Study setting
The Neonatology Section with 40 ventilated NICU beds is considered the largest section in the Pediatric Department at KAMC. It provides a high standard of care for high risk newborn infants free of charge. Neonatal services consist of the care in NICU, and can accommodate up to 40 beds (LEVEL III) and 30 beds in ICN (LEVEL II). Admission Nursery can accommodate up to 50 beds, all operated with full capacity. The NICU accepts 23 weeks gestation to term infants requiring level II and III specialized care. The Neonatal Team consists of six consultants, two assistant consultants, ten staff physicians, two Perinatal-Neonatal fellows, and three rotating pediatrics residents. A total of 140 NICU well trained and skilful nurses are available, with a nurse to patient ratio of 1:1–2. It provides a family-centered approach to care; encompassing the parents and the sick infant as a single unit.
Study subjects
All extremely low birthweight neonates (< 1000 g) who were admitted to the neonatal unit of the KAMC, within 3 years between January 1st, 2005 and December 31st, 2007, constituted the target of this study (n = 117). These children were identified from the obstetric and delivery logbook of the maternity unit. Patients’ charts were retrieved and data on maternal and neonatal demographics, clinical course and outcome (status at discharge from the unit) was extracted.
All these children were contacted to follow them up yearly till the age of six. A research coordinator was allocated for the follow up of cases via home visits in case of drop out. Every child was followed up twice by both a developmental pediatrician and a psychologist, in prescheduled visits, within the age of 3 to 6 years.
Study design
This is a retrospective/prospective cohort study. This approach is useful for exposures that have both short term and long term outcomes. It includes exposure baseline in the past (extremely low birth weight), and a follow up period (past to present to future). Data collection went in both directions. We looked through records for birth event and started to follow up these infants into the future for neurological, cognitive and educational outcomes at different ages till the age of six.
Data collection and variables
Retrospective phase
A data collection sheet was used to collect the following data:
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1.
Maternal reasons for the prematurity; preeclampsia, intrauterine growth restriction, preterm labor, premature rupture of membranes, or multi-fetal pregnancy (multiple gestation), previous pregnancy losses, previous preterm delivery, antepartum hemorrhage and anemia.
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2.
Neonatal interventions, such as; the use of antenatal corticosteroids for women at risk for preterm delivery, surfactant for the prevention and treatment of neonatal respiratory distress syndrome, postnatal steroids for chronic lung disease (CLD), and modes of respiratory support for neonates with respiratory distress (conventional ventilation, high frequency ventilation, any assisted ventilation, nasal CAPA), and red cell transfusions [5].
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3.
Demographic and birth data: Gestational age (< 27 weeks vs > 27 weeks), based on the date of the last menstrual period and confirmed with ultra-sonographic findings, gender, multiple birth, weight (between 450 and 600 g and 801-995 g), presentation (vertex or non-vertex), 5 min Apgar, and mode of delivery (SVD vs LSCS)
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4.
Outcome in terms of: death at discharge and neonatal morbidity including pneumothorax; respiratory distress, defined as the need for oxygen therapy; chronic lung disease, defined as an oxygen dependency at 36 weeks; patent ductus arteriosus, confirmed with echocardiography; episodes of sepsis, defined as clinical signs of infection with a positive blood culture; necrotizing enterocolitis (NEC); intraventricular hemorrhage (IVH) and peri-ventricular leukomalacia (PVL).
Prospective phase
Surviving children were assessed at 3 and 6 years of age, corrected for prematurity, by a developmental pediatrician and a psychologist. Neurological (neurosensory impairments and disabilities), cognitive, and educational outcomes were measured for children according to their current ages.
The pediatric assessment includes a neurological examination to determine outcomes such as cerebral palsy. Visual acuity was assessed by an optometrist. Modified Denver Developmental Screening test (DDST) for Arab Children [17] was used for assessment of developmental delay. Every child was assessed for the 4 areas of development (gross motor, fine motor/adaptive, personal/social, and language). For each area of development, if the developmental age achieved by the child is equal to the actual age, then he/she is considered normal, if exceeds the actual age, he/she is advanced, and if below the actual age, he/she is developmentally delayed. Developmental quotient (DQ) was estimated accordingly [17].
Children were considered blind if visual acuity in both eyes is assessed as worse than 6/60. Children were usually screened for major hearing loss at birth by auditory brain stem response (ABR), and at 7–8 months of corrected age by distraction testing with calibrated noise makers. Those who had not been screened or those with suspected deafness or delayed language at 2 years of age were referred again for audiological assessment.
The psychological assessment includes standardized assessments of cognitive ability, educational progress, and behavior problems. Wechsler Intelligence Scale for Children-Revised (WISC-R) [18] was applied for all ELBW children at the age of six. An Arabic, previously validated version of the scale was used [19]. Children were classified based on the IQ range into: very super (130 and above), super (120–129), high average (110–119), average (90–109), low average (80–89), borderline or slow learner (70–79), mild (55–69), moderate (40–54), and severe intellectual disability (25–39). Figure 1 is a flowchart showing the follow up process of ELBW infants.
The approval of the IRB of the Ministry of National Guard-Health Affairs was obtained to conduct the NICU review (Ref. # RC09/079). Consent to participate was obtained verbally from the parents/guardians of the child participants. Obtaining verbal consent was approved by the IRB.
Statistical analysis
Demographics and clinical characteristics were summarized and reported for the study cohort. Continuous variables such as; age, weight at birth, GA, etc. were summarized and reported in terms of measures of central tendency (mean and median) as well as measures of variability (i.e. Standard deviation). Categorical variables such as; age gender, etc. were summarized and reported in terms of frequency and proportions. All demographics and clinical characteristics were compared across the study groups using t-test or Chi-square test for continuous and categorical variables, respectively. All results were reported in terms of difference in proportions and means, with corresponding 95% confidence intervals (CI) and P-values. All two-way interactions between explanatory variables were tested and found to be non-significant. To test birthweight and GA as predictors of death among ELBW group, a logistic regression model was applied, adjusting for sex, mode of delivery and 5 min Apgar score, and the results were summarized in terms of odds ratios and their corresponding 95% CI. Significance was considered at p ≤ 0.05.