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  • Journal article
    Montaldo P, Lally PJ, Oliveira V, Thayyil Set al., 2018,

    Hypothermic neuroprotection for neonatal encephalopathy in low-and middle-income countries: A new approach to an old problem

    , NeoReviews, Vol: 19, Pages: e735-e741

    © 2018, American Academy of Pediatrics. All rights reserved. Little progress has been made over the past decade in improving the outcomes of infants with neonatal encephalopathy in low-and middle-income countries (LMICs), and millions of infants still die or sustain permanent neurodisability every year. One of the key reasons for this lack of progress is a disconnect between encephalopathy research in high-income countries and LMICs. The majority of the neonatal encephalopathy research has been conducted in high-income countries with a low disease burden, without the involvement of LMICs. Here we discuss how a collaborative approach—particularly between middle-income countries and high-income countries—enables the use of state-of-the-art magnetic resonance biomarkers and host gene expression profiling for effective disease stratification. Using the example of the Hypothermia for Encephalopathy in Low-and middle-Income countries (HELIX) trial, we describe how this approach may result in a paradigm shift in global perinatal brain research over the next decade.

  • Journal article
    Oliveira V, Martins R, Liow N, Teiserskas J, von Rosenberg W, Adjei T, Shivamurthappa V, Lally PJ, Mandic D, Thayyil Set al., 2018,

    Prognostic accuracy of heart rate variability analysis in neonatal encephalopathy: a systematic review

    , Neonatology, Vol: 115, Pages: 59-67, ISSN: 1661-7800

    BACKGROUND: Heart rate variability analysis offers real-time quantification of autonomic disturbance after perinatal asphyxia, and may therefore aid in disease stratification and prognostication after neonatal encephalopathy (NE). OBJECTIVE: To systematically review the existing literature on the accuracy of early heart rate variability (HRV) to predict brain injury and adverse neurodevelopmental outcomes after NE. DESIGN/METHODS: We systematically searched the literature published between May 1947 and May 2018. We included all prospective and retrospective studies reporting HRV metrics, within the first 7 days of life in babies with NE, and its association with adverse outcomes (defined as evidence of brain injury on magnetic resonance imaging and/or abnormal neurodevelopment at ≥1 year of age). We extracted raw data wherever possible to calculate the prognostic indices with confidence intervals. RESULTS: We retrieved 379 citations, 5 of which met the criteria. One further study was excluded as it analysed an already-included cohort. The 4 studies provided data on 205 babies, 80 (39%) of whom had adverse outcomes. Prognostic accuracy was reported for 12 different HRV metrics and the area under the curve (AUC) varied between 0.79 and 0.94. The best performing metric reported in the included studies was the relative power of high-frequency band, with an AUC of 0.94. CONCLUSIONS: HRV metrics are a promising bedside tool for early prediction of brain injury and neurodevelopmental outcome in babies with NE. Due to the small number of studies available, their heterogeneity and methodological limitations, further research is needed to refine this tool so that it can be used in clinical practice.

  • Journal article
    Chalak LF, Nguyen K-A, Prempunpong C, Heyne R, Thayyil S, Shankaran S, Laptook AR, Rollins N, Pappas A, Koclas L, Shah B, Montaldo P, Techasaensiri B, Sánchez PJ, Sant'Anna Get al., 2018,

    Prospective research in infants with mild encephalopathy identified in the first six hours of life: neurodevelopmental outcomes at 18-22 months

    , Pediatric Research, Vol: 84, Pages: 861-868, ISSN: 0031-3998

    BACKGROUND: Studies of early childhood outcomes of mild hypoxic-ischemic encephalopathy (HIE) identified in the first 6 h of life are lacking. OBJECTIVE: To evaluate neurodevelopmental outcomes at 18-22 months of PRIME study. STUDY DESIGN: Multicenter, prospective study of mild HIE defined as ≥1 abnormality using the modified Sarnat within 6 h of birth and not meeting cooling criteria. Primary outcome was disability with mild: Bayley III cognitive 70-84 or ≥85 and either Gross Motor Function Classification System (GMFCS) 1 or 2, seizures, or hearing deficit; moderate: cognitive 70-84 and either GMFCS 2, seizures, or hearing deficit; severe: cognitive <70, GMFCS 3-5. RESULTS: Of the 63 infants enrolled, 51 (81%) were evaluated at 19 ± 2 months and 43 (68%) completed Bayley III. Of the 43 infants, 7 (16%) were diagnosed with disability, including 1 cerebral palsy and 2 autism. Bayley scores < 85 in either cognition, motor, or language were detected in 17 (40%): 14 (32%) language, 7 (16%) cognitive, and 6 (14%) motor domain. Infants with disability had more abnormalities on discharge examination and brain MRI, with longer hospital stay (p < 0.001). CONCLUSIONS: In this contemporary untreated cohort of mild HIE, disability occurred in 16% of infants at 18-22 months.

  • Conference paper
    Chalak LF, Prempunpong C, Garfinkle J, Rollins N, Nguyen K-A, Pappas A, Montaldo P, Thayyil S, Sanchez PJ, Shankaran S, Laptook AR, Sant'Anna Get al., 2017,

    PROSPECTIVE STUDY OF INFANTS WITH MILD ENCEPHALOPATHY: PRIME STUDY

    , XXV Biennial Meeting of the International Perinatal Collegium, Publisher: WILEY, Pages: 9-9, ISSN: 0803-5253
  • Journal article
    Montaldo P, Oliveira V, Lally PJ, Chaban B, Atreja G, Kirmi O, Thayyil Set al., 2016,

    Therapeutic hypothermia in neonatal cervical spine injury

    , Archives of Disease in Childhood: Fetal & Neonatal Edition, Vol: 101, Pages: F468-F468, ISSN: 1468-2052
  • Journal article
    Montaldo P, Addison S, Oliveira V, Lally PJ, Taylor AM, Sebire NJ, Thayyil S, Arthurs OJet al., 2016,

    Quantification of Maceration Changes using Post Mortem MRI in Fetuses

    , BMC MEDICAL IMAGING, Vol: 16, ISSN: 1471-2342

    BackgroundPost mortem imaging is playing an increasingly important role in perinatal autopsy, andcorrect interpretation of imaging changes is paramount. This is particularly importantfollowing intra-uterine fetal death, where there may be fetal maceration. The aim of thisstudy was to investigate whether any changes seen on a whole body fetal post mortemmagnetic resonance imaging (PMMR) correspond to maceration at conventionalautopsy.Methods: We performed pre-autopsy PMMR in 75 fetuses using a 1.5 Tesla SiemensAvanto MR scanner (Erlangen, Germany). PMMR images were reported blinded to theclinical history and autopsy data using a numerical severity scale (0 = no macerationchanges to 2 = severe maceration changes) for 6 different visceral organs (total 12).The degree of maceration at autopsy was categorized according to severity on anumerical scale (1 = no maceration to 4 = severe maceration). We also generatedquantitative maps to measure the liver and lung T2.Results: The mean PMMR maceration score correlated well with the autopsymaceration score (R2=0.93). A PMMR score of ≥ 4.5 had a sensitivity of 91%,specificity of 64%, for detecting moderate or severe maceration at autopsy. Liver andlung T2 were increased in fetuses with maceration scores of 3-4 in comparison tothose with 1-2 (liver p=0.03, lung p=0.02).Conclusions: There was a good correlation between PMMR maceration score and theextent of maceration seen at conventional autopsy. This score may be useful ininterpretation of fetal PMMR.

  • Journal article
    Arthurs OJ, Thayyil S, Olsen OE, Addison S, Wade A, Jones R, Norman W, Scott RJ, Robertson NJ, Taylor AM, Chitty LS, Sebire NJ, Owens CMet al., 2014,

    Diagnostic accuracy of post-mortem MRI for thoracic abnormalities in fetuses and children

    , European Radiology, Vol: 24, Pages: 2876-2884, ISSN: 1432-1084

    Objectives To compare the diagnostic accuracy of postmortemmagnetic resonance imaging (PMMR) specificallyfor non-cardiac thoracic pathology in fetuses and children,compared with conventional autopsy.Methods Institutional ethics approval and parental consentwas obtained. A total of 400 unselected fetuses and childrenunderwent PMMR before conventional autopsy, reportedblinded to the other dataset.Results Of 400 non-cardiac thoracic abnormalities, 113(28 %) were found at autopsy. Overall sensitivity and specificity(95 % confidence interval) of PMMR for any thoracicpathology was poor at 39.6 % (31.0, 48.9) and 85.5 % (80.7,89.2) respectively, with positive predictive value (PPV)53.7 % (42.9, 64.0) and negative predictive value (NPV)77.0 % (71.8, 81.4). Overall agreement was 71.8 % (67.1,76.2). PMMR was most sensitive at detecting anatomicalabnormalities, including pleural effusions and lung or thoracichypoplasia, but particularly poor at detecting infection.Conclusions PMMR currently has relatively poor diagnosticdetection rates for the commonest intra-thoracic pathologiesidentified at autopsy in fetuses and children, including respiratorytract infection and diffuse alveolar haemorrhage. Thereasonable NPV suggests that normal thoracic appearancesat PMMR exclude the majority of important thoraciclesions at autopsy, and so could be useful in the contextof minimally invasive autopsy for detecting non-cardiacthoracic abnormalities.

  • Journal article
    Addison S, Munroe P, Mein C, Cohen M, Fowler D, Sebire NJ, Peebles D, Taylor A, Abrams D, Thayyil Set al., 2014,

    8.2 cardiac ion channelopathies in unexplained stillbirths.

    , Arch Dis Child Fetal Neonatal Ed, Vol: 99 Suppl 1

    Although cardiac ion channelopathies are reported in up to 15% of sudden infant deaths, the prevalence in unexplained stillbirths is not known.

  • Journal article
    Lally P, Price D, Bainbridge A, Pauliah S, Satodia P, Wayte S, Abernethy L, Turner M, Basheer A, Alavi A, Kirmi O, Jones B, Shankaran S, Cady E, Thayyil Set al., 2014,

    PC.26 Feasibility of Magnetic Resonance Spectroscopy in Examining Thalamic Metabolite Concentrations in a Multi-Centre Study of Neonatal Encephalopathy.

    , Arch Dis Child Fetal Neonatal Ed, Vol: 99 Suppl 1, Pages: A44-A45

    Proton magnetic resonance spectroscopy (MRS) has high prognostic value in hypoxic ischaemic encephalopathy (HIE), however its multi-centre application is limited by inconsistencies between scanners and protocols. N-acetylaspartate (NAA) is predominantly neuronal: cerebral NAA concentration may be a more reliable HIE-severity biomarker than lactate/NAA.

  • Journal article
    Pauliah S, Lally P, Price D, Bainbridge A, Kurien J, Sivaswami N, Cowan F, Balraj G, Swamy R, Madhavan V, Nair M, Krishnakumar P, Cady E, Shankaran S, Thayyil Set al., 2014,

    PC.106 Cerebral Injury and Early Childhood Neurodevelopmental Outcome following Neonatal Encephalopathy in a Middle-income Country.

    , Arch Dis Child Fetal Neonatal Ed, Vol: 99 Suppl 1, Pages: A72-A73

    Although neonatal encephalopathy (NE), accounts for 1 million neonatal deaths annually in low-and middle-income countries (LMIC), underlying brain injury and long term outcomes are not well characterised in LMIC.

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