Comparative efficacy of volume expansion, inotropes and vasopressors in preterm neonates with probable transitional circulatory instability in the first week of life: a systematic review and network meta-analysis.

BACKGROUND: There exists limited agreement on the recommendations for the treatment of transitional circulatory instability (TCI) in preterm neonates OBJECTIVE: To compare the efficacy of various interventions used to treat TCI METHODS: Medline and Embase were searched from inception to 21st July 2023. Two authors extracted the data independently. A Bayesian random effects network meta-analysis was used. Recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. INTERVENTIONS: Dopamine, dobutamine, epinephrine, hydrocortisone, vasopressin, milrinone, volume and placebo. MAIN OUTCOME MEASURES: Mortality, major brain injury (MBI) (intraventricular haemorrhage > grade 2 or cystic periventricular leukomalacia), necrotising enterocolitis (NEC) ≥stage 2 and treatment response (as defined by the author). RESULTS: 15 Randomized Controlled Trials (RCTs) were included from the 1365 titles and abstracts screened. Clinical benefit or harm could not be ruled out for the critical outcome of mortality. For the outcome of MBI, epinephrine possibly decreased the risk when compared to dobutamine and milrinone (very low certainty). Epinephrine was possibly associated with a lesser risk of NEC when compared with dopamine, dobutamine, hydrocortisone and milrinone (very low certainty). Dopamine was possibly associated with a lesser risk of NEC when compared with dobutamine (very low certainty). Vasopressin possibly decreased the risk of NEC compared with dopamine, dobutamine, hydrocortisone and milrinone (very low certainty). Clinical benefit or harm could not be ruled out for the outcome response to treatment. CONCLUSIONS: Epinephrine may be used as the first-line drug in preterm neonates with TCI, the evidence certainty being very low. We suggest future trials evaluating the management of TCI with an emphasis on objective criteria to define it.

Hemodynamic effects of noradrenaline in neonatal septic shock: a prospective cohort study.

BACKGROUND: The incidence of neonatal septic shock in low-income countries is 26.8% with a mortality rate of 35.4%. The evidence of the hemodynamic effects of noradrenaline in neonates remains sparse. This study was carried out to evaluate the effects of noradrenaline in neonates with septic shock. METHODS: This was a single-center prospective cohort study in a tertiary care hospital's level III neonatal intensive care unit. Neonates with septic shock and those who received noradrenaline as a first-line vasoactive agent were included. Clinical and hemodynamic parameters were recorded before and after one hour of noradrenaline infusion. The primary outcomes were: response at the end of one hour after starting noradrenaline infusion and mortality rate. RESULTS: A total of 21 babies were analyzed. The cohort comprised 17 preterm neonates. The mean age of presentation with septic shock was 74.3 h. Resolution of shock at one hour after starting noradrenaline was achieved in 76.2% of cases. The median duration of hospital stay was 14 days. The mean blood pressure improved after the initiation of noradrenaline from 30.6 mm of Hg [standard deviation (SD) 6.1] to 37.8 mm of Hg (SD 8.22, p < 0.001). Fractional shortening improved after noradrenaline initiation from 29% (SD 13.5) to 45.1% (SD 21.1, p < 0.001). The mortality rate was 28.6% in our study. CONCLUSION: Noradrenaline is a potential drug for use in neonatal septic shock, with improvement in mean blood pressure and fractional shortening; however, further studies with larger sample sizes are needed to confirm our findings before it can be recommended as first-line therapy in neonatal septic shock.

Neonatal sepsis is one of the leading causes of neonatal mortality. In neonates with septic shock, mortality is high at 35.4% in low- and middle-income countries. The evidence of the hemodynamic effects of noradrenaline in neonates is still sparse, so we carried out a study in our tertiary care neonatal intensive care unit to evaluate the effects of noradrenaline in neonates with septic shock. Neonates with septic shock and those who received noradrenaline as a first-line vasoactive agent were included. Clinical and hemodynamic parameters were recorded before and after one hour of noradrenaline infusion. The primary outcomes were: response at the end of one hour after starting noradrenaline infusion and mortality rate. A total of 21 babies were analyzed. We found that there was a statistically significant improvement in the mean blood pressure and fractional shortening after noradrenaline initiation. The mortality rate was 28.6% in our study. We conclude that noradrenaline is a relatively safe and effective drug for the treatment of neonatal septic shock. However, further studies with larger sample sizes are needed to confirm our findings before it can be recommended as first-line therapy in neonatal septic shock.

Diagnostic utility of lung ultrasound in predicting the need for surfactant therapy in preterm neonates with respiratory distress.

Background: Lung ultrasound is an accurate and early predictor for surfactant replacement therapy in respiratory distress syndrome (RDS) as compared to clinical parameters and chest x-ray. However, lung pathologies for respiratory distress at birth have overlapping symptomatology and low middle-income countries have a higher incidence of congenital pneumonia, in addition to RDS, making the immediate diagnosis difficult. Thus, there is a need for assessing a cutoff for lung ultrasound scores in the given setting. Objectives: The primary objective was to determine the diagnostic accuracy of the lung ultrasound score (LUS) in predicting the need for surfactant therapy in preterm neonates with respiratory distress. Secondary objectives were to correlate LUS with corresponding oxygen saturation to the fraction of inspired oxygen ratio (SpO2/FiO2), arterial/Alveolar oxygen pressure ratio (a/A), and chest x-ray (CXR) findings. Methodology: A prospective observational study was carried out at a tertiary-level neonatal intensive care unit in India in 2022 enrolling 100 neonates <34 weeks gestational age with respiratory distress at birth. After initial stabilization of the neonate, LUS was performed and baseline parameters were noted. Surfactant was administered as per the 2019 European Consensus guidelines and LUS was repeated after 6 h of therapy. Results: The mean gestation of enrolled neonates was 31.06 ± 2.12 weeks and the mean birthweight was 1,412 ± 391 g. Approximately 58% were diagnosed with RDS and 30% had congenital pneumonia. Surfactant was administered to 40% of neonates. The cutoff LUS for surfactant therapy was 7 [area under the curve (AUC) 0.977; 95% CI, 0.947-1; P < 0.001; with sensitivity 92.5%, specificity 96.67%, PPV 94.87%, and NPV 95.08%] and the cutoff LUS for the second dose of surfactant was 10 (AUC 0.964; 95% CI, 0.913-1; P < 0.001). The score decreased by 3.24 (2.44-4.05) after 6 h of the first dose and correlated significantly with SpO2/FiO2 ratio (-0.750), a/A ratio (-0.650), and CXR findings (0.801). Conclusion: The study predicted an optimal LUS cutoff of 7 and 10 for the need for the first dose of surfactant and re-treatment, respectively, in neonates <34 weeks gestational age with respiratory distress.

Point-of-care Ultrasound to Diagnose and Monitor the Course of Necrotizing Enterocolitis.

Context: Neonatal gut ultrasound (US) is an emerging clinical tool for quick diagnosis and prognosis in various abdominal pathologies. In this review, we summarize normal gut US findings and concentrate on the specifications of diagnosing necrotizing enterocolitis. Evidence: A comprehensive literature search was conducted across numerous sources with relevant keywords along with the specified age group of 0-28 days of life. Findings: This review describes the normal gut US picture with the basic technicalities needed to master the art of point-of-care (POC) abdominal US. This modality is gaining importance due to its accuracy, applicability, safety, and affordability. Key findings include altered bowel perfusion, decreased peristalsis, and bowel wall thickening with better precision compared to abdominal X-ray (AXR). Many meta-analyses and narrative reviews have already demonstrated their usefulness. The high specificity and positive predictive value could make this tool a guide for early identification and prompt surgical intervention in the dreaded diagnosis of necrotizing enterocolitis. Conclusion: Emerging evidence and expertise in the field of abdominal US will make it a valuable tool for early diagnosis and prognosis of necrotizing enterocolitis.

Randomised controlled trial to compare the effect of PIOMI (structured) and routine oromotor (unstructured) stimulation in improving readiness for oral feeding in preterm neonates.

Background: Oral motor stimulation interventions improve oral feeding readiness and earlier full oral feeding in preterm neonates. However, using a structured method may improve the transition time to full oral feeds and feeding efficiency with respect to weight gain and exclusive breastfeeding when compared to an unstructured intervention. Objective: To compare the effect of Premature Infant Oral Motor Intervention (PIOMI) and routine oromotor stimulation (OMS) on oral feeding readiness. Methods: Randomised controlled trial conducted in a neonatal intensive care unit between June-December 2022. Preterm neonates, 29+0-33+6 weeks corrected gestational age, were studied. The intervention group received PIOMI and the control group received OMS. Primary outcome: time to oral feeding readiness by Premature Oral Feeding Readiness Assessment Scale (POFRAS) score ≥30. Secondary outcomes: time to full oral feeds, duration of hospitalisation, weight gain, and exclusive breastfeeding rates. Results: A total of 84 neonates were included and were randomised 42 each in PIOMI and OMS groups. The mean chronological age and time to oral feeding readiness were lower by 4.6 and 2.7 days, respectively, for PIOMI. The transition time to full oral feeds was 2 days lower for PIOMI and the duration of hospitalisation was 8 days lower. The average weight gain was 4.9 g/kg/day more and the exclusive breastfeeding rates at 1 month and 3 months post-discharge were higher by 24.5% and 27%, respectively, for the PIOMI group. The subgroup analysis of study outcomes based on sex and weight for gestational age showed significant weight gain on oral feeds in neonates receiving PIOMI. Similarly, the subgroup analysis based on gestational age favoured the PIOMI group with significantly earlier transition time and weight gain on oral feeds for the neonates >28 weeks of gestational age. The odds of achieving oral feeding readiness by 30 days [OR 1.558 (0.548-4.426)], full oral feeds by 45 days [OR 1.275 (0.449-3.620)], and exclusive breastfeeding at 1 month [OR 6.364 (1.262-32.079)] and 3 months [3.889 (1.186-12.749)] after discharge were higher with PIOMI. Conclusion: PIOMI is a more effective oromotor stimulation method for earlier and improved oral feeding in preterm neonates. Clinical trial registration: https://ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=70054&EncHid=34792.72281&modid=1&compid=19','70054det', identifier, CTRI/2022/06/043048.

Assessment of systemic circulation using ultrasound Doppler in late onset neonatal sepsis and its clinical correlation: an observational study.

OBJECTIVES: To measure the Doppler velocimetry parameters in the anterior cerebral artery (ACA), superior mesenteric artery (SMA), and main renal artery (RA) in neonates with late-onset sepsis and correlate it with associated clinical morbidities. METHODOLOGY: Prospective observational study carried out at a tertiary-level neonatal intensive care unit in India in 2022, enrolling 20 neonates with late-onset neonatal sepsis (LONS). Baseline characteristics and sepsis parameters obtained. Serial ultrasound performed on days 1, 3, and 7 from the day of clinical sepsis in the ACA, SMA, and RA and velocimetry measurements obtained. The findings were compared with 20 gestational age (GA) matched neonates in the control arm. RESULTS: The mean GA of neonates with LONS was 31.03 ± 2.79 weeks and their mean birthweight was 1474 ± 509.99 g. The peak systolic velocity, resistive and pulsatility indices were significantly higher in ACA, SMA, and RA and the end-diastolic velocity was significantly lower in ACA and RA (P < 0.05) in LONS. The incidences of intraventricular hemorrhage (IVH), necrotising enterocolitis (NEC), and acute kidney injury (AKI) in neonates with LONS were 45%, 50%, and 10% respectively. A subgroup analysis of the Doppler velocimetry parameters in the neonates with LONS and for neonates with and without clinical outcomes did not suggest a significant difference. CONCLUSION: LONS is associated with alterations in cerebral, splanchnic, and renal perfusion seen as abnormal blood flow velocimetry and vascular resistance which may predispose to IVH, NEC, and AKI.

Evidence-Based Consensus Recommendations for Skin Care in Healthy, Full-Term Neonates in India.

Purpose: Neonatal skin care practices guided by personal experience and preferences might be substantially different across different hospital settings. The aim of this consensus recommendation is to provide clinical practice guidance to healthcare practitioners on evidence-based neonatal skin care practices from delivery-to-discharge, in hospital settings. Patients and Methods: A Scientific Advisory Board meeting on "Evidence-based Neonatal Skin Care Practices and Protocols" was held in December 2020 with an expert panel comprising neonatologists, pediatricians, obstetricians and gynecologists and pediatric dermatologist. Comprehensive literature search was performed up to 23 March 2021 using PubMed and Google Scholar to retrieve relevant evidence. Results: Recommendations were developed on critical aspects of skin care in healthy full-term neonates including cleansing at birth, skin-to-skin care, cord care, diaper area care, initial and routine bathing, cleansers and emollients use, and criteria to choose appropriate skin care products. Recommendations include inclusion of skin assessment in routine neonatal care, first bath timing after cardio-respiratory and thermal stabilization, 6-24 hours after birth; bathing with water alone or adding a mild liquid cleanser could be considered appropriate as it does not impact the developing skin barrier; use of emollients is recommended for neonates with higher risk of development of eczema to maintain and enhance skin barrier function and integrity; and inclusion of skin care advice in neonatal discharge checklist. Importance of rigorous quality control, high-quality clinical trials for assessment of baby products, usage of products that are formulated appropriately for newborns, and full label transparency for baby products were highlighted. The panel identified gaps in literature and discussed the scope for future research. Conclusion: These recommendations may help to standardize evidence-based skin care for healthy full-term neonates in Indian hospital settings to improve the quality of care that neonates receive in hospital and facilitate improvement in overall neonatal health outcomes.

Management of neonatal pulmonary hypertension-a survey of neonatal intensive care units in India.

BACKGROUND: Persistent pulmonary hypertension of the newborn (PPHN) is a common neonatal condition associated with significant morbidity and mortality. First-line diagnostic and treatment options such as echocardiography and inhaled nitric oxide (iNO) are not routinely available in resource limited settings and alternative treatment modalities need to be utilized. This study was conducted to assess current diagnostic and management strategies used for PPHN in Indian neonatal intensive care units (NICUs). METHODS: A questionnaire in multiple choice question format was sent to practising neonatologists in India via an online survey tool between July to August 2021. Information pertaining to demographic data, diagnostic criteria and management strategies of PPHN was requested. The responses were collated and information processed. RESULTS: There were 118 respondent NICUs (response rate 74%). The majority of neonatal units (65%) admitted an average of 1-3 patients of PPHN per month. Targeted neonatal echocardiography (TnECHO) was practised in 80% of the units. Most common management strategies being followed were pulmonary vasodilators (88.1%), inotropes (85.6%), conventional ventilation (68.6%) and high frequency ventilation (59.3%). The most preferred pulmonary vasodilator was sildenafil (79%) and inotropic agent was milrinone (32%). Only 25% of respondents reported use of iNO. None of the participating units used extracorporeal membrane oxygenation. CONCLUSION: We found wide variability in management practices of PPHN across Indian NICUs. Non-selective pulmonary vasodilators are more widely used than iNO. There is an urgent need for structured TnECHO training programs and evidence based national guidelines for standardized management of PPHN as per availability of resources in India. Additional research on low cost alternative therapies to iNO in Indian settings might be helpful.

A scoping review of echocardiographic and lung ultrasound biomarkers of bronchopulmonary dysplasia in preterm infants.

Despite recent improvements in neonatal care, moderate to severe bronchopulmonary dysplasia (BPD) is still associated with high mortality and with an increased risk of developing pulmonary hypertension (PH). This scoping review provides an updated overview of echocardiographic and lung ultrasound biomarkers associated with BPD and PH, and the parameters that may prognosticate their development and severity, which could be clinically helpful to undertake preventive strategies. A literature search for published clinical studies was conducted in PubMed using MeSH terms, free-text words, and their combinations obtained through appropriate Boolean operators. It was found that the echocardiography biomarkers for BPD, and especially those assessing right ventricular function, are reflective of the high pulmonary vascular resistance and PH, indicating a strong interplay between heart and lung pathophysiology; however, early assessment (e.g., during the first 1-2 weeks of life) may not successfully predict later BPD development. Lung ultrasound indicating poor lung aeration at day 7 after birth has been reported to be highly predictive of later development of BPD at 36 weeks' postmenstrual age. Evidence of PH in BPD infants increases risk of mortality and long-term PH; hence, routine PH surveillance in all at risk preterm infants at 36 weeks, including an echocardiographic assessment, may provide useful information. Progress has been made in identifying the echocardiographic parameters on day 7 and 14 to predict later development of pulmonary hypertension. More studies on sonographic markers, and especially on echocardiographic parameters, are needed for the validation of the currently proposed parameters and the timing of assessment before recommendations can be made for the routine clinical practice.

Point-of-Care Ultrasound in Neonatology in India: The Way Forward.

The clinician-performed point-of-care ultrasound (POCUS) is a useful tool, and its scope includes bedside assessment of pulmonary (e.g., pneumothorax, pleural effusion), cardiac (e.g., pulmonary hypertension, ductus arteriosus), gastrointestinal (e.g., necrotising enterocolitis), and intracranial (e.g., intraventricular hemorrhage, cerebral blood flow velocities) pathologies, procedural guidance and rapid assessment of etiologies of acute clinical deterioration (e.g., pneumothorax, poor cardiac contractility, intraventricular hem-orrhage). Despite its potential to improve patient care, a curriculum and a structured program for POCUS training is lacking in India. Homogenous approach to training and ongoing quality assurance is essential to optimize benefits of POCUS as an effective tool in clinical practice. The training needs, the legal and infrastructural barriers to successful implementation of POCUS, and strategies to implement the program at the national level are discussed.

Point-of-care ultrasound (POCUS) protocol for systematic assessment of the crashing neonate-expert consensus statement of the international crashing neonate working group.

Sudden unexpected clinical deterioration or cardiorespiratory instability is common in neonates and is often referred as a "crashing" neonate. The established resuscitation guidelines provide an excellent framework to stabilize and evaluate these infants, but it is primarily based upon clinical assessment only. However, clinical assessment in sick neonates is limited in identifying underlying pathophysiology. The Crashing Neonate Protocol (CNP), utilizing point-of-care ultrasound (POCUS), is specifically designed for use in neonatal emergencies. It can be applied both in term and pre-term neonates in the neonatal intensive care unit (NICU). The proposed protocol involves a stepwise systematic assessment with basic ultrasound views which can be easily learnt and reproduced with focused structured training on the use of portable ultrasonography (similar to the FAST and BLUE protocols in adult clinical practice). We conducted a literature review of the evidence-based use of POCUS in neonatal practice. We then applied stepwise voting process with a modified DELPHI strategy (electronic voting) utilizing an international expert group to prioritize recommendations. We also conducted an international survey among a group of neonatologists practicing POCUS. The lead expert authors identified a specific list of recommendations to be included in the proposed CNP. This protocol involves pre-defined steps focused on identifying the underlying etiology of clinical instability and assessing the response to intervention.Conclusion: To conclude, the newly proposed POCUS-based CNP should be used as an adjunct to the current recommendations for neonatal resuscitation and not replace them, especially in infants unresponsive to standard resuscitation steps, or where the underlying cause of deterioration remains unclear. What is known? • Point-of-care ultrasound (POCUS) is helpful in evaluation of the underlying pathophysiologic mechanisms in sick infants. What is new? • The Crashing Neonate Protocol (CNP) is proposed as an adjunct to the current recommendations for neonatal resuscitation, with pre-defined steps focused on gaining information regarding the underlying pathophysiology in unexplained "crashing" neonates. • The proposed CNP can help in targeting specific and early therapy based upon the underlying pathophysiology, and it allows assessment of the response to intervention(s) in a timely fashion.

A detailed echocardiographic evaluation of ventricular functions in stable full term small for gestational age babies.

PURPOSE: SGA infants with fetal growth restriction have reduced ability to adapt themselves to the postnatal life because of certain epigenetic changes in cardiac function. The aim of the present study is to assess and compare the cardiac functions of fetal growth restricted SGA newborns to the term stable AGA newborns, and evaluate any differences in the cardiac functions during the postnatal transitional circulation. METHOD: This observational study was conducted at a multispecialty tertiary care hospital in Western India from June to November 2021. The newborns were evaluated using bedside echocardiography at 24-48 h and repeat screening after 48 h. The echocardiographic assessment of the systolic function was done using EF, FS, FAC and TAPSE; diastolic function using E/A wave ratio and global functioning using LV MPI. RESULT: Twnety-four babies were included in cases and 30 in the control arm of the study. Maternal and newborn characteristics were comparable between the two groups. FS, EF for left ventricle and TAPSE, FAC for right ventricular systolic function were significantly lower in SGA group (p = 0.02, 0.02, 0.00 and 0.01; respectively). The current study revealed a lower tricuspid E/A ratio and higher mitral E/A ratio with a significant difference beyond 48 h in the first week of life (p value 0.00). Left ventricular MPI was significantly higher in SGA infants compared to AGA infants during two subsequent readings in immediate newborn period with p values 0.01 and 0.02 respectively. The subgroup analysis revealed that fetal growth-restricted neonates with absent end-diastolic flow had a greater impact on ventricular functions. CONCLUSION: Present study showed a significant systolic and diastolic dysfunction during initial newborn period in growth restricted SGA infants.

Hemodynamics in neonates with polycythemia before and after partial exchange transfusion: an observational study.

Introduction: The current recommendations for the management of neonatal polycythemia are that partial exchange transfusion (PET) should be performed if the hematocrit is >70% in an asymptomatic neonate, or if the haematocrit is >65% in a symptomatic neonate. The hemodynamic effects of PET for neonatal polycythemia have not been well researched. Objectives: To evaluate the hemodynamic effects of PET in neonates with polycythemia. Methodology: Prospective observational study conducted in a neonatal intensive care unit of a tertiary care teaching hospital enrolling 21 neonates with polycythemia who underwent PET. Hemodynamic and echocardiographic parameters were obtained prior to PET and 6 h after procedure. Results: The mean gestational age of neonates with polycythemia was 35.08 ± 2.35 weeks with a mean birth weight of 1,929 ± 819.2 g. There was a significant improvement noted in heart rate and oxygen saturation post PET procedure (p < 0.05). Right ventricular systolic function parameters showed significant improvement (Tricuspid annular plane systolic excursion, fractional area change, right ventricular output) (p < 0.05). Left ventricular function parameters showed significant improvement (Fractional shortening, left ventricular output, E:A ratio) (p < 0.05). Resolution of symptoms was noted after PET procedure with no adverse events associated with PET. Conclusion: PET maybe effective in improving heart rate and oxygen saturation levels in polycythemic neonates. It has good short-term hemodynamic stability with improvement in right ventricular systolic, as well as left ventricular systolic and diastolic function. It is a safe and effective procedure with minimal adverse effects. Further studies with larger sample size and a control group would be required to corroborate our findings.

Oral versus intravenous sildenafil for pulmonary hypertension in neonates: a randomized trial.

BACKGROUND: Sildenafil is the drug of choice for neonatal pulmonary hypertension in developing countries where inhaled nitric oxide is not available. Available as oral and intravenous preparation - no study has been done in the past to compare the two forms. Each has its own benefits - but requires comparison in terms of efficacy and safety. This study was done to compare the efficacy of oral versus intravenous (IV) sildenafil in infants with mild to moderate pulmonary hypertension. METHODS: An open labelled randomized trial was conducted in a neonatal intensive care unit of urban tertiary hospital in western India between February 2019 to December 2020. Infants born after 34 weeks of gestation with Pulmonary arterial pressure (PAP) > 25 mm Hg measured by echocardiography, within 72 h of birth, were enrolled for the study. Participants were randomly assigned to receive sildenafil either orally or by intravenous route. Primary outcome was the time taken for PAP to decrease below 25 mm Hg. Secondary outcomes were time taken for oxygenation index to decrease by 25%, duration of invasive and non-invasive mechanical ventilation, nasal oxygen, hospital stay, time to achieve full feeds, mortality, and side effects. RESULTS: Forty patients were enrolled. The baseline characteristics of neonates in both groups were similar except for APGAR scores at 1 min and 5 min, with oral group having lower score [MEDIAN (IQR) 5.00 (4.00- 7.00) and 7.00 (6.00- 8.00)] compared to IV group [MEDIAN (IQR) 7.00 (6.00-8.00) and 9.00 (8.00-9.00)] respectively. Time taken for PAP to decrease below 25 mm was not statistically different between the oral and intravenous groups. Systemic hypotension occurred in 4 neonates of the intravenous group but none in the oral group. CONCLUSION: Oral and intravenous sildenafil had equal efficacy at reducing PAP in neonatal pulmonary hypertension, albeit intravenous sildenafil use was associated with a greater complication rate. TRIAL REGISTRATION: Trial was registered in the clinical trials registry of India [ CTRI/2019/04/018781 ][25/04/2019].

Hemodynamic parameters after Delayed Cord Clamping (DCC) in term neonates: a prospective observational study.

BACKGROUND: Delayed cord clamping (DCC) is practiced worldwide, as standard care in both term and preterm babies. Our aim was to determine the hemodynamic effects of DCC on transitional circulation. MATERIAL AND METHODS: This prospective observational study was carried out in a tertiary care hospital, at Pune, India, from May 2018 to October 2019.Term neonates born during the study period were included. The primary outcome variables of the study were right ventricular output (RVO), left ventricular output (LVO), superior vena cava (SVC) flow (ml/kg/min) and heart rate(HR) at 12 ± 6 and 48 ± 6 h of life measured by point of care functional echocardiography. Inter-observer and intra-observer variability was calculated for these parameters. RESULTS: Out of a total of 2744 deliveries during the study period, 620 babies were included. Mean gestational age of the enrolled babies was 38.96 ± 1.08 weeks and mean birth weight was 2.9 ± 0.39 kg. Mean heart rate of babies recorded at 12 ± 6 h of life was 127 beats per minute (bpm) whereas it was 128 bpm at 48 ± 6 h of life. RVO {mean (SD)} was 209.55(44.89) and 205.85(46.35) ml/kg/min, LVO {mean (SD)} was 133.68(31.15) and 134.78(29.84) ml/kg/min whereas SVC flow {mean (SD)} was 106.85(26.21) and 109.29(25.11) ml/kg/min at 12 ± 6 and 48 ± 6 h of life respectively. There was good intra-observer agreement in all the variables. SGA babies had a significantly higher heart rate at 12 ± 6 h of life as compared to AGA babies, although this difference in heart rate could not be appreciated at 48 ± 6 h of life. However SGA babies had a higher LVO, RVO and SVC flow than AGA babies at both the time points of observation. CONCLUSION: After DCC there is less fluctuation in the hemodynamic parameters (heart rate, cardiac output) at the two time points of observation.. As compared to AGA babies, SGA babies had a significantly higher baseline heart rate, LVO, RVO and SVC flow. LVO of SGA babies after delayed cord clamping is found to be significantly lower than LVO seen in other studies, favoring the cardio-stabilizing effect of DCC. BRIEF RATIONALE: This is the first study with a large sample size evaluating the hemodynamic effects of DCC in term neonates by functional echocardiography. The normative data of heart rate and cardiac output of term, stable babies with small for gestational age(SGA) as a special subgroup undergoing DCC requires further evaluation.

Does abnormal Doppler on cranial ultrasound predict disability in infants with hypoxic-ischaemic encephalopathy? A systematic review.

AIM: To evaluate whether abnormal resistive index or cerebral blood flow velocity (CBFV) on cranial ultrasound predicts disability (≥1 year) in infants with hypoxic-ischaemic encephalopathy (HIE). METHOD: This was a systematic review and meta-analysis of studies comparing developmental outcomes of infants with HIE with normal versus abnormal resistive index or CBFV. RESULTS: Twenty-six studies were included (pre-therapeutic hypothermia era, 20; therapeutic hypothermia era, six). Data from 15 studies (pre-therapeutic hypothermia, 10; therapeutic hypothermia, five) were available for meta-analysis. Pooled sensitivity and specificity, summary area under the receiver operating characteristic curve, and diagnostic odds ratio of resistive index or CBFV for predicting 'death or severe disability' were as follows. Pre-therapeutic hypothermia era: 0.83 (95% confidence interval [CI] 0.45-0.97) and 0.92 (95% CI 0.74-0.98), 0.94 (95% CI 0.92-0.96), 54 (95% CI 7-391). Therapeutic hypothermia era (measurements before therapeutic hypothermia): 0.62 (95% CI 0.41-0.80) and 0.96 (95% CI 0.88-0.99), 0.93 (95% CI 0.89-0.94), 23 (95% CI 6-91). Therapeutic hypothermia era (measurements during/after therapeutic hypothermia): 0.51 (95% CI 0.24-0.78) and 0.83 (95% CI 0.73-0.90), 0.81 (95% CI 0.78-0.85), 5 (95% CI 2-13). Overall Grading of Recommendations Assessment, Development and Evaluation (GRADE) rating of evidence was 'low' or 'very low'. INTERPRETATION: Low-level evidence suggests that abnormal resistive index or CBFV can predict death or disability with high sensitivity and specificity in infants with HIE who are not cooled. The specificity of these tests was high when performed before starting cooling in infants who received therapeutic hypothermia. WHAT THIS PAPER ADDS: Cerebral doppler ultrasound may be useful in predicting death or disability in infants with hypoxic-ischaemic encephalopathy who are not cooled. Cerebral doppler ultrasound may also be useful in infants who are cooled, if done before starting cooling. Cerebral doppler ultrasound may not be useful when performed during or after completing cooling.

OBJETIVO: Avaliar se o índice de resistência anormal ou a velocidade do fluxo sanguíneo cerebral (VFSC) na ultrassonografia craniana prediz incapacidade (≥1 ano) em bebês com encefalopatia hipóxico-isquêmica (EHI). MÉTODO: Esta foi uma revisão sistemática e meta-análise de estudos comparando os resultados do desenvolvimento de bebês com EHI com índice de resistência normal versus anormal ou VFSC. RESULTADOS: Vinte e seis estudos foram incluídos (hipotermia pré-terapêutica, 20; hipotermia terapêutica, 6). Dados de 15 estudos (hipotermia pré-terapêutica, 10; hipotermia terapêutica, 5) estavam disponíveis para meta-análise. Sensibilidade e especificidade agrupadas, área de resumo sob a curva característica de operação do receptor e razão de chances de diagnóstico do índice resistivo ou VFSC para prever "morte ou incapacidade grave" foram os seguintes. (1) Hipotermia pré-terapêutica: 0,83 (intervalo de confiança de 95% [IC] 0,45-0,97) e 0,92 (IC 95% 0,74-0,98), 0,94 (IC 95% 0,92-0,96),54 (IC 95% 7-391). (2) Hipotermia terapêutica (medições antes da hipotermia terapêutica): 0,62 (IC 95% 0,41-0,80) e 0,96 (IC 95% 0,88-0,99), 0,93 (IC 95% 0,89-0,94), 23 (IC 95% 6-91). (3) Hipotermia terapêutica (medidas durante/após a hipotermia terapêutica): 0,51 (IC 95% 0,24-0,78) e 0,83 (IC 95% 0,73-0,90), 0,81 (IC 95% 0,78-0,85),5 (IC 95% 2 -13). A classificação geral das evidências de Avaliação, Desenvolvimento e Avaliação de Recomendações (GRADE) foi 'baixa' ou 'muito baixa'. INTERPRETAÇÃO: Evidências de baixo nível sugerem que anormalidades índice resistivo ou VFSC pode prever morte ou incapacidade com alta sensibilidade e especificidade em bebês com EHI que não são resfriados. A especificidade desses testes foi alta quando realizados antes do início do resfriamento em bebês que receberam hipotermia terapêutica.

Sirolimus used for treatment of retroperitoneal arteriovenous malformation in a premature neonate.

We describe a case of a premature infant with antenatally detected retroperitoneal arteriovenous malformation (AVM) with extensive intraspinal extension. Treatment of the malformation with embolectomy and sclerotherapy was not feasible in view of intraspinal extensions and small size of vessels of the lesion. During a trial of propranolol over 20 days, the lesion progressed in size, roughly doubling in volume and was accompanied with deranged coagulation parameters. Treatment was therefore switched to oral prednisolone and sirolimus. The steroid was stopped after 6 weeks and sirolimus was continued with serum drug level monitoring and serial imaging of the malformation. After 4 months of sirolimus, the AVM remained at the same size as at the start of treatment, thus we propose that the drug may have arrested the growth of the lesion. This case highlights the use of sirolimus in management of AVMs in infants.

Perinatal transmission of SARS-CoV-2 and transfer of maternal IgG/neutralizing anti-SARS-CoV-2 antibodies from mothers with asymptomatic infection during pregnancy.

PURPOSE: COVID-19 pandemic remains a serious public health threat worldwide. In view of the limited data on the risk of perinatal transmission of SARS-CoV-2 and transfer of maternal anti-SARS-CoV-2 antibodies, the present study was undertaken. METHODS: A prospective study including 57 pregnant women with a positive SARS-CoV-2 RNA test (SARS-CoV-2-RNA+) and 59 neonates born to them was conducted at Pune, India. 39 viral RNA negative (SARS-CoV-2-RNA-negative) pregnant women and their 39 neonates were included as controls. Neonatal nasal swab/cord blood samples were subjected to SARS-CoV-2 RNA detection by RT-PCR for investigation of perinatal transmission. Transfer of maternal antibodies was studied using ELISA and PRNT. RESULTS: 10/57 SARS-CoV-2-RNA+ mothers were symptomatic. The duration between COVID-19 diagnosis and delivery was ≤ 7 days for 82.4%. Perinatal transmission as evidenced by viral RNA in the neonatal nasal swab/cord blood (CB) was 3.6%. IgG-anti-SARS-CoV-2 positivity was 21.6%. Of the 39 neonates born to SARS-CoV-2-RNA-negative mothers, 20 (51%) and none, respectively, were positive for IgG-anti-SARS-CoV-2 and viral RNA. Preterm deliveries were higher in SARS-CoV-2-RNA+ (18.6%) than SARS-CoV-2 RNA-negative (0/39) mothers (p < 0.005). Respiratory distress at birth (< 4 h) was higher among neonates of SARS-CoV-2-RNA+ (20/59, 33.9%) than SARS-CoV-2-RNA-negative mothers (3/39, 7.7%; p < 0.001). ~ 75% IgG-positives exhibited neutralization potential with mean PRNT titers of 42.4 ± 24 (SARS-CoV-2-RNA+) and 72.3 ± 46.7 (SARS-CoV-2 RNA-negative); higher in the latter (p < 0.05). CONCLUSION: The rate of perinatal transmission was low. Transfer of maternal antibodies was lower among SARS-CoV-2-RNA+ mothers than SARS-CoV-2-RNA-negative mothers with subclinical infection during pregnancy. Presence of neutralizing antibodies in majority of IgG-positives suggests protection from SARS-CoV-2 in early life.

Pulmonary hypertension in late onset neonatal sepsis using functional echocardiography: a prospective study.

PURPOSE: Pulmonary hypertension (PH) in the newborn period is associated with significant morbidity and mortality. Sepsis has been identified as an independent risk factor for PH in newborns. Data on the proportion and severity of PH in association with neonatal sepsis are scarce. This study was aimed to measure the pulmonary artery systolic pressure (PASP) in neonates with late onset sepsis (LOS) and to estimate the proportion of PH in neonatal sepsis using functional echocardiography (FnECHO). METHODS: This prospective observational study was conducted at a tertiary neonatal intensive care unit (NICU). All neonates admitted in the NICU with suspected LOS underwent FnECHO within 6 hours of onset of clinical signs and PASP was recorded. Pulmonary hypertension was defined as PASP of > 35 mmHg. PASP of neonates with positive culture results (proven LOS) was compared with that of gestational age-matched stable controls without sepsis. RESULTS: Thirty three neonates with proven LOS were analysed (study group). Sixteen neonates (49%) in the study group had PH. Mean PASP of the study group was significantly higher than that of the control group (35.3 ± 10.13 mmHg and 12.58 ± 3.92 mmHg, respectively; P < 0.0001). None of the neonates in the control group had PH. CONCLUSION: Pulmonary artery pressure was higher in neonates with late onset neonatal sepsis as compared to that of stable babies without sepsis. Pulmonary hypertension was seen in nearly half of term as well as preterm neonates with late onset sepsis.