Long-Term Maternal Metabolic and Cardiovascular Phenotypes after a Pregnancy Complicated by Mild Gestational Diabetes Mellitus or Obesity.

OBJECTIVE: The aim of this study was to evaluate the association of mild gestational diabetes mellitus (GDM) and obesity with metabolic and cardiovascular markers 5 to 10 years after pregnancy. STUDY DESIGN: This was a secondary analysis of 5- to 10-year follow-up study of a mild GDM treatment trial and concurrent observational cohort of participants ineligible for the trial with abnormal 1-hour glucose challenge test only. Participants with 2-hour glucose tolerance test at follow-up were included. The primary exposures were mild GDM and obesity. The outcomes were insulinogenic index (IGI), 1/homeostatic model assessment of insulin resistance (HOMA-IR), and cardiovascular markers vascular endothelial growth factor, (VEGF), vascular cell adhesion molecule 1 (VCAM-1), cluster of differentiation 40 ligand (CD40L), growth differentiation factor 15 (GDF-15), and suppression of tumorgenesis 2 (ST-2). Multivariable linear regression estimated the association of GDM and obesity with biomarkers. RESULTS: Of 951 participants in the parent study, 642 (68%) were included. Lower 1/HOMA-IR were observed in treated and untreated GDM groups, compared with non-GDM (mean differences, -0.24 and -0.15; 95% confidence intervals [CIs], -0.36 to -0.12 and -0.28 to -0.03, respectively). Lower VCAM-1 (angiogenesis) was observed in treated GDM group (mean difference, -0.11; 95% CI, -0.19 to -0.03). GDM was not associated with IGI or other biomarkers. Obesity was associated with lower 1/HOMA-IR (mean difference, -0.42; 95% CI, -0.52 to -0.32), but not other biomarkers. CONCLUSION: Prior GDM and obesity are associated with more insulin resistance but not insulin secretion or consistent cardiovascular dysfunction 5 to 10 years after delivery. KEY POINTS: · Mild GDM increases the risk of insulin resistance 5 to 10 years postpartum but not pancreatic dysfunction.. · Obesity increases the risk of insulin resistance 5 to 10 years postpartum but not pancreatic dysfunction.. · Neither mild GDM nor obesity increased the risk of cardiovascular dysfunction 5 to 10 years postpartum..

Post-Cesarean Opioid Use after Implementation of Enhanced Recovery after Surgery Protocol.

OBJECTIVE: This study aimed to evaluate whether implementation of an enhanced recovery after surgery (ERAS) protocol is associated with lower maternal opioid use after cesarean delivery (CD). STUDY DESIGN: We performed a pre- and postimplementation (PRE and POST, respectively) study of an ERAS protocol for cesarean deliveries. ERAS is a multimodal, multidisciplinary perioperative approach. The four pillars of our protocol include education, pain management, nutrition, and early ambulation. Patients were counseled by their outpatient providers and given an educational booklet. Pain management included gabapentin and acetaminophen immediately prior to spinal anesthesia. Postoperatively patients received scheduled acetaminophen and ibuprofen. Oxycodone was initiated as needed 24 hours after spinal analgesia. Preoperative diet consisted of clear carbohydrate drink consumed 2 hours prior to scheduled operative time with advancement as tolerated immediately postoperation. Women with a body mass index (BMI) <40 kg/m2 and scheduled CD were eligible for ERAS. PRE patients were randomly selected from repeat cesarean deliveries (RCDs) at a single site from October 2017 to September 2018, BMI <40 kg/m2, without trial of labor. The POST cohort included women who participated in ERAS from October 2018 to June 2019. PRE and POST demographic and clinical characteristics were compared. Primary outcome was total postoperative morphine milligram equivalents (MMEs). Secondary outcomes included length of stay (LOS) and maximum postoperative day 2 (POD2) pain score. RESULTS: All women in PRE (n = 70) had RCD compared with 66.2% (49/74) in POST. Median total postoperative MMEs were 140.0 (interquartile range [IQR]: 87.5-182.5) in PRE compared with 0.0 (IQR: 0.0-72.5) in POST (p < 0.001). Median LOS in PRE was 4.02 days (IQR: 3.26-4.27) compared with 2.37 days (IQR: 2.21-3.26) in POST (p < 0.001). Mean maximum POD2 pain score was 5.28 (standard deviation [SD] = 1.86) in PRE compared with 4.67 (SD = 1.63) in POST (p = 0.04). CONCLUSION: ERAS protocol was associated with decreased postoperative opioid use, shorter LOS, and decreased pain after CD. KEY POINTS: · ERAS protocol was associated with decreased postoperative opioid use after CD.. · ERAS protocol was associated with shorter length of stay after CD.. · ERAS protocol was associated with decreased postoperative pain after CD..

Evidence for a Complex Relationship Among Weight Retention, Cortisol and Breastfeeding in Postpartum Women.

Objective To assess the relationship between cortisol slope, a biologic marker of stress, and postpartum weight retention. Methods We included 696 women in a secondary analysis from a multi-site study conducted using principles of community-based participatory research to study multi-level sources of stress on pregnancy outcomes. As a stress marker, we included salivary cortisol slope; the rate of cortisol decline across the day. Pre-pregnancy weight and demographic data were obtained from the medical records. At 6 months postpartum, patients were weighed and returned saliva samples. We built stepwise regression models to assess the effect of demographic variables, cortisol slope and cortisol covariates (wake time, tobacco use and breastfeeding) on postpartum weight retention. Results 45.5 % of participants were African American, 29.2 % White, and 25.3 % Hispanic. Of the Hispanic women 62.5 % were Spanish speaking and 37.5 % were English speaking. In general, participants were young, multiparous, and overweight. Postpartum, almost half (47.6 %) of women studied retained >10 lbs. In multivariable analysis including age, pre-pregnancy BMI and public insurance, cortisol slope was significantly associated with weight retention (ß = -1.90, 95 % CI = 0.22-3.58). However, when the model was adjusted for the cortisol covariates, breastfeeding (ß = -0.63, 95 % CI = -1.01 to -0.24) and public insurance (ß = 0.62, 95 % CI = 0.20-1.04) were the two strongest correlates of weight retention. Conclusions for Practice The association between cortisol slope and postpartum weight retention appears to be influenced breastfeeding status.

Urolithiasis in pregnancy: a cost-effectiveness analysis of ureteroscopic management vs ureteral stenting.

OBJECTIVE: The purpose of this study was to determine the cost-effectiveness of serial stenting vs ureteroscopy for treatment of urolithiasis during pregnancy as a function of gestational age (GA) at diagnosis. STUDY DESIGN: We built decision analytic models for a hypothetical cohort of pregnant women who had received a diagnosis of symptomatic ureteral calculi and compared serial stenting to ureteroscopy. We assumed ureteral stent replacement every 4 weeks during pregnancy, intravenous sedation for stent placement, and spinal anesthetic for ureteroscopy. Outcomes were derived from the literature and included stent infection, migration, spontaneous kidney stone passage, ureteral injury, failed ureteroscopy, postoperative urinary tract infection, sepsis, and anesthetic complications. Four separate analyses were run based on the GA at diagnosis of urolithiasis. Using direct costs and quality-adjusted life years, we reported the incremental costs and effectiveness of each strategy based on GA at kidney stone diagnosis and calculated the net monetary benefit. We performed 1-way and Monte-Carlo sensitivity analyses to assess the strength of the model. RESULTS: Ureteroscopy was less costly and more effective for urolithiasis, irrespective of GA at diagnosis. The incremental cost of ureteroscopy increased from -$74,469 to -$7631, and the incremental effectiveness decreased from 0.49 to 0.05 quality-adjusted life years for a kidney stone diagnosed at 12 and 36 weeks of gestation, respectively. The net monetary benefit of ureteroscopy progressively decreased for kidney stones that were diagnosed later in pregnancy. The model was robust to all variables. CONCLUSION: Ureteroscopy is less costly and more effective relative to serial stenting for urolithiasis, regardless of the GA at diagnosis. Ureteroscopy is most beneficial for women who received the diagnosis early during pregnancy.

Periprostatic adipose tissue from obese prostate cancer patients promotes tumor and endothelial cell proliferation: a functional and MR imaging pilot study.

BACKGROUND: Obesity, particularly visceral adiposity, confers a worse prognosis for prostate cancer (PCa) patients, and increasing periprostatic adipose (PPA) tissue thickness or density is positively associated with more aggressive disease. However, the cellular mechanism of this activity remains unclear. Therefore, in this pilot study, we assessed the functional activity of PPA tissue secretions and established a biochemical profile of PPA as compared to subcutaneous adipose (SQA) tissues from lean, overweight and obese PCa patients. METHODS: Adipose tissues were collected from PCa patients undergoing surgical prostate removal. Tissues were analyzed by histologic and magnetic resonance (MR) techniques. Explant tissue culture secretions were used in proliferation assays on PCa and endothelial cells. RESULTS: PPA secretions obtained from obese patients were significantly more pro-proliferative in both PCa and endothelial cells as compared to PPA obtained from lean or overweight men and SQA tissues. Consistent with this, PPA microvessel density was increased, and the T2 relaxation time was decreased, compared to SQA tissues, and we observed a modest, inverse correlation between the T2 and tumor stage. Moreover, the ratio of unsaturated to saturated fatty acids, obtained using MR spectroscopy, showed a modest, inverse correlation with Gleason score. CONCLUSIONS: These pilot data show that PPA stimulates PCa cell proliferation and angiogenesis and that obesity intensifies this activity, thus generating a mechanistic hypothesis to explain the worse prognosis observed in obese PCa patients. Our pilot study also shows that MR technology may be useful in further elucidating the relationship between obesity and PCa progression.

PEDF & stem cells: niche vs. nurture.

Anti-angiogenic pigment epithelium-derived factor (PEDF) is a multifunctional 50kD secreted glycoprotein emerging as a key factor in stem cell renewal. Characteristics of the stem cell niche can be highly dependent on location, access to the vasculature, oxygen tension and neighboring cells. In the neural stem cell (NSC) niche, specifically the subventricular zone, PEDF actively participates in the self renewal process and promotes stemness by upregulating Notch signaling effectors Hes1 and Hes5. The local vascular endothelial cells and ependymal cells are the likely sources of PEDF for the NSC while mesenchymal and retinal stem cells can actually produce PEDF. The opposing actions of PEDF and VEGF on various cells are recapitulated in the NSC niche. Intraventricular injection of PEDF promotes stem cell renewal, while injection of VEGF prompts differentiation and neurogenesis in the subventricular zone. Enhancing the expression of PEDF in stem cells has promising therapeutic implications. Bone marrow mesenchymal stem cells overexpressing PEDF effectively inhibited pathologic angiogenesis in the murine eye and these same cells suppressed hepatocellular carcinoma growth. As a protein with bioactivities in nearly all normal organ systems, it is likely that PEDF will continue to gain visibility as an essential component in the development and delivery of novel stem cell-based therapies to combat disease.

Cost-effectiveness analysis of rubella screening strategies using electronic medical records.

OBJECTIVE: The redundancy of routine laboratory tests in medicine has become increasingly more apparent in the age of electronic medical records (EMRs). The purpose of this study was to determine whether targeted screening strategies are more cost-effective than the current standard of universal screening of pregnant women for immunity to rubella. STUDY DESIGN: A decision analysis model was used to evaluate three strategies: universal screening, screening if a previous titer was not available, and use of an "alert" in the EMR to prompt screening. Cost, probability, and utility values were derived from the literature and institutional data from Lyndon B. Johnson General Hospital. One-way sensitivity analyses were performed on all cost and probability values. RESULTS: The strategy of an EMR alert was most cost-effective, with a cost of $0.27 per quality-adjusted life years (QALY). The model was robust to all costs and probability values over their respective ranges. CONCLUSIONS: Although all strategies were cost-effective compared with traditional industry benchmarks of $50,000/QALY, the EMR alert strategy is most cost-effective. Implementing an EMR alert may lead to a more cost-effective approach to prenatal evaluation of rubella immunity.

Shepherd hook anomaly of ductus arteriosus with sudden intrapartum fetal demise: two case reports.

Patency of the ductus arteriosus is critical in maintaining fetal circulation, and premature closure is associated with fetal and early neonatal death. We present 2 cases of sudden demise in the delivery room associated with atypical ductal anatomy with obstruction due to kinking and intraluminal intimal ridges. Shepherd hook anomaly of the ductus arteriosus may represent a new congenital heart lesion associated with poor fetal outcome.

Decreased expression of pigment epithelium derived factor (PEDF), an inhibitor of angiogenesis, in placentas of unexplained stillbirths.

Normal placental vascular development depends upon the complex interactions between angiogenic inducers and inhibitors within the placenta. Alterations within the placental microenvironment can promote an imbalance in angiogenic mediators which may be associated with adverse perinatal outcomes. The purpose of this study was to investigate the placentas of infants with unexplained stillbirth as compared to live-born infants and to determine whether alterations in angiogenic inducer vascular endothelial growth factor (VEGF) or inhibitor pigment epithelium-derived factor (PEDF) are associated with altered angiogenesis, vascular remodeling and stillbirth. Placentas of 22 unexplained stillbirths and 44 age-matched live-born controls were scored for microvascular density (MVD), vasculopathy and microvascular permeability. A subset was scored for expression of angiogenic inducer VEGF and inhibitor pigment epithelium-derived factor. Stillborn placentas demonstrated higher MVD than controls (mean+SD: 116.6+/-46.3 v. 60.8+/-13.5, respectively, p<0.001). Vasculopathy was present in 10/22 (45%) stillbirths compared to 0/44 (0%) controls (p<0.001); increased vascular permeability was present in 15/22 (68%) cases and 5/44 (11%) controls (p<0.001). PEDF expression was significantly lower in stillborn placentas (1.7+/-0.3) than live-born controls (3.6+/-0.8, p<0.01) while VEGF expression was similar (3.3+/-0.7 v. 3.7+/-0.4, respectively, p>0.05). In conclusion, we found that unexplained stillbirth is associated with loss of angiogenic inhibitor PEDF, vasculopathy and heightened angiogenesis in the placenta.

Health literacy and patient understanding of screening tests for aneuploidy and neural tube defects.

OBJECTIVE: To determine if health literacy is associated with patient understanding of prenatal screening tests for fetal aneuploidy and neural tube defects. METHODS: We performed a prospective observational study on a cohort of English-speaking patients receiving prenatal care in two resident-staffed ambulatory clinics. Health literacy was measured using the Rapid Estimate of Adult Literacy in Medicine-7. Understanding of the prenatal screening tests was assessed using a modified Maternal Serum Screening Knowledge Questionnaire. RESULTS: Over an 8-month period, 125 patients were approached, and 101 (81%) consented to the study. Thirty-eight (38%) women demonstrated low health literacy. Patients with low health literacy were more likely to demonstrate inadequate understanding when compared to those with adequate health literacy (97% versus 11%, respectively; P < 0.01). Similarly, patients with < 12th grade education were more likely to have inadequate understanding when compared to patients with > 12th grade education (53% versus 30%, respectively; P = 0.02). Health literacy is a more sensitive and specific predictor of inadequate understanding than education (sensitivity 84% versus 70%, respectively, P < 0.05; specificity 98% versus 47%, respectively, P < 0.05). CONCLUSION: Patients with low health literacy are more likely to demonstrate inadequate understanding of these prenatal screening tests than women with adequate health literacy.

Routine hepatitis C virus screening in pregnancy: a cost-effectiveness analysis.

OBJECTIVE: The purpose of this study was to determine whether routine hepatitis C virus screening in pregnancy is cost-effective. STUDY DESIGN: A decision tree with Markov analysis was developed to compare 3 approaches to asymptomatic hepatitis C virus infection in low-risk pregnant women: (1) no hepatitis C virus screening, (2) hepatitis C virus screening and subsequent treatment for progressive disease, and (3) hepatitis C virus screening, subsequent treatment for progressive disease, and elective cesarean delivery to avert perinatal transmission. Lifetime costs and quality-adjusted life years were evaluated for mother and child. RESULTS: In our base case, hepatitis C virus screening and subsequent treatment of progressive disease was dominated (more costly and less effective) by no screening, with an incremental cost of 108 US dollars and a decreased incremental effectiveness of 0.00011 quality-adjusted life years. When compared with no screening, the marginal cost and effectiveness of screening, treatment, and cesarean delivery was 117 US dollars and 0.00010 quality-adjusted life years, respectively, which yields a cost-effectiveness ratio of 1,170,000 US dollars per quality-adjusted life year. CONCLUSION: The screening of asymptomatic pregnant women for hepatitis C virus infection is not cost-effective.

The importance of physician gender in the selection of an obstetrician or a gynecologist.

OBJECTIVE: The purpose of this study was to determine the importance of gender in the selection of an obstetrician or a gynecologist. STUDY DESIGN: At a university-based hospital, 46 patients after delivery and 79 patients after gynecologic surgery who had selected their physician within the previous year were interviewed to determine the importance of physician gender in the selection of an obstetrician or gynecologist. Chi-square test, Fisher exact test, and the Student t test were used for statistical analysis. RESULTS: Of the 125 women who were surveyed, 52.8% of the women preferred a female physician, 9.6% of the women preferred a male physician, and 37.6% of the women stated no gender preference, with no significant difference between the obstetric and gynecologic groups. The groups were similar with respect to ranking the importance of gender; 24.8% of the women who were interviewed considered gender to be one of the 3 most important factors in the selection of a physician. When participants were asked to choose gender over physician experience, bedside manner, or competency, gender was selected by 12%, 10.4%, and 0.8%, respectively, with no significant differences between the groups. CONCLUSION: For most women, physician gender is not of primary importance in the selection of an obstetrician or gynecologist.