Health-risk Investigation Among First-grade School Children From Shanghai Chemical Industry Park (SCIP): A Cross-sectional Study

Background Shanghai Chemical Industry Park (SCIP), located in Jinshan District, is the largest industrial zone in China. However, the impact on the residents’ health has not been assessed. The study aimed to identify the impact of living in chemical industrial areas on the health of rst-grade students Method A cross-sectional study was conducted among rst-graders between May and June 2016 in Jinshan District using experimental examinations and questionnaires. Demographic statistics and hematological parameters were summarized. Geographical distribution and high-risk clusters of prevalence of diseases and birth status were depicted. Multivariate logistic model was used to analyze the differences in the prevalence of diseases and symptoms between chemical and nonchemical industrial areas after adjusting for potential factors. Result A of was The prevalence of respiratory, digestive, and skin diseases was 0.042, and respectively. We observed one spatial cluster each for respiratory diseases (RD) and skin diseases, respectively. Signicant differences in birth defects were not observed. Some signicantly different hematological parameters and higher prevalence of RD in nonchemical industrial areas might indicate pollutant exposures in nonchemical industrial areas. The study revealed a possible positive association between environmental factors and RD. parents need to pay more attention to indoor and other environmental management. Long-term health effects of chemical industries should be continuously monitored.


Introduction
Chemical industries play an important role in the development of the Chinese economy. Up to now, China is the largest chemical-producing country in the world. There have been 22 multimillion-ton re nery and in the Yangtze River Delta, the Pearl River Delta, and the Bohai Rim Delta. Chemical industries bring huge economic bene ts, but simultaneously cause chemical pollution and accidents [1]. The development of chemical industries poses a big challenge to the local environment. Toxic chemicals such as nitrogen oxides [2] and sulfur oxides [3] from the chemical industrial parks have adverse effects on the environment and seriously threaten the surrounding residents' health [4]. Long-term exposure to chemical pollutants (e.g. persistent organic pollutants, heavy metals, particulate matters [PMs]) can lead to acute or chronic symptoms on the human respiratory, digestive, integumentary, nervous, and hematopoietic systems [5].
Maternal exposure to toxic chemicals, particularly to heavy metals, reduces fetal development to a certain extent (e.g., preterm delivery, low birth weight) [5,6]. Due to the biological vulnerability of children, they are more likely to be affected by the chemical toxicants in the environment than individuals in other age groups [7,8]. Thus, the health problems of children living near chemical industrial areas (CIA) should pay more attention.
Shanghai Chemical Industry Park (SCIP) is the largest chemical industry park in China, located in the Jinshan District of Shanghai. It is also the rst chemical development zone specialized in the development of petrochemical and ne chemistry businesses in China, the leading chemical industry park in the Yangtze River Delta. In the 11 th Five-Year Plan (2006)(2007)(2008)(2009)(2010), an industrial structure characterized by the gathering of chemical industry was o cially formed in the southern part of Jinshan District. In 2008, the three major regions of SCIP, consisting of Shanghai chemical industry zone, Shanghai petrochemical industry zone, and Jinshan second industrial zone, were all completed and put into production. Hence, it is a suitable research site to clarify whether the chemical industries would affect the residents' health. Previous studies from China have mainly focused on the identi cation of chemical risk sources and individual risk assessment [9][10][11]. Although both the local government and residents are concerned with the health problems caused by chemical industries, population-based epidemiological studies focusing on the health effects of these chemical industries are insu cient due to potential political issues.
This was a comprehensive school-based cross-sectional study involving all rst-grade school children born in 2008 (considering children's vulnerability to chemical pollution, the time the chemical industries initiated their operation, the homogeneity of subjects' characteristics, feasibility of the study and followup studies) to investigate the potential in uence of the chemical industry on residents' health, especially school children.

Study sites
Jinshan District is in the southwest suburb of Shanghai Municipality, with a population of 520,404, nearly half of which are urban population in 2016. The area is 44 km long from east to west and 26 km wide from north to south. It includes 11 townships with a total area of 613 km 2 . Jinshan District is the only districts in Shanghai where the economy is dominated primarily by chemical industries and agriculture. Based on the location of the chemical industrial zones (Shanghai chemical industry zone in CJ, Shanghai petrochemical industry zone in SH, and Jinshan second industrial zone in JSW) in Jinshan, the 11 townships were divided into CIA and nonchemical industrial areas (non-CIA) (Figure 1a). CIA include three townships, CJ, JSW, and SH. Non-CIA include eight townships: FJ, LvX, LX, SY, ZY, ZJ, TL, and JSGYQ.

Subjects
General surveys including questionnaires and measurements were conducted on the rst-grade school children enrolled in 2015 during the fall semester in all the 28 primary schools within the 11 townships in Jinshan District, Shanghai. Measurements were completed between May and June 2016, while all the questionnaire surveys were nished in September 2016.

Questionnaires
The questionnaires consisted of the following three main parts: (1) general demographic information of rst-grade school children, (2) health status of rst-graders, and (3) children's environmental exposures including indoor pollution and surrounding potential pollution sources within 300 m of the residence.
The basic demographic information investigated included school, class, townships, sex, date of birth, birth weight, birth outcome, parents' occupations, and parents' educational levels.
The health problems included diseases diagnosed by physicians in the previous year and acute symptoms experienced at least once in the last month. Diseases were de ned as follows: (1) respiratory diseases (RD): recurrent respiratory infection, pneumonia, asthma, tracheitis, allergic rhinitis, or other respiratory diseases; (2) digestive diseases: gastritis, peptic ulcer, acute diarrhea, gastroesophageal re ux, or other digestive diseases; and (3) skin diseases: pruritus, eczema, urticaria, conjunctivitis, trachoma, or other skin diseases. Acute symptoms were de ned as follows: (1) respiratory symptoms: throat irritation, nasal obstruction, discomfort, cough, expectoration, shortness of breath, or other respiratory symptoms; (2) eye symptoms: eye irritation or other eye symptoms; (3) neurological symptoms: headache, dizziness, weakness, insomnia, memory loss, inattention, abnormal sensation, limb pain, or other neurological symptoms; (4) digestive symptoms: anorexia, nausea and vomiting, stomachache, or other digestive symptoms; and (5) skin symptoms: itch, eczema, alopecia, or other skin symptoms.
Indoor pollution included household smoking, pollutants from indoor decorations, or pollutants after purchasing furniture the previous year, use of air eliminators, and use of heaters during winter.
Surrounding sources included tra c trunks, barbecue restaurants, and nonchemical enterprises. The investigators explained the questionnaires consistently to all participants, and the participating students lled out the questionnaire with the help of their parents.

Measurements
Measurements included physical examinations and hematological tests. The subjects were asked to take off their shoes and wear light clothes before measurement, and an ultrasonic height and weight meter was used to measure these parameters. Fasting was also required before obtaining blood samples, and all the blood samples were collected and analyzed by physicians in clinical pathology-accredited laboratories. Complete blood count (CBC) parameters were examined (Table A2).

Data processing
Weight status was classi ed as underweight (≤13.4 kg/m 2 for girls, ≤13.9 kg/m 2 for boys), normal weight ( year-old children [12]. Moreover, BMI was calculated. To eliminate the strong correlation between parents' educational background, we used a new variable, parents' educational level (the higher educational level received by any parent), rather than separately analyzing the father and the mother's educational level. Additionally, because few parents have completed junior high school or below, junior high school or below and senior high school were combined into one variable to avoid extreme values and guarantee the stability of models.

Statistical analysis
We rst summarized the demographic statistics and CBC parameters of rst-graders. Subsequently, we used t-test for continuous variables such as height and χ 2 test for categorical variables such as sex to analyze the differences between non-CIA and CIA. Then, we assessed the geographical distribution and detected high-risk clusters of prevalence of diseases and birth status in rst-graders based on school locations using the Kulldorff method of spatial scan statistic based on a discrete Poisson model with maximum spatial cluster size of 30% of population at risk using SaTScan (version 9.6, Martin Kulldorff and Information Management Services Inc). Mapping was performed in QGIS Desktop (version 3.0.3, https://www.qgis.org/).
Finally, the logistic regression model was used to measure the differences in the prevalence of diseases and acute symptoms between CIA and non-CIA. We included all the variables with value p>0.1 under the univariate analysis into the multivariate logistic regression model, and the "backward elimination" method was used to screen the potential risk variables. Potential confounding variables were considered during the modeling process including sex, parents' educational levels and occupations, indoor pollutant exposures, and outdoor environmental exposures within 300 m of the residence. Adjusted odds ratios (ORs) and corresponding 95% con dence intervals (CIs) were calculated. All statistical analyses were performed using R 3.5.3 (R Project for Statistical Computing, http://cran.r-project.org). non-CIA. Parents of these children were more engaged in the chemical industry in CIA (16.77% for fathers and 5.75% for mothers) than parents in non-CIA ( Table 1).
Distribution of diseases' phenotypes in rst-grade school children diagnosed by physicians in the previous year is shown in Figure 1. The prevalence of RD (Figure 1b), digestive diseases (Figure 1c), and skin diseases (Figure 1d) was 22.9%, 4.2%, and 16.8%, respectively. Conclusively, tracheitis, allergic rhinitis, pruritus, eczema, conjunctivitis, and acute diarrhea were the common diseases diagnosed in rstgrade school children in Jinshan. A higher number of school children diagnosed with diseases were observed in non-CIA than in CIA.
Geographic distribution and high-risk clusters of diseases indices, including Platelet distribution width (PDW), Platelet larger cell ratio (P-LCR), Mean platelet volume (MPV), and Absolute lymphocyte counts (Abs Ly), were slightly higher in non-CIA than in CIA.

Discussion
Signi cant differences were observed in some CBC parameter levels in school children between CIA and non-CIA. Recent studies have reported the association between air pollution and hematological parameters. To some extent, associations between CBC parameters and pollution exposure could be clari ed. Experimental and epidemiological studies indicate that exposure to air pollutants is negatively associated with RBC, HCT, and Hgb [13][14][15]. An animal experimental study [16] indicated that mediumterm exposure to air pollutants decreases RBC and monocytes and increases lymphocytes. A epidemiological study reported that long-term tra c-related air exposure to air pollution had been positively associated with monocyte counts [17]. Platelet indices (PLT, PDW, P-LCR, MPV) are closely associated with thrombosis and hemostasis. PDW is used to evaluate the variability of platelet. High PDW re ects platelet anisocytosis [18]. P-LCR re ects the percentage of larger platelets used to monitor platelet activity [19]. MPV re ects platelet volume. There exists a negative association between platelet number (PLT) and size (MPV), which represents PLT and MPV having signi cant association [20,21]. Evidence from previous epidemiological studies reported that the pollutant exposures were positively associated with MPV, PDW, and P-LCR and negatively associated with PLT [22][23][24][25]. Compared to CIA, signi cant differences in CBC parameter levels indicate that pollutant exposure in non-CIA might exist.
However, there is a slight difference in the average levels of hematological parameters between CIA and non-CIA. Similarly, average levels are within the normal parameter reference range. Thus, the CBC parameters, speci cally platelets, need to be monitored closely and continuously.
Tracheitis, allergic rhinitis, skin pruritus, eczema, conjunctivitis, and acute diarrhea were common diseases diagnosed in rst-grade school children in Jinshan District. School children living in non-CIA had higher prevalence of diseases than children living in CIA. From the perspective of the spatial distribution of diseases and birth status, school children living in TL were more likely to have diseases and birth defects than children living in other towns. Larger tra c volume in northern regions, speci cally ZJ and TL, was related to the higher prevalence of RD diagnosed. High humidity in southeastern regions (SH and SY) close to the seas causes the high prevalence of skin diseases diagnosed. Considering the sparse school distribution, spatial scanning technology detected one small-scale spatial cluster for respiratory and skin diseases in nonchemical and CIA, respectively.
To examine the association between CIA and the prevalence of diseases, risk factor analysis for diseases was performed after adjusting for confounding factors. Overall, chemical industries have not caused health risk in rst-grade school children in Jinshan District. First-grade school children living near non-CIA contracted signi cantly more RD than the rst-grade children living near CIA. From the geographic distribution of RD, the subjects living in northern regions in Jinshan have higher risk of RD than subjects living other part of Jinshan. Northern regions in Jinshan District is more inland and have much higher volume of transportation, which might result in poorer air quality, while the southeastern region in Jinshan is closer to the coast and a previous study found that the relatively better air quality is caused by the unique meteorological condition of the region (the wind causes movement of the air pollutants) [26]. Additionally, previous environmental monitoring in Jinshan showed that respirable PM (PM2.5 and PM10) levels in the northern regions were higher than those in the southern regions. These reasons might lead to a signi cantly higher respiratory disease prevalence in non-CIA than in CIA.
Boys were at higher risk of RD than girls, which is consistent with the result of the Koch's study [27]. Generally, boys are more active and more involved in outdoor activities so that they generally have more exposure to risk factors than girls. School children with well-educated parents were more likely to experience RD, consistent with the result of Chen's study [28]. Considering diseases were diagnosed by physicians and reported by parents, parents with better educational level might pay more attention to their children's health problems. These diseases and symptoms might be underestimated or ignored by poorly educated parents.
School children who lived in conditions that included household smoking or newly purchased furniture in the previous year had a greater likelihood of having RD than school children who lived without these conditions. Those living within 300 meters of road trunks also had a higher risk of RD than those who did not. These results are consistent with the results of several previous studies [8,27,29,30]. Smoking and road trunks increase the presence of pollutants such as nitrogen dioxide [31,32]. Children whose household used heating devices during winter had higher prevalence of respiratory illnesses than children whose household did not. One possible explanation is that, there is signi cant difference between indoor and outdoor temperature, so children living in houses that did not use heating devices during winter might have better resistance to cold and diseases and consequently, are less susceptible to illnesses than children using heating devices.
A higher ratio of boys is overweight and obese than girls, which is consistent with the ndings of some previous studies [33,34]. In Chinese tradition, fat boys are considered healthier than thin boys. Thus, boys enjoy more of the family's resources [35]. As a result, the prevalence of obesity in rst-grade school children in Jinshan is 11.5%, which is signi cantly higher than the data in the previous studies (9.0%) using the WGOC weight status criteria [34]. The local government should intervene in this health problem by disseminating knowledge regarding healthy diet and scienti c methods of weight loss.
Our study has some major limitations. First, we divided Jinshan District into CIA and non-CIA based on the location of chemical industries without considering individual chemical exposures. Therefore, the method in determining exposure to chemical pollutions may not be precise. Second, some information (e.g., self-reported diseases, symptoms, and environmental factors) reported by parents were not objective, which might cause recall bias. Additionally, the completed time of measurements and questionnaires were not at the same time and the evaluation of some outcomes especially hematological parameters could be in uenced by different timeframes or seasons. Thus, we merely analyzed the difference of hematological parameters between CIA and non-CIA. Moreover, we tried to analyze the relationship of birth outcome and industrial exposures. However, the lack of detailed information of prenatal care may lead to misclassi cation bias.