Table 18. The effect of maternal vitamin D status in gestation on offspring asthma and atopy— Observational studies.
| First Author and year |
Bias score |
Cohort details | Study type |
Adjustments | When was maternal serum 25 OH D measured | Mean (SD) or median (IQR) 25OHD3 concentration (nmol/l-unless other stated) | Risk of Asthma/Wheeze/ Eczema | Conclusion | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Camargo, 2007 106 | 2 (med) | Massachusetts, USA Cohort = 2128 women 1194 (56%) studied for outcome |
Cohort | Sex, birth weight, income, maternal age, pre-pregnancy BMI, passive smoking exposure, breastfeeding duration, number of children in household, maternal and paternal history of asthma, dietary intake of fish, fruit and vegetables | Not measured Based on modification to validated food frequency questionnaire at initial prenatal visit and 26-28 weeks gestation. |
Not measured Mean vitamin D intake (mean of early pregnancy and 26-28 week for each participant) was 548 (167) IU/day. |
In comparison to the lowest quartile, mothers in the highest quartile of daily vitamin D intake had a lower risk of having a child with recurrent wheeze at 3years (OR 0.38; 95%CI 0.22−0.65). | A higher maternal intake of vitamin D during pregnancy was associated with a lower risk of recurrent wheeze in children at 3 years of age | ||||
| Devereux, 2007 27 | −1 (high) | Aberdeen, Scotland Cohort = 1924 mother-offspring pairs 1212 (63%) children included in questionnaire follow up at 5 years; 797 (41%) children had lung function assessment and skin prick testing at 5 years |
Cohort | Adjusted for maternal atopy, age, smoking, education, social class, deprivation index based on area of residence, breastfeeding, infant sex, infant antibiotic use in first year, birth weight, birth order, season of last menstrual period, maternal intakes of vitamin E, zinc and calcium. | Not measured Estimated from food frequency questionnaire at 32 weeks gestation. |
Not measured Median maternal vitamin D intake 131 (102-173)IU/day |
In models adjusted for potential confounders, including the children’s vitamin D intake, compared to the lowest quintile, the highest quintile of maternal vitamin D intake displayed lower risk of “ever wheeze” (OR: 0.48; 95%CI: 0.25-0.91), and “wheeze in the previous year” (OR: 0.35; 95%CI 0.15-0.83) at 5years determined by parental questionnaire. No differences in atopic sensitization or spirometry. | Low maternal vitamin D intakes during pregnancy are associated with increased wheezing symptoms in children at 5 years. | ||||
| Gale, 2008 25 | 4 (med) | Princess Ann Cohort, Southampton, UK n= 440 at 9 months n=178 at 9 years |
Cohort | Nil | Late pregnancy Median (IQR)= 32.6 (33-33.4) weeks |
50 (30-75.3) 50.4% had 25(OH)D >50nmol/k 28.3% had levels 27.5-50 nmol/l 21.1% had levels <27.5 nmol/l |
OR (95% CI) for eczema or asthma | |||||
| 25(OH)D | <30 | 30-50 | 50-75 | >75 | ||||||||
| Visible eczema on examination at 9 months | 1.0 | 0.59 (0.14-2.50) | 0.79 (0.21-3.00) | 3.26 (1.15-9.29) | ||||||||
| Atopic eczema at 9 months (UK working party criteria) | 1.0 | 1.11 (0.43-2.84) | 1.75 (0.73-4.17) | 1.62 (0.67-3.89) | ||||||||
| Reported eczema at 9 years | 1.0 | 0.71 (0.15-3.39) | 0.49 (0.08-2.68) | 1.89 (0.51-6.99) | ||||||||
| Reported asthma at 9 years | 1.0 | 2.05 (0.36-11.80) | 2.05 (0.36-11.80) | 5.40 (1.09-26.65) | ||||||||
| Erkkola, 2009 104 | −1 (high) | Finland — 3 university hospitals Cohort = 4193 women 1669 (40%) studied for outcome |
Cohort | Adjusted for sex, area of birth, gestation, maternal age, maternal education, smoking during pregnancy, siblings, parental asthma, atopic eczema, pets in house before 1 years, maternal intake of vitamin C, vitamin E, selenium and zinc | Not measured Estimated from food frequency questionnaire. Completed retrospectively after delivery for 8th month of pregnancy. |
Not measured Mean total maternal vitamin D intake 260 (152)IU/day. |
After adjustment, maternal total vitamin D intake associated with reduced risk of asthma (HR 0.76; 95%CI 0.59-0.99) and allergic rhinitis (HR 0.84; 95% CI 0.72-0.98) but not atopic eczema (OR 0.94; 95% CI 0.83-1.07) at 5 years | Maternal vitamin D intake during pregnancy inversely associated with the development of asthma and allergic rhinitis | ||||
| Miyake, 2010 105 | −1 (high) | Osaka, Japan Cohort = 1002 women 763 (76%) studied for outcome |
Cohort | Adjusted for maternal age, gestation at baseline, residential municipality during pregnancy, family income, maternal and parental education, history of asthma, atopic eczema and allergic rhinitis, season, changes in diet, smoking, older siblings, sex, birth weight, age at child assessment. | Not measured Self administered validated questionnaire of dietary intake. Measured between 5 and 39 weeks of pregnancy. |
Not measured Mean intake of vitamin D= 248 (148) IU/day |
Consumption of ≥4.309 mcg/day vitamin D associated with a decreased risk of wheeze (adjusted OR 0.64; 95% CI 0.43-0.97) and eczema (adjusted OR 0.41-0.98) at 16-24 months of age. | Higher consumption of vitamin D in pregnancy was associated with a lower risk of wheeze and eczema in infancy. | ||||
| Nwaru, 2010 111 | 3 (med) | Finland Cohort = 1175 women 931 (79%) studied for outcome |
Cohort | Place and season of birth, sex, siblings, gestational age at birth, parental asthma and allergic rhinitis, maternal age at delivery, maternal smoking, and maternal education. | Not measured Estimated from food frequency questionnaire. Completed retrospectively after delivery for 8th month of pregnancy. |
The mean daily intake of vitamin D during pregnancy by the mothers was 208(112) IU/day. Of the women, 28% had taken vitamin D supplements during pregnancy with a mean intake of 44 (96) IU/day. |
Increasing maternal intake of vitamin D was inversely association with sensitization (specific IgE≥0.35KU/l) to food allergens (adjusted OR 0.56 (95%CI 0.35-0.91, p<0.026) but not inhaled allergens (adjusted OR 0.76 (95%CI 0.50-1.17) at 5 years of age. | Increasing maternal intake of vitamin D was inversely associated with sensitization to food allergens. | ||||
| Camargo, 2011 107 | 3 (med) | Wellington and Christchurch, New Zealand Cohort = 922 women 823 (89%) studied for outcome |
Cohort | Season of birth, study site, maternal age, parental history of asthma, gestational age, birth weight, child’s gender and ethnicity, smoking, number of children in household, during of exclusive breastfeeding. | Not measured Cord blood 25(OH)D were measured |
Not measured Median cord blood 25(OH)D= 44nmol/L (IQR 29−78). |
Adjusting for season, the OR for cumulative wheeze at 5 years increased across categories of 25(OH)D (1.00 [reference] for ≥75 nmol/L, 1.63 [95% CI: 1.17-2.26] for 25−74 nmol/L, and 2.15 [95% CI: 1.39−3.33] for <25 nmol/L). No association with incident asthma at 5 years | Cord-blood levels of 25(OH)D had inverse associations with childhood wheezing but no association with incident asthma. | ||||
| Cremers, 2011 110 | 3 (med) | Netherlands Cohort = 2834 women (2343 women with a conventional lifestyle; 491 women with an alternative lifestyle with regards to child rearing practices, diet an vaccination programmes) 415 (14.6%) studied for outcome |
Cohort | Recruitment group (conventional or alternative lifestyle), maternal age, maternal education, maternal smoking, alcohol consumption, pre-pregnancy BMI, child’s BMI at 2 years, birth weight, exposure to tobacco smoke, season of blood sampling, physical activity | 36 weeks gestation | 46.0(18.2) nmol/l | No association between maternal plasma 25(OH)D at 36weeks gestation and offspring FEV1 (p=0.99) nor FVC p=0.59) at 6-7 years | No association between maternal late pregnancy 25-hydroxyvitamin D levels and lung function in children aged 6-7 years. | ||||
| Rothers, 2011 108 | 2 (med) | Tucson, Arizona, USA Cohort = 482 women 219 (45%) studied for outcome |
Cohort | Maternal ethnicity, household smoking, birth season | Not measured Plasma levels of 25(OH)D measured in cord blood specimens |
Not measured Median cord blood 25(OH)D = 64 nmol/L (IQR 49-81) |
Both total and inhalant allergen specific IgE showed non-linear associations with cord blood 25(OH)D in that levels were highest in those with cord blood 25(OH)D<50nmol/l and >100nmol/l. Greater risk of skin-prick testing positivity to aeroallergens at 5 years in children with cord 25(OH)D ≥100nmol/l compared with reference group (25(OH)D 50-74.9nmol/l): OR3.4; 95%CI 1.0-11.4, p=0.046) |
Non-linear relationship between vitamin D status at both and markers of atopy at 5 years | ||||
| Morales 2012 109 | 3 (med) | Spain, Cohort=2860 women enrolled in the INMA project (Infancia y Medio Ambiente) 1233 (43%) children studied for outcome |
Cohort | Offspring sex, maternal pre-pregnancy BMI, maternal history of asthma, maternal educational level, maternal smoking in pregnancy, breastfeeding duration, day-care attendance in the first year of life, and area of study | Between 12-23 weeks gestation Mean (SD) =12.6 (2.5) weeks | Median= 73.6 (56.2-92.6) nmol/l | No significant association seen between maternal 25(OH)-vitamin D and: wheeze at 1 year (unadjusted p=0.453, adjusted p=0.441 wheeze at 4 years (unadjusted p=0.559, adjusted p=0.708 asthma at 4-6 years (unadjusted p=0.339; adjusted p=0.481 |
No association seen between maternal 25(OH)-vitamin D and offspring wheeze at 1 year and 4 years, or offspring asthma at 4-6 years | ||||