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LINC study

Chemical exposures and health of children

The LINC study started in 2011 with pregnant women from the regions Den Helder, Purmerend and Zwolle, the Netherlands. Several measurements were done during pregnancy and the children were followed in their first years after birth.

Children are exposed to chemicals on a daily basis, mostly through everyday products and practices. Exposure starts, however, already as early as before birth, as chemicals present in the body of the mother may pass the placenta to reach the unborn child. Certain chemicals may disrupt the endocrine system (endocrine disrupting chemicals, EDCs), and early life exposure to EDCs may be particularly detrimental due to the vulnerability of the fetus. 

The LINC study is a prospective birth cohort and was designed to study early life exposure to chemicals and health effects in children. The LINC study had three locations in the Netherlands (Zwolle, Den Helder, Purmerend). Information on chemical exposure was mainly collected around birth (cord blood, placenta, child’s urine, meconium and breast milk). Development, both physical and behavioral, of the children was tracked. Furthermore we collected data on the environment of the children, with a particular focus on the indoor home environment.

The LINC study is designed to study associations between early life environmental exposures and child health, including growth and neurodevelopment. As such it creates possibilities to validate findings from experimental studies, but also to generate hypotheses that can be tested in vitro and/or in vivo. We assessed exposure to a multitude of chemicals very early in life (currently over 90 compounds assessed). As various samples are collected, the LINC study offers a wealth of opportunity to study potential pathways between exposure and outcome. 

Results and scientific publications

Selection of results:

LINC cohort profile
The protocol of the first phase of the LINC study is outlined.

de Cock, M., Quaak, I., Sugeng, E. J., Legler, J., & van de Bor, M. (2016). LInking EDCs in maternal Nutrition to Child health (LINC study)–protocol for prospective cohort to study early life exposure to environmental chemicals and child health. BMC Public Health, 16, 1-12.

Exposure and birth weight

Girls with a higher exposure to DDE and PFOS had a higher birthweight than lower exposed peers. There are indications for similar effects for exposure to DEHP (a phthalate) metabolites.

de Cock, M., de Boer, M. R., Lamoree, M., Legler, J., & van de Bor, M. (2016). Prenatal exposure to endocrine disrupting chemicals and birth weight-A prospective cohort study. Journal of Environmental Science and Health - Part A Toxic/Hazardous Substances and Environmental Engineering.

Exposure and first-year growth

Boys with a lower exposure to DDE, MEOHP, and MECPP had a higher BMI during the first year, and showed an increase in BMI during six and eleven months of age.

de Cock, M., de Boer, M. R., Lamoree, M., Legler, J., & van de Bor, M. (2014). First Year Growth in Relation to Prenatal Exposure to Endocrine Disruptors — A Dutch Prospective Cohort Study. International Journal of Environmental Research and Public Health 2014, Vol. 11, Pages 7001-7021, 11(7), 7001–7021.

Exposure and thyroid hormone

Thyroid hormone is an important hormone in brain development. Girls with the highest DDE and perfluorooctanoic acid (PFOA) levels had higher thyroxine (T4) levels. A negative association was found for boys exposed to the second quartile versus the first quartile.

de Cock, M., De Boer, M. R., Lamoree, M., Legler, J., & van de Bor, M. (2014). Prenatal exposure to endocrine disrupting chemicals in relation to thyroid hormone levels in infants-a Dutch prospective cohort study. Environmental Health: A Global Access Science Source, 13(1), 1–10.

PFAS in cord blood and behavior

This article examines the associations of PFAS concentrations in cord blood with behavior in 18-month-old children. Prenatal exposure to PFOA was negatively associated with externalizing behavior in boys. Results differed for boys and girls. Considering the small sample size, results must be interpreted with caution.

Quaak, I., De Cock, M., De Boer, M., Lamoree, M., Leonards, P., & Van de Bor, M. (2016). Prenatal exposure to perfluoroalkyl substances and behavioral development in children. International journal of environmental research and public health, 13(5), 511.

Flame retardants in the indoor environment

Characteristics of electronic devices were associated with higher organophosphate flame retardant levels (OPFRs) in house dust. For example, households with increased use (operation hours per day) had higher OPFR levels and households with devices on the stand-by function had higher OPFR levels compared to households with switched-off devices. Moreover, increased frequency of vacuum cleaning and dusting was associated with lower flame retardant levels in dust.

Sugeng, E. J., de Cock, M., Leonards, P. E., & van de Bor, M. (2018). Electronics, interior decoration and cleaning patterns affect flame retardant levels in the dust from Dutch residences. Science of the Total Environment, 645, 1144-1152.

Flame retardants on the hands of 8-18 month-old children

All hand wipes we collected from the children contained flame retardant chemicals. Children playing with electronics multiple times per week had higher tris-(1,3-dichloro-isopropyl) phosphate (TDCIPP) on their hands compared to children playing with electronics once per month or never.

Sugeng, E. J., de Cock, M., Leonards, P. E., & van de Bor, M. (2020). Toddler behavior, the home environment, and flame retardant exposure. Chemosphere, 252, 126588.

List of publications:

Čechová, E., Vojta, Š., Kukučka, P., Kočan, A., Trnovec, T., Murínová, Ľ. P., de Cock, M., van de Bor, M., Askevold, J., Eggesbø, M., & Scheringer, M. (2017). Legacy and alternative halogenated flame retardants in human milk in Europe: Implications for children’s health. Environment International, 108, 137–145. https://doi.org/10.1016/J.ENVINT.2017.08.008

de Cock, M., de Boer, M. R., Lamoree, M., Legler, J., & van de Bor, M. (2014). First Year Growth in Relation to Prenatal Exposure to Endocrine Disruptors — A Dutch Prospective Cohort Study. International Journal of Environmental Research and Public Health 2014, Vol. 11, Pages 7001-7021, 11(7), 7001–7021. https://doi.org/10.3390/IJERPH110707001

de Cock, M., de Boer, M. R., Lamoree, M., Legler, J., & van de Bor, M. (2016). Prenatal exposure to endocrine disrupting chemicals and birth weight-A prospective cohort study. Journal of Environmental Science and Health - Part A Toxic/Hazardous Substances and Environmental Engineering. https://doi.org/10.1080/10934529.2015.1087753

de Cock, M., De Boer, M. R., Lamoree, M., Legler, J., & van de Bor, M. (2014). Prenatal exposure to endocrine disrupting chemicals in relation to thyroid hormone levels in infants-a Dutch prospective cohort study. Environmental Health: A Global Access Science Source, 13(1), 1–10.
https://doi.org/10.1186/1476-069X-13-106

de Cock, M., Quaak, I., Sugeng, E. J., Legler, J., & van de Bor, M. (2016). Linking EDCs in maternal Nutrition to Child health (LINC study) - Protocol for prospective cohort to study early life exposure to environmental chemicals and child health. BMC Public Health, 16(147).
https://doi.org/10.1186/s12889-016-2820-8

Govarts, E., Iszatt, N., Trnovec, T., de Cock, M., Eggesbø, M., Palkovicova Murinova, L., van de Bor, M., Guxens, M., Chevrier, C., Koppen, G., Lamoree, M., Hertz-Picciotto, I., Lopez-Espinosa, M. J., Lertxundi, A., Grimalt, J. O., Torrent, M., Goñi-Irigoyen, F., Vermeulen, R., Legler, J., & Schoeters, G. (2018). Prenatal exposure to endocrine disrupting chemicals and risk of being born small for gestational age: Pooled analysis of seven European birth cohorts. Environment International, 115, 267–278.
https://doi.org/10.1016/J.ENVINT.2018.03.017

Legler, J., Hamers, T., Van Eck Van Der Sluijs-van De Bor, M., Schoeters, G., Van Der Ven, L., Eggesbo, M., Koppe, J., Feinberg, M., & Trnovec, T. (2011). The OBELIX project: early life exposure to endocrine disruptors and obesity. The American Journal of Clinical Nutrition, 94(6), S1933–S1938. https://doi.org/10.3945/AJCN.110.001669

Quaak, I., de Cock, M., de Boer, M., Lamoree, M., Leonards, P., & van de Bor, M. (2016). Prenatal exposure to perfluoroalkyl substances and Behavioral development in children. International Journal of Environmental Research and Public Health, 13(5), 511.
https://doi.org/10.3390/ijerph13050511

Quaak, I., de Cock, M., de Boer, M., & van de Bor, M. (2015). Infant Sleep Duration is Related to Externalizing Behavior at the Age of 18 Months: Results from a Dutch Cohort Study. Journal of Sleep Disorders & Therapy, 5(229). https://doi.org/10.4172/2167-0277.1000229

Sugeng, E. J., de Cock, M., Leonards, P. E. G., & van de Bor, M. (2018). Electronics, interior decoration and cleaning patterns affect flame retardant levels in the dust from Dutch residences. Science of the Total Environment, 645, 1144–1152. https://doi.org/10.1016/j.scitotenv.2018.07.127

Sugeng, E. J., de Cock, M., Leonards, P. E. G., & van de Bor, M. (2020). Toddler behavior, the home environment, and flame retardant exposure. Chemosphere, 252, 126588. https://doi.org/10.1016/j.chemosphere.2020.126588

Sugeng, E. J., de Cock, M., Leonards, P. E. G., & van de Bor, M. (2021). Association of exposure to organophosphate flame retardants and children’s behavior at a median age of 18 months. Environmental Advances, 100077. https://doi.org/10.1016/j.envadv.2021.100077

Sugeng, E. J., Leonards, P. E. G., & van de Bor, M. (2017). Brominated and organophosphorus flame retardants in body wipes and house dust, and an estimation of house dust hand-loadings in Dutch toddlers. Environmental Research, 158, 789–797. https://doi.org/10.1016/J.ENVRES.2017.07.035

Contact and collaborations
For information on collaborations, please contact Dr. Eva Sugeng.

Staff involved in this project

Project team:

Funding
The LINC study was funded by the European Commission’s Seventh Framework Programme [FP7/2007-2013] under grant agreements OBELIX n° 227391, INFLAME n° 264600, and  DENAMIC n° 282957.

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