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Background Lactation is a demanding period for women, and a good nutrition is crucial for optimal health of mothers and infants. Objectives To provide new data and summarize the overall evidence on maternal nutrient intakes during lactation in developed countries, we present a systematic review (SR) of the literature and concurrently original results of the Italian MEDIDIET study. We compared nutrient intakes with dietary reference values (DRVs) proposed by the European Food Safety Authority. Methods Studies were identified searching PubMed/Embase databases up to February 2020. Observational studies reporting at least energy and macronutrient intakes of healthy breastfeeding mothers who followed non-restricted and non-specific diets were included. Studies on populations with severe nutritional deficiencies were excluded. The MEDIDIET study enrolled 300 healthy breastfeeding mothers at 6 ± 1 wk postpartum. Usual diet was concomitantly evaluated through a validated and reproducible FFQ. Nutrient intakes were estimated using a food composition database. Results Twenty-eight articles regarding 32 distinct study populations were included. Maternal nutrient intakes were generally in agreement across studies included in the SR and conforming to DRVs. Within micronutrients, vitamin D intake was below the recommendation. In the MEDIDIET study, mean intakes of energy (1950 ± 445 kcal/d), carbohydrates (270 ± 20.1 g/d), proteins (87.8 ± 20.1 g/d), and fats (65.6 ± 18.9 g/d) were similar to those observed in the SR. Moreover, observed intakes seemed to reflect the typical Mediterranean diet, with low intakes of carbohydrates, SFAs, and PUFAs and high intakes of MUFAs and vitamins. Conversely, protein intake was mainly derived from animal sources. Conclusions This SR showed that nutrient intakes of breastfeeding mothers in developed countries are generally in line with DRVs despite different dietary patterns worldwide. Some nutritional deficiencies emerged, highlighting the need for additional nutritional advice. Mothers participating in the MEDIDIET study showed a nutritional profile in agreement with the Mediterranean diet.

Background and AimsThe content of fatty acids (FA) in human milk may be influenced by maternal nutrition. We evaluated the role of a Mediterranean diet in influencing the content of FA in human milk among 282 breastfeeding mothers participating in the MEDIDIET study.Materials and MethodsMediterranean Diet Score (MDS), a composite index, was used to evaluate adherence to the Mediterranean diet. It includes 9 components (i.e., vegetables, fruit, cereals, legumes, monounsaturated to saturated FA ratio – MUFA/SFA, fish, dairy products, meat, and alcohol) and therefore potentially ranges from 0 (no adherence) to 9 (complete adherence) points. None of the mothers obtained the highest score due to the low alcohol consumption in the study population. Mothers were categorized in approximate tertiles of adherence: 0–3 (34.4%), 4 (26.2%), and 5–8 points (39.4%). The mean content of FA across categories of MDS was compared using ANOVA and test for trend.ResultsA high adherence of breastfeeding mothers to the Mediterranean diet was associated with lower content of SFA in human milk (42.58 ± 4.36 for MDS = 0–3, 42.58 ± 4.89 for MDS = 4, and 40.92 ± 5.22% of fats for MDS = 5–8 points; p ANOVA and p for trend = 0.02). Conversely, a high adherence was associated with higher content of MUFA in human milk (43.27 ± 4.27 for MDS = 0–3, 43.27 ± 4.47 for MDS = 4, and 45.24 ± 5.22% of fats for MDS = 5–8 points; p ANOVA and p for trend < 0.01), ω-3 FA (1.07 ± 0.25 for MDS = 0–3, 1.22 ± 0.49 for MDS = 4, and 1.31 ± 0.51% of fats for MDS = 5–8 points; p ANOVA and p for trend < 0.01), and the major types of ω-3 FA (i.e., α-linolenic acid – ALA, eicosapentaenoic acid – EPA, docosahexaenoic acid – DHA, docosapentaenoic acid – DPA). These associations were mainly driven by the adherence to the vegetables, MUFA/SFA, fish, and dairy products components of the Mediterranean diet.ConclusionA high adherence to the Mediterranean diet was associated with human milk showing a lower content of SFA and higher content of MUFA and ω-3 FA, including DHA. The Mediterranean diet may contribute in human milk production with higher content of specific FA which is directly involved in infant’s neural and visual development, as reported by previous studies.

(1) Background: Several studies have reported associations between maternal diet in terms of single foods or nutrients and human milk compounds, while the overall role of maternal diet and related dietary patterns has rarely been investigated. (2) Methods: Between 2012 and 2014, we enrolled 300 healthy Italian mothers, who exclusively breastfed their infant. During a hospital visit at 6 weeks postpartum, a sample of freshly expressed foremilk was collected and information on maternal dietary habits in the postpartum period was obtained through an interviewer-administered food frequency questionnaire. We applied principal component factor analysis to selected nutrients in order to identify maternal dietary patterns, and assessed correlations in human milk macronutrients and fatty acids across levels of dietary patterns. (3) Results: Five dietary patterns were identified, named "Vitamins, minerals and fibre", "Proteins and fatty acids with legs", "Fatty acids with fins", "Fatty acids with leaves", "Starch and vegetable proteins". These dietary patterns were correlated with some milk components, namely fatty acids, and in particular ω-3 and its subcomponents. (4) Conclusions: This study showed that overall maternal dietary habits during breastfeeding may influence human milk composition, suggesting the importance of adequate maternal nutrition during lactation not only for the mother herself but also to provide the infant with milk containing adequate amount and quality of nutrients for a balanced nutrition.

Introduction. Attributable fraction (AF), proposed by Levin, quantifies the reduction in the disease prevalence that could be achieved by eliminating the exposure (or risk factor) of interest from the population. Disease etiology involves multiple risk factors that may act simultaneously in the occurrence of disease and the optimal approach to quantify the individual and the joint effects of different risk factors on the disease burden is one of the goals in epidemiological research. Adjusted AFs quantify the effect of one risk factor after controlling of other factors (i.e., risk factors that may act together to cause disease, adjustment variables or confounders). Adjusted AFs may add up more than the joint AF (i.e., the AF for eliminating all risk factors from the population) and in some situation may add up to more than 1, leading to the conclusion that adjusted AFs should not be used to the purpose of partitioning the joint effect into individual contributions. Eide and Gefeller proposed a way to accomplish this task. Sequential AFs quantify the additional effect of one risk factor on the disease risk after the preceding risk factors have already been removed in a specified order from the population. However, sequential AFs depend on the order in which risk factors are removed from the population. Average AFs overcome this shortcoming by averaging sequential AFs for a risk factor over all orders by which risk factors can be removed from the population. Average AFs quantify the additional effect of one risk factor on the disease risk after the preceding factors selected randomly have already been removed from the population. Objective. This work aims to illustrate the main methodologies to estimate AFs and corresponding confidence intervals in presence of multiple risk factors with a focus on case-control study design. Moreover, we provide AF estimates for the major risk factors using Italian case-control data on oral cavity and breast cancers. Modification of case-control study design. In the original notation, sequential and average AFs could not be used in case-control study design, since the ratio of controls to cases in the sample is fixed a priori and the resulting AF estimates will be biased. Ferguson et al. proposed a prevalence-based weighting approach to correct the imbalance between controls and cases. The method consists in weighting the likelihood function of the model used to estimate sequential and average AFs for the disease prevalence. Variance estimation. The main approaches for estimating AF confidence intervals (CIs) are based on asymptotic approximation (Delta method) and simulations (Monte Carlo method). Ferguson proposed a method based on Monte Carlo simulations for constructing average AF variance. They also proposed the ?averisk? R package for calculating average AFs and corresponding CIs in both prospective and case-control studies. In this work, we proposed a modification of the Ferguson?s method to account for sequential AF variability on the total variability. Variances comparison. We compared our and Ferguson?s methods to estimate average AF variance using simulated data. We generate two classes of simulated dataset. Each class included four scenarios according to different correlation structure: from independence (scenario 1) to strong correlation among risk factors (scenario 4). The two classes differed in the prevalence and strength of the association between risk factors. In particular, the first class had a high prevalence and modest relative risks, whereas the second class had a low prevalence and huge relative risks. For both classes of simulated data, standard deviation increment (i.e., the relative difference between our and Ferguson?s methods) became gradually larger increasing the number of independent risk factors (from two to ten). Conversely, standard deviation increment decreased incrementing the number of correlated risk factors. Although in some situations (i.e., for correlated risk factors) the contribution of our method could have a substantial relative impact on total AF variability (up to 88%), the absolute standard deviation differences between two methods were very small (less than 0.15) indicating a limited contribution of our method than the Feguson?s one. Application to real data. We estimated average AFs using a case-control study conducted in Italy on 946 oral cavity cases and 2492 controls. Risk factors considered for AF estimation were smoking, alcohol drinking, red meat intake, vegetables intake, fruit intake, and family history of oral cavity cancer. The final model included also terms for sex, age, study centre, years of education, BMI, and non-alcohol energy intake to account for possible confounding effect. We set a prevalence of oral cavity cancer according to statistics from the consortium of Italian Cancer Registry (AIRTUM) to adjust average AFs for case-control data structure. Eighty-eight percent (95% CI: 78%; 98%) of oral cavity cases were attributable to the considered risk factors. In particular, the average AF for smoking was 0.34 (95% CI: 0.27; 0.41), indicating that 34% of oral cavity cases would not has occurred if smoking was randomly removed from the population over all possible risk factor removal orders. For the remaining risk factors, average AFs were 0.27 (95% CI: 0.17; 0.37) for alcohol drinking, 0.11 (95% CI: 0.06; 0.17) for low vegetables intake, 0.08 (95% CI: 0.02; 0.15) for low fruit intake, 0.06 (95% CI: 0.01; 0.12) for high red meat intake, and 0.009 (95% CI: -0.001; 0.02) for family history. We analyzed a further case-control study on 2569 breast cancer cases and 2588 controls. We set a prevalence of breast cancer to adjust average AFs for case-control data structure. The final model included alcohol drinking, parity, breastfeeding, use of oral contraceptives (OCs), and family history of breast cancer as risk factors; study centre, age, years of education, smoking, age at menarche and use of hormonal replacement therapy (HRT) as adjusting factors. The joint AF was 0.49 (95% CI: 0.35; 0.63) indicating that approximately half of the breast cancer cases would not has occurred if all risk factors were simultaneously eliminated from the population. In particular, average AFs were 0.27 (95% CI: 0.16; 0.39) for parity, 0.12 (95% CI: 0.06; 0.18) for alcohol drinking, 0.04 (95% CI: -0.02; 0.10) for breastfeeding (No or

Background: The purpose of this study was to describe the placental lesions in pregnancies complicated by hypertensive disorders (HDP) and/or fetal growth restriction (FGR) and in uneventful control pregnancies. Methods: This is a case control study that included singleton pregnancies with HDP and normally grown fetus (HDP-AGA fetus), with HDP and FGR, early FGR, late FGR, and uneventful pregnancies. Feto-placental Doppler velocimetry and sFlt-1/PlGF ratio were performed. Placental histology was evaluated blinded according to the Amsterdam Consensus criteria. Results: Placental lesions with maternal vascular malperfusion (MVM) were significantly more frequent in HDP-FGR and early FGR (92% and 83%). MVM were significantly associated with abnormal feto-placental Doppler parameters, especially in early FGR. Delayed villous maturation (DVM) was associated with late FGR (83%). HDP-AGA fetus cases presented a heterogeneous pattern of placental lesions, including 60% of cases with MVM, but were not associated with abnormal Doppler feto-placental velocimetry. Conclusions: We found a prevalence of placental maternal vascular malperfusion in HDP-FGR and early FGR groups. These lesions were also associated with abnormal, anti-, and angiogenic markers. Conversely HDP-AGA fetus and late FGR presented more heterogeneous placental lesions not severe enough to cause feto-placental Doppler anomalies. These conditions are likely associated with different etiologies, such as maternal pre-pregnancy risk factors for metabolic syndrome. These findings suggest a possible preventive nutritional approach in addition to low-dose aspirin in pregnant women with predisposing factors for HDP-AGA fetuses and late FGR.

Objectives The aim of this study was to evaluate whether the association between the inflammatory potential of one's diet and cancer risk varies across age groups in a population characterized by widespread use of the Mediterranean diet. Methods We analyzed data from a network of case-control studies conducted in Italy between 1991 and 2014. The studies included cancers of the oral cavity (n = 509), pharynx (n = 436), nasopharynx (n = 198), larynx (n = 459), esophagus (n = 304), stomach (n = 230), colon (n = 1225), rectum (n = 728), liver (n = 184), pancreas (n = 326), breast (n = 2569), endometrium (n = 454), ovary (n = 1031), prostate (n = 1294), kidney (n = 767), and bladder (n = 690). Controls were 13 563 patients hospitalized for acute, non-neoplastic conditions. Dietary inflammatory index (DII) scores were computed based on 31 food parameters assessed using a reproducible and validated food frequency questionnaire. Odds ratios were estimated through logistic regression models adjusting for recognized confounding factors. Results The DII increased with age, with lower scores among men than women, in individuals located in northern rather than in central or southern Italy, and in controls more than in cancer cases. After adjustment for cancer-specific potential confounders, an increasing DII score was directly associated with cancer risk for all considered cancer sites, except for liver and endometrium. Although the DII level varied across age groups, no heterogeneity in cancer risk emerged for any of the considered cancer sites. Conclusions In the Italian population, DII scores were higher in elderly than in middle-aged individuals. Although not directly affecting cancer risk, this finding may have important implications for the older population because elevated DII scores, indicating a proinflammatory diet, also have been associated with frailty.

The attributable fraction is the candidate tool to quantify individual shares of each risk factor on the disease burden in a population, expressing the proportion of cases ascribable to the risk factors. The original formula ignored the presence of other factors (i.e. multiple risk factors and/or confounders), and several adjusting methods for potential confounders have been proposed. However, crude and adjusted attributable fractions do not sum up to their joint attributable fraction (i.e. the number of cases attributable to all risk factors together) and their sum may exceed one. A different approach consists of partitioning the joint attributable fraction into exposure-specific shares leading to sequential and average attributable fractions. We provide an example using Italian case–control data on oral cavity cancer comparing crude, adjusted, sequential, and average attributable fractions for smoking and alcohol and provide an overview of the available software routines for their estimation. For each method, we give interpretation and discuss shortcomings. Crude and adjusted attributable fractions added up over than one, whereas sequential and average methods added up to the joint attributable fraction = 0.8112 (average attributable fractions for smoking and alcohol were 0.4894 and 0.3218, respectively). The attributable fraction is a well-known epidemiological measure that translates risk factors prevalence and disease occurrence in useful figures for a public health perspective. This work endorses their proper use and interpretation.

Previous studies have reported that Mediterranean diet is inversely related to the risk of several neoplasms, however, limited epidemiological data are available for bladder cancer. Thus, we examined the association between Mediterranean diet and this neoplasm in an Italian multicentric case-control study consisting of 690 bladder cancer cases and 665 controls. We assessed the adherence to the Mediterranean diet via a Mediterranean Diet Score (MDS), which represents the major characteristics of the Mediterranean diet and ranges from 0 to 9 (from minimal to maximal adherence, respectively). We derived odds ratios (ORs) of bladder cancer according to the MDS score from multiple logistic regression models, allowing for major confounding factors. The ORs of bladder cancer were 0.72 (95% confidence interval, CI, 0.54&ndash, 0.98) for MDS of 4&ndash, 5 and 0.66 (95% CI, 0.47&ndash, 0.93) for MDS of 6&ndash, 9 (p for trend = 0.02) compared to MDS = 0&ndash, 3. Results were similar in strata of sex, age, and education, while the risk appeared somewhat lower in never-smokers and patients with pT1&ndash, pT4 bladder carcinomas. Among individual components of the MDS, we observed inverse associations for greater consumption of legumes, vegetables, and fish. In our study, which was carried out on an Italian population, the higher adherence to the Mediterranean diet was related to a lower risk of bladder cancer.