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Urinary phthalate metabolite concentrations and adolescent sleep duration

Background: Some environmental chemicals, such as phthalates, are capable of disrupting endocrine function related to the development and regulation of sleep patterns. However, the contribution of phthalate exposure to inadequate sleep during adolescence is unknown. We aim to evaluate the association between phthalate exposure and short sleep duration during adolescence. Methods: We used data from participants 16–17 years of age in the 2005–2010 cycles of the National Health and Nutrition Examination Survey. Participants reported typical sleep duration during weekdays, which we categorized into short sleep duration (less than 8 hours per night) and adequate sleep duration (8 or more hours) based on consensus guidelines. We used weighted logistic regression to evaluate the association between log10-transformed urinary phthalate metabolite concentrations and odds of short sleep duration. Results: An interquartile range increase in di(2-ethylhexyl) phthalate metabolites, monocarboxynonyl phthalate, monocarboxyoctyl phthalate, and mono-isobutyl phthalate was associated with 1.48 (95% confidence interval [95% CI] = 1.02, 2.16), 1.64 (95% CI = 1.17, 2.32), 1.46 (95% CI = 0.99, 2.16), and 1.92 (95% CI = 1.08, 3.43) times the odds of short sleep duration, respectively. Furthermore, we observed monotonic dose-response relations between some phthalate metabolites and odds of short sleep duration. Conclusions: Our results suggest that higher urinary concentrations of several phthalate metabolites are associated with short sleep duration during adolescence. Understanding the contribution of modifiable environmental factors to inadequate sleep duration is of great public health importance because inadequate sleep can have substantial health implications.


Introduction
In the United States, approximately 58% of middle schoolers and 73% of high schoolers did not get the recommended duration of sleep required for optimal health. 1 Adolescents are susceptible to short sleep durations due to psychosocial influences and behavioral factors, as well as physiologic changes driven by gonadal hormones. [2][3][4] Accumulating evidence suggests that phthalates-anthropogenic chemicals added to personal care and household products-affect the homeostasis or action of gonadal hormones, glucocorticoids, and thyroid hormones, potentially altering neurodevelopment and cardiometabolic health. [5][6][7][8] Both early life and adolescent phthalate exposure could contribute to insufficient sleep during adolescence by disrupting neuronal circuitry and impeding maturation of hormonally mediated mechanisms that regulate development and sleep. However, we are not aware of any studies that have investigated if phthalates, or any endocrine-disrupting chemicals, impact sleep health during adolescence. Understanding the contribution of modifiable environmental factors, such as phthalate exposure, to sleep is of great public health importance because inadequate sleep can negatively impact behavior and increase obesity risk. 9, 10 We hypothesized that higher urinary phthalate metabolite concentrations would be associated with short sleep durations during adolescence.

Methods
We investigated our hypothesis using data from 322 participants 16-17 years of age in the 2005-2010 cycles of the National Health and Nutrition Examination Survey (NHANES), a nationally representative cross-sectional study. We limited our analysis to these cycles because phthalates were assessed in a different subsample in 2011-012 compared with prior years and the sleep duration question was modified in 2015-2016. Participants 16 years and older were asked about sleep duration with the following question: "How much sleep do you usually get at night on weekdays or workdays?" with responses recorded in hours. We dichotomized average responses into short (less than 8 hours) and adequate (8 hours or more) sleep Background: Some environmental chemicals, such as phthalates, are capable of disrupting endocrine function related to the development and regulation of sleep patterns. However, the contribution of phthalate exposure to inadequate sleep during adolescence is unknown. We aim to evaluate the association between phthalate exposure and short sleep duration during adolescence. Methods: We used data from participants 16-17 years of age in the 2005-2010 cycles of the National Health and Nutrition Examination Survey. Participants reported typical sleep duration during weekdays, which we categorized into short sleep duration (less than 8 hours per night) and adequate sleep duration (8 or more hours) based on consensus guidelines. We used weighted logistic regression to evaluate the association between log 10 -transformed urinary phthalate metabolite concentrations and odds of short sleep duration. Results: An interquartile range increase in di (2-ethylhexyl)  , and mono-(3-carboxypropyl) phthalate [MCPP], mono-(2-ethyl)-hexyl phthalate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, and mono-2-ethyl-5-carboxypentyl phthalate) were quantified using high performance liquid chromatography-electrospray ionization-tandem mass spectrometry. We   Based on NHANES Analytical Guidelines, we used weighted logistic regression to evaluate the association between log 10 -transformed urinary phthalate metabolite concentrations and odds of short sleep duration. We adjusted for log 10 -transformed urinary creatinine concentrations to account for urine dilution. We selected covariates a priori and included child race, age, and sex, NHANES wave, family poverty-to-income ratio, education level for the head of household, and children's log 10 -transformed serum cotinine concentrations (a biomarker of tobacco smoke exposure). We assessed dose-response by categorizing phthalate metabolite concentrations into quartiles, assigning observations in each quartile the median concentration, and assessing the P-value for this term. We evaluated the robustness of our results by replicating our analysis in the sample of adolescents 16-18 years of age from the 2013 to 2014 NHANES cycle.

Results
Approximately half (49%) of the 322 adolescents reported short sleep duration, averaging less than the recommended 8 hours per night. Demographic characteristics of adolescents with short sleep duration were similar to those reporting adequate sleep.
When we applied similarly adjusted models to adolescents [16][17]

Discussion
In this hypothesis-generating analysis, higher concentrations of some phthalate metabolites were cross-sectionally associated with shorter sleep duration during adolescence. We also found consistent, albeit attenuated, relations between ΣDEHP, MCNP, MCOP, and odds of short sleep duration when we replicated our analysis in a smaller sample from a subsequent NHANES cycle. However, in these sensitivity analyses, results for MIBP were inconsistent and should be interpreted with caution.
Our results should be interpreted within the context of several limitations. Our analysis used self-reported sleep duration which is moderately correlated with estimates of sleep duration measured using actigraphy. 29 Furthermore, healthy sleep requires more than adequate sleep duration. Sleep quantity is both influenced by and overlaps with dimensions of sleep quality, such as sleep efficiency and regularity in the timing of sleep periods. Further exploration of our research question with different types of sleep assessments and measures is warranted. Because sleep health can be influenced by a number of behaviors and environmental characteristics, such as light exposure, electronic screen use, environmental noise, and temperature, future research should also consider the possibility that these other factors may confound associations between phthalates and sleep outcomes.
Given that sleep questions were only administered to adolescents at age 16 years or older, our results may not be generalizable to younger adolescents who may have different sleep patterns. Additionally, the cross-sectional design of the NHANES precludes us from drawing conclusions about the directionality of these relations. It is possible that adolescents who stay up later and have short sleep durations may be more likely to have unhealthy dietary habits, and therefore consume more phthalate-containing foods. 30,31 Previous research suggests that consuming more ultra-processed foods, for example, hamburgers and fries that are commonly sold at restaurants, is associated with higher urinary concentrations of MCNP, MCOP, and MCPP. 32 Regardless of the direction, further investigation using a prospective study could potentially identify interventions to reduce phthalate exposure or improve adolescent sleep, both of which could ultimately lead to better health.