Associations between brominated flame retardants in human milk and thyroid-stimulating hormone (TSH) in neonates☆
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)
- et al.
Environmental exposure to PBDEs and thyroid function among New York anglers
Environ. Toxicol. Pharm
(2008) - et al.
Interpretation of thyroid function in children
Paediatr. Child Health
(2007) - et al.
Fourth WHO-coordinated survey of human milk for persistent organic pollutants (POPs): Belgian results
Chemosphere
(2008) - et al.
Levels of hexachlorobenzene (HCB) in breast milk in relation to birth weight in a Norwegian cohort
Environ. Res.
(2009) - et al.
Brominated flame retardant concentrations and trends in abiotic media
Chemosphere
(2006) - et al.
Polybrominated diphenyl ether (PBDE) concentrations in house dust are related to hormone levels in men
Sci Total Environ
(2009) - et al.
Levels of chlorinated pesticides and polychlorinated biphenyls in Norwegian breast milk (2002–2006), and factors that may predict the level of contamination
Sci Total Environ
(2009) - et al.
Possible mechanisms of thyroid hormone disruption in mice by BDE 47, a major polybrominated diphenyl ether congener
Toxicol. Appl. Pharmacol.
(2008) - et al.
Automated solid-phase extraction for the determination of polybrominated diphenyl ethers and polychlorinated biphenyls in serum—application on archived Norwegian samples from 1977 to 2003
J. Chromatogr. B Anal.. Technol. Biomed. Life Sci
(2007) - et al.
Determinants of brominated flame retardants in breast milk from a large scale Norwegian study
Environ. Int.
(2010)
Thyroid function tests in preterm infants born to preeclamptic mothers with placental insufficiency
J. Pediatr. Endocrinol. Metab.
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
Evaluation of the Fetus and Newborn Exposure to Brominated Flame Retardant Type Endocrine Disruptors
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
Associations between prenatal exposure to polychlorinated biphenyls and neonatal thyroid-stimulating hormone levels in a Mexican–American population, Salinas Valley, California
Environ. Health Perspect.
Hexabromocyclododecanes (HBCDs) in the environment and humans: A review
Environ. Sci. Technol.
Thyroid function and plasma concentrations of polyhalogenated compounds in Inuit adults
Environ. Health Perspect.
Individual characteristics associated with PBDE levels in U.S. human milk samples
Environ. Health Perspect.
Brominated flame retardants as possible endocrine disrupters
Int. J. Androl.
The disorders induced by iodine deficiency
Thyroid
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.
Temporal trends of polybrominated diphenyl ethers and hexabromocyclododecane in milk from Stockholm mothers, 1980–2004
Mol. Nutr. Food Res.
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2021, Science of the Total EnvironmentCitation Excerpt :Lastly, we did not adjust for PBDEs, another family of thyroid-active chemicals. Although PBDEs have also been detected in MoBa pregnant women (Caspersen et al., 2016; Haug et al., 2018), the concentrations are at least an order of magnitude lower than that in the United States (Buttke et al., 2013) and previous studies of PBDEs in Norway did not find associations with neonatal thyroid function (Eggesbo et al., 2011) nor ADHD (Lenters et al., 2019). Therefore, it is possible that PBDE exposure in this study population may not exceed the threshold to exhibit adverse health effects.
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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.