Neonatal Onset Research Articles

Deficiency of acyl-CoA synthetase 5 is associated with a severe and treatable failure to thrive of neonatal onset.

Failure to thrive (FTT) causes significant morbidity, often without clear etiologies. Six individuals of a large consanguineous family presented in the neonatal period with recurrent vomiting and diarrhea, leading to severe FTT. Standard diagnostic work up did not ascertain an etiology. Autozygosity mapping and whole exome sequencing identified homozygosity for a novel genetic variant of the long chain fatty acyl-CoA synthetase 5 (ACSL5) shared among the affected individuals (NM_203379.1:c.1358C>A:p.(Thr453Lys)). Autosomal recessive genotype-phenotype segregation was confirmed by Sanger sequencing. Functional in vitro analysis of the ACSL5 variant by immunofluorescence, western blotting and enzyme assay suggested that Thr453Lys is a loss-of-function mutation without any remaining activity. ACSL5 belongs to an essential enzyme family required for lipid metabolism and is known to contribute the major activity in the mouse intestine. Based on the function of ACSL5 in intestinal long chain fatty acid metabolism and the gastroenterological symptoms, affected individuals were treated with total parenteral nutrition or medium-chain triglyceride-based formula restricted in long-chain triglycerides. The patients responded well and follow up suggests that treatment is only required during early life.

The Phenotype and Genotype of Congenital Myopathies Based on a Large Pediatric Cohort

BackgroundCongenital myopathies (CMs) are a clinically and genetically heterogeneous group of hereditary muscular disorders. The distribution of genetic and histologic subtypes has been addressed in only a few cohorts, and the relationship between phenotypes and genotypes is only partially understood. MethodsThis is a retrospective cross-sectional data collection study conducted at a single center. The clinical, histopathological, and molecular characterization of 104 patients with CM is reported. ResultsThe most common histopathological subtype was core myopathy (42%). Patients with severe endomysial fibrosis were more commonly unable to walk than patients with only a mild-grade endomysial fibrosis (56% vs 16%). Inability to walk was also more prevalent in patients with severe fatty replacement (44% vs 19%). The genetic etiology was more frequently identified among those patients with “specific” histologic findings (74% vs 62%). A definite molecular diagnosis was reached in 65 of 104 patients (62%), with RYR1 (24/104) and TTN (8/104) being the most frequent causative genes. Neonatal onset occurred in 56%. Independent ambulation was achieved by 74%. Patients who walked late were more likely to become wheelchair-dependent. Respiratory support was needed in one of three patients. Gastrostomy placement was required in 15%. Cardiac involvement was observed in 3%, scoliosis in 43%, and intellectual disability in 6%. ConclusionsThis study provides an updated picture of the clinical, histopathological, and molecular landscape of CMs. Independently of the causative gene, fibrosis and fatty replacement in muscle biopsy specimens are associated with clinical severity. Mutations in TTN are responsible for a higher proportion of cases than previously thought.

Neonatal epidermolysis bullosa: lessons to learn about genetic counseling

Background Epidermolysis Bullosa (EB) is a heterogeneous group of congenital blistering diseases that usually presents in the neonatal period. EB is classified into three major categories, each with many subtypes based on the precise location at which separation or blistering occurs, namely epidermolysis bullosa simplex (EBS), junctional epidermolysis bullosa (JEB) and dystrophic epidermolysis bullosa (DEB).Methods We describe genetics of neonatal EB in Hong Kong.Results Two neonates of consanguineous Pakistani parents had the EB-Pyloric Atresia (EB-PA) variant. One had a 4 kb homozygous deletion of exon 19–25 of the ITGB4 gene, and the other with only a histopathological diagnosis. Both died of sepsis in infancy. Aberrant COL7A1 mutations in the dominant and recessive EB were described. Genetic analysis, together with histopathological classification is important to aid prognosis and counseling. JEB and EB-PA are associated with consanguinity and mortality during infancy. Morbidity and prognosis of the autosomal dominant DEB are optimistic. The autosomal recessive DEB is more severe, with neonatal onset and recurrent blistering. It is also associated with chronicity and malignant changes when the child reaches adulthood.Conclusion Exact genetic diagnosis aids in counseling of the family concerning the prognosis in the affected child and the risk of affected children in future pregnancies.

Consensus on diagnosis and treatment of ornithine trans-carbamylase deficiency

Ornithine transcarbamylase deficiency(OTCD)is a most common ornithine cycle (urea cycle) disorder. It is a X-link inherited disorder caused by OTC gene mutation that in turn leads to reduction or loss of OTC enzyme activity. Its onset time is related to the lack of enzyme activity. Patients with neonatal onset usually have complete absence of OTC enzyme activity, which is mainly associated with male semi-zygotic mutations; and the disease progresses rapidly with high mortality rates. Patients with late onset vary in onset age and clinical manifestations, and the course of disease can be progressive or intermittent. The acute attack mainly manifests neuropsychiatric symptoms accompanied by digestive symptoms like liver function damage or even acute liver failure. Elevated blood ammonia is the main biochemical indicator of OTCD patients. Increased glutamine, decreased citrulline in blood, and increased orotic acid in urine are typical clinical manifestations for OTCD patients. Genetic testing of OTC gene is important for OTCD diagnosis. The goal of treatment is to minimize the neurological damage caused by hyperammonemia while ensuring the nutritional needs for patient development. For patients with poor response to medication and diet, liver transplantation is recommended under the condition of stable metabolic state and absence of severe neurological damage. During long-term treatment, physical growth indicators, nutrition status, liver function, blood ammonia and amino acids should be regularly monitored. This consensus aims to standardize the diagnosis and treatment of OTCD, improve the prognosis, reduce the mortality and disability of patients.

Neonatal sepsis: Bacteriological profile,molecular detection and antimicrobial susceptibility test among pre-term pediatrics in Erbil city, Iraq

Background and objective: Neonatal sepsis refers to infection occurring within the neonatal period, the first 28 days of life for a term baby, and up to 4 weeks beyond the expected date of delivery in a pre-term baby. This study was designed to determine the frequency of neonatal early onset sepsis and late onset sepsis in some hospitals in Erbil city. Methods: Out of 170 neonate samples from Neonatal Intensive Care Unit in Rapareen Pediatric Teaching Hospital and Maternity Obstetric Hospital randomly were studied through isolation and identification of causative bacteria using the traditional approach, VITEK 2 compact system, molecular detection using PCR technique, moreover, C-reactive protein and white blood cell count detected as biomarker assay. The isolated bacteria tested against some widely used antibiotics. Results: The sepsis was confirmed in 54 (31.76%) patients of total neonates with suspected cases of sepsis by clinical signs and symptoms. EOS was 42 (77.77%) were detected, and late onset sepsis was 12 (22.23%). Identification of the isolated bacteria by the traditional method, and VITEK 2 compact system were performed. In addition, molecular detection via the PCR system through the detection of the specific genes was performed. Antimicrobial Susceptibility test indicated that most of the isolated bacteria were developed resistant to the most widely used antimicrobials. Conclusion: Our study showed a high incidence of neonatal early onset sepsis more than late onset sepsis, mostly associated with Gram-negative bacteria than Gram-positive bacteria.

Adherence to World Health Organisation guidelines for treatment of early onset neonatal sepsis in low-income settings; a cohort study in Nepal

BackgroundNeonatal sepsis is one of the major causes of death during the first month of life and early empirical treatment with injectable antibiotics is a life-saving intervention. Adherence to World Health Organisation guidelines on first line antibiotics is crucial to mitigate the risks of increased antimicrobial resistance. The aim of this paper was to evaluate if treatment of early onset neonatal sepsis in a low-income facility setting observe current guidelines and if compliance is influenced by contextual factors.MethodsThis cohort study used data on antimicrobial treatment of neonatal sepsis onset within 72 h of life from 12 regional hospitals participating in a scale-up trial of a neonatal resuscitation quality improvement package intervention in Nepal. Infants treated according to guidelines were compared with those receiving other antimicrobials. A multiple logistic regression analysis adjusted for the intervention and time trend was applied.Results1564 infants with a preliminary diagnosis of early onset sepsis were included. A majority (74.9%) were treated according to guidelines and adherence was increasing over time. Infants born at larger facilities (adjusted Odds Ratio 5.6), those that were inborn (adjusted Odds Ratio 1.97) or belonging to a family of dis-advantaged caste (adjusted Odds Ratio 2.15) had higher odds for treatment according to guidelines. A clinical presentation of lethargy or tachypnoea was associated with adherence to guidelines.ConclusionAdherence to guidelines for antibiotic treatment of early neonatal sepsis was moderately high in this low-income setting. Odds for observing guidelines increased with facility size, for inborn infants and if the family belonged to a dis-advantaged caste. Cefotaxime was a common alternative choice when guidelines were not followed, highly relevant for the risk of increased antimicrobial resistance.Trial registrationISRCTN, ISRCTN30829654, registered 17th of May, 2017.

Structure-Function Properties in Sodium Channelopathies: Considerations for Targeted Therapy.

Biological Concepts in Human Sodium Channel Epilepsies and Their Relevance in Clinical Practice Brunklaus A, Du J, Steckler F, Ghanty II, Johannesen KM, Fenger CD, Schorge S, Baez-Nieto D, Wang H-R, Allen A, Pan JQ, Lerche H, Heyne H, Symonds JD, Zuberi SM, Sanders S, Sheidley BR, Craiu D, Olson HE, Weckhuysen S, DeJonge P, Helbig I, Esch HV, Tiffany B, Milh M, Isidor B, Depienne C, Poduri A, Campbel AJ, Dimidschstein J, Møller RS, Lal D. Epilepsia. 2020;61(3):387-399. doi.org/10.1111/epi.16438Objective:Voltage-gated sodium channels (SCNs) share similar amino acid sequence, structure, and function. Genetic variants in the 4 human brain-expressed SCN genes SCN1A/2A/3A/8A have been associated with heterogeneous epilepsy phenotypes and neurodevelopmental disorders. To better understand the biology of seizure susceptibility in SCN-related epilepsies, our aim was to determine similarities and differences between SCN disorders, allowing us to develop a broader perspective on precision treatment than on an individual gene level alone.Methods:We analyzed genotype–phenotype correlations in large SCN-patient cohorts and applied variant constraint analysis to identify severe SCN disease. We examined temporal patterns of human SCN expression and correlated functional data from in vitro studies with clinical phenotypes across different SCN disorders.Results:Comparing 865 epilepsy patients (504 SCN1A, 140 SCN2A, 171 SCN8A, 4 SCN3A, 46 copy number variation [CNV] cases) and analysis of 114 functional studies allowed us to identify common patterns of presentation. All 4 epilepsy-associated SCN genes demonstrated significant constraint in both protein truncating and missense variation when compared to other SCN genes. We observed that age at seizure onset is related to SCN gene expression over time. Individuals with gain-of-function SCN2A/3A/8A missense variants or CNV duplications share similar characteristics, most frequently present with early onset epilepsy (<3 months), and demonstrate good response to SCN blockers (SCBs). Direct comparison of corresponding SCN variants across different SCN subtypes illustrates that the functional effects of variants in corresponding channel locations are similar; however, their clinical manifestation differs, depending on their role in different types of neurons in which they are expressed.Significance:Variant function and location within one channel can serve as a surrogate for variant effects across related SCNs. Taking a broader view on precision treatment suggests that in those patients with a suspected underlying genetic epilepsy presenting with neonatal or early onset seizures (<3 months), SCBs should be considered.

Improving outcomes in neonatal late onset sepsis: Where every second matters

Late onset sepsis (LOS) in the neonatal period is an infection that occurs 72 h after birth and can result in morbidities and mortality when untreated. Signs and symptoms of infection can be very nonspecific, making LOS difficult to diagnose. The current recommendations are to administer antibiotics within 1 h of suspected LOS. Therefore, a quality improvement project was initiated in which the average time to antibiotics administration was observed, followed by specific interventions in an attempt to decrease the time to antibiotic administration. The goal was administration of antibiotics within 1 h of suspected LOS. Initially the average time to antibiotic administration was 141 min, well exceeding recommendations. Following education and initiation of an order set in the electronic medical record system, the average time was decreased to 99 min, with p = 0.07. These interventions allowed the time to antibiotic administration to decrease by 42 min when the concern for LOS arose.

P28 Gentamicin-related incidents in neonates before and after the introduction of electronic prescribing and medicines administration (ePMA)

AimGentamicin is widely used to treat early neonatal sepsis as part of a regimen recommended by NICE.1 However, it is frequently implicated in clinical incidents relating to errors in prescribing and administration. This project aimed to evaluate whether the introduction of ePMA had an effect on the frequency and type of incidents that occur relating to the use of gentamicin in neonates.MethodA paper gentamicin prescription chart was used from July 2013 until the implementation of ePMA on 28th January 2019. Using ePMA, prescribers were encouraged to use a pre-set template for ‘neonatal early onset sepsis’, listing benzylpenicillin and gentamicin (in mg/kg). Prescribers had to input the date and time of the first dose, and the system would automatically calculate the dose and time of subsequent administrations. A visual cue was used by the system to signal to nurses that a dose was due. Data was extracted from our local incident reporting system between the periods of 1st July 2013 to 27th January 2019 (‘pre-ePMA’) and 28th January 2019 to 30th June 2019 (‘post-ePMA’), where ‘gentamicin’ was mentioned in the incident description under the ‘neonates’ specialty. The data was examined, categorised into ‘prescribing-related’, ‘administration-related’, or ‘other’ and within the former two, grouped into identified themes.ResultsPre-ePMA 55 incidents were reported (mean=9/year, range 6–16/year), of which 41 (75%) were deemed to have the potential to cause harm. 27 (49%) incidents were prescribing-related and 19 (35%) were administration-related. The rest of the incidents were classed as ‘other’ eg. mislabelling blood samples. The most common prescribing-related incidents were incorrect frequency intervals, accidental omission, incorrect dose, or failing to meet prescribing standards. The most common administration-related incidents were doses being given too early, too late or missed. Four incidents were reported in the 5-month period post-ePMA (2 prescribing-related, 1 administration-related, 1 other). All prescribing- and administration-related incidents were deemed to have the potential to cause harm. One incident was due to incorrect frequency (first dose was given before arrival and prescriber had to manually calculate interval), one incident related to unintended doses prescribed and given (only benzylpenicillin was indicated), and one administration incident from poor documentation (dose given but not signed for). Compared with the same 5-month period in 2018 (pre-EPMA), 1 more incident had been reported this year compared to the previous year where only 3 incidents were reported.ConclusionThe introduction of ePMA may not reduce the number of reported incidents relating to gentamicin in neonates. A longer period of study is needed to evaluate the effects of transitioning from paper to ePMA. Our results suggest that ePMA can eliminate or reduce the risk of some types of errors, but can also make no difference to others, and can create new types of system-related errors, which can still have the potential to cause harm. This is consistent with the outcomes of a similar study in 2016 in another centre.2ReferencesNational Institute for Health and Care Excellence (NICE). Neonatal infection (early onset): antibiotics for prevention and treatment. Manchester: NICE; 2012.Kitson G. Implementation of an electronic prescription chart for gentamicin for neonatal units and postnatal wards. Arch Dis Child, 2016;101e2.

Induced pluripotent stem cell-derived monocytic cell lines from a NOMID patient serve as a screening platform for modulating NLRP3 inflammasome activity.

Curative therapeutic options for a number of immunological disorders remain to be established, and approaches for identifying drug candidates are relatively limited. Furthermore, phenotypic screening methods using induced pluripotent stem cell (iPSC)-derived immune cells or hematopoietic cells need improvement. In the present study, using immortalized monocytic cell lines derived from iPSCs, we developed a high-throughput screening (HTS) system to detect compounds that inhibit IL-1β secretion and NLRP3 inflammasome activation from activated macrophages. The iPSCs were generated from a patient with neonatal onset multisystem inflammatory disease (NOMID) as a model of a constitutively activated NLRP3 inflammasome. HTS of 4,825 compounds including FDA-approved drugs and compounds with known bioactivity identified 7 compounds as predominantly IL-1β inhibitors. Since these compounds are known inflammasome inhibitors or derivatives of, these results prove the validity of our HTS system, which can be a versatile platform for identifying drug candidates for immunological disorders associated with monocytic lineage cells.

Fatal case of newborn Lassa fever virus infection mimicking late onset neonatal sepsis: a case report from northern Nigeria

BackgroundLassa fever is a zoonotic viral infection endemic to the West Africa countries. It is highly fatal during pregnancy and as such reports of neonatal onset Lassa fever infections are rare in scientific literature. We report a fatal case of Lassa fever in a 26-day-old neonate mimicking the diagnosis of late-onset neonatal sepsis.Case presentationThe patient is a 26-day-old neonate who was admitted with a day history of fever, poor feeding, pre-auricular lymphadenopathy and sudden parental death. He was initially evaluated for late onset neonatal sepsis. He later developed abnormal bleeding and multiple convulsions while on admission, prompting the need to evaluate for Lassa fever using reverse transcription polymerase chain reaction (RT-PCR). He died 31 h into admission and RT-PCR result was positive for Lassa fever.ConclusionsNeonatal Lassa fever infection is highly fatal and can mimic neonatal sepsis. High index of suspicion is needed particularly for atypical presentations of neonatal sepsis in Lassa fever endemic areas.

Congenital laryngeal webs: from diagnosis to surgical outcomes

IntroductionCongenital laryngeal webs are rare, may be associated with other airway abnormalities and be one of many features of microdeletion 22q11. Meticulous evaluation is imperative when deciding which surgical technique to use. The choice of appropriate stenting may be decisive to avoid persistent anterior commissure synechia and poor voice results. ObjectiveTo report outcomes for endoscopic and open surgical approaches in the treatment of congenital laryngeal webs and the challenges one may encounter while applying the current classification and deciding for the best treatment option. MethodsRetrospective review of medical and surgical charts for congenital laryngeal webs treated in two tertiary university centers. ResultsSeven patients were included; following Cohen’s classification there were: three type II webs, one of them with an atypical posterior synechia, two type III webs and two type IV webs. Six patients were submitted to laryngotracheal reconstruction and one was treated with an endoscopic approach. Description of precise glottic and subglottic involvement and tailored surgical options are presented. The LT mold® stent was used for long-term stenting that varied between 40 to 60 days. All patients were successfully decannulated with good voice quality and after follow-up of over one year, there were no complications associated with the surgeries. ConclusionCongenital laryngeal webs should be suspected and thoroughly evaluated in the presence of neonatal dysphonia and early onset of laryngitis. Otolaryngologists must be familiar with associated lesions and genetic conditions that may be associated to congenital laryngeal webs. Congenital laryngeal webs may be successfully treated at an early age. The correct choice of surgical technique after meticulous evaluation of glottic and subglottic components of the web, presence of concomitant lesions and appropriate stenting, is imperative to avoid persistent scarring and poor voice quality.

ASSOCIATION BETWEEN SEPSIS RISK CALCULATOR AND INFECTION PARAMETERS FOR NEONATES WITH RISK OF EARLY ONSET SEPSIS

C-reactive protein (CRP) is an acute-phase reactant protein that is primarily induced by the IL-6 action during the acute phase of an inflammatory or infectious process. Bacterial infection is a potent stimulus, leading to a rapid elevation of CRP levels within hours while the CBC and symptom are often misleading and/or absent. American Academy of paediatrics (AAP) is recommended routine blood examination test Complete Blood Count (CBC), C-reactive protein (CRP), and blood culture along with empirical antibiotic in neonates with early onset sepsis risk (EOS) risk even asymptomatic. Previous study is showed there were no correlation of CRP and EOS risk. The aim of this study is to evaluate the CRP and CBC profile in neonate with risk of EOS. Methods of this study is using the sepsis risk calculator (SRC) to calculate the probability of neonatal early onset sepsis (EOS) based on maternal risk and infant’s clinical presentation. Neonates with ≥34 weeks of gestation who were started on antibiotic treatment after laboratory examination and blo odculture were taken. EOS risk estimation were compared including CRP, leukocyte, and thrombocyte count. ANOVA applied to distinguished laboratory examination between stratified risk groups. The result is showed using 82 subjects who met the inclusion and exclusion criterias, EOS risk level was stratified into green, yellow, and red group. The p value of CRP level, platelets, white blood cell were 0.35,0.54 and 0.48 where p value was considered as significant if &lt; 0.5. The conclusion of this study is there were no correlation of CRP level and EOS riskASSOCIATION BETWEEN SEPSIS RISK CALCULATOR AND INFECTION PARAMETERS FOR NEONATES WITH RISK OF EARLY ONSET SEPSIS

Childhood-onset epileptic encephalopathy due to FGF12 exon 1-4 tandem duplication.

Fibroblast growth factor 12 ( FGF12 ) spans 5 exons and encodes for a cytosolic voltage-gated sodium channel binding protein that modulates neuronal excitability.1,2 A recurrent activating FGF12 mutation (NM_021032, [GRCh37] 192053223C>T, p.R114H in A-isoform, p.R52H in B-isoform) causes epileptic encephalopathy (EE) with neonatal onset and intellectual disability (ID).2–6 Recently, a tandem duplication involving exons 1–4 of the FGF12 gene was related to a later onset EE phenotype.7 Here, we characterize a second case harboring a FGF12 exon 1–4 duplication. This study makes use of data generated by the DECIPHER community. A full list of centers that contributed to the generation of the data is available at [decipher.sanger.ac.uk][1] and can be shared via email upon request (decipher{at}sanger.ac.uk). Funding for the project was provided by the Wellcome Trust. The authors thank Prof. Dr. Phillip Pearl, Boston, Harvard Medical School, for discussion on current EEG terminology commonly used in the United States. [1]: http://decipher.sanger.ac.uk

Clinical Profile of Neonatal Early Onset Sepsis: A Study on the Current Scenario

Background: Neonatal early onset sepsis remains to be a challenge in India, owing to its variable presentation, diagnostic difficulty and high fatality. An attempt needs to be made to study its clinical profile for easy identification of such babies, with new antibiotic guidelines formulated based on current microorganisms isolated. The aim of the study is to study the clinical profile of early onset sepsis in neonates in terms of the risk factors, clinical factors and etiology, and ascertain factors associated with definite sepsis. Subjects and Methods: This hospital based cross-sectional study enrolled neonates with suspected early onset sepsis. Those with congenital anomalies, surgical conditions, gestation &lt;28 weeks and birth weight &lt;1kg excluded. Subjects were subjected to sepsis screen and blood culture, and their perinatal history recorded. Blood culture positive babies were considered to have definite sepsis. Data was analysed using Chi square with SPSS 18. Results: Among 300 babies enrolled, 70 babies had definite sepsis. The most common organism isolated was Klebsiella (27.1%) and Staphylococcus hemolyticus (21.4%), most showing sensitivity to Ampicillin and Gentamicin. Respiratory distress was the commonest presentation (71.3%). A significant association with definite sepsis was seen with prematurity (p =0.0026) and low birth weight (p =0.0052), perinatal risk factors namely premature rupture of membranes (p =0.004), foul smelling liquor (p=0.016) and birth asphyxia (p-value=0.02). 28.3% had positive sepsis screen, which was significant (p = 0.001). Conclusion: Early onset sepsis needs prompt identification and treatment initiation, possible with aid of sepsis screen and high index of suspicion with certain perinatal risk factors and gestational age and birth weight.

Zebrafish Models of LAMA2-Related Congenital Muscular Dystrophy (MDC1A).

LAMA2-related congenital muscular dystrophy (CMD; LAMA2-MD), also referred to as merosin deficient CMD (MDC1A), is a severe neonatal onset muscle disease caused by recessive mutations in the LAMA2 gene. LAMA2 encodes laminin α2, a subunit of the extracellular matrix (ECM) oligomer laminin 211. There are currently no treatments for MDC1A, and there is an incomplete understanding of disease pathogenesis. Zebrafish, due to their high degree of genetic conservation with humans, large clutch sizes, rapid development, and optical clarity, have emerged as an excellent model system for studying rare Mendelian diseases. They are particularly suitable as a model for muscular dystrophy because they contain at least one orthologue to all major human MD genes, have muscle that is similar to human muscle in structure and function, and manifest obvious and easily measured MD related phenotypes. In this review article, we present the existing zebrafish models of MDC1A, and discuss their contribution to the understanding of MDC1A pathomechanisms and therapy development.

Time to positive blood culture in early onset neonatal sepsis: A retrospective clinical study and review of the literature.

Neonatal early onset sepsis (EOS) is a low-incidence, high-risk disease which has prompted significant overtreatment with antibiotics for the standard duration of 48 h. The aims of this study were to determine whether blood cultures collected from term and late preterm neonates for EOS would return a positive result for pathogenic bacteria within 24 h and to review the literature to supplement the results. This is a retrospective observational study of time to positive blood culture in the BACTEC culture system from neonates ≥34 weeks in a single referral centre between 1999 and 2018. A literature review was conducted through PubMed, MEDLINE and Embase using search terms of 'neonatal sepsis' AND 'blood culture'. Studies were included if they reported time to positive blood culture in EOS. Forty positive cultures were included in this report, with 39 (98%) showing bacterial growth within 24 h. One culture, obtained after commencement of antibiotics, became positive at 3 days. Sixteen papers were included in our literature review and six presented data for an EOS cohort; a median of 96.5% of pathogenic EOS blood cultures become positive within 24 h. All pathogenic blood cultures collected pre-therapy from neonates ≥34 weeks suspected of EOS returned a positive result within 24 h of incubation. Similar studies have found that 92-100% of cultures are positive by 24 h. This data could contribute to re-evaluation of the current standard duration of antibiotic use in term and late preterm neonates with suspected EOS.

Improving Antibiotic Stewardship Among Asymptomatic Newborns Born at or Greater than 36 Weeks Using the Neonatal Early Onset Risk Calculator

Background: The potential deleterious effects of antibiotic use in newborns have made antibiotic stewardship for asymptomatic newborns a priority. In January 2016, we instituted a newborn sepsis protocol based largely on the 2012 AAP guidelines. By December 2016, we determined that our antibiotic use had not decreased, and resolved to conduct a PDSA cycle to decrease antibiotic usage. Beginning in June of 2017, we adopted a clinical algorithm which integrated the use of the Neonatal Early Onset Sepsis (EOS) Risk Calculator at birth. We were able to decrease the use …

Improving Antibiotic Stewardship Among Asymptomatic Newborns Born at or Greater than 36 Weeks Using the Neonatal Early Onset Risk Calculator

Improving Antibiotic Stewardship Among Asymptomatic Newborns Born at or Greater than 36 Weeks Using the Neonatal Early Onset Risk Calculator

Forecasting the possibility of neonatal early onset sepsis based on perinatal risk factors

Background: Neonatal sepsis remains a leading cause of neonatal mortality and morbidity, diagnosis of which remains difficult due to variable presentations. With the increasing threat of antimicrobial resistance, it is important to identify perinatal risk factors which are associated with higher incidence of definite sepsis, to initiate empirical antibiotics, while awaiting blood culture reports.Methods: This was hospital based cross-sectional study done in SVPPGIP, Cuttack, Odisha during January 2019 to April 2019, enrolling all neonates ≥37 weeks gestation and aged less than 72 hours, with suspected early onset sepsis. Neonates with TORCH infections, congenital anomalies, syndromic baby or with surgical conditions were excluded. After obtaining informed consent, blood culture was sent for all and their perinatal risk factors noted. Blood culture positive newborns were considered to have definite sepsis. Data was analysed with Chi-square test and percentages, using SPSS 18.Results: Among the 200 cases, incidence of definite sepsis was 26%. The most common risk factor was low birth weight and birth asphyxia. Majority (67%) had single or lesser risk factor and number of risk factors was significantly associated with definite sepsis. A significant association was seen between blood culture positivity with low birth weight (p=0.003), foul smelling liquor (p= 0.025), birth asphyxia (p 0.018) and premature rupture of membranes (p= 0.016). The combination of maternal fever and unclean vaginal examination was also significantly associated with the same.Conclusions: Protocols for initiating empiric antibiotics need to be formulated, taking into account the significant risk factors, in resource limited settings, to avoid resource and time wastage.