Association between parental occupational exposure and the risk of asthma in offspring: A meta-analysis and systematic review

Abstract

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.

1. Introduction

Asthma is a significant health issue worldwide and the most common noncommunicable disease in childhood. It is characterized by widespread and variable reversible limitation of expiratory airflow, resulting in recurrent respiratory symptoms such as wheezing, breathlessness, chest tightness, and cough.^[1–3] Since the latter half of the 20th century, the global incidence of childhood asthma has shown a significant upward trend,^[2,4] particularly in low- and middle-income countries where the growth rate is higher.^[3–5] The prevalence of asthma among 13 to 14-year-old children in Latin America is rapidly increasing at a rate of 0.32% per year, with countries such as New Zealand and Brazil reporting rates as high as 21.3% to 28%.^[2] In recent years, although the number of global hospitalizations and deaths due to asthma has decreased,^[6,7] it remains a significant determinant of disability-adjusted life years in children worldwide,^[8] severely impacting their physical and mental health as well as growth and development, and increasing healthcare expenditure and socioeconomic burden.^[9] Given the substantial burden of childhood asthma, primary prevention of this disease remains critically important.^[10]

The etiology and progression of childhood asthma are driven by the interaction between the environment and genes.^[10] Among these factors, environmental influences are believed to be the most significant contributors to allergic diseases in children.^[11] It has been found that the prenatal and early life periods are crucial windows for the development of the immune and respiratory systems in children,^[12] and they represent an opportunity window for asthma prevention.^[3] High levels of occupational environmental exposure during pregnancy and early life in parents may be permanently stored through reproductive epigenetic marks and inherited by the next generation, thereby influencing the risk of asthma development.^[13,14] Additionally, various environmental exposures during early life, such as air pollution,^[15] allergens,^[16,17] and irritants,^[18] can induce airway inflammation and hyperresponsiveness, enhance oxidative stress, reduce lung function in children, and thereby trigger and accelerate the progression of asthma.^[16,19,20] Currently, researchers have increasingly been attentive to the relationship between parental occupational exposures and the health of their offspring. Some systematic reviews and meta-analyses have demonstrated that parental occupational exposure to pesticides, organic solvents, or tremendously low-frequency magnetic fields can increase the risk of neurodevelopmental disorders, neurologic tumors, and brain tumors in their children.^[21–23] However, there is inconsistent evidence regarding the relationship between parental occupational exposures and offspring asthma. Tagiyeva et al^[24] found that parental occupational exposure to insecticides and fungicides can increase the risk of offspring asthma, while Pape et al^[25] reported inconsistent results in a cohort study conducted in Denmark. These discrepancies may be attributable to factors such as sample size and outcome assessment. Given the existing inconsistencies and limitations in the reported studies, we carried out this meta-analysis to systematically evaluate the correlation between parental occupational exposures and offspring asthma.

In this systematic review and meta-analysis, we comprehensively and systematically collected the currently available epidemiological data to quantify the correlation between parental occupational exposures and the risk of offspring asthma.

2. Methods

This report was designed and carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA 2020) guidelines.^[26] The study protocol has been registered on the PROSPERO website (Registration number: CRD42023413122).

2.1. Database search methods

The search strategy for this study employed a pattern of subject terms and free-text terms. We independently examined relevant studies available in Cochrane Library, Embase, PubMed, and Web of Science databases from the inception of databases to March 17, 2023. Non-English studies were excluded during the search. The specific search strategy can be found in Appendix 1, Supplemental Digital Content, http://links.lww.com/MD/K896.

2.2. Literature selection

The following criteria were used to include studies: The study design was a cohort study; Complete information on parental occupational exposures was available; The outcome of interest was a diagnosis of asthma or wheezing in offspring; The study reported odds ratios (ORs) and their 95% confidence intervals (CIs) or provided raw data that could be used for calculations.

Studies that met the following criteria were excluded: Reviews, conference papers, meta-analysis, study protocols, case reports, clinical trials or; Abstracts, replies, or letters; Studies with unavailable data or significant flaws.

Two researchers (RXT and WZT) independently screened the literature based on the above criteria and cross-checked the results upon completion. Any disagreements encountered during the study selection process were resolved through consensus reached by discussion or by involving a third researcher. When multiple studies reported similar study periods on the same population, preference was given to publications with larger sample sizes and further comprehensive information.

2.3. Data extraction

Independently, 2 researchers (RXT and WZT) extracted the data from the eligible papers, and any discrepancies in data extraction were resolved by involving a third researcher. The extracted information included the publication year, study design, first author, country and region, sample size, exposure object, exposure window period, exposure substances, covariates, and other relevant details. ORs and 95% CIs related to the outcome of interest were prioritized for extraction from multivariable analysis. In cases where multivariable analysis was not available, results were extracted from univariate analysis or calculated from event counts.

2.4. Quality assessment

Independently, 2 authors (RXT and WZT) evaluated the quality of the included studies through employing Newcastle-Ottawa Scale (NOS).^[27] The NOS scale comprises 3 main sections: comparability, selection of the study population, and exposure/outcome. The total score ranges from 0 to 9, and based on the score, studies can be categorized as low (0–3 points), medium (4–6 points), or high (7–9 points) quality.

2.5. Outcome measures

We analyzed the impact of parental occupational exposure to allergens or irritants on asthma/wheezing in offspring. Asthma was the primary outcome of interest. The exposure levels were determined based on the asthma-specific job exposure matrix (JEM).^[28] In addition, the 30 agents by the JEM were summarized into 2 distinct categories (allergens/irritants).^[29] The allergen agents primarily include food, fish/shellfish, animals, flour, plant-related dust, plant mites, indoor mites, enzymes, storage mites, textiles, latex, medications, fatty amines, epoxy resins, isocyanates, acrylic esters, persulfates/nail dust, wood, and paraphenylenediamine. The irritant agents mainly include textiles, endotoxins, molds, high-level chemical disinfectants, fatty amines, epoxy resins, isocyanates, acrylic esters, persulfates/nail dust, wood, metals, metalworking herbicides, indoor cleaning agents, fluids, insecticides, fungicides, organic solvents, bleaching agents, and exhaust fumes.

2.6. Data integration and statistical analysis

Statistical analysis was conducted using Stata 15.0 software (StataCorp LP, College Station, TX). We employed the Q test and I² test to evaluate study heterogeneity. If (I² > 50%, P < .1) no significant heterogeneity is detected, we introduced the fixed-effects model (Mantel–Haenszel method). Otherwise, a random-effects model (DerSimonian–Laird method) was introduced. The association between parental occupational exposure and childhood asthma and wheezing was assessed by computing the pooled ORs and their corresponding 95% (CIs).

Subgroup analysis and regression analysis were performed based on the type of exposure agent (allergens/irritants), exposure object (mothers/fathers), exposure window period (prenatal/postnatal), and exposure level (low-dose/medium-dose/high-dose) to investigate the heterogeneity magnitude and sources among studies. Sensitivity analysis was carried out by systematically excluding each included study to measure the robustness of the pooled results. Publication bias was preliminarily assessed by funnel plots, and statistically determined by Egger or Begg tests. In the case of significant publication bias, the trim-and-fill method was adapted to evaluate the effect of publication bias on the results.

3. Results

3.1. Literature selection results and flowchart

A total of 2471 articles were initially retrieved from the databases, and no additional studies were found through reference browsing. After removing duplicates, 1850 articles were screened based on titles and abstracts. Among them, 1742 articles were excluded as a result of not meeting the inclusion criteria, and 108 articles underwent a full-text review. Finally, a total of 10 studies were included in this meta-analysis.^{[24,25,29–36]} The process of article selection is presented in Figure 1.

Figure 1.

Flowchart of literature selection process.

3.2. Study characteristics and quality assessment

3.2.1. Study characteristics.

A total of 10 eligible studies were included in this meta-analysis. These studies were all cohort studies published between 2006 and 2023. Among them, 8 studies were conducted in Europe,^{[24,25,29–31,34–36]} and 2 studies were conducted in Asia.^[32,33] A total of 89,571 parent-child pairs were included, with the age range of the offspring being 0 to 18 years. Among the 10 studies, 6 studies reported only maternal occupational exposure^[30–34,36]; one study reported only paternal occupational exposure,^[35] and 3 studies provided data on both parental (father/mother/both) occupational exposures.^[24,25,29] The exposure duration varied from prepregnancy to post-birth, and parental occupational exposure information was assessed using the JEM,^{[24,25,29–31,36]} or self-reported exposure status.^[32–35] Occupational determinations were classified based on the Danish International Standard Classification of Occupations codes,^[31] International Standard Classification of Occupations-1988,^[25,29,36] Japanese Standard Occupational Classification 2009,^[32,33] International Standard Classification of Occupations 1968 version,^[34] or Standard Occupational Classification 2000 codes.^[24] The fundamental characteristics of the included studies are detailed in Table 1.

Table 1.

Basic characteristics of included studies.

First author	Year	Country	Study design	Exposure source	Substance of exposure	Exposure assessment	Exposure period	Sample size		Age of offspring(yr)	Outcomes	Adjusted confounders
								Exposed group	nonexposed group
Bajeux et al	2014	France	Cohort study	Maternal	Oxidizing solvents, petroleum, chlorinated solvents	JEM	Pregnancy	504	862	26.7 (2.2) mo	Asthma Eczema	Maternal age at delivery, child age, child sex, family history of allergy, history of prenatal and postnatal tobacco exposure, preterm birth, number of born siblings, type of delivery, day care services, fish consumption
Christensen et al	2013	Denmark	Cohort study	Maternal	HMW agents HMW and LMW mixed agents	DISCO and JEM	Pregnancy (12–16, 30–35 wk) Postnatal (child was 6–18 mo)	18,438	23,286	0–7	Asthma	Maternal age, prepregnancy BMI, atopy, smoking during pregnancy, use of medication during pregnancy (dichotomous variables for the use of acetyl salicylic acid, paracetamol, folic acid and antibiotics), parity and furry animal ownership during pregnancy, child birth weight, child sex, education level, socioeconomic level.
Forster et al	2023	Germany	Cohort study	Parental	Allergens and irritants	ISCO-88 and JEM	Preconception	NM	NM	0–1	Wheeze Eczema	Education status, occupational status, household socioeconomic status, ethnicity, Parental age at child’s birth.
Kojima et al	2021	Japan	Cohort study	Maternal	Hair dye	The 2009 Japan Standard Occupational Classification	Pregnancy	7333	69,970	0–3	Asthma Allergic rhinitis	Maternal history of allergies, age, indoor smoking, maternal body mass index, household income, mode of delivery, sex of the child, preterm, birthweight, older siblings, exclusive breast feeding, daycare attendance at 1 yr old, and a history of respiratory syncytial virus infection.
Kojima et al	2022	Japan	Cohort study	Maternal	Disinfectant	The 2009 Japan Standard Occupational Classification	Pregnancy (22–28 wk)	5248	10,947	0–3	Wheeze Eczema	Maternal and paternal history of allergy, maternal body mass index, maternal exposure to indoor cigarette smoke, maternal alcohol consumption during pregnancy,maternal age at pregnancy, household income, mode of delivery, preterm birth, child birth weight, child sex, older siblings, exclusive breastfeeding, child daycare attendance at 1 yr, maternal occupation.
Magnusson et al	2006	Sweden	Cohort study	Maternal	Organic solvents	ISCO-68	Pregnancy	490	5851	14–18	Asthma Wheeze	Socioeconomic group, maternal educational level, maternal age, parity, maternal smoking, gender, postnatal parental smoking, and breast feeding.
Pape et al	2021	Denmark	Cohort study	Parental	Microorganisms, Pesticides, Allergens and Chemicals	ISCO-88 and JEM	Preconception only, Preconception and postpartum Postnatal	1324	2661	0–15	Asthma	Study center, offspring’s sex and parent’s characteristic (age, asthma before the age of 10 yr, asthma after the age of 10 yr, place of upbringing, and smoking) as well as parent’s and grandparent’s educational level.
Svanes et al	2017	Norway	Cohort study	Paternal	Welding or metal fumes	Questionnaires	Preconception and pregnancy	1854	6773	10	Asthma	Offspring age, paternal characteristics (age, education, smoking status), study center, cluster by family.
Tagiyeva et al	2010	UK	Cohort study	Parental	Wood, diisocyanate, flour, glues/resins, animals, solder, enzymes, biocides/fungicides, foods,natural rubber latex and dyes	SOC and JEM	Pregnancy (18 wk) Postnatal (21 mo)	Pregnancy = 7283 Postnatal = 3333	Pregnancy = 13,383 Postnatal = 6613	0–102 mo	Asthma	Sex, birthweight, gestational age at delivery and maternal asthma, age at delivery, parity, highest educational qualification, smoking during pregnancy and home ownership status
Tjalvin et al	2022	Norway	Cohort study	Maternal	Cleaning products/detergents and low/intermediate-level disinfectants	ISCO-88 and JEM	Preconception only, Preconception and postpartum Postnatal	1307	2011	0–10	Asthma Asthma with nasal allergies Wheezing and/or asthma	Mother’s level of education (primary, secondary, and college/university), maternal smoking in 3 categories (no smoking, during pregnancy and/or childhood, during childhood) and maternal ever asthma.

DISCO = Danish International Standard classification of Occupations, HMW = High-molecular-weight, ISCO-88 = International Standard Classification of Occupations, Revised edition 1988, ISCO-68 = International Standard Classification of Occupations, Revised edition 1968, JEM = the asthma-specific job exposure matrix, job exposure matrix, LMW = Low-molecular-weight, NM = not mentioned, SOC =Standard Occupational Classification.

3.2.2. Quality assessment.

The results of the NOS assessment indicated that all included studies^{[24,25,29–36]} scored between 7 and 9 points, suggesting high-quality, as presented in Table 2. Most studies scored high in the comparability section, while the scores for the adequacy of follow-up were lower. This could be attributed to the long follow-up duration, leading to varying degrees of loss to follow-up and affecting the completeness of follow-up.

Table 2.

Quality assessment of included studies.

Study	Selection				Comparability	Outcome			Quality scores
	Representativeness of the exposed cohort	Selection of the nonexposed cohort	Ascertainment of exposure	Demonstration that outcome of interest was not present at start of study	Comparability of cohorts on the basis of the design or analysis*	Assessment of outcome	Was follow-up long enough for outcomes to occur†	Adequacy of follow-up of cohorts‡
Bajeux 2014	✻	✻	✻	✻	✻	✻	✻	-	7
Christensen 2013	✻	✻	✻	✻	✻	✻	✻	-	7
Forster 2023	✻	✻	✻	✻	✻	✻	✻	-	7
Kojima 2021	✻	✻	✻	✻	✻	✻	✻	✻	8
Kojima 2022	✻	✻	✻	✻	✻	✻	✻	✻	8
Magnusson 2006	✻	✻	✻	✻	✻	✻	✻	-	7
Pape 2021	✻	✻	✻	✻	✻	✻	✻	-	7
Svanes 2017	✻	✻	✻	✻	✻	✻	✻	✻	8
Tagiyeva 2010	✻	✻	✻	✻	✻	✻	✻	-	7
Tjalvin 2022	✻	✻	✻	✻	✻✻	✻	✻	✻	9

^*We selected “sex and birth year” as the most important adjusting factors.

^†A mean duration of follow-up of at least 1 year was considered as long enough for outcome to occur in this meta-analysis.

^‡It was regarded adequate when the follow-up rate was at least 80%, or a follow-up rate >70%, and the loss of follow-up was describe.

3.3. Meta-analysis

3.3.1. Correlation between parental exposure to allergens and offspring asthma.

Four studies^{[24,25,31,32]} reported the correlation between parental exposure to allergens and offspring asthma. The random-effects model was used to pool data. The analysis results indicated a borderline significant relationship between parental occupational exposure to allergens and the occurrence of offspring asthma (OR = 1.11; 95% CI: 1.00, 1.23; P = .051), as depicted in Figure 2A. Moreover, there was statistically substantial heterogeneity among the included studies (I² = 53.3%, P = .045). Sensitivity analysis results revealed that the conclusion was robust, as the pooled results did not change after systematically excluding individual trials, as shown in Figure 2B. The funnel plot and Begg publication bias test denoted no potential bias among the included studies (P = 1.000).

Figure 2.

(A) Forest plot for the relationship between parental exposure to allergens and offspring asthma. (B) Sensitivity analysis of the relationship between parental exposure to allergens and offspring asthma. (C) Forest plot for the relationship between parental exposure to irritants and offspring asthma. (D) Sensitivity analysis of the relationship between parental exposure to irritants and offspring asthma.

3.3.2. Relationship between parental exposure to irritants and offspring asthma.

Seven studies^{[24,25,30,31,33–35]} reported the association between parental occupational exposure to 11 types of irritants (cleaning agents, disinfectants, organic solvents, etc.) and offspring asthma. Heterogeneity analysis showed no statistically substantial heterogeneity among the included studies (I² = 19.1%, P = .246), thus a fixed-effects model was introduced to pool the effect sizes. The results indicated that parental occupational exposure to irritant substances increased the risk of offspring asthma (OR = 1.19; 95% CI: 1.07, 1.32; P = .001), as shown in Figure 2C. Sensitivity analysis demonstrated the robustness of the results as the exclusion of any individual study did not affect the overall results, as illustrated in Figure 2D. The funnel plot and Begg test denoted no potential bias (P = .063).

3.3.3. Relationship between parental exposure to allergens and offspring wheezing.

Two studies^[24,29] were included to measure the relationship between parental occupational exposure to allergens and offspring wheezing. No significant heterogeneity was observed among the studies (I² = 0.0%, P = .624), thus a fixed-effects model was introduced to summarize the results. The findings revealed a substantial association between occupational exposure to allergens and offspring wheezing (OR = 1.22; 95% CI: 1.11, 1.35; P < .001), as depicted in Figure 3A. Sensitivity analysis further confirmed the robustness of the results, as shown in Figure 3B. The funnel plot and Begg test denoted no potential bias among the included studies (P = .734).

Figure 3.

(A) Forest plot for the relationship between parental exposure to allergens and offspring wheezing. (B) Sensitivity analysis of the relationship between parental exposure to allergens and offspring wheezing. (C) Forest plot for the relationship between parental exposure to irritants and offspring wheezing. (D) Sensitivity analysis of the relationship between parental exposure to irritants and offspring wheezing.

3.3.4. Relationship between parental exposure to irritants and offspring wheezing.

Five studies^{[24,29,30,34,36]} discussed the relationship between parental exposure to irritants and offspring wheezing. The random-effects model was used to pool data. The analysis results revealed that parental occupational exposure to irritant substances resulted in a substantial increase in the risk of offspring wheezing (OR = 1.19; 95% CI: 1.08, 1.32; P = .001), as shown in Figure 3C. No significant heterogeneity was observed among the included studies (I² = 0%, P = .659). Sensitivity analysis demonstrated that the association between exposure to irritant substances and offspring wheezing remained unchanged when any individual study was omitted, as displayed in Figure 3D. The funnel plot and Begg test denoted no potential bias among the included studies (P = .466).

3.4. Subgroup analysis

Subgroup analysis was performed to explore the effects of different exposure objects, exposure window periods, and exposure levels on offspring wheezing, the main disease outcome of interest.

For occupational exposure to allergens, subgroup analysis based on exposure objects^{[24,25,31,32]} showed that maternal occupational exposure to allergenic substances significantly increased the risk of offspring wheezing (OR = 1.07; 95% CI: 1.02, 1.12; P = .008). In contrast, no statistically substantial association was noted between paternal exposure to allergenic substances and offspring wheezing (OR = 0.79; 95% CI: 0.53, 1.19; P = .256), as demonstrated in Figure S1A, Supplemental Digital Content, http://links.lww.com/MD/K895. Based on the subgroup analysis by exposure window periods,^[24,31,32] parental occupational exposure to allergens, both prenatally and postnatally, may increase the risk of offspring wheezing (OR = 1.05; 95% CI: 0.99, 1.10; P = .088 and OR = 1.42; 95% CI: 1.16, 1.74; P = .001), whereas Pape et al^[25] did not find a substantial association between prenatal and postnatal exposure in their longitudinal observation (OR = 1.05; 95% CI: 0.81, 1.35; P = .724), as depicted in Figure S1B, Supplemental Digital Content, http://links.lww.com/MD/K895. Regression analysis further confirmed the significant difference in the impact of exposure windows on offspring wheezing (P = .009). Subgroup analysis based on different exposure levels^[24,32] revealed that high-dose allergen exposure was associated with the occurrence of offspring wheezing (OR = 1.26; 95% CI: 1.10, 1.46; P = .001), while the association was weaker for low-dose and moderate-dose exposures (OR = 1.17; 95% CI: 0.89, 1.55; P = .265 and OR = 1.09; 95% CI: 1.00, 1.19; P = .054), as described in Figure S1C, Supplemental Digital Content, http://links.lww.com/MD/K895.

In terms of occupational exposure to irritants, subgroup analysis based on exposure objects^{[24,25,30,33–36]} showed that maternal occupational exposure to irritant substances significantly increased the risk of offspring wheezing (OR = 1.13; 95% CI: 1.05, 1.21; P = .001). On the other hand, no statistically significant association was observed between paternal exposure to these substances and offspring wheezing (OR = 0.93; 95% CI: 0.69, 1.24; P = .612), as shown in Figure S1D, Supplemental Digital Content, http://links.lww.com/MD/K895. Based on the subgroup analysis by exposure window periods,^{[24,25,30,33–36]} occupational exposure to irritants, both prenatally and postnatally, increased the risk of offspring wheezing (OR = 1.10; 95% CI: 1.02, 1.19; P = .011 and OR = 1.26; 95% CI: 1.06, 1.49; P = .009). However, Tjalvin et al^[36] found no substantial association between prenatal and postnatal exposure in their longitudinal observation (OR = 0.95; 95% CI: 0.71, 1.25; P = .681), as presented in Figure S1E, Supplemental Digital Content, http://links.lww.com/MD/K895. Subgroup analysis based on different exposure levels^{[24,33,34,36]} revealed that high-dose exposure to irritants was associated with the occurrence of offspring wheezing (OR = 1.30; 95% CI: 1.16, 1.47; P < .001), while the association was weaker for low/medium-dose exposures (OR = 1.05; 95% CI: 0.96, 1.15; P = .262), as described in Figure S1F, Supplemental Digital Content, http://links.lww.com/MD/K895. Regression analysis further confirmed the substantial difference in the effect of exposure levels of irritant substances on offspring wheezing (P = .006).

4. Discussion

The results of this study indicate that parental occupational exposure to allergens and irritants was associated with an increased risk of childhood asthma and wheezing. Subgroup analysis suggests that maternal exposure is the primary risk factor for childhood asthma. Furthermore, the postnatal period is an important window of vulnerability to allergen exposure, and both postnatal and prenatal exposure to irritants significantly increase the risk of childhood asthma. Regarding exposure levels, a higher level of exposure has a more pronounced impact on childhood asthma.

Previous studies have reported similar findings,^[37–40] indicating that the risk of asthma in offspring increases with parental occupational exposure to allergens or irritants. Occupational allergens or irritants can adhere to contaminated clothing or skin and be brought home, resulting in indirect exposure for children from their parents work environment, thereby increasing the risk of asthma^[39,41] and affecting children’s lung function. This may be related to prenatal developmental effects or postnatal stimulation of airway development.^[42] It is well known that the prenatal period and early life of children are critical periods for the development of the immune and respiratory systems and sensitive window periods of exposure to chemicals.^[12,43,44] During this period, some chemicals in allergens and irritants can pass through the placental barrier and directly impact fetal development.^[36,45] Previous animal and cell studies have reported potential mechanisms by which parental exposure to allergens and irritants leads to the development of asthma in offspring. Exposure of parents to substances such as plasticizers and organic solvents can induce epigenetic changes in gene expression,^[46] participate in the expression of genes involved in TH2 differentiation,^[47] alter the development of the immune system through T-cell polarization,^[43] leading to an imbalance in Th1/Th2 immune responses^[48] and increasing the risk of asthma in offspring.^[49] In addition, the gut microbiota during pregnancy and early life can promote the maturation of the human immune system,^[44,50,51] which is closely correlated with the occurrence and development of the offspring allergic diseases.^[52–54] Studies have shown that exposure to cleaning agents or disinfectants during pregnancy may influence the diversity of maternal microbial flora, thereby affecting fetal immune development and the establishment and maturation of gut microbiota, increasing the risk of offspring allergic diseases.^{[33,36,55,56]} These findings may help explain how parental occupational exposure to allergens or irritants elevates the risk of asthma in offspring.

We found that the risk of asthma development in offspring was greatly affected by maternal occupational exposure. The potential reason may be that maternal reproductive cells are more vulnerable during pregnancy.^[35,57] Along with the increasing time of exposure, higher levels of environmental toxins accumulate in reproductive cells, leading to an increased incidence of the novo mutations and epigenetic changes.^[58] Additionally, the interaction between microbiota and immune system in the maternal-infant dyad also influences the development of childhood asthma.^[59,60] Maternal exposure to allergens or irritants can cause alterations in microbial diversity, which, through vertical transmission from mother to child, affects fetal immune development and leads to a higher incidence of asthma in offspring.^[52] This also explains the lack of significant association observed between prenatal exposure to allergens and asthma in offspring in our subgroup analysis, as including paternal prenatal exposure data might have confounded the results.

Our study has several strengths. Firstly, to our knowledge, this is the first meta-analysis estimating the association between parental occupational exposure and the risk of asthma/wheezing in offspring. Secondly, subgroup analysis was conducted based on exposure objects, exposure window periods, and exposure levels to investigate the effects of different influencing factors on the risk of childhood asthma. Thirdly, our study included a total of 89,571 parent-child pairs, ensuring sufficient statistical power for conducting the meta-analysis. Lastly, our analysis is free from publication bias. However, our study also has some limitations. Firstly, the assessment of parental occupational exposure was mainly based on questionnaire surveys and/or asthma-specific job exposure matrices without a unified criterion. Therefore, self-reported data might lead to exposure misclassification, introducing potential bias. Secondly, due to the limited number of retrieved studies, we categorized exposure substances into allergens and irritants without conducting a more detailed subgroup analysis. In the future, with an adequate number of observational studies available, we will perform further refined meta-analysis for more specific exposure categories. Thirdly, our study conclusions may be influenced by the included articles, and more large-scale, high-quality cohort studies are warranted to provide further evidence for our findings.

5. Conclusion

Parental occupational exposure to allergens and irritants increases the risk of asthma and wheezing in offspring, particularly with maternal exposure, postnatal exposure, and high-dose exposure being the primary risk factors for childhood asthma. Therefore, parents are recommended to avoid occupational exposure to harmful substances as much as possible, take appropriate personal protective measures during exposure, and ensure thorough cleaning before returning to the home environment to protect the early immune and respiratory system development of their children. In future research, more detailed investigations into specific categories of exposure substances and their association with asthma in offspring can be conducted, combining epidemiological and experimental studies to elucidate the underlying mechanisms of asthma development.

Author contributions

Conceptualization: Xiaoting Ren, Lie Wang, Zhongtian Wang, Lei Wang, Yibu Kong, Yinan Guo, Liping Sun.

Formal analysis: Xiaoting Ren, Zhongtian Wang, Yibu Kong.

Funding acquisition: Yibu Kong, Yinan Guo, Liping Sun.

Investigation: Xiaoting Ren, Zhongtian Wang, Yibu Kong.

Methodology: Xiaoting Ren, Zhongtian Wang, Lei Wang.

Resources: Lie Wang, Liping Sun.

Supervision: Lie Wang, Yinan Guo, Liping Sun.

Writing – original draft: Xiaoting Ren, Liping Sun.

Writing – review & editing: Xiaoting Ren, Lie Wang, Zhongtian Wang, Lei Wang, Yibu Kong, Yinan Guo, Liping Sun.