Long-term effects of an intensive care admission during childhood

Approved 18/10/2024, Ethics Committee Research UZ/KU Leuven (Herestraat 49, Leuven, 3000, Belgium; +32 (0)16 34 86 00; ec@uzleuven.be), ref: S69234

1. Clinical assessment of growth (measured height and body weight, calculated BMI, total body fat mass and total body muscle mass as measured via dual-energy X-ray absorption [DEXA] scan) at 12-year follow-up
2. The developmental stage of puberty at 12-year follow-up, as based on interrogation of Tanner stages with the use of a sex-specific questionnaire

All outcomes are measured at the 12-year follow-up:
1. Health status: diagnosis of a somatic illness, diagnosis of a psychiatric illness, and incidence of hospital admission for medical, surgical or psychiatric reasons during the past 12 years for participants in the control group or during the 12 years following admission to the PICU for PEPaNIC participants. Measured by a structured interview with the parents or caregivers, and/or the participants if competent and old enough.
2. Additional measures of physical growth: measurement of leg length and sitting height, and calculation of the proportion of leg length over total height and sitting height ratio at 12-year follow-up.
3. Additional measures of body composition:
3.1. Total bone mass and localised (arms, legs, and trunk) bone mass, fat mass and lean tissue mass measured via dual-energy X-ray absorption (DEXA) scan at 12-year follow-up
3.2. Surrogate markers of body composition (waist circumference as a measure of central adiposity/obesity, skinfold thickness as a measure of subcutaneous body fat at the triceps and subscapular level (allowing estimation of body fat with the use of the Slaughter equation), a combination of mid-upper arm circumference and triceps skinfold as a marker of muscle mass.
4. Additional measures of pubertal and further development:
With the use of sex-specific questionnaires on pubertal development also interrogates other aspects of puberty development and the time of reaching specific a priori defined stages:
4.1. Development of axillary hair
4.2. Acne
4.3. Menarche
4.4. Growth of facial hair
4.5. First ejaculation of semen
4.6. Voice break
5. During the interrogation of medical history related to the occurrence of somatic illness or hospital admission, health conditions or previous therapies will be documented, including those that may interfere with pubertal development.
6. Where possible, the researchers also aim to evaluate the next crucial developmental stage going in the direction of measures of reproductive health/fertility:
6.1. Female participants will be asked about the heaviness and regularity of their menstruation/menstrual cycle
6.2. For male participants, serum inhibin B levels will be quantified as marker of the level of spermatogenesis, providing a valuable alternative for sperm sample analysis.
7. Biological parents of the participants will be interrogated regarding timing of their pubertal development (“normal”, “delayed” or “precocious” for the father; age menarche for the mother).
8. Bone age as determined by hand X-ray at 12-year follow-up
9. Cardiometabolic risk factors: systolic and diastolic blood pressure, glycated haemoglobin (HbA1c), insulin, glucose, high-molecular-weight adiponectin, leptin, triglycerides, LDL- and HDL-cholesterol at 12-year follow-up
10. Physical activity: daily physical activity assessed with an activity-tracking device (Actigraph accelerometer), measured for 7 days following the 12-year follow-up appointment.
11. Neurocognitive functioning at 12-year follow-up:
11.1. General intelligence measured using the Wechsler Intelligence Scale for Children or Adults
11.2. Visuo-motor integration measured using the Beery-Buktenica Developmental Test of Visual-Motor Integration
11.3. Attention and executive functions measured using the computerised tasks of the Amsterdam Neuropsychological Tasks system
11.4. Immediate and delayed verbal-auditory and visual memory measured using Children/Wechsler Memory Scales
11.5. Executive functioning measured using the Behaviour Rating Inventory of Executive Function questionnaire, with use of different informant-specific versions (parents/caregivers or participant self-report)
12. Emotional and behavioural problems will be assessed with internationally recognised and validated questionnaires:
12.1. Child Behaviour Checklist (CBCL) or Adult Behaviour Checklist (ABCL) to be completed by the parents/caregivers
12.2. Youth (YSR) or Adult Self Report (ASR) to be completed by the participants if competent
13. Daily life impact:
13.1. Interrogation of the participants’ school participation, highest level of education and/or employment status, leisure-time spending, ability to participate in social roles and activities, relationships, and use of follow-up services (semi-structured interview combined with PROMIS ability to participate in social roles and activities questionnaire items).
13.2. Subjective evaluation of physical, emotional, and social functioning of the participants in daily life: health-related quality-of-life questionnaires. For participants up to 17 years, the PROMIS Short Forms will be used.