Trilead dioxide phosphonate

Epidemiological data

Administrative data

Endpoint:

epidemiological data

Type of information:

not specified

Adequacy of study:

key study

Study period:

1987-1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The rationale for the reliability scoring is based upon a Lead Study Quality Asessment tool for Pediatric Neurological Effects developed by the Scientific Advisory Panel assembled to provide independent academic review of the Voluntary Risk Assessment for Lead. The Pediatric Assessment assessed study quality on the basis of the following major aspects of study design, data collection, and analysis: Adequacy of Cohort Definition and Size Nature and Extent of Lead Exposure Indices Examiner Training and Procedures for Data Collection and Analysis Precision of Endpoint Definition Extent of Correction for Major Confounding Variables

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1991

Materials and methods

Study type:

cohort study (prospective)

Endpoint addressed:

developmental toxicity / teratogenicity

Principles of method if other than guideline:

Epidemiological-Prospective Cohort Study

Test material

Test material information

Constituent 1

Reference substance name:

Lead

EC Number:

231-100-4

EC Name:

Lead

Cas Number:

7439-92-1

Molecular formula:

Pb

IUPAC Name:

lead

Test material form:

not specified

Method

Type of population:

other: General population-Pregnant Mothers and Offspring

Ethical approval:

confirmed and informed consent free of coercion received

Details on study design:

HYPOTHESIS TESTED (if cohort or case control study): The objective of this follow-up analysis was to assess the independent association of lead exposure with indices of stature during the period 18 to 33 months of age.


METHOD OF DATA COLLECTION
- Type: Interview / Questionnaire / Record review / Work history / Clinical tests / other:
- Details: In utero lead exposure was indexed by maternal PbB measured from samples collected by venipuncture at the first pre-natal visit. Postnatal PbB was measured at 10 days of age (corrected for gestational age), at 3 months of age, and every 3 months thereafter. Leangth measurements were taken at 18, 21, 24, 27, 30, and 33 months.


STUDY PERIOD: 1987-1991


SETTING: Lower socioeconomic status women living in predesinated lead-hazardous areas of Cincinnati.


STUDY POPULATION
- Total population (Total no. of persons in cohort from which the subjects were drawn): 260
- Selection criteria: Twenty-five had three or fewer length measurements during the 18-33 month period and therefore had inadequate growth data.. Consequently they were excluded from further analyses
- Total number of subjects participating in study: 235
- Sex/age/race:
- Smoker/nonsmoker:
- Total number of subjects at end of study:
- Matching criteria:
- Other:


COMPARISON POPULATION
- Type: State registry / Regional registry / National registry / Control or reference group / Other comparison group:
- Details:


HEALTH EFFECTS STUDIED
- Disease(s): Developmental Toxicity
- ICD No.:
- Year of ICD revision:
- Diagnostic procedure:
- Other health effects:


OTHER DESCRIPTIVE INFORMATION ABOUT STUDY: The following questions were examined: 1). Are lead-related deficits in growth still evident during the 18 to 33-month interval? 2) What combination of prenatal and/or postnatal lead exposure is most strongly associated with lead-related growth deficits? 3) Is there any evidence of an exposure threshod for this effect?

Exposure assessment:

measured

Details on exposure:

See Table (Any other info on mats. and meths. incl. tables)

Statistical methods:

A set of candidate confounders/covariates was chosen based on their a priori probability of being related to growth rate and/or length at 33 months. Two key response variables, namely growth rate (18 to 33 months) and stature at 33 months, plus one key exposure variable, ie, mean blood lead level during 18 to 33 months (mean PbB), were examined for bivariate correlation with a host of candidate confounders/covariates. For exploring the hyposthesis that some combination of prenatal and postnatal blood lead levels affect growth during the period 18 to 33 months. The authors categorized past lead exposure histories (both prenatal and early postnatal) into four groups based on median splits of prenatal PbB (7,78ug/dl) and mean PbB during 3-15 months (10.77ug/dl). This resulted in four combinations (ie, low-low, low-high, high-low, and high-high) of earlier lead exposure histories. The relationships between mean PbB (18-33 months) as well as mean PbB (18 to 33 months) and length at 33 months were examined via stepwise multiple regression with particular emphasis on understanding which, if any, of the four lead history combinations were exhibiting lead-growth or lead stature relationships.

Results and discussion

Results:

Shukla et al. report an effect on length with prenatal lead exposure in the Cincinnati cohort with blood lead levels of 1 - 27 µg/dL. This association was, however, evidenced only among those children who had mean bloos lead levels greater than the cohort median (>/=10.77 ug/dl) during the 3 to 15 month interval.Potential deficiencies in control for lifestyle confounders could account for this finding. the results also suggest that the effect of lead exposure (both in utero as well as during the first year of life) are transient provided that subsequent exposure to lead is not excessive.



















































































































































































































Shukla et al. report an effect on length with prenatal lead exposure in the Cincinnati cohort with blood lead levels of 1 - 27 µg/dL. This association was, however, evidenced only among those children who had mean blood lead levels greater than the cohort medain (>/=10.77ug/dl) during the 3 to 15 month interval. The results also suggest that the effect of lead exposure (both in utero as well as duuring the first year of life) are transient provide that subsequent exposure to lead ins not excessive. It appears that maintaining an average blood lead of 25ug/dl or more during the second and third year of life was detrimental to the child's attained staure at 33 months of age. Potential deficiencies in control for lifestyle confounders, could account for this finding.

Confounding factors:

Cigarette use. child's race, HOME, maternal height, total iron-binding capacity, socioeconomic status, sex, stature at 18 months

Any other information on results incl. tables

Multiple Regression Results for Recumbent Length at 33 months*

Independent Variable	Coefficient	SE	P Value
Intercept	3.80
Mean PbB (3 -15 months)	5.60	2.22	.01
Mean PbB (18 -33 months)	-0.13	0.57	.83
Mean PbB (3 -15 months) x mean PbB (18 -33 months)	-1.81	0.80	.025
Sex**	0.55	0.27	.05
Race***	0.81	0.42	.06
Cigarette use during pregnancy	-0.40	0.18	.03
Mean total iron-binding capacity (18 -33 months)	0.01	0.004	.009
Maternal height (cm)	0.10	0.02	.0001
Length at 18 months (cm)	0.84	0.05	.0001

* PbB, blood lead concentration

** 1=male, 2=female

*** 1=white, 2=black

Applicant's summary and conclusion

Conclusions:

Shukla et al. report an effect on length with prenatal lead exposure in the Cincinnati cohort with blood lead levels of 1 - 27 µg/dL. This association was, however, evidenced only among those children who had mean bloos lead levels greater than the cohort median (>/=10.77 ug/dl) during the 3 to 15 month interval. Potential deficiencies in control for lifestyle confounders could account for this finding. The results also suggest that the effect of lead exposure (both in utero as well as during the first year of life) are transient provided that subsequent exposure to lead is not excessive.

Executive summary:

This report is a follow-up of an earlier study of the effects of low to moderate prenatal and postnatal lead exposure on children's growth in stature. Two hundred thirty-five subjects were assessed every 3 months for lead exposure (blood lead level) and stature (recumbent length) up to 33 months of age. Fetal lead exposure was indexed by maternal blood lead level during pregnancy. The adverse effects of lead on growth during the first year of life were reported previously. This analysis covers essentially the second and third years of life. The results indicate that mean blood lead level during this period was negatively associated with attained height at 33 months of age (P=.002). This association was, however, evidenced only among those who had mean blood lead levels greater than the cohort median (>/= 10.77ug/dl) during the 3 to 15 month interval. The results also suggest that the effect of lead exposure (both in utero as well as during the first year of life) are transient provided that subsequent exposure to lead is not excessive. It appears that maintaining an average blood lead level of 25ug/dl or more during the second and third year of life was detrimental to the child's attained stature at 33 months of age. Approximately 15% of this cohort expserienced these levels of lead exposure. Potential deficiencies in control for lifestyle confounders could account for this finding.