Respiratory outcomes in early childhood following antenatal vitamin C and E
supplementation
Anne Greenough, Seif O Shaheen, Andrew Shennan, Paul T Seed, Lucilla Poston.
Online Depository
Vitamins in Pre-eclampsia (VIP) trial
The trial protocol (ISRCTN 62368611) has been described in detail elsewhere.[1] Briefly,
women were included in the VIP trial if they were between 14 weeks and 21 weeks plus 6 days
of gestation with one or more of the following risk factors:
chronic hypertension, pre-gestational diabetes, antiphospholipid syndrome/SLE with renal
involvement, chronic renal disease, abnormal uterine artery Doppler waveform identified
between 18 and 22 weeks of gestation, multiple pregnancy, BMI>30 in the first pregnancy,
previous history of eclampsia, HELLP syndrome or, in the preceding pregnancy, pre-eclampsia
requiring delivery before 37 weeks of gestation.
2422 women from 25 hospitals in the UK and one in Amsterdam were randomised to receive
either 1000 mg of vitamin C and 400 iu of vitamin E (RRR- tocopherol) (vitamin group) or
placebo (placebo group) from 14 to 22 weeks of gestation until delivery; 2404 as described in
the original paper; 18 randomised after 31 Nov 2005. The placebo was matched for taste with
the active agent and thus there was no unblinding in the VIP trial. After completion of the trial,
women were invited to ask for their treatment codes. One hundred and fourty-four women with
no infant surviving to 28 days were excluded. Approximately 30% of participants subsequently
asked about their allocation; it was not recorded which women asked for this information.
Maternal and infant outcomes were recorded by a study research midwife onto the VIP
database. Fetal growth restriction was assessed by calculation of adjusted birthweight
centiles.[2]
REFERENCES
1
Poston L, Briley AL, Seed PT, et al. Vitamins in Pre-eclampsia (VIP) Trial Consortium.
Vitamin C and vitamin E in pregnant women at risk for pre-eclampsia (VIP trial):
randomised placebo-controlled trial. Lancet 2006;367:1145-1154.
2
Gardosi J, Clausson B, Francis A. The value of customised centiles in assessing
perinatal mortality risk associated with parity and maternal size. BJOG
2009;116:1356-1363.
Table 1: Characteristics by maternal completion of the respiratory questionnaire.
Mothers with no infant surviving to 28 days were excluded.
Data are demonstrated as mean (SD) or n (%)
Questionnaire
No Questionnaire
Comparison (95% CI)
Maternal age
n=643 32.16 (5.17)
n=1698 30.46 (5.94)
1.70 (1.21 to 2.19)
Height
n=643 165.05 (6.43)
n=1698 163.66 (6.88)
1.39 (0.80 to 1.99)
Weight
n=643 79.88 (18.69)
n=1698 82.31 (20.54)
-2.43 (-4.17 to -0.69)
BMI
n=643 29.33 (6.74)
n=1698 30.66 (7.10)
-1.33 (-1.95 to -0.71)
Gestational age at recruitment
n=643 18.48 (2.54)
n=1698 18.53 (2.49)
-0.05 (-0.27 to 0.18)
Mother's ethnic group (ONS categories)
n=643
n=1698
n=2341
Asian
24 (4%)
87 (5%)
-1% (-3 to 0)
Black
30 (5%)
194 (11%)
-7% (-9 to -5)
Other
17 (3%)
41 (2%)
0% (-1 to 2)
White
572 (89%)
1376 (81%)
8% (5 to 11)
Parity (>24 wks) n=643
n=1698
n=2341
0
335 (52%)
847 (50%)
2% (-2 to 7)
1
229 (36%)
533 (31%)
4% (-0 to 9)
>1
79 (12%)
318 (19%)
-6% (-10 to -3)
Occupational category
n=643
n=1698
n=2341
Working/Maternity leave/Self-employed
501 (78%)
1181 (70%)
8% (4 to 12)
Home maker
93 (14%)
297 (17%)
-3% (-6 to 0)
Student
6 (1%)
34 (2%)
-1% (-2 to -0)
186 (11%)
-4% (-7 to -2)
Sickness/invalidity/Unemployed
43 (7%)
Education (highest qualification)
n=643
n=1698
n=2341
None
31 (5%)
156 (9%)
-4% (-7 to -2)
GCSE
269 (42%)
798 (47%)
-5% (-10 to -1)
A level
98 (15%)
287 (17%)
-2% (-5 to 2)
College/University
232 (36%)
406 (24%)
12% (8 to 16)
Vocational (BTEC, NVQ etc.)
13 (2%)
51 (3%)
-1% (-2 to 0)
Housing
n=643
n=1698
n=2341
Own home
497 (77%)
998 (59%)
19% (15 to 23)
Rented from Council/Housing association
54 (8%)
315 (19%)
-10% (-13 to -7)
Rented privately
47 (7%)
204 (12%)
-5% (-7 to -2)
Other
181 (11%)
-4% (-6 to -1)
Smoking status
n=643
n=1698
n=2341
Never
951 (56%)
4% (-0 to 9)
Current smoker >=1/day
50 (8%)
227 (13%)
-6% (-8 to -3)
Occasional/social
3 (0%)
20 (1%)
-1% (-1 to 0)
Stopped before present pregnancy
154 (24%)
352 (21%)
3% (-1 to 7)
Stopped during pregnancy
48 (7%)
148 (9%)
-1% (-4 to 1)
467 (27.5%)
2.20 (-1.92 to 6.32)
374 (22.0%)
6.28 ( 2.28 to 10.28)
45 (7%)
388 (60%)
Folate supplementation
191 (29.7%)
Multivitamin use
Pregnancy specific
182 (28.3%)
Other
21 ( 3.3%)
58 ( 3.4%)
-0.15 (-1.77 to 1.47)
198 (30.8%)
419 (24.7%)
6.12 ( 2.00 to 10.23)
Chronic hypertension
244/643 (37.9%)
591/1698 (34.8%)
3.14 (-1.24 to 7.52)
BMI >= 30 in first pregnancy
197/643 (30.6%)
589/1698 (34.7%)
-4.05 (-8.27 to 0.17)
HELLP/eclampsia/most recent PE
156/643 (24.3%)
381/1698 (22.4%)
1.82 (-2.04 to 5.69)
Multiple pregnancy
109/643 (17.0%)
261/1698 (15.4%)
1.58 (-1.79 to 4.95)
Diabetes
129/1698 (7.6%)
2.05 (-0.56 to 4.65)
n=1698 1.21 (0.45)
0.06 (0.02 to 0.11)
Any
62/643 (9.6%)
Number of distinct risk factors
n=643 1.27 (0.51)
Table 2: Characteristics of women who did and did not complete the health utilisation
study. Mothers with no infant surviving to 28 days were excluded
HUS
No HUS data
Comparison (95%
CI)
Maternal age n=99 33.02 (4.86)
n=1694 30.45 (5.95)
2.57 (1.57 to 3.56)
Height
n=99 166.33 (6.24)
n=1694 163.65 (6.87)
2.68 (1.42 to 3.95)
Weight
n=99 74.84 (18.68)
n=1694 82.35 (20.52)
-7.51 (-11.30 to -3.72)
BMI
n=99 27.05 (6.59)
n=1694 30.68 (7.09)
-3.63 (-4.97 to -2.30)
Gestational age at recruitment
n=99 18.24 (2.44)
n=1694 18.53 (2.49)
-0.29 (-0.78 to 0.20)
Mother's ethnic group (ONS categories)
n=99
n=1694
n=1793
Asian
8 (8%)
86 (5%)
3% (-2 to 8)
Black
18 (18%)
192 (11%)
7% (-1 to 15)
Other
10 (10%)
41 (2%)
8% (2 to 14)
White
63 (64%)
1375 (81%)
-18% (-27 to -8)
Parity (>24 wks)
n=99
n=1694
n=1793
0
43 (43%)
847 (50%)
-7% (-17 to 3)
1
43 (43%)
529 (31%)
12% (2 to 22)
>1
13 (13%)
318 (19%)
-6% (-13 to 1)
Occupational category
n=99
n=1694
n=1793
Working/Maternity leave/Self-employed
69 (70%)
1179 (70%)
0% (-9 to 9)
Home maker
14 (14%)
297 (18%)
-3% (-10 to 4)
Student
3 (3%)
33 (2%)
1% (-2 to 5)
Sickness/invalidity/Unemployed
13 (13%)
Education (highest qualification)
n=99
185 (11%)
2% (-5 to 9)
n=1694
n=1793
None
0 (0%)
156 (9%)
-9% (-11 to -8)
GCSE
28 (28%)
798 (47%)
-19% (-28 to -10)
A level
12 (12%)
287 (17%)
-5% (-11 to 2)
College/University
58 (59%)
402 (24%)
35% (25 to 45)
Vocational (BTEC, NVQ etc.)
1 (1%)
51 (3%)
-2% (-4 to 0)
Housing
n=99
n=1694
n=1793
Own home
65 (66%)
996 (59%)
7% (-3 to 17)
Rented from Council/Housing association
14 (14%)
313 (18%)
-4% (-11 to 3)
Rented privately
12 (12%)
204 (12%)
0% ((-7 to 7)
Other
8 (8%)
181 (11%)
-3% (-8 to 3)
Smoking status
n=99
n=1694
n=1793
Never
58 (59%)
948 (56%)
3% (-7 to 13)
Current smoker >=1/day
7 (7%)
227 (13%)
-6% (-12 to -1)
Occasional/social
20 (1%)
-1% (-2 to -1)
351 (21%)
6% (-3 to 14)
0 (0%)
Stopped before present pregnancy
26 (26%)
Stopped during pregnancy
8 (8%)
Folate supplementation
55 (55.6%)
Multivitamins
Pregnancy-specific
30 (30.3%)
148 (9%)
-1% (-6 to 5)
465 (27.4%)
28.11 (18.09 to 38.12)
373 (22.0%)
8.28 (-0.98 to 17.55)
Other multivitamins
6 ( 6.1%)
Any multivitamins
33 (33.3%)
56 ( 3.3%)
2.75 (-2.02 to 7.53)
416/ (24.6%)
8.78 (-0.73 to 18.29)
Chronic hypertension
32/ 99 (32.3%)
588/1694 (34.7%)
-2.39 (-11.88 to 7.10)
BMI >= 30 in first pregnancy
20/ 99 (20.2%)
589/1694 (34.8%)
-14.57 (-22.80 to -6.34)
HELLP/eclampsia/most recent PE
24/ 99 (24.2%)
379/1694 (22.4%)
1.87 (-6.80 to 10.54)
Multiple pregnancy
19/ 99 (19.2%)
261/1694 (15.4%)
3.78 (-4.16 to 11.73)
Diabetes
129/1694 (7.6%)
9/ 99 (9.1%)
Number of distinct risk factors
n=99 1.29 (0.56)
n=1694 1.21 (0.45)
1.48 (-4.33 to 7.28)
0.08 (-0.03 to 0.19)