Biomarkers of hepatic injury and function in neonatal hypoxic ischemic encephalopathy and with therapeutic hypothermia

Muniraman, Hemananda; Gardner, Danielle; Skinner, Jane; Paweletz, Anna; Vayalakkad, Anitha; Chee, Ying Hui; Clifford, Clare; Sanka, Sunil; Venkatesh, Vidheya; Curley, Anna; Victor, Suresh; Turner, Mark A.; Clarke, Paul

doi:10.1007/s00431-017-2956-2

Cited by 36 publications

(32 citation statements)

References 28 publications

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“…In our study, CRP levels were elevated above the threshold of 10 mg/L in as much as 54.02% of the included 225 newborns, rising to 62.9% when only cases of moderate or severe HIE under TH treatment are considered. This is consistent with previous data 5,6,21 reporting elevated CRP in 68, 82, and 64.3% of patients with moderate-severe HIE, respectively. This is not to say that the levels of CRP in HIE and infection are comparable, in fact, there seem to be differences between infected and hypoxic-ischemic newborns.…”

Section: Discussionsupporting

confidence: 93%

“…In the past few years, there has been published research supporting an effect of TH in the course of CRP levels. 5,7,18,21 In our study, TH newborns had lower initial CRP levels, but reached higher maximum CRP and their peak was later in NT newborns. These results are analogous to those presented by Muniraman et al, 21 with a higher proportion of newborns with elevated CRP levels in the TH group compared with NT (62.6 vs. 49.6%), and a delayed peak in TH cases.…”

Section: Discussionsupporting

confidence: 48%

“…5,7,18,21 In our study, TH newborns had lower initial CRP levels, but reached higher maximum CRP and their peak was later in NT newborns. These results are analogous to those presented by Muniraman et al, 21 with a higher proportion of newborns with elevated CRP levels in the TH group compared with NT (62.6 vs. 49.6%), and a delayed peak in TH cases. However, it is relevant that in the work by Muniraman et al, mild cases of HIE are included both in the NT (69/138, 50% of the NT cases) and TH groups (32/223, 14.4% of the TH cases).…”

Section: Discussionsupporting

confidence: 48%

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Effect of Hypothermia and Severity of Hypoxic-Ischemic Encephalopathy in the Levels of C-Reactive Protein during the First 120 Hours of Life

et al. 2019

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Objective This study aimed to describe normal C-reactive protein (CRP) levels of newborns diagnosed with hypoxic-ischemic encephalopathy (HIE) and assess the influence of therapeutic hypothermia (TH) and the severity of HIE. Study Design We prospectively recruited infants ≥35 weeks of gestational age diagnosed with HIE from 2000 to 2013 and compared CRP levels in the first 120 hours of life according to the severity of HIE and the use of TH, which was introduced in 2009. Results Moderate HIE was diagnosed in 115 newborns, severe HIE in 90 (hypothermia was performed in 151 cases), and mild HIE in 20. Cooled newborns showed lower levels of CRP in the first 34 hours, but reached higher median maximum CRP levels (15.4 vs. 8.5 mg/L), and at a significantly older age (53 vs. 17 hours). Levels of CRP in mild HIE were lower than those of moderate–severe forms. Moderate and severe HIE had similar CRP levels, but time to maximum CRP was significantly less in moderate cases. Conclusion CRP levels of mild HIE are similar to healthy newborns, while CRP elevations can be expected in newborns with moderate–severe HIE. TH produced a slower rise, with a higher and late maximum CRP peak level.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 48%

Section: Discussionsupporting

confidence: 48%

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Effect of Hypothermia and Severity of Hypoxic-Ischemic Encephalopathy in the Levels of C-Reactive Protein during the First 120 Hours of Life

et al. 2019

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“…During the hypoxic-ischemic event, both the kidneys and liver are deprived of oxygen, resulting in possible functional nephron and hepatocyte damage. [23][24][25][26][27] Additionally, cardiac output might also be hampered due to a loss in myocardial function. 28 After resuscitation and stabilization at the NICU, gradual recovery of organ function after birth was anticipated.…”

Section: Recovery Of Organ Functionmentioning

confidence: 99%

Prediction of Drug Exposure in Critically Ill Encephalopathic Neonates Treated With Therapeutic Hypothermia Based on a Pooled Population Pharmacokinetic Analysis of Seven Drugs and Five Metabolites

Favié

Haan

Bijleveld

et al. 2020

Clin Pharma and Therapeutics

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Drug dosing in encephalopathic neonates treated with therapeutic hypothermia is challenging; exposure is dependent on body size and maturation but can also be influenced by factors related to disease and treatment. A better understanding of underlying pharmacokinetic principles is essential to guide drug dosing in this population. The prospective multicenter cohort study PharmaCool was designed to investigate the pharmacokinetics of commonly used drugs in neonatal encephalopathy. In the present study, all data obtained in the PharmaCool study were combined to study the structural system specific effects of body size, maturation, recovery of organ function, and temperature on drug clearance using nonlinear mixed effects modeling. Data collected during the first 5 days of life from 192 neonates treated with therapeutic hypothermia were included. An integrated population pharmacokinetic model of seven drugs (morphine, midazolam, lidocaine, phenobarbital, amoxicillin, gentamicin, and benzylpenicillin) and five metabolites (morphine‐3‐glucuronide, morphine‐6‐glucuronide, 1‐hydroxymidazolam, hydroxymidazolam glucuronide, and monoethylglycylxylidide) was successfully developed based on previously developed models for the individual drugs. For all compounds, body size was related to clearance using allometric relationships and maturation was described with gestational age in a fixed sigmoidal Hill equation. Organ recovery after birth was incorporated using postnatal age. Clearance increased by 1.23%/hours of life (95% confidence interval (CI) 1.03–1.43) and by 0.54%/hours of life (95% CI 0.371–0.750) for high and intermediate clearance compounds, respectively. Therapeutic hypothermia reduced clearance of intermediate clearance compounds only, by 6.83%/°C (95% CI 5.16%/°C–8.34%/°C). This integrated model can be used to facilitate drug dosing and future pharmacokinetic studies in this population.

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“…This could be attributed to the effects of various stress factors on an immature liver, which in turn result in low levels of coagulation factors in patients with hypofibrinogenemia. Indeed, 35.8% of the neonates had an abnormal liver function, and approximately 29.7% of them experienced asphyxia or hypoxia, which was associated with hepatic dysfunction (28). Therefore, taken together, the possibility of occurrence of hypofibrinogenemia needs to be considered in neonates with liver function damage or a previous history of hypoxia/ischemia.…”

Section: Discussionmentioning

confidence: 99%

Clinical Characteristics of Hospitalized Neonates With Hypofibrinogenemia: A Retrospective Cohort Study

Zhou¹,

He²,

Li³

et al. 2020

Front. Pediatr.

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Background: Neonatal hypofibrinogenemia is often asymptomatic but can manifest as hemorrhage. Objective: This study was conducted to characterize clinical characteristics of neonates with hypofibrinogenemia and identify factors associated with hemorrhage. Methods: This was a retrospective study of neonates with plasma fibrinogen level (FIB) ≤1.0 g/L who were hospitalized at the Neonatology Department, People's Hospital, Chongqing, China, from January 2012 to December 2017. Based on severity, patients were grouped into severe, moderate, and mild hypofibrinogenemia (FIB < 0.5 g/L, 0.5 g/L ≤ FIB <0.7 g/L, and 0.7 g/L ≤ FIB ≤ 1.0 g/L, respectively). Clinical characteristics associated with hemorrhage were analyzed. Results: Among 330 neonates, 52.7% showed mild hypofibrinogenemia, 25.5% had moderate hypofibrinogenemia, and 21.8% had severe hypofibrinogenemia. Severe hypofibrinogenemia was not associated with gestational age, but the mild form was frequent in neonates with low/normal birthweight (P = 0.018). Approximately 80.6% of neonates presented hypofibrinogenemia as variable combinations of thrombocytopenia or coagulopathies. Hemorrhage occurred in 38.8% of the cases, 60.9% of which were mild. Hemorrhage manifested as puncture site bleeding (47.7%) or spontaneous skin/mucous membrane bleeding (34.2%). The degree of hypofibrinogenemia was not associated with the severity or occurrence of hemorrhage. Among patients with hypofibrinogenemia and bleeding, 53.4% of the cases with coagulopathies showed mild hemorrhage, 85.7% of the cases with thrombocytopenia had moderate bleeding, while 53.8% of the cases with coagulopathy and thrombocytopenia showed severe hemorrhage. Conclusion: Neonatal hypofibrinogenemia is often comorbid and occurs with thrombocytopenia and/or coagulopathies. Although hemorrhage is not associated with the degree of hypofibrinogenemia, it may be severe when hypofibrinogenemia co-occurs with coagulopathies and/or thrombocytopenia.

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Biomarkers of hepatic injury and function in neonatal hypoxic ischemic encephalopathy and with therapeutic hypothermia

Cited by 36 publications

References 28 publications

Effect of Hypothermia and Severity of Hypoxic-Ischemic Encephalopathy in the Levels of C-Reactive Protein during the First 120 Hours of Life

Effect of Hypothermia and Severity of Hypoxic-Ischemic Encephalopathy in the Levels of C-Reactive Protein during the First 120 Hours of Life

Prediction of Drug Exposure in Critically Ill Encephalopathic Neonates Treated With Therapeutic Hypothermia Based on a Pooled Population Pharmacokinetic Analysis of Seven Drugs and Five Metabolites

Clinical Characteristics of Hospitalized Neonates With Hypofibrinogenemia: A Retrospective Cohort Study

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