Elsevier

Environmental Research

Volume 111, Issue 6, August 2011, Pages 737-743
Environmental Research

Associations between brominated flame retardants in human milk and thyroid-stimulating hormone (TSH) in neonates

https://doi.org/10.1016/j.envres.2011.05.004Get rights and content

Abstract

Background

Brominated flame retardants (BFRs) have been in widespread use in a vast array of consumer products since the 1970s. The metabolites of some BFRs show a structural similarity to thyroid hormones and experimental animal studies have confirmed that they may interfere with thyroid hormone homeostasis. A major concern has been whether intrauterine exposure to BFRs may disturb thyroid homeostasis since the fetal brain is particularly susceptible to alterations in thyroid hormones. However, few reports on newborns have been published to date.

Objectives

To evaluate the association between BFRs and neonatal thyroid-stimulating hormone (TSH).

Methods

We studied six polybrominated diphenyl ethers (PBDEs) measured in milk samples from 239 women who were part of the “Norwegian Human Milk Study” (HUMIS), 2003–2006. Hexabromocyclododecane (HBCD) and BDE-209 were measured in a subset of the women (193 and 46 milk samples, respectively). The milk was sampled at a median of 33 days after delivery. TSH was measured in babies three days after delivery as part of the routine national screening program for early detection of congenital hypothyroidism. Additional information was obtained through the Medical Birth Registry and questionnaires to the mothers.

Results

The PBDE concentrations in human milk in Norway were comparable to concentrations reported from other European countries and Asia, but not the US and Canada where levels are approximately one order of higher magnitude. We observed no statistically significant associations between BDE-47, 99, 153, 154, 209 and HBCD in human milk and TSH in models adjusted for possible confounders and other environmental toxicants including polychlorinated biphenyls (PCBs).

Conclusions

We did not observe an association between TSH and exposure to HBCD and PBDEs within the exposure levels observed.

Highlights

► Exposure to brominated flame retardants may disturb thyroid homeostasis. ► We examined the association between eight BFRs in human milk and TSH measured three days after delivery. ► We did not observe an association between TSH and exposure to HBCD and PBDEs.

Introduction

Brominated flame retardants (BFRs) are a group of chemical compounds which have been in widespread use since the 1970s, in a vast array of consumer products. Two of the three groups of BFRs which account for most of the world's production are hexabromocyclododecane (HBCD) and polybrominated diphenyl ethers (PBDEs). The recent ban in the US, Europe and Japan on the commercial PBDE mixtures i.e., Penta-BDE and Octa-BDE, as well as voluntary actions, has led to a decline in exposure to the congeners that were constituents (Fangstrom et al., 2008, Thomsen et al., 2010). The commercial mixture deca-BDE (consisting mainly of BDE-209) has only been restricted in Europe so far, while HBCD is still in unrestricted use, and their use may increase as a result of the ban on other BFRs (Fangstrom et al., 2008, Hale et al., 2006). More knowledge of the potential health effects of exposure to BDE-209 and HBCD is therefore called for, although exposure to the Penta- and Octa-PBDEs mixtures will also continue for decades to come.

PBDEs share many toxicological properties with polychlorinated biphenyls (PCBs). A number of experimental animal studies have confirmed that PBDEs can interfere with thyroid hormone homeostasis (Darnerud, 2008). Among the many possible mechanisms for this interference, the evidence is strongest for effects mediated by changes in uridine diphosphate glucoronosyltransferase and by binding to transport protein (Darnerud, 2008, Richardson et al., 2008). During the pre- and postnatal period even slight disturbances in thyroid hormone homeostasis may cause long term effects on cognitive function, memory and hearing (Haddow et al., 1999, Morreale de et al., 2004, Porterfield, 1994). Subtle neurodevelopment effects were reported after exposure to relatively low doses of BFRs in experimental animal studies (Darnerud, 2008, Sand et al., 2004), including permanent effects on behavior, learning and memory that became more pronounced with increasing age (Eriksson et al., 2002, Viberg et al., 2003). These effects may have been mediated through thyroid disruption. It is worth noting that these effects were induced by exposure during neonatal brain development and not by exposure at later age stages, thereby indicating studies on newborns and children are needed.

To date, only two studies on the effect of PBDEs on thyroid function among neonates have been published. The results in one study suggest an association between exposure to PBDEs and a disruption in the levels of thyroid hormones (Herbstman et al., 2008b), whereas no association was observed in another study which included only nine subjects (Mazdai et al., 2003). However, concentrations of PBDEs may differ substantially across studies and give rise to different results.

In the present paper, we examined the association between BFRs in human milk and thyroid-stimulating hormone (TSH) as a measure of thyroid function. We studied six PBDEs in mother's milk from 239 mothers who were part of the “Norwegian Human Milk Study” (HUMIS). In addition, the levels of HBCD and BDE-209 were measured in a subset of 193 and 46 milk samples, respectively. We obtained TSH levels, measured in whole blood three days after delivery, from the nationwide neonatal screening program.

Section snippets

Study population

HUMIS is a multi-center cohort of mothers who have recently given birth and their babies. The participants were recruited from six counties in Norway which covers northern, southern, inland and coastal areas of Norway. The majority of the participants were from five counties (Telemark, Oppland, Troms, Finmark and Rogaland) and within approximately two weeks of giving birth they were recruited by public health nurses who saw the subjects at home as part of a routine follow-up of all mothers in

Study population and levels

The study population was similar to both the general population of recent mothers in Norway and to all participants recruited to the HUMIS study with the exception of smoking, which was less frequent in the present study sample (Suppl. Table A.1). There were no participants diagnosed with congenital hypothyroidism.

The mean concentration of TSH was 1.4 mU/L (median 1.1 mU/L), ranging from 0.0 to 17.3 mU/L, and the difference between the 10th and the 90th percentiles was 2.4 mU/L. The median TSH

Discussion

The present study did not find any associations between the levels of BFR measured in human milk and TSH levels in newborns. Our results do not exclude the possibility that exposure to higher levels of BFRs, such as those reported in North America or at the higher end of our population exposure distribution, may affect thyroid homeostasis. Furthermore, our study size, especially for BDE-209, was small.

Our study is limited by the retrospective assessment of exposure since human milk was sampled

Acknowledgments

Anuschka Polder is acknowledged for PCB analysis, Sharon Lynn Broadwell for sample preparation and the Public health nurses for recruitment of mothers, and the mothers for their great efforts.

References (46)

  • N. Belet et al.

    Thyroid function tests in preterm infants born to preeclamptic mothers with placental insufficiency

    J. Pediatr. Endocrinol. Metab.

    (2003)
  • S. Biswas et al.

    A longitudinal assessment of thyroid hormone concentrations in preterm infants younger than 30 weeks' gestation during the first 2 weeks of life and their relationship to outcome

    Pediatrics

    (2002)
  • R. Cariou

    Evaluation of the Fetus and Newborn Exposure to Brominated Flame Retardant Type Endocrine Disruptors

    (2006)
  • A. Carrascosa et al.

    Thyroid function in seventy-five healthy preterm infants thirty to thirty-five weeks of gestational age: A prospective and longitudinal study during the first year of life

    Thyroid

    (2004)
  • J. Chevrier et al.

    Associations between prenatal exposure to polychlorinated biphenyls and neonatal thyroid-stimulating hormone levels in a Mexican–American population, Salinas Valley, California

    Environ. Health Perspect.

    (2007)
  • Chevrier J, Kim, G., Harley, K.G., Bradman, A., Gharbi, M., Sjödin, A., Eskenazi, B., 2010. Polybrominated...
  • A. Covaci et al.

    Hexabromocyclododecanes (HBCDs) in the environment and humans: A review

    Environ. Sci. Technol.

    (2006)
  • R. Dallaire et al.

    Thyroid function and plasma concentrations of polyhalogenated compounds in Inuit adults

    Environ. Health Perspect.

    (2009)
  • J.L. Daniels et al.

    Individual characteristics associated with PBDE levels in U.S. human milk samples

    Environ. Health Perspect.

    (2010)
  • P.O. Darnerud

    Brominated flame retardants as possible endocrine disrupters

    Int. J. Androl.

    (2008)
  • F. Delange

    The disorders induced by iodine deficiency

    Thyroid

    (1994)
  • P. Eriksson et al.

    A brominated flame retardant, 2,2′,4,4′,5-pentabromodiphenyl ether: uptake, retention, and induction of neurobehavioral alterations in mice during a critical phase of neonatal brain development

    Toxicol. Sci.

    (2002)
  • B. Fangstrom et al.

    Temporal trends of polybrominated diphenyl ethers and hexabromocyclododecane in milk from Stockholm mothers, 1980–2004

    Mol. Nutr. Food Res.

    (2008)
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    Funding and approvals: This research was supported by a grant from the European Community's Seventh Framework Program [FP7/2007-2013] under grant agreement OBELIX no. 227391 and the intramural research program of the National Institute of Environmental Health Sciences.

    The study was approved by the Regional Ethics Committee for Medical Research in Norway (ref. S-02122) and the Norwegian Data Inspectorate (refs. 2002/1398-2 and 02/01398-7), and participation did not occur until after informed consent was obtained.

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