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Maternal vitamin D status in pregnancy and risk of lower respiratory
tract infections, wheezing and asthma in offspring
Eva Morales, Isabelle Romieu, Stefano Guerra, Ferrán Ballester, Marisa Rebagliato,
Jesús Vioque, Adonina Tardón, Cristina Rodriguez Delhi, Leonor Arranz, Maties
Torrent, Mercedes Espada, Mikel Basterrechea, Jordi Sunyer, on behalf of the INMA
Project
eTable 1. Lower respiratory tract infections, wheeze and asthma prevalences, overall
and by area of study, the INMA Project.
eTable 2. Association between offspring’s outcomes and selected characteristics, the
INMA Project.
eTable 3. Association between circulating vitamin D level in pregnancy with selected
maternal characteristics, the INMA Project (n=1,724).
eTable 4. Meta-analysis of the association* (Odds ratios and 95% confidence intervals)
between maternal circulating 25-hydroxyvitamin D (25(OH)D) concentrations in
pregnancy and offspring’s respiratory outcomes risk of being diagnosed of LRTI within
the INMA Project areas of study.
eTable 5. Comparison between included and non-excluded subjects, the INMA Project
(N=2,502 children followed until birth).
eTable 1. Lower respiratory tract infections, wheeze, and asthma prevalences (n cases/n controls (%)),
overall and by area of study, the INMA Project.
LRTI at 1 y
(n=1,693)
Area of study
Gipuzkoa
Sabadell
Valencia
Menorca
Total
159/260 (38)
163/233 (41)
187/446 (30)
108/137 (44)
617/1076 (37)
Wheeze at 1 y
(n=1,724)
149/270 (36)
151/242 (38)
167/466 (26)
57/222 (20)
524/1200 (30)
Wheezy at 4 y
(n=1,233)
83/325 (20)
102/445 (19)
35/243 (13)
220/1013 (18)
Asthma at 4-6 y
(n=1,233)
91/317 (22)
112/435 (20)
50/228 (18)
253/980 (20)
eTable 2. Association between offspring’s outcomes and selected characteristics, the INMA Project.
LRTI at 1 year (n=1,693)
Sex male; %
Firstborn; %
Preterm; %
Maternal pre-pregnancy body
mass index (kg/m2); %
<18.5
18.5-25
25-30
>30
Maternal social class; %
I-II Managers/Technicians
III-IV Skilled manual & nonmanual
V Semi-skilled/Unskilled
Maternal educational level; %
Primary or less
Secondary
High
Maternal asthma; %
Maternal smoking pregnancy;
%
Day care attendance; %
Breastfeeding duration
(weeks); %
0
>0-16
16-24
>24
Season of birtha; %
Winter
Spring
Summer
Yes
(n=617)
57
47
5
No
p value
(n=1,076)
48 <0.001
60 <0.001
4 0.058
Wheeze at 1 year (n=1,724)
Yes
(n=524)
58
44
5
No
p value
(n=1,200)
48 <0.001
60 <0.001
4 0.329
Current asthma at 4-6 y
(n=1,233)
Yes
No
p value
(n=253) (n=980)
56
50 0.077
55
55 0.940
7
4 0.044
4
67
19
9
5 0.114
72
17
7
5
67
19
9
5 0.237
71
17
7
4
64
23
9
4 0.117
71
17
8
36
41
39 0.384
41
35
41
38 0.345
42
30
47
33 0.580
46
23
20
23
20
23
21
32
39
29
9
20
28 0.185
39
32
6 0.011
16 0.034
30
39
31
10
23
31 0.971
39
30
6 0.002
16 <0.001
38
39
24
9
23
35 0.650
40
25
8 0.507
18 0.058
38
28 <0.001
39
28 <0.001
23
28 0.089
14
28
15
43
12 0.250
26
16
46
15
28
17
41
13 0.191
26
16
46
16
29
12
43
13 0.138
27
17
44
23
22
26
30 0.002
23
19
26
21
26
27 0.028
23
20
26
23
22
27 0.943
24
21
Fall
a
29
28
27
30
30
Winter: December to February; Spring: March to May; Summer: June to August; Fall: September to November.
29
eTable 3. Association between circulating vitamin D level sin pregnancy
with selected maternal characteristics, the INMA Project (n=1,724).
Siblings at birth
First born
No first born
Maternal age
20-29
>=30
<20
Maternal ethnic group
Caucasian
Non Caucasian
Maternal BMI pre-pregnancy (kg/m2)
<18.5
18.5-25
25-30
>30
p-value*
N
Mean (SE)
954
770
29.8 11.1
30.8 11.2
0.045
443
1268
13
28.9 10.5
30.8 11.3
25.1 11.9
0.001
1661
55
30.3 11.0
31.0 15.2
0.847
80
1207
310
127
28.1
30.5
29.8
30.6
12.0
11.0
11.5
11.2
0.086
1602
122
30.3 11.2
30.5 10.4
0.801
529
668
527
29.4 10.6
30.0 11.1
31.4 11.7
0.033
610
686
349
31.2 11.5
29.8 10.5
29.7 11.9
0.052
1418
306
30.6 11.2
28.8 10.8
0.013
Maternal asthma
No
Yes
Maternal education level
Primary or less
Secondary
High
Maternal social class
I-II Managers/Technicians
III-IV Skilled manual & non-manual
V Semi-skilled/Unskilled
Maternal smoking in pregnancy
No
Yes
eTable 4. Meta-analysis of the association* (Odds ratios and 95% confidence intervals) between
maternal circulating 25-hydroxyvitamin D (25(OH)D) concentrations in pregnancy and offspring’s
respiratory outcomes within the INMA Project areas of study.
Area of study
Gipuzkoa
Sabadell
Valencia
Menorca
P of heterogeneity
Combined
Fixed effects
Random effects
*
LRTI at 1 y
(n=1,693)
Wheeze at 1 y
(n=1,724)
Wheezy at 4 y
(n=1,233)
Asthma at 4-6 y
(n=1,233)
0.56 (0.31-1.03)
0.81 (0.43-1.52)
0.81 (0.48-1.38)
0.48 (0.22-1.06)
0.614
0.71 (0.39-1.30)
1.35 (0.71-2.59)
1.04 (0.61-1.78)
0.64 (0.25-1.63)
0.421
0.99 (0.50-1.97)
0.89 (0.46-1.71)
1.37 (0.49-3.85)
0.786
0.77 (0.39-1.50)
0.95 (0.51-1.76)
1.19 (0.46-3.06)
0.751
0.68 (0.50-0.92)
0.68 (0.50-0.92)
0.94 (0.68-1.30)
0.94 (0.68-1.30)
1.00 (0.65-1.54)
1.00 (0.65-1.54)
0.91 (0.61-1.38)
0.91 (0.61-1.38)
Estimates for subjects with circulating 25(OH)D concentrations in the upper cohort- and season-specific
quartile in comparison with the lower quartile.
All models adjusted for sex, maternal education, siblings at birth, breastfeeding duration, maternal smoking in
pregnancy, day-care attendance, maternal asthma, and maternal pre-pregnancy body mass index.
eTable 5. Comparison between included and non-excluded subjects, the INMA Project
(N=2,502 children followed until birth).
Included Not included p value
N=1,724
N=878
n=1724
n=691
Child sex; n (%)
Male
883 (51)
358 (52) 0.793
n=1724
954 (55)
n=1717
70 (4)
First born; n (%)
Yes
Preterm; n (%)
Yes
Birth weight; grs
Mean (sd)
n=776
395 (51) 0.040
n=766
41 (5) 0.155
n=1720
n=765
3250.3 (465.1) 3216.9 (526.2) 0.412
n=1724
31.5 (4.3)
Maternal age; years
Mean (sd)
n=1724
Maternal pre-pregnancy BMI (kg/m2);
n (%)
<18.5
18.5-24.99
25-29.99
≥ 30
n=686
31.1 (4.5) 0.125
n=759
80 (5)
1207 (70)
310 (18)
127 (7)
n=1724
529 (31)
668 (39)
527 (31)
38 (5) 0.195
559 (74)
113 (15)
49 (7)
n=757
266 (35) 0.081
281 (37)
210 (28)
Maternal social class; n (%)
I-II Managers/Technicians
III-IV Skilled manual & non-manual
V Semi-skilled/Unskilled
n=1645
610 (37)
686 (42)
349 (21)
n=730
235 (32) 0.059
336 (46)
159 (22)
Maternal smoking in pregnancy; n (%)
Yes
n=1724
306 (18)
n=737 0.924
132 (18)
Breastfeeding duration (weeks); n (%)
0
>0-16
16-24
>24
n=1724
228 (13)
454 (26)
273 (16)
769 (45)
n=589
72 (12) 0.540
158 (27)
107 (18)
252 (43)
Day care attendance at age 1y; n (%)
Yes
n=1724
542 (31)
n=536
181 (34) 0.312
Maternal circulating vitamin D levels in
pregnancy (ng/mL)
Mean (sd)
n=1724
30.3 (11)
n=534
31.0 (12) 0.315
Maternal education level; n (%)
Primary or less
Secondary
High
n=1688
Lower respiratory tract infection at 1 year;
n=529
n (%)
Yes
Wheeze at 1 year; n (%)
Yes
Wheeze at 4 year; n (%)
Yes
Current asthma at 4-6 years; n (%)
612 (36)
n=1724
524 (30)
n=1112
191 (17)
n=1111
7
224 (42) 0.012
n=549
160 (29) 0.578
n=391
72 (18) 0.579
n=381
Yes
219 (20)
8
81 (21) 0.515