Browsing by Author "Sumanasena, S."

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6503 Using anthropometric data to investigate the nutritional status of children included on the Sri Lankan cerebral palsy register.
(BMJ Publishing Group Ltd, 2024) Sumanasena, S.; Fernando, R.; Kurukulaarachchi, S.; Heiyanthuduwage, T.M.; Sheedy, H.S.; Wijesekara, S.; Jagoda, J.; Muttiah, N.
OBJECTIVES The nutritional data from children with cerebral palsy (CP) in low and middle income countries (LMIC) is sparse. In high income countries (HICs) well established nutritional care plans, commercial products and good psycho-social support are available.1 A multitude of complications arise due to malnutrition leading to poor quality of life.2 Here we investigated the nutritional status of children included in the Sri Lankan Cerebral Palsy Register (SLCPR).METHODS The study included 768 children aged 0–18 years with CP, attending three teaching hospitals in the Western Province, from September 2018 to November 2021. Data included clinical profile and anthropometry [weight (Kg), height (cm), BMI, mid upper arm circumference (MUAC) (cm), and OFC (cm)] based on WHO. Average was calculated using three repeated measurements. Children who could not stand independently (GMFCS level 4/5) underwent height estimations with the knee height equation: height = (2.69 X Knee height) + 24.2.Indicators used to measure the nutritional status were: weight for age Z score (WAZ), height for age Z score (HAZ), weight for height Z score (WHZ), BMI for age Z score (BAZ), and MUAC for age Z score (MUACZ). WHO Anthro and WHO AnthroPlus software calculated all Z scores.4 HAZ and BAZ were calculated for children aged <18 years, WAZ was calculated for children aged <10.1 years, and WHZ and MUACZ were calculated for children aged <5.1 years. The z scores < -2.0 SD were categorized as underweight (WAZ), stunted (HAZ), wasted (WHZ or MUAC), thin (BAZ).RESULTS Total of 768 children (mean age 59.6 months, SD 44.9, 62.5% males) participated. There were (n=431) children under 61 months and (n=520) from 0–10 years. Of them, 51.3% (n = 267/520) were underweight, 59.8% (n = 258/431) were stunted and 27.3% (n = 210/768) were thin. Among children aged < 5 years, 26.7% (n = 115/431) had severe wasting and severe acute malnutrition (SAM) according to MUACZ < -3SD. Both underweight and stunting were significantly higher among children with spastic CP compared with others (p<0.05). In the 5–19 year group 16.9% (n= 57/337) were obese (BAZ > + 2SD).CONCLUSION Predominant stunting and underweight in this population calls for urgent action to minimize chronic malnutrition. It is imperative to further explore nutritional intake and feeding difficulties in this group and offer structured nutritional care plans. The trend observed in older children towards obesity possibly indicates the need for coordinated nutrition and exercise programmes. It is recommended to regularly monitor growth and nutritional status of all children with CP as there may be serious implications for their activity levels.
6542 Clinical profiles of children less than 5 years presenting with or high risk of cerebral palsy in the Western Province of Sri Lanka
(BMJ, 2024) Sumanasena, S.; Heiyanthuduwage, T.M.; Fernando, R.; Sheedy, H.S.; Jagoda, J.; Wijesekara, S.; Wanigasinghe, J.; Muttiah, N.; Rathnayake, P.; Kitnasamy, G.; Khandaker, G.
OBJECTIVES Cerebral palsy (CP) is the commonest physical disability in children globally.1 It is a clinical diagnosis based on clinical and neurological findings. International clinical practice guidelines recommend early diagnosis and CP specific interventions to invest in neural plasticity and achieve optimal functional levels.2 In the past diagnosis was confirmed at 12–24 months but now it is advanced to confirm or identify as high risk for CP before the age of six months.3 4 Sri Lanka is one of the few Asian countries that initiated a CP register and National Guidelines on management of CP.5 The objective of this paper is to describe the clinical profiles of children less than 5 years presenting to Western Province hospitals in Sri Lanka based on the data from the Sri Lanka Cerebral Palsy Register (SLCPR).METHODS A cross sectional hospital-based study was conducted in the Western Province from September 2018 – October 2021 in three teaching hospitals to collect a minimum data set for the Sri Lanka SLCPR. Data of children less than 60 months was extracted with a confirmed clinical diagnosis of CP or identified formally as ‘high risk’ of CP.Information on sociodemographic, pre/peri/neonatal, and post neonatal risk factors, and associated impairments were collected using hospital records and clinic notes. Clinical motor type, topography, and associated impairments were evaluated.RESULTS Data of 431 children were extracted, 254 (58.9%) were males. Mean age at diagnosis was 28.73 months (median 27, SD 14.98). Most children (n= 422, 97.9%) acquired CP in the pre/peri/neonatal period. The mean birth weight was 2304.4 g (median 37, SD 825.58g) and the mean POA was 35.82 months (median 37, SD 4.88). Main risk factors identified were prematurity (n=190, 44.1%), hypoxic ischaemic encephalopathy (HIE) (n= 234, 54.3%), jaundice (n=31, 7.2%) and sepsis (n= 13, 3.0%). While 183 children (42.5%) showed evidence of definitive spastic motor type, 184 (42.7%) showed predominant dyskinesia.CONCLUSION The age at diagnosis of this population from Sri Lanka is significantly lower than from other LMICs. HIE and prematurity, both preventable conditions remain the highest risk factors. Longitudinal follow up will ascertain the final motor outcomes as a higher proportion of children showed dyskinesia. The SLCPR is an important resource which will support new research towards investigating opportunities for prevention and service planning for children.
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
(Elsevier, 2024) Burgod, C.; Mazlan, M.; Pant, S.; Krishnan, V.; Garegrat, R.; Montaldo, P.; Muraleedharan, P.; Bandiya, P.; Kamalaratnam, C.N.; Chandramohan, R.; Manerkar, S.; Jahan, I.; Moni, S.C.; Shahidullah, M.; Rodrigo, R.; Sumanasena, S.; Sujatha, R.; Sathyanathan, B.P.; Joshi, A.R.; Pressler, R.R.; Bassett, P.; Shankaran, S.; Thayyil, S.
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. FUNDING: National Institute for Health Research.
Effect of a play-based training program on interactive skills of caregivers of children with autism
(Faculty of Medicine, University of Kelaniya, Sri Lanka, 2021) Wanniachchi, P.M.; Sumanasena, S.
Introduction: Children with autism spectrum disorder (ASD) have impairments in social communication and interaction skills and show restricted repetitive behaviours. Evidence shows that early detection and parent mediated intervention programs lead to better social communication and functional outcomes highlighting parents as the most natural human resource. Objectives: To evaluate caregiver acquisition of interaction skills to engage with children aged 2-4 years with ASD during play following a parent training protocol and to describe associated socio-demographic factors Methods: Thirty (30) caregivers of newly diagnosed children aged 24-48 months, attending a multidisciplinary clinic were recruited. A mixed method research including pre¬post interventional study determined the acquisition of interactive skills following a 2 hour play based training program. Adapted Quality of Caregiver-Child Interactions for Infants and Toddlers (Q-CCIIT); checklist assessed pre-post caregiver-child interactions by 10- minutes video recordings of each child two weeks following the training. A questionnaire collected socio-demographic data. Data was analysed using nonparametric tests by SPSS software. Results: QCCITT percentage of mean scores improved significantly in all 30 caregivers (p<0.005) for all three areas assessed; support for social emotional development as an average 8.80 to 22.83, cognitive development 4.63 to 14.13 and language development 6.97 to 12.97. Age and education level of parents positively influenced the skills (p< 0.05). Conclusions: There was a significant improvement of caregiver interaction skills. Social emotional skills improvement was also significant.
Hypothermia for moderate or severe neonatal encephalopathy in low-income and middle-income countries (HELIX): a randomised controlled trial in India, Sri Lanka, and Bangladesh
(Elsevier Ltd., 2021) Thayyil, S.; Pant, S.; Montaldo, P.; Shukla, D.; Oliveira, V.; Ivain, P.; Bassett, P.; Swamy, R.; Mendoza, J.; Moreno-Morales, M.; Lally, P.J.; Benakappa, N.; Bandiya, P.; Shivarudhrappa, I.; Somanna, J.; Kantharajanna, U.B.; Rajvanshi, A.; Krishnappa, S.; Joby, P.K.; Jayaraman, K.; Chandramohan, R.; Kamalarathnam, C.N.; Sebastian, M.; Tamilselvam, I.A.; Rajendran, U.D.; Soundrarajan, R.; Kumar, V.; Sudarsanan, H.; Vadakepat, P.; Gopalan, K.; Sundaram, M.; Seeralar, A.; Vinayagam, P.; Sajjid, M.; Baburaj, M.; Murugan, K.D.; Sathyanathan, B.P.; Kumaran, E.S.; Mondkar, J.; Manerkar, S.; Joshi, A.R.; Dewang, K.; Bhisikar, S.M.; Kalamdani, P.; Bichkar, V.; Patra, S.; Jiwnani, K.; Shahidullah, M.; Moni, S.C.; Jahan, I.; Mannan, M.A.; Dey, S.K.; Nahar, M.N.; Islam, M.N.; Shabuj, K.H.; Rodrigo, R.; Sumanasena, S.; Abayabandara-Herath, T.; Chathurangika, G.K.; Wanigasinghe, J.; Sujatha, R.; Saraswathy, S.; Rahul, A.; Radha, S.J.; Sarojam, M.K.; Krishnan, V.; Nair, M.K.; Devadas, S.; Chandriah, S.; Venkateswaran, H.; Burgod, C.; Chandrasekaran, M.; Atreja, G.; Muraleedharan, P.; Herberg, J.A.; Chong, W.K.K.; Sebire, N.J.; Pressler, R.; Ramji, S.; Shankaran, S.; HELIX consortium
BACKGROUND: Although therapeutic hypothermia reduces death or disability after neonatal encephalopathy in high-income countries, its safety and efficacy in low-income and middle-income countries is unclear. We aimed to examine whether therapeutic hypothermia alongside optimal supportive intensive care reduces death or moderate or severe disability after neonatal encephalopathy in south Asia. METHODS: We did a multicountry open-label, randomised controlled trial in seven tertiary neonatal intensive care units in India, Sri Lanka, and Bangladesh. We enrolled infants born at or after 36 weeks of gestation with moderate or severe neonatal encephalopathy and a need for continued resuscitation at 5 min of age or an Apgar score of less than 6 at 5 min of age (for babies born in a hospital), or both, or an absence of crying by 5 min of age (for babies born at home). Using a web-based randomisation system, we allocated infants into a group receiving whole body hypothermia (33·5°C) for 72 h using a servo-controlled cooling device, or to usual care (control group), within 6 h of birth. All recruiting sites had facilities for invasive ventilation, cardiovascular support, and access to 3 Tesla MRI scanners and spectroscopy. Masking of the intervention was not possible, but those involved in the magnetic resonance biomarker analysis and neurodevelopmental outcome assessments were masked to the allocation. The primary outcome was a combined endpoint of death or moderate or severe disability at 18-22 months, assessed by the Bayley Scales of Infant and Toddler Development (third edition) and a detailed neurological examination. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02387385. FINDINGS: We screened 2296 infants between Aug 15, 2015, and Feb 15, 2019, of whom 576 infants were eligible for inclusion. After exclusions, we recruited 408 eligible infants and we assigned 202 to the hypothermia group and 206 to the control group. Primary outcome data were available for 195 (97%) of the 202 infants in the hypothermia group and 199 (97%) of the 206 control group infants. 98 (50%) infants in the hypothermia group and 94 (47%) infants in the control group died or had a moderate or severe disability (risk ratio 1·06; 95% CI 0·87-1·30; p=0·55). 84 infants (42%) in the hypothermia group and 63 (31%; p=0·022) infants in the control group died, of whom 72 (36%) and 49 (24%; p=0·0087) died during neonatal hospitalisation. Five serious adverse events were reported: three in the hypothermia group (one hospital readmission relating to pneumonia, one septic arthritis, and one suspected venous thrombosis), and two in the control group (one related to desaturations during MRI and other because of endotracheal tube displacement during transport for MRI). No adverse events were considered causally related to the study intervention. INTERPRETATION: Therapeutic hypothermia did not reduce the combined outcome of death or disability at 18 months after neonatal encephalopathy in low-income and middle-income countries, but significantly increased death alone. Therapeutic hypothermia should not be offered as treatment for neonatal encephalopathy in low-income and middle-income countries, even when tertiary neonatal intensive care facilities are available. FUNDING: National Institute for Health Research, Garfield Weston Foundation, and Bill & Melinda Gates Foundation. TRANSLATIONS: For the Hindi, Malayalam, Telugu, Kannada, Singhalese, Tamil, Marathi and Bangla translations of the abstract see Supplementary Materials section.
Ohtahara syndrome due to bilateral perisylvian polymicrogyria
(Sri Lanka College of Paediatricians, 2014) Wanigasinghe, J.; Gamaathige, N.I.S.; Sumanasena, S.; Weerasekera, M.
No abstract available
Randomized, single-blind, parallel clinical trial on efficacy of oral prednisolone versus intramuscular corticotropin on immediate and continued spasm control in West syndrome
(Elsevier Science Publishing, 2015) Wanigasinghe, J.; Arambepola, C.; Sri Ranganathan, S.; Sumanasena, S.; Attanapola, G.
OBJECTIVE: A single-center, single-blind, parallel-group, randomized clinical trial was performed to test the null hypothesis that adrenocorticotropic hormone is not superior to high-dose prednisolone for treatment of newly diagnosed West syndrome. METHODS: Newly diagnosed infants with West syndrome were randomized to receive 14 days of oral prednisolone (40-60 mg/day) or a synthetically prepared intramuscular long-acting adrenocorticotropic hormone (40-60 IU/every other day [0.5-0.75 mg]) according to the United Kingdom Infantile Spasm Study protocol. They were blindly evaluated for infantile spasm remission by day 14, electroclinical remission (spasm cessation + resolution of hypsarrhythmia on a 30-minute electroencephalograph) by day 14 and continued spasm freedom for 28 days. RESULTS: Ninety-seven patients were enrolled in the study, with 48 of them receiving prednisolone and 49 receiving ACTH. There was no significant difference in the baseline characteristics or risk factors for the two treatment groups. By day 14, cessation of infantile spasms occurred in 28/48 (58.3%) infants on prednisolone compared with only 18/49 (36.7%) infants given adrenocorticotropic hormone (P = 0.03) and electroclinical remission in 21 on prednisolone compared with nine on adrenocorticotropic hormone (P = 0.007). Sustained spasm control for 28 consecutive days following electroclinical remission occurred in 15 on prednisolone compared with six on adrenocorticotropic hormone (P = 0.008). The total number of days required for spasm cessation was significantly less in those treated with prednisolone (3.85 days ± 2.4) compared with adrenocorticotropic hormone (8.65 days ± 3.7) (P = 0.001). Among patients who did not achieve remission, there was a non-significant trend toward greater quantitative reduction of spasms with prednisolone than with adrenocorticotropic hormone (P = 0.079). CONCLUSION: Synthetic adrenocorticotropic hormone of 40-60 IU/every other day did not yield superior rates of electroencephalographic or clinical remission when compared with prednisolone of 40-60 mg/day. Significantly, more patients achieved electroclinical remission when treated with prednisolone than with adrenocorticotropic hormone. Copyright © 2015 Elsevier Inc. All rights reserved.
Randomized, single-blind, parallel clinical trial on efficacy of oral prednisolone versus intramuscular corticotropin: A 12-month assessment of spasm control in west syndrome
(Elsevier-Professional Publications, 2017) Wanigasinghe, J.; Arambepola, C.; Ranganathan, S.S.; Sumanasena, S.
OBJECTIVE: We earlier completed a single-blind, parallel-group, randomized clinical trial to test the null hypothesis that adrenocorticotropic hormone (ACTH) is not superior to high-dose prednisolone for short-term control of West syndrome. We now present long-term follow-up data for spasm control for individuals who completed this earlier trial. METHODS: Infants with untreated West syndrome were randomized to receive 14 days of prednisolone (40 to 60 mg/day) or intramuscularlong-acting ACTH (40 to 60 IU every other day). They were evaluated at three, six, and 12 months to evaluate long-term spasm control. RESULTS: The total number of infants treated was 97 (48 prednisolone; 49 ACTH). All completed the treatment course. Eighty-five, 82, and 76 children were available for follow-up at three, six, and 12 months. Number lost to follow-up at each interval was not statistically different. Likelihood of spasm freedom at three months was significantly higher for prednisolone (64.6%) than for ACTH (38.8%) (P = 0.01; odds ratio = 2.9; 95% confidence interval = 1.3 to 6.6). At six months (P = 0.19) and twelve months (P = 0.13), the control of spasms was not statistically different, although a trend in favor of prednisolone was documented at both these time points (58.3% versus 44.9% for ACTH at six months and 56.2% versus 40.8% with ACTH at 12 months). After initial remission by day 14 (n = 46), the likelihood of a relapse within the next 12 months was not statistically different between the two treatment groups (P = 0.1). CONCLUSIONS: Control of spasms at three months was significantly better if initially treated with prednisolone. Control of spasms at six and 12 months was not significantly different despite a trend favoring prednisolone. Risk of relapse following initial remission was similar in the two groups.
Telehealth services for children with neuro-developmental disabilities in the Asia-Pacific region: A systematic review
(Oxford, 2024) Devagiri, B.; Ariyasena, A.D.K.; Siriwardhana, D.D.; Sumanasena, S.
BACKGROUND: In recent years telehealth became a popular and a rational health service delivery approach, especially amidst multiple challenges posed while providing health care interventions during the COVID-19 pandemic. AIM: We synthesized available evidence on telehealth for managing children with NDDs in the Asia-Pacific region with the aim of identifying successful methods. METHODOLOGY: We systematically reviewed six electronic databases: MEDLINE, AMED, EMBASE, PsychInfo, Web of Science, and (CINAHL plus) using the keywords and database-specific subject headings from their inception to 25th August 2021. Review findings were synthesized narratively, and harvest plots were used to demonstrate the effect of interventions. The protocol and reporting the findings of this review adhered to PRISMA 2020 guidelines. PROSPERO registration: CRD 340690. RESULTS: We harvested 30,823 records; 17,563 duplicates were removed, and 196 full-text articles were assessed for eligibility. 16 studies with multiple research designs were included in the review. Eight were from the Pacific region and eight represented Asia. The interventions targeted families and children with a variety of NDDs (autism spectrum disorder, Down syndrome, cleft lip and palate, hearing impairment, cerebral palsy etc.) via telehealth. Telehealth packages consisted of direct and indirect methods of synchronous, asynchronous, and hybrid approaches. All studies used parent-led intervention strategies. Telehealth reported a positive effect in 7/16 studies while five showed a neutral effect. CONCLUSIONS: According to published evidence telehealth for children with NDDs is an evolving, evidence-based service facilitation modality in the Asia-Pacific region, with only a few published randomized controlled trials. The systematic review shows promising telehealth practices emerging across the region despite the diversity in NDDs studied.
Whole-Blood gene expression profile after hypoxic-ischemic encephalopathy
(American Medical Association, 2024) Montaldo, P.; Burgod, C.; Herberg, J.A.; Kaforou, M.; Cunnington, A.J.; Mejias, A.; Cirillo, G.; Giudice, E.M.D.; Capristo, C.; Bandiya, P.; Kamalaratnam, C.N.; Chandramohan, R.; Manerkar, S.; Rodrigo, R.; Sumanasena, S.; Krishnan, V.; Pant, S.; Shankaran, S.; Thayyil, S.
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 gestational age of 39.2 (38.9-40.4) weeks. A total of 1793 significant genes in the HIC cohort and 99 significant genes in the South Asia cohort were associated with adverse outcome (false discovery rate <0.05). Only 11 of these genes were in common, and all had opposite direction in fold change. The most significant pathways associated with adverse outcome were downregulation of eukaryotic translation initiation factor 2 signaling in the HIC cohort (z score = -4.56; P < .001) and aldosterone signaling in epithelial cells in the South Asia cohort (z score = null; P < .001). The genome expression profile of neonates with HIE (n = 35) at birth, 24 hours, 48 hours, and 72 hours remained significantly different from that of age-matched healthy controls in the HIC cohort (n = 14). CONCLUSIONS AND RELEVANCE: This case-control study found that disease mechanisms underlying HIE were primarily associated with acute hypoxia in the HIC cohort and nonacute hypoxia in the South Asia cohort. This finding might explain the lack of hypothermic neuroprotection.
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
(American Medical Association, 2023) Thayyil, S.; Montaldo, P.; Krishnan, V.; Ivain, P.; Pant, S.; Lally, P.J.; Bandiya, P.; Benkappa, N.; Kamalaratnam, C.N.; Chandramohan, R.; Manerkar, S.; Mondkar, J.; Jahan, I.; Moni, S.C.; Shahidullah, M.; Rodrigo, R.; Sumanasena, S.; Sujatha, R.; Burgod, C.; Garegrat, R.; Mazlan, M.; Chettri, I.; Babu, S.P.; Joshi, A.R.; Swamy, R.; Chong, K.; Pressler, R.R.; Bassett, P.; Shankaran, S.
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 = .22). Magnetic resonance data from 267 neonates (80 inborn and 187 outborn) were analyzed. In the hypothermia vs control groups, the mean (SD) thalamic NAA levels were 8.04 (1.98) vs 8.31 (1.13) among inborn neonates (odds ratio [OR], -0.28; 95% CI, -1.62 to 1.07; P = .68) and 8.03 (1.89) vs 7.99 (1.72) among outborn neonates (OR, 0.05; 95% CI, -0.62 to 0.71; P = .89); the median (IQR) thalamic lactate to NAA peak area ratios were 0.13 (0.10-0.20) vs 0.12 (0.09-0.18) among inborn neonates (OR, 1.02; 95% CI, 0.96-1.08; P = .59) and 0.14 (0.11-0.20) vs 0.14 (0.10-0.17) among outborn neonates (OR, 1.03; 95% CI, 0.98-1.09; P = .18). There was no difference in brain injury scores or white matter fractional anisotropy between the hypothermia and control groups among inborn or outborn neonates. Whole-body hypothermia was not associated with reductions in death or disability, either among 123 inborn neonates (hypothermia vs control group: 34 neonates [58.6%] vs 34 [56.7%]; risk ratio, 1.03; 95% CI, 0.76-1.41), or 285 outborn neonates (hypothermia vs control group: 64 neonates [46.7%] vs 60 [43.2%]; risk ratio, 1.08; 95% CI, 0.83-1.41). CONCLUSIONS AND RELEVANCE: In this nested cohort study, whole-body hypothermia was not associated with reductions in brain injury after HIE among neonates in South Asia, irrespective of place of birth. These findings do not support the use of whole-body hypothermia for HIE among neonates in LMICs.