The neurotoxicity of methylmercury has been demonstrated
by serious poisoning episodes. Although the most severe toxicity was apparently
due to prenatal methylmercury exposure, poisoning cases in Minamata were
also documented in infants who had been exposed to methylmercury only after
birth (
1). In Iraq, human milk was the suspected source of methylmercury
exposure of several poisoned infants (
2). Human milk contains mercury,
partly in the form of methylmercury, and the mercury concentration in milk
is proportional to that in maternal blood (
3-
5). Experimental
evidence in rodents suggests that considerable transfer of mercury to pups
may occur through milk from methylmercury-exposed dams (
6,
7).
However, the public health significance of methylmercury transfer through
human milk is unclear.
The retention of methylmercury in humans is reflected by the mercury
concentrations in scalp hair (8). Mercury concentration profiles
in hair from adult poisoning victims suggest an average elimination half-life
of 70 days after cessation of methylmercury exposure (3). In nursing
mothers, the half-life may be as short as 45 days (2), perhaps due
to considerable excretion of mercury in the milk. In a small number of infants
exposed to methylmercury in utero during the poisoning episode in
Iraq, postnatal decrease of mercury concentrations in hair was very slow;
this slow decrease was thought to be due to continued exposure from the
milk (9).
According to experimental studies, methylmercury elimination depends
on the presence of demethylating bacteria in the gut (10,11).
These bacteria tend to become established after weaning and then metabolize
methylmercury from the bile into mercuric ions that are eliminated with
the feces; unconverted methylmercury is reabsorbed from the gut. Thus, as
long as the infant is nursing, mercury elimination is likely to be limited.
In vitro studies have demonstrated that demethylation may also occur
by the action of rat liver microsomes (12), but whether similar reactions
occur in humans is unknown.
Evidence from poisoning episodes (8) and a small population study
in New Zealand (13) suggests that methylmercury exposure may cause
neurobehavioral damage to the fetus at exposures corresponding to a maternal
hair mercury level above about 10 µg/g. In some fishing communities,
this limit may be exceeded, as recorded in the Faroe Islands where the mercury
concentrations in maternal hair or in umbilical cord blood were above the
safe limit in approximately one out of every five births (14). The
Faroe Islands are located in the North Atlantic between Scotland and Iceland,
and the population of about 45,000 relies to a large extent on seafood,
including pilot whale, which has a high mercury concentration. If the meat
from locally caught whales was evenly distributed to the whole Faroese population,
the annual catch would, during some years, represent a mercury intake above
the World Health Organization/Food and Agriculture Organization (WHO/FAO)
provisional tolerable weekly intake (PTWI) for the whole population (15).
Thus, the available evidence suggests that mercury transfer from human
milk may be of relevance, but its toxicokinetic behavior in small children
is poorly known. Due to the neurotoxic potential of methylmercury, these
factors may be of importance for risk assessments. We therefore conducted
a study of mercury burdens at about 12 months of age in Faroese children
that had been breast-fed for different lengths of time or not at all.
A cohort was identified from consecutive deliveries from 1 March 1986
to the end of 1987 at all three Faroese hospitals in Tórshavn, Klaksvik,
and Suderoy. During the active sampling period, we obtained questionnaire
data and samples of umbilical cord blood and maternal hair for mercury analysis
from 1022 singleton births (75.1% of all deliveries) (14). (One mother
first included in the cohort was not a permanent resident of the Faroe Islands
and was subsequently excluded.) The study protocol was approved by the regional
ethical review committee.
As an integral part of the Faroese health care system, families with
small children are visited by district health nurses. For children belonging
to the birth cohort, the nurses filled out a questionnaire on developmental
data and, at about 1 year of age, a hair sample was collected. Breast-feeding
was separated into two periods: one in which the infant received maternal
milk only, and a subsequent period where formula and/or baby food was added
to the diet.
We obtained questionnaire information and a hair sample sufficient for
analysis from 583 children (57.0% of the cohort). Hair samples of at least
100 mg were cut with a pair of scissors close to the root in the occipital
area of the head; the hair was tied with a plastic clamp and saved in a
small, marked plastic bag. For 557 children (95.6%), hair collection took
place at 12 months of age; the rest of the samples (N = 26) were
collected about 1-2 months before or after this date, depending on the scheduling
of the nurse's visits. The length of the hair collected was generally 2-3
cm, and the sample was analyzed in toto.
The children included in the study were mainly characterized by their
residence in districts served by nurses and the willingness and need of
the mother to receive the nurse at home during the first year after the
child's birth. Thus, the children may not necessarily reflect the average
for the Faroe Islands. No district health nurse was available at Suderoy
during the study period, and the coverage in the Tórshavn area was
incomplete (36.6%) as compared to other districts where questionnaire data
and hair samples were obtained from 432 (78.3%) of the children. Based on
mercury concentrations in maternal hair at the time of delivery, the prenatal
mercury exposures were slightly higher in the children who were visited
by a nurse during the first year of life than in those who were not (Table
1). This difference can be explained by the higher intake of whale meat
outside Tórshavn.
To determine mercury concentrations in the children's hair, we placed
an accurately weighed hair sample of 0.01-0.1 g in a poly(tetrafluoroethylene)-lined
digestion vessel before microwave digestion and preparation as described
by Pineau et al. (16). Mercury analysis in duplicate was performed
by flow-injection cold-vapor atomic absorption spectrometry (Perkin-Elmer
model 5100 with FIAS-200 and AS-90). The detection limit for the dissolved
sample was estimated to be 0.20 µg/l, i.e., three times the standard
deviation of the blank. The total analytical imprecision was estimated to
be 12.2, 6.8, and 4.6% at mercury concentrations of 0.24, 0.66, and 11.9
µg/g, respectively. The accuracy of the mercury determinations in
human hair was ensured by using the certified reference material CRM 397
(BCR, Brussels, Belgium) and powdered hair HH-1 (IAEA, Vienna, Austria)
(17) as quality control materials; the mercury concentrations of
these samples averaged 11.9 µg/g and 1.6 µg/g, respectively
(assigned values, 12.3 ± 0.5 µg/g and 1.7 µg/g). All
results were converted to SI units, where 1.0 µg = 5.0 nmol.
All mercury concentration data conformed with a Gaussian distribution
after logarithmic transformation. Other parameters required the use of nonparametric
statistical methods. Nursing periods were split approximately according
to the quartiles, and dummy variables were made for the regression analyses.
We performed all calculations using SPSS-PC software (Chicago).
The mercury concentration in the infants' hair showed a geometric mean
of 5.5 nmol/g and a maximum of 44.1 nmol/g. The mercury concentration in
the infant hair correlated with that in maternal hair at the time of delivery
(r = 0.38, p < 0.0001) and with that in umbilical cord
blood (r = 0.41, p < 0.0001) (logarithmic transformations).
Results from Japan (18) suggest that, at the time of birth, the mercury
concentration in the hair of the baby would probably be similar to that
of the mother. In this study, however, the concentration in the child's
hair at 1 year of age was only about 25% (geometric mean) of that of the
mother at the time of delivery. A total of 79 of the maternal hair samples
(13.6%) contained a mercury concentration above the 50 nmol/g (10 µg/g)
limit, but the mercury concentration in hair from these children at 1 year
of age showed a geometric mean of only 9.1 nmol/g, the mean ratio between
the mercury concentrations in child and mother being 0.13.
Most of the infants (97.4%) were nursed for at least a month. Fifteen
were not nursed at all. Human milk was the sole source of nutrition for
a median of 4 months; 18 children (3.1%) were fed human milk exclusively
for more than 6 months. At 12 months, 160 children (27.4%) were still being
nursed, but all of these children also received other food at that time.
The median time interval from the full termination of breast-feeding to
the collection of the hair sample (weaning-sampling interval) was 5 months.
For quartile groups of nursing periods, the mercury concentrations of
the infants' hair are shown in Table 2. Those nursed throughout the first
year showed the highest geometric mean (9.0 nmol/g). For comparison, those
children not nursed at all (N = 15) showed a geometric mean of 3.0
nmol/g.
Both the period where nursing was the only source of nutrition and the
period where human milk was supplemented with other food contributed to
the mercury concentration in the child's hair (Fig. 1). In a multiple regression
analysis where the logarithm of the mercury concentration was the dependent
variable, breast-feeding without supplements for at least 4 months was a
significant predictor (Table 3). Adjustment for the length of continued
nursing with supplementary food caused only small changes in the regression
coefficients (Table 3). The total duration of the breast-feeding period
was not a better predictor than the period where no supplement was given.
Figure 1. Mercury concentration in hair of
583 12-month-old infants in relation to the length of the nursing period.
The mercury concentrations are given as geometric means. The duration of
breast-feeding has been separated into the period where breast milk constituted
the full diet (horizontal scale) and the period where the diet included
other food (right-hand scale). Each of these periods has been split into
four groups according to the quartiles.
The correlation with nursing time could, at least in part, be due to
an effect of the milk diet on the infant's ability to excrete methylmercury,
as suggested above. According to this hypothesis, elimination of methylmercury
previously absorbed would then begin to increase during the weaning-sampling
interval. The weaning-sampling time interval was therefore entered as an
independent parameter in the multiple regression analyses (Table 3). The
regression coefficients for this parameter were relatively small and barely
reached statistical significance. However, the inverse relationship between
the weaning-sampling interval and the duration of breast-feeding makes these
calculations difficult to interpret.
A similar analysis was therefore conducted using the data for the 239
children who had been nursed for no more than 5 months, as the length of
breast-feeding was only weakly associated with the mercury concentration
in hair in this subgroup at 1 year of age (geometric mean, 3.6 nmol/g) (Fig.
1). All but 11 of the hair samples were obtained at 12 months of age. As
expected, the mercury concentration in the hair of these infants strongly
correlated with the mercury concentrations in both maternal hair (r
= 0.40, p < 0.0001) and cord blood (r = 0.49, p
< 0.0001) (logarithmic transformations). However, it remained independent
of the weaning-sampling time interval (Spearman's rs =
-0.06; p = 0.35) (Fig. 2). No elimination half-life could therefore
be estimated. The duration of nursing was not related to prenatal mercury
exposure. Accordingly, adjustment for maternal hair mercury concentration
at delivery produced only small changes in the regression equations (Table
3). Finally, the regression analyses showed almost identical results when
carried out only for the slightly smaller group of 432 children from the
districts with the most complete sampling (data not shown).
Figure 2. Mercury concentration in hair of
12-month-old infants who had been nursed no more than 5 months in relation
to the time interval between weaning and hair sample collection. The mercury
concentrations are shown as geometric means and interquartile ranges. The
number of children in each group is given below the bar.
The high methylmercury exposure in the Faroe Islands is due to the seafood
diet, especially the consumption of pilot whale meat (14). The average
mercury concentration in whale meat is about 3 µg/g, half of which
is in the form of methylmercury (15). The group of children studied
is not quite a representative sample from the original birth cohort (Table
1). However, findings based on the children that constitute 57% of the cohort
are similar to those seen in the subgroup that represents 78% of the children
born to mothers residing in the northern islands. Thus, selection factors
do not appear to affect the toxicokinetic patterns revealed in this study,
and the increased mercury retention in the infant related to breast-feeding
could reflect a general pattern.
The mercury concentration in a child's hair at 1 year of age was much
lower than that in the maternal hair at the time of delivery. As the mercury
concentration in the newborn is expected to match the mercury concentration
in the mother's hair (18), a considerable decrease must have taken
place. During the first year, the weight of the infants tripled, and the
expanded distribution space may have contributed to this decrease. Also,
increases in hair growth rate (19) and changes in hair structure
during infancy (20) may have played a role. The relative significance
of these factors is unknown at present, and methylmercury retention in the
infants can therefore only be evaluated on a relative scale.
Compared to mercury concentrations in the hair of 1-year-old children
who had not been nursed, the concentration doubled when breast-feeding lasted
at least 6 months, and a three-fold increase occurred in those nursed throughout
the first year of life (Table 2, Fig. 1). The length of nursing was independent
of the maternal mercury burden. Accordingly, the increased retention of
methylmercury in the infants who were breastfed for the longest period must
be due to increased uptake and/or decreased excretion of this compound.
Mercury concentrations in human milk correspond to about 8% of the concentration
in whole blood (3,4), but some of the mercury occurs as mercuric
ions (2,5). As the median cord blood mercury concentration
is about 120 nmol/l (24 µg/l) in the Faroese cohort (14), an
average concentration in milk of about 10 nmol/l (2 µg/l) would be
expected. Limited analyses are in general agreement with this calculation
(unpublished data). The safety of methylmercury exposure from human milk
can be estimated from the WHO/FAO PTWI limit of 0.3 mg of total mercury
for an adult, i.e., a daily dose of about 0.6 µg per kg body weight.
The average milk intake during the nursing period is about 125 ml/kg body
weight/day (21). Without taking into account possible differences
in susceptibility to methylmercury exposure, the PTWI would then correspond
to a milk mercury concentration of 24 nmol/l (4.8 µg/l). The data
on maternal blood-mercury concentrations in the Faroes (14) suggest
that this limit will be exceeded in one out of eight mothers in the Faroe
Islands. Published data on mercury in human milk include averages of 3 µg/l
(15 nmol/l) in Sweden (5), 3.6 µg/l (18 nmol/l) in Japan (18),
and 7.6 µg/l (38 nmol/l) in coastal Alaska (22). In Italy (23)
and Slovenia (24), single samples of human milk have shown mercury
concentrations above the level corresponding to the PTWI. Thus, in several
parts of the world, infants may be exposed to considerable amounts of mercury
through human milk.
Although adults can eliminate methylmercury after intestinal demethylation,
infants may not have this ability due to the absence of demethylating bacteria
in the gut (10,11). Exactly when such bacteria colonize the
gut is unknown, and interindividual variation could be considerable. Also,
although liver microsomes may well induce demethylation (12), the
possible significance of this potential in infants is unclear. Had the Faroese
infants been capable of demethylating the methylmercury, in particular after
weaning, then elimination of methylmercury would presumably have been reflected
in the mercury concentrations. A decrease in mercury concentration of hair
should then be apparent as a function of the time interval from weaning
to hair sampling (Fig. 2). The regression analyses failed to document any
change in mercury in hair in relation to time intervals from 7 to 12 months.
Figure 1. Mercury concentration in hair of 583 12-month-old infants in relation
to the length of the nursing period. The mercury concentrations are given
as geometric means. The duration of breast-feeding has been separated into
the period where breast milk constituted the full diet (horizontal scale)
and the period where the diet included other food (right-hand scale). Each
of these periods has been split into four groups according to the quartiles.
In interpreting this finding, two caveats must be considered. While seafood
would not normally be included in baby food, some infants may have received
small, though probably insignificant, amounts of methylmercury from sources
other than human milk. More importantly, account must be taken of the fact
that the hair strands analyzed were generally 2-3 cm long. With a hair growth
rate of 0.5-1 cm per month (19), each sample represented a period
of approximately 3-4 months before hair sampling. Nonetheless, an elimination
half-life of 70 days, as seen in adults (3), would be extremely unlikely,
given the data shown in Figure 2.
Thus, the findings of this study could be explained by a considerable
absorption of methylmercury from human milk and a slow or absent elimination
of this compound during the first year of life. These toxicokinetic factors
are of considerable importance in the risk assessment for methylmercury.
Although prenatal exposures seem most dangerous, continued exposure to methylmercury
during the early postnatal period can adversely affect the nervous system
(1,2,8). However, the dose-response relationship has
not yet been worked out.
As human milk in some communities may constitute an important exposure
source for methylmercury, the implications for nursing practices should
be considered. In this regard, the unquestionable benefits of nursing must
be recognized (25). Thus, potential methylmercury exposures should
preferably be prevented by means other than advising against breast-feeding,
at least with regard to the first 6 months or so. Skerfving (5) recommended
that both pregnant and lactating women should refrain from eating fish contaminated
with methylmercury. However, for the individual consumer, fish high in mercury
may not necessarily be easy to separate from fish that is safe, and a general
warning against all seafood would seem difficult to defend. The health authorities
in the Faroe Islands currently advise pregnant women to avoid eating pilot
whale. As pilot whale is the main source of methylmercury exposure in the
Faroes (14), the present study would suggest that this recommendation
should also refer to the breast-feeding period. In communities where substantial
mercury exposure from seafood is difficult to prevent by such recommendations
or by pollution abatement, the prudence of prolonged nursing, i.e., beyond
6 months, may need to be considered.