Study Design, Participants, and Settings
This is a retrospective, single-center cohort study conducted in El-Ekhaa specialized hospital, a maternity and children hospital in an area ravaged with military conflict in the North-West of Syria, between July 2020 and July 2021. The hospital is located in the middle of dozens of refugee camps, which accommodate about 600,000 refugees. It offers both in-patient and out-patient pediatric and gynecological services. In addition to antenatal care clinics and performing normal deliveries, the hospital services include instrumental and cesarian deliveries and both major and minor gynecological surgeries. The pediatric services include a 25-bed general inpatient service, a 3-bed pediatric intensive care unit (PICU), in addition to the neonatal intensive care unit (NICU) equipped with 10 incubators and conventional and non-invasive mechanical ventilation devices. The NICU offers a wide range of neonatal services, such as phototherapy, exchange transfusion, and surfactant replacement therapy. The hospital also has an emergency department that serves women's and children's emergencies around the clock. It is an academic and research center in the region that previously published on children's and women's health.(13,14)
Calgary University’s HIE calculator was used to facilitate treatment decisions. (https://play.google.com/store/apps/details?id=com.radsun.hiecalculator&hl=en_CA&gl=US)
Patients were cooled if they were ≥ 35 weeks and a birth weight ≥ 1800 grams with evidence of perinatal depression as indicated by the presence of either one of the following (criteria A):
- PH ≤ 7 or Base Excess ≤ -16 on cord blood gas analysis or one performed within 1 hour after delivery; or
- the need for positive pressure ventilation for ≥10 minutes, or Apgar score ≤ 5 at 10 minutes
With the presence of (criteria B): Hypoxic ischemic encephalopathy (HIE) stage II or III according to modified Sarnat classification (15), or convulsion.
Patients were excluded if they had severe congenital malformations, high oxygen requirement (FiO2 ≥ 90%), or severe coagulopathy with uncontrolled bleeding.
The treating team consists of in-hospital pediatricians with an online consulting team that includes three neonatologists providing around-the-clock coverage, a radiologist, and other pediatric sub-specialists, including a pediatric neurologist, nephrologist, and hematologist.
If a patient is deemed eligible, the case was discussed with the online on-call neonatologist. Detailed maternal and perinatal histories with all available investigations, including the radiographs, were forwarded through a mobile app (Telegram).
When the decision of cooling was made, the passive cooling process was initiated; the radiant warmer was switched off, followed by transferring the patient to an incubator with starting temperature of 30°C. Later, the temperature was adjusted as needed to keep the infant’s core temperature within the target range (33-34 °C). Morphine was administered as an adjunct therapy to decrease pain and achieve better control of the temperature. When available, a rectal probe was used for continuous monitoring of core temperature; otherwise, a skin probe was used for this purpose, with hourly determinations of core (rectal) temperature using a mercury thermometer. In some cases, if the temperature remained out of range, further measures were taken, including ice bags and adjusting room temperature.
Laboratory investigations performed on all infants included CBC (Complete Blood Count), hepatic and renal function tests, PT (Prothrombin Time), aPTT (activated partial thromboplastin time), and CRP (C-Reactive Protein). Blood cultures were not performed in any of these infants due to unavailability. However, empiric antibiotics (ampicillin and cefotaxime) were used in all of them due to the tentative diagnosis of “clinical sepsis” and were upgraded in case of clinical deterioration.
Videos of the baby upon admission and later, if he developed convulsion or any abnormal movement, were recorded and forwarded to the neonatologist and pediatric neurologist through the mobile application (Telegram). Plans for treating the convulsions and the duration of the anticonvulsant therapy were discussed with the pediatric neurologist. Brain CT (computerized tomography) or MRI (magnetic resonance imaging) scans were also sent to the radiologist for reading through telemedicine.
Age at the consultation requested, time for the neonatologist’s response, and the time-lapse between the referral and the point of cooling initiation were recorded.
Short-term outcomes include duration of respiratory support, time to reach full feeding, and survival to discharge. All cases were given an appointment for follow-up in the pediatric clinic.
We performed descriptive statistics on the total cohort of patients without stratification. Analysis was performed using Excel software (Microsoft Company, Seattle, WA, USA). As the data were non-normally distributed, we reported numerical variables as median and interquartile ranges. Categorical variables were reported as percentages. No meaningful comparisons within the cohort were possible due to the small sample size.