Effects of exposure to environmental chemicals on development during adolescence

Several chemicals used in industry do not disappear after its use, but end up
in the environment. Studies done by other groups as well as by our group have
shown that exposure to these compounds, also at background levels, interfere
with the development of the fetus and newborn infant. The fetus and newborn
infants are more vulnerable to the negative effects of these compounds because
of their rapid development of organs. Previous studies mainly studied infants
during the first two years of life. In a recent study we showed that the
effects of these compounds were still detectable at 5-6 years of age. One
potential mechanism by which these compounds have an effect is disruption of
hormonal processes. Endocrine disruption might be a persistent phenomenon,
influencing thyroid hormone metabolism and psycho-motor development, but also
pubertal development and energy metabolism. In the present study, we will
during adolescence re-evaluate development of infants included in two cohorts
in which prenatal exposure to chemicals has been studied in the newborn period.

The aim of the study is to determine whether prenatal and current exposure to
environmental chemicals is associated with developmental outcome in
adolescents. We will investigate whether this exposure is associated with the
thyroid hormone homeostasis, the neuropsychological status, the pubertal
development and energy metabolism in adolescents. A second aim is to determine
the current exposure levels of polychlorinated biphenyls (PCBs), hydroxylated
PCBs (OH-PCBs) and polybrominated diphenyl ethers (PBDEs) in adolescents, and
compare them to known prenatal exposure levels.

The design of this study is a prospective, longitudinal and observational
cohort study. We will invite 190 adolescents of two existing cohorts to
participate in this follow-up study. Blood samples will be taken for
measurement of thyroid hormone parameters, sex hormones, energy metabolism
parameters and the current PCB, OH-PCB and PBDE levels. Urine samples will be
collected for assessment of bisphenol A (BPA), phthalates and polyfluoralkyl
chemicals (PFCs). The adolescents will perform tests on cognition, motor skills
and fill in a questionairre on pubertal development. Measurements of weight,
height, waist circumference and assessment of body fat and pubertal stage will
be performed. Parents will be asked to fill in questionnaires on behavior.

For investigating the effects of prenatal and current exposure to environmental
chemicals on development during adolescence, we will invite all 190 infants to
participate in a follow-up study. We will invite them to come one time to the
research site after an overnight fast. During that visit:
- Neuropsychological tests will be performed, which will take 2,5 to 3 hours,
including instructions and two short breaks of 10-15 minutes.
- Physical examination, including measurements of blood pressure, weight,
length, waist circumference and body fat will be performed. For estimating body
fat percentage Bioelectrical Impedance Analysis (BIA) will be used. For
assessment of pubertal development, pubertal assessment according to Tanner
stages and measurement of testicular volume in boys will be performed by the
examiner. A questionnaire on pubertal development will be filled in by the
adolescents. In case of refusal for pubertal assessment by the examiner, the
infant will be asked for self-assessment of pubertal stage using realistic
colored pictures of sexual maturation status and an orchidometer for boys. The
total physical examination will take 30 minutes.
- Parents will be asked to fill in four questionnaires on the behavior of the
infant.
- Vena punctures will be performed to obtain blood samples (10 ml) for
assessment of thyroid hormone homeostasis parameters, sex hormones, energy
metabolism parameters and levels of PCBs, OH-PCBs and PBDEs.
- Morning urine samples will be collected for assessment of levels of BPA,
phthalates and PFCs.

The burden and risks for the subjects included in the study are minimal. Risks
of the vena puncture can be: excessive bleeding; fainting or feeling
light-headed; hematoma or blood accumulating under the skin; infection (a
slight risk any time the skin is broken); multiple punctures to locate veins.

Data for this study cannot be obtained in another population, as the intention
is to study associations of prenatal levels of environmental chemicals with
developmental outcomes during adolescence. The results of this study will give
more insight into the prenatal and current exposure to environmental chemicals,
and the impact of this exposure on various developmental outcomes in
adolescents. Our findings may lead to social-medical consequences including
potential intervention strategies.