Plasma polyamines during pregnancy and their relationships with maternal allergies and the immune response of the neonates.

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.

Fat intake pattern in women with polycystic ovary syndrome.

RESEARCH QUESTION: Do women with polycystic ovary syndrome (PCOS) have a different fat intake pattern to women without PCOS? DESIGN: Case-control study of 276 women between 20 and 35 years old from the Murcia region of Spain. Cases (n = 121) attended the Department of Gynaecology and Obstetrics of the University Clinical Hospital and were diagnosed with PCOS using Rotterdam criteria. Controls (n = 155) were women without PCOS attending the gynaecological outpatient clinic for routine gynaecological examinations. Data from clinical, gynaecological and analytical examinations were collected, including a food frequency questionnaire. Associations between fat intake and presence of PCOS and its phenotypes were examined using multiple logistic regression, adjusting for potential confounding factors. RESULTS: Although no association was found between fatty acid intake and PCOS, significant associations were observed for some PCOS phenotypes. The PCOS phenotype characterized by hyperandrogenism + oligo/amenorrhoea + polycystic ovarian morphology ('H+O+POM') was significantly associated with a higher intake of polyunsaturated fat (odds ratio [OR] 4.0; 95% confidence interval [CI] 1.1-14.2; fourth quartile of highest intake [Q4] versus lowest intake quartile as reference [Q1]) and omega-6 fatty acids (OR 3.5; 95% CI 1.01-12.4; Q3 versus Q1). The 'H+O' phenotype was positively associated with saturated fat intake (OR 6.9; 95% CI 1.1-41.6; Q4 versus Q1). CONCLUSION: This exploratory study suggests that higher intakes of specific fatty acids are related to some PCOS phenotypes although no association was found for PCOS on a global basis. It is recommended that studies with larger sample size be performed to further explore these associations, thus contributing to establishing recommendations about fat intake adapted to different PCOS phenotypes.

Does the anogenital distance change across pregnancy?

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 (AGDAC), and from the posterior fourchette to the upper verge of the anus (AGDAF) 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, AGDAC 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 AGDAF 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 AGDAF and AGDAC, when adjusted by BMI, do not change throughout gestation despite maternal anthropometric variations during pregnancy. AGDAF may be a meaningful measurement at any time during pregnancy without considering BMI. Therefore, maternal AGDAF may be used as a prenatal biomarker of the mother's in-uteru hormonal exposure even during pregnancy.

Health-related quality of life in women with polycystic ovary syndrome attending to a tertiary hospital in Southeastern Spain: a case-control study.

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.

In vivo kinetic study of materno-fetal fatty acid transfer in obese and normal weight pregnant women.

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.

Are there differences in basal thrombophilias and C-reactive protein between women with or without PCOS?

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.

Phospholipids in lipoproteins: compositional differences across VLDL, LDL, and HDL in pregnant women.

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.

Increased Alkaline Phosphatase in Cord Blood of Obese Diabetic Mothers Is Associated to Polyunstaurated Fatty Acid Levels.

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 (ß = -6.18, p = 0.005) and to placental MFSD2a (ß = -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.

Assessment of anogenital distance as a diagnostic tool in polycystic ovary syndrome.

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 (AGDAC), and from the posterior fourchette to the upper verge of the anus (AGDAF). 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: AGDAC, but not AGDAF, 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 AGDAC 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: AGDAC could moderately discriminate the presence of PCOS and may be a useful clinical tool.

Comparability between adult female anogenital distance and perineal measurements standardized by POP-Q system (GH and PB).

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 (AGDAC ); AGD from the anus to the fourchette (AGDAF ); 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 AGDAC and GH + PB, though higher for AGDAF 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.

Presence of polycystic ovary syndrome is associated with longer anogenital distance in adult Mediterranean women.

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.

Investigation of anogenital distance as a diagnostic tool in endometriosis.

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 (AGDAC), and another one from the posterior fourchette to the upper verge of the anus (AGDAF). 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 AGDAF, but not AGDAC, 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 AGDAF measurement, with a sensitivity and specificity of 84.4% and 91.4%, respectively. AGDAF can therefore efficiently discriminate the presence of DIE and may be a useful clinical tool.

Endometriomas and deep infiltrating endometriosis in adulthood are strongly associated with anogenital distance, a biomarker for prenatal hormonal environment.

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.

Materno-fetal transfer of docosahexaenoic acid is impaired by gestational diabetes mellitus.

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.

Influence of gestational diabetes on circadian rhythms of children and their association with fetal adiposity.

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.

Anogenital distance and anti-Müllerian hormone combined improves the diagnosis of polycystic ovary syndrome.

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 (AGDAC); and (ii) from the posterior fourchette to the upper verge of the anus (AGDAF). Data were assessed by receiver operator characteristic (ROC) curves. Women with PCOS (n = 126) had significantly larger AGDAC (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 AGDAC was 0.87 (95% CI: 0.83-0.91). The combined model for predicting PCOS based on AMH and AGDAC has better diagnostic accuracy than that of AMH or AGDAC alone. This model could be useful for clinicians and improve diagnosis and clinical management of these women.

Maternal urinary concentrations of bisphenol A during pregnancy are associated with global DNA methylation in cord blood of newborns in the "NELA" birth cohort.

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.

Associations between maternal circulating 25-hydroxyvitamin D concentration and birth outcomes-Mode of delivery and episiotomy rate: A prospective cohort study.

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]).

Body Composition and Characterization of Skinfold Thicknesses from Polycystic Ovary Syndrome Phenotypes. A Preliminar Case-Control Study.

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.

Is Maternal Use of Paracetamol during Pregnancy Associated with Anogenital Distance in Male Newborns? The Results from the NELA Birth Cohort.

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.