Association between plasma leptin and cesarean section after induction of labor: a case control study.

BACKGROUND: Obesity in pregnancy is common, with more than 50% of pregnant women being overweight or obese. Obesity has been identified as an independent predictor of dysfunctional labor and is associated with increased risk of failed induction of labor resulting in cesarean section. Leptin, an adipokine, is secreted from adipose tissue under the control of the obesity gene. Concentrations of leptin increase with increasing percent body fat due to elevated leptin production from the adipose tissue of obese individuals. Interestingly, the placenta is also a major source of leptin production during pregnancy. Leptin has regulatory effects on neuronal tissue, vascular smooth muscle, and nonvascular smooth muscle systems. It has also been demonstrated that leptin has an inhibitory effect on myometrial contractility with both intensity and frequency of contractions decreased. These findings suggest that leptin may play an important role in dysfunctional labor and be associated with the outcome of induction of labor at term. Our aim is to determine whether maternal plasma leptin concentration is indicative of the outcome of induction of labor at term. We hypothesize that elevated maternal plasma leptin levels are associated with a failed term induction of labor resulting in a cesarean delivery. METHODS: In this case-control study, leptin was measured in 3rd trimester plasma samples. To analyze labor outcomes, 174 women were selected based on having undergone an induction of labor (IOL), (115 women with successful IOL and 59 women with a failed IOL). Plasma samples and clinical information were obtained from the UI Maternal Fetal Tissue Bank (IRB# 200910784). Maternal plasma leptin and total protein concentrations were measured using commercially available assays. Bivariate analyses and logistic regression models were constructed using regression identified clinically significant confounding variables. All variables were tested at significance level of 0.05. RESULTS: Women with failed IOL had higher maternal plasma leptin values (0.5 vs 0.3 pg, P = 0.01). These women were more likely to have obesity (mean BMI 32 vs 27 kg/m2, P = 0.0002) as well as require multiple induction methods (93% vs 73%, p = 0.008). Logistic regression showed Bishop score (OR 1.5, p < 0.001), BMI (OR 0.92, P < 0.001), preeclampsia (OR 0.12, P = 0.010), use of multiple methods of induction (OR 0.22, P = 0.008) and leptin (OR 0.42, P = 0.017) were significantly associated with IOL outcome. Specifically, after controlling for BMI, Bishop Score, and preeclampsia, leptin was still predictive of a failed IOL with an odds ratio of 0.47 (P = 0.046). Finally, using leptin as a predictor for fetal outcomes, leptin was also associated with of fetal intolerance of labor, with an odds ratio of 2.3 (P = 0.027). This association remained but failed to meet statistical significance when controlling for successful (IOL) (OR 1.5, P = 0.50). CONCLUSIONS: Maternal plasma leptin may be a useful tool for determining which women are likely to have a failed induction of labor and for counseling women about undertaking an induction of labor versus proceeding with cesarean delivery.

The outcomes and experience of pregnancy in limb girdle muscular dystrophy type R9.

INTRODUCTION: Published information about the experiences of pregnancy in limb girdle muscular dystrophy (LGMD) is limited and does not specify LGMD type, limiting utility. We describe the experience and outcomes of pregnancy in a cohort of women with LGMD type R9 (LGMDR. METHODS: All women 18 y of age or older with a genetic and clinical diagnosis of LGMDR9 who are enrolled in the University of Iowa Wellstone dystroglycanopathy natural history study (clinicaltrials.gov NCT00313677) were invited to complete a questionnaire about their pregnancy experiences, including questions about pregnancy complications, muscle symptoms experienced during pregnancy, and post-partum course. RESULTS: A total of 22 women responded to the survey. Thirteen women reported 26 live births. The majority of pregnancies that resulted in a live birth were uncomplicated (n = 19, 73%), and most infants had no complications (n = 25, 96%). The rates of assisted vaginal delivery (n = 9, 35%) and induction of labor (n = 18, 70%) were both significantly higher than the national average. Almost half of pregnancies (n = 11, 42%) resulted in increased weakness during pregnancy; only one returned to pre-pregnancy baseline. DISCUSSION: The data presented here suggest that women with LGMDR9 who are considering a pregnancy should be counseled that they might have a higher likelihood of assisted vaginal delivery and could experience progression of weakness. These results are generally consistent with previous reports, but future studies of pregnancy in defined subtypes of LGMD will be required to confirm these findings and determine if risks vary by genotype.

Arginine vasopressin infusion is sufficient to model clinical features of preeclampsia in mice.

Copeptin, a marker of arginine vasopressin (AVP) secretion, is elevated throughout human pregnancies complicated by preeclampsia (PE), and AVP infusion throughout gestation is sufficient to induce the major phenotypes of PE in mice. Thus, we hypothesized a role for AVP in the pathogenesis of PE. AVP infusion into pregnant C57BL/6J mice resulted in hypertension, renal glomerular endotheliosis, intrauterine growth restriction, decreased placental growth factor (PGF), altered placental morphology, placental oxidative stress, and placental gene expression consistent with human PE. Interestingly, these changes occurred despite a lack of placental hypoxia or elevations in placental fms-like tyrosine kinase-1 (FLT1). Coinfusion of AVP receptor antagonists and time-restricted infusion of AVP uncovered a mid-gestational role for the AVPR1A receptor in the observed renal pathologies, versus mid- and late-gestational roles for the AVPR2 receptor in the blood pressure and fetal phenotypes. These findings demonstrate that AVP is sufficient to initiate phenotypes of PE in the absence of placental hypoxia, and indicate that AVP may mechanistically (independently, and possibly synergistically with hypoxia) contribute to the development of clinical signs of PE in specific subtypes of human PE. Additionally, they identify divergent and gestational time-specific signaling mechanisms that mediate the development of PE phenotypes in response to AVP.

Lipopolysaccharide-induced maternal inflammation induces direct placental injury without alteration in placental blood flow and induces a secondary fetal intestinal injury that persists into adulthood.

PROBLEM: Premature birth complicates 10%-12% of deliveries. Infection and inflammation are the most common etiologies and are associated with increased offspring morbidity and mortality. We hypothesize that lipopolysaccharide (LPS)-induced maternal inflammation causes direct placenta injury and subsequent injury to the fetal intestine. METHOD OF STUDY: Pregnant C57Bl6 mice were injected intraperitoneally on day 15.5 with 100 µg/kg LPS or saline. Maternal serum, amniotic fluid, placental samples, and ileal samples of offspring were obtained assessed for inflammation and/or injury. Maternal placental ultrasounds were performed. Placental DNA was isolated for microbiome analysis. RESULTS: Maternal injection with LPS caused elevated IL-1ß, IL-10, IL-6, KC-GRO, and TNF. Placental tissue showed increased IL-1ß, IL-6, and KC-GRO and decreased IL-10, but no changes were observed in amniotic fluid. Placental histology demonstrated LPS-induced increases in mineralization and necrosis, but no difference in placental blood flow. Most placentas had no detectable microbiome. Exposure to maternal LPS induced significant injury to the ilea of the offspring. CONCLUSION: Lipopolysaccharide causes a maternal inflammatory response that is mirrored in the placenta. Placental histology demonstrates structural changes; however, placental blood flow is preserved. LPS also induces an indirect intestinal injury in the offspring that lasts beyond the neonatal period.

Surgical site infections and cellulitis after abdominal hysterectomy.

OBJECTIVES: To identify risk factors for and outcomes of surgical site infections and cellulitis after abdominal hysterectomies. STUDY DESIGN: We used logistic regression analysis to analyze data from a case-control study of 1104 patients undergoing abdominal hysterectomies at a university hospital between Jan. 1, 2007 and Dec. 30, 2010. RESULTS: Factors significantly associated with surgical site infections and with cellulitis were: pulmonary disease, operations done in Main Operating Room East, and seroma. Body mass index >35, no private insurance, and fluid and electrolyte disorders were risk factors for surgical site infections. The mean prophylactic dose of cefazolin was significantly higher for controls than for patients with surgical site infections. Preoperative showers with Hibiclens (Molnlycke Health Care US, LLC, Norcross, GA) and cefazolin prophylaxis were associated with a significantly decreased cellulitis risk. Surgical site infections and cellulitis were significantly associated with readmissions and return visits and surgical site infections were associated with reoperations. CONCLUSION: Preoperative showers, antimicrobial prophylaxis, surgical techniques preventing seromas, and the operating room environment may affect the risk of surgical site infections and cellulitis after abdominal hysterectomies.

Overexpression of the SK3 channel alters vascular remodeling during pregnancy, leading to fetal demise.

The maternal cardiovascular system undergoes hemodynamic changes during pregnancy via angiogenesis and vasodilation to ensure adequate perfusion of the placenta. Improper vascularization at the maternal-fetal interface can cause pregnancy complications and poor fetal outcomes. Recent evidence indicates that small conductance Ca(2+)-activated K(+) channel subtype 3 (SK3) contributes to vascular remodeling during pregnancy, and we hypothesized that abnormal SK3 channel expression would alter the ability of the maternal cardiovascular system to adapt to pregnancy demands and lead to poor fetal outcomes. We investigated this hypothesis using transgenic Kcnn3(tm1Jpad)/Kcnn3(tm1Jpad) (SK3(T/T)) mice that overexpress the channel. Isolated pressurized uterine arteries from nonpregnant transgenic SK3(T/T) mice had larger basal diameters and decreased agonist-induced constriction than those from their wild-type counterparts; however, non-receptor-mediated depolarization remained intact. In addition to vascular changes, heart rates and ejection fraction were increased, whereas end systolic volume was reduced in SK3(T/T) mice compared with their wild-type littermates. Uterine sonography of the fetuses on pregnancy day 14 showed a significant decrease in fetal size in SK3(T/T) compared with wild-type mice; thus, SK3(T/T) mice displayed an intrauterine growth-restricted phenotype. The SK3(T/T) mice showed decreased placental thicknesses and higher incidence of fetal loss, losing over half of their complement of pups by midgestation. These results establish that the SK3 channel contributes to both maternal and fetal outcomes during pregnancy and point to the importance of SK3 channel regulation in maintaining a healthy pregnancy.

Abnormal uterine bleeding: a management algorithm.

Abnormal uterine bleeding is a common problem, and its management can be complex. Because of this complexity, concise guidelines have been difficult to develop. We constructed a concise but comprehensive algorithm for the management of abnormal uterine bleeding between menarche and menopause that was based on a systematic review of the literature as well as the actual management of patients seen in a gynecology clinic. We started by drafting an algorithm that was based on a MEDLINE search for relevant reviews and original research. We compared this algorithm to the actual care provided to a random sample of 100 women with abnormal bleeding who were seen in a university gynecology clinic. Discrepancies between the algorithm and actual care were discussed during audiotaped meetings among the 4 investigators (2 family physicians and 2 gynecologists). The audiotapes were used to revise the algorithm. After 3 iterations of this process (total of 300 patients), we agreed on a final algorithm that generally followed the practices we observed, while maintaining consistency with the evidence. In clinic, the gynecologists categorized the patient's bleeding pattern into 1 of 4 types: irregular bleeding, heavy but regular bleeding (menorrhagia), severe acute bleeding, and abnormal bleeding associated with a contraceptive method. Subsequent management involved both diagnostic and treatment interventions, which often occurred simultaneously. The algorithm in this article is designed to help primary care physicians manage abnormal uterine bleeding using strategies that are consistent with the evidence as well as the actual practice of gynecologists.