Nutrients 2013, 5(8), 3212-3234; doi:10.3390/nu5083212

Review
Improving Asthma during Pregnancy with Dietary Antioxidants: The Current Evidence
Jessica A. Grieger 1, Lisa G. Wood 2 and Vicki L. Clifton 1,*
1
Robinson Institute, School of Paediatrics and Reproductive Health, Adelaide University, Lyell McEwin Hospital, Haydown Road, Elizabeth Vale, SA 5112, Australia; E-Mail: jessica.grieger@adelaide.edu.au
2
Hunter Medical Research Institute, School of Biomedical Science and Pharmacy, University of Newcastle, Kookaburra Circuit, New Lambton Heights, NSW 2305, Australia; E-Mail: lisa.wood@newcastle.edu.au
*
Author to whom correspondence should be addressed; E-Mail: vicki.clifton@adelaide.edu.au; Tel.: +61-8-8133-2133; Fax: +61-8-8282-1646.
Received: 14 June 2013; in revised form: 6 August 2013 / Accepted: 7 August 2013 /
Published: 14 August 2013

Abstract

: The complication of asthma during pregnancy is associated with a number of poor outcomes for the mother and fetus. This may be partially driven by increased oxidative stress induced by the combination of asthma and pregnancy. Asthma is a chronic inflammatory disease of the airways associated with systemic inflammation and oxidative stress, which contributes to worsening asthma symptoms. Pregnancy alone also intensifies oxidative stress through the systemic generation of excess reactive oxidative species (ROS). Antioxidants combat the damaging effects of ROS; yet antioxidant defenses are reduced in asthma. Diet and nutrition have been postulated as potential factors to combat the damaging effects of asthma. In particular, dietary antioxidants may play a role in alleviating the heightened oxidative stress in asthma. Although there are some observational and interventional studies that have shown protective effects of antioxidants in asthma, assessment of antioxidants in pregnancy are limited and there are no antioxidant intervention studies in asthmatic pregnancies on asthma outcomes. The aims of this paper are to (i) review the relationships between oxidative stress and dietary antioxidants in adults with asthma and asthma during pregnancy, and (ii) provide the rationale for which dietary management strategies, specifically increased dietary antioxidants, might positively impact maternal asthma outcomes. Improving asthma control through a holistic antioxidant dietary approach might be valuable in reducing asthma exacerbations and improving asthma management during pregnancy, subsequently impacting perinatal health.
Keywords:
asthma; pregnancy; nutrition, antioxidants; oxidative stress

1. Introduction

1.1. Asthma

Allergic diseases such as asthma, hay fever, and rhinitis are amongst the most common chronic diseases affecting people in developed countries [1,2,3,4]. Over the last 40 years, there has been an increase in the prevalence of allergic diseases, particularly in Western countries, with about 300 million people suffering from asthma [1,5]. The financial cost of asthma is high. In 2004–2005, $606 million was spent on asthma in Australia, with more than half spent on medication [6].

Asthma prevalence in Australia is one of the highest in the world, with a prevalence of ~10% in adults [7]. By the age of four to five years, nearly a quarter of children have reported asthma or wheeze at some stage, with diagnosis of asthma in 11.5% [6]. The likelihood of having asthma in childhood is increased when the mother has asthma [8], suggesting the disease has an intergenerational impact that may not be related to genetic susceptibility alone.

1.2. Asthma in Pregnancy

Asthma is the most prevalent chronic medical disease to complicate pregnancies worldwide, with a prevalence in pregnancy of 8%–13% [9,10,11]. In Australia, it affects around 12% of pregnant women or 36,000 pregnancies each year [12]. Asthma in pregnancy has been shown to be associated with a number of poor outcomes for the mother and fetus. In a retrospective cohort study from 223,512 singleton deliveries from 12 clinical centres across the United States, it was found that pregnant women with asthma were more likely to develop preeclampsia (adjusted odds ratio (aOR) 1.14; 95% CI: 1.06–1.22), gestational diabetes (aOR 1.11; 95% CI: 1.03–1.19), and delivering preterm (aOR 1.17; 95% CI; 1.12–1.23) [13]. In a retrospective study from Australia (n = 16,672), pregnant women with asthma had smaller babies (3294 g vs. 3353 g), a higher percentage were smokers (34% vs. 28%), and a higher percentage had essential hypertension (3% vs. 2%) compared to non-asthmatics [14]. In addition, male neonates of asthmatic mothers were more likely to be small for gestational age (SGA) and have smaller head circumference than those of the non-asthmatic mothers [14]. In a meta-analysis of adverse perinatal outcomes among women with asthma, the presence of asthma in pregnancy was associated with an increased relative risk (RR) of low birth-weight (RR 1.46; 95% CI 1.22–1.75), SGA (RR 1.22; 95% CI: 1.14–1.31), preterm delivery (RR 1.41; 95% CI: 1.22–1.61), and pre-eclampsia (RR 1.54; 95% CI: 1.32–1.81) [15]. Maternal asthma has also been associated with bronchiolitis in infancy [16], childhood asthma [17,18], and atopy in children [19].

Asthma exacerbations are common in pregnancies complicated by asthma affecting at least 35% to 55% of pregnancies [20,21]. This particular event has been shown to be associated with a greater risk for low birth-weight (RR 3.02; 95% CI: 1.87–4.89) and preterm delivery (RR 1.54; 95% CI: 0.89–2.69) [22] suggesting the management of asthma during pregnancy is essential to avoid asthma exacerbations and for improved fetal outcomes.

2. Pathophysiology of Asthma

Asthma is a complex inflammatory disease of the airways with symptoms including excess mucus production, wheeze, dyspnoea, cough, fatigue, anxiety, tachycardia, and chest tightness [23,24]. The acute inflammatory response induces asthmatic symptoms such as mucus hypersecretion, plasma exudation, and bronchoconstriction [23,25], and may lead to reversible airway obstruction. However, as the disease progresses, persistent airway inflammation leads to repeated attacks, bronchial constriction and hyper-responsiveness [26]. This is characterised by long-term airway remodeling, with sub-epithelial fibrosis, epithelial cell injury, mucus hypersecretion, angiogenesis, and smooth muscle hypertrophy and hyperplasia [23,25].

A central feature of asthma is inflammatory cell infiltration of the respiratory tract by neutrophils, eosinophils, mast cells [27], and lymphocytes [23]. Airway inflammation in asthma is heterogeneous and may be dominated by an allergen-specific acquired immune response with IL-5 mediated eosinophilic inflammation, or a dysregulation of innate immune responses involving IL-8-induced neutrophilic airway inflammation [28,29]. Importantly, both pathways lead to the production of reactive oxygen species (ROS). The continuous exposure of the respiratory tract to environmental oxidants and airway inflammatory cell-generated ROS creates a high level of oxidative stress in the lung [30,31].

2.1. Oxidative Stress

Activation of inflammatory cells such as mast cells, macrophages, eosinophils, netrophils, lymphocytes, and platelets in the airways [25,32] by stimuli such as allergens, viruses, endotoxin, and smoking, leads to a respiratory burst [33,34] of activated inflammatory cells with increased oxygen consumption [35]. Experimental studies in humans have demonstrated that this respiratory burst can generate various ROS such as superoxide anions, hydrogen peroxide, and hydroxyl radicals, leading to increased quantities of free radicals both in the blood and airway tissues [36,37,38,39]. Cell culture studies in humans and animals have shown ROS can amplify airway inflammation by activating redox-sensitive transcription factors such as NF-κB [40] and JAK-STAT [41], and hydrogen peroxide can activate extracellular signal-regulated kinase Raf-1 [42], leading to further amplification of the transcription of pro-inflammatory genes. This increase in inflammation subsequently impacts the airways [43]. Evidence of oxidative stress in the airways in asthma has been demonstrated by increased exhaled nitric oxide [44,45,46], increased exhaled lipid peroxidation products such as thiobarbituric acid-reactive substances [47], and increased superoxide anion radicals in bronchoalveloar lavage fluid in asthmatics compared to controls [48]. The redox imbalance is not only confined to the lungs but measurable systemically in asthma (e.g., plasma isoprostanes and malondialdehyde) [49,50,51]. Oxidative stress markers have also been shown to be increased during acute asthma exacerbation in adults [52,53], during exacerbation in children [54], and highest in those with severe asthma [55]. Managing asthma and asthma control through minimising oxidative damage appears a necessary factor for reducing asthma severity.

2.2. Pregnancy, Oxidative Stress, and Asthma

Pregnancy is a stressful condition in which many maternal physiological and metabolic functions are altered. In normal human pregnancies, there is increased production of superoxide anions in early gestation [56,57,58,59] and which continues throughout gestation [60,61]. This increased oxidative stress is considered a normal part of pregnancy and levels return to normal post-partum [61]. At this time, an increase in a variety of antioxidant mechanisms controls redox balance [62,63]. However, when the oxidant-antioxidant balance is offset by either heightened oxidative stress or limited antioxidant capacity, excess ROS can contribute to clinical symptoms of gestational diabetes [64], pre-eclampsia [65,66], and asthma [67]. In addition to systemic oxidative stress, oxidative stress manifests at the maternal-fetal interface and contributes to normal placental development. Maternal circulation to the placenta is only fully established at 10–12 weeks of gestation [68], and as a result, leads to high rates of ROS [69,70]. Placental antioxidant enzymes and associated factors are increased [62,71,72], possibly serving as protection of the fetus and the maintenance of pregnancy.

The adverse effects of asthma on the fetus may be due, in-part, to the increase in oxidative stress. Experimental evidence for heightened oxidative stress in pregnancies complicated by asthma was first shown by Clifton et al., in which placentae of pregnant women with asthma had higher levels of lipid peroxidation markers and oxidative stress markers compared to placentae of women without asthma [67]. Later, increased placental cytokine mRNA expression was also identified in placentae of pregnancies complicated by mild- and moderate-severe asthma, compared to placentae from non-asthmatic women [73].

Oxidative stress increases in the presence of asthma exacerbations [53] but it has not been examined in exacerbations during pregnancy. The effects of oxidative stress produced by the complication of asthma and asthma exacerbation during pregnancy could potentially be alleviated through an increase in antioxidant supplementation.

3. The Role of Antioxidants in Asthma

The lungs have endogenous antioxidant mechanisms to combat the damaging effects of ROS. The major enzymatic antioxidants in the lungs are superoxide dismutase, glutathione peroxidase and catalase [74]. Important non-enzymatic antioxidants include vitamin E, vitamin C, albumin, uric acid, ceruloplasmin, and glutathione [75,76,77]. Some studies have demonstrated that levels of antioxidants in the lungs and circulation are reduced in asthmatics. In asthmatic adults, induced sputum carotenoid levels were lower compared to carotenoids measured in whole blood and plasma, and total- and individual carotenoids were lower in whole blood in asthmatic adults compared to healthy controls [78]. Further, Wood et al. identified that adults with airway hyperresponsiveness had reduced levels of whole blood β-carotene, α-tocopherol, and total tocopherols compared with those without airway hyperresponsiveness [79]. Those with severe-persistent asthma had reduced whole-blood levels of α-tocopherol compared with those with mild-moderate asthma; and in those with stable, but poorly controlled asthma, plasma antioxidant potential was lower compared with those with controlled or partly controlled asthma [79]. Other studies have also found that antioxidant concentrations both systemically and in the lungs are consistently reduced in asthmatic patients [48,80,81,82,83], as well as during asthma exacerbations in both adults [52] and children [54]. Oxidative stress is evident in asthma and antioxidant status, measured both systemically and in the lungs, is compromised. Hence, balancing the oxidant-antioxidant system may prove to be an appropriate target for ameliorating oxidative stress in asthma.

Only two separate studies in human asthma research have reported on antioxidant status in pregnancy. First, the study by Clifton et al. reported that antioxidant enzyme activity in the placenta was up-regulated in pregnancies complicated by asthma compared to non-asthmatics [67]. A later study identified that pregnant women with moderate-severe asthma had increased plasma concentrations of total carotenoids and other dietary antioxidants late in gestation, compared to those women with mild asthma and healthy pregnant controls [84]. Moreover, pregnant asthmatic women with low circulating concentrations of various antioxidants had poorer fetal growth outcomes such as head circumference and birth weight. This suggests there is a compensatory increase in antioxidant production and distribution to protect the fetus from the increased oxidative stress that occurs with the combination of asthma and pregnancy.

3.1. The Potential for Dietary Antioxidants to Improve Asthma

Dietary/non-enzymatic antioxidants are the first line of defence against ROS and include vitamin C, lycopene, γ-tocopherol, α-tocopherol, selenium, carotenoids and flavonoids. Table 1 describes some food sources of various antioxidants found in the diet, as well as their function relevant to asthma. In short, α-tocopherol acts to break free radical chain reactions involved in lipid peroxidation [85], thus converting the peroxyl and oxidative radicals to less reactive forms [86], and maintaining fatty acid membrane integrity [87]. As such, increased α-tocopherol might provide protection against oxidative damage to the lungs [86]. α-tocopherol has been shown to inhibit markers of inflammation in human lung epithelial A549 cells, thereby potentially acting as an anti-asthma agent [88]. Carotenoids are fat soluble phytochemical plant pigments which include α- and β-carotene, lutein, lycopene, and β-cryptoxanthin [89]. Twenty four carotenoids have been reported to provide health benefits due to their antioxidant properties [90]. In particular, lycopene and β-carotene have been shown to scavenge ROS [91,92]. An increase in dietary antioxidants may improve asthma during pregnancy, however, further studies are required.

Table 1. Dietary antioxidants, food sources, and their function relevant to asthma.

Click here to display table

Table 1. Dietary antioxidants, food sources, and their function relevant to asthma.
AntioxidantFruitsVegetablesOther food sourcesFunction relevant to asthma
Vitamin COrange, kiwi fruit, grapefruit, apricot.Potato, red capsicum, snowpeas, broccoli, spinach. Accelerates histamine metabolism, direct effects on smooth muscle, and cyclic adenosine monophosphate [93]. Vitamin C has been shown to block TNF-α mediated activation of the transcriptional factor NF-κB, a key regulator of inflammation [94].
Vitamin E Almonds, vegetable oils, meat, poultry, nuts, eggs.Increases COX-2 activity and prostaglandin E-2 production by macrophages, promoting the differentiation of T cells to Th-2 lymphocytes [95]; directly affects T cells by down-regulating the expression of interleukin-4 mRNA in T-cells [96]. Suppresses neutrophil migration and inhibits IgE production [75,97].
Carotenoids (i.e., β-carotene, α-carotene, γ-carotene, lycopene, β-cryptoxanthin, and lutein-zeaxanthin)Orange, pumpkin, sweet potato.Carrots, sweet potatoes, spinach, tomato, pumpkin, red capsicum, juice, tomato juice, carrot juice.Pistachio nuts.Antioxidant activities, participation in cell signaling pathways, and decreasing inflammation [98].
Flavonoids (i.e., catechins, quercetin, epicatechin)Citrus fruits.Tomato, red onion, onion.Tea (green), cocoa, red wine.Scavenge nitric oxide [99]; inhibit release of histamine, arachidonic acid, and production of cytokines [100].

Antioxidant food sources identified from NUTTAB 2010 online database (except flavanoids [101]).

3.2. Epidemiologic Studies Assessing Antioxidant-Rich Foods and Antioxidant Intakes and Asthma

Epidemiologic studies suggest that the daily intake of antioxidant-rich fruits and vegetables in Australia are below recommended levels. In the most recent Australian Health Survey it was reported that 48.3% of Australians aged 18 years and over “usually” met the guideline for daily fruit intake (two servings or 300 g/day), while only 8.3% met the guideline for daily vegetable intake (five servings or 375 g/day) [102]. Overall, 3.0% of Australians aged 25–34 years consumed the recommended intake of fruit and vegetables, compared to 9.6% of those 65–74 years [102]. Similar results were found globally: Currently in the USA, just under 50% of the population consume ≥2 servings/day of fruit or ≥3 servings/day vegetables [103], while in Europe, the mean vegetable intake (including pulses and nuts) is 220 g/day and the mean fruit intake is 166 g/day, with >50% of the countries of the World Health Organisation European Region consuming lower than 400 g/day of fruit and vegetables [104]. Nationwide, it is evident that consumption of antioxidant-rich fruits and vegetables is poor and further strategies aimed at increasing intakes are warranted. Dietary intakes of specific antioxidant vitamins such as vitamin C generally meet recommendations [105], however tend to be lower for vitamin A and for vitamin E [106,107,108].

A number of epidemiologic studies have assessed dietary antioxidant intakes and their association with asthma, asthma control, wheeze, bronchitis and atopy in adults. However evidence from clinical trials demonstrating an improvement in asthma is lacking. Data from adults participating in the first National Health and Nutrition Examination Survey (NHANES 1) (1971–1974) identified that there were significant differences in lung function (i.e., lower forced expiratory volume in one second (FEV1)) (2530 mL vs. 2550 mL vs. 2570 mL) in those with lower vitamin C intake (≤17 mg vs. 66 mg/day vs. ≥178 mg/day) [109]. Other studies have reported mixed results between vitamin C intake and lung function (as measured by FEV1 or forced vital capacity (FVC)) [110,111,112,113,114,115]. In multivariate analyses, a number of studies have reported no significant associations between intakes of vitamin E [111,113,114,115,116] or β-carotene [110,111,115,116] and FEV1. Table 2 describes the studies in adults in which higher intakes of the antioxidant vitamins C, E and A, were positively associated with increased FEV1. In NHANES III, assessment of all nutrient intakes revealed that for every one standard deviation increase in vitamin C (113 mg/day), vitamin E (9.1 mg/day), and β-carotene (1170 retinol equivalents/day), there was an increase in FEV1 of 24.6 mL [117], which was higher than all nutrients assessed individually. This suggests that it is the synergistic effects of all the antioxidants that improve lung function and supplementation with an individual antioxidant may not be of benefit. One study assessing dietary carotenoid intakes reported no association between cryptoxanthin or lycopene and FVC or FEV1, however vitamin E was correlated with FEV1, and lutein-zeaxanthin was correlated with FVC% [118]. There is inconclusive evidence for an association between vitamins C, E, and A intakes and atopy [97,116] or wheeze [116,119] but vitamin C may be beneficial in bronchitis [119]. In a population-based cohort from the UK, dietary vitamin C and E intakes were not associated with asthma [114]; nor was there a positive effect of dietary antioxidant intake and lung function/asthma in a meta-analysis of seven observational studies [120]. Furthermore, one study in Dutch adults reported negative findings, such that dietary intakes of vitamin E and β-carotene were associated with cough (OR: 1.26; 1.02–1.56) and wheeze (OR: 1.27; 1.04–1.55), respectively [113].

Most of the observational evidence points towards a positive effect of higher vitamin C intake and lung function but not for reducing risk of asthma. It appears that for an approximate 88 mg/day increase in vitamin C, there is an associated increase in FEV1 of 31 mL, and for vitamin E, an increase in 3.6 mg/day appears to be associated with a 28 mL increase in FEV1. To observe this effect on FEV1 with vitamin C and vitamin E intake, respectively, this would be equivalent to eating four apricots/day or 22 almonds (25 g/day). A change of >12% or 200 mL FEV1 asthmatic patients has been suggested a clinically significant change in lung function [121,122]. Dietary intakes of antioxidant vitamins would therefore need to be increased further to produce a clinically significant change.

Table 2. Cross-sectional associations between dietary intakes of antioxidant vitamins C, E, and A, and lung function in adults with asthma.

Click here to display table

Table 2. Cross-sectional associations between dietary intakes of antioxidant vitamins C, E, and A, and lung function in adults with asthma.
Author, country, populationAge rangenMean intake/dayChange in intakeEffect of change in intake on FEV1 (predicted difference: 95% CI)Effect of change in intake on FVC (predicted difference: 95% CI)
Vitamin C
McKeever et al., UK, general population [116]27–80 years1346Not reported↑ 100 mg/day66.8 (12.2–121.4) mLNot measured
Hu et al., 69 countries in rural China [123]35–64 years3085151 mg↑ 100 mg/day21.6 (−0.4–43.5) mL24.9 (0.2–49.6) mL
Hu et al., USA, NHANES general population [117]≥17 years16,693111 mg↑ 1 SD (113 mg/day)9.5 (−0.2–19.2) mLNot measured
Britton et al., UK, general population [124]18–70 years263399.2 mg↑ 1 SD (40 mg/day)25 (5.2–44.8) mL23.3 (0.94–45.7) mL
Vitamin E
Butland et al., UK, men [110]45–59 years251251.4 mg↑ 1 SD (2 mg/day)31.7 (0.9–62.5) mLNot measured
Hu et al., USA, NHANES general population [117]≥17 years16,6939.2 mg↑ 1 SD (9.1 mg/day)16.4 (5.5–27.4) mLNot measured
Britton et al., UK, general population [124]18–70 years26336.2 mg↑ 1 SD (2.2 mg/day)20.1 (1.3–40.4) mL23.1 (1.0–45) mL
Dow et al., UK, general population [112]70–96 years1785.3 mg (median)↑ 1 mg/day42 (39–45) mL53 (18–88) mL
Vitamin A
Hu et al., USA, NHANES general population [117]≥17 years16,693567 µg↑ 1 SD (1107 µg/day)18.2 (8.7–27.6) mLNot measured

↑: increase.

There have been few studies assessing antioxidant-rich fruit and vegetable intake on asthma and lung function. From the three studies identified, there is inconclusive evidence indicating higher fruit intake over five years [110] or higher fruit and vegetable intake over 10 years [115] is associated with increased FEV1. However, a large decrease in fruit consumption over seven years was associated with decreases in FEV1 by approximately 89 mL/year and 133 mL/year, respectively, compared with those with stable fruit consumption [125]. Consumption of ≥2 apples/day was associated with an increase in FEV1 of 138 mL compared to no consumption of apples [110]. Fruits and vegetables contain a range of antioxidant vitamins and carotenoids, and although a couple of studies indicate an improvement in asthma control with higher consumption, further studies assessing fruit and vegetable intake in asthmatic adults are needed. These studies would be of particular importance as, in addition to antioxidant vitamins, fruits and vegetables are high in fibre and low in fat. Importantly, lower fibre, higher fat diets have also been linked to worse airway inflammation and lung function in severe asthmatics [126]. Altering food intake patterns towards an antioxidant diet, which is also fibre-rich and low in fat, might be protective in asthma.

3.3. Randomized Controlled Trials Assessing Antioxidant Supplements in Adults with Asthma

Given the number of epidemiologic studies assessing the effect of antioxidant intakes on asthma and lung function, there have been relatively few supplementation studies (Table 3). The few available studies provide inconsistent evidence to support antioxidant use to improve asthma. At present, there is little evidence to recommend a specific role for vitamin C in the treatment or management of asthma. Importantly, the majority of the studies that were included in a Cochrane review [127] were of poor quality and several studies were not included in the analysis due to no placebo group, non-RCT design, or because the vitamin C was combined with other/non-antioxidant micronutrients.

For β-carotene, there is some evidence demonstrating a protective role against exercise induced asthma [128]. For vitamin E, there was no effect of 500 mg/day vitamin E for six weeks on any measure of asthma control [129]. One short-term (seven day) study assessing lycopene supplementation, reported no clinical effects on asthma following 45 mg/day lycopene, however, increases in plasma carotenoid concentrations and decreased percentage of neutrophils in sputum were observed [130]. There is mixed evidence for one week of lycopene supplementation (30 mg/day) on lung function after exercise [131,132]. Only one RCT has examined the effect of manipulated antioxidant intake through changing intake of whole foods on asthma outcomes and lung function in asthmatic adults [133]. Specifically, compared to a high fruit (≥2 servings/day) and vegetable (≥5 servings/day) diet for 14 weeks, the asthmatic subjects who consumed a low fruit (<1 serving/day) and vegetable (<2 servings/day) diet had a 2.26 increased risk of asthma exacerbation [133].

To date, supplementation with individual antioxidants has not been shown to be beneficial in improving lung function or asthma control in adults with asthma. This is supported by two recent reviews indicating that there appears to be little clinical support for dietary antioxidant supplementation in asthma [134,135]. Although some positive studies were found using supplementation with β-carotene and lycopene, further studies are required to support this. Supplementation with vitamin E does not appear beneficial. Changing the dietary intake to antioxidant-rich fruit and vegetables, rather than supplementation, was an effective approach for reducing asthma exacerbations. Further studies to confirm the use of dietary manipulation as a management strategy for asthma are warranted.

Table 3. Intervention studies assessing antioxidant supplementation on asthma outcomes in adults with asthma.

Click here to display table

Table 3. Intervention studies assessing antioxidant supplementation on asthma outcomes in adults with asthma.
Study populationDesignInterventionOutcomes
Vitamin C
Cochrane Review in adults and/or children with chronic stable asthma, seasonal asthma, or EIA [127]Review: 9 RCTs (n = 330). 3 parallel studies, 6 cross-over studies. Only 5 studies contributed numerical data.3 studies used long-term supplementation: 1 g/day vitamin C for 14 weeks, 6 months and 16 weeks; 500 mg/day vitamin C for 7 days; 1500 mg over 2 weeks. 4 studies used single doses of vitamin C (2 g, 2 g, 2 g and 500 mg).Primary outcomes
  • FEV1%:

    -

    Change in FEV1 (L)—post-exercise challenge: (MD 0.13; 95% CI −0.05–0.31) [136].

    -

    Significant ↓ intervention post-exercise (−6.4 ± 2.4%) vs. usual (−14.3 ± 1.6%) and placebo (−2.9 ± 2.4%) [137].

    -

    FEV1 (mL) at 4 months: (MD −11.00; 95% CI −91.36–69.36) [138].

  • FVC:

    -

    Change in FVC (L)—post-exercise challenge: (MD 0.13; 95% CI −0.03–0.29) [136].


Secondary outcomes:
-

Significant improvement in asthma symptom scores (Asthma Quality of Life Questionnaire): Intervention (6.3; 95% CI 5.8–6.8) vs. placebo (5.8; 5.1–6.2) vs. usual (5.6; 5.0–6.3) [137].

-

IgE (IU/mL serum): absolute values at 1 month: (MD 4.00; 95% CI −140.42–148.42) 3 months (MD −312.00; −628.21–4.21) and 6 months (MD −143.00; −425.38–139.38) [139].

-

NS for inhaled corticosteroid use [138].

β-carotene
38 patients with EIA [128]Randomized,
double-blind, placebo controlled trial.
64 mg/day β-carotene vs. placebo for 1 week.
-

All 38 patients taking placebo revealed a significant post-exercise reduction of more than 14% in their FEV1.

-

20 (53%) of the 38 patients with daily β-carotene supplementation were protected against EIA.

Vitamin E
72 participants from a clinical trial register of 18–60 year olds with asthma [129]Randomized, placebo controlled, double blind parallel group clinical trial.500 mg/day natural vitamin E or matched placebo for 6 weeks.
-

No effect of vitamin E supplementation on measures of asthma control (FEV1, FVC), mean morning and evening peak flow, symptom scores, bronchodilator use, or serum IgE.

Lycopene
32 asthmatic adults, 52 years of age [130] Low antioxidant diet for 10 days, then commenced a randomized, cross-over trial involving 3 × 7 day treatment arms: placebo, tomato extract (45 mg/day lycopene) and tomato juice (45 mg/day lycopene).Low antioxidant diet:
Plasma:
-

42% ↓ in plasma lycopene.

-

NS for α- and γ-tocopherol.


Asthma control
-

↓ % predicted FEV1: 79.4 (71.6–87.2) vs. 76.5 (68.9–84.1).

-

↓ % predicted FVC: 93.0 (87.1–98.9) vs. 90.4 (84.3–96.5).

-

↓ Asthma Control Score: 1.0 (0.6–1.4) vs. 1.4 (1.0–1.8).

-

↑ % neutrophils in induced sputum: 31.0 (13.1–45.9) vs. 41.0 (24.2–56.6).


Supplementation:
-

Significant ↑ in plasma carotenoid concentrations.

-

↓ in % neutrophils (55% vs. 42%).

-

NS for % predicted FEV1, % predicted FVC or FeNO.

-

NS for asthma control score.

19 adults with exercise-related difficulty in breathing [131]Randomized cross-over study, with 2 weeks wash-out.30 mg/day lycopene vs. placebo for 1 week.Asthma control
-

NS in FEV1 after exercise with lycopene treatment vs. placebo (12% vs. 11%).

20 patients with EIA [132]Not reported if randomized. Double blinded.30 mg/day lycopene vs. placebo for 1 week.
-

Lycopene for 1 week significantly protected against EIA in 11 of 20 patients.

-

All 20 patients taking placebo revealed a significant post-exercise reduction of more than 14% in their FEV1.

FEV1: forced expiratory volume in 1 s; MD: mean difference; IgE: Immunoglobulin E; NS: not significant; EIA: exercise induced asthma; FVC: forced vital capacity; ↑: increase; ↓: decrease; FeNO: fractional exhaled nitric oxide.

3.4. Antioxidants in Pregnancies Complicated by Asthma

Dietary energy and nutrient requirements are generally increased during pregnancy [105,140]. As such, maternal nutrition has the potential to influence fetal growth and development. Over the past 20 years, there has been a shift from higher consumption of traditional plant based foods to diets higher in processed foods [5,102,141,142]. This increased intake of processed foods and higher intake of fat, specifically saturated fat, and sugar, parallels the reduced intake of fruits and vegetables that contain antioxidants [143,144,145]. Current evidence indicates that in normal pregnancy, despite sufficient maternal energy and macronutrient intakes, several key maternal micronutrients including folate, iron, zinc, calcium, vitamin D and essential fatty acids are less than optimal [84,146,147,148]. Regarding dietary antioxidant intakes, in a sample of 300 pregnant women from Perth, Western Australia, with family history of allergic disease, dietary intakes of vitamin C, β-carotene, selenium and copper were generally greater than the recommended dietary intake, however intakes of vitamin E and zinc was lower [149]. Dietary intake of vitamin C during the first and second trimesters was higher than US recommendations, with vitamin E intake at the recommended intake [95]. Similar intakes of vitamin C (174 mg) and vitamin E (8.4 mg) were reported in 1704 pregnant mothers in the UK [150].

There has been only one study assessing antioxidant intakes in pregnant women with asthma in which there was no significant difference in antioxidant intakes between women with moderate-severe asthma (n = 34), mild asthma (n = 25) or controls (n = 32) [84]. However, in that study, in the asthmatic women, low systemic antioxidant concentrations were associated with reduced fetal growth, whereas in non-asthmatics, no such association was found [84], suggesting the need to improve antioxidant status in pregnant asthmatic women. In an eight-week pilot study in pregnant women with history of asthma, a food-based exchange intervention to increase vitamin E containing foods was reported to be feasible and acceptable [151]. However, asthma outcomes and antioxidant concentrations were not reported in that publication. There is currently no published data on the relationship between asthma in pregnancy and how dietary antioxidant intakes modify circulating antioxidant concentrations. The introduction of an antioxidant-rich diet to pregnant asthmatic women may be of benefit to maternal asthma severity and fetal growth and development; studies in this area need to be conducted.

4. Current Evidence

Although there has been a number of reviews on diet and asthma in the past five years, these reviews focused on the impact of foods and nutrients on the risk of children developing allergies such as wheeze and asthma [1,152] either perinatally [153,154], or postnatally [154], or reviewed the evidence on anti-inflammatory oils [155,156]. Collectively, two further reviews reporting on nutrition and asthma [135] and on antioxidants and allergic disease [134] concluded that despite some relationships observed between antioxidants and asthma, further high quality research on asthma in adults is required to disentangle the effects of nutrition, specifically antioxidants, on asthma outcomes. This current review echoes these findings and updates the previous literature with additional recent publications. A recently published randomized controlled trial by Wood et al. [133] demonstrated the positive effects of a high fruit and vegetable diet on asthma control; however additional intervention studies are required to support this.

Regarding antioxidants and asthma in pregnancy, the work by Scott et al. [73], McLernon et al. [84], and Murphy et al. [15] provides the most up-to-date work on this topic and provides compelling information regarding altered oxidant-antioxidant mechanisms in pregnant women with asthma, as well as the impact of poor asthma control in pregnancy on perinatal outcomes. The information reported in this review suggests the need for dietary interventions to support the prospective relationships observed in those studies.

5. Conclusions

Both asthma and pregnancy are associated with increased oxidative stress. The increased oxidative load with asthma suggests that manipulation of dietary antioxidants might be important. Currently however, there are few randomized controlled trials in asthmatic subjects to confirm this, and only one study revealed that a diet high in antioxidants improved asthma outcomes in adults. Importantly, this was achieved through a whole food approach rather than a single antioxidant supplement. It is established that asthma in pregnancy affects maternal and neonatal health; oxidative stress may be a key player promoting these adverse outcomes. Pregnancy is considered a key time for dietary modification to support fetal development. Nutritional strategies that can lower maternal oxidative stress during pregnancy may also improve pregnancies complicated by asthma.

Acknowledgments

We acknowledge the funding support provided by the National Health and Medical Research Council Senior Research Fellowship (ID 510703 to VLC).

Conflict of Interest

The authors declare no conflict of interest.

References

  1. Allan, K.; Devereux, G. Diet and asthma: Nutrition implications from prevention to treatment. J. Am. Diet. Assoc. 2011, 111, 258–268, doi:10.1016/j.jada.2010.10.048.
  2. Nagel, G.; Weinmayr, G.; Kleiner, A.; Garcia-Marcos, L.; Strachan, D.P.; Group, I.P.T.S. Effect of diet on asthma and allergic sensitisation in the International Study on Allergies and Asthma in Childhood (ISAAC) Phase Two. Thorax 2010, 65, 516–522, doi:10.1136/thx.2009.128256.
  3. Ngoc, P.L.; Gold, D.R.; Tzianabos, A.O.; Weiss, S.T.; Celedon, J.C. Cytokines, allergy, and asthma. Curr. Opin. Allergy Clin. Immunol. 2005, 5, 161–166, doi:10.1097/01.all.0000162309.97480.45.
  4. Tamasi, L.; Horvath, I.; Bohacs, A.; Muller, V.; Losonczy, G.; Schatz, M. Asthma in pregnancy—Immunological changes and clinical management. Respir. Med. 2011, 105, 159–164, doi:10.1016/j.rmed.2010.11.006.
  5. Seaton, A.; Godden, D.J.; Brown, K. Increase in asthma: A more toxic environment or a more susceptible population? Thorax 1994, 49, 171–174, doi:10.1136/thx.49.2.171.
  6. Australian Centre for Asthma Monitoring. Asthma in Australia 2011. Available online: http://www.asthmamonitoring.org/ (accessed on 5 January 2013).
  7. Australian Institute of Health and Welfare. Australian Centre for Asthma Monitoring 2011: With a Focus Chapter on Chronic Obstructive Pulmonary Disease; AIHW: Canberra, ACT, Australia. Available online: http://www.aihw.gov.au/publication-detail/?id=10737420159 (accessed on 13 June 2013).
  8. Risnes, K.R.; Belanger, K.; Murk, W.; Bracken, M.B. Antibiotic exposure by 6 months and asthma and allergy at 6 years: Findings in a cohort of 1,401 US children. Am. J. Epidemiol. 2011, 173, 310–318, doi:10.1093/aje/kwq400.
  9. Clark, J.M.; Hulme, E.; Devendrakumar, V.; Turner, M.A.; Baker, P.N.; Sibley, C.P.; D’Souza, S.W. Effect of maternal asthma on birthweight and neonatal outcome in a British inner-city population. Paediatr. Perinat. Epidemiol. 2007, 21, 154–162, doi:10.1111/j.1365-3016.2007.00784.x.
  10. Kurinczuk, J.J.; Parsons, D.E.; Dawes, V.; Burton, P.R. The relationship between asthma and smoking during pregnancy. Women Health 1999, 29, 31–47.
  11. Kwon, H.L.; Belanger, K.; Bracken, M.B. Asthma prevalence among pregnant and childbearing-aged women in the United States: Estimates from national health surveys. Ann. Epidemiol. 2003, 13, 317–324, doi:10.1016/S1047-2797(03)00008-5.
  12. Wilson, D.H.; Adams, R.J.; Tucker, G.; Appleton, S.; Taylor, A.W.; Ruffin, R.E. Trends in asthma prevalence and population changes in South Australia, 1990–2003. Med. J. Aust. 2006, 184, 226–229.
  13. Mendola, P.; Laughon, S.K.; Mannisto, T.I.; Leishear, K.; Reddy, U.M.; Chen, Z.; Zhang, J. Obstetric complications among US women with asthma. Am. J. Obstet. Gynecol. 2013, 208, e1–e8.
  14. Clifton, V.L.; Engel, P.; Smith, R.; Gibson, P.; Brinsmead, M.; Giles, W.B. Maternal and neonatal outcomes of pregnancies complicated by asthma in an Australian population. Aust. N. Z. J. Obstet. Gynaecol. 2009, 49, 619–626, doi:10.1111/j.1479-828X.2009.01077.x.
  15. Murphy, V.E.; Namazy, J.A.; Powell, H.; Schatz, M.; Chambers, C.; Attia, J.; Gibson, P.G. A meta-analysis of adverse perinatal outcomes in women with asthma. BJOG 2011, 118, 1314–1323, doi:10.1111/j.1471-0528.2011.03055.x.
  16. Carroll, K.N.; Gebretsadik, T.; Griffin, M.R.; Dupont, W.D.; Mitchel, E.F.; Wu, P.; Enriquez, R.; Hartert, T.V. Maternal asthma and maternal smoking are associated with increased risk of bronchiolitis during infancy. Pediatrics 2007, 119, 1104–1112, doi:10.1542/peds.2006-2837.
  17. Lim, R.H.; Kobzik, L.; Dahl, M. Risk for asthma in offspring of asthmatic mothers versus fathers: A meta-analysis. PLoS One 2010, 5, e10134, doi:10.1371/journal.pone.0010134.
  18. Litonjua, A.A.; Carey, V.J.; Burge, H.A.; Weiss, S.T.; Gold, D.R. Parental history and the risk for childhood asthma. Does mother confer more risk than father? Am. J. Respir. Crit. Care Med. 1998, 158, 176–181, doi:10.1164/ajrccm.158.1.9710014.
  19. Martel, M.J.; Beauchesne, M.F.; Malo, J.L.; Rey, E.; Perreault, S.; Forget, A.; Blais, L. Maternal asthma, its control and severity in pregnancy, and the incidence of atopic dermatitis and allergic rhinitis in the offspring. J. Pediatr. 2009, 155, 707–713, doi:10.1016/j.jpeds.2009.05.004.
  20. Murphy, V.E.; Clifton, V.L.; Gibson, P.G. Asthma exacerbations during pregnancy: Incidence and association with adverse pregnancy outcomes. Thorax 2006, 61, 169–176, doi:10.1136/thx.2005.049718.
  21. Murphy, V.E.; Gibson, P.; Talbot, P.I.; Clifton, V.L. Severe asthma exacerbations during pregnancy. Obstet. Gynecol. 2005, 106, 1046–1054, doi:10.1097/01.AOG.0000185281.21716.02.
  22. Namazy, J.A.; Murphy, V.E.; Powell, H.; Gibson, P.G.; Chambers, C.; Schatz, M. Effects of asthma severity, exacerbations and oral corticosteroids on perinatal outcomes. Eur. Respir. J. 2013, 41, 1082–1090, doi:10.1183/09031936.00195111.
  23. Parker, M.J. Asthma. Otolaryngol. Clin. N. Am. 2011, 44, 667–684, doi:10.1016/j.otc.2011.04.001.
  24. Tortora, G.J.; Derrickson, B.H. Principles of Anatomy and Physiology (Tortora, Principles of Anatomy and Physiology), 13th ed. ed.; Wiley: New York, NY, USA, 2012.
  25. Barnes, P.J.; Chung, K.F.; Page, C.P. Inflammatory mediators of asthma: An update. Pharmacol. Rev. 1998, 50, 515–596.
  26. Murdoch, J.R.; Lloyd, C.M. Chronic inflammation and asthma. Mutat. Res. 2010, 690, 24–39, doi:10.1016/j.mrfmmm.2009.09.005.
  27. Hart, P.H. Regulation of the inflammatory response in asthma by mast cell products. Immunol. Cell Biol. 2001, 79, 149–153, doi:10.1046/j.1440-1711.2001.00983.x.
  28. Baines, K.J.; Simpson, J.L.; Bowden, N.A.; Scott, R.J.; Gibson, P.G. Differential gene expression and cytokine production from neutrophils in asthma phenotypes. Eur. Respir. J. 2010, 35, 522–531, doi:10.1183/09031936.00027409.
  29. Simpson, J.L.; Grissell, T.V.; Douwes, J.; Scott, R.J.; Boyle, M.J.; Gibson, P.G. Innate immune activation in neutrophilic asthma and bronchiectasis. Thorax 2007, 62, 211–218, doi:10.1136/thx.2006.061358.
  30. Killeen, K.; Skora, E. Pathophysiology, diagnosis, and clinical assessment of asthma in the adult. Nurs. Clin. N. Am. 2013, 48, 11–23, doi:10.1016/j.cnur.2012.11.001.
  31. Wood, L.G.; Gibson, P.G.; Garg, M.L. Biomarkers of lipid peroxidation, airway inflammation and asthma. Eur. Respir. J. 2003, 21, 177–186, doi:10.1183/09031936.03.00017003a.
  32. Tulic, M.K.; Christodoulopoulos, P.; Hamid, Q. Small airway inflammation in asthma. Respir. Res. 2001, 2, 333–339, doi:10.1186/rr83.
  33. Besnard, A.G.; Sabat, R.; Dumoutier, L.; Renauld, J.C.; Willart, M.; Lambrecht, B.; Teixeira, M.M.; Charron, S.; Fick, L.; Erard, F.; et al. Dual Role of IL-22 in allergic airway inflammation and its cross-talk with IL-17A. Am. J. Respir. Crit. Care Med. 2011, 183, 1153–1163, doi:10.1164/rccm.201008-1383OC.
  34. Dozor, A.J. The role of oxidative stress in the pathogenesis and treatment of asthma. Ann. N. Y. Acad. Sci. 2010, 1203, 133–137, doi:10.1111/j.1749-6632.2010.05562.x.
  35. Dahlgren, C.; Karlsson, A. Respiratory burst in human neutrophils. J. Immunol. Methods 1999, 232, 3–14, doi:10.1016/S0022-1759(99)00146-5.
  36. Cluzel, M.; Damon, M.; Chanez, P.; Bousquet, J.; Crastes de Paulet, A.; Michel, F.B.; Godard, P. Enhanced alveolar cell luminol-dependent chemiluminescence in asthma. J. Allergy Clin. Immunol. 1987, 80, 195–201, doi:10.1016/0091-6749(87)90129-1.
  37. Jarjour, N.N.; Calhoun, W.J. Enhanced production of oxygen radicals in asthma. J. Lab. Clin. Med. 1994, 123, 131–136.
  38. Marcal, L.E.; Rehder, J.; Newburger, P.E.; Condino-Neto, A. Superoxide release and cellular gluthatione peroxidase activity in leukocytes from children with persistent asthma. Braz. J. Med. Biol. Res. 2004, 37, 1607–1613, doi:10.1590/S0100-879X2004001100003.
  39. Teramoto, S.; Shu, C.Y.; Ouchi, Y.; Fukuchi, Y. Increased spontaneous production and generation of superoxide anion by blood neutrophils in patients with asthma. J. Asthma 1996, 33, 149–155, doi:10.3109/02770909609054546.
  40. Biagioli, M.C.; Kaul, P.; Singh, I.; Turner, R.B. The role of oxidative stress in rhinovirus induced elaboration of IL-8 by respiratory epithelial cells. Free Radic. Biol. Med. 1999, 26, 454–462, doi:10.1016/S0891-5849(98)00233-0.
  41. Simon, A.R.; Rai, U.; Fanburg, B.L.; Cochran, B.H. Activation of the JAK-STAT pathway by reactive oxygen species. Am. J. Physiol. 1998, 275, C1640–C1652.
  42. Abe, M.K.; Kartha, S.; Karpova, A.Y.; Li, J.; Liu, P.T.; Kuo, W.L.; Hershenson, M.B. Hydrogen peroxide activates extracellular signal-regulated kinase via protein kinase C, Raf-1, and MEK1. Am. J. Respir. Cell Mol. Biol. 1998, 18, 562–569, doi:10.1165/ajrcmb.18.4.2958.
  43. Zhou, M.; Liu, Y.; Duan, Y. Breath biomarkers in diagnosis of pulmonary diseases. Clin. Chim. Acta Int. J. Clin. Chem. 2012, 413, 1770–1780, doi:10.1016/j.cca.2012.07.006.
  44. Dupont, L.J.; Demedts, M.G.; Verleden, G.M. Prospective evaluation of the validity of exhaled nitric oxide for the diagnosis of asthma. Chest 2003, 123, 751–756, doi:10.1378/chest.123.3.751.
  45. Kharitonov, S.A. Exhaled markers of inflammatory lung diseases: Ready for routine monitoring? Swiss Med. Wkly. 2004, 134, 175–192.
  46. Powell, H.; Murphy, V.E.; Taylor, D.R.; Hensley, M.J.; McCaffery, K.; Giles, W.; Clifton, V.L.; Gibson, P.G. Management of asthma in pregnancy guided by measurement of fraction of exhaled nitric oxide: A double-blind, randomised controlled trial. Lancet 2011, 378, 983–990, doi:10.1016/S0140-6736(11)60971-9.
  47. Antczak, A.; Nowak, D.; Shariati, B.; Krol, M.; Piasecka, G.; Kurmanowska, Z. Increased hydrogen peroxide and thiobarbituric acid-reactive products in expired breath condensate of asthmatic patients. Eur. Respir. J. 1997, 10, 1235–1241, doi:10.1183/09031936.97.10061235.
  48. Nadeem, A.; Chhabra, S.K.; Masood, A.; Raj, H.G. Increased oxidative stress and altered levels of antioxidants in asthma. J. Allergy Clin. Immunol. 2003, 111, 72–78, doi:10.1067/mai.2003.17.
  49. Ozaras, R.; Tahan, V.; Turkmen, S.; Talay, F.; Besirli, K.; Aydin, S.; Uzun, H.; Cetinkaya, A. Changes in malondialdehyde levels in bronchoalveolar fluid and serum by the treatment of asthma with inhaled steroid and beta2-agonist. Respirology 2000, 5, 289–292, doi:10.1046/j.1440-1843.2000.00260.x.
  50. Rahman, I.; Morrison, D.; Donaldson, K.; MacNee, W. Systemic oxidative stress in asthma, COPD, and smokers. Am. J. Respir. Crit. Care Med. 1996, 154, 1055–1060, doi:10.1164/ajrccm.154.4.8887607.
  51. Wood, L.G.; Fitzgerald, D.A.; Gibson, P.G.; Cooper, D.M.; Garg, M.L. Lipid peroxidation as determined by plasma isoprostanes is related to disease severity in mild asthma. Lipids 2000, 35, 967–974.
  52. Nadeem, A.; Raj, H.G.; Chhabra, S.K. Increased oxidative stress in acute exacerbations of asthma. J. Asthma 2005, 42, 45–50.
  53. Wood, L.G.; Garg, M.L.; Simpson, J.L.; Mori, T.A.; Croft, K.D.; Wark, P.A.; Gibson, P.G. Induced sputum 8-isoprostane concentrations in inflammatory airway diseases. Am. J. Respir. Crit. Care Med. 2005, 171, 426–430.
  54. Al-Abdulla, N.O.; Al Naama, L.M.; Hassan, M.K. Antioxidant status in acute asthmatic attack in children. J. Pak. Med. Assoc. 2010, 60, 1023–1027.
  55. Samitas, K.; Chorianopoulos, D.; Vittorakis, S.; Zervas, E.; Economidou, E.; Papatheodorou, G.; Loukides, S.; Gaga, M. Exhaled cysteinyl-leukotrienes and 8-isoprostane in patients with asthma and their relation to clinical severity. Respir. Med. 2009, 103, 750–756, doi:10.1016/j.rmed.2008.11.009.
  56. Fait, V.; Sela, S.; Ophir, E.; Khoury, S.; Nissimov, J.; Tkach, M.; Hirsh, Y.; Khotaba, S.; Tarasova, L.; Oettinger, M. Hyperemesis gravidarum is associated with oxidative stress. Am. J. Perinatol. 2002, 19, 93–98, doi:10.1055/s-2002-23554.
  57. Holthe, M.R.; Staff, A.C.; Berge, L.N.; Lyberg, T. Leukocyte adhesion molecules and reactive oxygen species in preeclampsia. Obstet. Gynecol. 2004, 103, 913–922, doi:10.1097/01.AOG.0000124806.39111.ba.
  58. Nagaeva, O.; Jonsson, L.; Mincheva-Nilsson, L. Dominant IL-10 and TGF-beta mRNA expression in gammadeltaT cells of human early pregnancy decidua suggests immunoregulatory potential. Am. J. Reprod. Immunol. 2002, 48, 9–17, doi:10.1034/j.1600-0897.2002.01131.x.
  59. Reinhard, G.; Noll, A.; Schlebusch, H.; Mallmann, P.; Ruecker, A.V. Shifts in the TH1/TH2 balance during human pregnancy correlate with apoptotic changes. Biochem. Biophys. Res. Commun. 1998, 245, 933–938, doi:10.1006/bbrc.1998.8549.
  60. Hung, T.H.; Lo, L.M.; Chiu, T.H.; Li, M.J.; Yeh, Y.L.; Chen, S.F.; Hsieh, T.T. A longitudinal study of oxidative stress and antioxidant status in women with uncomplicated pregnancies throughout gestation. Reprod. Sci. 2010, 17, 401–409, doi:10.1177/1933719109359704.
  61. Toescu, V.; Nuttall, S.L.; Martin, U.; Kendall, M.J.; Dunne, F. Oxidative stress and normal pregnancy. Clin. Endocrinol. (Oxf.) 2002, 57, 609–613, doi:10.1046/j.1365-2265.2002.01638.x.
  62. Qanungo, S.; Mukherjea, M. Ontogenic profile of some antioxidants and lipid peroxidation in human placental and fetal tissues. Mol. Cell. Biochem. 2000, 215, 11–19, doi:10.1023/A:1026511420505.
  63. Sies, H. Oxidative stress: From basic research to clinical application. Am. J. Med. 1991, 91, 31S–38S, doi:10.1016/0002-9343(91)90281-2.
  64. Mordwinkin, N.M.; Ouzounian, J.G.; Yedigarova, L.; Montoro, M.N.; Louie, S.G.; Rodgers, K.E. Alteration of endothelial function markers in women with gestational diabetes and their fetuses. J. Matern. Fetal Neonatal Med. 2013, 26, 507–512, doi:10.3109/14767058.2012.736564.
  65. Granger, J.P.; Alexander, B.T.; Llinas, M.T.; Bennett, W.A.; Khalil, R.A. Pathophysiology of hypertension during preeclampsia linking placental ischemia with endothelial dysfunction. Hypertension 2001, 38, 718–722, doi:10.1161/01.HYP.38.3.718.
  66. Roberts, J.M.; Gammill, H.S. Preeclampsia: Recent insights. Hypertension 2005, 46, 1243–1249, doi:10.1161/01.HYP.0000188408.49896.c5.
  67. Clifton, V.L.; Vanderlelie, J.; Perkins, A.V. Increased anti-oxidant enzyme activity and biological oxidation in placentae of pregnancies complicated by maternal asthma. Placenta 2005, 26, 773–779, doi:10.1016/j.placenta.2004.10.018.
  68. Burton, G.J.; Jauniaux, E. Oxidative stress. Best Pract. Res. Clin. Obstet. Gynaecol. 2011, 25, 287–299, doi:10.1016/j.bpobgyn.2010.10.016.
  69. Watson, A.L.; Palmer, M.E.; Jauniaux, E.; Burton, G.J. Variations in expression of copper/zinc superoxide dismutase in villous trophoblast of the human placenta with gestational age. Placenta 1997, 18, 295–299, doi:10.1016/S0143-4004(97)80064-1.
  70. Watson, A.L.; Skepper, J.N.; Jauniaux, E.; Burton, G.J. Changes in concentration, localization and activity of catalase within the human placenta during early gestation. Placenta 1998, 19, 27–34, doi:10.1016/S0143-4004(98)90095-9.
  71. Qanungo, S.; Sen, A.; Mukherjea, M. Antioxidant status and lipid peroxidation in human feto-placental unit. Clin. Chim. Acta Int. J. Clin. Chem. 1999, 285, 1–12, doi:10.1016/S0009-8981(99)00051-0.
  72. Sacks, G.P.; Studena, K.; Sargent, K.; Redman, C.W. Normal pregnancy and preeclampsia both produce inflammatory changes in peripheral blood leukocytes akin to those of sepsis. Am. J. Obstet. Gynecol. 1998, 179, 80–86, doi:10.1016/S0002-9378(98)70254-6.
  73. Scott, N.M.; Hodyl, N.A.; Murphy, V.E.; Osei-Kumah, A.; Wyper, H.; Hodgson, D.M.; Smith, R.; Clifton, V.L. Placental cytokine expression covaries with maternal asthma severity and fetal sex. J. Immunol. 2009, 182, 1411–1420.
  74. Birben, E.; Sahiner, U.M.; Sackesen, C.; Erzurum, S.; Kalayci, O. Oxidative stress and antioxidant defense. World Allergy Organ. J. 2012, 5, 9–19, doi:10.1097/WOX.0b013e3182439613.
  75. Heffner, J.E.; Repine, J.E. Pulmonary strategies of antioxidant defense. Am. Rev. Respir. Dis. 1989, 140, 531–554, doi:10.1164/ajrccm/140.2.531.
  76. Toth, K.M.; Clifford, D.P.; Berger, E.M.; White, C.W.; Repine, J.E. Intact human erythrocytes prevent hydrogen peroxide-mediated damage to isolated perfused rat lungs and cultured bovine pulmonary artery endothelial cells. J. Clin. Investig. 1984, 74, 292–295, doi:10.1172/JCI111414.
  77. Van Asbeck, B.S.; Hoidal, J.; Vercellotti, G.M.; Schwartz, B.A.; Moldow, C.F.; Jacob, H.S. Protection against lethal hyperoxia by tracheal insufflation of erythrocytes: Role of red cell glutathione. Science 1985, 227, 756–759.
  78. Wood, L.G.; Garg, M.L.; Blake, R.J.; Garcia-Caraballo, S.; Gibson, P.G. Airway and circulating levels of carotenoids in asthma and healthy controls. J. Am. Coll. Nutr. 2005, 24, 448–455, doi:10.1080/07315724.2005.10719490.
  79. Wood, L.G.; Gibson, P.G. Reduced circulating antioxidant defences are associated with airway hyper-responsiveness, poor control and severe disease pattern in asthma. Br. J. Nutr. 2010, 103, 735–741, doi:10.1017/S0007114509992376.
  80. Nadeem, A.; Masood, A.; Siddiqui, N. Oxidant—Antioxidant imbalance in asthma: Scientific evidence, epidemiological data and possible therapeutic options. Ther. Adv. Respir. Dis. 2008, 2, 215–235, doi:10.1177/1753465808094971.
  81. Powell, C.V.; Nash, A.A.; Powers, H.J.; Primhak, R.A. Antioxidant status in asthma. Pediatr. Pulmonol. 1994, 18, 34–38, doi:10.1002/ppul.1950180109.
  82. Riccioni, G.; Bucciarelli, T.; Mancini, B.; Di Ilio, C.; Della Vecchia, R.; D’Orazio, N. Plasma lycopene and antioxidant vitamins in asthma: The PLAVA study. J. Asthma 2007, 44, 429–432, doi:10.1080/02770900701421880.
  83. Shanmugasundaram, K.R.; Kumar, S.S.; Rajajee, S. Excessive free radical generation in the blood of children suffering from asthma. Clin. Chim. Acta Int. J. Clin. Chem. 2001, 305, 107–114, doi:10.1016/S0009-8981(00)00425-3.
  84. McLernon, P.C.; Wood, L.G.; Murphy, V.E.; Hodyl, N.A.; Clifton, V.L. Circulating antioxidant profile of pregnant women with asthma. Clin. Nutr. 2012, 31, 99–107, doi:10.1016/j.clnu.2011.09.006.
  85. Greene, L.S. Asthma, oxidant stress, and diet. Nutrition 1999, 15, 899–907, doi:10.1016/S0899-9007(99)00209-9.
  86. De Luis, D.A.; Armentia, A.; Aller, R.; Asensio, A.; Sedano, E.; Izaola, O.; Cuellar, L. Dietary intake in patients with asthma: A case control study. Nutrition 2005, 21, 320–324, doi:10.1016/j.nut.2004.06.027.
  87. Traber, M.G.; Atkinson, J. Vitamin E, antioxidant and nothing more. Free Radic. Biol. Med. 2007, 43, 4–15, doi:10.1016/j.freeradbiomed.2007.03.024.
  88. Wang, Y.; Moreland, M.; Wagner, J.G.; Ames, B.N.; Illek, B.; Peden, D.B.; Jiang, Q. Vitamin E forms inhibit IL-13/STAT6-induced eotaxin-3 secretion by up-regulation of PAR4, an endogenous inhibitor of atypical PKC in human lung epithelial cells. J. Nutr. Biochem. 2012, 23, 602–608, doi:10.1016/j.jnutbio.2011.03.003.
  89. Britton, G. Structure and properties of carotenoids in relation to function. FASEB J. 1995, 9, 1551–1558.
  90. Krinsky, N.I.; Johnson, E.J. Carotenoid actions and their relation to health and disease. Mol. Asp. Med. 2005, 26, 459–516, doi:10.1016/j.mam.2005.10.001.
  91. Mortensen, A.; Skibsted, L.H. Real time detection of reactions between radicals of lycopene and tocopherol homologues. Free Radic. Res. 1997, 27, 229–234.
  92. Truscott, T.G.; McGarvey, D.; Lambert, C.; Hill, T.; Tinkler, J.; Conn, P.; Bohm, F.; Land, E.J.; Schalch, W. The interaction of carotenoids with reactive oxy-species. Biochem. Soc. Trans. 1995, 23, 252S.
  93. Mohsenin, V.; DuBois, A.B. Vitamin C and airways. Ann. N. Y. Acad. Sci. 1987, 498, 259–268, doi:10.1111/j.1749-6632.1987.tb23766.x.
  94. Carcamo, J.M.; Pedraza, A.; Borquez-Ojeda, O.; Golde, D.W. Vitamin C suppresses TNF alpha-induced NF kappa B activation by inhibiting I kappa B alpha phosphorylation. Biochemistry 2002, 41, 12995–13002, doi:10.1021/bi0263210.
  95. Litonjua, A.A.; Rifas-Shiman, S.L.; Ly, N.P.; Tantisira, K.G.; Rich-Edwards, J.W.; Camargo, C.A., Jr.; Weiss, S.T.; Gillman, M.W.; Gold, D.R. Maternal antioxidant intake in pregnancy and wheezing illnesses in children at 2 y of age. Am. J. Clin. Nutr. 2006, 84, 903–911.
  96. Li-Weber, M.; Giaisi, M.; Treiber, M.K.; Krammer, P.H. Vitamin E inhibits IL-4 gene expression in peripheral blood T cells. Eur. J. Immunol. 2002, 32, 2401–2408, doi:10.1002/1521-4141(200209)32:9<2401::AID-IMMU2401>3.0.CO;2-S.
  97. Fogarty, A.; Lewis, S.; Weiss, S.; Britton, J. Dietary vitamin E, IgE concentrations, and atopy. Lancet 2000, 356, 1573–1574, doi:10.1016/S0140-6736(00)03132-9.
  98. Fawzi, W.W.; Rifas-Shiman, S.L.; Rich-Edwards, J.W.; Willett, W.C.; Gillman, M.W. Calibration of a semi-quantitative food frequency questionnaire in early pregnancy. Ann. Epidemiol. 2004, 14, 754–762, doi:10.1016/j.annepidem.2004.03.001.
  99. Van Acker, S.A.; Tromp, M.N.; Haenen, G.R.; van der Vijgh, W.J.; Bast, A. Flavonoids as scavengers of nitric oxide radical. Biochem. Biophys. Res. Commun. 1995, 214, 755–759, doi:10.1006/bbrc.1995.2350.
  100. Kimata, M.; Shichijo, M.; Miura, T.; Serizawa, I.; Inagaki, N.; Nagai, H. Effects of luteolin, quercetin and baicalein on immunoglobulin E-mediated mediator release from human cultured mast cells. Clin. Exp. Allergy 2000, 30, 501–508, doi:10.1046/j.1365-2222.2000.00768.x.
  101. Yao, L.H.; Jiang, Y.M.; Shi, J.; Tomas-Barberan, F.A.; Datta, N.; Singanusong, R.; Chen, S.S. Flavonoids in food and their health benefits. Plant Foods Hum. Nutr. 2004, 59, 113–122, doi:10.1007/s11130-004-0049-7.
  102. Australian Bureau of Statistics. Daily Intake of Fruit and Vegetables. 4338.0—Profiles of Health 2011–2013; Australian Bureau of Statistics: Canberra, ACT, Australia, 2012. Available online: http://www.abs.gov.au/ausstats/abs@.nsf/Lookup/by%20Subject/4338.0~2011-13~Main%20Features~Daily%20intake%20of%20fruit%20and%20vegetables~10009 (accessed on 5 January 2013).
  103. Centre for Disease Control and Prevention. State-Specific Trends in Fruit and Vegetable Consumption among Adults-United States, 2000–2009. Morbidity and Mortality Weekly Report; CDC: Atlanta, GA, USA, 2010. Available online: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5935a1.htm?s_cid=mm5935a1_w (accessed on 19 October 2012).
  104. European Food Information Council. Fruit and Vegetable Consumption in Europe—Do Europeans Get Enough? European Food Information Council: Brussels, Belgium, 2012. Available online: http://www.eufic.org/article/en/expid/Fruit-vegetable-consumption-Europe/ (accessed on 22 January 2013).
  105. National Health and Medical Research Council. Nutrient Reference Values for Australia and New Zealand Including Recommended Dietary Intakes; National Health and Medical Research Council: Canberra, ACT, Australia, 2005. Available online: http://www.nhmrc.gov.au/_files_nhmrc/publications/attachments/n35.pdf (accessed on 10 September 2012).
  106. Australian Bureau of Statistics. Nutrient Intakes and Physical Measurements. 4805.0—National Nutrition Survey; Australian Bureau of Statistics: Canberra, ACT, Australia, 1995. Available online: http://www.abs.gov.au/ausstats/abs@.nsf/Lookup/95E87FE64B144FA3CA2568A9001393C0 (accessed on 20 September 2012).
  107. Ibiebele, T.I.; Hughes, M.C.; Nagle, C.M.; Bain, C.J.; Whiteman, D.C.; Webb, P.M.; Study of Digestive Heathy; Australian Cancer Study. Dietary antioxidants and risk of Barrett’s esophagus and adenocarcinoma of the esophagus in an Australian population. Int. J. Cancer. 2013, 133, 214–224, doi:10.1002/ijc.28016.
  108. Kubota, Y.; Iso, H.; Date, C.; Kikuchi, S.; Watanabe, Y.; Wada, Y.; Inaba, Y.; Tamakoshi, A.; Group, J.S. Dietary intakes of antioxidant vitamins and mortality from cardiovascular disease: The Japan Collaborative Cohort Study (JACC) study. Stroke 2011, 42, 1665–1672, doi:10.1161/STROKEAHA.110.601526.
  109. Schwartz, J.; Weiss, S.T. Relationship between dietary vitamin C intake and pulmonary function in the First National Health and Nutrition Examination Survey (NHANES I). Am. J. Clin. Nutr. 1994, 59, 110–114.
  110. Butland, B.K.; Fehily, A.M.; Elwood, P.C. Diet, lung function, and lung function decline in a cohort of 2512 middle aged men. Thorax 2000, 55, 102–108, doi:10.1136/thorax.55.2.102.
  111. Chen, R.; Tunstall-Pedoe, H.; Bolton-Smith, C.; Hannah, M.K.; Morrison, C. Association of dietary antioxidants and waist circumference with pulmonary function and airway obstruction. Am. J. Epidemiol. 2001, 153, 157–163, doi:10.1093/aje/153.2.157.
  112. Dow, L.; Tracey, M.; Villar, A.; Coggon, D.; Margetts, B.M.; Campbell, M.J.; Holgate, S.T. Does dietary intake of vitamins C and E influence lung function in older people? Am. J. Respir. Crit. Care Med. 1996, 154, 1401–1404, doi:10.1164/ajrccm.154.5.8912755.
  113. Grievink, L.; Smit, H.A.; Ocké, M.C.; van’t Veer, P.; Kromhout, D. Dietary intake of antioxidant (pro)-vitamins, respiratory symptoms and pulmonary function: The MORGEN study. Thorax 1998, 53, 166–171, doi:10.1136/thx.53.3.166.
  114. Shaheen, S.O.; Sterne, J.A.; Thompson, R.L.; Songhurst, C.E.; Margetts, B.M.; Burney, P.G. Dietary antioxidants and asthma in adults: Population-based case-control study. Am. J. Respir. Crit. Care Med. 2001, 164, 1823–1828, doi:10.1164/ajrccm.164.10.2104061.
  115. Tabak, C.; Smit, H.A.; Rasanen, L.; Fidanza, F.; Menotti, A.; Nissinen, A.; Feskens, E.J.; Heederik, D.; Kromhout, D. Dietary factors and pulmonary function: A cross sectional study in middle aged men from three European countries. Thorax 1999, 54, 1021–1026, doi:10.1136/thx.54.11.1021.
  116. McKeever, T.M.; Scrivener, S.; Broadfield, E.; Jones, Z.; Britton, J.; Lewis, S.A. Prospective study of diet and decline in lung function in a general population. Am. J. Respir. Crit. Care Med. 2002, 165, 1299–1303, doi:10.1164/rccm.2109030.
  117. Hu, G.; Cassano, P.A. Antioxidant nutrients and pulmonary function: The Third National Health and Nutrition Examination Survey (NHANES III). Am. J. Epidemiol. 2000, 151, 975–981, doi:10.1093/oxfordjournals.aje.a010141.
  118. Schunemann, H.J.; McCann, S.; Grant, B.J.; Trevisan, M.; Muti, P.; Freudenheim, J.L. Lung function in relation to intake of carotenoids and other antioxidant vitamins in a population-based study. Am. J. Epidemiol. 2002, 155, 463–471, doi:10.1093/aje/155.5.463.
  119. Schwartz, J.; Weiss, S.T. Dietary factors and their relation to respiratory symptoms. The Second National Health and Nutrition Examination Survey. Am. J. Epidemiol. 1990, 132, 67–76.
  120. Gao, J.; Gao, X.; Li, W.; Zhu, Y.; Thompson, P.J. Observational studies on the effect of dietary antioxidants on asthma: A meta-analysis. Respirology 2008, 13, 528–536, doi:10.1111/j.1440-1843.2008.01286.x.
  121. Pellegrino, R.; Viegi, G.; Brusasco, V.; Crapo, R.O.; Burgos, F.; Casaburi, R.; Coates, A.; van der Grinten, C.P.; Gustafsson, P.; Hankinson, J.; et al. Interpretative strategies for lung function tests. Eur. Respir. J. 2005, 26, 948–968, doi:10.1183/09031936.05.00035205.
  122. Santanello, N.C.; Zhang, J.; Seidenberg, B.; Reiss, T.F.; Barber, B.L. What are minimal important changes for asthma measures in a clinical trial? Eur. Respir. J. 1999, 14, 23–27, doi:10.1034/j.1399-3003.1999.14a06.x.
  123. Hu, G.; Zhang, X.; Chen, J.; Peto, R.; Campbell, T.C.; Cassano, P.A. Dietary vitamin C intake and lung function in rural China. Am. J. Epidemiol. 1998, 148, 594–599, doi:10.1093/oxfordjournals.aje.a009685.
  124. Britton, J.R.; Pavord, I.D.; Richards, K.A.; Knox, A.J.; Wisniewski, A.F.; Lewis, S.A.; Tattersfield, A.E.; Weiss, S.T. Dietary antioxidant vitamin intake and lung function in the general population. Am. J. Respir. Crit. Care Med. 1995, 151, 1383–1387, doi:10.1164/ajrccm.151.5.7735589.
  125. Carey, I.M.; Strachan, D.P.; Cook, D.G. Effects of changes in fresh fruit consumption on ventilatory function in healthy British adults. Am. J. Respir. Crit. Care Med. 1998, 158, 728–733, doi:10.1164/ajrccm.158.3.9712065.
  126. Berthon, B.S.; Macdonald-Wicks, L.K.; Gibson, P.G.; Wood, L.G. Investigation of the association between dietary intake, disease severity and airway inflammation in asthma. Respirology 2013, 18, 447–454, doi:10.1111/resp.12015.
  127. Kaur, B.; Rowe, B.H.; Arnold, E. Vitamin C supplementation for asthma. Cochrane Database Syst. Rev. 2009, doi:10.1002/14651858.CD000993.pub3.
  128. Neuman, I.; Nahum, H.; Ben-Amotz, A. Prevention of exercise-induced asthma by a natural isomer mixture of beta-carotene. Ann. Allergy Asthma Immunol. 1999, 82, 549–553, doi:10.1016/S1081-1206(10)63165-1.
  129. Pearson, P.J.; Lewis, S.A.; Britton, J.; Fogarty, A. Vitamin E supplements in asthma: A parallel group randomised placebo controlled trial. Thorax 2004, 59, 652–656, doi:10.1136/thx.2004.022616.
  130. Wood, L.G.; Garg, M.L.; Powell, H.; Gibson, P.G. Lycopene-rich treatments modify noneosinophilic airway inflammation in asthma: Proof of concept. Free Radic. Res. 2008, 42, 94–102, doi:10.1080/10715760701767307.
  131. Falk, B.; Gorev, R.; Zigel, L.; Ben-Amotz, A.; Neuman, I. Effect of lycopene supplementation on lung function after exercise in young athletes who complain of exercise-induced bronchoconstriction symptoms. Ann. Allergy Asthma Immunol. 2005, 94, 480–485, doi:10.1016/S1081-1206(10)61119-2.
  132. Neuman, I.; Nahum, H.; Ben-Amotz, A. Reduction of exercise-induced asthma oxidative stress by lycopene, a natural antioxidant. Allergy 2000, 55, 1184–1189, doi:10.1034/j.1398-9995.2000.00748.x.
  133. Wood, L.G.; Garg, M.L.; Smart, J.M.; Scott, H.A.; Barker, D.; Gibson, P.G. Manipulating antioxidant intake in asthma: A randomized controlled trial. Am. J. Clin. Nutr. 2012, 96, 534–543, doi:10.3945/ajcn.111.032623.
  134. Allan, K.; Kelly, F.J.; Devereux, G. Antioxidants and allergic disease: A case of too little or too much? Clin. Exp. Allergy 2010, 40, 370–380, doi:10.1111/j.1365-2222.2009.03413.x.
  135. Varraso, R. Nutrition and asthma. Curr. Allergy Asthma Rep. 2012, 12, 201–210, doi:10.1007/s11882-012-0253-8.
  136. Schachter, E.N.; Schlesinger, A. The attenuation of exercise-induced bronchospasm by ascorbic acid. Ann. Allergy 1982, 49, 146–151.
  137. Tecklenburg, S.L.; Mickleborough, T.D.; Fly, A.D.; Bai, Y.; Stager, J.M. Ascorbic acid supplementation attenuates exercise-induced bronchoconstriction in patients with asthma. Respir. Med. 2007, 101, 1770–1778, doi:10.1016/j.rmed.2007.02.014.
  138. Fogarty, A.; Lewis, S.A.; Scrivener, S.L.; Antoniak, M.; Pacey, S.; Pringle, M.; Britton, J. Oral magnesium and vitamin C supplements in asthma: A parallel group randomized placebo-controlled trial. Clin. Exp. Allergy 2003, 33, 1355–1359, doi:10.1046/j.1365-2222.2003.01777.x.
  139. Anderson, R.; Hay, I.; van Wyk, H.A.; Theron, A. Ascorbic acid in bronchial asthma. S. Afr. Med. J. 1983, 63, 649–652.
  140. Kaiser, L.L.; Allen, L. Position of the American Dietetic Association: Nutrition and lifestyle for a healthy pregnancy outcome. J. Am. Diet. Assoc. 2002, 102, 1479–1490, doi:10.1016/S0002-8223(02)90327-5.
  141. Australian Bureau of Statistics. 4102.0—Australian Social Trends; Australian Bureau of Statistics: Canberra, ACT, Australia, 1998. Available online: http://www.abs.gov.au/AUSSTATS/abs@.nsf/2f762f95845417aeca25706c00834efa/0157f86c1e697839ca2570ec00192aa5!OpenDocument (accessed on 20 October 2012).
  142. McLennan, W.; Podger, A. 4804.0—National Nutrition Survey: Foods Eaten, 1995, Australia; Australian Bureau of Statistics: Canberra, ACT, Australia, 1999. Available online: http://www.abs.gov.au/AUSSTATS/abs@.nsf/0/9A125034802F94CECA2568A9001393CE?OpenDocument (accessed on 7 October 2012).
  143. Bannerman, E.; Magarey, A.M.; Daniels, L.A. Evaluation of micronutrient intakes of older Australians: The National Nutrition Survey-1995. J. Nutr. Health Aging 2001, 5, 243–247.
  144. UK Department of Environmental Farming and Rural Affairs. Family Food in 2005–06; Department for Environment, Food & Rural Affairs: England, UK, 2007. Available online: http://www.defra.gov.uk/statistics/foodfarm/food/familyfood/datasets/ (accessed on 7 October 2012).
  145. Ni Mhurchu, C.; Lawes, C. National food supply: A major opportunity to improve population health. N. Z. Med. J. 2005, 118, U1750.
  146. Gautam, V.P.; Taneja, D.K.; Sharma, N.; Gupta, V.K.; Ingle, G.K. Dietary aspects of pregnant women in rural areas of Northern India. Matern. Child Nutr. 2008, 4, 86–94.
  147. Hure, A.; Young, A.; Smith, R.; Collins, C. Diet and pregnancy status in Australian women. Public Health Nutr. 2009, 12, 853–861, doi:10.1017/S1368980008003212.
  148. Rifas-Shiman, S.L.; Rich-Edwards, J.W.; Willett, W.C.; Kleinman, K.P.; Oken, E.; Gillman, M.W. Changes in dietary intake from the first to the second trimester of pregnancy. Paediatr. Perinat. Epidemiol. 2006, 20, 35–42, doi:10.1111/j.1365-3016.2006.00691.x.
  149. West, C.E.; Dunstan, J.; McCarthy, S.; Metcalfe, J.; D’Vaz, N.; Meldrum, S.; Oddy, W.H.; Tulic, M.K.; Prescott, S.L. Associations between maternal antioxidant intakes in pregnancy and infant allergic outcomes. Nutrients 2012, 4, 1747–1758, doi:10.3390/nu4111747.
  150. Devereux, G. Maternal diet during pregnancy: An emerging risk factor for childhood asthma. Expert Rev. Clin. Immunol. 2008, 4, 663–668, doi:10.1586/1744666X.4.6.663.
  151. Clark, J.; Craig, L.; McNeill, G.; Smith, N.; Norrie, J.; Devereux, G. A novel dietary intervention to optimize vitamin E intake of pregnant women to 15 mg/day. J. Acad. Nutr. Diet. 2012, 112, 297–301, doi:10.1016/j.jada.2011.08.033.
  152. Nurmatov, U.; Devereux, G.; Sheikh, A. Nutrients and foods for the primary prevention of asthma and allergy: Systematic review and meta-analysis. J. Allergy Clin. Immunol. 2011, 127, 724–733, doi:10.1016/j.jaci.2010.11.001.
  153. Chatzi, L.; Kogevinas, M. Prenatal and childhood Mediterranean diet and the development of asthma and allergies in children. Public Health Nutr. 2009, 12, 1629–1634, doi:10.1017/S1368980009990474.
  154. Robison, R.; Kumar, R. The effect of prenatal and postnatal dietary exposures on childhood development of atopic disease. Curr. Opin. Allergy Clin. Immunol. 2010, 10, 139–144, doi:10.1097/ACI.0b013e32833667a8.
  155. Anandan, C.; Nurmatov, U.; Sheikh, A. Omega 3 and 6 oils for primary prevention of allergic disease: Systematic review and meta-analysis. Allergy 2009, 64, 840–848, doi:10.1111/j.1398-9995.2009.02042.x.
  156. Klemens, C.M.; Berman, D.R.; Mozurkewich, E.L. The effect of perinatal omega-3 fatty acid supplementation on inflammatory markers and allergic diseases: A systematic review. BJOG 2011, 118, 916–925, doi:10.1111/j.1471-0528.2010.02846.x.
Nutrients EISSN 2072-6643 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert