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Prenatal Lead Exposure and Puberty Timing in Girls

Maisonet, Mildred; Jaakkola, Jouni J. K.; Taylor, Caroline M.; Marcus, Michele; Golding, Jean

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doi: 10.1097/EDE.0000000000000021
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To the Editor:

Findings from cross-sectional epidemiologic studies suggest that blood lead concentrations predict later development of secondary sexual characteristics and reproductive maturation in adolescent girls.1–6 Evidence on the role of prenatal lead exposure on puberty timing is lacking. We examined data from mother-daughter pairs enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC) to determine this association.

Whole blood samples were collected from pregnant mothers at enrollment (1991–1992) and analyzed for lead content using inductively coupled plasma mass spectrometry. The median gestational age of blood collection was 11 weeks. Repeated assessments of pubertal status were obtained from daughters, beginning at age 8 and continuing through age 17. Participants were asked to examine line drawings and descriptions of the five Tanner stages for breast size and pubic hair and to record which drawing most closely resembled their own stage of development. At each assessment, participants were asked whether their first menstrual period had occurred and when it had occurred.7 We restricted our analyses to singleton white daughters.

The following covariates were selected a priori and included in all adjusted analyses: maternal smoking during pregnancy, maternal education, previous births, and daughters’ height at age 7. Data collection instruments and methods have been described elsewhere (

We used parametric survival models to obtain the median age and cumulative probabilities of attainment of pubertal markers to describe unadjusted patterns in pubertal markers over time, assuming a Normal distribution. Hazards ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards models, using the group with prenatal lead concentrations <5 µg/dl as the reference. The proportional hazards assumption was assessed for all variables in the models. Time to menarche was based on the age of attainment given by participants or right-censored using the age of the last completed assessment. For Tanner stages, time to event was defined using the midpoint between two assessments. Alternatively, the data were left-censored if the participant reported a stage 2 or greater on their first returned assessment or right-censored if stage 2 was not attained.

Human subject protection was assessed and approved by the ALSPAC Law and Ethics Committee, the Local Research Ethics Committees, and the Centers for Disease Control and Prevention Institutional Review Board.

Menarche analyses (n = 918) comprised data for the full follow-up period, whereas Tanner stage analyses (n = 765) were based on status up to 14 years of age. The median age at menarche was 150 months (12.5 years), median age at breast stage ≥2 was 130 months (10.8 years), and median age at pubic hair stage ≥2 was 135 months (11.3 years). The median prenatal lead concentration was 3.4 µg/dl (range, 0.8–19.1 µg/dl). Fifteen percent of mothers had lead concentrations ≥5 µg/dl. The median age at menarche in daughters with prenatal concentrations ≥5 µg/dl did not vary from those with lead concentrations <5 µg/dl (both were 150 months). The two groups were also similar regarding breast stage ≥2 (129 vs. 131 months, respectively) and pubic hair stage ≥2 (133 vs. 135 months).

Unadjusted survival distributions for age at menarche by exposure category did not vary over time (Figure). Curves for breast and pubic hair attainment showed similar patterns. The rate of attainment of pubertal markers in daughters with prenatal lead concentrations ≥5 µg/dl did not differ from those with lower lead concentrations. Attainment of menarche (adjusted HR = 1.00 [95% CI = 0.82–1.21]), breast stage ≥2 (1.08 [0.87–1.35]), and pubic hair stage ≥2 (1.02 [0.83–1.26]) were all unrelated to prenatal lead concentrations. Our findings are not consistent with those of cross-sectional studies, which have suggested an antiestrogenic effect of lead in adolescent girls.

Unadjusted survival distribution for menarche attainment by categories of prenatal lead ≥5 µg/dl and <5 µg/dl.


We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses.

Mildred Maisonet

Jouni J. K. Jaakkola

Center for Environmental and Respiratory Health Research, University of Oulu, Oulu, Finland, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland,

Caroline M. Taylor

Centre for Child and Adolescent Health, University of Bristol, Bristol, United Kingdom

Michele Marcus

Kaiser Permanente Center for Health Research, Atlanta, GA

Jean Golding

Centre for Child and Adolescent Health, University of Bristol, Bristol, United Kingdoml


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