Eight-year follow-up

Every attempt was made to find children from the original trial using location data from previous follow-up. The follow-up study was powered at 81% to detect a difference of 0.2 standard deviation scores between allocation groups, with a sample size of 400 per group, at 5% significance. Thus, we aimed to re-measure >800 of the original sample.

Anthropometry was measured according to ICH guidelines, adapted from Lohman and colleagues [24] and the WHO Multi-Centre Growth Reference Study [25]. Standing height was measured in duplicate barefoot, with head in the Frankfort plane (Leicester stadiometer, Invicta Plastics, UK), accurate to 0.1 cm. Sitting height was measured in duplicate using a custom-made stool, with base of the spine touching the stadiometer and head in the Frankfort plane. Leg length was calculated as the difference between sitting height and height. Relative leg length was calculated as (leg length/height). Girths of the head, mid-upper arm, chest, waist, hip and mid-upper arm were measured in duplicate using a non-stretchable tape.

Weight and body composition were measured using a Tanita BC-418 scale (Tanita Corp, Japan) accurate to 0.1 kg. Children wore standardised clothing weighing 200 g. Raw impedance was converted to body composition values using a sample-specific isotope-calibration study [26]. Body mass index (BMI) was calculated as weight/height [2], and weight, height and BMI z-scores calculated using WHO reference data [25]. Skinfold thicknesses at biceps, triceps, subscapular and suprailiac sites were measured in triplicate using a Harpenden calliper (Assist Creative Resource, Wrexham, UK), accurate to 0.2 mm.

Blood pressure was measured with an Omron M6 electronic monitor (Omron Healthcare Ltd, Japan) with paediatric or adult cuff as required. Measurements followed GOSH guidelines [27]. Blood pressure was recorded after the child had been seated for ≥1 min with legs uncrossed. Two readings were taken one minute apart, with the cuff deflated fully between them. The lowest value was recorded.

Ultrasound measurements of kidney size were taken by a local clinician trained in ultrasonography (Aloka SDD-500 instrumentation, 2–8 MHz convex probe, Aloka Co ltd, Japan), accurate to 1 mm. Maximum renal length and antero-posterior diameter were recorded, ensuring the sinus and parenchyma were visualised using predefined landmarks. Technical error of the mean (TEM) values, calculated from repeat measurements in a 5% subsample, were 0.21 cm (2.6%) and 0.16 cm (1.9%) for right and left kidney lengths, respectively, and 0.14 cm (4.7%) and 0.19 cm (5.7%) for the right and left kidney antero-posterior diameters. There was no systematic bias between first/second measurements.

Lung function was measured using two EasyOne World Spirometers (ndd Medical, Zurich, Switzerland), auto-calibrated before use and alternated fortnightly. American Thoracic Society/European Respiratory Society quality control criteria for spirometry [28], adapted for use in children [29], were used. Parents were requested to bring their children for assessment only if they were well. Three local investigators were trained to conduct spirometry tests. The child performed spirometry wearing a nose clip while seated. All spirographs were interpreted by a clinician (DD) and one in ten over-read by a respiratory physiologist.

Children in whom an illness was suspected were referred to a local paediatrician for more detailed investigation if required, for which the costs were covered. Children whose weight-for-height was <−2 SD or BMI-for-age was <−3 were referred to a local nutrition centre. All children were given a T-shirt, refreshments, and a voucher to be seen by a local paediatrician, external to the research team, with the costs of minor acute treatments covered.