Inter-observer reproducibility of the 2021 AAGL Endometriosis Classification.

BACKGROUND: Inter-observer agreement for the American Association of Gynecologic Laparoscopists (AAGL) 2021 Endometriosis Classification staging system has not been described. Its predecessor staging system, the revised American Society for Reproductive Medicine (rASRM), has historically demonstrated poor inter-observer agreement. AIMS: We aimed to determine the inter-observer agreement performance of the AAGL 2021 Endometriosis Classification staging system, and compare this with the rASRM staging system. MATERIALS AND METHODS: A database of 317 patients with coded surgical data was retrospectively analysed. Three independent observers allocated AAGL surgical stages (1-4), twice. Observers made their own interpretation of how to apply the tool in the first staging allocation. Consensus rules were then developed for a second staging allocation. RESULTS: First staging allocation: odds ratio (OR) (and 95% CI) for observer 1 to score higher than observer 2 was 8.08 (5.12-12.76). Observer 1 to score higher than observer 3 was 12.98 (7.99-21.11) and observer 2 to score higher than observer 3 was 1.61 (1.03-2.51). This represents poor agreement. Second staging allocation (after consensus): OR for observer 1 to score higher than observer 2 was 1.14 (0.64-2.03), observer 1 to score higher than observer 3 was 1.81 (0.99-3.28) and observer 2 to score higher than observer 3 was 1.59 (0.87-2.89). This represents good agreement. CONCLUSIONS: These findings suggest that in its current format the AAGL 2021 Endometriosis Classification staging system has poor inter-observer agreement, not superior to the rASRM staging system. However, performance improved when additional measures were taken to simplify and clarify areas of ambiguity in interpreting the staging system.

External Validation of the "2021 AAGL Endometriosis Classification": A Retrospective Cohort Study.

STUDY OBJECTIVE: Externally validate the American Association of Gynecologic Laparoscopists (AAGL) staging system against surgical complexity and compare diagnostic accuracy with revised American Society for Reproductive Medicine (rASRM) stage, as was done in original publication. DESIGN: Retrospective, diagnostic accuracy study. SETTING: Multicenter (Sydney, Australia). PATIENTS: A total of 317 patients (January 2016-October 2021) were used in the final analysis. INTERVENTIONS: A database of patients with coded surgical data was analyzed. MEASUREMENTS AND MAIN RESULTS: Three independent observers assigned an AAGL surgical stage (1-4) as the index test and surgical complexity level (A-D) as the reference standard. Results from the most accurate of the 3 observers were used in the final analysis. The weighted kappa score for the overall performance of AAGL stage and rASRM to predict AAGL level was 0.48 and 0.48, respectively (no difference). This represents weaker agreement with AAGL level than was observed in the reference paper, which reported a weighted kappa of 0.62. Diagnostic accuracy (sensitivity, specificity, positive predictive value, and negative predictive value) for stage 1 to predict level A was 98.5%, 64.3%, 66.3%, and 98.3%; stage 2 to predict level B 31.2%, 90.5%, 27.0%, and 92.1 %; stage 3 to predict level C 12.3%, 94.1%, 59.3%, and 60.7%; stage 4 to predict level D 95.65%, 88.10%, 38.60%, and 99.62%. Area under the receiver operating characteristic curve for A vs B/C/D (cut point 9) was 0.87, A/B vs C/D (cut point 16) was 0.78, and A/B/C vs D (cut point 22) was 0.94. CONCLUSION: There was weak to moderate agreement between AAGL stage and AAGL surgical complexity level. Across all key indicators, the AAGL system did not perform as well in this external validation, nor did it outperform rASRM as it did in the reference paper. Results suggest the system is not generalizable.

Maternal Perfluoroalkyl Substances, Thyroid Hormones, and DIO Genes: A Spanish Cross-sectional Study.

Results of studies on perfluoroalkyl substances (PFASs) and thyroid hormones (THs) are heterogeneous, and the mechanisms underlying the action of PFASs to target THs have not been fully characterized. We examined the relation between first-trimester maternal PFAS and TH levels and the role played by polymorphisms in the iodothyronine deiodinase 1 (DIO1) and 2 (DIO2) genes in this association. Our sample comprised 919 pregnant Spanish women (recruitment = 2003-2008) with measurements of perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), and free thyroxine (FT4), and we genotyped for single-nucleotide polymorphisms in the DIO1 (rs2235544) and DIO2 (rs12885300) genes. We performed multivariate regression analyses between PFASs and THs and included the interaction term PFAS-genotypes in the models. PFHxS was associated with an increase in TSH (% change in outcome [95% CI] per 2-fold PFAS increase = 6.09 [-0.71, 13.4]), and PFOA and PFNA were associated with a decrease in TT3 (-7.17 [-13.5, -0.39] and -6.28 [-12.3, 0.12], respectively). We found stronger associations between PFOA, PFNA, and TT3 for DIO1-CC and DIO2-CT genotypes, although interaction p-values were not significant. In conclusion, this study found evidence of an inverse association between PFOA and TT3 levels. No clear effect modification by DIO enzyme genes was observed.

A Multicenter International Temporal and External Validation Study of the Ultrasound-based Endometriosis Staging System.

STUDY OBJECTIVE: The aim of this study was to validate temporally and externally the ultrasound-based endometriosis staging system (UBESS) to predict the level of complexity of laparoscopic surgery for endometriosis. DESIGN: A multicenter, international, retrospective, diagnostic accuracy study was carried out between January 2016 and April 2018 on women with suspected pelvic endometriosis. SETTING: Four different centers with advanced ultrasound and laparoscopic services were recruited (1 for temporal validation and 3 for external validation). PATIENTS: Women with pelvic pain and suspected endometriosis. INTERVENTIONS: All women underwent a systematic transvaginal ultrasound and were staged according to the UBESS system, followed by classification of laparoscopic level of complexity according to the Royal College of Obstetricians and Gynaecologists (RCOG) levels 1 to 3. MEASUREMENTS AND MAIN RESULTS: UBESS I, II, and III were then correlated with RCOG levels 1, 2, and 3, respectively. A comparison between temporal and external sites (skipping "A") and between each site was performed in terms of the diagnostic accuracy of UBESS to predict RCOG laparoscopic skill level. A total of 317 consecutive women who underwent laparoscopy with suspected endometriosis were included. Complete transvaginal ultrasound and laparoscopic surgical outcomes were available for 293/317 (92.4%). At the temporal site, the accuracy, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of UBESS I to predict RCOG level 1 were 80.0%,73.8%, 94.9%, 97.2%, 60.2%, 14.5%, and 0.3%, respectively; of UBESS II to predict RCOG level 2 were 81.0%, 70.6%, 82.0%, 26.7%, 96.8%, 3.9%, and 0.3%, respectively; of UBESS III to predict RCOG level 3 were 91.0%, 85.7%, 92.4%, 75.0%, 96.1%, 11.3%, and 0.2%, respectively. At the external sites, the results of UBESS I to predict RCOG level 1 were 90.3%, 92.0%, 88.4%, 90.2%, 90.5%, 7.9%, and 0.1% respectively; UBESS II to predict RCOG level 2 were 89.2%, 100.0%, 88.5%, 37.5%, 100.0%, 8.7%, and 0.0%, respectively; and UBESS III to predict RCOG level 3 were 86.0%, 67.6%, 98.2%, 96.2%, 82.1%, 37.8%, and 0.3%, respectively. When patients requiring ureterolysis (i.e., RCOG level 3) in the absence of bowel endometriosis were excluded (n = 54), the sensitivity of UBESS III to correctly classify RCOG level 3 increased from 85.7% to 96.7% at the temporal site (n = 42) and from 67.6% to 96.0% at the external sites (n = 12) (p <.005). CONCLUSION: The results from this external validation study suggest that UBESS in its current form is not generalizable unless there is either or both bowel deep endometriosis and cul-de-sac obliteration present. The major limitation appears to be the misclassification of women who require surgical ureterolysis in the absence of bowel endometriosis.

Similarities and differences of dietary and other determinants of iodine status in pregnant women from three European birth cohorts.

PURPOSE: As a component of thyroid hormones, adequate iodine intake is essential during pregnancy for fetal neurodevelopment. Across Europe, iodine deficiency is common in pregnancy, but data are lacking on the predictors of iodine status at this life stage. We, therefore, aimed to explore determinants of iodine status during pregnancy in three European populations of differing iodine status. METHODS: Data were from 6566 pregnant women from three prospective population-based birth cohorts from the United Kingdom (ALSPAC, n = 2852), Spain (INMA, n = 1460), and The Netherlands (Generation R, n = 2254). Urinary iodine-to-creatinine ratio (UI/Creat, µg/g) was measured in spot-urine samples in pregnancy (≤ 18-weeks gestation). Maternal dietary intake, categorised by food groups (g/day), was estimated from food-frequency questionnaires (FFQs). Multivariable regression models used dietary variables (energy-adjusted) and maternal characteristics as predictors of iodine status. RESULTS: Median UI/Creat in pregnant women of ALSPAC, INMA, and Generation R was 121, 151, and 210 µg/g, respectively. Maternal age was positively associated with UI/Creat in all cohorts (P < 0.001), while UI/Creat varied by ethnicity only in Generation R (P < 0.05). Of the dietary predictors, intake of milk and dairy products (per 100 g/day) was positively associated with UI/Creat in all cohorts [ALSPAC (B = 3.73, P < 0.0001); INMA (B = 6.92, P = 0.002); Generation R (B = 2.34, P = 0.001)]. Cohort-specific dietary determinants positively associated with UI/Creat included fish and shellfish in ALSPAC and INMA, and eggs and cereal/cereal products in Generation R. CONCLUSIONS: The cohort-specific dietary determinants probably reflect not only dietary habits but iodine-fortification policies; hence, public-health interventions to improve iodine intake in pregnancy need to be country-specific.

Transvaginal Ultrasound Can Accurately Predict the American Society of Reproductive Medicine Stage of Endometriosis Assigned at Laparoscopy.

STUDY OBJECTIVE: To evaluate the diagnostic accuracy of transvaginal ultrasound in predicting a laparoscopic, surgically assigned, revised American Society of Reproductive Medicine (ASRM) endometriosis stage. DESIGN: A multicenter, retrospective, diagnostic accuracy study. SETTING: The patients visited 1 of 2 academic gynecologic ultrasound units and underwent laparoscopy led by 1 of 6 surgeons in metropolitan Sydney, Australia, between 2016 and 2018. PATIENTS: Patients with suspected endometriosis (n = 204). INTERVENTIONS: Ultrasound followed by laparoscopy. MEASUREMENTS AND MAIN RESULTS: Surgical cases were identified. The preoperative ultrasound report and surgical operative notes were each used to retrospectively assign an ASRM score and stage. The breakdown of surgical findings was as follows: ASRM 0 (i.e., no endometriosis), 24/204 (11.8%); ASRM 1, 110/204 (53.9%); ASRM 2, 22/204 (10.8%); ASRM 3, 16/204 (7.8%); ASRM 4, 32 204 (15.7%). The overall accuracy of ultrasound in predicting the surgical ASRM stage was as follows: ASRM 1, 53.4%; ASRM 2, 93.8%; ASRM 3, 89.7%; ASRM 4, 93.1%; grouped ASRM 0, 1, and 2, 94.6%; and grouped ASRM 3 and 4 of 94.6%. Ultrasound had better test performance in higher disease stages. When the ASRM stages were dichotomized, ultrasound had sensitivity and specificity of 94.9% and 93.8%, respectively, for ASRM 0, 1, and 2 and of 93.8% and 94.9%, respectively, for ASRM 3 and 4. CONCLUSION: Ultrasound has high accuracy in predicting the mild, moderate, and severe ASRM stages of endometriosis and can accurately differentiate between stages when ASRM stages are dichotomized (nil/minimal/mild vs moderate/severe). This can have major positive implications on patient triaging at centers of excellence in minimally invasive gynecology for advanced-stage endometriosis.

The Use of Ultrasound in Detecting Endometriosis: Endometriotic Nodule Detected on Ultrasound but not Visualized on Laparoscopy.

The gold standard for diagnosis of endometriosis remains direct visualization at laparoscopy and histological confirmation. However, ultrasound is emerging as a key modality in detecting endometriosis. This case demonstrates how ultrasound has the ability to detect lesions that may not be visible on laparoscopy. A left uterosacral ligament (LUSL) deep endometriosis (DE) nodule was detected on preoperative ultrasound. During laparoscopy, no abnormalities were visualized at that site. Given ultrasound's high specificity for DE, the LUSL was resected; histopathology confirmed DE. This case demonstrates the utility of ultrasound and its ability to detect lesions that may not be visible to a surgeon's eye at laparoscopy. Laparoscopy may fail to identify not only sites of endometriosis but also the extent of infiltration of the disease. The utility of ultrasound for pre-operative mapping can guide surgeons in targeted excision of all lesions at the time of surgery, potentially leading to lower rates of suboptimal resection and residual disease. Interestingly, this case may support the theory of müllerianosis, whereby, during fetal organogenesis, misplaced endometrial tissue develops into endometriosis, allowing it to potentially later manifest as DE.

Ureter Visualization With Transvaginal Ultrasound: A Learning Curve Study.

OBJECTIVES: To evaluate the learning curve of gynecologic surgical fellows (ie, in training) to properly identify the ureters in real time while simultaneously performing and interpreting transvaginal ultrasound (TVUS) examinations. METHODS: We performed a prospective study, which took place at 2 centers in Sydney, Australia, from December 2017 to December 2018. Three fellows (F1-F3), of varying prestudy ultrasound (US) experience, were recruited to participate. One hundred fifty predetermined examinations were planned. A TVUS examination was performed by the study reference standard (an expert in gynecologic US). Subsequently, the fellows performed a focused component to identify bilateral ureters, having been blinded to the patient's clinical history and reference standard findings. Immediate feedback and hands-on teaching were provided after each of the fellow's evaluations were complete. To evaluate the number of scans needed to gain competency, the cumulative summation test for the learning curve was used. RESULTS: A total of 150 examinations were performed on 145 patients. One patient had a single ureter, and 1 patient had US evidence of hydroureter. The cumulative summation test for the learning curve for bilateral ureter identification showed that F1 did not reach competency by 50 TVUS examinations, whereas F2 and F3 required 41 and 31 TVUS examinations to reach competency, respectively. CONCLUSIONS: Contrary to other studies on the topic, this study suggests that although it is feasible for surgical fellows to learn TVUS identification of bilateral ureters, not all fellows can reach competency during a program based on a predefined number of scans. We advocate for an individualized, competency-based medical education model in learning US for identifying the ureters.

One-Size-Fits-All Approach Does Not Work for Gynecology Trainees Learning Endometriosis Ultrasound Skills.

OBJECTIVES: To evaluate whether gynecologic surgical trainees (fellows) can become competent in the real-time classification of the pouch of Douglas (POD) obliteration state and direct visualization of bowel deep endometriosis (DE) during a program with a prespecified number of transvaginal ultrasound (TVUS) examinations. METHODS: We performed a prospective study between December 2017 and December 2018. Three fellows (F1-F3) performed 50 scans each, which were all supervised by an expert sonologist, who performed the reference standard TVUS examination. The fellows performed a focused TVUS examination to assess the bowel and POD state, having been blinded to the patient's clinical history and reference standard findings. Immediate feedback and hands-on teaching were provided after each of the fellow's official classifications. To evaluate the number of scans needed to gain competency, the cumulative summation test for the learning curve was used. RESULTS: A total of 150 examinations were performed on 145 patients. Twenty-six (17.9%) patients had a diagnosis of bowel DE, and 34 (23.4%) were classified as having a negative sliding sign by the reference standard. The overall accuracy of the presence/absence of bowel DE was 90% (range, 82%-94%). The overall accuracy of POD state classification was 93% (range, 90%-96%). The cumulative summation test for the learning curve for bowel DE showed that F1 did not reach competency by 50 scans, whereas F2 and F3 required 21 and 25 scans, respectively. For POD obliteration, F2 did not reach competency, whereas F1 and F3 required 40 and 22 scans. CONCLUSIONS: Not all trainees can reach competency for TVUS evaluations of POD obliteration and bowel DE in a predefined number of scans.

Newborn screening for homocystinurias: Recent recommendations versus current practice.

PURPOSE: To assess how the current practice of newborn screening (NBS) for homocystinurias compares with published recommendations. METHODS: Twenty-two of 32 NBS programmes from 18 countries screened for at least one form of homocystinuria. Centres provided pseudonymised NBS data from patients with cystathionine beta-synthase deficiency (CBSD, n = 19), methionine adenosyltransferase I/III deficiency (MATI/IIID, n = 28), combined remethylation disorder (cRMD, n = 56) and isolated remethylation disorder (iRMD), including methylenetetrahydrofolate reductase deficiency (MTHFRD) (n = 8). Markers and decision limits were converted to multiples of the median (MoM) to allow comparison between centres. RESULTS: NBS programmes, algorithms and decision limits varied considerably. Only nine centres used the recommended second-tier marker total homocysteine (tHcy). The median decision limits of all centres were ≥ 2.35 for high and ≤ 0.44 MoM for low methionine, ≥ 1.95 for high and ≤ 0.47 MoM for low methionine/phenylalanine, ≥ 2.54 for high propionylcarnitine and ≥ 2.78 MoM for propionylcarnitine/acetylcarnitine. These decision limits alone had a 100%, 100%, 86% and 84% sensitivity for the detection of CBSD, MATI/IIID, iRMD and cRMD, respectively, but failed to detect six individuals with cRMD. To enhance sensitivity and decrease second-tier testing costs, we further adapted these decision limits using the data of 15 000 healthy newborns. CONCLUSIONS: Due to the favorable outcome of early treated patients, NBS for homocystinurias is recommended. To improve NBS, decision limits should be revised considering the population median. Relevant markers should be combined; use of the postanalytical tools offered by the CLIR project (Collaborative Laboratory Integrated Reports, which considers, for example, birth weight and gestational age) is recommended. tHcy and methylmalonic acid should be implemented as second-tier markers.

Ultrasound-Based Endometriosis Staging System: Validation Study to Predict Complexity of Laparoscopic Surgery.

STUDY OBJECTIVE: To validate the preoperative ultrasound-based endometriosis staging system (UBESS) for predicting the correct Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) and Australasian Gynaecological Endoscopy and Surgery (AGES) Society's level of laparoscopic skill required for endometriosis surgery. DESIGN: Multi-center retrospective cohort study (Canadian Task Force classification II-2). SETTING: Tertiary teaching hospital and a private gynecologic clinic. PATIENTS: 155 women presenting with chronic pelvic pain and/or a history of endometriosis. INTERVENTIONS: Women underwent detailed specialized transvaginal ultrasound (TVS) in a tertiary referral unit to diagnose and stage endometriosis using the 3 stages of the UBESS. The UBESS was correlated to RANZCOG/AGES laparoscopic skill levels. The UBESS classifications were correlated as follows: UBESS I to predict RANZCOG/AGES surgical skill level 1/2, UBESS II to predict RANZCOG/AGES skill level ¾, and UBESS III to predict RANZCOG/AGES skill level 6. MAIN RESULTS: The accuracy, sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios of the UBESS I to predict the RANZCOG/AGES surgical skill levels 1/2 were 99.4%, 98.9%, 100%, 100%, 98.5%, not applicable, and .011; those of UBESS II to predict surgical skill levels 3/4 were: 98.1%, 96.8%, 98.4%, 93.8%, 99.2%, 60 and .033, respectively, and those for UBESS III to predict surgical skill level 6 were: 98.7%, 97.2%, 99.2%, 97.2%, 99.2%, 115.7, and 0.028, respectively. The rate of correctly predicting the exact level of skills needed was 98.1%, and Cohen's kappa statistic for the agreement between UBESS prediction and levels of training required at surgery was 0.97, indicating almost perfect agreement. CONCLUSIONS: The UBESS can be used to predict the level of complexity of laparoscopic surgery for endometriosis based on the RANZCOG/AGES skills levels for laparoscopy. It now awaits external validation in multiple centers with various surgical skill level classification systems to assess its general applicability.

A Novel Ultrasound Technique Called Saline Infusion SonoPODography to Visualize and Understand the Pouch of Douglas and Posterior Compartment Contents: A Feasibility Study.

Women with infertility are often investigated with saline-infusion sonohysterography and hysterosalpingo-contrast-sonography. The high prevalence of endometriosis in this population also warrants an evaluation with transvaginal ultrasound for deep endometriosis. To minimize investigations, we prospectively evaluated the feasibility of a novel combined ultrasound technique called saline-infusion sonoPODography. In most patients, the fluid infused to assess the cavity and tubal patency spilled through patent tubes and filled the pouch of Douglas, yielding a "standoff" view of posterior compartment structures, including uterosacral ligaments, rectovaginal septum, and the pouch of Douglas. We believe this improved our ability to evaluate this space.

Doppler Color Scoring System in Women With an Incomplete Miscarriage: Interobserver and Intraobserver Reproducibility Study.

OBJECTIVES: Doppler Color Scoring (DCS) has been used to predict successful expectant management of incomplete miscarriage. The aim of this study was to assess inter- and intraobserver reproducibility of the DCS system in women with incomplete miscarriage noted on transvaginal sonography. METHODS: This was a prospective reproducibility study involving offline analysis of 32 prerecorded video sets on transvaginal sonography in real time of women with incomplete miscarriage. Vascularization of retained products of conception was recorded using the DCS system adopted from the International Ovarian Tumor Analysis group. Five gynecologic sonologists of varying experience assigned a DCS classification to each video in the analysis. The same videos were reanalyzed, in a different order, at least 7 days later, to assess intraobserver agreement. Inter- and intraobserver correlations were performed to determine agreement. Interobserver agreement was also measured between each observer and the reference standard (G.C.). A Cohen's κ coefficient value less than 0 suggests poor agreement, 0.01 to 0.20 slight, 0.21 to 0.40 fair, 0.41 to 0.60 moderate, 0.61 to 0.80 substantial, and 0.81 and 0.99 almost perfect. RESULTS: Interobserver agreement for all observers for DCS allocation ranged from 0.480 to 0.751. Overall interobserver agreement for 5 observers was substantial (κ, 0.626). Overall interobserver agreements for the 2 inexperienced and 3 experienced observers compared to G.C. were 0.521 and 0.618, respectively. Experienced observers achieved overall almost perfect intraobserver agreement, compared to substantial agreement for inexperienced sonologists. CONCLUSIONS: DCS interobserver reproducibility between all observers and GC ranged from moderate to substantial. DCS intraobserver reproducibility was substantial to almost perfect. The DCS system appears to be a reproducible tool in evaluating women with incomplete miscarriage.

Comparison of urinary iodine levels in women of childbearing age during and after pregnancy.

PURPOSE: Median urinary iodine concentration (UIC) is used to describe the iodine status of a population. However, the link between UIC and iodine intake may vary during pregnancy. The aim of this study was to compare UIC during and after pregnancy, adjusting for factors that affect iodine intake. METHODS: Two repeated measures of UIC and data on maternal iodine intake estimated through questionnaires were collected during pregnancy and 1-4 years after pregnancy in a subsample of women (n = 598) from a mother and child cohort study in Spain. Random-effects interval regression was used to assess the changes in UIC according to pregnancy status. RESULTS: Median UIC was similar during (133 µg/L) and after pregnancy (139 µg/L). After adjusting for iodised salt, iodine supplement consumption, and socio-demographic related variables, UIC was 24.0% (95% CI 11.3, 38.2) higher after than during pregnancy. This difference was maintained in a subsample of women with exhaustive information on diet (n = 291): 26.2%, 95% CI 10.3, 44.4. CONCLUSIONS: In an iodine sufficient area for the general population, iodine excretion was lower during than after pregnancy when factors affecting iodine intake were controlled for. Current recommendations of median UIC during pregnancy are based on the equivalence between iodine intake and UIC estimated from studies in non-pregnant populations, which might lead to overestimation of iodine deficiency during gestation. Further studies should evaluate the equivalence between iodine intake and its urinary excretion during pregnancy.

To determine the optimal ultrasonographic screening method for rectal/rectosigmoid deep endometriosis: Ultrasound "sliding sign," transvaginal ultrasound direct visualization or both?

INTRODUCTION: The study aim was to evaluate the transvaginal sonography (TVS) "sliding sign" alone, direct visualization of the bowel with TVS, and the combination of both methods (ie "sliding sign" and direct visualization of the bowel), to determine the optimal TVS method for the prediction of rectal/rectosigmoid deep endometriosis (DE). MATERIAL AND METHODS: Multicenter prospective observational study (January 2009-February 2017). All women underwent TVS to determine whether the "sliding sign" was positive/negative and whether rectal/rectosigmoid DE was present, followed by laparoscopic surgery. The association between a negative TVS "sliding sign" alone and the direct visualization of a rectal/rectosigmoid DE nodule alone during the TVS were correlated with the presence of rectal/rectosigmoid DE at laparoscopy. Accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratios (LRs) were evaluated. Data were analyzed using Fisher's exact test. RESULTS: During the recruitment period, 410 consecutive women with suspected endometriosis were included. Complete TVS and laparoscopic surgical outcomes were available for 376 of the women (91.7%). Complete TVS and laparoscopic data were available for 376 women. Of the 376 women 76 (20.2%) had rectal/rectosigmoid DE at laparoscopy. The accuracy, sensitivity, specificity, PPV, NPV, positive and negative LRs for each method to predict bowel DE were: negative "sliding sign": 87%, 73.7%, 90.3%, 65.9%, 93.1%, 7.62, and 0.29, respectively; direct visualization: 91.0%, 86.8%, 92.3%, 74.2%, 96.5%, 11.3, and 0.14, respectively; combined approach: 90.2%, 69.7%, 95.3%, 79.1%, 92.6%, 14.94, and 0.32, respectively. A negative TVS "sliding sign" was significantly associated with the need for bowel surgery (P < 0.05). CONCLUSIONS: The combination of the TVS "sliding sign" and direct visualization of the bowel during TVS appears to provide the most accurate assessment for the identification of rectal/rectosigmoid DE preoperatively.

Sonographic Evaluation of Fetal Adrenal Gland in Gestational Diabetes: Relation to Fetal Growth and Maternal Biochemical Markers.

OBJECTIVES: To relate measurements and volume of the fetal adrenal gland in third trimester ultrasound in diabetic pregnancies (1) to birth weight; (2) to other sonographic markers of diabetic fetopathy (expected fetal weight, sectional area, and fractional volume in fetal limbs); and (3) to maternal biochemical markers of diabetes (HbA1c, leptin). METHODS: Fetal adrenal gland measurements were obtained between 32 and 34 weeks. The gland length, width, depth, and volume (by Virtual Organ Computer-Aided Analysis [VOCAL]) were measured for total gland and fetal zone. Fetal total and fat sectional area and fractional volume were obtained in arm and thigh. A maternal blood sample was obtained. Univariate and multivariate models were used to assess the associations. RESULTS: Thirty-nine diabetic pregnancies were included. Birth weight related significantly to total and fetal zone adrenal depth, and total adrenal volume in third trimester. Total adrenal length and corrected adrenal gland volume also showed a significant correlation to birth weight percentile in univariate and multivariate models. Total adrenal volume associated significantly to total and fat areas and volumes in fetal limbs. Both maternal leptin and HbA1c levels found a significant positive relation to fetal total adrenal volume and corrected adrenal gland volume. Total adrenal gland volume showed a significant association to maternal HbA1c level in multivariate model. CONCLUSIONS: An enlargement of the fetal adrenal gland may be observed in gestational diabetes, not only related to birth weight, but also to distinctive features of diabetic pregnancies, such as fat tissue fetal deposits or maternal biochemical markers.

Vitamin D Status in Pregnancy and Determinants in a Southern European Cohort Study.

BACKGROUND: Population-based data on vitamin D status in pregnancy in southern European countries are scarce. We assessed the prevalence and determinants of vitamin D insufficiency and deficiency in pregnancy in Spain. METHODS: Plasma 25-hydroxyvitamin D3 (25(OH)D3) concentration was measured at the first trimester of gestation in 2,036 pregnant women from several geographical areas of Spain (latitude 39-42°N). Uni- and multivariable regression models were conducted to identify predictors of circulating 25(OH)D3 concentration and vitamin D insufficiency (20-30 ng/mL) and deficiency (<20 ng/mL). RESULTS: Thirty-one per cent and 18% of women were vitamin D insufficient and deficient, respectively. Season at blood collection, latitude, age, social class, tobacco smoking, physical activity and use of vitamin D supplements were identified as independent determinants of 25(OH)D3 concentration. Lower risk of vitamin D insufficiency and deficiency was associated with summer season at blood collection (RR for insufficiency = 0.34, confidence intervals (CI) 0.25, 0.48; and RR for deficiency = 0.07, 95% CI 0.04, 0.12), southern latitude (RR for insufficiency = 0.71, 95% CI 0.50, 1.02; RR for deficiency = 0.60, 95% CI 0.38, 0.94); use of vitamin D supplements (RR for insufficiency = 0.50, 95% CI 0.35, 0.71; RR for deficiency = 0.24, 95% CI 0.14, 0.41); and strong physical activity (RR for insufficiency = 0.80, 95% CI 0.58, 1.09; and RR for deficiency = 0.67, 95% CI 0.46, 1.03). Higher risk of vitamin D deficiency was related to lower social class (RR = 1.94, 95% CI 1.19, 3.16) and smoking (RR = 1.76, 95% CI 1.23, 2.54). CONCLUSIONS: Vitamin D insufficiency and deficiency are highly prevalent in pregnancy. Recommendations and policies to detect and prevent hypovitaminosis D during pregnancy should be developed taking into account the associated factors.

Second-hand smoke exposure in 4-year-old children in Spain: Sources, associated factors and urinary cotinine.

INTRODUCTION: Second-hand smoke exposure (SHS) in children remains as a major pollution problem, with important consequences for children's health. This study aimed to identify the sources of exposure to SHS among 4-year-old children, comparing self-reports to a urinary biomarker of exposure, and characterize the most important variables related to SHS exposure in this population. METHODS: 4-year-old children's exposure to SHS was assessed by a parental-reported questionnaire and by urinary cotinine (UC) measurements in 1757 participants from 4 different areas of the Spanish INMA (INfancia y Medio Ambiente - Environment and Childhood) Project. The questionnaire about SHS included information about smoking habits at home by household members, and about exposure to SHS in other places including other homes, bars, restaurants or transportation. The association between quantified UC levels (>4ng/ml) and sociodemographic variables and the different sources of SHS exposure was examined using logistic regression. RESULTS: Based on parental reports, 21.6% of the children were exposed to SHS at home and 47.1% elsewhere; making a total 55.9% of the children exposed to SHS. In addition, 28.2% of the children whose parents reported being not regularly exposed to SHS had quantified UC values. Children from younger mothers (<34 vs. ≥39.4 y) had a higher odds of exposure to SHS [OR (95% CI): 2.28 (1.70-3.05) per year], as well as from families with a lower educational level [OR secondary: 2.12 (1.69-2.65); primary or less: 2.91 (2.19-3.88)]. The odds of quantifiable UC in children dropped after the smoking ban in public places [OR=0.59 (0.42-0.83)]. Regarding the sources of SHS exposure we observed that quantifiable UC odds was increased in children whose parents smoked at home in their presence [OR mother occasionally: 13.39 (7.03-25.50); mother often: 18.48 (8.40-40.66); father occasionally: 10.98 (6.52-18.49); father often: 11.50 (5.96-22.20)] or in children attending other confined places, mainly other houses where people smoked [OR: 2.23 (1.78-2.80)]. CONCLUSIONS: Children's SHS exposure is nowadays an unresolved major public health problem in Spain. After the ban of smoking in public places health care professionals should put more emphasis to the parents on the importance of controlling the exposure of their children in private spaces.