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OAR Box 1126 

Prepped by Ollie Stewart 

Document Number: 

47)11-1-169 

Docket Number: 

A-83-22 

Printed 4/18/2008 9:58:23 AM Sheet 47 of 182 
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TTW^agpTl

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t V BBl l W E 

MAR I 3 1992 

EPA AIR DOCKET 

JPi:-M 

Determinants of Elevated Blood Lead during Pregnancy in a 

Population Surrounding a Lead Smelter in Kosovo, Yugoslavia 

Running Head: Determinants of Elevated Blood Lead during 

Pregnancy 

Joseph H. Graziano3, Dusan Popovacb, Pam Factor-Litvaka, Patrick 

Shroutac, Jennie Klineac, Mary J. Murphya, Yu-hua zhaoa, Ali 

Mehmetid, Gemail Ahmedib, Biljana Rajovicd, Zorica Zvicerb, 

Dragoslav U. Nenezicb, Nancy J. LoIaconoa, Zena Steinac 

Address reprint requests to Dr. Joseph H. Graziano, Department of 

Pharmacology, Columbia University, College of Physicians & 

Surgeons, New York, New York 10032. (Tel: 212-305-4001) 

aColumbia University, College of Physicians & Surgeons, New York, 

NY 10032 

bUniversity of Pristina Medical School, Pristina, Yugoslavia 

cNew York State Psychiatric Institute, New York, NY 10032 

dMedicinski Centar, Titova Mitrovica, Yugoslavia 
P.3 

Acknowledgements 

With financial support from the National Institute of 

Environmental Health Sciences (ROl ES-03460) , the U. S. 

Environmental Protection Agency (7D1763NASA), the Andrew Mellon 

Foundation, and the Lucille P. Markey Charitable Trust. 
P.4 

Abstz-act 

We aire prospectively examining the relation between environmental 

lead exposure and pregnancy outcome in cohorts of women exposed 

to a wide range of air lead concentrations. Titova Mitrovica, 

Yugoslavia, is the site of a large lead smelter, refinery and 

battery factory. At mid-pregnancy, 602 women in T. Mitrovica and 

900 women in Pristina, a non-Pb-exposed control town, were 

interviewed. Blood was obtained for blood lead (BPb) , 

hemoglobin, erythrocyte protoporphyrin (EP) and serum ferritin 

measurements. Women were seen again at delivery, at which time 

maternal and umbilical cord blood samples were obtained. 

While many demographic and social characteristics were similar 

across the two towns, women in Pristina were more likely to 

report employment outside the home, cigarette smoking and alcohol 

use during pregnancy. As expected, BPb's were substantially 

higher in the smelter town. At mid-pregnancy, BPb geometric 

means were 17.1 ug/dl in T. Mitrovica and 5.1 ug/dl in Pristina; 

86% of the pregnant women in T. Mitrovica, compared to 3.4% of 

those in Pristina, had BPb's > 10 ug/dl. 

Within T. Mitrovica, distance between the home and the smelter 

was the most important predictor of BPb at mid-pregnancy and 

delivery. Husband's employment ih the lead industry was 

associated with a significant increase in maternal BPb's 

independent of place of residence. Higher maternal serum 
P.5 

ferritin concentrations were associated with lower BPb's, 

suggesting that dietary iron inhibits lead absorption. Overall, 

the placenta was a poor barrier to lead; the relationship between 

maternal BPb and umbilical cord BPb was linear across a wide 

range of BPb's. 
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Introduction 

The effects of environmental lead have only occasionally been 

examined in relation to human reproduction, most often in 

populations with extremely high exposure. Evidence of possible 

effects of lead on pregnancy first appeared in the literature 

near the turn of the century (1) . Women employed in the lead 

industry were reported to have more miscarriages, stillbirths, 

premature infants and neonatal deaths as compared to women in 

other occupations. Several more recent reviews have reported an 

excess of spontaneous abortions among lead-exposed women working 

in the printing industry in Italy and Germany (2-4). Nordstrom 

et al (5) , in Sweden, found a significantly increased frequency 

of spontaneous abortions and low birthweight infants (apparently 

intrauterine growth retardation [IUGR]) among female employees 

working in a lead smelter. Similar observations were made on 

populations living in close proximity to that smelter (6, 7) . 

Needleman and co-workers have described an increased rate of 

minor malformations among newborns with cord BPb's of 8 ug/dl or 

more (8) , the first evidence of such an effect in association 

with extremely low exposure. More recently, however, a 

prospective study of women living in Port Pirie, a smelter town 

in Australia, reported no association between blood lead 

concentration (BPb) and spontaneous abortion, low birthweight 

(for term births), IUGR, premature rupture of membranes, and 

congenital anomalies (9) . 
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With the exception of the latter two reports, these studies have 

not adequately controlled for important factors known to be 

associated with reproductive outcomes, such as maternal weight, 

height, parity, smoking and socioeconomic status (SES). With 

this in mind, we embarked upon a prospective study of lead 

exposure during pregnancy which will ultimately follow growth and 

development during early childhood. 

We have examined the relation between environmental lead exposure 

and pregnancy outcome in cohorts of women exposed to relatively 

high and low air lead concentrations. The Autonomous Province of 

Kosovo, Yugoslavia, is a mountainous farm region currently in the 

process of industrialization due to its vast mineral and coal 

reserves. A large lead smelter, refinery and battery factory are 

major elements of the economy of the city of Titova Mitrovica, 

which is approximately 40 km north of Pristina, the capitol city 

of Kosovo (Figure 1) . Surveys conducted in 1978 and 1980 found 

the population of T. Mitrovica to have markedly elevated BPb's 

due to industrial air lead emissions (10) . In contrast, lead 

exposure in Pristina is minimal; mean BPb's in children (10) are 

lower than those reported for U.S. children (11). 

This paper has two objectives. First, we introduce the study 

design and methods used in the study of pregnancy outcomes. 

Second, we explore predictors of elevated BPb during pregnancy. 

Two subsequent papers will describe the actual pregnancy outcome 
P.8 

\ 

findings, the preliminary results of which were presented at this 

conference. 

Methods 

The study recruited subjects from areas in and around the 

Yugoslavian cities of T. Mitrovica and Pristina. Near the center 

of each town, there is a single out-patient clinic which provides 

routine prenatal care. Attendance in the clinics is largely 

determined by distance from the home. During the period from 

May, 1985, through December, 1986, women who were approximately 

12-20 weeks gestation were invited to participate in the study. 

Since trained staff were occasionally unavailable, not all women 

who came to the clinic were asked to participate. Because of the 

promise of a photograph of the baby at birth, the vast majority 

of those asked agreed to participate. The final sample size 

consisted of 900 women in Pristina and 602 in T. Mitrovica; the 

unequal sample sizes reflect the differences in the sizes of the 

clinics, Pristina being the larger of the two. 

Two predominant languages are spoken in the region: SerboCroatian and Albanian. Therefore, at intake women were 

interviewed by a bilingual nurse on sociodemographic 

characteristics, medical, reproductive, and occupational 

histories of the both parents, and cigarette smoking and alcohol 

consumption during pregnancy. Height, weight and blood pressure 

were measured, and a urine specimen obtained and examined for 
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blood, bilirubin, ketones, sugar, protein and pH. 

Within approximately 12 hours of delivery, each woman was again 

interviewed. Maternal blood and umbilical cord blood were 

obtained for four measurements described below. The placenta was 

trimmed of membranes, weighed, and a piece frozen for subsequent 

biochemical analyses. A trained neonatologist examined every 

baby, utilizing a structured examination for gestational age (12) 

and malformations. For those women who did not deliver in 

hospital, a visiting nurse was sent to the home to determine the 

outcome of the pregnancy. 

Blood samples were obtained at intake and at delivery for the 

measurement of BPb (13), EP (14), serum ferritin (15), and 

hemoglobin concentrations. Blood specimens were refrigerated on 

site and transported on wet ice to Columbia University (CU) where 

all blood analyses were conducted. The CU lab participates in 

th€! CDC's BPb and EP quality control programs, and is certified 

by OSHA. Over the course of the study, agreements with CDC 

values for BPb and EP, measured by intraclass correlation 

coefficients, were 0.95 and 0.99, respectively. 

Address location in relation to the smelter served as an 

indicator for exposure to airborne lead. Zones were defined by 

concentric circles of 2, 4, 6 and 8 km in radius drawn around the 

lead smelter-refinery complex in Zvecan, an immediate suburb of 

8 
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\ 

T. Mitrovica; these were designated as zones 1 through 4, 

respectively (Figure 1) . The city of T. Mitrovica fell within 

Zone l. Zone 5 consisted of all territory from 8 km of T. 

Mitrovica to Pristina, while zone 6 was Pristina itself and all 

areas to the south. Of the 1502 subjects in the study, we were 

unable to assign a zone to 24 women. 

Statistical Analysis: The relationship between BPb (at both midpregnancy and delivery) and social, demographic and biologic 

variables was examined using least squares multiple regression 

analysis. Independent variables of interest were address zone of 

residence, husband's place of employment, and maternal iron 

stores (i.e., serum ferritin concentrations); reference 

categories for these variables were the Pristina zone (zone 6), 

employment outside the lead industry, and serum ferritin > 10 

ng/ml, respectively. Potentially confounding variables were 

identified a priori and assessed by evaluating changes in the 

regression coefficients of the independent exposure variables. 

These included cigarette smoking, maternal age, ethnic group, and 

maternal education. 

Results 

Table 1 compares demographic and social characteristics of women 

in the two towns. At entry to the study, the gestational age of 

women in Pristina was 131.4 days, as compared to 118.3 days in T. 

Mitrovica. Women in T. Mitrovica were, on average, six months 

9 
P.11 

younger and more likely to be of neither Serbian nor Albanian 

ethnicity. Their spouses were of similar age and ethnicity to 

spouses of women in Pristina. Mitrovica women were slightly 

shorter, a result consistent with the fewer number of Albanians 

among them. Alcohol use (defined as consumption of any alcohol 

during pregnancy) was less common in T. Mitrovica (5.1%) than in 

Pristina (9.3%). In each town, on average, the women had had 

more than two previous pregnancies. More women in Pristina 

reported having a job outside the home, although of those with 

jobs, comparable proportions, about 75%, were still working at 

the time of the interview. Mean monthly household income was 

therefore slightly lower in T. Mitrovica. The women were 

similar, however, with respect to other measures of socioeconomic 

status, not all of which are shown. 

The mean monthly BPb's at intake in T. Mitrovica fluctuated 

substantially from month-to-month, presumably a consequence of 

the highly variable industrial lead emissions, and were higher 

than in Pristina, where they varied little (Figure 2) . The 

frequency distribution of BPb's revealed that 86.0 % of the 

pregnant women in T.Mitrovica, but only 3.4% in Pristina, had 

BPb's > 10 ug/dl (Figure 3) . The geometric means for BPb were 

17.1 ug/dl in T. Mitrovica and 5.1 ug/dl in Pristina (Table 2). 

Elevated EP concentrations are considered to be indicative of 

lead toxicity and/or iron deficiency. The mean serum ferritin 

10 
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concentration, a measure of the adequacy of tissue iron stores, 

was slightly higher in T. Mitrovica than in Pristina. Despite 

the higher iron stores, the mean EP was elevated in T. Mitrovica 

(Table 2), clearly reflecting some degree of metabolic inhibition 

of red cell heme synthesis due to lead. 

Within T. Mitrovica, zone of residence was the most important 

predictor of elevated maternal BPb, both at mid-pregnancy (Table 

3) and delivery (Table 4) ; BPb's declined as the distance from 

the smelter to the home increased. Husband's employment in the 

lead smelter, refinery or battery factory, was associated with an 

increase in adjusted mean maternal BPb, both at mid-pregnancy 

(Table 3) and at term (Table 4) , independent of address zone. 

This finding is illustrated graphically in Figure 4. Cigarette 

smoking was not a particularly important predictor of BPb, either 

in the entire study population or in T. Mitrovica alone. 

Maternal education was associated with the BPb at delivery (Table 

4 ), but not BPb at mid-pregnancy (Table 3). Ethnic group was an 

important predictor of both the mid-pregnancy and delivery BPb's; 

Albanian women had the lowest BPb's. We suspect that the 

Albanian custom of removing shoes at the entrance to the home 

reduces the tracking of soil and dust lead into the home. The 

non-Albanian and non-Serbian women, a group consisting primarily 

of Gypsies, exhibited higher BPb's than the Albanians or Serbians 

after holding constant other variables. 

11 
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The role of nutritional factors on gastrointestinal Pb absorption 

has been addressed in earlier presentations at this symposium by 

Drs. Mahaffey (16) and Ziegler (17). We have had the opportunity 

to examine two nutritional factors in these analyses: iron, as 

assessed by serum ferritin concentrations, and milk consumption 

during pregnancy. At mid-pregnancy, women who had serum ferritin 

concentrations of < 5 ng/ml had significantly higher BPb's than 

those with ferritins of 10 ng/ml or more (Table 3). [WHO 

considers 10 ng/ml to be the lower limit of normal in nonpregnant women (18)]. By delivery, however, a strong doseresponse effect was observed (Table 4) ; the higher the serum 

ferritin, the lower the BPb. 

When we examined the influence of milk consumption during 

pregnancy on maternal BPb, the data initially suggested that BPb 

was positively associated with milk consumption (data not shown). 

This association persisted in multiple regression analyses. We 

hypothesized that the effect of milk would be strongest in those 

address zones most heavily exposed to lead. However, contrary to 

expectations, the relationship between BPb and milk consumption 

was not consistent in all address zones. Further analysis showed 

that this apparent relationship was due to extremely elevated 

BPb's in several women who were milk drinkers; their elevated 

BPb's proved to be due to other factors. 

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Finally, we have examined the relationship between maternal BPb 

at delivery and the umbilical cord BPb in 888 mother-infant pairs 

who were between 28 and 44 weeks of gestation. The strong 

relationship between maternal BPb and umbilical cord BPb (Figure 

5) (slope = 0.928, r = 0.920) was linear across a wide range of 

BPb's. 

Discussion 

Because lead readily distributes from blood into bone, BPb is 

considered to be a marker of recent exposure to lead, rather than 

total body lead burden. It is therefore not surprising that the 

BPb's of pregnant women in T. Mitrovica were highest among those 

residing nearest the smelter, where air lead concentrations are 

the highest. A 1980 survey of BPb in residents of zone 1 

reported a mean (arithmetic) BPb of 32.4 ug/dl in non-pregnant 

women, reflecting the extremely high mean monthly air lead 

concentrations which ranged from 21.3 to 29.2 ug/m3 (10); the 

allowable concentration of air lead is 0.7 ug/m3 in Yugoslavia. 

Immediately prior to the current study, as a result of the 

construction of a new smokestack and air filtration system at the 

smelter, air lead concentrations fell into the range of 0.9 to 

12.8 ug/m3 (data not shown). While, this represents some 

improvement in air quality, and BPb's have declined somewhat, 

residents of T. Mitrovica are obviously exposed to unacceptably 

high air lead levels. 

13 
P.15 

The transfer of lead dust on the clothing, skin and hair of leadworkers from workplace to the home has been documented as a major 

source of hazard to children of lead workers (19-21). We have 

observed a risk of undue lead absorption in pregnant wives of 

lead-workers. Thus, since lead freely crosses the placenta, 

paternal employment in the lead-industry poses a risk of lead 

exposure to the unborn child. We therefore urge the lead 

industry to institute highly effective occupational hygiene 

measures capable of preventing the transport of lead from the 

workplace into the home. Among our subjects in T. Mitrovica, 

wives of battery workers had higher BPb's than those of smelter 

or refinery workers. 

In his presentation at this symposium, Dr. Ziegler has correctly 

pointed out that nutritional supplementation is not a "solution" 

to the problem of undue lead absorption (17). Our finding 

concerning the apparent protective effect of adequate iron stores 

against lead absorption, however, should not be overlooked. 

Clearly, certain subsets of the population, such as pregnant 

women and children of low SES, require iron supplementation 

simply to prevent the syndrome of iron deficiency. Those same 

subsets, however, are most at risk for the consequences of undue 

lead absorption. Since iron deficiency increases the risk for 

elevated lead absorption, the health care system could reduce the 

prevalence of elevated BPb by redoubling its efforts to prevent 

iron deficiency in populations at risk. Baghurst and co-workers, 

14 
P.16 

in a study of pregnant women living near the Port Pirie lead 

smelter, have previously reported that women who received iron 

supplementation during pregnancy had lower BPb's than those not 

supplemented (22). 

Observations made more than a century ago suggested that milk 

consumption prevented the occurrence of plumbism in workers in 

the white-lead industry (23). Since that time, animal studies 

have revealed that some components of milk, such as lactose (24-

27) and fat (24, 28), increase gastrointestinal lead absorption, 

while others, such as calcium (29), decrease absorption; the Port 

Pirie study has reported lower mean BPb among women who consumed 

less than 500 mg dietary calcium/day in comparison to those who 

consumed larger amounts (22). To our knowledge, the present 

study represents the first attempt to examine the influence of 

milk consumption on BPb in humans. The failure of this study to 

document an association between milk consumption and BPb suggests 

that the effects of the biochemical constituents of milk on lead 

absorption may counteract each other. 

15 
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References 

1. Oliver, T. Lead poisoning and the race. Brit. Med. J. 1: 

1096-1098 (1911). 

2. Bell, J.U., and Thomas, J.A. Effects of lead on mammalian 

reproduction. JEn: Lead Toxicity. (R.L. Singhal and J.A. Thomas, 

Eds.), Urban & Schwartzenberg, Baltimore, 1980, pp. 169-185. 

3. Rom, W.N. Lead in pregnancy. Mt. Sinai J. Med. 43: 542-

570 (1976). 

4. Hamilton, A., and Hardy, M.L. Lead, Xn, Industrial 

Toxicology. Publishing Sciences Group, Littleton Mass., 1974, pp. 

85-121. 

5. Nordstrom, S., Beckman, L., and Nordenson, I. Occupational 

and environmental risks in and around a smelter in northern 

Sweden. V. Spontaneous abortion among female employees and 

decreased birth weight in their offspring. Hereditas 90: 291-

296 (1979). 

6. Nordstrom, S., Beckman, L., and Nordenson, I. Occupational 

and environmental risks in and around a smelter in northern 

Sweden. I. Variations in birth weight. Hereditas 88: 43-46 

(1978). 

16 
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7. Nordstrom, S., Beckman, L., and Nordenson, I. Occupational 

and environmental risks in and around a smelter in northern 

Sweden. III. Frequencies of spontaneous abortion. Hereditas 

88: 51-54 (1978). 

8. Needleman, H.L., Rabinowitz, M., Leviton, A., Linn, S., and 

Schoenbaum, S. The relationship between prenatal exposure to 

lead and congenital anomalies. J. Amer. Med. Assoc. 251: 2956-

2959 (1984). 

9. McMichael, A.J., Vimpani, G.V., Robertson, E.F., Baghurst, 

P.A., and Clark, P.D. The Port Pirie cohort study: maternal 

blood lead and pregnancy outcome. J. Epidemiol. Comm. Health 40: 

18-25 (1986). 

10. Popovac, D., Graziano, J., Seaman, C , Kaul, B., Colakovic, 

B., Popovac, R., Osmani, I., Haxhiu, M., Begraca, M., Bozovic, 

Z., and Mikic, M. Elevated blood lead in a population near a 

lead smelter in Kosovo, Yugoslavia. Arch. Environ. Health 37: 

19-23 (1982). 

11. Mahaffey, K.R., Annest, J.L., Roberts, J., and Murphy, R.S. 

National estimates of blood lead levels: United States 1976-

1980. Association with selected demographic and socioeconomic 

factors. N. Eng. J. Med. 307: 573-579 (1982). 

17 
P.19 

12. Ballard, J.L., Novak, K.K., and Driver, M. A simplified 

score for assessment of fetal maturation of newly born infants. 

J. P€id. 95: 769-774 (1979). 

13. Fernandez, F., and Hilligoss, D. An improved graphite 

furnace method for the determination of lead in blood using 

matrix modification and the L'vov platform. Atomic Spectr. 3: 

130-131 (1982). 

14. Piomelli, S. A micromethod for free erythrocyte porphyrins: 

The FEP test. J. Lab. Clin. Med. 81: 932-940 (1973). 

15. Miles, L.E.M., Sipschitz, D.A., Bieter, C.P., Cook, J.D. 

Measurement of serum ferritin by a 2-site immunoradiometric 

assay. Anal. Chem. 61: 209-224 (1974). 

16. Mahaffey, K. Reference the presentation at this sypmosium. 

17. Ziegler, E. Reference the presentation at this symposium. 

18. World Health Organization (WHO). Control of nutritional 

anaemia with special references to iron deficiency. WHO 

technical report series 580 (1975). 

18 
19. Baker, E.L. Jr., Folland, D.S., Taylor, T.A., Frank, M., 

Peterson, W., Lovejoy, G., Cox, D., Houseworth, J., and 

Landrigan, P.H. Lead poisoning in children of lead workers: 

home contamination with industrial dust. N. Eng. J. Med. 296: 

260-261 (1977). 

20. Morton, E., Saah, A.J., Silberg, S.L., Owens, W.L., Roberts, 

M.A., and Saah, M.D. Lead absorption in children of employees in 

a lead-related industry. Amer. J. Epidemiol. 115: 549-555 

(1982). 

21. Moore, M.R. Sources of lead exposure, In, Lead Toxicity: 

History and Environmental Impact (R. Lansdown, and W. Yule, 

eds.), The Johns Hopkins University Press, Baltimore, 1986, pp. 

168-177. 

22. Baghurst, P.A., McMichael, A.J., Vimpani, G.V., Robertson, 

E.F., Clark, P.D., and Wigg, N.R. Determinants of blood lead 

concentrations of pregnant women living in Port Pirie and 

surrounding areas. Med. J. Australia 146: 69-73 (1987). 

23. Tanquerel des Planches, L. Lead Diseases: A Treatise. 

With Notes and Additions on the Use of Lead Pipe and Substitutes. 

Translated by S.L. Dana, Daniel Bixby and Co., Lowell Mass., 

1848, pp. 333-334. 

19 
P.21 

24. Stephens, R., and Waldron, H.A. The influence of milk and 

related dietary constituents on lead metabolism. Food Cosmet. 

Toxicol. 13: 555-563 (1975). 

25. Bell, R.R., and Spickett, J.T. The influence of milk in the 

diet on the toxicity of orally ingested lead in rats. Food 

Cosmet. Toxicol. 19: 429-436 (1981). 

26. Bushnell, P.J., DeLuca, H.F. Lactose facilitates intestinal 

absorption of lead in weanling rats. Science 211: 61-63 (1981). 

27. Bushnell, P.J., DeLuca, H.F. The effects of lactose on the 

absorption and retention of dietary lead. J. Nutr. 113: 365-

378 (1983). 

28. Barltrop, D., and Khoo, H.E. The influence of nutritional 

factors on lead absorption. Postgrad. Med. J. 51: 795-800 

(1975) . 

29. Mahaffey-Six, K., Goyer, R. A. Experimental enhancement of 

lead toxicity by low dietary calcium. J. Lab. Clin. Med. 76: 

933-941 (1970). 

20 
Table 1: Characteristics of the Populations* 

Number of Women in Study 

Gestation at Interview 

(days) 

Maternal Age (yrs) 

Paternal Age (yrs) 

Maternal Ethnicity: 

% Albanian 

% Serbian 

% Other 

Paternal Ethnicity: 

% Albanian 

% Serbian 

% Other 

Maternal Weight (kg) 

Maternal Height (cm) 

% Cigarette Smokers 

% Alcohol Users 

T. Mitrovica 

118.3 

26.4 

30.5 

56.2 

25.3 

18.5 

59.4 

25.0 

15.5 

63.5 

159.3 

24.8 

5.1 

602 

(26.0) 

(5.3) 

(6.1) 

(10.9) 

(7.4) 

Pristina 

131.4 

26.9 

30.5 

61.2 

24.8 

14.0 

61.8 

22.9 

15.3 

63.9 

161.6 

28.3 

9.3 

900 

(29.6 

(5.0) 

(5.7) 

(10.2) 

(5.9) 

Number of Previous 

Pregnancies 

% With a Job 

% Working during 

Pregnancyb 

Maternal Education (yrs) 

Paternal Education (yrs) 

Monthly Income in Home 

(U.S. dollars)0 

2.1 (2.2) 

32.5 

76.4 

8.9 (4.2) 

11.7 (2.8) 

2.3 (2.4) 

45.6 

75.8 

9.0 (4.1) 

11.4 (3.1) 

237.7 (161.8) 259.9 (176.1) 

Type of Home: 

% House 

% Apartment 

% Farm 

% Owning Their Homes 

50.6 

27.0 

22.5 

29.6 

64.8 

20.7 

14.5 

26.3 

a Data are means + standard deviation (sd) 

b Of those with a job 

c In order to adjust for inflation, the mean monthly dinar income 

was converted to U.S. dollars using the rate effective during the 

month of the interview. 

21 
P.23 

Table 2: Hematologic Findings at Mid-Pregnancy3 

Mitrovica Pristina 

BPb (ug/dl) 17.1 (6.9, 42.6) 5.1 (2.5, 10.6) 

EP (ug/dl) 36.0 (9.9, 130.3) 25.4 (10.4, 61.7) 

Serum 

ferritin (ng/ml) 14.1 (2.0, 98.0) . 11.5 (1.5, 88.3) 

Hemoglobin (g/dl) 12.4 (10.3, 14.5) 12.3 (10.0, 14.7) 

a Data for BPb, EP and serum ferritin are geometric means (95% 

confidence intervals). Geometric means were calculated as 1/n 

[logio (xi) + logi0 (x2) +...+logip (xn)]. The means for 

hemoglobin concentrations are arithmetic. 

22 
Table 3: Regression Model for the Prediction 

of Mid-Pregnancy Blood Lead Concentration3 

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Variable Estimate S.E. 95% C.lJ p value 

Address Zone: 

<2 km vs Pristina 0.5555 

2-4 km vs Pristina 0.4506 

4-6 km vs Pristina 0.3913 

6-8 km vs Pristina 0.4085 

>=8 km vs Pristina 0.1072 

Husband Employed 

in the Lead Industry: 

Yes vs No 0.0491 

Ethnic Group: 

Serbian vs Albanian 0.0335 

Other vs Albanian 0.0433 

Serum Ferritin: 

<5.0 vs >=10.0 0.0255 

5.0-9.9 vs >=10.0 0.0078 

.0115 .5780,.5330 <.0001 

.0311 .5116,.3896 <.0001 

.0240 .4383,.3443 <.0001 

.0319 .4710,.3460 <.0001 

.0166 .1397,.0747 <.0001 

.0160 .0805,.0177 .0022 

.0111 .0553,.0117 .0025 

.0132 .0692,-0174 .0010 

.0123 .0496,.0014 .0393 

.0115 .0303,-.0147 .4961 

Intercept 0.6707 

Model N = 1452 

Model R2 = 69.1% 

log (base 10) of blood lead (ug/dl) adjusted to hemoglobin of 

12.0 (g/dl) 

confidence interval 

23 
Table 4: Regression Model for the Prediction of Maternal 

Blood Lead Concentration at 

Variable 

Address Zone: 

<2 km vs Pristina 

2-4 km vs Pristina 

4-6 km vs Pristina 

6-8 km vs Pristina 

>=8 km vs Pristina 

Husband Employed 

in the Lead Industry: 

Yes vs No 

Ethnic Group: 

Serbian vs Albanian 

Other vs Albanian 

Cigarette Smoking: 

Yes vs No 

Maternal Age: 

Maternal Education: 

Serum Ferritin 

at Delivery: 

<5.0 vs >= 10.0 

5.0-9.9 vs >= 10.0 

Intercept: 

Model N = 989 

Model R2 = 75.5% 

Estimate 

0.5778 

0.5357 

0.4658 

0.4985 

0.1602 

0.0416 

0.0361 

0.0611 

-0.0193 

0.0028 

0.0030 

0.0527 

0.0331 

0.7035 

3 log (base 10) of blood lead 

12.0 (g/dl) 

" confidence interval 

S.E. 

.0125 

.0382 

.0271 

.0392 

.0199 

.0171 

.0125 

.0161 

.0118 

.0011 

.0014 

.0128 

.0121 

Delivery3 

95% C.I.fe 

.6023,.5533 

.6106,.4608 

.5189,.4127 

.5753,.4217 

.1992,.1212 

.0751,.0081 

.0606,.0116 

.0927,.0295 

.0038,-.0424 

.0050,.0006 

.0057,.0003 

.0778,.0276 

.0568,.0094 

p value 

<.0001 

<.0001 

<.0001 

<.0001 

<.0001 

.0150 

.0040 

.0002 

.1016 

.0099 

.0150 

<.0001 

.0064 

(ug/dl) adjusted to hemoglobin of 

24 

\ 

\ 

•r 

1 

i 
Legends to Figures: 

Figure 1: The Autonomous Province of Kosovo, Yugoslavia. Zones 

of residence were defined by the concentric circles of 2, 4, 6 

and 8 km in radius drawn around the lead smelter/refinery 

complex; these were designated as zones 1 through 4, 

respectively. The city of T. Mitrovica fell within Zone 1. Zone 

5 consisted of all territory from 8 km of T. Mitrovica to 

Pristina, while zone 6, the reference zone, was Pristina itself. 

Figure 2: Mean mid-pregnancy BPb (ug/dl) of women recruited into 

the study during the months of May, 1985 through January, 1987. 

Each point represents a different group of women, i.e., those 

recruited during that month. 

Figure 3: Frequency distribution of mid-pregnancy BPb's (ug/dl) 

for subjects in Pristina (N = 900) and T. Mitrovica (N = 602). 

Figure 4: Mean BPb's (ug/dl) of women residing in zones 1 

through 6; see legend to Figure 1 for zone definitions. within 

each zone, wives of lead workers had higher mean BPb's than wives 

of non-lead workers. 

Figure 5: A strong linear relationship was observed between 

maternal BPb at delivery and umbilical cord BPb (N = 888, slope = 

0.928, r = 0.920). 

25 
P.27 

Figure 1 

26 
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0) 

XJ 

o 

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GO 

30 

27 

24 ^ 

21 

18 

15 H 

12 

9 

6 

3 

0 

• • -T. Mitrovica Blood Lead 

# # -Pristina Blood Lead \ / \ / 

• • 

/ A .•-• 

-•"*'•-.... • 

/ 

r-

~i 1 r r -i 1 r T 1 1 r T 1 1 r 

MayJ JASO N DJan F MAMJJulASO N D Jan 

Month of Recruitment 

(5/85-1/87) 

Figur e 2 
Percent of Total 

P.29 

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<//////////////A 

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28 
BLOOD LEAD CONCENTRATION (jug/dl) 

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10 20 30 40 50 

Maternal Delivery Blood Lead (/xg/dl) 

o 

Figur e 5