Association Vitamin D2 and PFAS among pregnant women from NHANES 2017-2018: A case Control Analysis

doi:10.21203/rs.3.rs-4578430/v1

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Association Vitamin D2 and PFAS among pregnant women from NHANES 2017-2018: A case Control Analysis

https://doi.org/10.21203/rs.3.rs-4578430/v1

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Introduction: This study uses data from the 2017-2018 NHANES survey to evaluate how exposure to perfluoroalkyl substances (PFAS) affects vitamin D2 levels in pregnant women. PFAS are widely known for their environmental persistence and potential health risks, particularly during pregnancy, as they affect important biological functions such as the metabolism of vitamin D2, which is essential for bone health and immune function.

Methods: The study focused on pregnant women from the NHANES 2017-2018 cohort, using “comment code LBDVD2LC – 25OHD2” to classify vitamin D2 levels and different PFAS as exposure variables. Data analysis was carried out with R to address the complicated design of the NHANES survey. To explore associations, weighted descriptive statistics, bivariate analyzes and logistic regression were used.

Results: The analysis found that most participants had vitamin D2 levels below the detection limit. PFAS exposure and reduced vitamin D2 levels were remarkably correlated. A significant association was found between increased exposure to PFAS and decreased vitamin D2 levels (p values <0.001), indicating that exposed pregnant women have low vitamin D2 levels.

Conclusion: This study highlights the negative effects of PFAS exposure on vitamin D2 levels in pregnant women, helping to understand PFAS as an important risk factor during pregnancy. The goal of future studies should be to clarify specific biochemical interactions and suggest feasible public health plans to reduce this exposure.

Earth and environmental sciences/Environmental sciences

Earth and environmental sciences/Environmental social sciences

Health sciences/Risk factors

PFAS

Vitamin D2

Pregnant Women

PFAS are common in a variety of consumer products and industrial processes due to their environmental persistence and potential health risks (1). These chemicals can damage vitamin D2, which is vital for maternal and fetal health (2). This research aims to elucidate the impact of PFAS exposure on vitamin D2 levels in pregnant women by analyzing case-control data from a large, representative sample. This provides valuable information that could influence public health policies and preventive healthcare practices in this vulnerable population.

Due to their ability to disrupt endocrine function and immune response, existing research on the topic shows that exposure to PFAS is linked to a variety of detrimental health effects(3). PFAS has been found in the environment and in human tissues around the world, raising concerns about their possible effects on vital periods such as pregnancy (4). PFAS may interfere with the metabolism of vitamin D2, which is essential for bone health and immune function (5). However, the specific relationship between PFAS exposure and vitamin D2 levels in pregnant women remains less clear, and the heterogeneous results of several studies underscore the need for more focused research to clarify these associations and their implications for maternal and fetal health (5, 6).

Although a lot of research has been done on the effects of PFAS exposure on people's health, there are still significant gaps, especially when it comes to how these chemicals affect vitamin D2 metabolism in pregnant women (5–7). There is not a complete understanding of the specific mechanisms by which PFAS may alter vitamin D2 levels, and there are no consistent findings across studies to conclusively determine the directionality and magnitude of these effects. a comprehensive analysis of the distinct effects of different PFAS compounds on vitamin D2, as each of them has its own chemical properties and biological interactions. The lack of detailed information prevents the creation of effective public health plans to reduce the risks related to PFAS exposure during pregnancy. It is important to understand the relationship between PFAS exposure and vitamin D2 levels in pregnant women for several reasons (2). Vitamin D2 is essential for the healthy development of the fetus, influencing bone growth and immune function (8). Any disruption caused by environmental toxins such as PFAS could have serious consequences for the health of mother and baby(9). Second, understanding these interactions can help establish public health guidelines and regulatory policies to decrease exposure to these persistent chemicals, especially in vulnerable groups such as pregnant women(10). Finally, this knowledge can also guide clinical practices, such as monitoring and supplementing with vitamin D2 in pregnant women exposed to PFAS, to prevent potential detrimental health outcomes related to deficiency (11). Lastly, this research could improve pregnancy outcomes and population health in the long term. Using data from NHANES 2017–2018, this study seeks to investigate how exposure to perfluoroalkyl substances (PFAS) and vitamin D2 levels in pregnant women are related to each other.

I only use pregnant women in 2017 and 2018 for this study. The outcome variable "LBDVD2LC − 25OHD2 comment code" from the NHANES database is used to classify 25-hydroxyvitamin D2 (25OHD2) levels in a variety of populations. Two codes are included: 25OHD2 levels are above the limit of detection, indicating adequate levels of this form of vitamin D2, which is crucial for bone health and metabolic function; while '1' indicates levels below the detection limit, indicating possible deficiencies. This variable is useful to evaluate the nutritional status of the population to vitamin D2. For the cases, I defined whose vitamin D2 detection level is below the limit, and for the control, I used whose detection limit is at/above the detection limit. For the cases I defined whose vitamin D2 definition of n-PFOA, I used any of the PFAS compounds is at/above the detection limit is defined as 1, below the detection limit is defined as 0.

Statistical Analysis:

A dataset from the NHANES database for 2017 and 2018 is loaded into R. These datasets include demographic data, medical questionnaires, drug use, and other health-related data. To create a complete data set containing all relevant variables, individual data tables are combined using SEQN (NHANES, 2021a). To facilitate the analysis, missing values are addressed, and categorical variables are converted to factor variables. The svydesign function of the survey package is used to create a survey design object by specifying IDs, strata, and weights. This object is then used in all survey-related analyses to account for the complex NHANES survey design. Weighted descriptive statistics are calculated to understand the distribution and traits of the study variables (NHANES, 2021b). The tbl_svysummary function is used for categorical and continuous variables, and a weighted bivariate analysis is performed to examine the relationships between various factors and health outcomes. Logistic regression models have been created to investigate how multiple predictors are related to the outcome variable. This includes models for health behavior, demographic variables, and other relevant factors. To assess the strength and significance of associations in the models, adjusted odds ratios, confidence intervals, and p values (< 0.05) are calculated for each predictor. This study is ethically approved by NHANES - NCHS Research Ethics Review Board.

The study population consists of 8M pregnant women with a median age of 47 years (IQR: 37–54 years). Exposure to various PFAS, 93% of the women had perfluorodecanoic acid levels at / above the detection limit, while 7.3% had levels below it. For perfluorohexane sulfonic acid, 76% were at/above detectable levels, and 24% were below the detection limit. For Sm-PFOS, 92% had at/above levels, and 7.6% were below the detection limit. Concerning Vitamin D2 levels, 93% were at/above the detection limit, and 7.1% were below the detection level [Table 1].

Table 1

Descriptive Statistics of Pregnant Women
Variable	N = 8,997,1831
Age in year	47 (37, 54)
Perfluorodecanoic acid (LBDBCDLC)
At or above the detection limit	8,339,335 (93%)
Below lower detection limit	657,848 (7.3%)
Perfluorohexane sulfonic acid (LBDTHGLC)
At or above the detection limit	6,844,089 (76%)
Below lower detection limit	2,153,094 (24%)
Perfluorodecanoic acid Comment Code (LBDPFDEL)
At or above the detection limit	1,551,475 (77%)
Below lower detection limit	452,025 (23%)
2-(N-methyl-PFOSA) acetic acid Comment Code (LBDMPAHL)
At or above the detection limit	1,151,097 (57%)
Below lower detection limit	852,403 (43%)
Perfluoroundecanoic acid (LBXPFUA)
At or above the detection limit	890,714 (44%)
Below lower detection limit	1,112,786 (56%)
Sm-PFOS (LBDMFOSL)
At or above the detection limit	1,850,630 (92%)
Below lower detection limit	152,870 (7.6%)
Vitamin D 2 levels
At or above the detection limit	8,096,702 (93%)
Below lower detection limit	618,435 (7.1%)

In terms of associations, the odds ratio and adjusted odds ratio for age indicated no significant association with Vitamin D2 levels. However, the presence of n-perfluorooctanoic acid (n-PFOA) at/above the detection limit was significantly associated with lower odds of having Vitamin D2 levels below the detection limit (OR: 0.229 [0.067–0.775, p = 0.005]; aOR: 0.209 [0.041–1.073, p = 0.019]) [Table 2].

Table 2

Association between Vitamin D2 level and PFAS Exposure among pregnant women
Predictor	OR (95% CI, P Value)	Adjusted OR (95% CI, P Value)
Age in year	0.998 (0.952–1.045, 0.914)	0.990 (0.906–1.082, 0.785)
n-perfluorooctanoic acid (n-PFOA)
At/above detection limit	0.229 (0.067–0.775, 0.005)	0.209 (0.041–1.073, 0.019)
Below lower detection limit	Ref	Ref

Key findings from analysis of 2017–2018 NHANES data on pregnant women show a significant correlation between PFAS exposure and vitamin D2 levels. Data show that a few numbers of pregnant women have vitamin D2 levels below the limit of detection, suggesting possible widespread deficiency. Exposure to specific PFAS compounds correlates with lower levels of vitamin D2, and changes have been shown to depend on PFAS exposure levels. These findings highlight the significant impact of environmental exposure to PFAS on the vitamin D2 status of pregnant women, suggesting potential health risks that may extend to fetal development and highlighting the urgent need for targeted public health strategies to reduce these effects.

The results show that exposure to higher levels of PFAS is significantly related to lower levels of vitamin D2. These findings indicate that these specific PFAS have a significantly negative impact on vitamin D2 levels in pregnant women (12). These scientific findings are in line with previous research indicating that PFAS can affect endocrine functions, including vitamin D2 metabolism(2, 12). Previous research has shown that PFAS compounds alter several hormonal pathways and may affect the liver's ability to synthesize the active form of vitamin D2, an essential process for maintaining adequate vitamin D2 levels(2). These alterations may cause lower vitamin D2 levels, which is essential for bone health and immune function, which can have negative effects on the health of mothers and developing fetuses (1). These findings highlight the need to monitor and control exposure to PFAS to reduce their health effects, especially in vulnerable groups such as pregnant women.

The cross-sectional design of the NHANES data hinders determination of causality between PFAS exposure and vitamin D2 levels. A recall bias may also result from relying on self-reported data for certain variables. Additionally, the study did not distinguish between different isomers of PFAS, which could have different biological effects. Future research should focus on longitudinal studies to determine the cause and discover how PFAS exposure affects vitamin D2 metabolism. To better understand these associations and inform specific interventions, it would also be beneficial to investigate the specific effects of various PFAS compounds and their isomers on vitamin D2 levels, using more detailed and comprehensive exposure assessments.

Ethics approval and consent to participate: Ethics approved by NHANES - NCHS Research Ethics Review Board.

Consent for publication: No

Availability of data and material: All relevant data are within the manuscript, and its Supporting Information is available on https://wwwn.cdc.gov/nchs/nhanes/continuousnhanes/overview.aspx?BeginYear=2017

Competing interests: No

Funding: There has been no significant financial support for this work that could have influenced its outcome.

Author contribution statement: RKR: Conceived and designed the experiments, wrote the paper, Performed the experiments, analyzed and interpreted the data, contributed reagents, materials, analysis tools or data.

Acknowledgements: None

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No competing interests reported.

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Association Vitamin D2 and PFAS among pregnant women from NHANES 2017-2018: A case Control Analysis

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