Oxygen therapy in premature low birth weight infants is associated with capillary loss and increases in blood pressure: a pilot study

Low birth weight (LBW) and premature birth are known risk factors for future cardiovascular disease and in particular essential hypertension (EH). Capillary rarefaction (CR) is an established hallmark of EH and is known to occur in individuals with a history of LBW. We previously reported that LBW infants do not have CR at birth but rather increased capillary density (CD). We hypothesized that LBW infants undergo a process of accelerated CR in early life, triggered in part by oxygen therapy. We studied 26 LBW infants, of whom 10 infants received oxygen therapy, and compared them to 14 normal birth weight (NBW) infants. We measured CD at 1, 5 and 10 days after birth and again after 40 weeks adjusted gestational age equivalent to birth at full term. We confirmed that LBW infants had higher CD at birth compared to NBW infants and found that significant structural CR occurred at term age in LBW infants who had received oxygen therapy (mean difference −22 capillaries/field, p = 0.007) and in those who did not receive oxygen therapy (mean difference −29 capillaries/field, p < 0.001) compared to baseline at birth. Both LBW groups showed a significant rise in BP at 40 weeks adjusted term age and the rise in systolic (mean difference 24 mm Hg, p < 0.0001) and diastolic BP (mean difference 14 mm Hg, p < 0.001) was more pronounced in the oxygen treated group compared to the nonoxygen group (mean difference 14 mm Hg, p = 0.043 and mean difference = 9 mm Hg p = 0.056 respectively). In conclusion, oxygen therapy in premature LBW infants may induce significant increases in their BP in early life

Physical activity for smoking cessation in pregnancy: randomised controlled trial

OBJECTIVE: To determine the effectiveness of a physical activity intervention for smoking cessation during pregnancy. DESIGN: Parallel group, randomised controlled, multicentre trial. SETTING: 13 hospitals in England, April 2009 to January 2014. PARTICIPANTS: 789 pregnant smokers, aged 16-50 years and at 10-24 weeks' gestation, who smoked at least one cigarette daily and were prepared to quit smoking one week after enrollment were randomised (1:1); 785 were included in the intention to treat analyses, with 392 assigned to the physical activity group. INTERVENTIONS: Interventions began one week before a target quit date. Participants were randomised to six weekly sessions of behavioural support for smoking cessation (control) or to this support plus 14 sessions combining supervised treadmill exercise and physical activity consultations. MAIN OUTCOME MEASURES: The primary outcome was continuous smoking abstinence from the target quit date until end of pregnancy, validated by exhaled carbon monoxide or salivary cotinine levels. To assess adherence, levels of moderate-vigorous intensity physical activity were self reported and in a 11.5% (n=90) random subsample of participants, physical activity was objectively measured by an accelerometer. RESULTS: No significant difference was found in rates of smoking abstinence at end of pregnancy between the physical activity and control groups (8% v 6%; odds ratio 1.21, 95% confidence interval 0.70 to 2.10). For the physical activity group compared with the control group, there was a 40% (95% confidence interval 13% to 73%), 34% (6% to 69%), and 46% (12% to 91%) greater increase in self reported minutes carrying out physical activity per week from baseline to one week, four weeks, and six weeks post-quit day, respectively. According to the accelerometer data there was no significant difference in physical activity levels between the groups. Participants attended a median of four treatment sessions in the intervention group and three in the control group. Adverse events and birth outcomes were similar between the two groups, except for significantly more caesarean births in the control group than in the physical activity group (29% v 21%, P=0.023). CONCLUSION: Adding a physical activity intervention to behavioural smoking cessation support for pregnant women did not increase cessation rates at end of pregnancy. During pregnancy, physical activity is not recommended for smoking cessation but remains indicated for general health benefits. Trial registration Current Controlled Trials ISRCTN48600346

Early Life Microcirculatory Plasticity and Blood Pressure Changes in Low Birth Weight Infants Born to Normotensive Mothers: A Cohort Study.

BACKGROUND: Capillary rarefaction (CR) is an established hallmark of essential hypertension (EH). The aim of this study was to examine early changes in capillary density (CD) and blood pressure (BP) in low birth weight (LBW) infants who are at risk of developing EH in later life. METHODS: We studied 77 LBW infants and 284 normal birth weight (NBW) infants, all born to mothers with normotension, in a longitudinal multicenter study. Intravital capillaroscopy was used to measure functional basal capillary density (BCD) and maximal capillary density (MCD) at birth, 3, 6, and 12 months. RESULTS: We found that LBW infants, born preterm and at term, had a significantly higher CD at birth, then underwent significant CR in the 1st 3 months culminating in a CD similar to that seen in NBW infants. NBW infants showed a gradual reduction in CD between birth and 12 months. Non-Caucasian ethnicity and preterm birth were significant predictors of a higher CD at birth. Systolic BP in NBW infants increased significantly from birth to 3 months, and we identified a significant negative correlation between systolic BP and MCD. CONCLUSIONS: This study has identified a process of early "accelerated capillary remodeling" in LBW infants, which corrects their higher CD at birth. This remodeling is unlikely to explain the CR seen in adult individuals with, or at risk of developing EH. Further follow-up studies are required to determine the timing and mechanisms involved in CR, which is likely to occur after the 1st year of life but before early adulthood

Could Perimenopausal Estrogen Prevent Breast Cancer? Exploring the Differential Effects of Estrogen-Only Versus Combined Hormone Replacement Therapy.

Breast cancer is the commonest cancer among women in the western world, accounting for up to 30% of all cancers in women. There is a long-standing controversy about the potential link to hormone replacement therapy (HRT), with large observational studies suggesting that HRT increases the risk, while the Women's Health Initiative (WHI), a prospective, randomized placebo-controlled trial, has reported several times over a period of 20 years that combined (estrogen and progestogen) HRT increases the risk, while estrogen-only HRT given to women who have had a prior hysterectomy, is associated with a significantly reduced risk of developing breast cancer. Evidence from the randomized trial shows a significant reduction in both incidence of and mortality from breast cancer in women who took estrogen replacement therapy; this message needs to be presented clearly and robustly so that it can help women with decision making when considering HRT for menopause

Uterine artery embolization versus surgical treatment in patients with symptomatic uterine fibroids: Protocol for a systematic review and meta-analysis of individual participant data.

OBJECTIVE: Uterine fibroids are the most common benign tumours in women of the reproductive age. Symptoms of heavy menstrual bleeding, abdominal discomfort and infertility may seriously affect a woman's quality of life. Uterine artery embolization is a safe and effective alternative treatment to hysterectomy or myomectomy for symptomatic uterine fibroids. Which treatment provides the highest quality of life, least complications, symptom reduction and least chance intervention, has not been established and might depend on strict patient selection. This study aims to identify which specific subgroups benefit most of each treatment by analyzing individual participant data derived from randomized controlled trials of women undergoing embolization or surgical treatment. This study will primarily assess the effectiveness of both treatment groups by evaluating the effect on quality of life of embolization in comparison to surgery on specific patient and fibroid characteristics and the possible need for re-intervention for fibroid-related symptoms. DATA SOURCES: PubMed/MEDLINE, Embase and The Cochrane Library were searched up to August 2020. STUDY ELIGIBILITY CRITERIA: We will collect individual participant data from randomized controlled trials that studied clinical and procedural outcomes of premenopausal women with symptomatic uterine fibroids, who were randomized between uterine artery embolization and surgery. STUDY APPRAISAL AND SYNTHESIS METHODS: Individual participant data from all eligible trials will be sought and analysed according to intention-to-treat principle. Risk of Bias will be done by using version 2 of the Cochrane tool for Risk of Bias in randomized trials. Subgroup analyses to explore the effect of e.g. age, fibroid characteristics and fibroid complaints will be performed, if data is available. This individual patient data meta-analysis will be analysed according to a one-stage model

Randomised Controlled Trial of Particles Used in Uterine fibRoid Embolisation (PURE): Non-Spherical Polyvinyl Alcohol Versus Calibrated Microspheres.

PURPOSE: The PURE study is a randomised controlled trial (RCT) comparing the clinical and MRI outcomes of patients treated with non-spherical polyvinyl alcohol, ns-PVA (Contour PVA-Boston Scientific-355-500 & 500-700 microns) versus calibrated hydrogel microspheres (Embozene-Varian Inc-700 & 900 microns) for symptomatic uterine fibroids. MATERIALS AND METHODS: Prospective, ethically approved non-sponsored RCT in 84 patients in a single UK tertiary IR unit, ISRCTN registry trial number ISRCTN18191539 in 2013 and 2014. All patients with symptomatic fibroid disease were eligible. UAE followed a standardised protocol with UFS-QOL and contrast-enhanced MRI before and 6 months post UAE. Outcome measures included: (1) Uterine Fibroid Symptom and Quality of Life questionnaire (UFS-QOL). (2) Percentage total and dominant fibroid infarction. (3) Uterine and dominant fibroid volume reduction. (4) Volume of embolics. RESULTS: Sixty-three patients completed the QOL follow-up (33 ns-PVA vs 30 Embozenes), the groups were equivalent at baseline. Patients were followed up for 6 months following UAE. There was no significant difference in symptom scores or HR-QOL between ns-PVA and Embozenes, p = 0.67 and 0.21, respectively. 92.7% of patients treated with ns-PVA achieved > 90% dominant fibroid infarction versus 61.8% treated with Embozenes (p = 0.0016). 66% of patients treated with ns = PVA achieved > 90% total fibroid percentage infarction compared with 35% in the Embozene group (p = 0.011). The mean vials/syringes used were 5.2 with Embozenes versus 4.1 using PVA (p = 0.08). CONCLUSION: The PURE study informs IRs regarding the efficacy of embolic agents in UAE, with superior fibroid infarction on MRI using ns-PVA versus Embozenes however no significant difference in clinical outcomes at 6 months after UAE

Predicting the Fibroid-Migratory Impact of UAE: Role of Pre-embolization MRI Characteristics.

AIM: To investigate potential factors on MR imaging that could be used to predict migration of uterine fibroids post-UAE. METHODS AND MATERIALS: We retrospectively reviewed patients referred for UAE having pre-procedural and 6 months post-procedural MRI, at a tertiary centre, over a 1-year period. Pre- and post-UAE images were reviewed in 64 women by two radiologists to identify the sub-type, dimensions, and infarction rate of each dominant fibroid. The shortest distance between the fibroid and the endometrial wall was measured to determine intramural fibroid movement. Paired sample T tests and two-sample T tests were used to compare between pre- and post-embolization variations and between migrated and non-migrated intramural fibroids, respectively. After preliminary results suggested potential predictors of intramural fibroids migration, we tested our findings against the non-dominant intramural fibroids in the same patients. RESULTS: Review of images revealed 35 dominant intramural fibroids, of which eight migrated to become submucosal fibroids, while five were either partially or completely expelled. These 13 migrated fibroids had a shorter pre-procedural minimum endometrial distance (range 1-2.4 mm) and greater maximum fibroid diameter (range 5.1-18.1 cm), when compared to non-migrating fibroids. On image reassessment, the migrated non-dominant intramural fibroids had a minimum endometrial distance and maximum fibroid diameter within the same range. CONCLUSION: Intramural fibroids with a minimum endometrial distance less than 2.4 mm and a maximum fibroid diameter greater than 5.1 cm have a high likelihood of migrating towards the endometrial cavity after UAE

Effects on heavy menstrual bleeding and pregnancy of uterine artery embolization (UAE) or myomectomy for women with uterine fibroids wishing to avoid hysterectomy: The FEMME randomized controlled trial.

OBJECTIVE: To determine treatment options (myomectomy vs. uterine artery embolization (UAE)) for women wishing to avoid hysterectomy. METHODS: A multicenter randomized controlled trial was conducted on 254 women and data were collected on fibroid-specific quality of life (UFS-QOL), loss of menstrual blood, and pregnancy. RESULTS: At 4 years, the mean difference in the UFS-QOL was 5.0 points (95% confidence interval (CI) -1.4 to 11.5; P = 0.13) in favor of myomectomy. This was not statistically significant as it was at 2 years. There were no differences in bleeding scores, rates of amenorrhea, or heavy bleeding. Of those who were still menstruating, the majority reported regular or fairly regular periods: 36 of 48 (75%) in the UAE group and 30 of 39 (77%) in the myomectomy group. Twelve women after UAE and six women after myomectomy became pregnant (4 years) with seven and five live births, respectively (hazard ratio 0.48, 95% CI 0.18-1.28). There was no difference between the levels of hormones associated with the uterine reserve in each group. CONCLUSION: Leiomyoma are common in reproductive-aged women, causing heavy menses and subfertility. Among women with uterine fibroids, myomectomy resulted in better fibroid-related quality of life at 4 years, compared with UAE but the treatments decreased menstrual bleeding equally. There was also no significant difference in the impact of treatment on ovarian reserve

Uterine artery embolisation versus myomectomy for premenopausal women with uterine fibroids wishing to avoid hysterectomy: the FEMME RCT.

BACKGROUND: Uterine fibroids are the most common tumour in women of reproductive age and are associated with heavy menstrual bleeding, abdominal discomfort, subfertility and reduced quality of life. For women wishing to retain their uterus and who do not respond to medical treatment, myomectomy and uterine artery embolisation are therapeutic options. OBJECTIVES: We examined the clinical effectiveness and cost-effectiveness of uterine artery embolisation compared with myomectomy in the treatment of symptomatic fibroids. DESIGN: A multicentre, open, randomised trial with a parallel economic evaluation. SETTING: Twenty-nine UK hospitals. PARTICIPANTS: Premenopausal women who had symptomatic uterine fibroids amenable to myomectomy or uterine artery embolisation were recruited. Women were excluded if they had significant adenomyosis, any malignancy or pelvic inflammatory disease or if they had already had a previous open myomectomy or uterine artery embolisation. INTERVENTIONS: Participants were randomised to myomectomy or embolisation in a 1 : 1 ratio using a minimisation algorithm. Myomectomy could be open abdominal, laparoscopic or hysteroscopic. Embolisation of the uterine arteries was performed under fluoroscopic guidance. MAIN OUTCOME MEASURES: The primary outcome was the Uterine Fibroid Symptom Quality of Life questionnaire (with scores ranging from 0 to 100 and a higher score indicating better quality of life) at 2 years, adjusted for baseline score. The economic evaluation estimated quality-adjusted life-years (derived from EuroQol-5 Dimensions, three-level version, and costs from the NHS perspective). RESULTS: A total of 254 women were randomised - 127 to myomectomy (105 underwent myomectomy) and 127 to uterine artery embolisation (98 underwent embolisation). Information on the primary outcome at 2 years was available for 81% (n = 206) of women. Primary outcome scores at 2 years were 84.6 (standard deviation 21.5) in the myomectomy group and 80.0 (standard deviation 22.0) in the uterine artery embolisation group (intention-to-treat complete-case analysis mean adjusted difference 8.0, 95% confidence interval 1.8 to 14.1, p = 0.01; mean adjusted difference using multiple imputation for missing responses 6.5, 95% confidence interval 1.1 to 11.9). The mean difference in the primary outcome at the 4-year follow-up time point was 5.0 (95% CI -1.4 to 11.5; p = 0.13) in favour of myomectomy. Perioperative and postoperative complications from all initial procedures occurred in similar percentages of women in both groups (29% in the myomectomy group vs. 24% in the UAE group). Twelve women in the uterine embolisation group and six women in the myomectomy group reported pregnancies over 4 years, resulting in seven and five live births, respectively (hazard ratio 0.48, 95% confidence interval 0.18 to 1.28). Over a 2-year time horizon, uterine artery embolisation was associated with higher costs than myomectomy (mean cost £7958, 95% confidence interval £6304 to £9612, vs. mean cost £7314, 95% confidence interval £5854 to £8773), but with fewer quality-adjusted life-years gained (0.74, 95% confidence interval 0.70 to 0.78, vs. 0.83, 95% confidence interval 0.79 to 0.87). The differences in costs (difference £645, 95% confidence interval -£1381 to £2580) and quality-adjusted life-years (difference -0.09, 95% confidence interval -0.11 to -0.04) were small. Similar results were observed over the 4-year time horizon. At a threshold of willingness to pay for a gain of 1 QALY of £20,000, the probability of myomectomy being cost-effective is 98% at 2 years and 96% at 4 years. LIMITATIONS: There were a substantial number of women who were not recruited because of their preference for a particular treatment option. CONCLUSIONS: Among women with symptomatic uterine fibroids, myomectomy resulted in greater improvement in quality of life than did uterine artery embolisation. The differences in costs and quality-adjusted life-years are very small. Future research should involve women who are desiring pregnancy. TRIAL REGISTRATION: This trial is registered as ISRCTN70772394. FUNDING: This study was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme, and will be published in full in Health Technology Assessment; Vol. 26, No. 22. See the NIHR Journals Library website for further project information