Sandra Martínez

Reduced Intellectual Development in Children with Prenatal Lead Exposure

Objective Low-level postnatal lead exposure is associated with poor intellectual development in children, although effects of prenatal exposure are less well studied. We hypothesized that prenatal lead exposure would have a more powerful and lasting impact on child development than postnatal exposure. Design We used generalized linear mixed models with random intercept and slope to analyze the pattern of lead effect of the cohort from pregnancy through 10 years of age on child IQ from 6 to 10 years. We statistically evaluated dose–response nonlinearity. Participants A cohort of 175 children, 150 of whom had complete data for all included covariates, attended the National Institute of Perinatology in Mexico City from 1987 through 2002. Evaluations/Measurements We used the Wechsler Intelligence Scale for Children–Revised, Spanish version, to measure IQ. Blood lead (BPb) was measured by a reference laboratory of the Centers for Disease Control and Prevention (CDC) quality assurance program for BPb. Results Geometric mean BPb during pregnancy was 8.0 μg/dL (range, 1–33 μg/dL), from 1 through 5 years was 9.8 μg/dL (2.8–36.4 μg/dL), and from 6 through 10 years was 6.2 μg/dL (2.2–18.6 μg/dL). IQ at 6–10 years decreased significantly only with increasing natural-log third-trimester BPb (β = −3.90; 95% confidence interval, −6.45 to −1.36), controlling for other BPb and covariates. The dose–response BPb–IQ function was log-linear, not linear–linear. Conclusions Lead exposure around 28 weeks gestation is a critical period for later child intellectual development, with lasting and possibly permanent effects. There was no evidence of a threshold; the strongest lead effects on IQ occurred within the first few micrograms of BPb. Relevance to Clinical Practice Current CDC action limits for children applied to pregnant women permit most lead-associated child IQ decreases measured over the studied BPb range.

Impact of an After-School Physical Activity Program on Obesity in Children

OBJECTIVE To assess the impact of a 2-year recreational physical activity program in 1044 fourth- and fifth-grade primary schoolchildren from the Province of Cuenca, Spain. STUDY DESIGN Cluster-randomized controlled trial with 10 intervention and 10 control schools. The program consisted of 3 90-minute sessions of physical activity per week,during 28 weeks every year.Changes in endpoints between baseline (September 2004) and the end of follow-up (June 2006) were compared between the control and intervention group by using mixed regression models, with adjustment for the baseline endpoint value, age, and the school. RESULTS Compared with control subjects, intervention girls reduced the frequency of overweight (odds ratio, 0.55; 95% CI, 0.39-0.78; P<.001). However, intervention was associated with an increase in the percentage of body fat in boys (0.97%; 95% CI, 0.14-1.81; P=.02). Girls in the intervention group had lower total cholesterol level (-6.86 mg/dL; 95% CI, -9.70--4.01; P<.001) and apolipoprotein B level (-3.61 mg/dL; 95% CI, -6.27--0.95; P=.008) than control subjects. Results were similar in boys. CONCLUSION In 2 years, the physical activity program lowered the frequency of overweight in girls and reduced total cholesterol and apolipoprotein B in both girls and boys.

Temporal pattern in the effect of postnatal blood lead level on intellectual development of young children

To determine the temporal pattern of the effect of postnatal blood lead level on the General Cognitive Index (GCI) of the McCarthy Scales of Childrens Abilities, we used data from 112 children of the Mexico City Prospective Lead Study with complete evaluations from 36 to 60 months of age at 6-month intervals. We measured blood lead level every 6 months from 6 to 54 months. We controlled for 5-min Apgar, birth weight, birth order, sex, socioeconomic level, maternal IQ, and maximum maternal educational level in a repeated measures ANCOVA using child blood lead level grouped by 6-18 month (geometric mean 10.1 microg/dl, range 3.5-37.0 microg/dl), 24-36 month (geometric mean 9.7 microg/dl, range 3.0-42.7 microg/dl), and 42-54 month (geometric mean 8.4 microg/dl, range 2.5-44.8 microg/dl) averages. There were significant interactions between the 6-18 month blood lead level and age with GCI as the endpoint and between 24-36 month blood lead level and age. The regression coefficient of blood lead at 6-18 months became more negative with age until 48 months, when the rate of decline moderated (linear polynomial contrast p=0. 047). The regression coefficient of blood lead at 24-36 months with CGI became more negative as well from 36 to 48 months but then started decreasing toward zero from 48 to 60 months (quadratic polynomial contrast p=0.019). Significant between-subjects lead effects on GCI were found for 24-36 month blood lead level at 48 months (p=0.021) and at 54 months (p=0.073). The greatest effect (at 48 months) was a 5.8-point GCI decrease with each natural log unit increase in blood lead. Significant between-subjects lead effects on GCI were found for 42-54 month blood lead level at 54 months (p=0. 040) and at 60 months (p=0.060). The effect of postnatal blood lead level on GCI reaches its maximum approximately 1-3 years later, and then becomes less evident. Four to five years of age appears to be a critical period for the manifestation of the earlier postnatal blood lead level effects.

Blood Lead Secular Trend in a Cohort of Children in Mexico City (1987–2002)

We determined the secular trend in blood lead levels in a cohort of 321 children born in Mexico City between 1987 and 1992. Blood lead level was measured every 6 months during a 10-year period. We modeled the effect of yearly air lead concentration nested within the calendar year in which the child was born, family use of lead-glazed pottery, socioeconomic status, year in which the child was born, age of the child at the time of blood lead measurement, place of residence, and an indicator variable for subjects with complete or incomplete blood lead values. The yearly mean of air lead of the Valley of Mexico decreased from its highest level of 2.80 μg/m3 in 1987 to 0.07 μg/m3 in 2002. The contribution of air lead to blood lead according to year of birth was strongest for subjects born in 1987 and fell to nearly zero for children born in 1992. The geometric mean of the entire cohort rose from 8.4 μg/dL in the first year of life to 10.1 μg/dL in the second and decreased thereafter until it reached 6.4 μg/dL at 10 years of age. Children of families who used lead-glazed ceramics had blood lead levels 18.5% higher than did children of nonusing families. Children who belonged to the lowest socioeconomic levels had blood lead levels 32.2% higher than did those of highest socioeconomic levels. Children who lived in the northeast part of the city had blood lead levels 10.9% higher compared with those who lived in the southwest.

Pre- and postnatal lead effect on head circumference: a case for critical periods.

We examined the association of maternal prenatal [range of median blood lead level 7.5-9.0 microg/dl (0.36-0.43 micromol/l) during pregnancy] and child postnatal blood lead level [range of median blood lead level from birth to 48 months 7.0-10.0 microg/dl (0.34-0.48 micromol/l)] with head circumference in from 119 to 199 children from the Mexico City Prospective Lead Study. We used repeated multiple regression modeling with a standard set of control variables, entering blood lead level last. Using Bonferroni-corrected probability values to control for inflation of Type I error due to multiple testing at each age, we found significant negative associations (p<0.05, two-tailed) between 6-month head circumference and 36-week maternal blood lead level, and 36-month head circumference and 12-month blood lead level. Over the 25-75% interquartile range of measured blood lead, head circumference decreased around 0.4 cm. Over the 1-35 microg/dl (0.05-1.68 micromol/l) range of maternal blood lead at 36 weeks, the estimated reduction in 6-month head circumference was 1.9 cm (95% CI = 0.9-3.0 cm). These results suggest that children are more vulnerable to certain effects of lead exposure at specific age ranges, and that the effect of lead on head circumference only becomes evident for brief periods in the first 4 years of life. We discuss various artifacts as well as possible mechanisms by which lead might have produced the observed pattern of results. We suggest that higher lead exposure prevalent several decades ago might have subtly influenced published normative human growth data.