Publications
72 results found
Krishnan V, Ujjanappa V, Vegda H, et al., 2024, Sequential levetiracetam and phenytoin in electroencephalographic neonatal seizures unresponsive to phenobarbital: a multicenter prospective observational study in India, The Lancet Regional Health - Southeast Asia, ISSN: 2772-3682
Background:Although levetiracetam and phenytoin are widely used antiseizure medications (ASM) in neonates, their efficacy on seizure freedom is unclear. We evaluated electroencephalographic (EEG) seizure freedom following sequential levetiracetam and phenytoin in neonatal seizures unresponsive to phenobarbital.Methods:We recruited neonates born ≥35 weeks and aged <72 h who had continued electrographic seizures despite phenobarbital, from three Indian hospitals, between 20 June 2020 and 31 July 2022. The neonates were treated with intravenous levetiracetam (20 mg/kg x 2 doses, second line) followed by phenytoin (20 mg/kg x 2 doses, third line) if seizures persisted. The primary outcome was complete seizure freedom, defined as an absence of seizures on EEG for at least 60 min within 40 min from the start of infusion.Findings:Of the 206 neonates with continued seizures despite phenobarbital, 152 received levetiracetam with EEG. Of these one EEG was missing, 47 (31.1%) were in status epilepticus, and primary outcome data were available in 145. Seizure freedom occurred in 20 (13.8%; 95% CI 8.6%–20.5%) after levetiracetam; 16 (80.0%) responded to the first dose and 4 (20.0%) to the second dose. Of the 125 neonates with persisting seizures after levetiracetam, 114 received phenytoin under EEG monitoring. Of these, the primary outcome data were available in 104. Seizure freedom occurred in 59 (56.7%; 95% CI 46.7%–66.4%) neonates; 54 (91.5%) responded to the first dose and 5 (8.5%) to the second dose.Interpretation:With the conventional doses, levetiracetam was associated with immediate EEG seizure cessation in only 14% of phenobarbital unresponsive neonatal seizures. Additional treatment with phenytoin along with levetiracetam attained seizure freedom in further 57%. Safety and efficacy of higher doses of levetiracetam should be evaluated in well-designed randomised controlled trials.Funding:National Institute for Health and Care Research (NIHR) Research a
Montaldo P, Burgod C, Herberg JA, et al., 2024, Whole-blood gene expression profile after hypoxic-ischemic encephalopathy, JAMA Network Open, Vol: 7, ISSN: 2574-3805
Importance Induced hypothermia, the standard treatment for hypoxic-ischemic encephalopathy (HIE) in high-income countries (HICs), is less effective in the low-income populations in South Asia, who have the highest disease burden.Objective To investigate the differences in blood genome expression profiles of neonates with HIE from an HIC vs neonates with HIE from South Asia.Design, Setting, and Participants This case-control study analyzed data from (1) a prospective observational study involving neonates with moderate or severe HIE who underwent whole-body hypothermia between January 2017 and June 2019 and age-matched term healthy controls in Italy and (2) a randomized clinical trial involving neonates with moderate or severe HIE in India, Sri Lanka, and Bangladesh recruited between August 2015 and February 2019. Data were analyzed between October 2020 and August 2023.Exposure Whole-blood RNA that underwent next-generation sequencing.Main Outcome and Measures The primary outcomes were whole-blood genome expression profile at birth associated with adverse outcome (death or disability at 18 months) after HIE in the HIC and South Asia cohorts and changes in whole-genome expression profile during the first 72 hours after birth in neonates with HIE and healthy controls from the HIC cohort. Blood samples for RNA extraction were collected before whole-body hypothermia at 4 time points (6, 24, 48, and 72 hours after birth) for the HIC cohort. Only 1 blood sample was drawn within 6 hours after birth for the South Asia cohort.Results The HIC cohort was composed of 35 neonates (21 females [60.0%]) with a median (IQR) birth weight of 3.3 (3.0-3.6) kg and gestational age of 40.0 (39.0-40.6) weeks. The South Asia cohort consisted of 99 neonates (57 males [57.6%]) with a median (IQR) birth weight of 2.9 (2.7-3.3) kg and gestational age of 39.0 (38.0-40.0) weeks. Healthy controls included 14 neonates (9 females [64.3%]) with a median (IQR) birth weight of 3.4 (3.2-3.7) kg and
Rivetti G, Montaldo P, Marzuillo P, 2024, Editorial on the Special Issue “Advances in Pediatric Acute Kidney Injury”, Children, Vol: 11
Burgod C, Mazlan M, Pant S, et al., 2024, Duration of birth depression and neurodevelopmental outcomes after whole-body hypothermia for hypoxic ischemic encephalopathy in India, Sri Lanka and Bangladesh – an exploratory analysis of the HELIX trial, Lancet Regional Health - Southeast Asia, Vol: 20, ISSN: 2772-3682
Background:Effect of duration of birth depression on neurodevelopmental outcomes in low- and middle-income countries (LMICs) is not known. We examined the association of birth depression with brain injury, neurodevelopmental outcomes, and hypothermia after hypoxic ischemic encephalopathy (HIE) in south Asia.Methods:We compared cerebral magnetic resonance (MR) at 2 weeks, and adverse outcomes (death or moderate or severe disability) at 18 months in 408 babies with moderate or severe HIE who had long birth depression (positive pressure ventilation (PPV) >10 min or Apgar score<6 at 10 min or cord pH < 7.0) and short birth depression (PPV for 5–10 min or Apgar score<6 at 5 min, but ≥6 at 10 min).Findings:Long depression group (n = 201) had more severe HIE (32.8% versus 6.8%), mortality (47.5% versus 26.4%), death or disability at 18 months (62.2% versus 35.4%) (all p < 0.001), MR injury (Odds ratio; 95% CI) to basal ganglia (2.4 (1.3, 4.1); p = 0.003), posterior limb of internal capsule (2.3 (1.3, 4.3); p < 0.001) and white matter (1.7 (1.1, 2.7); p = 0.021), and lower thalamic N-acetylaspartate levels (7.69 ± 1.84 versus 8.29 ± 1.60); p = 0.031) than short depression group (n = 207). Three babies had no heartbeat at 5 min, of which 1 died and 2 survived with severe disability. No significant interaction between the duration of birth depression and whole-body hypothermia was seen for any of the MR biomarker or clinical outcomes.Interpretation:Long birth depression was associated with more brain injury and adverse outcomes than short depression. Effect of hypothermia was not modified by duration of birth depression.
Puzone S, Diplomatico M, Caredda E, et al., 2023, Hypoglycaemia and hyperglycaemia in neonatal encephalopathy: a systematic review and meta-analysis, Archives of Disease in Childhood: Fetal and Neonatal Edition, Vol: 109, Pages: 18-25, ISSN: 1359-2998
Importance Although hypoglycaemia and hyperglycaemia represent the most commonmetabolic problem in neonates, there is still uncertainty regarding the effects of glucosehomeostasis on the neurological outcomes of infants with neonatal encephalopathy (NE).Objective To systematically investigate the association between neonatal hypo andhyperglycaemia with adverse outcome in children who suffered from NE.Study selection We searched Pubmed, Embase, and Web of Science databases to identifystudies which reported prespecified outcomes and compared infants with NE who had beenexposed to neonatal hypoglycaemia or hyperglycaemia with infants not exposed.Data analysis We assessed the risk of bias (ROBINS-I), quality of evidence (GRADE) foreach of the studies. REVMAN was used for meta-analysis (inverse variance, fixed effects).Main outcome Death or neurodevelopmental outcomes at 18 months of age or later.Results Eighty-two studies were screened, 28 reviewed in full, and 12 included. Childrenwho were exposed to neonatal hypoglycaemia had higher odds of neurodevelopmentalimpairment or death (6 studies, 685 infants; 40.6 vs. 25.4%; OR= 2.17, 95%CI=1.46– 3.25;p=0.0001). Neonatal exposure to hyperglycaemia was associated with death or neurodisability at 18 months or later (7 studies, 807 infants; 46.1 vs. 28.0%; OR=3.07,95%CI=2.17– 4.35; p<0.00001). These findings were confirmed in the subgroup analysis,which included only the infants who underwent therapeutic hypothermia.Conclusions These data suggest that neonatal hypoglycaemia and hyperglycaemia may beassociated with the neurodevelopmental outcome later on in infants with NE. Further studieswith long-term follow-up are needed to optimise the metabolic management of these highrisk infants.
Thayyil S, Montaldo P, Krishnan V, et al., 2023, Whole-body hypothermia, cerebral magnetic resonance biomarkers, and outcomes in neonates with moderate or severe hypoxic-ischemic encephalopathy born at tertiary care centers vs other facilities: a nested study within a randomized clinical trial, JAMA Network Open, Vol: 6, Pages: 1-16, ISSN: 2574-3805
Importance The association between place of birth and hypothermic neuroprotection after hypoxic-ischemic encephalopathy (HIE) in low- and middle-income countries (LMICs) is unknown.Objective To ascertain the association between place of birth and the efficacy of whole-body hypothermia for protection against brain injury measured by magnetic resonance (MR) biomarkers among neonates born at a tertiary care center (inborn) or other facilities (outborn).Design, Setting, and Participants This nested cohort study within a randomized clinical trial involved neonates at 7 tertiary neonatal intensive care units in India, Sri Lanka, and Bangladesh between August 15, 2015, and February 15, 2019. A total of 408 neonates born at or after 36 weeks’ gestation with moderate or severe HIE were randomized to receive whole-body hypothermia (reduction of rectal temperatures to between 33.0 °C and 34.0 °C; hypothermia group) for 72 hours or no whole-body hypothermia (rectal temperatures maintained between 36.0 °C and 37.0 °C; control group) within 6 hours of birth, with follow-up until September 27, 2020.Exposure 3T MR imaging, MR spectroscopy, and diffusion tensor imaging.Main Outcomes and Measures Thalamic N-acetyl aspartate (NAA) mmol/kg wet weight, thalamic lactate to NAA peak area ratios, brain injury scores, and white matter fractional anisotropy at 1 to 2 weeks and death or moderate or severe disability at 18 to 22 months.Results Among 408 neonates, the mean (SD) gestational age was 38.7 (1.3) weeks; 267 (65.4%) were male. A total of 123 neonates were inborn and 285 were outborn. Inborn neonates were smaller (mean [SD], 2.8 [0.5] kg vs 2.9 [0.4] kg; P = .02), more likely to have instrumental or cesarean deliveries (43.1% vs 24.7%; P = .01), and more likely to be intubated at birth (78.9% vs 29.1%; P = .001) than outborn neonates, although the rate of severe HIE was not different (23.6% vs 17.9%; P =&thin
Montaldo P, Thayyil S, 2023, Hippocampus and hypothermia: a missing link, Developmental Medicine and Child Neurology, Vol: 65, Pages: 303-304, ISSN: 0012-1622
Montaldo P, Puzone S, Caredda E, et al., 2023, Magnetic Resonance Biomarkers and Neurological Outcome of Infants with Mild Hypoxic-Ischaemic Encephalopathy Who Progress to Moderate Hypoxic-Ischaemic Encephalopathy, NEONATOLOGY, Vol: 120, Pages: 153-159, ISSN: 1661-7800
Monari C, Spagnuolo F, Pisaturo M, et al., 2023, Bloodstream Infection Due to a VIM-Metallo-β-Lactamase-Producing Klebsiella pneumoniae Treated with Cefiderocol in a Preterm Newborn, Infectious Diseases and Therapy, Vol: 12, Pages: 727-734, ISSN: 2193-8229
Background: The prevalence of certain multidrug-resistant organisms (MDROs), especially Gram-negative bacteria, is dramatically increasing in patient care settings, including pediatric and neonatal units. However, most of the new drugs available for the treatment of MDROs have not yet been studied in children and newborns. Case report: We report the clinical case of a preterm neonate, born at 31 weeks gestation + 1 day of age by emergency Cesarean Section (CS), with a bloodstream infection (BSI) due to a Verona integron-borne metallo-β-lactamase (VIM)-producing Klebsiella pneumoniae. We successfully treated the infection with cefiderocol in an off-label regimen at the following dose: loading dose 60 mg/kg and then 40 mg/kg every 8 h in extended infusion for 9 days. The baby showed a quick clinical and biochemical improvement and tolerated well the treatment. Follow-up blood cultures at 48 h after the start of cefiderocol were negative. Conclusions: Antimicrobial-resistant pathogens are of increasing concern in neonatal settings. More studies in this unique population are necessary to better describe the pharmacokinetic and pharmacodynamic profile of the new drugs against MDROs, such as cefiderocol, and to define a proper effective dose.
Galdo F, Trappan A, Cossovel F, et al., 2023, Ultrasonographic measurements of the inferior vena cava diameter in newborns: is it a useful tool for choosing an umbilical venous catheter?, Frontiers in Pediatrics, Vol: 11
Objectives: The primary outcomes of this study were to evaluate the diameters of the inferior vena cava (IVC) in a cohort of newborns and the correlation between newborn weight and IVC diameter. The secondary outcome was to evaluate the concordance between the measurements performed by the two investigators. Methods: Two blind examiners performed an ultrasonographic (US) evaluation of the IVC diameter in neonates with a weight ranging from 2 to 4 kg. The exclusion criteria included hemodynamic instability, known vascular malformations, and major congenital malformations. Results: A total of 143 neonates were enrolled between June 2019 and January 2021. All the US examinations were performed in the first 3 days of life. After dividing the patients into two groups according to their weight at the time of examination (2.0–2.99 kg and 3.0–4.0 kg), the median IVC diameters measured by examiner 1 were 3.1 mm (interquartile range 2.8–3.4) and 3.4 mm (interquartile range 2.9–3.8) (p = 0.003) for the two groups, respectively. The median IVC diameters measured by examiner 2 were 3.1 mm (interquartile range 2.6–3.3) and 3.3 mm (interquartile range 2.8–3.8) (p = 0.004) for the two groups, respectively. The intraclass correlation coefficient was 0.93 (95% CI: 0.90–0.95). Conclusion: The IVC diameter values varied widely from 1.2 to 5.2 mm in newborns weighing 2–4 kg, and a low correlation between newborn weight and IVC diameter was found, so measuring IVC diameter may be a recommended step prior to inserting a umbilical venous catheter (UVC). The concordance between operators was good. We contemplated that the IVC diameter could be a potentially useful tool to identify the most appropriate UVC, thus reducing the risk of catheter-related thrombosis.
Petrillo F, Petrillo A, Marrapodi M, et al., 2022, Characterization and Comparison of Ocular Surface Microbiome in Newborns, Microorganisms, Vol: 10
The ocular microbiome is of fundamental importance for immune eye homeostasis, and its alteration would lead to an impairment of ocular functionality. Little evidence is reported on the composition of the ocular microbiota of term infants and on the impact of antibiotic prophylaxis. Methods: A total of 20 conjunctival swabs were collected from newborns at birth and after antibiotic treatment. Samples were subjected to 16S rRNA sequencing via system MiSeq Illumina. The data were processed with the MicrobAT software and statistical analysis were performed using two-way ANOVA. Results: Antibiotic prophylaxis with gentamicin altered the composition of the microbiota. In detail, a 1.5- and 2.01-fold reduction was recorded for Cutibacterium acnes (C. acnes) and Massilia timonae (M. timonae), respectively, whereas an increase in Staphylococcus spp. of 6.5 times occurred after antibiotic exposure. Conclusions: Antibiotic prophylaxis altered the ocular microbiota whose understanding could avoid adverse effects on eye health.
Marzuillo P, Di Sessa A, Iafusco D, et al., 2022, Heart rate cut-offs to identify non-febrile children with dehydration and acute kidney injury, EUROPEAN JOURNAL OF PEDIATRICS, Vol: 181, Pages: 1967-1977, ISSN: 0340-6199
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Montaldo P, Puzone S, Caredda E, et al., 2022, Impact of intrauterine growth restriction on cerebral and renal oxygenation and perfusion during the first 3 days after birth, Scientific Reports, Vol: 12, Pages: 1-9, ISSN: 2045-2322
Intrauterine growth restriction (IUGR) is associated with a higher incidence of perinatal complications as well as cardiovascular and renal diseases later on. A better insight into the disease mechanisms underlying these sequalae is important in order to identify which IUGR infants are at a higher risk and find strategies to improve their outcome. In this prospective case–control study we examined whether IUGR had any effect on renal and cerebral perfusion and oxygen saturation in term neonates. We integrated near-infrared spectroscopy (NIRS), echocardiographic, Doppler and renal function data of 105 IUGR infants and 105 age/gender-matched controls. Cerebral and renal regional oxygen saturation values were measured by NIRS during the first 12 h after birth. Echocardiography alongside Doppler assessment of renal and anterior cerebral arteries were performed at 6, 24, 48 and 72 h of age. Glomerular and tubular functions were also assessed. We found a left ventricular dysfunction together with a higher cerebral oxygen saturation and perfusion values in the IUGR group. IUGR term infants showed a higher renal oxygen saturation and a reduced oxygen extraction together with a subclinical renal damage, as indicated by higher values of urinary neutrophil gelatinase-associated lipocalin and microalbumin. These data suggest that some of the haemodynamic changes present in growth-restricted foetuses may persist postnatally. The increased cerebral oxygenation may suggest an impaired transition to normal autoregulation as a consequence of intra-uterine chronic hypoxia. The higher renal oxygenation may reflect a reduced renal oxygen consumption due to a subclinical kidney damage.
Zanfardino A, Carpentieri M, Piscopo A, et al., 2022, Sensor Augmented Pump Therapy is Safe and Effective in Very Low Birth Weight Newborns Affected by Neonatal Diabetes Mellitus, With Poor Subcutaneous Tissue: Replacement of the Insulin Pump Infusion Set on the Arm, a Video Case Report, JOURNAL OF DIABETES SCIENCE AND TECHNOLOGY, Vol: 16, Pages: 254-255, ISSN: 1932-2968
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Inserra E, Colella U, Caredda E, et al., 2022, Safety and effectiveness of intranasal dexmedetomidine together with midazolam for sedation in neonatal MRI, PEDIATRIC ANESTHESIA, Vol: 32, Pages: 79-81, ISSN: 1155-5645
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Burgod C, Pant S, Morales MM, et al., 2021, Effect of intra-partum Oxytocin on neonatal encephalopathy: a systematic review and meta-analysis, BMC Pregnancy and Childbirth, Vol: 21, Pages: 1-7, ISSN: 1471-2393
BackgroundOxytocin is widely used for induction and augmentation of labour, particularly in low- and middle-income countries (LMICs). In this systematic review and meta-analysis, we examined the effect of intra-partum Oxytocin use on neonatal encephalopathy.MethodsThe protocol for this study was registered with PROSPERO (ID: CRD42020165049). We searched Medline, Embase and Web of Science Core Collection databases for papers published between January 1970 and May 2021. We considered all studies involving term and near-term (≥36 weeks’ gestation) primigravidae and multiparous women. We included all randomised, quasi-randomised clinical trials, retrospective studies and non-randomised prospective studies reporting intra-partum Oxytocin administration for induction and/or augmentation of labour. Our primary outcome was neonatal encephalopathy. Risk of bias was assessed in non-randomised studies using the Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I) tool. The RoB 2.0 tool was used for randomised studies. A Mantel-Haenszel statistical method and random effects analysis model were used for meta-analysis. Odds ratios were used to determine effect measure and reported with 95% confidence intervals.ResultsWe included data from seven studies (6 Case-control studies, 1 cluster-randomised trial) of which 3 took place in high-income countries (HICs) and 4 in LMICs. The pooled data included a total of 24,208 women giving birth at or after 36 weeks; 7642 had intra-partum Oxytocin for induction and/or augmentation of labour, and 16,566 did not receive intra-partum Oxytocin. Oxytocin use was associated with an increased prevalence of neonatal encephalopathy (Odds Ratio 2.19, 95% CI 1.58 to 3.04; p < 0.00001).ConclusionsIntra-partum Oxytocin may increase the risk of neonatal encephalopathy. Future clinical trials of uterotonics should include neonatal encephalopathy as a key outcome.
Moreno Morales M, Montaldo P, Ivain P, et al., 2021, Association of Total Sarnat Score with brain injury and neurodevelopmental outcomes after neonatal encephalopathy, Archives of Disease in Childhood: Fetal and Neonatal Edition, Vol: 106, Pages: 669-672, ISSN: 1359-2998
We examined the association of Total Sarnat Score (TSS) with brain injury on neonatal magnetic resonance (MR) and adverse neurodevelopmental outcome (NDO) (death or moderate or severe disability) at 2 years of age in 145 infants undergoing therapeutic hypothermia for neonatal encephalopathy. TSS was associated with basal ganglia/thalamic injury on conventional MR (p=0.03) and thalamic N-acetyl aspartate on MR spectroscopy (R2=0.16, p=0.004) at 2 weeks of age, and Bayley Composite Cognitive (R2=0.18, p=0.01), Motor (R2=0.15, p=0.02) and Language (R2=0.11, p=0.01) Scores at 2 years of age after adjustment for seizures at the time of neurological assessment. The accuracy of TSS (area under the curve (AUC)=0.71) for predicting adverse NDO was similar to the modified Sarnat staging (AUC=0.72). TSS of >12 within 6 hours of birth indicated high risk of adverse NDO, while TSS of <4 indicated intact survival and was reassuring of a good outcome among cooled infants.
De Lucia M, Puzone S, Caredda E, et al., 2021, Glomerular and tubular function in intrauterine growth restricted term newborns, Publisher: SPRINGERNATURE, Pages: 12-13, ISSN: 0031-3998
Puzone S, Caredda E, Pugliese U, et al., 2021, Effect of intrauterine growth restriction on regional perfusion and tissue oxygenation in term neonates after birth, Publisher: SPRINGERNATURE, Pages: 11-11, ISSN: 0031-3998
Jenkins DD, Moss HG, Brown TR, et al., 2021, Nac and vitamin d improve cns and plasma oxidative stress in neonatal hie and are associated with favorable long-term outcomes, Antioxidants, Vol: 10, Pages: 1-21, ISSN: 2076-3921
N-acetylcysteine (NAC) and vitamin D provide effective neuroprotection in animal mod-els of severe or inflammation-sensitized hypoxic ischemic encephalopathy (HIE). To translate these FDA-approved drugs to HIE neonates, we conducted an early phase, open-label trial of 10 days of NAC (25, 40 mg/kg q12h) + 1,25(OH)2D (calcitriol 0.05 mg/kg q12h, 0.03 mg/kg q24h), (NVD), for pharmacokinetic (PK) estimates during therapeutic hypothermia and normothermia. We paired PK samples with pharmacodynamic (PD) targets of plasma isoprostanoids, CNS glutathione (GSH) and total creatine (tCr) by serial MRS in basal ganglia (BG) before and after NVD infusion at five days. Infants had moderate (n = 14) or severe HIE (n = 16), funisitis (32%), and vitamin D deficiency (75%). NVD resulted in rapid, dose-responsive increases in CNS GSH and tCr that correlated positively with plasma [NAC], inversely with plasma isofurans, and was greater in infants with lower baseline [GSH] and [tCr], suggesting increases in these PD markers were titrated by neural demand. Hypothermia and normothermia altered NAC PK estimates. NVD was well tolerated. Excluding genetic syndromes (2), prolonged ECMO (2), lost-to-follow-up (1) and SIDS death (1), 24 NVD treated HIE infants have no evidence of cerebral palsy, autism or cognitive delay at 24–48 months. These data confirm that low, safe doses of NVD in HIE neonates decreased oxidative stress in plasma and CNS, improved CNS energetics, and are associated with favorable developmental outcomes at two to four years.
Chandrasekaran M, Galdo F, Puzone S, et al., 2021, Enteral nutrition during therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy: The need for more evidence, ACTA PAEDIATRICA, Vol: 110, Pages: 2545-2547, ISSN: 0803-5253
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Thayyil S, Pant S, Montaldo P, et al., 2021, Hypothermia for moderate or severe neonatal encephalopathy in low and middle-income countries (HELIX): a randomised control trial in India, Sri Lanka and Bangladesh, The Lancet Global Health, Vol: 9, Pages: e1273-e1285, ISSN: 2214-109X
Background: Although therapeutic hypothermia reduces death or disability after neonatal encephalopathy in high-income countries, its safety and efficacy in low- and middle-income countries (LMICs) remains unclear. We examined if therapeutic hypothermia alongside optimal supportive intensive care reduces death or disability after neonatal encephalopathy in South Asia. Methods: We conducted a multi-country open label randomised controlled trial involving seven tertiary neonatal intensive care units in India, Sri Lanka and Bangladesh, between August 2015 and September 2020. We allocated infants born at or after 36 weeks of gestation with moderate or severe neonatal encephalopathy into whole body hypothermia (33·5 0 C) for 72 hours using a servo-controlled cooling device, or usual care (control group), within six hours of birth. All recruiting sites had facilities for invasive ventilation, cardiovascular support and access to 3 Telsa magnetic resonance imaging and spectroscopy. The primary outcome was a combined end point of death or moderate or severe disability at 18 to 22 months of age, assessed by Bayley scales of infant development (Version III).Findings: Of 576 eligible infants, we assigned 202 to hypothermia and 206 to control group. Primary outcome data were available for 394 (96·5%) infants, and occurred in 98(50·3%) of the hypothermia and 94 (47·2%) of the control group (Risk Ratio (RR) 1·06;95% confidence intervals (CI) 0·87 to 1·30 (p = 0·55). Eighty-four infants (42·4%) in the hypothermia group and 63 (31·3%) (p = 0·02) infants in the control group died, of whom 72 (35·6%) and 49 (23·8%) (p = 0·009) died during neonatal hospitalisation. Interpretation: Therapeutic hypothermia did not reduce the combined outcome of death or disability at18 months after neonatal encephalopathy in LMICs, but significantly increased mortality. Therapeutic hypothermia should not
Marzuillo P, Iafusco D, Zanfardino A, et al., 2021, Acute Kidney Injury and Renal Tubular Damage in Children With Type 1 Diabetes Mellitus Onset., J Clin Endocrinol Metab, Vol: 106, Pages: e2720-e2737
CONTEXT: Acute kidney injury (AKI) and renal tubular damage (RTD), especially if complicated by acute tubular necrosis (ATN), could increase the risk of later chronic kidney disease. No prospective studies on AKI and RTD in children with type1diabetes mellitus (T1DM) onset are available. OBJECTIVES: To evaluate the AKI and RTD prevalence and their rate and timing of recovery in children with T1DM onset. DESIGN: Prospective study. SETTINGS AND PATIENTS: 185 children were followed up after 14 days from T1DM onset. The patients who did not recover from AKI/RTD were followed-up 30 and 60 days later. MAIN OUTCOME MEASURES: AKI was defined according to the KDIGO criteria. RTD was defined by abnormal urinary beta-2-microglobulin and/or neutrophil gelatinase-associated lipocalin and/or tubular reabsorption of phosphate < 85% and/or fractional excretion of Na (FENa) > 2%. ATN was defined by RTD+AKI, prerenal (P)-AKI by AKI+FENa < 1%, and acute tubular damage (ATD) by RTD without AKI. RESULTS: Prevalence of diabetic ketoacidosis (DKA) and AKI were 51.4% and 43.8%, respectively. Prevalence of AKI in T1DM patients with and without DKA was 65.2% and 21.1%, respectively; 33.3% reached AKI stage 2, and 66.7% of patients reached AKI stage 1. RTD was evident in 136/185 (73.5%) patients (32.4% showed ATN; 11.4%, P-AKI; 29.7%, ATD). All patients with DKA or AKI presented with RTD. The physiological and biochemical parameters of AKI and RTD were normal again in all patients. The former within 14 days and the latter within 2months. CONCLUSIONS: Most patients with T1DM onset may develop AKI and/or RTD, especially if presenting with DKA. Over time the physiological and biochemical parameters of AKI/RTD normalize in all patients.
Patterson JK, Pant S, Jones DF, et al., 2021, Informed consent rates for neonatal randomized controlled trials in low- and lower middle-income versus high-income countries: a systematic review, PLoS One, Vol: 16, Pages: 1-14, ISSN: 1932-6203
Objective: Legal, ethical, and regulatory requirements of medical research uniformly call for informed consent. We aimed to characterize and compare consent rates for neonatal randomized controlled trials in low- and lower middle-income countries versus high-income countries, and to evaluate the influence of study characteristics on consent rates.Methods: In this systematic review, we searched MEDLINE, EMBASE and Cochrane for randomized controlled trials of neonatal interventions in low- and lower middle-income countries or high-income countries published 01/01/2013 to 01/04/2018. Our primary outcome was consent rate, the proportion of eligible participants who consented amongst those approached, extracted from the article or email with the author. Using a generalised linear model for fractional dependent variables, we analysed the odds of consenting in low- and lower middle-income countries versus high-income countries across control types and interventions.Findings: We screened 3523 articles, yielding 300 eligible randomized controlled trials with consent rates available for 135 low- and lower middle-income country trials and 65 high-income country trials. Median consent rates were higher for low- and lower middle-income countries (95.6%; interquartile range (IQR) 88.2–98.9) than high-income countries (82.7%; IQR 68.6–93.0; p<0.001). In adjusted regression analysis comparing low- and lower middle-income countries to high-income countries, the odds of consent for no placebo-drug/nutrition trials was 3.67 (95% Confidence Interval (CI) 1.87–7.19; p = 0.0002) and 6.40 (95%CI 3.32–12.34; p<0.0001) for placebo-drug/nutrition trials.Conclusion: Neonatal randomized controlled trials in low- and lower middle-income countries report consistently higher consent rates compared to high-income country trials. Our study is limited by the overrepresentation of India among randomized controlled trials in low- and lower middle-income countries. This st
Passariello A, Montaldo P, Palma M, et al., 2020, Neonatal painful stimuli: skin conductance algesimeter index to measure efficacy 24% of sucrose oral solution, JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE, Vol: 33, Pages: 3596-3601, ISSN: 1476-7058
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Montaldo P, Cunnington A, Oliveira V, et al., 2020, Transcriptomic profile of adverse neurodevelopmental outcomes after neonatal encephalopathy, Scientific Reports, Vol: 10, Pages: 1-7, ISSN: 2045-2322
A rapid and early diagnostic test to identify the encephalopathic babies at risk of adverse outcome may accelerate the development of neuroprotectants. We examined if a whole blood transcriptomic signature measured soon after birth,predicts adverse neurodevelopmental outcomeeighteenmonths after neonatal encephalopathy.We performed next generation sequencing on whole blood ribonucleic acid obtained within sixhours of birth from the first 47encephalopathic babies recruited to the Hypothermia for Encephalopathy in Low and middle-income countries (HELIX)trial. Two infants with blood culture positive sepsis were excluded, and the data from remaining 45 were analysed. A total of 855genes were significantly differentially expressed between the good and adverse outcome groups, of which RGS1and SMC4 werethe most significant. Biological pathway analysis adjusted for gender, trial randomisation allocation (cooling therapy versus usual care) and estimated blood leukocyte proportions revealed over-representation of genes from pathways related to melatoninand polo-like kinase in babieswith adverse outcome. These preliminary data suggest that transcriptomic profiling may be a promising tool for rapid risk stratification in neonatal encephalopathy. It may provide insights into biological mechanismsand identify novel therapeutic targetsfor neuroprotection.
Burgod C, Thayyil S, Montaldo P, 2020, The use of gene expression as a disease stratification tool of neonatal encephalopathy, Pediatric Research, Vol: 89, Pages: 12-13, ISSN: 0031-3998
Montaldo P, Caredda E, Pugliese U, et al., 2020, Continuous glucose monitoring profile during therapeutic hypothermia in encephalopathic infants with unfavorable outcome, PEDIATRIC RESEARCH, Vol: 88, Pages: 218-224, ISSN: 0031-3998
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- Citations: 20
Montaldo P, 2020, Early Career Investigator-August 2020, PEDIATRIC RESEARCH, Vol: 88, Pages: 147-147, ISSN: 0031-3998
Kariholu U, Montaldo P, Markati T, et al., 2020, Therapeutic hypothermia for mild neonatal encephalopathy: A systematic review and meta-analysis, Archives of Disease in Childhood. Fetal and Neonatal Edition, Vol: 105, Pages: 225-228, ISSN: 1359-2998
Objectives To examine if therapeutic hypothermia reduces the composite outcome of death, moderate or severe disability at 18 months or more after mild neonatal encephalopathy (NE).Data source MEDLINE, Cochrane database, Scopus and ISI Web of Knowledge databases, using ‘hypoxic ischaemic encephalopathy’, ‘newborn’ and ‘hypothermia’, and ‘clinical trials’ as medical subject headings and terms. Manual search of the reference lists of all eligible articles and major review articles and additional data from the corresponding authors of selected articles.Study selection Randomised and quasirandomised controlled trials comparing therapeutic hypothermia with usual care.Data extraction Safety and efficacy data extracted independently by two reviewers and analysed.Results We included the data on 117 babies with mild NE inadvertently recruited to five cooling trials (two whole-body cooling and three selective head cooling) of moderate and severe NE, in the meta-analysis. Adverse outcomes occurred in 11/56 (19.6%) of the cooled babies and 12/61 (19.7%) of the usual care babies (risk ratio 1.11 (95% CIs 0.55 to 2.25)).Conclusions Current evidence is insufficient to recommend routine therapeutic hypothermia for babies with mild encephalopathy and significant benefits or harm cannot be excluded.
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