Tertiary Neonatal Intensive Care Unit Research Articles

Neonatal Endotracheal Intubation: Comparison of Existing Formulae for Accuracy

Background There are several formulae proposed to calculate the ideal depth of insertion of the endotracheal tube (ETT) in neonates, none of which are universally accurate. Our objective is to identify the most accurate of these formulae and to determine the most suitable formula for babies weighing less than 1 kg. Methods This is a retro-prospective observational study conducted in a tertiary neonatal intensive care unit. All intubated babies, irrespective of their gestational age, were included in this study. Those with congenital airway anomalies or syndromes with involvement of the upper airway and those who required short-term ventilation restricted to the theatre complex were excluded. The ideal insertion depth was determined via a chest X-ray (CXR) with the ETT projecting between thoracic vertebrae 2 and 3. Predictions from eight formulae investigated in the Indian population were analysed using paired Wilcoxon tests and Bland–Altman plots. Results The sample size was 83, of which 16 weighed less than 1 kg. Neither weight-based nor naso-tragal length (NTL)-based formulae were universally accurate in the prediction of the ideal depth of insertion, and using either of the formulae resulted in a high rate of malpositioning. Amongst the NTL-based formulae, Tatwavedi and Singh’s adjustments worked better than the original. Conclusion The currently available formulae remain inaccurate in the prediction of the ideal length of insertion of ETT, more so in babies less than 1 kg in our study population.

Umbilical arterial catheter duration as risk factor for Bell's Stage III necrotizing enterocolitis in preterm neonates

AbstractObjectivesTo explore risk factors for Stage‐III necrotizing enterocolitis (NEC‐III) in preterm neonates.MethodsThis was a retrospective case‐control study of neonates born <33 weeks gestational age (GA) who were admitted to a tertiary neonatal intensive care unit, between 2015 and 2018. NEC‐III cases were compared with Stage‐II NEC (NEC‐II) and non‐NEC controls. Two to four non‐NEC controls were matched by GA ± 1 week and date of birth ± 3 months, to one NEC‐III case. Univariate and multivariate analyses were used to examine risk factors for NEC‐III.ResultsOf 1360 neonates born <33 weeks, 71 (5.2%) had NEC‐II and above, with 46% being NEC‐III. Mean age of onset of NEC‐III was 13.7 days versus 23.9 days for NEC‐II (p = 0.01). Neonates with NEC‐III were of lower GA (NEC‐III 25.4 weeks, NEC‐II 27.3 weeks, and non‐NEC 26 weeks; p = 0.0008) and had higher Score for Neonatal Acute Physiology Perinatal Extension‐II scores (NEC‐III 47.5, NEC‐II 28.4 and non‐NEC 37, p = 0.003). Multivariate analysis showed duration of umbilical arterial catheter (UAC) >5 days was significantly associated with the development of NEC‐III with adjusted odds ratio (AOR) 3.8; 95% confidence interval (CI) (1.05–13.66) for NEC‐III versus non‐NEC and AOR 5.57; 95% CI (1.65–18.73), p = 0.006 for NEC‐III versus NEC‐II. Rupture of membranes (ROM) >1 week was associated with NEC‐III (AOR 6.93; 95% CI [1.56–30.69] vs. non‐NEC and AOR 11.74; 95% CI [1.14–120.34] vs. NEC‐II).ConclusionThe increased association of NEC‐III with duration of UAC and ROM could be further examined in prospective studies, and an upper limit for UAC duration could be considered in NEC prevention bundles.

Whole-Body Hypothermia vs Targeted Normothermia for Neonates With Mild Encephalopathy

Although whole-body hypothermia is widely used after mild neonatal hypoxic-ischemic encephalopathy (HIE), safety and efficacy have not been evaluated in randomized clinical trials (RCTs), to our knowledge. To examine the effect of 48 and 72 hours of whole-body hypothermia after mild HIE on cerebral magnetic resonance (MR) biomarkers. This open-label, 3-arm RCT was conducted between October 31, 2019, and April 28, 2023, with masked outcome analysis. Participants were neonates at 6 tertiary neonatal intensive care units in the UK and Italy born at or after 36 weeks' gestation with severe birth acidosis, requiring continued resuscitation, or with an Apgar score less than 6 at 10 minutes after birth and with evidence of mild HIE on modified Sarnat staging. Statistical analysis was per intention to treat. Random allocation to 1 of 3 groups (1:1:1) based on age: neonates younger than 6 hours were randomized to normothermia or 72-hour hypothermia (33.5 °C), and those 6 hours or older and already receiving whole-body hypothermia were randomized to rewarming after 48 or 72 hours of hypothermia. Thalamic N-acetyl aspartate (NAA) concentration (mmol/kg wet weight), assessed by cerebral MR imaging and thalamic spectroscopy between 4 and 7 days after birth using harmonized sequences. Of 225 eligible neonates, 101 were recruited (54 males [53.5%]); 48 (47.5%) were younger than 6 hours and 53 (52.5%) were 6 hours or older at randomization. Mean (SD) gestational age and birth weight were 39.5 (1.1) weeks and 3378 (380) grams in the normothermia group (n = 34), 38.7 (0.5) weeks and 3017 (338) grams in the 48-hour hypothermia group (n = 31), and 39.0 (1.1) weeks and 3293 (252) grams in the 72-hour hypothermia group (n = 36). More neonates in the 48-hour (14 of 31 [45.2%]) and 72-hour (13 of 36 [36.1%]) groups required intubation at birth than in the normothermic group (3 of 34 [8.8%]). Ninety-nine neonates (98.0%) had MR imaging data and 87 (86.1%), NAA data. Injury scores on conventional MR biomarkers were similar across groups. The mean (SD) NAA level in the normothermia group was 10.98 (0.92) mmol/kg wet weight vs 8.36 (1.23) mmol/kg wet weight (mean difference [MD], -2.62 [95% CI, -3.34 to -1.89] mmol/kg wet weight) in the 48-hour and 9.02 (1.79) mmol/kg wet weight (MD, -1.96 [95% CI, -2.66 to -1.26] mmol/kg wet weight) in the 72-hour hypothermia group. Seizures occurred beyond 6 hours after birth in 4 neonates: 1 (2.9%) in the normothermia group, 1 (3.2%) in the 48-hour hypothermia group, and 2 (5.6%) in the 72-hour hypothermia group. In this pilot RCT, whole-body hypothermia did not improve cerebral MR biomarkers after mild HIE, although neonates in the hypothermia groups were sicker at baseline. Safety and efficacy of whole-body hypothermia should be evaluated in RCTs. ClinicalTrials.gov Identifier: NCT03409770.

The effect of developmental care on the length of hospital stay and family centered care practice for very low birth weight infants in neonatal intensive care units: A cluster randomized controlled trial

BackgroundDespite previous studies suggesting that developmental care can provide benign stimulation to promote neural development of newborns, more evidence is needed regarding the other clinical benefits of developmental care. ObjectiveTo evaluate the effect of implementing developmental care on the length of hospital stay, the improvement of care practice in neonatal intensive care units, as well as the short-term outcome of very low birth weight infants. DesignCluster-randomized controlled trial. Setting(s) and participantsFrom March 1, 2021 to March 1, 2022, 1400 very low birth weight infants were recruited from 14 tertiary neonatal intensive care units in China. MethodsWe assigned 14 neonatal intensive care units to either developmental care or standard care. The length of hospital stay of the infants was the primary outcome analyzed at the individual level. Secondary outcomes were family centered care practice including parental involvement, the skin to skin care, exclusive breast milk, oral immune therapy and breastfeeding. The environmental management (noise and light) and the short-term outcomes were also evaluated. ResultsThe length of hospital stay for the developmental care group was 65 % as long as that for the control group (HR: 0.65, 95 % CI, 0.451–0936, p = 0.021). After controlling the covariables, the adjusted HR = 0.755 (95 % CI, 0.515 to 1.107, p = 0.150). When compared to the control group, the developmental care group had greater access to SSC, with 22 infants (3.8 %) in the developmental care group compared to 13 infants (1.7 %) in the standard care group (p = 0.013). A greater proportion of infants in the developmental care group were fed at the breast, than those in the standard care group (136 [23.6 %] vs 9 [1.1 %]; p = 0.029). Compared to the control group, exclusively breast milk was significantly more favorable in the developmental care group (435 [75.6 %] vs 114 [15.0 %]; p = 0.001). The difference remained significant even after adjusting for covariates. However, the rate of oral immune therapy and parental involvement was similar in the two groups. The average noise and light levels in the developmental care group were significantly lower than those in the standard care group. After adjusting for confounders, the difference remained significant. There were no significant differences among groups in the mortality and major morbidity. ConclusionsDevelopmental care might have developed an accumulated effect over time on the length of hospital stay among very low birth weight infants. The implementation of developmental care can greatly improve family centered care practices and the neonatal intensive care unit environment. RegistrationClinicalTrials.govNCT05166720. Registration date: 1 March, 2021.

Quantitative Lung Ultrasonography to Guide Surfactant Therapy in Neonates Born Late Preterm and Later.

Surfactant administration may be needed in late preterm through full-term neonates, but the pathophysiology of their respiratory failure can be different from that of early preterm neonates. The lung ultrasonography score (LUS) is accurate to guide surfactant replacement in early preterm neonates, but to our knowledge, it has not yet been studied in the late preterm through full-term neonatal population. To assess whether LUS is equally accurate to predict surfactant need in late preterm through full-term neonates as in early preterm neonates. This prospective, international, multicenter diagnostic study was performed between December 2022 and November 2023 in tertiary academic neonatal intensive care units in France, Italy, Spain, and the US. Late preterm through full-term neonates (≥34 weeks' gestation) with respiratory failure early after birth were enrolled. Point-of-care lung ultrasonography to calculate the neonatal LUS (range, 0-18, with higher scores indicating worse aeration), which was registered in dedicated research databases and unavailable for clinical decision-making. The main outcomes were the area under the curve (AUC) in receiver operating characteristic analysis and derived accuracy variables, considering LUS as a replacement for other tests (ie, highest global accuracy) and as a triage test (ie, highest sensitivity). Sample size was calculated to assess noninferiority of LUS to predict surfactant need in the study population compared with neonates born more prematurely. Correlations of LUS with the ratio of hemoglobin oxygen saturation as measured by pulse oximetry (SpO2) to fraction of inspired oxygen (FiO2) and with the oxygen saturation index (OSI) were assessed. A total of 157 neonates (96 [61.1%] male) were enrolled and underwent lung ultrasonography at a median of 3 hours (IQR, 2-7 hours) of life; 32 (20.4%) needed surfactant administration (pretest probability, 20%). The AUC was 0.87 (95% CI, 0.81-0.92). The highest global accuracy and sensitivity were reached for LUS values higher than 8 or 4 or lower, respectively. Subgroup analysis gave similar diagnostic accuracy in neonates born late preterm (AUC, 0.89; 95% CI, 0.81-0.97; n = 111) and early term and later (AUC, 0.84; 95% CI, 0.73-0.96; n = 46). After adjusting for gestational age, LUS was significantly correlated with SpO2:FiO2 (adjusted β, -10.4; 95% CI, -14.0 to -6.7; P < .001) and OSI (adjusted β, 0.2; 95% CI, 0.1-0.3; P < .001). In this diagnostic study of late preterm through full-term neonates with respiratory failure early after birth, LUS accuracy to predict surfactant need was not inferior to that observed in earlier preterm neonates. An LUS higher than 8 was associated with highest global accuracy (replacement test), suggesting that it can be used to guide surfactant administration. An LUS value of 4 or lower was associated with the highest sensitivity (triage test), suggesting it is unlikely for this population to need surfactant.

Size and Location of Preterm Brain Injury and Associations With Neurodevelopmental Outcomes.

We examined associations of white matter injury (WMI) and periventricular hemorrhagic infarction (PVHI) volume and location with 18-month neurodevelopment in very preterm infants. A total of 254 infants born <32 weeks' gestational age were prospectively recruited across 3 tertiary neonatal intensive care units (NICUs). Infants underwent early-life (median 33.1 weeks) and/or term-equivalent-age (median 41.9 weeks) MRI. WMI and PVHI were manually segmented for quantification in 92 infants. Highest maternal education level was included as a marker of socioeconomic status and was defined as group 1 = primary/secondary school; group 2 = undergraduate degree; and group 3 = postgraduate degree. Eighteen-month neurodevelopmental assessments were completed with Bayley Scales of Infant and Toddler Development, Third Edition. Adverse outcomes were defined as a score of less than 85 points. Multivariable linear regression models were used to examine associations of brain injury (WMI and PVHI) volume with neurodevelopmental outcomes. Voxel-wise lesion symptom maps were developed to assess relationships between brain injury location and neurodevelopmental outcomes. Greater brain injury volume was associated with lower 18-month Motor scores (β = -5.7, 95% CI -9.2 to -2.2, p = 0.002) while higher maternal education level was significantly associated with higher Cognitive scores (group 3 compared 1: β = 14.5, 95% CI -2.1 to 26.9, p = 0.03). In voxel-wise lesion symptom maps, brain injury involving the central and parietal white matter was associated with an increased risk of poorer motor outcomes. We found that brain injury volume and location were significant predictors of motor, but not cognitive outcomes, suggesting that different pathways may mediate outcomes across domains of neurodevelopment in preterm infants. Specifically, assessing lesion size and location may allow for more accurate identification of infants with brain injury at highest risk of poorer motor outcomes. These data also highlight the importance of socioeconomic status in cognitive outcomes, even in preterm infants with brain injury.

Umbilical Cord Blood as an Alternative to Neonatal Blood for Complete Blood Count: A Comparison Study

ObjectiveTo assess concordance between umbilical cord blood (UCB) and neonatal blood (NB) laboratory test results at birth. Study designThis retrospective study considered very preterm neonates (<32 weeks' gestational age) admitted to a tertiary neonatal intensive care unit from 2012 to 2023. Inclusion criteria required neonates with a complete blood count measured in both UCB and NB drawn within 2 hours after birth. Median hemoglobin (Hb) and hematocrit (Hct) concentrations were compared between UCB (venous samples) and NB (venous, arterial, or capillary samples). ResultsA total of 432 neonates with paired UCB and NB values were included in the study. Hb concentration in UCB was 14.7 g/dL (interquartile range [IQR] 13.5-16.1 g/dL) compared with 14.8 g/dL (IQR 12.6-19.3 g/dL) in venous NB samples, 13.9 g/dL (IQR 12.9-15.3 g/dL) in arterial NB and 18.7 g/dL (IQR 16.6-20.8 g/dL) in capillary NB. The regression equation showed a correction factor of 1.08 for converting Hb values from UCB to venous NB. Median Hct concentration in UCB was 0.45 L/L (IQR: 0.41-0.49 L/L) compared with 0.48 L/L (IQR 0.43-0.54 L/L) in venous NB, 0.42 L/L (IQR 0.38-0.45 L/L) in arterial NB and 0.57 L/L, (IQR 0.51-0.63 L/L) in capillary NB. ConclusionsHb and Hct concentrations measured in UCB are similar to those measured in venous blood in very preterm infants and are valid alternatives for NB tests at birth. Hb and Hct concentrations in arterial and capillary NB are respectively lower and higher compared with UCB measurements.

Clinical and Laboratory Features of Culture-positive Neonatal Sepsis: A 5-year Single-center Experience at Tertiary Neonatal Intensive Care Unit in Turkey

Clinical and Laboratory Features of Culture-positive Neonatal Sepsis: A 5-year Single-center Experience at Tertiary Neonatal Intensive Care Unit in Turkey

Analysis of mild and severe neonatal enterovirus infections in a Chinese neonatal tertiary center: a retrospective case-control study.

To compare the clinical characteristics, virus serotype, and outcome in cases of mild and severe enteroviral infection at a tertiary neonatal intensive care unit in China. A retrospective analysis of cases hospitalized between June and August 2019. Samples (stool or throat swabs) were examined using reverse transcription polymerase chain reaction. Positive cases were divided into two groups: mild infection and severe infection. A total of 149 cases were assigned to one of two groups: mild infection (n = 104) and severe infection (n = 45). There were no significant differences between the groups in terms of sex, gestational age, birth weight, mode of delivery, and onset within 7 days. Clinical symptoms in both groups mostly resembled sepsis (fever, rash, poor feeding, and lethargy); however, there were significant variations in concomitant symptoms such as hepatitis, thrombocytopenia, encephalitis, coagulopathy, and myocarditis. Severe cases were more likely to have abnormal complete blood counts, biochemical parameters, and cerebrospinal fluid markers. The predominant serotypes implicated in neonatal enterovirus infections were echoviruses and Coxsackievirus B. Invasive ventilation, intravenous immunoglobulin, vasoactive medications, and blood product transfusions were often required, with high mortality rates among severe cases. We found significant differences between mild and severe cases of neonatal enterovirus infection with respect to complications, laboratory findings, and enterovirus serotypes. It is crucial to exercise caution when newborns exhibit symptoms of sepsis, during an enterovirus outbreak. Anemia, thrombocytopenia, abnormal liver function, and coagulation dysfunction should be monitored closely as they could indicate the presence of a severe enteroviral infection.

Proactive Diagnosis and Tailor-Made Treatment of Patent Ductus Arteriosus in Very Preterm Infants with Routine Echocardiography in Japan: A post hoc Analysis of the PLASE Study

Introduction: A feature of the management of extremely preterm infants in Japan is proactive circulatory management using early routine echocardiography performed by neonatologists. Methods: This study was a post hoc analysis of the Patent ductus arteriosus and Left Atrial Size Evaluation in preterm infants (PLASE) study, which is a prospective cohort study including preterm infants admitted to 34 tertiary neonatal intensive care units in Japan between October 2015 and December 2016. We described the details of the treatment strategy of patent ductus arteriosus (PDA) based on early routine echocardiography. Results: In total, 613 preterm infants were included into the analysis. Twenty percent of infants with prophylactic indomethacin were switched to therapeutic cyclooxygenase inhibitor (COX-I) before the completion of the full prophylactic indomethacin course. Therapeutic COX-I was mostly administered based on echocardiographic findings before PDA became symptomatic or hemodynamically significant. Therapeutic COX-I was frequently discontinued after one or two doses before the full course (three doses) was completed. The proportion of infants requiring additional treatment (additional therapeutic COX-I course or surgical PDA closure) after discontinued COX-I courses (<3 doses) compared to infants after completed 3 doses course was significantly lower (after the first therapeutic COX-I course 46% vs. 68%, p < 0.001) or without a significant difference (after the second or third course). Conclusions: The clinical management of PDA in Japan featured (1) COX-I administration based on echocardiographic findings before symptomatic or hemodynamically significant PDA appeared and (2) frequent discontinuation of therapeutic COX-I before completing the standard three doses course.

Partnering Early to Provide for Infants At Risk of Cerebral Palsy (PĒPI ARC): protocol for a feasibility study of a regional hub for early detection of cerebral palsy in Aotearoa New Zealand.

Cerebral palsy (CP) can now be diagnosed in infants with identified CP risk factors as early as three months of age; however, many barriers prevent equitable access to early detection pathways. The "Partnering Early to Provide for Infants At Risk of Cerebral Palsy" feasibility study (PĒPI ARC) seeks to trial a new approach to decrease inequitable health service in Aotearoa New Zealand for high-risk infants and their families. PĒPI ARC incorporates face-to-face clinics, an in-person and virtual Hub, and the use of telehealth to enable flexible access to CP assessments and support for health professionals in early CP detection. A non-randomised feasibility study was conducted from a tertiary Neonatal Intensive Care Unit (NICU) in Wellington and included seven regional referral centres, servicing nearly 30% of the total population in New Zealand (NZ). The families of infants with a high risk of neurodevelopmental impairment and health professionals interacting with the Hub were invited to participate. Mixed methods were used to evaluate the (i) equitable implementation of an early detection pathway, (ii) acceptability, (iii) demand among families and health professionals, (iv) efficacy in relation to reducing the age of receipt of CP diagnosis, and (v) the experiences around communication and information sharing. The NZ Health and Disability Ethics Committee approved this study (HDEC: 2022 FULL 13434). The findings will be disseminated in peer-reviewed journals, in conference presentations, and via professional networks. Australian New Zealand Clinical Trials Registry: ACTRN12623000600640.

Nutritional support during the first week for infants with bronchopulmonary dysplasia and respiratory distress: a multicenter cohort study in China

BackgroundBronchopulmonary dysplasia (BPD) is a major complication affecting the survival rate and long-term outcomes of preterm infants. A large, prospective, multicenter cohort study was conducted to evaluate early nutritional support during the first week of life for preterm infants with a gestational age < 32 weeks and to verify nutritional risk factors related to BPD development.MethodsA prospective multicenter cohort study of very preterm infants was conducted in 40 tertiary neonatal intensive care units across mainland China between January 1, 2020, and December 31, 2021. Preterm infants who were born at a gestational age < 32 weeks, < 72 h after birth and had a respiratory score > 4 were enrolled. Antenatal and postnatal information focusing on nutritional parameters was collected through medical systems. Statistical analyses were also performed to identify BPD risk factors.ResultsThe primary outcomes were BPD and severity at 36 weeks postmenstrual age. A total of 1410 preterm infants were enrolled in this study. After applying the exclusion criteria, the remaining 1286 infants were included in this analysis; 614 (47.7%) infants were in the BPD group, and 672 (52.3%) were in the non-BPD group. In multivariate logistic regression model, the following six factors were identified of BPD: birth weight (OR 0.99, 95% CI 0.99–0.99; p = 0.039), day of full enteral nutrition (OR 1.03, 95% CI 1.02–1.04; p < 0.001), parenteral protein > 3.5 g/kg/d during the first week (OR 1.65, 95% CI 1.25–2.17; p < 0.001), feeding type (formula: OR 3.48, 95% CI 2.21–5.49; p < 0.001, mixed feed: OR 1.92, 95% CI 1.36–2.70; p < 0.001; breast milk as reference), hsPDA (OR 1.98, 95% CI 1.44–2.73; p < 0.001), and EUGR ats 36 weeks (OR 1.40, 95% CI 1.02–1.91; p = 0.035).ConclusionsA longer duration to achieve full enteral nutrition in very preterm infants was associated with increased BPD development. Breastfeeding was demonstrated to have a protective effect against BPD. Early and rapidly progressive enteral nutrition and breastfeeding should be promoted in very preterm infants.Trial registrationThe trial was registered in the Chinese Clinical Trial Registry (No. ChiCTR2000030125 on 24/02/2020) and in www.ncrcch.org (No. ISRCTN84167642 on 25/02/2020).

Neonatal Outcomes in Different Maternal Diabetes Types: Experience from a Tertiary Care Unit

Objective: Infants of mothers with diabetes (IMD) may require hospitalization in neonatal intensive care units (NICU) for various reasons. In our study, our objective was to compare clinical and laboratory findings, as well as malformations and morbidities among IMD based on the types of maternal diabetes. Material and Methods: The diabetic status of mothers of 4713 infants admitted to tertiary neonatal intensive care unit (NICU) at Ankara Bilkent City Hospital between January 1, 2020, and January 1, 2022, was examined. We retrospectively analyzed demographic data, clinical and laboratory characteristics, and morbidities for 616 infants born to mothers with impaired glucose tolerance (IGT), gestational diabetes mellitus (GDM), or pre-existing gestational diabetes mellitus (Pre-GDM). Results: Of the 616 cases, 167 (27.1%) were infants of mothers with IGT, 394 (64%) with GDM and 55 (8.9%) with Pre-GDM. The prevalence of macrosomia was significantly higher in Pre-GDM (30.9%) than in the IGT (15%) and GDM (19.3%) groups (p=0.033). The most common malformations in the cases were related to the cardiovascular system (CVS) (77.4%). The frequency of septal hypertrophy was significantly higher in the Pre-GDM group compared to the IGT and GDM groups, and in the GDM group compared to the IGT group (p&amp;lt;0.001). The rates of septal hypertrophy, CVS malformation, LGA/macrosomia, and hypocalcemia were found to be significantly higher in infants of mothers with insulin requirement and high HbA1c levels, particularly in Pre-GDM group (p&amp;lt;0.001). According to the ROC analysis for the optimum maternal HbA1c value predicting septal hypertrophy, the threshold value was found to be 6% (AUC=0.693) with 62% sensitivity and 66% specificity. In logistic regression analysis, macrosomia and maternal HbA1c ≥6% were determined as independent risk factors for the presence of septal hypertrophy. Conclusion: Despite variations in the type of maternal diabetes, IDM experience significant clinical challenges when hospitalized and monitored in the NICU. Infants born to mothers with IGT may also be subjected to maternal hyperglycemia. The likelihood of certain complications rises in infants born to pregnant women with inadequate glycemic control, particularly those with elevated HbA1c levels. By ensuring maternal glycemic control and closely monitoring these infants, it is possible to reduce both mortality and morbidity.

Azithromycin therapy for prevention of chronic lung disease of prematurity (AZTEC): a multicentre, double-blind, randomised, placebo-controlled trial

Systematic reviews have reported conflicting evidence on whether macrolide antibiotics reduce rates of chronic lung disease of prematurity (CLD) in at-risk preterm infants born at less than 30 weeks' gestation, including in those colonised with pulmonary Ureaplasma spp. Since an adequately powered trial has been lacking, we aimed to assess if the macrolide azithromycin improved survival without the development of physiologically defined moderate or severe CLD in preterm infants. AZTEC was a multicentre, double-blind, randomised, placebo-controlled trial conducted in 28 tertiary neonatal intensive care units in the UK. Infants were eligible if they were born at less than 30 weeks' gestation and had received at least 2 h of either non-invasive (continuous positive airway pressure or humidified high flow nasal cannula therapy) or invasive respiratory support (via endotracheal tube) within 72 h of birth. Eligible infants were randomly allocated in a 1:1 ratio using random permuted blocks of four to receive either intravenous azithromycin at 20 mg/kg per day for 3 days followed by 10 mg/kg for 7 days, or to placebo. Allocation was stratified by centre and gestational age at birth (<28 weeks vs ≥28 weeks). Azithromycin and placebo vials were encased in tamper-evident custom cardboard cartons to ensure masking for clinicians, parents, and the research team. The primary outcome was survival without development of physiologically defined moderate or severe CLD at 36 weeks' postmenstrual age. Outcomes and safety were analysed on an intention-to-treat basis (all randomly allocated infants, regardless of any post-randomisation events). The study was registered with ISRCRN (11650227) and is closed. Infants were recruited between Oct 9, 2019, and March 22, 2022. 799 (53·1%) of 1505 eligible infants underwent random allocation; three infants were withdrawn, including consent to use their data, leaving 796 infants for analysis. Survival without moderate or severe CLD occurred in 166 (42%) of 394 infants in the intervention group and 179 (45%) of 402 in the placebo group (three-level adjusted OR [aOR] 0·84, 95% CI 0·55-1·29, p=0·43). Pulmonary Ureaplasma spp colonisation did not influence treatment effect. Overall, seven serious adverse events were reported for the azithromycin group (five graded as severe, two as moderate), and six serious adverse events were reported in the placebo group (two severe, two moderate, and two mild), as assessed by the local principal investigators. Since prophylactic use of azithromycin did not improve survival without development of physiologically-defined CLD, regardless of Ureaplasma spp colonisation, it cannot be recommended in clinical practice. UK National Institute for Health and Care Research.

Pain Exposure and Brain Connectivity in Preterm Infants

Early-life exposure to painful procedures has been associated with altered brain maturation and neurodevelopmental outcomes in preterm infants, although sex-specific differences are largely unknown. To examine sex-specific associations among early-life pain exposure, alterations in neonatal structural connectivity, and 18-month neurodevelopment in preterm infants. This prospective cohort study recruited 193 very preterm infants from April 1, 2015, to April 1, 2019, across 2 tertiary neonatal intensive care units in Toronto, Canada. Structural connectivity data were available for 150 infants; neurodevelopmental outcomes were available for 123 infants. Data were analyzed from January 1, 2022, to December 31, 2023. Pain was quantified in the initial weeks after birth as the total number of invasive procedures. Infants underwent early-life and/or term-equivalent-age magnetic resonance imaging with diffusion tensor imaging to quantify structural connectivity using graph theory measures and regional connection strength. Eighteen-month neurodevelopmental outcomes were assessed with the Bayley Scales of Infant and Toddler Development, Third Edition. Stratifying by sex, generalized estimating equations were used to assess whether pain exposure modified the maturation of structural connectivity using an interaction term (early-life pain exposure × postmenstrual age [PMA] at scan). Generalized estimating equations were used to assess associations between structural connectivity and neurodevelopmental outcomes, adjusting for extreme prematurity and maternal education. A total of 150 infants (80 [53%] male; median [IQR] gestational age at birth, 27.1 [25.4-29.0] weeks) with structural connectivity data were analyzed. Sex-specific associations were found between early-life pain and neonatal brain connectivity in female infants only, with greater early-life pain exposure associated with slower maturation in global efficiency (pain × PMA at scan interaction P = .002) and local efficiency (pain × PMA at scan interaction P = .005). In the full cohort, greater pain exposure was associated with lower global efficiency (coefficient, -0.46; 95% CI, -0.78, to -0.15; P = .004) and local efficiency (coefficient, -0.57; 95% CI, -1.04 to -0.10; P = .02) and regional connection strength. Local efficiency (coefficient, 0.003; 95% CI, 0.001-0.004; P = .005) and regional connection strength in the striatum were associated with cognitive outcomes. In this cohort study of very preterm infants, greater exposure to early-life pain was associated with altered maturation of neonatal structural connectivity, particularly in female infants. Alterations in structural connectivity were associated with neurodevelopmental outcomes, with potential regional specificities.

Daptomycin Use for Persistent Coagulase-Negative Staphylococcal Bacteremia in a Neonatal Intensive Care Unit.

During the last two decades, the incidence of late-onset sepsis (LOS) has increased due to improved survival of premature neonates. Persistent bacteremia (PB) in LOS is defined as more than two positive blood cultures obtained on different calendar days during the same infectious episode. Although rare, PB should be treated aggressively to prevent adverse outcomes. Daptomycin, a lipopeptide antibiotic, has been used in neonates with persistent coagulase-negative staphylococci (CoNS) bacteremia with promising results, but studies reporting on the efficacy and safety of the agent are scarce. The purpose of this study was to evaluate the efficacy and safety of daptomycin use for persistent CoNS bacteremia in a neonatal cohort. This is a retrospective, observational, single-center study of neonates treated with daptomycin during 2011-2022 in the Tertiary Neonatal Intensive Care Unit (NICU) of the University General Hospital of Patras, Greece. For the years 2011-2022, there were 3.413 admissions to the NICU. During the last 3 years (2020-2022)-the active epidemiological surveillance period-123 infants (out of 851 admissions, 14.4%) developed CoNS bacteremia (LOS). During the study period, twelve infants with PB were treated with daptomycin. They had a median gestational age of 32 weeks (IQR 31-34) and mean (SD) birth weight of 1.840 (867) grams. CoNS bacteremia isolates were s. epidermidis (50%), s. haemolyticus (20%), s. hominis (20%) and s. warneri (10%). The decision to start daptomycin (6 mg/kg/dose twice daily) was taken on median day 10 (ΙQR 7-15) of infection. None of the infants had focal complications or meningitis. Daptomycin therapy caused no renal, hepatic, muscular or gastrointestinal adverse events. One neonate developed seizures, and one death occurred due to multiple complications of prematurity. Most infants (11/12) were successfully treated and eventually had negative blood culture. Daptomycin monotherapy showed an adequate cure rate in premature neonates with persistent CoNS bacteremia in a tertiary NICU. In our study, daptomycin was effective and well tolerated; the safety profile, however, needs to be confirmed in larger studies and randomized controlled trials.

Neonatal mortality risk assessment using SNAPPE-2 score in a neonatal intensive care unit in moderate-to-late preterm Newborns

Background: In 1993, Richardson et al. introduced the score for neonatal acute physiology (SNAP), a 34-parameter system predicting mortality and morbidity in neonates. To enhance simplicity, it was later refined to nine parameters and renamed SNAP-II. Additionally, a perinatal extension known as SNAP Perinatal Extension, Version II (SNAPPE-II) was developed for broader applicability. Objectives: To determine the validity of SNAPPE-II in predicting the outcome in terms of mortality in premature babies of gestational age between 32 and 36 weeks in a tertiary care neonatal intensive care unit (NICU) of Cheluvamba Hospital, Mysore, Karnataka. Materials and Methods: The diagnostic study was conducted in the NICU of a tertiary care center in Mysore, India. The sample size of 138 subjects was calculated using a formula, and simple random sampling was used. The study included newborns with gestational ages between 32 and 36 weeks, and data was collected within 48 h of birth as per the proforma. The study assessed the correlation between the SNAPPE II score and mortality rate in babies admitted to the NICU. Data were analyzed using various statistical methods. Results: This study finds that the SNAPPE-II score has a moderate ability to distinguish between those newborns who will end up with mortality and those who will survive, as indicated by an area under ROC curve of 0.724, and has moderate diagnostic accuracy as indicated by a Youden index of 0.3974. The associated criterion for the SNAPPE-II score is &gt;57, indicating newborns are more likely to have mortality. Conclusion: The SNAPPE-II score can be used to predict neonatal mortality rates in moderate-to-late preterm babies of gestational age between 32 and 36 weeks.

Validation of a Costing Algorithm and Cost Drivers for Neonates Admitted to the Neonatal Intensive Care Unit.

Neonatal intensive care units (NICUs) account for over 35% of pediatric in-hospital costs. A better understanding of NICU expenditures may help identify areas of improvements. This study aimed to validate the Canadian Neonatal Network (CNN) costing algorithm for seven case-mix groups with actual costs incurred in a tertiary NICU and explore drivers of cost. A retrospective cohort study of infants admitted within 24 hours of birth to a Level-3 NICU from 2016 to 2019. Patient data and predicted costs were obtained from the CNN database and were compared to actual obtained from the hospital accounting system (Coût par Parcours de Soins et de Services). Cost estimates (adjusted to 2017 Canadian Dollars) were compared using Spearman correlation coefficient (rho). Among 1,795 infants included, 169 (9%) had major congenital anomalies, 164 (9%) with <29 weeks' gestational age (GA), 189 (11%) with 29 to 32 weeks' GA, and 452 (25%) with 33 to 36 weeks' GA. The rest were term infants: 86 (5%) with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia, 194 (11%) requiring respiratory support, and 541 (30%) admitted for other reasons. Median total NICU costs varied from $6,267 (term infants admitted for other reasons) to $211,103 (infants born with <29 weeks' GA). Median daily costs ranged from $1,613 to $2,238. Predicted costs correlated with actual costs across all case-mix groups (rho range 0.78-0.98, p < 0.01) with physician and nursing representing the largest proportion of total costs (65-82%). The CNN algorithm accurately predicts NICU total costs for seven case-mix groups. Personnel costs account for three-fourths of in-hospital total costs of all infants in the NICU. · Very preterm infants born below 33 weeks of gestation account for most of NICU resource use.. · Human resources providing direct patient care represented the largest portion of costs.. · The algorithm strongly predicted total costs for all case-mix groups..

Falls in oxygen saturations accompany electrographic seizures in term neonates: an observational study.

Effective seizure detection is important however, clinical signs of seizure activity may be subtle in neonates. This study aimed to systematically investigate SpO2 and respiratory pattern changes associated with EEG seizures in term-born neonates. An observational study in term neonates at risk of seizures admitted to a single tertiary level neonatal intensive care unit. Synchronised high-resolution physiological data (ECG, pulse oximetry, respiration) and EEG/amplitude-integrated EEG (aEEG) monitoring were recorded. Sections of traces with evidence of clear EEG seizure activity were compared with physiological data recorded at the same time. 22/44 (50%) neonates who had aEEG monitoring were noted to have electrographic seizures. Physiologic download measurements were available for 11 of these neonates. In nine of these, an acute drop in oxygen saturation (SpO2) of at least 5% was noted in at least one seizure. Accompanying apnoeas were noted in three neonates. Acute decreases in SpO2 were seen in term neonates associated with seizures and these were not always accompanied by an apnoeic episode. Physiologic download in association with EEG monitoring may assist in improving seizure detection. Unexplained drops in SpO2 could indicate further investigation for possible seizures in at-risk neonates. A decrease in blood oxygen saturation (SpO2) associated with EEG seizures can occur in term infants with HIE or perinatal stroke. Drops in SpO2 associated with EEG seizures in term infants with HIE or stroke may occur in the absence of apnoeas. Unexplained acute falls in SpO2 in sick neonates may suggest possible seizures. Drops in SpO2 associated with seizures in term infants can occur over less than 3 minutes. Physiological monitoring alongside EEG monitoring could help to improve seizure detection.

Corticosteroid use in neonatal hypotension: A survey of Canadian neonatologists

ObjectiveTo assess prescribing practices and perspectives regarding the use of corticosteroids in the management of neonatal hypotension. MethodsCross-sectional questionnaire-based electronic survey of neonatologists (n = 206) practicing at tertiary neonatal intensive care units across 30 academic centres in Canada. ResultsThe overall response rate was 33% (72/206), with a completion rate was 94%. Most (48/72, 64%) worked in a unit that covered both inborn and outborn infants, and 53% (37/70) worked in units with >100 very low birth weight infants admitted annually. Among the 72 respondents, 39% use a loading dose, of whom most (57%) use 2 mg/kg. Dosing ranges were variable, most using either 0.5 mg/kg or 1 mg/kg, q6h. Among the 56% (40/72) of neonatologists who reported measuring cortisol before initiation of hydrocortisone, cut-offs for initiation of hydrocortisone varied from <100 to <500 nmol/L, most of whom (48%) used <100 nmol/L. Of 71 respondents, 92% (65) indicated that a randomized control trial examining the use of corticosteroids in neonatal hypotension is needed, of whom 52% (37) indicated that the intervention group should receiving hydrocortisone after one vasopressor/inotrope. ConclusionsThis survey provides insight into the prescribing practices of tertiary neonatologists with regards to the use of corticosteroids in neonatal hypotension. While corticosteroids are frequently prescribed, there is variability in the indication, dosing, and duration of corticosteroid use. The findings from this survey can be used to inform further research, including a clinical trial, regarding the practice in the management of neonatal hypotension.