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007) 84–92
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Environment International 33 (2
Fetal methylmercury exposure as measured by cord blood mercury
concentrations in a mother–infant cohort in Hong Kong
Tai F. Fok a,⁎, Hugh S. Lam a, Pak C. Ng a, Alexander S.K. Yip b, Ngai C. Sin a, Iris H.S. Chan c,
Goldie J.S. Gu a, Hung K. So a, Eric M.C. Wong d, Christopher W.K. Lam c
a Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong
b Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong
c Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong
d Centre for Epidemiology and Biostatistics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong
Received 27 May 2006; accepted 4 August 2006
Available online 8 September 2006
Abstract
This study was designed to examine newborn infants in Hong Kong prenatally exposed to levels of methylmercury considered to increase risk
of neurotoxic effects and to examine subject characteristics that modify the degree of prenatal mercury exposure. Mercury concentrations in 1057
sets of maternal and cord blood samples and 96 randomly selected maternal hair samples were measured. Subject characteristics were measured or
collected by questionnaire. Of the 1057 cord blood samples collected only 21.6% had mercury concentrations less than 29 nmol/L (5.8 μg/L).
Median maternal hair mercury concentration was 1.7 ppm. The geometric mean cord to maternal blood mercury ratio was 1.79 to 1. Increasing
maternal fish consumption and maternal age were found to be associated with increased cord blood mercury concentrations. Marine fish
consumption increased cord blood mercury concentrations more than freshwater fish (5.09%/kg vs 2.86%/kg). Female babies, maternal alcohol
consumption and increasing maternal height were associated with decreased cord blood mercury concentrations. Pregnant women in Hong Kong
consume large amounts of fish and as a result, most of their offspring have been prenatally exposed to moderately high levels of mercury. In this
population, pregnant women should choose freshwater over marine fish and limit fish consumption.
© 2006 Elsevier Ltd. All rights reserved.
Keywords: Cord blood mercury concentrations; Fetal methylmercury exposure; Maternal fish consumption
Mercury is a heavy metal that is widespread in the environ-
ment and has many toxic effects. Since the first cases of meth-
ylmercury poisonings in England during the 1860s when this
chemical was first synthesized, and subsequent outbreaks in
Japan, Iraq, Pakistan and Guatemala (Clarkson et al., 2003;
Clarkson and Strain, 2003; Elhassani, 1982; Harada, 1995), it
has become increasingly clear that this form of organic mercury
poses a major public health hazard.
Numerous studies regarding the toxic effects of methylmer-
cury in humans have been performed (NRC, 2000). Examples
of large-scale methylmercury exposure to the public include the
Abbreviations: CI, confidence interval; ppm, parts per million.
⁎ Corresponding author. Department of Paediatrics 6/F, Clinical Sciences
Building, Prince of Wales Hospital, Sha Tin, New Territories, Hong Kong.
Tel.: +852 2632 2851; fax: +852 2636 0020.
E-mail address: taifaifok@cuhk.edu.hk (T.F. Fok).
0160-4120/$ - see front matter © 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.envint.2006.08.002
contamination of aquatic food chains around Minamata Bay in
Japan and the mass consumption of mercury-containing fungi-
cide-coated seed grain products in Iraq. These catastrophes
illustrate the striking complications of prenatal exposure to large
doses of methylmercury: cerebral palsy, seizures, microcephaly,
mental retardation and visual and hearing problems (Elhassani,
1982; Harada et al., 1999; Harada, 1995; Davidson et al., 2004).
Furthermore, recent epidemiological studies strongly suggest
that there are long-term neurodevelopmental consequences of
fetal methylmercury exposure at doses as low as 29 nmol/L
(5.8 μg/L) as measured in cord blood or 1.2 ppm as measured in
maternal hair (Trasande et al., 2005; Steuerwald et al., 2000;
Oken et al., 2005; Murata et al., 2004b; Grandjean et al., 2004;
Grandjean et al., 1997; NRC, 2000). Many international and
national organizations have produced guidelines regarding
methylmercury exposure (JEFCA, 2003; NRC, 2000). Previ-
ously the guidelines were largely based on data of the toxic
mailto:taifaifok@cuhk.edu.hk
http://dx.doi.org/10.1016/j.envint.2006.08.002
Table 1
Types of freshwater and marine fish commercially available at Hong Kong
markets
Freshwater fish
Mud carp
Snake head
Grass fish
Japanese eel
Big head
Fresh grouper
Gold carp
Grey mullet
Marine fish
Big-eye
Hair-tail
Japanese sea-perch
Macau sole
Bombay duck
Pampno
Rabbit-fish
Russell's snapper
Sea-bass
Spotted sand-borer
Mackerel
Sweet lip
White pomfret
Yellow croaker
Yellow-fin
Grouper
Red-fish
Tung-sing
False-halibut
Flat-head
Golden-thread
85T.F. Fok et al. / Environment International 33 (2007) 84–92
effects of methylmercury as seen in Japan and Iraq. In recent
years, more emphasis has been placed on large epidemiological
studies of the neurotoxic effects of relatively low-dose methyl-
mercury exposure in populations such as the Faroe Islands and
the Republic of Seychelles (Grandjean et al., 1997; NRC, 2000;
Steuerwald et al., 2000; ATSDR, 1999; Myers et al., 2003). The
United States Environmental Protection Agency's (US EPA)
reference dose of 0.1 μg/kg/day of methylmercury is based on
extensive analyses of these recent data (Rice et al., 2003; Rice,
2004; NRC, 2000). Further large-scale studies from different
populations will help examine the applicability of these guide-
lines to local populations and generate good quality data to help
fill the gaps in our knowledge regarding the toxic effects of low-
dose prenatal methylmercury exposure.
Hong Kong has not been subject to the massive methyl-
mercury poisonings witnessed in the 1950–1960s at Minamata
Bay and Niigata in Japan (Counter and Buchanan, 2004;
Harada, 1995). Nevertheless there are increasing concerns
regarding chronic low-dose mercury exposure amongst the
local population. Southern areas of China, including much of
Guangdong province (the area surrounding Hong Kong), have
undergone rapid industrialization in recent years. Of particu-
lar concern is the densely industrialized area to the north of
Hong Kong, where power plants and factories discharge large
amounts of industrial waste into tributaries which drain into
the Pearl River and via Hong Kong's waters into the South
China Sea (Parsons, 1998). Already there is evidence to link
the increase in mercury exposure in Hong Kong with male
subfertility (Dickman et al., 1998). There is evidence to show
that Hong Kong Asians tend to consume large amounts of
fish (Dickman et al., 1998; Ip et al., 2004). A study in Hong
Kong (FEHD, 2002), found that a cohort of school chil-
dren consumed an average of 78.6 g fish and 50.5 g non-fish
seafood per day. The average mercury exposure was estimated
to be 2.98 μg/kg/week, while the high consumer (95th per-
centile) was estimated to be exposed to 6.41 μg/kg/week of
mercury. These figures are substantially higher than the re-
commendations of either the World Health Organization of
1.6 μg/kg/week (JEFCA, 2003), or the US EPA of 0.1 μg/kg/
day (Rice, 2004).
This study was therefore designed to assess the proportion of
the local population exposed prenatally to relatively low-dose
methylmercury (cord blood mercury concentration≥29 nmol/L).
Further, the study would quantify the level of prenatal mercury
exposure in a mother–infant cohort and examine the population-
specific characteristics that can influence exposure, as reflected by
cord blood mercury concentrations. Data from this study could
then serve as a basis for further epidemiological studies of toxic
effects (such as neurodevelopmental deficits) of low-dose meth-
ylmercury exposure inthis population.
1. Materials and methods
A cohort of 1057 mother–infant pairs was created by recruiting mothers and
infants from consecutive births between July 2000 and December 2001 at a local
tertiary hospital. All mothers who delivered term infants within this period were
recruited if they consented. This study was approved by the Ethics Committee
on Clinical Research of the Chinese University of Hong Kong.
1.1. Maternal, paternal and neonatal characteristics
The recruited mothers filled in standard questionnaires. Details such as
occupations of the participants and their spouses, type of accommodation and
living environment, complications associated with the pregnancy, cooking and
eating utensils, nutritional habits, presence of dental amalgams, and the use
of alcohol, tobacco, cosmetic creams and herbal remedies were documented.
Newborn crown-heel length, birth weight and head circumference were
measured after birth with standardized equipment and recorded along with the
other neonatal characteristics. In addition, we focused on the mother's dietary
history in a food frequency questionnaire. The frequency, amount and type of
specific food items such as marine and freshwater fish, non-fish seafood, rice,
vegetables, fruits, and meats consumed by the mother during the third trimester
of pregnancy were recorded. The third trimester of pregnancy was chosen as
cord blood mercury concentrations are thought to predominantly reflect mater-
nal mercury exposure during this time (NRC, 2000). Table 1 shows the
commonly available freshwater and marine fish available at Hong Kong wet
markets. To increase the accuracy and reproducibility of the data obtained in the
food frequency questionnaire, two trained interviewers conducted a dietary
survey within 48 h of delivery. Photographs consisting of food items commonly
consumed by the local population in portions of varying sizes were shown to
the mothers to facilitate memory recall. In order to ensure the reliability of
the dietary record, a three-day dietary recall was further obtained from 100
randomly selected mothers for the purposes of crosschecking the available data.
1.2. Measuring hair and blood mercury concentrations
2.5 mL each of maternal and cord blood samples were collected into
mercury-free EDTA bottles at delivery. At least 100 mg of hair was collected
Table 2
Distribution of maternal and cord blood mercury and maternal hair mercury
concentrations (cutpoints for toxicity: 16 nmol/L for maternal blood and
29 nmol/L for cord blood)
Maternal blood
mercury
concentration
Cord blood
mercury
concentration
Maternal hair
mercury
concentration
Total number, N 1057 1057 96
Non-toxic (%) 211 (20.0%) 228 (21.6%) Non-applicable
Toxic (%) 846 (80.0%) 829 (78.4%) Non-applicable
Median, nmol/L 24.6 nmol/L 44.0 nmol/L 1.7 ppm
Interquartile range 18.2, 34.3 nmol/L 31.6, 61.6 nmol/L 1.4, 2.4 ppm
Table 3
Distribution of maternal, paternal and neonatal characteristics
Characteristics (continuous variables) Median Percentiles
25th 75th
Monthly freshwater fish consumption, g 480 200 1050
Monthly marine fish consumption, g 594 200 1362.5
Monthly seafood consumption, g 180 50 400
Maternal age, years 29 25 33
Time In HK of mother, years 21 2 30
Maternal height, m 1.58 1.55 1.62
Maternal weight at labor, kg 65 60 71.2
Gravidity 2 1 3
Parity 1 1 2
Gestation, weeks 39 38 40
Birth weight, g 3234 2975 3485
Crown-heel length, mm 500 485 511
Baby's head circumference, mm 344 336 350
Apgar score at 1 min 9 8 9
Apgar score at 5 min 10 9 10
Characteristics (categorical variables) Category %
Maternal occupation Housewife 58
Working mother 42
Maternal education University 9
Secondary school 85
Primary school or
below
7
Maternal traditional Chinese herbal medicine
consumption
42
Maternal dental amalgam fillings 41
Maternal alcohol consumption 10
Maternal smoking 12
Paternal smoking 40
Paternal alcohol consumption 49
Monthly family income (categorical) b$10000 28
$10,000–$20,000 44
$20,000–$30,000 17
N$30,000 12
Sex of baby Male 53
86 T.F. Fok et al. / Environment International 33 (2007) 84–92
from each mother by cutting her hair close to the hair root from the occipital
area. The hair samples were washed several times over with Triton X-100
detergent, and digested with 1.0 mol/L nitric acid in the CEM MDS-2000
Microwave Digestion System (CEM Corp., Matthews, NC, USA). The total
mercury concentrations of both the hair and blood samples were measured using
the FIMS-400 Flow Injection Mercury System (Perkin Elmer Corp., Norwalk,
CT, USA). Hair specimens from 96 subjects were randomly chosen for maternal
hair mercury determination.
Data from the National Center for Health Statistics show that as total blood
mercury concentrations rise, the fraction of blood mercury that is organic
mercury (predominantly methylmercury) increases. More specifically, of the
female participants of the National Health and Nutrition Examination Survey in
1999 and 2000, greater than 90% of total mercury was estimated to be organic
mercury at total blood mercury concentrations as low as 20 nmol/L (Mahaffey
et al., 2004). A Swedish study differentiating cord blood methylmercury and
inorganic mercury found a median inorganic mercury concentration of less than
2.5 nmol/L even when mothers reported having greater than 10 dental amal-
gams. Amongst this cohort of Swedish women the maximum inorganic mercury
concentration was less than 6 nmol/L (Vahter et al., 2000). In view of these data,
and also because we could not identify any other major source of mercury
exposure in the history such as mercury-containing cosmetic creams, or occu-
pational risk factors, we did not differentiate the species of mercury and assumed
that total whole blood mercury was a reasonable and reliable measure of
methylmercury.
1.3. Statistical analyses
To calculate the average cord to maternal blood mercury concentration ratio
both variables were log-transformed. Themean difference and standard deviation
were back-transformed and used to obtain the geometricmean of cord tomaternal
bloodmercury concentration ratios and its 95% confidence interval. Significance
testing was performed with the paired-sample t-test.
For univariate analyses, the distributions of cord and maternal blood mercury
concentrations were calculated for each category of each maternal, paternal and
neonatal characteristic. For continuous variables, suitable cut-points were arbi-
trarily defined (most variables were divided into four categories using the quartile
values as cut-points, while others such as gestation and Apgar scores were
divided into clinically relevant categories). In view of the skewed data, the cord
and maternal blood mercury concentration results were log-transformed so that
the t-test or ANOVA could be used to compare blood mercury concentrations
between categories within each characteristic.
Although less sensitive to small effects of characteristics on cord blood
mercury concentrations, non-parametric tests (Mann–Whitney U-test and chi-
squared test as appropriate) were also used to analyze the data in terms of toxic
and non-toxic cord blood mercury concentrations. For the purposes of this study
cord bloodmercury concentrationwas defined as toxic or non-toxic using the cut-
point of 29 nmol/L (5.8 μg/L) (Trasande et al., 2005; Rice, 2004; NRC, 2000).
This value was chosen after considering the evidence of neurotoxic effects of low
dose methylmercury exposure from the Faroe Islands (Grandjean et al., 1997),
New Zealand (Crump et al., 1998), Madeira (Murata et al., 2002; Murata et al.,
2004a), and the U.S. (Oken et al., 2005). For each characteristic analyzed, the
data was divided into two groups according to whether the cord blood mercury
concentration was greater than or equal to or less than this dichotomizing value.
For continuous data the medians and 25th and 75th percentiles were calcula-
ted for each group. For categorical data the percentages of toxic and non-toxic
subjects distributed within each characteristicwere calculated. The Mann–
Whitney U-test or chi-squared test were used as appropriate to calculate which
characteristics showed significantly different distributions between these two
groups.
Multivariate linear regression analysis was performed using the character-
istics obtained from univariate analyses (pb0.1) as predictors for both cord and
maternal blood mercury concentrations. Regression models were further refined
using a backward selection method. After log-transformation of the outcome
variables the models met all standard assumptions, such as normality of
residuals, homoscedasticity and independence of predictors. A further analysis
including the natural log-transformed maternal blood mercury concentration as a
predictor of the natural log-transformed cord blood mercury concentration was
performed to identify characteristics that were significantly associated with the
outcome while correcting for maternal blood mercury concentration. For ease of
interpretation, the regression coefficients were converted to percentage change
in outcome per unit change in predictor for all three models. A p-value b0.05
was defined as significant. All tests were two-tailed. SPSS 11.5 for Windows
(SPSS Inc., Chicago, Illinois) was used for the statistical calculations.
2. Results
After the initial mother–infant pairs were recruited, an interim
assessment revealed that 1000 sets of data were needed to achieve 90%
Table 4
Distribution of cord blood mercury concentrations by maternal, paternal and neonatal characteristics (continuous characteristics divided by quartiles defined in Table 3)
Characteristics Categories Median Percentiles p-value
25th 75th
Monthly freshwater fish consumption None 40 20 54 b0.01
b25th percentile 41 29 55
25th to 50th percentile 43 30 60
50th to 75th percentile 48 35 69
N75th percentile 46 34 67
Monthly marine fish consumption None 33 20 48 b0.01
b25th percentile 37 24 52
25th to 50th percentile 42 31 57
50th to 75th percentile 49 35 66
N75th percentile 51 38 74
Monthly seafood consumption None 40 28 55 b0.01
b25th percentile 43 29 61
25th to 50th percentile 41 29 58
50th to 75th percentile 48 34 65
N75th percentile 47 35 68
Maternal alcohol consumption Yes 38 26 52 b0.01
No 45 32 63
Maternal smoking Yes 37 27 55 0.01
No 45 32 62
Maternal traditional Chinese herbal medicine consumption Yes 45 34 64 0.04
No 44 29 60
Maternal dental amalgam fillings Yes 45 33 63 0.08
No 43 30 60
Maternal age b25th percentile 42 28 55 0.01
25th to 50th percentile 43 32 63
50th to 75th percentile 44 33 60
N75th percentile 50 34 67
Maternal time living in HK b25th percentile 42 29 57 0.03
25th to 50th percentile 45 29 61
50th to 75th percentile 44 33 63
N75th percentile 46 35 67
Maternal height b25th percentile 46 30 64 0.01
25th to 50th percentile 46 35 65
50th to 75th percentile 45 33 60
N75th percentile 42 28 57
Maternal weight at labor b25th percentile 42 32 60 0.05
25th to 50th percentile 42 29 60
50th to 75th percentile 47 32 65
N75th percentile 45 32 65
Maternal occupation Housewife 42 29 60 0.01
Working mother 46 34 64
Maternal education Tertiary education 46 33 61 0.20
Secondary school 44 31 61
Primary school or below 46 33 67
Monthly family income (HK dollars) b$10,000 42 29 58 0.02
$10,000–$20,000 44 30 60
$20,000–$30,000 46 35 64
$30,000–$40,000 52 38 66
N$40,000 48 33 77
Gravidity 1 44 32 62 0.21
2 44 32 60
3 46 32 65
4 or more 42 31 58
Parity 1 43 31 60 0.72
2 44 32 62
3 45 32 68
4 or more 47 31 60
Paternal characteristics
Paternal alcohol consumption Yes 44 30 60 0.04
No 45 33 62
Paternal smoking Yes 41 28 58 b0.01
(continued on next page)
87T.F. Fok et al. / Environment International 33 (2007) 84–92
Table 4 (continued)
Characteristics Categories Median Percentiles p-value
25th 75th
Neonatal characteristics
Sex of baby Male 45 32 65 0.05
Female 43 31 59
Gestation b38 weeks 44 34 61 0.69
38 to 39 weeks 43 32 62
39 to 40 weeks 44 30 61
N40 weeks 45 30 63
Neonatal birth weight b25th percentile 43 32 65 0.94
25th to 50th percentile 44 32 59
50th to 75th percentile 43 31 61
N75th percentile 46 31 62
Neonatal crown-heel length b25th percentile 42 32 60 0.41
25th to 50th percentile 43 29 60
50th to 75th percentile 46 31 63
N75th percentile 46 33 64
Neonatal head circumference b25th percentile 42 32 62 0.80
25th to 50th percentile 45 31 59
50th to 75th percentile 45 33 64
N75th percentile 45 30 62
Apgar score at 1 min b8 46 35 66 0.19
8 44 31 59
9 45 31 64
10 42 30 59
Apgar score at 5 min b8 55 36 69 0.28
8 47 36 77
88 T.F. Fok et al. / Environment International 33 (2007) 84–92
power to demonstrate an effect size as small as 0.01 at a 0.05 sig-
nificance level. A total of 1057 mother–infant pairs were therefore
recruited.
Table 5
Differences in distribution of categorical characteristics for infants with non-toxic v
Characteristics Category
Maternal occupation Housewife
Working mothe
Maternal education Tertiary educat
Secondary scho
Primary school
Maternal dental amalgam fillings Yes
No
Maternal alcohol consumption Yes
No
Maternal smoking Yes
No
Paternal alcohol consumption Yes
No
Paternal smoking Yes
No
Monthly family income (HK dollars) b$10,000
$10,000–$20,0
$20,000–$30,0
$30,000–$40,0
N$40,000
Sex of baby Male
Female
Maternal traditional Chinese herbal medicine consumption Yes
No
Geometric mean of cord to maternal blood mercury concentration
ratios was 1.79:1 (95% confidence interval 1.76:1 to 1.82:1, pb0.01).
The Spearman correlation coefficient between cord and maternal blood
s toxic cord blood mercury concentrations
b29 nmol/L ≥29 nmol/L p-value
N % N %
150 66 468 56 0.01
r 78 34 361 44
ion 15 7 75 9 0.04
ol 205 90 692 83
or below 8 4 62 7
79 35 353 43 0.03
149 65 476 57
31 14 70 8 0.01
197 86 759 92
36 16 88 11 0.03
192 84 741 89
127 56 392 47 0.02
101 44 436 53
112 49 306 37 b0.01
116 51 522 63
75 33 219 26 0.01
00 108 47 353 43
00 24 11 154 19
00 11 5 53 6
10 4 50 6
112 49 448 54 0.19
116 51 381 46
79 35 370 45 b0.01
149 65 459 55
Table 6
Differences in distribution of continuous characteristics for infants with non-toxic vs toxic cord blood mercury concentrations
Characteristics b29 nmol/L ≥29 nmol/L p-value
Median Percentiles Median Percentiles
25 75 25 75
Monthly freshwater fish consumption, g 300 90 800 550 209 1139 b0.01
Monthly marine fish consumption, g 265 53 788 700 300 1500 b0.01
Monthly seafood consumption, g 150 26 300 200 60 410 b0.01
Maternal age, years 28 24 32 29 26 33 b0.01
Maternal time living in HK 19 1 27 22 2 30 b0.01
Gravidity 2 1 3 2 1 3 0.65
Parity 1 1 2 1 1 2 0.37
Gestation, weeks 39 38 40 39 38 40 0.08
Neonatal birth weight, g 3248 3010 3504 3225 2975 3478 0.88
Neonatal crown-heel length, mm 500 489 510 500 485 512 0.83
Neonatal head circumference, mm 344 337 351 344 336 350 0.84
Apgar score at 1 min 9 8 9 9 8 9 0.21
Apgar score at 5 min 10 9 10 10 9 10 0.08
Maternal height, m 1.58 1.55 1.63 1.58 1.55 1.62 0.17
Maternal weight at labor, kg 64.3 60.2 71.4 65.4 60.0 71.2 0.52
Table 7
Multivariate linear regression model using natural log-transformed cord blood
mercury concentration as outcome, adjusted for maternal blood mercury
concentration (R2=0.745)
Characteristics % increase in outcome per unit change in
characteristic
% increase 95% CI p-value
Monthly freshwater fish
consumption, kg
1.18% 0.10%, 2.28% 0.03
Monthly marine fish
consumption, kg
2.23% 1.35%, 3.13% b0.01
Maternal alcohol consumption −6.18% −0.56%, −12.11% 0.03
Maternal age, years −0.40% −0.10%, −0.70% 0.01
Sex of baby (female vs male) −4.31% −7.31%, −1.22% 0.01
Ln (maternal blood
mercury concentration)
0.83%a 0.79%, 0.86%a b0.01
a % change in outcome per % change in predictor.
89T.F. Fok et al. / Environment International 33 (2007) 84–92
mercury concentration was 0.843, pb0.01. Table 2 summarizes the
distributions of cord and maternal blood mercury concentrations, and
maternal hair mercury concentrations. Blood mercury concentrations
were defined as toxic or non-toxic using the dichotomizing values of
29 nmol/L for cordblood and 16 nmol/L (calculated using the cord to
maternal mercury concentration ratio of 1.79:1) for maternal blood.
None of the women participating in our study exhibited any clinical
features of mercury toxicity. As can be seen, 78.4% of the offspring in
this cohort were exposed to cord blood concentrations ≥29 nmol/L.
This was in agreement with the maternal hair mercury results, most of
which were greater than 1.2 ppm (interquartile range 1.4 to 2.4 ppm).
Median total maternal monthly fish consumption for this cohort was
1300 g (interquartile range 600 to 2502 g). The other maternal, paternal
and neonatal characteristics are shown in Table 3.
Table 4 illustrates the distributions of cord blood mercury con-
centrations within each of the maternal, paternal and neonate
characteristics investigated. Cord blood mercury concentrations
significantly increase with increasing consumption of freshwater fish,
marine fish and seafood (pb0.01). Characteristics associated with
decreased cord blood mercury concentrations include maternal and
paternal alcohol consumption, maternal and paternal smoking, and
female sex of the baby. Increasing maternal age, increasing time mother
had lived in Hong Kong, decreasing maternal height, increasing
maternal weight, working mothers, increasing family income and use
of traditional Chinese herbal medicine all showed significantly in-
creased cord blood mercury concentrations. Characteristics not signi-
ficantly associated with cord blood mercury concentration included
maternal education level, maternal dental amalgams, and, apart from
sex of baby, all neonatal characteristics. The distributions of maternal
blood mercury concentrations within the characteristics showed similar
patterns to cord blood (data not shown). There were, however, notable
exceptions, such as lack of association with sex of baby, maternal age
and maternal height. Of note was the lack of a significant association
between maternal blood mercury concentrations and number of
maternal dental amalgams.
Tables 5 and 6 show the distribution of toxic versus non-toxic cord
blood mercury concentrations for each characteristic using the dichot-
omizing value of 29 nmol/L. The results are qualitatively in agreement
with the results shown in Table 4. However with this analysis, the
presence or absence of maternal dental amalgams and level of maternal
education are significantly associated with whether the cord blood
mercury concentrations are toxic or not.
Several of the characteristics that were statistically significant
according to the univariate analyses, were no longer significant when
analyzed by multivariate linear regression analysis (Table 7). In-
creasing freshwater and marine fish consumption were significantly
associated with both increased cord (2.86%/kg, p=0.01 and 5.09%/
kg, pb0.01 respectively) and maternal blood mercury concentrations
(2.45%/kg, p=0.02 and 3.31%/kg, pb0.01 respectively). The effect
of fish consumption on cord blood mercury concentrations remained
even after correction by maternal blood mercury concentrations
(1.18%/kg and 2.23%/kg). Increasing seafood consumption was
associated with increased blood mercury concentrations, but was only
statistically significant with cord (8.42%/kg, p=0.02), not maternal
blood (6.91%/kg, p=0.07). Increasing maternal age was significant-
ly associated with increasing cord blood mercury concentrations
(0.72%/year, p=0.02) even when corrected by maternal blood mer-
cury concentrations (0.4%/year, p=0.01). Decreasing maternal height
90 T.F. Fok et al. / Environment International 33 (2007) 84–92
and increasing maternal weight were both associated with increased
maternal blood mercury concentrations (−62.36%/m, pb0.01 and
0.66%/kg, pb0.01 respectively). However, they are no longer
associated with cord blood mercury concentrations when corrected
for by maternal blood mercury concentration. Maternal alcohol
consumption and paternal smoking were associated with decreased
maternal blood mercury concentrations (−12.07%, p=0.04 and
−10.04%, pb0.01 respectively). The effect of paternal smoking
was insignificant after correction while the effect of maternal alcohol
consumption remained significant. Female sex was associated with
lower cord blood mercury concentrations and was statistically
significant after correction by maternal blood mercury concentrations
(−4.31%, p=0.01).
3. Discussion
In this study pregnant women consume relatively large
amounts of fish compared with other populations. For example,
while our cohort of pregnant women had a mean monthly fish
consumption of 2012 g (median 1300 g), a North American
cohort (Mahaffey et al., 2004) of women of childbearing age
had a mean consumption of just 56 g of fish per month. As
expected, the median blood mercury concentrations of our
cohort of mothers (median 24.6 nmol/L, 95th percentile
51.2 nmol/L) were higher than this American cohort (median
4.7 nmol/L, 95th percentile 35.5 nmol/L). This means that a
substantial proportion of the local population is at risk from
low-dose methylmercury exposure.
Consistent with similar studies (Stern and Smith, 2003;
Vahter et al., 2000), the cord blood mercury concentrations were
significantly higher than the corresponding maternal blood
mercury concentrations. The average increase of cord blood
mercury concentrations by a factor of 1.79 could not be fully
explained by the increased packed cell volume of the infant
(average hematocrit 1.3 times that of the mother). Therefore,
although the large consumption of fish in our local population is
unlikely to give rise to methylmercury toxicity in adults, the
shift towards higher, albeit asymptomatic, maternal blood
mercury concentrations has pushed the prenatal methylmercury
exposure of a large number of fetuses into a range associated
with increased risk of neurodevelopmental impairment. More
specifically this ratio has implications on whether the reference
dose for methylmercury suggested by the US EPA (which
assumes a cord to maternal blood mercury ratio of 1:1) is
directly applicable to our population (Stern and Smith, 2003;
Rice et al., 2003).
There is ample evidence in the literature that increased ma-
ternal fish consumption increases fetal exposure to methylmer-
cury (Mahaffey et al., 2004; Oken et al., 2005; Sato et al., 2006).
Our study confirms this and quantifies the relationship between
maternal fish consumption and fetal methylmercury exposure
for our population. In particular, in this locality, freshwater fish
consumption is associated with less of an increase in cord blood
mercury concentrations than marine fish consumption (Table 7).
Part of the difficulty in controlling methylmercury intake by
limiting fish intake is the potential benefits of dietary fish (Oken
et al., 2005). Therefore in our population, it would be prudent
for pregnant women to choose freshwater fish over marine fish
in order to enjoy the benefits of dietary fish while trying to
minimize methylmercury exposure.
This study shows that most of the cohort, and probably most
of the local population suffers from low-dose prenatal methyl-
mercury exposure. The long-term effects of methylmercury
exposure in this population must therefore be further studied.
The data provided here can serve as an important foundation for
such outcome studies. With data from such further studies we
will be able to more appropriately advise our population, in
particular pregnant women, the quantity and types of fish to
consume.
There are important gender-related differences with regard to
the effects of mercury exposure. Investigators studying the
effects of prenatal methylmercury exposure in Iraq found that
male infants suffered worse complications from mercury ex-
posure than did female infants (Myers et al., 1998). A retro-
spective study of births in Minamata City during the 1950s, a
time when methylmercury pollution was at its worst, revealed a
decrease in the proportion of male livebirths, and an increase in
the proportion of male stillbirths (Sakamotoet al., 2001). A
Canadian study found that prenatal methylmercury exposure
correlated with abnormal tendon reflexes in boys, but not in
girls (McKeown-Eyssen et al., 1983). Our finding that male
infants have slightly increased cord blood mercury concentra-
tions when adjusted by maternal blood mercury concentrations
suggests that male fetuses accumulate more mercury than
female fetuses from their mothers. This tendency for male
subjects to accumulate significantly more mercury has been
alluded to in previous studies. For example a study in Hong
Kong found that men had an average of 60% higher hair
mercury concentrations than women (Dickman et al., 1998) and
differences between male and female subjects in the metabolism
and rate of elimination of methylmercury have been suggested
before (ATSDR, 1999). It has been observed that there is limited
distribution of methylmercury to fatty tissue (Vahter et al.,
1994). It is possible that the differential accumulation of whole
blood mercury between the sexes in humans is related at least
in part to differences in fat composition. In a previous study
cohort, geometric mean cord blood mercury concentration was
greater in boys than girls, although the difference was not
statistically significant (Grandjean et al., 1997). Many other
studies of low-dose toxic effects of methylmercury used ma-
ternal hair mercury as the biomarker of exposure (Myers et al.,
2003; McKeown-Eyssen et al., 1983; Oken et al., 2005; Crump
et al., 1998), and therefore cannot help answer the question of
whether male fetuses accumulate more mercury from the
mother and whether or not they are more sensitive to the toxic
effects of methylmercury. Further investigation into this issue is
therefore warranted.
The older, heavier or shorter the mother, the higher the cord
and maternal blood mercury concentrations were. The associa-
tions between maternal height and weight and cord blood
mercury concentrations are not statistically significant after
adjustment by maternal blood mercury concentrations. It is
possible that the association between blood mercury concentra-
tions and age, height and weight may at least be partly explained
by differences in fat distribution. Maternal age is not
91T.F. Fok et al. / Environment International 33 (2007) 84–92
significantly associated with maternal blood mercury concen-
trations, but is with cord blood mercury concentrations even
after adjustment. This suggests that maternal age may affect the
process of transfer of methylmercury from the mother to the
fetus.
The associations between maternal alcohol consumption and
decreased cord and maternal blood mercury concentrations
were substantial. The effect on cord blood was significant even
after adjustment by maternal blood mercury concentration
(6.18% reduction, p=0.03). Despite alcohol's effect on blood
mercury concentrations, its overall effect on fetal methylmer-
cury toxicity is not clear as some studies show that the presence
of alcohol can increase the toxic effects of mercury in animal
models (NRC, 2000). An outcome study using these data will
be required to evaluate the overall impact of maternal alcohol
consumption.
The mechanism of the association between paternal smoking
and a decrease in blood mercury concentrations is unclear.
However, the association with cord blood disappears after
adjustment by maternal blood mercury concentration. This
suggests that paternal smoking is associated with decreased
maternal blood mercury concentration, but not directly with
cord blood mercury concentration.
In summary, this study does not show any strong reason to
doubt the applicability of results from established literature to
our population. A large proportion of infants in our population
(78.4%) are exposed prenatally to levels of mercury that is
shown to be associated with both neurodevelopmental impair-
ment (Steuerwald et al., 2000; Grandjean et al., 1997; Oken et
al., 2005; NRC, 2000) and cardiovascular effects (Grandjean et
al., 2004). In order to decrease the risk of prenatal mercury
exposure, pregnant women should be advised to consume ap-
propriate amounts and types of fish. Until further large-scale
studies are performed, the US EPA reference dose of 0.1 μg/kg/
day should be followed. For pregnant women in Hong Kong
freshwater fish should be chosen over marine fish in order to
reap the benefits of dietary fish while limiting the risk of
increasing fetal methylmercury exposure.
Acknowledgement
This study was funded by a grant from the Health Services
Research Committee, Hong Kong SAR, China.
References
Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological
profile for mercury. Atlanta, GA: U.S. Department of Health and Human
Services, Public Health Service; 1999.
Clarkson TW, Strain JJ. Nutritional factors may modify the toxic action of methyl
mercury in fish-eating populations. J Nutr 2003;133(5 Suppl 1):1539S–43S.
Clarkson TW, Magos L, Myers GJ. The toxicology of mercury—current
exposures and clinical manifestations. N Engl J Med 2003;349(18):1731–7.
Counter SA, Buchanan LH. Mercury exposure in children: a review. Toxicol
Appl Pharmacol 2004;198(2):209–30.
Crump KS, Kjellstrom T, Shipp AM, Silvers A, Stewart A. Influence of prenatal
mercury exposure upon scholastic and psychological test performance:
benchmark analysis of a New Zealand cohort. Risk Anal 1998;18
(6):701–13.
Davidson PW, Myers GJ, Weiss B. Mercury exposure and child development
outcomes. Pediatrics 2004;113(4 Suppl):1023–9.
Dickman MD, Leung CK, Leong MK. Hong Kong male subfertility links to
mercury in human hair and fish. Sci Total Environ 1998;214:165–74.
Elhassani SB. The many faces of methylmercury poisoning. J Toxicol Clin
Toxicol 1982;19(8):875–906.
Food and Environmental Hygiene Department Hong Kong Special Admin-
istrative Region (FEHD). Chemical hazard evaluation—dietary exposure
to heavy metals of secondary school students. Risk Assessment Studies,
vol. 10B; 2002.
Grandjean P, Weihe P, White RF, Debes F, Araki S, Yokoyama K, et al. Cognitive
deficit in 7-year-old children with prenatal exposure to methylmercury.
Neurotoxicol Teratol 1997;19(6):417–28.
Grandjean P, Murata K, Budtz-Jorgensen E,Weihe P. Cardiac autonomic activity
in methylmercury neurotoxicity: 14-year follow-up of a Faroese birth cohort.
J Pediatr 2004;144(2):169–76.
Harada M. Minamata disease: methylmercury poisoning in Japan caused by
environmental pollution. Crit Rev Toxicol 1995;25(1):1-24.
Harada M, Akagi H, Tsuda T, Kizaki T, Ohno H. Methylmercury level in
umbilical cords from patients with congenital Minamata disease. Sci Total
Environ 1999;234(1–3):59–62.
Ip P, Wong V, Ho M, Lee J, Wong W. Environmental mercury exposure in
children: South China's experience. Pediatr Int 2004;46(6):715–21.
Joint Food and Agriculture Organization of the United Nations/World Health
Organization Expert Committee on Food Additives (JEFCA). Summary and
conclusions of the sixty-first meeting—food additives and contaminants.
Rome; 2003.
Mahaffey KR, Clickner RP, Bodurow CC. Blood organic mercury and dietary
mercury intake: National Health and Nutrition Examination Survey, 1999
and 2000. Environ Health Perspect 2004;112(5):562–70.
McKeown-Eyssen GE, Ruedy J, Neims A. Methyl mercury exposure in northern
Quebec. II. Neurologic findings in children. Am J Epidemiol 1983;118
(4):470–9.
Murata K, Budtz-Jorgensen E, Grandjean P. Benchmark dose calculations for
methylmercury-associated delays on evoked potential latencies in two
cohorts of children. Risk Anal 2002;22(3):465–74.
Murata K, Sakamoto M, Nakai K, Weihe P, Dakeishi M, Iwata T, et al. Effects of
methylmercury on neurodevelopment in Japanese children in relation to the
Madeiran study. Int Arch Occup Environ Health 2004a;77(8):571–9.
Murata K, Weihe P, Budtz-Jorgensen E, Jorgensen PJ, Grandjean P. Delayed
brainstem auditory evoked potential latencies in 14-year-old children
exposed to methylmercury. J Pediatr 2004b;144(2):177–83.
Myers GJ, Davidson PW, Shamlaye CF. A review of methylmercuryand child
development. Neurotoxicology 1998;19(2):313–28.
Myers GJ, Davidson PW, Cox C, Shamlaye CF, Palumbo D, Cernichiari E, et al.
Prenatal methylmercury exposure from ocean fish consumption in the
Seychelles child development study. Lancet 2003;361(9370):1686–92.
National Research Council (NRC). Toxicological effects of methylmercury.
Washington, DC: National Academy Press; 2000.
Oken E, Wright RO, Kleinman KP, Bellinger D, Amarasiriwardena CJ, Hu
H, et al. Maternal fish consumption, hair mercury, and infant cognition in
a U.S. cohort. Environ Health Perspect 2005;113(10):1376–80.
Parsons EC. Trace metal pollution in Hong Kong: implications for the health of
Hong Kong's Indo-Pacific hump-backed dolphins (Sousa chinensis). Sci
Total Environ 1998;214:175–84.
Rice DC. The US EPA reference dose for methylmercury: sources of uncertainty.
Environ Res 2004;95(3):406–13.
Rice DC, Schoeny R, Mahaffey K. Methods and rationale for derivation of a
reference dose for methylmercury by the U.S. EPA. Risk Anal 2003;23
(1):107–15.
Sakamoto M, Nakano A, Akagi H. Declining Minamata male birth ratio
associated with increased male fetal death due to heavy methylmercury
pollution. Environ Res 2001;87(2):92–8.
Sato RL, Li GG, Shaha S. Antepartum seafood consumption and mercury levels
in newborn cord blood. Am J Obstet Gynecol 2006;194(6):1683–8.
Stern AH, Smith AE. An assessment of the cord blood:maternal blood
methylmercury ratio: implications for risk assessment. EnvironHealth Perspect
2003;111(12):1465–70.
92 T.F. Fok et al. / Environment International 33 (2007) 84–92
Steuerwald U, Weihe P, Jorgensen PJ, Bjerve K, Brock J, Heinzow B, et al.
Maternal seafood diet, methylmercury exposure, and neonatal neurologic
function. J Pediatr 2000;136(5):599–605.
Trasande L, Landrigan PJ, Schechter C. Public health and economic
consequences of methyl mercury toxicity to the developing brain. Environ
Health Perspect 2005;113(5):590–6.
Vahter M, Mottet NK, Friberg L, Lind B, Shen DD, Burbacher T.
Speciation of mercury in the primate blood and brain following long-
term exposure to methyl mercury. Toxicol Appl Pharmacol 1994;124
(2):221–9.
Vahter M, Akesson A, Lind B, Bjors U, Schutz A, Berglund M. Longitudinal
study of methylmercury and inorganic mercury in blood and urine of
pregnant and lactating women, as well as in umbilical cord blood. Environ
Res 2000;84(2):186–94.
	Fetal methylmercury exposure as measured by cord blood mercury concentrations in a mother–infan.....
	Materials and methods
	Maternal, paternal and neonatal characteristics
	Measuring hair and blood mercury concentrations
	Statistical analyses
	Results
	Discussion
	Acknowledgement
	References