Longitudinal Study of Daily Intake and Excretion of Lead in Newly-born Infants

Brian L. Gulson^1,2, Karen J. Mizon^1,2, Jacqueline M. Palmer², Nicole Patison², Alistair J. Law², Michael J. Korsch², Kathryn R. Mahaffey³ John B. Donnelly⁴

¹Graduate School of the Environment, Macquarie University, Sydney NSW 2109 Australia (bgulson@gse.mq.edu.au); ²CSIRO/DEM, POB 136, North Ryde NSW 1670, Australia; ³U.S. Environmental Protection Agency, Washington DC, ⁴ Statistical consultant, Castle Hill, Australia

ABSTRACT

We have obtained estimates of the daily lead intake and excretion/intake for 13 newly-born infants monitored for at least 6 months postpartum. Lead concentrations were as follows: in breast milk, from 0.09 to 3.1 mg/kg (geometric mean 0.55 mg/kg); infant formula, from 0.07 to 11.4 mg/kg (gm 1.6 mg/kg); and beikost, from 1.1 to 27 mg/kg (gm 2.9 mg/kg). Daily lead intakes ranged from 0.04 to 0.83 mgPb/kg body weight/day (gm 0.22 mgPb/kg body weight/day) and excretion/intake ranged from 0.7 to 22 (gm 2.9). Estimates of contribution of diet to blood are: for breast milk only as the dietary source 40 to 65%; for breast milk and formula as the dietary sources 20 to 80% ; and for formula and beikost 20 to 80%. The increased excretion over intake and other evidence reflect mobilization of infant tissues arising especially from rapid bone turnover at this stage of life.

INTRODUCTION

Toxic compounds such as lead impact most severely on the new born at a time when neural development of synaptic connections in the cortex are rapidly increasing. Apart from contributions from maternal bone sources during pregnancy, other potential lead sources for the infant are mainly dietary, from breast milk, infant formula and baby foods. Estimated uptake of lead from the diet in young infants is poorly quantified and relies almost solely on the 1970’s reports by Alexander et al., (1974), Ziegler et al., (1978), and Ryu et al., (1985) obtained during decades when environmental lead was higher, and control of laboratory contamination was less complete. We have obtained estimates of the dietary intake and urinary excretion by using data obtained from a longitudinal study into mobilization of lead from the maternal skeleton during pregnancy and lactation. In the study, newly-born infants were monitored for 6 months postpartum to evaluate the effects of the local environment on lead body burden of the infant.

MATERIALS AND METHODS

The current study is methodologically different from the earlier metabolic balance studies. The methods of the current study are based on the mixing of lead isotopes from two dominant sources with different lead isotope ratios. The two sources are maternal tissue stores (predominantly bone) and the ambient environment. The ratio in the ambient environment is established by measurement of stable isotope ratios and lead concentrations in air, house dust, water, infant formula, and beikost.

Sixteen infants (migrant infants) were born to 15 migrant mothers and their data were compared with 8 infants (Australian infants) who were born to six multi-generational Australian controls. The skeletal lead isotopic composition in the migrant subjects, estimated from the first blood sample after arrival in Australia, was different from that in their current environment. Venous blood samples were available at four times (i.e., cord blood, 60, 120, and 180 days postpartum). Urine samples were collected 10, 30, 60, 90,120,150, and 180 days into pediatric urine collectors and transferred into precleaned polyethylene bottles. To estimate total urinary lead excretion from the measured urinary lead concentrations and isotope ratios, total urinary lead excretion was estimated using the ratio of urine/fecal excretions of 1 to 0.27 for infants with dietary lead intakes < 5 mg/kg bw/day measured by Ziegler et al. (1978) and a volume of 1 liter. Breast milk and infant formula were collected monthly. When intake of solid food began, a composited meal was prepared by the mother and dispensed into pre-cleaned polyethylene containers. Lead isotopic compositions and concentrations were measured by thermal ionization mass spectrometry.

Results and Discussion

Lead concentrations in breast milk ranged from 0.09 to 3.0 mg/kg breast milk with a geometric mean of 0.55 mg/kg (n=72, where n in this and the other following cases denotes the number of separate samples analyzed). Lead concentrations in formula were generally low with a geometric mean of 1.6 mg/kg (median 1.6) and a range from 0.07 to 11.4 mg/kg (n =68). Lead concentrations in the beikost ranged from 1.1 to 27 mg/kg with a geometric mean of 2.9 mg/kg (median 3.1 mg/kg). The differences in lead concentration between beikost and formula were statistically significant (p<0.01, two-tailed t-test).

Drinking and boiled water had low concentrations of lead and the isotopic ratios, expressed as the ²⁰⁶Pb/²⁰⁴Pb ratio, were well below 17 in all these residences (Gulson et al., 1997a, 1997b). Estimated mean daily intake was 0.29 mg Pb/kg body weight (bw)/day and varied from 0.04 to 0.83 mg/kg bw/day; the geometric mean was 0.22 mg Pb/kg bw/day. There was no significant difference for the whole group of 13 infants at the 5% level in daily intake over the two postpartum The estimated excretion rate exceeded intake by an overall factor of 3 (geometric mean 2.9). The contributions of infants’ diet to blood lead estimated using differences in isotopic composition were as follows: for breast milk as the only food source the range was from 40% to 65% (n=3); for diets composed of breast milk and formula, the range was from 20% to 80% (n=7); for diets composed of formula and beikost, the range was from 20% to 80% (n=11). The arithmetic mean value for the full 6-month period is approximately 50% (median 45%, geometric mean 45%).

Dietary Intake- The intakes are very low compared with earlier estimates from the 1970’s and early 1980’s, a time of much higher environmental lead exposures; these intakes were >20 times higher than the values reported by us. This difference has also been observed in total dietary intake. In the 1990’s, the dietary intake for 0-1 year old U.S. infants was ~7 mg Pb/day (US EPA 1994) and contrasted with those from the 1970’s. The available dietary data for very young infants are severely limited. For example, subjects investigated by Alexander et al. (1974) included only one child who was aged less than 6 months. The intakes for the full cohort of 8 subjects of Alexander et al. (1974), ranging in age from 3 months to 8 years, averaged 10.6 mg Pb/kg bw/day and varied from 5 to 17 with absorption averaging 53% of intake and retention averaging 18% of intake. Ziegler et al. (1978) reported data for 12 infants ranging in age from 14 to 746 days; only one infant was studied from birth (14 days), two were studied from 72 to 83 days respectively, and the rest were over 4 months old. Of 61 metabolic balance studies with lead intakes greater than 5 mg/kg bw/day the average absorption was 41.5% and net retention was 31.7%. In their study of 9 infants aged 0 to 3 months, Barltrop and Strehlow (1978) measured an average dietary intake of 9 mg/kg bw/day. The largest study of young infants was that by Ryu et al. (1985). Over the period 8-195 days, the mean dietary intake for the low lead exposure group from all sources (milk formula or formula plus beikost) was ~2.9 mg/kg bw/day for infants fed milk supplied in cartons and 11 mg/kg bw/day for infants fed milk or formula supplied in cans.

Excretion and Skeletal Lead- The estimated total excretion by urine and feces is about three-times higher than dietary intake, assuming that inputs from air, soil, and dust are minimal. Lead in urban air, where most of the infants reside, is currently < 0.1 mg Pb/m³ ,has a ²⁰⁶Pb/²⁰⁴Pb ratio of < 17 (Chiaradia et al., 1997) and thus contributes minimally to lead in blood or urine (Gulson et al, 1997b). Soil and dust in these young infants is thought to contribute little to their lead intake, as they had not reached the stage of crawling. Airborne dust in the residences monitored for ongoing 3-month intervals for the maternal aspects of the study usually has a low lead loading and low ²⁰⁶Pb/²⁰⁴Pb ratios (Gulson et al., 1995a, 1997b). The minor impact of airborne dust on these infants’ blood lead concentrations and stable isotope ratios is shown by the low ²⁰⁶Pb/²⁰⁴Pb ratio and low blood lead concentration. If dust were important, there would have been a rapid decrease in ²⁰⁶Pb/²⁰⁴Pb ratios in blood and urine. In the Ziegler et al. (1978) investigations, 7 of the 28 balance studies with lead intakes of < 5 mg/kg bw/day were negative, i.e., fecal excretion exceeded intake. We interpret the increased excretion over intake as an indication that the infants are mobilizing lead stores from their tissues, especially associated with rapid bone turnover. O’Flaherty (1995) suggested that turnover of bone calcium is as much as several-fold per year in infants and children so that the whole skeleton turns over in the first 12 months-of-life. Mobilization of lead from the skeleton of migrant infants would result in lead with a higher ²⁰⁶Pb/²⁰⁴Pb ratio indicative of the skeletal lead.

Contribution of Diet to Blood Lead- The percentage contribution of dietary formula and beikost to blood lead ranged from 20% to 80% with a mean value of about 50%. The metabolic balance studies conducted in the 1970’s (Ziegler et al., 1978; Alexander et al., 1974) showed the fractional absorption of lead by very young children was much higher than observed among adults. The most complete data set during that period estimated infants, aged 14 through 746 days, absorbed 41.5% of dietary lead and had a net retention of 31.7% of dietary intake. These data were obtained when dietary intake was > 5 mg/kg bw/day. At exposures < 5 mg/kg bw/day it was not certain whether or not the infants were in net positive balance for lead. Our data presented here for newly-born infants through 6 months of life suggest that the uptake of lead in blood for very young infants is close to the estimates by Ziegler et al. (1978) even at exposures that are approximately 20-fold lower.

The question remains, however, at what age fractional absorption in the child approximates that of adults. Angle et al. (1995) proposed that uptake from diet in infants aged 2 months to 3 years was 10% to 15%, similar to that well-established from numerous studies in adults. Gulson et al. (1998a, 1997b) have estimated that lead uptake in children ages 7 to 12 years was similar to that of their mothers, although as with the Angle et al. (1995) study, the quantitative estimates are not possible for children because of problems in accurately quantifying the different exposures at very low blood lead levels.

Acknowledgments.We thank: Mary Salter for phlebotomy and Paul Mushak for substantial comments on an earlier version of this manuscript.. This research was supported by the U.S. National Institute of Environmental Health Sciences through grant NO1-ES-05292.

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Fig. 1. Time series plot for the lead isotopic composition for Australian infant 2057 as an example of increases in ²⁰⁶Pb/²⁰⁴Pb in blood and urine arising from consumption of infant beikost that contained lead from a source with a high ²⁰⁶Pb/²⁰⁴Pb and also elevated lead concentrations.