Parents' Views on Prolonged Maternal Hospital Stay With Sick Newborn Infants in a Tertiary Neonatal Unit in Sri Lanka.

BACKGROUND: Mothers of infants in most Sri Lankan neonatal units are required to be "inpatients" during the entirety of their infant's stay. This traditional practice is closely aligned to the relatively newer model of family-integrated care. PURPOSE: Exploration of parent's views regarding the expectation for mothers to remain in hospital for the entire duration of their infant's neonatal unit stay. METHODS: Cross-sectional study of parents of infants admitted to the University neonatal unit of Colombo North Teaching Hospital, Ragama, Sri Lanka, using self-administered questionnaires in 2017. RESULTS: We found that 40% (19/48) of mothers and 43% (16/37) of fathers preferred that mothers traveled from home, rather than being inpatients continuously, in order to care for older children, receive psychological support from family, and also due to other practical inconveniences of living in the hospital. The main barriers to women being able to travel from home were the need to safely provide expressed human milk for their hospitalized infants and current hospital administrative and societal attitudes. IMPLICATIONS FOR PRACTICE AND RESEARCH: We found that a considerable number of parents with infants in the neonatal intensive care unit in Sri Lanka would like the option of the mother being able travel from home, rather than being confined to hospital. To facilitate this option, changes in hospital protocols and further research into storage and transportation of expressed mother's milk will be required. Improving facilities in hospital and providing more opportunities for families to interact with infants in neonatal intensive care unit will encourage mothers to remain in hospital continuously.

Whole-Blood Gene Expression Profile After Hypoxic-Ischemic Encephalopathy.

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.

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.

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.

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.

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. Trial Registration: ClinicalTrials.gov Identifier: NCT02387385.

Milky pleural effusion in a neonate and approach to investigating chylothorax.

Neonatal chylothorax is a rare presentation leading to significant respiratory distress, thus requiring timely diagnosis. A preterm neonate was resuscitated and ventilated, following which she clinically improved but subsequently developed respiratory distress with a right-sided pleural effusion. Interestingly, thoracentesis fluid appeared 'milky' with elevated triglycerides and lymphocytes, suggesting chylothorax. As fluid triglyceride level was lower than the established diagnostic criterion for chylothorax (1.24 mmol/L), a high fluid-to-serum triglyceride ratio was used as a surrogate diagnostic marker, later confirmed by lipoprotein electrophoresis. As observed in the index patient, a critically ill neonate would have a lower-than-average fat intake leading to less chylomicron production, thus lower triglyceride levels in chyle than expected, which may still fail to meet the amended cut-off limit. This case highlights the challenges in diagnosing neonatal chylothorax due to the lack of age-specific triglyceride levels in chyle and low oral fat intake in critically ill patients.

Bacterial Growth in Expressed Mother's Milk Stored and Transported Under Different Simulated Conditions in a Tropical Country.

Background: Research on how storage and transport of expressed human milk in a tropical country affect the milk bacterial count is limited. Materials and Methods: A cross-sectional descriptive study of 50 mothers of infants in a Sri Lankan tertiary neonatal unit was performed. Expressed mother's milk was divided into three bottles and kept under varied environmental conditions to simulate different storage and transport methods. Initial bacterial culture of milk was performed <30 minutes after expression, with further cultures at predetermined times. Bottles A and B were stored at room temperature and in a cool bag for the first 6 hours, respectively, and then refrigerated; and bottle C was refrigerated for 24 hours, transported in a cool bag for 6 hours, and rerefrigerated until 72 hours. Total colony counts >105 colony-forming units (CFU)/mL of viable microorganisms or >104 CFU/mL of either Enterobacteriaceae or Staphylococcus aureus were considered positive. Results: Initial culture was positive in 30% (15/50) of samples; majority, 87% (13/15), of these were S. aureus. For bottle A, 26% (13/50), 36% (18/50), 34% (17/50), and 26% (13/50) of samples were positive at 4, 6, 24, and 72 hours, respectively. For bottle B, positive cultures were found in 26% (13/50) and 17% (8/47) of samples at 24 and 72 hours, respectively. For bottle C, results were similar to bottle B. Conclusions: Transportation of expressed mother's milk for 4 hours in a tropical climate using a low-cost cool bag, with refrigeration at other times, maintained acceptable bacterial counts for up to 72 hours after expression. Hygienic practices at collection are extremely important as most samples with significant bacterial growth were positive on initial culture.

Human Milk Expression, Storage, and Transport by Women Whose Infants Are Inpatients at a Tertiary Neonatal Unit in Melbourne, Australia: An Exploratory Study.

BACKGROUND: Expression and storage of mothers' own milk at home and its transportation to hospital neonatal units are a common practice worldwide when newborns are inpatients. Studies assessing adherence to hospital protocols and guidelines for this are not widely published. PURPOSE: To explore the advice received and practices followed by mothers when expressing, storing, and transporting their milk from home to the hospital, with a substudy exploring the factors related to temperature maintenance of refrigerated milk at recommended values. METHODS: Cross-sectional descriptive study at the neonatal intensive care unit of Mercy Hospital for Women, Melbourne, Australia. Mothers who were discharged home after birth of the infant, but whose infant(s) remained in the neonatal unit for 7 days or more participated. All participants completed a self-administered questionnaire. In the substudy, home refrigerator temperature and surface temperature of milk on arrival to the hospital were recorded. RESULTS: The questionnaire was completed by 100 mothers; 38 participated in the substudy. Median travel time from home to the hospital was 32 minutes (range, 2-135 minutes). Lactation consultants were the largest group providing information, with 44 participants (45%) identifying them as the primary information source. Knowledge about recommended refrigerator storage times for expressed milk was correct in 53 mothers (54%). Coolness of milk was better maintained when transported in an insulated food container than nonuse (surface temperature: mean 9.1°C vs 12.2°C; P = .007). Distance and travel duration were not correlated with temperature. IMPLICATIONS FOR PRACTICE: More diligent monitoring of conditions under which mothers' own milk is transported to hospital is required, and the use of an insulated food container for refrigerated/frozen milk, even for a short duration, should be strongly recommended. Staff to be trained and better equipped to provide uniform, concise information on expressed human milk management to mothers. IMPLICATIONS FOR RESEARCH: Further research to correlate factors associated with transporting human milk expressed at home and infant health outcome is needed.

Maternal Perception of Adequacy of Mother's Milk Among Mothers Giving Birth at a Teaching Hospital in Sri Lanka.

BACKGROUND:: Sri Lanka boasts high rates of early and exclusive breastfeeding. Perceived inadequacy of milk, a global problem, is the main cause for early cessation of breastfeeding. RESEARCH AIMS:: The aims of this study are to (a) determine the prevalence, (b) identify the risk factors, and (c) ascertain the association that maternal psychological distress has with perceived inadequacy of milk (PIM), among mothers during the early postpartum period. Identifying and addressing modifiable risk factors for PIM may improve mothers' satisfaction with breastfeeding. METHODS:: A cross-sectional descriptive study of mothers ( n = 249) during the first week after birth was conducted at Colombo North Teaching Hospital (Ragama, Sri Lanka) from May 1, 2016, to June 10, 2016. Participants were recruited when the infant was more than 24 hours but less than 7 days old. A self-administered questionnaire, including the six-item Kessler Psychological Distress Scale, was used. RESULTS:: The majority of mothers (78%) perceived their milk quantity to be adequate. A family member telling mothers that their milk supply was low had the most significant associations with perceived inadequacy. Other associations were antenatal maternal complications and birth by cesarean section. Kessler scores indicating psychological distress occurred in 26% of all participating mothers, with a higher mean score in those with PIM. CONCLUSIONS:: Sri Lankan family members should be educated further about normal patterns of milk production during the postpartum period. The authors recommend that PIM be included in screening tools for postpartum depression in Sri Lanka.

Review of guidelines on expression, storage and transport of breast milk for infants in hospital, to guide formulation of such recommendations in Sri Lanka.

BACKGROUND: Sick newborns in neonatal units who are unable to breastfeed are fed expressed breast milk. In Sri Lanka, most mothers stay in hospital throughout baby's stay to provide this milk freshly. In other countries mothers go home, express breast milk at home and bring it to hospital. There are concerns about the safety of transported expressed milk if used in a tropical middle-income country. The aim of this paper is to compare and contrast advice offered by different hospitals and organizations on how to express, store and transport breast milk safely. METHODS: We assessed guidelines used by hospital staff of the four Level 3 neonatal units in Melbourne, Australia, National Health Service UK, guidelines and training manuals of the Human Milk Banking Association of North America, the World Health Organization and an information leaflet from Family Health Bureau, Sri Lanka. Information on breast milk expression, storage and transport provided by the guidelines were tabulated under seven topics: general information; container for milk collection; hand expression; using a pump for expression; storage; thawing / warming; and transport of expressed breast milk. The AGREE II tool was used to assess the guidelines written for hospital staff. RESULTS: There was considerable agreement on most recommendations provided by these sources, but no single source covered all topics in full. Most recommend hand expression as the initial method for expressing of breast milk, followed by breast pump use, except the Sri Lankan recommendations which strongly discourages the use of breast pumps. Durations of storage under various conditions are generally similar in the different recommendations. Most guidelines recommend a 'cool box' or container with ice or freezer packs for transportation of milk. CONCLUSION: A single document containing recommendations on all aspects of expressing, storing and transporting breast milk should be available for each unit, with the same basic information for mothers and the healthcare staff and further technical details for staff if required. The Sri Lankan recommendations need to be updated based on current worldwide practices and further studies are needed to establish a safe method of transport of expressed breast milk in Sri Lanka.

Hypothermia for encephalopathy in low and middle-income countries (HELIX): study protocol for a randomised controlled trial.

BACKGROUND: Therapeutic hypothermia reduces death and disability after moderate or severe neonatal encephalopathy in high-income countries and is used as standard therapy in these settings. However, the safety and efficacy of cooling therapy in low- and middle-income countries (LMICs), where 99% of the disease burden occurs, remains unclear. We will examine whether whole body cooling reduces death or neurodisability at 18-22 months after neonatal encephalopathy, in LMICs. METHODS: We will randomly allocate 408 term or near-term babies (aged ≤ 6 h) with moderate or severe neonatal encephalopathy admitted to public sector neonatal units in LMIC countries (India, Bangladesh or Sri Lanka), to either usual care alone or whole-body cooling with usual care. Babies allocated to the cooling arm will have core body temperature maintained at 33.5 °C using a servo-controlled cooling device for 72 h, followed by re-warming at 0.5 °C per hour. All babies will have detailed infection screening at the time of recruitment and 3 Telsa cerebral magnetic resonance imaging and spectroscopy at 1-2 weeks after birth. Our primary endpoint is death or moderate or severe disability at the age of 18 months. DISCUSSION: Upon completion, HELIX will be the largest cooling trial in neonatal encephalopathy and will provide a definitive answer regarding the safety and efficacy of cooling therapy for neonatal encephalopathy in LMICs. The trial will also provide important data about the influence of co-existent perinatal infection on the efficacy of hypothermic neuroprotection. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02387385 . Registered on 27 February 2015.