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Arsenic in birth cord blood increases risk of myopia in males by 2X, but reduced by Vitamin D - Jan 2025
Associations of prenatal arsenic exposure with myopia in primary school children: Modifying effects of vitamin D levels
Environmental Research Vol 264, Part 1, 1 January 2025, https://doi.org/10.1016/j.envres.2024.120366
A portion of the above chart
The increasing role of environmental pollutants and nutrients in the development of myopia. Further longitudinal evidence is needed to elucidate the effects of early-life environmental pollutants on myopia and nutrients to protect against pollutant-induced myopia. We used mother-child dyads from the Ma'anshan Birth Cohort (n = 2028) to explore the modifying effects of maternal vitamin D status of prenatal and childhood arsenic exposure with refractive parameters and myopia. We measured serum or plasma arsenic concentrations during three trimesters, in cord blood, in childhood (5-year-old), and performed cycloplegic refraction in children aged 7–9 years (n = 1616). Primary outcomes were myopia and refractive parameters including axial length (AL), corneal radius of curvature, and spherical equivalent refraction error. Linear regression, logistic regression, and multiple informant models were performed for the association of prenatal and childhood arsenic exposure with vision health. Sex- and vitamin D status stratification analyses were also conducted. Cord serum arsenic was positively associated with AL (β = 0.15, 95%CI: 0.01, 0.29) and the risk of developing myopia (OR = 1.72, 95%CI: 1.07,， 2.75). Among boys, a 1 ng/L increase in cord serum log10-transformed arsenic resulted in larger AL and a higher risk of myopia. In the vitamin D deficient group (<20 ng/mL), cord serum arsenic showed positive associations with AL (0.26 [0.06, 0.46]) and the risk of myopia (1.99 [1.01, 3.90]). Late pregnancy arsenic exposure likely affects offspring development of myopia, especially in boys. Maternal sufficient vitamin D may confer protective effects against the development of myopia.
Introduction
Myopia, also known as short-sightedness or near-sightedness, is a common condition when excessive elongation of the eye results in images of distant objects coming into focus in front of the retina, resulting in blurred distance vision (Baird et al., 2020). Myopia has emerged as a global public issue and typically appears during primary school (Du et al., 2021a; Zadnik et al., 2015). The prevalence of childhood myopia has increased gradually in China over the past two decades, and with the progression of myopia, individuals with high myopia are at increased risk of pathological ocular changes, leading to irreversible vision loss (Dolgin, 2015; Pan and Lan, 2024). Several studies have shown that the prevalence of myopia is higher in girls than in boys (Jones-Jordan et al.; Lee et al., 2022; Wang et al., 2018), but not in all studies (Rudnicka et al., 2010; Tideman et al., 2019). Disagreements in studies on myopia and sex may be attributed to the age of the children and the statistical power of the studies, which depend on sample size and age-specific myopia incidence (Rudnicka et al., 2016). Pregnancy or early childhood exposure to various environmental factors, including environmental pollutants, plays an important role in inducing and exacerbating myopia (Enthoven et al., 2019; Wei et al., 2019). This evidence suggests that adverse early-life environments may contribute to the development of myopia later in life.
As a top-ranked priority pollutant, arsenic is widely distributed throughout the environment in air, water, and soil (Agency for Toxic Substances and Disease Registry (ATSDR), 2019). Arsenic predominantly exists in two forms, organic (oAs) and inorganic (iAs), with the latter commonly found in groundwater (Agency for Toxic Substances and Disease Registry (ATSDR), 2007). The main route of arsenic exposure in populations originates from contaminated groundwater (Podgorski and Berg, 2020). Globally, 94 to 220 million people are estimated to be exposed to unsafe levels of groundwater arsenic, exceeding the World Health Organization standard of 10 μg/L (Podgorski and Berg, 2020) The exposure of pregnant women and children to arsenic is inevitable. Animal and cell experiments observed that arsenic exposure had detrimental effects on decreases in the thickness of the retinal pigmented epithelium (RPE) layer and retina nerve fiber layer, downregulated the levels of PPT1 protein concerning retinal development and function, and induced intraocular inflammation, which may be involved in refractive development regulation and the development of myopia (Amuno et al., 2020; Babich and Van Beneden, 2019; Chen et al., 2024a; McBrien and Gentle, 2003; Yu et al., 2023; Zhylkibayev et al., 2023). However, available epidemiological studies for the effects of early-life arsenic exposure on myopia in children are scarce.
Sufficient vitamin D has been shown to alleviate the inflammatory response caused by arsenic (Parvez et al., 2022). As a fat-soluble vitamin, vitamin D can regulate scleral growth through its anti-proliferative effect and modulate hypertrophic smooth ciliary muscle by promoting the absorption of calcium-binding protein (Carroll et al., 2011; Mutti and Marks, 2011; Yu et al., 2024). Furthermore, vitamin D may influence ocular development by involving the regulation of DNA transcription and dopamine metabolism (Bloomfield and Volgyi, 2009; Jiang et al., 2014; de Borst et al., 2011; Alsalem et al., 2014). Moreover, cross-sectional studies have revealed that vitamin D levels are inversely associated with the risk of myopia in children (Gao et al., 2021; Tideman et al., 2018). However, the abovementioned results have not yet been verified in mother-child dyads. Only one longitudinal study conducted in Denmark reported no associations between prenatal vitamin D levels and myopia in young adult men (Specht et al., 2020). The inconsistent results between vitamin D levels and vision health may be due to differences in study design and study participants' characteristics including age and sex. Further exploration of the moderating effect of maternal vitamin D status may provide insights into preventive measures against the adverse effects of arsenic exposure in vulnerable populations.
Using data from a longitudinal and ongoing maternal-child birth cohort in China, this study aimed to explore the associations of prenatal and childhood arsenic exposure with refractive parameters and myopia in primary school children. We also evaluated the sex-specific associations between arsenic exposure and vision health. Furthermore, the associations of maternal and childhood arsenic levels with children's refractive parameters and myopia in different vitamin D level groups were examined.
Section snippets
Study participants
The Ma'anshan Birth Cohort (MABC) study has observed a cohort of participants since their prenatal periods from May 2013 to September 2014, when 3474 pregnant women were recruited from the Ma'anshan Maternal and Child Health Care Hospital in Ma'anshan, Anhui Province, China. The specific procedure of MABC study enrollment and follow-up has been introduced in previous literature and Supplemental Fig. S1 (Gan et al., 2024). A total of 2038 children aged 8 years old had completed eye examinations.
Characteristics of participants
Table 1 summarizes the basic characteristics of 2028 mother-child dyads. Children were an average of 8.45 (0.51) years old, whereby 48% were girls. The AL was 23.40 (0.89) mm, AL/CR was 3.00 (0.10), SER was +0.21 (1.20) D, and screen exposure score was 8.92 (3.79). Most children had an outdoor exposure of more than 1 h/day (61%) and a sleep duration of more than 9 h/day (78%), respectively. More than half of all pregnant women are deficient in vitamin D during pregnancy. Among the 1616 children ...
Discussion
We assessed the associations of prenatal and childhood arsenic exposure with refractive parameters and myopia and the modifying effect of maternal vitamin D status in 2028 mother-child dyads from the MABC. The results revealed that cord serum arsenic exposure was associated with a larger AL and a higher risk of myopia. Moreover, these positive associations between cord blood arsenic levels and AL and the risk of myopia were prominent in boys and the vitamin D deficiency groups in pregnant women.
Conclusion
In summary, arsenic exposure during late pregnancy likely affects the development of myopia in offspring, especially in boys. Sufficient levels of vitamin D during pregnancy may confer a protective effect against the development of myopia. Further exploration is needed to better understand sex-specific responses to early-life environmental pollutants in terms of myopia. Additionally, research is needed to elucidate the plausible mechanism linking arsenic exposure with refractive parameters and ...
Chart of Arsenic in groundwater 2020
Myopia trend