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Does vitamin E prevent asthma or wheeze in children: A systematic review and meta-analysis
Accepted Manuscript Review Does vitamin E prevent asthma or wheeze in children: a systematic review and meta-analysis Wu Hui, Chunwei Zhang, Yongqing Wang, Yanlin Li PII: DOI: Reference:
S1526-0542(17)30093-3 https://doi.org/10.1016/j.prrv.2017.08.002 YPRRV 1237
To appear in:
Paediatric Respiratory Reviews
Please cite this article as: W. Hui, C. Zhang, Y. Wang, Y. Li, Does vitamin E prevent asthma or wheeze in children: a systematic review and meta-analysis, Paediatric Respiratory Reviews (2017), doi: https://doi.org/10.1016/j.prrv. 2017.08.002
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Does vitamin E prevent asthma or wheeze in children: a systematic review and meta-analysis Wu Hui, Chunwei Zhang, Yongqing Wang, Yanlin Li1＊ Department of Pediatrics, the First People Hospital of Changzhou and the Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213000, China.
Communicated by Peter de Winter First author: Hui Wu [email protected]
Second Author: Chunwei Zhang [email protected]
Third Author : Yongqing Wang [email protected]
Corresponding author: Yanlin Li
＊
[email protected]
1 Department of Pediatrics, The Third Affiliated Hospital of Soochow University，Changzhou 213003, Jiangsu Province, China
Summary
Asthma is a heterogeneous disease with multiple phenotypes. Epidemiologic studies suggest a close relationship between vitamin E and the occurrence of asthma, wheezing and atopic conditions during childhood. Previous results on its effects have been conflicting. The aim of this meta-analysis was to critically examine the current evidence on the association of vitamin E with childhood asthma and wheezing. We searched electronic databases for observational studies in English-language journals published from 2000 to 2016. The initial search found 420 titles; nineteen studies were eligible according to the abstracts and details, which included reporting asthma or wheeze as an outcome. None of the articles included in this meta-analysis reported side effects of vitamin E supplementation during pregnancy.This meta-analysis found that vitamin E supplementation during pregnancy influenced the risk of asthma. To better understand the effectiveness and safety of vitamin E in children with asthma, large-scale, well-designed and randomized controlled trials are needed.
Key words: Asthma, Wheezing, Vitamin E, Childhood Educational Aims: The reader will be able:
* To examine the current evidence on the association of serum vitamin E with childhood asthma and wheezing. * To analyse of the relationship of supplemental vitamin E with childhood asthma and wheezing.
* To assess the effect of vitamin E supplementation during pregnancy in childhood asthma.
In recent years, allergic diseases, especially childhood wheezing and asthma, have presented a global problem, and children suffer the highest burden of these conditions. Food allergies, wheeze, asthma and eczema are the most common allergic disorders in children
[1]
. In the United States (US), the prevalence of these disorders increased
from 7.3% in 2001 to 8.4% in 2010 (and from 3.5% in the 1970s). In 2010, an estimated 25.7 million people in the US had current or active asthma, including 18.7 million adults and 7 million children [2]. The direct and indirect yearly costs of asthma to the US economy have been estimated to be $18 billion. Increasing evidence has shown that environmental factors have an important role in the onset of complex
conditions such as allergic diseases and that the role of fixed genetic variation is much smaller than previously believed [3].
Therefore, new approaches to disease prevention with an emphasis on early interventions, such as before and/or during pregnancy, should be widely investigated. Current evidence suggests that future studies should focus on the role of maternal diet during pregnancy in subsequent disease development [4], as many immune modulatory processes may start in utero. Some researchers have proposed that the increased prevalence of allergic disorders may be related to diets.
Dietary changes have been hypothesized to contribute to the increase in asthma and atopic disease observed in economically developed countries
[5]
. Additionally, early
life factors are known to play critical roles in the development of asthma and atopic disease. Studies have related maternal or childhood dietary status to the development of childhood atopic diseases. Maternal dietary changes in pregnancy are a key environmental factor implicated in the allergy epidemic [6]. Animal studies and studies with pregnant women suggest that appropriate fetal exposure to vitamin E confers enhanced lifetime resistance to asthma. Some studies have also examined serum vitamin E or supplemental vitamin E during childhood but with conflicting results. The preventive role of vitamin E is complex and involves functional variations of the different isoforms. In the first months of life, eczema and food allergy are often evident, and a better understanding of the role of early life exposures is thus needed.
As the maternal diet supplies all nutrients during pregnancy, it has significant potential to modify the success or failure of immune tolerance and to affect the development of allergic disease in the offspring
[7]
. Previous epidemiological studies
have suggested an association between lower intake of antioxidant-rich foods (such as fresh fruits and vegetables) and deficits in lung function childhood wheezing
[8]
and increased risk of
[9]
. Recently, dietary antioxidants have been implicated in the
development of fetal and infant immune response and the occurrence of allergic disease
[10]
. Oxidative stress is more important in many diseases. An increasing
number of studies have investigated the effects of maternal antioxidant intake, especially vitamin E, and the incidence of allergic diseases, but none have specifically targeted a population at high risk of developing asthma. But in other diseases, such as bronchopulmonary dysplasia (BPD) which is the most likely to suffer from respiratory morbidity
[11]
, oxidative stress has been implicated in the development of BPD, and
prematurely born infants have impaired antioxidant defenses [12].
Therefore, the aim of this study was to assess the effects of supplemental and serum vitamin E and the risk of asthma and wheeze in offspring.
Study selection criteria： ：
We searched the PubMed, Medline, and Web of Science electronic databases using
the following keywords: (asthma OR Bronchial Asthma OR wheezing OR Respiratory Sound OR Wheezing) OR (serum vitamin E) AND [maternal OR pregnancy] AND (offspring OR infant OR child) AND vitamin E. The reference lists of relevant publications were also searched for additional studies. Furthermore, we searched in other data sources, including web search results, references of relevant included publications and pharmaceutical industry websites. We attempted to contact the authors to obtain any missing information.
To be included in the meta-analysis, studies had to meet the following criteria: (i) systematic recording of serum vitamin E or vitamin E supplementation during pregnancy or childhood; (ii) use of at least two comparison groups (asthma versus control); (iii) use of asthma in offspring as an outcome; and (iv) presentation of associations as relative risks (RR) or odds ratios (ORs) with respect to some measure of vitamin E intake. The primary outcome was the prevalence of asthma among offspring during childhood. The exclusion criteria were as follows: 1) studies that were not written in English; 2) letters, review papers, meeting records, commentaries, case reports, or clinical guidelines; 3) studies that lacked critical data, such as ORs and 95% confidence intervals (CIs); and 4) studies on asthma or experimental animal studies. Finally, when several articles included overlapping data, the study with the largest sample size was reviewed.
Data extraction from the included studies One reviewer (Wu Hui) extracted information including the first author's name, year of publication, country in which the study was conducted, ethnicity, sample size, duration of follow-up, vitamin E intake, serum vitamin E, and RRs and 95% CIs for asthma (physician's diagnosis and/or objective criteria) or wheezing (Tables 1-3). During the data extraction process, any disagreements about the interventions and outcomes were discussed and resolved by the review team. The reviewer was not blinded to the name of the authors, institutions, journals, or outcomes of the trials during the process. The details were then independently checked by a second reviewer (Chunwei Zhang).
Quality assessment of the included studies
Two researchers independently assessed the quality of each study using the Newcastle-Ottawa quality assessment scale (NOS)
[13]
. The NOS for case-control
studies was applied to assess the quality of the included studies regarding three main categories: study selection, comparability of groups and determination of outcomes. The quality scores ranged from 0 (lowest) to 9 (highest), and studies with scores of 6 or more were considered to be of high quality.
Statistical analysis
We calculated the pooled ORs, RRs, and hazard ratios (HRs) with 95% CIs for categorical outcomes. The clinical and statistical appropriateness of a meta-analysis were considered for all exposures/outcomes. Heterogeneity was assessed using the I² statistic and chi-square test. Significant heterogeneity was assumed for I² >50%. Meta-analyses were performed using fixed effect modeling (the Mantel-Haenszel method) when I²<50%, and random effects modeling (the DerSimonian-Laird method) was used when I²>50% or P-value<0.1. In contrast with fixed effect modeling, random effects modeling does not assume a single underlying effect size and therefore generates more conservative estimates of precision. The net effect is that these 2 modeling techniques result in essentially identical point estimates of effect but with the random effects-derived models generating wider 95% CIs around these estimates. Subgroup analyses were conducted with groups divided by area, quality of evidence, and follow-up time. Sensitivity analyses were performed to evaluate the effect of each study on the pooled ORs. Furthermore, we performed Begg's and Egger's tests to provide quantitative evidence of publication bias. All statistical tests were two-sided, and noticeably asymmetric funnels plots indicated publication bias. For Begg’s and Egger’s tests, the significance level was set at 0.05. Data analyses were performed using STATA version 12.0 (Stata Corporation, College Station, TX, USA).
Search results： ：
The literature search and screening process is shown in Figure 1. The database search
identified 420 potentially relevant publications in PubMed, EMBASE, and Web of Science. After scanning the title, abstract, publication type, and full text of the 420 publications, we excluded 289 articles as being clearly irrelevant. Of the remaining articles, 12 were excluded, five lacked some important data, and seven did not report ORs or RRs. Therefore, a total of 19 studies were included in our meta-analysis
[10,
14-31]
.
Figure 1 Main characteristics of all studies included in the meta-analysis
Characteristics of included studies： ：
Basic information on the studies that met the inclusion criteria was collected. These studies were published between 2006 and 2014, and all were cohort studies, as shown in Table 1. Five were conducted in the United Kingdom, and one each was performed
in Finland, Japan, United States, Australia, and Denmark. The studies assessed 2 major ethnic populations; 9 were conducted in Western settings, while 1 study was conducted in Eastern contexts. Of these studies, 3 studies reported on both asthma and wheezing. Thus, 6 articles addressed childhood asthma, and 7 articles investigated childhood wheeze. More details are shown in Tables 1-3.
Table 1 Main characteristics of the 10 studies on maternal vitamin E intake included in the meta-analysis Autho r
Cou ntry/ Year
Typ e of area
Study design
Sa mpl e size
Stephe UK nW /201 Turner 0
Wes tern
Longit udinal birth cohort study
101 Physi 8 cianconfir med asthm a; Whee zing
Ekater ina Maslo va
Wes tern
Cohort study
28, Physi 399 cianconfir med asthm
Den mar k /201 4
Asth ma diagn osis
Variables in risk adjustment
Materna l vitamin E intake during pregnan cy Not describe d
Adjusted for maternal smoking status at first trimester scan, history of maternal asthma, birth order, Scottish Index of Multiple Deprivation (SIMD), birth weight, breastfeeding, use of antibiotics by the child in the first year of life and maternal intake of vitamin C, vitamin D and zinc. Adjusted for 14-18 maternal age, mg/d socio-economic status, parity, pre-pregnancy BMI,
Follo w-up
5 years
7 years
a
Keith M. Allan
UK /201 4
Wes tern
Birth cohort study
934 Physi cianconfir med asthm a; Whee zing
Augus USA Wes to A /200 tern Litonj 6 ua
Prospe ctive, observ ational cohort study
103 Whee 8 zing
maternal physical activity, maternal smoking during pregnancy, breastfeeding duration, child sex, maternal history of asthma, maternal history of allergies, paternal history of asthma, paternal history of allergies, season of last menstrual period, and intake of energy, fruit, vegetables, fish fatty acids (EPA, DPA, DHA), folic acid, vitamins D and C, Se and Zn (all in quintiles). Odds ratios were 7.91-9.1 10 adjusted for maternal 6 mg/d years smoking during pregnancy, maternal atopy, birth order, child’s sex, maternal age at recruitment, Scottish Index of Multiple Deprivation, birth weight, birth crown-heel length, birth head circumference and maternal vitamin D intake. Adjusted for body 15 mg/d 2 weight, sex, maternal years age, maternal BMI during pregnancy, maternal asthma, paternal asthma, family income,
Christ ina E. West
West ern Aust ralia /201 2 Sheela UK gh /200 Marti 5 ndale
Wes tern
Cohort study
300 Whee zing
Wes tern
Cohort study
137 Whee 4 zing
Y. Miyak e
East Cohort ern study
763 Whee zing
Japa n /201 0
passive smoke exposure, breastfeeding, and other children less than 12 years old in the home. Maternal education and delivery method were included in the multiple logistic regression model adjusted for gender, maternal age, paternal social class, maternal atopy, maternal smoking, other children in the home, antibiotic use and vitamin C Adjustment for maternal age, gestation at baseline, residential municipality at baseline, family income, maternal and paternal education, maternal and paternal history of asthma, atopic eczema, and allergic rhinitis, changes in maternal diet in the previous 1 month, season when baseline data were collected, maternal smoking during pregnancy, baby’s older siblings, baby’s sex, baby’s birth weight, household smoking in same
17.4 mg/d
1 year
Not 2 describe years d
9.7 mg/d
16-2 4 mont hs
Graha m Dever eux
UK /200 6
Wes tern
Longit udinal cohort study
BI Nwar u
Finl and /201 1
Wes tern
Birth cohort study
Anne Green ough
UK /201 0
Wes tern
Birth cohort study
room as infant, breastfeeding duration, and age of infant at third survey. 125 Physi Adjusted for 3 cian maternal age, -confi maternal atopy, rmed maternal smoking, asthm maternal vitamin C a; intake, maternal zinc Whee intake, father’s zing social class, maternal age when leaving full-time education, deprivation index, birth weight, birth head circumference, birth crown-heel length, child’s sex, birth order, breastfeeding, and use of antibiotics by child in first year of life. 352 Physi Adjustment for 3 cian maternal intake of -confi vitamin D, rmed polyunsaturated fatty asthm acids, month of birth a and parental history of allergy (parental rhinitis or asthma) 643 Physi No cian -confi rmed asthm a
13.2 mg/d
5 years
11 mg/d
5 years
400 mg/d
1 year
Table 2 Main characteristics of the 4 studies on serum vitamin E included in the meta-analysis
Author
Country/Year Area
Raida I. USA Harik-Khan1 /2004
Rachel N
Denmark /2003
Study design
Sample Asthma size diagnosis
Variables in risk adjustment
Physician4,093 confirmed None asthma All models were adjusted for age, sex, race, body mass index, passive smoke exposure, active smoke exposure, parental history of asthma and/or hay fever, urban environment, Cross-sectional, household Physicianmultistage, crowding, Western 4110 confirmed complex years of asthma sample survey education of the head of household, childhood history of hay fever, and avoidance of pet ownership caused by allergy. Models with vitamin E or β-carotene were also adjusted for total serum Case-control Western study
Okuda M
Japan /2010
Tricia M. McKeever
USA /2004
Eastern
Nested case-control design
396
Western
Cross-sectional survey
4271
cholesterol and triglycerides Odds ratios were adjusted for age groups, gender, serum cholesterol, fasting before blood draw, BMI z score, Physicianhousehold confirmed smoking, asthma single parent, and number of siblings, with nested clustering design effects of area and school taken into account. Adjusted for age, sex, and race/ethnicity; Physicianfindings in confirmed bold, total asthma cholesterol and triglycerides.
Table 3 Main characteristics of the 5 studies on vitamin E intake in childhood included in the meta-analysis
Author
Country/Year
Area
Study design
Kozue Nakamura1
Japan /2012
Eastern
Cross-sectional study
H. Rosenlund
Sweden/2012
Western cohort study
Sample Asthma size diagnosis
452
Physicianconfirmed asthma
2442
Physicianconfirmed asthma
Variables in risk adjustment
Adjusted for child’s age, child’s sex, child’s BMI, breastfeeding, child’s history of food allergy, mother’s age, parental history of allergy, maternal education level, the number of siblings and household smoking. Adjusted for maternal age, socio-economic status, parity, pre-pregnancy BMI, maternal physical activity, maternal smoking during pregnancy, breastfeeding duration, child sex, maternal history of asthma, maternal history of allergies, paternal history of asthma, paternal history of allergies, season of last menstrual period, and intake of energy, fruit,
Maternal vitamin E intake during pregnancy
5.09 mg/d (SD ± 1.6)
7.1 mg (SD ± 1.2)
Eastern
Cross-sectional study
1111
Physicianconfirmed asthma
UK/2009
Western
Cross-sectional study
861
Physicianconfirmed asthma
Netherlands /1998
Cross-sectional Western study
8012
Physicianconfirmed asthma
So-Yeon Lee1
South Korea/2015
S. Patel
Grievink
vegetables, fish fatty acids (EPA, DPA, DHA), folic acid, vitamins D and C, Se and Zn (all in quintiles). Adjusted by age, sex, BMI (continuous), parental history of asthma, exposure to environmental tobacco smoke, maternal education, household income, and log-transformed total energy intake Adjusted for gender, parental atopy, socioeconomic status and BMI SDS. Adjusted for age, sex, energy intake, smoking status, pack-years of smoking, presented for subjects in the 90th percentile versus subjects in the 10th percentile of antioxidant intake.
7-10 mg/d
3.52 mg/d
16.3 mg/d
Quality assessment： ：
The NOS scores for the 19 studies ranged from 5 to 9, with a median of 6; 15 of them were scored as having high (>6) methodological quality. Higher scores indicated better methodological quality.
Meta-analysis results： ：
Maternal intake of vitamin E： ：
Ten studies on maternal intake of vitamin E were eligible for inclusion. The corresponding meta-analysis revealed that maternal intake of vitamin E was associated with lower odds of asthmatic diseases [Random effects model OR=0.76, 95% CI=0.63-0.90, p=0.002], asthma [Fixed effects model OR=0.98, CI=0.96-0.99, p<0.05], and wheeze [Fixed effects model OR=0.65, CI=0.26-0.75, p<0.001] during childhood. The main results of this meta-analysis are shown in Figures 2A-2C.
Figure 2 Meta-analysis ORs of vitamin E supplementation during pregnancy and childhood asthmatic diseases. (A) The OR of vitamin E supplementation during pregnancy and childhood asthma. (B) The OR of vitamin E supplementation during pregnancy and childhood wheezing. (C) The OR of serum vitamin E in childhood asthma. (D) The OR of supplemental vitamin E in childhood asthma. (E)
Serum vitamin E： ： Serum vitamin E had no effect on asthmatic diseases. The main results of this meta-analysis are shown in Figure 2D.
Supplemental vitamin E during childhood： ： Supplemental vitamin E during childhood had no effect on asthmatic diseases. The main results of this meta-analysis are shown in Figure 2E.
Subgroup analysis: To explore the heterogeneity between the 10 studies on maternal intake of vitamin E, the outcomes were further evaluated via subgroup analysis based on several main features, including area, sample size, and follow-up time (Table 4).
Table 4 Subgroup analysis results of maternal intake of vitamin E in asthmatic children. Heterogeneity Variables
Outcome
Studies
Patients
OR (95% CI)
P value
Model I2
All Type of area Eastern Western Sample size >1000 <1000 Follow-up time <6 years >6 years
P
Asthma Wheezing
6 7
53250 26116
0.98(0.95, 1.00) 0.73 (0.65, 0.82)
0.042 <0.001
Fixed Fixed
49.8% 45.9%
0.008 0.088
Asthma Wheezing Asthma Wheezing
0 1 6 6
0 763 53205 8543
0.54(0.32, 0.91) 0.98(0.95,1.00) 0.74(0.67,0.84)
0.02 0.042 <0.001
Fixed Fixed Fixed
0.0% 49.8% 48.6%
0.000 0.018 0.084
Asthma Wheezing Asthma Wheezing
5 6 1 2
52927 8093 330 1213
0.87(0.73,1.48) 0.61(0.47,0.81) 1.02(0.7,1.48) 0.67(0.47,0.91)
0.109 0.001 0.917 0.018
Random Random Fixed Fixed
59.6% 58.8% 0.0% 0.0%
0.042 0.046 0.000 0.322
Asthma Wheezing Asthma Wheezing
4 6 2 1
6687 7382 46518 1924
0.84(0.73,0.96) 0.76(0.67,0.86) 0.98(0.96,1.00) 0.59(0.43,0.82)
0.11 <0.001 0.108 0.001
Fixed Fixed Fixed Fixed
32% 45.6% 0.0% 0.0%
0.22 0.102 0.418 <0.001
Sensitivity analysis: The sensitivity analysis showed that the study by Maslova et al [15] was the only one that significantly altered the results; this article was the main source of heterogeneity in the asthma analyses. Additionally, each cohort included in our meta-analysis was removed in turn to determine whether individual studies influenced the results. The results remained similar to the overall findings, indicating the stability of this study and the relative reliability of its findings (data not shown).
Assessment of risk of bias of the included studies: Every effort was made to identify unpublished studies by searching abstracts and ongoing trials databases. The publication bias of all enrolled studies was evaluated using funnel plots and Egger's and Begg's tests. The funnel plots were almost symmetrical (Figure 3). Furthermore, the P-values of Egger's and Begg's tests were all greater than 0.05 (maternal intake of vitamin E and asthma, P=0.348 for Begg's test, P=0.133 for Egger's test; maternal intake of vitamin E and wheeze, P=0.176 for Begg's test, P=0.052 for Egger's test; serum vitamin E, P=0.174 for Begg's test, P=0.335 for Egger's test; supplemental vitamin E in childhood, P=0.327 for Begg's test, P=0.312 for Egger's test). Therefore, there was no significant publication bias in our meta-analysis.
Figure 3 Funnel plots based on the outcomes. A. The rate of maternal intake of vitamin E in asthmatic children. B. The rate of maternal intake of vitamin E in childhood wheezing. C. The rate of serum vitamin E in childhood asthma. D. The rate of serum vitamin E supplementation in childhood asthma
Discussion:
Our systematic review identified nineteen studies, which were analyzed to assess the relationship of vitamin E with childhood asthma and wheeze. None of the identified studies reported on the effects of vitamin E supplementation on mortality, quality of life, or adverse effects. Our final results indicated that maternal intake of vitamin E during pregnancy was associated with reduced odds of asthmatic diseases. Additionally, in the subgroup analysis, we found that maternal vitamin E intake was negatively associated with childhood wheezing and childhood asthma (OR=0.98, CI 0.95-1.00, I2=49.8%), especially childhood wheezing, regardless of sample size and follow-up time. We also found that the type of area could affect the occurrence of asthma or wheezing. Our findings regarding vitamin E are consistent with those of previous reviews
[10, 19, 21, 32]
, which concluded that maternal dietary intake of vitamin
E may protect against childhood wheezing. Other studies have reported no association of vitamin E intake with wheezing or asthma
[18, 33]
. Due to the differences in study
design and population and the omission of the levels of vitamin E intake in the exposure groups in some studies
[16, 21]
, the potential threshold level of vitamin E
intake that confers optimal immunity is difficult to establish.
Vitamin E deficiency can predispose individuals to asthma, and a direct correlation between low levels of vitamin E and inflammatory disorders such as asthma has been established. Some studies [24, 34] have confirmed the relation between vitamin E deficiency and development of asthma. However, in our analysis, serum vitamin E and supplemental vitamin E during childhood had no association with the prevalence of asthma; further large-scale, well-designed and randomized controlled trials are needed to confirm this finding.
Allergic disease often begins in utero or in early childhood, when environmental factors affect the development of risk of allergic illnesses (food allergy, asthma, allergic rhinitis, and eczema)[35]; therefore, identifying and modifying these exposures could have a significant impact on public health. In asthmatic diseases, the airways exhibit specific inflammatory abnormalities related to increased generation of reactive oxygen species and tissue damage by free radicals. The antioxidant system of the respiratory tract protects against exposure to noxious oxidants, and an imbalance between oxidants and antioxidants in favor of oxidants will lead to oxidative stress[36] The development of allergic responses and distinct dendritic cell subsets can be prevented in offspring of allergic mothers by maternal supplementation with the α-tocopherol isoform of vitamin E[37]. Vitamin E is a fat-soluble vitamin that has several isoforms with the following effects: antioxidation, protection of tissues and
cells from free radical damage generated by oxidized fats and some chemicals, anti-inflammation, and prevention or reversal of lung inflammation, including the lung inflammation present in chronic asthma or asthma exacerbations due to infection [38]
. Specifically, several recent animal studies have demonstrated the ability of
vitamin E to decrease lung inflammation during exposure to respiratory infection and allergic inflammation. Moreover, studies have shown that exposures from as early as the first trimester may be important determinants of lung development and respiratory disease during childhood [19]. Additionally, articles have indicated that the association between vitamin E and respiratory outcomes may be mediated by fetal size and/or growth [39]. In the UK, the mean vitamin E intake of women of childbearing age is approximately 8 mg/day, with 93-97% reporting a vitamin E intake below the recommended daily amount (RDA) of 15 mg/day proposed by the US National Institutes of Health and 80% below the European Union’s RDA of 10 mg/day [17]. Clark et al [40] demonstrated for the first time that pregnant women with a personal and/or partner history of asthma were able to use a novel food-based exchange intervention to increase their dietary vitamin E intake to 15 mg/day.
Limitations： There were several limitations in this study: first, only 19 studies were included in our meta-analysis, i.e., there was a relatively small sample size. Second, there was heterogeneity between studies that may have been caused by differences in region or follow-up time. In addition, the meta-analyses lacked sufficient data.
Conclusion:
In conclusion, this meta-analysis clarified that the use of supplemental vitamin E during pregnancy can prevent asthmatic diseases. However, additional studies (either observational longitudinal studies or clinical trials of maternal supplementation) are needed to determine whether prenatal supplementation of vitamin E is warranted, particularly given the potential and long-lasting adverse effects.
Practice Points: * Vitamin E supplementation during pregnancy influenced the risk of wheezing illness in young children and asthma. *. *We need more large-scale, well-designed and randomized controlled trials to determnine whether maternal intake of vitamin E can effectively prevent asthma
Conflicts of interest Conflict of interest: None.
Directions for future research: * Can dietary manipulation in pregnancy influence the development of childhood asthma?
* * Can early dietary intervention in childhood prevent childhood wheezing / asthma?.
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S1526-0542(17)30093-3 https://doi.org/10.1016/j.prrv.2017.08.002 YPRRV 1237
To appear in:
Paediatric Respiratory Reviews
Please cite this article as: W. Hui, C. Zhang, Y. Wang, Y. Li, Does vitamin E prevent asthma or wheeze in children: a systematic review and meta-analysis, Paediatric Respiratory Reviews (2017), doi: https://doi.org/10.1016/j.prrv. 2017.08.002
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Does vitamin E prevent asthma or wheeze in children: a systematic review and meta-analysis Wu Hui, Chunwei Zhang, Yongqing Wang, Yanlin Li1＊ Department of Pediatrics, the First People Hospital of Changzhou and the Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213000, China.
Communicated by Peter de Winter First author: Hui Wu [email protected]
Second Author: Chunwei Zhang [email protected]
Third Author : Yongqing Wang [email protected]
Corresponding author: Yanlin Li
＊
[email protected]
1 Department of Pediatrics, The Third Affiliated Hospital of Soochow University，Changzhou 213003, Jiangsu Province, China
Summary
Asthma is a heterogeneous disease with multiple phenotypes. Epidemiologic studies suggest a close relationship between vitamin E and the occurrence of asthma, wheezing and atopic conditions during childhood. Previous results on its effects have been conflicting. The aim of this meta-analysis was to critically examine the current evidence on the association of vitamin E with childhood asthma and wheezing. We searched electronic databases for observational studies in English-language journals published from 2000 to 2016. The initial search found 420 titles; nineteen studies were eligible according to the abstracts and details, which included reporting asthma or wheeze as an outcome. None of the articles included in this meta-analysis reported side effects of vitamin E supplementation during pregnancy.This meta-analysis found that vitamin E supplementation during pregnancy influenced the risk of asthma. To better understand the effectiveness and safety of vitamin E in children with asthma, large-scale, well-designed and randomized controlled trials are needed.
Key words: Asthma, Wheezing, Vitamin E, Childhood Educational Aims: The reader will be able:
* To examine the current evidence on the association of serum vitamin E with childhood asthma and wheezing. * To analyse of the relationship of supplemental vitamin E with childhood asthma and wheezing.
* To assess the effect of vitamin E supplementation during pregnancy in childhood asthma.
In recent years, allergic diseases, especially childhood wheezing and asthma, have presented a global problem, and children suffer the highest burden of these conditions. Food allergies, wheeze, asthma and eczema are the most common allergic disorders in children
[1]
. In the United States (US), the prevalence of these disorders increased
from 7.3% in 2001 to 8.4% in 2010 (and from 3.5% in the 1970s). In 2010, an estimated 25.7 million people in the US had current or active asthma, including 18.7 million adults and 7 million children [2]. The direct and indirect yearly costs of asthma to the US economy have been estimated to be $18 billion. Increasing evidence has shown that environmental factors have an important role in the onset of complex
conditions such as allergic diseases and that the role of fixed genetic variation is much smaller than previously believed [3].
Therefore, new approaches to disease prevention with an emphasis on early interventions, such as before and/or during pregnancy, should be widely investigated. Current evidence suggests that future studies should focus on the role of maternal diet during pregnancy in subsequent disease development [4], as many immune modulatory processes may start in utero. Some researchers have proposed that the increased prevalence of allergic disorders may be related to diets.
Dietary changes have been hypothesized to contribute to the increase in asthma and atopic disease observed in economically developed countries
[5]
. Additionally, early
life factors are known to play critical roles in the development of asthma and atopic disease. Studies have related maternal or childhood dietary status to the development of childhood atopic diseases. Maternal dietary changes in pregnancy are a key environmental factor implicated in the allergy epidemic [6]. Animal studies and studies with pregnant women suggest that appropriate fetal exposure to vitamin E confers enhanced lifetime resistance to asthma. Some studies have also examined serum vitamin E or supplemental vitamin E during childhood but with conflicting results. The preventive role of vitamin E is complex and involves functional variations of the different isoforms. In the first months of life, eczema and food allergy are often evident, and a better understanding of the role of early life exposures is thus needed.
As the maternal diet supplies all nutrients during pregnancy, it has significant potential to modify the success or failure of immune tolerance and to affect the development of allergic disease in the offspring
[7]
. Previous epidemiological studies
have suggested an association between lower intake of antioxidant-rich foods (such as fresh fruits and vegetables) and deficits in lung function childhood wheezing
[8]
and increased risk of
[9]
. Recently, dietary antioxidants have been implicated in the
development of fetal and infant immune response and the occurrence of allergic disease
[10]
. Oxidative stress is more important in many diseases. An increasing
number of studies have investigated the effects of maternal antioxidant intake, especially vitamin E, and the incidence of allergic diseases, but none have specifically targeted a population at high risk of developing asthma. But in other diseases, such as bronchopulmonary dysplasia (BPD) which is the most likely to suffer from respiratory morbidity
[11]
, oxidative stress has been implicated in the development of BPD, and
prematurely born infants have impaired antioxidant defenses [12].
Therefore, the aim of this study was to assess the effects of supplemental and serum vitamin E and the risk of asthma and wheeze in offspring.
Study selection criteria： ：
We searched the PubMed, Medline, and Web of Science electronic databases using
the following keywords: (asthma OR Bronchial Asthma OR wheezing OR Respiratory Sound OR Wheezing) OR (serum vitamin E) AND [maternal OR pregnancy] AND (offspring OR infant OR child) AND vitamin E. The reference lists of relevant publications were also searched for additional studies. Furthermore, we searched in other data sources, including web search results, references of relevant included publications and pharmaceutical industry websites. We attempted to contact the authors to obtain any missing information.
To be included in the meta-analysis, studies had to meet the following criteria: (i) systematic recording of serum vitamin E or vitamin E supplementation during pregnancy or childhood; (ii) use of at least two comparison groups (asthma versus control); (iii) use of asthma in offspring as an outcome; and (iv) presentation of associations as relative risks (RR) or odds ratios (ORs) with respect to some measure of vitamin E intake. The primary outcome was the prevalence of asthma among offspring during childhood. The exclusion criteria were as follows: 1) studies that were not written in English; 2) letters, review papers, meeting records, commentaries, case reports, or clinical guidelines; 3) studies that lacked critical data, such as ORs and 95% confidence intervals (CIs); and 4) studies on asthma or experimental animal studies. Finally, when several articles included overlapping data, the study with the largest sample size was reviewed.
Data extraction from the included studies One reviewer (Wu Hui) extracted information including the first author's name, year of publication, country in which the study was conducted, ethnicity, sample size, duration of follow-up, vitamin E intake, serum vitamin E, and RRs and 95% CIs for asthma (physician's diagnosis and/or objective criteria) or wheezing (Tables 1-3). During the data extraction process, any disagreements about the interventions and outcomes were discussed and resolved by the review team. The reviewer was not blinded to the name of the authors, institutions, journals, or outcomes of the trials during the process. The details were then independently checked by a second reviewer (Chunwei Zhang).
Quality assessment of the included studies
Two researchers independently assessed the quality of each study using the Newcastle-Ottawa quality assessment scale (NOS)
[13]
. The NOS for case-control
studies was applied to assess the quality of the included studies regarding three main categories: study selection, comparability of groups and determination of outcomes. The quality scores ranged from 0 (lowest) to 9 (highest), and studies with scores of 6 or more were considered to be of high quality.
Statistical analysis
We calculated the pooled ORs, RRs, and hazard ratios (HRs) with 95% CIs for categorical outcomes. The clinical and statistical appropriateness of a meta-analysis were considered for all exposures/outcomes. Heterogeneity was assessed using the I² statistic and chi-square test. Significant heterogeneity was assumed for I² >50%. Meta-analyses were performed using fixed effect modeling (the Mantel-Haenszel method) when I²<50%, and random effects modeling (the DerSimonian-Laird method) was used when I²>50% or P-value<0.1. In contrast with fixed effect modeling, random effects modeling does not assume a single underlying effect size and therefore generates more conservative estimates of precision. The net effect is that these 2 modeling techniques result in essentially identical point estimates of effect but with the random effects-derived models generating wider 95% CIs around these estimates. Subgroup analyses were conducted with groups divided by area, quality of evidence, and follow-up time. Sensitivity analyses were performed to evaluate the effect of each study on the pooled ORs. Furthermore, we performed Begg's and Egger's tests to provide quantitative evidence of publication bias. All statistical tests were two-sided, and noticeably asymmetric funnels plots indicated publication bias. For Begg’s and Egger’s tests, the significance level was set at 0.05. Data analyses were performed using STATA version 12.0 (Stata Corporation, College Station, TX, USA).
Search results： ：
The literature search and screening process is shown in Figure 1. The database search
identified 420 potentially relevant publications in PubMed, EMBASE, and Web of Science. After scanning the title, abstract, publication type, and full text of the 420 publications, we excluded 289 articles as being clearly irrelevant. Of the remaining articles, 12 were excluded, five lacked some important data, and seven did not report ORs or RRs. Therefore, a total of 19 studies were included in our meta-analysis
[10,
14-31]
.
Figure 1 Main characteristics of all studies included in the meta-analysis
Characteristics of included studies： ：
Basic information on the studies that met the inclusion criteria was collected. These studies were published between 2006 and 2014, and all were cohort studies, as shown in Table 1. Five were conducted in the United Kingdom, and one each was performed
in Finland, Japan, United States, Australia, and Denmark. The studies assessed 2 major ethnic populations; 9 were conducted in Western settings, while 1 study was conducted in Eastern contexts. Of these studies, 3 studies reported on both asthma and wheezing. Thus, 6 articles addressed childhood asthma, and 7 articles investigated childhood wheeze. More details are shown in Tables 1-3.
Table 1 Main characteristics of the 10 studies on maternal vitamin E intake included in the meta-analysis Autho r
Cou ntry/ Year
Typ e of area
Study design
Sa mpl e size
Stephe UK nW /201 Turner 0
Wes tern
Longit udinal birth cohort study
101 Physi 8 cianconfir med asthm a; Whee zing
Ekater ina Maslo va
Wes tern
Cohort study
28, Physi 399 cianconfir med asthm
Den mar k /201 4
Asth ma diagn osis
Variables in risk adjustment
Materna l vitamin E intake during pregnan cy Not describe d
Adjusted for maternal smoking status at first trimester scan, history of maternal asthma, birth order, Scottish Index of Multiple Deprivation (SIMD), birth weight, breastfeeding, use of antibiotics by the child in the first year of life and maternal intake of vitamin C, vitamin D and zinc. Adjusted for 14-18 maternal age, mg/d socio-economic status, parity, pre-pregnancy BMI,
Follo w-up
5 years
7 years
a
Keith M. Allan
UK /201 4
Wes tern
Birth cohort study
934 Physi cianconfir med asthm a; Whee zing
Augus USA Wes to A /200 tern Litonj 6 ua
Prospe ctive, observ ational cohort study
103 Whee 8 zing
maternal physical activity, maternal smoking during pregnancy, breastfeeding duration, child sex, maternal history of asthma, maternal history of allergies, paternal history of asthma, paternal history of allergies, season of last menstrual period, and intake of energy, fruit, vegetables, fish fatty acids (EPA, DPA, DHA), folic acid, vitamins D and C, Se and Zn (all in quintiles). Odds ratios were 7.91-9.1 10 adjusted for maternal 6 mg/d years smoking during pregnancy, maternal atopy, birth order, child’s sex, maternal age at recruitment, Scottish Index of Multiple Deprivation, birth weight, birth crown-heel length, birth head circumference and maternal vitamin D intake. Adjusted for body 15 mg/d 2 weight, sex, maternal years age, maternal BMI during pregnancy, maternal asthma, paternal asthma, family income,
Christ ina E. West
West ern Aust ralia /201 2 Sheela UK gh /200 Marti 5 ndale
Wes tern
Cohort study
300 Whee zing
Wes tern
Cohort study
137 Whee 4 zing
Y. Miyak e
East Cohort ern study
763 Whee zing
Japa n /201 0
passive smoke exposure, breastfeeding, and other children less than 12 years old in the home. Maternal education and delivery method were included in the multiple logistic regression model adjusted for gender, maternal age, paternal social class, maternal atopy, maternal smoking, other children in the home, antibiotic use and vitamin C Adjustment for maternal age, gestation at baseline, residential municipality at baseline, family income, maternal and paternal education, maternal and paternal history of asthma, atopic eczema, and allergic rhinitis, changes in maternal diet in the previous 1 month, season when baseline data were collected, maternal smoking during pregnancy, baby’s older siblings, baby’s sex, baby’s birth weight, household smoking in same
17.4 mg/d
1 year
Not 2 describe years d
9.7 mg/d
16-2 4 mont hs
Graha m Dever eux
UK /200 6
Wes tern
Longit udinal cohort study
BI Nwar u
Finl and /201 1
Wes tern
Birth cohort study
Anne Green ough
UK /201 0
Wes tern
Birth cohort study
room as infant, breastfeeding duration, and age of infant at third survey. 125 Physi Adjusted for 3 cian maternal age, -confi maternal atopy, rmed maternal smoking, asthm maternal vitamin C a; intake, maternal zinc Whee intake, father’s zing social class, maternal age when leaving full-time education, deprivation index, birth weight, birth head circumference, birth crown-heel length, child’s sex, birth order, breastfeeding, and use of antibiotics by child in first year of life. 352 Physi Adjustment for 3 cian maternal intake of -confi vitamin D, rmed polyunsaturated fatty asthm acids, month of birth a and parental history of allergy (parental rhinitis or asthma) 643 Physi No cian -confi rmed asthm a
13.2 mg/d
5 years
11 mg/d
5 years
400 mg/d
1 year
Table 2 Main characteristics of the 4 studies on serum vitamin E included in the meta-analysis
Author
Country/Year Area
Raida I. USA Harik-Khan1 /2004
Rachel N
Denmark /2003
Study design
Sample Asthma size diagnosis
Variables in risk adjustment
Physician4,093 confirmed None asthma All models were adjusted for age, sex, race, body mass index, passive smoke exposure, active smoke exposure, parental history of asthma and/or hay fever, urban environment, Cross-sectional, household Physicianmultistage, crowding, Western 4110 confirmed complex years of asthma sample survey education of the head of household, childhood history of hay fever, and avoidance of pet ownership caused by allergy. Models with vitamin E or β-carotene were also adjusted for total serum Case-control Western study
Okuda M
Japan /2010
Tricia M. McKeever
USA /2004
Eastern
Nested case-control design
396
Western
Cross-sectional survey
4271
cholesterol and triglycerides Odds ratios were adjusted for age groups, gender, serum cholesterol, fasting before blood draw, BMI z score, Physicianhousehold confirmed smoking, asthma single parent, and number of siblings, with nested clustering design effects of area and school taken into account. Adjusted for age, sex, and race/ethnicity; Physicianfindings in confirmed bold, total asthma cholesterol and triglycerides.
Table 3 Main characteristics of the 5 studies on vitamin E intake in childhood included in the meta-analysis
Author
Country/Year
Area
Study design
Kozue Nakamura1
Japan /2012
Eastern
Cross-sectional study
H. Rosenlund
Sweden/2012
Western cohort study
Sample Asthma size diagnosis
452
Physicianconfirmed asthma
2442
Physicianconfirmed asthma
Variables in risk adjustment
Adjusted for child’s age, child’s sex, child’s BMI, breastfeeding, child’s history of food allergy, mother’s age, parental history of allergy, maternal education level, the number of siblings and household smoking. Adjusted for maternal age, socio-economic status, parity, pre-pregnancy BMI, maternal physical activity, maternal smoking during pregnancy, breastfeeding duration, child sex, maternal history of asthma, maternal history of allergies, paternal history of asthma, paternal history of allergies, season of last menstrual period, and intake of energy, fruit,
Maternal vitamin E intake during pregnancy
5.09 mg/d (SD ± 1.6)
7.1 mg (SD ± 1.2)
Eastern
Cross-sectional study
1111
Physicianconfirmed asthma
UK/2009
Western
Cross-sectional study
861
Physicianconfirmed asthma
Netherlands /1998
Cross-sectional Western study
8012
Physicianconfirmed asthma
So-Yeon Lee1
South Korea/2015
S. Patel
Grievink
vegetables, fish fatty acids (EPA, DPA, DHA), folic acid, vitamins D and C, Se and Zn (all in quintiles). Adjusted by age, sex, BMI (continuous), parental history of asthma, exposure to environmental tobacco smoke, maternal education, household income, and log-transformed total energy intake Adjusted for gender, parental atopy, socioeconomic status and BMI SDS. Adjusted for age, sex, energy intake, smoking status, pack-years of smoking, presented for subjects in the 90th percentile versus subjects in the 10th percentile of antioxidant intake.
7-10 mg/d
3.52 mg/d
16.3 mg/d
Quality assessment： ：
The NOS scores for the 19 studies ranged from 5 to 9, with a median of 6; 15 of them were scored as having high (>6) methodological quality. Higher scores indicated better methodological quality.
Meta-analysis results： ：
Maternal intake of vitamin E： ：
Ten studies on maternal intake of vitamin E were eligible for inclusion. The corresponding meta-analysis revealed that maternal intake of vitamin E was associated with lower odds of asthmatic diseases [Random effects model OR=0.76, 95% CI=0.63-0.90, p=0.002], asthma [Fixed effects model OR=0.98, CI=0.96-0.99, p<0.05], and wheeze [Fixed effects model OR=0.65, CI=0.26-0.75, p<0.001] during childhood. The main results of this meta-analysis are shown in Figures 2A-2C.
Figure 2 Meta-analysis ORs of vitamin E supplementation during pregnancy and childhood asthmatic diseases. (A) The OR of vitamin E supplementation during pregnancy and childhood asthma. (B) The OR of vitamin E supplementation during pregnancy and childhood wheezing. (C) The OR of serum vitamin E in childhood asthma. (D) The OR of supplemental vitamin E in childhood asthma. (E)
Serum vitamin E： ： Serum vitamin E had no effect on asthmatic diseases. The main results of this meta-analysis are shown in Figure 2D.
Supplemental vitamin E during childhood： ： Supplemental vitamin E during childhood had no effect on asthmatic diseases. The main results of this meta-analysis are shown in Figure 2E.
Subgroup analysis: To explore the heterogeneity between the 10 studies on maternal intake of vitamin E, the outcomes were further evaluated via subgroup analysis based on several main features, including area, sample size, and follow-up time (Table 4).
Table 4 Subgroup analysis results of maternal intake of vitamin E in asthmatic children. Heterogeneity Variables
Outcome
Studies
Patients
OR (95% CI)
P value
Model I2
All Type of area Eastern Western Sample size >1000 <1000 Follow-up time <6 years >6 years
P
Asthma Wheezing
6 7
53250 26116
0.98(0.95, 1.00) 0.73 (0.65, 0.82)
0.042 <0.001
Fixed Fixed
49.8% 45.9%
0.008 0.088
Asthma Wheezing Asthma Wheezing
0 1 6 6
0 763 53205 8543
0.54(0.32, 0.91) 0.98(0.95,1.00) 0.74(0.67,0.84)
0.02 0.042 <0.001
Fixed Fixed Fixed
0.0% 49.8% 48.6%
0.000 0.018 0.084
Asthma Wheezing Asthma Wheezing
5 6 1 2
52927 8093 330 1213
0.87(0.73,1.48) 0.61(0.47,0.81) 1.02(0.7,1.48) 0.67(0.47,0.91)
0.109 0.001 0.917 0.018
Random Random Fixed Fixed
59.6% 58.8% 0.0% 0.0%
0.042 0.046 0.000 0.322
Asthma Wheezing Asthma Wheezing
4 6 2 1
6687 7382 46518 1924
0.84(0.73,0.96) 0.76(0.67,0.86) 0.98(0.96,1.00) 0.59(0.43,0.82)
0.11 <0.001 0.108 0.001
Fixed Fixed Fixed Fixed
32% 45.6% 0.0% 0.0%
0.22 0.102 0.418 <0.001
Sensitivity analysis: The sensitivity analysis showed that the study by Maslova et al [15] was the only one that significantly altered the results; this article was the main source of heterogeneity in the asthma analyses. Additionally, each cohort included in our meta-analysis was removed in turn to determine whether individual studies influenced the results. The results remained similar to the overall findings, indicating the stability of this study and the relative reliability of its findings (data not shown).
Assessment of risk of bias of the included studies: Every effort was made to identify unpublished studies by searching abstracts and ongoing trials databases. The publication bias of all enrolled studies was evaluated using funnel plots and Egger's and Begg's tests. The funnel plots were almost symmetrical (Figure 3). Furthermore, the P-values of Egger's and Begg's tests were all greater than 0.05 (maternal intake of vitamin E and asthma, P=0.348 for Begg's test, P=0.133 for Egger's test; maternal intake of vitamin E and wheeze, P=0.176 for Begg's test, P=0.052 for Egger's test; serum vitamin E, P=0.174 for Begg's test, P=0.335 for Egger's test; supplemental vitamin E in childhood, P=0.327 for Begg's test, P=0.312 for Egger's test). Therefore, there was no significant publication bias in our meta-analysis.
Figure 3 Funnel plots based on the outcomes. A. The rate of maternal intake of vitamin E in asthmatic children. B. The rate of maternal intake of vitamin E in childhood wheezing. C. The rate of serum vitamin E in childhood asthma. D. The rate of serum vitamin E supplementation in childhood asthma
Discussion:
Our systematic review identified nineteen studies, which were analyzed to assess the relationship of vitamin E with childhood asthma and wheeze. None of the identified studies reported on the effects of vitamin E supplementation on mortality, quality of life, or adverse effects. Our final results indicated that maternal intake of vitamin E during pregnancy was associated with reduced odds of asthmatic diseases. Additionally, in the subgroup analysis, we found that maternal vitamin E intake was negatively associated with childhood wheezing and childhood asthma (OR=0.98, CI 0.95-1.00, I2=49.8%), especially childhood wheezing, regardless of sample size and follow-up time. We also found that the type of area could affect the occurrence of asthma or wheezing. Our findings regarding vitamin E are consistent with those of previous reviews
[10, 19, 21, 32]
, which concluded that maternal dietary intake of vitamin
E may protect against childhood wheezing. Other studies have reported no association of vitamin E intake with wheezing or asthma
[18, 33]
. Due to the differences in study
design and population and the omission of the levels of vitamin E intake in the exposure groups in some studies
[16, 21]
, the potential threshold level of vitamin E
intake that confers optimal immunity is difficult to establish.
Vitamin E deficiency can predispose individuals to asthma, and a direct correlation between low levels of vitamin E and inflammatory disorders such as asthma has been established. Some studies [24, 34] have confirmed the relation between vitamin E deficiency and development of asthma. However, in our analysis, serum vitamin E and supplemental vitamin E during childhood had no association with the prevalence of asthma; further large-scale, well-designed and randomized controlled trials are needed to confirm this finding.
Allergic disease often begins in utero or in early childhood, when environmental factors affect the development of risk of allergic illnesses (food allergy, asthma, allergic rhinitis, and eczema)[35]; therefore, identifying and modifying these exposures could have a significant impact on public health. In asthmatic diseases, the airways exhibit specific inflammatory abnormalities related to increased generation of reactive oxygen species and tissue damage by free radicals. The antioxidant system of the respiratory tract protects against exposure to noxious oxidants, and an imbalance between oxidants and antioxidants in favor of oxidants will lead to oxidative stress[36] The development of allergic responses and distinct dendritic cell subsets can be prevented in offspring of allergic mothers by maternal supplementation with the α-tocopherol isoform of vitamin E[37]. Vitamin E is a fat-soluble vitamin that has several isoforms with the following effects: antioxidation, protection of tissues and
cells from free radical damage generated by oxidized fats and some chemicals, anti-inflammation, and prevention or reversal of lung inflammation, including the lung inflammation present in chronic asthma or asthma exacerbations due to infection [38]
. Specifically, several recent animal studies have demonstrated the ability of
vitamin E to decrease lung inflammation during exposure to respiratory infection and allergic inflammation. Moreover, studies have shown that exposures from as early as the first trimester may be important determinants of lung development and respiratory disease during childhood [19]. Additionally, articles have indicated that the association between vitamin E and respiratory outcomes may be mediated by fetal size and/or growth [39]. In the UK, the mean vitamin E intake of women of childbearing age is approximately 8 mg/day, with 93-97% reporting a vitamin E intake below the recommended daily amount (RDA) of 15 mg/day proposed by the US National Institutes of Health and 80% below the European Union’s RDA of 10 mg/day [17]. Clark et al [40] demonstrated for the first time that pregnant women with a personal and/or partner history of asthma were able to use a novel food-based exchange intervention to increase their dietary vitamin E intake to 15 mg/day.
Limitations： There were several limitations in this study: first, only 19 studies were included in our meta-analysis, i.e., there was a relatively small sample size. Second, there was heterogeneity between studies that may have been caused by differences in region or follow-up time. In addition, the meta-analyses lacked sufficient data.
Conclusion:
In conclusion, this meta-analysis clarified that the use of supplemental vitamin E during pregnancy can prevent asthmatic diseases. However, additional studies (either observational longitudinal studies or clinical trials of maternal supplementation) are needed to determine whether prenatal supplementation of vitamin E is warranted, particularly given the potential and long-lasting adverse effects.
Practice Points: * Vitamin E supplementation during pregnancy influenced the risk of wheezing illness in young children and asthma. *. *We need more large-scale, well-designed and randomized controlled trials to determnine whether maternal intake of vitamin E can effectively prevent asthma
Conflicts of interest Conflict of interest: None.
Directions for future research: * Can dietary manipulation in pregnancy influence the development of childhood asthma?
* * Can early dietary intervention in childhood prevent childhood wheezing / asthma?.
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