Bibian van der Voorn

108 CHAPTER 8 METHODS STUDY POPULATION This study was part of the Project on Preterm and Small-for-Gestational-Age (POPS) study that recruited in 1983 at birth 94% (n=1,338) of all live born very preterm (GA <32 wks) and/or very low birth weight (<1,500 g) neonates in the Netherlands. The aim of this nationwide, multicenter, prospective follow-up study was to investigate causes of mortality and morbidity among this group 18 . The flowchart in figure 1 represents the stepwise inclusion of subjects from the POPS birth cohort for the present study. All subjects of the POPS birth cohort, born <32wks GA n=1,012 Who survived n=676 Who attended the follow-up at 19yrs of age n=422 Of whom the GR and MR genotype was known n=344 FIGURE 1. Flowchart of the inclusion procedure. Responders and non-responders at age 19 did not differ in the perinatal risk factors small for gestational age (SGA) and mechanical ventilation to men, non-whites and subjects born to low-educated mothers were underrepresented 19 . Approval of the medical ethical committees of all participating centers was obtained, as well as written informed consent from all participants. GLUCOCORTICOID TREATMENT Seventy-one subjects had received antenatal glucocorticoid treatment. The antenatal glucocorticoid treatment protocol at that time consisted of two doses, with a 24-h interval, of 12 mg betamethasone. It is acknowledged that the side effects of a therapy can be studied with an observational study as reliably as with a randomized controlled trial, provided that these cannot be predicted from clinical data at the time of prescription 20 . In analogy, for the POPS study we have previously argued 21 that it is plausible that the limited knowledge in 1983 about long-term neurobiological side effects of antenatal glucocorticoid treatment precluded obstetricians from guiding their decisions by relevant prognostic data (e.g., level of parental education). Postnatal glucocorticoid treatment had been given to 3 subjects who had also received glucocorticoids antenatally and to 27 subjects who had not received antenatal treatment.