Forty-one premature infants had at least one urine sample available for analysis of BPA and MePB (42 for TCS, BP-3, and PrPB). We detected BPA in all of the first set of urine samples collected from these infants at total concentrations ranging from 1.6 to 946 μg/L; the geometric mean was 30.3 μg/L (). MePB and PrPB were also detected in all of the samples and BP-3 in all but two samples (). TCS was detected in approximately 19% of the samples and therefore was not included in any further statistical analysis. Of interest, the free species of some of these phenols were detected slightly less frequently and at substantially lower concentrations than the conjugated species (). For example, free BPA was detected in 92% of the samples; the median (1.7 μg/L) and highest concentrations (17.3 μg/L) were an order of magnitude lower than the total concentrations. Of interest, the concentrations of free and conjugated species of BPA showed a linear relationship (Spearman correlation, r = 0.86) throughout the range of total BPA concentrations observed (). Because of the limited amount of urine available for analysis, the concentration of free species could not be measured in all samples.
Distribution of the urinary concentrations of phenols (μg/L)a in hospitalized premature infants.
Correlation between free and total BPA urinary concentrations for 37 premature infants, displayed in log-10 scale (r = 0.86).
The infants in this study were roughly equally distributed between the two institutions, and about 38% (information on sex was missing for one of the infants) were male (). Fewer infants were exposed to DEHP-containing products at low intensity of use than at medium or high intensity of use ().
Median and 25th and 75th percentile concentrations of urinary phenols (μg/L) in hospitalized premature infants, by intensity of use of products containing DEHP, institution, and sex.
Two or more replicate samples were available for 14 infants (13 for BPA); we used the first two of these samples to assess variability in urinary concentrations within individual infants (). The repeated urinary measurements from the same infants were highly correlated for BPA and BP-3, and also correlated, although to a lesser extent, for MePB and PrPB. As expected, the correlations between the concurrent (i.e., more than one urine sample collected from a single diaper or cotton gauze) measurements were excellent (all Spearman r ≥ 0.95) ().
Spearman correlations between repeated urinary concentrations among premature infants (first two specimens).
As has been reported (Ye et al. 2006a
), we found that institution-adjusted urinary concentrations of MePB and PrPB were highly correlated (Spearman r
= 0.73, p
< 0.0001), suggesting that human exposures to these para-bens most likely share common pathways. BPA was moderately correlated with MePB (r
= 0.40, p
= 0.01). Notably, however, BPA was correlated with the phthalate metabolites, including the three metabolites of DEHP among which it was strongly correlated with DEHP oxidative metabolites mono(2-ethyl-5-hydroxy-hexyl phthalate (r
= 0.57, p
< 0.0001) and mono(2-ethyl-5-oxohexyl) phthalate (r
= 0.57, p
< 0.0002). The remaining institution-adjusted correlations among the different phenols with each other and with the phthalate metabolites measured before (Green et al. 2005
; Weuve et al. 2006
) were weak to moderate ().
Institution-adjusted Spearman correlations between the total urinary concentrations of different analytes among premature infants (all n = 41 or 42).
Of the 41 infants who had at least one BPA measure, gestational age data were available for only 16 of them. After dividing the group roughly along the median gestational age (25–27 weeks vs. 28–34 weeks), the median total BPA concentrations was higher (Kruskal–Wallis p-value = 0.06) for the younger (242 μg/L) than for the older (29 μg/L) infants (based on gestational age). For the 25 infants for whom we had information about length of stay in the NICU, BPA concentrations did not appear to vary across long (14–90 days) versus short (2–13 days) length of stay. The difference in BPA concentrations for the breast-fed (or fed breast milk) infants (n = 4) and the formula fed infants (n = 14) was not statistically significant (p = 0.7).
In the crude analyses, urinary BPA concentrations were significantly higher among infants at institution A than at institution B (p < 0.0001; ). Concentrations of the other phenols measured were similar across institutions (). Urinary concentrations of BPA and the other three phenols did not vary substantially by infants’ sex, and no consistent associations were present between intensity of DEHP-containing product use and urinary concentrations of any of the phenols examined ().
On adjusting for infants’ sex and intensity of use of products containing DEHP, the association between institution and BPA concentrations persisted (). On average, urinary concentrations of BPA among infants hospitalized at institution A were almost 17 times greater than concentrations among infants at institution B (p < 0.0001). By contrast, infants hospitalized at Institution A had BP-3 urinary concentrations that were, on average, about one-third the concentrations among infants at institution B (p = 0.04). Concentrations of the two parabens did not vary consistently by DEHP-containing product use group or institution. In these adjusted analyses, none of the phenol concentrations varied by infants’ sex.
Multivariable-adjusteda relative urinary concentrations of the phenolsb (95% CI) in hospitalized premature infants, by use of DEHP-containing products, infant’s sex, and institution.
The institution- and sex-adjusted associations between the use of medical products containing DEHP group and urinary concentrations were highly significant for BPA but not for any of the other phenols (). Compared with infants exposed at low intensity to DEHP-containing products, infants exposed at medium intensity had BPA concentrations that were 3.42 times as high [95% confidence interval (CI), 1.45–8.09], and infants exposed at high intensity had concentrations that were 8.75 times as high (95% CI, 3.36–22.8). The results of this sex- and institution-adjusted analysis differed from the crude analyses, shown in , which did not show marked differences in BPA concentration by DEHP group. Similarly, results from linear mixed effects regression models of BPA that did not adjust for sex or institution also showed no significant differences in BPA concentration by DEHP-containing product use group (data not shown). These different findings were most likely attributable to negative confounding by institution; infants at institution B had lower BPA concentrations but were much more likely than infants at institution A to be exposed at high intensity (29% vs. 7%) to DEHP-containing products.