Serial tissue Doppler imaging in the evaluation of bronchopulmonary dysplasia-associated pulmonary hypertension among extremely preterm infants: a prospective observational study.

Objectives: To evaluate serial tissue Doppler cardiac imaging (TDI) in the evolution of bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) among extremely preterm infants. Design: Prospective observational study. Setting: Single-center, tertiary-level neonatal intensive care unit. Patients: Infant born <28 weeks gestation. Main outcome measures: Utility of TDI in the early diagnosis and prediction of BPD-PH and optimal timing for screening of BPD-PH. Results: A total of 79 infants were included. Of them, 17 (23%) had BPD-PH. The mean gestational age was 25.9 ± 1.1 weeks, and mean birth weight was 830 ± 174 g. The BPD-PH group had a high incidence of hemodynamically significant patent ductus arteriosus (83% vs. 56%, p < 0.018), longer oxygen days (96.16 ± 68.09 vs. 59.35 ± 52.1, p < 0.008), and prolonged hospital stay (133.8 ± 45.9 vs. 106.5 ± 37.9 days, p < 0.005). The left ventricular eccentricity index (0.99 ± 0.1 vs. 1.1 ± 0.7, p < 0.01) and the ratio of acceleration time to right ventricular ejection time showed a statistically significant trend from 33 weeks (0.24 ± 0.05 vs. 0.28 ± 0.05, p < 0.05). At 33 weeks, the BPD-PH group showed prolonged isovolumetric contraction time (27.84 ± 5.5 vs. 22.77 ± 4, p < 0.001), prolonged isovolumetric relaxation time (40.3 ± 7.1 vs. 34.9 ± 5.3, p < 0.003), and abnormal myocardial performance index (0.39 ± 0.05 vs. 0.32 ± 0.03, p < 0.001). These differences persisted at 36 weeks after conceptional gestational age. Conclusions: TDI parameters are sensitive in the early evolution of BPD-PH. Diagnostic accuracy can be increased by combining the TDI parameters with conventional echocardiographic parameters. BPD-PH can be recognizable as early as 33-34 weeks of gestation.

Clinical Course and Outcomes of Infants with Streptococcus bovis/Streptococcus Gallolyticus subspecies pasteurianus Infection: A Systematic Review and Meta-analysis.

BACKGROUND: Streptococcus gallolyticus subspecies pasteurianus (SGP), a subtype of Streptococcus bovis, is an uncommon but important cause of neonatal sepsis. Although uncommon, SGP infections during infancy have been associated with an increased risk of morbidity and mortality. METHODS: This is a systematic review and meta-analysis of available literature on the clinical course and outcomes of infants with SGP infection. Studies were identified using the following MeSH keywords: "Streptococcus gallolyticus," "Streptococcus bovis," "newborn" and "infant." Data including perinatal factors, clinical presentation, investigations, treatment and outcomes were extracted and analyzed. RESULTS: A total of 46 articles were identified (116 cases: 60 S. bovis, 56 SGP). The cases were predominantly term (52%), male (57%) and born via vaginal delivery (67%). The most common symptom was fever [67% (95% confidence interval (CI): 43%-84%)], lethargy [66% (95% CI: 32%-89%)], tachypnea [59% (95% CI: 27%-85%)] and irritability [59% (95% CI: 34%-79%)]. Infants with early-onset infections (<3 days of life) were more likely to have respiratory symptoms and bacteremia (73%), whereas late-onset infections presented predominantly with gastrointestinal symptoms. Four mortalities were reported which occurred before antibiotic administration. Isolated bacteria were mostly penicillin-susceptible [95% (95% CI: 78-99%)] and cases treated with penicillin derivative had good recovery. CONCLUSIONS: SGP is an important cause of neonatal sepsis and meningitis. Penicillin derivative is an effective treatment for SGP, and outcomes appear to be favorable.

Colorimetric CO2 Detector to Improve Effective Mask Ventilations in Very Preterm Infants: A Pilot Randomized Controlled Study.

INTRODUCTION: End-tidal CO2 (ETCO2) detector is currently recommended for confirmation of endotracheal tube placement during neonatal resuscitation. Whether it is feasible to use ETCO2 detectors during mask ventilation to reduce risk of bradycardia and desaturations, which are associated with increased risk of death in preterm babies, is unknown. METHODS: This is a pilot randomized controlled trial (NCT04287907) involving newborns 24 + 0/7 to 32 + 0/7 weeks gestation who required mask ventilation at birth. Infants were randomized into groups with or without colorimetric ETCO2 detectors. Combined duration of any bradycardia (<100 bpm) and time below prespecified target oxygen saturation (SpO2) as measured by pulse oximetry were compared. RESULTS: Fifty participants were randomized, 47 with outcomes analysed (2 incomplete data, 1 postnatal diagnosis of trachea-oesophageal fistula). Mean gestational age and birthweight were 28.5 ± 1.9 versus 29.4 ± 1.6 weeks (p = 0.1) and 1,252.7 ± 409.7 g versus 1,334.6 ± 369.1 g (p = 0.5) in the intervention and control arm, respectively. Mean combined duration of bradycardia and desaturation was 276.7 ± 197.7 s (intervention) and 322.7 ± 277.7 s (control) (p = 0.6). Proportion of participants with any bradycardia or desaturation at 5 min were 38.1% (intervention) and 56.5% (control) (p = 0.2). No chest compressions, epinephrine administration, or death occurred in the delivery room. CONCLUSION: This pilot study demonstrates the feasibility of a trial to evaluate colorimetric ETCO2 detectors during mask ventilation of very preterm infants to reduce bradycardia and low SpO2. Further assessment with a larger population will be required to determine if ETCO2 detector usage at resuscitation reduces risk of adverse outcomes, including death and disability, in very preterm infants.

Global disease burden of and risk factors for acute lower respiratory infections caused by respiratory syncytial virus in preterm infants and young children in 2019: a systematic review and meta-analysis of aggregated and individual participant data.

BACKGROUND: Infants and young children born prematurely are at high risk of severe acute lower respiratory infection (ALRI) caused by respiratory syncytial virus (RSV). In this study, we aimed to assess the global disease burden of and risk factors for RSV-associated ALRI in infants and young children born before 37 weeks of gestation. METHODS: We conducted a systematic review and meta-analysis of aggregated data from studies published between Jan 1, 1995, and Dec 31, 2021, identified from MEDLINE, Embase, and Global Health, and individual participant data shared by the Respiratory Virus Global Epidemiology Network on respiratory infectious diseases. We estimated RSV-associated ALRI incidence in community, hospital admission, in-hospital mortality, and overall mortality among children younger than 2 years born prematurely. We conducted two-stage random-effects meta-regression analyses accounting for chronological age groups, gestational age bands (early preterm, <32 weeks gestational age [wGA], and late preterm, 32 to <37 wGA), and changes over 5-year intervals from 2000 to 2019. Using individual participant data, we assessed perinatal, sociodemographic, and household factors, and underlying medical conditions for RSV-associated ALRI incidence, hospital admission, and three severity outcome groups (longer hospital stay [>4 days], use of supplemental oxygen and mechanical ventilation, or intensive care unit admission) by estimating pooled odds ratios (ORs) through a two-stage meta-analysis (multivariate logistic regression and random-effects meta-analysis). This study is registered with PROSPERO, CRD42021269742. FINDINGS: We included 47 studies from the literature and 17 studies with individual participant-level data contributed by the participating investigators. We estimated that, in 2019, 1 650 000 (95% uncertainty range [UR] 1 350 000-1 990 000) RSV-associated ALRI episodes, 533 000 (385 000-730 000) RSV-associated hospital admissions, 3050 (1080-8620) RSV-associated in-hospital deaths, and 26 760 (11 190-46 240) RSV-attributable deaths occurred in preterm infants worldwide. Among early preterm infants, the RSV-associated ALRI incidence rate and hospitalisation rate were significantly higher (rate ratio [RR] ranging from 1·69 to 3·87 across different age groups and outcomes) than for all infants born at any gestational age. In the second year of life, early preterm infants and young children had a similar incidence rate but still a significantly higher hospitalisation rate (RR 2·26 [95% UR 1·27-3·98]) compared with all infants and young children. Although late preterm infants had RSV-associated ALRI incidence rates similar to that of all infants younger than 1 year, they had higher RSV-associated ALRI hospitalisation rate in the first 6 months (RR 1·93 [1·11-3·26]). Overall, preterm infants accounted for 25% (95% UR 16-37) of RSV-associated ALRI hospitalisations in all infants of any gestational age. RSV-associated ALRI in-hospital case fatality ratio in preterm infants was similar to all infants. The factors identified to be associated with RSV-associated ALRI incidence were mainly perinatal and sociodemographic characteristics, and factors associated with severe outcomes from infection were mainly underlying medical conditions including congenital heart disease, tracheostomy, bronchopulmonary dysplasia, chronic lung disease, or Down syndrome (with ORs ranging from 1·40 to 4·23). INTERPRETATION: Preterm infants face a disproportionately high burden of RSV-associated disease, accounting for 25% of RSV hospitalisation burden. Early preterm infants have a substantial RSV hospitalisation burden persisting into the second year of life. Preventive products for RSV can have a substantial public health impact by preventing RSV-associated ALRI and severe outcomes from infection in preterm infants. FUNDING: EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe.

International Online Survey on the Management of Patent Ductus Arteriosus.

INTRODUCTION: There is uncertainty and lack of consensus regarding optimal management of patent ductus arteriosus (PDA). We aimed to determine current clinical practice in PDA management across a range of different regions internationally. MATERIALS AND METHODS: We surveyed PDA management practices in neonatal intensive care units using a pre-piloted web-based survey, which was distributed to perinatal societies in 31 countries. The survey was available online from March 2018 to March 2019. RESULTS: There were 812 responses. The majority of clinicians (54%) did not have institutional protocols for PDA treatment, and 42% reported variable management within their own unit. Among infants <28 weeks (or <1,000 g), most clinicians (60%) treat symptomatically. Respondents in Australasia were more likely to treat PDA pre-symptomatically (44% vs. 18% all countries [OR 4.1; 95% CI 2.6-6.5; p < 0.001]), and respondents from North America were more likely to treat symptomatic PDA (67% vs. 60% all countries [OR 2.0; 95% CI 1.5-2.6; p < 0.001]). In infants ≥28 weeks (or ≥1,000 g), most clinicians (54%) treat symptomatically. Respondents in North America were more likely to treat PDAs in this group of infants conservatively (47% vs. 38% all countries [OR 2.3; 95% CI 1.7-3.2; p < 0.001]), and respondents from Asia were more likely to treat the PDA pre-symptomatically (21% vs. 7% all countries [OR 5.5; 95% CI 3.2-9.8; p < 0.001]). DISCUSSION/CONCLUSION: There were marked international differences in clinical practice, highlighting ongoing uncertainty and a lack of consensus regarding PDA management. An international conglomeration to coordinate research that prioritises and addresses these areas of contention is indicated.

Optimal Delivery Management for the Prevention of Early Neonatal SARS-CoV-2 Infection: Systematic Review and Meta-analysis.

OBJECTIVE: Delivery management interventions (DMIs) were recommended to prevent delivery-associated transmission of maternal SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) to infants without evidence of effect on early neonatal SARS-CoV-2 infection (ENI) and neonatal death <28 days of life (ND). This systematic review describes different DMI combinations and the frequency of ENI and ND. STUDY DESIGN: Individual patient data were collected from articles published from January 1, 2020 to December 31, 2021 from Cochrane review databases, Medline, and Google Scholar. Article inclusion criteria were: documented maternal SARS-CoV-2 polymerase chain reaction (PCR)-positive status 10 days before delivery or symptomatic at delivery with a positive test within 48 hours, known delivery method, and known infant SARS-CoV-2 PCR result. Primary outcomes were ENI (positive PCR at 12 hours to 10 days) and ND. All characteristics were pooled using the DerSimonian-Laird inverse variance method. Primary outcome analyses were performed using logit transformation and random effect. Pooled results were expressed as percentages (95% confidence intervals). Continuity correction was applied for all pooled results if any included study has 0 event. RESULTS: A total of 11,075 publications were screened. 117 publications representing 244 infants and 230 mothers were included. All publications were case reports. ENI and ND were reported in 23.4% (18.2-29.18) and 2.1% (0.67-4.72) of cases, respectively. Among cases with available information, DMIs were reported for physical environment (85-100%), delivery-specific interventions (47-100%), and infant care practices (80-100%). No significant comparisons could be performed between different DMI combinations due to small sample size. CONCLUSION: The evidence supporting any DMI in SARS-CoV-2-infected mothers to prevent ENI or ND is extremely limited. Limitations of this meta-analysis include high risk of bias, small sample size, and large confidence intervals. This identifies the need for multinational database generation and specific studies designed to provide evidence of DMI guidelines best suited to prevent transmission from mother to neonate. KEY POINTS: · In this review we analyzed 2 years of maternal SARS-CoV-2 published cases.. · We assessed association of delivery management interventions with infant SARS-CoV-2 infection.. · We found no evidence supporting any DMI for that purpose..

Strain-resolved metagenomic analysis of the gut as a reservoir for bloodstream infection pathogens among premature infants in Singapore.

BACKGROUND: Gut dysbiosis contributes to the high risk of bloodstream infection (BSI) among premature infants. Most prior studies of the premature infant gut microbiota were conducted in Western countries and prior to development of current tools for strain-resolved analysis. METHODS: We performed metagenomic sequencing of weekly fecal samples from 75 premature infants at a single hospital in Singapore. We evaluated associations between clinical factors and gut microbiota composition using PERMANOVA and mixed effects linear regression. We used inStrain to perform strain-level analyses evaluating for gut colonization by BSI-causing strains. RESULTS: Median (interquartile range) gestation was 27 (25, 29) weeks, and 63% of infants were born via Cesarean section. Antibiotic exposures (PERMANOVA; R2 = 0.017, p = 0.001) and postnatal age (R2 = 0.015, p = 0.001) accounted for the largest amount of variability in gut microbiota composition. Increasing postnatal age was associated with higher relative abundances of several common pathogens (Enterococcus faecalis: p < 0.0001; Escherichia coli: p < 0.0001; Klebsiella aerogenes: p < 0.0001; Klebsiella pneumoniae: p < 0.0001). Antibiotic exposures were generally associated with lower relative abundances of both frequently beneficial bacteria (e.g., Bifidobacterium species) and common enteric pathogens (e.g., Enterobacter, Klebsiella species). We identified strains identical to the blood culture isolate in fecal samples from 12 of 16 (75%) infants who developed BSI, including all infections caused by typical enteric bacteria. CONCLUSIONS: Antibiotic exposures were the dominant modifiable factor affecting gut microbiota composition in a large cohort of premature infants from South-East Asia. Strain-resolved analyses indicate that the gut is an important reservoir for organisms causing BSI among premature infants.

Evaluation of the Neonatal Sequential Organ Failure Assessment and Mortality Risk in Neonates with Early-Onset Infection.

BACKGROUND: The discriminative utility of the neonatal sequential organ failure assessment (nSOFA) for early-onset sepsis (EOS) mortality in the neonatal intensive care unit (NICU) is unknown. OBJECTIVES: The objective of the study was to determine the utility of nSOFA for EOS mortality. METHODS: Multicenter, retrospective cohort study of NICU patients with EOS between 2012 and 2023. nSOFA scores of survivors and non-survivors were compared, and area under the receiver operating characteristics curve (AUROC) for mortality was calculated. RESULTS: 104 subjects were identified (88 lived, 16 died). AUROC at blood culture collection (T0), 6 h after collection (T6), and the maximum nSOFA at T0 or T6 (T0-6max) were 0.76 (95% CI: 0.62, 0.91), 0.89 (0.80, 0.99), and 0.87 (0.77, 0.97), respectively. Analyses restricted to birthweight (<1.5, <1 kg) or gestational age (<32, <29 week) cutoffs revealed AUROC ranges of 0.86-0.92 for T6 and 0.82-0.84 for T0-6max. CONCLUSIONS: The nSOFA showed good-to-excellent discrimination of mortality among infants with EOS in the NICU.

Early-life surface colonization with multi-drug resistant organisms in the neonatal intensive care unit.

OBJECTIVES: In this study, we aim to describe the patterns of early-life surface colonization with multi-drug resistant (MDR) organisms (MDROs) among newborns admitted to the neonatal intensive care unit (NICU). METHODS: We conducted a retrospective descriptive study of infants with culture-positive external ear surface swabs performed immediately after admission to our NICU from January 1, 2017 - December 31, 2021. Clinical characteristics, culture and antibiotic susceptibility data were extracted from the department data collection and hospital electronic databases. RESULTS: A total of 314 infants were included - median 34 weeks gestation (interquartile range [IQR] 30, 38) and median birthweight 2147 g (IQR 1470, 2875). Of the 379 bacterial isolates obtained, 259 (68.3%) were gram-negative with Escherichia coli (149/379, 39.3%) and Klebsiella spp (57/379, 15.0%) the most common gram-negatives isolated. MDROs accounted for 17.4% (45/259) of gram-negative isolates. There was no methicillin-resistant Staphylococcus aureus (0/22 isolates) or vancomycin-resistant Enterococcus (0/68) detected among isolates tested. A total of 27 (8.6%) infants developed bacteremia, of which 21/27 (77.8%) had concordant bacteria isolated from surface cultures, with identical resistance patterns, and 4/21 (19.0%) isolates were MDROs. CONCLUSION: In our setting where gram-negative bacteria accounted for a high proportion of initial colonization, MDR gram-negatives accounted for up to 17% of colonizing gram-negative bacteria detected.

Perceptions and acceptance of COVID-19 vaccine among pregnant and lactating women in Singapore: A pre-vaccine rollout cross-sectional study.

Introduction: Vaccination is critical in controlling the coronavirus disease 2019 (COVID-19) pandemic. However, vaccine perception and acceptance among pregnant and lactating women is unknown in Singapore. We aimed to determine the acceptance of COVID-19 vaccination among these two groups of women in Singapore and the factors associated with vaccine acceptance. Methods: We conducted an anonymous, online survey on the perceptions of the COVID-19 vaccine and its acceptance by pregnant and lactating women at a tertiary maternal and child hospital in Singapore from 1 March to 31 May 2021. Information on their demographics and knowledge was collected. These factors were assessed for their relationship with vaccine acceptance. Results: A total of 201 pregnant and 207 lactating women participated. Vaccine acceptance rates in pregnant and lactating women were 30.3% and 16.9%, respectively. Pregnant women who were unsure or unwilling to take the vaccine cited concerns about safety of the vaccine during pregnancy (92.9%), while lactating women were concerned about its potential long-term negative effects on the breastfeeding child (75.6%). Factors that were positively associated with vaccine acceptance included a lower monthly household income or education level, appropriate knowledge regarding vaccine mechanism and higher perceived maternal risk of COVID-19. Most pregnant (70.0%) and lactating women (83.7%) were willing to take the vaccine only when more safety data during pregnancy and breastfeeding were available. Conclusion: COVID-19 vaccine acceptance was low among pregnant and lactating women in Singapore. Addressing the safety concerns when more data are available and education on the mechanism of vaccine action will likely improve acceptance among these women.

"Mild'' Hypoxic-Ischaemic Encephalopathy and Therapeutic Hypothermia: A Survey of Clinical Practice and Opinion from 35 Countries.

INTRODUCTION: We aimed to determine global professional opinion and practice for the use of therapeutic hypothermia (TH) for treating infants with mild hypoxic-ischaemic encephalopathy (HIE). METHODS: A web-based survey (REDCap) was distributed via emails, social networking sites, and professional groups from October 2020 to February 2021 to neonatal clinicians in 35 countries. RESULTS: A total of 484 responses were obtained from 35 countries and categorized into low/middle-income (43%, LMIC) or high-income (57%, HIC) countries. Of the 484 respondents, 53% would provide TH in mild HIE on case-to-case basis and only 25% would never cool. Clinicians from LMIC were more likely to routinely offer TH in mild HIE (25% v HIC 16%, p < 0.05), have a unit protocol for providing TH (50% v HIC 26%, p < 0.05), use adjunctive tools, e.g., aEEG (49% v HIC 32%, p < 0.001), conduct an MRI post TH (48% v HIC 40%, p < 0.05) and less likely to use neurological examinations as a HIE severity grading tool (80% v HIC 95%, p < 0.001). The majority of respondents (91%) would support a randomized controlled trial that was sufficiently large to examine neurodevelopmental outcomes in mild HIE after TH. CONCLUSIONS: This is the first survey of global opinion for TH in mild HIE. The overwhelming majority of professionals would consider "cooling" an infant with mild HIE, but LMIC respondents were more likely to routinely cool infants with mild HIE and use adjunctive tools for diagnosis and follow-up. There is wide practice heterogeneity and a sufficiently large RCT designed to examine neurodevelopmental outcomes, is urgently needed and widely supported.

Knowledge and Expectations of Perinatal Care Among Pregnant Women During the COVID-19 Pandemic.

Introduction: This study aimed to investigate the knowledge and expectations of pregnant women on perinatal care during the coronavirus disease 2019 (COVID-19) pandemic. Methods: A cross-sectional survey was conducted among pregnant women ≥21 years, without a history of confirmed COVID-19, attending antenatal clinics between August and September 2020 via a secure online platform. The survey consisted of 10 questions which evaluated the knowledge and expectations on perinatal and neonatal care during the current pandemic. Results: A total of 313 pregnant women completed the survey. The mean age of the participants was 30 years (SD 4; range 22-43 years). The median gestational age was 25 weeks (range 4-40 weeks). The participants were predominantly multiparous (54%) and almost all (98%) had completed secondary level education. Majority of participants were aware of the spread of COVID-19 by respiratory secretions and contact (90%), and the importance of prevention strategies (94%). Up to 72% agreed or strongly agreed that in-utero transmission of SARS-CoV-2 was possible. Most were unsure of the optimal mode of delivery (77%) and only 22% believed that breastfeeding was safe in a pregnant woman with active COVID-19. Although 46% were concerned about increased transmission risk with antenatal clinic visits, only 37% were agreeable to teleconferencing of clinic appointments. Maternal age >35 years was significantly associated with agreement with separation of mother-infant after birth [AOR 1.89 (95% CI 1.05, 3.39)], restrictions of visitors during the postnatal period [1.92 (1.05, 3.49)] and having their confinement practices were affected [2.3 (1.26, 4.17)]. Pregnant women who were multiparous disagreed that breastfeeding was safe in women with active COVID-19 [0.42 (0.23, 0.75)]. Conclusions: There was significant uncertainty about the optimal delivery method and safety of breastfeeding with COVID-19 among expectant mothers, along with variable agreement with alterations to routine perinatal care.

Guidance for the clinical management of infants born to mothers with suspected/confirmed COVID-19 in Singapore.

In this paper, we provide guidance to clinicians who care for infants born to mothers with suspected/confirmed COVID-19 during this current pandemic. We reviewed available literature and international guidelines based on the following themes: delivery room management; infection control and prevention strategies; neonatal severe acute respiratory syndrome coronavirus 2 testing; breastfeeding and breastmilk feeding; rooming-in of mother-infant; respiratory support precautions; visiting procedures; de-isolation and discharge of infant; outpatient clinic attendance; transport of infant; and training of healthcare staff. This guidance for clinical care was proposed and contextualised for the local setting via consensus by members of this workgroup and was based on evidence available as of 31 July 2020, and may change as new evidence emerges.

Serotype distribution and incidence of invasive early onset and late onset group B streptococcal disease amongst infants in Singapore.

BACKGROUND: The current group B streptococcal (GBS) preventive measures had reduced invasive GBS early onset disease (EOD) incidences worldwide, but the late onset disease (LOD) incidences had remained unchanged. Administration of a safe and effective GBS vaccine in addition to the current strategies were thought to be the next steps in reducing the incidences of invasive GBS infection especially LOD. In this study, we aimed to examine the causative GBS serotypes in invasive GBS disease, determine the incidences of EOD and LOD, and compare the risk factors between EOD and LOD. METHODS: A retrospective study of infants ≤ 90-day-old over an 8-year period (2010-2017). The incidences of EOD and LOD were obtained by using patients with EOD and LOD who were born in our institution as the numerator and the live births in our institution per year of the study period as the denominator. Available GBS isolates were serotyped by the National Public Health Laboratory using capsular serotyping methods. The risk factors of EOD and LOD were compared. RESULTS: A total of 71 infants were identified; 16 (22.5%) and 55 (77.5%) of them had EOD and LOD, respectively. Serotype III (n = 42, 71.2%) was the most common serotype amongst the 59 isolates available for serotyping. Serotypes Ia, Ib, II, III, and V accounted for 98.3% (n = 58) of the invasive GBS diseases. The overall incidence was 0.42 per 1000 live births. The mean incidences of EOD and LOD were 0.13 per 1000 live births and 0.29 per 1000 live births, respectively. On multivariate analysis, risk factors for LOD as compared to EOD were: Chinese ethnicity (OR 27.1, 95% CI 3.0-243.1, p = 0.003) and negative/unknown maternal GBS status (OR 20.0, 95% CI 2.0-250.0, p = 0.012). Prematurity and intrapartum risk factors (peripartum maternal pyrexia, prolonged rupture of membrane) of EOD were not associated with LOD. CONCLUSIONS: The LOD incidence had remained higher than EOD incidence in our cohort. A GBS vaccine that covers the major causative serotypes found in our cohort can potentially reduce the overall GBS disease burden in the country.

Oxygen for the delivery room respiratory support of moderate-to-late preterm infants. An international survey of clinical practice from 21 countries.

AIM: The aim of this study was to determine clinician opinion regarding oxygen management in moderate-late preterm resuscitation. METHODS: An anonymous online questionnaire was distributed through email/social messaging platforms to neonatologists in 21 countries (October 2020-March 2021) via REDCap. RESULTS: Of the 695 respondents, 69% had access to oxygen blenders and 90% had pulse oximeters. Respondents from high-income countries were more likely to have oxygen blenders than those from middle-income countries (72% vs. 66%). Most initiated respiratory support with FiO2 0.21 (43%) or 0.3 (36%) but only 45% titrated FiO2 to target SpO2 . Most (89%) considered heart rate as a more important indicator of response than SpO2 . Almost all (96%) supported the need for well-designed trials to examine oxygenation in moderate-late preterm resuscitation. CONCLUSION: Most clinicians resuscitated moderate-late preterm infants with lower initial FiO2 but some cannot/will not target SpO2 or titrate FiO2 . Most consider heart rate as a more important indicator of infant response than SpO2 .Large and robust clinical trials examining oxygen use for moderate-late preterm resuscitation, including long-term neurodevelopmental outcomes, are supported amongst clinicians.

A Virus-Specific Immune Rheostat in the Immunome of Patients Recovering From Mild COVID-19.

An accurate depiction of the convalescent COVID-19 immunome will help delineate the immunological milieu crucial for disease resolution and protection. Using mass cytometry, we characterized the immune architecture in patients recovering from mild COVID-19. We identified a virus-specific immune rheostat composed of an effector T (Teff) cell recall response that is balanced by the enrichment of a highly specialized regulatory T (Treg) cell subset. Both components were reactive against a peptide pool covering the receptor binding domain (RBD) of the SARS-CoV-2 spike glycoprotein. We also observed expansion of IFNγ+ memory CD4+ T cells and virus-specific follicular helper T (TFH) cells. Overall, these findings pinpoint critical immune effector and regulatory mechanisms essential for a potent, yet harmless resolution of COVID-19 infection.

Effectiveness of Palivizumab Against Respiratory Syncytial Virus Hospitalization Among Preterm Infants in a Setting With Year-Round Circulation.

BACKGROUND: The year-round respiratory syncytial virus (RSV) circulation in tropical regions leads to different transmission patterns and burden of disease among infants born very preterm. METHODS: We conducted a retrospective cohort study to estimate the effectiveness of palivizumab in preventing RSV hospitalization at 6 and 12 months after discharge, among infants born at <32 weeks' gestation in our tropical setting. RESULTS: A total of 109 infants (26.3%) received palivizumab at discharge, of 415 who were eligible. All patients received ≥4 doses, with 105 infants (96.3%) completing 5 doses. Within 1 year after discharge, there were 35 RSV-associated admissions (3 [2.8%] in the palivizumab vs 32 [10.5%] in the nonpalivizumab group; P = .02). After adjustment for confounders, the effectiveness of palivizumab against RSV hospitalization was estimated to be 90% (95% confidence interval, 10%-99%) up to 6 months after discharge. The median time to RSV hospitalization was shorter in the nonpalivizumab than in the palivizumab group (median [range], 155 [15-358] vs 287 [145-359] days, respectively; P = .11). Five infants (14.3%), all from the nonpalivizumab group, required admission to the intensive care unit. CONCLUSIONS: In our setting with year-round RSV circulation, palivizumab prophylaxis was effective in reducing RSV hospitalization among high-risk preterm infants of <32 weeks' gestation within the initial 6 months after discharge.

Risk Factors for Mortality From Late-Onset Sepsis Among Preterm Very-Low-Birthweight Infants: A Single-Center Cohort Study From Singapore.

OBJECTIVE: To determine the risk factors for mortality associated with late onset sepsis (LOS) among preterm very-low-birthweight (VLBW) infants. STUDY DESIGN: We performed a retrospective cohort study of infants born <32 weeks gestation and <1,500 gm admitted to a Singaporean tertiary-level neonatal intensive care unit. We determined the clinical, microbial, and laboratory risk factors associated with mortality due to culture-positive LOS in this cohort. RESULTS: A total of 1,740 infants were admitted, of which 169 (9.7%) developed LOS and 27 (16%) died. Compared to survivors, those who died had lower birth gestational age (median 24 vs. 25 weeks, p = 0.02) and earlier LOS occurrence (median 10 vs. 17 days, p = 0.007). There was no difference in the incidence of meningitis (11.1 vs. 16.9%, p = 0.3), NEC (18.5 vs. 14.8%, p = 0.6), or intestinal surgery (18.5 vs. 23.3%, p = 0.6) among infants who died compared to survivors. Gram-negative bacteria accounted for 21/27 (77.8%) LOS-associated deaths and almost all (13/14, 93%) fulminant episodes. The presence of multiorgan failure, as evidenced by the need for mechanical ventilation (100 vs. 79.0%, p = 0.008), elevated lactate (12.4 vs. 2.1 mmol/L, p < 0.001), and inotropic support (92.6 vs. 37.5%, p < 0.001), was significantly associated with mortality. Infants who died had significantly lower white blood cell (WBC) counts (median 4.2 × 109/L vs. 9.9 × 109/L, p = 0.001), lower platelet count (median 40 × 109/L vs. 62 × 109/L, p = 0.01), and higher immature to total neutrophil (I: T) ratio (0.2 vs. 0.1, p = 0.002). Inotrope requirement [AOR 22.4 (95%CI 2.9, 103.7)], WBC <4 × 109/L [AOR 4.7 (1.7, 13.2)], and I: T ratio >0.3 [AOR 3.6 (1.3, 9.7)] were independently associated with LOS mortality. CONCLUSIONS: In a setting with predominantly Gram-negative bacterial infections, the need for inotropic support, leukopenia, and elevated I: T ratio were significantly associated with LOS mortality among preterm VLBW infants.