccharide) stimulation. Lung tissue injury was evaluated by wet/dry ratios and histopathological examination. LCN2 expression was detected by qRT-PCR and Western blot. Inflammatory factors, oxidative stress and apoptosis were also detected. Ferroptosis was identified by detection of Fe2+ level and ferroptosis-associated protein expressions. Mitogen-activated protein kinases (MAPK)/extracellular signal-regulated kinase (ERK) pathway signaling was examined by Western blot analysis. The data revealed that LCN2 expression was significantly upregulated in neonatal mice with ARDS. Interference with LCN2 protected LPS-induced lung in neonatal mouse by reducing the radio of wet/dry and alleviating pathological damages. In addition, LCN2 silencing repressed LPS-induced inflammation, oxidative stress in vivo and in vitro, as well as apoptosis. Meanwhile, decreased level of Fe2+ and transferrin while increased levels of ferritin heavy chain 1 (FTH1) and glutathione peroxidase 4 (GPX4) were observed. The expression MAPK/ERK pathway was inhibited by depletion of LCN2. The present results suggest that LCN2 knockdown protected LPS-induced ARDS model via inhibition of ferroptosis-related inflammation and oxidative stress by inhibiting the MAPK/ERK pathway, thereby presenting a novel target for the treatment of ARDS.

Effects on extravascular lung water of lung protective ventilation strategy applied on piglets with acute respiratory distress syndrome induced by paraquat / 中华劳动卫生职业病杂志

Objective: To study the effects on extravascular lung water of lung protective ventilation strategy applying on piglets with acute respiratory distress syndrome (ARDS) induced by paraquat (PQ) under pulse indicating continuous cardiac output (PiCCO) monitoring. Methods: The piglets models with ARDS induced by PQ were established in June 2020 and all of them were received mechanical ventilation and divided into three groups according to tidal volume (V(T)) : small V(T) group (6 ml/kg) , middle V(T) group (10 ml/kg) and large V(T) group (15 ml/kg) , there were 5 piglets in each group. The positive end expiratory pressure (PEEP) were all setup on 10 cmH(2)O. The indexes such as arterial blood gas analysis, oxygenation index (OI) , extravascular lung water index (ELWI) and pulmonary vascular permeability index (PVPI) were monitored at time of before the model was established (baseline) , time of the model was established (t(0)) and 2 h (t(2)) , 4 h (t(4)) , 6 h (t(6)) after mechanical ventilation. Lung tissue were punctured at time of baseline, t(0) and t(6) to be stained by Hematoxylin-eosin (HE) staining and pulmonary pathology were observed under light microscopy. Results: The heart rate (HR) , mean arterial pressure (MAP) and partial pressure of carbon dioxide (PaCO(2)) of all groups were higher than the base value while the pH values, partial pressure of oxygen (PaO(2)) and OI were lower than the base value when the models were established (P<0.05) . After mechanical ventilation, the HR and MAP values of all groups at t(2), t(4) and t(6) were lower than t(0) while the PaCO(2) of t(4) and t(6) were all higher than t(0), the differences were statistically significant (P<0.05) . The PaO(2) and OI of all groups showed a trend of rising at first and then decreasing after mechanical ventilation. The MAP, PaO(2), PaCO(2) and OI of the middle V(T) group and large V(T) group were apparently lower than that of the small V(T) group at t(2), t(4) and t(6) (P<0.05) . The ELWI and PVPI at t(0) of all groups were higher than that of baseline (P<0.05) . The ELWI of the small V(T) group at t(6) were lower than t(0) of the same group and t(6) of the middle V(T) group and large V(T) group (P<0.05) . HE staining showed congestion and edema of alveolar tissue, swelling of capillaries, exudation of red blood cells and widening of alveolar septum in piglets after successful modeling. And further widening of alveolar septum and rupture of alveolar septum could be seen in the lung tissues of each group at t(6), and the injury was the slightest in the small V(T) group. Conclusion: The lung protective ventilation strategy can alleviate the extravascular lung water and ARDS induced by PQ and improve oxygenation.

Comparison of respiratory distress syndrome amongst preterm twins (28-34 Weeks) born within and after two weeks of completion of single antenatal corticosteroid course: A bidirectional cohort study.

BACKGROUND: The literature on neonatal outcomes in preterm twins delivered before 34 weeks but within and after 14 days of a single initial steroid course is limited. MATERIAL AND METHODS: This bidirectional (226 prospective and 42 retrospectives) cohort study was performed at a tertiary care teaching hospital in South India. We compared the respiratory distress syndrome and neonatal death amongst preterm twins from 28 to 34 weeks born < 14 days (Group A, n=268) and after 14 days (Group B, n=268) of completion of a single course of antenatal steroids. We used multivariable regression analysis (log-binomial model) to adjust for confounding variables. We generated a propensity-matched score with probit regression to analyse outcomes (respiratory distress and neonatal deaths). RESULTS: The two groups had significant differences in the distribution of birthweight, gestation period and mode of delivery. On adjusted analysis, the period of gestation below 33 weeks and weight below 1.5 kg had the maximum influence on respiratory and other morbidities, and weight less than 1 kg on neonatal death. [adjusted relative risk (ARR) 26.06, (95%CI=2.37-285.5), p=0.008]. On propensity scoring after matching all these variables, we found an [ARR of 2.0 (95% CI: 1.03-3.88), P=0.017] for neonatal death after 14 days of steroid injection. The ARR for respiratory distress syndrome was 1.13 in those born after 14 days of steroids, though it did not reach statistical significance. CONCLUSION: On propensity scoring, the steroid-delivery interval more than 14 days was associated with a significantly increased risk (ARR of 2) of neonatal death.

Controversies in antenatal corticosteroid treatment.

Antenatal corticosteroids are now established as one of the cornerstones of therapy in the prevention of neonatal morbidity and mortality prior to preterm birth. Although this practice is widely accepted, a significant number of controversies exist. This review explores the knowledge gaps regarding the use of antenatal corticosteroids in the preterm, late preterm and term populations. Furthermore, the role of antenatal corticosteroids in special populations, such as diabetes, multiple pregnancies and periviable gestations, where high-quality data from randomized controlled trials are lacking, is also considered.

Complications of Antenatal Corticosteroids in Infants Born by Early Term Scheduled Cesarean Section.

OBJECTIVE: To compare neonatal hypoglycemia and respiratory morbidity rates in pregnancies complicated by diabetes following early term scheduled cesarean section (ETSCS) with and without maternal corticosteroid administration. RESEARCH DESIGN AND METHODS: In a retrospective cohort study, women with any form of diabetes in pregnancy undergoing ETSCS were included. Primary outcomes were admission rates to the neonatal intensive care unit (NICU) for respiratory distress syndrome (RDS)/transient tachypnea of the newborn (TTN) and/or neonatal hypoglycemia. RESULTS: NICU admission rates for neonatal hypoglycemia were significantly higher (24.2% vs. 4.4%, P = 0.003) and RDS/TTN rates were nonsignificantly higher (15.2% vs. 7.2%, P = 0.209) following corticosteroid administration. CONCLUSIONS: Corticosteroids were not beneficial among women with any form of diabetes in pregnancy undergoing ETSCS and, indeed, may be harmful. In our hospital, we have ceased the use of corticosteroids for women under these circumstances.

Brimonidine Toxicity Secondary to Topical Use for an Ulcerated Hemangioma.

Combigan (Allergan, Irvine, CA) is an ophthalmic solution that combines 0.2% brimonidine, a selective α-2 adrenergic agonist, with 0.5% timolol, a nonselective ß-adrenergic antagonist. It is approved for the reduction of intraocular pressure in patients with glaucoma or ocular hypertension. There have been recent reports of successful treatment of superficial infantile hemangiomas (IHs) using Combigan topically. We report the case of a 2-month-old girl who developed life-threatening brimonidine toxicity requiring intubation and mechanical ventilation secondary to central nervous system depression and apnea after topical application to an ulcerated IH.

Relation between time interval from antenatal corticosteroids administration to delivery and neonatal outcome in twins.

AIM: The aim of this study was to evaluate the perinatal outcome in twins, who were administered one complete course of antenatal corticosteroids (ACS) depending on the time interval from corticosteroids to delivery. METHODS: We carried out a retrospective analysis of medical data of women with twins who received a course of ACS and delivered before 34 weeks within or beyond 7 days after ACS were given. Among 652 twin deliveries between 2006 and 2014, 106 met the criteria (50 patients delivered <7 days and 56 ≥ 7 days after ACS administration). RESULTS: There were no differences in the mean gestational age at labor, mean birthweight, perinatal mortality or newborns' general condition between women who delivered <7 and ≥7 days after corticosteroids. Newborns in the ≥7 days group suffered from respiratory disorders significantly more often (74.1% vs 54.5%, P = 0.003) and were hospitalized longer (42.6 ± 19.1 vs 33.4 ± 21.7 days, P < 0.001). Significantly more infants in the <7 days group were administered antibiotics (55.6% vs 25%, P = 0.001). In the multiple logistic regression analysis, the only factors significantly influencing the incidence of respiratory complications in twins were delivery following ACS therapy within 7 days (adjusted odds ratio, 0.16; 95% confidence interval, 0.02-0.90) and female sex (adjusted odds ratio, 0.71; 95% confidence interval 0.40-0.90). CONCLUSION: There is a relation between neonatal outcomes in twins and time interval between ACS administration and birth. Therefore, a single ACS course should be administered with caution in order to allow for the completion of the treatment without exceeding an interval of 7 days to delivery. © 2016 Japan Society of Obstetrics and Gynecology.

[Insulin treatment of gestational diabetes and respiratory outcome in late-preterm and term babies]. / Diabète gestationnel traité par insuline et risque de détresse respiratoire sévère chez le nouveau-né de plus de 34 semaines d'aménorrhée.

While the incidence of diabetes mellitus (DM) during pregnancy has been steadily increasing in recent years, the link between gestational DM and respiratory outcome in neonates has not been firmly established. To address this gap in understanding, we asked whether DM status and its treatment during pregnancy influence risk of neonatal respiratory distress. We conducted retrospective analysis of a large cohort to determine the relationship between maternal DM status (non-DM, insulin-treated DM [DTI], and non-insulin-treated DM [DTR]) and respiratory distress in term and near-term singletons, born at Robert-Debré Hospital over a 7-year period. Of 18,095 singletons delivered at 34 weeks of gestation or later, 412 (2.3%) were admitted to the NICU for respiratory distress within the first hours of life. The incidence of NICU admissions due to respiratory distress was 2.2% in the non-DM group, 2.1% in the DTR group, and 5.7% in the DTI group. Insulin treatment of DM, together with several other perinatal factors, was associated with an increased risk for severe respiratory distress. In a multivariate model, we found that DTI, but not DTR, was a risk factor independent of gestational age and cesarean section, with an IRR of 1.44 (95% CI, 1.00-2.08). The data indicate that newborns of mothers with DM treated with diet are not at risk for severe respiratory distress. Conversely, newborns of mothers with DM treated with insulin are associated with elevated risk for severe respiratory disease and should therefore be closely monitored.

Insulin treatment of maternal diabetes mellitus and respiratory outcome in late-preterm and term singletons.

OBJECTIVES: While the incidence of diabetes mellitus (DM) during pregnancy has been steadily increasing in recent years, the link between gestational DM and respiratory outcome in neonates has not been definitely established. We asked the question whether DM status and its treatment during pregnancy could influence the risk of neonatal respiratory distress. DESIGN: We studied in a large retrospective cohort the relationship between maternal DM status (non-DM, insulin-treated DM (IT-DM) and non-insulin-treated DM (NIT-DM)), and respiratory distress in term and near-term inborn singletons. RESULTS: Among 18,095 singletons delivered at 34 weeks of gestation or later, 412 (2.3%) were admitted to the neonatal intensive care unit (NICU) for respiratory distress within the first hours of life. The incidence of NICU admission due to respiratory distress groups was 2.2%, 5.7% and 2.1% in the non-DM, IT-DM and NIT-DM groups, respectively. Insulin treatment of DM, together with several other perinatal factors, was associated with a significant increased risk for respiratory distress. Several markers of the severity of respiratory illness, including durations of mechanical ventilation and supplemental oxygen, and hypertrophic cardiomyopathy were also found increased following IT-DM as compared with NIT-DM. In a multivariate model, we found that IT-DM, but not NIT-DM, was significantly associated with respiratory distress independent of gestational age and caesarean section, with an incidence rate ratio of 1.44 (1.00-2.08). CONCLUSIONS: This study shows that the treatment of maternal DM with insulin during pregnancy is an independent risk factor for respiratory distress in term and near-term newborns.

Postnatal development and LPS responsiveness of pulmonary adenosine receptor expression and of adenosine-metabolizing enzymes in mice.

BACKGROUND: Adenosine levels are regulated by ecto-5'-nucleotidase/CD73 and adenosine deaminase (ADA). Adenosine regulates endothelial permeability and anti-inflammatory responses via adenosine receptors. Here, the adenosine receptors and purine-converting enzymes were studied during postnatal development and inflammation. METHODS: Newborn, 1-, 10-, 14-d-old and adult C57BL/6 mice were challenged intraperitoneally (i.p.) with lipopolysaccharide (LPS) for 6 h. The inflammatory response was evaluated by histochemistry. Expression levels of adenosine receptors (A1, A2A, A2B, and A3), CD73, and ADA were measured by quantitative reverse transcription polymerase chain reaction. A1 was studied by immunohistochemistry, and enzyme activities were analyzed by thin-layer chromatography. RESULTS: LPS caused respiratory distress in newborns within 24 h. LPS induced neutrophils at the basal stage and alveolar congestion. Low activity and expression of CD73 increased after birth. Expression of ADA after LPS increased 16-fold in adults and 2-fold in newborns (P < 0.05). A1 expression was high in newborns and increased after LPS (P < 0.05). A1 was localized to endothelial membranes. A2A decreased after LPS in newborns and increased in adults (P < 0.05). The expression of A3 increased in newborns and adults after LPS. CONCLUSION: Low pulmonary CD73 expression, LPS-induced suppression of A2A, LPS-induced increase of A1 expression, and severe respiratory distress were distinguishing responses in the newborns from those in the adults.

The use of antidepressant medication in pregnancy.

The use of antidepressant medications during pregnancy has stimulated much professional and public debate. As a consequence, considerable data on the reproductive safety of antidepressants has been generated that exceeds the available information for most, if not all, other classes of medications that may be used in the perinatal period. Despite progress to date, definitive conclusions are limited by the methodological issues inherent to clinical research involving illness versus treatment effects in pregnancy. A notable shortcoming is the limited discussion of statistically significant (a mathematical determination) versus clinically significant (incorporation of incidence and effect sizes into practical relevance). Research emphasises completing an individualised 'risk-benefit' assessment, which is a laudable goal but falls short in providing succinct practical guidelines that includes the key educational points for patients. In this chapter, we focus on areas in which the preponderance of data are consistent, and there is concordance with the preclinical literature to generate a practical approach for antidepressant use in pregnancy.

The effect of prenatal antidepressant exposure on neonatal adaptation: a systematic review and meta-analysis.

OBJECTIVE: Conflicting reports on potential risks of antidepressant exposure during gestation for the infant have been reported in the literature. This systematic review and meta-analysis on immediate neonatal outcomes were conducted to clarify what, if any, risks are faced by infants exposed to antidepressants in utero. Subanalyses address known methodological limitations in the field. DATA SOURCES: MEDLINE, EMBASE, CINAHL, and PsycINFO were searched from their start dates to June 2010. Various combinations of keywords were utilized including, but not limited to, depressive/mood disorder, pregnancy/pregnancy trimesters, antidepressant drugs, and neonatal effects. STUDY SELECTION: English language and cohort and case-control studies reporting on a cluster of signs defined as poor neonatal adaptation syndrome (PNAS) or individual clinical signs (respiratory distress and tremors) associated with pharmacologic treatment were selected. Of 3,074 abstracts reviewed, 735 articles were retrieved and 12 were included in this analysis. DATA EXTRACTION: Two independent reviewers extracted data and assessed the quality of the articles. RESULTS: Twelve studies were retrieved that examined PNAS or the signs of respiratory distress and tremors in the infant. There was a significant association between exposure to antidepressants during pregnancy and overall occurrence of PNAS (odds ratio [OR] = 5.07; 95% CI, 3.25-7.90; P < .0001). Respiratory distress (OR = 2.20; 95% CI, 1.81-2.66; P < .0001) and tremors (OR = 7.89; 95% CI, 3.33-18.73; P < .0001) were also significantly associated with antidepressant exposure. For the respiratory outcome, studies using convenience samples had significantly higher ORs (Q1 = 5.4, P = .020). No differences were found in any other moderator analyses. CONCLUSIONS: An increased risk of PNAS exists in infants exposed to antidepressant medication during pregnancy; respiratory distress and tremors also show associations. Neonatologists need to be prepared and updated in their management, and clinicians must inform their patients of this risk.

Maternal antidepressant use and adverse outcomes: a cohort study of 228,876 pregnancies.

OBJECTIVE: The purpose of this study was to describe antidepressant medication use patterns during pregnancy and pregnancy outcomes. STUDY DESIGN: We evaluated a cohort of 228,876 singleton pregnancies that were covered by Tennessee Medicaid, 1995-2007. RESULTS: Of 23,280 pregnant women with antidepressant prescriptions before pregnancy, 75% of them filled none in the second or third trimesters of pregnancy, and 10.7% of them used antidepressants throughout pregnancy. Filling 1, 2, and ≥3 antidepressant prescriptions during the second trimester was associated with shortened gestational age by 1.7 (95% confidence interval [CI], 1.2-2.3), 3.7 (95% CI, 2.8-4.6), and 4.9 (95% CI, 3.9-5.8) days, when controlled for measured confounders. Third-trimester selective serotonin reuptake inhibitor use was associated with infant convulsions; adjusted odds ratios were 1.4 (95% CI, 0.7-2.8); 2.8 (95% CI, 1.9-5.5); and 4.9 (95% CI, 2.6-9.5) for filling 1, 2, and ≥3 prescriptions, respectively. CONCLUSION: Most women discontinue antidepressant medications before or during the first trimester of pregnancy. Second-trimester antidepressant use is associated with preterm birth, and third-trimester selective serotonin reuptake inhibitor use is associated with infant convulsions.

Effect of antenatal corticosteroids on respiratory morbidity in singletons after late-preterm birth.

OBJECTIVE: To evaluate whether neonates born to women who previously had received antenatal corticosteroids and then delivered a late-preterm-birth neonate had less respiratory morbidity compared with those not exposed to antenatal corticosteroids. METHODS: This is a secondary analysis from a multicenter observational study regarding mode of delivery after previous cesarean delivery. We compared women who received one course of antenatal corticosteroids with unexposed parturients and evaluated various respiratory outcomes among those having a singleton, late-preterm-birth neonate. We controlled for potential confounders including gestational age at delivery, diabetes, mode of delivery, and maternal race. RESULTS: Five thousand nine hundred twenty-four patients met the inclusion criteria; 550 received steroids and 5,374 did not. In the univariable model, compared with unexposed women, those who received antenatal corticosteroids appeared more likely to have neonates who required ventilatory support (11.5% compared with 8.6%, P=.022), had respiratory distress syndrome (RDS) (17.1% compared with 12.2%, P=.001), developed transient tachypnea of the newborn (12.9% compared with 9.8%, P=.020), or required resuscitation in the delivery room (55.8% compared with 49.7%, P=.007). After controlling for confounding factors, we found no significant differences among the groups regarding all of the above outcomes with an odds ratio for RDS of 0.78 (95% confidence interval, 0.60-1.02) and ventilator support of 0.75 (95% confidence interval, 0.55-1.03). CONCLUSION: Exposure to antenatal corticosteroids does not significantly affect respiratory outcomes among those with a subsequent late-preterm birth.