Pregnancy-Induced Perturbation of Urinary Androgenic Steroid Disposition.

OBJECTIVE: To investigate the excretion and conjugation profile of testosterone (T), Epitestosterone (EpiT), and other androgen metabolites in different phases of pregnancy and postpregnancy as a reflection of the "androgenic exposure." DESIGN: Consecutive recruitment of pregnant women. SETTING: Maternity outpatient low-risk pregnancy clinic. PATIENTS: Seventy-seven pregnant women. INTERVENTIONS: Collection of urine for analyses of sulfate (S) and glucuronide (G) conjugates and metabolic ratios of androgens and androgen metabolites using liquid chromatography-tandem mass spectrometry. MAIN OUTCOME MEASURES: Excretion profiles and metabolic ratios of G and S conjugates of T, EpiT, dehydroepiandrosterone (DHEA), androsterone (A), etiocholanolone (Etio), and dihydrotestosterone in relation to trimester and postpartum, body mass index, fetal sex, and ethnicity. RESULTS: T-S excretion increased significantly between the second and third trimester, whereas excretion of T-G did not change. In contrast, both conjugates of EpiT increased markedly, more so for the S-(17-fold) than the G-conjugate (1.6-fold). The preference for S over G conjugation was conspicuous for EpiT and DHEA (S/G ratio 2.1 and 4.7, respectively, in the third trimester), whereas the reverse was true for T, A, and Etio (S/G 0.6, 0.13, and 0.11, respectively). CONCLUSIONS: Pregnancy influences the androgen excretion profile, with the most profound change being an increase in EpiT excretion throughout the trimesters. EpiT may modulate the effect of T, but its exact role during pregnancy is not known. There were marked differences in the S/G conjugate ratios between androgens upstream and downstream from T in the metabolic network. These results are interesting to compare with the androgen disposition in women with endocrine disorders or abuse of steroids.

Neutrophils to lymphocytes ratio and platelets to lymphocytes ratio in pregnancy: A population study.

BACKGROUND: Neutrophils to lymphocytes ratio (NLR) and platelets to lymphocytes ratio (PLR) are both inflammatory ratios that can be easily calculated from a simple blood count. They are frequently reported and tested as prognostic factors in several medical disciplines. Pregnancy involves special reference values for laboratory assays. OBJECTIVE: The aim of this study was to define pregnancy-related reference values for NLR and PLR according to trimester, background morbidity and according to the patient's age. STUDY DESIGN: A retrospective analysis of a large cohort undergoing community-based pregnancy surveillance between the years 2011-2016. Data were analyzed according to high-risk patient versus normal-risk patient. RESULTS: A total of 11,415 patients were included. Mean PLR and NLR values were 136.3±44.3, 2.6±1, respectively during the first trimester, 144.6±47.1, 4.0±1.4 respectively during the second trimester and 118.1±42.0, 3.5±1.2 respectively during the third trimester. No difference was detected between the high-risk and the normal population (P-values 0.3, 0.5 and 0.4 for PLR in each trimester respectively and 0.3, 0.4, 0.6 for NLR in each trimester, respectively). No differences were detected among parity categories. The correlation between patient's age and either PLR and NLR was a weak positive correlation (though statistically significant). Both PLR and NLR reached a maximum value during the second trimester. The differences between mean NLR and PLR between trimesters were significant (P <0.01 for all differences tested). PLR rises in the presence of anemia, reaching statistical significance (P-value for PLR in each trimester was <0.01). NLR showed an opposite trend (P-values for NLR were 0.4, 0.005 and 0.06 in each trimester, respectively). CONCLUSIONS: In our cohort, there were generally no differences between the high-risk and the normal population, excluding patients with a fibroid uterus or inflammatory bowel disease who presented a significantly elevated PLR through all trimesters. Both PLR and NLR reached a maximum value during the second trimester and were positively correlated with age. We anticipate that the population-based data will assist in providing accurate reference values for future research testing NLR and PLR measures during pregnancy.

Pregnancy greatly affects the steroidal module of the Athlete Biological Passport.

Concentrations of urinary steroids are measured in anti-doping test programs to detect doping with endogenous steroids. These concentrations are combined into ratios and followed over time in the steroidal module of the Athlete Biological Passport (ABP). The most important ratio in the ABP is the testosterone/epitestosterone (T/E) ratio but this ratio is subject to intra-individual variations, especially large in women, which complicates interpretation. In addition, there are other factors affecting T/E. Pregnancy, for example, is known to affect the urinary excretion rate of epitestosterone and hence the T/E ratio. However, the extent of this variation and how pregnancy affect other ratios has not been fully evaluated. Here we have studied the urinary steroid profile, including 19-norandrosterone (19-NA), in 67 pregnant women and compared to postpartum. Epitestosterone was higher and, consequently, the T/E and 5αAdiol/E ratios were lower in the pregnant women. Androsterone/etiocholanolone (A/Etio) and 5αAdiol/5ßAdiol, on the other hand, were higher in the first trimester as compared to postpartum (p<0.0001 and p=0.0396, respectively). There was no difference in A/T during pregnancy or after. 19-NA was present in 90.5% of the urine samples collected from pregnant women. In this study, we have shown that the steroid profile of the ABP is affected by pregnancy, and hence can cause atypical passport findings. These atypical findings would lead to unnecessary confirmation procedures, if the patterns of pregnancy are not recognized by the ABP management units.

Canadian women's attitudes toward noninvasive prenatal testing of fetal DNA in maternal plasma (.).

OBJECTIVE: To determine the perceptions and attitudes of Canadian women to Noninvasive Prenatal Testing of fetal DNA. STUDY DESIGN: A designed questionnaire was administered to women attending the outpatient antenatal clinic at a tertiary urban hospital. Attitudes to current and new prenatal screening modalities were assessed using a five-point Likert scale. Bowker's test of symmetry was used to compare individual responses regarding the two screening modalities. Changes in women's responses pre- and post-delivery were also compared. RESULTS: One hundred and twenty-nine women were enrolled in this study. 88% of women state that they would perform prenatal screening via fetal DNA in the maternal plasma if available. When compared to conventional screening, significantly less women believe that the NIPT should be available upon request for non-medical traits (36.4% versus 60.4%, p < 0.001). When compared to their answer before delivery, more women agreed that screening with fetal DNA in maternal plasma could be used in a negative way to select for desired non-medical traits such as gender. CONCLUSIONS: The use of fetal DNA in the maternal plasma is widely accepted in our Canadian population as a future method of noninvasive prenatal screening despite recognition of certain ethical concerns. This information can be used when implementing new genetic screening programs.

Safety of vaginal delivery in very low birthweight vertex singletons: a meta-analysis.

OBJECTIVE: The objective of this study is to assess the safety of vaginal delivery in VLBW singletons in the vertex presentation. METHODS: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science databases were searched for studies on mode of delivery and neonatal outcome in VLBW singletons in the vertex presentation. A total of 28 studies met our inclusion criteria. RESULTS: Vaginal delivery was not associated with an increase in overall neonatal mortality compared with cesarean delivery (OR 0.87, 95% CI 0.72-1.04). Vaginal delivery was associated with a significant decrease in mortality for the 1250-1500 g birthweight category (OR 0.57, 95% CI 0.36-0.92), while an increase in mortality in the 500-750 g category was not significant (OR 1.5, 95% CI 0.86-2.61). Severe intraventricular hemorrhage (IVH) was not associated with mode of delivery (OR 1.05, 95% CI 0.85-1.29), but the only two high quality study that assessed IVH of all grades found an increase in risk for IVH in vaginal delivery (OR 1.33, 95% CI 1.16-1.51). CONCLUSIONS: Vaginal delivery does not appear to increase the risk for neonatal mortality. However, current available data on neonatal morbidity are limited. More high-quality studies are needed to assess the association between mode of delivery and neonatal morbidity.

The use of antidepressants in pregnancy: focus on maternal risks.

Studies have consistently reported a decrease in the use of antidepressants during pregnancy compared with the pre-pregnancy period. Multiple recent studies have focused on the potential fetal risks of selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs), with very little attention paid to maternal risks. The maternal risks of these medications are the focus of this review. Untreated depression is associated with increased risks of maternal morbidity, both somatic and psychiatric. In contrast, use of antidepressants has been associated with increased risks of hypertension, preeclampsia, and bleeding. In this review we present the evidence for maternal risks in an attempt to develop a risk-benefit ratio.

Les études indiquent uniformément une baisse du recours aux antidépresseurs pendant la grossesse, par comparaison avec la période prégrossesse. De multiples études récentes se sont centrées sur les risques fœtaux potentiellement liés aux inhibiteur sélectif du recaptage de la sérotonine (ISRS) et aux inhibiteur sélectif du recaptage de la norépinéphrine (ISRN), tout en ne portant que très peu attention aux risques maternels. La présente analyse est axée sur les risques maternels qui sont liés à ces médicaments. La dépression ne faisant pas l'objet d'un traitement est associée à des risques accrus de morbidité maternelle, tant somatique que psychiatrique. Par contre, l'utilisation d'antidépresseurs a été associée à des risques accrus d'hypertension, de prééclampsie et de saignement. Dans le cadre de la présente analyse, nous présentons les données dont nous disposons au sujet des risques maternels afin de tenter d'établir un rapport risques-avantages.