Associations Between the Maternal Diet Index and Childhood Asthma: The NorthPop and Healthy Start Cohorts

A systematic review showed limited associations between pregnancy diet and offspring allergy. We developed a maternal diet index during pregnancy that was associated with offspring allergy outcomes. Data came from Healthy Start, a Colorado pre-birth cohort of mother/offspring dyads. Food propensity questionnaires were completed during pregnancy. Offspring allergic rhinitis, atopic dermatitis, asthma, wheeze, and food allergy diagnosis up to age four were verified from electronic medical records. Data were randomized into test and replication sets. The index included the weighted combination of variables that best predicted a combined outcome of any allergy in the test set. Index utility was verified in the replication set. Separate adjusted and unadjusted logistic models estimated associations between the index and each offspring allergy diagnosis in the full sample. The index included weighted measures of intake of vegetables, yogurt, fried potatoes, rice/grains, red meats, pure fruit juice, and cold cereals. Vegetables and yogurt were associated with the prevention of any allergy, while other components were associated with increased disease. In adjusted models, a one-unit increase in the index was significantly associated with reduced odds of offspring allergic rhinitis (odds ratio (CI) 0.82 [0.72-0.94]), atopic dermatitis (0.77 [0.69-0.86]), asthma (0.84 [0.74-0.96]), and wheeze (0.80 [0.71-0.90]), but not food allergy (0.84 [0.66-1.08]). This is the first study that has shown associations between an index of maternal dietary intake during pregnancy and multiple offspring allergic diseases. The results give hope for prevention of allergic diseases in utero.

Previous maternal use of the oral contraceptive pill (OCP) has been linked with asthma in subsequent offspring and has been implicated in the increased prevalence of childhood asthma in recent decades. We conducted a matched case-control study to test the hypothesis that maternal OCP used close to conception is associated with asthma in the offspring, particularly in children with coexistent eczema. We examined maternal OCP exposure in relation to asthma in the offspring (n = 6730) compared with offspring with no asthma (n = 6730) further stratifying by eczema, age group, treatment category and gender of the offspring. Maternal use of OCP was classified as: no OCP use in the 2 years prior to conception; past OCP use within 2 years but >6 months before conception; and recent OCP use within 6 months of conception. The adjusted odds ratio (OR) for asthma in the offspring was 1.16 [95% confidence interval 1.06, 1.27] among mothers who were recent users of the OCP when compared with mothers who had not used the OCP. Past OCP use was not associated with asthma in the offspring. In the stratified analyses, we observed weak but statistically significant associations between recent maternal OCP use and asthma in the offspring among children: without a history of eczema (adjusted OR 1.22 [1.09, 1.36]), those aged < or = 3 years (adjusted OR 1.24 [1.12, 1.37]), those not on treatment for their asthma (adjusted OR 1.33 [1.12, 1.58]) and among females (adjusted OR 1.34 [1.13, 1.51]). We did not find convincing evidence for a causal relationship between maternal OCP used close to conception and asthma in the offspring. The small statistically significant associations were not among children with characteristic features of asthma such as those with eczema and may be due to bias, uncontrolled confounding or chance.

Maternal obesity during pregnancy as a risk for early-life asthma

Maternal asthma and preeclampsia have independently been reported to be associated with increased asthma incidence in children of affected mothers. Maternal asthma is also associated with increased risk of preeclampsia development. However, the joint effect of these maternal conditions on child asthma risk is unknown. To study whether development of preeclampsia among pregnant women with asthma was associated with higher risk of childhood asthma in the VDAART (Vitamin D Antenatal Asthma Reduction Trial). A total of 806 pregnant women and their offspring at high risk of asthma or atopy, who were followed from VDAART enrollment (10-18 wk of gestation) through the child's third birthday, were included in this cohort analysis. Preeclampsia status was determined by chart review, obstetrician diagnosis, and adjudication by a panel of obstetricians. Child asthma was the main outcome as determined by parental report of a physician diagnosis, and the risk of child asthma was also examined if accompanied by recurrent wheeze. The main risk variable of interest was a four-level ordered variable defined for each mother, with values without asthma without preeclampsia, without asthma with preeclampsia, with asthma without preeclampsia, and with asthma with preeclampsia during their pregnancy. We examined the trend of outcome proportions across these categories. To account for differences in maternal and child characteristics, we used a Weibull regression model for interval-censored data to compare the incidence of child asthma by age of 3 years across the maternal variable categories. The incidence of asthma in 3-year-old children was 9.90% (44/445), 17.95% (7/39), 22.11% (65/294), and 32.14% (9/28) among those born to mothers without asthma and without preeclampsia, mothers without asthma with preeclampsia, mothers with asthma without preeclampsia, and mothers with asthma with preeclampsia, respectively. The incidences demonstrated an increasing trend in risk of child asthma across the maternal groups (P for trend <0.001). After accounting for potential confounders and using time to report of childhood asthma as analysis outcome, risk of asthma was greater among children born to mothers with asthma without preeclampsia, compared with mothers without asthma without preeclampsia (adjusted hazard ratio, 2.18; 95% confidence interval, 1.46-3.26). This risk was 50% greater for children born to mothers with asthma who developed preeclampsia during pregnancy (adjusted hazard ratio, 2.68; 95% confidence interval, 1.30-5.61). The trend in asthma and recurrent wheeze proportions across the maternal groups' children also indicated a higher risk for children born to mothers with asthma with preeclampsia (adjusted hazard ratio, 4.73; 95% confidence interval, 2.20-10.07; P for trend <0.001). Preeclampsia is associated with increased risk of early life childhood asthma in children less than 3 years old over and above that associated with maternal asthma alone. The results implicate the interplay between maternal factors as strong predictors of offspring asthma and in utero maternal-fetal immune perturbations and developmental dysregulations associated with preeclampsia.

The relationship between assisted reproductive techniques (ART) and the risk of asthma and allergic rhinitis (AR) is controversial. Thus, we aimed to investigate the relationship between ART and the risk of asthma and AR in a nationwide, large-scale birth cohort. This study utilized the National Health Insurance Service data in South Korea to conduct a nationwide, large-scale, population-based birth cohort. We included all infants born between 2017 and 2018. AR, asthma, food allergies, and atopic dermatitis were defined using the International Classification of Diseases tenth edition codes. Asthma was classified as allergic or non-allergic based on accompanying allergic diseases (AR, food allergy, or atopic dermatitis). Using 1:10 propensity score matching, we compared infants conceived through ART with those conceived naturally (non-ART). After matching, logistic regression was used to compare the hazard ratio for asthma and AR between the two groups. We included 543,178 infants [male infants, 280,194 (51.38%)]. After matching, 8,925 and 74,229 infants were selected for the ART and non-ART groups, respectively. The ART group showed a decreased risk of asthma in the offspring [adjusted hazard ratio (aHR), 0.45; 95% confidence interval (CI), 0.41-0.48]. Similarly, for AR, being conceived by ART was associated with a decreased risk of AR (aHR, 0.25; 95% CI, 0.12-0.37). ART offspring showed a decreased risk of asthma and AR in offspring compared to that observed in non-ART offspring. Our study offers important insights for clinicians, researchers, and parents regarding the health outcomes of ART-conceived infants and enhances our understanding of ART's impact on respiratory health.

Previous studies have yielded conflicting results regarding the link between maternal perinatal depression and asthma in children. To provide a clearer understanding of this relationship, a comprehensive meta-analysis was carried out to evaluate the association mentioned above. A comprehensive review of observational studies was conducted by searching electronic databases including Medline, Embase, and Web of Science. The data were combined using a randomized-effects model taking into account potential variations. Subgroup analyses were performed to evaluate the possible impact of study characteristics on outcomes. Ten cohort studies, which included 833,230 mother-child pairs, were examined in the analysis. Maternal depressive symptoms during the perinatal period were associated with an increased risk of asthma in offspring (risk ratio [RR]: 1.24, 95% confidence interval [CI]: 1.19 to 1.30, p < 0.001; I2 = 0%). Further sensitivity analyses restricted to multivariate studies (RR: 1.24, 95% CI: 1.19 to 1.30, p < 0.001; I2 = 0%) or studies where asthma was diagnosed in children aged three years or older (RR: 1.24, 95% CI: 1.19 to 1.30, p < 0.001; I2 = 0%) revealed consistent outcomes. Subgroup analyses according to study design, methods for the diagnosis of maternal depression, timing for the evaluation of maternal depression, methods for the validation of asthma in offspring, adjustment of maternal smoking during pregnancy and of maternal asthma, or study quality score showed similar results (p for subgroup difference all > 0.05). Maternal perinatal depression appears to be significantly linked to a higher occurrence of childhood asthma in children.

BackgroundMaternal stressors during pregnancy are potential risk factors for asthma in offspring. However, previous studies have been limited by the use of self-reported data focusing on stressors either in private life or at work. This study examined the association between maternal stressors both in private life and at work during pregnancy and asthma in offspring.MethodsIn the Danish National Birth Cohort, 75 156 live-born singletons born during 1996–2002 were identified. Maternal information on job title were available around weeks 12–16 of gestation. Data on maternal bereavement, life-threatening illness, suicide attempt and alcohol or drug abuse of a close relative and offspring childhood asthma (3–10 years of age) were obtained from Danish nationwide registers. Maternal psychosocial work stressors (job control, psychological job demands, emotional job demands, work-related violence and threats of work-related violence) were estimated by the use of job-exposure matrices. The association between maternal stress and childhood asthma was analysed in Cox models adjusted for maternal age, comorbidity and parity.ResultsNeither private-life nor work stressors were related to onset of asthma in offspring. Separate analyses by parental atopy or onset of asthma in offspring supported the main findings.ConclusionsThis study does not support an elevated risk of childhood asthma related to exposure to stress during pregnancy.

Young maternal age at delivery is associated with asthma in adult offspring

Maternal preconception occupational exposure to cleaning products and disinfectants and offspring asthma

Vegetable intake during childhood may reduce the risk of subsequent asthma. We verified the effect of maternal intake during pregnancy on asthma risk in offspring, which has rarely been studied. In a hospital-based birth cohort study conducted in Tokyo, we administered a food frequency questionnaire at two periods during the respondents' pregnancy: early and mid to late periods. In addition, a questionnaire including the International Study of Asthma and Allergies in Childhood questionnaire was conducted when the offspring were 2 years old. Multivariate Poisson regression adjusting for maternal baseline demographics was used to elucidate the association between maternal vegetable intake and the incidence of wheeze in the offspring. Among 310 singletons, 82 (26.5%) experienced wheeze at 2 years of age. Women with the highest intake of cruciferous, and folate-rich vegetables during early pregnancy reported a significantly lower prevalence of wheeze in their child at 2 years of age in comparison with those who reported the lowest intake (adjusted risk ratio: 0.48 and 0.47, 95% confidence interval: 0.26-0.89, and 0.25-0.87, respectively). In trend analysis, a higher maternal intake of cruciferous, folate-rich vegetables, and total vegetables during early pregnancy was less likely to be associated with wheeze in the offspring at 2 years old (p for trend: 0.038, <0.001, and 0.028, respectively). Maternal vegetable intake during mid to late pregnancy was not associated with wheeze in the offspring. Maternal vegetable intake during early pregnancy may have a protective effect against asthma in offspring at 2 years of age.

BackgroundMaternal diabetes might be related to a high risk of allergic disease in offspring. However, it remains unknown if maternal gestational diabetes mellitus (GDM) is also associated with a high incidence of childhood asthma in offspring. A systematic review and meta-analysis was performed to investigate the above association.MethodsRelevant observational studies were obtained by search of electronic databases including Medline, Embase, Cochrane Library, and Web of Science. A randomized-effects model was selected to pool the data by incorporating the influence of potential heterogeneity. The Newcastle-Ottawa Scale was used for study quality evaluation. Subgroup analyses were performed to evaluate the potential influences of study characteristics on the outcome.ResultsTen datasets from seven moderate to high quality cohort studies, involving 523,047 mother-child pairs were included in the meta-analysis. Overall, maternal GDM was associated with a higher risk of childhood asthma in offspring (risk ratio [RR]: 1.22, 95% confidence interval [CI]: 1.07 to 1.39, p = 0.003; I2 = 30%). Subgroup analyses showed that the association was not significantly affected by study design, validation methods for GDM, or diagnostic strategy for asthma (p for subgroup analyses all > 0.05). The association between maternal GDM and asthma in offspring was more remarkable after adjusting maternal body mass index in early pregnancy (RR: 1.50 versus 1.06, p < 0.001), but significantly weakened after adjusting hypertensive disorders during pregnancy (RR: 1.08 versus 1.50, p = 0.001).ConclusionsMaternal GDM may be associated with an increased incidence of childhood asthma in offspring.

Background:Previous epidemiological studies have shown inconsistent results regarding the relation between the risk of asthma in offspring and parental occupational exposure. Therefore, we conducted a comprehensive and systematic collection of currently available epidemiological data to quantify the correlation between the 2.Methods:Related studies published before March 2023 were identified through searches of the Cochrane Library, Embase, PubMed, and Web of Science databases. The quality of included studies was assessed using the Newcastle-Ottawa Scale, while pooled odds ratios (ORs) with 95% confidence intervals (CIs) were computed using fixed-effect or random-effects models.Results:This systematic review included 10 cohort studies, with a total of 89,571 parent-child pairs included in the quantitative analysis. The results exhibited a substantial association between parental occupational exposure to allergens (OR = 1.11; 95% CI: 1.00, 1.23; P = .051) and irritants (OR = 1.19; 95% CI: 1.07, 1.32; P = .001) and an increased risk of asthma in offspring. This association was also observed in the analysis of wheezing (OR = 1.22; 95% CI: 1.11, 1.35; P < .001 and OR = 1.19; 95% CI: 1.08, 1.32; P = .001). Subgroup analysis demonstrated that maternal occupational exposure to allergens (OR = 1.07; 95% CI: 1.02, 1.12; P = .008) and irritants (OR = 1.13; 95% CI: 1.05, 1.21; P = .001) significantly increased the risk of childhood asthma. Furthermore, parental postnatal occupational exposure to allergens (OR = 1.26; 95% CI: 1.10, 1.46; P = .001) and irritants (OR = 1.26; 95% CI: 1.06, 1.49; P = .009) had a more pronounced impact on childhood asthma. Higher levels of exposure (OR = 1.26; 95% CI: 1.10, 1.46; P = .001 and OR = 1.30; 95% CI: 1.16, 1.47; P < .001) were recognized as significant risk factors for childhood asthma.Conclusion:Parental occupational exposure to allergens and irritants increases the risk of asthma and wheezing in offspring, with maternal exposure, postnatal exposure, and high-dose exposure being the primary risk factors for childhood asthma.

A farm upbringing has been associated with lower risk of asthma and methylation of asthma-related genes. As such, a farm upbringing has the potential to transfer asthma risk across generations, but this has never been investigated. We aimed to study the generational effects from a parental farm upbringing on offspring asthma. Our study involved three generations: 5759 participants from the European Community Respiratory Health Survey (ECRHS) study (born 1945-1971, denoted G1), their 9991 parents (G0) and their 8260 offspring (G2) participating in RHINESSA (Respiratory Health In Northern Europe, Spain and Australia). Questionnaire data were collected on G0 and G1 from G1 in 2010 and on G2 from themselves in 2013. The parental/grandparental place of upbringing was categorized: (i) both parents from farm; (ii) mother from farm, father from village/city; (iii) father from farm, mother from village/city; (iv) both parents from village or one parent from village and one from city; (v) both parents from city (reference group). Grandparental upbringing was equivalently categorized. Offspring asthma was self-reported and data were analysed using Cox-regression models with G2 age as the time scale. A parental farm upbringing was not associated with offspring asthma when compared with city upbringing [hazard ratio (HR) 1.12, 95% confidence interval (CI) 0.74-1.69]. Findings remained similar when stratified by offspring upbringing and asthma phenotypes. Quantitative bias analyses showed similar estimates for alternative data sources. A grandparental farm upbringing was not associated with offspring asthma in either the maternal (HR 1.05, 95% CI 0.67-1.65) or paternal line (HR 1.02, 95% CI 0.62-1.68). This multigenerational analysis suggests no evidence of an association between parental/grandparental farm upbringing and offspring asthma.

Background: Timing is important for understanding the mechanisms by which maternal distress may affect asthma. Aim: To determine whether there is a critical exposure period for maternal distress on offspring asthma and to explore the mechanisms that may be involved by assessing paternal distress. Methods: The study population included all children born in Sweden from July 2006 to Dec 2008 (n=254150). Information about childhood asthma (diagnosis or medication at 5 years), parental distress (diagnosis or medication for depression or anxiety) and covariates (gender, parental education and asthma, parity, smoking in pregnancy) was obtained from the Swedish National health registers. Four exposure time periods were tested: 2 years prior to pregnancy, pregnancy, 1 year post-natal, and 1 to 5 years post-natal. The association between parental distress and offspring asthma was assessed with logistic regression. A dose response effect was also assessed. Results: Maternal distress at each exposure period was associated with childhood asthma. When each model was adjusted for maternal distress at other exposure periods the odds ratios reduced or attenuated. However, maternal distress 1-5 years post-natal remained significantly associated with asthma regardless of earlier distress, OR 1.30 (95% CI 1.25,1.36). A dose response was seen for increasing number of exposure periods adjOR 1.17 (95% CI 1.14,1.19). There was no association between paternal distress and childhood asthma, except for 1-5 years post-natal, OR 1.10 (95% CI 1.04,1.17). Conclusion: We did not find a critical exposure period of maternal distress causing offspring asthma, however, exposure to parental distress over childhood seems to play a role in asthma aetiology.

Asthma is a chronic inflammatory airway disease characterized by airway hyperresponsiveness, inflammation, and remodeling. Asthma often develops during childhood and causes lifelong decrements in lung function and quality of life. Risk factors for childhood asthma are numerous and include genetic, epigenetic, developmental, and environmental factors. Uncontrolled maternal asthma during pregnancy exposes the developing fetus to inflammatory insults, which further increase the risk of childhood asthma independent of genetic predisposition. This review focuses on the role of maternal asthma in the development of asthma in offspring. We will present maternal asthma as a targetable and modifiable risk factor for childhood asthma and discuss the mechanisms by which maternal inflammation increases childhood asthma risk. Topics include how exposure to maternal asthma in utero shapes structural lung development with a special emphasis on airway nerves, how maternal type-2 cytokines such as IL-5 activate the fetal immune system, and how changes in lung and immune cell development inform responses to aero-allergens later in life. Finally, we highlight emerging evidence that maternal asthma establishes a unique "asthma signature" in the airways of children, leading to novel mechanisms of airway hyperreactivity and inflammatory cell responses.