Thermoregulation and golden hour practices in extremely preterm infants: an international survey.

BACKGROUND: Are thermoregulation and golden hour practices in extremely preterm (EP) infants comparable across the world? This study aims to describe these practices for EP infants based on the neonatal intensive care unit's (NICUs) geographic region, country's income status and the lowest gestational age (GA) of infants resuscitated. METHODS: The Director of each NICU was requested to complete the e-questionnaire between February 2019 and August 2021. RESULTS: We received 848 responses, from all geographic regions and resource settings. Variations in most thermoregulation and golden hour practices were observed. Using a polyethylene plastic wrap, commencing humidity within 60 min of admission, and having local protocols were the most consistent practices (>75%). The odds for the following practices differed in NICUs resuscitating infants from 22 to 23 weeks GA compared to those resuscitating from 24 to 25 weeks: respiratory support during resuscitation and transport, use of polyethylene plastic wrap and servo-control mode, commencing ambient humidity >80% and presence of local protocols. CONCLUSION: Evidence-based practices on thermoregulation and golden hour stabilisation differed based on the unit's region, country's income status and the lowest GA of infants resuscitated. Future efforts should address reducing variation in practice and aligning practices with international guidelines. IMPACT: A wide variation in thermoregulation and golden hour practices exists depending on the income status, geographic region and lowest gestation age of infants resuscitated. Using a polyethylene plastic wrap, commencing humidity within 60 min of admission and having local protocols were the most consistent practices. This study provides a comprehensive description of thermoregulation and golden hour practices to allow a global comparison in the delivery of best evidence-based practice. The findings of this survey highlight a need for reducing variation in practice and aligning practices with international guidelines for a comparable health care delivery.

Term neonates with infection and shock display high cortisol precursors despite low levels of normal cortisol.

AIM: Neonatal therapy-resistant septic shock is a common problem in middle and low-income countries. We investigated whether newborn infants with infection and therapy-resistant hypotension showed evidence of abnormal levels of cortisol or cortisol precursors. METHODS: A total of 60 term or near term neonates with evidence of infection were enrolled after informed consent. Of these, 30 had an infection and refractory shock and 30 had an infection without shock. There were no detectable differences between the groups in the length of gestation, birth weight or gender distribution. Serum was obtained during days four and 14 after birth. Cortisol and cortisol precursor concentrations were analysed using liquid chromatography-tandem mass spectrometry. RESULTS: The cortisol concentrations were low considering the expected responses to stress and they did not differ between the groups. The infants with infection and shock had higher serum dehydroepiandrosterone (DHEA) levels than those without shock (319.0 ± 110.3 µg/dL, versus 22.3 ± 18.3 µg/dL; p < 0.0001) and they also had higher 17-hydroxy-pregnenolone, pregnenolone and progesterone concentrations. There were no detectable differences in the levels of 17-hydroxy-progesterone, 11-deoxy-cortisol, cortisol or cortisone. CONCLUSION: Septic newborn infants with therapy-resistant hypotension had very high DHEA levels, suggesting that 3-beta-hydroxysteroid dehydrogenase activity limited the rate of cortisol synthesis.

Fecal Calprotectin and Cow's Milk-Related-Symptoms Score in Children with Cow's Milk Protein Allergy.

Purpose: The cow's milk-related-symptom-score (CoMiSS) tool was developed as an awareness tool for the assessment of cow's milk-related symptoms in infants or children. Fecal calprotectin (FC) is a noninvasive biomarker of gut inflammation that can be measured in serum and stool. This study aimed to investigate the relationship between FC levels and CoMiSS scores in infants with cow's milk protein allergy. Methods: Infants (aged 6-12 months) who were allergic to cow's milk protein were enrolled prospectively. Following completion of the CoMiSS scoring, the infants were divided into group 1 (positive CoMiSS scores ≥12) and group 2 (negative CoMiSS scores <12). FC was measured using immunoassay. Results: Of the 120 infants enrolled in this study, 60 (50.0%) had positive CoMiSS scores (group 1), while 60 (50.0%) had negative scores (group 2). The mean FC level was higher in the infants in group 1 than those in group 2 (2,934.57 µg/g vs. 955.13 µg/g; p<0.001). In addition, there was a positive correlation between FC and CoMiSS scores (R=0.168, p<0.0001). A FC level of 1,700 µg/g provided a sensitivity of 98.3%, specificity of 93.3%, and accuracy of 95.8% for the diagnosis of cow's milk protein allergy (CMPA). Conclusion: FC measurement may have a role in the assessing infants with CMPA.

Global variation in skin injures and skincare practices in extremely preterm infants.

BACKGROUND: Globally, are skincare practices and skin injuries in extremely preterm infants comparable? This study describes skin injuries, variation in skincare practices and investigates any association between them. METHODS: A web-based survey was conducted between February 2019 and August 2021. Quantifying skin injuries and describing skincare practices in extremely preterm infants were the main outcomes. The association between skin injuries and skincare practices was established using binary multivariable logistic regression adjusted for regions. RESULTS: Responses from 848 neonatal intensive care units, representing all geographic regions and income status groups were received. Diaper dermatitis (331/840, 39%) and medical adhesive-related skin injuries (319/838, 38%) were the most common injuries. Following a local skincare guideline reduced skin injuries [medical adhesive-related injuries: adjusted odds ratios (aOR) = 0.63, 95% confidence interval (CI) = 0.45-0.88; perineal injuries: aOR = 0.66, 95% CI = 0.45-0.96; local skin infections: OR = 0.41, 95% CI = 0.26-0.65; chemical burns: OR = 0.46, 95% CI = 0.26-0.83; thermal burns: OR = 0.51, 95% CI = 0.27-0.96]. Performing skin assessments at least every four hours reduced skin injuries (abrasion: aOR = 0.48, 95% CI = 0.33-0.67; pressure: aOR = 0.51, 95% CI = 0.34-0.78; diaper dermatitis: aOR = 0.71, 95% CI = 0.51-0.99; perineal: aOR = 0.52, 95% CI = 0.36-0.75). Regional and resource settings-based variations in skin injuries and skincare practices were observed. CONCLUSIONS: Skin injuries were common in extremely preterm infants. Consistency in practice and improved surveillance appears to reduce the occurrence of these injuries. Better evidence regarding optimal practices is needed to reduce skin injuries and minimize practice variations.

Causes of Neonatal Acute Renal Injury during Critical Illnesses.

The aim of the study was to assess acute kidney injury (AKI) and its contributing risk factors among neonates to reduce morbidity and mortality. The study included 310 neonates who were admitted to the neonatal intensive care unit (NICU). Serum creatinine (SCr) was elevated at admission, after 48 h, and before discharge or death. AKI was defined by either an acute rise in SCr of at least 0.3 mg/dL within 48 h or an increasing or persistently high level of SCr >1.5 mg/dL after 48-72 h of life. The patients who developed AKI were studied regarding the most common risk factors and outcomes. The prevalence of AKI in these neonates was 11.9%. Nephrotoxic drugs were the highest risk factor among patients with AKI, but this was not statistically significant different from patients without AKI. Perinatal asphyxia (59.5%), respiratory distress syndrome (48.6%), shock (43.2%), prematurity (40.5%), and sepsis (37.8%) were the main risk factors of AKI following the nephrotoxic drugs (64.9%). The mortality rate for cases with AKI was 62.1%, with a statistically significant difference from non-AKI neonates. The death rate was higher among neonates born before 36 weeks' gestation. There was no statistical difference between oliguric and non-oliguric neonates with AKI regarding the outcome. The overall incidence of AKI in sick neonates admitted to the NICU was 11.9%. Nephrotoxic drugs, perinatal asphyxia, shock, and prematurity were the main risk factors for developing AKI.

Salivary Lactate Dehydrogenase in Relationship to the Severity of Hypoxic-Ischemic Encephalopathy among Newborn Infants.

INTRODUCTION: Hypoxic-ischemic encephalopathy (HIE) is defined as a neurological complication that results from perinatal asphyxia. Previous studies had investigated various markers to early detect HIE; however, these markers appeared to have several drawbacks, especially in resource-limited settings. AIM: This study aimed at evaluating the predictive value of the salivary lactate dehydrogenase level as a potential predictor of hypoxic-ischemic encephalopathy for newborns. MATERIALS AND METHODS: We included 30 neonates with HIE due to perinatal asphyxia and 30 healthy newborns that serve as controls, admitted at the intensive care unit for neonates and maternity ward at Ismailia area Clinics and Hospitals. We measured the LDH levels by using saliva samples that were collected for neonates maximum by 12 h after birth. RESULTS: It was found that patients with HIE had a statistically significant higher salivary LDH level (1927 ± 390.3 IU/L) than patients without HIE (523.6 ± 142.8 IU/L) (p < 0.001). Moreover, salivary LDH showed a good discriminative ability where the AUC was 0.966 regarding salivary LDH (95% CI: 0.917-1.0) (p < 0.001). The best cutoff value was 1420 IU/L or more which showed the best results in predicting the occurrence of HIE with 98.3% and 97.6% sensitivity and specificity, respectively. CONCLUSION: Salivary LDH can be considered as a useful noninvasive laboratory marker that can accurately predict HIE incidence among neonates with asphyxia within 12 hours from birth. The cases in the HIE group were assigned into three stages according to the Sarnat and Sarnat staging system: stage I: mild (irritable, normal, or hypertonia and poor feeding); stage II: moderate (lethargy, hypotonia, and frequent seizure); stage III: severe (coma, flaccid, absent reflexes, and frequent seizure). There is a positive association between LDH levels and the severity of HIE.

Salivary Interleukin-6 and C-Reactive Protein/Mean Platelet Volume Ratio in the Diagnosis of Late-Onset Neonatal Pneumonia.

Neonatal pneumonia is a serious respiratory infectious disease with a high rate of case fatality in developing countries. Salivary cytokines could serve as interesting noninvasive markers in the diagnosis of neonatal pneumonia. The aim was to assess the diagnostic role of salivary and serum interleukin-6 (IL-6), C-reactive protein/mean platelet volume (CRP/MPV) ratio, and the combination of these markers in the diagnosis of late-onset neonatal pneumonia in full-term neonates. Seventy full-term neonates, 35 with late-onset neonatal pneumonia and 35 controls, were enrolled in this prospective case-control study. Complete blood count (CBC), salivary and serum IL-6, and CRP concentrations were measured for all the study subjects. The sensitivity, specificity, positive predictive value, and negative predictive value of salivary IL-6, serum IL-6, and CRP/MPV ratio for the diagnosis of late-onset neonatal pneumonia were determined. At the cutoff point of >34 pg/ml, salivary IL-6 showed 82.86% sensitivity and 91.43% specificity. CRP/MPV ratio showed a sensitivity of 97.14% and specificity of 85.71% at a cutoff value > 0.88. The combination of salivary IL-6 and CRP/MPV ratio improved the sensitivity and specificity to 100%. The current study shows for the first time that both salivary IL-6 and CRP/MPV ratio are suitable markers for the diagnosis of late-onset neonatal pneumonia in full-term neonates.

Salivary and Serum Interleukin-10, C-Reactive Protein, Mean Platelet Volume, and CRP/MPV Ratio in the Diagnosis of Late-Onset Neonatal Sepsis in Full-Term Neonates.

Salivary markers could serve as potential noninvasive markers in the diagnosis of neonatal infections. We aimed to investigate the diagnostic role of salivary and serum interleukin 10 (IL-10), C-reactive protein (CRP), mean platelet volume (MPV), and CRP/MPV ratio in the diagnosis of late-onset neonatal sepsis in full-term neonates. Seventy full-term neonates were enrolled in this prospective case-control study, 35 with late-onset neonatal sepsis, and 35 controls. Salivary IL-10, serum IL-10, and CRP concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Complete blood (CBC) count was measured by an automated blood cell counter. The salivary IL-10, serum IL-10, CRP, MPV, and CRP/MPV ratio levels were much higher in neonates with late-onset sepsis than in control (220 ± 150 vs. 18 ± 9 pg/ml, P < 0.001), (316 ± 198 vs. 23.7 ± 14 pg/ml, P < 0.001), (78.2 ± 34 vs. 3.3 ± 1.7 mg/L, P < 0.001), (11.2 ± 0.9 vs. 8.6 ± 0.4 fL), and (7.08 ± 3.3 vs. 0.4 ± 0.2, P < 0.001), respectively. At the cutoff point of >31 pg/ml, salivary IL-10 showed 97.1% sensitivity and 94.3% specificity. Serum IL-10 at a cutoff value of ≥33.6 pg/ml had a sensitivity of 97.1% and specificity of 80%. MPV showed a sensitivity of 100% and specificity of 94.4% at a cutoff value ≥ 9.2 fL. CRP/MPV ratio showed a sensitivity of 100% and specificity of 97.1% at a cutoff value > 0.9. Salivary and serum IL-10 showed a positive correlation with CRP and CRP/MPV ratio in septic neonates. The current study shows for the first time that both salivary IL-10 and CRP/MPV showed statistically significant differences between neonates with late-onset sepsis and controls. Accordingly, salivary IL-10 could serve as a potential noninvasive biomarker for the diagnosis of late-onset sepsis in full-term neonates.

Cortisol precursors in neonates with vasopressor-resistant hypotension in relationship to demographic characteristics.

OBJECTIVE: To correlate between cortisol precursors in neonates with vasopressor resistant hypotension and demographic characteristics. METHODS: We investigated 48 neonates with vasopressor-resistant hypotension. Gestation at birth ranged from 34 to 42 weeks and postnatal age from 4 to 14 days. Cortisol and precursor steroids were measured soon after the onset of volume expansion and inotropes for treatment of shock. Their concentrations were determined using liquid chromatography/mass spectrometry. RESULTS: In neonates with vasopressor-resistant hypotension, the serum levels of cortisol were within normal nonstress range. There was a strong negative linear association between postnatal age and dehydroepiandrosterone level (r = -0.50, p < .01), which decreased with neonatal age. In addition, there was a significant positive association between gestational age at birth and 17-hydroxy-pregnenolone (r = 0.33, p = .02). No further significant associations were evident between the neonatal weight, duration of gestation or gender and of the levels of cortisol or the other steroids (p > .05). The cause of therapy-resistant hypotension did not appear to influence the steroid levels. CONCLUSIONS: Cortisol stress response is absent in these severely ill late preterm and term infants. This may be due to inhibition of the distal pathway of cortisol synthesis.

Hyperdehydroepiandrosterone in neonates with hypoxic ischemic encephalopathy and circulatory collapse.

BACKGROUND: Circulatory collapse is a very common complication of the critical illnesses in neonates including neonates with hypoxic ischemic encephalopathy; it can be the end result and cause of death of several conditions. Often, despite treatment with fluid resuscitation and vasopressor agents, circulatory collapse persist, and blood pressure can remain critically low, compromising adequate blood flow to vital organs and brain. Low blood pressure has been associated with increased mortality. METHOD: To investigate adrenal function in newborn infants who suffer from circulatory collapse during hypoxic ischemic encephalopathy. A total of 30 infants were analyzed in the study: 15 neonates in group A (neonates had hypoxic ischemic encephalopathy with vasopressor resistant hypotension) and 15 neonates in group B (neonates with hypoxic ischemic encephalopathy without vasopressor resistant hypotension). All the studied patients were subjected to history, examinations and laboratory investigation including serum cortisol concentrations and cortisol precursor's levels. RESULTS: The cortisol concentrations did not differ significantly between the two groups: (12.9 ± 4.3) µg/dL and (12.1 ± 2.4) µg/dL in group A and group B, respectively. There are highly significant differences between groups A and B regarding Dehydroepiandrosterone (342.1 ± 101.3) µg/dL, (33.4 ± 16.5) µg/dL, respectively. CONCLUSION: In this study, we noticed that cortisol concentrations did not differ between both groups in contrast to the expectation that neonates with critical illnesses should have higher cortisol concentrations than normal neonates. However, the marked increase in dehydroepiandrosterone DHEA may cause decrease cortisol function, so those neonates having accumulation of dehydroepiandrosterone may suffer from manifestation of adrenal insufficiency and vasopressor resistant hypotension in spite of normal cortisol level.

Cortisol intermediates and hydrocortisone responsiveness in critical neonatal disease.

OBJECTIVE: Therapy-resistant hypotension complicates diseases in neonates. Our objective was to investigate whether lack of therapeutic response to plasma expanders and inotropes associates with serum levels of cortisol and its precursors. METHODS: We investigated 96 infants with hypotension and critical neonatal disease for cortisol metabolism and are divided into responders and non-responders to plasma expanders and inotropes. Serum concentrations of steroids were analysed soon after the onset of volume expansion and inotrope treatment for shock. The 48 non-responders were treated with intravenous hydrocortisone (HC) and serum cortisol concentrations were monitored a week later. RESULTS: The mean cortisol concentrations did not differ between the responders and non-responders: 13.6 ± 2.5 and 12.5 ± 4.5 µg/dL, respectively. Dehydroepiandrosterone (37.3 ± 19.5 versus 324.0 ± 106.3; p < 0.0001) and 17-hydroxy-pregnenolone concentrations were lower in responders than in non-responders. Dehydroepiandrosterone levels in non-responders were inversely associated with postnatal age (r = 0.50, p < 0.0001). There were no differences in 17-hydroxy-progesterone, 11-deoxy-cortisol and cortisone between the responders and non-responders. Hydrocortisone administration acutely increased blood pressure. Six non-responders who died despite HC administration had low levels of cortisol. The responders had normal serum cortisol after HC treatment. CONCLUSION: Precursors of cortisol, proximal to the 3ß-hydroxysteroid dehydrogenase activity, accumulated in neonates with hypotension, responding to HC treatment.

Serum cystatin C as an earlier predictor of acute kidney injury than serum creatinine in preterm neonates with respiratory distress syndrome.

In this study, we aimed to evaluate serum cystatin C (sCysC) as an early predictor of acute kidney injury (AKI) in preterm neonates with respiratory distress syndrome (RDS). Sixty preterm neonates diagnosed with RDS and 40 healthy controls (28-36 weeks) admitted to the neonatal Intensive Care Unit were investigated. AKI was defined on the 3rd day of life (DOL-3) as an increase in serum creatinine (sCr) of >0.3 mg/dL from baseline (the lowest previous sCr). sCysC levels were measured on DOL-1, -3 and -7. Of the 60 neonates with RDS, 24 (40%) developed AKI. Five patients (79.17%) were classified as AKI Network (AKIN-1) and 19 patients (20.83%), as AKIN-2. At DOL-3, the mean sCysC values were significantly higher among neonates with RDS and AKI (1.68 ± 0.37) compared with controls (0.79 ± 0.83) and those with RDS and no AKI (0.85 ± 0.20) (P <0.001). sCysC levels significantly increased among neonates with AKI from DOL-3 to DOL-7 (P = 0.002). The sCr values showed no significant difference between those with RDS with AKI, RDS, and no AKI or control groups at DOL-1 and -3. Only as late as DOL-7, the mean values of sCr were higher among neonates with AKI compared with no AKI and controls (P <0.001). The receiver operating characteristic curves area under the curve was 0.97 for predicting the development of AKI within 72 h (P = 0.001). With the best cutoff value of ≥1.28 mg/L, the sensitivity and specificity of sCysC for detecting AKI within 72 h were 100 and 83.3%, respectively. In conclusion, sCysC is an early marker for AKI in neonates with RDS.

Fecal calprotectin levels in preterm infants with and without feeding intolerance.

OBJECTIVES: To assess the level of fecal calprotectin in preterm neonates with feeding intolerance, as well as to evaluate it as a marker of feeding intolerance and to determine a cut-off level of fecal calprotectin in feeding intolerance. METHODS: Analytical, multicenter, case-control study, which was carried out in neonatal intensive care units in Egypt, in a period from August 1, 2014 to March 1, 2015 on 52 preterm neonates. Neonates were classified into two groups; a study group including 26 neonates who met inclusion criteria and a control group including 26 neonates for comparison. RESULTS: Fecal calprotectin levels ranged from 3.9µg/g to 971.8µg/g, and there was a significant increase in fecal calprotectin in the study group when compared to the control group (334.3±236.6µg/g vs. 42.0±38.2µg/g, respectively) with moderate inverse significant correlation between fecal calprotectin and birth weight. Furthermore, there was moderate, significant correlation between fecal calprotectin and duration of breastfeeding range. On the other hand, there was no correlation between fecal calprotectin and post-natal age, gestational age, or volume of feeding. A cut-off at the 67.0µg/g level, with 100.0% sensitivity and 76.9% specificity, was considered. CONCLUSION: Fecal calprotectin level increased significantly in neonates with feeding intolerance; it can be used to detect early cases with necrotizing enterocolitis in neonates, but this subject still needs more investigations on more patients.

Fecal calprotectin levels in preterm infants with and without feeding intolerance / Níveis de calprotectina fecal em neonatos prematuros com e sem intolerância alimentar

Abstract Objectives: To assess the level of fecal calprotectin in preterm neonates with feeding intolerance, as well as to evaluate it as a marker of feeding intolerance and to determine a cut-off level of fecal calprotectin in feeding intolerance. Methods: Analytical, multicenter, case-control study, which was carried out in neonatal intensive care units in Egypt, in a period from August 1, 2014 to March 1, 2015 on 52 preterm neonates. Neonates were classified into two groups; a study group including 26 neonates who met inclusion criteria and a control group including 26 neonates for comparison. Results: Fecal calprotectin levels ranged from 3.9 µg/g to 971.8 µg/g, and there was a significant increase in fecal calprotectin in the study group when compared to the control group (334.3 ± 236.6 µg/g vs. 42.0 ± 38.2 µg/g, respectively) with moderate inverse significant correlation between fecal calprotectin and birth weight. Furthermore, there was moderate, significant correlation between fecal calprotectin and duration of breastfeeding range. On the other hand, there was no correlation between fecal calprotectin and post-natal age, gestational age, or volume of feeding. A cut-off at the 67.0 µg/g level, with 100.0% sensitivity and 76.9% specificity, was considered. Conclusion: Fecal calprotectin level increased significantly in neonates with feeding intolerance; it can be used to detect early cases with necrotizing enterocolitis in neonates, but this subject still needs more investigations on more patients.

Resumo Objetivos Avaliar o nível de calprotectina fecal em neonatos prematuros com intolerância alimentar, além de avaliá-lo como um indicador de intolerância alimentar e determinar um nível de corte da calprotectina fecal na intolerância alimentar. Métodos Estudo caso-controle analítico, feito em um multicentro de unidades de terapia intensiva neonatais no Egito, de 1° de agosto de 2014 a 1° de março de 2015, com 52 neonatos prematuros. Os neonatos foram classificados em dois grupos; um grupo de estudo incluindo 26 neonatos que atenderam aos critérios de inclusão e um grupo de controle incluindo 26 neonatos para comparação. Resultados Os níveis de calprotectina fecal variaram de 3,9 µg/g a 971,8 µg/g e houve um aumento significativo da calprotectina fecal no grupo de estudo quando comparado com o grupo de controle (334,3 ± 236,6 µg/g em comparação com 42,0 ± 38,2 µg/g, respectivamente) com correlação inversa, moderada e significativa entre a calprotectina fecal e o peso ao nascer. Adicionalmente, houve correlação moderada significativa entre a calprotectina fecal e a duração do intervalo de amamentação. Por outro lado, não houve correlação entre a calprotectina fecal e a idade pós-natal, a idade gestacional ou o volume de amamentação. Foi considerado um corte nos níveis de 67,0 µg/g; com sensibilidade de 100,0% e especificidade de 76,9%. Conclusão O nível de calprotectina fecal aumentou significativamente em neonatos com intolerância alimentar e podemos usá-lo para detectar casos precoces com enterocolite necrosante em neonatos, porém ainda são necessárias mais investigações em mais pacientes.’.