Diagnostic Accuracy of Point-of-Care Testing of C-Reactive Protein, Interleukin-6, and Procalcitonin in Neonates with Clinically Suspected Sepsis: A Prospective Observational Study.

OBJECTIVE: Sepsis often prompts clinicians to start empirical antibiotics in suspected neonates while awaiting diagnosis. The next-generation testing with point-of-care (POC) techniques offers a lead-time advantage that could bridge the gap by providing a timely diagnosis. MATERIALS AND METHODS: We conducted a prospective diagnostic study in 82 neonates enrolled between May and October 2022 in a level III neonatal intensive care unit. All neonates with a new episode of clinically suspected sepsis were included. Diagnostic accuracy of POC testing of C-reactive protein (CRP), interleukin-6 (IL-6), and procalcitonin (PCT) with standard laboratory methods was performed. RESULTS: The mean gestation age and birth weight of the neonates were 33.17 ± 4.25 weeks and 1,695.4 ± 700.74 grams, respectively. Most neonates were preterm (75%) with nearly equal proportions of early (51.22%) and late-onset (48.78%) sepsis. The POC CRP correlated well with standard CRP (r = 0.8001, 95% CI: 0.706-0.867, p < 0.0001). Among the three biomarkers, CRP had the maximum diagnostic accuracy (area under the curve [AUC] - 0.73) followed by PCT (AUC - 0.65) and IL-6 (0.55). There was no significant difference in the diagnostic accuracy of CRP (p = 0.46), PCT (p = 0.29), and IL-6 (p = 0.60) in early- and late-onset sepsis. The mean time for POC estimation of IL-6, PCT, and CRP was 12 ± 3 min which was significantly less compared to 366 ± 61 min for standard techniques (p < 0.001). CONCLUSION: POC CRP correlates well with standard techniques of estimation, and CRP alone and in combination with PCT has good diagnostic accuracy in neonatal sepsis.

Multisystem inflammatory syndrome in neonates (MIS-N): a systematic review.

Recently, a new pattern of multisystem inflammatory syndrome following an infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged globally. The initial cases were described in the adult population followed by sporadic cases in the pediatric population also. By the end of 2020, similar reports were recognised in the neonatal age group. The purpose of this study was to systematically review clinical characteristics, laboratory parameters, treatment, and outcomes of neonates with multisystem inflammatory syndrome in neonates (MIS-N). A systematic review was conducted after registering with PROSPERO and electronic databases including MEDLINE, EMBASE, PubMed, SCOPUS, Google Scholar, and Web of Science were searched from January 1st 2020 till September 30th 2022. A total of 27 studies describing 104 neonates were analysed. The mean gestation age and birth weight was 35.9 ± 3.3 weeks and 2255.7 ± 783.7 g respectively. A large proportion (91.3%) of the reported cases belonged to the South-East Asian region. The median age of presentation was 2 days (range: 1-28 days) with cardiovascular system being the predominant system involved in 83.65% followed by respiratory (64.42%). Fever was noted in only 20.2%. Commonly elevated inflammatory markers were IL-6 in 86.7% and D-dimer in 81.1%. Echocardiographic evaluation suggested ventricular dysfunction in 35.8% and dilated coronary arteries in 28.3%. Evidence of SARS-CoV-2 antibodies (IgG or IgM) was seen in 95.9% neonates and evidence of maternal SARS-CoV-2 infection, either as history of COVID infection or positive antigen or antibody test, was noted in 100% of the cases. Early MIS-N was reported in 58 (55.8%) cases, late MIS-N in 28 (26.9%), and 18 cases (17.3%) did not report the timing of presentation. There was a statistically increased proportion of preterm infants (67.2%, p < 0.001), and a trend towards increased low birth weight infants, in the early MIS-N group when compared to the infants with late MIS-N. Fever (39.3%), central nervous system (50%), and gastrointestinal manifestations (57.1%) were significantly higher in the late MIS-N group (p = 0.03, 0.02, 0.01 respectively). The anti-inflammatory agents used for the treatment of MIS-N included steroids 80.8% which were given for a median of 10 (range 3-35) days and IVIg in 79.2% with a median of 2 (range 1-5) doses. The outcomes were available for 98 cases, of whom 8 (8.2%) died during treatment in hospital and 90 (91.8%) were successfully discharged home.   Conclusion: MIS-N has a predilection for late preterm males with predominant cardiovascular involvement. The diagnosis is challenging in neonatal period due to overlap with neonatal morbidities and a high risk of suspicion is warranted, especially in presence of supportive maternal and neonatal clinical history. The major limitation of the review was inclusion of case reports and case series, and highlights need of global registries for MIS-N. What is Known: • A new pattern of multisystem inflammatory syndrome following SARS-CoV-2 infection has emerged in adult population with sporadic cases now being reported in neonates. What is New: • MIS-N is an emerging condition with a heterogeneous spectrum and has a predilection for late preterm male infants. Cardiovascular system is the predominant system involved  followed by respiratory, however fever remains an uncommon presentation unlike other age-groups. There are two subtypes based on timing of presentation, with early MIS-N being reported more in preterm and low-birth weight infants.

Favourable outcome of a severe bradyarrhythmia in a neonate: a case report.

We report the case of a term neonate with severe fetal bradycardia with an unusually benign clinical course with follow-up till infancy.

A single-center observational study on clinical features and outcomes of 21 SARS-CoV-2-infected neonates from India.

Coronavirus disease-19 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an ongoing pandemic with significant morbidity and mortality. Neonates represent a vulnerable population, in which we have limited knowledge of its natural history, optimal management, and outcomes. In this retrospective observational study from a low-middle-income setting, clinical characteristics and outcomes of neonatal SARS-CoV-2 infection were evaluated. We report an incidence of 10.6% of SARS-CoV-2 infection (21 neonates), among a group of 198 neonates with suspected infection. Most of the SARS-CoV-2-infected neonates were term (80.9%) and none required any resuscitation. The infection was detected by a positive nasopharyngeal swab reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV-2. Neonatal COVID-19 manifestations developed in one-third (33.3%) of the infected neonates. Most of them demonstrated the involvement of respiratory (33.3%) and gastrointestinal systems (4.8%). Laboratory parameters suggested multi-systemic involvement, with elevated creatine kinase (CK) (76.2%), creatine kinase-myocardial band (CK-MB) (76.2%), and lactate dehydrogenase (LDH) (71.4%) levels. Supportive treatment was given to infected neonates with intensive care required in six neonates (28.6%). This included four preterm and two term neonates, of which two received non-invasive and one received invasive ventilation with intra-tracheal surfactant instillation. IgM antibodies against COVID-19 were detected in one neonate. All neonates with COVID-19 improved and were successfully discharged.Conclusion: SARS-CoV-2 in neonates has a wide clinical spectrum. Further studies are needed which are adequately powered to completely understand the course of this infection in neonates, its implications not only in the neonatal period but also on long-term follow-up. What is Known: • SARS-CoV-2 infection has a predilection for all age groups but with limited literature on clinical profile, outcomes, and long-term follow-up in neonates. What is New: • SARS-CoV-2 infection in neonates has a wide clinical spectrum and displays a significant overlap with common neonatal conditions. • Most neonates with COVID-19 improved with supportive care, though a subset required intensive care, emphasizing the need for cautious monitoring and management.

Long-Term Growth and Neurodevelopmental Outcomes of Neonates Infected with SARS-CoV-2 during the COVID-19 Pandemic at 18-24 Months Corrected Age: A Prospective Observational Study.

INTRODUCTION: During the early coronavirus disease (COVID-19) pandemic in 2020, researchers cautioned about the potential neuroinvasive capability of the virus and long-term neurological consequences. Although a few preliminary studies have found delayed communication, fine motor, and problem-solving skills in infants after COVID-19 infection, there continues to be a paucity of data on long-term development of neonates diagnosed with COVID-19. METHODS: We conducted a prospective study of 20 neonates who acquired severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection during the first wave of the pandemic (April-July 2020). At 18-24 months corrected age, we assessed neurodevelopment by Bayley Scales of Infant and Toddler Development, the third edition (BSID-III), along with growth, hearing, and vision evaluation. RESULTS: The mean corrected age at assessment was 21 months 11 days ± 1 month 28 days. We found developmental delay in nearly half of the children with scores below one standard deviation in either of the BSID-III domains. Mild delay in either motor, cognitive, or language domains was found in 9 (45%) children and moderate delay in 2 (10%). Expressive language, fine motor, and receptive language were predominantly affected. None of the children had hearing impairment, blindness, or significant growth faltering including clinically severe microcephaly. The mean composite cognitive, language, and motor scores were significantly lower in those with neurodevelopmental delay (p value - 0.02, 0.000, and 0.03, respectively) without any differences in their disease characteristics. CONCLUSION: Neonates infected with SARS-CoV-2 have an increased risk of developmental delays in expressive language, fine motor, and receptive language skills at 18-24 months of age. The severity of delays is predominantly mild.

Antimicrobial Stewardship Programs in Neonates: A Meta-Analysis.

BACKGROUND AND OBJECTIVES: Neonatal sepsis is a significant contributor to mortality and morbidity; however, the uncontrolled use of antimicrobials is associated with significant adverse effects. Our objective with this article is to review the components of neonatal antimicrobial stewardship programs (ASP) and their effects on clinical outcomes, cost-effectiveness, and antimicrobial resistance. METHODS: We selected randomized and nonrandomized trials and observational and quality improvement studies evaluating the impact of ASP with a cutoff date of May 22, 2023. The data sources for these studies included PubMed, Medline, Embase, Cochrane CENTRAL, Web of Science, and SCOPUS. Details of the ASP components and clinical outcomes were extracted into a predefined form. RESULTS: Of the 4048 studies retrieved, 70 studies (44 cohort and 26 observational studies) of >350 000 neonates met the inclusion criteria. Moderate-certainty evidence reveals a significant reduction in antimicrobial initiation in NICU (pooled risk difference [RD] 19%; 95% confidence interval [CI] 14% to 24%; 21 studies, 27 075 infants) and combined NICU and postnatal ward settings (pooled RD 8%; 95% CI 6% to 10%; 12 studies, 358 317 infants), duration of antimicrobial agents therapy (pooled RD 20%; 95% CI 10% to 30%; 9 studies, 303 604 infants), length of therapy (pooled RD 1.82 days; 95% CI 1.09 to 2.56 days; 10 studies, 157 553 infants), and use of antimicrobial agents >5 days (pooled RD 9%; 95% CI 3% to 15%; 5 studies, 9412 infants). Low-certainty evidence reveals a reduction in economic burden and drug resistance, favorable sustainability metrices, without an increase in sepsis-related mortality or the reinitiation of antimicrobial agents. Studies had heterogeneity with significant variations in ASP interventions, population settings, and outcome definitions. CONCLUSIONS: Moderate- to low-certainty evidence reveals that neonatal ASP interventions are associated with reduction in the initiation and duration of antimicrobial use, without an increase in adverse events.

Risk Calculator for Bronchopulmonary Dysplasia in Preterm Neonates: A Prospective Observational Study.

OBJECTIVES: To determine the incidence, risk factors, and accuracy of a previously published risk estimator in predicting Bronchopulmonary dysplasia (BPD) in a very preterm cohort from India. METHODS: A single-center prospective observational study was conducted in preterm neonates born at 23-30 wk of gestation with a birth weight of 501-1249 g. The incidence and risk factors of BPD were evaluated, and the accuracy of BPD prediction at six pre-specified time points using the National Institute of Child Health and Human Development (NICHD) BPD risk estimator was assessed by comparing the estimated risk with the observed rates. RESULTS: A total of 310 neonates with mean gestation age of 28.7±1.5 wk and birth weight of 1023.6±171.4 g were enrolled in the study. The study cohort had 49.7% males and 32.3% neonates requiring resuscitation. Any BPD was observed in 54 (17.4%) neonates with severity being mild, moderate, and severe in 29 (53.7%), 17 (31.5%), and 8 (14.8%) neonates respectively. Hundred (32.3%) neonates died before discharge from the hospital. Sepsis, patent ductus arteriosus, retinopathy of prematurity, intraventricular hemorrhage, and blood transfusion were significant risk factors for the development of BPD. The calculator was accurate for the prediction of death or moderate-severe BPD on days 1 and 3 with the area under the curve of 0.82 and 0.77 respectively. CONCLUSIONS: The NICHD BPD estimator helped to accurately predict moderate-severe BPD early in Indian preterm infants.

A Quality Improvement Initiative to Increase the Milk Donation to the Human Milk Bank Post-Coronavirus Disease-19 Pandemic.

Background and Objective: Donor human milk (DHM) from the human milk bank (HMB) is the next best alterative in circumstances when mother's own milk is not available. There was a steep decline in the volume of DHM collected during the coronavirus disease-19 (COVID-19) pandemic due to various factors, while DHM demand increased. Hence, a quality improvement (QI) study was conducted to increase the volume of milk donation to HMB from postpandemic baseline of 300-400 to 1,000 mL/day over 8 weeks. Materials and Methods: Fish bone analysis was used to identify the potential barriers, and four Plan-Do-Study-Act (PDSA) cycles were conducted from January 2021 to March 2021 to address the key barriers. In the first PDSA cycle, training of health care providers was done. Sessions for educating mothers in the second PDSA cycle and individualized one-to-one counseling of mothers by a mother support group were done in the third PDSA cycle. The availability of breast pump was increased in the fourth PDSA cycle. Sustainability of the interventions was studied for 6 months and data were analyzed. Results: The average DHM collected per day at the end of each PDSA cycle was 900, 1,500, 1,000, and 1,100 mL. Although the sustenance phase was affected by the second COVID-19 wave, prompt identification of the issues and timely interventions prevented the donated volume from dropping to preintervention levels. Conclusion: QI initiatives customized for local settings can result in significant improvement in voluntary milk donation in HMB, which can result in more availability of DHM to premature babies.

Neonatal palliative care practices: an Indian perspective.

BACKGROUND: Neonatal palliative care (NPC) aims to prevent and relieve the suffering of neonates who are not going to recover. Although an integral part of neonatal care, it remains in nascent stages in many parts of the world. AIM: To describe neonatologists' level of knowledge and understanding of NPC, and to describe current practices and barriers to its delivery. METHODS: The study, a cross-sectional web-based national survey, was undertaken between 2019 and 2020. A structured form of 22 questions about NPC was completed by neonatologists across level III neonatal intensive care units in India. RESULTS: Of the 145 questionnaires sent out, 65 responses were returned (44.8%). The participating units were in both public (38.5%) and private/corporate hospitals (61.5%). The concept of NPC was known to 90.8%, and 93.8% could identify conditions necessitating palliation. However, 81.5% of units lacked a palliative team, and few had teams of only neonatologists and neonatal nurses. Only 10.8% of the units had a structured policy, but none addressed all aspects of neonatal palliation. The creation of memories by parents spending time with their neonate (38.9%), photography (75.9%), footprints (13%) or collecting memorabilia was allowed at many centres. Frequently encountered barriers included inadequate knowledge (16.9%), poor infrastructure (21.5%), inadequate human resources (24.6%) and a lack of structured guidelines and legal support (15.4%). CONCLUSION: This is the first study to highlight a large gap in neonatal end-of-life care in India and it reflects an urgent need to facilitate its incorporation into routine care. ABBREVIATIONS: NICU: neonatal intensive care unit; NPC: neonatal palliative care.

Fetal vascular malperfusion (FVM): diagnostic implications and clinical associations.

INTRODUCTION: Fetal vascular malperfusion (FVM) is diagnosed by the presence of vascular lesions in the muscularized fetal vessels in the placenta and the resultant changes in the downstream villi. The Amsterdam Placental Working Group recognizes two patterns of FVM namely segmental and global. The aim of this study was to estimate the frequency of FVM lesion in our population and to understand its neonatal associations. METHODS: Fifty-four placentas with FVM and 56 controls collected over 34 months. The maternal and neonatal details were collected from the case charts. The patterns and grades of FVM lesions were related to the clinical factors and significance analyzed statistically using the Chi-square test and t-test and p < .05 was considered significant. RESULTS: The frequency of FVM was 8.7%. The FVM group showed lower mean gestational age, birth weight, and placental weight with a higher frequency of IUGR. Poor neonatal survival, non-reassuring fetal status, neurological abnormalities, neonatal sepsis, asphyxia, low Apgar, and respiratory support requirement were significantly higher in the FVM group. A similar frequency of segmental and global lesions was seen. High grade lesions (n = 35) were common than low grade (n = 19). Neonatal associations were more often seen in segmental and high-grade lesions. DISCUSSION: In the absence of antenatal diagnostic tools to identify FVM, placental examination is critical and the only definitive method to diagnose FVM, which alerts the clinician to monitor for several neonatal morbidities. Identification and typing the lesion as per the new guidelines proves significant risk associations with specific types of FVM.

Short-term outcome and complications of therapeutic hypothermia in neonates with moderate-to-severe hypoxic ischaemic encephalopathy: a single-centre retrospective observational study in a hospital in Mumbai, India.

BACKGROUND: Although shown to reduce death or disability in moderate-to-severe hypoxic ischaemic encephalopathy (HIE), therapeutic hypothermia (TH) has recently been associated with an increase in adverse events in low- and middle-income countries (LMIC). AIM: To determine the clinical characteristics, complications and short-term outcome in neonates receiving TH in King Edward Memorial Hospital, Mumbai, India. METHODS: A retrospective single-centre study of neonates with moderate-to-severe HIE who received TH from 1 January 2018 to 31 December 2021 was undertaken. TH was provided as per the unit's protocol using either a servo-controlled device or a phase-changing material (PCM). RESULTS: One hundred and fifty-five neonates were included with 94.2% intramural births. Mean gestation and birthweight were 38.6 (1.5) weeks and 2776.7 (431) g, respectively. HIE staging was moderate in 87.1% and severe in 12.9%, with a mean cord pH of 6.93 (0.14) and seizures in 38.7%. Adverse events included shock (50.3%), clinically significant bleeding (16%), acute kidney injury (6.7%), culture-positive sepsis (11.6%), persistent pulmonary hypertension (9%), bradycardia (9%), food intolerance (14.9%) and premature termination (7.1%). A servo-controlled device (15.5%) or PCM (84.5%) was used, with comparable adverse events. 84.5% of the neonates were discharged, 7.1% discharged against medical advice and 8.4% died. Detailed neurological assessment at discharge/discharge against medical advice suggested neurological impairment in 128 (87.1%) neonates. CONCLUSION: Adverse events during TH range from asymptomatic laboratory abnormalities to life-threatening complications, which are manageable in well equipped units. Neurological impairment at discharge in neonates who received cooling mandates strict neurological follow-up.Abbreviations: aEEG: amplitude-integrated EEG; AKI: acute kidney injury; BW: birthweight; EEG: electro-encephalogram; GA: gestational age; HELIX: hypothermia for encephalopathy in low- and middle-income countries; HIE: hypoxic ischaemic encephalopathy; IVH: intraventricular haemorrhage; LMIC: low- and middle-income countries; NICHD: National Institute of Child Health and Human Development; NICU: neonatal intensive care unit; PPHN: persistent pulmonary hypertension of newborn; PCM: phase-changing material; SGA: small-for-gestational age; TH: therapeutic hypothermia.