SUPPLEMENTARY ONLINE MATERIAL
APPENDIX 1 HEALTH OUTCOMES AT AGE FOUR
Health outcomes refer to the following specific questions asked at age four:
Wheeze - “Has your child had wheezing or whistling in the chest in the last 12 months?”;Doctor
diagnosed asthma – “Did a doctor diagnose asthma in your child in the last 12 months?”; Dry cough at
night without cold – “Has your child ever had cough during the night, when she/he did not have a cold or
an infection in the chest in the last 12 months?”; Doctor diagnosed bronchitis – “Did a doctor diagnose
bronchitis in your child in the last 12 months?”; Ear, nose throat (E,N,T) infections – Did your child have
3 or more serious respiratory - and/or throat-, nose,- ear infections, such as cold, infection of the throat,
infection of the middle ear, sinusitis, bronchitis or pneumonia in the last 12 months?”; Doctor diagnosed
influenza – “Did a doctor diagnose flu or serious cold in your child in the last 12 months?” Itchy rash –
“Has your child had an itchy rash which was coming and going in the last 12 months?”; Doctor diagnosed
eczema – “Did a doctor ever diagnose eczema in your child?”
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APPENDIX 2 HEALTH OUTCOMES EVER
Health outcomes refer to the following specific questions: Wheeze - “Has your child ever had wheezing
or whistling in the chest?”; Doctor diagnosed asthma – “Did a doctor ever diagnose asthma in your
child?”; Possible asthma – (according to guidelines of the Dutch General Practitioners Association [1])
which is based on positive symptom diagnosis of recurrent cough, wheeze or congested chest; Probable
asthma – (according to guidelines of the Dutch General Practitioners Association) is based on positive
symptom diagnosis, as described above, with the addition of 1 or more factors that make an asthma
diagnosis more likely: constitutional eczema; asthma, allergic rhinitis or constitutional eczema in first
degree family members; indications that allergic stimuli (animals, pollen, house dust smoke) produce
symptoms; occurrence of wheeze with exercise; allergy, based on questionnaire or serum IgE levels;
symptoms of wheeze, shortness of breath, chest tightness keeping the child awake at night;
Late/Early/Persistent Wheeze – is based on a positive response to the question “ Did your child have
wheeze OR shortness of breath/tightness of chest in the past 12 months?” according to the 3 rd and 4th year
questionnaire. Positive for year 3 and not year 4 indicates early wheeze. Positive for year 4 and not year 3
indicates late wheeze. Positive for years 3 and 4 indicates persistent wheeze;
Early/Late/Persistent
Frequent Wheeze – is based on a similar algorithm to the preceding outcome with the additional criteria of
having 4 or more episodes of wheeze per year; Doctor diagnosed bronchitis – “Did a doctor ever diagnose
bronchitis in your child?”; Doctor diagnosed eczema – “Did a doctor ever diagnose eczema in your
child?”; Itchy rash (eczema) – based upon reporting of itchy rash being present in one either the folds of
the elbows, back of the knee, front of the ankles, on the neck or around the eyes and ears on any of the
annual questionnaires; Allergic - criteria of allergy is based upon responses on the year 4 questionnaire
indicating positive responses to the questions a)”Has your child ever been tested for allergy?” b) “Has
your child ever tested positive for allergy?” and a positive response to one or more of : c) “Is your child
allergic to:
- house dust / house dust mite / mould / pets / grass or tree pollen.
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Variable
a
Mother smoking during pregnancy
b
Smoking in home
a
Intervention study
a
natural history study
a
Mattress cover (allergen-free)
c
Mother < Medium level professional education
c
Mother > High school education
c
Father < Medium level professional education
c
Father > High school education
b
Male
b
Female
b
Gas stove
b
Gas water heater (unvented)
b
Any other siblings
d
Netherlands ethnicity
d
Other ethnicity
b
Any breastfeeding at 3 months
c
Any mold in home
b
Any pets in home
a
Allergic mother
b
Allergic father
a
Residence in North region of country
a
Residence Middle region of country
a
Residence in West region of country
b
Mother’s age [mean, years] (number of responses)
NO2 [mean, g/m3] (number estimated)
Soot [mean, filter absorbance, 10-5 m-1] (number estimated)
PM2.5 [mean, g/m3] (number estimated)
n (N)*
125 (566)
167 (398)
247 (608)
361 (608)
93 (608)
165 (294)
129 (294)
167 (280)
113 (280)
210 (406)
196 (406)
346 (403)
29 (383)
213 (401)
225 (246)
21 (246)
146 (398)
112 (292)
210 (398)
290 (604)
161 (564)
146 (608)
210 (608)
252 (608)
29.2 (398)
27.8 (603)
1.81 (603)
17.3 (603)
Prevalence (%)
22.1 #
42.0 #
40.6 #
59.4 #
15.3 #
56.1 #
43.9 #
59.6 #
40.4 #
51.7
48.3
85.9
7.6 #
53.1
91.5
8.5
36.7 #
38.4 #
52.8
48.0 #
28.5
24.0 #
34.5 #
41.5 #
#
#
#
#
Table A1. Prevalence of selected potential confounders in the subset of the cohort that had dropped
out prior to the age 4 questionnaire. Data collected from apregnancy, b3 month, c1 year, d2 year
questionnaires. * Number reporting characteristic (total number responding to relevant question(s)) /
prevalence of subjects with the characteristic, except Mother’s age and exposures for which means are
presented.
**Includes presence of molds, water damage and visible moisture in any of four specified
rooms. ***”Any pet” refers to cats, dogs, rodents or birds. # Significantly different (p<0.05) from
members of cohort with 4 years of follow up.
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Variable
N*
Prevalence (%)
Wheeze
Doctor diagnosed asthma
Dry cough at night w/o cold
Doctor diagnosed bronchitis
Itchy rash
Doctor diagnosed eczema
E,N,T infections
Doctor diagnosed flu, serious
cold
118 (708)
42 (710)
203 (713)
59 (706)
230 (709)
137 (708)
218 (714)
16.7 #
5.9 #
28.5 #
8.4 #
32.4 #
19.4 #
30.5
167 (709)
23.6
Table A2. Prevalence of selected health outcomes at age four in the subset of the cohort with blood
sampling. All outcomes refer to incidence or diagnoses within the past 12 months, the period between 3
and 4 years of age (Online Supplementary Material - Appendix 1). * number (total valid in parentheses,
based on completion of year 4 questionnaire and allergy testing) of subjects with the symptom or
condition. E,N,T = ear, nose, throat. # Significantly different (p<0.05) from full cohort (Table 1 of
manuscript)
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Variable
a
Mother smoking during pregnancy
b
Smoking in home
e
Smoking in home
a
Intervention study
a
natural history study
a
Mattress cover (allergen-free)
c
Mother < Medium level professional education
c
Mother > High school education
c
Father < Medium level professional education
c
Father > High school education
b
Male
b
Female
b
Gas stove
e
Gas stove
b
Gas water heater (unvented)
e
Gas water heater (unvented)
b
Any other siblings
e
Any other siblings
d
Netherlands ethnicity
d
Other ethnicity
b
Any breastfeeding at 3 months
c
Any mold in home
e
Any mold in home**
b
Any pets in home
e
Any pets in home***
a
Allergic mother
b
Allergic father
a
Residence in North region of country
a
Residence Middle region of country
a
Residence in West region of country
n (N)*
86 (734)
182 (732)
150 (711)
326
413
171 (739)
315 (718)
403 (718)
311 (689)
378 (689)
405 (736)
331 (736)
613 (733)
517 (647)
27 (705)
15 (650)
403 (735)
617 (702)
665 (712)
47 (712)
374 (729)
254 (715)
281 (706)
345 (732)
336 (693)
493 (734)
225 (723)
221 (739)
285 (739)
233 (739)
Prevalence (%)
11.7 #
24.9 #
21.1 #
55.9 #
44.1 #
23.1 #
43.9
56.1
45.1 #
54.9 #
55.0 #
45.0 #
83.6
79.9
3.8
2.3
54.8 #
87.9 #
93.4
6.6
51.3 #
35.5
39.8
47.1 #
48.5 #
67.2 #
31.1
29.9
38.6
31.5
Table A3. Prevalence of selected potential confounders in the subset of the cohort with blood
sampling. Data collected from apregnancy, b3 month, c1 year, d2 year, e4 year questionnaires (shaded
rows). * Number reporting characteristic (total number responding to relevant question(s)) / prevalence
of subjects with the characteristic **Includes presence of molds, water damage and visible moisture in
any of four specified rooms. ***”Any pet” refers to cats, dogs, rodents or birds. Prevalence of pets, gas
water heater and gas stove at year 4 may not be completely accurate due to incomplete data (questions at
each year are asked only for cases in which there was a change since previous year’s questionnaire) which
leads to a slight increase in missing values. # Significantly different (p<0.05) from full cohort (Table 3 of
manuscript)
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References
A1. Dirksen WJ, Geijer RMM, de Haan M, De Koning G, Flikweert S, Kolnaar BGM. NHG Standaard
astma bij kinderen (eerste herziening) (in Dutch). Huisarts Wet 1998; 41(3); 130-43.
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