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Research Area: Reproductive Health

Mediterranean-style diet in pregnant women with metabolic risk factors (ESTEEM): A pragmatic multicentre randomised trial.

Al Wattar, B.H., J. Dodds, A. Placzek, L. Beresford, E. Spyreli, A. Moore, A. Moore, F.J. Gonzalez Carreras, F. Austin, N. Murugesu, T.J. Roseboom, M. Bes-Rastrollo, G.A. Hitman, R. Hooper, K.S. Khan, S. Thangaratinam, for the ESTEEM study group, 2019. Mediterranean-style diet in pregnant women with metabolic risk factors (ESTEEM): A pragmatic multicentre randomised trial. PLoS Med 16(7): e1002857. https://doi.org/10.1371/journal. pmed.1002857

Background: Pregnant women with metabolic risk factors are at high risk of complications. We aimed to assess whether a Mediterranean-style diet reduces adverse pregnancy outcomes in highrisk women. Methods and findings: We conducted a multicentre randomised trial in 5 maternity units (4 in London and 1 in Birmingham) between 12 September 2014 and 29 February 2016. We randomised inner-city pregnant women with metabolic risk factors (obesity, chronic hypertension, or hypertriglyceridaemia) to a Mediterranean-style diet with high intake of nuts, extra virgin olive oil, fruits, vegetables, nonrefined grains, and legumes; moderate to high consumption of fish; low to moderate intake of poultry and dairy products; low intake of red and processed meat; and avoidance of sugary drinks, fast food, and food rich in animal fat versus usual care. Participants received individualised dietary advice at 18, 20, and 28 weeks’ gestation. The primary endpoints were composite maternal (gestational diabetes or preeclampsia) and composite offspring (stillbirth, small for gestational age, or admission to neonatal care unit) outcomes prioritised by a Delphi survey. We used an intention-to-treat (ITT) analysis with multivariable models and identified the stratification variables and prognostic factors a priori. We screened 7,950 and randomised 1,252 women. Baseline data were available for 593 women in the intervention (93.3% follow-up, 553/593) and 612 in the control (95.6% follow-up, 585/612) groups. Over a quarter of randomised women were primigravida (330/1,205; 27%), 60% (729/1,205) were of Black or Asian ethnicity, and 69% (836/1,205) were obese. Women in the intervention arm consumed more nuts (70.1% versus 22.9%; adjusted odds ratio [aOR] 6.8, 95% confidence interval [CI] 4.3–10.6, p ≤ 0.001) and extra virgin olive oil (93.2% versus 49.0%; aOR 32.2, 95% CI 16.0–64.6, p ≤ 0.001) than controls; increased their intake of fish (p < 0.001), white meat (p < 0.001), and pulses (p = 0.05); and reduced their intake of red meat (p < 0.001), butter, margarine, and cream (p < 0.001). There was no significant reduction in the composite maternal (22.8% versus 28.6%; aOR 0.76, 95% CI 0.56–1.03, p = 0.08) or composite offspring (17.3% versus 20.9%; aOR 0.79, 95% CI 0.58– 1.08, p = 0.14) outcomes. There was an apparent reduction in the odds of gestational diabetes by 35% (aOR 0.65, 95% CI 0.47–0.91, p = 0.01) but not in other individual components of the composite outcomes. Mothers gained less gestational weight (mean 6.8 versus 8.3 kg; adjusted difference −1.2 Kg, 95% CI −2.2 to −0.2, p = 0.03) with intervention versus control. There was no difference in any of the other maternal and offspring complications between both groups. When we pooled findings from the Effect of Simple, Targeted Diet in Pregnant Women With Metabolic Risk Factors on Pregnancy Outcomes (ESTEEM) trial with similar trials using random effects meta-analysis, we observed a significant reduction in gestational diabetes (odds ratio [OR] 0.67, 95% CI 0.53–0.84, I2 = 0%), with no heterogeneity (2 trials, 2,397 women). The study’s limitations include the use of participant reported tools for adherence to the intervention instead of objective biomarkers. Conclusions: A simple, individualised, Mediterranean-style diet in pregnancy did not reduce the overall risk of adverse maternal and offspring complications but has the potential to reduce gestational weight gain and the risk of gestational diabetes.

A Mediterranean diet with an enhanced consumption of extra virgin olive oil and pistachios improves pregnancy outcomes in women without gestational diabetes mellitus: A sub-analysis of the St. Carlos Gestational Diabetes Mellitus Prevention Study.

Assaf-Balut, C., N. García de la Torre, A. Duran, M. Fuentes, E. Bordiú, L. Del Valle, C. Familiar, J. Valerio, I. Jiménez, M.A. Herraiz, N. Izquierdo, M.J. Torrejon, M.Á. Cuadrado, I. Ortega, F.J. Illana, I. Runkle, P. de Miguel, I. Moraga, C. Montañez, A. Barabash, M. Cuesta, M.A. Rubio, A.L. Calle-Pascual, 2019. A Mediterranean diet with an enhanced consumption of extra virgin olive oil and pistachios improves pregnancy outcomes in women without gestational diabetes mellitus: A sub-analysis of the St. Carlos Gestational Diabetes Mellitus Prevention Study. Ann Nutr Metab. 74(1):69-79.

AIMS: The aim of the study was to evaluate the effect of a Mediterranean diet (MedDiet), enhanced with extra virgin olive oil (EVOO) and nuts, on a composite of adverse maternofoetal outcomes of women with normoglycemia during pregnancy. METHODS: This was a sub-analysis of the St Carlos gestational diabetes mellitus Prevention Study. Only normoglycemic women were analysed (697). They were randomized (at 8-12th gestational weeks) to: standard-care control group (337), where fat consumption was limited to 30% of total caloric intake; or intervention group (360), where a MedDiet, enhanced with EVOO and pistachios (40-42% fats of total caloric intake) was recommended. The primary outcome was a composite of maternofoetal outcomes (CMFOs): at least having 1 event of emergency C-section, perineal trauma, pregnancy-induced hypertension and preeclampsia, prematurity, large-for-gestational-age and small-for gestational-age. RESULTS: Crude relative risk showed that the intervention was associated with a significant reduction in the risk of CMFOs (0.48 [0.37-0.63]; p = 0.0001), with a number-needed-to-treat = 5. Risk of urinary tract infections, emergency C-sections, perineal trauma, large-for-gestational-age and small-for gestational age new-borns were also significantly reduced. CONCLUSION: A MedDiet, enhanced with EVOO and nuts, was associated with a risk reduction of CMFOs in over 50% in normoglycemic pregnant women. Therefore, it might be a potentially adequate diet for pregnant women.

Effect of nut consumption on semen quality and functionality in healthy men consuming a Western-style diet: a randomized controlled trial.

Salas-Huetos, A., R. Moraleda, S. Giardina, E. Anton, J. Blanco, J. Salas-Salvadó, M. Bulló, 2018. Effect of nut consumption on semen quality and functionality in healthy men consuming a Western-style diet: a randomized controlled trial. Am J Clin Nutr. 108:953–962.

Background: Human semen quality has declined in industrialized countries. Pollution, smoking, and the consumption of a Western style diet are all hypothesized as potential causes. Objective: We evaluated the effect of chronic consumption of nuts on changes in conventional semen parameters and the potential mechanisms implicated. Design: The FERTINUTS study was a 14-wk randomized, controlled, parallel trial. A total of 119 healthy men, aged 18–35 y, were allocated to 1 of 2 intervention groups: one group was fed the usual Western-style diet enriched with 60 g of a mixture of nuts/d (nut group), and the other was fed the usual Western-style diet avoiding nuts (control group). Semen and blood samples were collected at baseline and at the end of the intervention. Dietary information was recorded throughout the trial. Changes in conventional semen parameters (pH, volume, sperm count and concentration, motility, and morphology) were determined as primary outcomes. The effect of nut consumption on sperm DNA fragmentation (SDF), reactive oxygen species (ROS) production, chromosome anomalies (X, Y, and 18), total DNA methylation, and microRNA expression were measured in sperm samples as potential causes of the changes in the seminogram. Results: Compared with the control group, improvements in total sperm count (P = 0.002) and vitality (P = 0.003), total motility (P = 0.006), progressive motility (P = 0.036), and morphology of sperm (P = 0.008) were observed in the nut group. Participants in the nut group showed an increase in the consumption of total fat, monounsaturated fatty acids, polyunsaturated fatty acids, magnesium, vitamin E, α-linolenic acid, total omega-3 (n–3) and ω-3: ω-6 ratio intake during the intervention. Participants in the nut group showed a significant reduction in SDF (P < 0.001) and in the expression of hsa-miR-34b-3p (P = 0.036). No significant changes in ROS, sperm chromosome anomalies, or DNA methylation were observed between groups. Conclusions: The inclusion of nuts in a Western-style diet significantly improves the total sperm count and the vitality, motility, and morphology of the sperm. These findings could be partly explained by a reduction in the sperm DNA fragmentation. This trial was registered at ISRCTN as ISRCTN12857940.

Effectiveness of a walnut-enriched diet on murine sperm: involvement of reduced peroxidative damage.

Coffua, L.S., P.A. Martin-Deleon, 2017. Effectiveness of a walnut-enriched diet on murine sperm: involvement of reduced peroxidative damage. Heliyon. 2017 Feb 20;3(2):e00250. doi: 10.1016/j.heliyon.2017.e00250.

Abstract: A walnut supplement for a Western-style diet in men was shown to improve sperm motility, vitality, and morphology. To gain further insights into factors underlying this improvement, we administered a parallel walnut-enriched diet to mice [including those with a defect in sperm motility due to deletion of Plasma Membrane Ca2+-ATPase 4 (Pmca4−/−)] to determine if there is a similar improvement that is accompanied by reduced sperm membrane peroxidative damage. Although sperm vitality and acrosome reaction rate were unaffected, the diet led to a significant improvement in motility (P < 0.05) and morphology (P < 0.04) in wild-type sperm and in morphology (P < 0.01) in Pmca4−/−, confirming the diet’s efficacy, which appeared to be more modest in mice than in humans. In both strains of mice, the diet resulted in a significant decrease in sperm lipid peroxidation (oxidative stress) levels, but did not rescue the significantly increased apoptotic levels seen in the testis and epididymis of Pmca4 nulls. Our findings support the effectiveness of walnuts on sperm quality, associated with reduced peroxidative damage; and suggest that oxidative stress is involved in the mechanism(s) underlying male reproductive defects in Pmca4−/−.