Efficacy of corticosteroids in prevention of acute kidney injury in neonates undergoing cardiac surgery-A randomized controlled trial.

BACKGROUND: Heart surgery requiring cardiopulmonary bypass (CPB) causes an inflammatory response which may further induce acute kidney injury (AKI). In the present randomized controlled study we evaluated whether corticosteroids can prevent CPB related AKI in neonates undergoing heart surgery. METHODS: Forty neonates were randomized to receive 2 mg/kg methylprednisolone followed by hydrocortisone infusion 0.2 mg/kg/h perioperatively with tapering doses for 5 days, or placebo administered in a similar fashion. The primary outcome was the inflammatory response (plasma concentrations of interleukins 6 and 10). The correspondence of the interleukin concentrations with AKI was analysed as secondary outcome. In addition, plasma and urine neutrophil gelatinase-associated lipocalin (NGAL), plasma cystatin C, and urine kidney injury molecule-1 (KIM-1) levels were measured. RESULTS: Six patients (15%) developed post-operative AKI. No significant difference in the AKI occurrence between the treatment (n = 2) and the placebo (n = 4) groups could be found (risk ratio 2.00, 95% confidence interval 0.41-9.71; P = .661) despite significant reduction in inflammatory response in the treatment group. One patient in the treatment group and two patients in the placebo group required acute peritoneal dialysis. Plasma creatinine and cystatin C or urine NGAL and KIM-1 concentrations did not differ between the treatment and the placebo group. CONCLUSIONS: Significantly reduced inflammatory reaction induced by corticosteroid treatment in neonates undergoing cardiac surgery did not reduce the incidence of AKI defined by KDIGO classification or decrease the rise of AKI biomarkers.

A case of primary JC polyomavirus infection-associated nephropathy.

A 15-year-old boy with a posterior urethral valve received a deceased donor kidney transplant (KT) in March 2011. Basiliximab induction followed by tacrolimus-based triple medication was used as immunosuppression. Eleven months after KT, the graft function deteriorated and the biopsy demonstrated interstitial nephritis suggestive of acute rejection. BK polyomavirus (BKPyV) surveillance in urine and plasma was negative. The patient received methylprednisolone pulses and anti-thymocyte globulin. Immunohistochemistry was positive for simian virus 40 (SV40) large T-antigen (LTag) in the biopsies, and quantitative polymerase chain reaction for JC polyomavirus (JCPyV) indicated high viral loads in urine and borderline levels in plasma. Immunosuppression was reduced and follow-up biopsies showed tubular atrophy and interstitial fibrosis. Two years after KT, antibody-mediated rejection resulted in graft loss and return to hemodialysis. Retrospective serologic work-up indicated a primary JCPyV infection with seroconversion first for IgM, followed by IgG, but no indication of BKPyV infection. In the SV40 LTag positive biopsies, JCPyV deoxyribonucleic acid (DNA) with archetype noncoding control region was detected, while BKPyV DNA was undetectable. To the best of our knowledge, this is the first reported case of primary JCPyV infection as the cause of PyV-associated nephropathy in KT.

Oral findings in paediatric patients with severe heart, liver, and kidney failure prior to organ transplantation.

PURPOSE: Organ transplantation is an effective treatment for children with severe heart, liver, and kidney diseases. These patient groups may have more oral and dental diseases than healthy controls. It is important to eliminate oral infection foci before transplantation and to maintain good oral health to avoid potential post-transplant complications. The aim of this study was to describe and compare oral health in Finnish paediatric heart, liver, and kidney transplant recipients prior to organ transplantation. METHODS: Eighty-six children who received a heart (n = 21), liver (n = 19), or kidney (n = 46) transplant in Finland during the years 2014-2018 were included in this study. The inclusion criterion was a pre-transplantation oral examination. Oral hygiene, enamel anomalies, and the number of decayed, missing, and filled teeth (dmft/DMFT) were analyzed retrospectively from medical and dental records and compared between the three patient groups. RESULTS: Children with liver (p = 0.043) or heart (p = 0.047) disease had higher combined primary and permanent dentition dmft/DMFT scores compared to children with kidney disease. A higher combined dmft/DMFT score was associated with poor oral hygiene (p = 0.005). No significant differences in oral hygiene between the patient groups were found. Furthermore, all patient groups had a high prevalence of developmental dental defects. CONCLUSION: Children with liver or heart disease seem to have a higher combined dmft/DMFT score, indicating a higher prevalence of caries compared to children with kidney disease. Prevention of dental caries, along with promoting a good oral hygiene routine and regular check-ups, is suggested in these patient groups.

HLA associations with tubulointerstitial nephritis with or without uveitis in Finnish pediatric population: a nation-wide study.

The human leukocyte antigen (HLA) genotype has been shown to associate with tubulointerstitial nephritis (TIN) and tubulointerstitial nephritis with uveitis syndrome (TINU). The association of HLA genes with TIN was examined in this nation-wide study. HLA genotyping was performed in 31 pediatric patients with biopsy-proven TIN. All patients were examined by an ophthalmologist to diagnose possible uveitis. Class II HLA genotypes of TIN patients were compared with the Finnish reference population. We found a significant association between the HLA alleles DQA1*04:01 [risk ratio (RR) 5.0, 95% confidence interval (CI) 2.0-11.2], DQB1*04:02 (RR 2.7, 95% CI 1.4-5.3), and DRB1*08 (RR 3.8, 95% CI 1.5-8.4) and TIN. Uveitis was found in 20/31 (64.5%) patients. HLA genotyping of the TINU patients showed additional risk HLA alleles: DQA1*01:04 (RR 6.1, 95% CI 1.5-17.8), and DRB1*14 (RR 8.2, 95% CI 2.2-22.1). The alleles DQA1*01:04 (RR 8.8, 95% CI 2.2-26.5), DQA1*04:01 (RR 3.2, 95% CI 1.2-7.3), and DRB1*14 (RR 12.0, 95% CI 3.2-33.0) were more frequent in patients with TIN and chronic uveitis than in reference population. The HLA class II haplotype DQA1*04:01/DQB1:04:02/DRB1*08 was the most common combination in our study population (58.1%). None of the patients had haplotype DQA1*04:01/DQB1*06:02/DRB1*15, which is common in Finland. HLA genotype did not predict the renal outcome. We found a strong association between certain HLA genotypes both in TIN and TINU patients. The TIN/TINU-associated HLA alleles appear to vary depending on study population.

Clinical and biological markers of premature aging after autologous SCT in childhood cancer.

The aim of this study was to analyze the prevalence of frailty and physical health limitations among long-term survivors of high-risk neuroblastoma (HR NBL) and to investigate whether frail health is associated with variables of cardiovascular function, markers of inflammation and telomere length. A national study cohort of 19 (median age 22, range 16-30 years) long-term (>10 years) HR NBL survivors was studied and the findings were compared with 20 age- and sex-matched controls. Frailty was defined as ⩾3 of the following conditions: low muscle mass, low energy expenditure, slow running and weakness. The prevalence of frailty was significantly higher among the HR NBL survivors 9/19 (47%) than among the controls (0%). Thirteen (68%) of the survivors reported significant physical health limitations in vigorous activities, as opposed to none of the controls. The HR NBL survivors had significantly shorter telomere length and higher serum levels of high sensitivity C-reactive protein than did the controls. Frail health and poor physical functioning are prevalent among HR NBL survivors and suggest premature aging. Survivors with gonadal damage, very low fat mass percentage, low glycosylated hemoglobin A1c and increased common carotid artery intima-media thickness may be more prone to early aging after high dose therapy.

Amifostine protects against early but not late toxic effects of doxorubicin in infant rats.

The improved prognosis and increased expected lifetime among long-term survivors of childhood malignancies have made these patients especially sensitiveto the late toxicity of cancer therapy and prone to secondary malignancies. Recently, new strategies aiming to protect against cancer treatment toxicity have been developed, including the drug amifostine (Ethyol), which is suggested to protect normal tissues from the toxic effects of radiation and cytotoxic agents. In the present study, the possible protective effect of amifostine against toxicity induced by a single injection of doxorubicin (3 mg/kg) in immature rats was evaluated. Specifically, we evaluated the protection against long-term toxicity and the effects of amifostine on growing immature tissues. Amifostine (50-200 mg/kg) given 15 min before doxorubicin had a significant protective effect against doxorubicin-induced early alopecia in young rats. Significant protection against cataract formation was obtained by the use of low-dose amifostine (50 mg/kg). However, amifostine did not protect young rats against the late toxic effect of doxoubicin on linear growth, body weight, plasma leptin levels, and heart or testicular tissue. Worrisome, and in contrast to earlier studies in adult rats, an increased doxorubicin toxicity actually was observed and mortality was increased when the higher doses of amifostine (100-200 mg/kg) were used. The present results suggest that more data from growing immature animal models are needed to analyze the safety of amifostine treatment and its mechanisms of action before wider clinical use of this drug in pediatric cancer patients is recommended.

Bacteremic urinary tract infection in children.

OBJECTIVE: To assess the clinical characteristics of bacteremic urinary tract infection (UTI) in children. DESIGN: Clinical data of Finnish children with bacteremic UTI (n = 134) from 1985 to 1994 were analyzed. Their symptoms, laboratory and imaging findings were compared with those of age- and sex-matched patients hospitalized for blood culture negative UTI. RESULTS: Generally, no major differences were seen in clinical findings between bacteremic and nonbacteremic patients. Bacteremic children had more frequent feeding problems (P = 0.02), and children > or =12 months of age tended more often to have abdominal pain and vomiting than did nonbacteremic patients. Fever was the major initial symptom in both study groups, but no significant difference occurred in the mean highest temperature or in the mean of duration of fever before admission to the hospital. The mean concentration of serum C-reactive protein on admission was significantly higher in bacteremic patients (116 vs. 76 mg/l; P < 0.01). After onset of antimicrobial treatment fever lasted significantly longer in bacteremic patients than in control patients (means, 2.3 vs. 1.1 days; P < 0.01). Anatomic or functional abnormalities in the urinary tract were detected in 51% vs. 46%, respectively. Obstruction of the urinary tract (9% vs. 1%, P < 0.01) and Grade 3 to 5 vesicoureteral reflux (30% vs. 16%, P = 0.02) were significantly more frequent in bacteremic patients with UTI. Obstruction or vesicoureteral reflux was found in 46% of children with bacteremic UTI caused by Escherichia coli vs. 89% of children with non-E. coli infection (P < 0.01). CONCLUSIONS: Clinical symptoms do not significantly distinguish bacteremic from nonbacteremic children with UTI. Outcome of bacteremic UTI was comparable with that of nonbacteremic UTI. Bacteremic children, especially those with non-E. coli UTI, more often had anatomical or functional abnormalities in the urinary tract.

Outcome of Henoch-Schoenlein nephritis with nephrotic-range proteinuria.

PATIENTS AND METHODS: All children with Henoch-Schoenlein glomerulonephritis (HSP-GN) and nephrotic-range proteinuria (> 40 mg/h/m2), treated at 5 university hospitals and in 1 central hospital in Finland during in 1990-1997, were analyzed retrospectively. The mean age of these 19 patients (8 girls, 11 boys) at the time of diagnosis was 9.9 years (range 4.6-15.1 years). A renal biopsy had been performed in all cases, giving findings according to the classification used in the International Study of Kidney Diseases in Children (ISKDC) of grade II (4 patients), grade III (10), grade IV (4) and grade V (1). Six patients underwent a second biopsy. RESULTS: The yearly incidence of nephrotic-range HSP-GN in Finland was 2 per 1 million children under 15 years of age. After a mean follow-up of 4.6 years (range 9 months-9.1 years), 3 patients (15.7%) had no signs of nephritis, 11 (57.9%) had proteinuria < 1 g/day or microscopic hematuria, 2 (10.5%) had proteinuria > 1 g/day, and 3 (15.7%) had developed ESRD or uremia. 47% of the patients needed medication for proteinuria at the time of the latest follow-up. The first kidney biopsy did not predict the outcome of HSP-GN, since all the patients with the poorest outcome had only ISKDC II-III findings in their first biopsy. CONCLUSION: According to our series, the morbidity in cases of HSP-GN with nephrotic-range proteinuria is high and a close clinical follow-up is needed. The treatment of HSP-GN patients should be based on the clinical presentation rather than on the biopsy findings.

Skin blood flow oscillations respond more effectively to rhythmic thermal stimulation than to continuous or periodic breathing in newborn infants.

Effect of continuous (n = 30) and periodic (n = 5) breathing on forehead skin blood flow (SBF) oscillations was studied in healthy 3-day-old preterm and term infants. Femoral SBF was measured in 10 of the term infants during continuous breathing. Respiratory and SBF signals were analysed by power spectrum during the control period. The signal analysis was repeated during rhythmic thermal stimulation which was applied to the skin of each infant in order to synchronise spontaneous SBF oscillations. During the control period, the forehead and femoral SBF of all the studied infants oscillated at frequencies corresponding to the frequency of regular continuous breathing. External thermal stimulation decreased these high-frequency oscillations of forehead SBF in both preterm and term infants. Oscillations in femoral SBF of term infants remained unchanged. During periodic breathing, the spontaneous forehead SBF oscillation was synchronised to the frequency of respiratory amplitude variation. Despite periodic breathing, thermal stimulation was able to resynchronise the SBF oscillation to the stimulation frequency in 4/5 infants. Forehead SBF oscillates at the frequency of both continuous and periodic breathing in preterm as well as in term infants on postnatal day 3. Rhythmic thermal stimulation synchronises SBF and affects SBF more effectively than continuous or periodic breathing. These results suggest functional neural control of cutaneous vasculature at birth.

Post-prandial effects in reactivity of forehead and mid-femoral skin blood flow and heart rate in neonates.

The effect of post-prandial period on the cutaneous vascular reactivity was studied in twelve full-term infants on their 3rd postnatal day. The differences in vasomotor reactions between the forehead and femoral skin were also investigated. Two 10-min control registrations about 30 and 90 min after feeding were followed by a registration of equal duration during thermal stimulation of the skin. The lower extremity of each infant was stimulated by warm and cool air currents (5 cycles/min) to induce periodic vasomotor changes. The fast Fourier transform was used to compute variability spectra for the recorded skin blood flow, heart rate and respiratory wave form signals. The skin blood flow became synchronised to the thermal stimulation in both skin regions. Neither the spontaneous nor synchronised oscillations of the skin blood flow differed significantly between femoral skin and forehead. The post-prandial time did not have any influence on this synchronisation. Heart rate variability was synchronised to the periodicity of thermal stimulation more 1.5 h after feeding than 0.5 h after feeding. Respiration was not affected. The results show that increasing post-prandial time has no influence on the synchronised oscillations of skin blood flow. However, it potentiates reactivity of heart rate to perturbations in the peripheral vasculature.

Dynamics of vasomotor thermoregulation of the skin in term and preterm neonates.

Eighteen fullterm infants and 17 preterm infants were studied on their 3rd day of life to investigate the reactivity of skin blood flow to thermal stimulation. The infants were studied during quiet sleep. After a 10-min control period a constant air current was used to synchronise the external cutaneous stimulus to the distal lower extremity of each infant: the heating element of an air blower was automatically switched on and off to generate successive warm and cool periods of equal duration (5 cycles/min). Heart rate (HR), skin blood flow (SBF) and respiratory waveform signals were recorded and their variability was analysed using the fast Fourier transform and spectral analysis. Fullterm infants showed a clear response to external thermal stimulation: both HR and SBF were synchronised to the stimulation frequency. A response of preterm infants was present but it was markedly attenuated in comparison to term infants. The effect of stimulation did not seem to be dependent on postnatal age. The results suggest that the vasomotor control is immature in preterm infants.

Transcephalic electrical impedance in the study of cerebral circulation in a juvenile pig model.

Transcephalic electrical impedance offers a technique for non-invasive, cot-side monitoring of neonatal cerebral circulation but the exact nature of the signal is somewhat ambiguous. The impedance signal is examined in an animal project where the ventilator settings are adjusted (20 min-1-10 min-1-40 min-1 for 10 min periods each) to produce circulatory changes. Six juvenile pigs are intubated, and ECG, arterial blood pressure, carotid flow (CF) by electromagnetic flowmeter and impedance are continuously monitored and stored on analogue tape. Cardiac output by thermodilution, blood oxygen (pO2) and carbon dioxide (pCO2) tensions are measured. ECG is converted to heart rate, mean blood pressure is integrated, and the high-frequency (1.50-4.00 Hz) component of the impedance signal delta Z is computed using autoregressive spectral estimation. Stroke volume, peripheral vascular resistance (PVR) and cerebral vascular resistance (CVR) are calculated. pCO2 and CF increase and pO2 decreases during hypoventilation. CF correlates positively with cardiac output, stroke volume, delta Z and pCO2, and negatively with pO2 and CVR. delta Z correlates positively with heart rate and cardiac output, and negatively with PVR and CVR. It is concluded that the impedance signal is related to the amount of blood transmitted to the brain by every beat of the heart, depending on the changes in both the systemic circulation and the cerebral vascular compliance.

Antenatal glucocorticoids and renal function after birth.

Antenatal glucocorticoid treatment is widely used in cases of threatening preterm delivery. Both human and animal studies have confirmed that glucocorticoids promote pulmonary maturation in fetuses. Several studies indicate that prenatal glucocorticoids also stimulate renal maturation. Although the current knowledge about the effects of glucocorticoids on kidney function is mainly concentrated on short-term effects, there are animal studies suggesting that antenatal glucocorticoid treatment may also cause permanent changes in kidney morphology and renal function. It still remains to be investigated if antenatal glucocorticoid treatment induces long-term effects in humans.

Adenosine triphosphate treatment for meconium aspiration-induced pulmonary hypertension in pigs.

To investigate the pulmonary haemodynamic effects of meconium aspiration and subsequent adenosine triphosphate (ATP) treatment, 12 anaesthetized and ventilated pigs (wt 24-28 kg) received either ATP or an equal volume of saline into the right heart in doses of 0.02 to 0.80 mumol kg-1 min-1 after intratracheal administration of 2 mL kg-1 of human meconium. Meconium instillation induced significant increases in pulmonary vascular pressures and total and postarterial resistances calculated from pulmonary artery occlusion studies, but did not affect the systemic haemodynamics, except for a fall in heart rate and increase in central venous pressure. Infusion of ATP at the lowest doses (0.02 and 0.08 mumol kg-1 min-1) selectively decreased the pulmonary arterial pressure and vascular resistance and at 0.32 and 0.80 mumol kg-1 min-1 reduced both the pulmonary and systemic resistances. In the lung circulation the increasing doses of ATP reduced preferably the arterial but also the postarterial resistance. Withdrawal of ATP infusion led to a significant rebound effect especially in the postarterial segment of the lung circulation. Meconium aspiration thus induces an acute, predominantly postarterial obstruction in the lung circulation and infusion of ATP at low doses selectively dilates the pulmonary vascular bed and may help to preclude elevation of capillary pressures in meconium aspiration-induced pulmonary hypertension.

Reactivity of skin blood flow and heart rate to external thermal stimulation in anencephaly.

Oscillations of skin blood flow and heart rate can be synchronised using external rhythmic thermal stimulation in healthy adults and infants. We examined the effect of thermal stimulation on the cutaneous circulation and heart rate of an anencephalic neonate using cutaneous laser Doppler flowmetry and ECG monitoring. The results suggest that synchronisation of SBF and HR to thermal stimulation can also be induced in an anencephalic newborn.

Reactivity of skin blood flow and heart rate to thermal stimulation in infants during the first postnatal days and after a two-month follow-up.

The reactivity of skin blood flow and heart rate to periodic thermal stimulation was studied in 10 term small-for-gestational age (SGA) infants, in 9 preterm and 8 term normal-sized infants during the first two postnatal months. During the first postnatal days, the increase in thermally stimulated skin blood flow oscillations was absent in SGA infants but was clearly present in both preterm (p < 0.01) and term (p < 0.01) normal-sized infants. The responsiveness of SGA infants improved during the follow-up (p < 0.05). The response of the periodic heart rate variability of SGA and preterm infants was inferior to term normal-sized infants until the age of 2 months. The cardiovascular responsiveness of growth-retarded infants seems abnormal during the first days of life, and may impair their ability to meet stress, e.g. changes of ambient temperature.

Responsiveness of cutaneous vasculature to thermal stimulation during phototherapy in neonatal jaundice.

The present study was performed to measure the vasoregulatory reactions to dynamic changes in local skin temperature during open bed phototherapy. Periodic thermal stimulation using warm and cool air currents was applied to the skin of ten term infants with physiological jaundice, before and during open bed phototherapy. The reactivity of skin blood flow (SBF) and heart rate was measured using laser Doppler flowmetry and power spectral analysis. The baseline SBF increased significantly by 70% (P = 0.008) during phototherapy without any significant change in skin or rectal temperature. Before phototherapy, the rhythmic (0.08 Hz) thermal skin stimulation increased the oscillations of SBF (from 89 +/- 26 au to 213 +/- 37 au, P = 0.02) at the stimulation frequency band. This response was further increased (P = 0.03) during phototherapy (from 198 +/- 54 au to 658 +/- 115 au, P = 0.004). Phototherapy increased SBF in icteric otherwise healthy neonates. The cutaneous vasodilatation augments the cardiovascular responsiveness to thermal stimulation. These results suggest that open bed phototherapy does not inhibit the cardiovascular responsiveness to local thermal skin stimulation in healthy term infants.

Neonatal monitoring after maternal fentanyl analgesia in labor.

OBJECTIVE: To characterize different methods of monitoring neonatal effects associated with maternal opioid analgesia. Special focus was on the static-charge-sensitive bed (SCSB), which could potentially serve as a non-invasive neonatal monitor. METHODS: 12 healthy, term newborns from normal pregnancies were included in this prospective, randomized, controlled study. Maternal labor analgesia was either intravenous fentanyl (n = 5) or paracervical bupivacaine blockade (n = 7). Neonatal recording from delivery to the age of 12 hours included continuous SCSB monitoring with ECG and oximeter for sleep states, respiration, oxygenation, heart rate, and body movements. In addition, umbilical blood pH, Apgar, Amiel-Tison's Neurologic and Adaptive Capacity Scoring (NACS), skin cyanosis scoring, blood pressure, rectal and skin temperatures, and skin blood flow measurements were performed. RESULTS: The study was interrupted, because one baby in the fentanyl group had a significant decrease in oxyhemoglobin saturation (SpO2) to 59%. This was considcred to be residual effect of fentanyl and was treated with naloxone. SpO2 was generally lower in the fentanyl group. Epochs with SpO2 < 90% were more frequent in the fentanyl group, especially during active sleep (mean +/- SD 11.9 +/- 10.7% vs. 2.0 +/- 1.7% of epochs, p = 0.034). Mean heart rate values were lower in the fentanyl group (121.1 +/- 6.4 vs. 132.6 +/- 6.8 beats per minute, p = 0.02), and this difference was seen during wake and all sleep states. Maximum heart rate values were lower in the fentanyl group, too. The opiate group had less quiet sleep than controls (9.6 +/- 2.8% vs. 18.3 +/- 8.3%, p = 0.05). NACS after birth was lower in the fentanyl group (median [range] 15 [13-26] vs. 22 [20-25], p = 0.004). CONCLUSIONS: Several differences were seen between the fentanyl and the control group babies. The SCSB method proved sensitive enough to find neonatal effects of maternal analgesia. Together with ECG and SpO2 monitoring, SCSB gives plentiful information on neonatal well-being in a non-invasive way. Results of this study emphasize the importance of neonatal monitoring after maternal opiate use in labor.

The balance of the autonomic nervous system is normal in colicky infants.

UNLABELLED: Excessively crying, hard-to-soothe infants are described as colicky. The self-limiting course of infantile colic during early infancy suggests an etiology of transient developmental dysmaturation. It has been proposed that emotional characteristics such as temperament and self-soothing ability are correlated with the balance of the autonomic nervous system. Heart rate variability (HRV) analysis was used for evaluating the balance of the autonomic nervous system in colicky and control infants during and after the colicky period. HRV analysis was carried out on 12 colicky infants and 14 control infants at the age of 2 mo, and repeated on 10 colicky and 11 normal infants at the age of 7 mo. Measurements were performed during polygraphically confirmed slow-wave sleep (sleep stages 3 and 4). Three HRV frequency bands were defined, including a high (0.2-1.0 Hz), middle (0.12-0.2 Hz) and low (0.025-0.12 Hz) frequency variability. There were no differences between the study groups in any of the three HRV frequency bands analyzed. The high frequency variability increased significantly with age in both study groups (p = 0.009). CONCLUSION: The findings suggest that imbalance between the parasympathetic and the sympathetic nervous system is not associated with infantile colic and that, in accordance with previous findings, control of HRV shifts in a parasympathetic direction with increasing age during the first year of life.