Plasma soluble fms-like tyrosine kinase 1 to placental growth factor ratio of 11.5 multiples of median predicts preeclampsia with severe features within 2 weeks of testing.

BACKGROUND: Angiogenic imbalances, characterized by an excess of antiangiogenic factors (soluble fms-like tyrosine kinase 1) and reduced angiogenic factors (vascular endothelial growth factor and placental growth factor), contribute to the mechanisms of disease in preeclampsia. The ratio of soluble fms-like tyrosine kinase 1 to placental growth factor has been used as a biomarker for preeclampsia, but the cutoff values may vary with gestational age and assay platform. OBJECTIVE: This study aimed to compare multiples of the median of the maternal plasma soluble fms-like tyrosine kinase 1 to placental growth factor ratio, soluble fms-like tyrosine kinase 1, placental growth factor, and conventional clinical and laboratory values in their ability to predict preeclampsia with severe features. STUDY DESIGN: We conducted a cohort study across 18 United States centers involving hospitalized individuals with hypertension between 23 and 35 weeks' gestation. Receiver operating characteristic curve analyses of maternal plasma biomarkers, highest systolic or diastolic blood pressures, and laboratory values at enrollment were performed for the prediction of preeclampsia with severe features. The areas under the curve were compared, and quasi-Poisson regression models were fitted to estimate relative risks. The primary outcome was preeclampsia with severe features within 2 weeks of enrollment. Secondary outcomes were a composite of severe adverse maternal outcomes (elevated liver enzymes, low platelets count, placental abruption, eclampsia, disseminated intravascular coagulation, and pulmonary edema) and a composite of severe adverse perinatal outcomes (birth weight below the third percentile, very preterm birth [<32 weeks' gestation], and fetal or neonatal death). RESULTS: Of the 543 individuals included in the study, preeclampsia with severe features within 2 weeks was observed in 33.1% (n=180) of them. A receiver operating characteristic curve-derived cutoff of 11.5 multiples of the median for the soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio provided good sensitivity (90.6%), specificity (76.9%), positive predictive value (66.0%), negative predictive value (94.3%), positive likelihood ratio (3.91), negative likelihood ratio (0.12), and accuracy (81.4%) for preeclampsia with severe features within 2 weeks. This cutoff was used to compare test positive cases (≥ cutoff) and test negative cases (< cutoff). Preeclampsia with severe features (66.0% vs 5.7%; P<.001) and composites of severe adverse maternal (8.11% vs 2.7%; P=.006) or perinatal (41.3% vs 10.14%; P=.001) outcomes within 2 weeks were more frequent in test positive cases than in test negative cases. A soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio ≥11.5 multiples of the median was independently associated with preeclampsia with severe features (adjusted incidence rate ratio, 9.08; 95% confidence interval, 6.11-14.06; P<.001) and a composite of severe adverse perinatal outcomes (adjusted incidence rate ratio, 9.42; 95% confidence interval, 6.36-14.53; P<.001) but not with a composite of severe adverse maternal outcomes (adjusted incidence rate ratio, 2.20; 95% confidence interval, 0.95-5.54; P=.08). The area under the curve for the soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio in multiples of the median (0.91; 95% confidence interval, 0.89-0.94) for preeclampsia with severe features within 2 weeks was significantly higher (P<.001 for all comparisons) than either plasma biomarker alone or any other parameter with the exception of absolute soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio values. CONCLUSION: A soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio ≥11.5 multiples of the mean among hospitalized patients with hypertension between 23 and 35 week's gestation predicts progression to preeclampsia with severe features and severe adverse perinatal outcomes within 2 weeks.

The Association between Maternal Body Mass Index and the Risk of Perinatal Depression.

OBJECTIVE: The aim of this study was to evaluate whether the risk of perinatal depression is associated with body mass index (BMI) category. STUDY DESIGN: We performed a retrospective cohort study of women who completed an Edinburgh Postnatal Depression Scale (EPDS) questionnaire during the antepartum period at an integrated health system from January 2003 to May 2018. Risk of perinatal depression was defined as a score of ≥10 on the EPDS or an affirmative response to thoughts of self-harm. Risk of perinatal depression was compared by first trimester BMI category, defined as underweight (BMI: <18.5 kg/m2), normal weight (BMI: 18.5-24.9 kg/m2), overweight (BMI: 25.0-29.9 kg/m2), or obese (BMI: ≥30.0 kg/m2). Univariable analyses were performed using χ 2, Fisher's exact test, analysis of variance, Kruskal-Wallis, and Wilcoxon rank-sum tests as appropriate to evaluate the association between maternal BMI category, demographic and clinical characteristics, and risk of perinatal depression. Logistic multivariable regression models were performed to adjust for potential confounders identified as variables with p < 0.10 in univariable analysis. RESULTS: Our analysis included 3,420 obese women, 3,839 overweight women, 5,949 normal weight women, and 1,203 underweight women. The overall median gestational age at EPDS administration was 27 weeks (interquartile range: 23-29). Overweight and obese women were more likely to be non-Hispanic Black, Hispanic, multiparous, to have public insurance, prepregnancy diabetes, and chronic hypertension as compared with normal or underweight women (p < 0.001). In univariable analysis, the risk of perinatal depression was not significantly different among underweight (10.8%, odds ratio [OR]: 0.86, 95% confidence interval [CI]: 0.79-1.18) or overweight women (12%, OR: 0.96, 95% CI: 0.79-1.18); however, the risk was higher among obese women (14.7%, 95% CI: 1.21-1.55) compared with normal weight women (11.2%). In multivariable analysis, obesity remained associated with an increased risk of perinatal depression (adjusted OR: 1.19, 95% CI: 1.04-1.35). CONCLUSION: Obesity is associated with an increased risk of perinatal depression as compared with women of normal weight. KEY POINTS: · Maternal obesity is associated with an increased risk of perinatal depression.. · Maternal BMI is associated with increased risk of perinatal depression.. · Maternal obesity is an independent risk factor for perinatal depression..

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..

Discontinuation of Oxytocin in the Second Stage of Labor and its Association with Postpartum Hemorrhage.

OBJECTIVE: The objective of the study was to evaluate whether patients with oxytocin discontinued during the second stage of labor (≥30 minutes prior to delivery) had a lower rate of postpartum hemorrhage (PPH) compared with those with oxytocin continued until delivery or discontinued <30 minutes prior to delivery. STUDY DESIGN: Retrospective cohort study was performed from August 1, 2014 to July 31, 2019. Singleton pregnancies of 24 to 42 weeks gestation were included if they reached the second stage of labor and received oxytocin during labor. Patients on anticoagulants were excluded. Patients with oxytocin discontinued ≥30 minutes prior to delivery represented STOPPED and those with oxytocin continued until delivery or discontinued <30 minutes prior to delivery represented CONTINUED. Patient data were abstracted from the electronic medical record. The primary outcome was PPH (≥1,000 mL blood loss). Univariable analyses were performed to compare groups. Multi-variable logistic regression was performed to adjust for prespecified confounders. Planned sub-group analyses by the route of delivery were performed. RESULTS: Of 10,421 total patients, 1,288 had oxytocin STOPPED and 9,133 had oxytocin CONTINUED. There were no significant differences in age, race, or ethnicity, body mass index, public insurance, gestational diabetes, or pregnancy-induced hypertension between STOPPED and CONTINUED. The PPH rate was 15.2 and 5.7% in STOPPED and CONTINUED, respectively (p < 0.001). After adjusting for confounders, STOPPED remained at higher odds for PPH (adjusted odds ratio 2.859, 95% confidence interval 2.394, 3.414, p < 0.001). Among cesarean deliveries only, there was no significant difference in the rate of PPH between STOPPED and CONTINUED (38.0 vs. 36.4%, respectively, p = 0.730). However, among vaginal deliveries, the rate of PPH was actually lower in STOPPED than CONTINUED (3.4 vs. 5.2%, respectively, p = 0.024). CONCLUSION: The rate of PPH was higher in patients with oxytocin STOPPED compared with CONTINUED. However, among vaginal deliveries, there was a significantly lower rate of PPH in STOPPED. These disparate findings may be explained by the variable impact of second-stage oxytocin on PPH as a function of delivery type. KEY POINTS: · It is unclear if oxytocin use in the second stage of labor may independently increase the risk of hemorrhage.. · Patients with oxytocin discontinued during the second stage of labor had a higher rate of PPH.. · PPH was significantly lower among vaginal deliveries in patients with oxytocin discontinued..

Maternal Diabetes and Intrapartum Fetal Electrocardiogram.

OBJECTIVE: Fetal electrocardiogram (ECG) ST changes are associated with fetal cardiac hypoxia. Our objective was to evaluate ST changes by maternal diabetic status and stage of labor. METHODS: This was a secondary analysis of a multicentered randomized-controlled trial in which laboring patients with singleton gestations underwent fetal ECG scalp electrode placement and were randomly assigned to masked or unmasked ST-segment readings. Our primary outcome was the frequency of fetal ECG tracings with ST changes by the stage of labor. ECG tracings were categorized into mutually exclusive groups (ST depression, ST elevation without ST depression, or no ST changes). We compared participants with DM, gestational diabetes mellitus (GDM), and no DM. RESULTS: Of the 5,436 eligible individuals in the first stage of labor (95 with pregestational DM and 370 with GDM), 4,427 progressed to the second stage. ST depression occurred more frequently in the first stage of labor in participants with pregestational DM (15%, adjusted odds ratio [aOR] 2.20, 95% confidence interval [CI] 1.14-4.24) and with GDM (9.5%, aOR 1.51, 95% CI 1.02-2.25) as compared with participants without DM (5.7%). The frequency of ST elevation was similar in participants with pregestational DM (33%, aOR 0.79, 95% CI 0.48-1.30) and GDM (33.2%, aOR 0.91, 95% CI 0.71-1.17) as compared with those without DM (34.2%). In the second stage, ST depression did not occur in participants with pregestational DM (0%) and occurred more frequently in participants with GDM (3.5%, aOR 2.01, 95% CI 1.02-3.98) as compared with those without DM (2.0%). ST elevation occurred more frequently in participants with pregestational DM (30%, aOR 1.81, 95% CI 1.02-3.22) but not with GDM (19.0%, aOR 1.06, 95% CI 0.77-1.47) as compared with those without DM (17.8%). CONCLUSION: ST changes in fetal ECG occur more frequently in fetuses of diabetic mothers during labor. CLINICALTRIALS: gov number, NCT01131260. PRECIS: ST changes in fetal ECG, a marker of fetal cardiac hypoxia, occur more frequently in fetuses of diabetic parturients. KEY POINTS: · Fetal hypertrophic cardiomyopathy (HCM) and cardiac dysfunction occur frequently among fetuses of diabetic patients.. · Fetal ECG changes such as ST elevation and depression reflect cardiac hypoxia.. · Fetuses of diabetic patients demonstrate a higher prevalence of fetal ECG tracings with ST changes..

Elevated Glucose Challenge Test in a Nondiabetic Index Pregnancy and Gestational Diabetes in a Subsequent Pregnancy.

OBJECTIVE: The aim of this study was to evaluate whether a 1-hour glucose challenge test (GCT) ≥140 mg/dL in a nondiabetic index pregnancy is associated with the development of gestational diabetes mellitus (GDM) in a subsequent pregnancy. STUDY DESIGN: We performed a retrospective cohort study from a single institution from June 2009 to December 2018. Women with a nondiabetic index singleton gestation who underwent a 1-hour GCT at 24 to 28 weeks and had a successive singleton delivery were included. GDM was defined by a 1-hour GCT of ≥ 200 mg/dL, ≥2 of 4 elevated values on a 3-hour GCT, or a diagnosis of GDM defined by International Classification of Disease codes in the electronic medical record. Univariable analyses were performed to evaluate the associations between an elevated 1-hour GCT result in the index pregnancy, maternal characteristics, and the development of GDM in the subsequent pregnancy. Variables found to be significant (p < 0.05) were included in multivariable analysis. RESULTS: A total of 2,423 women were included. Of these, 340 (14.0%) had an elevated 1-hour GCT in the index pregnancy. Women with an elevated 1-hour GCT in the index pregnancy compared with those without were significantly more likely to be older, married, privately insured, of Hispanic ethnicity or Asian race, chronically hypertensive, have a higher body mass index (BMI), have a shorter inter-pregnancy interval, and to develop GDM in the subsequent pregnancy (14.4 vs. 3.3%, p < 0.001). In multivariable analysis, an elevated 1-hour GCT (adjusted odds ratio [aOR]: 4.54, 95% confidence interval [CI]: 3.02-6.81), first-trimester BMI ≥30 kg/m2 in the index pregnancy (aOR: 3.10, 95% CI: 2.03-4.71), Asian race (aOR: 2.96, 95% CI: 1.70-5.12), Hispanic ethnicity (aOR: 2.11, 95% CI: 1.12-4.00), and increasing age (aOR: 1.07, 95% CI: 1.02-1.12) were significantly associated with an increased risk of GDM in the subsequent pregnancy. CONCLUSION: An elevated 1-hour GCT in a nondiabetic index pregnancy is associated with a fourfold increased risk of GDM in a subsequent pregnancy. KEY POINTS: · An abnormal 1 hour GCT in an index pregnancy is associated with GDM in a subsequent pregnancy.. · An abnormal 1 hour GCT may be an independent risk factor for GDM in a subsequent pregnancy.. · An abnormal 1 hour GCT is associated with a 4 fold increased risk of GDM in a subsequent pregnancy..

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..

Obesity increases the risk of failure of noninvasive prenatal screening regardless of gestational age.

BACKGROUND: Noninvasive prenatal screening has become an increasingly prevalent choice for women who desire aneuploidy screening. Although the test characteristics are impressive, some women are at increased risk for noninvasive prenatal screen failure. The risk of test failure increases with maternal weight; thus, obese women may be at elevated risk for failure. This risk of failure may be mitigated by the addition of a paternal cheek swab and screening at a later gestational age. OBJECTIVE: The purpose of this study was to evaluate the association among obesity, gestational age, and paternal cheek swab in the prevention of screening failure. STUDY DESIGN: A retrospective cohort study was performed for women who were ≥35 years old at delivery who underwent screening at NorthShore University HealthSystem, Evanston, IL. Maternal weight, body mass index, gestational age, and a paternal cheek swab were evaluated in univariate and multivariable logistic regression analyses to assess the association with failed screening. RESULTS: Five hundred sixty-five women met inclusion criteria for our study. The mean body mass index was 25.9 ± 5.1 kg/m(2); 111 women (20%) were obese (body mass index, ≥30 kg/m(2)). Forty-four women (7.8%) had a failed screen. Obese women had a failure rate of 24.3% compared with 3.8% in nonobese women (P < .01). Gestational age was not associated with failure rate (mean ± standard deviation, 13 ± 3 weeks for both screen failure and nonfailure; P = .76). The addition of a paternal cheek swab reduced the failure rate from 10.2% in women with no swab to 3.8% in women with a swab (P < .01). In multivariable analysis, obesity and lack of a paternal cheek swab were independent predictors of screen failure (odds ratio, 9.75; 95% confidence interval, 4.85-19.61; P < .01; and odds ratio, 3.61; 95% confidence interval, 1.56-8.33; P < .01, respectively). CONCLUSION: The addition of a paternal cheek swab significantly improved noninvasive prenatal screen success rates in obese women. However, delaying testing to a later gestational age did not.

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.

The cost-effectiveness of a trial of labor accrues with multiple subsequent vaginal deliveries.

OBJECTIVE: The purpose of this study was to estimate costs and outcomes of subsequent trials of labor after cesarean delivery (TOLAC) compared with elective repeat cesarean deliveries (ERCD). STUDY DESIGN: To compare TOLAC and ERCD, maternal and neonatal decision analytic models were built for each hypothetic subsequent delivery. We assumed that only women without previa would undergo TOLAC for their second delivery, that women with successful TOLAC would desire future TOLAC, and that women who chose ERCD would undergo subsequent ERCD. Main outcome measures were maternal and neonatal mortality and morbidity rates, direct costs, and quality-adjusted life years. Values were derived from the literature. One-way and Monte-Carlo sensitivity analyses were performed. RESULTS: TOLAC was less costly and more effective for most models. A progression of decreasing incremental cost and increasing incremental effectiveness of TOLAC was found for maternal outcomes with increasing numbers of subsequent deliveries. This progression was also displayed among neonatal outcomes and was most prominent when neonatal and maternal outcomes were combined, with an incremental cost and effectiveness of -$4700.00 and .073, respectively, for the sixth delivery. Net-benefit analysis showed an increase in the benefit of TOLAC with successive deliveries for all outcomes. The maternal model of the second delivery was sensitive to cost of delivery and emergent cesarean delivery. Successive maternal models became more robust, with the models of the third-sixth deliveries sensitive only to cost of delivery. Neonatal models were not sensitive to any variables. CONCLUSION: Although nearly equally effective relative to ERCD for the second delivery, TOLAC becomes less costly and more effective with subsequent deliveries.

Elevated neonatal insulin-like growth factor I is associated with fetal hypertrophic cardiomyopathy in diabetic women.

OBJECTIVE: We sought to determine if fetal hypertrophic cardiomyopathy (HCM) or cardiac dysfunction is associated with elevated maternal or neonatal insulin-like growth factor (IGF)-I levels in women with diabetes. STUDY DESIGN: In a prospective cohort study, fetal echocardiogram findings at 36 weeks' gestation in women with pregestational diabetes mellitus were compared to those in women without diabetes mellitus. HCM was defined as septal or free wall thickness ≥5 mm and cardiac dysfunction as a modified myocardial performance index ≥0.43. Cord serum IGF-I levels at delivery were measured with enzyme-linked immunosorbent assay. Neonates with abnormal fetal echocardiogram were followed up until resolution or 6 months of life. RESULTS: In all, 75 participants completed fetal echocardiography (55 diabetics and 20 controls). In the diabetic group, 33 of 55 (60%) had abnormal fetal echocardiograms with cardiac dysfunction in 21 of 55 (38.2%) and HCM in 8 of 55 (14.5%) and both in 4 of 55 (7.3%). At 6 months of age, 1 of 12 (8%) had persistent HCM. None in the comparison group had abnormal findings. There were no significant clinical differences in those diabetic women with normal vs abnormal fetal echocardiograms. However, among diabetic women, mean neonatal IGF-I was significantly higher in fetuses with HCM (80 ± 16 ng/mL) as compared to those without HCM (61 ± 18 ng/mL), (P < .001). CONCLUSION: Elevated neonatal IGF-I appears to be associated with fetal HCM in fetuses of diabetic women.

Duration of Induction of Labor for Second-Trimester Medication Abortion and Adverse Outcomes.

OBJECTIVE: To evaluate the relationship between duration of labor during second-trimester medication abortion and adverse outcomes. METHODS: We conducted a retrospective cohort study including all individuals with a singleton gestation undergoing second-trimester medication abortion without evidence of advanced cervical dilation, rupture of membranes, or preterm labor at four centers. The primary exposure was duration of labor (ie, hours spent from receiving misoprostol to fetal expulsion). The primary outcome was composite morbidity , defined as uterine rupture, need for blood transfusion, clinical chorioamnionitis, intensive care unit admission, or need for readmission. We performed bivariate and multivariate negative binomial analyses. A post hoc subgroup analysis was performed to assess for the risk of the primary outcome by gestational age. We performed tests of homogeneity based on history of uterine scarring and parity. RESULTS: Six hundred eighty-one individuals were included. The median duration of labor was 11 hours (interquartile range 8-17 hours). One hundred thirty-one (19.2%) experienced the primary outcome. When duration of labor was evaluated continuously, a longer duration of labor was associated with an increased frequency of morbidity (adjusted ß=0.68, 95% CI, 0.32-1.04). When duration of labor was evaluated categorically, those experiencing the highest quartile of duration (ie, 17 hours or more) had a statistically higher risk for experiencing morbidity compared with individuals in all other quartiles (adjusted relative risk 1.99, 95% CI, 1.34-2.96). When we focused on components of the composite outcome, clinical chorioamnionitis was significantly different between those experiencing a longer duration and those experiencing a shorter duration of labor (26.2% vs 10.6%, P <.001). On subgroup analysis, gestational age was not associated with the risk of composite morbidity. Tests of homogeneity demonstrated no significant difference in the risk for morbidity among individuals with a history of uterine scarring or based on parity. CONCLUSION: Duration of labor was independently associated with risks for adverse maternal outcomes during second-trimester medication abortion, specifically clinical chorioamnionitis.

Post-Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) After Infection During Pregnancy.

OBJECTIVE: To estimate the prevalence of post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) after infection with SARS-CoV-2 during pregnancy and to characterize associated risk factors. METHODS: In a multicenter cohort study (NIH RECOVER [Researching COVID to Enhance Recovery]-Pregnancy Cohort), individuals who were pregnant during their first SARS-CoV-2 infection were enrolled across the United States from December 2021 to September 2023, either within 30 days of their infection or at differential time points thereafter. The primary outcome was PASC , defined as score of 12 or higher based on symptoms and severity as previously published by the NIH RECOVER-Adult Cohort, at the first study visit at least 6 months after the participant's first SARS-CoV-2 infection. Risk factors for PASC were evaluated, including sociodemographic characteristics, clinical characteristics before SARS-CoV-2 infection (baseline comorbidities, trimester of infection, vaccination status), and acute infection severity (classified by need for oxygen therapy). Multivariable logistic regression models were fitted to estimate associations between these characteristics and presence of PASC. RESULTS: Of the 1,502 participants, 61.1% had their first SARS-CoV-2 infection on or after December 1, 2021 (ie, during Omicron variant dominance); 51.4% were fully vaccinated before infection; and 182 (12.1%) were enrolled within 30 days of their acute infection. The prevalence of PASC was 9.3% (95% CI, 7.9-10.9%) measured at a median of 10.3 months (interquartile range 6.1-21.5) after first infection. The most common symptoms among individuals with PASC were postexertional malaise (77.7%), fatigue (76.3%), and gastrointestinal symptoms (61.2%). In a multivariable model, the proportion PASC positive with vs without history of obesity (14.9% vs 7.5%, adjusted odds ratio [aOR] 1.65, 95% CI, 1.12-2.43), depression or anxiety disorder (14.4% vs 6.1%, aOR 2.64, 95% CI, 1.79-3.88) before first infection, economic hardship (self-reported difficulty covering expenses) (12.5% vs 6.9%, aOR 1.57, 95% CI, 1.05-2.34), and treatment with oxygen during acute SARS-CoV-2 infection (18.1% vs 8.7%, aOR 1.86, 95% CI, 1.00-3.44) were associated with increased prevalence of PASC. CONCLUSION: The prevalence of PASC at a median time of 10.3 months after SARS-CoV-2 infection during pregnancy was 9.3% in the NIH RECOVER-Pregnancy Cohort. The predominant symptoms were postexertional malaise, fatigue, and gastrointestinal symptoms. Several socioeconomic and clinical characteristics were associated with PASC after infection during pregnancy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT05172024.

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.

Low first-trimester fetal fraction is associated with chronic inflammation in the placenta.

BACKGROUND: Some data suggest an association between abnormal fetal fraction on noninvasive prenatal screening and adverse pregnancy outcomes, including low birthweight, preeclampsia, and preterm birth in the absence of aneuploidy. These findings suggest that abnormal fetal fraction may be associated with placental pathologic processes in early gestation. OBJECTIVE: This study aimed to determine the independent association of fetal fraction on genetic noninvasive prenatal screening with histologic placental types. STUDY DESIGN: This was a retrospective cohort study at a single institution in the period between January 2017 and March 2021, including live births at ≥24 weeks for which noninvasive prenatal screening was performed and placental pathology results were available. Results were stratified by trimester of noninvasive prenatal screening. Clinical characteristics were compared by quartile of fetal fraction using chi-square tests. Linear regression was used to model continuous fetal fraction as a function of 3 histologic types representing chronic placental injury-chronic inflammation, maternal vascular malperfusion, and fetal vascular malperfusion. Inverse probability weighting was used to account for selection bias in characteristics of patients with placental pathology examination. RESULTS: A total of 1374 patients had noninvasive prenatal screening in the first trimester and 262 in the second trimester. Preterm birth and hypertensive disorders of pregnancy were most common in the lowest quartile of fetal fraction. Chronic inflammation was associated with a 0.56 percentage point reduction in fetal fraction (95% confidence interval, -0.95 to -0.16), and maternal vascular malperfusion was associated with a 0.48 percentage point reduction in fetal fraction (95% confidence interval, -0.91 to -0.04) in adjusted models. The association with maternal vascular malperfusion was no longer statistically significant after accounting for selection bias in placentas sent for pathologic examination. Second-trimester fetal fraction was not associated with placental pathology. CONCLUSION: Chronic inflammation is associated with lower first-trimester fetal fraction even after accounting for selection bias. Higher fetal fraction in the second trimester was associated with fetal vascular pathology, although this association was no longer statistically significant after inverse probability weighting to account for selection bias. First-trimester fetal fraction may be a biomarker of adverse outcomes associated with chronic inflammation.

The association between a single abnormal glucose and fetal c-peptide.

AIM: We aimed to evaluated if fetuses of subjects with one elevated value on the 3-h GTT had a measurable physiologic difference in fetal C-peptide levels as compared to those with no elevated values on the GTT. METHODS: We performed a prospective cohort study to evaluate insulin levels in singleton non-anomalous fetuses of subjects with one elevated value on the GTT as compared to subjects with no elevated values on their GTT. Fetal insulin levels were measured by fetal C-peptide in cord blood. Distribution of data was assessed and outliers representing values > the 99th and < the 1st percentiles were excluded. Data were log transformed to achieve normal distribution and univariable analyses were performed to compare fetal C-peptide levels, baseline maternal characteristics and perinatal outcomes in subjects with one elevated value as compared those with no elevated values. RESULTS: Our analysis included 99 subjects, with 49 subjects in the one elevated value group and 50 subjects in the no elevated values group. Fetal C-peptide levels (picomoles per liters, pmol/L), were significantly higher in the elevated value group as compared to the no elevated value group (mean ± SD; 4.6 ± 0.8 vs. 4.3 ± 0.7, P = 0.046, respectively). In univariable analysis, there was no significant difference in maternal characteristics or adverse composite perinatal outcomes. CONCLUSION: Fetuses of subjects who had one elevated value on their GTT had a measurable physiologic difference in C-peptide levels as compared to fetuses of subjects with no elevated values on the GTT.

Researching COVID to enhance recovery (RECOVER) pregnancy study: Rationale, objectives and design.

Importance: Pregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER- Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads. Methods: RECOVER-Pregnancy cohort is a combined prospective and retrospective cohort that proposes to enroll 2,300 individuals with a pregnancy during the COVID-19 pandemic and their offspring exposed and unexposed in utero, including single and multiple gestations. Enrollment will occur both in person at 27 sites through the Eunice Kennedy Shriver National Institutes of Health Maternal-Fetal Medicine Units Network and remotely through national recruitment by the study team at the University of California San Francisco (UCSF). Adults with and without SARS-CoV-2 infection during pregnancy are eligible for enrollment in the pregnancy cohort and will follow the protocol for RECOVER-Adult including validated screening tools, laboratory analyses and symptom questionnaires followed by more in-depth phenotyping of PASC on a subset of the overall cohort. Offspring exposed and unexposed in utero to SARS-CoV-2 maternal infection will undergo screening tests for neurodevelopment and other health outcomes at 12, 18, 24, 36 and 48 months of age. Blood specimens will be collected at 24 months of age for SARS-CoV-2 antibody testing, storage and anticipated later analyses proposed by RECOVER and other investigators. Discussion: RECOVER-Pregnancy will address whether having SARS-CoV-2 during pregnancy modifies the risk factors, prevalence, and phenotype of PASC. The pregnancy cohort will also establish whether there are increased risks of adverse long-term outcomes among children exposed in utero. Registration: NCT05172024.

Researching COVID to enhance recovery (RECOVER) pregnancy study: Rationale, objectives and design.

IMPORTANCE: Pregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER-Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads. METHODS: RECOVER-Pregnancy cohort is a combined prospective and retrospective cohort that proposes to enroll 2,300 individuals with a pregnancy during the COVID-19 pandemic and their offspring exposed and unexposed in utero, including single and multiple gestations. Enrollment will occur both in person at 27 sites through the Eunice Kennedy Shriver National Institutes of Health Maternal-Fetal Medicine Units Network and remotely through national recruitment by the study team at the University of California San Francisco (UCSF). Adults with and without SARS-CoV-2 infection during pregnancy are eligible for enrollment in the pregnancy cohort and will follow the protocol for RECOVER-Adult including validated screening tools, laboratory analyses and symptom questionnaires followed by more in-depth phenotyping of PASC on a subset of the overall cohort. Offspring exposed and unexposed in utero to SARS-CoV-2 maternal infection will undergo screening tests for neurodevelopment and other health outcomes at 12, 18, 24, 36 and 48 months of age. Blood specimens will be collected at 24 months of age for SARS-CoV-2 antibody testing, storage and anticipated later analyses proposed by RECOVER and other investigators. DISCUSSION: RECOVER-Pregnancy will address whether having SARS-CoV-2 during pregnancy modifies the risk factors, prevalence, and phenotype of PASC. The pregnancy cohort will also establish whether there are increased risks of adverse long-term outcomes among children exposed in utero. CLINICAL TRIALS.GOV IDENTIFIER: Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.