Residual risk associations between initial hyperglycemia and adverse pregnancy outcomes in a large cohort including 6709 women with gestational diabetes.

AIMS: To estimate the residual risk associations between hyperglycemia and adverse pregnancy outcomes after glycemia-controlling intervention. METHODS: Among 41,067 Chinese women, those with gestational diabetes mellitus (GDM), according to the IADPSG criteria, received standard interventions to control glycemia. Risk associations of plasma glucose (PG) levels with excess newborn birth weight, primary cesarean section, and preterm delivery were estimated and compared with those in the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study, where hyperglycemia was left untreated. RESULTS: A total of 6,709 (16.3%) women developed GDM and thus received predominantly lifestyle interventions. The incidence of excess newborn birth weight, primary cesarean section, and preterm delivery was 6.1%, 19.1%, and 4.0%, respectively. Higher fasting and higher post-load PG levels during 75-g oral glucose tolerance test (OGTT) were statistically significantly associated with increased risks of excess newborn birth weight and pre-term delivery. Compared with the HAPO study, the association of fasting PG level with excess newborn birth weight showed similar strength and dose-response pattern, contrasting with considerably weakened associations for post-load PG levels that involved glycemic control. Contrary risk associations were seen across GDM subtypes compared with non-GDM, isolated fasting GDM was associated with increased, whereas isolated post-load GDM was associated with decreased, risks of excess newborn birth weight and primary cesarean section. Limiting the analysis to non-GDM women and GDM women with low HbA1c (<6.0%) ≥30 days after interventions overall attenuated the risk associations. CONCLUSIONS: Residual risk associations exist between hyperglycemia and adverse pregnancy outcomes despite seemingly appropriate glycemic control.

Historical Origins for the Overestimation of Mammographic Sensitivity.

The sensitivity of screening mammography for the early detection of breast cancer has improved over the years due to advances in technology. However, guidelines for screening mammography are often based on the mortality reductions demonstrated in the historic trials, where sensitivity with the first-generation mammography was relatively low. With attempts to establish risk:benefit ratios for population screening, it is important to understand the wide range of sensitivities that have been reported for mammography.  Original calculations for mammographic sensitivity were often based on studies that included palpable tumors, thus generating inflated numbers not fully applicable to non-palpable tumors. If restricted to asymptomatic screening, sensitivity calculations were often based on the inverse of interval cancers, a relatively inaccurate method since breast cancers missed on mammography can remain undetected clinically for several years. It was not until multi-modality imaging was developed, primarily ultrasound and MRI, where sensitivity determinations could be made in real time by cross-checking outcomes with each modality. From this, it became apparent that there was a strong correlation between breast density levels and sensitivity levels, such that a single number to denote mammographic sensitivity was disingenuous. The increasing awareness that mortality reductions in the historic trials were achieved with a low sensitivity tool has prompted great interest in additional technologic improvements in mammography, as well as multi-modality imaging approaches for women with high density and/or high risk. In order to appreciate the potential benefit of these new approaches, it is helpful to understand the historical basis behind overestimating the sensitivity of screening mammography.

Feasibility of Breast MRI as the Primary Imaging Modality in a Large Asian Cohort.

Purpose Contrast-enhanced MRI has repeatedly demonstrated significantly enhanced sensitivity compared to mammography and ultrasound in breast cancer detection. The purpose of this study was to evaluate the feasibility and outcomes of using breast MRI as the initial imaging study for screening and diagnosis.  Materials and methods In this retrospective review of a cohort of 10,374 breast MRI scans in 7967 patients in Taitung County, Taiwan, a total of 5619 participants met inclusion criteria and were included in our analysis. We reviewed all biopsies that were performed subsequent to MRI studies in women (screening vs. diagnostic). The primary outcomes were false-positive (FP) biopsy rates and positive predictive value (PPV) of MRI - parameters that have historically been associated with performance that restricts more widespread use of MRI. False-positive rate based on benign biopsies (FPR-3) and the positive predictive value (PPV-3) were calculated. Results Without complementary imaging or follow-up to identify false negatives, the study of performance characteristics was limited to false positives and PPV. There were 351 benign biopsies generated by MRI out of the cohort of 5555 participants (5619 minus the malignant biopsies), generating a false-positive rate of 6.3%. Sixty-four patients out of 415 biopsies were malignant, generating a PPV-3 of 15.4%. Conclusion In this Asian cohort, utilizing breast MRI as the initial study for screening and/or diagnosis appears to be limited more by practical considerations such as cost and patient flow efficiency than by feasibility based on performance characteristics. With well-established superior sensitivity, coupled with improved interpretive skills and techniques that allow for low false-positive rates, MRI should be further studied for its role as the primary imaging modality in breast screening and diagnosis.

Are there differences in pain intensity between two consecutive vaginal childbirths? A retrospective cohort study.

BACKGROUND: Pain assessment is crucial for in-labour pain management. Even though women's self-rated pain intensity is the standard for pain relief or analgesic administration, multiparas appear to receive worse in-labour pain management than primiparas do. The discrepancy in pain perception between primiparas and multiparas remains unclear. Healthcare providers tend to think that multiparas endure the pain and report less pain because they have experienced childbirth. OBJECTIVE: To retrospectively analyse the intensity of in-labour pain during first and second vaginal childbirth within the same group of women and explore whether parity may be an influential factor in labour pain intensity. DESIGN: Retrospective cohort study. SETTING: Labour and delivery in a large academic specialized hospital in Guangzhou, China. PARTICIPANTS: Women were included if they had two consecutive vaginal childbirths with singleton cephalic presentations and cervical dilation ≤ 3 cm for the first childbirth and ≤ 2 cm for the second childbirth. The final study sample consisted of 417 women. METHODS: All childbirth case records between January 2015 and August 2018 were scanned using a structured electronic medical system. Maternal and neonatal demographics as well as obstetric and neonatal outcomes were extracted. The in-labour pain for each childbirth was compared between first and second births. Paired t-tests, McNemar's chi-square tests and mixed-effects modelling were applied to compare the differences in labour pain intensity between the two vaginal childbirths and explore the factors that influenced maximum labour pain scores during the second childbirth. RESULTS: Four hundred seventeen women were included, with an average birth interval of 1.7 years. The average maximum labour pain score during the latent phase was 6 (5,6) for the first childbirth and 5 (4,6) for the second childbirth (paired t =-6.13, P <0.001). Pain scores decreased in 28.1% (117/417) of women and increased in 13.7% (57/417) of women from the first to the second childbirth. More than half of the women in our study experienced the same maximum labour pain score during the first and second labour. Mixed-effects modelling revealed that parity, education and pregnancy complications were independently associated with maximum labour pain scores. CONCLUSIONS: From a clinical point of view, in-labour pain is not clinically different for women when comparing their first and second labours. Health care professionals may underestimate in-labour pain in primiparas when comparing them with nulliparas. More studies are warranted to explore options for achieving better pain management for women with more childbirths.

Association between serum progesterone concentration in early pregnancy and duration of pregnancy: a cohort study.

Objective: To examine the association between progesterone concentration in early pregnancy and duration of pregnancy and risk of preterm delivery.Methods: Women enrolled in the Born in Guangzhou Cohort Study from 2013-2014, with a singleton pregnancy, who had serum progesterone measured at least one time between 4 and 10 weeks of gestation were included. The association between progesterone concentration both continuous and as categorical variable (quartile) and the risk of preterm delivery was assessed with Cox proportional hazards regression. Differences of length of gestation in four progesterone concentration quartiles were assessed using the Log-rank test.Results: We studied 1860 mother-newborn pairs. The mean overall progesterone concentration was 65.7 ± 21.3 nmol/L, with mean progesterone concentrations in the four quartiles of 42.4 ± 6.2 nmol/L (n = 463), 56.2 ± 3.3 nmol/L (n = 462), 68.9 ± 4.5 nmol/L (n = 470), and 95.1 ± 15.3 nmol/L (n = 465). There was no significantly difference in duration of gestation in four progesterone concentration groups (p=.511). There was no relation between progesterone level and preterm delivery (adjusted hazard ratio (HR) per 10 nmol/l progesterone level 1.00 (95% confidence interval (CI) 0.90, 1.11)). After adjusting for potential confounders, the HR of any preterm delivery for quartiles 1, 2 and 3 versus the highest quartile of progesterone level (> 77.3 nmol/L) was 1.04 (95% CI 0.52, 2.07), 1.17 (95% CI 0.60, 2.28), and 1.46 (95% CI 0.76, 2.78), respectively. When analysis was done for spontaneous preterm delivery only, also no association with first trimester progesterone was found.Conclusion: Lower first trimester serum progesterone concentration is not associated with reduction of length of gestation or increased risk of preterm delivery.

Predicting poor outcomes and the need for surgical treatment in neonates with meconium peritonitis.

OBJECTIVE: The objective of this study is to determine factors associated with poor outcomes and the need for surgical treatment in neonates with meconium peritonitis (MP). METHODS: We evaluated the association between prenatal ultrasound features, maternal characteristics, and the likelihood of surgery, mortality, and serious morbidity in 49 neonates with a prenatal diagnosis of MP, who were born in Guangzhou Women and Children's Medical Center between January 2011 and December 2016. RESULTS: Thirty of 49 neonates (61.2%) required surgical treatment, and 17 (34.7%) had a poor outcome. Independent predictors of need for surgical treatment were polyhydramnios, maternal intrahepatic cholestasis of pregnancy (associated with lower risk), and persistence of peritoneal fluid. The model correctly predicted 70.0% of the neonates who required surgery (at a 10% false-positive rate; area under the curve [AUC]: 0.86 [95% CI, 0.75-0.97]). For poor outcomes, independent predictors were low gestational age at birth, persistence of peritoneal fluid, and polyhydramnios. For the latter, the model only achieved a detection rate of 52.9% (10% false-positive rate, AUC: 0.82 [95% CI, 0.70-0.94]). CONCLUSIONS: A combination of prenatal ultrasound features and maternal characteristics correctly predicted 70.0% the need for neonatal surgery. Prediction of poor outcome-based prenatal ultrasound features and gestational age did not perform well.

Understanding and management of gestational trophoblastic disease.

Gestational trophoblastic disease or neoplasia covers a spectrum of benign and malignant conditions arising from pregnancies with highly abnormal development of trophoblastic tissue. In this brief review, we discuss the different features of these different conditions and their origins and risk factors and introduce some of the more novel and controversial treatment options currently being explored.

Proteomics of Uterosacral Ligament Connective Tissue from Women with and without Pelvic Organ Prolapse.

PURPOSE: Damage to the uterosacral ligaments is an important contributor to uterine and vaginal prolapse. The aim of this study is to identify differentially expressed proteins (DEPs) in the uterosacral ligaments of women with and without pelvic organ prolapse (POP) and analyze their relationships to cellular mechanisms involved in the pathogenesis of POP. EXPERIMENTAL DESIGN: Uterosacral ligament connective tissue from four patients with POP and four control women undergo iTRAQ analysis followed by ingenuity pathway analysis (IPA) of DEPs. DEPs are validated using Western blot analysis. RESULTS: A total of 1789 unique protein sequences are identified in the uterosacral ligament connective tissues. The expression levels of 88 proteins are significantly different between prolapse and control groups (≥1.2-fold, p < 0.05). IPA demonstrates the association of 14 DEPs with "Connective Tissue Function." Among them, fibromodulin, collagen alpha-1 (XIV) chain, calponin-1, tenascin, and galectin-1 appear most likely to play a role in the etiology of POP. CONCLUSIONS AND CLINICAL RELEVANCE: At least six proteins not previously associated with the pathogenesis of POP with biologic functions that suggest a plausible relationship to the disorder are identified. These results may be helpful for furthering the understanding of the pathophysiological mechanisms of POP.

Neuroimaging findings in women who develop neurologic symptoms in severe preeclampsia with or without eclampsia.

Eclampsia is a leading cause of maternal and fetal morbidity and mortality worldwide, and its pathogenesis remains elusive. Our objective was to investigate neuroimaging findings in women who developed neurologic symptoms in severe preeclampsia with or without eclampsia to further understand the relationship between neuroimaging findings and the pathogenesis of eclamptic seizures. This retrospective study included 79 women with severe preeclampsia/eclampsia who underwent brain MRI/CT examination between 2005 and 2017. We analyzed imaging findings, clinical data, and laboratory data in order to compare patients with severe preeclampsia to those with eclampsia and patients with abnormal imaging findings to those with normal CT or MRI. A total of 41 of 79 women were diagnosed with eclampsia, 36 (88.80%) of which had abnormal neuroimaging findings, including cerebral edema (19 cases), infarction (5 cases), cerebral venous thrombosis (5 cases), and cerebral hemorrhage (7 cases). Five patients died of cerebral hemorrhage. Of the 38 cases of severe preeclampsia, 21 (55.26%) cases had abnormal imaging findings, including cerebral edema (20 cases), and 1 case had cerebral hemorrhage. Serum uric acid was significantly higher in patients with abnormal imaging findings than in patients without them (P = 0.004). The imaging findings in women with neurologic symptoms were similar between the severe preeclampsia and eclampsia groups. Our results suggest that eclampsia may not be a diagnosis with a unique pathogenesis; rather, it may be best considered a severe symptom of the intracranial pathophysiology of preeclampsia. We suggest that cranial imaging should be performed early in the management of patients with severe preeclampsia who develop new neurologic symptoms.

Optimal use of peri-operative human chorionic gonadotrophin concentrations to identify persistent ectopic pregnancy after laparoscopic salpingostomy: a retrospective cohort study.

The aim of this study was to improve clinical decision-making for the identification of persistent ectopic pregnancy after linear salpingostomy. The study identified 854 laparoscopic salpingostomies performed between 2011 and 2016; 794 had a human chorionic gonadotrophin (HCG) <10 mIU/ml documented in the electronic medical record within 1 month after surgery ('successes'). Sixty (7%) received either methotrexate or repeat surgery for persistent ectopic pregnancy ('failures'). Five hundred and seventeen, including 46 'failures', had two or more immediate post-operative HCG measurements available. The most clinically useful prediction rule was calculated by dividing the difference between the first and second post-operative HCG values by the first post-operative HCG value (i.e. [HCG1 - HCG2]/HCG1). When this ratio exceeded 0.75, it reliably ruled out persistent ectopic with a negative predictive value = 99%. When this ratio was less than 0.2, it identified persistent ectopics with a positive predictive value = 88%. It appears that this simple arithmetic calculation involving two early post-operative HCG values may allow for efficient triage of patients before post-operative day 5. If validated in prospective studies, this could help minimize the risk, inconvenience and expense of requiring several weeks of frequent follow up to rule in/rule out persistent ectopic pregnancy.

Infection of ectocervical tissue and universal targeting of T-cells mediated by primary non-macrophage-tropic and highly macrophage-tropic HIV-1 R5 envelopes.

BACKGROUND: HIV-1 variants carrying non-macrophage-tropic HIV-1 R5 envelopes (Envs) are predominantly transmitted and persist in immune tissue even in AIDS patients who have highly macrophage-tropic variants in the brain. Non-macrophage-tropic R5 Envs require high levels of CD4 for infection contrasting with macrophage-tropic Envs, which can efficiently mediate infection of cells via low CD4. Here, we investigated whether non-macrophage-tropic R5 Envs from the acute stage of infection (including transmitted/founder Env) mediated more efficient infection of ectocervical explant cultures compared to non-macrophage-tropic and highly macrophage-tropic R5 Envs from late disease. RESULTS: We used Env+ pseudovirions that carried a GFP reporter gene to measure infection of the first cells targeted in ectocervical explant cultures. In straight titrations of Env+ pseudovirus supernatants, mac-tropic R5 Envs from late disease mediated slightly higher infectivities for ectocervical explants although this was not significant. Surprisingly, explant infection by several T/F/acute Envs was lower than for Envs from late disease. However, when infectivity for explants was corrected to account for differences in the overall infectivity of each Env+ pseudovirus (measured on highly permissive HeLa TZM-bl cells), non-mac-tropic early and late disease Env+ pseudoviruses mediated significantly higher infection. This observation suggests that cervical tissue preferentially supports non-mac-tropic Env+ viruses compared to mac-tropic viruses. Finally, we show that T-cells were the main targets for infection regardless of whether explants were stimulated with T-cell or monocyte/macrophage cytokines. There was no evidence of macrophage infection even for pseudovirions carrying highly mac-tropic Envs from brain tissue or for the highly mac-tropic, laboratory strain, BaL, which targeted T-cells in the explant tissue. CONCLUSIONS: Our data support ectocervical tissue as a favorable environment for non-mac-tropic HIV-1 R5 variants and emphasize the role of T-cells as initial targets for infection even for highly mac-tropic variants.

Mesh extrusion through the internal cervical os: an unusual complication following laparoscopic sacrocervicopexy.

Mesh extrusion or exposure is a known complication of procedures using synthetic mesh for vaginal vault and pelvic organ suspension. Preservation of the uterine cervix is thought to be protective against such complications, as the well-vascularized in situ cervix provides an added barrier between the mesh and the colpotomy incision, limiting potential exposure to the vaginal flora. We describe a case of a 55-year-old multipara, who presented with vaginal discharge following a supracervical hysterectomy with sacrocervicopexy and was found to have a delayed mesh extrusion though the endocervical os.

Laparoscopic repair of vesicouterine fistula.

BACKGROUND: Vesicouterine fistulae are the least common type of urogenital fistulae found in women and are often the result of inadvertent bladder injury at the time of cesarean delivery. Few case reports exist on the management and repair of these fistulae. CASE: A 41-year-old woman with a history of three cesarean deliveries with persistent urinary incontinence who underwent laparoscopic repair of a vesicouterine fistula. CONCLUSION: Whereas in the past, these fistulae were predominantly repaired via a transvaginal or abdominal approach, vesicouterine fistulae can be successfully repaired endoscopically.

'I'd rather just go on as I am'--pelvic floor care preferences of frail, elderly women in residential care.

Little is known about how frail, elderly women in assisted living and long-term care facilities view pelvic floor dysfunctions and treatments. Twenty-five residents reflect on these issues, and quality of life.

It's not all about birth: biomechanics applied to pelvic organ prolapse prevention.

Pelvic organ prolapse is a common and costly women's health problem. Prevention of prolapse continues to play a role in the debate about the risks and benefits of elective cesarean section, making this an important topic for midwives to understand. While some women appear to be at higher risk for prolapse because of intrinsic anatomic and physiologic factors, others have modifiable risk factors that can be addressed by health care providers. This article discusses the current knowledge related to the etiology of prolapse and related components of pelvic anatomy. Biomechanical principles are then applied to enhance the understanding of prolapse development and prevention. Clinical recommendations are based on current evidence regarding topics such as physical activity during pregnancy, treatment of vaginal atrophy, and optimal pelvic floor muscle exercises.

Vaginal pressure during lifting, floor exercises, jogging, and use of hydraulic exercise machines.

We recorded vaginal pressure in 12 women without risk factors for prolapse during two activity and exercise sessions, compared exercise and cough pressure, and evaluated method reproducibility and patterns of relative pressure. Portable urodynamic equipment, repeated measures descriptive design, and purposeful sampling were used with nonparametric analysis and visual comparison of pressure graphs. Mean participant age was 31.1 years (range 20-51), and mean body mass index was 22.7 (range 18.5-29.3). Mean pressures (in cm H(2)O): cough, 98.0 (48.0-133.7); standing, 24.0 (15.9-28.5); supine exercise, 34.0 (6.3-91.9); exercise machines, 37.0 (20.3-182.3). Repeated measures correlations for selected measures ranged from 0.66 (p

Midline anterior repair alone vs anterior repair plus vaginal paravaginal repair: a comparison of anatomic and quality of life outcomes.

Our aim was to study the anatomic recurrence rates and quality of life outcomes of patients who had undergone either anterior colporrhaphy (AC) or anterior colporrhaphy and vaginal paravaginal repair (AC + VPVR) as part of surgery for pelvic organ prolapse. Chart reviews were used to identify anatomic prolapse recurrence. Phone interviews assessed quality of life outcomes [Urogenital Distress Inventory (UDI) and the Incontinence Impact Questionnaire (IIQ)] outcomes. There was a trend towards longer time to anatomic recurrence (any compartment > or =grade 2) in the AC group compared with the AC + VPVR group (median 24 vs 13 months, p=0.069). If only patients who had undergone previous surgery were compared, time to anatomic recurrence appeared significantly longer in the AC group (median 41 vs 12 months, p=0.022). There were 55% of women in the AC group and 46% of women in the AC + VPVR group who reported significant bladder or bulge symptoms based on responses to the phone-administered UDI and IIQ (p=0.89). Our retrospective study did not suggest that adding VPVR was superior in terms of anatomic or quality of life outcomes. Prospective assessment of the role of VPVR in the treatment of pelvic organ prolapse is needed.