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Background: Some studies have reported that polyamine levels may influence immune system programming. The aim of this study was to evaluate the polyamine profile during gestation and its associations with maternal allergy and cytokine production in cord blood cells in response to different allergenic stimuli., Methods: Polyamines were determined in plasma of pregnant women (24 weeks, N = 674) and in umbilical cord samples (N = 353 vein and N = 160 artery) from the Mediterranean NELA birth cohort. Immune cell populations were quantified, and the production of cytokines in response to different allergic and mitogenic stimuli was assessed in cord blood., Results: Spermidine and spermine were the most prevalent polyamines in maternal, cord venous, and cord arterial plasma. Maternal allergies, especially allergic conjunctivitis, were associated with lower spermine in umbilical cord vein. Higher levels of polyamines were associated with higher lymphocyte number but lower Th2-related cells in cord venous blood. Those subjects with higher levels of circulating polyamines in cord showed lower production of inflammatory cytokines, especially IFN-α, and lower production of Th2-related cytokines, mainly IL-4 and IL-5. The effects of polyamines on Th1-related cytokines production were uncertain., Conclusions: Spermidine and spermine are the predominant polyamines in plasma of pregnant women at mid-pregnancy and also in umbilical cord. Maternal allergic diseases like allergic conjunctivitis are related to lower levels of polyamines in cord vein, which could influence the immune response of the newborn. Cord polyamine content is related to a decreased Th2 response and inflammatory cytokines production, which might be important to reduce an allergenic phenotype in the neonate., (© 2024 The Author(s). Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background & Aims: Prenatal folate exposure may alter epigenetic marks in the offspring. We aimed to evaluate associations between prenatal exposure to folic acid (FA) in preconception and in utero with cord blood DNA methylation in long interspersed nuclear element 1 (LINE-1) and Alu short interspersed nuclear elements (SINEs) as markers of global DNA methylation levels., Methods: Data come from 325 mother-child pairs participating in the Nutrition in Early Life and Asthma (NELA) birth cohort (2015-2018). Pregnant women were asked about supplement use, including brand name and dose, one month before pregnancy (preconception) and through the trimesters of pregnancy. Maternal dietary folate intake was assessed using a validated food frequency questionnaire with additional questions for FA supplement use. Folate serum levels were measured in mothers at 24 weeks of gestation and in cord blood of newborns. DNA methylation was quantitatively assessed by bisulfite pyrosequencing on 5 LINE-1 and 3 Alu different elements. Associations were estimated using multivariable linear regression models., Results: A reduction in methylation levels of LINE-1 in newborns was associated with the use of FA supplements below the recommended doses (<400 ug/day) during preconception (-0.50; 95% CI: -0.91, -0.09; P = 0.016), and from preconception up to 12 weeks of gestation (-0.48; 95% CI: -0.88, -0.08; P = 0.018). Maternal use of FA supplements above the tolerable upper intake level of 1000 ug/day from preconception until 12 weeks of gestation was also related to lower methylation in LINE-1 at birth (-0.77; 95% CI: -1.52, -0.02; P = 0.044). Neither FA supplement use after 12 weeks of gestation nor maternal total folate intake (diet plus supplements) were associated with global DNA methylation levels at birth., Conclusions: Maternal non-compliance with the use of FA supplement recommendations from preconception up to 12 weeks of gestation reduces offspring global DNA methylation levels at birth., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: The female reproductive tract harbours unique microbial communities (known as microbiota) which have been associated with reproductive functions in health and disease. While endometrial microbiome studies have shown that the uterus possesses higher bacterial diversity and richness compared to the vagina, the knowledge regarding the composition of the Fallopian tubes (FT) is lacking, especially in fertile women without any underlying conditions., Methods: To address this gap, our study included 19 patients who underwent abdominal hysterectomy for benign uterine pathology, and 5 women who underwent tubal ligation as a permanent contraceptive method at Hospital Clínico Universitario Virgen de la Arrixaca (HCUVA). We analyzed the microbiome of samples collected from the FT and endometrium using 16S rRNA gene sequencing., Results: Our findings revealed distinct microbiome profiles in the endometrial and FT samples, indicating that the upper reproductive tract harbors an endogenous microbiome. However, these two sites also shared some similarities, with 69% of the detected taxa Being common to both. Interestingly, we identified seventeen bacterial taxa exclusively present in the FT samples, including the genera Enhydrobacter, Granulicatella, Haemophilus, Rhizobium, Alistipes , and Paracoccus , among others. On the other hand, 10 bacterial taxa were only found in the endometrium, including the genera Klebsiella, Olsenella, Oscillibacter and Veillonella (FDR <0.05). Furthermore, our study highlighted the influence of the endometrial collection method on the findings. Samples obtained transcervically showed a dominance of the genus Lactobacillus, which may indicate potential vaginal contamination. In contrast, uterine samples obtained through hysterescopy revealed higher abundance of the genera Acinetobacter, Arthrobacter, Coprococcus, Methylobacterium, Prevotella, Roseburia, Staphylococcus , and Streptococcus ., Discussion: Although the upper reproductive tract appears to have a low microbial biomass, our results suggest that the endometrial and FT microbiome is unique to each individual. In fact, samples obtained from the same individual showed more microbial similarity between the endometrium and FT compared to samples from different women. Understanding the composition of the female upper reproductive microbiome provides valuable insights into the natural microenvironment where processes such as oocyte fertilization, embryo development and implantation occur. This knowledge can improve in vitro fertilization and embryo culture conditions for the treatment of infertility., 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 Canha-Gouveia, Pérez-Prieto, Rodríguez, Escamez, Leonés-Baños, Salas-Espejo, Prieto-Sánchez, Sánchez-Ferrer, Coy and Altmäe.)

Endocrine disrupting chemicals (EDCs) set a public health risk through disruption of normal physiological processes. The toxicoepigenetic mechanisms of developmental exposure to common EDCs, such as bisphenol A (BPA), are poorly known. The present study aimed to evaluate associations between perinatal maternal urinary concentrations of BPA, bisphenol S (BPS) and bisphenol F (BPF) and LINE-1 (long interspersed nuclear elements) and Alu (short interspersed nuclear elements, SINEs) DNA methylation levels in newborns, as surrogate markers of global DNA methylation. Data come from 318 mother-child pairs of the `Nutrition in Early Life and Asthma´ (NELA) birth cohort. Urinary bisphenol concentration was measured by dispersive liquid-liquid microextraction and ultrahigh performance liquid chromatography with tandem mass spectrometry detection. DNA methylation was quantitatively assessed by bisulphite pyrosequencing on 3 LINEs and 5 SINEs. Unadjusted linear regression analyses showed that higher concentration of maternal urinary BPA in 24th week's pregnancy was associated with an increase in LINE-1 methylation in all newborns (p = 0.01) and, particularly, in male newborns (p = 0.03). These associations remained in full adjusted models [beta = 0.09 (95 % CI = 0.03; 0.14) for all newborns; and beta = 0.10 (95 % CI = 0.03; 0.17) for males], including a non-linear association for female newborns as well (p-trend = 0.003). No associations were found between maternal concentrations of bisphenol and Alu sequences. Our results suggest that exposure to environmental levels of BPA may be associated with a modest increase in LINE-1 methylation -as a relevant marker of epigenomic stability- during human fetal development. However, any effects on global DNA methylation are likely to be small, and of uncertain biological significance., 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 © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Objective: Mode of delivery is one of the issues that most concerns obstetricians. The caesarean section rate has increased progressively in recent years, exceeding the limit recommended by health institutions. Obstetricians generally lack the necessary technology to help them decide whether a caesarean delivery is appropriate based on antepartum and intrapartum conditions., Methods: In this study, we have tested the suitability of using three popular artificial intelligence algorithms, Support Vector Machines, Multilayer Perceptron and, Random Forest, to develop a clinical decision support system for the prediction of the mode of delivery according to three categories: caesarean section, euthocic vaginal delivery and, instrumental vaginal delivery. For this purpose, we used a comprehensive clinical database consisting of 25,038 records with 48 attributes of women who attended to give birth at the Service of Obstetrics and Gynaecology of the University Clinical Hospital "Virgen de la Arrixaca" in the Murcia Region (Spain) from January of 2016 to January 2019. Women involved were patients with singleton pregnancies who attended to the emergency room on active labour or undergoing a planned induction of labour for medical reasons., Results: The three implemented algorithms showed a similar performance, all of them reaching an accuracy equal to or above 90% in the classification between caesarean and vaginal deliveries and somewhat lower, around 87% between instrumental and euthocic., Conclusions: The results validate the use of these algorithms to build a clinical decision system to help gynaecologists to predict the mode of delivery., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

The objective of this study was to assess the accuracy of the combination of anogenital distance (AGD) and anti-Müllerian hormone (AMH) in the diagnosis of polycystic ovary syndrome (PCOS). The study included women diagnosed with PCOS and a control group who attended the Clinical University Hospital 'Virgen de la Arrixaca' in Murcia (Spain). Serum concentrations of AMH were measured and two AGD measurements were obtained: (i) from the anterior clitoral surface to the upper verge of the anus (AGD AC ); and (ii) from the posterior fourchette to the upper verge of the anus (AGD AF ). Data were assessed by receiver operator characteristic (ROC) curves. Women with PCOS ( n  = 126) had significantly larger AGD AC (80.5 ± 11.3 versus 76.0 ± 10.4 mm; p  < 0.001) and higher AMH (7.2 ± 4.7 versus 3.1 ± 2.2; p  < 0.001) compared to control women ( n  = 159). Women with serum AMH above 3.8 ng/mL (clinical cut-off used in PCOS) were 9.1 times more likely to have PCOS (95% CI: 5.1-16.2). The area under the ROC curve of combined model of AMH and AGD AC was 0.87 (95% CI: 0.83-0.91). The combined model for predicting PCOS based on AMH and AGD AC has better diagnostic accuracy than that of AMH or AGD AC alone. This model could be useful for clinicians and improve diagnosis and clinical management of these women.

Background: Primary prevention strategies for asthma are lacking. Its inception probably starts in utero and/or during the early postnatal period as the developmental origins of health and disease (DOHaD) paradigm suggests., Objectives: The main objective of Nutrition in Early Life and Asthma (NELA) cohort study is to unravel whether the following factors contribute causally to the developmental origins of asthma: (1) maternal obesity/adiposity and foetal growth; (2) maternal and child nutrition; (3) outdoor air pollution; (4) endocrine disruptors; and (5) maternal psychological stress. Maternal and offspring biological samples are used to assess changes in offspring microbiome, immune system, epigenome and volatilome as potential mechanisms influencing disease susceptibility., Population: Randomly selected pregnant women from three health areas of Murcia, a south-eastern Mediterranean region of Spain, who fulfilled the inclusion criteria were invited to participate at the time of the follow-up visit for routine foetal anatomy scan at 19-22 weeks of gestation, at the Maternal-Fetal Medicine Unit of the "Virgen de la Arrixaca" University Clinical Hospital over a 36-month period, from March 2015 to April 2018., Design: Prospective, population-based, maternal-child, birth cohort study., Methods: Questionnaires on exposures and outcome variables were administered to mothers at 20-24 gestation week; 32-36 gestation week; and delivery. Children were surveyed at birth, 3 and 18 months of age and currently at 5 years. Furthermore, physical examinations were performed; and different measurements and biological samples were obtained at these time points., Preliminary Results: Among the 1350 women invited to participate, 738 (54%) were finally enrolled in the study and 720 of their children were eligible at birth. The adherence was high with 612 children (83%) attending the 3 months' visit and 532 children (72%) attending the 18 months' visit., Conclusion: The NELA cohort will add original and unique knowledge to the developmental origins of asthma., (© 2021 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

Aim: The objective of this study was to evaluate associations between maternal concentrations of 25-hydroxyvitamin D (25(OHD)) and birth outcomes: mode of delivery and episiotomy rate., Design and Methods: One hundred and seventeen pregnant women were enrolled in an observational, longitudinal, prospective cohort study. Multivariable linear regression analyses were performed to assess relationships between maternal 25(OHD) concentrations and mode of delivery. To account for systematic temporal variation in 25(OHD), a cosinor model to the data was fitted., Results: No significant statistical associations were found between adjusted maternal 25(OHD) concentrations and risk of eutocic vaginal delivery, instrumented delivery (OR 1.05 [95% CI: 0.97-1.13]), primary Caesarean section (OR 0.99 [95% CI: 0.88-1.11]) or Caesarean section for any other causes (OR 1.04 [95% CI: 0.95-1.14]). High 25(OHD) levels tended to show a protective effect on performance of episiotomy, without reaching statistical significance (OR 0.36 [95% CI: 0.09, 1.37])., (© 2021 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Culture media supplemented with reproductive fluids (RF) have been used in livestock species, improving the efficiency and quality of in vitro produced embryos. However, usefulness in humans is still unknown. In this study, we collected human reproductive fluids (HRFs) ex vivo (from 25 patients undergoing abdominal hysterectomy plus bilateral salpingectomy) and in vivo (from 31 oocyte donors). Afterward, protocols to evaluate their osmolality, pH, total protein concentration, endotoxin level, and sterility were optimized, establishing security ranges for their use as natural additives. In addition, a functional assay was developed with bovine embryos grown in vitro in a medium supplemented with 1% of collected HRFs. Finally, a proof of concept was performed with six patients on post ovulation day 2 to evaluate the full-term viability of embryos grown in media supplemented with autologous uterine fluid, collected under in vivo conditions. Two of the embryos resulted in successful pregnancy and delivery of healthy babies. In conclusion, this study establishes a complete quality control sheet of HRFs as additives for embryo culture media and shows first preliminary data on obtaining healthy offspring derived from embryos grown in media supplemented with HRFs., 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. The reviewer MH declared a past collaboration with one of the authors PC., (Copyright © 2021 Canha-Gouveia, Prieto-Sánchez, Sánchez-Ferrer, Mollá, Martínez-Soto, París-Oller, Soriano-Úbeda, Landeras and Coy.)

Anthropometric assessment during pregnancy is a widely used, low-technology procedure that has not been rigorously evaluated. Our objective is to investigate fat mass distribution during pregnancy by examining changes in anthropometrics measures, in order to evaluate the reliability of these measures. An observational, longitudinal, prospective cohort study was performed in 208 pregnant women. Anthropometric measurements were taken following the ISAK protocol during the three trimesters and a generalized linear model for repeated measures was used to evaluate differences. Variability was assessed using the coefficient of variation, and Propagated Error (PE) was used to sum of skinfold thicknesses (SFT). SFT showed a general increase in fat mass during the three trimesters of pregnancy (∑SFT7 p = 0.003), and was observed in specific anatomical locations as well: arms (∑Arm SFT, p = 0.046), trunk (∑Trunk SFT, p = 0.019), legs (∑Leg SFT, p = 0.001) and appendicular (∑Appendicular SFT, p = 0.001). Anthropometric measures for skinfold thickness were taken individually during pregnancy and were reliable and reproducible during the three trimesters, which could help to prevent adverse pregnancy outcomes.

Paracetamol is the one of the most commonly used medications during pregnancy. However, its potential antiandrogenic effect has been suggested. The objective of this study was to evaluate associations between maternal paracetamol use during pregnancy and anogenital distance (AGD) in male newborns from a Spanish birth cohort. The study included two hundred and seventy-seven mother-male child pairs with self-reported paracetamol use and frequency during each trimester of pregnancy. AGD measurements were taken employing standardized methods. The associations between maternal paracetamol use and AGD measures were evaluated using linear regression models, adjusting for potential confounders and covariates. Overall, 61.7% of pregnant women consumed paracetamol at any time of pregnancy with an average of 9.43 (SD = 15.33) days throughout pregnancy. No associations between the maternal use of paracetamol or its frequency and AGD measures among different trimesters or during the whole pregnancy were found in the adjusted final models. A non-differential misclassification error may have occurred-the recall of paracetamol intake independent of AGD measurements-introducing bias towards the null hypothesis. Nevertheless, the current evidence suggests that paracetamol might have a potential antiandrogenic effect especially in the early stages of fetal development. Thus, it would be highly recommendable to pursue further studies to elucidate the potential effects of paracetamol in human perinatal health and its use among pregnant women.

Endometriosis is a disabling disease that may significantly compromise a woman's social relationships, sexuality, and mental health. Considering the impact of endometriomas and deep infiltrating endometriosis (DIE) on quality of life and the limited number of papers on this topic, the objective of this study was to assess health-related quality of life (HRQoL) in adult Spanish women with the condition. A case-control study was conducted on a group of 99 patients with ovarian endometriomas or DIE and 157 controls. Women underwent physical and gynecological examinations, and they completed health questionnaires including the Short Form-12v2 (SF-12v2), a survey for HRQoL. Eight scales and two component summary scores (Physical (PCS) and Mental (MCS), respectively) were calculated. Women with endometriomas or DIE had significantly worse PCS: 47.7 ± 9.7 vs. 56.1 ± 5.9, respectively ( p < 0.001) compared to controls, as well as lower scores on seven out of the eight scales ( p < 0.01). No significant differences were found for the MCS. Conclusions: HRQoL was significantly lower in patients with endometriomas or DIE compared to controls. If confirmed, these results may have important implications for prevention, clinical practice, and intervention.

To describe whether polycystic ovary syndrome (PCOS) phenotypes vary in their body composition and skinfold (SKF) thicknesses and if they differ from women without PCOS, a preiminar case-control study was performed. A total of 117 cases were diagnosed using the Rotterdam criteria. Gynecological examinations and transvaginal ultrasound were performed in all women (266 women). Anthropometric measurements including SKF thickness were taken according to the restricted profile protocol of the international standards for the anthropometric evaluation according to the International Society of the Advancement of Kinanthropometry (ISAK). Women with PCOS had higher body mass index and percentage of fat mass with respect to controls. The endomorphy component was also significantly higher in women with PCOS than in controls. Each PCOS phenotype displayed a different representation in the somatochart respect to the others phenotypes and also compared to controls. Women with PCOS had significantly higher ∑7 SKF ( p = 0.013), ∑appendicular SKF ( p = 0.017) and ∑arm SKF ( p = 0.019) than controls. H-O-POM phenotype had higher 7∑ SKF ( p = 0.003), ∑appendicular SKF ( p = 0.01), ∑arm SKF (0.005), ∑leg SKF, and ∑trunk SKF (0.008) and also a higher fast mass percentage than controls ( p = 0.011). In conclusion, body composition evaluated by ISAK protocol is different in women with PCOS, especially in the complete phenotype (H-O-POM). This could have relevant implications in terms of clinical evaluation and follow-up of these women, although more researches in this field are needed.

Maternal supplementation of docosahexaenoic acid (DHA) during pregnancy has been recommended due to its role in infant development, but its effect on materno-fetal DHA status is not well established. We evaluated the associations between DHA supplementation in pregnant women with obesity or gestational diabetes mellitus (GDM) and maternal and neonatal DHA status. Serum fatty acids (FA) were analyzed in 641 pregnant women (24 weeks of gestation) and in 345 venous and 166 arterial cord blood samples of participants of the NELA cohort. Obese women ( n = 47) presented lower DHA in serum than those lean ( n = 397) or overweight ( n = 116) before pregnancy. Linoleic acid in arterial cord was elevated in obese women, which indicates lower fetal retention. Maternal DHA supplementation (200 mg/d) during pregnancy was associated with enhanced maternal and fetal DHA levels regardless of pre-pregnancy body mass index (BMI), although higher arterial DHA in overweight women indicated an attenuated response. Maternal DHA supplementation was not associated with cord venous DHA in neonates of mothers with GDM. The cord arteriovenous difference was similar for DHA between GDM and controls. In conclusion, maternal DHA supplementation during pregnancy enhanced fetal DHA status regardless of the pre-pregnancy BMI while GDM may reduce the effect of DHA supplementation in newborns.

Introduction: Endometriosis is a chronic painful condition characterized by high prognostic uncertainty, as well as the threat of infertility and emotional symptoms that may affect many aspects of women, including psychological characteristics like dispositional optimism. Considering the impact of endometriosis on psychological health and the paucity of papers on this topic, the aim of this study is to explore optimism and associated factors in endometriosis., Methods: A case-control study was performed on a group of 95 women with endometriosis and 156 controls. All participants completed the Life Orientation Test-Revised (LOT-R), a self-administered tool for assessing dispositional optimism. Pain severity, medication, gynecological and socio-demographic information was also collected., Results: Low optimism was observed for women with endometriosis compared to controls even after covariate adjustment (LOT-R global scores: 14.5 vs. 15.9 points, p = .045)., Conclusions: This study provides the first evidence that a personality dimension with many prognostic implications may be altered in women with endometriosis. Our findings highlight the importance of a broader understanding of this condition, treating this disorder from a biopsychosocial perspective and suggests the need for non-medical attention within a multidisciplinary team.

Polycystic ovary syndrome (PCOS) is a chronic endocrinopathy characterized by hyperandrogenism and anovulation that may pervade psychological dimensions such as dispositional optimism. Considering how PCOS influences mental health and the lack of studies on this matter, this research was aimed at assessing optimism and associated factors in PCOS. A case-control study of 156 patients with PCOS and 117 controls was conducted. All woman filled out the Life Orientation Test-Revised (LOT-R), a self-report questionnaire for measuring dispositional optimism. Medication, pain severity, gynecological, and sociodemographic information was also collected. Lower optimism was found in patients with PCOS compared to controls, even after covariate adjustment (LOT-R global scores: 14.1 vs. 15.9, p = 0.020). Our study provides evidence that a personality characteristic with important implications in illness prognosis may be affected in PCOS. We propose to assess dispositional optimism with the LOT-R scale in the gynecological appointment and tailor medical attention accordingly as a way to improve the comprehensive care of these patients within a multidisciplinary team.

Research Question: Does the length of the anogenital distance (AGD), an anthropometric biomarker of fetal androgen exposure, change across pregnancy? It has been suggested that AGD remains stable during adulthood with no changes across the menstrual cycle. No studies, however, have been carried out during pregnancy, during which women are exposed to important hormonal and anthropometric variations., Design: A cohort study of 186 singleton pregnant women recruited in the first trimester of pregnancy. Measurements from the anterior clitoral surface to the upper verge of the anus (AGD AC ), and from the posterior fourchette to the upper verge of the anus (AGD AF ) and body mass index (BMI) were obtained in each trimester. Generalized linear model for repeated measures was carried out to assess differences in AGDs and BMI across the three trimesters of the pregnancy., Results: In crude analyses, AGD AC was progressively and significantly longer as the pregnancy developed (first trimester: 87.69 ± 13.14mm; second trimester: 89.69 ± 13.47mm; third trimester: 91.95 ± 13.25 mm; P < 0.001), whereas AGD AF did not significantly change throughout pregnancy (first trimester: 28.37 ± 6.94 mm; second trimester: 28.09 ± 7.66 mm; third trimester: 28.94 ± 6.7 mm). In the multivariable mixed-effect models for fixed effect (trimester) and time-covariate (BMI), AGDs did not show significant associations with trimesters of pregnancy when BMI was included in the model., Conclusions: Our results suggest that AGD AF and AGD AC , when adjusted by BMI, do not change throughout gestation despite maternal anthropometric variations during pregnancy. AGD AF may be a meaningful measurement at any time during pregnancy without considering BMI. Therefore, maternal AGD AF may be used as a prenatal biomarker of the mother's in-uteru hormonal exposure even during pregnancy., (Copyright © 2020 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Polycystic ovary syndrome (PCOS) is a chronic condition with symptoms affecting many women at reproductive age and evaluating their health-related quality of Life (HRQoL) is an important issue. Moreover, differences in the HRQoL between women with different PCOS phenotypes have never been analyzed. Therefore, the aim of our study was to compare the HRQoL between women with PCOS -and its phenotypes- and controls attending to a tertiary hospital., Methods: A group of 117 women with PCOS and 153 controls were studied between 2014 and 2016. Controls were women without PCOS attending the gynecological outpatient clinic for routine examinations. Cases were women attending the same setting and diagnosed with PCOS. PCOS diagnose was performed following the Rotterdam Criteria and women were further classified by anovulatory or ovulatory phenotypic subtype. Women underwent physical and gynecological exams and completed health questionnaires including the Short Form-12v2. Eight scales and two component summary scores [Physical (PCS) and Mental (MCS), respectively] were calculated. Bivariate and multivariate analyses were performed to assess differences in HRQoL between women with PCOS and controls., Results: All women with PCOS and anovulatory PCOS presented lower score in PCS compared to controls [mean (95%CI): 53.7 (52.5-54.9) and 52.9 (51.5-54.4) vs. 55.8 (54.8-56.8); p-values< 0.01], as well as lower scores for five out of the eight scales (p-values < 0.05) after adjusting by age, body mass index, infertility, educational level and current occupation. No significant differences were observed for the MCS between women with or without PCOS or its phenotypic subtypes., Conclusions: HRQoL was significantly decreased in adult women with PCOS and its anovulatory phenotype compared to controls attending the outpatient clinic of a tertiary hospital. These results may have implications for the clinical practice and suggest the need for specific interventions in women with PCOS.

Background & Aims: Maternal obesity at conception is considered a major predictor of offspring obesity. This could by driven at least in part by an altered placental fat transfer. However, the pathophysiological mechanisms involved are not fully understood. We investigated the in vivo materno-fetal transfer of fatty acids (FAs) in obese pregnant women using stable isotopes., Methods: Ten obese and ten normo-weight pregnant women (control) received orally a bolus of 13 C-labeled FAs 12 h before elective caesarean section: oleic acid ( 13 C-OA), linoleic acid ( 13 C-LA) and docosahexaenoic acid ( 13 C-DHA). Maternal blood samples were collected at -12 (basal), -8, -4, -2, 0 h relative to the time of cesarean section. At the time of birth, arterial and venous cord bloods as well as placental tissue were collected. FAs composition was determined by gas-liquid chromatography and isotopic enrichment by gas chromatography-combustion-isotope ratio mass spectrometry., Results: Maternal plasma insulin and placental weight tended to higher values in obese pregnant women although they did not present serum hyperlipidemia. Higher concentrations of 13 C-LA and 13 C-DHA were found in non-esterified FAs fraction in maternal plasma of obese mothers. The ratio of placental uptake for 13 C-LA and 13 C-DHA was lower in obese women compared to normal weight pointing toward a limited capacity of FA placental transfer, especially of essential FAs. Maternal insulin was associated to this lower placenta/maternal plasma ratio for both 13 C-LA (R = -0.563, P = 0.012) and 13 C-DHA (R = -0.478, P = 0.033). In addition, the ratio cord/maternal plasma of 13 C-LA was significantly lower in obese women compared to controls., Conclusions: In conclusion, obese mothers without hyperlipidemia showed a reduced materno-fetal transfer of polyunsaturated FAs which could affect fetal development. This affect dietary recommendation for obese pregnant women., Trial Registry Number: ISRCTN69794527., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Gestational diabetes mellitus (GDM) is a world-wide health challenge, which prevalence is expected to increase in parallel to the epidemic of obesity. Children born from GDM mothers have lower levels of docosahexaenoic acid (DHA) in cord blood, which might influence their neurodevelopment. Recently, the membrane transporter Major Family Super Domain 2a (MFSD2a) was associated with the selective transportation of DHA as lysophospholipids. The expression of the DHA membrane transporter MFSD2a is lower in GDM placentas, which could affect materno-fetal DHA transport. Humans with homozygous inactivating mutations in the MFSD2a gene present severe microcephaly and intellectual impairments. Herein, we intended to identify early blood biomarkers that may be of use during pregnancy to monitor the offspring development and the adequate nutritional interventions, such as nutritional supplementation, that may be selected to improve it. We evaluated MFSD2a expression in maternal blood at the third trimester of pregnancy, and its potential relationship with the expression of placental MFSD2a at delivery and child outcomes. Three groups of pregnant women were recruited: 25 controls, 23 GDM with dietary treatment, and 20 GDM with insulin treatment. Maternal and neonatal anthropometric and biochemical parameters were evaluated. MFSD2a was analyzed in placenta, blood and serum. MFSD2a protein expression in maternal blood was significantly lower in GDM groups and correlated with placental MFSD2a and Z-score neonatal head circumference during the first 6 months of life. The cord/maternal serum ratio of DHA, a solid indicator of materno-fetal DHA transport, was reduced in GDM groups and correlated with MFSD2a in maternal blood at the third trimester and in placenta at delivery. This indicates that altered MFSD2a levels in maternal blood during pregnancy might influence placental nutrient transport and fetal neurodevelopment. Furthermore, MFSD2a levels in maternal blood on the third trimester were inversely correlated to DHA in maternal serum lyso-PL. Thus, the level of MFSD2a in maternal blood could be used as a potential biomarker for the early detection of disturbances of MFSD2a expression during pregnancy and the subsequent consequences for the neurodevelopment of the child, as well as it may help to choose the optimal treatment approach for the affected subjects., (Copyright © 2020 Sánchez-Campillo, Ruiz-Palacios, Ruiz-Alcaraz, Prieto-Sánchez, Blanco-Carnero, Zornoza, Ruiz-Pastor, Demmelmair, Sánchez-Solís, Koletzko and Larqué.)

Objective: To determine the contribution of short femur diaphysis length (FDL) at 19-22 weeks of gestation in the prediction of adverse pregnancy outcomes., Methods: The study included singleton pregnant women who underwent a routine anomaly scan at 19-22 weeks of gestation at the Virgen de la Arrixaca University Clinical Hospital (Murcia, Spain) between August 2011 and August 2012. Fetal biometry and Doppler ultrasound of uterine arteries were assessed as part of the anomaly scan, and the mean pulsatility index of both uterine arteries was recorded. Maternal obstetric characteristics, such as ethnicity, age, weight, parity, cigarette smoking, and medical history including hypertension and diabetes mellitus were collected from our database system., Results: A total of 6,366 women were included in the study after excluding cases with abnormal karyotype, major fetal abnormalities, or termination of pregnancy. There were 88 cases of preeclampsia (PE) (1.4%). Logistic regression was performed including maternal and fetal characteristics. Short FDL at 19-22 weeks was significantly associated with subsequent development of PE (OR = 0.89, 95% CI: 0.80-0.99, p = 0.025). The best model to predict PE from our sample included gestational age at scan, parity, maternal weight, chronic hypertension, mean pulsatility index in the uterine arteries, and FDL (AUC = 0.78, 95% CI: 0.71-0.84). Regarding small for gestational age (SGA) neonates, there were also significant differences in FDL and FDL <5th centile between the control group and SGA newborns below the 3rd, 5th, and 10th centile. In the groups of preterm births (delivery before 32, 34, and 37 weeks), there were no differences in FDL compared with the control group (term births)., Discussion: Our results suggest that FDL at 19-22 weeks of gestation is an independent predictor of PE and SGA newborns., (© 2020 S. Karger AG, Basel.)

The improvement of the embryo culture media is of high relevance due to its influence on successful implantation rates, pregnancy, neonatal outcomes, and potential effects in adult life. The ideal conditions for embryo development are those naturally occurring in the female reproductive tract, i.e., the oviductal and uterine fluids. To shed light on the differences between chemical and natural media, we performed the first comparative study of the low abundance proteins in plasma, uterine, and oviductal fluid collected, simultaneously, from healthy and fertile women that underwent a salpingectomy. The rationale for this design derives from the fact that high-abundant proteins in these fluids are usually those coming from blood serum and frequently mask the detection of low abundant proteins with a potentially significant role in specific processes related to the embryo-maternal interaction. The proteomic analysis by 1D-nano LC ESI-MSMS detected several proteins in higher amounts in oviductal fluid when compared to uterine and plasma samples (RL3, GSTA1, EZRI, DPYSL3, GARS, HSP90A). Such oviductal fluid proteins could be a target to improve fertilization rates and early embryo development if used in the culture media. In conclusion, this study presents a high-throughput analysis of female reproductive tract fluids and contributes to the knowledge of oviductal and uterine secretome., Competing Interests: The authors declare no conflict of interest.

Key Points: Placental structure and function can be modified as a result of maternal obesity affecting materno-fetal fatty acids (FA) transport. We report for the first time, in humans and in vivo, the kinetics of placental FA transfer in normo-weight and in normolipemic obese pregnant women using stable isotopes. The administration of different tracer FA with similar behaviour to the mother at different time points allows the collection of kinetic information on materno-fetal transfer of FA despite only one sample of placenta and cord can be collected per subject. Computational modelling showed a good fit to the data when considering all maternal plasma lipid classes but not when based only on non-esterified FA. The novel approach using multiple tracer FA administration combined with computational modelling shows a consistent time course of placental tracer FA and predicted total FA accumulation., Abstract: We analyse for the first time the in vivo materno-fetal kinetic transfer of fatty acids (FA) labelled with stable isotopes in control and obese (OB) pregnant women. Labelled FA with a similar metabolism (stearic acid: 13 C-SA; palmitic acid: 13 C-PA; oleic acid: 13 C-OA) were orally administered at -4 h, -8 h and -12 h, respectively prior to elective caesarean section to 10 pregnant women with a body mass index >30 (OB) and 10 with a body mass index in the range 20-25 (NW). Placenta, venous and arterial cord blood were collected obtaining a wide range of FA enrichments. A combined experimental and computational modelling analysis was applied. FA fractional synthesis rate (FSR) in placenta was 11-12% h -1 . No differences were observed between NW and normo-lipidemic OB. It was not possible to estimate FA FSR in cord blood with this oral bolus dose approach. Computational modelling demonstrated a good fit to the data when all maternal plasma lipid classes were included but not with modelling based only on the non-esterified FA fraction. The estimated materno-fetal 13 C-FA transfer was ∼1%. In conclusion, our approach using multiple 13 C-FA tracers allowed us to estimated FSR in placental/maternal plasma but not in fetal/maternal compartments. Computational modelling showed a consistent time course of placental 13 C-FA transfer and predicted total fetal FA accumulation during the experiment. We conclude that, in addition to non-esterified FA fraction in the maternal circulation, maternal plasma very low-density lipoprotein and other lipoproteins are important contributors to placental FA transfer to the fetus., (© 2019 The Authors. The Journal of Physiology © 2019 The Physiological Society.)

Background and Objective: Ectopic pregnancy is an important cause of morbidity and mortality worldwide. An early diagnosis, as well as the choice of the most suitable treatment for the patient is crucial to avoid possible complications. According to different factors an ectopic pregnancy must be treated from surgery, using a pharmacological treatment or following a conservative treatment. In this paper, a clinical decision support systems based on artificial intelligence algorithms has been developed to help clinicians to choose the initial treatment to be followed by the patient., Methods: A decision support system based on a three stages classifier has been developed. Each stage acts as a filter and allows re-evaluation of the classification made in the previous stage in order to find diagnostic errors. This classifier has been implemented and tested for four different aid algorithms: Multilayer Perceptron, Deep Learning, Support Vector Machine and Naives Bayes., Results: The results prove that the evaluated algorithms Support Vector Machine and Multilayer Perceptron can be useful to help gynecologists in their decisions about initial treatment, especially with Support Vector Machine that presents accuracy, sensitivity and specificity outcomes about 96.1%, 96% and 98%, respectively., Conclusions: According to the results, it is feasible to develop a clinical decision support system using the algorithms that present a higher precision. This system would help gynecologists to take the most accurate decision about the initial treatment, thus avoiding future complications., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Research Question: Polycystic ovary syndrome (PCOS) women have increased cardiovascular risks, although it is unclear whether the haemostatic system and coagulation contribute to that increased risk., Design: Women attending the Gynecology Unit of the 'Virgen de la Arrixaca' University Hospital (Murcia, Spain) for routine gynaecological examinations between September 2014 and May 2016 were assessed for PCOS using the Rotterdam criteria (hyperandrogenism [H], oligo/amenorrhoea [O] and polycystic ovarian morphology [POM]) and were classified into four phenotypic. In total, 126 cases were identified and 159 control women were selected. All women underwent physical and gynaecological examinations, and blood tests between the second and fifth day of the menstrual cycle. Differences in hormonal, basal thrombophilia and metabolic parameters, and C-reactive protein (CRP) between PCOS and controls were analysed., Results: After adjusting by BMI and age, PCOS women had higher LH (P < 0.001), testosterone (P < 0.001), free testosterone (P = 0.01) and anti-Müllerian hormone (P < 0.001) and lower FSH (P = 0.03) compared with controls, whereas sex hormone-binding globulin was no different. Cases showed significantly higher protein S, glucose, insulin and insulin resistance (HOMA-IR) compared with controls (P < 0.05). There were no differences in protein C levels, antithrombin III, prothrombin time, homocysteine, D-dimer, factor V Leyden, prothrombin G20210A polymorphism or CRP. The H+O phenotype showed the poorest results for insulin and HOMA-IR (P = 0.04 and 0.05)., Conclusions: The results suggest that there are no differences in the basal thrombophilias between women with and without PCOS. However, PCOS with H+O shows the poorest metabolic profile., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to analyse the differences in the phospholipid composition of very low density (VLDL), low density (LDL) and high density lipoprotein (HDL) monolayers in pregnant lean and obese women., Methods: LDL, HDL, and VLDL were isolated from plasma samples of 10 lean and 10 obese pregnant women, and their species composition of phosphatidylcholines (PC) and sphingomyelins (SM) was analysed by liquid-chromatography tandem mass-spectrometry. Wilcoxon-Mann-Whitney U test and principal component analysis (PCA) were used to investigate if metabolite profiles differed between the lean/obese group and between lipoprotein species., Results: No significant differences have been found in the metabolite levels between obese and non-obese pregnant women. The PCA components 1 and 2 separated between LDL, HDL, and VLDL but not between normal weight and obese women. Twelve SM and one PCae were more abundant in LDL than in VLDL. In contrast, four acyl-alkyl-PC and two diacyl-PC were significantly higher in HDL compared to LDL. VLDL and HDL differed in three SM, seven acyl-alkyl-PC and one diacyl-PC (higher values in HDL) and 13 SM (higher in VLDL). We also found associations of some phospholipid species with HDL and LDL cholesterol., Conclusion: In pregnant women phospholipid composition differs significantly in HDL, LDL and VLDL, similar to previous findings in men and non-pregnant women. Obese and lean pregnant women showed no significant differences in their lipoprotein associated metabolite profile.

Introduction: Recent studies indicate that alkaline phosphatase (ALP) may affect expression and activity of fatty acid (FA) transport proteins in placenta and other tissues., Objective: To evaluate if disturbed FA profile in offspring of gestational diabetes mellitus (GDM) with different maternal pregestational weight could be related to maternal or neonatal ALP., Methods: Prospective observational study of pregnant women recruited in the third trimester (25 controls, 23 lean-GDM, 20 obese-GDM). Fetal ultrasound was performed. At delivery, FAs were analyzed in placenta, maternal, and venous cord blood. Western blotting analysis of lipid carriers was performed in placenta., Results: Newborns from obese-GDM tended to higher birthweight (p = 0.059) than those from both lean-GDM and controls. ALP in maternal blood tended to be lower in GDM (p = 0.170) while increased significantly in cord blood of obese-GDM with respect to controls (p = 0.039). Saturated FA percentages in cord blood were significantly higher (p < 0.000), while polyunsaturated FA (PUFA) percentages were lower (p = 0.003) in both GDM, which could be due to a lower expression of major family domain 2a receptor (MFSD2a) in the placenta. Plasma ALP in the offspring of obese-GDM was inversely associated to cord essential PUFAs (β = -6.18, p = 0.005) and to placental MFSD2a (β = -38.46, p = 0.014)., Conclusions: Cord PUFA and placental MFSD2a are decreased in both lean and obese-GDM pregnancies. Higher ALP in cord blood of obese-GDM could play a role in the FA levels in these pregnancies., (© 2019 S. Karger AG, Basel.)

Objective: To assess the predictive ability of a combination of anogenital distance (AGD) and anti-Müllerian hormone (AMH) to diagnosis the presence of endometriosis without surgery., Methods: The present study included women diagnosed with endometriosis and a control group who attended the "Virgen de la Arrixaca" University Hospital, Murcia, Spain, between September 1, 2014, and May 31, 2015. Serum concentrations of AMH were measured, and two AGD measurements were obtained: from the anterior clitoral surface to the upper verge of the anus (AGD AC ), and from the posterior fourchette to the upper verge of the anus (AGD AF ). Data were assessed by receiver operator characteristic (ROC) curves., Results: Women in the endometriosis group (n=57) had significantly shorter AGD AF (22.8 ± 4.6 vs 27.2 ± 5.7 mm; P<0.001) and lower AMH (2.2 ± 2.5 vs 3.3 ± 1.9 ng/mL; P<0.003) compared with the control group (n=93). Women with serum AMH below the clinical cut-off (1 ng/mL) were 17.40-times more likely to have endometriosis (95% confidence interval [CI] 5.64-53.82). The area under the ROC curve of combined AMH and AGD AF was 0.77 (95% CI 0.70-0.85)., Conclusion: The model for predicting endometriosis on the basis of AMH and AGD could be useful for clinicians and epidemiologists to improve diagnosis and prognosis of this condition., (© 2018 International Federation of Gynecology and Obstetrics.)

Research Question: Is anogenital distance (AGD) a useful clinical tool for predicting polycystic ovarian syndrome (PCOS) and its main National Institutes of Health (NIH) phenotypes?, Design: Case-control study conducted between September 2014 and May 2016 at the Department of Obstetrics and Gynecology of the University Clinical Hospital 'Virgen de la Arrixaca' in the Murcia region (south-eastern Spain). One hundred and twenty-six cases of PCOS and 159 controls without PCOS were included. AGD measurements were taken from the anterior clitoral surface to the upper verge of the anus (AGD AC ), and from the posterior fourchette to the upper verge of the anus (AGD AF ). Parametric and non-parametric tests and receiver operating characteristic (ROC) curves were used to assess associations between AGD and the presence of PCOS and its phenotypes., Results: AGD AC , but not AGD AF , was associated with PCOS and all its phenotypes (P-values < 0.001 to 0.048). The highest area under the curve (0.62; 95% confidence interval 0.55 to 0.71) was obtained for all PCOS with AGD AC with a sensitivity and specificity of 50.0% and 73.0%, and positive and negative predictive value of 59.0% and 64.4%, respectively., Conclusions: AGD AC could moderately discriminate the presence of PCOS and may be a useful clinical tool., (Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Purpose: The purpose of this study is to investigate the potential role of the mean external iliac artery pulsatility index (EIA-PI) as a predictor of adverse obstetric outcomes such as preeclampsia, gestational hypertension and small for gestational age (SGA)., Methods: In women attending for first trimester screening at 11 + 0-13 + 6 weeks of gestation, we recorded maternal characteristics and measured EIA mean PI and uterine artery mean PI. We compared EIA mean PI in those that developed preeclampsia (n = 84), gestational hypertension (n = 50) or small for gestational age (n = 444) with those unaffected (n = 3736). Regression analysis was used to first determine which of the factors among the maternal variables were significant predictors of EIA mean PI in the unaffected group and, second, to predict adverse pregnancy outcomes., Results: In the unaffected group, EIA mean PI increased with maternal age and decreased with mean blood pressure. Additionally, EIA mean PI was lower in cigarette smokers. Compared with the unaffected group, EIA mean PI was significantly lower in women who develop gestational hypertension or SGA below third centile., Conclusion: EIA mean PI in the first trimester is decreased in women who develop gestational hypertension and in those complicated by SGA below third centile. More studies are needed to confirm these findings.

Aims: Anogenital distance (AGD) has been proposed as a marker of the prenatal hormonal milieu and potential environmental insults. The measures of the Pelvic Organ Prolapse-Questionnaire (POP-Q) system is being widely used in the evaluation of the perineum in women with POP pathologies. Genital hiatus (GH) and perineal body (PB) lengths have been related to both prolapse incidence and recurrence and for pessary treatment failure. The use of AGD in female human studies is now emerging and its comparability with other anthropometric measurements could be relevant. The aim of the study was to compare AGD and POP-Q system in adult females., Methods: The study included 155 pregnant women in the first stage of labor. Perineal measurements were performed on women in the lithotomy position: AGD from the anus to the clitoris (AGD AC ); AGD from the anus to the fourchette (AGD AF ); GH from the external urethral meatus to the posterior midline hymen, and length of the PB from the posterior midline hymen to the mid-anal opening. Coefficients of variations (CV) were calculated. Intraclass correlation coefficients (ICC) and Bland-Altman graphs were used to compare both set of measurements., Results: CV were below 15% for AGD AC and GH + PB, though higher for AGD AF and PB (20% and 17%, respectively). ICCs for each pair of measurements were above 80%, (excellent agreement between methods). Concordance between measurements was confirmed by Bland-Altman graphs., Conclusions: Comparable measurements were obtained using AGDs and POP-Q system. Further studies are needed to explore clinical and epidemiological implications of these findings., (© 2018 Wiley Periodicals, Inc.)

Anogenital distance (AGD) is a sexually dimorphic attribute, twice longer in males than in females, and a marker of intrauterine hormonal environment. Interest in AGD measurements is increasing due to mounting evidence on their potential clinical implications. A parallel set of perineal measurements, the Pelvic Organ Prolapse Quantification System (POP-Q), include similar, but not exactly the same, landmarks: the perineal body (PB) and the genital hiatus (GH) lengths. However, clinical reproducibility of both perineal measurements and their usefulness to describe perineal anthropometry needs to be elucidated. To our knowledge, there is no publication in video format showing the methodology of these measurements. The main objective of this work is to show how to properly perform perineal anthropometry, including measurements of the AGD in its two variants [anoclitoral (AGDAC) and anofourchette (AGDAF)], genital hiatus (GH) and perineal body (PB). Moreover, we explored if there were differences in these measurements in women with and without Pelvic Organ Prolapse (POP). We research whether the anthropometric characteristics of the perineum, such as AGD (which is determined prenatally), may be altered in these women and be an independent etiological factor for pelvic floor dysfunction. We show two different ways of measuring perineal lengths, as they might be quite comparable. Our suggestion is that unifying perineal measurements could be useful for clinical and biomedical investigation. More studies are needed in order to compare GH and PB measurements and its AGD counterparts to analyze which procedures are more reproducible with less intra and interobserver variability.

Study Question: Is polycystic ovary syndrome (PCOS) associated with anogenital distance (AGD), a biomarker of fetal androgen exposure, in adult Mediterranean women?, Summary Answer: Longer AGD is associated with PCOS in adult Mediterranean women., What Is Known Already: AGD is a biomarker of prenatal androgen milieu. Human observational studies have reported that associations between AGD and reproductive parameters in both sexes. Exposure of the female fetus to intrauterine androgens may be a risk factor for PCOS in adulthood., Study Design, Size, Duration: This was a case-control study of 126 women with PCOS and 159 controls between September 2014 and May 2016., Participants/materials, Setting, Methods: Cases were attending the gynecology unit of the 'Virgen de la Arrixaca' University Clinical Hospital (Murcia, Spain), and were diagnosed following the Rotterdam criteria. Phenotypic subtypes of PCOS were also assessed. Both prevalent and incident (newly diagnosed) cases were included. Controls were women without PCOS attending the gynecological outpatient clinic for routine gynecological exams. All women completed health questionnaires, and underwent physical and gynecological examinations, including transvaginal ultrasound and blood draw. We obtained measures from the anterior clitoral surface to the upper verge of the anus (AGDAC), and from the posterior fourchette to the upper verge of the anus (AGDAF). Gynecologists performing the AGD measures were blind to the status of the patients. We used unconditional multiple logistic regression to evaluate the association between AGD measurements and PCOS while accounting for relevant covariates and confounders, such as BMI, age and episiotomy., Main Results and the Role of Chance: Cases showed significantly longer AGDAF and AGDAC compared to controls in bivariate analyses (P-values < 0.05). In the final adjusted models, AGDAC, but not AGDAF, was associated with the presence of PCOS (P-values = 0.002-0.008). Women with AGDAC in the upper compared to the lowest tertile were 2.9-times (95% CI 1.4-5.9; P-trend = 0.008) more likely to have PCOS. AGDAC measures were also significantly associated with all of the different phenotypic subtypes of PCOS (ORs = 3.1-5.1; P-values < 0.05)., Limitations Reasons for Caution: We took into account known and suspected covariates and confounders, but the possibility of chance findings or residual confounding should be noted. As with all observational studies, causal inference is limited, and study selection and information bias should not be ruled out., Wider Implications of the Findings: Our results support the hypothesis that PCOS has an intrauterine origin, and that the hormonal environment in which the fetus develops may be highly relevant., Study Funding/competing Interest: This work was supported by the Ministry of Economy and Competitiveness, Instituto de Salud Carlos III (ISCIII) (AES, Acción Estratégica en Salud), grant No. PI13/01237, and The Seneca Foundation, Murcia Regional Agency of Science and Technology, grant No. 19443/PI/14. There are no competing interests., Trial Registration Number: Not applicable., (© The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com)

There is little information available on the effect of Gestational diabetes mellitus (GDM) treatment (diet or insulin) on placental lipid carriers, which may influence fetal fat accretion. Insulin may activate placental insulin receptors protein kinase (AKT) and extracellular signal regulated kinase ERK mediators, which might affect lipid metabolism. Placenta was collected from 25 control women, 23 GDM-Diet and 20 GDM-Insulin. Western blotting of insulin signaling mediators and lipid carriers was performed. The human choricarcinoma-derived cell line BeWo was preincubated with insulin inhibitors protein kinase (AKT) and extracellular signal regulated kinase (ERK) and ERK inhibitors to evaluate insulin regulation of lipid carriers. Maternal serum insulin at recruitment correlated to ultrasound fetal abdominal circumference in offspring of GDM and placental endothelial lipase (EL). Lipoprotein lipase in placenta was significantly reduced in both GDM, while most of the other lipid carriers tended to higher values, although not significantly. There was a significant increase in both phosphorylated-Akt and ERK in placentas from GDM-Insulin patients; both were associated to placental fatty acid translocase (FAT), fatty acid binding protein (A-FABP), and EL. BeWo cells treated with insulin pathway inhibitors significantly reduced A-FABP, fatty acid transport protein (FATP-1), and EL levels, confirming the role of insulin on these carriers. We conclude that insulin promotes the phosphorylation of placental insulin mediators contributing to higher levels of some specific fatty acid carriers in the placenta and fetal adiposity in GDM., Competing Interests: The authors declare no conflict of interest.

Central pontine myelinolysis (CPM) is a rare condition usually caused by rapid sodium correction in hyponatraemia after a severe neurological syndrome. Only few cases have been reported during pregnancy, most of which were reported in patients with hyperemesis. We describe the successful management of the first case of twin pregnancy in a patient who presented with CPM after treatment for premature labour and then review the literature on CPM in pregnancy (aetiology, diagnosis and management). Our patient required emergency delivery to achieve electrolyte and fluid balance. At six months, the twins remained asymptomatic and the mother had minor sequelae. The aetiology is not clear, and there is no evidence regarding the optimal treatment or prognosis of CPM. In our patient, desmopressin-contaminated atosiban showed a certain probability in the Karch-Lasagne algorithm of a causality relationship between hyponatraemia and the drug. To our knowledge, this is the first case of myelinolysis reported in a twin pregnancy possibly related to desmopressin-contaminated atosiban.

An association between anogenital distance (AGD) and endometriosis has been reported, suggesting that AGD may be a useful clinical tool in endometriosis. The predictive ability of AGD of women in discriminating presence and type of endometriosis was examined. A case-control study was conducted at the University Hospital 'Virgen de la Arrixaca', Murcia, Spain, between 2014 and 2015. A total of 114 participants diagnosed with endometriosis using ultrasound findings and 105 controls were recruited. Two AGD measurements were obtained: one from the anterior clitoral surface to the upper verge of the anus (AGD AC ), and another one from the posterior fourchette to the upper verge of the anus (AGD AF ). Parametric and non-parametric tests andreceiver operator characterstic analyses were used to determine relationships between AGD and presence of endometriosis and subgroups (ovarian endometriomas or deep infiltrating endometriosis [DIE]). The AGD AF , but not AGD AC , was associated with presence of endometriomas, DIE (P-values, <0.001-0.02), or both. The highest area under curve (0.91; 95% CI 0.84 to 0.97) was obtained for the DIE subgroup with the AGD AF measurement, with a sensitivity and specificity of 84.4% and 91.4%, respectively. AGD AF can therefore efficiently discriminate the presence of DIE and may be a useful clinical tool., (Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: Maternal-fetal transfer of docosahexaenoic acid (DHA) is impaired by gestational diabetes mellitus (GDM), but the underlying mechanisms are still unknown. MFSD2a was recently recognized as a lyso-phospholipid (lyso-PL) transporter that facilitates DHA accretion in brain. The role of this transporter in placenta is uncertain. We evaluated effects of GDM and its treatment (diet or insulin) on phospholipid species, fatty acid profile in women, cord blood and placental fatty acid carriers., Methods: Prospective observational study of pregnant women recruited in the third trimester (25 controls, 23 GDM-diet, 20 GDM-insulin). Fetal ultrasound was performed at gestational week 38. At delivery, maternal and neonatal anthropometry was performed, and fatty acids in total lipids and phospholipid species were analyzed in placenta, maternal and venous cord blood. Western-blot analyses were performed for placental fatty acid carriers., Results: Fetal abdominal circumference z-score at 38 weeks tended to higher values in GDM (P = 0.071), pointing toward higher fetal fat accretion in these babies. DHA percentage in cord serum total lipids (P = 0.029) and lyso-PL (P = 0.169) were reduced in GDM. Placental MFSD2a was reduced in both GDM groups and was positively correlated to DHA values in cord serum total lipids (r = 0.388, P = 0.003). Among established placental lipid carriers, only FATP4 was correlated to DHA concentration in placental lyso-PL. In all compartments, DHA percentage was inversely correlated to fetal abdominal circumference., Conclusions: In offspring of women with GDM treated either with diet or insulin, higher fetal fat accretion and lower placental MFSD2a contribute to reduce DHA availability. Lyso-PL appear to contribute to materno-fetal DHA transport., (Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Study Question: Is the length of the anogenital distance (AGD), a biomarker of the in-utero prenatal hormonal environment, associated with the presence of endometriomas and deep infiltrating endometriosis (DIE)?, Summary Answer: Shorter AGD is associated with presence of endometriomas and DIE., What Is Known Already: It is debated whether hormonal exposure to estrogens in utero may be a risk factor for endometriosis in adulthood. AGD is a biomarker of prenatal hormonal environment and observational studies have shown an association between AGD and reproductive parameters in both sexes., Study Design, Size, Duration: This case-control study of 114 women with endometriosis (endometriomas and/or DIE) and 105 controls was conducted between September 2014 and May 2015., Participants/materials, Setting, Methods: Cases were attending the Endometriosis Unit of the Hospital. Prevalent as well as incident cases, diagnosed by transvaginal ultrasound (TVUS), were included. Controls were women without endometriosis attending the gynecological outpatient clinic for routine gynecological exams. Participants completed health questionnaires, followed physical and gynecological examinations, including TVUS. Measurements from the anterior clitoral surface to the upper verge of the anus (AGDAC), and from the posterior fourchette to the upper verge of the anus (AGDAF) were obtained in all subjects. Unconditional multiple logistic regression was used to estimate the association between AGD measurements and presence of endometriomas and/or DIE while accounting for important confounders and covariates, including age, body mass index, vaginal delivery or episiotomy., Main Results and the Role of Chance: AGDAF was related to presence of endometriomas and/or DIE. For all cases of endometriosis (endometriomas and DIE), women in the lowest tertile of the AGDAF distribution, compared with the upper tertile, were 7.6-times (95% CI 2.8-21.0; P-trend < 0.001) more likely to have endometriosis. With regard to DIE, women with AGDAF below the median, compared with those with AGDAF above the median, were 41.6-times (95% CI 3.9-438; P-value = 0.002) more likely to have endometriosis., Limitations, Reasons for Caution: In case-control studies, information and selection bias has to be ruled out. Physicians conducting the measurement were blind to the status of the patients. Controls came from the same population as the cases. We adjusted for known and suspected confounders and covariates, but the possibility of residual confounding or chance findings should always be considered. As with all observational studies, causal inference is limited., Wider Implications of the Findings: This study suggests that endometriosis, especially the DIE, might have a prenatal origin that may be traced back to the hormonal milieu in which the fetus develops., Study Funding/competing Interest: This work was supported by the Ministry of Economy and Competitiveness, ISCIII (AES), grant no. PI13/01237 and the Seneca Foundation, Murcia Regional Agency of Science and Technology, grant no. 19443/PI/14. The authors have no competing interests to declare., Trial Registration Number: Not applicable., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.)

Objective: Adipokines play an important role in the pathogenesis of insulin resistance during pregnancy. We studied the association of genetic variants linked with type 2 diabetes in gestational diabetes mellitus (GDM) subjects and its influence on maternal adipokines., Study Design: We recruited 25 healthy pregnant women (Controls) and 45 women with GDM at 24-28 weeks of gestation. Maternal blood samples were collected at recruitment and delivery. Adipokines were determined at both sampling times. Genomic DNA was extracted from recruitment samples and FTO rs9939609, TCF7L2 rs4506565, rs7901695, rs12243326, rs12255372 and rs7903146, INSIG2 rs7566605, SREBF1 rs114001633, rs45535737 and rs12941356 and FATP4 rs2003560 genotyped., Results: Serum adiponectin was significantly lower in GDM than Controls at recruitment and showed a similar trend at delivery (p=0.060). In contrast, resistin tended to higher levels in GDM only at recruitment. TCF7L2 rs4506565 (OR=2.31, 95% CI: 1.97-5.01; p=0.031) and FTO rs9939609 (OR=2.17, 95% CI: 1.07-4.41; p=0.039) were associated with GDM risk. Women carrying the T allele of TCF7L2 rs4506565 had increases in plasma resistin of 9.38 μg/L (95% CI 1.39-17.37; p=0.022) per allele; this association remained significant after adjusting for pre-gestational body weight., Conclusion: TCF7L2 rs4506565 variant (T/T) is associated with increased risk of GDM and plasma resistin concentrations in women with GDM., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Better knowledge on the disturbed mechanisms implicated in materno-fetal long-chain polyunsaturated fatty acid (LC-PUFA) transfer in pregnancies with gestational diabetes mellitus (GDM) may have potentially high implications for later on in effective LC-PUFA supplementation. We studied in vivo placental transfer of fatty acids (FA) using stable isotope tracers administrated to 11 control and 9 GDM pregnant women (6 treated with insulin). Subjects received orally [(13)C]palmitic, [(13)C]oleic and [(13)C]linoleic acids, and [(13)C]docosahexaenoic acid ((13)C-DHA) 12 h before elective caesarean section. Maternal blood samples were collected at -12, -3, -2, and -1 h, delivery, and +1 h. Placental tissue and venous cord blood were also collected. FA were quantified by gas chromatography (GC) and (13)C enrichments by GC-isotope ratio mass spectrometry. [(13)C]FA concentration was higher in total lipids of maternal plasma in GDM vs. controls, except for [(13)C]DHA. Moreover, [(13)C]DHA showed lower placenta/maternal plasma ratio in GDM vs. controls and significantly lower cord/maternal plasma ratio. For the other studied FA, ratios were not different between GDM and controls. Disturbed [(13)C]DHA placental uptake occurs in both GDM treated with diet or insulin, whereas the last ones also have lower [(13)C]DHA in venous cord. The tracer study pointed toward impaired placental DHA uptake as critical step, whereas the transfer of the rest of [(13)C]FA was less affected. GDM under insulin treatment could also have higher fetal fat storage, contributing to reduce [(13)C]DHA in venous cord. DHA transfer to the fetus was reduced in GDM pregnancies compared with controls, which might affect the programming of neurodevelopment in their neonates.

Objective: To analyse the circadian rhythm maturation of temperature, activity and sleep during the first year of life in offspring of diabetic mothers (ODM) and its relationship with obesity markers., Methods: A prospective analysis of the children of 63 pregnant women (23 controls, 21 gestational diabetes mellitus (GDM) controlled with diet and 19 GDM with insulin). Fetal abdominal circumference was evaluated ecographically during gestation. Skin temperature and rest-activity rhythms were monitored for 3 consecutive days in children at 15 days and 1, 3 and 6 months. Anthropometrical parameters of the children were evaluated during the first year of life., Results: Children from the GDM groups tended to higher fetal abdominal circumference z-score than controls at the beginning of the last trimester (p = 0.077) and at delivery (p = 0.078). Mean skin temperature or activity was not different among the groups. The I < O sleep index pointed to increasing concordance with parental sleeping at 3 and 6 months but no significant GDM-dependent differences. However, some of the parameters that define temperature maturation and also the circadian function index from the temperature-activity variable were significantly lower at 6 months in the GDM + insulin group. Fetal abdominal circumference z-score, as a predictor of fetal adiposity, correlated negatively with parameters related to circadian rhythm maturation as the circadian/ultradian rhythm (P1 /Pult ratio)., Conclusions: Fetal adiposity correlated with a worse circadian rhythm regulation in ODM. In addition, ODM insulin-treated showed a disturbed pattern of the circadian function index of temperature activity at 6 months of age., (Copyright © 2013 John Wiley & Sons, Ltd.)

Pregnancy is associated with a reduction in maternal serum docosahexaenoic acid (DHA, 22:6 n-3) percentage and its possible depletion in the maternal store. Since the synthesis of long chain polyunsaturated fatty acids (LCPUFA) in the fetus and placenta is low, both the maternal LCPUFA status and placental function are critical for their supply to the fetus. Maternal supplementation with DHA up to 1 g/d or 2·7 g n-3 LCPUFA did not have any harmful effect. DHA supplementation in large studies slightly the enhanced length of gestation (by about 2 days), which may increase the birth weight by about 50 g at delivery. However no advice can be given on their general using to avoid preterm deliveries in low or high risk pregnancies. Several studies, but not all, reported improvements of the offspring in some neurodevelopmental tests as a result of DHA supplementation during gestation, or, at least, positive relationships between maternal or cord serum DHA percentages and cognitive skills in young children. The effect seems more evident in children with low DHA proportions, which raises the question of how to identify those mothers who might have a poor DHA status and who could benefit from such supplementation. Most studies on the effects of n-3 LCPUFA supplementation during pregnancy on maternal depression were judged to be of low-to-moderate quality, mainly due to small sample sizes and failure to adhere to Consolidated Standards of Reporting Trials guidelines. In contrast, the effects of n-3 LCPUFA supplementation on reducing allergic diseases in offspring are promising.

Considerable amounts of long-chain polyunsaturated fatty acids (LC-PUFAs), particularly arachidonic acid and docosahexaenoic acid (DHA, 22:6n-3), are deposited in fetal tissues during pregnancy; and this process is facilitated by placental delivery. Nevertheless, the mechanisms involved in LC-PUFA placental transfer remain unclear. Stable isotope techniques have been used to study human placental fatty acid transfer in vivo. These studies have shown a significantly higher ratio of (13)C-DHA in cord to maternal plasma compared with other fatty acids, which reflects a higher placental DHA transfer. In addition, a selective DHA accumulation in placental tissue, relative to other fatty acids, has been reported. The materno-fetal transfer of fatty acids is a slow process that requires ≥12 h. A high incorporation of dietary (13)C-DHA into maternal plasma phospholipids appears to be important for placental uptake and transfer. DHA in cord blood lipids correlates with placental messenger RNA expression of fatty acid transport protein (FATP)-4, compatible with a role of FATP-4 in DHA transfer. Impaired materno-fetal LC-PUFA transport has been proposed in pregnancies complicated by abnormal placental function (eg, due to gestational diabetes mellitus or intrauterine growth restriction), which should be addressed in future studies. Given that placental DHA transfer is important for child outcomes, elucidation of its potential modulation by transport mechanisms, maternal diet, and disease appears to be important.