Karen Mizon

Mobilization of lead from human bone tissue during pregnancy and lactation—a summary of long-term research

The skeleton is potential endogenous source of lead during pregnancy and lactation. We have undertaken a longitudinal investigation into the mobilization of lead from the human maternal skeleton to determine whether lead is mobilized from the maternal skeleton during pregnancy and lactation, and if so, when and how much is released. Subjects in the study were migrants to Australia (n=15) whose skeletal lead isotopic composition (endogenous lead) was different to that prevailing in the Australian environment (exogenous lead). This migrant cohort was compared with 6 multi-generational Australian controls. Biological and environmental samples were taken pre-pregnancy where possible, throughout pregnancy and postpartum for at least 6 months. Newly-born infants of the migrant and Australian mothers were monitored for 6 months. Blood lead concentrations for the migrant mothers ranged from 1.5 to 20 microg/dl (geometric mean 2.8) and for Australian mothers ranged from 1.9 to 4.3 microg/dl (geometric mean 2.9). There was minimal change in lead isotopic composition of the Australian pregnant controls although there were increases of approximately 40% in blood lead concentration in 3 of 6 cases during the postpartum period and from 0 to 12% in the other 3. In the migrant pregnant subjects, the geometric mean skeletal lead contribution to blood lead using the isotopic composition was approximately 33% (range 10-88%) for 14 subjects using a revised estimate for exogenous lead. Skeletal contribution to blood lead during the postpartum period was significantly greater than during pregnancy (P<0.001). The skeletal contributions to blood lead are higher and the changes are more consistent in those subjects who conceived within 100 days of arrival in Australia compared with those who conceived longer than 100 days. In the migrant subjects, changes in blood lead concentration during pregnancy and postpartum varied from subject to subject with an overall 20% increase; the increases during the postpartum period were greater than during pregnancy (P<0.001). It was estimated that the amount of maternal skeletal lead mobilized during pregnancy and transferred to the infant via cord blood averaged approximately 79%. The increased skeletal contribution to blood lead is attributed to a low daily calcium intake of approximately 500 mgCa/day, a condition which was present in both migrant and Australian subjects. An ongoing clinical trial is providing a new cohort with calcium supplements. A summary of other aspects of the study is included and covers: additional flux released from the skeleton during pregnancy and postpartum; XRF bone lead results; urinary excretion of lead during pregnancy and postpartum; dietary contribution to blood lead in female adults and children; comparison of rates of exchange of lead in blood of newly-born infants and mothers; relationships of lead in breast milk to lead in blood, urine and diet of the infant and mother; changes in blood lead after cessation of breastfeeding; urinary lead isotopes during pregnancy and postpartum indicate no preferential partitioning of endogenous lead into plasma; a comparison of some aspects of the nonhuman primate and human pregnancy studies.

Non-orebody sources are significant contributors to blood lead of some children with low to moderate lead exposure in a major lead mining community

High precision lead isotope ratios in blood from 58 children aged 1-11 years from the Broken Hill lead mining community have been measured to determine the source and pathways of lead in their blood. Sources of lead are from the Pb-Zn-Ag orebody (lead), from paint and from petrol. Thirty-five of the 58 children (60%) had blood leads (PbB) > or = 0.72 micromol/l (15 microg/dl), the current level of personal exposure and source remediation/abatement compared with a background level of approximately 0.29 micromol/l (6 microg/dl), estimated from adult females who were generally mothers of the children. Six of 17 children aged 7 years or older, had PbBs > or = 0.72 micromol/l (15 microg/dl). Even though the orebody lead is the major contributor to PbB in Broken Hill children, of the 35 children whose PbB is > or = 0.72 microm/l (15 microg/dl), 12 (34%) have approximately 50% or more of their PbB derived from sources such as paint and petrol or both by isotopic identification. The identification of elevated PbB in older children is a concern, especially for females, as there is potential for release of endogenous lead during pregnancy and lactation.

Importance of monitoring family members in establishing sources and pathways of lead in blood

High precision lead isotope measurements were undertaken to establish the sources and pathways in blood and environmental samples of five families from the Broken Hill lead mining community, New South Wales, Australia. The five families were selected from 27 families investigated to illustrate the different sources and pathways of lead into blood and the importance of monitoring the whole family. The results illustrate that although the major source of lead is from the orebody, paint and petrol can be significant contributors to both house dust and blood leads. The results also show that the sources and pathways can be from the fathers occupation and hence monitoring of families is important, especially in high risk locations. In two cases, the elevated blood leads in the children did not derive from their current residence but from other residences in the community.

Pathways of Pb and Mn observed in a 5-year longitudinal investigation in young children and environmental measures from an urban setting

We monitored 108 children ≤5 years on a 6-month basis for up to 5 years in a major urban setting. Samples (n ∼ 7000) included blood, urine, handwipes (interior, and after exterior playing), 6-day duplicate diet, drinking water, interior house and day care dust-fall accumulation using petri dishes, exterior dust-fall accumulation, exterior dust sweepings, paint, soil and urban air. The geometric mean blood Pb (PbB) was 2.1 μg/dL and blood Mn (MnB) was 10.0 μg/L. Following a path modelling approach, mixed model analyses for a fully adjusted model showed the strongest associations for PbB were with interior house dust and soil; for MnB there were no significant associations with any predictors. Predictor variables only explained 9% of the variance for Pb and 0.7% for Mn. Relationships between environmental measures and PbB in children are not straightforward; soil and dust sweepings contribute only about 1/5th of the amounts to PbB found in other studies.

Longitudinal monitoring of selected elements in blood of healthy young children

There are limited data on essential nutrients in the whole blood of young children. As part of a longitudinal study of the impact on young children and the environment from the introduction of an organic Mn compound into unleaded gasoline in Australia, we have measured a suite of elements in whole blood. The children, aged between 6 and 31 months at recruitment, have been monitored at 6-month intervals for up to 5 years. Blood samples were analysed by inductively coupled plasma mass spectrometry for Ca, Mg, Fe, Mn, Cu, Zn and Pb. Mixed model analyses of 665 blood samples using backward elimination showed significant positive relationships between Ca, Mg and Zn and season, variable relationships with time, but no association with gender or traffic exposure. The elements Ca, Mg and Zn showed higher concentrations in summer compared with winter, whereas Fe and Pb showed lower concentrations in summer compared with winter. Concentrations of all elements except Fe showed significant effects over time: Ca, Cu, Mg, Pb and Mn showed decreases over time, whereas Zn showed an increase. The mixed model analyses with the individual elements as the dependent variable showed some interesting relationships and require further follow-up as some of these appear to conflict with pre-existing concepts, although the multi-element data on which these concepts are based are limited. The variance for blood Pb and blood Mn arising from the other elements was small with 0.5% in the case of blood Pb and 3.7% for blood Mn.

Limited seasonality effects on blood lead for a small cohort of female adults and children

Many blood lead surveys, especially during the 1970s and 1980s have shown variations of up to 35% in blood lead concentration, with higher values in summer over winter. We have monitored 13 adult females and seven children for periods from 348 to 1337 days as non-pregnant controls in a longitudinal study of mobilization of lead from the maternal skeletal during pregnancy and lactation. Samples of blood, 6-day duplicate diet and environmental samples were analyzed by high-precision thermal ionization mass spectrometry for lead isotope ratios and lead concentrations. There was no statistically significant difference between seasons for blood lead concentrations and dietary intake although there were small differences in the isotopic composition for blood. One explanation for the lack of a seasonal effect in blood lead of our cohort may be the absence of climatic extremes in Sydney. The minimal effects from seasonality observed in this cohort make this an especially useful cohort within which to study effects that could be obscured by seasonal factors.

Revisiting mobilisation of skeletal lead during pregnancy based on monthly sampling and cord/maternal blood lead relationships confirm placental transfer of lead

Lead (Pb) can be released from the maternal skeleton during pregnancy and lactation and transferred to the infant. Most support for this hypothesis comes from blood Pb (PbB) studies involving limited sampling during pregnancy, the maximum usually being five samplings, including at delivery. We provide longitudinal data for PbB concentrations and Pb isotopic ratios for three cohorts of pregnant females (nxa0=xa031), two of which are based on monthly sampling and the other on quarterly sampling. We also provide data for samples collected post-partum. The data are compared with changes observed in a matched, by country and age, non-pregnant control cohort (nxa0=xa05). The monthly data illustrate the variability between subjects, which is also apparent when the data are compared on a trimester basis. Mixed model analyses showed that, in the third trimester, the mean PbB level was significantly lower for women (nxa0=xa010) who took a calcium (Ca) supplement (PbB 1.6xa0µg/dL) than those whose Ca intake was low (low-Ca cohort; nxa0=xa015; PbB 2.5xa0µg/dL) because low Ca means more mobilisation is required for homoeostasis so that more Pb was mobilised from the skeleton. For women who took the supplement, post-partum PbB levels were significantly higher than those in the other periods (2.7 vs 1.4–1.6xa0µg/dL). For women in the low-Ca cohort, PbB levels were higher at post-partum than in pre-pregnancy and in the first and second trimesters (3.1 vs 1.8xa0µg/dL), while the levels in the third trimester were higher than those in the first and second trimesters. Importantly, the increase in PbB during gestation was delayed until the third trimester in the Ca-supplemented cohort compared with the low-Ca cohort. Regression analysis showed that the changes over trimester were very similar for PbB and the 206Pb/204Pb ratio providing convincing evidence for extra mobilisation of Pb from the maternal skeleton during pregnancy and lactation. Isotopic ratios in the cord blood samples were similar to those in the maternal blood samples taken prior to parturition with an R2 0.94 for the migrant subjects and R2 0.74 for Australian subjects for 206Pb/204Pb ratios, supporting the concept of placental transfer of mobilised skeletal stores of Pb.

Urinary excretion of lead during pregnancy and postpartum

We have compared lead isotopic ratios and lead concentrations in 53 spot urine and 59 24-h urine samples from 13 subjects covering the interval from pre-pregnancy through 180 days postpartum to estimate the amount of lead excreted in urine and renal clearance relative to blood. The total amount of lead excreted in 24-h urine samples ranges from 0.8 to 5.9 microg Pb with an arithmetic mean of 2.2+/-1.1 microg (geometric mean 1.90 microg). This compares with amounts of 0.9-10 microg of extra lead per day estimated to be released into blood from the skeleton during pregnancy and postpartum. There were no differences in excretion rates during the trimesters of pregnancy and between pregnancy and postpartum time periods. The renal clearance relative to blood ranged from 0.8 to 10 g/h (arithmetic mean 3.2+/-1.9; geometric mean 2.7). Renal clearance relative to blood was somewhat higher in trimesters 2 and 3 compared with postpartum 150-180 days (P = 0.004, 0.006, respectively). Reassessment of earlier published blood and dietary data for Australian pregnant controls indicates there is no increased gastrointestinal absorption of lead during pregnancy and postpartum. This differs from calcium, which shows increased absorption during late pregnancy. In light of the inconvenience of sampling and potential contamination at the low levels of lead found in most of these subjects, we do not consider the 24 h urines to provide sufficient useful information.

Changes in manganese and lead in the environment and young children associated with the introduction of MMT in gasoline

This is a 4-year longitudinal study to evaluate changes to the environment and exposure of young children associated with the introduction of methylcyclopentadienyl manganese tricarbonyl (MMT) into Australia in 2000. The cohort includes 57 females and 56 males; age range of 0.29 to 3.9 years. Samples are collected every 6 months from children in residences located at varying distances from major traffic thoroughfares in Sydney. Environmental samples: air, house and day care dustfall, soil, dust sweepings and gasoline. Samples from children: blood, urine, handwipes prior to and after playing outdoors, and a 6-day duplicate diet. All samples are analyzed for a suite of 20 elements using ICP-MS. Results are presented for the first three 6-month sampling periods for Pb and Mn. For dustfall accumulation, there was no significant change over the 3 sampling periods (time) for Pb or Mn, and a positive relationship between traffic exposure (traffic volume and proximity to the road) and Pb but not Mn. For handwipes, Pb and Mn in wipes taken from children after playing outdoors were usually significantly greater than for wipes taken prior to playing. There was no significant association between Pb or Mn in handwipes with traffic exposure. Dustfall accumulation was a significant predictor for Pb in the handwipes, and dust sweepings were a significant predictor of Mn in handwipes. Blood lead (PbB) ranged from 0.6 to 19 ~tg/dL (GM 2.6) (n=269), and manganese in blood (MnB) ranged from 1.8 to 45 txg/L (GM 11.6) (n=254). There was no significant difference between females and males for either mean PbB or MnB; over time there was a significant decline in PbB but no significant change in MnB. The only significant predictor for PbB was dust-fall accumulation. The only significant predictor for MnB was Mn in handwipes prior to playing. At this early stage of the investigation we have not been able to detect any increases in Mn in these environmental samples or blood samples associated with the use of MMT.