Neonatology最新文献

Introduction: Melatonin has been suggested an adjunctive therapy in neonatal encephalopathy (NE). Melatonin reduces oxidative stress and neutrophil activation; however, the immunological effects in NE have not been studied.

Methods: Infants with NE and neonatal controls were prospectively recruited. Whole blood was sampled in the first week of life. Following endotoxin and or melatonin treatment, diurnal variation was measured by RT PCR for circadian rhythm genes (brain and Muscle Arnt-Like protein [BMAL1], circadian locomotor output cycles kaput [CLOCK], Nuclear Receptor Subfamily 1 Group D Member 2 [REV Erβ], and cryptochrome circadian clock [CRY]). Neutrophil and monocyte cell surface markers of activation CD11b, reactive oxygen intermediates (ROIs), and Toll-like receptor (TLR)-4 were also examined by flow cytometry in matching samples.

Results: Serum and RNA samples from forty infants were included (controls n = 20; NE n = 20) over the first week of life. Melatonin reduced neutrophil CD11b and TLR-4 expression in response to LPS in infants with NE compared to controls. There were no differences in ROIs. BMAL1 and CLOCK baseline gene expression levels were similar. BMAL1 was significantly decreased with LPS stimulation in NE. There was no significant diurnal variation in melatonin, neutrophil, and monocyte function or circadian genes.

Conclusions: Melatonin alters immune function ex vivo in infants with NE. Infants with NE have altered immune circadian responses following LPS stimulation, which have potential for modulation.

Introduction: Recent reports have raised concerns of cardiorespiratory deterioration in some infants receiving respiratory support at birth. We aimed to independently determine whether respiratory support with a facemask is associated with a decrease in heart rate (HR) in some late-preterm and term infants.

Methods: Secondary analysis of data from infants born at ≥32+0 weeks of gestation at 2 perinatal centres in Melbourne, Australia. Change in HR up to 120 s after facemask placement, measured using 3-lead electrocardiography, was assessed every 3 s until 60 s and every 5 s thereafter from video recordings.

Results: In the 15 s after facemask placement, 10/68 (15%) infants had a decrease in mean HR by >10 beats per minute (bpm) compared with their individual baseline mean HR in the 15 s before facemask placement. In 4 (6%) infants, HR decreased to <100 bpm. Nine out of 68 (13%) infants had an increase in mean HR by >10 bpm; 7 of these infants had a baseline HR <120 bpm. In univariable comparisons, the following characteristics were found not to be risk factors for a decrease in HR by >10 bpm: prematurity; type of respiratory support; hypoxaemia; early cord clamping; mode of birth; HR <120 bpm before mask placement. Six out of 63 infants (10%) who had HR ≥120 bpm after facemask placement had a late decrease in HR to <100 bpm between 30 and 120 s after facemask placement.

Conclusion: Facemask respiratory support at birth is temporally associated with a decrease in HR in a subset of late-preterm and term infants.

Objectives: Inhaled nitric oxide (iNO) is an effective pulmonary vasodilator. However, the efficacy of iNO in former premature infants with established bronchopulmonary dysplasia (BPD) has not been studied. This study aimed to determine the efficacy of iNO in reducing pulmonary artery pressure in infants with severe BPD as measured by echocardiography.

Study design: Prospective, observational study enrolling infants born at less than 32 weeks gestation and in whom (1) iNO therapy was initiated after admission to our institution, or (2) at the outside institution less than 48 h before transfer and received an echocardiogram prior to iNO initiation, and (3) had severe BPD. Data were collected at three time-points: (1) before iNO; (2) 12-48 h after initiation of iNO; and (3) 48-168 h after initiation of iNO. The primary outcome was the effect of iNO on pulmonary artery pressure measured by echocardiography in patients with severe BPD between 48 and 168 h after initiating iNO therapy.

Results: Of 37 enrolled, 81% had echocardiographic evidence of pulmonary arterial hypertension (PAH) before iNO and 56% after 48 h of iNO (p = 0.04). FiO2 requirements were significantly different between time-points (1) and (3) (p = 0.05). There were no significant differences between Tricuspid Annular Plane Systolic Excursion (TAPSE) Z-Scores, time to peak velocity: right ventricular ejection time (TPV:RVET), and ventilator changes.

Conclusions: Although we found a statistically significant reduction of PAH between time-point (1) and (3), future trials are needed to further guide clinical care.

The skin of preterm infants is a delicate organ with critical structural and functional differences as compared to term born infants. Unique features contribute to an increased susceptibility to injury, infection, thermal instability, and water loss. During rapid, often accelerated adaption of the physical barrier function of preterm skin, a parallel and mutual development of host skin immunity and skin microbiome seem to be crucial for skin homeostasis. Recent advances in molecular biology have enabled researchers to gain a deeper understanding of the microbial community composition of preterm skin and the important relationship with microbiome composition of other body sites. Nevertheless, several questions remain to be answered, including niche factors and environmental influences on skin maturation. In line with that, evidence-based guidelines on skin care practice in preterm infants are missing. This review articles aims to provide an overview of the current knowledge of preterm infant skin development including immune and barrier function, host-microbial interactions, and potential clinical implications.

Background: Deep medullary vein (DMV) thrombosis is a rare cause of brain damage in both preterm and full-term neonates. In this study, we aimed to collect data on clinical and radiological presentation, treatment, and outcome of neonatal DMV thrombosis.

Methods: Systematic literature review on neonatal DMV thrombosis was carried out in PubMed, ClinicalTrial.gov, Scopus, and Web of Science up to December 2022.

Results: Seventy-five published cases of DMV thrombosis were identified and analysed (preterm newborns were 46%). Neonatal distress, respiratory resuscitation, or need for inotropes were present in 34/75 (45%) of patients. Signs and symptoms at presentation included seizures (38/75, 48%), apnoea (27/75, 36%), lethargy or irritability (26/75, 35%). At magnetic resonance imaging (MRI), fan-shaped linear T2 hypointense lesions were documented in all cases. All had ischaemic injuries, most often involving the frontal (62/74, 84%) and parietal lobes (56/74, 76%). Signs of haemorrhagic infarction were present in 53/54 (98%). Antithrombotic treatment was not mentioned in any of the studies included. Although mortality was low (2/75, 2.6%), a large proportion of patients developed neurological sequelae (intellectual disability in 19/51 [37%] and epilepsy in 9/51 [18%] cases).

Conclusions: DMV thrombosis is rarely identified in the literature, even if it is possibly under-recognized or under-reported. Presentation in neonatal age is with seizures and non-specific systemic signs/symptoms that often cause diagnostic delay, despite the pathognomonic MRI picture. The high rate of morbidity, which determines significant social and health costs, requires further in-depth studies aimed at earlier diagnosis and evidence-based prevention and therapeutic strategies.

Background: Hypertensive disorders of pregnancy cause fetal growth restriction and increased maternal morbidity and mortality, especially in women of African ancestry. Recently, preeclampsia risk was associated with polymorphisms in the apolipoprotein L1 (APOL1) gene in women of African ancestry.

Objectives: We assessed APOL1 genotype effects on pregnancies with and without preeclampsia.

Method: We conducted an unmatched case-control study of 1,358 mother-infant pairs from two independent cohorts of black women.

Results: Term preeclampsia cases with high-risk APOL1 genotypes were more likely to be small for gestational age compared to APOL1 low-risk term cases (odds ratio [OR] 2.8) and APOL1 high-risk controls (OR 5.5). Among preterm pregnancies, fetal APOL1 genotype was associated with preeclampsia.

Conclusions: Fetal APOL1 genotype was associated with preeclampsia in preterm infants and with altered fetal growth in term infants. This may indicate APOL1 genotype impacts a spectrum of pregnancy complications mediated by a common pathophysiological event of placental insufficiency.

Respiratory distress syndrome (RDS) care pathways evolve slowly as new evidence emerges. We report the sixth version of "European Guidelines for the Management of RDS" by a panel of experienced European neonatologists and an expert perinatal obstetrician based on available literature up to end of 2022. Optimising outcome for babies with RDS includes prediction of risk of preterm delivery, appropriate maternal transfer to a perinatal centre, and appropriate and timely use of antenatal steroids. Evidence-based lung-protective management includes initiation of non-invasive respiratory support from birth, judicious use of oxygen, early surfactant administration, caffeine therapy, and avoidance of intubation and mechanical ventilation where possible. Methods of ongoing non-invasive respiratory support have been further refined and may help reduce chronic lung disease. As technology for delivering mechanical ventilation improves, the risk of causing lung injury should decrease, although minimising time spent on mechanical ventilation by targeted use of postnatal corticosteroids remains essential. The general care of infants with RDS is also reviewed, including emphasis on appropriate cardiovascular support and judicious use of antibiotics as being important determinants of best outcome. We would like to dedicate this guideline to the memory of Professor Henry Halliday who died on November 12, 2022.These updated guidelines contain evidence from recent Cochrane reviews and medical literature since 2019. Strength of evidence supporting recommendations has been evaluated using the GRADE system. There are changes to some of the previous recommendations as well as some changes to the strength of evidence supporting recommendations that have not changed. This guideline has been endorsed by the European Society for Paediatric Research (ESPR) and the Union of European Neonatal and Perinatal Societies (UENPS).

Objective: Malposition of peripherally inserted central catheters (PICCs) is common. Recommendations for PICC insertion depths are scarce and comprise complex equations. This study aimed to develop diagrams and tables for the recommendation of PICC insertion depths in neonates based on anthropometric parameters.

Study design: In this retrospective single-center study, the individual optimal PICC insertion depths were correlated with body weight, length, and head circumference. Using linear regression analysis, line charts and tables for the recommendation of PICC insertion depth were generated and compared with previously published recommendations.

Result: PICC insertion depths of 204 infants (gestational age at PICC installation: 24.0-44.9 weeks) with 131 (64%) PICC in the upper extremities and 73 (36%) in the lower extremities were analyzed. Linear logistic regression models revealed R2 values between 0.387 and 0.884.

Conclusion: The charts and table developed in this study enable a fast and accurate determination of recommended PICC insertion depths in neonates.

Background: Early diagnosis of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) by monitoring heart rate characteristics (HRC) of preterm infants might reduce the risk of death and morbidities. We aimed to systematically assess the effects of HRC monitoring on death, LOS, and NEC.

Methods: A systematic search was performed in MEDLINE, Embase, Cochrane Library, and Web of Science.

Results: Fifteen papers were included in this review. Three of these papers reported results from the only identified randomized controlled trial (RCT). This RCT showed that HRC monitoring resulted in a small but significant reduction in mortality (absolute risk reduction 2.1% [95% confidence interval 0.01-4.14]) without any differences in neurodevelopmental impairment. The risk of bias was rated high due to performance and detection bias and failure to correct for multiple testing. Most diagnostic cohort studies showed high discriminating accuracy in predicting LOS but lacked sufficient quality and generalizability. No studies for the detection of NEC were identified.

Conclusion: Supported by multiple observational cohort studies, the RCT identified in this systematic review showed that HRC monitoring as an early warning system for LOS might reduce the risk of death in preterm infants. However, methodological weaknesses and limited generalizability do not justify implementation of HRC in clinical care. A large international RCT is warranted.