الفهرس 
Early Onset Neonatal SepsisOnly 14 pages are availabe for public view
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Abstract
N
eonatal sepsis is a clinical syndrome in an infant 28 days of life or younger manifested by systemic signs of infection and/or isolation of a bacterial pathogen from the blood stream. Early-onset neonatal sepsis is defined as the onset of symptoms within the first days of life; first 3 or first 7 days.
Rapid diagnosis is problematic because the signs and symptoms of sepsis are subtle and nonspecific. In neonatology, currently, no single test fulfills the criteria of an ideal diagnostic test which can reliably diagnose sepsis in the newborn.
Subtle neurological damage associated with sepsis is difficult to detect clinically, biochemical brain damage markers such as NSE would be of great value for diagnosis as they are objective, convenient and cheap.
Also, transcranial Doppler studies may show impairment of cerebrovascular reactivity in patients with sepsis. Moreover, altered CBF may also be used as a surrogate marker for the diagnosis of early onset neonatal sepsis.
Neuroinflammation during the perinatal period has a high risk of causing substantial long-term neurological morbidity. Survivors may have long-term cognitive impairment and lower health-related quality of life. Developmental tests such as the Griffith mental developmental scale have been recognised as valuable tools for assessing the development of infants and young children. It was noticed that neonatal biomarkers of inflammation in sepsis associated with a lower neurodevelopmental scores.
This work was designed to assess the clinical utility of transcranial Doppler sonographic cerebral blood flow velocity measurements and serum neuron-specific enolase (NSE) determination in newly born infants for
prediction of early-onset neonatal sepsis, evaluation of sepsis-induced cerebral injury, prognosis of the clinical outcome of sepsis and detection of the possible impact of sepsis on the infant’s neurodevelopment.
This study included 100 neonates who were admitted to the NICUs of Ain Shams University Hospitals with clinical suspicion of sepsis from December 2013 till July 2015. Neonate with evidence of major congenital birth defects or chromosomal anomalies, delivery room resuscitation with the use of intubation and mechanical ventilation, evidence suggestive of perinatal asphyxia/hypoxic ischemic encephalopathy and hemodynamically significant cardiac abnormalities were excluded. The study included 53 males and 47 females with gestational age ranged between 30 and 41 weeks, 43 delivered vaginally and 57 delivered by caesarean section, the studied neonates were divided into two distinct groups, group A with established diagnosis of EOS and non-sepsis neonates as group B.
Established EOS was diagnosed based on Tollner’s score ≥ 10, Rodwell’s hematological score ≥ 3, CRP ≥ 6, with or without positive blood culture within the first 72 hours postnatal age. Both groups were comparable in terms of the maternal characteristics; maternal age, gravidity, maternal diseases or risk factors of sepsis as maternal fever, rupture of membranes for more than 18 hours and chorioamnionitis.
As regards the demographic and clinical data of the included newborns, there were also no statistically significant differences between both studied groups in terms of gestational age, mode of delivery, Apgar score, length, occipitofrontal circumference and gender. Birth weight was significantly lower in sepsis group than non sepsis one.
The most common organism in sepsis group was staphylococcus aureus then coagulase negative staphylococci and citrobacter.
Sepsis group showed higher statistically significant use and duration of respiratory support, use and duration of inotropes, incidence of encephalopathy and multisystem organ failure (MSOF) than the non-sepsis group.
Doppler ultrasound was done measuring resistive index (RI), peak systolic velocity (PSV),end diastolic velocity (EDV) of the anterior cerebral artery (ACA), middle cerebral artery (MCA) within the first 48 hours postnatal. Sepsis group showed an increase in cerebral blood flow which was diagnosed by a significant decrease in ACA and MCA resistive indices and a significant increase in PSV and EDV of ACA and MCA. ROC curve showed that the highest AUC is of ACA RI (0.91) with a cut off value ≤ 0.65, sensitivity of 87.5% and a specificity of 87.5% followed by MCA RI with AUC 0.89, cut off value ≤ 0.69, sensitivity of 85.42% and specificity of 73.08%. Comparison between areas under the curves revealed no significant difference between the use of ACA and MCA resistive indices.
The base line NSE (which was withdrawn within 48 hours postnatal age) is significantly higher in sepsis group when compared to the non-septic group. NSE can predict the EOS with a cutoff value > 64.08ng/ml with a sensitivity of 75% and a specificity of 78.85% hours. Follow up NSE showed a significant reduction in its level in sepsis patients with complications.
Sepsis group needed significantly higher hospital admission rate, more length of hospital stay, longer duration of antibiotic therapy,more abnormal cranial US findings at discharge and more mortality than non sepsis group.
The Griffiths mental developmental scale (GMDS) at 3 months in sepsis group was lower than in non- sepsis group yet did not reach statistically significant level. Moreover, There is no significant difference between both groups at 6 months. Furthermore we found that there was a significant increase in mental age and IQ in Griffith mental developmental scale and subscales in sepsis group at 6 months with p < 0.05, except General quotient (GQ) and quotient of locomotor subscale (AQ) which were higher than at 3 months yet did not reach statistical significance.
There was a significant correlation between baseline NSE as a neuroinflammatory biomarker and cerebral Doppler indices in the whole study groups. A decrease in RI and an increase in PSV and EDV of both ACA and MCA were associated with a significant increase in NSE.This correlation was present in sepsis group in PSV and EDV of ACA and MCA and was found in PSV of both ACA and MCA in non sepsis group.
There was no significant correlation between baseline NSE and neurodevelopment assessed by GMDS in 3 and 6 months in infants with and without sepsis and in the whole study population.
Assessment of the relation between cerebral Doppler indices and neurodevelopment in the whole study population at the age of 3 months, there was only one marginal significant negative correlation between MCA EDV and mental age and intelligence quotient of locomotor subscale (AQ) with a correlation co-efficient that could be neglected. On the other hand, no significant correlation between other cerebral Doppler parameters and GMDS at 3 or 6 months postnatal age.
As regards non- sepsis group, there was a non significant correlation between cerebral Doppler indices and GMDS at 3 or 6 months postnatal age except in MCA PSV. There was a marginal significant correlation between an increase in MCA PSV and worsening of mental age as a whole. Furthermore, in the sepsis group, there was a non significant correlation between cerebral Doppler indices and GMDS at 3 or 6 months postnatal age.
By the end of our study, we may conclude that vasodilatation, increased cerebral blood flow and neuron specific enolase (NSE) in early hours of life can be used as early tests for diagnosis of early onset neonatal sepsis.
Early onset sepsis showed no effect on neuro-development at 3 or 6 months of age.