Mercury, Cadmium, and Lead Levels in Human Placenta: A Systematic Review

1During gestation, potentially harmful pollutants circulating in the blood of pregnant women can reach the fetus, although possible mother-to-child transmission of these toxic substances is modulated by the placenta. Some authors have proposed the use of placental tissue as a noninvasive exposure biomarker for different organic and inorganic pollutants. This tissue, usually discarded after birth, is easy to obtain and may furnish information on the exposure of both mother and fetus.

2Among the contaminants eligible for being studied in this tissue, some heavy metals are of special interest when it comes to gestation. Exposure to either mercury (Hg) or lead (Pb) has well known deleterious effects on the intellectual development of children, and embryotoxic and fetotoxic effects associated with exposure to cadmium (Cd) have also been described.

3We reviewed published research on total Hg, Cd, and Pb levels in human placenta, both in pregnant women from the general population and in those with specific exposures, as well as the factors related to such levels, in order to summarize available information for researchers considering the use of placenta to biomonitor exposure to these metals.

4Search strategy. The systematic search and review processes were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement criteria. We searched PubMed/MEDLINE (http://www.ncbi.nlm.nih.gov/pubmed/), EMBASE (http://www.embase.com/home), LILACS (http://lilacs.bvsalud.org/en/), OSH (http://www.oshupdate.com/), and Web of Science (http://www.accesowok.fecyt.es) databases using the following MeSH terms: “placenta” successively combined with “pollutants,” “cadmium,” “mercury,” “lead,” and “biomonitoring.” This was supplemented by manual searches based on the references cited in the papers initially identified. We considered only studies on human subjects published in English or Spanish from January 1976 through November 2011. This strategy yielded 1,629 references [see Supplemental Material, Figure S1 (http://dx.doi.org/10.1289/ehp.1204952)]. From these, we selected the studies that furnished original quantitative data on total Hg, Cd, or Pb levels measured in human placental tissue samples.

5Data extraction. Using a standard, purpose-designed form, we extracted the following data from each paper: a) study design, date and place, participants, sampling method and size, inclusion and exclusion criteria, and request for informed consent; b) protocol for collection, storage, processing, and analysis of biologic specimens; and, c) results, including metal levels and related factors. Where concentrations were expressed in dry weight (dw), we calculated wet weight (ww) by dividing the figure by the dw/ww ratio, if provided, or by a value of 6, if the dw/ww ratio was not provided; where the type of weight was unspecified, we allocated ww or dw in light of the range of values used. We report the arithmetic and/or geometric mean, and we include SD, median, and range where provided. In view of the heterogeneous results displayed by the original studies, we felt that quantitative pooling was inappropriate.

6We included a total of 79 reports on 73 different studies. Twenty-four studies reported placental Hg levels, 46 reported Cd levels, and 46 reported Pb levels; papers frequently provided results on more than one trace metal. The main characteristics of each study are described in Supplemental Material, Table S1 (http://dx.doi.org/10.1289/ehp.1204952), and metal levels are summarized in Supplemental Material, Tables S2–S4. The full text was unavailable for 8 papers; for those papers, data shown in the summary tables came from the abstracts or from reviews of those studies. The number of papers increased over time, reaching a peak in the past decade because of studies addressing placental Cd and Pb (see Supplemental Material, Figure S2). Whereas older studies were mainly undertaken in the United States and Western Europe, studies targeting populations in India, China, Eastern Europe, and South America began to be published in the 1990s, and accounted for the bulk of published works from 2000 and later.

7Design: designated objectives and study subjects. Most of the papers reviewed were cross-sectional studies with three distinct types of objective, often combined in the same report. Most studies adopted a biomonitoring standpoint. Among these, some included variability by region of origin, rurality, or lifestyle aspects, with smoking being the determinant most frequently studied, especially in studies measuring Cd. Another objective was the acquisition of in-depth knowledge on the metabolism of metals and their passage through the placenta, assessing the placenta’s possible barrier effect by examining the link between placental levels and other related biomarkers. Indeed, 25 studies collected other complementary biologic specimens, such as maternal and umbilical cord blood, cord tissue, maternal milk, maternal or newborn hair and urine, or meconium. Finally, some researchers assessed the association between metal levels and disorders in the progress of pregnancy or newborn development, including premature membrane rupture or preterm births; gestational age and anthropometric data; oligohydramnios; intrauterine growth restriction (IUGR); Apgar score at birth; and fetal malformations or stillbirths.

8Most studies included small groups of women, and only 19 included > 100 participants. Just 2 papers provided participation rates, which was > 90% in both cases, and another study specified the dropout rate after recruitment. The inclusion criteria were frequently poorly described, and in some cases were limited to a mere reference to geographic origin. The most common practice of the reviewed studies was to include nonrandomly selected convenience samples of healthy pregnant women without known risk exposures and who had full-term births and normal neonates. However, some studies included pregnant women with a higher probability of environmental exposure to heavy metals, whether by occupational exposure or high environmental exposure. Other studies targeted women who experienced problems with fetal development or pregnancy. Some studies used type of delivery as an inclusion criterion, although only 15 reports provided this information. Of these, 9 covered only noncomplicated vaginal births, 4 combined vaginal and cesarean (C)-section births, and 1 exclusively included placentas from C-section births. Regarding ethical considerations, 28 papers expressly referred to informed consent as a prerequisite for study participation and 14—mostly recent—mentioned the approval of an ethics committee.

9Analytical methodology: collection, processing, and analysis of biologic specimens. Pretreatment of the placenta, which was not always specified, varied widely. In general, the organ was frozen and stored, either whole, processed, or in the form of the specimen collected. Usually, the placenta had an initial washing to remove blood or clots; in some studies the decidua basalis, chorionic plate, or connective tissue and blood vessels were eliminated, whereas in others only the cotyledon was analyzed. In most instances, a single spot specimen of placenta weighing only a few grams was obtained, without specifying the placental area sampled. Other researchers collected several specimens from different areas, typically to analyze them jointly and sometimes to carry out intercomparisons among the individual results. Finally, in other studies the complete placenta or one of its halves was homogenized, and part of this preparation was analyzed.

10In general, different types of spectrometry were used, except in one case in which both Cd and Pb were determined using a hanging Hg drop electrode and in five studies in which Hg was measured using an unspecified Hg analyzer or instrumental neutron activation analysis. These details were not always provided.

11Information on laboratory quality controls differed between the earliest and the more recent papers: Before the year 2000, only 11 studies (26.8%) specified having internal quality controls and 6 studies (14.6%) mentioned external controls. In contrast, all studies published after 2000 except 1 reported the use of standardized quality control procedures that generally comprised evaluation of accuracy and precision by analysis of certified reference material, and 2 studies included additional interlaboratory comparisons. Only half of the studies specified the limit of detection (LOD), merely stating the value or including the procedure used to treat values below it.

12In the reviewed studies, there was no uniform pattern for reporting results: 28 studies described levels in terms of wet weight, 26 in terms of dry weight, and the remainder did not specify this aspect. Four papers used their own data to calculate the dw/ww ratio, which was 6.32, 6.2, 6.9 ± 1.3 (mean ± SD; ) and 5.7 (range, 4.8–7.7), respectively, whereas 2 papers used a fixed ratio of 6.0. As units of measurement, most authors used nanograms or micrograms per unit weight, although nanomoles and parts per billion were also employed; some reports seemed to contain errors in the units.

13Statistical analysis and reporting of results. Most of the studies (84.7%) provided arithmetic means, usually accompanied by SDs. Other widely used indicators were median (29 studies) and range (28 studies); geometric mean was reported in 7 papers. With one exception, authors did not include confidence intervals nor did they mention the evaluation of outliers or the use of robust measures of central trend.

14Studies assessing associations with risk factors generally furnished correlation coefficients drawn from univariate analyses, or differences in means derived from stratified analyses; few reports carried out multivariate analyses.

15The individual results yielded by studies on Hg, Cd, and Pb that we reviewed are presented in Supplemental Material, Tables S2, S3, and S4, respectively (http://dx.doi.org/10.1289/ehp.1204952).

16Total Hg. Twenty-four studies reported total Hg levels, although only 4 included > 100 women [see Supplemental Material, Table S2 (http://dx.doi.org/10.1289/ehp.1204952)]. The arithmetic mean Hg levels reported in those studies having this information are presented in Figure 1. Hg concentrations varied widely; the highest were found in China (Shanghai) and Japan, where the mean exceeded 50 ng/g, and in the Faroe Islands, with a median of approximately 90 ng/g. In contrast, in Germany and the Ukraine, most samples were < LOD. Three studies also provided the proportion of organic to inorganic Hg.

17Relationship between Hg in the placenta and other specimens. Studies that compared Hg concentration in the placenta with levels in maternal or cord blood yielded conflicting results. In general, higher Hg levels were observed in the placenta, suggesting an accumulation of this metal during pregnancy. Nevertheless, other authors reported placental levels that were lower than blood levels.

18Almost all studies reported a positive correlation between placental Hg and venous or arterial cord blood, umbilical tissue, or maternal and neonate hair Hg. For maternal blood, however, results were inconsistent.

19Association between Hg, maternal characteristics, and exposure to possible risk factors. In general, no association was found with maternal age or parity, although described a significant association with body mass index (BMI) after controlling for possible confounders.

20Fish intake, the most common source of population exposure to Hg, was the risk factor that was most widely studied for Hg levels. The highest levels were found in regions with high fish consumption, such as Japan and the Faroe Islands. In a small study on Eskimo women, also observed a positive association between diets very rich in fish or whale meat and placental Hg. However, in two studies, differences in intake during pregnancy were not associated with Hg levels in populations whose diet included lower fish consumption, although an association with consumption prior to pregnancy was suggested.

21Few studies have examined the role of nondietary exposures to Hg. Some researchers have reported an absence of association with drinking habits, dental fillings, or tobacco abuse. Some studies reported contradictory results related to residence in areas with industrial exposure, whereas others found no differences between women living in rural and urban settings. Data on occupational exposures were equally sparse: One small study of Chinese women exposed to Hg at a lamp factory reported elevated placental levels, yet we found no studies that had measured placental Hg levels among other occupationally exposed women, such as dentists or chloralkali plant workers.

22Possible effects of Hg on the placenta or pregnancy. described a possible inhibitory effect of Hg on some placental enzymes implicated in the metabolism of carbohydrates and steroids; however, no studies reported an association between total placental Hg and the anthropometric variables of neonates or gestational age. A similar result was found in a study of fetuses with malformations of unknown origin, in which failed to observe evidence of Hg implication.

23Cd. We located 46 studies reporting placental levels of Cd; 17 of these had > 100 participants [see Supplemental Material, Table S3 (http://dx.doi.org/10.1289/ehp.1204952)]. The average level of Cd varied widely (Figure 2)—ranging from 1.2 ng/g in Shanghai to 53 ng/g in an urban area of the United States—and was particularly high, with values >20 ng/g, in some groups of pregnant women from Japan, Bangladesh, Turkey, and Eastern Europe.

24Comparative analysis of Cd in placenta and other specimens. Cd concentrations in the placenta were much higher than those found in maternal and cord blood in all studies except one. Placental Cd concentrations were 10 times higher than that detected in maternal blood in one study and up to 100 times higher than that of cord blood in another. These data, along with the difference in placental Cd levels between the first trimester and at term, indicate that Cd accumulates in the placenta during gestation and support the view that this organ is an efficient or partially efficient barrier against this metal.

25The Cd concentration in placenta was reported to be positively correlated with maternal blood Cd—both in plasma and in erythrocytes—and with maternal urinary Cd. The relationship between placental and cord blood levels was somewhat less clear; although some studies found a correlation between them, others failed to do so. No association with Cd levels in breast milk was observed, although few studies assessed this association.

26Effects of collection, processing, and preservation of specimens. Pretreatment of placentas may be associated with higher levels of Cd in the specimen. In terms of the metal’s distribution in this organ, available data were contradictory: Some studies suggested that Cd was uniformly distributed throughout the placenta, and others described differences between samples from the central and peripheral areas, without any clear gradient. In placentas from smokers, the Cd concentration seemed to be higher on the maternal side. Higher levels of Cd were also observed in placentas with parenchymal calcifications, regardless of smoking habit, gestational age, or birth weight. reported that Cd levels were lower in fetal membranes.

27Association between maternal characteristics and exposure to possible risk factors. The efficiency of the placenta as a barrier against the passage of Cd might be modulated by maternal polymorphisms in genes that code for metal-binding metallothionein protein. Most studies found no association between placental Cd and parity or maternal age, although in some cases higher levels were detected in older mothers. In another U.S. study, a higher Cd concentration was observed in multiparous women, albeit exclusively among smokers.

28Among environmental exposures, smoking was the most widely studied factor. Published results clearly show that placental Cd levels in pregnant smokers are two to three times higher than those in pregnant nonsmokers. Several authors reported a positive correlation with the number of cigarettes smoked daily; however, in a small study in the Netherlands, very heavy smokers (20 to 60 cigarettes/day) had lower levels than did intermediate smokers, suggesting that a limited amount of Cd could be retained in the placenta. Furthermore, some studies found no evidence of any association between tobacco use and placental levels of Cd. Only one Turkish study specifically reported Cd levels in women with passive tobacco exposure, and levels were higher in those women compared with nonsmokers.

29Important differences in placental Cd levels have been observed among pregnant nonsmokers by geographic region of origin, indicating that these levels also reflect variations in other environmental exposures. Several studies in residents in heavily polluted areas or in the vicinity of metal installations, such as Pb smelters or iron mines, generally registered high levels of Cd. Urban pollution also seemed to increase placental Cd, even when smoking was taken into account. In addition, a recent study in China suggested an association with indoor pollution. The few studies of occupational settings did not show a clear relationship with Cd levels.

30In terms of diet, one study reported lower placental Cd in women with high iron levels and low intake of cereals at the end of pregnancy; no association was found with drinking habits.

31Possible effects of Cd on the placenta or pregnancy. Because Cd accumulates in the placenta, higher levels would be expected in pregnancies of longer duration. Nonetheless, the studies we reviewed either found no association with gestational age or reported an inverse relationship. One small study observed higher Cd levels in preterm compared with full-term C-section placentas, although this difference was not statistically significant. However, found no association with prematurity. In regard to other gestational problems, observed higher levels in placentas from pregnancies with severe oligohydramnios.

32Research in this field has also assessed fetal development and neonatal anthropometric data. Three small studies reported higher Cd in placentas from pregnancies with IUGR, although the differences were not always statistically significant. Other studies described a negative correlation with birth weight, neonatal length, and chest circumference. However, a few studies failed to find any association between Cd and infant measures or neonatal Apgar score.

33In terms of placental metabolism, the aspect most commonly described was the direct link between placental Cd and high levels of placental metallothionein. Although this metalloprotein is considered a protective cellular mechanism against Cd, its increase might, in turn, affect the passage of zinc into the fetus. Other reported effects of Cd include a decrease in placental synthesis of leptin and increased activity of enzymes implicated in the metabolism of carnitine and carbohydrates. found no association between Cd and placental bulky DNA adduct levels.

34Pb. Placental Pb concentrations were reported in 46 studies, 15 of which had > 100 participants [see Supplemental Material, Table S4 (http://dx.doi.org/10.1289/ehp.1204952)]. Average Pb levels ranged from 500 ng/g in women residing in Silesia, a heavily polluted region of Poland, to 1.18 ng/g in Shanghai (China). Figure 3 presents the reported arithmetic means of placental Pb. Although concentrations > 100 ng/g were commonly observed in Western Europe and North America in the 1970s, since the 1980s Pb levels have remained < 50 ng/g. Some studies conducted during the last 20 years in Eastern Europe, South America, Asia, and North Africa still reflect very high levels of placental Pb, particularly in India.

35Comparative analysis of Pb in the placenta and other specimens. Placental Pb levels were usually lower than those found in maternal or cord blood, both in plasma and erythrocytes. However, the opposite has also been reported, and some authors described interindividual variations in the transference of Pb from maternal blood to the placenta.

36A positive correlation between placental and maternal blood Pb has been reported, both in antenatal controls and in specimens collected on the day of birth. Similarly, placental levels showed a positive correlation with cord blood levels, with the one exception. No correlation was observed between placental and maternal milk levels.

37Effects of collection, processing, or preservation of specimens. Some data indicate that pretreatment of the placenta, elimination of fluids, and freezing may modify Pb levels. Regarding placental distribution of Pb, reported that, in 33% of placentas, Pb concentration differed by a factor of approximately 2 among different lobuli within the same placenta, and reported that Pb particulate deposits were more frequently found in syncytiotrophoblasts than at other sites. In contrast, another study failed to detect differences among samples taken from different parts of the same placenta. Several studies indicated that Pb levels were higher in amniotic membranes.

38Association between maternal characteristics and exposure to possible risk factors. In a recent study, suggested that differences in placental Pb levels could be influenced by polymorphisms in genes that coded for metallothionein, in a manner similar to that of Cd. With respect to other maternal factors, contradictory results were found regarding the association between placental Pb and maternal age and with parity. One study reported an association between Pb and BMI.

39Of the three metals reviewed, Pb displayed the widest geographical variation: Levels in placentas from normal pregnancies were very high in India and Saudi Arabia and lowest in China and Canada.

40High placental Pb concentrations have been reported in studies of women residing in polluted areas and in the proximity of an e-waste recycling area, with positive correlations between Pb levels and both parents’ length of residence in the area and the father’s e-waste-related work. Of the four studies that assessed placental Pb in the vicinity of Pb smelters, only one (which included only pregnant nonsmokers) reported a significant increase in Pb among exposed women. In studies that examined the influence of urban pollution on placental Pb levels, some authors found no association, whereas others reported higher Pb levels in urban areas. Only one study addressed and reported seasonal variations.

41Among lifestyle-related habits, reports on smoking and placental Pb yielded inconclusive results: Whereas some researchers described a clear association with smoking, others failed to confirm these results. There were isolated reports of a negative correlation between placental Pb and maternal poultry and mushroom consumption or with daily coffee consumption, as well as a positive association with ingestion of tap water containing Pb concentrations > 50 μg/L. In addition, Pb levels might be related to wine consumption before but not during pregnancy. Increased placental Pb levels were also present in long-term pottery industry workers, and painters in particular.

42Possible effects of Pb on the placenta or pregnancy. Several studies found an association between placental Pb levels and some gestational problems. Whereas data on pregnancies with early membrane ruptures were inconclusive, consistently high placental Pb levels—not always statistically significant—were reported for stillbirths, neonatal deaths, and malformed infants, as well as for women reporting previous miscarriages. Although some researchers observed high Pb levels in placentas from preterm deliveries, overall, placental Pb was not associated with gestational age except in one study.

43The relationship of Pb with birth weight also yielded contradictory results. Most studies observed no association, but two found a positive correlation between Pb levels and birth weight. In contrast, other authors reported an inverse correlation, with higher levels of Pb in placentas of low-birth-weight babies (< 2500 g). In addition, pregnancies with IUGR had placental levels that were high but not statistically significant.

44Of the studies that examined whether Pb-related gestational problems might be linked to oxidative stress measured via placental biomarkers, a positive association in preterm gestation was reported by, but observed no correlation in neonates with low birth weight for gestational age. Finally, one study showed that placental Pb levels correlated negatively with activity of steroid sulfatase, an enzyme implicated in the metabolism of steroids.

45In this review we provide a structured breakdown of the results of studies published from 1976 through 2011 on Hg, Cd, and Pb levels in human placentas. We found that the use of the placenta as a biomarker of exposure to heavy metals is not properly developed because of the heterogeneity among the studies. This heterogeneity applies not only to the populations selected but also to the processing of specimens and presentation of results.

46Most of the studies reporting placental levels of these trace metals were conducted on small convenience samples of healthy pregnant women, and the authors did not always describe the inclusion/exclusion criteria they used. These factors limit the external validity of the results. Furthermore, adjusted analyses considering basic potential confounders, such as age or smoking, were not always provided. Specific aspects of these studies, such as type of birth, must be deemed confounding factors. The different ways of obtaining placentas in C-sections and vaginal births, taken together with the circumstances that indicate which technique was used, might result in differences unrelated to environmental exposures.

47The lack of universally accepted protocols for collecting and processing placental specimens also hinders comparison of the results. The procedure for collection, pretreatment, storage, and preparation of the placenta prior to analysis varied among studies, although available data suggest that such processes may influence the magnitude and comparability of the trace metal concentrations. Particularly relevant is the representativeness of the placenta specimen vis-à-vis the organ as a whole. In many studies, a single spot tissue specimen was obtained. In practice, this implies an assumption that trace metals are uniformly distributed throughout the placenta. Nevertheless, published data, particularly in the case of Cd and Pb, question this assumption. To solve this problem, some authors have suggested homogenizing the complete organ or instead obtaining and then aggregating and homogenizing random specimens of multiple parts of the placenta. With regard to the methodology used for laboratory analysis, our search was confined to studies undertaken in 1976 and later, a time when fundamental analytical techniques, such as nuclear activation and atomic absorption spectrophotometry in particular, were being developed for the purpose of obtaining reliable results in the quantification of trace metals in placental tissue. Nevertheless, we failed to locate studies that compared the performance of the various analytical approaches specifically in placental tissue. Thus, we cannot rule out possible variability over time attributable to the different analytical methods used and the fine-tuning and improvement of the related quality-control measures.

48Because our review was limited to studies published in English or Spanish, results published in other languages are underrepresented. In addition, we were unable to retrieve the full text of some studies (mainly nonindexed), even after requesting copies directly from the authors. A further limitation is that the heterogeneity of the original studies prevented us from providing any reliable quantitative summary measure. Despite the limitations of validity and comparability, some conclusions can be drawn.

49Few studies reported total Hg in placentas. Existing studies show a good correlation between Hg levels in placenta and commonly accepted biomarkers of children’s exposure, such as Hg in maternal and newborn blood and hair. Perhaps the existence of these classic indicators justifies in part the limited interest shown in placental Hg. Although higher Hg levels were found in Asian countries, the lack of association with dietary fish intake in the few studies conducted on women with moderate consumption might generate doubts about its possible utility as a biomarker of exposure in these settings. The role of placenta as a barrier for this metal is not yet clear, and even though the Hg level might have some effect on normal functioning of the placenta, it does not seem to be associated with deleterious effects on pregnancy.

50Extracted data indicate that Cd accumulates in the placenta; this may explain why placental levels usually correlate with maternal but not cord blood levels. However, if Cd levels in the placenta, as well as the placenta’s efficacy as a barrier, are modulated by maternal polymorphisms linked to metallothionein, this information should be considered in the assessment of this biomarker in terms of exposure. Clarification is also needed with respect to the possible existence of a saturation threshold above which the placenta becomes unable to accumulate Cd, because this may limit the utility of specimens in environmental monitoring. The single determinant most clearly associated with this metal is exposure to smoking during pregnancy. Accordingly, it is essential that studies furnishing information on placental Cd levels give detailed information on the smoking habits of the women and provide separate estimators for nonsmokers. Reported results also suggest a possible relationship between Cd and IUGR or low anthropometric neonatal parameters, which need to be confirmed by additional research.

51Pb was the pollutant that presented the clearest geographic differences in placental concentration. The wide range of values seen for this metal in the placenta suggests that the placenta could be a good choice for biomonitoring environmental Pb exposure. Available studies showed that Pb crosses the placenta but does not accumulate. They also suggested an association between placental Pb levels and some gestational disorders, such as stillbirths; however, the data were contradictory and failed to clarify a possible relationship with low birth weight, IUGR, or prematurity.

52The associations between placental metal levels and birth weight or gestational age could be biased because exposure to some pollutants might be related to spontaneous abortion, as could also be possible in women with high Pb levels. Prospective studies of maternal exposure early in pregnancy could clarify these issues and evaluate whether pregnancy-related diseases may cause metal accumulation in placental tissue. None of the reviewed studies focused on the association between placental levels and any long-term effect. This is particularly relevant in comparing the utility of placental determinations of Hg or Pb in terms of biomonitoring because associations between children’s neurological development and levels of these metals have indeed been described.

53In our opinion, international biomonitoring committees should propose compulsory requirements and quality standards for all research involving the use of placentas to measure exposures. Studies should be required to have an appropriate epidemiologic design that is focused on ensuring the representativeness of the target population. They must clearly define inclusion/exclusion criteria and collect data on maternal (sociodemographic, clinical, pollutant-related exposures) and gestational characteristics (complications during pregnancy, gestational age, type of birth, seasonality, result of gestation, and birth weight). Tissue collection, preservation, and processing of specimens likewise require standardization. In biomonitoring studies, initial washing of the placenta to remove blood, followed by homogenization of the whole organ, might enable more comparable results to be obtained by researchers. However, sampling of specific parts of the placenta could be useful for research focused on understanding metal deposit in this organ, as well as the possible association between metal concentration and gestational problems.

54Quality assurance procedures should be applied to laboratory processes. Among the available techniques, those with low detection limits (e.g., graphite furnace–atomic absorption spectrometry, inductively coupled plasma–mass spectrometry) might be especially suitable for measuring metal levels in the general population in low-exposure environments. Finally, all of this information should be adequately described in the study reports. We recommend that metal levels be reported in standardized units (e.g., in nanograms per gram wet weight) and that appropriate descriptive statistics and their corresponding confidence intervals be combined with multivariate analyses to identify real risk factors associated with high levels of these pollutants.

55Although interest in the study of heavy-metal levels in the placenta has increased in recent decades, published studies are excessively heterogeneous. Standardized criteria for placenta collection, preservation, processing, and analysis are therefore needed to ensure that comparable results can be obtained. This will allow clarification of the possible effects of these metals in pregnancy, as well as the incorporation of placental tissue into environmental monitoring systems based on human biological samples.