RESEARCH

Studies & Findings

PRENATAL LEAD EXPOSURE IN A HIGHLY POLLUTED AREA IN KAZAKHSTAN: EFFECTS ON AMINOLEVULINIC ACID DEHYDRATASE

Yona Amitai, M.D.1, Max Koifman, M.D., Ph.D.
Turmekhan Orenbayev, M.D., Ph.D2.,
Shlomo Almog, Ph.D3., Maya Tepferberg, M.Sc3,
Anatoly Dimitriev, Ph.D2, and Lena Vakhlis, M.Sc4

Introduction

Lead poisoning is quite frequent among children in the US and many other countries, and may result in impaired cognitive development, particularly in young children (1). Lead crosses placenta, and prenatal lead exposure, assessed by maternal blood lead level (BLL) at birth and umbilical cord blood lead level (UCBLL), and it impairs neurobehavioral development of infants (2-4).

Bellinger et al. have demonstrated a significant impairment in cognitive functions at 1-2 years of age in a cohort of infants with UCBLL > 10 m g/dl (mean of 14.6 m g/dl) (2). Deitrich et al. observed a reduction in Bayley Mental Developmental Index (MDI) at the ages of 3 and 6 months in infants with mild elevations of UCBLL (3). Subsequently the action level for childhood lead poisoning in the US has been lowered from 25 m g/dl to 10 m g/dl. Since prenatal lead exposure has been recognized as potentially harmful to the developing brain, it has been extensively studied. Although there are no good data on lead exposure in the USSR, lead exposure from industrial and environmental pollution and housing conditions in East Europe and the ex-USSR is probably worse than in the US (5). To the best of our knowledge there are no reports on prenatal lead exposure from the ex-USSR.

A potential industrial source of lead pollution exists in Chimkent, Kazakhstan, a city with about 600,000 inhabitants. A lead plant which served the USSR military industry till 1990 is located at the south-west border of the town. It employed up to 15,000 workers, about 30% being women. The plant has cut down its production over the past decade, but in view of the persistence of lead in the environment, lead remains an environmental hazard.

Management of infants with sub-clinical lead poisoning is problematic. While lead exposure is indicated by elevated BLL, lead poisoning is indicated by clinical or laboratory markers of the effect of lead in various body systems. Elevation of zinc protoporphyrin (ZPP), frequently used in the past, has a threshold of BLL elevation above 20 m g/dl. Thus it is not useful as a marker of sub-clinical lead toxicity. On the other hand inhibition of aminolevulinic acid dehydratase (ALAD) by lead is more sensitive and has been shown to have a threshold of 5 m g/dl in adults and in children. We are not aware of previous reports where ALAD was used as a marker of low level lead exposure in newborns.

We undertook a study to assess the risk of prenatal lead exposure among newborns of mothers residing in this region, and its effect on neurobehavioral development of these infants. As a part of the assessment of lead effect in these infants, we have studied the correlation between lead exposure and ALAD.

Patients and Methods

Mothers of 156 newborns residing <3 kms. from the lead plant (Group A) were interviewed, and their newborns were examined. Similarly, 175 control newborns residing 3-10 kms. from the plant were examined (Group B). Maternal blood samples (prenatal) and umbilical cord blood (neonatal) samples were collected at delivery and assayed for lead levels, ZPP, ALAD activity, and hemoglobin. Neurobehavioral development was assessed at 6 months using the Bayley MDI Score.

Results

Blood lead levels (BLL) among mothers in Group A were higher than in Group B (5.34+7ug./dL and 4.54+2.5ug./dL respectively, p=0.013). Umbilical cord BLL were also higher in Group A than in Group B (4.99+3.6m g/dl and 3.74+2.3 m g/dl respectively, p=0.0001).

Maternal and umbilical cord BLL decreased with distance from the plant. By contrast, hemoglobin levels in umbilical cord blood increased with distance. There was a significant correlation between BLL in mother-newborn pairs in Groups A (r=0.83) and B (r=0.56). There were no differences in the mean ZPP and ALAD between the groups, However in newborns with higher UCBLL (>11m g/dl) ALAD activity was lower, and inversely related with UCBLL.

At six months of age MDI of infants in Group A was slightly lower than controls (M= 106.9 and 108.2, respectively, p=0.09). However, the MDI of infants with cord BLL > 20 m g/dl was significantly lower than those with cord BLL <20 m g/dl (106.0 and 107.5, respectively, p=0.00024).

Conclusions

Lifetime environmental exposure to lead results in accumulation of this element in the body. Since lead freely crosses placenta, maternal exposure to lead results in fetal exposure, and is reflected in UCBLL. Indeed, our study showed a significant correlation between maternal blood lead level and neonatal lead levels, indicated by UCBLL.

While increased blood lead levels indicate exposure to lead, determination of lead poisoning requires other biochemical markers indicating deleterious effects of lead in body systems. Various effects of lead on the heme synthesis are used. The expression of lead poisoning on elevation of ZPP is less practical as a marker of lead toxicity in infants, since it is not sensitive to low level lead exposure (< 20 m g/dl). A decrease in ALAD activity is a much more sensitive indicator of lead toxicity, at lead levels as low as 5 m g/dl, but it is not used as a marker of lead toxicity in the newborn. Our data suggest that reduction in ALAD could be used as a marker of low level lead toxicity also in newborns.

Our finding of impairment in neurobehavioral development at the age of 6 months in infants with prenatal lead exposure, although subtle, are in accordance with findings of the classical studies in this area (2-4) but is reported for the first time among infants in the Shimkent area. Because this exposure may involve many thousands of infants, these findings have significant bearing and require a large-scale operation in screening infants at risk and taking the necessary steps to reduce lead exposure, and to treat those infants who are at risk.

The following specific conclusions can be drawn:

(1) Our survey of an endemic area for lead pollution in Kazakhstan revealed a significant intrauterine lead exposure, which was inversely related to distance from the source. These findings require a large scale operation in screening of newborns and infants in this endemic area, and treating those at risk.

(2) Inhibition of ALAD activity by lead occurs also in newborns, with a threshold at 11m g/dl, and can be used as a sensitive and practical marker of low level lead exposure.

(3) Prenatal lead exposure impairs neurobehavioral development.

References

  1. Amitai Y, Hryhorczuk D. Lead poisoning. In: Strange et al. Eds. Pediatric Emergency Medicine. McGraw-Hill pub. Pp.548-51: 1996
  2. Bellinger D, Leviton A, Waternaux C, Needelman H, Rabinowitz M. Longitudinal analysis of prenatal and postnatal lead exposure and early cognitive development. NEJM 1987: 316: 1037-43.
  3. Dietrich KN, Kraft KM, Bornschein RL et. Al. Low-level fetal lead exposure effect on neurobehavioral development in early infancy. Pediatrics 1987: 80: 721-30.
  4. McMichael AJ, Baghurst PA, Wigg NR et al. Port Pierie cohort study: environmental exposure to lead and children’s ability at the age of four years. NEJM 1988: 319: 468-75.
  5. Emerson T. Lead and your kids: Lead is the Number 1 environmental threat to the young, public-health officials say, but America has been slow to respond - and Europe slower. Newsweek, Cover Story, February 17, 1992, pp 32-37.

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