developmental exposures to environmental chemicals have become an important public health concern because of their possible toxic impact on sensitive development and programming of organ functions ( 1 ) .
unfortunately , the degree to which different persistent pollutants pass from the mother to the child is only partially known ( 2 ) .
thus , the partition between maternal and fetal tissues is of importance to the risk assessment of environmental chemicals and to selection of samples for biological monitoring .
cord blood has the advantage of being a noninvasive sample and has been used for assessing exposure to a variety of metals and organohalogen compounds ( 38 ) . while collecting the umbilical cord
is easy , this tissue has been utilized only occasionally for exposure assessment , e.g. , for methylmercury ( 9 ) . despite a low lipid content ,
the placenta is a more complex tissue , because of its mixed maternal / fetal origin , thus ideally requiring removal of the maternal part before chemical analysis ( 7,13 ) .
finally , human milk concentrations reflect the maternal body burden as well as the nursing infant s lactational exposure ( 7,17,18 ) . the relation between concentrations of environmental chemicals in maternal and fetal tissues and tissue fluids , and the conversion factors for concentrations in commonly used samples
previous studies of paired samples suggest that organohalogen pollutant concentrations , when expressed on a lipid basis , tend to be somewhat higher in milk than in maternal serum , which again contains higher levels than umbilical cord serum ( 6,1925 ) . while the distribution may depend on the molecular weight of the compound , molecular size , differences in lipophilicity , and affinities to biological molecules ( 26 ) , the overall effect of the physicochemical properties is difficult to predict .
the present study therefore aimed at determining the extent to which important environmental chemicals follow similar partitions between media frequently used for biological monitoring purposes .
we collected paired motherchild samples to measure the concentrations of 87 environmental chemicals , including 20 polychlorinated dibenzo - p - dioxins ( pcdds ) , polychlorinated dibenzofurans ( pcdfs ) , and coplanar polychlorinated biphenyls ( pcbs ) ; 58 other pcbs , organochlorine pesticides , and polybrominated diphenyl ethers ( pbdes ) ; five perfluorinated compounds ; and four trace elements .
these substances are also part of the centers for disease control and prevention s national human health and nutrition examination survey ( nhanes ) , which is a biannual survey of the noninstitutionalized population of the united states ( 27 ) .
matched motherchild samples were obtained in connection with consecutive normal parturitions in the faroe islands .
we chose to carry out the study in this fishing community because of an anticipated wide range of exposures .
the traditional faroese diet includes pilot whale , which accumulates high concentrations of pcbs , certain pesticides , and other persistent lipophilic compounds in the blubber , while methylmercury is accumulated in the meat ( 28,29 ) .
in connection with the recruitment of a cohort from consecutive births at the national hospital in torshavn , faroe islands ( 30 ) , maternal blood , maternal hair ( for mercury analysis ) , placenta ( fetal part ) , umbilical cord tissue , cord blood , and milk were obtained .
detailed information on sampling , chemical analyses , and abbreviations is given in the supporting information ( s1 ) .
two weeks after childbirth , each mother was interviewed by use of a questionnaire on the frequency of meals and portion sizes that included traditional foods , such as pilot whale meat , pilot whale blubber , fish , fulmars , and other seabirds .
hair from all sample sets was first analyzed for mercury , and all milk samples were analyzed for major pcb congeners .
on the basis of these initial results , 15 complete sample setsmaternal hair , whole blood , serum and milk , placenta , and infant cord tissue , whole blood , and serumwere selected for pollutant analyses .
five sets represented mothers who had not eaten whale meat or blubber at all during pregnancy ( group 1 ) .
five represented the highest hair - mercury concentrations among the samples analyzed , as a likely reflection of a high intake of whale meat in the recent past ( group 2 ) .
the last five sets of samples had the highest milk - pcb concentrations as an indication of a high lifetime blubber intake ( group 3 ) .
the project was approved by the faroese ethical review committee and subsequently by the irb at harvard school of public health ; written informed consent was obtained from each mother .
concentration ratios were calculated for the various matrices in regard to the concentration in maternal blood .
each set of pairwise data was processed when at least five pairs of samples had results for the specific analyte above the detection limit , and an average concentration ratio was calculated if pearson s correlation coefficient was at least 0.7 ( r  0.5 ) . for each matrix , the ratios obtained for the analytes were ranked , and extreme results were eliminated sequentially until the overall average showed a coefficient of variation of no more than 20% .
this strategy ensured that almost all individual ratios for the different analytes were within one standard deviation from the overall average .
if based on results with correlation coefficients above 0.7 , outlier ratios are reported separately as the arithmetic means .
concentration dependence of the ratios was assessed by calculating regression coefficients , where the regression line was forced through the origin .
apart from increased uncertainty of results close to the detection limit , regression coefficients were in accordance with the average ratios , and regression analyses are therefore not reported .
maternal age , parity , body weight , and weight gain during the 15 pregnancies are shown in table 1 .
the three exposure - based groups differed only slightly from one another in regard to background information . whereas maternal serum and milk were analyzed for the complete set of 87 environmental chemicals , the 20 pcdds , pcdfs , and coplanar pcbs were not determined in cord blood , cord tissue , and placenta due to insufficient sample sizes combined with low lipid contents .
the perfluorinated compounds ( pfcs ) were analyzed in 12 sets of maternal serum , cord serum , and milk .
of the 58 organohalogen compounds determined in fetal samples , only 2,2,5,5,8,9,9,10,10-nonachlorobornane ( parlar-62 ) , bde-85 , and pcb-18 were below the detection limit for all samples .
parlar-62 was detected in maternal serum , although in only three samples . in general , environmental chemical concentrations for group 1 , who did not eat traditional food during pregnancy , tended to be lower than the results for the two other groups , and the results for group 3 with the high milk - pcb concentrations were among the highest also for most of the chemicals analyzed .
concentrations in umbilical cord serum and milk , and to a lesser extent those from cord tissue and placenta , correlated well with the maternal serum concentrations . in cord serum , only pentachlorobenzene ( pcbz ) and -hch seemed to diverge from this pattern . in placenta and cord
tissue , the highly chlorinated pcbs correlated the best with the maternal serum concentration , whereas pcb congeners 28 , 44 , 49 , 52 , 66 , 101 , 105 , 128 , and 149 showed much scattering .
the a priori requirement of at least five sample pairs with detectable concentrations reduced the numbers of sample pairs to 43 , 45 , 50 , and 59 for cord serum , cord tissue , placenta , and milk , respectively .
a correlation coefficient of at least 0.7 resulted in further reduction to 39 , 34 , 29 , and 56 sample pairs .
based on the required agreement with an overall ratio in regard to maternal serum , the partition ratios for the four specimens were based on 33 , 22 , 21 , and 38 sample pairs . based on the overall mean ratios , cord serum , cord tissue , and placenta had lower lipid - based concentrations of organohalogen substances than maternal serum , while the relative lipid - based concentrations in milk were higher ( table 2 ) .
support for these overall results was also obtained from several median ratios calculated for sample pairs with correlation coefficients below 0.7 ( tables s1s3 ) . among the brominated substances , bde-47 and , less clearly , bde-100 tended to show increased concentrations in tissue and milk compared to maternal serum ( table s1 ) .
the chlorinated pesticides pcbz and -hch showed a relative excess in fetal samples ( table s2 ) . when compared to the -hch concentrations , the results for the gamma isomer were generally almost 2 orders of magnitude lower in maternal serum and milk , but of similar magnitude in the fetal samples .
p , p - dde concentrations showed averages about 50-fold higher than those of the ddt isomers , which had less stable ratios .
several pesticides showed concentrations in milk that were higher than anticipated from the overall average ratio .
for the sum of polychlorinated biphenyls ( figure 1 ) , the lipid - based cord serum concentration correlated very well with that of the maternal serum ( r = 0.99 ) and showed a concentration ratio of 0.56 . for milk ,
the correlation was not as close ( r = 0.87 ) , and the average ratio was 1.35 .
cord tissue pcb concentrations correlated as well as milk ( r = 0.88 ) , although with an average ratio of 0.64 , while placenta concentrations showed a poorer correlation of 0.53 .
lipid - based concentration ( ng / g ) of the sum of all quantified polychlorinated biphenyl congeners in milk and fetal tissues ( identified by different symbols ) , as compared to the concentration in maternal serum in fifteen sets of samples .
some pcb congeners showed higher lipid - based concentrations in fetal samples than in maternal serum and milk ( table s3 ) , but some of these ratios may be imprecise due to concentrations close to the detection limit and poor correlations between paired samples .
when the pcbs were grouped according to chlorination , the partition between maternal serum and milk decreased at higher number of chlorine substitutions ( figure 2 ) . for the other paired samples , correlations between partitions and the degree of chlorination were less clear and more variable .
average partition ratio between lipid - based concentrations of polychlorinated biphenyl congeners in milk and maternal serum from 15 sample pairs in regard to the number of chlorine substitutions of each congener measured .
still , several pcdds and pcdfs , and pcb congeners 126 and 169 , showed high correlations between paired maternal serum and milk samples , and they were in agreement with regard to the relative distribution in the two matrices .
overall , the partitioning between the lipid phases agreed with the ratio of approximately 1.5 for milk versus maternal serum for 1,2,3,7,8-pentachlorodibenzo - p - dioxin ( 12378d ) , 123478d , 123678d , 2,3,4,7,8-pentachlorodibenzofuran ( 23478f ) , 123478f , 123678f , and pcb congeners 126 and 169 . although sufficient numbers of detectable concentrations were not available for several dioxin - like substances , increased chlorination tended to show a lower ratio between milk and maternal serum concentrations .
perfluorooctanic acid ( pfoa ) , perfluorooctane sulfonic acid ( pfos ) , perfluorononanoic acid ( pfna ) , and perfluorodecanoic acid ( pfda ) revealed excellent correlation between maternal and cord serum concentrations , with ratios of 0.72 , 0.34 , 0.50 , and 0.29 , respectively ( table 3 ) .
perfluorohexane sulfonic acid ( pfhxs ) showed a poor correlation , but the median ratio of 0.74 confirmed that transplacental passage occurred .
in the milk samples , only pfoa was detected , and then only in 7 of 11 samples analyzed . assuming a pfoa concentration of 0 in the milk samples below the detection limit , the correlation with the maternal serum pfoa concentration was 0.80 and with cord blood was 0.72 .
four of eleven samples available had a pfoa concentration below the detection limit , and none of the other analytes were detected . in regard to the trace elements ( table 4 ) , lead was below the detection limit in all cord tissue samples . although poorly correlated , the average lead concentrations were quite similar in cord blood and milk , but higher in the placenta .
cadmium showed a 100-fold excess in placenta in comparison to that in cord blood , but blood concentrations close to the detection limit made partition calculations unstable .
mercury and selenium showed similar partition ratios , although the average ratio for cord tissue versus cord blood was much higher for mercury than for selenium .
mercury showed excellent correlations among concentrations in different matrices ( figure 3 ) , while selenium showed much scattering . in the matrices
analyzed , the two elements correlated only poorly ( e.g. , r = 0.27 for cord blood ) , and the average molar concentration of selenium in cord blood , placenta , and milk exceeded that of mercury by approximately 20-fold .
total mercury concentrations in cord tissue and placenta ( left vertical scale ) , and maternal hair ( right vertical scale ) in relation to those in cord blood ( horizontal scale ) from 15 sets of samples .
this study addressed the partition between maternal and fetal tissues for a large number of environmental chemicals of toxicological interest .
the samples were selected from normal births in a fishing community , where elevated exposures to marine contaminants occur .
a range of exposures was intended for determination of relative partitions at different concentration levels .
the results cover a large number of important environmental chemicals , particularly substances commonly present in human samples .
virtually all substances detected in the samples were present in fetal tissues and cord blood as an indication that transplacental passage had occurred .
concentrations of cadmium were relatively increased in the placenta , thus suggesting a partial barrier for this trace element , as also reported in previous publications ( 1416 ) . for the lipophilic substances ,
possible placental accumulation was observed only for some low - chlorination pcbs , although increases also occurred for concentrations in cord tissue and cord serum .
cord serum concentrations of lipophilic substances averaged slightly more than half of the levels in maternal serum after adjustment for lipid concentrations .
g / l ) , and on a volume basis , concentrations in cord serum therefore averaged only 20% of those occurring in maternal serum .
lipids are likely to pass more rapidly than the contaminants into the fetal circulation , but may then be metabolized , thereby lowering the concentration on the fetal side .
lipid - adjusted concentrations in placenta and cord tissue were slightly more than one - third of the results observed for maternal serum .
the lipid concentration of the placenta was about 5-fold higher than in cord tissue , but only small differences occurred in the number of samples of these tissues with detectable concentrations of the lipophilic substances .
overall , the correlations between paired samples and the partition of lipophilic substances in maternal and fetal samples extend similar observations reported in previous studies ( 38 ) .
the lipid - based concentration of dioxins tended to be about 50% higher in human milk , but the ratio was not constant for all analytes .
two highly chlorinated substances  ocdd and 1234678d  were excreted to a lesser extent into milk compared to maternal serum concentrations .
this finding suggests that the passage into milk may be more difficult for larger molecular sizes ( 5,24 ) , as also seen for pcb congeners ( figure 2 ) .
although the dioxin - related substances were not measured in fetal samples , other studies suggest that some degree of barrier may exist in the placenta ( 31 ) .
considerable differences have been reported in lipid - adjusted concentrations of some environmental chemicals in maternal serum and milk from the same individual ( 32 ) .
in particular , a uniform distribution in the lipid phase between the samples had been called into question for pcbz , -hch , hcb , and the more lightly chlorinated pcbs ( 8,25 ) .
the present study confirmed that several substances deviate from a uniform pattern of distribution , in particular pcbs with low chlorination , such as congeners 28 , 44 , 49 , 52 , 66 , 101 , 110 , and 149 . compared to their concentrations in maternal serum , the gamma , but not the beta , hch stereoisomer showed much higher concentrations in cord serum and fetal tissues .
the reasons for such discrepancies are unclear , but they could reflect a difference between maternal and immature fetal metabolism or an enantiospecific uptake . however , the observation that some lipophilic contaminants differ in their relative distribution across the placenta must also be considered in regard to short - term toxicokinetic differences . because the maternal serum was collected in the 32nd week of pregnancy , analytical results are compared for samples collected up to two months apart .
the relatively short elimination half - life of lightly chlorinated pcbs could therefore lead to unstable tissue concentrations , and variable exposures could then easily affect the calculated partition coefficients .
however , such variability would not be likely to explain the large differences in average concentrations .
brominated substances have been previously reported to be less efficiently transferred into cord blood , while much higher concentrations are present in human milk than in serum ( 33 ) .
thus , bde47 concentrations were reported to be similar in maternal and cord blood plasma , but poor correlations were obtained for the more highly brominated congeners , bde99 , bde100 , and bde153 , which tended to show lower concentrations in cord blood plasma , thereby suggesting a less efficient passage through the placenta ( 34 ) .
these substances have been reported to accumulate in the fetal liver , while very little is retained in the placenta ( 35 ) . in the present study ,
a low ratio for bde153 in cord serum was corroborated and our findings also support the notion of increased milk concentrations of bde congeners 47 and 100 , while congeners 99 and 153 were closer to the overall average ratio , and pbb153 was lower .
these results suggest that relative bromination may affect the partition to a greater extent than chlorination , perhaps as a result of differences in molecular size .
the pfc concentrations were higher in maternal serum than in cord serum , and the ratio suggested that the length of pfc chain as well as the active group affected the ability to pass the placenta .
pfcs with a short chain length showed higher relative cord serum concentrations than pfcs with a longer chain length .
pfcs with sulfonic acid as the active group seemed to pass more easily into the fetal circulation than pfcs with carboxylic acid as the active group .
these results appear to fit in well with the findings of a previous study that examined maternal and cord serum concentrations of four pfcs ( 36 ) .
while a significant association with serum levels was found for pfos , the milk concentrations were very low , as has previously been reported ( 37,38 ) . among the trace elements , mercury showed excellent correlations among concentrations in different matrices ;
the correlations thus support the use of all the specimens included in the present study , including easily collected umbilical cord tissue ( 39 ) .
however , much greater variability was seen with cadmium , lead , and selenium ( 15,40 ) .
the close correlation between lipid - based concentrations in maternal serum and milk for a large number of lipophilic substances supports the notion that either matrix is appropriate for assessment of exposure levels .
a general proportionality factor can be considered as a feasible approximation for comparing the results , as only few of the contaminants commonly measured will require a substance - specific conversion factor .
. however , measured concentrations in cord tissue and placenta are more variable , the former perhaps affected by the low lipid content .
these matrices are therefore not as useful for monitoring purposes , except perhaps for cadmium , which accumulates in the placenta . although dekoning et al .
( 20 ) recommended that several types of specimens be collected to assess perinatal exposure levels , the present study suggests that an efficient strategy would emphasize specimens with a high rate of detectable concentrations .
the main finding of this study is that the contaminants tend to be present in all matrices examined .
in general , lipid - based concentrations of lipophilic chemicals in maternal serum are correlated with concentrations in the other media .
however , the transfer to the fetal circulation results in lower concentrations , while milk levels tend to be about 50% higher than the maternal serum .
these patterns are complex , and the complexity must be taken into account when selecting samples for analysis and when interpreting the results .
 passage of environmental chemicals across the placenta has important toxicological consequences , as well as for choosing samples for analysis and for interpreting the results . to obtain systematic data , we collected in 2000 maternal and cord blood , cord tissue , placenta , and milk in connection with births in the faroe islands , where exposures to marine contaminants is increased . in 15 sample sets , we measured a total of 87 environmental chemicals , almost all of which were detected both in maternal and fetal tissues . 
 the maternal serum lipid - based concentrations of organohalogen compounds averaged 1.7 times those of cord serum , 2.8 times those of cord tissue and placenta , and 0.7 those of milk . for organohalogen compounds 
 detectable in all matrices , a high degree of correlation between concentrations in maternal serum and the other tissues investigated was generally observed ( r2 > 0.5 ) 
 . greater degree of chlorination resulted in lower transfer from maternal serum into milk . 
 concentrations of pentachlorbenzene , -hexachlorocyclohexane , and several polychlorinated biphenyl congeners with low chlorination were higher in fetal samples and showed poor correlation with maternal levels . 
 perfluorinated compounds occurred in lower concentrations in cord serum than in maternal serum . 
 cadmium , lead , mercury , and selenium were all detected in fetal samples , but only mercury showed close correlations among concentrations in different matrices . although the environmental chemicals examined pass through the placenta and are excreted into milk , partitions between maternal and fetal samples are not uniform . 
Introduction
Materials and Methods
Results
Discussion