Comparison of Blood Lead Levels in Children and Adolescents with and without Functional Abdominal Pain

Abstract

Background:

Functional abdominal pain is a health concern with chronic abdominal discomfort without clear etiology. Several etiologic factors are raised in this regard, one related to environmental factors. This study aimed to compare blood lead levels between children and adolescents with and without functional abdominal pain.

Materials and Methods:

This case–control study was performed in 2019–2020 in Isfahan, Iran. The sample size was calculated as 70 cases and an equal number of controls. Cases were children and adolescents with functional gastrointestinal disorder (FGID), and controls were grouped age- and sex-matched. Controls were randomly selected from those referred for routine health screening. Both groups obtained blood lead, iron, and calcium levels. All participants completed the FFQ Food Consumption and Environmental Pollutants Questionnaire.

Results:

Participants were 139 children (68 cases and 71 controls). The mean (SD) age was 9.40 (3.91) years in the FGID group and 8.79 (3.46) years in the controls (P = 0.330). The mean (SD) blood lead level was not significantly different between the FGID group and the controls (3.98 ± 2.56 vs 3.81 ± 1.96 μg/dl, respectively, P = 0.670). We found that 55.3% of children with high lead levels had FGID, while 44.4% of children with lower lead levels had FGID, but the difference was not statistically significant (P = 0.33).

Conclusion:

We found that the lead level was higher in patients with FGID than in the controls; however, this difference was not significantly different. This might be because of elevated lead levels in both groups. Future ecological studies with a large sample size are necessary in this regard.

INTRODUCTION

Lead is a heavy metal that is found in nature.[1] It is a neurotoxic metal that is dangerous for the human brain, especially the developing brain in young children.[2] In addition, lead, as a toxic substance in the human environment, can affect almost every organ and system in the body.[1] Due to the higher absorption of lead in children from the environment, they are more susceptible to acute or chronic lead poisoning.[3] Lead is produced and entered to the body via conventional sources such as fuel, leaded gasoline, toxic substances in the fuel, waste,[1] cosmetics, some furniture, porcelain, some polyvinyl chloride (PVC) pipes, imported jewelry, greenhouse gases, solder,[4,5] toxic dyes,[6] and even electric kettles and samovars.[7] It also enters the body through ingestion, inhalation, or skin contact.[8] Effects of lead poisoning are usually nonspecific and include items such as nonspecific abdominal pain, constipation, irritability, muscle aches, headache, loss of appetite, decreased libido, concentration difficulties, and unnecessary surgery because of misdiagnosis of acute abdomen, cholecystitis, pancreatitis.[1,3] Therefore, it is important to pay attention to the serum level of lead in patients with similar clinical manifestations, especially chronic functional pain.

Functional or recurrent abdominal pains are one of the most common types of digestive disorders. They are defined as at least three episodes of abdominal pain in the prior three months that interfere with normal functioning without any organic cause.[9] Unfortunately, these pains are often accompanied by the impaired performance of the child at school and there is no definite treatment for it.[10]

Actually, serum lead levels of more than 5 micrograms per deciliter for children are considered lead poisoning.[11] In Iran, 18.5% to 85% of lead poisoning has been reported in children in different years,[12] which shows the importance of addressing this issue and the need for epidemiological studies related to lead poisoning. However, since these events are more prevalent in developing countries and there is no study in our region, and given the relatively high prevalence of functional abdominal pain, we decided to determine the lead level in these patients.

MATERIALS AND METHODS

This case–control study was performed in 2019–2020 in Isfahan, Iran. Given the lack of information about the prevalence of lead poisoning, we considered the data of a previous study in Iran that compared lead levels between children with gastrointestinal problem and controls. To reach a significant difference with a type one error of less than 5%, the sample size was considered 70 individuals in each of case and control groups.

Cases were 68 children and adolescents (5–15 years old) with functional gastrointestinal disorder (FGID). They were those patients referred during the study period to the gastrointestinal clinic of two educational hospitals. The controls were 71 children, age- and sex-matched controls who were randomly selected from those referred for routine health screening. Matching in this study was a group matching [Table 1].

Table 1.

Comparison of characteristics in children with functional gastrointestinal disorders and controls

	Control (n=71)	Case (n=68)	P
Gender, n (%)			0.75a
Female	29 (40.8)	26 (38.2)
Male	42 (59,2)	42 (61.8)
Age (year), mean±SD	8.79±3.46	9.40±3.91	0.33b
Age group, n (%)			0.67a
<8 year	28 (39.4)	23 (33.8)
8–12 year	30 (42.3)	29 (42.6)
>12 year	13 (18.3)	16 (23.5)
Weight (kg), median (IQR)	26 (19,26)	28 (20,40.7)	0.48c
Height (cm), median (IQR)	129 (109,136)	130 (110.5,156.76)	0.28c
BMI (kg/m2), median (IQR)	15.62 (14.27,17.75)	16.53 (14.87,20.19)	0.24c

^aChi-square test, ^bindependent-samples t-test, ^cMann–Whitney t-test

In both groups, blood lead, iron, and calcium levels were obtained. All participants completed the FFQ Food Consumption and Environmental Pollutants Questionnaire. The blood lead level of participants was classified into two categories: less the 5 μg/dl and equal to or more than 5 μg/dl.

Patients’ demographic information was also recorded. After obtaining informed consent, sampling was performed to measure lead levels. A blood lead sample was taken by 2 ccs of blood sample in ethylenediaminetetraacetate (EDTA) medium, and since blood lead level is affected by iron and calcium levels in the blood, calcium and iron levels were also measured (5 cc of blood clot).[13,14] Baradaran Laboratory. The blood lead level over 5 micrograms/dl is abnormal.

Inclusion criteria: It includes children and adolescents (5–15 years old) with functional abdominal pain based on ROME 4 criteria after ruling out pathological cases.

Exclusion criteria: It includes lack of cooperation in completing the study and diagnosis of any systemic disease.

Ethical considerations: This study was approved by the Ethical Committee of Isfahan University of Medical Sciences: IR.MUI.REC.1396.2.047.

Statistical analysis

Quantitative variables are described by mean ± standard deviation (SD) and qualitative variables by number (percent). Differences between the control and case groups in terms of sample characteristics were tested using independent-samples t-tests (or Mann–Whitney's test) and Chi-squared tests (χ2) for continuous and categorical data, respectively. Subgroup analysis was carried out for gender and age groups. The association of blood lead level and a chance of FGID was investigated using a multiple logistic regression model. P values < 0.05 were considered significant for two-tailed tests. Statistical analyses were performed using Statistical Package for the Social Sciences (SPSS) version 22.0 (SPSS Statistics, Armonk, NY, IBM Corp., 2013).

RESULTS

The FGID group consisted of 68 participants, 42 (61.8%) were boys, and the mean (SD) age was 9.40 ± 3.91 years, and controls were 71 children, of them 42 (59.2%) were boys and the mean (SD) age was 8.79 ± 3.46 years. As presented in Table 1, there were no statistically significant differences between the case and control groups in age, gender, height, weight, and body mass index (BMI).

The blood lead level was consistent for both males (3.74 ± 2.27) and females (4.21 ± 2.55) (P = 0.355).

The mean blood lead level in the FGID group was not significantly higher compared with the control group (3.98 ± 2.56 μg/dl vs. 3.81 ± 1.96 μg/dl, P = 0.67).

Blood lead level of participants was classified into two categories: less the 5 μg/dl and equal to or more than 5 μg/dl. We found that 55.3% of children with lead level ≥5 had FGID while 44.4% of children with lead <5 g/dl had FGID, but the difference was not statistically significant. In a subgroup analysis, we determined the mean blood lead in male and female participants [Table 2]. Males’ mean blood level was 3.59 ± 2.27 and 3.90 ± 1.87 in the FGID and control groups, respectively. Even though the mean lead in female participants with FIGD was higher compared with females in the control group (4.63 ± 2.94 vs 3.68 ± 2.11) [Figure 1, Table 2], the insignificant association of blood lead level and FIGD was statistically consistent across males and females (P = 0.155). The association of blood lead level and chance of FGID was as well statistically consistent across age groups (P = 0.904).

Table 2.

Mean (SD) lead level of the case and control groups according to age and gender

	Control	Case	Total	P
Overall	3.81±1.96	3.98±2.56	3.89±2.27	0.68a
Lead <5 µg/dl, n (%)	45 (53.6)	39 (44.4)	84	0.33b
Lead ≥5 µg/dl, n (%)	21 (44.7)	26 (55.3)	47
Gender				0.16c
Female	3.68±2.11	4.63±2.94	4.21±2.55
Male	3.90±1.87	3.59±2.27	3.74±2.27
Age group (years)				0.90c
<8	4.23±1.94	4.83±2.45	4.49±2.18
8-12	3.50±1.74	3.28±2.56	3.39±2.17
>12	3.62±2.46	4.13±2.49	3.90±2.44

^aIndependent-samples t-test, ^bChi-square test, ^cP value for the interaction of lead level and subgroup variables derived from logistic regression

Figure 1.

Blood lead level in cases and controls according to gender by male and females

The association of one SD increases in blood lead level. The chance of FGID was also investigated in a multiple regression model adjusted for gender, age, and weight [Table 3]. The results of the adjusted model implied a direct but nonsignificant association between blood lead level and FGID.

Table 3.

Univariate and multivariate investigation for the association of lead level and FGID

	Crude model OR	P	Adjusted model OR	P a
Lead	1.08 (0.76,1.7)	0.67	1.13 (0.80,1.70)	0.49
Sex (Ref. male)	1.12 (0.57,2.20)	0.75	1.57 (.75,3.26)	0.23
Age	1.18 (0.84,1.65)	0.33	1.23 (0.73,2.09)	0.43
Weight	1.07 (0.76,1.51)	0.69	0.94 (0.55,1.59)	0.81

Logistic regression derived odds ratio of functional pain for a standard deviation increase in lead level, age, and weight. ^aAdjusted for gender, age, and weight

A total of 40 (27.8) children and adolescents included in this study had near (> =4) or above the upper limit of normal (>5) lead level. The most common sources of lead exposure of children were as follows: spices and turmeric (85%), playing with soil (47.5%), colored candy and snacks (42.5%), painting and pottery (37.5%) finger painting (30%), playing with colored toys (30%), consumption of Indian rice (27.5%), living near industrial centers or factories (25%), chewing pencil behavior (25), living in old houses (22.5%), cooking and serving foods in ceramic vessels (12%), and living near the gas station (12%).

Table 4 shows different exposure sources of lead and the exposure rate among children with less than 4 μg/dl and equal higher or than 4 μg/dl. A total of 57 (43.5) children and adolescents included in this study had near or above the upper limit of normal lead level (≥4 μg/dl). The most common sources of lead exposure in children were as follows: spices and turmeric (85%), playing with soil (47.5%), colored candy and snacks (42.5%), painting and pottery (37.5%), finger painting (30%), playing with colored toys (30%), consumption of Indian rice (27.5%), living near industrial centers or factories (25%), chewing pencil behavior (25), living in old houses (22.5%), cooking and serving foods in ceramic vessels (12%), and living near the gas station (12%). The exposure rate to most of the sources was higher in children with above-normal levels of lead (P < 0.05).

Table 4.

Exposure rate to lead-containing materials

	Lead >4	Lead ≤4
Number (%)	57 (43.5)	74 (56.5)
Old houses >30 y	9 (22.5)	11 (11.0)
Soil playing	19 (47.5)	21 (21.0)
Living near the industrial center	10 (25.0)	6 (6.0)
Living near a gasoline station	5 (12.0)	6 (6.0)
Pencil-in-mouth behavior	10 (25.0)	16 (16.0)
Finger painting	12 (30.0)	17 (17.0)
Painting and pottery	15 (37.5)	18 (18.0)
Ceramic pans	5 (12.0)	5 (5.0)
Colored toy playing	12 (30.0)	14 (14.0)
Colored candies	17 (42.5)	18 (18.0)
Indian rice	11 (27.5)	11 (11.0)
Spices and turmeric	34 (85.0)	29 (29.0)

*Chi-square test

DISCUSSION

Lead poisoning is one of the health problems around the world, and it can be associated with deleterious consequences. Therefore, paying attention to this health problem is important and necessary.

According to CDC USA, the high-risk areas for lead poisoning are areas where at least 12% of children tested have a lead level over 10 micrograms/dl.[3] According to this definition, the city of Isfahan is a low-risk area for lead poisoning. However, the lead level of patients with lead poisoning should be in the range of 5–9 micrograms per deciliter, and it should be checked every 3 months to ensure its decline.[15] Although the level of lead in children in Isfahan was not as high as in high-risk areas, 27% of all subjects in the study had lead levels close to or above normal [Figure 2].

Figure 2.

Average lead level of 15 different geographic regions in Isfahan city

Other signs and symptoms of chronic lead poisoning are anemia with basophilic stippling of RBC black–blue deposits on gum and lead line in bone radiology.[10,16] The usual presentations consist of abdominal pain, anemia and basophilic stippling of RBCs, blue–black precipitates on the gingiva, and a lead line on joint X-ray.[10,16] These symptoms propose that in the approach of chronic abdominal pain, in addition to the common medical causes, we should also consider lead poisoning. Nevertheless, new research suggests that even lead values that were traditionally considered normal may induce cognitive disorders, neurobehavioral illnesses, neurological impairment, hypertension, and kidney damage.[17]

One study in Berlin (1997) showed that the patients with higher lead level had significant radiographic findings (29% Vs 18%).[18] What is clear from the present study was that lead levels in patients with functional abdominal pain were not different from those in normal children.

Salehi et al.[19] also emphasized that abdominal pain was higher in lead poisoning addicts. Moawad et al.[20] reported an effective and significant relationship between gender and lead poisoning, although no effective relationship was found in the present study.[21] In addition, in other studies, a significant relationship was observed between high BMI and lead poisoning, which was not found in the present study.[22] In a 1976 study of 63 patients who had recovered from lead poisoning due to industrial pollution, colic abdominal pain improved with chelation treatment.[23] A study showed that dermal absorption of lead can cause lead poisoning that might cause chronic abdominal pain and constipation, which is named painters colic.[24] There are many case reports about lead intoxication and chronic resistant abdominal pain.[15,16,25] A study that was conducted in 2017–2018 among Iranian patients with unexplained abdominal pain showed that the lead level equal or greater than 30 μg/dL (1.45 μmol/L) was accompanied by gastrointestinal symptoms. The main source of lead exposure among these patients was prolonged opium addiction.[26]

In the current study, the nonsignificant difference in lead levels in the case and control groups might be because of high blood lead level in both groups, which implies high exposure of Iranian children to lead.

The cause of lead poisoning may vary from community to community. A study in Bangladesh in 2018 found that lead levels in children in this country were higher than the average lead in the United States, and the cause was reported to be inhalation of polluted air.[27] Lead water pipe in old houses is considered a major cause of lead intoxication.[28]

In 2016, researchers found that lead-contaminated food and water might be the origin of lead toxicity. The packing procedures, cooking methods and kitchen wares, and method of storage of food materials also play an important role in this regard.[29,30]

The lead content of the soil in which plants and vegetables and harvests grow is found as a major source of lead exposure.[31]

As mentioned above, drinking water can be one of the causes of lead toxicity. Using outdated fixtures and solders and metallic pipes is one major source of lead exposure in some populations.[32]

Long-term eating of special food (rasam) and cooking in vessels coated with lead are reported as a source of high lead exposure resulting in colicky abdominal pain.[33]

Some painted toys are also reported that may be a significant way for lead absorption and lead intoxication.[34]

House paint also can be a source of lead exposure for young children during playing and silent ingestion of house dust.[35]

Unbranched medicines,[36] some religious powders, for example, sindoor or surma,[37] some Indian spices, and adulteration of turmeric powder with lead chromate[38] are some other important sources of lead intoxication in India.

The tinning process with lead and tin inside of jugs, cooking in ceramic or earthenware pans, and storing foods in crystal or even glass bottles may cause intoxication.[30]

Soldering, welding, and using bronze and brass vessels also should be considered.[39]

Oil paintings and gasoline puffing are among the important things.[40]

Symptoms linked to lead intoxication are nonspecific, and diagnosing these conditions based on the symptoms alone is challenging.

In many patients, detecting the source of lead poisoning is not possible, and these cases would remain undiagnosed for a long time.[41] For instance, in one study among children living in Gaza Strip, the battery industry and computer-related jobs were the cause of their lead poisoning.[41]

In our study, the most common sources of lead exposure were using spices and turmeric, playing with soil, colored candy and snacks, painting, and pottery, followed by finger painting, playing with colored toys, consuming Indian rice, living near the industrial centers or factories, chewing pencil behavior, living in old houses, cooking and serving foods in ceramic bowls, and living near the gas station. Public education should be provided for families to reduce the exposure of their children to these sources of lead.

The limitation of this study was the insufficient sample size due to the low cooperation of participants, especially healthy children for blood sampling.

The strength of the study is considering details of the gastrointestinal problem and the precise history taking and information about sources of lead exposure.

CONCLUSION

In the current study, we found that the lead level was higher in patients with FGID than in the controls; however, this difference was not significantly different. This might be because of elevated lead levels in both groups. Public and individual interventions are necessary to reduce the exposure of children to lead. Future ecological studies with large sample size are necessary to determine the impact of blood lead level on functional abdominal pain in children.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.