How Did the COVID-19 Lockdown Affect Maternal Vitamin D (25(OH)D) Levels in Pregnant Women through Improved Air Quality? †

Presented


Introduction
During the 2019 coronavirus disease (COVID-19) pandemic, a lockdown was implemented and came into force on March 23 as a logical continuation of the course of the virus in Greece, which likely reduced maternal vitamin D (25(OH)D) levels in pregnancy due to reduced sun exposure from social distancing measures and confinement at home.A as far as we know, vitamin D production is mainly through skin synthesis when exposed to the sun's ultraviolet (UV) light, 290-315 nm in length [1].This is probably enhanced by pregnancy itself, since, according to studies, the prevalence of vitamin D deficiency (VDD) in the general population is very high, and pregnancy is one of the known risk factors (RFs) for this deficiency, with VDD being reported between 47 and 83% in pregnant black and white women, respectively [2].At the same time, however, due to the lockdown and the ban on the free movement of vehicles, the emissions of many atmospheric pollutants also decreased.
Atmospheric pollution is one of the main factors that determine the extent of solar ultraviolet B radiation (UVB) radiation reaching the earth's surface, resulting in insufficient radiation, which leads to reduced skin synthesis of vitamin D [3].Hosseinpanah et al. [4], who tried to determine whether air pollution and low ground levels of UVB light (UVB; 290-315) can deteriorate the body's vitamin D status in healthy women, saw that living in a polluted area plays a significant independent role in VDD and, hence, where they reside can potentially be one of the main reasons of vitamin D status in women.Several studies have associated maternal VDD with undesirable effects during pregnancy [5][6][7][8] and other disorders in neonates [7,9,10].The reduction in air pollution likely produced positive changes in maternal 25(OH)D levels.Ambient air pollution in urban and industrial areas in Greece was a serious environmental problem that was connected with rapid urbanization of cities, anarchic housing development without basic infrastructures, and an expansion of the motor vehicle fleet in urban regions [11].Athens, in particular, witnessed severe air pollution problems in the 1960s and 1970s and the formation of the infamous brown-yellow smog [11].But in recent years, the air quality in Greece has greatly improved in most urban areas because of better fuels, a gradual replacement of old polluting vehicles, and the benefits that resulted from the lockdown, as already mentioned [11].As a result, the prevalence of hypovitaminosis D in city dwellers can be twice that of rural residents [4].After accounting for meteorological variations, lockdown events brought about by the global response to the COVID-19 pandemic have resulted in unprecedented reductions of the population-weighted concentration of nitrogen dioxide and particulate matter levels by about 60% and 31%, respectively, in 34 countries, with mixed effects on ozone [12].The study by Grivas et al. [13] supported all of the above for Greece as well.As the lockdown in Greece also brought about an improvement in air pollution levels [12], we took for granted the improvement of air pollution in this period.
We hypothesized that, due to quarantine, lockdown, and the restrictions on going out of the house, the accompanying lower solar exposure would reduce the 25(OH)D levels in the mother-infant pair.Or, did the reduction in air pollution actually improve the 25(OH)D levels of both the mother and the newborn?If air pollution in Greece is recognized as an independent factor for VDD, it is possible to abate it through government interventions and warnings, thereby reducing the adverse effects of VDD on the health of pregnant women and their newborns.

Materials and Methods
We conducted an observational study of 248 Greek pregnant mothers, who delivered in the obstetrics and gynecology clinic of the Tzaneio General Hospital of Piraeus from September 2019 until January 2022.In this study, all parents signed an informed consent form.This study was approved by the scientific committee of the Tzaneio General Hospital of Piraeus.The bibliography was created from international databases, such as PubMed, Web of Science, Cochrane Library, and Embase, to identify relevant studies from September 2019 to January 2022, without restriction on language, population, or year.We searched for studies assessing any effects of air pollution on maternal vitamin D status, considering maternal 25(OH)D concentrations in pregnancy, as well as intake or non-prenatal vitamin D supplementation, alone or in combination with other vitamins or metals (Ca, Mg, Zn).Season, time of day, cloudiness, smog, skin melanin content, and sunscreens were among the factors also assessed as potentially influencing UV exposure and vitamin D synthesis.The data collected were assessed by two researchers to improve the quality of the research.We studied serum 25(OH)D on the mother with stratified random sampling.We divided our sample into the pre-COVID period and the post-COVID period.The Chi-square test was used to find an association between maternal 25(OH)D concentrations within the COVID-19 period.Quantitative results of 25(OH)D vitamin levels on the mother were converted to qualitative variables assessing lack of 25(OH)D, adequacy, deficiency, and severe deficiency of maternal concentrations and, thus, defined in that way.Additionally, the means ± standard deviations (SD) of maternal 25(OH)D levels are presented by frequencies and percentages.p ≤ 0.05 indicated a statistically significant association.Participants with medical conditions or taking drugs that affect vitamin D status were excluded.
Maternal vitamin D concentrations were evaluated according to the American Endocrine Society.The parturients were divided into those with (a) adequate levels of vitamin 25(OH)D (>30 ng/mL) [14]; (b) deficiency of vitamin 25(OH)D (21-29 ng/mL) [14]; and (c) lack of vitamin 25(OH)D (<20 ng/mL) [14].Perhaps another category should be included: (d) significant vitamin deficiency.Amrein et al. [15] provided a review of the current situation in the world Here, perhaps there is an another category (d) severe vitamin deficiency 25(OH)D (<12 ng/mL) that could be added, given a review by Amrein et al. [15], which informed about the current situation, worldwide, regarding 25(OH)D and the risks arising from its severe lack, with a dramatic increase in the risk of mortality, infections, but also many other diseases [15].A deficiency and severe deficiency of 25(OH)D was defined for clinical hypovitaminosis.

Results
A statistical study was performed to demonstrate whether Greek mothers' 25(OH)D levels differed in the pre-COVID versus post-COVID period.Our sample involved 93 pregnant mothers from the pre-COVID-19 period and 155 pregnant mothers in the COVID-19 period.In the pre-COVID-19 period, the mean of maternal 25(OH)D levels was 17.32 ± 10.12 ng/mL (95%CI: 0.87-1.30)(Table 1), and in the COVID-19 period and after, it was 22.04 ± 12.08 ng/mL (95%CI: 1.28-1.61)(Table 2).The mean value of the mother's 25(OH)D levels after COVID-19 was 4.72 units higher than the mean of maternal 25(OH)D levels in the pre-COVID-19 period.A statistical test was performed to investigate the existence of statistical significance.The normality of the sample was tested with the Kolmogorov-Smirnov test (Table 3), and although a significance level of 5% was found, the average values of 25(OH)D levels of the mothers did not follow a normal distribution, since the statistical significance was calculated as zero.Therefore, in order to study whether there is a statistically significant difference in the mean values of the pre-and post-COVID-19 period, the non-parametric Mann-Whitney U test was used (Table 3).The test showed that the difference in mean values between maternal vitamin D levels in pre-and post-COVID-19 was statistically significant.Because the p-value (p) was p = 0.002, this led to the rejection of the null hypothesis.Therefore, the existence of a statistically significant difference in the average values of the maternal 25(OH)D levels in the pre-and post-COVID-19 period was proved.

Discussion
It is plausible that the paradoxical fact of higher vitamin D in Greek mothers during the COVID-19 period can be explained by three factors.First of all, it could be due to quarantine, during which many people, thus, including expectant mothers, sent the required SMS messages to allow them to get out of their houses for physical exercise or individual sports.If we combine the fact that this walk or exercise was taken in the morning hours, since physical presence at work had been suspended and most people carried out their work mainly online, there was flexibility for these activities or sports to be completed in the morning hours and to benefit from the advantages of the sun, resulting in an abundant production of vitamin D in the skin.Secondly, another possible reason for the higher vitamin D levels in expectant mothers in this period may have been their fear of contracting COVID-19 and, therefore, being more regular in taking vitamin D or taking multivitamin supplements with vitamin D. Finally, we should not forget that the traffic bans improved the air quality, with the result that the synthesis of 25(OH)D, through the sun, is more effective.

Conclusions
In conclusion, pregnant women should be encouraged to exercise and take leisurely walks in the sun, similar to those short but sun-filled morning walks they took during the pandemic.It is necessary to inform pregnant women about all the benefits of vitamin D and not just about its contribution to immunity to viruses, as it seems that when they thought they were at risk, they took a more conscientious approach.Finally, in general, the state should try to regulate the traffic load and give incentives to citizens to change existing vehicles, aiming for cleaner and more efficient engine operation, resulting in less air pollution.Thus, the optimal health of individuals will be achieved, reaping the maximum benefits of vitamin D.

Table 1 .
Comprehensive display of all the statistics on maternal 25(OH)D levels for the pre-COVID-19 period and the COVID-19 period.

Table 2 .
Confidence intervals (CIs) for maternal means of 25(OH)D in the pre-and post-COVID-19 period.

Table 3 .
Kolmogorov-Smirnov Test and Mann-Whitney U Test.