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 approximately one month after TSH was measured. Although a retrospective assessment of exposure is generally not raised as a major concern in studies on persistent organic pollutants due to their long half lives, variation in feeding patterns as well as toxicokinetics may introduce a differential change in concentrations. On the other hand, recent studies indicate that while variable, the average monthly decrease in milk PBDEs is only 2–3% (Daniels et al., 2010
; Hooper et al., 2007
). In accordance with this, no significant association between the duration of breastfeeding and the sum of the six PBDEs was observed in our data: the crude association between the amount of previous breastfeeding and the sum of six PBDEs was: beta; 0.013 (CI −0.04 to 0.06), p- value: 0.62. (See Suppl. Text A
). Finally, the sensitivity analysis performed with adjustment for total breastfeeding before the sampling date revealed no changes in the results.
Milk levels are being used as a proxy for maternal blood levels in this study. A high correlation between PBDEs in milk and maternal serum has been reported (BDE-153; r = 0.85 for maternal serum-milk) (Cariou, 2006
; Guvenius et al., 2003
), as has a similar correlation between milk and cord blood (BDE-153; 0.84 for cord-milk) (Cariou, 2006
). For lower brominated congeners, the correlation may be even higher (BDE-47; r = 0.94, p < 0.01, for cord blood-human milk) (Guvenius et al., 2003
), which may be explained by their lower mass which probably enables easier transport through the placental barrier (Guvenius et al., 2003
). Thus, the levels of higher brominated congeners in human milk may overestimate prenatal exposure. However, milk levels may still appropriately rank subjects according to their exposure levels unless the placenta barrier functions differently among women.
The PBDE exposure levels observed in the present study are comparable to concentrations in human milk from most other Asian and European countries, except for the UK and the Faroe Islands where slightly higher levels were reported and for the US and Canada where levels are approximately one order of magnitude higher (reviewed in (Frederiksen et al., 2008
). The HBCD and BDE-209 levels observed in the present study are also comparable to the levels reported in Europe, except somewhat higher levels of BDE-209 have been reported in Spain (Covaci et al., 2006
; Frederiksen et al., 2008
Human studies on this topic are still scarce. Studies among adults have reported an association between exposure to BFRs and subtle differences in thyroid hormones among sport fishermen, workers occupationally exposed to BFRs, Inuit adults and subfertile men (Dallaire et al., 2009
; Hagmar et al., 2001
; Julander et al., 2005
; Meeker et al., 2009
; Turyk et al., 2008
), while others report no effects among sport fishermen (Bloom et al., 2008
). Among pregnant women an inverse association between TSH levels and concentrations of BFRs in serum was observed (Chevrier et al., 2010
). Finally, two studies report that prenatal exposure to BFRs is associated with neurodevelopmental findings in young children (Herbstman et al., 2010
; Roze et al., 2009
). Concentrations of PBDEs may differ substantially across studies from different countries and give rise to different results.
Of greater relevance to the current study is a study in which three PBDEs were examined in relation to thyroid function in infants (Herbstman et al., 2008b
). BDE-100 and BDE-153 were weakly associated with increased odds of having a cord blood total T4 in the lower quintile. Furthermore, BDE-47 was associated with reduced odds of having a cord serum TSH level in the upper 20th percentile. Compared to the latter study, our levels are 5–15 times lower, which could explain the discrepant finding. No association was observed between total and free T4 thyroid hormone levels and the sum of six PBDEs in a study from Indianapolis which, however, only included 9 babies (Mazdai et al., 2003
A limitation in our study is the lack of measurement of thyroxin. However, TSH is regarded as a sensitive marker of thyroid disruption in humans since incremental changes in free T4 hormone concentrations will lead to logarithmic changes in TSH (Bursell et al., 2007
). TSH has also been extensively evaluated as a marker of thyroid disruption in newborns due to its frequent use in screening programs. On the other hand, a number of experimental animal studies on BFRs failed to detect any association with TSH (Hallgren et al., 2001
) in the presence of an association with thyroxin. The mechanism by which BFRs could affect thyroxin but not TSH remains unclear. Nevertheless, some animal studies do report an effect on TSH by BFRs (Stoker et al., 2004
; van der Ven et al., 2006
). In conclusion, we cannot exclude the possibility that thyroid homeostasis was disrupted in ways that are not reflected in altered TSH levels.
We did not have data on iodine status but due to fortification of cattle fodder iodine deficiency is rare in Norway (Delange, 1994
), and none of the subjects in the present study had a clinically elevated TSH.
To the best of our knowledge, this is the first study in which milk was sampled over a prolonged period of time (eight days). This was done in order to reduce the within-subject variability in milk that has been demonstrated for other persistent organic pollutants (Skaare et al., 1990
; Thomsen et al., 2010
One strength of this study is that TSH was measured at a median of 70 hours after birth, thereby allowing for the birth-related temporary spike in TSH and hormone levels to abate. TSH in newborns has been reported to be associated with a number of factors; however, this is mainly in relation to TSH levels measured in cord blood (Herbstman et al., 2008a
). Studies of TSH measured 24 hours or longer after birth generally report no associations between TSH and factors such as preeclampsia (Belet et al., 2003
), preterm delivery (Carrascosa et al., 2004
) or mode of delivery (Turan et al., 2007
). Furthermore, studies with repeated measurements have shown that preterm delivery is significantly associated with TSH only within the first 24 hours after birth and not after 24 hours, although this may not hold true for very preterm babies (Biswas et al., 2002
; Murphy et al., 2004
). This indicates that these factors are related to the TSH-surge after birth and not to the thyroid function per se. In our study, only two infants had their TSH measured earlier than 48 hours after delivery, which probably accounts for why no covariates showed any association with TSH.
An advantage of the present study was the availability of data on coexisting environmental contaminants. Since environmental contaminants coexist in exposure sources and may have additive or antagonistic effects, this may be important. Still, adjustment for other contaminants can only be partially achieved, and we cannot exclude the possibility of confounding by other as yet unmeasured persistent organic pollutants that are strongly correlated with BFR exposure in Norway.
One weakness of our study is the low final response rate. Hence, the results may not be generalizable to the entire population. However, a comparison between our study sample and the general population of recent mothers did not reveal any strong selection with regard to the covariates available for comparison (Suppl. Table A.1
). A differential selection that is related to both exposure to brominated flame retardants and to TSH levels is possible though seems unlikely.