Table 3.

Detailed description of collected data and measurements in the BILD cohort during Phases 1 and 2

Data collection from hospital records, questionnaires and telephone interviews	Study Phase 1 (pregnancy until age 1 year)	Study Phase 2 (age 1 year until age 6 years)
General health condition	Source: hospital records  Maternal warning signs during delivery   Amount, quality of amniotic fluid, aspiration of amniotic fluid, colour of amniotic fluid (meconium)   Weight and quality of placenta   Premature rupture of membranes   Infection, antibiotics, chorioamnionitis  Perinatal warning signs   Apgar score   Apnoea, tachypnea, bradycardia, cyanosis, expiratory groaning, signs of dyspnea, bradycardia, abnormality cardiotocogram   pH measured in blood from umbilical vein and artery, acidosis or alkalosis	Source: Questionnaires 2 and 3  Common colds, infections (especially upper and lower respiratory tract, ear, nose, throat), number and duration  Atopic rhinitis or conjunctivitis, seasonality of symptoms, months of occurrence, effect of symptoms on indoor and outdoor activities, hay fever  Asthma, severity; triggers, number and severity of attacks; nocturnal/diurnal, doctor-diagnosed asthma,  Atopic dermatitis  Behavioural problems, enuresis (primary, secondary, diurnal, nocturnal)  Medication, paracetamol 12 months prior to follow-up  Level and impairment of indoor and outdoor activity, type of activity, indoor swimming  Medications 12 months prior to follow-up, alternative medications and remedies used
Respiratory symptoms	Source: weekly telephone interviews during first year of life52,53	Source: Questionnaires 2 and 3
	Respiratory symptoms (including cough and wheeze during day and night, difficulty breathing, feeding difficulties, reduced activity)  Using standardized score to group symptoms into four levels according to severity and with high sensitivity for lower respiratory-tract infections  Main outcome parameter: weeks with severe respiratory symptoms (defined as total number of weeks with day or night score of ≥353	Cough, type of cough, cough without infection, triggers of cough, cough severity, subjective assessment of first time of cough, last time of cough, duration free of cough during 12 months prior to follow-up, seasonality of cough, months of occurrence  Audible wheeze, triggers of wheeze, nocturnal, diurnal, subjective assessment of first time of wheeze, last time of wheeze, seasonality of wheeze, months of occurrence  Rales or rhonchi, triggers of rales, rhonchi, nocturnal, diurnal  Snoring, sleep disturbance, tonsillectomy
Environmental exposures	Source: Questionnaire 1, weekly telephone interviews during first year of life52,53	Source: Questionnaires 2 and 3
	Pets and exact type of pet at home, during/after pregnancy  Pets given away due to allergy/atopy in family  Farming exposure, animal type  Traffic exposure at home (trucks)  Type of heating, type of stove, chimney, open fire place  Sleeping environment child (mattress, encasement, sheepskin rug use)  Damage due to damp at home, assessment of exposure to mould  Maternal active or passive smoking, ETS exposure, number of cigarettes, smoking cessation, coffee/tee and number of cups, caffeine containing soft drinks, vitamin supplement intake, fruit intake, antibiotics, steroid treatment, respiratory infections, gastrointestinal infections, urinary tract infections, vaginitis, colpitis, worm infections, other infections during pregnancy and during first year of life  Paternal active smoking, number of cigarettes, smoking cessation during pregnancy and first year of life	Pets and exact type of pet at home  Pets given away due to allergy/atopy in family  Farming exposure, animal type  Traffic exposure at home (trucks)  Type of heating, type of stove, chimney, open fire place  Living conditions (type of dwelling, rural/urban, number of rooms, number of people in household)  Diet (fruit, vegetables, sweets, chocolate, fast food, snacks, unpasteurized milk)  Maternal active or passive smoking, ETS exposure, number of cigarettes, smoking cessation until first major follow-up at the age of 6 years  Maternal and paternal active or passive smoking, number of cigarettes, smoking cessation until first major follow-up at the age of 6 years

Objective measurements	Study Phase 1 (pregnancy until age 1 year)	Study Phase 2 (age 1 year until age 6 years)
Measurements of lung function and inflammation of airways	Tidal breathing measurements12,50   Unsedated infants, during quiet natural sleep   Ultrasonic flowmeter (Spiroson®, EcoMedics AG, Duernten, Switzerland) with infant face mask   Main outcome parameters: minute ventilation (tidal volume multiplied by respiratory rate) and expiratory flow   Measurement of fraction of exhaled nitric oxide (FeNO)53   Rapid-response chemoluminescence analyzer (CLD 88, EcoMedics AG, Duernten, Switzerland), with a range of 0–100 parts per billion (ppb), infant face mask   Breath-by-breath measurement   Main outcome parameter: mean FeNO  Multiple Breath Washouts (Sulfurhexafluoride)32   Ultrasonic flowmeter (see above), infant face mask   Main outcome parameters: lung volume (FRC) and ventilation inhomogeneity (LCI)  Interrupter resistance measurement   Ultrasonic flowmeter (see above), shutter box, infant face mask   Main outcome parameter: Rint  Anthropometric data at study date: body weight and length, head circumference	Tidal breathing measurements   Quiet tidal breathing   Ultrasonic flowmeter (see left) with mouth-piece, filter and nasal clamp   Main outcome parameters: minute ventilation (tidal volume multiplied by respiratory rate) and expiratory flow   Measurement of FeNO53   Rapid-response chemoluminescence analyzer (CLD 88, EcoMedics AG, Duernten, Switzerland), with a range of 0–100 ppb   Breath-by-breath measurement and single-breath manoeuvre, no nasal clamp   Main outcome parameter: mean FeNO  Multiple Breath Washouts (Helium)   Ultrasonic flowmeter (see above), nasal clamp   Main outcome parameters: lung volume (FRC) and ventilation inhomogeneity (LCI)  Interrupter resistance measurement   Ultrasonic flowmeter (see above), nasal clamp   Main outcome parameter: Rint  Spirometry (bodyplethysmography)   MasterScreen Body, Jaeger, Germany; mouthpiece, filter, nasal clamp   Main outcome parameters: lung volume (FRC, intrathoracic gas volume), forced expiratory flows and volumes  Anthropometric data at study date: body weight and length
Skin-prick test	Maternal skin-prick test	Child skin-prick test
	Dog dander, cat dander, Dermatophagoides pteronyssinus, mixed tree pollens, mixed grass pollens, Alternaria tenuis, positive control (histamine), negative control (NaCl), Allergomed, Switzerland	Dog dander, Cat dander, Dermatophagoides pteronyssinus, mixed tree pollens, mixed grass pollens, Alternaria tenuis, positive control (histamine), negative control (NaCl), Allergomed, Switzerland
Immunology	Specimen: cord blood
	Haematocrite, haemoglobin count, white blood cell count, leucocyte subtypes   Total IgE, eosinophil cationic protein, eosinophil protein X, interleukin subtypes, interferon subtypes   Mannose-binding lectin (MBL) measured as described previously with commercially available ELISA kits (Antibodyshop, Gentofte, Denmark)60
Microbiology	Specimen: anterior nasal swabs
	Taken at any first acute respiratory infection, which is defined as >2 days with cough or wheeze, together with fever >38°C, acute rhinitis, otitis media or pharyngitis; specimens are analysed by polymerase chain reaction (PCR) based assays, e.g. Taqman real-time PCR, targeting 16 different respiratory viruses commonly infecting humans54,60
Genetics	deoxyribonucleic acid (DNA) extraction from white blood cells from cord blood	DNA extraction from mucosa cells retrieved per buccal swabs or from saliva collection
	Analysis of single nucleotide polymorphisms (SNPs)   Analysis of copy number variants in genes involved in lung growth per DNA chip analysis	Analysis of SNPs and   Analysis of copy number variants in genes involved in lung growth per DNA chip analysis
ETS and caffeine	Specimen: first urine after birth and urine during first lower respiratory-tract infection
	Nicotine and cotinine   Caffeine
Air pollution at community level	Swiss National Air Pollution Monitoring Network (Nationales Beobachtungsnetz für Luftfremdstoffe, NABEL) measurement sites12   Daily mean levels of particulate matter with aerodynamic diameter of <10 µm (PM10)   Daily mean levels of nitrogen dioxide (NO2)   Daily maximum of mean hourly levels of ozone (O3)  Stationary passive samplers (Palmes Tubes) at measurement sites: daily mean levels of NO2	Swiss NABEL measurement sites12   Daily mean levels of PM10   Daily mean levels of NO2   Daily maximum of mean hourly levels of O3  Stationary passive samplers (Palmes Tubes) at measurement sites: daily mean levels of NO2
Air pollution at individual level	Mobile passive samplers: daily mean levels of PM2.5 and PM10  Stationary passive samplers (Palmes Tubes) at study participants’ homes: daily mean levels of NO2	Mobile passive samplers: daily mean levels of PM2.5 and PM10  Stationary passive samplers (Palmes Tubes) at study participants’ homes: daily mean levels of NO2

Extraction of routine data

Study Phases 1–2 (until age 6 years)

Sources: Questionnaires 1–3, telephone  interviews

Study participant: name, gender, date of birth, maternity hospital, gestational age, birth weight, birth length, multiple birth, birth order, vaccinations Feeding (breastfed, gastroesophageal reflux, hypoallergenic supplement), supplementary alimentation, later diet Maternal and paternal hay fever, atopic dermatitis, asthma, therapy due to asthma or difficulty breathing Demographic and socio-economic information: mother and father: names, birth dates, occupation throughout study, nationality, religion, country of birth and language, all home addresses from pregnancy throughout study Families’ paediatrician name and address as well as of general practitioner, family history