Epidemiology, Clinical Profile, Intensive Care Needs and Outcome in Children with SARS-CoV-2 Infection Admitted to a Tertiary Hospital During the First and Second Waves of the COVID-19 Pandemic in India

Objectives To compare the epidemiological, clinical profle, intensive care needs and outcome of children hospitalized with SARS-CoV-2 infection during the frst and second waves of the pandemic. Methods This was a retrospective study of all children between 1 mo and 14 y, admitted to a dedicated COVID-19 hospital (DCH) during the frst (1st June to 31st December 2020) and second waves (1st March to 30th June 2021). Results Of 217 children, 104 (48%) and 113 (52%) were admitted during the frst and second waves respectively. One hundred ffty-two (70%) had incidentally detected SARS-CoV-2 infection, while 65 (30%) had symptomatic COVID-19. Comorbidities were noted in 137 (63%) children. Fifty-nine (27%) and 66 (30%) children required high-dependency unit (HDU) and ICU care respectively. Severity of infection and ICU needs were similar during both waves. High-fow oxygen (n=5, 2%), noninvasive ventilation [CPAP (n=34, 16%) and BiPAP (n=8, 5%)] and invasive ventilation (n=45, 21%) were respiratory support therapies needed. NIV use was more during the second wave (26% vs. 13%; p=0.02). The median (IQR) length (days) of DCH stay among survivors was longer during the frst wave [8 (6–10) vs. 5.5 (3–8); p=0.0001]. Conclusions Disease severity, associated comorbidities, PICU and organ support need and mortality were similar in the frst and second waves of the pandemic. Children admitted during the second wave were younger, had higher proportion of NIV use and shorter length of COVID-19 hospital stay.

Clinical characteristics & outcome of SARS-CoV-2 infected neonates presenting to paediatric emergency

Background & objectives: Data on neonatal COVID-19 are limited to the immediate postnatal period, with a primary focus on vertical transmission in inborn infants. This study was aimed to assess the characteristics and outcome of COVID-19 in outborn neonates. Methods: All neonates admitted to the paediatric emergency from August 1 to December 31, 2020, were included in the study. SARS-CoV-2 reverse transcription- (RT)-PCR test was done on oro/nasopharyngeal specimens obtained at admission. The clinical characteristics and outcomes of SARS-CoV-2 positive and negative neonates were compared and the diagnostic accuracy of a selective testing policy was assessed. Results: A total of 1225 neonates were admitted during the study period, of whom SARS-CoV-2 RT-PCR was performed in 969. The RT-PCR test was positive in 17 (1.8%). Mean (standard deviation) gestation and birth weight of SARS-CoV-2-infected neonates were 35.5 (3.2) wk and 2274 (695) g, respectively. Most neonates (11/17) with confirmed COVID-19 reported in the first two weeks of life. Respiratory distress (14/17) was the predominant manifestation. Five (5/17, 29.4%) SARS-CoV-2 infected neonates died. Neonates with COVID-19 were at a higher risk for all-cause mortality [odds ratio (OR): 3.1; 95% confidence interval (CI): 1.1-8.9, P=0.03]; however, mortality did not differ after adjusting for lethal malformation (OR: 2.4; 95% CI: 0.7-8.7). Sensitivity, specificity, accuracy, positive and negative likelihood ratios (95% CI) of selective testing policy for SARS-CoV-2 infection at admission was 52.9 (28.5-76.1), 83.3 (80.7-85.6), 82.8 (80.3-85.1), 3.17 (1.98-5.07), and 0.56 (0.34-0.93) per cent, respectively. Interpretation & conclusions: SARS-CoV-2 positivity rate among the outborn neonates reporting to the paediatric emergency and tested for COVID-19 was observed to be low. The selective testing policy had poor diagnostic accuracy in distinguishing COVID-19 from non-COVID illness.

Congenital Rubella Syndrome as a possible cause for persistent thrombocytopenia in early infancy: The Forgotten Culprit

Abstract We present a case of a late preterm intrauterine growth-restricted neonate with isolated and persistent severe thrombocytopenia. At birth, the neonate did not have a complete clinical spectrum of congenital rubella syndrome (CRS) but later developed peculiar findings that helped clinch the diagnosis. The neonate also had interstitial pneumonia and died secondary to superimposed acute viral infection leading to acute respiratory distress syndrome. The serology was positive for IgM antibodies against the rubella virus. The constellation of clinical manifestations of congenital rubella in the presence of positive IgM antibody against rubella and consistent histopathology confirmed the diagnosis of CRS.

Reducing Healthcare-associated Infections in Neonates by Standardizing and Improving Compliance to Aseptic Non-touch Techniques: A Quality Improvement Approach

Objective: To standardize and improve compliance to Asepticnon-touch techniques (ANTT) for commonly performedprocedures in Neonatal intensive care unit (NICU) throughapplication of Model for improvement, and study its impact onHealthcare-associated infection (HCAI) rates.Design: Quality improvement project utilizing multiple Plan-Do-Study-Act (PDSA) cycles.Setting: Tertiary-care neonatal unit.Participants: All resident doctors and nurses working in neonatalunit were subjects for assessment of compliance to ANTT. Alladmitted neonates staying in hospital for more than 48 hours weresubjects for HCAI data collection.Procedure: Most frequently performed procedures in NICU wereidentified and pictorial Standard Operating Procedures (SOP)were developed. Implementation and uptake was reinforced bymeans of PDSA cycles. Compliance to ANTT was assessed asproportion of components to which adherence was documented.Trend of HCAI rates in unit were analyzed using process controlcharts.Main outcome measure: Change in compliance to ANTT formost frequently performed procedures.Results: Significant improvement in compliance to ANTTpractices was observed, specifically in use of procedure tray/trolley (16% to 49%, P=0.001), iv hub scrubbing (0% to 60%,P=0.001), local skin cleaning (33% to 67%, P=0.004), personalprotective equipment use (55% to 80%, P=0.02) and disposal(27% to 51%, P=0.03), use of non-touch technique (50% to 70%,P=0.001) and reduction in key part contamination (45% to 31%,P=0.03). A modest decrease in HCAI rates was seen in the shortperiod of observation after implementation.Conclusions: Substantial improvements in compliance toaseptic non-touch techniques can be ensured by adopting acombination of initial intensive teaching and sustaining throughmultiple PDSA cycles, targeting specific areas revealed by audits.

Fluid Supplementation versus No Fluid Supplementation in Late Preterm and Term Neonates with Asymptomatic Polycythemia: A Randomized Controlled Trial.

Objective: To compare supplemental intravenous fluids with no supplementation in asymptomatic polycythemic late preterm and term neonates. Methods: 55 infants with venous haematocrit of 65-75 were randomly allocated to receive either 25 mL/kg IV normal saline over 6-8 hours or routine fluids. They were followed up for 48 hours. Results: There was no significant difference between fluid supplementation and control groups regarding need for partial exchange transfusion [6/27 (22.2%) vs 8/28 (28.6%); P=0.59]. Conclusions: We did not find any evidence of clinical benefit with IV fluid supplementation in late preterm and term neonates with asymptomatic polycythemia (PCV 65-75).

Stress in Fathers of Premature Newborns Admitted in a Neonatal Intensive Care Unit.

Objective: To study stress in fathers of preterm infants admitted in a neonatal intensive care unit. Methods: Questionnaire-based study. Questionnaire included domains on infant’s health, maternal illness, staff behavior, parental role, home affairs and finances. Eligible fathers were repeatedly interviewed on day 7 (n=80), day 17 (n=59) and day 27 (n=28). Raw and standardized stress scores were calculated. Results: Financial burden was the main stressor at all times. Stress related to staff behavior and altered parental role reduced with time. Birthweight and father’s age, occupation and education independently predicted stress. Conclusions: Fathers of preterm infants admitted in hospital are stressed, primarily due to financial burden.

Intestinal Colonization Among Very Low Birth Weight Infants in First Week of Life.

Objective: To study intestinal colonization patterns in very low birth weight infants in the first week of life in a neonatal intensive care unit. Methods: Meconium/stool specimens were obtained on days 1, 3, 5 and 7 from 38 very lowbirth- weight infants in a level III neonatal intensive care unit. Results: On day 1, 45% had sterile guts, and by day 3, all infants were colonized. E. coli, K. pneumoniae and Enterococcus fecalis were predominant organisms. Lactobacilli was found in one isolate and Bifidobacteria was not detected during the study period. There was an association between formula feeding and E. coli colonization. Conclusions: Very low birth weight infants admitted in neonatal intensive care units have abnormal intestinal colonization patterns.

Predictors of Mortality in Neonates with Meconium Aspiration Syndrome.

Objective: To identify risk factors for mortality in neonates with meconium aspiration syndrome. Methods: All neonates (2004-2010) with meconium aspiration syndrome, irrespective of gestation were included. Risk factors were compared between those who died and survived. Results: Out of 172 included neonates, 44 (26%) died. Mean (SD) gestation and birth weight were 37.9 (2.3) weeks and 2545 (646g), respectively. Myocardial dysfunction [aOR 28.4; 95% CI (8.0-101); P<0.001] and higher initial oxygen requirement [aOR 1.04; 95% CI (1.02-1.07); P<0.001] increased odds of dying while a higher birth weight [aOR 0.998; 95% CI (0.997-1.00); P=0.005] reduced the odds of dying. Conclusions: Meconium aspiration syndrome is associated with significant mortality. Myocardial dysfunction, birth weight, and initial oxygen requirement are independent predictors of mortality.

Short Course Versus 7-Day Course of Intravenous Antibiotics for Probable Neonatal Septicemia: A Pilot, Open-label, Randomized Controlled Trial.

Objective: To compare a short course of antibiotics (48 to 96 hours) and a standard course of antibiotics (7 days) for probable neonatal sepsis. Design: Randomized, controlled, open-labeled trial with blocking and stratification according to birth weight. Setting: Tertiary care, referral, teaching hospital in Northern India. Participants: Neonates >30 wks gestation and >1000 g at birth, with probable sepsis (clinical signs of sepsis, raised C-reactive protein) were enrolled. Babies with major malformations, severe birth asphyxia, meningitis, bone or joint or deep-seated infection, those who were already on antibiotics, and those undergoing surgery were excluded. Neonates, who had clinically remitted on antibiotic therapy – by the time a sterile blood culture report was received – were randomized. Intervention: In the intervention arm, antibiotics were stopped after the 48-hour culture was reported sterile. In the control arm, antibiotics were continued to a total of 7 days. Main outcome measure: “Treatment failure” defined as reappearance of signs suggestive of sepsis within 15 days of stopping antibiotics, supported by laboratory evidence and adjudicated by a blinded expert committee. Results: 52 neonates were randomized to receive a short course or 7-day course (n=26 each). Baseline variables were balanced in the 2 groups. There was no significant difference in the treatment failures between the 2 groups (3 babies in the 7-day group vs none in short course group, P=0.23). Conclusion: No difference in the treatment failure rates could be identified between short course and 7-day groups among neonates >30 weeks and >1000 grams with probable sepsis.

Score for neonatal acute physiology II predicts mortality and persistent organ dysfunction in neonates with severe septicemia.

Objective: To investigate the relationship between score for neonatal acute physiology II (SNAP II) applied within 12 hours from the onset of severe sepsis, and death and persistent organ dysfunction (OD). Design: Prospective cohort study. Setting: Level III neonatal intensive care unit. Participants: Neonates with severe sepsis. Intervention:SNAP II was applied within the first 12 hours from the onset of severe sepsis. Neonates with major malformations, severe asphyxia and prior blood products were excluded. Major outcome measure: Death at day 14 from enrolment. Results: Forty neonates completed the study. Twenty-five died within 14 days. The median SNAP II was significantly higher in babies who died versus those who survived [median (IQR): 43 (36 – 53.5) vs 18 (16 - 37), P<0.001]. A SNAP II greater than 40 had 88% positive predictive value for death and persistent OD each, and 86.6% and 86% specificity for death and persistent OD, respectively. On day 14 from enrolment, more organs normalized/improved in the subjects with SNAP II of £40. Perfusion related SNAP II parameters were significantly associated with death and organ dysfunction. Conclusions: Severely septicemic neonates with high SNAP II scores (>40) have a higher risk of dying and persistent organ dysfunction. Individual SNAP II parameters do not contribute equally in prediction of mortality.

Single versus multiple courses of antenatal betamethasone and neonatal outcome: a randomized controlled trial.

OBJECTIVES: This study compared the beneficial and adverse neonatal effects of a single versus repeated courses of antenatal betamethasone. SETTING: Tertiary care hospital DESIGN: Open labeled, randomized controlled trial. PARTICIPANTS: Pregnant women (26-33 weeks) at risk of preterm delivery, who received one course of antenatal betamethasone and remained undelivered for 7 days.Those with uncertain gestation, major malformations and frank chorioamnionitis were excluded. INTERVENTIONS: Subjects were randomized to receive weekly antenatal betamethasone until 34 weeks or no further betamethasone. OUTCOME MEASURES: Primary: incidence of severe respiratory distress syndrome (RDS). Secondary: incidence of non-severe RDS and other neonatal morbidity; birth weight, length and occipito-frontal circumference (OFC); and, development and growth at 6 mo corrected age. RESULTS: 38 subjects were allocated to each group. Severe RDS was similar in multiple and single course groups (7% vs. 3% respectively, P=0.34), as was incidence of other morbidity. Composite outcome of RDS and or death within 28 days tended to be less in multiple course group (P=0.07). Birth anthropometry was similar in the 2 groups. At 6 mo corrected age (n=44), weight and length were significantly lower in multiple course group (p=0.003 and P=0.007, respectively), whereas OFC was not different (P=0.1). There were no differences vis a vis neurodevelopmental outcomes. CONCLUSIONS: A single course of antenatal betamethasone was as efficacious as multiple courses, with respect to prevention of neonatal morbidity. Multiple antenatal betamethasone courses have long-term adverse effects on infant weight and length growth, but not on OFC and neurodevelopment.

Evaluation of lactate dehydrogenase, creatine kinase and hepatic enzymes for the retrospective diagnosis of perinatal asphyxia among sick neonates.

It is difficult to make a retrospective diagnosis of perinatal asphyxia in symptomatic neonates delivered non-institutionally. We studied serum creatine kinase muscle-brain fraction (CK-MB), lactate dehydrogenase (LDH), glutamic oxaloacetic transaminase (SGOT) and glutamic pyruvate transaminase (SGPT) for differentiating asphyxiated (n=25) from non-asphyxiated (n=20) neonates who present with non-specific signs of sickness. CK-MB was assayed at 8 and 24 h; and LDH, SGOT and SGPT at 72 h of life. On comparing cases and controls, median 8-hr CK-MB [80 U/L vs. 26 U/L respectively, P< 0.001], median 24-hr CK-MB [33.5 U/L vs. 21.5 U/L respectively, P=0.009] and median LDH [965 U/L vs. 168 U/L respectively, P< 0.001] were higher in asphyxiated neonates. Raised LDH had 100% sensitivity, while CK-MB had 100% specificity for asphyxia. LDH had the highest area under ROC curve (0.998). We conclude that LDH at 72 hr of life is most accurate at differentiating asphyxiated from non-asphyxiated symptomatic neonates.