Screening and diagnosis of primary aldosteronism. Consensus document of all the Spanish Societies involved in the management of primary aldosteronism.

Primary aldosteronism (PA) is the most frequent cause of secondary hypertension (HT), and is associated with a higher cardiometabolic risk than essential HT. However, PA remains underdiagnosed, probably due to several difficulties clinicians usually find in performing its diagnosis and subtype classification. The aim of this consensus is to provide practical recommendations focused on the prevalence and the diagnosis of PA and the clinical implications of aldosterone excess, from a multidisciplinary perspective, in a nominal group consensus approach by experts from the Spanish Society of Endocrinology and Nutrition (SEEN), Spanish Society of Cardiology (SEC), Spanish Society of Nephrology (SEN), Spanish Society of Internal Medicine (SEMI), Spanish Radiology Society (SERAM), Spanish Society of Vascular and Interventional Radiology (SERVEI), Spanish Society of Laboratory Medicine (SEQC(ML)), Spanish Society of Anatomic-Pathology, Spanish Association of Surgeons (AEC).

Practical consensus for the treatment and follow-up of primary aldosteronism: a multidisciplinary consensus document.

Primary aldosteronism (PA) is the most frequent cause of secondary hypertension and is associated with a higher cardiometabolic risk than essential hypertension. The aim of this consensus is to provide practical clinical recommendations for its surgical and medical treatment, pathology study and biochemical and clinical follow-up, as well as for the approach in special situations like advanced age, pregnancy and chronic kidney disease, from a multidisciplinary perspective, in a nominal group consensus approach of experts from the Spanish Society of Endocrinology and Nutrition (SEEN), Spanish Society of Cardiology (SEC), Spanish Society of Nephrology (SEN), Spanish Society of Internal Medicine (SEMI), Spanish Radiology Society (SERAM), Spanish Society of Vascular and Interventional Radiology (SERVEI), Spanish Society of Laboratory Medicine (SEQC(ML)), Spanish Society of Anatomic-Pathology and Spanish Association of Surgeons (AEC).

Isolated hypoaldosteronism is a cause of hypovolemic but not euvolemic hyponatremia.

Introduction: Hypoaldosteronism is characterized by hyperkalemia, and/or hypovolemic hyponatremia (HH), often accompanied by metabolic acidosis. HH is typical of hypoaldosteronism, whereas euvolemic hyponatremia (EH) is not. The purpose of the current study is to describe the characteristics of hyponatremia in hypoaldosteronism and elucidate whether EH can be considered part of the disease's spectrum. Methods: In a hypoaldosteronism cohort, we analyzed the factors associated with hyponatremia, comparing the characteristics of EH and HH and their associated factors. Correlation analyses of mineralocorticoid biomarkers, such as the transtubular potassium gradient (TTKG), the urinary Na+/K+ ratio (UNa+/UK+) with serum, and urinary electrolytes were performed in both types of hyponatremia. Results: Of 112 hypoaldosteronism episodes, 77.7% were ≥65 years old, 44.6% were women, and 80 (71.4%) had hyponatremia. Hyponatremia was negatively associated with the presence of chronic kidney disease, and positively with a hypovolemic state, malnutrition, a prior history of hyponatremia, and glucocorticoid therapy. HH: 61/80 and EH: 19/80 episodes. HH was associated with an age ≥65 years and the use of diuretics, as well as factors related to an aldosterone deficit and/or mineralocorticoid resistance. In HH but not in EH, urinary potassium was correlated with the TTKG, and urinary sodium with both the TTKG and the UNa+/UK+. Conclusion: Both HH and EH can be observed in hypoaldosteronism. However, only the former would be related to insufficient mineralocorticoid activity. Significance statement: Isolated hypoaldosteronism is a poorly understood and underdiagnosed endocrinological disorder, classically recognized only when hyperkalemia is present. The development of hypovolemic hyponatremia, however, is also easily explained by the physiopathology of the disorder. The current study addresses the features of hyponatremia when found in the context of mineralocorticoid insufficiency, and confirms an association between hypovolemic hyponatremia and isolated hypoaldosteronism. Thus, the clinical spectrum of hypoaldosteronism is extended to include hypovolemic hyponatremia as a frequent manifestation of the disorder.

Modifiable Risk Factors and Trends in Changes in Glucose Regulation during the First Three Years Postdelivery: The St Carlos Gestational Diabetes Mellitus Prevention Cohort.

OBJECTIVE: Evaluation of the influence of potential risk factors (RFs) on glycemic changes at 3 years postpartum. METHODS: The glycemic status of 1400 women, in absence of a new pregnancy, was evaluated at 3 months (3 m) and 3 years (3 y) postpartum, after participation in the St. Carlos Gestational Study (2228 normoglycemic pregnant women followed from before gestational week 12 to delivery, from 2015-2017). Abnormal glucose regulation (AGR) was defined as fasting serum glucose ≥ 100 mg/dL and/or HbA1c ≥ 5.7% and/or 2 h 75 g OGTT glucose ≥ 140 mg/dL. In total, 12 modifiable and 3 unmodifiable RFs were analyzed. RESULTS: 3 m postpartum, 110/1400 (7.9%) women had AGR; 3 y postpartum, 137 (9.8%) women exhibited AGR (110 with 3 m normal glucose tolerance [NGT]); 1263 (90.2%) had NGT (83 with 3 m AGR). More women with gestational diabetes mellitus (GDM) progressed to AGR at 3 y (OR: 1.60 [1.33-1.92]) than women without GDM. Yet, most women with 3 m and/or 3 y AGR had no GDM history. Having ≥2 unmodifiable RFs was associated with increased risk for progression to AGR (OR: 1.90 [1.28-2.83]) at 3 y postpartum. Having >5/12 modifiable RFs was associated with increased progression from NGT to AGR (OR: 1.40 [1.00-2.09]) and AGR persistence (OR: 2.57 [1.05-6.31]). Pregestational BMI ≥ 25 kg/m2 (OR: 0.59 [0.41-0.85]), postdelivery weight gain (OR: 0.53 [0.29-0.94]), and waist circumference > 89.5 cm (OR: 0.54 [0.36-0.79]) reduced the likelihood of NGT persisting at 3 y. CONCLUSIONS: 3-month and/or 3-year postpartum AGR can be detected if sought in women with no prior GDM. Modifiable and unmodifiable RF predictors of AGR at 3 y postpartum were identified. Universal screening for glycemic alterations should be considered in all women following delivery, regardless of prior GDM. These findings could be useful to design personalized strategies in women with risk factors for 3 y AGR.

An Early Mediterranean-Based Nutritional Intervention during Pregnancy Reduces Metabolic Syndrome and Glucose Dysregulation Rates at 3 Years Postpartum.

A Mediterranean diet (MedDiet)-based intervention reduces the rate of immediate postpartum maternal metabolic disorders. Whether these effects persist long-term remains to be determined. A total of 2526 normoglycemic women were randomized before the 12th gestational week (GW). IG women followed a MedDiet with extra virgin olive oil (EVOO) (>40 mL/day) and a handful of nuts daily, whereas CG women had to restrict all kinds of dietary fat. At 3 months postpartum, a motivational lifestyle interview was held. The endpoint of the study evaluated the rate of abnormal glucose regulation (AGR) and metabolic syndrome (MetS) at 3 years postpartum in women of the San Carlos cohort. A total of 369/625 (59%) CG women and 1031/1603 (64.3%) IG women were finally analyzed. At 3 months and 3 years postdelivery, the IG women showed higher adherence to the MedDiet, which was associated with lower values of body mass index (BMI) and lipid and glycemic profiles. Body weight change and waist circumference were lower in the IG women. After applying multiple regression analysis, the ORs (95%CI) resulted in AGR (3.18 (2.48-4.08); p < 0.001)/MetS (3.79 (1.81-7.95); p = 0.001) for women with GDM and higher OR for development of MetS in CG women (3.73 (1.77-7.87); p = 0.001). A MedDiet-based intervention early in pregnancy demonstrated persistent beneficial effects on AGR and MetS rates at 3 years postpartum.

Clinical manifestations and associated factors in acquired hypoaldosteronism in endocrinological practice.

Introduction: Hypoaldosteronism can be congenital or acquired, isolated or part of primary adrenal insufficiency, and caused by an aldosterone deficit, resistance, or a combination of both. Reduced mineralocorticoid action can induce a decrease in urine K+ and H+ excretion and an increase in urine Na+ excretion, leading to hyperkalemia, and/or hyponatremia, often combined with metabolic acidosis. We aimed to characterize the clinical manifestations of hypoaldosteronism, and their associated factors. Methods: Retrospective analysis of 112 episodes of hypoaldosteronism diagnosed in 86 adult patients from 2012-2019 by the Endocrinology and Nutrition Department of a tertiary hospital. The frequency of hyperkalemia, hypovolemic hyponatremia (HH) and metabolic acidosis (MA), and their associated factors were evaluated. Results: Patients had a median age of 77 [65 - 84], 55.4% were male. 94.6% cases showed hyperkalemia, 54.5% HH, and 60.3% MA. The mean serum K+ of all cases was 5.4 ± 0.5 mmol/L, Na+: 132.1 ± 6.3 mmol/L, HCO3: 22.6 ± 3.3 mmol/L. Hypoaldosteronism was isolated in the majority of cases: only 6/112 (5%) had primary adrenal insufficiency. Hypovolemia was associated with hyponatremia and a more florid clinical presentation. HH was associated with a combined presence of aldosterone-lowering and mineralocorticoid resistance factors. MA was associated with the presence of mineralocorticoid resistance factors. Conclusions: Hypoaldosteronism in adult endocrinological clinical practice is primarily isolated, and acquired. It predisposes not only to the development of hyperkalemia and MA, but also to that of HH. Hypoaldosteronism must be considered in the differential diagnosis of HH with urinary sodium wasting.

Changes in Serum Creatinine Levels Can Help Distinguish Hypovolemic from Euvolemic Hyponatremia.

Background and Objectives: Differentiating between hypovolemic (HH) and euvolemic hyponatremia (EH) is crucial for correct diagnosis and therapy, but can be a challenge. We aim to ascertain whether changes in serum creatinine (SC) can be helpful in distinguishing HH from EH. Materials and Methods: Retrospective analysis of patients followed in a monographic hyponatremia outpatient clinic of a tertiary hospital during 1 January 2014−30 November 2019. SC changes during HH and EH from eunatremia were studied. The diagnostic accuracy of the SC change from eunatremia to hyponatremia (∆SC) was analyzed. Results: A total of 122 hyponatremic patients, median age 79 years (70−85), 46.7% women. In total, 70/122 patients had EH, 52/122 HH. During hyponatremia, median SC levels increased in the HH group: +0.18 mg/dL [0.09−0.39, p < 0.001], but decreased in the EH group: −0.07 mg/dL (−0.15−0.02, p < 0.001), as compared to SC in eunatremia. HH subjects presented a higher rate of a positive ∆SC than EH (90.4% vs. 25.7%, p < 0.001). EH subjects presented a higher rate of a negative/null ∆SC than HH (74.3% vs. 9.6%, p < 0.001). ROC curve analysis found an AUC of 0.908 (95%CI: 0.853 to 0.962, p < 0.001) for ∆SC%. A ∆SC% ≥ 10% had an OR of 29.0 (95%CI: 10.3 to 81.7, p < 0.001) for HH. A ∆SC% ≤ 3% had an OR of 68.3 (95%CI: 13.0 to 262.2, p < 0.001) for EH. Conclusions: The assessment of SC changes from eunatremia to hyponatremia can be useful in distinguishing between HH and EH.

Laparoscopic adrenalectomy vs. radiofrequency ablation for the treatment of primary aldosteronism. A single center retrospective cohort analysis adjusted with propensity score.

BACKGROUND: Laparoscopic adrenalectomy (LA) is the gold standard treatment for unilateral primary aldosteronism. However, satisfactory results have also been published with radiofrequency ablation (RFA). The aim of this study was to compare LA and RFA for the treatment of primary aldosteronism. METHODS: A retrospective cohort study of the patients who underwent LA or RFA in a single center was performed. Morbidity and long-term effectiveness (cure rate and blood pressure control) were analyzed. A multivariate analysis with a propensity score was also performed. RESULTS: Thirty-four patients were included in the study, 24 in the LA group and 10 in the RFA group. Hypertension had been diagnosed a median of 12 years before the intervention. Hypertension was properly controlled before the intervention in 55.9% of the patients. Hypertensive crisis was more common during RFA (4.2% vs. 70.0%, p < 0.001), although no patient suffered any complication because of these crises. LA was longer (174.6 vs. 105.5 min, p = 0.001) and had a longer length of stay (median 2 vs 1 days, p < 0.001). No severe complications were observed in any of the patients. After a median follow-up of 46.2 months, more patients had hypertension cured and blood pressure controlled in the LA group (29.2% vs. 0%, p = 0.078 and 95.5% vs. 50.0%, p = 0.006, respectively). Also, patients in the LA group were taking less antihypertensive drugs (1.8 vs. 3.0, p = 0.054) or mineralocorticoid receptor antagonists (41.7% vs. 90.0%, p = 0.020). Multivariate analysis adjusted by propensity score showed that LA had an OR = 11.3 (p = 0.138) for hypertension cure and an OR = 55.1 (p = 0.040) for blood pressure control. CONCLUSIONS: Although RFA was a less invasive procedure than LA, hypertension was cured and blood pressure was properly controlled in more patients from the LA group. Patients who underwent LA were taking less antihypertensive drugs than patients who had undergone RFA.

The Consumption of Food-Based Iodine in the Immediate Pre-Pregnancy Period in Madrid Is Insufficient. San Carlos and Pregnancy Cohort Study.

A pre-gestational thyroid reserve of iodine is crucial to guarantee the increased demand for thyroid hormone production of early pregnancy. An iodine intake ≥150 µg/day is currently recommended. The objective of this study was to assess average pre-gestational food-based iodine consumption in pregnant women at their first prenatal visit (<12 gestational weeks), and its association with adverse materno-fetal events (history of miscarriages, early fetal losses, Gestational Diabetes, prematurity, caesarean sections, and new-borns large/small for gestational age). Between 2015-2017, 2523 normoglycemic women out of 3026 eligible had data in the modified Diabetes Nutrition and Complication Trial (DNCT) questionnaire permitting assessment of pre-gestational food-based iodine consumption, and were included in this study. Daily food-based iodine intake was 123 ± 48 µg, with 1922 (76.1%) not reaching 150 µg/day. Attaining this amount was associated with consuming 8 weekly servings of vegetables (3.84; 3.16-4.65), 1 of shellfish (8.72; 6.96-10.93) and/or 2 daily dairy products (6.43; 5.27-7.86). Women who reached a pre-gestational intake ≥150 µg had lower rates of hypothyroxinemia (104 (17.3%)/384 (21.4%); p = 0.026), a lower miscarriage rate, and a decrease in the composite of materno-fetal adverse events (0.81; 0.67-0.98). Reaching the recommended iodine pre-pregnancy intake with foods could benefit the progression of pregnancy.

Early Levothyroxine Treatment for Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy: The St Carlos Gestational and Thyroid Protocol.

The optimal maternal levels of thyroid hormones (TH) during the first trimester of gestation have not been established, nor has the ideal moment to initiate levothyroxine treatment (LT) to improve the evolution of gestation and fetal development. Cut-off points for Thyroid-stimulating hormone (TSH) <2.5 µIU/mL and free thyroxine (FT4)>7.5 pg/mL have been recommended. There are no data on whether initiation of LT <9th Gestational Week (GW) can have a favourable impact. Objective: To define the TSH/FT4 percentiles corresponding with 2.5 µIU/mL and 7.5 pg/mL levels, respectively, at GW8 (Study 1), and evaluate the effects of protocol-based LT before GW9 on gestation evolution, in women with TSH ≥2.5 µIU/mL and/or FT4≤ 7.5 pg/mL (study 2). Subjects: 2768 consecutive pregnant women attending the first gestational visit from 2013-2014 and 3026 from 2015-2016 were eligible for Study I and 2 respectively. A final 2043 (study 1) and 2069 (study 2) women were assessed in these studies. Results: Study 1: The FT4 level of 7.5 pg/mL corresponds with the 17.9th percentile, a TSH level of 2.5 µIU/mL with the 75.8th. Women with TSH ≥2.5 µIU/mL had a history of fetal losses more frequently than those <2.5 (OR 2.33 (95%CI): 1.58-3.12), as did those with FT4 ≤7.5 pg/ml compared to those >7.5 (OR 4.81; 3.25-8.89). Study 2: A total of 1259 women had optimal TSH/FT4 levels (Group 1), 672 (32.4%, Group 2) had suboptimal TSH or T4l, and 138 (6.7%, Group 3) had suboptimal values of both. 393 (58.5%) in Group 2 and 88 (63.8%) in Group 3 started LT before GW9. Mean (SD) GW24 levels were TSH: 1.96 ± 1.22 µIU/mL and FT4: 7.07 ± 1.25 pg/mL. The highest FT4 value was 12.84 pg/mL. The adjusted risk for an adverse event if LT was started early was 0.71 (0.43-0.91) for Group 2 and 0.80 (0.66-0.94) for Group 3. Conclusions: Early LT in women with suboptimum levels of TSH/FT4 (≥2.5µIU/mL/≤7.5 pg/ml) at or before GW9 is safe and improves gestation progression. These data support the recommendation to adopt these cut-off points for LT initiation, which should be started as early as possible.

Exercise-Induced Hyponatremia: An Assessment of the International Hydration Recommendations Followed During the Gran Trail De Peñalara and Vitoria-Gasteiz Ironman Competitions.

Introduction: Hyponatremia often occurs during the practice of endurance sports. We evaluated the impact on hyponatremia of the hydration recommendations of the Third International Exercise-Associated Hyponatremia Consensus Development Conference 2015 (3IE-AHCD) during the 2017 Gran Trail de Peñalara marathon (GTP) and the Vitoria Gasteiz Ironman triathlon (VGI). Methods: Prospective study of GTP and VGI athletes participating in four information sessions in the months prior to the events, to explain that hydration should only be according to their level of thirst, per the recommendations of the 3IE-AHCD. Consenting event finishers were included in final analysis. Pre- and post-race anthropometric and biochemical parameters were compared. Results: Thirty-six GTP (33 male) and 94 VGI (88 male) finishers were evaluated. GTP race median fluid intake was 800 ml/h, with 900 ml/h in the VGI race. 83.3% GTPfin and 77.6% VGIfin remained eunatremic (blood sodium 135-145 mmol/L). Only 1/36 GTP and 1/94 VGI participant finished in hyponatremia, both with a sodium level of 134 mmol/L. Fourteen percent of GTP, and 21.2% of VGI participants finished in hypernatremia, with no increase in race completion times. No participating athlete required medical attention, except for musculoskeletal complaints. Pro-BNP and Copeptin levels rose significantly. Changes in copeptin levels did not correlate with changes in plasma osmolality, nor total body water content in impedance analysis. Conclusions: Recommending that athletes' fluid intake in endurance events be a function of their thirst almost entirely prevented development of hyponatremia, without induction of clinically significant hypernatremia, or a negative repercussion on race completion times.

Prognostic Impact of Hyponatremia and Hypernatremia in COVID-19 Pneumonia. A HOPE-COVID-19 (Health Outcome Predictive Evaluation for COVID-19) Registry Analysis.

Dysnatremia is associated with increased mortality in patients with community-acquired pneumonia. SARS-COV2 (Severe-acute-respiratory syndrome caused by Coronavirus-type 2) pneumonia can be fatal. The aim of this study was to ascertain whether admittance dysnatremia is associated with mortality, sepsis, or intensive therapy (IT) in patients hospitalized with SARS-COV2 pneumonia. This is a retrospective study of the HOPE-COVID-19 registry, with data collected from January 1th through April 31th, 2020. We selected all hospitalized adult patients with RT-PCR-confirmed SARS-COV2 pneumonia and a registered admission serum sodium level (SNa). Patients were classified as hyponatremic (SNa <135 mmol/L), eunatremic (SNa 135-145 mmol/L), or hypernatremic (SNa >145 mmol/L). Multivariable analyses were performed to elucidate independent relationships of admission hyponatremia and hypernatremia, with mortality, sepsis, or IT during hospitalization. Four thousand six hundred sixty-four patients were analyzed, median age 66 (52-77), 58% males. Death occurred in 988 (21.2%) patients, sepsis was diagnosed in 551 (12%) and IT in 838 (18.4%). Hyponatremia was present in 957/4,664 (20.5%) patients, and hypernatremia in 174/4,664 (3.7%). Both hyponatremia and hypernatremia were associated with mortality and sepsis. Only hyponatremia was associated with IT. In conclusion, hyponatremia and hypernatremia at admission are factors independently associated with mortality and sepsis in patients hospitalized with SARS-COV2 pneumonia. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04334291, NCT04334291.

TCF7L2 rs7903146 polymorphism modulates the association between adherence to a Mediterranean diet and the risk of gestational diabetes mellitus.

OBJECTIVE: There is sparse evidence for the impact of gene-diet interaction on gestational diabetes mellitus (GDM) onset. Recent findings have shown that late first-trimester high adherence to a Mediterranean diet (MedDiet) pattern is associated with a GDM risk reduction. The aim of this study was to investigate if this effect could be modulated by TCF7L2 rs7903146 polymorphism.Research design and methods: A total of 874 pregnant women participants in the St Carlos GDM prevention study, were stratified into three groups defined as "High,5-6 on targets", "Moderate, 2-4 on targets" or "Low, 0-1 on targets" adherence to Mediterranean diet according to late first-trimester compliance with six food targets: >12 servings/week of vegetables, >12 pieces/week of fruits, <2 servings/week of juice, >3 servings/week of nuts, >6 days/week and >40 mL/day consumption of extra virgin olive oil. All patients were genotyped for rs7903146 using Taqman technology. RESULTS: Logistic regression analysis revealed that the risk of developing GDM in those with high adherence versus low adherence was significantly reduced only in carriers of the T-allele (CT + TT), with an adjusted odds ratio of 0.15 (95% CI:0.05-0.48). This effect was not observed in CC carriers. Interaction analysis yielded significant rs7903146-MedDiet interaction in GDM risk (p < 0.03). CONCLUSIONS: Women carrying the rs7903146 T-allele who highly adhere to a MedDiet early in pregnancy have lower risk of developing GDM than CC carriers. This reinforces the importance of identifying patients at risk of GDM who would be especially sensitive to nutritional interventions based on their genetic characteristics.

The Effect of the Dose of Isotonic Saline on the Correction of Serum Sodium in the Treatment of Hypovolemic Hyponatremia.

BACKGROUND: Overcorrection of serum sodium (SNa) during therapy of hyponatremia can result in osmotic demyelination syndrome. Our aim was to determine the relationship between the isotonic saline solution dose (ISSD) administered and the 24-h SNa increase (24SNa) in patients with hypovolemic hyponatremia (HH). METHODS: Retrospective study of HH patients treated with ISS in a tertiary hospital of Madrid, Spain, between 1 January-30 May 2019. The 24-h ISSD received and corresponding 24SNa were calculated. The latter was classified as 3 groups: ≥8 mmol/L, ≥6 mmol/L, or <4 mmol/L. Multivariate regression analyses were performed and ROC curves calculated to study the relationship between ISSD and 24SNa. RESULTS: Thirty patients were included, age 72 years (60-80), 50% were women. 24SNa was ≥8 mmol/L/24 h in 33%, ≥6 mmol/L/24 h in 50%, and <4 mmol/L/24 h in 30%. Median ISSD in each group was: 32 mL/kg/24 h (29-37), 31 mL/kg/24 h (25-33), and 20 mL/kg/24 h (14-22), respectively. An ISSD ≥ 30 mL/kg/24 h had an odds ratio (OR) of 16 (95% CI: 2.5-95.1; p = 0.004) for a 24SNa ≥8 mmol/L, with a sensitivity and specificity of 80%. CONCLUSIONS: The 24SNa depends on ISSD. An ISSD between 23-30 mL/kg/24 h seems to be safe and effective.

Effect of a Mediterranean Diet-Based Nutritional Intervention on the Risk of Developing Gestational Diabetes Mellitus and Other Maternal-Fetal Adverse Events in Hispanic Women Residents in Spain.

Gestational diabetes mellitus (GDM) is the most frequent morbidity found in pregnancy, and it increases the risk for several maternal-fetal complications. Hispanic women are considered at high risk. The St. Carlos GDM prevention study is a randomized controlled trial (RCT) conducted from 2016-2017. Normoglycemic women were randomized at 12-14 Gestation week (WG) to an intervention group (IG) receiving recommendations based on the MedDiet (supplemented with ExtraVirgin Olive Oil/pistachios), or to a control group (CG), recommended to limit fat intake. After RCT conclusion, IG recommendations were applied to a real-world group (RW) in routine clinical practice. The primary endpoint of the current study is an assessment of the GDM rate in Hispanic participants of the aforementioned studies: 132 RCT, 128 CT, 284 RW participants. The GDM rate was lower in IG: 19/128(14.8%), p = 0.021, and RW: 38/284(13.4%), p = 0.029) than in CG: 34/132(25.8%). Adjusted RR (95%CI) for GDM: 0.72 (0.50-0.97), p = 0.037 in IG and 0.77 (0.61-0.97), p = 0.008 in RW. Rates of urinary tract infections, emergency caesarean-sections and perineal trauma were also lower in IG and RW. Other adverse outcomes were lower in IG vs. CG. In conclusion, a MedDiet-based intervention reduces the rate of GDM and several adverse maternal-fetal outcomes in Hispanic women residing in Spain.

Interaction between age and vitamin D deficiency in severe COVID-19 infection / Interacción entre la edad y el déficit de vitamina D en la COVID-19 grave

INTRODUCTION: coronavirus disease 2019 (COVID-19) can induce an exaggerated inflammatory response. Vitamin D is a key modulator of the immune system. We hypothesized that vitamin D deficiency (VDD) could increase the risk of developing severe COVID-19 infection. METHODS: patients with confirmed COVID-19 seen at the emergency department of our hospital with recent measurements of 25(OH)D were recruited. We explored the association of vitamin D deficiency (VDD), defined as 25-hydroxyvitamin D < 20 ng/mL, with a composite of adverse clinical outcomes. RESULTS: we included 80 patients, of which 31 (39 %) presented the endpoint. VDD tended to predict an increased risk of developing severe COVID-19 after adjusting for age, gender, obesity, cardiac disease, and kidney disease [OR 3.2 (95 % CI: 0.9-11.4), p = 0.07]. Age had a negative interaction with the effect of VDD on the composite outcome (p = 0.03), indicating that the effect was more noticeable at younger ages. Furthermore, male gender was associated with VDD and with severe COVID-19 at younger ages. CONCLUSIONS: in this retrospective study, vitamin D deficiency showed a signal of association with severe COVID-19 infection. A significant interaction with age was noted, suggesting VDD may have a greater impact in younger patients. These findings should be confirmed in larger, prospective, adequately powered studies

INTRODUCCIÓN: la enfermedad por coronavirus 2019 (COVID-19) puede inducir una respuesta inflamatoria exagerada. La vitamina D es un modulador clave del sistema inmune. Planteamos que la deficiencia de vitamina D (VDD) podría aumentar el riesgo de desarrollar infección grave por COVID-19. MÉTODOS: se reclutaron pacientes consecutivos que acudieron al servicio de urgencias de nuestro centro con diagnóstico de COVID-19 confirmado (PCR-COVID-19 positiva) y mediciones recientes de 25(OH)D. Exploramos la asociación de la deficiencia de vitamina D (VDD), definida como una 25-hidroxivitamina D < 20 ng/ml, con un compuesto de resultados clínicos adversos. RESULTADOS: se incluyeron 80 pacientes, de los cuales 31 (39 %) presentaron el criterio de valoración primario. El VDD tendió a predecir un mayor riesgo de desarrollar COVID-19 grave después de ajustar edad, sexo, obesidad, enfermedad cardíaca y enfermedad renal [OR: 3,2 (IC 95 %: 0,9-11,4), p = 0,07]. La edad tuvo una interacción negativa con el efecto de la VDD en el resultado compuesto (p = 0,03), lo que indica que el efecto fue más notable a edades más tempranas. Además, el género masculino se asoció con la VDD y con la COVID-19 grave en las edades más jóvenes. CONCLUSIONES: en este estudio retrospectivo, la deficiencia de vitamina D mostró una tendencia de asociación con la infección grave por COVID-19. Se observó una interacción significativa con la edad, lo que sugiere que la VDD puede tener un mayor impacto en los pacientes más jóvenes. Estos hallazgos deben confirmarse en estudios más grandes, prospectivos y con potencia adecuada

Interaction between age and vitamin D deficiency in severe COVID-19 infection.

INTRODUCTION: Background: coronavirus disease 2019 (COVID-19) can induce an exaggerated inflammatory response. Vitamin D is a key modulator of the immune system. We hypothesized that vitamin D deficiency (VDD) could increase the risk of developing severe COVID-19 infection. Methods: patients with confirmed COVID-19 seen at the emergency department of our hospital with recent measurements of 25(OH)D were recruited. We explored the association of vitamin D deficiency (VDD), defined as 25-hydroxyvitamin D < 20 ng/mL, with a composite of adverse clinical outcomes. Results: we included 80 patients, of which 31 (39 %) presented the endpoint. VDD tended to predict an increased risk of developing severe COVID-19 after adjusting for age, gender, obesity, cardiac disease, and kidney disease [OR 3.2 (95 % CI: 0.9-11.4), p = 0.07]. Age had a negative interaction with the effect of VDD on the composite outcome (p = 0.03), indicating that the effect was more noticeable at younger ages. Furthermore, male gender was associated with VDD and with severe COVID-19 at younger ages. Conclusions: in this retrospective study, vitamin D deficiency showed a signal of association with severe COVID-19 infection. A significant interaction with age was noted, suggesting VDD may have a greater impact in younger patients. These findings should be confirmed in larger, prospective, adequately powered studies.

INTRODUCCIÓN: Antecedentes: la enfermedad por coronavirus 2019 (COVID-19) puede inducir una respuesta inflamatoria exagerada. La vitamina D es un modulador clave del sistema inmune. Planteamos que la deficiencia de vitamina D (VDD) podría aumentar el riesgo de desarrollar infección grave por COVID-19. Métodos: se reclutaron pacientes consecutivos que acudieron al servicio de urgencias de nuestro centro con diagnóstico de COVID-19 confirmado (PCR-COVID-19 positiva) y mediciones recientes de 25(OH)D. Exploramos la asociación de la deficiencia de vitamina D (VDD), definida como una 25-hidroxivitamina D < 20 ng/ml, con un compuesto de resultados clínicos adversos. Resultados: se incluyeron 80 pacientes, de los cuales 31 (39 %) presentaron el criterio de valoración primario. El VDD tendió a predecir un mayor riesgo de desarrollar COVID-19 grave después de ajustar edad, sexo, obesidad, enfermedad cardíaca y enfermedad renal [OR: 3,2 (IC 95 %: 0,9-11,4), p = 0,07]. La edad tuvo una interacción negativa con el efecto de la VDD en el resultado compuesto (p = 0,03), lo que indica que el efecto fue más notable a edades más tempranas. Además, el género masculino se asoció con la VDD y con la COVID-19 grave en las edades más jóvenes. Conclusiones: en este estudio retrospectivo, la deficiencia de vitamina D mostró una tendencia de asociación con la infección grave por COVID-19. Se observó una interacción significativa con la edad, lo que sugiere que la VDD puede tener un mayor impacto en los pacientes más jóvenes. Estos hallazgos deben confirmarse en estudios más grandes, prospectivos y con potencia adecuada.

Benefits of Adhering to a Mediterranean Diet Supplemented with Extra Virgin Olive Oil and Pistachios in Pregnancy on the Health of Offspring at 2 Years of Age. Results of the San Carlos Gestational Diabetes Mellitus Prevention Study.

The intrauterine environment may be related to the future development of chronic diseases in the offspring. The St. Carlos gestational diabetes mellitus (GDM) prevention study, is a randomized controlled trial that evaluated the influence of the early (before 12th gestational week) Mediterranean diet (MedDiet) on the onset of GDM and adverse gestational outcomes. Out of 874 women assessed after delivery (440 control group (CG)/434 intervention group (IG)), 703 children were followed (365/338; CG/IG), with the aim to assess whether the adherence to a MedDiet during pregnancy induces health benefits for the offspring during the first two years of life. Logistic regression analysis showed that the IG in children of mothers with pre-gestational body mass index (BMI) < 25 kg/m2 and normal glucose tolerance (NGT), was associated with a lower risk (RR(95% CI)) of suffering from severe events requiring hospitalization due to bronchiolitis/asthma (0.75(0.58-0.98) and 0.77(0.59-0.99), respectively) or other diseases that required either antibiotic (0.80(0.65-0.98) and 0.80(0.65-0.99), respectively), corticosteroid treatment (0.73(0.59-0.90) and 0.79(0.62-1.00) respectively) or both (all p < 0.05). A nutritional intervention based on the MedDiet during pregnancy is associated with a reduction in offspring's hospital admissions, especially in women with pre-gestational BMI < 25 kg/m2 and NGT.

Consumption of fat-free dairy products is not associated with a lower risk of maternofetal adverse events.

BACKGROUND: The consumption of dairy products in pregnancy is widely extended. However, whether the consumption of low or high fat dairy produce is more beneficial for maternofetal health has yet to be established. RESEARCH DESIGN AND METHODS: This prospective cohort study evaluated the effect of consumption of dairy products during pregnancy on the frequency of gestational diabetes mellitus (GDM) and a composite of adverse maternofetal outcomes (CMFO). Pregnant women receiving obstetric care between 2014 and 2017 were eligible. Those who consumed ≥3 servings/day of dairy products at 24-28 gestational weeks (GWs) were included and analyzed (n=2004). The population was stratified into three groups according to intake of fat-free dairy products-skimmed milk and fat-free yoghurt and cheese-(days/week): infrequent (1-2), average (3-6) and regular (7). Logistic regression analysis compared ORs (95% CI) for GDM and CMFO between the three groups (where the group of reference was the 'infrequent' intake group). RESULTS: After adjusting for confounding factors, no significant associations were found between the degree of consumption of fat-free dairy products and the risk of GDM and a CMFO. Moreover, when categorized by the degree of adherence to the Mediterranean diet (above or below the median score), associations were found between the 'regular' intake group and an increased risk of having a CMFO in women with a high adherence to the Mediterranean diet (OR: 1.50; 95% CI: 1.01 to 2.22; p<0.05). Weight gain during pregnancy did not differ among groups. CONCLUSIONS: The consumption of fat-free dairy products during pregnancy does not seem to be beneficial for maternofetal health.

An Early, Universal Mediterranean Diet-Based Intervention in Pregnancy Reduces Cardiovascular Risk Factors in the "Fourth Trimester".

An early antenatal dietary intervention could play an important role in the prevention of metabolic diseases postpartum. The aim of this study is to evaluate whether an early, specific dietary intervention reduces women's cardiovascular risk in the "fourth trimester". This prospective cohort study compares 1675 women from the standard-care group (ScG/n = 676), who received standard-care dietary guidelines, with the intervention group (IG/n = 999), who received Mediterranean diet (MedDiet)-based dietary guidelines, supplemented with extra-virgin olive oil and nuts. Cardiovascular risk was determined by the presence of metabolic syndrome (MetS) and insulin resistance syndrome (IrS) (HOMA-IR 3.5) at 12-14 weeks postpartum. MetS was less frequent in the IG (11.3 vs. 19.3%, p < 0.05). The intervention was associated with a reduction in the relative risk of having MetS: 0.74 (95% CI, 0.60-0.90), but not in the risk of IrS. When analyzing the presence of having one or more components of the MetS, the IG had significantly higher rates of having 0 components and lower rates of having ≥1 (p-trend = 0.029). An early MedDiet-based nutritional intervention in pregnancy is associated with reductions in postpartum rates of MetS.