Abstract
The Interaction of Lead Exposure and Pregnancy
The toxic effectsof low-levellead exposure have been the subject of a good deal of research and media attention in recent times. In most countries, the acceptable occupational exposure limit for lead is being progressively K O’Halloran, BSc(Hons) decreased as the adverse health effects JT Spickett, BSc(Hons), MSc, PhD of lead are being identified at levels School of Public Health approaching those found in nonDivision of Health Sciences occupational environments. Due to the sensitive nature of the Curtin University ofTechnology fetus to hazardous substances, the ex- Perth, Australia posure to lead of the unborn child via maternal sources is of critical concern. Preterm delivery, congenital abnor- Introduction malities and decreases in growth stature have all been associated with pre- The risks to human heaIth from contamination of both the work and natal lead exposure at “acceptable” general environment are often subtle levels. and pervasive. As scientists and the There is an accumulationofevidence which indicates that maternal expo- medical profession are beginning to recognize the adverse health effects sures prior to conception can play an of low levels of toxic substances, important role in determining blood the acceptable occupational exposure lead levels during pregnancy. In light of these observations the practice of limits for these substances are being removing the pregnant woman from progressively decreased. For some of lead sources may be of questionable these substances, e.g. lead, the margin value with regards to providing SHI- between acceptable occupational cient protection for the fetus. This limits and the levels found in the enarticle reviews the relevant literature vironment is becoming difficult to identify. In many developing counpertaining to the mobiiization of lead from bone during pregnancy and the tries, increased emphasis is being toxicity of low-level lead exposure to placed on reducing exposure to both the fetus, and briefly discusses some toxic substances at work and industrial pollution in the environment. factors which may affect this toxicity. This emphasis is occurring as tradiKeywords: Adverse health effects, tional risks to health from infectious mobilization of lead, occupational and diseases and microbiological contamination of food and water are becomenviroampntal lead exposure, preging more controlled and the time and nancy. capital can be transferred in another, but no less important, direction. Lead is one example of a metal whose toxic effect has been known for centuries’. The potential danger to humans, particularly to the unborn or developing child, of exposure to lead has been a subject of public concern and has resulted in considerable research interest. With the improvement in scientific methods there has been a significant generation ofdata from both animal and human studies that indicatethehazardsofleadatlow levels which were previously considAddress for reprints: JT Spickett, School of ered non-toxic. From a public health Public Hcalth, Curtin University of Techperspective, the blood lead level of nology, GPO Box U 1987, Pcrth 6001, concern is 25 pg Pb/dL blood’. In the Australia.
USA. the Centers for Disease Control currektly recommends 25 pg Pb/dL as a level of but is expected Soon to this to 10-15 .u-d ~ ~ 3 . From an o&pational perspective, the World Health Organization (WHO) recommended exDosurelimit for maies is 40 &dL a n d for females of a reproductive age the limit is 30 pg/dL4, while the National Health a n d Medical Research Council (NHMRC) in Australia recommends maternal blood levels should be below 40 pg/dL5. However, lead-induced changes in the hemopoietic system have been reported at levels less than 25 pg/dL6?’. In light of this evidence, and as the value of the “acceptable” occupational lead level progressively decreases, environmental lead becomes an increasingly important issue. While blood leads are used to indicate the level of current or shortterm exposure, there is, however, a large pool of lead that resides in the skeleton which is slowly released into the blood, thus representingan “internal” exposure. Under certain conditions of stress such as bone fractures or acute infections, mobilization of this skeletal pool may occur, resulting in inexplicably high blood lead levels’.*. Recent evidence indicates that mobilization of lead may be occurring during pregnancy and lactation9*10.In pregnancy, lead in the mother’s circulatory system will be transferred to the fetus via the placenta as early as the 12th week of gestation”. Lead is also available to the suckling infant via maternal milk12*13.The reason for concern about the exposure of pregnant 35
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Asia-Pacific Journal of Public Health 1 9 9 2 993 ~ Vol. 6 No. 2 females to lead is due to the increased sensitivity of fetal tissues to toxic chemicals and its underdeveloped detoxifying and excretory mecha n i s m ~ ’ ~ In ~ ’light ~ . of the evidence which indicates the possibility of lead becoming mobilized during pregnancy, it may become necessary to consider a mother’s body burden of lead as well as her current blood lead status, in order to determine the risk of lead toxicity to the fetus. This article will review the toxicity of inorganic lead at low levels and the results of research that indicate lead mobilization during pregnancy and lactation, and include a discussion of the potential consequences to the employment ofwomen in the lead industry and the conflict that arises between discrimination against the fertile woman and the protection of the fetus. Storage and Mobilization of Lead from Bone Lead has a strong affinity for bone and, when in a state of equilibrium, the skeleton contains more than 90% of the total body burden16. Lead accumulates in bone throughout life, thus the lead content of bone will be indicative of long-term and past exposures whereas blood lead levels are more a reflection of current and recent exposures. Mobilization of lead stored in bone may occur concomitantly with episodes of bone demineralisation, for example during menopause. There is evidence to support the theory that bone lead stores are released into the blood at significant levels during the menopausal period. A comparison of blood leads between preand post-menopausal women (controlling for age) showed significantly higher (12.5%) blood lead concentrations in the post-rnenopausalgr~up'~. In addition, women who had never been pregnant had higher postmenopausal lead levels than those who hadgiven birth. Theauthors postulate that if pregnancy causes bone demineralisation then less lead will be available for mobilization at a later date. A recent retrospective study provides evidence which suggests that
lead levels released from the bones of women who had suffered from lead poisoning during their childhood may reach levels which are toxic to the fetus’*. In this study, a history of childhood plumbism was associated with known adverse lead effects on pregnancy outcome, such as spontaneous abortion, stillbirths and having children with learning disabilities. An Australiancase studyofa woman who had suffered a childhood lead poisoning episode reported the presence of elevated blood lead levels during pregnancy and lactation which was not due to a recent exposure”. In the frequentlyquoted study by Manton, a 50% decline in blood lead levels was recorded in a mother 11 months after childbirth’. The increased blood lead levels during pregnancy could not be justified in terms of environmental or dietary exposures. Skeletal lead is indicated as a third source oflead as its turnover rate would increase to meet the demands of late pregnancy and lactation. Further supporting evidence of the view that blood lead levels ofpregnant women reflect body burden rather than current status of exposure was found by Buchet and associates in their study of the influence of various epidemiological factors on the exposure of pregnant women to lead”. In this cross-sectional study, the distribution of blood lead levels ofmothers who had always lived in an urban or a rural areawvere different to those from mothers who had only lived in those areas for one to five years. This difference would not be expected if blood leads were a measure oFcurrent exposure. The blood lead levels of newborns also reflect this difference. It has also been found that lead levels in the placental tissue of women in the pottery industry in the UK increased with the length of maternal exposure, giving further reason for considering a mother’s accumulative lead levels, as opposed to current exposure, when assessing potential toxicity to the fetus2’. The mobilization of lead during pregnancy and lactation has not been specifically investigated in human studies and the evidence obtained has generally been secondary to a related
but separate set of data. Data from other studies have not always supported the theory oflead mobilization duringpregnancy and show no change in blood lead levels2’*22.A recent study showed significant increases in blood lead levels at six months postpartum compared to blood lead levels at birth23. Animal studies camed out in the last decade have provided furthersupport for the hypothesis that lead is being mobilized either during pregnancy andlor l a ~ t a t i o n ’ ~ * ~ ~ - ~ ~ . Lowlevel Lead Exposure and its Effects on Pregnancy Lead‘s adverse effect on pregnancy outcomes has been well documented for high lead doses and include sterility, spontaneous abortion a n d stillbirth27.However, the potential effects of low lead levels have only been investigated seriously in the last decade. The intrinsic difficulty with these types of studies is in the assessment of whether lead levels are the cause of the observed effect, or if the effect is due to a multitude of other variables. Careful planning of the experiment and thorough examination of the data is necessary. Most studies have been cross-sectional and only a few longitudinal projects have been completed. The results of research done on low levels of lead and pregnancy outcome are described in Table 1. Although low-lead-level effects are diflicult to define and the current research appears conflicting, some of the data does support the hypothesis that lead has a detrimental effect on pregnancy outcome at levels that are well within the “acceptable” range (less that 25 pg/dL)2’-22,24,28,30~32. Since it appears that placental lead increases significantly with a mother’s length ofoccupational exposure” and that blood leads in newborns are more a reflection of a mother’s body burden than of current exposure19,a close examination and possible re-evaluation of the state of the art “acceptable” levels of lead exposure are necessary. A number of points need to be considered:
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,
Asia-PacificJournal ofpublic Health 1992/1993 Vol. 6 NO.2 Table 1. Low-level lead effects on pregnancy
OUTCOME
MATERNALLEAD W d L blood)
Pretenn Delivery
9.85 f 4.4 17.1 19.0 f0.79 29. I & 0.54
No Effect Increased Risk No Effect Lead Associated
29 21 33 30
6 . 4 8 ~1.88
No Effect Increased Risk Lead Related Decreases No Effect Decrease
31 28 22
No Effect
33
CongenitalAnomalies Growth Stature Birth Weight
greater than 8.7*
greater than 7.7 11.2
greater than I5.0* 19.0 f0.79
EFFECT
REF
21
32
*Cord lead levels 1. Nutritional Status
The absorbance and hence the toxicity of lead, can be influenced by a number of dietary factors. Deficiencies of iron, calcium and zinc can increase lead absorption from thegd4. Diets high in phosphate or high in fat have been shown to enhancelead toxMilk enhances lead icity in absorptioninweanlingrats3’,andlactose appears to be the contributing factor”ss. Dietary calcium has an inverse relationshipwith blood lead levels in both rats3’ and humans4’. Given that pregnancy and lactation, particularly in the later stages, puts a nutritional demand on the mother, her nutritional status may significantly affect her blood lead levels. This situation may be more relevant in Third World countries where malnutrition existsanddietaryeducation is lacking. In addition, whole populations may be more or less sensitive to theeffects of lead, dependingon their dietary composition.
2. Body Burden of Lead Past exposuresand total body burden may play a much more important role in the toxicity of lead to the fetus than current maternal exposure. Research has indicated that lead may be released from bone during pregnancy particularly from womcn with a previous history of a moderate to high
lead exposure10*’8*20 (either occupational exposure or a lead poisoning episode). A close examination of a mother’s lead exposure history, prior to conception may be necessary in order to assessthe potential risk of her internal lcad stores to her unborn child.
3. Other Eflects of Low-levelLead Exposure Other health effects have been observed at blood lead concentrations below the current “acceptable” level. These include anaemia7 and n e u r o t ~ x i c i t y ’ - ~ ’ -in~ ~children. Moderately elevatedblood lead levels have been associatedwith adverse effects on the male reproductive sy~tem~~.~~.
The Employment of Womenin Lead Industrieshas Presented ConflictingLeg;slation 4.
In the face of their obligations under the Occupational Health and Safety Act, employersare obliged to provide a safe workplace for their workers. The unborn children of pregnant women are included in this duty of care. However, under thc sexual discrimination act, the employer cannot refuse employment on the basis of sex. For lead industries, a conflict arises from these two legislativedocuments.
Legislationin somestatesofAustralia b k women from employment in lead industries because the work is considered sufficiently dangerous to interfere with the health of the fetus she may carry. The exclusion of women in the lead industry is no longer viable and currently the National Occupational Health and Safety Commission is undertaking the dimcult task of devising a National Lead Standard which will reduce the health risk to all employees in “lead risk” operation^^^. The difficulty rests in finding a balance which encompasses the health risk to both the employee and the unborn child, without sexual discrimination and without seriously damaging the economic viability of the industry. In those states where current legislation does not prevent women from workingin lead industries,womenare removed from lead sourcesas soon as they inform their manager of their condition of pregnancy. In light of the fact that previous exposure may be reflected in the blood during pregnancy, and that prenatal exposure is implicated as a critical time for toxicity to the fetus, simply removing a pregnant woman from sourcesof lead exposure may not be providing the protection to the fetus that is intended. For a more detailed discussion, an article by Winder and Gunningham presentsareviewoftheeffectsof lead on reproduction and discusses protective legislation and discrimination in Australian lead industries4’. 5. Lead Toxicityin Developing
Countries
In the last fifty years there has been a considerableimprovementin lead exposure conditions. This, in conjunction with regular monitoringof blood lead levelsand strict hygiene enforcement, has controlled the incidenceof occupational lead poisoning in Westem countries. Unfortunately, industrializationof developingcountriesis occurringat a rate that isgreaterthan the development of occupational health and safety facilities in those countriesand as the main emphasisis on economicdevelopment, the application of preventive measuresagainst 37
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Asia-Pacific Journal of Public Health 1992/1993 Vol. 6 No. 2 adverse exposures to hazardous substances is lacking in both the industrial and environmental areas. The poor enforcement ofhealth measures, particularly in small-scale businesses, the general ignorance of the worker with regard to the toxicity oflead, and the lack of legislation for health protection and/or enforcement of such legislation, are some examples of the problems that need to be faced by developing countries. These sorts of problems could be addressed, at least partially, by placing conditions on international aid funding. For example, funds used for economic development could be tied to improving working conditions. In addition, as mentioned previously, nutritional statuscanaffect susceptibility to lead exposure. This factor, as well as others such as the presence of tropical diseases, the differences in the working populations (i.e. traditional jobs for women, higher percentages ofelderlyand very young workers), illiteracy and lack of education, are amongst many.additional points which require special attention in the protection of people in developing countries from harmful exposures to lead. The lessons learned about the toxicity of lead in the already developed countries should be utilized by developingcountries to ensure that exposures to lead are kept as low as possible.
Conclusion The lowlevel health effects of lead have been given increased attention over the past 20 years, particularly to the adverse neurological effects on the unborn and the developing child. Results of research in this area have provided evidence that currently acceptable exposures to lead may need to be re-evaluated. The possibility that lead can be mobilized from the bone in certain circumstances justifies a second look at the validity of removing women from sources of lead exposure prior to, oras soonas possibleafter,conception. If lead is, in certain instances, released from body stores which were previously considered to be inert, then a mother’s total body burden of lead, and hence her long-term
exposure prior to conception, may become a significant factor in determining the lead exposure of her unborn child. The evidence supporting the hypothesis that lead may be mobilized during pregnancy is 1imited:In addition, there has not been a single human study which specifically examines this phenomenon and all the available data has been obtained secondary to research conducted for alternative purposes or from animal studies. Several explanations for this apparent lack of information are proposed. It is already known that nutritional status may effect the absorption of lead. Mobilization of lead during pregnancy may also depend on the nutritional status of the mother. The majority of the research reported in the literature has been conducted in developed countries where the nutritional status of pregnant mothers is expected to be adequate. This may not be the case in developing countries. In addition, mobilization of lead may be significant only in those women with high body burdens of lead, such as those who have been occupationally exposed. These women a r e removed from lead sources with the advent of pregnancy and details of their blood lead levels throughout pregnancy are not available. There is a definite need to conduct specific investigations in humans to determine how certain conditions such as nutritional status, past lead exposures, skeletal lead stores, ethnic group, and disease may effect the process of lead mobilization, particularly during pregnancy and lactation. I n Australia, with antidiscrimination legislation to consider, removal of women from lead industry is no longer a viable alternative. In order to prevent harmful exposures of lead to humans and, in particular, to the unborn child, the “acceptable” blood lead values have been progressively decreasing. Currently the NHMRC occupational health guidelines recommend that maternal blood lead levels should be and WHO recombelow 40 mends that this level be 30pg/dL6. The NHMRC public health lead limit
recommends 25 pg/dL as a “level of concern”33.Evidence that lead effects c a n o c c u r a t levels less t h a n 25 pg/dL3*’ may lead to the further reduction in both occupational and public health lead limit levels. There is a wide range of variability in sensitivity to lead amongst individuals. Ideally, threshold limit values for lead exposure should be directed towards the protection of those who are more susceptible to exposure. From an occupational point of view this approach will reduce potential grounds for discrimination against women of child-bearing age, although pregnant women will still be removed from lead sources. The issue of different sensitivities of individuals to lead may also be relevant to different ethnic groups and this area may need serious attention with regard to the setting of “acceptable” exposure limits for lead in developing countries.
References 1. Hemberg S, Dodson VN, Zenz C. Lead and its compounds. In: Zenz C, editors. Occupational Medicine Principles and Practical Applications, 2nd Edition. USA: Year Book Medical Publishers, 1988, Chapter 36. 2. National Health and Medical Research Committee. Lead in Australians. ReportofNHMRC 103th Session. Canberra, 1987. 3. Alperstein G, Renzik RB, Duggins GG. Lead: subtle forms and new modes of poisoning. Med J ‘Aust 199 1; 155:407-9. 4. World Health Organization: Recommended Health-Based Limits in Occupational Exposure to Heavy Metals. Geneva: World Health Organization 198036-80. 5. National Health and Medical Rcsearch Committee. Lead (inorganic): Approved Occupational Health Guide. Approved in Report of NHMRC. 90th Session. Canberra, 1980. 6. World Health Organization. Environmental Healthcriteria 3 --Lead. Geneva:World Health Organization 1977: 104-12,130-1. 7. Moore MR, Goldberg A. Health implications of the hematopoietic effects of lead. In: Mahaffey KR, editor. Dietary and Environmental Lead: Human Health Effects.
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The Port Pirie Cohort Study: maternal blood lead and pregnancy outcome. J Epidemiol Community Health 1986;40:18-25. Shukla R, Bornschein RL, Dietrich KN et al. Foetal and infant lead exposure: Effects on growth in stature. Pediatrics 1989;84:604-12. Ernhart CB, Greene T. Postpartum changes in maternal blood lead concentrations. Br J Ind Med 1992; 49:ll-3. Bull RJ, McCauley PT, Taylor DH, Croftcn KM. The effects of lead on the developing central nervous syst e m o f rats. Neurotoxicology 1983;4: 1-1 8. Donald JM, Cutler MG, MooreMR. Effects of lead in the laboratory mouse. 1 . Influence upon absorption, retention and tissue distribution of radiolabeled lead. Environ Res 1986;4 1 :420-3 1. Buchet JP, Lauwerys R, Rods H, Hubermont G. Mobilization of lead during pregnancy in rats. Int Arch Occup Environ Hlth 1977;40:33-6. Rom WN.Effects of lead on the female and reproduction: A review. Mt Sinai J Med 1976;43:542-52. Needleman HL, Rabinowitz M, Leviton A, Linn S, Schoenbaum S. The relationship between prenatal exposure to lead and congenital anomalies. JAMA 1984;251:2956-9. Angel1NF, Lavery JP. The relationship of blood lead levels to obstetric outcome. Am J Obstet Gynecol 1982;142:40-6. Fahim MS, Fahim Z, Hall DG. Effects of subtoxic lead levels on pregnant women in thestateofMissouri. Res Commun Chem Pathol Pharmacol 1976;13:309-331. Ernhart CB, WolfBW, Kennard GJ, Erhard J, Filipovich HF, Sokol RJ. Interuterine exposure to low levels of lead: the status of the neonate. Arch Environ Hlth 1986;41:28791. Bellinger D, Leviton A, Rabinowitz M e t al. Weight gain and maturity in fetuses exposed to low levels of lead. Environ Res 1991;54: 151-8. LitvakPF, Graziano JH, N i n e JK et al. A prospcetive study of birth weight and length of gestation in a population surrounding a lead smelter in Kosovo, Yugoslavia. Int J Epidemiol 1991;20:722-8. Mahaffey KR. Biotoxicity of lead: Influence of various factors. Fed Proc 1983;42: 1730-4.
35. Spickett JT, Bell RR. The influence of dietary phosphate on the toxicity of orally ingested lead in rats. Food Chem Toxicol 1983;21:157-61. 36. Bell RR, Spickett JT. The influence ofdietary fat on the toxicityoforally ingested lead in rats. Food Chem Toxicol 1983;21:469-72. 37. Bell RR, Spickett JT. The influence of milk in the diet on the toxicity of orally ingested lead in rats. Food Cosmet Toxicol 198 1; 19:429-36. 38. Nzelibe CK, Knight EM, Adkins JS. Effects of carbohydrates on lead absorption and retention in weanling rats. Environ Res 1986;41:458-65. 39. Mahaffey KR. Nutritional factors and susceptibility to lead toxicity. Environ Health Perspect 1974;7: 107-1 2. 40. Kostial K, Dekanic D, Telisman S. Dietary calcium and blood lead levels in women. Biol Trace Elem Res 1991;28: 181-5. 41. Whetsell WO, Kappas A. Protective effect of exogenous haem against lead toxicity in mouse dorsal root ganglia. J Neuropathol Exptl Neurol (Abstract) 1981;40:334. 42. Mushak P, Davis JM, Crocetti AF, Grant LD. Prenatal and postnatal effects of lowlevel lead exposure: Integrated summary of a report to the US Congress on Childhood Lead Poisoning. Environ Res 1989;50: 11-36. 43. Bellinger D, Leviton A, Waternaux C et al. Longitudinal analysis of prenatal and postnatal lead exposure and early cognitive development. New Engl Med 1987;316:1037-43. 44. Lancranjan I, Popescu HI, Vanascu GA. Reproductive ability of workmen occupationally exposed to lead. Arch Environ Health 1975;30: 396-401. 45. Cullen MR, Kayne RD, Robins JM. Endocrine and reproductive dysfunction in men associated with occupational inorganic lead intoxication. Arch Environ Health 1984;39: 431-40. 46. National Occupational Health and Safety Commission. Draft National Lead Control Standard. February 1990. 47. Winder C, Gunningham N. Protective legislation and discrimination in employment in the Australian lead processing industries. J Occup Health Safety - Aust N Z 1988;4: 9-20.
39 Downloaded from aph.sagepub.com at Bobst Library, New York University on May 25, 2015
The Interaction of Lead Exposure and Pregnancy
The toxic effectsof low-levellead exposure have been the subject of a good deal of research and media attention in recent times. In most countries, the acceptable occupational exposure limit for lead is being progressively K O’Halloran, BSc(Hons) decreased as the adverse health effects JT Spickett, BSc(Hons), MSc, PhD of lead are being identified at levels School of Public Health approaching those found in nonDivision of Health Sciences occupational environments. Due to the sensitive nature of the Curtin University ofTechnology fetus to hazardous substances, the ex- Perth, Australia posure to lead of the unborn child via maternal sources is of critical concern. Preterm delivery, congenital abnor- Introduction malities and decreases in growth stature have all been associated with pre- The risks to human heaIth from contamination of both the work and natal lead exposure at “acceptable” general environment are often subtle levels. and pervasive. As scientists and the There is an accumulationofevidence which indicates that maternal expo- medical profession are beginning to recognize the adverse health effects sures prior to conception can play an of low levels of toxic substances, important role in determining blood the acceptable occupational exposure lead levels during pregnancy. In light of these observations the practice of limits for these substances are being removing the pregnant woman from progressively decreased. For some of lead sources may be of questionable these substances, e.g. lead, the margin value with regards to providing SHI- between acceptable occupational cient protection for the fetus. This limits and the levels found in the enarticle reviews the relevant literature vironment is becoming difficult to identify. In many developing counpertaining to the mobiiization of lead from bone during pregnancy and the tries, increased emphasis is being toxicity of low-level lead exposure to placed on reducing exposure to both the fetus, and briefly discusses some toxic substances at work and industrial pollution in the environment. factors which may affect this toxicity. This emphasis is occurring as tradiKeywords: Adverse health effects, tional risks to health from infectious mobilization of lead, occupational and diseases and microbiological contamination of food and water are becomenviroampntal lead exposure, preging more controlled and the time and nancy. capital can be transferred in another, but no less important, direction. Lead is one example of a metal whose toxic effect has been known for centuries’. The potential danger to humans, particularly to the unborn or developing child, of exposure to lead has been a subject of public concern and has resulted in considerable research interest. With the improvement in scientific methods there has been a significant generation ofdata from both animal and human studies that indicatethehazardsofleadatlow levels which were previously considAddress for reprints: JT Spickett, School of ered non-toxic. From a public health Public Hcalth, Curtin University of Techperspective, the blood lead level of nology, GPO Box U 1987, Pcrth 6001, concern is 25 pg Pb/dL blood’. In the Australia.
USA. the Centers for Disease Control currektly recommends 25 pg Pb/dL as a level of but is expected Soon to this to 10-15 .u-d ~ ~ 3 . From an o&pational perspective, the World Health Organization (WHO) recommended exDosurelimit for maies is 40 &dL a n d for females of a reproductive age the limit is 30 pg/dL4, while the National Health a n d Medical Research Council (NHMRC) in Australia recommends maternal blood levels should be below 40 pg/dL5. However, lead-induced changes in the hemopoietic system have been reported at levels less than 25 pg/dL6?’. In light of this evidence, and as the value of the “acceptable” occupational lead level progressively decreases, environmental lead becomes an increasingly important issue. While blood leads are used to indicate the level of current or shortterm exposure, there is, however, a large pool of lead that resides in the skeleton which is slowly released into the blood, thus representingan “internal” exposure. Under certain conditions of stress such as bone fractures or acute infections, mobilization of this skeletal pool may occur, resulting in inexplicably high blood lead levels’.*. Recent evidence indicates that mobilization of lead may be occurring during pregnancy and lactation9*10.In pregnancy, lead in the mother’s circulatory system will be transferred to the fetus via the placenta as early as the 12th week of gestation”. Lead is also available to the suckling infant via maternal milk12*13.The reason for concern about the exposure of pregnant 35
Downloaded from aph.sagepub.com at Bobst Library, New York University on May 25, 2015
Asia-Pacific Journal of Public Health 1 9 9 2 993 ~ Vol. 6 No. 2 females to lead is due to the increased sensitivity of fetal tissues to toxic chemicals and its underdeveloped detoxifying and excretory mecha n i s m ~ ’ ~ In ~ ’light ~ . of the evidence which indicates the possibility of lead becoming mobilized during pregnancy, it may become necessary to consider a mother’s body burden of lead as well as her current blood lead status, in order to determine the risk of lead toxicity to the fetus. This article will review the toxicity of inorganic lead at low levels and the results of research that indicate lead mobilization during pregnancy and lactation, and include a discussion of the potential consequences to the employment ofwomen in the lead industry and the conflict that arises between discrimination against the fertile woman and the protection of the fetus. Storage and Mobilization of Lead from Bone Lead has a strong affinity for bone and, when in a state of equilibrium, the skeleton contains more than 90% of the total body burden16. Lead accumulates in bone throughout life, thus the lead content of bone will be indicative of long-term and past exposures whereas blood lead levels are more a reflection of current and recent exposures. Mobilization of lead stored in bone may occur concomitantly with episodes of bone demineralisation, for example during menopause. There is evidence to support the theory that bone lead stores are released into the blood at significant levels during the menopausal period. A comparison of blood leads between preand post-menopausal women (controlling for age) showed significantly higher (12.5%) blood lead concentrations in the post-rnenopausalgr~up'~. In addition, women who had never been pregnant had higher postmenopausal lead levels than those who hadgiven birth. Theauthors postulate that if pregnancy causes bone demineralisation then less lead will be available for mobilization at a later date. A recent retrospective study provides evidence which suggests that
lead levels released from the bones of women who had suffered from lead poisoning during their childhood may reach levels which are toxic to the fetus’*. In this study, a history of childhood plumbism was associated with known adverse lead effects on pregnancy outcome, such as spontaneous abortion, stillbirths and having children with learning disabilities. An Australiancase studyofa woman who had suffered a childhood lead poisoning episode reported the presence of elevated blood lead levels during pregnancy and lactation which was not due to a recent exposure”. In the frequentlyquoted study by Manton, a 50% decline in blood lead levels was recorded in a mother 11 months after childbirth’. The increased blood lead levels during pregnancy could not be justified in terms of environmental or dietary exposures. Skeletal lead is indicated as a third source oflead as its turnover rate would increase to meet the demands of late pregnancy and lactation. Further supporting evidence of the view that blood lead levels ofpregnant women reflect body burden rather than current status of exposure was found by Buchet and associates in their study of the influence of various epidemiological factors on the exposure of pregnant women to lead”. In this cross-sectional study, the distribution of blood lead levels ofmothers who had always lived in an urban or a rural areawvere different to those from mothers who had only lived in those areas for one to five years. This difference would not be expected if blood leads were a measure oFcurrent exposure. The blood lead levels of newborns also reflect this difference. It has also been found that lead levels in the placental tissue of women in the pottery industry in the UK increased with the length of maternal exposure, giving further reason for considering a mother’s accumulative lead levels, as opposed to current exposure, when assessing potential toxicity to the fetus2’. The mobilization of lead during pregnancy and lactation has not been specifically investigated in human studies and the evidence obtained has generally been secondary to a related
but separate set of data. Data from other studies have not always supported the theory oflead mobilization duringpregnancy and show no change in blood lead levels2’*22.A recent study showed significant increases in blood lead levels at six months postpartum compared to blood lead levels at birth23. Animal studies camed out in the last decade have provided furthersupport for the hypothesis that lead is being mobilized either during pregnancy andlor l a ~ t a t i o n ’ ~ * ~ ~ - ~ ~ . Lowlevel Lead Exposure and its Effects on Pregnancy Lead‘s adverse effect on pregnancy outcomes has been well documented for high lead doses and include sterility, spontaneous abortion a n d stillbirth27.However, the potential effects of low lead levels have only been investigated seriously in the last decade. The intrinsic difficulty with these types of studies is in the assessment of whether lead levels are the cause of the observed effect, or if the effect is due to a multitude of other variables. Careful planning of the experiment and thorough examination of the data is necessary. Most studies have been cross-sectional and only a few longitudinal projects have been completed. The results of research done on low levels of lead and pregnancy outcome are described in Table 1. Although low-lead-level effects are diflicult to define and the current research appears conflicting, some of the data does support the hypothesis that lead has a detrimental effect on pregnancy outcome at levels that are well within the “acceptable” range (less that 25 pg/dL)2’-22,24,28,30~32. Since it appears that placental lead increases significantly with a mother’s length ofoccupational exposure” and that blood leads in newborns are more a reflection of a mother’s body burden than of current exposure19,a close examination and possible re-evaluation of the state of the art “acceptable” levels of lead exposure are necessary. A number of points need to be considered:
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Asia-PacificJournal ofpublic Health 1992/1993 Vol. 6 NO.2 Table 1. Low-level lead effects on pregnancy
OUTCOME
MATERNALLEAD W d L blood)
Pretenn Delivery
9.85 f 4.4 17.1 19.0 f0.79 29. I & 0.54
No Effect Increased Risk No Effect Lead Associated
29 21 33 30
6 . 4 8 ~1.88
No Effect Increased Risk Lead Related Decreases No Effect Decrease
31 28 22
No Effect
33
CongenitalAnomalies Growth Stature Birth Weight
greater than 8.7*
greater than 7.7 11.2
greater than I5.0* 19.0 f0.79
EFFECT
REF
21
32
*Cord lead levels 1. Nutritional Status
The absorbance and hence the toxicity of lead, can be influenced by a number of dietary factors. Deficiencies of iron, calcium and zinc can increase lead absorption from thegd4. Diets high in phosphate or high in fat have been shown to enhancelead toxMilk enhances lead icity in absorptioninweanlingrats3’,andlactose appears to be the contributing factor”ss. Dietary calcium has an inverse relationshipwith blood lead levels in both rats3’ and humans4’. Given that pregnancy and lactation, particularly in the later stages, puts a nutritional demand on the mother, her nutritional status may significantly affect her blood lead levels. This situation may be more relevant in Third World countries where malnutrition existsanddietaryeducation is lacking. In addition, whole populations may be more or less sensitive to theeffects of lead, dependingon their dietary composition.
2. Body Burden of Lead Past exposuresand total body burden may play a much more important role in the toxicity of lead to the fetus than current maternal exposure. Research has indicated that lead may be released from bone during pregnancy particularly from womcn with a previous history of a moderate to high
lead exposure10*’8*20 (either occupational exposure or a lead poisoning episode). A close examination of a mother’s lead exposure history, prior to conception may be necessary in order to assessthe potential risk of her internal lcad stores to her unborn child.
3. Other Eflects of Low-levelLead Exposure Other health effects have been observed at blood lead concentrations below the current “acceptable” level. These include anaemia7 and n e u r o t ~ x i c i t y ’ - ~ ’ -in~ ~children. Moderately elevatedblood lead levels have been associatedwith adverse effects on the male reproductive sy~tem~~.~~.
The Employment of Womenin Lead Industrieshas Presented ConflictingLeg;slation 4.
In the face of their obligations under the Occupational Health and Safety Act, employersare obliged to provide a safe workplace for their workers. The unborn children of pregnant women are included in this duty of care. However, under thc sexual discrimination act, the employer cannot refuse employment on the basis of sex. For lead industries, a conflict arises from these two legislativedocuments.
Legislationin somestatesofAustralia b k women from employment in lead industries because the work is considered sufficiently dangerous to interfere with the health of the fetus she may carry. The exclusion of women in the lead industry is no longer viable and currently the National Occupational Health and Safety Commission is undertaking the dimcult task of devising a National Lead Standard which will reduce the health risk to all employees in “lead risk” operation^^^. The difficulty rests in finding a balance which encompasses the health risk to both the employee and the unborn child, without sexual discrimination and without seriously damaging the economic viability of the industry. In those states where current legislation does not prevent women from workingin lead industries,womenare removed from lead sourcesas soon as they inform their manager of their condition of pregnancy. In light of the fact that previous exposure may be reflected in the blood during pregnancy, and that prenatal exposure is implicated as a critical time for toxicity to the fetus, simply removing a pregnant woman from sourcesof lead exposure may not be providing the protection to the fetus that is intended. For a more detailed discussion, an article by Winder and Gunningham presentsareviewoftheeffectsof lead on reproduction and discusses protective legislation and discrimination in Australian lead industries4’. 5. Lead Toxicityin Developing
Countries
In the last fifty years there has been a considerableimprovementin lead exposure conditions. This, in conjunction with regular monitoringof blood lead levelsand strict hygiene enforcement, has controlled the incidenceof occupational lead poisoning in Westem countries. Unfortunately, industrializationof developingcountriesis occurringat a rate that isgreaterthan the development of occupational health and safety facilities in those countriesand as the main emphasisis on economicdevelopment, the application of preventive measuresagainst 37
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Asia-Pacific Journal of Public Health 1992/1993 Vol. 6 No. 2 adverse exposures to hazardous substances is lacking in both the industrial and environmental areas. The poor enforcement ofhealth measures, particularly in small-scale businesses, the general ignorance of the worker with regard to the toxicity oflead, and the lack of legislation for health protection and/or enforcement of such legislation, are some examples of the problems that need to be faced by developing countries. These sorts of problems could be addressed, at least partially, by placing conditions on international aid funding. For example, funds used for economic development could be tied to improving working conditions. In addition, as mentioned previously, nutritional statuscanaffect susceptibility to lead exposure. This factor, as well as others such as the presence of tropical diseases, the differences in the working populations (i.e. traditional jobs for women, higher percentages ofelderlyand very young workers), illiteracy and lack of education, are amongst many.additional points which require special attention in the protection of people in developing countries from harmful exposures to lead. The lessons learned about the toxicity of lead in the already developed countries should be utilized by developingcountries to ensure that exposures to lead are kept as low as possible.
Conclusion The lowlevel health effects of lead have been given increased attention over the past 20 years, particularly to the adverse neurological effects on the unborn and the developing child. Results of research in this area have provided evidence that currently acceptable exposures to lead may need to be re-evaluated. The possibility that lead can be mobilized from the bone in certain circumstances justifies a second look at the validity of removing women from sources of lead exposure prior to, oras soonas possibleafter,conception. If lead is, in certain instances, released from body stores which were previously considered to be inert, then a mother’s total body burden of lead, and hence her long-term
exposure prior to conception, may become a significant factor in determining the lead exposure of her unborn child. The evidence supporting the hypothesis that lead may be mobilized during pregnancy is 1imited:In addition, there has not been a single human study which specifically examines this phenomenon and all the available data has been obtained secondary to research conducted for alternative purposes or from animal studies. Several explanations for this apparent lack of information are proposed. It is already known that nutritional status may effect the absorption of lead. Mobilization of lead during pregnancy may also depend on the nutritional status of the mother. The majority of the research reported in the literature has been conducted in developed countries where the nutritional status of pregnant mothers is expected to be adequate. This may not be the case in developing countries. In addition, mobilization of lead may be significant only in those women with high body burdens of lead, such as those who have been occupationally exposed. These women a r e removed from lead sources with the advent of pregnancy and details of their blood lead levels throughout pregnancy are not available. There is a definite need to conduct specific investigations in humans to determine how certain conditions such as nutritional status, past lead exposures, skeletal lead stores, ethnic group, and disease may effect the process of lead mobilization, particularly during pregnancy and lactation. I n Australia, with antidiscrimination legislation to consider, removal of women from lead industry is no longer a viable alternative. In order to prevent harmful exposures of lead to humans and, in particular, to the unborn child, the “acceptable” blood lead values have been progressively decreasing. Currently the NHMRC occupational health guidelines recommend that maternal blood lead levels should be and WHO recombelow 40 mends that this level be 30pg/dL6. The NHMRC public health lead limit
recommends 25 pg/dL as a “level of concern”33.Evidence that lead effects c a n o c c u r a t levels less t h a n 25 pg/dL3*’ may lead to the further reduction in both occupational and public health lead limit levels. There is a wide range of variability in sensitivity to lead amongst individuals. Ideally, threshold limit values for lead exposure should be directed towards the protection of those who are more susceptible to exposure. From an occupational point of view this approach will reduce potential grounds for discrimination against women of child-bearing age, although pregnant women will still be removed from lead sources. The issue of different sensitivities of individuals to lead may also be relevant to different ethnic groups and this area may need serious attention with regard to the setting of “acceptable” exposure limits for lead in developing countries.
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