Urinary specific gravity measures in the U.S. population: Implications for the adjustment of non-persistent chemical urinary biomarker data

Kuiper, Jordan R.; O’Brien, Katie M.; Ferguson, Kelly K.; Buckley, Jessie P.

doi:10.1016/j.envint.2021.106656

Cited by 82 publications

(43 citation statements)

References 27 publications

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“…For metabolites in ARCH, creatinine concentrations, measured with HPLC (Shimadzu LC-30 CE Series HPLC system, Shimadzu Corporation, Kyoto, Japan/Sciex 5500, ESI-MS/MS; Applied Biosystems, Foster City, CA) were used to adjust for urinary dilution, as described as Kuiper et al (2021) . For ARCH, raw concentrations were input into the following formula:

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Section: Methodsmentioning

confidence: 99%

Prenatal Exposures to Common Phthalates and Prevalent Phthalate Alternatives and Infant DNA Methylation at Birth

et al. 2022

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Phthalates are a diverse group of chemicals used in consumer products. Because they are so widespread, exposure to these compounds is nearly unavoidable. Recently, growing scientific consensus has suggested that phthalates produce health effects in developing infants and children. These effects may be mediated through mechanisms related to the epigenome, the constellation of mitotically heritable chemical marks and small compounds that guide transcription and translation. The present study examined the relationship between prenatal, first-trimester exposure of seven phthalates and epigenetics in two pregnancy cohorts (n = 262) to investigate sex-specific alterations in infant blood DNA methylation at birth (cord blood or neonatal blood spots). Prenatal exposure to several phthalates was suggestive of association with altered DNA methylation at 4 loci in males (all related to ΣDEHP) and 4 loci in females (1 related to ΣDiNP; 2 related to BBzP; and 1 related to MCPP) at a cutoff of q < 0.2. Additionally, a subset of dyads (n = 79) was used to interrogate the relationships between two compounds increasingly used as substitutions for common phthalates (ΣDINCH and ΣDEHTP) and cord blood DNA methylation. ΣDINCH, but not ΣDEHTP, was suggestive of association with DNA methylation (q < 0.2). Together, these results demonstrate that prenatal exposure to both classically used phthalate metabolites and their newer alternatives is associated with sex-specific infant DNA methylation. Research and regulatory actions regarding this chemical class should consider the developmental health effects of these compounds and aim to avoid regrettable substitution scenarios in the present and future.

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Section: Methodsmentioning

confidence: 99%

Prenatal Exposures to Common Phthalates and Prevalent Phthalate Alternatives and Infant DNA Methylation at Birth

et al. 2022

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“…19 However, the degree to which they are correlated is likely dependent on the homogeneity of the population in which they are measured. Given that measures of creatinine may be more influenced by factors such as age, 13,16,17 body size (e.g., BMI and height), 13,16 gender or sex, 13,16 race and ethnicity, 13,16 and certain health conditions (e.g., hypertension, diabetes, kidney disease), 16 a more diverse study population (with respect to these factors) would be expected to have a lower correlation between these two measures of dilution, generally. Additionally, different specimen collection and storage protocols across sites or studies may be another source of variability, even for the same measure of dilution.…”

Section: Discussionmentioning

confidence: 99%

“…The second approach, the Boeniger method, has traditionally been used for specific gravity but recently extended for use with creatinine as well. 16 This method uses the following formulae to directly adjust biomarker concentrations for urinary dilution. For specific gravity, Esg= Eo x SGmedian – 1SGo – 1, where E sg is the specific gravity-standardized exposure biomarker concentration, E o is the observed exposure biomarker concentration, SGmedian is the median of specific gravity values in the study sample, and SG o is the observed specific gravity value.…”

Section: Methodsmentioning

confidence: 99%

“…3 Although this approach circumvents the issue of noncompatible units of exposure, it does not directly address a second issue that these measures of dilution are often affected by multiple exogenous or endogenous factors, independent of underlying hydration status. 13,16,17 Several studies have shown that urinary creatinine (a waste product from skeletal muscle that is excreted by the kidneys) levels can be influenced by an individual's age, 13,16,17 height and body mass index (BMI), 13,16 gender or sex, 13,16 race and ethnicity, 13,16 certain health conditions (e.g., hypertension), 16 and time of day of sample collection. 16,18 Similarly, urinary specific gravity (a measure of the relative density of urine to water) can be influenced by the same factors as creatinine, 16,[18][19][20][21][22][23] though perhaps to a lesser extent.…”

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confidence: 99%

“…Several studies have shown that urinary creatinine (a waste product from skeletal muscle that is excreted by the kidneys) levels can be influenced by an individual’s age, 13,16,17 height and body mass index (BMI), 13,16 gender or sex, 13,16 race and ethnicity, 13,16 certain health conditions (e.g., hypertension), 16 and time of day of sample collection. 16,18 Similarly, urinary specific gravity (a measure of the relative density of urine to water) can be influenced by the same factors as creatinine, 16,18–23 though perhaps to a lesser extent.…”

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Combining Urinary Biomarker Data From Studies With Different Measures of Urinary Dilution

et al. 2022

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Background: Guidance is lacking for how to combine urinary biomarker data across studies that use different measures of urinary dilution, that is, creatinine or specific gravity. Methods: Among 741 pregnant participants from four sites of The Infant Development and Environment Study (TIDES) cohort, we assessed the relation of maternal urinary di-2-ethylhexyl phthalate (DEHP) concentrations with preterm birth. We compared scenarios in which all sites measured either urinary creatinine or specific gravity, or where measure of dilution differed by site. In addition to a scenario with no dilution adjustment, we applied and compared three dilution-adjustment approaches: a standard regression-based approach for creatinine, a standard approach for specific gravity (Boeniger method), and a more recently developed approach that has been applied to both (covariate-adjusted standardization method). For each scenario and dilution-adjustment method, we estimated the association between a doubling in the molar sum of DEHP (∑DEHP) and odds of preterm birth using logistic regression. Results: All dilution-adjustment approaches yielded comparable associations (odds ratio [OR]) that were larger in magnitude than when we did not perform dilution adjustment. A doubling of ∑DEHP was associated with 9% greater odds of preterm birth (OR = 1.09, 95% confidence interval [CI] = 0.91, 1.30) when applying no dilution-adjustment method, whereas dilution-adjusted point estimates were higher, and similar across all scenarios and methods: 1.13–1.20 (regression-based), 1.15–1.18 (Boeniger), and 1.14–1.21 (covariate-adjusted standardization). Conclusions: In our applied example, we demonstrate that it is possible and straightforward to combine urinary biomarker data across studies when measures of dilution differ.

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Associations Between Prenatal Urinary Biomarkers of Phthalate Exposure and Preterm Birth

et al. 2022

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and the Pooled Phthalate Exposure and Preterm Birth Study Group IMPORTANCE Phthalate exposure is widespread among pregnant women and may be a risk factor for preterm birth.OBJECTIVE To investigate the prospective association between urinary biomarkers of phthalates in pregnancy and preterm birth among individuals living in the US. DESIGN, SETTING, AND PARTICIPANTSIndividual-level data were pooled from 16 preconception and pregnancy studies conducted in the US. Pregnant individuals who delivered between 1983 and 2018 and provided 1 or more urine samples during pregnancy were included.EXPOSURES Urinary phthalate metabolites were quantified as biomarkers of phthalate exposure. Concentrations of 11 phthalate metabolites were standardized for urine dilution and mean repeated measurements across pregnancy were calculated. MAIN OUTCOMES AND MEASURESLogistic regression models were used to examine the association between each phthalate metabolite with the odds of preterm birth, defined as less than 37 weeks of gestation at delivery (n = 539). Models pooled data using fixed effects and adjusted for maternal age, race and ethnicity, education, and prepregnancy body mass index. The association between the overall mixture of phthalate metabolites and preterm birth was also examined with logistic regression. G-computation, which requires certain assumptions to be considered causal, was used to estimate the association with hypothetical interventions to reduce the mixture concentrations on preterm birth. RESULTSThe final analytic sample included 6045 participants (mean [SD] age, 29.1 [6.1] years). Overall, 802 individuals (13.3%) were Black, 2323 (38.4%) were Hispanic/Latina, 2576 (42.6%) were White, and 328 (5.4%) had other race and ethnicity (including American Indian/Alaskan Native, Native Hawaiian, >1 racial identity, or reported as other). Most phthalate metabolites were detected in more than 96% of participants. Higher odds of preterm birth, ranging from 12% to 16%, were observed in association with an interquartile range increase in urinary concentrations of mono-N-butyl phthalate (odds ratio [OR], 1.12 [95% CI, 0.98-1.27]), mono-isobutyl phthalate (OR, 1.16 [95% CI, 1.00-1.34]), mono(2-ethyl-5-carboxypentyl) phthalate (OR, 1.16 [95% CI, 1.00-1.34]), and mono(3-carboxypropyl) phthalate (OR, 1.14 [95% CI, 1.01-1.29]). Among approximately 90 preterm births per 1000 live births in this study population, hypothetical interventions to reduce the mixture of phthalate metabolite levels by 10%, 30%, and 50% were estimated to prevent 1.8 (95% CI, 0.5-3.1), 5.9 (95% CI, 1.7-9.9), and 11.1 (95% CI, 3.6-18.3) preterm births, respectively. CONCLUSIONS AND RELEVANCEResults from this large US study population suggest that phthalate exposure during pregnancy may be a preventable risk factor for preterm delivery.

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Urinary specific gravity measures in the U.S. population: Implications for the adjustment of non-persistent chemical urinary biomarker data

Cited by 82 publications

References 27 publications

Prenatal Exposures to Common Phthalates and Prevalent Phthalate Alternatives and Infant DNA Methylation at Birth

Prenatal Exposures to Common Phthalates and Prevalent Phthalate Alternatives and Infant DNA Methylation at Birth

Combining Urinary Biomarker Data From Studies With Different Measures of Urinary Dilution

Associations Between Prenatal Urinary Biomarkers of Phthalate Exposure and Preterm Birth

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