The Relationship between Body Mass Index, Obesity, and LINE-1 Methylation: A Cross-Sectional Study on Women from Southern Italy.

Uncovering the relationship between body mass index (BMI) and DNA methylation could be useful to understand molecular mechanisms underpinning the effects of obesity. Here, we presented a cross-sectional study, aiming to evaluate the association of BMI and obesity with long interspersed nuclear elements (LINE-1) methylation, among 488 women from Catania, Italy. LINE-1 methylation was assessed in leukocyte DNA by pyrosequencing. We found a negative association between BMI and LINE-1 methylation level in both the unadjusted and adjusted linear regression models. Accordingly, obese women exhibited lower LINE-1 methylation level than their normal weight counterpart. This association was confirmed after adjusting for the effect of age, educational level, employment status, marital status, parity, menopause, and smoking status. Our findings were in line with previous evidence and encouraged further research to investigate the potential role of DNA methylation markers in the management of obesity.

The Effect of Alcohol on Telomere Length: A Systematic Review of Epidemiological Evidence and a Pilot Study during Pregnancy.

Several studies-albeit with still inconclusive and limited findings-began to focus on the effect of drinking alcohol on telomere length (TL). Here, we present results from a systematic review of these epidemiological studies to investigate the potential association between alcohol consumption, alcohol-related disorders, and TL. The analysis of fourteen studies-selected from PubMed, Medline, and Web of Science databases-showed that people with alcohol-related disorders exhibited shorter TL, but also that alcohol consumption per se did not appear to affect TL in the absence of alcohol abuse or dependence. Our work also revealed a lack of studies in the periconceptional period, raising the need for evaluating this potential relationship during pregnancy. To fill this gap, we conducted a pilot study using data and samples form the Mamma & Bambino cohort. We compared five non-smoking but drinking women with ten non-smoking and non-drinking women, matched for maternal age, gestational age at recruitment, pregestational body mass index, and fetal sex. Interestingly, we detected a significant difference when analyzing relative TL of leukocyte DNA of cord blood samples from newborns. In particular, newborns from drinking women exhibited shorter relative TL than those born from non-drinking women (p = 0.024). Although these findings appeared promising, further research should be encouraged to test any dose-response relationship, to adjust for the effect of other exposures, and to understand the molecular mechanisms involved.

Vaccination Status of Mothers and Children from the 'Mamma & Bambino' Cohort.

According to the evidence demonstrating vaccines' safety and effectiveness in anticipation of and during pregnancy, several countries have established immunization programs during the periconceptional period. Here, we evaluated vaccination status among 220 mother-child pairs, using data from the 'Mamma & Bambino' cohort. The self-reported data were evaluated at delivery, and with planned follow-ups at 1-2 years after delivery. In general, we noted that the vaccination status among the women was heterogeneous, ranging from 8.3% (vaccine against Human Papillomavirus, HPV) to 65.6% (vaccine against Diphtheria Tetanus and Pertussis, DTaP). Excluding the women who contracted the diseases in the past, the main ground for refusal was the lack of information. We also demonstrated that increasing age was associated with higher odds of not being vaccinated against Measles-Mumps-Rubella (MMR; OR = 1.12; 95% CI = 1.04-1.21; p = 0.004), HPV (OR = 1.20; 95% CI = 1.08-1.33; p = 0.001) and DTaP (OR =1.09; 95% CI = 1.01-1.18; p = 0.040). As expected, we showed that the proportion of newborns vaccinated with the Hexavalent and Pneumococcal vaccines was high (99.5% and 98.6%, respectively), while the vaccination coverage against MMRV did not reach the auspicated threshold (84.1%). Overall, these results underlined the need for the improvement of women's knowledge about the recommendations for vaccination, especially during pregnancy.

Adherence to the Mediterranean diet partially mediates socioeconomic differences in leukocyte LINE-1 methylation: evidence from a cross-sectional study in Italian women.

Although previous research demonstrated that socioeconomic status (SES) might affect DNA methylation, social inequalities alone do not completely explain this relationship. We conducted a cross-sectional study on 349 women (Catania, Italy) to investigate whether behaviors might mediate the association between SES and long interspersed nuclear elements (LINE-1) methylation, a surrogate marker of global DNA methylation. Educational level, used as an indicator of SES, and data on behaviors (i.e. diet, smoking habits, physical activity, and weight status) were collected using structured questionnaires. Adherence to Mediterranean diet (MD) was assessed by the Mediterranean Diet Score (MDS). Leukocyte LINE-1 methylation was assessed by pyrosequencing. Mediation analysis was conducted using the procedure described by Preacher and Hayes. Women with high educational level exhibited higher MDS (ß = 0.669; 95%CI 0.173-1.165; p < 0.01) and LINE-1 methylation level (ß = 0.033; 95%CI 0.022-0.043; p < 0.001) than their less educated counterpart. In line with this, mediation analysis demonstrated a significant indirect effect of high educational level on LINE-1 methylation through the adherence to MD (ß = 0.003; 95%CI 0.001-0.006). Specifically, the mediator could account for 9.5% of the total effect. To our knowledge, this is the first study demonstrating the mediating effect of diet in the relationship between SES and DNA methylation. Although these findings should be confirmed by prospective research, they add value to the promotion of healthy dietary habits in social disadvantaged people.

Dietary Antioxidant Intake and Human Papillomavirus Infection: Evidence from a Cross-Sectional Study in Italy.

Several lines of evidence suggested that antioxidants might play a protective role against high-risk human papillomavirus (hrHPV) infection and cervical cancer. However, the effect of combined intake of antioxidants has not been investigated thus far. The current cross-sectional study aimed to understand the relationship between dietary antioxidant intake and the risk of high-risk HPV (hrHPV) infection among 251 Italian women with normal cervical cytology. Women were tested for hrHPV using the Digene HC2 HPV DNA Test. Dietary antioxidant intakes were assessed using a semi-quantitative food frequency questionnaire, and a Composite Dietary Antioxidant Index (CDAI) was constructed on the basis of zinc, selenium, manganese, vitamin A, vitamin C, vitamin E, carotenoid, and flavonoid intake. Logistic regression analysis was used to assess odds ratio (OR) and 95% confidence interval (95% CI) for the associations of antioxidant intakes or CDAI with hrHPV status, adjusting for age, smoking status, body mass index, parity, educational level, marital status, and use of multivitamins and oral contraceptives. We first observed that hrHPV-positive women (n = 84) reported lower intake of zinc, manganese, and vitamins A and C than non-infected women. Specifically, we found a negative association between dietary intake of zinc and hrHPV-positive status when all antioxidants were considered simultaneously (OR = 0.46; 95% CI = 0.27-0.80; p = 0.006). With respect to cumulative dietary antioxidant intake, we demonstrated that women with high CDAI (third tertile) had lower odds of being hrHPV-positive than those with low CDAI (first tertile) (OR = 0.39; 95% CI = 0.18-0.85; p = 0.018). To our knowledge, this is the first study demonstrating that a diet based on the combined intake of nutrients with antioxidant properties might reduce the risk of hrHPV infection. However, further research is needed to understand whether dietary antioxidant intake is associated with hrHPV infection or its persistence.

Dietary Folate Intake and Folic Acid Supplements among Pregnant Women from Southern Italy: Evidence from the "Mamma & Bambino" Cohort.

Folate requirement among women who plan to become pregnant should be raised to 600 µg/day during the periconceptional period. To meet this need, several countries began to promote the use of folic acid supplements before and during pregnancy. Here, we investigated prevalence and determinants of dietary folate intake and folic acid supplement use among 397 pregnant women (aged 15-50 years old, median = 37 years old). We also investigated their effects on neonatal outcomes in a subgroup of women who completed pregnancy. For doing that, we used data from the "Mamma & Bambino" project, an ongoing mother-child cohort settled in Catania (Italy). Inadequate folate intake was evaluated using a Food Frequency Questionnaire and defined as an intake < 600 µg/day. Women were also classified as non-users (i.e., women who did not use folic acid supplements), insufficient users (i.e., women who did not take folic acid supplements as recommended), and recommended users of folic acid supplements. Neonatal outcomes of interest were preterm birth (PTB) and small for gestational age (SGA). Nearly 65% of women (n = 257) reported inadequate folate intake, while 74.8% and 22.4% were respectively classified as insufficient or recommended users of supplements. We demonstrated higher odds of inadequate folate intake among smoking women (OR = 1.457; 95%CI = 1.046-2.030; p = 0.026), those who followed dietary restrictions (OR = 2.180; 95%CI = 1.085-4.378; p = 0.029), and those with low adherence to the Mediterranean Diet (OR = 3.194; 95%CI = 1.958-5.210; p < 0.001). In a subsample of 282 women who completed pregnancy, we also noted a higher percentage of SGA among those with inadequate folate intake (p < 0.001). Among 257 women with inadequate folate intake, those with low educational level were more likely to not take folic acid supplements than their more educated counterpart (OR = 5.574; 95%CI = 1.487-21.435; p = 0.012). In a subsample of 184 women with inadequate folate intake and complete pregnancy, we observed a higher proportion of SGA newborns among women who did not take supplement before pregnancy and those who did not take at all (p = 0.009). We also noted that the proportion of PTB was higher among non-users and insufficient users of folic acid supplements, but difference was not statistically significant. Our study underlined the need for improving the adherence of pregnant women with recommendations for dietary folate intake and supplement use. Although we proposed a protective effect of folic acid supplement use on risk of SGA, further research is encouraged to corroborate our findings and to investigate other factors involved.

Dietary Patterns are Associated with Leukocyte LINE-1 Methylation in Women: A Cross-Sectional Study in Southern Italy.

Bioactive food compounds have different effects on global DNA methylation, an epigenetic mechanism associated with chromosomal stability and genome function. Since the diet is characterized by a mixture of foods, we aimed to identify dietary patterns in women, and to evaluate their association with long interspersed nuclear elements (LINE-1) methylation, a surrogate marker of global DNA methylation. We conducted an observational cross-sectional study of 349 women from Southern Italy, with no history of severe diseases. Dietary patterns were derived by food frequency questionnaire and principal component analysis. LINE-1 methylation of leukocyte DNA was assessed by pyrosequencing. We observed that intake of wholemeal bread, cereals, fish, fruit, raw and cooked vegetables, legumes, soup, potatoes, fries, rice, and pizza positively correlated with LINE-1 methylation levels. By contrast, vegetable oil negatively correlated with LINE-1 methylation levels. Next, we demonstrated that adherence to a prudent dietary pattern-characterized by high intake of potatoes, cooked and raw vegetables, legumes, soup and fish-was positively associated with LINE-1 methylation. In particular, women in the 3rd tertile exhibited higher LINE-1 methylation level than those in the 1st tertile (median = 66.7 %5mC; IQR = 4.67 %5mC vs. median = 63.1 %5mC; IQR = 12.3 %5mC; p < 0.001). Linear regression confirmed that women in the 3rd tertile had higher LINE-1 methylation than those in the 1st tertile (ß = 0.022; SE = 0.003; p < 0.001), after adjusting for age, educational level, employment status, smoking status, use of folic acid supplement, total energy intake and body mass index. By contrast, no differences in LINE-1 methylation across tertiles of adherence to the Western dietary pattern were evident. Interestingly, women who exclusively adhered to the prudent dietary pattern had a higher average LINE-1 methylation level than those who exclusively or preferably adhered to the Western dietary pattern (ß = 0.030; SE = 0.004; p < 0.001; ß = 0.023; SE = 0.004; p < 0.001; respectively), or those with no preference for a specific dietary pattern (ß = 0.013; SE = 0.004; p = 0.002). Our study suggested a remarkable link between diet and DNA methylation; however, further mechanistic studies should be encouraged to understand the causal relationship between dietary intake and DNA methylation.

Determinants of Adherence to the Mediterranean Diet: Findings from a Cross-Sectional Study in Women from Southern Italy.

The Mediterranean diet (MD)-the dietary pattern usually consumed by Mediterranean populations-can help promote a favorable health status and better quality of life. Uncovering the main factors associated with the adherence to MD may be useful in understanding and counteracting the global shift toward a Western diet, which has been documented also in the Mediterranean region. Here, we evaluated the adherence to MD and its major social and behavioral determinants in women from Catania, Southern Italy. This cross-sectional study included 841 women, aged 25-64 years, with no history of severe diseases. Adherence to MD was assessed by the Food Frequency Questionnaire and Mediterranean Diet Score (MDS). Associations between variables were tested by multivariable logistic regression analysis and expressed as an odds ratio (OR) with a 95% confidence interval (CI). Among social factors, medium and high educational levels were associated with an ideal intake of alcohol (OR = 4.059; 95%CI = 1.311-12.570; p = 0.015; OR = 4.258 95%CI = 1.068-16.976; p = 0.040; respectively), living in a couple with ideal intake of cereals (OR = 2.801 95%CI = 1.188-6.602; p = 0.018), and having children with an ideal intake of fruits (OR = 3.149; 95%CI = 1.245-7.762; p = 0.015). With respect to behaviors, current smoking was negatively associated with an ideal intake of meat (OR = 0.449; 95%CI = 0.0220-0.917; p = 0.028), while more engagement in physical activity was associated with an ideal intake of vegetables (OR = 6.148; 95%CI = 1.506-25.104; p = 0.011) and legumes (OR = 5.832; 95%CI = 1.414-24.063; p = 0.015). In line with these findings, moderately or highly physically active women were more likely to show medium or high adherence to MD than those who performed less physical activity (OR = 6.024; 95%CI = 1.192-30.440; p = 0.040; OR = 9.965 95%CI = 1.683-58.993; p = 0.011; respectively). Our results confirm an urgent need for public health strategies, which should take into account determinants of diet quality. Particularly, our study indicates that more engagement in physical activity is a major positive determinant of the adherence to MD.