Registration Dossier

Toxicological information

Epidemiological data

Currently viewing:

Administrative data

Endpoint:
epidemiological data
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
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:
2006

Materials and methods

Study type:
longitudinal study
Endpoint addressed:
neurotoxicity
Principles of method if other than guideline:
Epidemiology Prospective Longitudinal Study

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Type of population:
other: general population pediatric
Ethical approval:
confirmed and informed consent free of coercion received
Details on study design:
HYPOTHESIS TESTED (if cohort or case control study): To characterize the functional form of the association between children's blood lead levels and neurodevelopment in a subgroup of children who participated in a prospective longitudinal study in Mexico City, Mexico for whom blood lead levels measured at both 12 nd 24 months of age did not exceed 10ug/dl.


METHOD OF DATA COLLECTION
- Type: Interview / Questionnaire / Record review / Work history / Clinical tests / other:
- Details: Blood Lead meadurements, Measurement of Child Development and Potential Confounders


STUDY PERIOD:


SETTING: Participants in this study are members of 2 cohorts of women and their offspring from Mexico City metropolitan area.


STUDY POPULATION
- Total population (Total no. of persons in cohort from which the subjects were drawn): The first cohort was recruited from January 1994 through June 1995, and the second was recruited from May 19997 through July 1999. Both cohorts were recruited form maternity hospitals that serve low- to middle-income population. Mothers in cohort 1 were recruited at the time of delivery. Mothers in cohort 2 were recruited during or before pregnancy.
- Selection criteria: The following exclusion criteria were applied to both cohorts: mother not a resident of Mexico City; mother planning to leave the area within 5 years; daily consumption of alcoholic beverages; addiction to illegal drugs; continuous use of prescription drugs; diagnosis of multiple pregnancy, preeclampsia, renal or heart disease, gestational diabetes, seizures that require medical treatment; and use of corticosteroids. In addition, eligibility for cohort 1 was restricted to women who were not anemic and who consumed no less than 860 mg of calcium per day by self-report on a food frequency questionnaire. A total of 588 mother-infant pairs met these criteria.
- Total number of subjects participating in study: 294-To be included in these analyses, a child had to meet the following additional criteria: venous blood lead concentration <10ug/dl at both 12 and 24 months of age, gestation of 37 weeks or longer, and birth weight >2000 grams. Finally, data had to be available on the following variables: neurodevelopmental status at 12 and 24 months, umbilical cord blood lead level, and maternal IQ. A total of 294 mother-infant pairs met all criteria.
- 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): Neurotoxicity
- ICD No.:
- Year of ICD revision:
- Diagnostic procedure:
- Other health effects:


OTHER DESCRIPTIVE INFORMATION ABOUT STUDY: Bayley Scales of infnat Development II, Maternal IQ calculated from subtests of teh Spanish Wechsler Adult Intelligence Scale. The outcomes of interest were the Mental Development Index and Psychomotor Development Index.
Exposure assessment:
measured
Details on exposure:
Cord lead mean-5.49 ug/dl
12 months mean-4.66 ug/dl
24 months mean-5.78 ug/dl
Statistical methods:
Differences between participants and nonparticipants were evaluated using t tests or Kruskal-Wallis tests for continuous or discrete variables, and X2 tests for categorical variables. Mental Development Index (MDI) and Psychomotor Development Index (PDI) scores were the primary dependent variables. Blood lead levels measured at 12 and 24 months were the primary exposure variables. Mixed-effects regression models with a random intercept were used to estimate the associations between blood lead levels and MDI or PDI scores at 12 and 24 monts of age. This approach takes into account the within-subject correlation structure as a result of the repeated measurements, reducing bias in the estimation of the SEs. An interaction term was included to evaluate whether the association between blood lead level and concurrent MDI and PDI scores at 12 months differed from the associations between blood lead level and concurrent MDI and PDI at 24 months. Nonlead variables that were related to BSID II scores with p>.1 in bivariate analyses were included in multivariate models. The authors also included variables that were considered to be biologically relevant to the association between children's blood lead levels and their BSID II scores, regardless of their statistical associations with BSID II scores, such as maternal age and IQ and children's gender and birth weight.
To estimate the effect of lead on the change in mental and psychomotor development from 12 to 24 months, the generated linear regression models of both MDI and PDI at 24 months that included MDI and DPDI at 12 months of age, respectively, as covariates. (See Any other information on materials and methods below)






























































































































































































Results and discussion

Results:
Blood lead at 24 months was significantly associated in an inverse direction, with both MDI and PDI. Twelve month PbB was not associated with concurrent MDI or PDI scores or with MDI at 24 months, but was significantly associated with PDI score at 24 months. MDI and PDI scores at 24 months of age for both the coefficients that were associated with concurrent PbB level were significantly larger among children with PbB levels <10 ug/dl than among children with levels >10ug/dl.

Confounding factors:
Maternal IQ was measured with the Wechsler Adulat Intelligence scale (Spanish) (Wechsler 1981B). An index was constructed for socioeconomic status (SES) based on head of household education and occupation, and family income. The degree of stimulation and quality of the caretaker-child interaction in the home environment was evaluated using the HOME Scale (Home inventory for Families of Infants and Toddlers) (Caldwell and Bradley 1984). All covariates used in statistical analyses were collected during pregnancy or in thee first 6 postpartum months. Maternal mental health was not considered, and other factors such as nutrition, and assessment of relevant co-exposures were not considered.

Any other information on results incl. tables

The psychological measures applied in this study are the MDI and PDI from the Bayley Scales of Infant Development - these tests have somewhat limited predictive capability for outcome measures later in life such as IQ and similar effects seen in other studies have attenuated with age. The major finding of this study is that among infants whose blood lead levels did not exceed 10ug/dl at 12 or 24 months of age, scores on both the MDI and the PDI of the Bayley Scales were inversely related to blood lead at 24 months, but it remains to be determined if an impact upon IQ will be observed. Furthermore, although adjustments for covariates such as maternal IQ, birth weight, and gender were made, HOME score data (or its equivalent) were not collected.

Applicant's summary and conclusion

Conclusions:
Tellez-Rojo et al. (2006) examined the longitudinal relationship between blood lead concentrations <10ug/dl and neurobehavioral development at 12 and 24 months of age. In addition to a cohort of children recruited at the time of birth, an additional prenatal cohort was recruited. The study population consisted of 294 children whose blood lead levels at both 12 months and 24 months of age were <10ug/dl. Blood lead levels at 24 months were inversely associated with Mental Development Index and Psychomotor Development scores at 24 months. Blood lead level at 12 months of age was not associated with concurrent Mental Development Index (MDI) or Psychomotor Development Index (PDI) scores or with MDI at 24 months of age, but was significantly associated with PDI score at 24 months. The relationships were not altered by adjustment for cord blood lead level or, in the analyses of 24-month MDI and PDI scores, or the 12-month MDI and PDI scores. For both MDI and PDI scores at 24 months of age, the coefficients that were associated with concurrent blood lead level were significantly larger among children with blood lead levels <10ug/dl than they were among children with levels >10ug/dl. The authors concluded that these analyses indicated that children’s neurobehavioural development is inversely related to their blood lead levels even in the range of <10ug/dl and that these findings are consistent with a supra-linear relationship between blood lead levels and neurobehavioral outcomes.
Executive summary:

Objective: Increasing evidence suggests that 10ug/dl, the current Centers for Disease Control and prevention screening guideline for children's blood lead level, should not be interpreted as a level at which adverse effects do not occur. Using data from a prospective study conducted in Mexico City, Mexico, the authors evaluated the dose-effect relationship between blood lead levels and neurodevelopment at 12 and 24 months of age.

Methods: The study population consisted of 294 children whose blood lead levels at both 12 and 24 months of age were <10ug/dl; blood lead levels were measured by graphite furnace atomic absorption spectroscopy; Bayley Scales of Infant Development II were administered at these ages. The outcomes of interest were the Mental Development Index and the Psychomotor Development Index.

Results: Adjusting for covariates, children's blood lead levels at 24 months were significantly associated, in an inverse direction, with both Mental Development Index and Psychomotor Development Index scores at 24 months. Blood lead level at 12 months of age was not associated with concurrent Mental Development Index or Psychomotor Development Index scores or with Mental Development at 24 months of age but was significantly associated with Psychomotor Development Index score at 24 months. The relationships were not altered by adjustment for cord blood lead level or, in the analyses of 24-month Mental Development Index and Psychomotor Development Index scores, for the 12-month Mental Development Index and Psychomotor Development Index scores. For both Mental Development Index and Pschomotor Development Index at 24 months of age, the coefficients that were associated with concurrent blood lead level were significantly larger among children with blood lead levels <10ug/dl than it was among children with levels >10ug/dl.

Conclusions: The analyses indicate that children's neurodevelopment is inversely related to their blood lead levels even in the range of <10ug/dl. The author's findings were consistent with a supralinear relationship between blood lead levels and neurobehavioral outcomes.

Comments:The psychological measures applied in this study are the MDI and PDI from the Bayley Scales of Infant Development - these tests have somewhat limited predictive capability for outcome measures later in life such as IQ and similar effects seen in other studies have attenuated with age. The major finding of this study is that among infants whose blood lead levels did not exceed 10ug/dl at 12 or 24 months of age, scores on both the MDI and the PDI of the Bayley Scales were inversely related to blood lead at 24 months, but it remains to be determined if an impact upon IQ will be observed. Furthermore, although adjustments for covariates such as maternal IQ, birth weight, and gender were made, HOME score data (or its equivalent) were not collected.