1. Investigación

Propósito/Contexto. En este artículo queremos evidenciar la existencia de la invisibilización médica y social producida en torno a las pérdidas embriofetales en madres gestantes. Metodología/Enfoque. Se hace una revisión bibliográfica de carácter narrativo y bioético de publicaciones que analizan específicamente cómo afecta a las madres gestantes el modo de comunicar del personal de salud cuando han de notificar la pérdida de su hijo por complicaciones en el desarrollo embriofetal. Revisamos si en esa comunicación se aplican los principios de la Bioética. Resultados/Hallazgos. Tras el análisis realizado encontramos que, con frecuencia, las madres gestantes que sufren esos abortos naturales, a menudo, experimentan una ausencia de empatía y humanidad en los profesionales de la salud que no cubren adecuadamente –éticamente– la magnitud que supone esa pérdida del hijo en desarrollo. Añadimos que esta situación se agrava por el sentimiento de fracaso y soledad, unido a la tristeza y el duelo por el que transitan. Discusión/Conclusiones/Contribuciones. Realzamos el valor ontológico y humano que le otorgan las madres a la muerte del que consideran su hijo, independientemente del momento del desarrollo en el que se encuentre. La muerte imprevista en las primeras semanas del embarazo no debería quedar reducida a un accidente meramente fisiológico y sin importancia a nivel comunicativo. Concluimos que es necesario asesorar a los profesionales de salud a través de protocolos médicos y éticos que les permitan abordar el cuidado de aquellos pacientes que atraviesan esta situación de perdida embriofetal. Consideramos desde la bioética que, ante estas críticas circunstancias, debería priorizarse el principio de beneficencia, habida cuenta de que una mala comunicación afecta negativamente al bienestar físico y psíquico de estas pacientes.

Two experiments were conducted in the Northern (UK) and Southern (Brazil) hemispheres to determine the effect of season (month of conception) on the development of supplementary CL (SCL) and the relationship with pregnancy loss. In experiment 1, 199 pregnancies were followed between Day 14 and term, to determine the number of SCL and pregnancy viability (Northern Hemisphere). From the 199 pregnancies, 178 were obtained from inseminations during the breeding season (March–September), while the rest, 21 pregnancies resulted from conceptions in the non-breeding season (October to February). Pregnancies conceived in the breeding season were more likely (P < 0.01) to have at least 1 SCL (75.8 %, 135/178) than pregnancies from the non-breeding season (33 %, 7/21). However, the pregnancy loss between Days 35 and 120 of pregnancy in mares with no SCL was similar (3.5 %, 2/57; P >0.1) than from mares with SCL (1.4 %, 2/142). In Experiment 2 (Southern Hemisphere), three groups of recipients were used based on their ovarian activity at the time of embryo transfer: Anestrus (n = 8), transitional (n = 7) and cyclic (n = 7) recipient mares. While all transitional and cyclic mares developed at least 1 SCL, only 50 % of anestrous recipients (4/8) developed SCL by 120 of gestation. In conclusion, the development of SCL in pregnant mares is influenced by the time of season of conception, therefore it appears to be regulated by the photoperiod and the endogenous seasonal variation in gonadotropin concentrations. Mares with no SCL were not at increased risk of pregnancy loss.

During pregnancy, maternal erythropoietic expansion and fetal development require greater mobilization of available iron (Fe) stores. These adjustments in Fe metabolism in humans and rodents are largely mediated by the hormone hepcidin (Hepc), which controls the expression of ferroportin (Fpn), a transporter responsible for exporting Fe from stores to extracellular fluid and plasma. These mechanisms based on the regulation of Hepc on the availability of Fe during gestation in healthy mares remain unknown. The objective of this study was to determine the existence of interrelationships among concentrations of Hepc, ferritin (Ferr), Fe, and estrone (E1) and progesterone (P4) in Spanish Purebred mares along the whole gestation. Blood samples were taken from 31 Spanish Purebred mares each month, during 11 months of pregnancy. Fe and Ferr significantly increased and Hepc decreased during pregnancy (P < 0.05). The secretion peak of estrone (E1) was reached in the 5th month and progesterone (P4) between the 2nd and 3rd months of gestation (P < 0.05). Fe and Ferr were weakly positively correlated (r = 0.57; P < 0.05). Fe and Ferr were negatively correlated with Hepc (r = −0.80 and r = −0.67, respectively) (P < 0.05). P4 was positively correlated with Hepc (r = 0.53; P < 0.05). Pregnancy in the Spanish Purebred mare was characterized by a progressive increase in Fe and Ferr and a reduction in Hepc concentrations. E1 was partially responsible for the suppression of Hepc; on the other hand, P4 induced its stimulation during pregnancy in the mare.

In woman and in animal models, estrogens are involved in iron (Fe) homeostasis supporting the hypothesis of the existence of an “estrogen-iron axis”. Since advancing age leads to a decrease in estrogen levels, the mechanisms of Fe regulation could be compromised. In cyclic and pregnant mares, to date, there is evidence linking the iron state with estrogens pattern. Then, the objective of this study was to determine the relationship among Fe, ferritin (Ferr), hepcidin (Hepc) and estradiol-17β (E2) in cyclic mares with advancing age. A total of 40 Spanish Purebred mares of different ranges of age was analyzed: 4–6 years (n = 10), 7–9 years (n = 10), 10–12 years (n = 10), and >12 years (n = 10). Blood samples were obtained on days −5, 0, +5 and + 16 of the cycle. Compared to mares of 4–6 years, serum Ferr was significantly higher (P < 0.01) and Fe significantly lower (P < 0.01) in mares >12 years of age. Hepc was significantly higher in mares >12 years (P < 0.01) than in those 7–9 years of age. E2 levels were higher in mares of 7–9 years (P < 0.01) than in 4–6 and >12 years of age. Fe and Ferr were negatively correlated with Hepc (r = −0.71 and r = −0.02, respectively). E2 was negatively correlated with Ferr and Hepc (r = −0.28 and r = −0.50, respectively), and positively with Fe (r = 0.31). There is a direct relationship between E2 and Fe metabolism, mediated by the inhibition of Hepc in Spanish Purebred mares. The reduction of E2 decreases the inhibitory effects on Hepc, increasing the levels of stored Fe and mobilizing less the free Fe in circulation. Based on the fact that ovarian estrogens participate in changes in the parameters indicative of iron status with age, the existence of an “estrogen-iron axis” in the mares'estrous cycle could be considered. Future studies are required to clarify these hormonal and metabolic interrelationships in the mare.

Ecological nutrition aims to unravel the extensive web of nutritional links that drives animals in their interactions with their ecological environments. Nutrition plays a key role in the success of European wild rabbit (Oryctolagus cuniculus) and could be affected by the breeding status of the animals and reflected in the metabolome of this species. As nutritional needs are considerably increased during pregnancy and lactation, the main objective of this work was to determine how the breeding status (pregnant and lactating) of European wild rabbit does affects nutritional requirements and their metabolome (using targeted and untargeted metabolomics), aiming to find a useful biomarker of breeding status and for monitoring nutritional requirements. To address this gap, 60 wild European rabbits were studied. Animals were divided according to their breeding status and only pregnant (n = 18) and lactating (n = 11) rabbit does were used (n = 29 in total). The body weight and length of each animal were analyzed. The relative and absolute chemical composition of the gastric content and whole blood sample were taken, and targeted and untargeted metabolomics were analyzed. As a main result, there were no differences in biometric measurements, gastric content, and targeted metabolomics, except for live weight and nonesterified fatty acids (NEFA), as pregnant animals showed higher live weight (+12%; p = 0.0234) and lower NEFA acid levels (−46%; p = 0.0262) than lactating females. Regarding untargeted metabolomics, a good differentiation of the metabolome of the two breeding groups was confirmed, and it was proven that pregnant animals showed higher plasmatic levels of succinic anhydride (3.48 more times; p = 0.0236), succinic acid (succinate) (3.1 more times; p = 0.0068) and propionic acid (3.98 more times; p = 0.0121) than lactating animals. However, lactating animals showed higher levels of N-[(3a,5b,7b)-7-hydroxy-24-oxo-3-(sulfoxide) cholan-24-yl]-Glycine (cholestadien) (2.4 more times; p < 0.0420), 4-maleyl-acetoacetate (MAA) (3.2 more times; p < 0.0364) and irilone (2.2 more times; p = 0.0451) than pregnant animals, any of these metabolites could be used as a potential biomarker. From these results, it can be concluded that the most notable changes were observed in the metabolome of individuals, with most of the changes observed being due to energy and protein mobilisation.

Background: PGF2α is commonly given at the end of embryo flushing (EF) to shorten the interval to the next oestrus and ovulation. Objectives: To determine the effect of repeated EF on plasma progesterone concentration, percentage of mares with endometritis, unwanted pregnancy and subsequent fertility in mares flushed without the use of PGF2α. Study design: Controlled experiments. Methods: Nine mares were inseminated in seven consecutive cycles (n = 63), to either perform an EF (n = 54) 7–9 days after ovulation or left pregnant (n = 9). PGF2α was not used to induce oestrus. Ultrasound examination and blood sampling were performed just before the EF and 72 h later to determine changes in progesterone concentration and signs of endometritis. Results: The overall percentage of positive EF/pregnancy was 55.5% (30/54) and 66.7% (6/9), respectively. The likelihood of pregnancy/positive EF in the first three cycles was 55.5% (15/29). This was not different (p > 0.1) from the fertility of the last four cycles (69.4%, 25/36). In five EF cycles (9.3%), mares had signs of endometritis and early luteolysis (progesterone <2 ng/mL) 72 h after EF. The reduction in progesterone concentration by 72 h after EF was greater (p < 0.05) for Day 9 (−2.3 ± 0.7 ng/mL) than Day 7 (−1.0 ± 0.8 ng/mL) or Day 8 (−1.3 ± 1.1 ng/mL) cycles. The progesterone concentration in non-flushed mares did not vary significantly during the sampled period (Day 7–12). There were 5 cycles in which the donor mare remained pregnant after the EF, although four were from a single mare. Main limitations: The mare population was limited to barren and maiden mares. The cycle order and operator allocation to each EF were not randomised. Conclusions: EF induces a subtle, but significant reduction in progesterone concentrations compared with non-EF cycles. However, the percentage of mares with EF-induced full luteolysis is low (9.3%). The fertility of mares after repeated EF without administration of PGF2α was unaffected; however, there is a considerable risk of unwanted pregnancy (5/27 = 18.5%) in donors from which an embryo was not recovered.

H2S, a gasotransmitter that can be produced both via the transsulfuration pathway and non-enzymatically, plays a key role in vasodilation and angiogenesis during pregnancy. In fact, the involvement of H2S production on plasma levels of sFLT1, PGF, and other molecules related to preeclampsia has been demonstrated. Interestingly, we have found that maternal fructose intake (a common component of the Western diet) affects tissular H2S production. However, its consumption is allowed during pregnancy. Thus, (1) to study whether maternal fructose intake affects placental production of H2S in the offspring, when pregnant; and (2) to study if fructose consumption during pregnancy can increase the risk of preeclampsia, pregnant rats from fructose-fed mothers (10% w/v) subjected (FF) or not (FC) to a fructose supplementation were studied and compared to pregnant control rats (CC). Placental gene expression, H2S production, plasma sFLT1, and PGF were determined. Descendants of fructose-fed mothers (FC) presented an increase in H2S production. However, if they consumed fructose during their own gestation (FF), this effect was reversed so that the increase disappeared. Curiously, placental synthesis of H2S was mainly non-enzymatic. Related to this, placental expression of Cys dioxygenase, an enzyme involved in Cys catabolism (a molecule required for non-enzymatic H2S synthesis), was significantly decreased in FC rats. Related to preeclampsia, gene expression of sFLT1 (a molecule with antiangiogenic properties) was augmented in both FF and FC dams, although these differences were not reflected in their plasma levels. Furthermore, placental expression of PGF (a molecule with angiogenic properties) was decreased in both FC and FF dams, becoming significantly diminished in plasma of FC versus control dams. Both fructose consumption and maternal fructose intake induce changes in molecules that contribute to increasing the risk of preeclampsia, and these effects are not always mediated by changes in H2S production.

La DMG es una enfermedad multifactorial, por lo que existe controversia en cuanto a los mecanismos implicados en su patogénesis. Nos preguntamos si el estilo de vida y los hábitos alimenticios influyen en la aparición y patogenia de la DMG. Para explorar este tema, el objetivo del presente estudio fue analizar las características de la dieta y el estilo de vida en el embarazo temprano y su influencia en el desarrollo de DMG en mujeres normoglucémicas y evaluar si los conocimientos previos y adquiridos mediante consultas de educación nutricional sobre un correcto manejo del control glucémico en mujeres con diagnóstico de DMG influyen y mejoran la obtención de resultados perinatales maternos y fetales óptimos. El estudio se realizó en el Hospital Universitario La Paz y fue aprobado por el comité de bioética del hospital. Se dividió en dos partes, la primera incluyó a 103 mujeres embarazadas que completaron un cuestionario sobre conocimientos nutricionales, estilo de vida y hábitos alimenticios a través del cual se obtuvo información sobre el estilo de vida pregestacional. La segunda parte incluyó a 51 mujeres con diagnóstico de DMG, las cuales completaron un cuestionario sobre conocimientos nutricionales implicados en el control glucémico y estilo de vida. En ambos grupos de estudio se realizó seguimiento del embarazo, obteniéndose resultados perinatales y bioquímicos, los cuales se compararon entre las mujeres normoglucémicas y aquellas que desarrollaron DMG. Los resultados obtenidos demuestran que existe una relación entre la dieta materna y estilo de vida en la aparición de DMG en mujeres normoglucémicas. Los conocimientos dietéticos y sobre el estilo de vida influyen en el control metabólico en mujeres con diagnóstico de DMG. Por lo que, la educación nutricional es fundamental al inicio de la gestación para que las mujeres adquieran hábitos dietéticos que puedan influir en la prevención del desarrollo de DMG o un correcto manejo glucémico en caso de diagnóstico y de esta manera intentar evitar las complicaciones que esta puede conllevar. El estudio demuestra la importancia de la educación nutricional antes y durante el embarazo.

The role of fructose in the global obesity and metabolic syndrome epidemic is widely recognized. However, its consumption is allowed during pregnancy. We have previously demonstrated that maternal fructose intake in rats induces detrimental effects in fetuses. However, these effects only appeared in adult descendants after a re-exposure to fructose. Pregnancy is a physiological state that leads to profound changes in metabolism and hormone response. Therefore, we wanted to establish if pregnancy in the progeny of fructose-fed mothers was also able to provoke an unhealthy situation. Pregnant rats from fructose-fed mothers (10% w/v) subjected (FF) or not (FC) to a fructose supplementation were studied and compared to pregnant control rats (CC). An OGTT was performed on the 20th day of gestation, and they were sacrificed on the 21st day. Plasma and tissues from mothers and fetuses were analyzed. Although FF mothers showed higher AUC insulin values after OGTT in comparison to FC and CC rats, ISI was lower and leptinemia was higher in FC and FF rats than in the CC group. Accordingly, lipid accretion was observed both in liver and placenta in the FC and FF groups. Interestingly, fetuses from FC and FF mothers also showed the same profile observed in their mothers on lipid accumulation, leptinemia, and ISI. Moreover, hepatic lipid peroxidation was even more augmented in fetuses from FC dams than those of FF mothers. Maternal fructose intake produces in female progeny changes that alter their own pregnancy, leading to deleterious effects in their fetuses.

Pregnancy and lactation are considered critical periods in a female’s life. Thus, the maternal diet must provide sufficient energy and nutrients to meet the mother’s higher than usual requirements as well as the needs of the growing fetus. The maternal diet must enable the mother to provide stores of nutrients required for adequate fetal development, and good health and quality of life in infancy and later adulthood. Among the food and beverage groups, milk and dairy products can play a very important role in achieving these targets due to their high nutrient density and bioavailability, as well as their availability and widespread consumption. The objective of this study was to evaluate the influence of maternal milk and dairy consumption on pregnancy and lactation outcomes in healthy women. This report mainly focuses on the effects of the mother’s intake of dairy products on infant birth weight and length, fetal femur length, head circumference, gestational weight gain, preterm birth, spontaneous abortion, breast milk consumption, and human milk nutritional value. A systematic review of available studies published up toMay 2018 was conducted. A preliminary broad search of the literature yielded 5,695 citations. Four of the investigators independently selected studies for inclusion according to predefined eligibility criteria. Thirty-seven full-text articles were evaluated for potential inclusion, and 17 studies were finally included. Six were prospective cohort studies, 3 were intervention studies, 3 were retrospective cohort studies, 3 were cross-sectional studies, and 2 were case-control studies. Although the number and types of studies prevent definite conclusions, there appears to be a trend that maternal milk intake during pregnancy is positively associated with infant birth weight and length. The lack of studies prevents any conclusions being drawn related to preterm deliveries, spontaneous abortion, and lactation. Adv Nutr 2019;10:S74–S87.