Prediction of fetal death in monochorionic twin pregnancies complicated by Type-III selective fetal growth restriction.

OBJECTIVE: Monochorionic diamniotic twin pregnancies complicated by Type-III selective fetal growth restriction (sFGR) are at high risk of fetal death. The aim of this study was to identify predictors of fetal death in these pregnancies. METHODS: This was an international multicenter retrospective cohort study. Type-III sFGR was defined as fetal estimated fetal weight (EFW) of one twin below the 10th percentile and intertwin EFW discordance of ≥ 25% in combination with intermittent absent or reversed end-diastolic flow in the umbilical artery of the smaller fetus. Predictors of fetal death were recorded longitudinally throughout gestation and assessed in univariable and multivariable logistic regression models. The classification and regression trees (CART) method was used to construct a prediction model of fetal death using significant predictors derived from the univariable analysis. RESULTS: A total of 308 twin pregnancies (616 fetuses) were included in the analysis. In 273 (88.6%) pregnancies, both twins were liveborn, whereas 35 pregnancies had single (n = 19 (6.2%)) or double (n = 16 (5.2%)) fetal death. On univariable analysis, earlier gestational age at diagnosis of Type-III sFGR, oligohydramnios in the smaller twin and deterioration in umbilical artery Doppler flow were associated with an increased risk of fetal death, as was larger fetal EFW discordance, particularly between 24 and 32 weeks' gestation. None of the parameters identified on univariable analysis maintained statistical significance on multivariable analysis. The CART model allowed us to identify three risk groups: a low-risk group (6.8% risk of fetal death), in which umbilical artery Doppler did not deteriorate; an intermediate-risk group (16.3% risk of fetal death), in which umbilical artery Doppler deteriorated but the diagnosis of sFGR was made at or after 16 + 5 weeks' gestation; and a high-risk group (58.3% risk of fetal death), in which umbilical artery Doppler deteriorated and gestational age at diagnosis was < 16 + 5 weeks' gestation. CONCLUSIONS: Type-III sFGR is associated with a high risk of fetal death. A prediction algorithm can help to identify the highest-risk group, which is characterized by Doppler deterioration and early referral. Further studies should investigate the potential benefit of fetal surveillance and intervention in this cohort. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Growth patterns of monochorionic twin pregnancy complicated by Type-III selective fetal growth restriction.

OBJECTIVES: Little is known regarding fetal growth patterns in monochorionic twin pregnancy complicated by Type-III selective fetal growth restriction (sFGR). We aimed to assess fetal growth and umbilical artery Doppler pattern in Type-III sFGR across gestation and evaluate the effect of changing Doppler flow pattern on growth and intertwin growth discordance. METHODS: This was a retrospective cohort study of all Type-III sFGR pregnancies managed at nine fetal centers over a 12-year time period. Higher-order multiple pregnancy and cases with major fetal anomaly or other monochorionicity-related complications at presentation were excluded. Estimated fetal weight (EFW) was assessed on ultrasound for each twin pair at five timepoints (16-20, 21-24, 25-28, 29-32 and > 32 weeks' gestation) and compared with singleton and uncomplicated monochorionic twin EFW. EFW and intertwin EFW discordance were compared between pregnancies with normalization of umbilical artery Doppler of the smaller twin later in pregnancy and those with persistently abnormal Doppler. RESULTS: Overall, 328 pregnancies (656 fetuses) met the study criteria. In Type-III sFGR, the smaller twin had a lower EFW than an average singleton fetus (EFW Z-score ranging from -1.52 at 16 weeks to -2.69 at 36 weeks) and an average monochorionic twin in uncomplicated pregnancy (Z-score ranging from -1.73 at 16 weeks to -1.49 at 36 weeks) throughout the entire gestation, while the larger twin had a higher EFW than an average singleton fetus until 22 weeks' gestation and was similar in EFW to an average uncomplicated monochorionic twin throughout gestation. As pregnancy advanced, growth velocity of both twins decreased, with the larger twin remaining appropriately grown and the smaller twin becoming more growth restricted. Intertwin EFW discordance remained stable throughout gestation. On multivariable longitudinal modeling, normalization of fetal umbilical artery Doppler was associated with better growth of the smaller twin (P = 0.002) but not the larger twin (P = 0.1), without affecting the intertwin growth discordance (P = 0.09). CONCLUSIONS: Abnormal fetal growth of the smaller twin in Type-III sFGR was evident early in pregnancy, while EFW of the larger twin remained normal throughout gestation. Normalization of umbilical artery Doppler was associated with improved fetal growth of the smaller twin. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Bilateral symmetry of breast tissue composition by magnetic resonance in young women and adults.

BACKGROUND: Some reports suggest that there is a slightly higher frequency of breast cancer in the left breast compared with the right in middle-aged women. The reasons for this association are unknown. The water and fat content of both breasts was compared using magnetic resonance (MR). Breast water by MR reflects fibro-glandular tissue and is strongly positively correlated with percent mammographic density, a strong risk factor for breast cancer. METHODS: Magnetic resonance was used to measure fat and water content of the breast in 400 young women aged 15-30 years and a random sample of 100 of their mothers. All MR examinations were carried out using a 1.5T MR system, and 45 contiguous slices were obtained in the sagittal plane. One reader identified the breast tissue in the image, and subsequently, fat and water content was calculated using a three-point Dixon technique. Left- and right-sided images were read independently in random order. RESULTS: In young women, mean percent water was on average 0.84 % higher in the right compared with the left breast (p < 0.001) and total breast water was on average 6.42 cm(3) greater on the right side (p < 0.001). In mothers, there were no significant differences in any breast measure between right and left sides. CONCLUSION: The small differences in breast tissue composition in young women are unlikely to be associated with large differences in breast cancer risk between sides. The reported excess of left-sided breast cancer in older women is unlikely to be explained by differences in breast tissue composition.

Impact of informed consent requirements on cardiac arrest research in the United States: exception from consent or from research?

INTRODUCTION: Research in patients with life-threatening illness such as cardiac arrest is challenging since they can not consent. The Food and Drug Administration addressed research under emergency conditions by publishing new criteria for exception from informed consent in 1996. We systematically reviewed randomized trials over a 10-year period to assess the impact of these regulations. METHODS: Case-control study of published trials for cardiac arrest (cases) and atrial fibrillation (controls.) Studies were identified by using structured searches of MEDLINE and EMBASE from 1992 to 2002. Included were studies using random allocation in humans with cardiac arrest or atrial fibrillation prior to enrollment. Excluded were duplicate publications. Number of American trials, foreign trials and proportion of trials of American origin were compared by using regression analysis. Changes in cardiac arrest versus atrial fibrillation trials were calculated as risk differences. RESULTS: Of 4982 identified cardiac arrest studies, 57 (1.1%) were randomized trials. The number of American cardiac arrest trials decreased by 15% (95% CI: 8, 22%) annually (P = 0.05). The proportion of cardiac arrest trials of American origin decreased by 16% (95% CI: 10, 22%) annually (P = 0.006). Of 5596 identified atrial fibrillation studies, 197 trials (3.5%) were randomized trials. The risk difference between cardiac arrest versus atrial fibrillation trials being of American origin decreased significantly (annual difference -5.8% (95% CI: -10, -0.1%), P = 0.03). INTERPRETATION: Fewer American cardiac arrest trials were published during the last decade, when federal consent requirements changed. Regulatory requirements for clinical trials may inhibit improvements in care and threaten public health.

Cost effectiveness of defibrillation by targeted responders in public settings.

BACKGROUND: Out-of-hospital cardiac arrest is frequent and has poor outcomes. Defibrillation by trained targeted nontraditional responders improves survival versus historical controls, but it is unclear whether such defibrillation is a good value for the money. Therefore, this study estimated the incremental cost effectiveness of defibrillation by targeted nontraditional responders in public settings by using decision analysis. METHODS AND RESULTS: A Markov model evaluated the potential cost effectiveness of standard emergency medical services (EMS) versus targeted nontraditional responders. Standard EMS included first-responder defibrillation followed by advanced life support. Targeted nontraditional responders included standard EMS supplemented by defibrillation by trained lay responders. The analysis adopted a US societal perspective. Input data were derived from published or publicly available data. Future costs and effects were discounted at 3%. Monte Carlo simulation and sensitivity analyses assessed the robustness of results. Standard EMS had a median of 0.47 (interquartile range [IQR]=0.32 to 0.69) quality-adjusted life years and a median of 14 100 dollars (IQR=8600 dollars to 21 900 dollars) costs per arrest. Targeted nontraditional responders in casinos had an incremental cost of a median 56 700 dollars (IQR=44 100 dollars to 77 200 dollars) per additional quality-adjusted life year. The results were sensitive to changes in time to defibrillation, incidence of arrest, and number of devices required to implement rapid defibrillation. CONCLUSIONS: Where cardiac arrest is frequent and response time intervals are short, rapid defibrillation by targeted nontraditional responders may be a good value for the money compared with standard EMS. The incidence of arrest should be considered when choosing locations to implement public access defibrillation.