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Exposure from the Chernobyl accident had adverse effects onerythrocytes, leukocytes, and, platelets in children in the
Narodichesky region, Ukraine: A 6-year follow-up study
Eugenia Stepanova1, Wilfried Karmaus*2, Marina Naboka3,
Vitaliy Vdovenko1, Tim Mousseau4, Viacheslav M Shestopalov3, John Vena2,
Erik Svendsen2, Dwight Underhill5 and Harris Pastides2
Address: 1Scientific Center for Radiation Medicine, Academy of Medical Sciences of Ukraine, Kyiv, Ukraine, 2Department of Epidemiology andBiostatistics, Norman J. Arnold School of Public Health, University of South Carolina, Columbia, South Carolina, USA, 3Radioecological Center,
Ukrainian National Academy of Sciences, Kyiv, Ukraine, 4College of Arts and Sciences, University of South Carolina, Columbia, South Carolina,
USA and 5Department of Environmental Health Science, Norman J. Arnold School of Public Health, University of South Carolina, Columbia,
South Carolina, USA
Email: Eugenia Stepanova - profstepanova@i.ua; Wilfried Karmaus* - karmaus@sc.edu; Marina Naboka - marinavn1@yahoo.com;
Vitaliy Vdovenko - xrisk06@yahoo.com; Tim Mousseau - mousseau@sc.edu; Viacheslav M Shestopalov - vsh@hydrosafe.kiev.ua;
John Vena - Jvena@gwm.sc.edu; Erik Svendsen - svendsee@gwm.sc.edu; Dwight Underhill - dmunderhill@gmail.com;
Harris Pastides - Pastides@gwm.sc.edu* Corresponding author

Published: 30 May 2008
Environmental Health 2008, 7:21

doi:10.1186/1476-069X-7-21

Received: 23 November 2007
Accepted: 30 May 2008

This article is available from: http://www.ehjournal.net/content/7/1/21© 2008 Stepanova et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract
Background: After the Chernobyl nuclear accident on April 26, 1986, all children in the contaminatedterritory of the Narodichesky region, Zhitomir Oblast, Ukraine, were obliged to participate in a yearly
medical examination. We present the results from these examinations for the years 1993 to 1998. Since
the hematopoietic system is an important target, we investigated the association between residential soil
density of 137Caesium (137Cs) and hemoglobin concentration, and erythrocyte, platelet, and leukocyte
counts in 1,251 children, using 4,989 repeated measurements taken from 1993 to 1998.
Methods: Soil contamination measurements from 38 settlements were used as exposures. Blood counts
were conducted using the same auto-analyzer in all investigations for all years. We used linear mixed
models to compensate for the repeated measurements of each child over the six year period. We
estimated the adjusted means for all markers, controlling for potential confounders.
Results: Data show a statistically significant reduction in red and white blood cell counts, platelet counts
and hemoglobin with increasing residential 137Cs soil contamination. Over the six-year observation period,
hematologic markers did improve. In children with the higher exposure who were born before theaccident, this improvement was more pronounced for platelet counts, and less for red blood cells andhemoglobin. There was no exposure×time interaction for white blood cell counts and not in 702 children
who were born after the accident. The initial exposure gradient persisted in this sub-sample of children.
Conclusion: The study is the first longitudinal analysis from a large cohort of children after the Chernobyl
accident. The findings suggest persistent adverse hematological effects associated with residential 137Cs
exposure.

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BackgroundAn explosion at the Chernobyl nuclear power plant on
April 26, 1986, the worst accident in the history of nuclear
power, resulted in radioactive pollution of much of thesurrounding area. In the Ukraine, 2,293 villages andtowns with a population of 2.6 million inhabitants were
contaminated. A plume of radioactive fallout drifted overparts of Europe and reaching eastern North America, as
well. Ever since, the public in these areas has been exposed
to radiation, both externally and internally via contaminated locally-grown food, water and air.
Estimates of detrimental health effects from chronic radiation exposure vary widely [1]. Nearly 20 years after the
Chernobyl disaster the World Health Organization in areport of the UN Chernobyl Forum found no evidence for
an increased incidence of leukemia [2]. However, thesame report found a complete lack of analytical studies inwhich dose and risks were estimated on an individuallevel. There were a few studies that analyzed white blood
cells but most were based on a small number of children,
focused mainly on micronuclei, and were often inconclusive [3-8]. Lenskaia et al., analyzed blood smears from 820
children living in a the Bryansk area in Russia and 46 controls from non-contaminated areas [9]. Using cytochemical assays (mucopolysaccharids) and esterase in 464
children with various exposure levels and 46 children
from non-contaminated areas the work showed a reduction of mature T-lymphocytes and an increase of immature B-lymphocytes. In 1994–1996, Vykhovanets et al.
and Chernyshov et al. studied T-lymphocytes in healthy
children, 219 and 120, respectively, and children sufferingfrom recurrent respiratory diseases (RRD) who resided
around Chernobyl. Both studies compared the exposedgroups with 148 non-exposed children, who were healthyor suffered from RRD. No information of leukocyte
counts was provided [10,11].
Regarding red blood cells, we identified six publishedstudies [5,12-16]. Stepanova et al. found more transitory,
prehemolytic and degenerative forms of erythrocytes (redblood cells) in exposed children in comparison with control children [14]. Cross-sectional results on blood indicesfor years 1986, 1992 and 1998 were provided by
Bebeshko et al. [16]. The authors examined children in thefollowing age-groups: up to 3, 4–7 and 8–15 years old,
residing in the Kiev, Zhytomyr, and Chernohiv provinceswith 137Cs soil contamination density of 37 kBq/m2 orless (37 kilo Bequerel/m2 = 1 Curie (Ci)/km2) and contamination densities between 38 and 55 kBq/m2. The
erythrocyte and leukocyte counts were significantly
decreased in children aged 0–3 years living in Zhytomyr
and in children age 8–15 years living in Chernihiv. The
authors found no differences in hemoglobin, erythrocyte,
leukocyte and platelet count in children residing in settle-

http://www.ehjournal.net/content/7/1/21

ments with 137Cs soil contamination density of 38–555
kBq/m2 compared to 37 kBq/m2.
The Chernobyl Sasakawa Health and Medical Cooperation project conducted the largest cross-sectional investigation of health effects in children [17]. Among a variety
of markers, hematological outcomes were determined in
118,773 children residing in more than 80 regions withdifferent radiation exposures from 1991 to 1996, including 779 children from the Narodichi region [18,19]. Eachregion represented a distinct exposed population rather
than a regional sample of the larger exposed population.
Children from each region were examined at a different
points in time and there was no follow-up of eachregional cohort in subsequent years. Some children werere-examined, but only those who presented a critical clinical outcome. The Chernobyl Sasakawa Health and Medical Cooperation project was a successful andcomprehensive screening project. However, the project
was not sufficiently designed to assess differences inhealth effects in regions and over time. For instance, theresult of the exams in different regions and times, though
presented as time trends, were confounded by different
regions examined in different years [19]. In addition,
improvements detected in the re-examinations of children
were judged as recovery. This ignores the fact that exclusive examination of observations above a critical value
will by chance produce 'recovery' due to chance movements of observations below the cut-off point in the reexam (regression to the mean). Although the results ofthis study have never been reported in peer-reviewed scientific journals, the project has been influential whenassessing the risk of the accident.
No study has yet investigated hematological follow-up
data in children exposed from the Chernobyl accident.
This motivated us to asses the association between residential soil density of 137Caesium (137Cs) and hemoglobin concentration, and erythrocyte, platelet, andleukocyte counts in repeated measurements taken from1993 to 1998.

Methods
Population
The settlements in the Narodichesky region (Zhitomir
Oblast, Ukraine) are approximately 80 km from the Chernobyl nuclear site (Figure 1). Approximately 11,400 people reside in this region, including about 2,000 children[20]. Three quarters of its population live in rural villages,
the others in small towns. The food supply is predominantly locally grown. To monitor the health effects of theaccident, since 1986 every child from birth to age 18 in thecontaminated territory was required to have a yearly medical examination. The Human Subject Committee at the
University of South Carolina has approved these analyses.

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Map
Figureof the1 Narodychi region's territory soil pollution by 137Cs
Figure Legends

Map of the Narodychi region's territory soil pollution by 137Cs.

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Exposure measurement
Following the Chernobyl accident, soil became contaminated with 137Cs, a nuclear fission product that has a halflife of 30 years, and emits both beta- and gamma-irradiation (Figure 1). The highest levels of 137Cs were found in
the surface layers of the soil where it is absorbed by plants
and mushrooms, thereby entering the local food supply.
Dosimetric assessments of settlements in the Ukraine contaminated by radionuclides were published from 1991 to2005 in 10 reports [21]. In addition, the Ministry of Emergency Situations provided spatial data on radiation [22].
Soil measurements used in this work represent the averageof numerous measurements in each village over several
years, in particular 1991–1993. These averages were officially named 'certifications' and documented in publications by the Ministry of Health. [21]. Since residential andindividual 137Cs levels are highly correlated, we used thecontamination in the residential area as an approximationof individual exposure [23].
Medical examination
The obligatory medical examination included weight andheight measurements, blood sampling, blood pressure,ultrasound measurements (thyroid, abdomen and kidney
and adrenals), lung function (starting with a height of 100cm), and a medical history. Gender and place of residence
were also noted. No other information on living conditions or tobacco smoke exposure was collected as a part ofthis exam. For these obligatory examinations, no parental
consent was required.

This work is a first in a series of longitudinal analyses.
Here we focus on hematologic function: erythrocytes (redblood cells), leukocytes (white blood cells), and thrombocyte (platelet) count and hemoglobin concentrations.
Blood was collected in tubes containing EDTA. A bloodcount, including erythrocytes, hemoglobin, leukocytes,
and thrombocytes, was conducted using Sysmex model F800 (TOA Medical Electronics Company, Kobe, Japan).
Normal blood smears were stained by the standardized
azure B-eosin GIEMSA Y Romanowsky procedure. Resultsof these investigations were entered into a database for theperiod of 1993 to1998.
Statistical Analysis
For descriptive purposes, values beyond clinical reference
levels were defined in Table 1[24].

Data were analyzed using the statistical package SAS Version 9.1 (SAS Institute Inc., Cary, NC, USA). We had six
repeated measurements of red and white blood cell markers. To determine whether the measurements agreed overtime, we estimated intraclass correlation coefficients forthe repeated measurements [25].
To investigate the effect of residential 137Cs radiation, weused linear models for repeated measurements (PROC
MIXED) [26]. This statistical method compensates for the
repeated measurements of each child over the six crosssectional models (1993–1998). For all markers, we estimated the adjusted means, controlling for confounders.
For the statistical estimation, the regular maximum likelihood method was applied. This model requires that the
random effects and the error vector are normally distributed, which was found to be the case for all markers. For
the within-subject association, modeling started with an
unstructured covariance model which required least constraints. For the repeated measurements, the initial model
used serial correlation structures (Gaussian). Based on the
Akaike information criterion (AIC), we could simplify the
random effect to variance component, but could not simplify the repeated measurement matrix.
The residential measurements of 137Cs were ranked into
five groups of nearly equal size (PROC RANK), with eachrank treated as an indicator variable, facilitating assessing
an exposure-response relationship. As for confounding
factors, the statistical models included gender, age, andyear of measurement. Age was categorized into 18 indicator variables of one-year intervals, with the first group 0–
1.5 years old. We used indicator variables for age and year

Table 1: Values beyond clinical reference levels.

Red blood cell count:

Hemoglobin:

Thrombocytes:
Leukocytes:

younger than 2 years:
2 years and younger than 6:
6 years and younger than 12:
12 years and younger than 18:
younger than 6 years:
6 years and younger than 12:
12 years and older:
all ages:
1 to 3 years:
4 to 7 years:
8 to 13 years:
13 years and older:≥3.7 × 1012cells/L≥3.9 × 1012cells/L≥4.0 × 1012cells/L≥4.5 × 1012cells/L≥5.59 mmol/L (9 g/dL)≥7.14 mmol/L (11.5 g/dL
≥7.76 mmol/L (12.5 g/dL)≥150 × 109platelets/L≥6–17.5 × 109cells/L≥5.5–15.5 × 109cells/L≥4.5–13.5 × 109cells/L≥4.5–11.0 × 109cells/L

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Table 2: Villages, soil contamination, number of participating children and measurements ψVillage

Quintile

Soil contamination 137Caesium (kBq/m2)

Children

Repeated measurements

Number% (n = 1247)

Number% (n = 4,981)

Brodnik

59

11

0.9

37

0.7

Slavkovci

67

9

0.7

36

0.7

Liplanchina

76

Vyasovka

79

60

4.8

262

5.3

80

50

4.0

205

4.1

4

0.3

14

0.3

Rubegivka

0Radcha82

Ovruch102

N. Radcha

104

Klochki

105

25

2.0

79

1.6

Gresla

102

5

0.4

29

0.6

Norinci

112

71

5.7

305

6.1

Guto-Mariatyn

116

24

1.9

97

1.9

Babinichi

126

9

0.7

45

0.9

Laski

127

75

6.0

317

6.4

130

28

2.2

111

2.2

Bolotnica

131

53

4.3

182

3.7

Davidki

132

8

0.6

38

0.8

Latashi

134

46

3.7

214

4.3

Snytiche

152

9

0.7

39

0.8

Bogdanovka

161

O. Dorogyn

165

51

4.1

220

4.4

Zakusily

165

35

2.8

120

2.4

N. Dorogin

169

22

1.8

71

1.4

Slavichina

170

7

0.6

30

0.6

190

6

0.5

11

0.2

Zalesie

198

55

4.4

217

4.4

Suharevka

210

20

1.6

64

1.3

Jerev

Odruby1

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Table 2: Villages, soil contamination, number of participating children and measurements ψ (Continued)

Moteyki

224

29

2.3

132

2.7

Gunichu

225

12

1.0

32

0.6

Megeliska

236

Yajberen

253

19

1.5

90

1.8

266

116

9.3

486

9.8

Rudnya Basarskaya

3

Selec

310

Narodichi

350

279

22.4

1,049

21.1

364

103

8.3

433

8.7

Rossohivske

608

6

0.5

16

0.3

Hristinovka

879

Basar

4

ψ Villages with a small number of children/observations were merged for descriptive purposes.

of observation to investigate whether their relationships
with the outcome variables were linear. If not, these indicator variables adjusted for non-linearity – for instance as
we did with erythrocyte counts and age in girls. To determine whether the change in the distribution of the blood
markers over the time of the observation depends also on
the residential radiation level, we included an interaction
term of time (year of measurement) and 137Cs. In addition, we investigated statistical differences in children
born before or after the accident.

Results
Children from 38 different settlements were included in
the cohort (Table 2). All villages had different soil measurements of 137Cs (Figure 1), ranging from 29 to 879 kBq/
m2 (Figure 1). The average measurements shown for eachsettlement within colored zones are based on contamination modeling. Average values and the colored zones wereretrieved from published data [21,22]. Three villages wereat the border or outside of the Narodichesky region(Bogdanovka, Gunichu, and Ovruch, total of 3 children).
Due to the distribution of 137Cs, quintiles of the exposure
did not produce equally sized groups (Table 3).
The exact number of children residing in the Narodichesky region between 1993 to 1998 is unknown. Of the
11,400 residents, approximately 2,000 children are children. Data of all exams (1993 to 1998) were included.
Officially, participation in the exams was obligatory.
However, authorities did not enforce participation.
Hence, the term 'obligatory' primarily reflects the opportunity of having annual examinations. Overall, approximately 75% participated in at least one of theexaminations (1,459 of about 2,000 children residing in
the region). Of these, 1,247 children had a blood sample
analyzed (86%), which resulted in 4,981 repeated measurements (Table 3). About one third of the children were
4.5 years and younger, but only 15.9% of the measurements came from these children, indicating a lower participation in blood sampling. The oldest child was born in
1979; the youngest in 1996. Data from the children bornin 1986 will be analyzed and reported in a separate paper.
Of our cohort, 549 children were born before and 698
after the accident (Table 3). In 75% of the available data,
the first participation was documented in 1993, however,
the measurements were nearly equally distributed
throughout the years. In 1993, we had 886 measurements;
786 in 1994; 787 in 1995; 783 in 1996; 1,030 in 1997;
and 709 in 1998.
Because erythrocyte count and hemoglobin concentration
measurement represent a nearly identical feature, thesemarkers are highly correlated (r = 0.72, Table 4). The othermarkers did not show high rank-correlations indicating
independent measurements.
The intraclass-correlation coefficients (ICC) for the four
markers over the six years are: erythrocyte count: ICC = 0.4(5% confidence level: 0.37), for hemoglobin: ICC = 0.59
(5% confidence level: 0.57), for thrombocyte count: ICC= 0.54 (5% confidence level: 0.52), and for leukocyte
count: ICC = ICC = 0.53 (5% confidence level: 0.51).
These results document substantial stability of the measurements.

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Table 3: Characteristics of the study population

Children participating (n = 1,247) %Total number of observations (n = 4,981) %

49.1

48.4

33.0
37.5
27.4
2.2

15.9
33.7
41.1
9.2

0.2
4.6
4.8
8.3
9.7
9.3
7.1

0.1
4.2
5.3
9.7
11.4
12.0
9.1

6.7
8.3
8.5
6.8
6.3
5.9
5.0
5.1
2.7
0.8

8.1
9.0
7.7
6.2
5.3
5.1
3.3
2.3
1.0
0.3

71.1
2.4
2.7
1.6
18.9
3.4

17.7
15.8
15.8
15.7
20.7
14.3

18.9
20.1
9.3
31.1
18.9

19.4
20.8
19.4
9.8
30.7

Sex
boys
Age groups (years) (first participation or year)
up to 4.5
>4.5 to 9.5>9.5 to 14.5
>14.5
Year of birth
1979
1980
1981
1982
1983
1984
1985
#
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
Year of first participation (or first entered into the data)
1993
1994
1995
1996
1997
1998
Quintiles of the area contamination: 137Caesium (kBq/m2)
29–112
116–156
165–253
266–310
350–879# Children born in 1986 being analyzed and reported in a separate paper

Table 4: Median, minimal and maximal values, and rank correlation of hematological markers #VariableMedianMinMax

Erythrocyte count (1012L)

4

2.1

5.7

Hemoglobin (g/dL)Φ

12.3

5.2

16.9

Leukocyte count (106L)

6.8

2

18.9

Platelet count (109L)

252

108

670

Rank correlation (Spearman) and p-value
Hemoglobin

Leukocyte

Platelets

0.72
0.00

0.25
0.00
0.18
0.00

0.22
0.00
0.16
0.00
0.35
0.00

# 4,981 repeated measurement of 1,247 children
Φ 1 g/dL equals about 0.6206 mmol/L.

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Including all cohort children, the repeated measurement
analyses (mixed models) showed significant effects for the
residential 137Cs measurements (quintiles), the time of
the medical examination, and the 137Cs × time interaction(Table 5). To illustrate the interactions of time and exposure, we extracted mean values for residential exposure
classes and years from the mixed models (see details in
Additional file 1).
The erythrocyte count shows a minor increase from 1993
to 1998 (Figure 2), starting from below 4 × 1012 cells perliter to more than 4.1 × 1012 cells per liter. The improvement is less in the two groups of children with higher residential exposures; thus the exposure gradient becomesstronger in 1998 compared to 1993. A similar trend isobvious for hemoglobin. Both markers show a dip in
1996, which is not explained by age in general nor by aparticular age in girls (age at menarche). For platelet
counts, it is obvious that children in all 137Cs exposuregroups improved over time (Figure 3). The exposure gradient is stronger in 1993, but diminished in 1998. Thereseems to be no further increase after 1997. Figures 2 and3 show lower values in 1996 in all exposure groups.
There appears to be exposure-response patterns in allgraphs; however, the second to the highest exposuregroup showed the strongest effect in all four outcomes.

Compared to the second highest group, the highest residential exposure group includes a higher proportion ofsemi-rural children, from Narodichi, the administrative
center of the region (Table 2).
For leukocyte counts, the exposure gradient did notchange between 1993 and 1998 (Table 6). Starting with asoil contamination of about 165 kBq/m2, the leukocyte
count is approximately 1 million cells per liter lower inthe group of children with the highest soil contamination.
A similar reduction was found for children born after theaccident in 1986 (data not shown). However, the countincreased over the time period from 1993 to 1996.
Children born after the accident and thus exposed during
pregnancy and childhood showed no 137Cs × time interaction (Table 7). For the three outcomes, erythrocyte andplatelet count and hemoglobin concentration, the values
are significantly lower in the two highest residential exposure groups; the effect is strongest for platelets and whiteblood cells. Compared with the measurements in 1998
there is an overall improvement over the six years ofobservation for erythrocyte, platelet, but no clear trend
regarding hemoglobin (data not shown).
Fifty-three percent of all erythrocyte counts were below
the clinical age-specific reference values, as were 19% of

Table 5: Statistics of the models including the interaction of area contamination and year of measurement #Numerator degree of freedom Denominator degree of freedom

Erythrocyte count
Quintiles of the area contamination with Caesium 137(kBq/m2)
Sex

FValueProb F

<0.00
1
<0.00
1
<0.00
1
<0.00
1
<0.00
1

4

3692

12.55

1

3692

12.11

Age groups

17

3692

13.42

Year of measurement

5

3692

102.42

Quintiles of the area contamination: 137Caesium (kBq/m2) ×
year

20

3692

5.37

Hemoglobin
Quintiles of the area contamination with Caesium 137(kBq/m2)
Sex
Age groups

4

3692

7.28

1
17

3692
3692

7.72
33.43

Year of measurement

5

3692

52.68

Quintiles of the area contamination: 137Caesium (kBq/m2) ×
year

20

3692

4.81

4

3690

9.71

1

3690

1.61

Platelet count
Quintiles of the area contamination with Caesium 137(kBq/m2)
Sex

<0.00
1
0.006
<0.00
1
<0.00
1
<0.00
1

<0.00
1
0.20

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Red blood cell count (1012/L)
1,247 children, 4,981 observations

Platelet count (109/L)
1,247 children, 4,981 observations
300

4.25

4.2

29-112 137Cs (kBq/m2)

290

29-112

137

165-253

2

Cs (kBq/m )

4.15

280

4.1

165-253270

350-8794.05

260

116-156

116-156

4

250
3.95

240

266-310350-879

3.9

266-310 137Cs (kBq/m2)

137

2

Cs (kBq/m )

230

3.85

220
3.8
1993

1994

1995

1996

1997

1998

210

Hemoglobin (g/dL)
1,247 children, 4,981 observations
12.8

29-112

137

165-253

12.6

116-134

350-87912266-310

137

1996

1997

2

Cs (kBq/m )

11.8
1993

1994

1995

1994

1995

1996

1997

1998

the hemoglobin measurements, 0.7% of the platelet and26.6% of the white blood cell counts. The proportion ofvalues below the clinical limit decreased from 1993 to
1996. The white blood cell counts also showed improvement, but an increasing proportion of mild leukocytosis(white blood cell count > 11 × 109cells per L; 1993: 0.1%,
1997: 3.2%, 1998: 2.0%).

12.4

12.2

1993

137
FigureChangesCs exposure
3of platelet counts over the years of observations by
Changes of platelet counts over the years of observations by 137Cs exposure. The 137Cs contamination isgrouped into quintiles.

2

Cs (kBq/m )

200

1998

137Cs exposure
FigureChangesyears
of 2observationsof erythrocyte
bycounts
and hemoglobin over the
Changes of erythrocyte counts and hemoglobin over
the years of observations by 137Cs exposure. The 137Cs
contamination is grouped into quintiles. For hemoglobin: 1 g/
dL equals about 0.6206 mmol/L.

Discussion
We analyzed markers of hematopoiesis from 1993 to1998 and their association with residential radiation
exposure and found an adverse effect on erythrocyte,
platelet, and white blood cell counts and on hemoglobin
concentration. When analyzing the total sample of children irrespective of whether the child was born before orafter the accident (exposure occurred in childhood vs. inutero and in childhood), we found that the recovery ofplatelets was more pronounced in children who were
exposed to higher residential contamination with 137Cs.
The recovery of erythrocytes and hemoglobin was smallerin the highly exposed children. White blood cell counts

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Table 5: Statistics of the models including the interaction of area contamination and year of measurement # (Continued)

Age groups

17

3690

5.58

Year of measurement

5

3690

92.61

Quintiles of the area contamination: 137Caesium (kBq/m2) ×
year

20

3690

2.08

<0.00
1
<0.00
1
0.003

# For the illustration of the results see Figure 2 and 3.

did not show an exposure × time interaction, but
remained lower in higher exposed children. Also in children born after the accident there was no such interaction
effect. An outcome improvement was obvious in all exposure groups, with the exception of hemoglobin, but the
exposure gradient did not diminish over the observation
period.
Overall, approximately 75% participated in the examinations (1,459 of about 2,000 children residing in theregion); blood samples were available for 63%. Officially,
participation in the exams was obligatory. However,authorities did not enforce participation.
This is a dynamic cohort study: children were entering andleaving the study. Regarding non-participation in one
exam, lower or higher levels of the three blood count variables in the preceding exam were not associated withmissing the next exam. Hence, we have no indication fora selection bias due to differential attrition.
The justification to enter and analyze only data for 1993
to 1998 was due to budgetary limitations. We are seeking
funding to extend the data entry and include more
repeated measurements. The 1993 to 1998 period waschosen since all exams were established during this timeframe. Another advantage of this period is that it includes
a comparable number of children who were born before
the accident in 1986 and thereafter. This facilitates a comparison of exposures occurring after birth in children born
before the accident in 1986 with exposure in children
born after the accident (persistent 137Cs exposure). The
variable "born before" addresses two aspects, first,

whether the child was exposed to other short-lived radionuclides immediately after the accident (for instance
131Iodine, in children born before 1986), and, second,
whether the child was exposed to 137Cs during pregnancy
and in its development (born after).
Originally, we planned to analyze radiation exposureusing individual effective equivalent dose in millisievert(mSv), which incorporates total external and internal
doses, including direct measurements with whole bodycounts [27], but there are uncertainties in the time periods
in which the measurements were taken and their documentation. In addition, the individual effective equivalentdose was not calculated for every child and exposure models for individual dosimetry were changed over time.
Although residential radiation exposure introduces more
non-differential misclassification and thus weakens possible associations, those data were our most complete available exposure data set. In addition, the Chernobyl
Sasakawa Health and Medical Cooperation project foundthat individual 137Cs levels in the bodies of children werehighly correlated (r = 0.7, p < 0.01) with the contamination level in the place of residence [23]. However, compared to the five groups of residential exposure, theindividual effective equivalent dose is highest in children
in the second to highest residential exposure group (meanindividual effective equivalent doses over increasing levelsof residential exposure groups: 13.6, 11.7, 16.7, 34.9, 19.6
mSv). Thus, it is likely that the stronger effect in the second highest residential exposure (266–310 137Cs kBq/m2)
follows from the higher individual dose in this group. We
note that the highest exposure group represents children
from Narodichi, the largest village of the region (Table 2),

Table 6: Estimate effects of 137Caesium and year of measurements on white blood cell counts ΨWhite blood cell count (106/L) 1,247 children, 4,981 measurement
EffectQuintiles of the area contamination: 137Caesium (kBq/m2)

29–112
116–156
165–253
266–310
350–879

Adj. Mean#

Lower

Upper

p

6.87
6.88
6.40
5.95
5.81

6.58
6.60
6.11
5.55
5.57

7.16
7.18
6.68
6.35
6.04

Ref.
0.94
0.01
<0.001<0.001

Ψ P-values are based on t-test compared with the reference (Ref.).
# Adjusted for age, sex, born after the accident, and year of measurement

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Environmental Health 2008, 7:21

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Table 7: Estimated effects of 137Caesium and year of measurements on erythrocyte count, hemoglobin, and platelet counts ΨErythrocyte count (1012/L) 698
children, 2,404 measurements
Adj. Mean#

EffectQuintiles of the area
contamination: 137Cs(kBq/m2)

Hemoglobin (g/dL)Φ 698 children,
2,404 measurements

Platelet count (109/L) 698 children,
2,403 measurements

5–95%
confidence
intervalp

Adj. Mean#

5–95%
confidence
intervalp

Adj. Mean#

5–95%
confidenc
e intervalp

29–112

4.02

3.98-

4.06

Ref.

12.2

12.1-

12.3

Ref.

284

274

294

Ref.

116–156
165–253
266–310
350–879

3.99
4.00
3.88
3.96

3.973.933.843.93-

4.03
3.93
3.93
3.99

0.29
0.42
<0.001
0.009

12.0
12.1
11.8
12.0

11.912.011.711.0-

12.2
12.2
12.0
12.1

0.039
0.34
0.001
0.033

273
281
255
264

266
273
242
256

282
290
267
271

0.07
0.52
<0.001<0.001Φ 1 g/dL equals about 0.6206 mmol/L.
Ψ P-value are based on t-test compared with the reference (Ref.) in children born after the accident.
# Adjusted for age, sex, and year of measurement

whereas the second to highest exposure group includes
more children from small villages and rural areas with alarger chance of direct exposure externally and internallyfrom food. Furthermore, compared to the virtue of individual measurements, using residential exposure data has
the advantage that it provides the information needed tocontribute to improved exposure regulations.
There are other sources of non-differential exposure misclassification, e.g., in landscapes with relatively low levelsof radioactive contamination of the soil, the population
may receive substantial radiation doses due to their consumption of contaminated food and vice versa. The
results also show decreased erythrocyte counts and hemoglobin concentrations in 1996 in all exposure groups (Figures 2 and 3). It is possible that there was an instrument
bias in 1996. Another explanation is that the winter in1996 was colder. Thus, children may have suffered from a
reduced supply of vitamins that are essential for thehematopoesis. Since the decline occurred in all exposuregroups, this represents a non-differential misclassification. Non-differential misclassifications tend to produce
results that underestimate effects and do not present a
threat to validity of the findings.
Our data provide only a little information on individual
characteristics such as age and gender. One may be
inclined to consider that other confounding factors suchas parental smoking or diet would increase the internal
validity of this study. Against that, we need to understandthe setting of this research. The Chernobyl accident
affected all groups of the population, irrespective ofwhether the parent exposed their children to second handsmoke or whether their diet was healthy or not. Thus,
smoking and other factors cannot act as confounders,since the accident resulted in a random distribution ofradiation in relation to various other health related risk

factors. Such a setting is referred to as quasi-experimental
or as a randomized natural experiment [28,29]. Although
this setting does not require the control of confounders,
we cannot exclude other risk factors that may have moderated the adverse effects of radiation (effect modification
or interaction). For instance, it is possible that poverty andunhealthy lifestyles have augmented adverse radiation
effects. The sample of children was homogeneous. All
families were poor villagers with a traditional diet basedon local food and comparable domestic conditions.
Given the setting of a randomized natural experiment, ourresults provide compelling evidence for the adverse effects
of residential 137Cs radiation on hematopoiesis.
Another limitation is that we have only computerized andstatistically analyzed data for a limited time-period(1993–1998). However, this is a first step, and there is aclear need to include additional data before 1993 andafter 1998. In addition, we had to start with a specific setof health outcomes and chose markers related to hematopoiesis. Other reports that document the various aspectsof the Chernobyl accident will follow. These children
seem to suffer from multiple diseases and co-morbidities
with repeated manifestations, a condition for which theterm 'frequently sick child' was defined by Stepanova andcoworkers [30].
According to data from the Ukrainian Ministry of Social
Protection (January 2005) and Ministry of Emergency,
more than half a million children reside in areas withchronic exposure to low radiation due to soil contamination with 137Cs. We believe that it is extremely importantto analyze not only cancer-related outcomes but also nonneoplastic effects [31], which are much more frequent
than cancer. It is surprising that the UN Chernobyl Forum
Report [2] did not consider multiple publications by
Ukrainian, Russian, and Byelorussian researchers about

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Environmental Health 2008, 7:21

the excess of non-cancer morbidity in children living in
the territory contaminated by the Chernobyl accident[9,32-37]. Because the Chernobyl accident was like few
others, there is a gap in knowledge regarding potential
health sequelae. The atomic bombing of Japan near theend of World War II did release fission isotopes over awide area, but the composition of this isotopic contamination was different [38]. The Chernobyl accident
involved the release of isotopes built up in the fuel rods
over time; these isotopes are far more persistent. As apotential consequence, the decreased blood counts show
lasting effects. This was not observed after non-persistentradiation exposure [39]. However, similar effects werereported for the River Techa accident, which happened in1957 [40]. The exposure was characterized by gamma andbeta irradiation due to 90Strontium and 137Cs. As in children residing in Narodichesky region, adverse hematologic effects were detected. A normalization of thehematologic outcomes occurred only 13 years after theaccident [40]. In investigating health sequelae in a cohortof children exposed to the Chernobyl accident, we expect
to find associations that have not been reported before.
This work is the first in a series using longitudinal epidemiology to uncover long-term effects of the Chernobyl
accident on children, leading to a better understanding of
how large and persistent the radiation exposure affects thegeneral population.

http://www.ehjournal.net/content/7/1/21

Svendsen analyzed the data. All the authors contributed toand approved the final manuscript.

Additional material
Additional file 1
Table with confidence limits. Estimated combined effects of 137Caesium
irradiation and year of measurements on erythrocyte count, hemoglobin,and platelet counts and their confidence limits.
Click here for file
[http://www.biomedcentral.com/content/supplementary/1476069X-7-21-S1.doc]

Acknowledgements
Funding for the data entry was provided by the Samuel Freeman Charitable
Foundation, the Walker Institute for International and Area Studies, andthe National Science Foundation. We thank Susan Davis, Curtis Travis,
Dmitry Afanasyev for their comments and and Wanzer Drane for the initialsteps of the data collection.

References
1.

2.

Conclusion
More than 10 years after the Chernobyl accident, children
in the Narodichesky region, Ukraine, approximately 80
km from Chernobyl, showed decreased counts for red andwhite blood cells and platelets, and a reduced concentration of hemoglobin associated with persistent residential
137Cs exposure. There are compelling reasons to investigate more closely the relationship of radioactive exposure
after the Chernobyl accident and health sequelae in children.

3.

4.

5.

Abbreviations
Intraclass correlation coefficient (ICC), ethylene diamine
tetraacetic acid (EDTA)

6.

Competing interests
The authors declare that they have no competing interests.

7.

Authors' contributions
Eugenia Stepanova and Vitaliy Vdovenko have contributed to developing the protocol of the medical exams andconducted the examinations and blood analyses. Wilfried
Karmaus, Marina Naboka, Vitaliy Vdovenko, Tim Mousseau, John Vena, and Harris Pastides developed the analytical plan. Marina Naboka, Viacheslav M. Shestopalov,and Dwight Underhill provided access and supported theassessment of exposure data. Wilfried Karmaus and Erik

8.

9.

Kinley D: Chernobyl's Legacy: Health, Environmental andSocio-Economic Impacts and Recommendations to the Governments of Belarus, the Russian Federation and Ukraine.
Second revised version. 2006 [http://www.iaea.org/Publications/
Booklets/Chernobyl/chernobyl.pdf].
Bennett B, Repacholi M, Carr Z: Health Effect of the Chernobyl
Accident and Special Health Care Programmes. Report of
the UN Chernobyl Forum Expert Group "Health". 2006
[http://www.who.int/ionizing_radiation/chernobyl/
WHO%20Report%20on%20Chernobyl%20Health%20Effects%20July%2006.pdf].
Vasil'eva IM, Unzhakov SV, Meliksetova IA, Zasukhina GD, Semiachkina AN, Kazantseva LZ: [The adaptive response in the lymphocytes of children from an area with an elevatedbackground of ionizing radiation]. Radiats Biol Radioecol 1995,
35:662-665.
Tedeschi B, Caporossi D, Vernole P, Padovani L, Mauro F: Do
human lymphocytes exposed to the fallout of the Chernobyl
accident exhibit an adaptive response? III. Challenge withbleomycin in lymphocytes from children hit by the initialacute dose of ionizing radiation. Mutat Res 1996, 354:77-80.
Fenech M, Perepetskaya G, Mikhalevich L: A more comprehensive
application of the micronucleus technique for biomonitoringof genetic damage rates in human populations – experiencesfrom the Chernobyl catastrophe. Environ Mol Mutagen 1997,
30:112-118.
Makedonov GP, Tskhovrebova LV, Unzhakov SV, Semiachkina AN,
Vasil'eva IM, Zasukhina GD: [Radioadaptive response in lymphocytes of children living in territories polluted by radionuclides as a result of the accident at the Chernobyl power
plant]. Radiats Biol Radioecol 1997, 37:640-644.
Padovani L, Stronati L, Mauro F, Testa A, Appolloni M, Anzidei P,
Caporossi D, Tedeschi B, Vernole P: Cytogenetic effects in lymphocytes from children exposed to radiation fall-out after
the Chernobyl accident. Mutat Res 1997, 395:249-254.
Mikhalevich LS, De Zwart FA, Perepetskaya GA, Chebotareva NV,
Mikhalevich EA, Tates AD: Radiation effects in lymphocytes ofchildren living in a Chernobyl contaminated region of Belarus. Int J Radiat Biol 2000, 76:1377-1385.
Lenskaia RV, Buiankin VM, Zakharova GA, Ikonnikova OA, Koliaskina
MG, Popova OA, Rumiantsev AG, Seleznev VA, Sterligova IA, Chernov VM: [Cytochemical lymphocytic markers as criteria suitable for mass and selective hematologic screening ofchildren living in areas contaminated by radionuclides].
Gematol Transfuziol 1993, 38:34-36.

Page 12 of 13(page number not for citation purposes)

Environmental Health 2008, 7:21

10.

11.

12.

13.

14.

15.

16.

17.
18.

19.

20.
21.
22.
23.

24.

Vykhovanets EV, Chernyshov VP, Slukvin II, Antipkin YG, Vasyuk A,
Colos V: Analysis of blood lymphocyte subsets in children living around Chernobyl exposed long-term to low doses ofcesium-137 and various doses of iodine-131. Radiat Res 2000,
153:760-772.
Chernyshov VP, Vykhovanets EV, Slukvin II, Antipkin YG, Vasyuk AN,
Strauss KW: Analysis of blood lymphocyte subsets in children
living on territory that received high amounts of fallout from
Chernobyl accident. Clin Immunol Immunopathol 1997, 84:122-128.
Livingston GK, Jensen RH, Silberstein EB, Hinnefeld JD, Pratt G, Bigbee WL, Langlois RG, Grant SG, Shukla R: Radiobiological evaluation of immigrants from the vicinity of Chernobyl. Int J Radiat
Biol 1997, 72:703-713.
Vartanian LS, Gurevich S, Kozachenko AI, Nagler LG, Burlakova EB:[Age-related peculiarities of effect of low dose ionizing radiation on blood antioxidant enzyme system status in Chernobyl's accident liquidation participant]. Adv Gerontol 2004,
14:48-54.
Stepanova EI, Davidenko OA, Vdovenko V: [Peculiarities of superficial architectonics of peripheral blood erythrocytes in children irradiated in utero and living in the radioactivecontaminated areas]. Tsitol Genet 2006, 40:40-43.
Spirichev VB, Donchenko GV, Blazheevich NV, Parkhomenko Iu M,
Aleinik SI, Golubkina NA, Vrzhesinskaia OA, Isaeva VA, Kodentsova
VM, Pereverzeva OG, Sokol'nikov AE, Iakushina LM: [To the 20th
anniversary of the Chornobyl accident study of vitamin status and provision with micro- and macroelements of limitedgroups of people at different time periods since the accident
at Chornobyl nuclear power plant]. Ukr Biokhim Zh 2006,
78:5-26.
Bebeshko VG, Bruslova EM, Tsvetkova NM: Hemopoietic system
state in children under the chronic radiation impact within
low dose range. In Clinical effects of the Chernobyl disaster Edited by:Bebesko VG, Kovalenko AN. Kiev: Academy of Medical Science;
1999:21.
Yamashita S, Shibata Y, (Eds): Chernobyl: A Decade. Proceedings of theFifth Chernobyl Sasakava Medical Cooperation Symposium, 14–15 October
1996 Kiev, Ukraine: Elsevier; 1996.
Avramenko A: Health conditions of children in the Kiev region
10 years after the Chernobyl nuclear power plant accident:
based on the results of health examination made by the
Chernoby Sasakawa Diagnostic Center (Kiev Regional Hospital No. 2). In Chernobyl: A Decade Proceedings of the Fifth Chernobyl
Sasakava Medical Cooperation Symposium, Kiev, Ukraine, 14–15 October
1996 Edited by: Yamashita S, Shibata Y. Amsterdam, Lausanne, New
York: Elsevier; 1997:3-10.
Karevskaya IV, Fokina MM, Kozyreva EA, Drozdovich VS, Averichev
AA, Demidenko AN, Derzhtskaya EV, Cot VA, Moiseyenko NV, Koulikova NV, Kroupnik TA, Sribnaya VD, Tkachuk LP, Avramenko AI,
Petrova AA, Voropai LV, Masyakin VB, Daniliuk LV, Daniliuk VV:
Hematological finding of the Chernoby Sasakawa Health andMedical Cooperation Project. In Chernobyl: A Decade Proceedingsof the Fifth Chernobyl Sasakava Medical Cooperation Symposium, Kiev,
Ukraine, 14–15 October 1996 Edited by: Yamashita S, Shibata Y.
Amsterdam, Lausanne, New York: Elsevier; 1997:45-57.
All-Ukrainian population census '2001[http://www.ukrcen
sus.gov.ua./eng/results/general/urban-rural/Zhytomyr]
Ministry of Health of the Ukraine: Certification doses for the settlementsof Ukraine located in contaminated territories after the Chernobyl accident,
Reports No 1 to 7 and 9 and 10. Kiev 2005.
Ministry of Emergency Situation of Ukraine: Atlas of radioactivity contamination of the Ukraine. Kiev 2002.
Sharifov VF, Koulikova NV, Voropai LV, Kroupnik TA, Masyakin VB,
Cot VA, Kovalev AI, Aksenov AS, Averichev AA, Moiseyenka MY,
Avramenko AI, Goncharenko OE, Daniliuk VV: Finding of theChernoby Sasakawa Health and Medical Cooperation
Project: 137 Cs concentrations among children around
Chernobyl. In Chernobyl: A Decade Proceedings of the Fifth Chernobyl
Sasakava Medical Cooperation Symposium, Kiev, Ukraine, 14–15 October
1996 Edited by: Yamashita S, Shibata Y. Amsterdam, Lausanne, New
York: Elsevier; 1997:39-44.
Nicholson JF, Pesce M: Reference Ranges for Laboratory Tests
and Procedures. In Nelson textbook of pediatrics 16th edition. Edited
by: Behrman RE, Kliegman RM, Jenson HB. Philadelphia: W.B. Saunders Company; 2000:2181-2229.

http://www.ehjournal.net/content/7/1/21

25.
26.
27.

28.
29.

30.
31.
32.

33.
34.

35.
36.
37.

38.
39.

40.

Armstrong B, White E, Saracci R: Principles of Exposure Measurement
in Epidemiology Oxford, New York, Tokyo: Oxford University Press;
1992.
Verbeke G, Molenberghs G: Linear Mixed Models for Longitudinal Data
New York: Springer-Verlag; 2000.
International Programme on the Health Effects of the Chernobyl
Accident: Health Consequences of the Chernobyl Accident. Results of the
IPHECA Pilot Projects and Related National Programmes. Scientific Report.
Geneva 1996.
Goldberg J, Richards MS, Anderson RJ, Rodin MB: Alcohol consumption in men exposed to the military draft lottery: a natural experiment. J Subst Abuse 1991, 3:307-313.
Carrozzi L, Giuliano G, Viegi G, Paoletti P, Di Pede F, Mammini U,
Carmignani G, Saracci R, Giuntini C, Lebowitz MD: The Po River
Delta epidemiological study of obstructive lung disease:sampling methods, environmental and population characteristics. Eur J Epidemiol 1990, 6:191-200.
Stepanova EI, Kolpakov I, Vdovenko VY: State of the functional systemin children exposed to radiation effect as a result of the Chernobyl catastrophe Kiev: Chernobyl Inform Press; 2003.
Busby C, Fucic A: Ionizing radiation and children's health: conclusions. Acta Paediatr Suppl 2006, 95:81-85.
Astakhova LN, Demidchuk EP, Davydova EV, Arinchin AN, Gres NA,
Zelenko SM, Drozd VM, Poliakova TI, Dardynskaia IV, Bazyl'chik SV:[Health status of Byelorussian children and adolescents
exposed to radiation as consequence of the Chernobyl AES
accident]. Vestn Akad Med Nauk SSSR 1991, 11:25-27.
Stepanova EI, Kondrashova VG, Davidenko OA, Kniazeva OB, Galichanskaia T: [The hematological effects of the Chernobyl accident in children]. Gematol Transfuziol 1992, 37:31-33.
Stepanova EI, Chaialo PP, Kolpakov IE, Kondrashova VG, Kurilo LV,
Galichanskaia T, Fediakova OB, Ivaniuk AG: [Effects of the consequences of the Chernobyl accident on the child's body]. Pediatria 1991, 12:8-13.
Lukyanova EM: Klinical and practical aspects of pediatrichealth nine years after the Chernobyl disaster. JAMS of Ukraine
1996, 1:21-23.
Bobylova OA: Health state estimate in children depending on
the occured radio-ecological situation after the ChNPP accident. Ukraine Radiology Journal 1996, 1:21-23.
Nyagu AI, Loganovsky KN, Nechaev SY, Pott-Born R, Repin VS,
Antipchuk EY, Bomko MA, Yurryev KL, Petrova IV: Effects of prenatal brain irradiation as a result of Chernobyl accident. Int J
Radial Med 2004, 6:1-4.
Baverstock K, Williams D: The chernobyl accident 20 years on:an assessment of the health consequences and the international response. Environ Health Perspect 2006, 114:1312-1317.
Scherthan H, Abend M, Muller K, Beinke C, Braselmann H, Zitzelsberger H, Kohn FM, Pillekamp H, Schiener R, Das O, Peter RU,
Herzog G, Tzschach A, Dorr HD, Fliedner TM, Meineke V: Radiation-induced late effects in two affected individuals of the
Lilo radiation accident. Radiat Res 2007, 167:615-623.
Akleyev AV, Kossenko MM, Silkina LA, Degteva MO, Yachmenyov
VA, Awa A, Akiyama M, Veremeyeva GA, Vozilova AV, Kyozumi S:
Health effects of radiation incidents in the southern Urals.
Stem Cells 1995, 13(Suppl 1):58-68.

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