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Purpose: Fetal stress and postnatal overfeeding are associated with programming of cardiometabolic diseases, but their relative role is not clearly established. By using specific animal models we aimed to address this issue comparing the perinatal alterations induced in several organs key for cardiometabolic control.Methods: Fetal stress was induced by maternal undernutrition (MUN) during pregnancy. MUN rats were fed ad libitum with standard chow from gestational day 1 to 10; with 50% of their daily intake from day 11 to the end of pregnancy and returned back to ad libitum during lactation (12 pups/litter). Postnatal overfeeding (POF) was induced in the offspring from ad libitum fed dams by reducing litter size during lactation (4 pups/litter). Control animals were offspring from dams ad libitum fed both during pregnancy and lactation (12 pups/litter). Tibial length and body, heart, kidney, liver and fat adipose tissue weights, as well as adipocites size, were assessed in the offspring at weaning (21 days). A group of MUN offspring was followed to measure body weight along perinatal development.Results: MUN offspring showed reduced tibial length and body weight from birth with progressive catch-up growth until month two, when body weight reached similar values to control rats. By weaning MUN offspring rats exhibited: 1) hyperglycemia; 2) heart and liver hypertrophy, 3) reduced kidney weight and 4) increased subcutaneous and periorganic fat deposits and adipocite size. POF offspring also exhibited increased glycemia together with liver, fat and body weight and adipocite size, but heart and kidney weights were not altered. There were no sex-related differences in either MUN or POF models in any of the parameters studied.Conclusions: We conclude that accelerated growth during postnatal life, rather than fetal stress, seems to be critical for metabolic control organs alterations. On the other hand, fetal stress induces changes in heart and kidney at an early age which might have a direct role on later cardiovascular disease development. [ABSTRACT FROM AUTHOR]

Introduction: Spontaneously hypertensive rats (SHR) have been used frequently as a model for human essential hypertension. However, both the SHR and its normotensive control, the Wistar Kyoto rat (WKY), consist of genetically different sublines. We tested the hypothesis that discrepant data in literature regarding the pathophysiology of vascular remodeling in hypertension result from the use of different rat sublines.Methods and results: We studied WKY and SHR from three different sources, at 6 weeks and 5 months of age. Both WKY and SHR showed significant differences in blood pressure, body weight, vascular remodeling, endothelial function, and vessel ultrastructure among sublines. Common features in vessels from SHR were an increase in wall thickness, wall-to-lumen ratio, and internal elastic lamina thickness. Using microarrays, we studied miRNA and mRNA expression in resistance arteries from all sublines. Principal component analysis and hierarchical clustering indicated that SHR, but particularly WKY, show clear differences in gene expression among sublines. Overall, both WKY and SHR showed an age-related expression pattern that involved many genes related to the extracellular matrix. In SHR, this pattern was more extensive and included a specific increase in miR-132-3p, and type III deiodinase. Comparison of WKY to SHR also yielded differences in gene expression common to all three sublines, including thrombospondin 4.Conclusions: These results indicate that abnormalities that are associated with hypertension, such as endothelial dysfunction, vascular stiffening, and inward remodeling of small arteries are subline-dependent. Herein both the specific SHR and WKY subline determine the outcome of the comparison. These findings may help to explain apparently discrepant data in literature regarding the pathophysiology of hypertension. [ABSTRACT FROM AUTHOR]

Purpose. Adverse intrauterine growth induced by maternal undernutrition during pregnancy (MUN) is associated with low birth weight of the offspring and later development of hypertension. This process, known as fetal programming, has less impact on female offspring, which exhibit lower levels of blood pressure in adult life compared to males. Given the role of oxidative stress in the development of cardiovascular diseases we aimed to asses if fetal programming induces perinatal alterations in oxidative-antioxidant balance and the possible differences between males and females.Methods. Sprague Dawley rats were used. Control (C) dams were fed ad libitum during pregnancy and lactation. MUN dams were fed 50% of the calculated ad libitum daily intake during the second half of gestation and returned to ad libitum diet during lactation. Offspring from both groups was standardized to 12 pups/litter (6 males and 6 females) and the rats were used at weaning (21 days). The rats were weighted at birth and at weaning. A blood sample was obtained by cardiac puncture at day 21 and the following parameters were measured in plasma: protein carbonyls, thiols, glutathion (spectrophotometric methods); total antioxidant capacity (TAC) and superoxide anion scavenging activity (SOSA) (luminometer) and catalase activity (Amplex red, fluorescence).Results. Compared to C offspring, MUN rats exhibited a reduced weight at birth and at weaning. The weight difference was similar in males and females. Male MUN rats showed: 1) reduced plasma thiols, glutation, and SOSA levels; 2) increased carbonyl levels and 3) no differences in TAC and catalase activity. Female MUN rats showed no differences in any of the parameters measured, compared to female control rats.Conclusions. These data suggest that fetal stress induced by maternal undernutrition in pregnancy affects the oxidative status at an early stage of development with a sex-dependent pattern. The lower level of plasma antioxidants in male offspring is likely to contribute to the higher level of hypertension developed by males compared to females in adult life. [ABSTRACT FROM AUTHOR]

Gastrointestinal motility disturbances are a hallmark of inflammatory bowel disease (IBD); however, their mechanisms remain unclear. This study utilized a dextran sulfate sodium (DSS)-induced colitis mouse model, deficient in mature B and T lymphocytes, to assess intestinal motility and the role of the adaptive immune system in health and IBD. In healthy mice, the absence of adaptive lymphocytes reduced acetylcholine (ACh) sensitivity in the ileum. During colitis, it decreases motility by reducing the intensity and frequency of spontaneous contractions while increasing cholinergic responsiveness. In the proximal colon, adaptive immunity deficiency led to increased contractility and reduced ACh sensitivity in homeostasis, while colitis reduced contractile capacity. In the mid-colon, immune-deficient mice have reduced ACh sensitivity in homeostasis and exacerbated contractile responses during colitis. In the distal colon, adaptive immunity loss reduced contractility in health and cholinergic responsiveness during colitis. These motility alterations were associated with altered acetylcholinesterase and M2/M3 muscarinic receptor expression. Notably, adaptive lymphocyte deficiency resulted in reduced tissue damage and lower TNF-α expression in the colon during colitis paralleling intestinal motility changes. Overall, the adaptive immune system critically regulates motility and inflammation across different intestinal segments in IBD., (Copyright © 2024. Published by Elsevier Inc.)

Fetal undernutrition establishes the foundations for hypertension development, with oxidative stress being a key hallmark. A growing interest in nutraceuticals for treating hypertension and environmental waste concerns prompted the present study aiming to evaluate whether supplementation with a polyphenol enriched extract from cocoa shell (CSE), a by-product from the chocolate industry with antioxidant properties, reduces hypertension of developmental origin, thus improving mesenteric resistance artery (MRA) vasodilatation. Adult male and female offspring from rats exposed to 50% food restriction from mid-gestation (maternal undernutrition, MUN) and controls were used. Supplementation was given through a gelatine (vehicle, VEH) or containing CSE (250 mg kg -1  day -1 ) 5 days week -1 for 3 weeks. Systolic blood pressure (SBP) was assessed by tail-cuff plethysmography. MRA function was studied by wire myography, and superoxide anion and nitric oxide were investigated by fluorescent indicators and confocal microscopy. Compared to control-VEH, MUN-VEH males showed significantly higher SBP, reduced MRA as well as relaxation to ACh, sodium nitroprusside and the AMPK agonist 5-aminoimidazole-4-carboxamide riboside, but not to isoproterenol. In MUN males, endothelial endothelium-derived hyperpolarizing factor and nitric oxide were unaltered, but MRA released a vasoconstrictor prostanoid and produced higher levels of superoxide anion. CSE normalized blood pressure and improved all above-mentioned MRA alterations in MUN males without an effect on control counterparts, except the reduction of superoxide anion. MUN-VEH females were normotensive and only showed a tendency towards larger superoxide anion production, which was abolished by CSE. CSE supplementation reduces SBP improving endothelium-dependent and independent MRA vasodilatation, related to local superoxide anion reduction, being a potential nutraceutical ingredient to counteract hypertension, in addition to contributing to the circular economy. KEY POINTS: Fetal undernutrition induces hypertension in males associated with deficient resistance artery vasodilatation, being normalized by cocoa shell extract (CSE). Release of a cyclooxygenase-derived contractile factor is the main endothelial alteration, which is abolished by CSE. AMPK and soluble guanylyl cyclase-mediated relaxation are also reduced in smooth muscle cells from maternal undernutrition resistance arteries, being improved by CSE. Vascular oxidative damage caused by excess superoxide anion generation can account for impaired vasodilatation, which is improved by CSE. The capacity of CSE to improve relaxation is probably related to its antioxidant bioactive factors, and thus cocoa shell is a potential food by-product to treat hypertension., (© 2024 The Author(s). The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Background/Objectives : Resources to cope with maternity and women's participation are essential modulators of maternal well-being. Therefore, it is relevant that the psychosocial factors of woman be monitored during maternity to promote adequate healthcare. This study involved the design and the validation of two new tools that identify women's knowledge of healthcare rights (MatCODE) and perception of resource scarcity (MatER) during pregnancy, labor and early postpartum; Methods : The content validity was carried out using the Aiken's V coefficient and the content validity index (CVI-i) based on five experts. In addition, for the face validity, the pilot cohort was considered the INFLESZ scale. Finally, the questionnaires were applied to 185 women, which allowed to assess the construct validation by factorial and Rasch analysis. The divergent validity was also studied with validated psychological questionnaires; Results : MatCODE and MatER questionnaires received CVI-i and Aiken's V > 0.80 values, and the INFLESZ demonstrated acceptable semantic understanding. The analysis confirms the unidimensionality of the questionnaires, with fit values for MatCODE of RMSEA = 0.113 [0.105; 0.122] and for MatER of RMSEA = 0.067 [0.063; 0.072]. The divergent validity showed significant and consistent correlations with the constructs assessed. For MatCODE, ω = 0.95 and α = 0.94, and for MatER, ω = 0.79 and α = 0.78; Conclusions : MatCODE and MatER are useful new tools for monitoring maternal healthcare, with adequate psychometric characteristics in the Spanish context.

Maternal obesity has been shown to impair the oxidative status in the placenta and newborns, potentially leading to adverse pregnancy outcomes and long-term effects on the programming of offspring metabolic status. This study aimed to investigate the impact of maternal obesity on maternal and umbilical cord plasma oxidative status, as well as placental oxidative adaptation. Maternal obesity ( n = 20), defined as a pre-pregnancy BMI ≥ 25 kg/m 2 , and maternal leanness ( n = 20), defined as a pre-pregnancy BMI < 23 kg/m 2 , were the group categories used in this study. Both groups were matched according to gestational age at delivery. Maternal blood, umbilical cord blood, and placental tissue were collected to assess nutritional content (cholesterol, triglyceride, and protein), oxidative stress markers (MDA and protein carbonyl), and antioxidant activity (SOD and catalase). Placental protein expression (SOD2, catalase, UCP2, and Nrf2) was evaluated using Western blot analysis. Catalase activity in maternal plasma significantly increased in the maternal obesity group ( p = 0.0200), with a trend toward increased MDA and protein carbonyl levels. In umbilical cord plasma, triglyceride, protein carbonyl, and catalase activity were significantly elevated in the maternal obesity group compared with the lean controls ( p = 0.0482, 0.0291, and 0.0347, respectively). Placental protein expression analysis revealed significantly decreased SOD2 ( p = 0.0011) and catalase ( p < 0.0001), along with Nrf2 downregulation ( p < 0.0001). An increase in mitochondrial antioxidant UCP2 expression was observed ( p = 0.0117). The neonatal protein carbonyl levels positively correlated with placental protein carbonyl (r = 0.7405, p < 0.0001) and negatively correlated with maternal catalase activity (r = -0.4332, p = 0.0052). This study thus provides evidence that maternal obesity is associated with placental and fetal oxidative stress, alongside a concurrent increase in placental antioxidant UCP2 expression.

An aortic aneurysm (AA) is a life-threatening condition. Oxidative stress may be a common pathway linking multiple mechanisms of an AA, including vascular inflammation and metalloproteinase activity. Endovascular aneurysm repair (EVAR) is the preferred surgical approach for AA treatment. During surgery, inflammation and ischemia-reperfusion injury occur, and reactive oxygen species (ROS) play a key role in their modulation. Increased perioperative oxidative stress is associated with higher postoperative complications. The use of volatile anesthetics during surgery has been shown to reduce oxidative stress. Individual biomarkers only partially reflect the oxidative status of the patients. A global indicator of oxidative stress (OXY-SCORE) has been validated in various pathologies. This study aimed to compare the effects of the main volatile anesthetics, sevoflurane and desflurane, on oxidative status during EVAR. Eighty consecutive patients undergoing EVAR were randomized into two groups: sevoflurane and desflurane. Plasma biomarkers of oxidative damage (protein carbonylation and malondialdehyde) and antioxidant defense (total thiols, glutathione, nitrates, superoxide dismutase, and catalase activity) were measured before surgery and 24 h after EVAR. The analysis of individual biomarkers showed no significant differences between the groups. However, the OXY-SCORE was positive in the desflurane group (indicating a shift towards antioxidants) and negative in the sevoflurane group (favoring oxidants) ( p < 0.044). Compared to sevoflurane, desflurane had a positive effect on oxidative stress during EVAR. The OXY-SCORE could provide a more comprehensive perspective on oxidative stress in this patient population.

The coffee pulp, a significant by-product of coffee processing, is often discarded but has potential for recycling and high-value uses. This study aimed to investigate the chemical composition of two coffee pulp ingredients, a flour (CPF) and an aqueous extract (CPE), and conducted acute and sub-chronic toxicity assays to determine their safety. The proximate composition revealed the high fiber content of both ingredients; the CPF mainly contained insoluble fiber, while CPE consisted exclusively of soluble pectic polysaccharides. The CPF had higher concentrations of amino acids and a better balance of essential/non-essential amino acids, whereas the CPE exhibited higher concentrations of free amino acids, ensuring higher bioavailability. Both ingredients showed elevated mineral content, while heavy-metal concentrations remained within acceptable limits. This study established the bioactive potential of the CPF and the CPE, demonstrating the high content of caffeine and gallic, protocatechuic, and 4-caffeoylquinic acids. The toxicity studies revealed that the CPF and the CPE exhibited safety when orally administered to mice. Administered doses were non-toxic, as they did not induce lethality or adverse effects in the mice or produce significant histopathological or biochemical adverse changes. This study represents a first step in valorizing the CPF and the CPE as safe novel food ingredients with health benefits for functional and nutritional foods.

Dendritic cells (DCs) play a crucial role in orchestrating immune responses, particularly in promoting IFNγ-producing-CD8 cytotoxic T lymphocytes (CTLs) and IFNγ-producing-CD4 T helper 1 (Th1) cells, which are essential for defending against viral infections. Additionally, the nuclear envelope protein lamin A/C has been implicated in T cell immunity. Nevertheless, the intricate interplay between innate and adaptive immunity in response to viral infections, particularly the role of lamin A/C in DC functions within this context, remains poorly understood. In this study, we demonstrate that mice lacking lamin A/C in myeloid LysM promoter-expressing cells exhibit a reduced capacity to induce Th1 and CD8 CTL responses, leading to impaired clearance of acute primary Vaccinia virus (VACV) infection. Remarkably, in vitro-generated granulocyte macrophage colony-stimulating factor bone marrow-derived DCs (GM-CSF BMDCs) show high levels of lamin A/C. Lamin A/C absence on GM-CSF BMDCs does not affect the expression of costimulatory molecules on the cell membrane but it reduces the cellular ability to form immunological synapses with naïve CD4 T cells. Lamin A/C deletion induces alterations in NFκB nuclear localization, thereby influencing NF-κB-dependent transcription. Furthermore, lamin A/C ablation modifies the gene accessibility of BMDCs, predisposing these cells to mount a less effective antiviral response upon TLR stimulation. This study highlights the critical role of DCs in interacting with CD4 T cells during antiviral responses and proposes some mechanisms through which lamin A/C may modulate DC function via gene accessibility and transcriptional regulation., (© 2024. The Author(s).)

The fulfillment of rights to maternal healthcare is a key factor for the wellbeing of women. However, there is a lack of an instrument to ascertain the experience of women during maternity to enable adequate monitoring. The aim of this study was to validate a new instrument to measure women's perception of the fulfillment of rights during healthcare in pregnancy and childbirth and immediately postpartum. The initial version of the instrument consists of 50 items and was validated using exploratory factor analysis. Additionally, the final version of the instrument consists of 29 items and was validated by confirmatory factor analysis and known-group validity. The instrument was applied to 185 Spanish women. The global Aiken's V of the initial instrument proposal was 0.89. The process resulted in an instrument with five factors (information, privacy, consent, support, and participation) that explained the 60% of the total variance. The score of the instrument was correlated with resilience, maternity beliefs, and positive and negative affect. External validation showed relations with age, gravida, and the number of times a woman has been in labor. Additionally, the Cronbach's α reliability was 0.93 [0.91; 0.94]. In conclusion, the instrument developed is consistent and has appropriate psychometric properties for assessing the fulfillment rights of maternity healthcare.

Introduction: Introduction: breastfeeding women often cannot adequately follow dietary and healthy habits recommendations. In addition, after delivery, their care is usually focused on the newborn and the mother´s health may be neglected. The Mediterranean Diet is the standard of healthy eating, with the Healthy Food Pyramid (HFP) being its graphic representation. Objective: the aim of this study was to determine whether a nutritional and lifestyle online intervention may improve HFP adherence in breastfeeding women. Methods: a total of 181 breastfeeding women in the first sixth months postpartum were enrolled in a non-randomized interventional pilot study. These women answered three questionnaires: sociodemographic and for adherence to Healthy Food Pyramid (APQ), before and after an online intervention for 13 weeks, providing information about nutrition and healthy habits. The APQ ranges from 0 to 10, with higher scores corresponding to greater adherence to HFP. The intervention consisted of lifestyle and nutritional information, which was provided through e-mail. Results: a low adherence to HFP was found, which was improved after 13 weeks of intervention. The online intervention significantly increased the scores for physical activity, grain, seeds and legumes consumption, olive oil use, dairy products, and ani-mal proteins, as well as the HFP adherence global score. The adjusted models showed that the online intervention was associated with adherence to the HFP and physical activity. Conclusion: we conclude that an online intervention for breastfeeding women had an impact on their lifestyle, improving nutritional and healthy habits, and can be a useful tool to monitor their health status. Given the importance of this stage for women and their newborns, this is an aspect postnatal healthcare professionals should consider.

Background: Adverse environmental conditions during intrauterine life, known as fetal programming, significantly contribute to the development of diseases in adulthood. Fetal programming induced by factors like maternal undernutrition leads to low birth weight and increases the risk of cardiometabolic diseases., Methods: We studied a rat model of maternal undernutrition during gestation (MUN) to investigate gene expression changes in cardiac tissue using RNA-sequencing of day 0-1 litters. Moreover, we analyzed the impact of lactation at day 21, in MUN model and cross-fostering experiments, on cardiac structure and function assessed by transthoracic echocardiography, and gene expression changes though qPCR., Results: Our analysis identified specific genes with altered expression in MUN rats at birth. Two of them, Agt and Pparg, stand out for being associated with cardiac hypertrophy and fibrosis. At the end of the lactation period, MUN males showed increased expression of Agt and decreased expression of Pparg, correlating with cardiac hypertrophy. Cross-fostering experiments revealed that lactation with control breastmilk mitigated these expression changes reducing cardiac hypertrophy in MUN males., Conclusions: Our findings highlight the interplay between fetal programming, gene expression, and cardiac hypertrophy suggesting that lactation period is a potential intervention window to mitigate the effects of fetal programming., Impact: Heart remodeling involves the alteration of several groups of genes and lactation period plays a key role in establishing gene expression modification caused by fetal programming. We could identify expression changes of relevant genes in cardiac tissue induced by undernutrition during fetal life. We expose the contribution of the lactation period in modulating the expression of Agt and Pparg, relevant genes associated with cardiac hypertrophy. This evidence reveal lactation as a crucial intervention window for preventing or countering fetal programming., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Women with twin pregnancies experience greater sleep disturbance compared to women with singleton pregnancies. The aims of this study were to explore the sleep quality in women with twin pregnancies and to compare their sleep dimensions with coetaneous single pregnancies. This was an observational study in which women were enrolled at the end of pregnancy in the Obstetric Service of Hospital La Paz (Spain). The women were classified as single ( n = 143) or twin pregnancy ( n = 62). Pregnant women responded to the Pittsburgh Sleep Quality Index to evaluate sleep quality, latency, duration, efficiency, perturbance, use of medication, and daytime dysfunction. The higher the index, the greater the alteration of sleep quality. Without statistical differences, a poor sleep quality was higher in women with single (66.7%) than women with twin pregnancies (22.8%). The good sleeper slept 6.8 h/day in single pregnancy and 7.3 h/day in twin pregnancy. The sleep perturbation and dysfunctionality were higher in women with twin than single pregnancies. The use of medication to sleep was significantly lower in women with twin than single pregnancies. In women with twin pregnancy, the body weight gain during first trimester had a positive correlation with worse sleep quality and sleep perturbations. Twin pregnancy needed more than 7 h/day to have a high sleep quality, showing greater sleep perturbations and daytime dysfunction than single pregnancies. The control of gestational body weight can improve the sleep quality, disturbances, and duration in twin gestations. Sleep screening during pregnancy would be necessary to handle sleep issues and increase benefits in twin gestational outcomes.

Postpartum depression (PPD) and post-traumatic stress disorder (PTSD) continue to be prevalent, and disabling women with mental disorders and obstetric violence (OV) may be a trigger for them, particularly during maternity. We aimed to analyze the association between manifestations of OV with the development of PPD and PTSD during pregnancy, childbirth, and postpartum. This systematic review was based on the PRISMA 2020 statement and explored original articles published between 2012 and 2022. A total of 21 articles were included in the analysis, and bias was assessed by the Effective Public Health Practice Project's Quality Assessment Tool. The highest rate of PPD symptoms appeared in women under 20 years old, multiparous, and with low education levels. The higher PTSD ratio was present in women under 35 years, primiparous, and with secondary studies. The mode of labor (instrumental or C-section) was identified as a major risk factor of PPD, being mediator variables of the informal coercion of health professionals and dissatisfaction with newborn healthcare. Instead, partner support during labor and high satisfaction with healthcare during birth were protective factors. Regarding PTSD, the mode of labor, several perineal tears, and the Kristeller technique were risk factors, and loss of autonomy and coercion modulated PTSD symptomatology. The protective factors for PTSD were respect for the labor plan, adequate communication with health professionals, social support during labor, and the skin-to-skin procedure. This systematic review provides evidence that OV contributes to PPD and PTSD, being important in developing standardized tools to prevent it. This study recommends changes in maternal healthcare policies, such as individualized healthcare assistance, humanized pregnancy protocols, and women's mental health follow-up, and improvements in the methodological quality of future research.

Cocoa shell is a by-product of cocoa manufacturing. We obtained an aqueous extract (CSE) rich in polyphenols and methylxanthines with antioxidant and vasodilatory properties. We aimed to evaluate the effects of CSE supplementation in aged hypertensive rats on blood pressure and the mechanism implicated. Eighteen-month-old male and female rats exposed to undernutrition during the fetal period who developed hypertension, with a milder form in females, were used (MUN rats). Systolic blood pressure (SBP; tail-cuff plethysmography) and a blood sample were obtained before (basal) and after CSE supplementation (250 mg/kg; 2 weeks, 5 days/week). Plasma SOD, catalase activity, GSH, carbonyls, and lipid peroxidation were assessed (spectrophotometry). In hearts and aortas from supplemented and non-supplemented age-matched rats, we evaluated the protein expression of SOD-2, catalase, HO-1, UCP-2, total and phosphorylated Nrf2 and e-NOS (Western blot), and aorta media thickness (confocal microscopy). MUN males had higher SBP compared with females, which was reduced via CSE supplementation with a significant difference for group, sex, and interaction effect. After supplementation with plasma, GSH, but not catalase or SOD, was elevated in males and females. Compared with non-supplemented rats, CSE-supplemented males and females exhibited increased aorta e-NOS and Nrf2 protein expression and cardiac phosphorylated-Nrf2, without changes in SOD-2, catalase, HO-1, or UCP-2 in cardiovascular tissues or aorta remodeling. In conclusion, CSE supplementation induces antihypertensive actions related to the upregulation of e-NOS and Nrf2 expression and GSH elevation and a possible direct antioxidant effect of CSE bioactive components. Two weeks of supplementation may be insufficient to increase antioxidant enzyme expression.

Fetal undernutrition predisposes to hypertension development. Since nitric oxide (NO) is a key factor in blood pressure control, we aimed to investigate the role of NO alterations in hypertension induced by fetal undernutrition in rats. Male and female offspring from dams exposed to undernutrition during the second half of gestation (MUN) were studied at 21 days (normotensive) and 6 months of age (hypertension developed only in males). In aorta, we analyzed total and phosphorylated endothelial NO synthase (eNOS, p-eNOS), 3-nitrotyrosine (3-NT), and Nrf2 (Western blot). In plasma we assessed L-arginine, asymmetric and symmetric dimethylarginine (ADMA, SDMA; LC-MS/MS), nitrates (NOx, Griess reaction), carbonyl groups, and lipid peroxidation (spectrophotometry). In iliac arteries, we studied superoxide anion production (DHE staining, confocal microscopy) and vasodilatation to acetylcholine (isometric tension). Twenty-one-day-old MUN offspring did not show alterations in vascular e-NOS or 3NT expression, plasma L-Arg/ADMA ratio, or NOx. Compared to control group, 6-month-old MUN rats showed increased aortic expression of p-eNOS/eNOS and 3-NT, being Nrf2 expression lower, elevated plasma L-arginine/ADMA, NOx and carbonyl levels, increased iliac artery DHE staining and reduced acetylcholine-mediated relaxations. These alterations in MUN rats were sex-dependent, affecting males. However, females showed some signs of endothelial dysfunction. We conclude that increased NO production in the context of a pro-oxidative environment, leads to vascular nitrosative damage and dysfunction, which can participate in hypertension development in MUN males. Females show a better adaptation, but signs of endothelial dysfunction, which can explain hypertension in ageing., (© 2023. The Author(s).)

Coffee and cocoa manufacturing produces large amounts of waste. Generated by-products contain bioactive compounds with antioxidant and anti-inflammatory properties, suitable for treating metabolic syndrome (MetS). We aimed to compare the efficacy of aqueous extracts and flours from coffee pulp (CfPulp-E, CfPulp-F) and cocoa shell (CcShell-E, CcShell-F) to ameliorate MetS alterations induced by a high-fat diet (HFD). Bioactive component content was assessed by HPLC/MS. C57BL/6 female mice were fed for 6 weeks with HFD followed by 6 weeks with HFD plus supplementation with one of the ingredients (500 mg/kg/day, 5 days/week), and compared to non-supplemented HFD and Control group fed with regular chow. Body weight, adipocyte size and browning (Mitotracker, confocal microscopy), plasma glycemia (basal, glucose tolerance test-area under the curve, GTT-AUC), lipid profile, and leptin were compared between groups. Cocoa shell ingredients had mainly caffeine, theobromine, protocatechuic acid, and flavan-3-ols. Coffee pulp showed a high content in caffeine, protocatechuic, and chlorogenic acids. Compared to Control mice, HFD group showed alterations in all parameters. Compared to HFD, CcShell-F significantly reduced adipocyte size, increased browning and high-density lipoprotein cholesterol (HDL), and normalized basal glycemia, while CcShell-E only increased HDL. Both coffee pulp ingredients normalized adipocyte size, basal glycemia, and GTT-AUC. Additionally, CfPulp-E improved hyperleptinemia, reduced triglycerides, and slowed weight gain, and CfPulp-F increased HDL. In conclusion, coffee pulp ingredients showed a better efficacy against MetS, likely due to the synergic effect of caffeine, protocatechuic, and chlorogenic acids. Since coffee pulp is already approved as a food ingredient, this by-product could be used in humans to treat obesity-related MetS alterations.

Drug safety and efficacy studies frequently use oral gavage, but repetitive usage may cause problems. Administration through voluntary ingestion represents an opportunity for refinement. We aimed to develop a protocol for voluntary ingestion of gelatin-based supplements in rats, assessing the influence of age, sex, fasting (4 h), and additives (vanilla, VF; sucralose, S), and to test it in lactating dams. Three-week-old and 5-month-old Sprague-Dawley rats were placed individually in an empty cage containing a gelatin cube and trained daily (5 days/week), recording the day the whole cube was consumed (latency). Rats trained prior to gestation were offered a gelatin containing 250 mg/kg cocoa shell extract (CSE) during lactation. Rats that did not eat the cube after 8 training days were considered non-habituated, with a proportion similar in young males (7.1%), young females (11.1%), and adult females (10.3%), but significantly higher in adult males (39.3%). Excluding non-habituated rats, latency was 2-3 days, without differences between young and adult rats ( p = 0.657) or between males and females ( p = 0.189). VF or VF + S in the gelatin did not modify latency, while fasting significantly reduced it in females ( p = 0.007) but not in males ( p = 0.501). During lactation, trained females ate the CSE-gelatin within 1-5 min without litter problems. Conclusions: Acceptance of a gelatin-based supplement is negatively influenced by male sex, facilitated by fasting, and not modified by additives. Training is remembered after 2 months and does not interfere with lactation. Gelatin-based voluntary ingestion is suitable to administer drugs that need to pass through the digestive system, ensuring adequate dosage, and is important to detect non-habituated rats prior to the study. The current protocol may be implemented by training the rats in their own cage.

Hypobaric hypoxia under chromic conditions triggers hypoxic pulmonary vasoconstriction (HPV) and right ventricular hypertrophy (RVH). The role of zinc (Zn) under hypoxia is controversial and remains unclear. We evaluated the effect of Zn supplementation in prolonged hypobaric hypoxia on HIF2α/MTF-1/MT/ZIP12/PKCε pathway in the lung and RVH. Wistar rats were exposed to hypobaric hypoxia for 30 days and randomly allocated into three groups: chronic hypoxia (CH); intermittent hypoxia (2 days hypoxia/2 days normoxia; CIH); and normoxia (sea level control; NX). Each group was subdivided (n = 8) to receive either 1% Zn sulfate solution (z) or saline (s) intraperitoneally. Body weight, hemoglobin, and RVH were measured. Zn levels were evaluated in plasma and lung tissue. Additionally, the lipid peroxidation levels, HIF2α/MTF-1/MT/ZIP12/PKCε protein expression and pulmonary artery remodeling were measured in the lung. The CIH and CH groups showed decreased plasma Zn and body weight and increased hemoglobin, RVH, and vascular remodeling; the CH group also showed increased lipid peroxidation. Zn administration under hypobaric hypoxia upregulated the HIF2α/MTF-1/MT/ZIP12/PKCε pathway and increased RVH in the intermittent zinc group. Under intermittent hypobaric hypoxia, Zn dysregulation could participate in RVH development through alterations in the pulmonary HIF2α/MTF1/MT/ZIP12/PKCε pathway.

Breast milk (BM) cytokines support and modulate infant immunity, being particularly relevant in premature neonates with adverse outcomes (NAO). This study aimed to examine, in a cohort of Spanish breastfeeding women, changes in BM cytokines in the first month of lactation, their modulation by neonatal factors (sex, gestational age, and NAO), maternal factors (obstetric complications, C-section, and diet), and their relationship with oxidative status. Sixty-three mother-neonate dyads were studied at days 7 and 28 of lactation. Dietary habits were assessed by a 72-h dietary recall, and the maternal dietary inflammatory index (mDII) was calculated. BM cytokines (IL-10, IL-13, IL-8, MCP-1, and TNFα) were assessed by ultra-sensitive chemiluminescence. Total antioxidant capacity was assessed by the ABTS method and lipid peroxidation by the MDA+HNE kit. From days 7 to 28 of lactation, the levels of IL-10 and TNFα remained stable, while IL-13 increased (β = 0.85 ± 0.12, p < 0.001) and IL-8 and MCP-1 levels decreased (β = -0.64 ± 0.27, p = 0.019; β = -0.98 ± 0.22, p < 0.001; respectively). Antioxidant capacity and lipid peroxidation also decrease during lactation. Neonatal sex did not influence any of the cytokines, but BM from mothers with male infants had a higher antioxidant capacity. Gestational age was associated with male sex and NAO, being inversely correlated with the BM proinflammatory cytokines IL-8, MCP-1, and TNFα. From days 7 to 28 of lactation, BM from women with NAO infants increased MCP-1 levels and had a larger drop in antioxidant capacity, with the opposite trend in lipid peroxidation. MCP-1 was also significantly higher in women undergoing C-section; this cytokine declined in women who decreased mDII during lactation, while IL-10 increased. Linear mixed regression models evidenced that the most important factors modulating BM cytokines were lactation period and gestational age. In conclusion, during the first month of lactation, BM cytokines shift towards an anti-inflammatory profile, influenced mainly by prematurity. BM MCP-1 is associated with maternal and neonatal inflammatory processes.

Introduction: Preterm birth is associated with altered growth patterns and an increased risk of cardiometabolic diseases, with breast milk (BM) being a counteracting factor. Preterm infants also show alterations in adipokines and gut hormones influencing appetite and metabolism. Since these hormones are present in BM, it is possible that their levels may equilibrate deficiencies improving infant growth. We aimed to assess 1) the BM levels of ghrelin, resistin, leptin, insulin, peptide YY, and the gastrointestinal peptide in women with preterm and term labor; 2) the relationship between BM hormones and neonatal growth; and 3) the influence of maternal body composition and diet on these BM hormones., Methods: BM from 48 women (30 term and 18 preterm labor) was collected at days 7, 14, and 28 of lactation. Maternal body composition was evaluated by bioimpedance, and neonate anthropometric parameters were collected from medical records. The maternal dietary pattern was assessed by a 72-h dietary recall at days 7 and 28 of lactation. BM hormones were analyzed by the U-Plex Ultra-sensitive method. Data were analyzed using linear regression models. BM from women with preterm labor had lower ghrelin levels, with the other hormones being significantly higher compared to women with term delivery., Results: In premature infants, growth was positively associated with BM ghrelin, while, in term infants, it was positively associated with insulin and negatively with peptide YY. In the first week of lactation, women with preterm labor had higher body fat compared to women with term labor. In this group, ghrelin levels were positively associated with maternal body fat and with fiber and protein intake. In women with term labor, no associations between anthropometric parameters and BM hormones were found, and fiber intake was negatively associated with peptide YY., Discussion: Preterm labor is a factor influencing the levels of BM adipokines and gut hormones, with BM ghrelin being a relevant hormone for premature infant growth. Since ghrelin is lower in BM from women with preterm labor and the levels are associated with maternal fat storage and some dietary components, our data support the importance to monitor diet and body composition in women who gave birth prematurely to improve the BM hormonal status., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ramiro-Cortijo, Singh, Herranz Carrillo, Gila-Díaz, Martín-Cabrejas, Martin and Arribas.)

In lactating women, breast milk (BM) fatty acids may come from the diet or stored adipose tissue. Our objective was to evaluate the influence of the adherence to the healthy food pyramid (HFP), the dietary pattern in the Mediterranean region, and the maternal body composition on the BM fatty acids pattern. Fifty breastfeeding women answered a socioeconomic survey and the adherence to the HFP questionnaire (AP-Q). In addition, they provided a BM sample at 7 ± 1, 14 ± 1, and 28 ± 1 days postpartum. The body's composition was analyzed at days 7 and 28 by bioimpedance. The BM fatty acids were analyzed by gas chromatography-mass spectroscopy. We found a negative association between the consumption of olive oil and the BM palmitic acid levels (β = -3.19 ± 1.40; p = 0.030), and the intake of cereals and legumes was positively associated with the BM saturated fatty acids (β = 11.48 ± 3.87; p = 0.005). The intake of proteins and vegetables was positively associated with the omega-3 fatty acids and negatively with the omega-6:omega-3 ratio in BM. A negative association between the maternal age (β = -0.43 ± 0.11; p = 0.001) and the α-linolenic acid (ALA) levels was observed, being overall AP-Q positively associated with the ALA levels (β = 0.39 ± 0.15; p = 0.016). Physical activity reduced both the omega-3 and omega-6 fatty acids in BM. Diet had a larger influence than the maternal body's composition on BM fatty acids during the first month of lactation, demonstrating a better adherence to the HFP and positively impacting on the omega-3 content in BM, a fact that is modulated by one's maternal age.

We previously observed that esmolol treatment for 48 h reduced vascular lesions in spontaneously hypertensive rats (SHRs). Therefore, we investigated whether this beneficial effect is persistent after withdrawal. Fourteen-month-old SHRs (SHR-Es) were treated with esmolol (300 μg/kg/min) or a vehicle for 48 h. Two separate groups were also given identical treatment, but they were then monitored for a further 1 week and 1 month after drug withdrawal. We analyzed the geometry and composition of the coronary artery, vascular reactivity and plasma redox status. Esmolol significantly decreased wall thickness (medial layer thickness and cell count), external diameter and cross-sectional area of the artery, and this effect persisted 1 month after drug withdrawal. Esmolol significantly improved endothelium-dependent relaxation by ACh (10 -9 -10 -4 mol/L); this effect persisted 1 week (10 -9 -10 -4 mol/L) and 1 month (10 -6 -10 -4 mol/L) after withdrawal. Esmolol reduced the contraction induced by 5-HT (3 × 10 -8 -3 × 10 -5 mol/L), and this effect persisted 1 week after withdrawal (10 -6 -3 × 10 -5 mol/L). Esmolol increased nitrates and reduced glutathione, and it decreased malondialdehyde and carbonyls; this enhancement was maintained 1 month after withdrawal. This study shows that the effect of esmolol on coronary remodeling is persistent after treatment withdrawal in SHRs, and the improvement in plasma oxidative status can be implicated in this effect.

Low birth weight (LBW) and accelerated growth during lactation are associated with cardiometabolic disease development. LBW offspring from rats exposed to undernutrition during gestation (MUN) develops hypertension. In this rat model, we tested if slower postnatal growth improves early cardiometabolic alterations. MUN dams were fed ad libitum during gestation days 1-10, with 50% of the daily intake during days 11-21 and ad libitum during lactation. Control dams were always fed ad libitum. Pups were maintained with their own mother or cross-fostered. Body weight and length were recorded weekly, and breastmilk was obtained. At weaning, the heart was evaluated by echocardiography, and aorta structure and adipocytes in white perivascular fat were studied by confocal microscopy (size, % beige-adipocytes by Mitotracker staining). Breastmilk protein and fat content were not significantly different between groups. Compared to controls, MUN males significantly accelerated body weight gain during the exclusive lactation period (days 1-14) while females accelerated during the last week; length growth was slower in MUN rats from both sexes. By weaning, MUN males, but not females, showed reduced diastolic function and hypertrophy in the heart, aorta, and adipocytes; the percentage of beige-type adipocytes was smaller in MUN males and females. Fostering MUN offspring on control dams significantly reduced weight gain rate, cardiovascular, and fat hypertrophy, increasing beige-adipocyte proportion. Control offspring nursed by MUN mothers reduced body growth gain, without cardiovascular modifications. In conclusion, slower growth during lactation can rescue early cardiovascular alterations induced by fetal undernutrition. Exclusive lactation was a key period, despite no modifications in breastmilk macronutrients, suggesting the role of bioactive components. Our data support that lactation is a key period to counteract cardiometabolic disease programming in LBW and a potential intervention window for the mother.

Sleep, mental health and physical activity are fundamental for wellbeing, and some of these factors are interrelated. However, these aspects are not usually considered during pregnancy and lactation, which are particularly vulnerable periods. Therefore, our aims were to conduct a cross sectional study to assess the psychological capital, quality of life, sleep hygiene and physical activity in a cohort of women during pregnancy and lactation periods. Women were recruited from Spanish maternity and lactation non-profit associations and social networks through an online platform with the following inclusion criteria: pregnancy (in any period of gestation) or breastfeeding period (≤6 months postpartum). The cohort was categorized into ≤12 weeks of gestation (n = 32), >12 weeks of gestation (n = 119) and lactation (n = 60). The women self-reported the sociodemographic data, obstetric complications and full breastfeeding or mixed practices. In addition, women responded to the psychological capital instrument, the health survey form, the Pittsburg sleep quality index and the pregnancy physical activity questionnaire. Overall, the groups were similar in sociodemographic variables. Women in the lactation period perceived lower social support compared to the gestation period. No statistically differences were found between groups in the psychological capital nor in the general health survey form. However, the models adjusted by employment and civil and economic status and perceived social support, demonstrated that the sleep duration negatively associated with the lactation period (β = 1.13 ± 0.56; p -Value = 0.016), and the household tasks were associated with this period (β = 2147.3 ± 480.7; p -Value < 0.001). A decrease in physical daily activities were associated with both the end of gestation and the lactation periods. In addition, the decreasing total activity was associated with the lactation period (β = 1683.67 ± 688.05; p -Value = 0.016). In conclusion, during lactation, the poorer sleep and physical activity, together with a lower social support of the woman, may lead to deficient mental health adjustment. Our data suggest that women are at higher risk of vulnerability in lactation compared to the gestation period.

Hypertension is of unknown aetiology, with sympathetic nervous system hyperactivation being one of the possible contributors. Hypertension may have a developmental origin, owing to the exposure to adverse factors during the intrauterine period. Our hypothesis is that sympathetic hyperinnervation may be implicated in hypertension of developmental origins, being this is a common feature with essential hypertension. Two-animal models were used: spontaneously hypertensive rats (SHR-model of essential hypertension) and offspring from dams exposed to undernutrition (MUN-model of developmental hypertension), with their respective controls. In adult males, we assessed systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), sympathetic nerve function ( 3 H-tritium release), sympathetic innervation (immunohistochemistry) and vascular remodelling (histology). MUN showed higher SBP/DBP, but not HR, while SHR exhibited higher SBP/DBP/HR. Regarding the mesenteric arteries, MUN and SHR showed reduced lumen, increased media and adventitial thickness and increased wall/lumen and connective tissue compared to respective controls. Regarding sympathetic nerve activation, MUN and SHR showed higher tritium release compared to controls. Total tritium tissue/tyrosine hydroxylase detection was higher in SHR and MUN adventitia arteries compared to respective controls. In conclusion, sympathetic hyperinnervation may be one of the contributors to vascular remodelling and hypertension in rats exposed to undernutrition during intrauterine life, which is a common feature with spontaneous hypertension., Competing Interests: The authors declare no conflict of interest.

Breast milk (BM) is the best food for newborns. Male sex is associated with a higher risk of fetal programming, prematurity, and adverse postnatal outcome, being that BM is an important health determinant. BM composition is dynamic and modified by several factors, including lactation period, prematurity, maternal nutritional status, and others. This study was designed to evaluate the influence of sex on BM composition during the first month of lactation, focused on macronutrients and antioxidants. Forty-eight breastfeeding women and their fifty-five newborns were recruited at the Hospital Clínico San Carlos (Madrid, Spain). Clinical sociodemographic data and anthropometric parameters were collected. BM samples were obtained at days 7, 14, and 28 of lactation to assess fat (Mojonnier method), protein (Bradford method), and biomarkers of oxidative status: total antioxidant capacity (ABTS and FRAP methods), thiol groups, reduced glutathione, superoxide dismutase and catalase activities, lipid peroxidation, and protein oxidation (spectrophotometric methods). Linear mixed models with random effects adjusted by maternal anthropometry, neonatal Z-scores at birth, and gestational age were used to assess the main effects of sex, lactation period, and their interaction. BM from mothers with male neonates exhibited significantly higher protein, ABTS, FRAP, and GSH levels, while catalase showed the opposite trend. No differences between sexes were observed in SOD, total thiols, and oxidative damage biomarkers. Most changes were observed on day 7 of lactation. Adjusted models demonstrated a significant association between male sex and proteins (β = 2.70 ± 1.20; p -Value = 0.048). In addition, total antioxidant capacity by ABTS (β = 0.11 ± 0.06) and GSH (β = 1.82 ± 0.94) showed a positive trend near significance ( p -Value = 0.056; p -Value = 0.064, respectively). In conclusion, transitional milk showed sex differences in composition with higher protein and GSH levels in males. This may represent an advantage in the immediate perinatal period, which may help to counteract the worse adaptation of males to adverse intrauterine environments and prematurity.

Hypoxic pulmonary hypertension (HPH) is characterized by sustained elevation of pulmonary artery pressure produced by vasoconstriction and hyperproliferative remodeling of the pulmonary artery and subsequent right ventricular hypertrophy (RVH). The search for therapeutic targets for cardiovascular pathophysiology has extended in many directions. However, studies focused on mitigating high-altitude pulmonary hypertension (HAPH) have been rare. Because AMP-activated protein kinase (AMPK) is involved in cardiovascular and metabolic pathology, AMPK is often studied as a potential therapeutic target. AMPK is best characterized as a sensor of cellular energy that can also restore cellular metabolic homeostasis. However, AMPK has been implicated in other pathways with vasculoprotective effects. Notably, cellular metabolic stress increases the intracellular ADP/ATP or AMP/ATP ratio, and AMPK activation restores ATP levels by activating energy-producing catabolic pathways and inhibiting energy-consuming anabolic pathways, such as cell growth and proliferation pathways, promoting cardiovascular protection. Thus, AMPK activation plays an important role in antiproliferative, antihypertrophic and antioxidant pathways in the pulmonary artery in HPH. However, AMPK plays contradictory roles in promoting HPH development. This review describes the main findings related to AMPK participation in HPH and its potential as a therapeutic target. It also extrapolates known AMPK functions to discuss the less-studied HAPH context.

Cocoa has cardiovascular beneficial effects related to its content of antioxidant phytochemicals. Cocoa manufacturing produces large amounts of waste, but some by-products may be used as ingredients with health-promoting potential. We aimed to investigate the vasoactive actions of an extract from cocoa shell (CSE), a by-product containing theobromine (TH), caffeine (CAF) and protocatechuic acid (PCA) as major phytochemicals. In carotid and iliac arteries from 5-month and 15-month-old rats, we investigated CSE vasoactive properties, mechanism of action, and the capacity of CSE, TH, CAF and PCA to improve age-induced endothelial dysfunction. Vascular function was evaluated using isometric tension recording and superoxide anion production by dihydroethidium (DHE) staining and confocal microscopy. CSE caused endothelium-dependent vasorelaxation, blocked by L-NAME, but not indomethacin, regardless of sex, age, or vessel type. CSE maximal responses and EC 50 were significantly lower compared to acetylcholine (ACh). Arterial preincubation with CSE, TH, CAF or PCA, significantly reduced the number of vascular DHE-positive cells. Compared to adult males, iliac arteries from aged males exhibited reduced ACh concentration-dependent vasodilatation but larger CSE responses. In iliac arteries from aged male and female rats, preincubation with 10 -4 M CSE and PCA, but not TH or CAF, improved ACh-relaxations. In conclusion, CSE has vasodilatory properties associated with increased nitric oxide bioavailability, related to its antioxidant phytochemicals, being particularly relevant PCA. Therefore, CSE is a potential food ingredient for diseases related to endothelial dysfunction.

Fetal stress is known to increase susceptibility to cardiometabolic diseases and hypertension in adult age in a process known as fetal programming. This study investigated the relationship between vascular RAS, oxidative damage and remodeling in fetal programming. Six-month old Sprague-Dawley offspring from mothers that were fed ad libitum (CONTROL) or with 50% intake during the second half of gestation (maternal undernutrition, MUN) were used. qPCR or immunohistochemistry were used to obtain the expression of receptors and enzymes. Plasma levels of carbonyls were measured by spectrophotometry. In mesenteric arteries from MUN rats we detected an upregulation of ACE, ACE2, AT 1 receptors and NADPH oxidase, and lower expression of AT 2 , Mas and MrgD receptors compared to CONTROL. Systolic and diastolic blood pressure and plasma levels of carbonyls were higher in MUN than in CONTROL. Vascular morphology evidenced an increased media/lumen ratio and adventitia/lumen ratio, and more connective tissue in MUN compared to CONTROL. In conclusion, fetal undernutrition indices RAS alterations and oxidative damage which may contribute to the remodeling of mesenteric arteries, and increase the risk of adverse cardiovascular events and hypertension.

Breastfeeding could be considered as a vulnerable period, rising the risk to shift from optimism to pessimism. Preterm delivery is an event that increases postpartum maternal stress and depression, which can have a negative impact on breastfeeding and maternal-filial wellbeing. The adherence to healthy habits may have a positive influence on this vulnerable population. We aimed to analyze the impact of prematurity on maternal psychological aspects during postpartum and to study if adherence to the Healthy Food Pyramid influences psychological variables. Fifty-five breastfeeding women being attended in the Hospital Clínico San Carlos (Madrid, Spain) were recruited during the first day postpartum. The medical data were collected from the obstetrical records. The women answered an auto-administered questionnaire with several sections: sociodemographic characteristics, Perceived Stress Scale (PSS), and Life Orientation Test (LOT), at 14 days and 6 months postpartum, Adherence to the Healthy Food Pyramid Questionnaire (AP-Q) at 28 days postpartum and the Edinburgh Postpartum Depression Scale (EPDS) at 6 months postpartum. The PSS and LOT scores were not statistically different in mothers with preterm compared to term delivery either at 14 days or at 6 months postpartum. Longitudinally, the PSS did not show significant differences, but the LOT score was lower at 6 months compared to 14 days postpartum ( p -Value = 0.046). A higher EPDS score was significantly found in mothers with preterm delivery (9.0 ± 4.7) than those with a term delivery (5.4 ± 4.2; p -value = 0.040). A significant and positive correlation was observed between the AP-Q score and LOT both at 14 days and 6 months postpartum. Conclusively, maternal optimism decreases during the postpartum period, women with preterm delivery being at risk of postpartum depression. Furthermore, there is a relationship between optimism and adherence to healthy habits. Healthcare professional counseling is essential during the entire breastfeeding period, particularly in vulnerable mothers with preterm delivery.

Adolescent pregnancy remains a health issue worldwide also in developed countries, since it has been associated with adverse maternal and neonatal outcomes. Some data suggest that very young adolescents have higher risk, likely due to immaturity. Therefore, we aimed to assess the influence of maternal age on complications during gestation and labor in pregnant women between 13 and 19 years of age. In particular, we evaluated the possible association between maternal age and obstetric, fetal and labor complications. This is a retrospective, observational and exploratory study conducted at Hospital Universitario La Paz (HULP, Madrid, Spain). The clinical history of 279 women who delivered between 2013 and 2018 was analyzed. Maternal age and the presence of maternal, fetal and labor complications, as well as risk of postpartum depression and breastfeeding intention, were recorded. General regression models were used to analyze the contribution of maternal age on each complication. The percentage of adolescent pregnancies at HULP between 2013 and 2018 was 0.9%. The risk of all the maternal complications analyzed decreased significantly with every year of age of the mother (hyperemesis, lower back pain, anemia, gestational diabetes mellitus, and threat of premature labor and premature rupture of membranes). Every year of maternal age decreased 0.8-fold [0.8; 0.9] the prevalence of fetal complications and also reduced the risk of C-section, postpartum hemorrhage and obstetrical hysterectomy. Furthermore, higher maternal age increased 1.1-fold [1.0; 1.2] the breastfeeding intention. In conclusion, young adolescents are at higher risk of complications during pregnancy and labor.

There are numerous dietary recommendations during pregnancy. However, there are limited recommendations during the lactation period, a nutritionally vulnerable period for women. The Mediterranean Diet and adherence to the Healthy Food Pyramid (HFP) is considered as the standard for healthy eating. In this study, we investigated the differences in adherence to the HFP in pregnant, lactating, and non-pregnant/non-lactating (NPNL) women concerning sociodemographic factors. A sociodemographic and nutritional and lifestyle questionnaire (AP-Q) were used to assess adherence to the HFP, including lifestyle. The AP-Q score ranges from 0 to 10 meaning the higher the score, the greater the adherence to the HFP. Lactating women had the lowest AP-Q score (6.13 [5.31; 6.82]) compared to the pregnant (6.39 [5.56; 7.05]) and NPNL women (6.27 [5.43; 6.88]), while pregnant women had the highest scores. Maternal age was positively correlated with AP-Q score in pregnant (rho = 0.22; p -Value < 0.001) and lactating women (rho = 0.18; p -Value < 0.001), but not in NPNL women. Educational level and monthly income had a positive influence on the degree of adherence to the HFP. In conclusion, breastfeeding mothers of young age and low socioeconomic and educational level would be the target population to carry out nutritional interventions that improve their adherence to the HFP. The knowledge gained from this study can help to design recommendation guidelines and nutritional educational interventions for a given population.

Fetal undernutrition is a risk factor for cardiovascular diseases. Male offspring from rats exposed to undernutrition during gestation (MUN) exhibit oxidative stress during perinatal life and develop cardiac dysfunction in ageing. Angiotensin-II is implicated in oxidative stress-mediated cardiovascular fibrosis and remodeling, and lactation is a key developmental window. We aimed to assess if alterations in RAS during lactation participate in cardiac dysfunction associated with fetal undernutrition. Control dams received food ad libitum , and MUN had 50% nutrient restriction during the second half of gestation. Both dams were fed ad libitum during lactation, and male offspring were studied at weaning. We assessed: ventricular structure and function (echocardiography); blood pressure (intra-arterially, anesthetized rats); collagen content and intramyocardial artery structure (Sirius red, Masson Trichromic); myocardial and intramyocardial artery RAS receptors (immunohistochemistry); plasma angiotensin-II (ELISA) and TGF-β1 protein expression (Western Blot). Compared to Control, MUN offspring exhibited significantly higher plasma Angiotensin-II and a larger left ventricular mass, as well as larger intramyocardial artery media/lumen, interstitial collagen and perivascular collagen. In MUN hearts, TGF-β1 tended to be higher, and the end-diastolic diameter and E/A ratio were significantly lower with no differences in ejection fraction or blood pressure. In the myocardium, no differences between groups were detected in AT1, AT2 or Mas receptors, with MrgD being significantly lower in the MUN group. In intramyocardial arteries from MUN rats, AT1 and Mas receptors were significantly elevated, while AT2 and MrgD were lower compared to Control. Conclusions . In rats exposed to fetal undernutrition, RAS disbalance and associated cardiac remodeling during lactation may set the basis for later heart dysfunction.

The first month of lactation is a vulnerable nutritional period for the mother. Our aims were (1) to evaluate the nutritional status of breastfeeding women in the first month of lactation, and (2) to explore different aspects of nutrition and lifestyle through a multidimensional approach. A total of 30 healthy breastfeeding women were enrolled in this study. Dietary pattern was assessed through a 72-hour dietary recall questionnaire (days 7 and 28 postpartum) and data were compared with Dietary Recommendation Values (DRV), and through the Adherence to Healthy Food Pyramid (HFP) questionnaire (day 28). Anthropometric parameters were evaluated by bioimpedance. Using factor analysis, nutritional dimensions were extracted, and linear regression models were used to analyze the association between anthropometric parameters and dimensions. Compared to the DRV, women showed insufficient energy, water, vitamin D, and potassium intake and excessive proteins, vitamins B1, B2, B3, B6, B12, and iron intake. We observed a moderate adherence to the HFP, with women being high in the fruits, vegetables, and oil categories, and low adherence to the physical activity, dairy products, and hydration categories. The nutritional dimension, including the HFP categories of physical activity, hydration, and animal protein intake together, was negatively associated with body weight (β = -3.7 ± 1.7; p -value = 0.047). In conclusion, during the first month postpartum, breastfeeding women exhibited several nutritional imbalances and poor physical activity negatively influencing anthropometric parameters. We propose a multidimensional approach to assess the nutritional status of breastfeeding women as a tool to detect specific deficiencies, allowing for personalized counseling.

Early detection of gestational complications is a priority in obstetrics. In our social context, this is linked to maternity age. Most studies are focused on biological factors. However, pregnancy is also influenced by social and psychological factors, which have not been deeply explored. We aimed to identify biopsychosocial risk and protective factors associated with the development of maternal and fetal complications. We enrolled 182 healthy pregnant women, and plasma melatonin and cortisol levels were measured in the first trimester by chemiluminescent immunoassays. At different time points along gestation, women answered several questionnaires (positive and negative affect schedule, hospital anxiety and depression scale, pregnancy concerns scale, life orientation test, resilience scale, life satisfaction scale and life-work conflicts scale). They were followed up until delivery and categorized as normal pregnancy, maternal or fetal complications. Maternal complications were associated with low melatonin (OR = 0.99 [0.98; 1.00]; p -value = 0.08) and life satisfaction (OR = 0.64 [0.41; 0.93]; p -value = 0.03) and fetal complications were associated with high cortisol (OR = 1.06 [1.02; 1.13]; p -value = 0.04), anxiety (OR = 2.21 [1.10; 4.55]; p -value = 0.03) and life-work conflicts (OR = 1.92 [1.04; 3.75]; p -value = 0.05). We conclude that psychological factors influence pregnancy outcomes in association with melatonin and cortisol alterations. High maternal melatonin and life satisfaction levels could be potential protective factors against the development of maternal complications during pregnancy. Low anxiety and cortisol levels and reduced work-life conflicts could prevent fetal complications.

Cognitive maternal adaptation during pregnancy may influence biological variables, maternal psychological, and neonatal health. We hypothesized that pregnant women with numerous general resources and less negative emotions would have a better coping with a positive influence on neonatal birth weight and maternal psychological health. The study included 131 healthy pregnant women. A blood sample was obtained in the first trimester to assess biological variables (polyphenols, hematological and biochemical parameters). Psychological variables (negative affect, anxiety, optimism, resilience, family-work conflicts, pregnancy concerns, general resources, and life satisfaction) were evaluated at several time points along gestation, and birth weight was recorded. Hierarchical linear regression models were used to associate the above parameters with maternal psychological outcome at the end of gestation (depression, resilience, and optimism) and neonatal outcome (birth weight). Maternal depression was associated with leukocytes (β = 0.08 ± 0.03, p -value = 0.003), cholesterol (β = 0.01 ± 0.002, p -value = 0.026), and pregnancy concerns (β = 0.31 ± 0.09, p -value = 0.001). Maternal resilience was associated with leukocytes (β = -0.14 ± 0.09, p -value = 0.010) and life satisfaction (β = 0.82 ± 0.08, p -value = 0.001), and maternal optimism was associated with polyphenol levels (β = 0.002 ± 0.001, p -value = 0.018) and life satisfaction (β = 0.49 ± 0.04, p -value = 0.001). Birth weight was associated with maternal resilience (β = 370.2 ± 97.0, p -value = 0.001), red blood cells (β = 480.3 ± 144.4, p -value = 0.001), and life satisfaction (β = 423.3 ± 32.6, p -value = 0.001). We found associations between maternal psychological, blood variables, and birth weight and maternal depression. This study reveals the relevance of psychological health during pregnancy for maternal and neonatal outcome, and it emphasizes the need to consider it in preventive policies in the obstetric field.

Fetal undernutrition programs cardiometabolic diseases, with higher susceptibility in males. The mechanisms implicated are not fully understood and may be related to sex differences in placental adaptation. To evaluate this hypothesis, we investigated placental oxidative balance, vascularization, glucocorticoid barrier, and fetal growth in rats exposed to 50% global nutrient restriction from gestation day 11 (MUN, n = 8) and controls ( n = 8). At gestation day 20 (G20), we analyzed maternal, placental, and fetal weights; oxidative damage, antioxidants, corticosterone, and PlGF (placental growth factor, spectrophotometry); and VEGF (vascular endothelial growth factor), 11β-HSD2, p22 phox , XO, SOD1, SOD2, SOD3, catalase, and UCP2 expression (Western blot). Compared with controls, MUN dams exhibited lower weight and plasma proteins and higher corticosterone and catalase without oxidative damage. Control male fetuses were larger than female fetuses. MUN males had higher plasma corticosterone and were smaller than control males, but had similar weight than MUN females. MUN male placenta showed higher XO and lower 11β-HSD2, VEGF, SOD2, catalase, UCP2, and feto-placental ratio than controls. MUN females had similar feto-placental ratio and plasma corticosterone than controls. Female placenta expressed lower XO, 11β-HSD2, and SOD3; similar VEGF, SOD1, SOD2, and UCP2; and higher catalase than controls, being 11β-HSD2 and VEGF higher compared to MUN males. Male placenta has worse adaptation to undernutrition with lower efficiency, associated with oxidative disbalance and reduced vascularization and glucocorticoid barrier. Glucocorticoids and low nutrients may both contribute to programming in MUN males.

Male fetal sex associates with higher rates of materno-fetal complications. Inflammation and inadequate vasoactive responses are mechanisms implicated in obstetric complications, and alterations in maternal plasma cytokine profile and nitric oxide (NO) metabolites are potential predictive biomarkers. We aimed to assess if these parameters are influenced by fetal sex. A prospective, observational study was carried out in 85 healthy pregnant women with singleton pregnancies in the first trimester of gestation. A blood sample was extracted at the tenth week of gestation. In plasma, we assessed: 1) cytokines (micro-array): pro-inflammatory (IL1α, IL1 β, IL6, TNFα), anti-inflammatory (IL4, IL10, IL13), and chemoattractant (IL8, MCP1, IFNγ), and 2) NO metabolites (liquid chromatography-tandem mass spectrometry and Griess reaction): L-arginine, ADMA, SDMA, nitrates (NOx). Women with a male fetus (n = 50) exhibited, compared with those with a female (n = 35): higher IL1β (OR = 1.09 with 95% CI: 0.97-1.28), and lower IL13 (OR = 0.93 with 95% CI: 0.87-0.99), and higher plasma NOx (OR = 1.14 with 95% CI: 1.03-1.31). Our data suggest that fetal sex influences maternal plasma cytokine profile and NO in early pregnancy. Women with a male fetus may have a worse capacity to counteract an inflammatory response. They may have better vasodilator capacity, but in the presence of an oxidative environment, a higher nitrosative damage may occur. These data reinforce the need to include sex as variable in predictive models., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

One of the consequences of high altitude (hypobaric hypoxia) exposure is the development of right ventricular hypertrophy (RVH). One particular type of exposure is long-term chronic intermittent hypobaric hypoxia (CIH); the molecular alterations in RVH in this particular condition are less known. Studies show an important role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex-induced oxidative stress and protein kinase activation in different models of cardiac hypertrophy. The aim was to determine the oxidative level, NADPH oxidase expression and MAPK activation in rats with RVH induced by CIH. Male Wistar rats were randomly subjected to CIH (2 days hypoxia/2 days normoxia; n = 10) and normoxia (NX; n = 10) for 30 days. Hypoxia was simulated with a hypobaric chamber. Measurements in the RV included the following: hypertrophy, Nox2, Nox4, p22phox, LOX-1 and HIF-1α expression, lipid peroxidation and H 2 O 2 concentration, and p38α and Akt activation. All CIH rats developed RVH and showed an upregulation of LOX-1, Nox2 and p22phox and an increase in lipid peroxidation, HIF-1α stabilization and p38α activation. Rats with long-term CIH-induced RVH clearly showed Nox2, p22phox and LOX-1 upregulation and increased lipid peroxidation, HIF-1α stabilization and p38α activation. Therefore, these molecules may be considered new targets in CIH-induced RVH.

Fetal undernutrition programs hypertension and cardiovascular diseases, and resistance artery remodeling may be a contributing factor. We aimed to assess if fetal undernutrition induces resistance artery remodeling and the relationship with hypertension. Sprague-Dawley dams were fed ad libitum (Control) or with 50% of control intake between days 11 and 21 of gestation (maternal undernutrition, MUN). In six-month-old male and female offspring we assessed blood pressure (anesthetized and tail-cuff); mesenteric resistance artery (MRA) structure and mechanics (pressure myography), cellular and internal elastic lamina (IEL) organization (confocal microscopy) and plasma MMP-2 and MMP-9 activity (zymography). Systolic blood pressure (SBP, tail-cuff) and plasma MMP activity were assessed in 18-month-old rats. At the age of six months MUN males exhibited significantly higher blood pressure (anesthetized or tail-cuff) and plasma MMP-9 activity, while MUN females did not exhibit significant differences, compared to sex-matched controls. MRA from 6-month-old MUN males and females showed a smaller diameter, reduced adventitial, smooth muscle cell density and IEL fenestra area, and a leftward shift of stress-strain curves. At the age of eighteen months SBP and MMP-9 activity were higher in both MUN males and females, compared to sex-matched controls. These data suggest that fetal undernutrition induces MRA inward eutrophic remodeling and stiffness in both sexes, independent of blood pressure level. Resistance artery structural and mechanical alterations can participate in the development of hypertension in aged females and may contribute to adverse cardiovascular events associated with low birth weight in both sexes.