Sarah E Little

The effect of cesarean delivery rates on the future incidence of placenta previa, placenta accreta, and maternal mortality.

Objective. The overall annual incidence rate of caesarean delivery in the United Sates has been steadily rising since 1996, reaching 32.9% in 2009. Primary cesareans often lead to repeat cesareans, which may lead to placenta previa and placenta accreta. This studys goal was to forecast the effect of rising primary and secondary cesarean rates on annual incidence of placenta previa, placenta accreta, and maternal mortality. Methods. A decision-analytic model was built using TreeAge Pro software to estimate the future annual incidence of placenta previa, placenta accreta, and maternal mortality using data on national birthing order trends and cesarean and vaginal birth after cesarean rates. Baseline assumptions were derived from the literature, including the likelihood of previa and accreta among women with multiple previous cesarean deliveries. Results.  If primary and secondary cesarean rates continue to rise as they have in recent years, by 2020 the cesarean delivery rate will be 56.2%, and there will be an additional 6236 placenta previas, 4504 placenta accretas, and 130 maternal deaths annually. The rise in these complications will lag behind the rise in cesareans by approximately 6 years. Conclusions. If cesarean rates continue to increase, the annual incidence of placenta previa, placenta accreta, and maternal death will also rise substantially.

Increased mitochondrial uncoupling proteins, respiratory uncoupling and decreased efficiency in the chronically infarcted rat heart.

Heart failure patients have abnormal cardiac high energy phosphate metabolism, the explanation for which is unknown. Patients with heart failure also have elevated plasma free fatty acid (FFA) concentrations. Elevated FFA levels are associated with increased cardiac mitochondrial uncoupling proteins (UCPs), which, in turn, are associated with decreased mitochondrial respiratory coupling and low cardiac efficiency. Here, we determined whether increased mitochondrial UCP levels contribute to decreased energetics in the failing heart by measuring UCPs and respiration in mitochondria isolated from the viable myocardium of chronically infarcted rat hearts and measuring efficiency (hydraulic work/O(2) consumption) in the isolated, working rat heart. Ten weeks after infarction, cardiac levels of UCP3 were increased by 53% in infarcted, failing hearts that had ejection fractions less than 45%. Cardiac UCP3 levels correlated positively with non-fasting plasma FFAs (r=0.81; p<0.01). Mitochondria from failing hearts were less coupled than those from control hearts, as demonstrated by the lower ADP/O ratio of 1.9+/-0.1 compared with 2.5+/-0.2 in controls (p<0.05). The decreased ADP/O ratio was reflected in an efficiency of 14+/-2% in the failing hearts when perfused with 1 mM palmitate, compared with 20+/-1% in controls (p<0.05). We conclude that failing hearts have increased UCP3 levels that are associated with high circulating FFA concentrations, mitochondrial uncoupling, and decreased cardiac efficiency. Thus, respiratory uncoupling may underlie the abnormal energetics and low efficiency in the failing heart, although whether this is maladaptive or adaptive would require direct investigation.

Gynecologic cancer prevention in Lynch syndrome/hereditary nonpolyposis colorectal cancer families

OBJECTIVE: Women from Lynch syndrome/hereditary nonpolyposis colorectal cancer (Lynch/HNPCC) families have an increased lifetime risk of developing endometrial and ovarian cancer. This study models a comparison of management strategies for women who carry a Lynch/HNPCC mutation. METHODS: A decision analytic model with three arms was designed to compare annual gynecologic examinations with annual screening (ultrasonography, endometrial biopsy, CA 125) and with hysterectomy with bilateral salpingo-oophorectomy at age 30 years The existing literature was searched for studies on the accuracy of endometrial and ovarian cancer screening using endometrial biopsy, transvaginal ultrasonography, and serum CA 125. The Surveillance, Epidemiology and End Results database from 1988 to 2001 was used to estimate cancer mortality outcomes. RESULTS: In the surgical arm, 0.0056% of women were diagnosed with ovarian cancer and 0.0060% of women with endometrial cancer. These numbers increased to 3.7% and 18.4% in women being screened, and 8.3% and 48.7% in women undergoing annual examinations, respectively. Surgical management led to the longest expected survival time at 79.98 years, followed by screening at 79.31 years, and annual examinations at 77.41 years. If starting at age 30 and discounting life years at 3%, surgery still leads to the greatest expected life years. When comparing prophylactic surgery with the screening option, one would need to perform 75 surgeries to save one womans entire life. For cancer prevention, however, only 28 and 6 prophylactic surgeries would need to be performed to prevent one case of ovarian and endometrial cancer, respectively. CONCLUSION: Risk-reducing hysterectomy and bilateral salpingo-oophorectomy may be considered in women with Lynch/HNPCC to prevent gynecologic cancers and their associated morbidities. LEVEL OF EVIDENCE: III

A cost-effectiveness analysis of prophylactic surgery versus gynecologic surveillance for women from hereditary non-polyposis colorectal cancer (HNPCC) Families

Women at risk for Lynch Syndrome/HNPCC have an increased lifetime risk of endometrial and ovarian cancer. This study investigates the cost-effectiveness of prophylactic surgery versus surveillance in women with Lynch Syndrome. A decision analytic model was designed incorporating key clinical decisions and existing probabilities, costs, and outcomes from the literature. Clinical forum where risk-reducing surgery and surveillance were considered. A theoretical population of women with Lynch Syndrome at age 30 was used for the analysis. A decision analytic model was designed comparing the health outcomes of prophylactic hysterectomy with bilateral salpingo-oophorectomy at age 30 versus annual gynecologic screening versus annual gynecologic exam. The literature was searched for probabilities of different health outcomes, results of screening modalities, and costs of cancer diagnosis and treatment. Cost-effectiveness expressed in dollars per discounted life-years. Risk-reducing surgery is the least expensive option, costing

Estimated fetal weight by ultrasound: a modifiable risk factor for cesarean delivery?

23,422 per patient for 25.71 quality-adjusted life-years (QALYs). Annual screening costs

Cost-effectiveness of elective induction of labor at 41 weeks in nulliparous women

68,392 for 25.17 QALYs; and annual examination without screening costs

Mitochondrial damage during myocardial ischemia

100,484 for 24.60 QALYs. Further, because risk-reducing surgery leads to both the lowest costs and the highest number of QALYs, it is a dominant strategy. Risk-reducing surgery is the most cost-effective option from a societal healthcare cost perspective.

Early-onset preeclampsia and neonatal outcomes

OBJECTIVE The purpose of this study was to investigate whether knowledge of ultrasound-obtained estimated fetal weight (US-EFW) is a risk factor for cesarean delivery (CD). STUDY DESIGN Retrospective cohort from a single center in 2009-2010 of singleton, term live births. CD rates were compared for women with and without US-EFW within 1 month of delivery and adjusted for potential confounders. RESULTS Of the 2329 women in our cohort, 50.2% had US-EFW within 1 month of delivery. CD was significantly more common for women with US-EFW (15.7% vs 10.2%; P < .001); after we controlled for confounders, US-EFW remained an independent risk factor for CD (odds ratio, 1.44; 95% confidence interval, 1.1-1.9). The risk increased when US-EFW was >3500 g (odds ratio, 1.8; 95% confidence interval, 1.3-2.7). CONCLUSION Knowledge of US-EFW, above and beyond the impact of fetal size itself, increases the risk of CD. Acquisition of US-EFW near term appears to be an independent and potentially modifiable risk factor for CD.

The cost-effectiveness of prenatal screening for spinal muscular atrophy

OBJECTIVE To investigate the cost-effectiveness of elective induction of labor at 41 weeks in nulliparous women. STUDY DESIGN A decision analytic model comparing induction of labor at 41 weeks vs expectant management with antenatal testing until 42 weeks in nulliparas was designed. Baseline assumptions were derived from the literature as well as from analysis of the National Birth Cohort dataset and included an intrauterine fetal demise rate of 0.12% in the 41st week and a cesarean rate of 27% in women induced at 41 weeks. One-way and multiway sensitivity analyses were conducted to examine the robustness of the findings. RESULTS Compared with expectant management, induction of labor is cost-effective with an incremental cost of

A Multi-State Analysis of Early-Term Delivery Trends and the Association With Term Stillbirth.

10,945 per quality-adjusted life year gained. Induction of labor at 41 weeks also resulted in a lower rate of adverse obstetric outcomes, including neonatal demise, shoulder dystocia, meconium aspiration syndrome, and severe perineal lacerations. CONCLUSION Elective induction of labor at 41 weeks is cost-effective and improves outcomes.