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Chinese herbal medicine, sibship and blood lead in children

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doi:10.1136/oem.55.8.573

1998;55;573-576

Occup. Environ. Med.

TJ Cheng, RH Wong, YP Lin, YH Hwang, JJ Horng and JD Wang

children

Chinese herbal medicine, sibship, and blood lead in

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SHORT REPORT

Chinese herbal medicine, sibship, and blood lead

in children

Tsun-Jen Cheng, Ruey-Hong Wong, Yi-Ping Lin, Yaw-Huei Hwang, Ji-Jen Horng, Jung-Der Wang

Abstract

Objectives—Risk factors for increased blood lead concentration (BPb) has been investigated. However, the eVect of sibship and Chinese herbal medicine on BPb has not been systematically studied. In this study BPb data from voluntary testing was used to determine if Chinese herbal medi-cine and sibship were associated with BPb.

Methods—319 children aged 1–7 were tested for BPb. Meanwhile, parents were interviewed to obtain information includ-ing consumption of Chinese herbal medi-cine, living environment, lifestyle, and sibship of the children tested.

Results—The mean (SD) BPb of 319 preschool children was 4.4 (2.4) µg/dl. The consumption of Ba-baw-san (a Chinese herbal medicine) was significantly associ-ated with increased BPb in children (p=0.038). Further multivariate regres-sion analysis of BPb in 50 pairs of siblings showed the factors of being brothers explained 75% of variation for BPb, and being sisters and brother-sister explained 51% and 41% of variation respectively. Conclusion—Chinese herbal medicine and children’s play patterns within the family expressed in diVerent types of sibship are the main determinants of low concentrations of BPb in preschool chil-dren of Taiwan.

(Occup Environ Med 1998;55:573–576)

Keywords: Chinese herbal medicine; sibship; blood lead

Previous studies have indicated that there is a dose-response relation between children’s cog-nitive development and blood lead concentra-tions (BPb).1–5

In the United States, the Center for Disease Control and Prevention has lowered the acceptable BPb for children from 25 µg/dl to 10 µg/dl and revised the guidelines for screening and management of increased BPb. The guidelines call for universal screening of children <6 years of age for increased BPb unless the community does not have a childhood lead poisoning problem.6

Similar

guidelines were adopted by the American Academy of Pediatrics in 1993.7

Children are exposed to lead from diVerent sources and through diVerent pathways. In Taiwan, children’s lead exposure has been reported to be associated with environmental pollution from factories that use lead in the neighbourhood8–10

and from leaded

petrolium.11

Also, Chinese herbal medicine was responsible for children’s lead poisoning in some case reports.12–13

As there is no routine lead screening for children in Taiwan, the distribution of BPb is not clear.

Having a sibling who had an increased BPb concentration was rated as one of the primary risk factors by United States paediatricians in screening their patients.14

Researchers indi-cated that having a sibling, housemate, or play-mate who was followed up or treated for lead poisoning was significantly associated with an increased adjusted odds ratio for increased BPb in both urban15

and rural16

settings. In a pedigree study of subjects aged 6–91, there was a 50% correlation of BPb concentrations for siblings living together, and only 10% in those living apart.17

However, the association of chil-dren’s BPb and sibship eVects has not been thoroughly studied.

In this study, we reported the results of a voluntary BPb test for children in the metro-politan Taipei area sponsored by the Depart-ment of Health of Taiwan. The source and pathway of lead exposure in children and the correlation of BPb between siblings of different combinations (brothers, sisters, and brother-sister) were also investigated.

Materials and methods

In mid-August 1995, the Consumer Protection Foundation in Taiwan reported that some sweet wrappers might contain high concentra-tions of lead. Parents who lived in the metropolitan Taipei area (including Taipei City, Taipei County, and Tau-Yuan County) were advised to bring their children to the Center for the Research of Environmental and Occupational Diseases for free BPb tests spon-sored by the Department of Health of Taiwan.18

A total of 319 children aged 1–7 were tested and their parents were interviewed to obtain information on children’s age, sex, diet, sweet

Graduate Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei, Taiwan

T-J Cheng R-H Wong Y-P Lin Y-H Hwang J-J Horng J-D Wang Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan T-J Cheng J-D Wang

Center for the Research of Environmental and Occupational Diseases, Taipei, Taiwan T-J Cheng J-D Wang Correspondence to: Dr Jung-Der Wang, Graduate Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, No. 1 Ren-Ai Rd, Sec 1, Taipei, 10018, Taiwan

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consumption, milk consumption, drinking water, and medical history including consump-tion of Chinese herbal medicine. Informaconsump-tion about their living environment was also ob-tained, including whether they lived in a newly painted house and the distance between their house and main streets. Information on family members engaged in lead related industries was also inquired.

Whole blood (2 ml) was drawn intravenously into a heparinised tube. The specimens were stored in a 4°C refrigerator until analysis. Blood lead concentration was measured with a graphite furnace atomic absorption

spectro-photometer in our laboratory within one week.19

Our laboratory has joined the Center for Disease Control and Prevention lead profi-ciency programme and maintained good qual-ity control since 1986.

As this was a voluntary testing programme, many parents brought in not only one child but all their children to the test. Among the 319 children tested, there were 58 sets of siblings (including 54 sets of twos, two sets of threes, and two sets of twins) which provide a unique chance for the researchers to investigate the relation of BPb and sibship. Fifty pairs of siblings were chosen for further analysis after one pair of children with increased BPb values (>10 µg/dl) and seven pairs of siblings with dif-ferent histories of taking Ba-baw-san were excluded. Among the seven pairs with discord-ant histories, there was one pair of brothers, one pair of sisters, and five pairs of cross sex siblings. In sibling sets of threes, the two younger ones were chosen. The association of BPb concentrations and sibship was explored in this study.

Data analyses were performed with SAS package software.20

Unpaired t test, analysis of variance (ANOVA), non-parametric tests, and multiple regression modelling were performed to explore the risk factors of BPb. Under the multiple regression analysis, BPb was modelled as a function of various risk factors, including sibling’s age, sex, milk consumption, various living environments, and lifestyle.

Results

The mean (SD) BPb of 319 children was 4.4 (2.4) µg/dl. Eight children (2.5% of the children tested, four boys and four girls) had BPb >10 µg/dl (11.4–20.8 µg/dl). Among the eight children with increased BPb, six of them had been taking Chinese herbal medicine (three of them taking Ba-baw-san). Two of these eight children were brothers, a boy and a girl had same sex siblings with lower BPbs, and the other four children did not have any sibling participating in the lead test.

Blood lead, age, height, weight, body mass index (BMI), drinking milk, and taking Chi-nese herbal medicine were not significantly dif-ferent between sexes (p>0.05, unpaired t test, table 1. Thirty five per cent of the paternal occupations were business, and about 30% were government employees, whereas 40.3% of the maternal occupations were housekeeping and 24.7% were business.

The univariate analysis showed that BPbs were significantly higher for children who had ever taken Chinese herbal medicine, drank tap water, or had kindred diagnosed as lead poisoned (p<0.05, unpaired t test, table 2). There were no significant associations between BPb and other factors including sex, age, con-sistently drinking milk, peeling paint in their living environment, and living on the first floor (table 2). Because the only Chinese herbal medicine that most children had taken was Ba-baw-san, further analysis was focused on the association between taking Ba-baw-san and BPb. Those who had ever taken Ba-baw-san, had a higher mean BPb than those who had

Table 1 Demographic characteristics of study subjects

Variables Boys (n=180) Girls (n=139)

Blood lead (µg/dl)* 4.51 (2.82) 4.16 (2.96) Age (y)* 4.37 (1.45) 4.42 (1.49) Height (cm)* 104.58 (11.52) 103.94 (11.84) Weight (kg)* 17.12 (4.39) 16.87 (3.94) BMI (kg/m2)* 15.79 (3.62) 15.35 (3.56)

Drinks milk regularly (%) 69.8 77.0 Chinese herbal medicine (%) 41.3 41.0

*Mean (SD).

Table 2 Blood lead concentrations by sex, age, diet, and living environment in children

Variables n Mean (SD) Sex: Boy 180 4.51 (2.93) Girl 139 4.16 (2.96) Age (y): 1 7 3.53 (2.41) 2 37 3.71 (3.50) 3 48 4.12 (2.73) 4 75 4.39 (2.32) 5 81 4.54 (2.78) 6 58 4.72 (3.15) 7 16 3.42 (2.66)

Have taken Chinese herbal medicine:

Yes 130 4.85 (2.91)

No 184 4.02 (2.83)*

Have taken Ba-baw-san:

Yes 66 4.96 (2.71)

No 233 4.13 (2.83)*

Drinks milk regularly:

Yes 282 4.41 (2.93)

No 32 3.83 (2.48)

Drinks tap water:

Yes 303 4.41 (2.90)

No† 12 3.11 (1.99)*

Living environment: House newly painted:‡

Yes 114 4.11 (3.02)

No 196 4.48 (2.74)

Peeling paint:

Yes 138 4.27 (2.50)

No 169 4.48 (3.17)

Lives on the first floor:

Yes 270 4.50 (2.71)

No 45 4.31 (2.94)

Kindred with lead poisoning:

Yes 8 5.95 (1.11)

No 307 4.31 (2.90)**

*0.01<p<0.05; **p<0.01.

†No tap water, only well water , spring water, or others.

‡Including children’s house, babysitter’s house, and nursery school.

Table 3 Demographic characteristics of 50 sibling pairs

Variables Elder sibling Younger sibling

BPb (µg/dl)† 3.93 (2.24) 3.96 (2.20) Male (%) 66.0 52.0 Age (y)† 5.24 (1.16) 2.95 (1.58)* Height (cm)† 112.4 (19.8) 94.7 (11.0)* Weight (kg)† 15.7 (4.5) 14.3 (3.4)* Body mass index(kg/m2)† 15.7 (2.4) 15.7 (2.8)

Drinking milk every day (%) 62.0 74.0 Chinese herbal medicine (%) 36.0 28.0

*p<0.05, Wilcoxon rank sum test. †Mean (SD).

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never taken it (4.96 (2.71) µg/dl v 4.13 (2.83) µg/dl, p<0.05). Among children who had taken Ba-baw-san (20.75% of all children tested) the mean BPb of boys was significantly higher than that of girls ( 5.63 (2.77) µg/dl v 4.21 (2.46) µg/dl, p<0.05). The mean BPb in those who had taken Ba-baw-san reached a peak at the age of 2–3. However, age was not significantly associated with BPb in children who had never taken Ba-baw-san. In further multiple regression analysis, only the factor of taking Ba-baw-san was positively associated with BPb (p=0.038).

Fifty pairs of siblings were chosen for further analysis. Table 3 shows the demographic char-acteristics of the 50 sibling pairs. The 50 pairs of siblings were further divided into three categories: brothers (18 pairs), sisters (10 pairs), and cross sex siblings (22 pairs). DiVer-ence in BPb between brothers was 0.8 µg/dl; it was 1.5 µg/dl between sisters and 1.6 µg/dl between cross sex siblings. DiVerence in BPb between brothers was significantly lower than that between cross sex siblings, and lower than that between sisters although not significantly. Regression analysis showed that the factor of being siblings could explain 75%, 51%, 41% of BPb variation in brothers, sisters, and cross sex siblings, respectively. Age diVerence and mean BPb were not significantly diVerent among these three categories (p>0.05, table 4).

Discussion

Data for BPb distribution in children are limited in Taiwan. In this study, the mean BPb of 319 children was 4.4 (2.4) µg/dl. The BPb might either underestimate the true value because the parents had high socioeconomic status, or overestimate because the children were brought in under the suspicion of increased lead absorption from sweet wrap-pers. Although the direction and magnitude of possible bias in this study could not be determined, the mean BPb was below the guideline of 10 µg/dl. With similar diet and cultural background, the BPb in Taiwanese children is much lower than that in children of China (mean BPb 21.8–67.9 µg/dl in diVerent areas).21

The introduction of unleaded petro-lium since 1984 in Taiwan could be the main reason for the lower BPb in Taiwanese children.

The episode of lead contaminated sweets was later proved to be an overstatement by the media,18

the low dose of lead in sweets could not have caused any adverse health eVect, and sweet consumption was not related to in-creased BPb in children. However, the popular

use of Chinese herbal medicine containing lead in Taiwanese families calls for more public health attention. The use of Chinese herbal medicine and lead poisoning has been reported in children and adults in Taiwan, China, and the United States.12–13 22–24

In this study, Chi-nese herbal medicine was the main source of exposure to lead for children with increased BPb in Taiwan. An amazingly large proportion of children enrolled in this study had been tak-ing Chinese herbal medicine (41.3% of boys and 41.0% of girls), especially Ba-baw-san. Ba-baw-san (Ba-baw-neu-hwang-san) has been used for treating infants and young children since China’s Song dynasty (960– 1279). It is used by many parents to detoxify infant’s “fetus poisoning”, to treat colic pain, or to pacify young children. The ingredients of many secret recipes varied with diVerent amounts of heavy metals including chromium, manganese, mercury, arsenic, and lead. The content of lead in Ba-baw-san ranged from 0.7 to 7.12 µg/g.12

Our study showed that Ba-baw-san was significantly associated with BPb (p=0.038). Moreover, BPb reached a peak at the age of 2–3 with Ba-baw-san, then gradually declined with age. In this study, boys who had ever taken Ba-baw-san had a significantly higher mean BPb than girls. It is possible that boys had taken higher doses of Ba-baw-san than girls because they were worse tempered or received more attention in Chinese families.

In tracing children’s environmental exposure to lead, play patterns and playtime activity may be important. A previous study of exposed children in a kindergarten near a battery recy-cling plant in Taiwan showed that boys had a significantly higher BPb than girls. The authors suggested that boys were more active so inhaled more air lead, and spent more time outdoors so ingested more lead contaminated soil.9

In this study of environmentally unexposed children, BPb was higher in boys than girls but not significantly. However, the BPb diVerences between brothers, sisters, and cross sex siblings probably provided another insight for the association of BPb and children’s play patterns. There is a cross cultural similarity of boys being involved in more strenuous games and athletic competitions.25

Observation by behav-iour scientists of sibship and play patterns also suggests that brothers interact diVerently from sisters and cross sex sibling sets.26

A 50% correlation for BPb in siblings aged 6–91 living together was reported in a previous pedigree study.17

In our study, the overall explainable variation of BPb between siblings was 48% after excluding seven pairs of siblings with dif-ferent histories of taking Ba-baw-san (table 4). Using the explainable proportion of variations of BPbs for cross sex siblings as baseline, com-mon heredity and comcom-mon environment can account for up to 41% of variation in BPb. The 51% of total variation among sisters and 75% among brothers can probably be explained by the presence of same sex sibship eVects.

We suggest that one cultural factor— Ba-baw-san—and one universal factor— sibling’s play pattern—help to predict low con-centrations of BPb in children. In tracing the

Table 4 Relation of blood lead concentrations (BPb) between siblings†

Blood lead concentrations Pairs (n) Age diVerence BPbmean (SD) BPb diVerence between siblings‡ R2 Brother-brother 18 2.3 (1.1) 4.1 (2.1) 0.8 (0.8) 0.75 Sister-sister 10 2.3 (1.1) 4.3 (2.1) 1.5 (1.5) 0.51 Cross sex 22 2.3 (0.7) 3.7 (2.3) 1.6 (1.2)* 0.41 Younger-elder sibling 50 2.3 (1.0) 3.9 (2.2) 1.3 (1.2) 0.48

*p<0.05, Wilcoxon rank sum test, v BPb diVerences among siblings. †Adjusted for administration of Ba-baw-san.

‡There was a significant diVerence among three categories (p<0.05, Kruskal-Wallis test). Values are mean (SD).

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source of exposure to lead in oriental children, the use of Chinese herbal medicine is critical. Furthermore, when one of the children showed increased BPb, all other children within the family should be screened for a similar problem, especially siblings of the same sex; and the play patterns between siblings as well as having a sibling with increased BPb, should be considered as a fisk factor for high BPb.

This study was supported in part by Grant DOH 86-HR504 from the Department of Health, Taiwan, Republic of China.

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2 Michael AJ, Baghurst PA, Wigg NR, et al. Port Pirie cohort study: environmental exposure to lead and children’s abili-ties at the age of four years. N Engl J Med 1988;319:465–8. 3 Baghurst PA, McMicheal AJ, Wigg NR, et al. Environmen-tal exposure to lead and children’s intelligence at age of seven years: the Port Pirie cohort study. N Engl J Med 1992;327:279–84.

4 Bellinger D, Levito, Waternaux C, et al. Longitudinal analy-sis of prenatal and postnatal lead exposure and early cogni-tive development. N Engl J Med 1987;316:1037–43. 5 Rabinowitz MB, Wang JD, Soong WT. Apparent threshold

of lead’s eVect on child intelligence. Bull Environ Contam

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8 Wang JD, Shy WY, Chen JS, et al. Parent occupational lead exposure and lead concentration of newborn cord blood.

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Environ Contam Toxicol 1992;49:23–30.

10 Jang CS, Wang JD, Hwang YH, et al. Lead poisoning in a bat-tery recycling smelter. J Occup Safety Health 1994;2:11–21.

11 Hwang YH, Wang JD. Temporal fluctuation of the lead level in the cord blood of neonates in Taipei. Arch Environ Health 1990;45:42–5.

12 Ban YW, Cheng SL, Yang MS, et al. Survey for heavy metal concentration in Ba-Baw-Neu-Hwang-San. Acta Paediatr

Sin 1993;34:181–90.

13 Hung IJ. Lead poisoning in two families. J Formos Med Assoc 1980;79:740–8.

14 Campbell JR, SchaVer SJ, Szilagyi PG, et al. Blood lead screening practices among US pediatricians. Pediatrics 1996;98:372–7.

15 Dalton MA, Sargent JD, Stukel TA. Utility of a risk assess-ment questionnaire in identifying children with lead expo-sure. Arch Pediatr Adolesc Med 1996;150:197–202. 16 SchaVer SJ, Kincaid MS, Endres N, et al. Lead poisoning

risk determination in a rural setting. Pediatrics 1996;97:84– 90.

17 Hopper JL, Mathews JD. Extensions to multivariate normal models for pedigree analysis II. Modeling the eVect of shared environment in the analysis of variation in blood levels. Am J Epidemiol 1983;117:344–55.

18 Wu TN, Yang GY, Shen CY, et al. Lead contamination of candy: an example of crisis management in public health [[letter]]. Lancet 1995;346:1437–8.

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Raton, FL: CRC Press, 1983;46–8.

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22 Li ZF. Poisoning with some lead containing Chinese traditional drugs—report of 11 cases. Chinese Journal of

Internal Medicine 1982;21:366–7.

23 Lightfoote J, Blair J, Cohen J. Lead intoxication in an adult caused by Chinese herbal medication. JAMA 1977;238: 1539.

24 Markowitz SB, Nunez CM, Klitzman S, et al. Lead poison-ing due to Hai Ge Fen. JAMA 1994;271:932–4. 25 Goodman ME. The culture of childhood. New York, NY:

Teachers College Press, Teachers’s College, Columbia University. 1978;131–40.

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數據

Table 3 Demographic characteristics of 50 sibling pairs

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