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Toxicological information

Epidemiological data

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Administrative data

Endpoint:
epidemiological data
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1979-1987
Reliability:
2 (reliable with restrictions)
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:
1987

Materials and methods

Study type:
cohort study (prospective)
Endpoint addressed:
developmental toxicity / teratogenicity
Principles of method if other than guideline:
Epidemiological-Prospective Study

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Type of population:
other: General Population: Pregnant mothers and their offspring
Ethical approval:
confirmed and informed consent free of coercion received
Details on study design:
HYPOTHESIS TESTED (if cohort or case control study): A prospective method was used in this study to assess the effects of fetal lead exposure on neurodevelopmental status in 3- and 6-month old infants.


METHOD OF DATA COLLECTION
- Type: Interview / Questionnaire / Record review / Work history / Clinical tests / other:
- Details:


STUDY PERIOD: 1979-1987


SETTING: The final follow-up study sample consisted of 305 mothers, recruited between 1979 and 1984, residing in predesignated lead-hazardous areas of Cincinnati. This geographical area has a history of having a relatively large number of children with lead poisoning according to city health department data. Results of other studies on the Cincinnati cohort have shown that lead from paint, dust, and generally poor housing stock is the major contributor to body burden.


STUDY POPULATION
- Total population (Total no. of persons in cohort from which the subjects were drawn): 305 Mothers and Newborns
- Selection criteria:
- Total number of subjects participating in study:
- 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:
Exposure assessment:
measured
Details on exposure:
See Below (Any other info on mats and mets incl. tables)
Statistical methods:
The data analytic procedures used in this study were designed to achieve the best possible compromise between the conflicting goals of reducing the probability of type 1 error (ie, false-positive lead effect) and type II error (ie, false-negative (no) lead effect). The analytic strategy involves a priori specification of potential developmental confounders and covariates, pretesting covariables for confounding potential (P

Results and discussion

Results:
An inverse relationship between prenatal and neonatal blood lead levels and performance on the Bayley Mental Development Index (PDI) was found at 3 and 6 months of age. This effect was found to be mediated through lead's effect on birth weight, growth and maturation.
Confounding factors:
Undue lead exposure is known to covary with a number of social and biologic risks that may mimic, obscure, or otherwise interact with the effects of toxicant exposure on child development. Therefore, a substantial amount of medical and social background data were collected on all subjects. The candidate confounders and covariates that were selected a priori based upon their theoretical and/or known empirical association with the effects of toxicant exposure on child development are as follows:
Perinatal Variables: Birthweight; gestational age b y examination; obstetrical complications; postnatal complications scale; composite index of tobacco and alcohol consumption; no. of cigarettes smoked per day; maternal age at birth of child; gravidity; parity; maternal total iron-binding capacity; race of child; sex of child.
Sociohereditary Variables: Socioeconomic Status; Developmental Stimulation (Home Observation for Measurement of the Environment Scale); No. of children in the home

Any other information on results incl. tables

Covariate-Adjusted Parameter Estimates for Fetal lead Exposure Variables on 3 -Month Bayley Mental Developmental Index*

 Prenatal (maternal)  Beta  SE  t value  P value  Range of Effect
 Umbilical cord  -.34  0.17  -1.96  .05  9.2
 Newborn (10 days)  -.60  0.26  -2.30  .02  16.8
 Newborn (3 months)  .06  0.22  0.26  .79  
   -.23  0.18  -1.30  .20  

*Other variables remaining in final models as statistically significant (P < .05) covariates included birth weight, gestation, maternal age, child race, child sex, and socioeconomic status. Neither Composite Index of Tobacco and Alcohol Consumption nor quantity of cigarettes smoked per day remained in the models as statistically significant covariates. P value calculated by two-tailed test.

Covariate-Adjusted Parameter Estimates for Fetal Lead Exposure Variables on 6 -Month Bayley Mental Developmental Index*

 Blood Source or Interaction  Beta  SE  t value  P value Range of Effect 
 Prenatal (maternal)  -0.76  0.34  -2.16  .02  22.7**
 Prenatal x child sex  1.27  0.51  2.49  .01  
 Umbilical cord  -.066  0.37  -1.76  .08  
 Newborn (10 d)  -3.49  1.29  2.69  .007  16.1***
 Newborn x socioeconomic status  0.18  0.07  2.45  .01  
 Newborn (3 months)          

*Other variables remaining in the final models as statistically significant (P<<.05) covariates included birth weight, gestation, maternal age, child race, child sex, and socioeconomic status. Neither Composite index of Tobacco and Alcohol Consumption nor quantity of cigarettes smoked per dqay remained in the models as statistically significant covariates. P value calculated by two-tailed test.

** In male infants

*** In infants with scores less than the median socioeconomic status score for the sample.

Applicant's summary and conclusion

Conclusions:
An inverse relationship between prenatal and neonatal blood lead levels and performance on the Bayley Mental Development Index (PDI) was found at 3 and 6 months of age. This effect was found to be mediated through lead's effect on birth weight, growth and maturation.
Executive summary:

A prospective method was used in this study to assess the effects of fetal lead exposure on neurodevelopmental status in 3- and 6- month old infants. At their first prenatal medical appointments, 305 lower socioeconomic status women residing in predesignated lead-hazardous areas of Cincinnati were recruited. lead was measured in whole blood in both the mother and fetal-placental unit (prenatal and cord) and the neonate (ten days and 3 months). All blood lead levels were less than 30 ug/dl. Infant development was assessed with the Bayley Scales at 3 and 6 months of age. Multiple regression analyses which treated perinatal health factors such as birth weight and gestation as confounders indicated an independent, inverse relationship between both prenatal and neonatal blood lead levels and performance on the Bayley Mental Development Index at both ages. The effect was found to be mediated through lead's effect on birth weight, growth and maturation. Male infants and infants from the poorest families appeared to be especially sensitive to these developmental influences.

A

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